EPR and 1H and 13C dynamic nuclear polarization studies of a molecularly doped polymer: bisphenol A polycarbonate doped with trianisylamine and trianisylaminium perchlorate. We have investigated the EPR and DNP behavior of a molecularly doped polymer modeling those used to transport electronic charge in electrophotography. The EPR spectra show no evidence of the superexchange reported for a closely related system based on tri-p-tolylamine. The difference may be due to larger charge-transfer matrix elements in the latter system. An unambiguous interpretation of the observed 1H DNP was rendered difficult by the unanticipated asymmetry of the EPR spectra. We report extensive data on the "three-spin" effect evident in the DNP-enhanced 13C NMR spectra, and comment on its potential for characterizing polymer interfaces.


On the 13C CP/MAS spectra of leucine.

On the 13C CP/MAS spectra of leucine. The CP/MAS 13C NMR spectra of crystalline L-leucine and DL-leucine at 7 T are compared with previously reported spectra at lower field strengths. An increasing dominance of chemical shift effects over residual 14N-13C dipolar interactions is observed on the C alpha and C beta splittings with increasing field strength. A new structure is observed in the 25 ppm region of both samples. The spectra in this region were assigned by application of the depolarisation-repolarisation method. The assignment showed differences in the ordering of peaks between solid state and liquid state chemical shifts.


Dipolar 31P NMR spectroscopy of crystalline inorganic phosphorus compounds. The ability of the 90 degrees-t1-180 degrees pulse sequence to produce accurate dipole-dipole coupling information in solids is investigated. To this end, the experimental 31P spin echo decays are measured for eighteen crystalline phosphides and phosphorus chalcogenides and compared with simulations, based on the known internuclear distances in these compounds. The experimental results are generally found accurate in compounds where the dominant contribution to the dipole-dipole coupling arises from nuclei in structurally inequivalent sites with large chemical shift anisotropies. For this situation, the quantum mechanical "flip-flop" term in the dipolar Hamiltonian is suppressed and the dipole-dipole coupling is entirely heteronuclear in character. All of those compounds that do not obey this condition show accelerated spin echo decays due to a fractional contribution of the flip-flop term and possibly incomplete refocusing of chemical shift terms on the time scale of the experiment. The results confirm on an empirical basis that the spin echo NMR technique can provide accurate dipole-dipole coupling information (and thus distance distributions) in disordered solids and glasses.


Phosphorus-31 NMR studies of stabilized phosphorus ylids in the solid state. Phosphorus-31 powder NMR spectra and high-resolution MAS spectra have been obtained for a number of stabilized phosphorus ylids under conditions of high-power proton decoupling and cross-polarization. The 31P CP/MAS spectra are compared to those obtained from isotropic solutions. The variation of chemical shift anisotropy and of the principal components of the 31P chemical shift tensor determined from 31P powder NMR line shapes are discussed in terms of the relative importance of accepted valence bond resonance structures. The results indicate that the invariance of the isotropic chemical shift, delta iso, observed in previous 31P NMR investigations of phosphorus ylids in solution is due to fortuitous cancellation of opposing changes in the principal components, delta 11 and delta 33, of the 31P chemical shift tensor. The 31P dipolar NMR powder spectrum of a typical stabilized ylid, (C6H5)3(31)P-13CHC(O)OCH2CH3, is analyzed in order to obtain the orientation of the 31P chemical shift tensor with respect to the 31P-13C alpha dipolar vector.


Assignments of solid-state 13C resonances for polymorphs of cortisone acetate using shielding tensor components. Carbon-13 CP/MAS spectra have been obtained for seven polymorphic and solvated forms of cortisone acetate. For signals in the high-frequency region, the spinning sideband manifolds of the spectra recorded under slow-spinning conditions have been analysed to obtain the shielding tensor components for the five resonances at the highest frequency. These show characteristic values for given types of carbon and have enabled assignments of the C5 and C22 signals to be made with some certainty, providing firm evidence of cross-over between the shifts for these carbons between different polymorphs. Assignments are suggested more tentatively for the resonances from C3, C11 and C20. Comparison of chemical shifts for those forms with published X-ray structures enables conclusions to be drawn regarding hydrogen bonding in the remaining forms. Hydrogen bonding induces a high-frequency change in the isotropic chemical shift of approximately 3 ppm.


1H NMR study of lithium D-lactate.

1H NMR study of lithium D-lactate. Polycrystalline D-lactic acid lithium salt [(R)-2-hydroxypropanoic acid lithium salt, lithium D-lactate] has been investigated by pulsed proton magnetic resonance methods between 77 and 300 K at 25 MHz. The main relaxation mechanism is methyl rotation; the motion is characterized by an activation energy Ea = 14.5 +/- 0.5 kJ/mol and time factor tau 0 = (1.5 +/- 0.5) x 10(-13) s. The activation energy is higher than the potential barrier obtained by ESR and ENDOR techniques for methyl rotation in the lactate radical. The methyl rotation is also responsible for a reduction of the dipolar second moment. Below 100 K the reduction of the dipolar second moment is ascribed to quantum-mechanical tunneling; an excitation energy of 6.1 +/- 1 kJ/mol is derived from a contribution to the spin-lattice relaxation times from the tunneling.


Proton relaxation NMR study of polycrystalline progesterone. Polycrystalline progesterone (4-pregnene-3,20-dione, C21H30O2) has been investigated by proton NMR methods between 80 and 350 K. A reduction in dipolar second moment is ascribed to methyl group reorientation. Minima in the spin-lattice relaxation time found in measurements at five frequencies from 7 to 200 MHz are attributed to reorientation of two of the three methyl groups in each molecule, characterized by activation energy Ea = 10.9 +/- 0.8 kJ/mol and tau o = (2.3 +/- 0.2) x 10(-13) s. Additional relaxation at lower temperatures is attributed to reorientation of the third methyl group with Ea approximately 3.4 kJ/mol. Measurements were also made of relaxation in the rotating frame.


Multinuclear MAS NMR study of the microporous aluminophosphate AlPO4-17 and the related silicoaluminophosphate SAPO-17. AlPO4-17 and SAPO-17 in their as-synthesized, calcined, and calcined and subsequently rehydrated forms have been studied by 27Al and 31P MAS NMR. Pronounced structural changes caused by template removal and rehydration can unambiguously be attributed to a change in the coordination number (on calcination: 5-->4, on rehydration/dehydration: 4<-->6) of part of the framework aluminium atoms. The different resonance lines can be assigned to crystallographically inequivalent sites present in the modified ERI framework. 27Al quadrupolar coupling parameters of the two aluminium sites in the calcined AlPO4-17 (CQ = 4.4 MHz and 2.1 MHz) were determined by recording spectra at different field strengths. The isotropic chemical shifts were obtained from rotation sidebands of the (+/- 3/2, +/- 1/2) satellite transitions. 2D 27Al nutation MAS NMR was used to corroborate the line assignment for the as-synthesized and the rehydrated AlPO4-17. By using 13C MAS NMR it was shown that the occluded template (cyclohexylamine) is present as ions. For the first time, a splitting of the 29Si NMR line caused by crystallographically inequivalent sites in a SAPO-type material is reported. The line splitting of 4.3 ppm is comparable with that observed for isostructural aluminosilicate erionite.


27Al and 23Na double-rotation NMR of sodalites. The 27Al NMR spectra of calcium tungstate aluminate sodalite (CAW), Ca8[Al12O24](WO4)2, and the 23Na NMR spectra of sodium aluminosilicate sodalites of general composition Na9[Si6Al6O24]A2 with A = B(OH)4- (SBS), SCN- (SRS) and A2 = SO4(2-) (SSS), MoO4(2-) (SMS) have been measured using magic-angle spinning (MAS) and double-rotation (DOR) techniques. Rotor synchronized pulse excitation is applied in the DOR experiments. Dramatic line narrowing is observed in the DOR spectra of all samples. The 27Al DOR NMR spectra of CAW measured at 9.4 and 11.7 T and spinning rates of 800-1150 Hz of the outer and 5 kHz of the inner rotor show seven sharp central lines accompanied by a manifold of spinning sidebands. These lines correspond to the seven crystallographically inequivalent Al sites of the CAW framework derived from X-ray structure analysis. From the difference of the line positions in the 9.4 and 11.7 T spectra the quadrupole coupling constant, QCC, quadrupole induced shift, sigma qs, and isotropic chemical shift, delta cs, of each Al site have been calculated. QCC values in the range of 5 to 9 MHz are obtained which reflect the strong tetragonal distortion of the AlO4 tetrahedra in CAW. delta cs shows only small changes in the range between 74.4 and 77.2 ppm. A tentative assignment of all lines to the distinct Al sites is derived from the correlation between QCC and a "shear strain parameter" describing quantitatively the distortion of the AlO4 tetrahedra.(ABSTRACT TRUNCATED AT 250 WORDS)


Study of a spin-3/2 system by a quadrupolar-echo sequence: suppression of spurious signals. The density matrix describing the evolution of a spin-3/2 system excited by a quadrupolar-echo sequence consisting of two rf pulses in quadrature phase, (X)-tau 2-(Y)-tau 4-[acquisition(y)], is calculated from the equilibrium state to the acquisition period. The interactions involved are the first-order quadrupolar interaction throughout the experiment and a local heteronuclear magnetic dipolar term between the two pulses and during the acquisition period. Three echoes, one due to a satellite transition at tau 4 = tau 2 and two due to the central transition at tau 4 = tau 2 and tau 4 = 3 tau 2, are predicted. They have similar expressions than those obtained with two rf pulses of the same phase, (X)-tau 2-(X)-tau 4-[acquisition(y)], except the signs. Moreover, it is shown experimentally that a combination of these two sequences, namely: (X)-tau 2-(X)-tau 4-[acquisition(y)]-recycle delay-(X)-tau 2-(-X)-tau 4-[acquisition(y)]-recycle delay-(X)-tau 2-(Y)-tau 4-[acquisition(-y)]-recycle delay-(X)-tau 2-(-Y)-tau 4-[acquisition(-y)]-recycle delay, cancels the spurious piezo-electric signals when studying a ferro-electric material in the single-crystal form.


Observation of nitrogen-14, carbon-13 indirect spin-spin coupling in high-resolution 13C CP/MAS spectra of solids. The 13C CP/MAS NMR spectrum of [(n-C3H7)4N][Cd(SCN)3], 1, indicates the presence of three non-equivalent thiocyanate ligands, in agreement with the results of a recent single-crystal X-ray diffraction study. Examination of the 13C MAS line shapes allows direct measurement of the indirect spin-spin coupling constants, 1J(14N, 13C) = 16 +/- 1 Hz and 2J(111/113Cd, 13C) = 75 +/- 5 Hz, for the unique N-bonded thiocyanate ligand. This is the first reported measurement of 1J(14N, 13C) and 2J(111/113Cd, 13C) in the solid state. Possible reasons for the failure to observe 1J(14N, 13C) values in previous high-resolution 13C CP/MAS NMR studies are summarized.


91Zr NMR characterisation of phases in transformation toughened zirconia. A detailed 91Zr NMR investigation is presented of the five component (cubic, monoclinic, tetragonal, orthorhombic and delta) phase mixture in the transformation toughened engineering ceramic, magnesia-partially-stabilised zirconia (MgPSZ). The phases are distinguished on the basis of the quadrupole interaction displayed in the powder pattern of the 91Zr(1/2, -1/2) transition. This paper reports: (i) the first characterisation of the magnesia-fully-stabilised cubic phase at the eutectic composition (13.5 mol% MgO); (ii) the observation of a poorly ordered tetragonal phase on fast cooling ZrO2 (9.3 mol% MgO) from the cubic phase field at 1720 degrees C, and the subsequent growth and ordering of the tetragonal phase precipitates due to further annealing; (iii) the observation of the (partial) transformation of the cubic phase to the ordered delta-phase (Mg2Zr5O12) on annealing MgPSZ at 1100 degrees C for 8 h; and (iv) the observation of the transformation of the tetragonal phase into the orthorhombic phase after cooling in liquid nitrogen, and the reverse transformation after heating to 600 degrees C.


A multinuclear magnetic resonance examination of the mineral grandidierite. Identification of a 27Al resonance from a well-defined AlO5 site. 11B, 27Al and 29Si magic angle spinning NMR results are reported for the boroaluminosilicate mineral grandidierite (Mg, Fe)Al3SiBO9. Three distinct aluminium sites are identified, two AlO6 and one AlO5. Despite overlap of the centrebands from these sites the use of three magnetic fields (9.4, 11.7 and 14.1 T) allows unambiguous values for the isotropic chemical shift (delta iso), quadrupolar coupling constant (Cq) and quadrupolar asymmetry parameter (eta) to be deduced for each site. The NMR spectrum from the AlO5 site is simulated with parameters Cq = 8.7 +/- 0.1 MHz, eta = 0.95 +/- 0.05 and delta iso = 41 +/- 1 ppm which are compared to values from other well-defined AlO5 units.


Selective saturation and inversion of multiple resonances in high-resolution solid-state 13C experiments using slow spinning CP/MAS and tailored DANTE pulse sequences. Taking advantage of the long 13C T1 values generally encountered in solids, selective saturation and inversion of more than one resonance in 13C CP/MAS experiments can be achieved by sequentially applying several DANTE pulse sequences centered at different transmitter frequency offsets. A new selective saturation pulse sequence is introduced composed of a series of 90 degrees DANTE sequences separated by interrupted decoupling periods during which the selected resonance is destroyed. Applications of this method, including the simplification of the measurement of the principal values of the 13C chemical shift tensor under slow MAS conditions, are described. The determination of the aromaticity of coal using a relatively slow MAS rate is also described.


Rotational frequencies of methyl group tunneling. Methyl tunnel frequencies, measured at 4 K, are found to be 455 +/- 8 kHz in methyl malonamide and 496 +/- 8 kHz in methyl ethyl ketone. The first is unaffected by deuteration of the amide groups. Measurements of the temperature dependence of the spin lattice relaxation time are also reported for methyl malonamide and a further test is made of a previously reported correlation between tunnel frequency and the temperature of the T1 minimum. The measurements are in good agreement with the universal correlation curve.


Magic-angle-spinning 31P NMR spectra of solid dihydrogen phosphates. Comparison of ordered and dynamically disordered compounds. High-resolution 31P NMR spectra are reported for several dihydrogen phosphates in the solid state. Shielding tensor components were retrieved by analysis of the sideband intensities. The results, together with previously published data, can be grouped according to the presence and type of proton exchange occurring in the crystals. Static MH2PO4 samples (M = Na, Li) show a shielding anisotropy delta sigma of approximately 120 ppm. In the case of M = Cs (one static P-OH bond and two oxygens attached to "half" hydrogens on the average) delta sigma is smaller (approximately 75 ppm) and can be understood in terms of the accepted, proton-exchange model. For highly disordered samples (M = K, NH4, Rb), where all four oxygens have nearby hydrogens with 50% occupancy, delta sigma is even smaller (approximately 30 ppm) but not zero. In the last-mentioned cases, 31P NMR information suggests that local PO4 environments may not have the symmetry that could be expected on the basis of the known crystal structures.


Time-domain calculation of chemical exchange effects in the NMR spectra of rotating solids. A simple method is described for the calculation of magic-angle-spinning (MAS) spectra of solids in the presence of chemical exchange. The method converges quickly, allowing rapid calculation of the spectra. Calculated spectra are given for molecular motion involving 2 and 6 sites.


Solid-state 27Al NMR studies of aluminophosphate molecular sieves. Enhanced resolution by quadrupole nutation and double-rotation. Solid-state 27Al NMR spectra of several aluminophosphate molecular sieves have been recorded with conventional magic-angle spinning (MAS), double-rotation (DOR) and quadrupole nutation with fast MAS. Enhanced resolution was obtained in the quadrupole nutation experiment at certain radiofrequency pulse strengths. This extra resolution can be comparable to that attainable using DOR, and does not introduce spinning sidebands.


A bi-symmetric square wave Zeeman modulator for nuclear quadrupole resonance. A simple circuit has been designed to generate a bi-symmetric square wave Zeeman modulation for the detection of nuclear quadrupole resonance. The square waveform not only provides an optimum result among bi-symmetric modulation waveforms, but also allows the observation of the Zeeman perturbed NQR powder pattern without the need for an extra external magnetic field.


A versatile method for rotation-synchronised 2D exchange spectroscopy of solids. A versatile, reliable, easy-to-use method to achieve rotor-synchronisation during the mixing time tau m in 2D magnetisation transfer experiments on rotating solids is shown. The limits of accuracy of the method are discussed and some examples of application are given. A full description of all technical details is provided.


The chemical shift interaction under weak radio frequency pulses. The chemical shift anisotropy of a nuclear spin system in a strong magnetic field can be comparable to the strength of the rf pulse (weak pulse condition). In this case, the commonly used assumption that the chemical shift interaction Hamiltonian in the duration of a rf pulse can be neglected is no longer effective. The rf response characteristics of a spin-1/2 system under a weak pulse condition is studied in detail. The relationships between the distortion of the chemical shift powder spectrum and the relative rf field amplitude under various conditions are given. The suppression of sidebands of a MAS spectrum is analysed as an example of solid multiple pulse experiments. The experimental results are in good agreement with computer simulations.


A study of tin dioxide and antimony tetroxide supported vanadium oxide catalysts by solid-state 51V and 1H NMR techniques. A series of vanadia catalysts with various V2O5 loadings supported on SnO2 and alpha-Sb2O4 are investigated by the application of X-ray diffraction and solid-state 51V and 1H NMR techniques. XRD results show no evidence for the formation of a crystalline vanadia phase on both supports. However, the 51V NMR spectra of the catalysts reveal the existence of two types of vanadia species on the surface of the support: one due to a dispersed vanadia phase at lower vanadia loadings and the other due to a crystalline vanadia phase at higher vanadium content. The quantity of the dispersed vanadia phase, however, depends on the nature of the support material. The 1H NMR results provide evidence for the existence or non-existence of a metal oxide support interaction through the support surface hydroxyl groups.


Nuclear spin-lattice relaxation in transition metal compounds with local tetragonal symmetry. We report on the various contributions to the total spin-lattice relaxation rate in metallic materials with local tetragonal symmetry. The analytical formulae are given in the tight-binding approximation. The calculations show the relation between various partial electron densities of states and corresponding contributions to the relaxation rates. The presented formulae can be used to compare theoretically calculated electron band structure parameters with those obtained from NMR spin-lattice relaxation time measurements.


Quadrupole parameters of 11B in crystalline CaO.B2O3. The quadrupole coupling constant (Qcc) and asymmetry parameter (eta) of 11B in crystalline CaO.B2O3 have been measured employing three different NQR and NMR methods: (1) 11B and 10B NQR; (2) 11B NQR and NMR; and (3) the 11B Zeeman NQR powder pattern. It is found that Qcc = 2594.3 +/- 0.5 kHz and eta = 0.515 +/- 0.001 at 77 K, and Qcc = 2573.5 +/- 0.5 kHz and eta = 0.511 +/- 0.002 at 300 K. These values are in agreement with, but far more accurate than, values obtained from a fourth procedure: measurement of the second-order quadrupolar effects evident in the m = + 1/2<-->m = - 1/2 transition of the 11B NMR spectrum.


27Al satellite transition spectroscopy (SATRAS) of polycrystalline aluminum borate 9Al2O3.2B2O3. 27Al NMR spectra of polycrystalline aluminum borate 9Al2O3.2B2O3 have been measured at 104, 130 and 156 MHz. The parameters of the quadrupole interaction and the isotropic chemical shifts have been obtained by fitting the CT/MAS pattern and consideration of the inner satellite transitions m = 3/2<-->1/2 and m = - 1/2<-->- 3/2. The gain in spectral resolution concerned with the observation of the MAS lines of the inner satellites leads to complete separation of the signals of AlO6, AlO5 and AlO4 polyhedra. Also signals of structural groups of one and the same coordination number can be distinguished. Experimental and theoretical lineshape calculations are compared.


Sidebands in dynamic angle spinning (DAS) and double rotation (DOR) NMR. A theory of dynamic angle spinning (DAS) and double rotation (DOR) NMR is described using average Hamiltonian and irreducible tensor methods. Sideband intensities in DAS and DOR spectra are analyzed by both the moment and Bessel function methods, and general formulae are derived. Results show that the DAS moments depend on the relative rotor phase between the first and the second evolution periods, whereas the second and third DOR moments are independent of the relative phase between the inner and outer rotors. Sideband intensities in DAS spectra also depend on the relative rotor phases between evolution at the first and second angles, as well as on the ratio of time spent at each angle. Sideband intensities and phases in DOR spectra are related to the relative rotor phases between the inner and outer rotors, and the sideband pattern is determined by the ratio of the inner and outer rotor spinning speeds. An inversion symmetry of the odd numbered DOR sidebands at the relative rotor phase gamma r = 0 degree, 180 degrees permits the elimination of these sidebands. Finally, numerical simulations are implemented and shown to agree with experimental results. Quadrupolar parameters can therefore be recovered either by calculating the second and third moments or by simulating the sideband intensities and phases.


Effects of lipids on cancer therapy.

Effects of lipids on cancer therapy. The fatty acid composition of cancer cell membranes can change substantially when the cells are exposed to different types of fat. Such change occurs when tumors are grown in animals fed high-fat diets that differ in degree of unsaturation or during culture in media supplemented with various fatty acids. Certain physical and functional properties of the membrane are modified when the polyunsaturated fatty acid content is increased, and the cells become more sensitive to hyperthermia or treatment with doxorubicin. These findings suggest a potential role for lipid nutrition in cancer therapy. By altering the properties of the membrane lipids, changes in the dietary fat intake may provide a new approach for enhancing the effectiveness of certain antineoplastic therapies.


[Pharmacologic interactions between quinolones and oral hypoglycemic agents. An experimental study on rabbits]. The association between antibiotics and oral hypoglycemic agents can determine various pharmacological interactions. The aim of our work has been to verify experimentally the eventual pharmacological interactions that may occur when some quinolones (nalidixic acid, ofloxacin, pefloxacin and sparfloxacin) are administered in association with oral hypoglycemic drugs (phenphormine and glibenclamide). Our results showed that ofloxacin, pefloxacin and sparfloxacin only at high dosages (not used in the human clinic) can increase the phenphormine and glibenclamide hypoglycemic effect. The nalidixic acid, just at therapeutic doses, is able to increase the hypoglycemic effect of the drugs studied.


Activity of two benzofuran-imidazoles, IM/B/4-62 and IM/B/4-66, against experimental infections with Candida albicans and Trichophyton mentagrophytes. The therapeutic activity of two new benzofuran-imidazoles, IM/B/4-62 and IM/B/4-66, formulated as 1% cream, has been evaluated against Candida albicans and Trichophyton mentagrophytes by inducing experimental vaginal candidosis in female rats and dermatophytosis in female guinea pigs. Results of the treatment were compared with those obtained by the same therapeutic regimen carried out with bifonazole. IM/B/4-66 proved to possess superior antimycotic activity to that of IM/B/4-62 and similar to that of bifonazole in both infections. Nmaley vaginal candidosis was cured in all the treated in animals at 6 days post-inoculation and skin lesions were healed in 9 of 10 animals at 15 days after infection, with negative cultures from all the infected sites.


Metabolic alkalosis in a patient with renal failure: role of antacids. A 75-year-old patient with anuric renal failure developed a significant metabolic alkalosis thought to be due to the enteral absorption of "nonsystemic" antacid administered in large daily doses for prevention of recurrent peptic ulcer disease.


Role of glycosylated vitamin B6 in human nutrition. A study of lactating women consuming mixed diets showed that the quantity of dietary glycosylated vitamin B6 had little influence on the vitamin B6 nutritional status of the mothers or their infants.


[Adhesion capacity of Enterococcus faecium (SF 68) and Enterococcus faecalis to various substrates]. The author's studied the adherence ability of Enterococcus faecium SF 68 compared to that of Enterococcus faecalis IM 11f, on various substrates: vascular catheters and cardiac valves of rabbit, immunodepressed rats and diabetic rats. The bacterial adherence test was calculated by the number of bacteria adhered for microscopic field enlarged to 2000. The data obtained by scanning electron microscope SEM (Cambridge Stereoscan 150 MK2) revealed a different adherence action of the two germs on the various substrates. All the adherence tests showed a higher and uniform adherence activity of E. faecalis compared to that of E. faecium.


Plasma dopa is unaffected by diet.

Plasma dopa is unaffected by diet. Significant amounts of bound 3,4-dihydroxyphenylalanine (DOPA), when present in dog food, did not affect plasma levels of DOPA or catecholamines in dogs. Thus, plasma DOPA is a useful index of activity of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis in these animals.


Zinc and the regulation of vitamin B6 metabolism. Pyridoxal kinase, a key enzyme in the formation of vitamin B6 coenzymes, requires a zinc-ATP complex as a substrate. Recent findings show that zinc-metallothionein facilitates the formation of the zinc-ATP complex. Thus, the concentration of zinc-metallothionein in tissues may serve in the regulation of vitamin B6 metabolism.


Preliminary study to antituberculosis chemotherapy in a region of sub-Saharian Africa: annual risk of tuberculosis infection calculation and tuberculin survey. A tuberculin survey was performed in Arua District (577,799 inhabitants, recent return of refugees from Zaire and Sudan) in 1987 prior to the implementation of antituberculosis Chemotherapy and Control Programme. 50 clusters (schools) of 30 pupils each were selected in the 7 Counties by Sistematic Random Sampling. 1110 students 10 year old without BCG vaccination scar were injected with 5 IU of PPD; 1016 of them (more than 6% of the estimated district population of 10 year of age) came back after 72 hours for reading. 125 of them were positives (more than 10 mm of induration). The Infection Rate detected was 1.23% +/- 0.19. Considering the infection rates found by the Ugandan National Surveys done in 1950 (2.6%) and in 1970 (2.3%), and the slight slope of the curve calculated on those values we have underestimated the real Infection Rate in the district. To avoid this bias we suggest to include schools in sampling (it is simple and cost-effective) only if the Student's population is likely to be representative of the general population.


Aminocarnitine and related compounds as inhibitors of carnitine transferases: physiologic implications. beta-Aminocarnitine and its N-acetyl and N-palmitoyl amides were examined as inhibitors of carnitine acetyltransferase, carnitine palmitoyltransferase, and of fatty-acid oxidation in whole animals, tissues, and hepatic microsomal systems. Results were consistent with subsequent findings that aminocarnitine and palmitoylcarnitine have significant antiketogenic and hypoglycemic effects in experimental animals.


Vitamin C regulation of cartilage maturation. Treatment of chondrocytes with vitamin C under defined conditions in cell culture initiates a differentiation program that closely mimics the normal maturation of cells in the growth plate of long bones.


HIV-infection in the autopsy material (Hamburg 1984-1989). 77 HIV-positive corpses were autopsied at the Institute of Forensic Medicine in Hamburg (in cooperation with the Bernhard-Nocht Institute) from August 1984 until September 31st, 1989. In the clinical autopsies (29 cases) the patients had always shown manifest AIDS symptoms, while 90% of the HIV-infected forensic autopsy cases had no AIDS symptoms during their lives and mostly died from drug overdose. Authors describe the clinical autopsy findings (Kaposi sarcoma, infections caused by opportunistic pathogenics), serological AIDS screen-examinations, and the precautions applied during the autopsies. They also describe their own methods for the prevention of infection with reference to hygiene in the dissecting rooms.


Ultrastructure of the developing myenteric plexus of chicken small intestine. The present ultrastructural study established the main morphological events that occur during the myenteric plexus formation in the chicken duodenum from the 7th day of incubation (E7) up to hatching, with special attention to the appearance of different axon profiles and synaptic contacts. Transmission electron microscopy revealed that the compartmentalization of the enteric mesenchyma into outer and inner zones precedes the sequential morphological maturation of the crest derived cells during myenteric plexus formation. On E7, a slender neuropil was present in the migrating cell clusters, but all the crest derived cells were uniform. In the following stages, the neuronal and enteroglial cells were distinguishable. The first significant sign of neuronal maturation was the morphological heterogeneity in the vesicle population on E11. Progressive changes in the synaptogenesis were identified, and the axosomatic synapses were characteristic around hatching. On E18, a transient direct muscle-ganglion contact with the circular muscle layer was observed, in addition to the permanent ganglionar contact to the longitudinal layer of the muscularis externa.


On the alteration of pulmonary arteries in different experimental pneumoconioses. CFY rats were treated intratracheally on one occasion with 60 mg of DQ12 quartz, illite (aluminosilicate) and enargite (dead rocks of a metal mine) suspended in 1 ml physiological saline. After a year, the structure of the pulmonary arterial system of pneumoconiotic rats was investigated by means of injection-corrosion cast and gelatin-India ink samples in thick preparations. In the identically treated animals, blood-gas analysis was made of samples of femoral arteries before and after intravenous treatment with noradrenaline and acetylcholine (40-40 micrograms/b.w.) under sodium pentobarbital narcosis. It has been stated that in focal alterations characteristic of different types of pneumoconioses, arborisation of the pulmonary arteries is and a newly developed and/or transformed vascular structure can be observed around the foci. In pneumonoconiotic lungs, arteriovenous shunts are more frequent. The authors assumed some connection between the vascularization of foci and the progression of the fibrotic process: richer vascularization around and inside the foci was accompanied by significant fibrosis. The blood-gas values suggested compensated respiratory acidosis. In the examined pneumoconioses, the effect of vasoactive substances - in terms of blood-gas values - had not changed significantly.


Determination of G1-S-G2 phase fraction ratios of tumour subpopulations from DNA histograms. Authors describe a new mathematical approach based on mixture decomposition and maximum likelihood method for the determination of subpopulations and G1-S-G2 phase fraction ratios in aneuploid, multiploid DNA histograms. A special computer routine was developed for this purpose (DAHSY). The present study relates to DNA histograms obtained by a Leitz Miamed DNA TV image analyser system. Altogether 23 normal, 14 dysplastic and 28 tumours Feulgen stained gastric imprint smears were measured. In addition to determination of subpopulations and G1-S-G2 phase fraction ratios, the authors also performed a morphometric analysis of Feulgen stained nuclei and determined the values of 5c exceeding rate (5cER) and the 2c deviation index (2cDI). More than one subpopulation were found only in tumours. The usual G1-S-G2 phase fraction rates in normal gastric smears were 85.5%, 9.04%, 4.9%, in dysplastic cases 74%, 15.4%, 10.2% and in tumours 53.8%, 22.9%, 18.8%. Significance of the differences were calculated by the T-test. The G1 phase fraction ratio clearly discriminates the malignant lesions from all others. The S+G2 phase fraction ratio, however, distinguishes the normal cases from the dysplastic ones. The 2cDi and 5cEr could support a multivariate diagnostic system. The cell nucleus area was found also to be of diagnostic value.


Chronic intestinal lymphocytic microphlebitis. The authors report two cases of a peculiar microphlebitis of the intestines, similar to that described by Saraga and Costa quite recently [5]. The patients had undergone hemicolectomy because of evolving ileus caused by cecal polyps or lipohyperplasia, respectively. Pseudomembranous-ulcerative inflammation of the cecum and variously intense lymphocytic infiltrates of numerous small submucosal veins and venules of the intestines were found in both cases. Thrombosis occurred very rarely in the affected vessels, although sometimes it was found in deeper and larger veins. Arteries, lymphatics, mesenterial veins and lymph nodes were normal. Parts of the distal ileum and ascending colon displayed the phlebitic changes without mucosal alterations. The authors hypothesize that it was not the abnormal local circulation, but some hitherto not fully clarified immunological disorder that resulted in the disease. In contrast to the claim of Saraga and Costa [5], it is suggested that thrombosis of the small veins does not have a significant role in the development of the lesions, but a complex process that includes the entry of antigens via the altered mucosa followed by an immunogenic inflammatory response of the small veins is responsible for the pathogenesis.


Cardiac changes in rheumatoid arthritis. We reviewed the autopsy material of 169 patients with rheumatoid arthritis (RA) and studied the cardiac changes is these patients. Systemic vasculitis was observed in 26 cases (15.38%) among 169 patients with RA. In 17 cases (10%) we found vasculitis of the subepicardial and/or intramural coronary vessels. Coronary arteritis or arteriolotis has led to multifocal small, and/or large myocardial infarctions in 10 cases (5.9%) and was the cause of progressive cardiac insufficiency, the direct cause of death. Multifocal circumscribed myocardial infarction reported in rheumatoid disease. In 8 cases rheumatoid nodules were found in the myocardium, 3 of them related to vasculitis. We suggest that rheumatoid nodules are the most severe form of necrotizing granulomatous vasculitis. Pathognomic nodular rheumatoid pericarditis was seen in 3 cases and diffuse rheumatoid pericarditis in another case. Pathognomic nodular valvulitis was found in 7 cases. Rheumatoid nodules localized to the epi-, myo-, or endocardium were observed on 9 patients. Generalized secondary amyloidosis was observed in 32 (18.93%) of the 169 patients with RA. Secondary amyloidosis was prevalent in the heart in 29 of 32 cases (relative frequency: 90.62%).


The diverse modification of N-butyl-N-(4-hydroxybutyl) nitrosamine induced carcinogenesis in urinary bladder by dibromodulcitol and dianhydrodulcitol. The effects of intravesical therapy with adriamycin, 1.6-dibromo-1.6-dideoxydulcitol (DBD) or with 1.6-dianhydrodulcitol (DAD) on bladder carcinogenesis were investigated in rats. To induce premalignant lesions in the urinary bladder female Sprague-Dawley rats received 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water for 4 weeks and then post-treated intravesically with one of the antitumor drugs and examined once a week for 3 months. These antitumor drugs in healthy rats (i.e. without the pre-administration of BBN) did not cause any significant morphological changes in the urinary bladder after intravesical application once a week for 3 months. In the applied dose BBN alone induced only premalignant lesions in the urinary bladder. However, neoplastic lesions occurred in the groups treated with BBN and adriamycin (9 papillomas and 3 carcinomas in 14 animals). Similarly intravesical application of DBD after BBN administration resulted 5 carcinomas among the 11 animals. On the contrary no urinary bladder tumor was found in the animals treated with BBN and DAD. As DAD is one of the conversion products of DBD it is conceivable that the difference between DBD and DAD action may be due to the formation of other solvolytic product from DBD than DAD.


Scanning electron microscopic (SEM) examination of structures which supply subcapsular and midcortical region postglomerular microcirculation in sheep kidney. Sheep kidneys were injected with polyester crystic (Dewilux 511-0196) and three dimensional forms of the structure forming the postglomerular microcirculation were examined by scanning electron microscope. During the examination of the afferent and efferent arterioles, a glomerulus with double efferent arterioles were examined and microdiverticular structures were observed in the terminal end of peritubular capillary plexus. It is concluded that these structures widen the surface area of the capillaries as a result of which diffusion across the capillary bed is facilitated.


Ultrastructure of normal and hepatitis virus infected human and chimpanzee liver: similarities and differences. Ultrastructure of liver biopsy specimens obtained from normal and hepatitis B (HBV) and hepatitis C virus (HCV) infected livers of patients and chimpanzees were compared. Nuclear alterations (glycogen particles, nuclear bodies, "vermicellar bodies", etc.), intracytoplasmic crystalloid inclusions were observed before and after the HBV and HCV infections both in human and chimpanzee hepatocytes, however, some of them were more common during the viral infection. Extreme endoplasmic reticulum dilatation characterized the human, while the presence of membranous cytoplasmic inclusions the hepatocytes of chimpanzees during HCV infection. Interferon-associated membrane alterations were noted during acute or chronic hepatitis, however, in slightly different forms in humans and chimpanzees. Data suggest to be precautions in the interpretation of the ultrastructural alteration observed in different species even to be so closely related as humans and chimpanzees especially during infection with hepatotropic viruses.


Proliferating cell nuclear antigen (PCNA) expression in childhood lymphomas. Paraffin sections from 21 cases of Hodgkin's disease (HD) and 28 cases (26 high-grade and 2 low-grade) of non-Hodgkin's lymphomas (NHL) occurring in childhood were examined for the presence of proliferating cell nuclear antigen using an anti-PCNA antibody. All cases of HD and NHL showed PCNA reactivity. In HD 50.9% (mean value) of Hodgkin and Reed-Sternberg (HRS) cells were PCNA positive and judged to be proliferating. PCNA reactivity was also found in a varying number of cells of the background population in HD (mean value = 11.7%). In NHL 61.2% (mean value) of cells were PCNA positive. In the 26 high grade tumours 63.6% (mean value) of cells were PCNA positive while only 32% (mean value) of cells were PCNA positive in the 2 low-grade tumours. Our results show that the proliferation rate of tumour cells in high-grade NHL is higher than those of tumour cells in low-grade NHL and HRS cells in HD. Moreover, we found a considerable variation of proliferation rate among individual cases of HD (range 31%-68%) of NHL (range 31%-78%). This suggests that PCNA assessment can help in the individual approach of the proliferation rate of each tumour, and, in conjunction with other parameters of the cell proliferation, could be useful for the understanding of the biological behavior of childhood lymphomas.


Expression of the Epstein-Barr virus encoded latent membrane protein in tumor cells of Hodgkin's disease occurring in childhood. Paraffin sections from 21 cases of Hodgkin's disease (HD), 28 cases of non-Hodgkin's lymphomas (NHL) and 34 cases of non-specific reactive lymphadenitides occurring in childhood were examined for the presence of the Epstein-Barr Virus (EBV)-encoded Latent Membrane Protein (LMP) using a double layer immunohistochemical method. LMP was detected in 12/21 (57%) cases of HD but not in NHL or reactive lymph nodes. LMP reactivity was restricted to Reed-Sternberg and Hodgkin's (HRS) cells in 4 of 9 (45%) cases of nodular sclerosis (NS), 6 of 9 (66%) cases of mixed cellularity (MC) and 2 of 2 (100%) cases of lymphocyte depletion (LD) while it was undetectable in the single case of lymphocyte predominance (LD) subtype. These results provide further evidence for an association between EBV and Hodgkin's disease, and they show that LMP expression occurs more frequently in the clinically more aggressive subtypes of HD. Furthermore, in view of the in vitro transforming potential of the LMP protein, the exclusive immunolocalization of LMP in HRS cells, suggests that EBV may be involved in the pathogenesis of a proportion of cases of HD.


Electron-microscopic studies on the effect of calcium pantothenate upon rat liver and locally irradiated epidermis. Calcium pantothenate was administered to Wistar rats in a dose of 180 mg/day/rat for 42 days, in order to investigate its effect upon the ultrastructure of the epidermis locally irradiated with a dose of 600 rep and upon partly hepatectomized liver and locally irradiated epidermis, as compared to control. The resulting data have revealed that calcium pantothenate is metabolized without entailing ultrastructural changes. Both liver and epidermis appear to be protected by calcium pantothenate, which greatly diminishes or even cancels the display of irradiation-induced negative effects. The changes brought about by irradiation are throughly presented and the subcellular mechanisms providing the radioprotection of epidermis and liver are accurately defined.


Absence of HTLV-I DNA sequences in cutaneous T-cell lymphoma/mycosis fungoides. Recently, the presence of deleted forms of the HTLV-I provirus was described in 6 out of 6 cases of CTCL. We investigated whether the presence of these viral genomes could be verified in 20 patients with CTCL using the polymerase chain reaction (PCR) and Southern blot analysis. Only one of the 20 cases showed a band corresponding to the pX region of HTLV-I. These data indicate that in the majority of CTCL cases, sequences closely related to HTLV-I are not present, or their copy number is below the limit of detection employed in this study.


Lectin staining studies on follicular atresia in house rat (Rattus rattus). Topographic distribution of terminal and intercalary carbohydrate moieties were studied using horseradish peroxidase conjugated Glycine max (GMA), Arachis hypogea (PNA), Lotus tetragonolobus (LTA), Bandirarea simplicifolia (BSA), and Dolichos biflorus (DBA) agglutinins. N-Gal NAc, alpha-D-Gal, alpha-L-Fuc, D-Gal (beta-1-3)-D-Gal NAc, and alpha-beta-D Gal NAc linked glyco-conjugates were exposed during follicular atresia in oocyte, zona pellucida and granulosa cells. Theca interna and interstitial gland tissue revealed homology in lectin binding.


DNASK--a new image analysis module for TV image cytometry. The DNASK is a PC-based image analysis module for quantitative cytological and histological examinations on Feulgen-Schiff preparations. The module consists of a frame grabber, a CCD black and white video camera and the DNASK software package which can be incorporated in an IBM compatible PC-AT joining to a standard pathological research photo microscope. The use of 386 IBM AT systems leads to significant decrease of the measurement's time. Mono- or color VGA graphics card should be used. The resolution of the images is 512 x 512 pixels and 256 gray values. The image caption is made in less than 0.5 second, the measurement of a cell nuclei (18 parameters) takes less, than 5 seconds (IBM AT 286). The camera is a standard CCD one. The microscope should be a good quality, modern microscope with built-in light source, however, the application of voltage stabiliser is strongly recommended. The software is able to measure the parameters mostly used and suggested in the international literature: 15 morpho- and densitometric parameters of the cell nuclei 6 DNA histogram parameters of the measured case, like DNA Index, 2c deviation Index, 5c exceeding rate, G1-S-G2 phase fraction ratio. The system supports the grouping of the measured cases and at the end of a study results of the single measurements can be collected and summarized in an ASCII file, which is readable by major statistical programpackages. The DNASK has a special graphical user interface for the control of the program.


Influence of chromatin condensation on the absorption spectra of nuclei stained with toluidine blue. To study the influence of chromatin condensation on the absorption spectra of nuclei stained with toluidine blue, DNA staining methods--which favour or prevent dye polymerization--were applied to the imprints of rat tissues that differed greatly in the density of chromatin packing. It is stated that all factors promoting dye polymerization cause a left shift of the spectra while the factors preventing it, a right one. It was found that condensation of the chromatin can raise prerequisites that both enhance and hinder polymerization, and that the final result depends on the staining method, the manner of chromatin folding, and the density of its packing.


A new computerized polarization--microscopic method for the demonstration of collagen fibers. A new computerized polarization microscopic method was developed for objective, quick quantitative analysis of anisotropic structures. The paper presents the technology on collagen fibers of kidney and liver preparations. According to the observations the birefringence of one fiber can be characterized not by a single number as it is accepted generally but by a series of data. It suggests that the process of compensation is gradual. One of the explanations of this fact might be that the collagen fibers are inhomogeneous at submicroscopic level. With regard to this assumption, first several birefringent capillary basement membranes of a whole glomerulum were measured simultaneously. In this case, the individual capillaries showed nearly the same retardation. Second, portal zones of normal and cirrhotic livers as functional units were analyzed simultaneously. In the latter case the individual fibers show different birefringence. Comparing the results obtained by their technique with the data of the classic measuring method authors found similarity that proved its validity. Data suggest that the new method seems to be useful in experimental and diagnostic pathology.


Generalized secondary amyloidosis in rheumatoid arthritis. The autopsy material of 215 RA patients was studied to determine 1) the frequency of generalized secondary amyloidosis (GSA), 2) the frequency and extent of amyloid deposits in various organs, 3) the chronological succession of amyloid deposition in various organs. The tissue specimens were fixed in 8% formaldehyde solution and embedded in paraffin. Serial sections were cut and stained with HE and Congo-red according to Romhányi, without alcoholic differentiation. The average amount of amyloid deposition in various organs was determined on a 0 to 4 plus scale. Thirty-seven cases were found to contain stainable amyloid (17.2%). The frequency and degree of amyloid deposition in different organs of RA cases with GSA are summarized in the following table. [table: see text] The frequency and extent of amyloid deposits in various organs may be linked to the ratio of cardiac output distributed over a different tissue mass. In conclusion, the tissues and organs often showing high quantities of amyloid are the sites where the deposits begin. Where deposits are infrequent or of low quantity deposits develop later. Amyloid deposits early in the wall of blood vessels, first of all within the GI tract, heart, kidneys, thyroid gland, spleen and the adrenal glands.


Etiological study on isolated proximal intercalary type of congenital limb deficiency in Hungary, 1975-1984. A population-based and validated data set of 14 cases with isolated proximal intercalary type of congenital limb deficiency born in Hungary between 1975-84 was evaluated. Two cases had phocomelia of upper limbs, while 12 cases were affected with classical intercalary defects mainly in femurs. Of 14 cases, 13 had unimelic manifestation and both sexes were equally affected. The intrauterine growth retardation, the excess of second birth order, a higher rate of acute maternal disorder of the respiratory system and the lack of familial cluster are noteworthy. The vascular disruption hypothesis seems to be the most plausible explanation for the origin of isolated proximal intercalary defects.


Morphological changes of cultured rat hepatocytes exposed to methylglyoxal. Calcium-independence of injury. Methylglyoxal-induced morphological changes were studied in cultured rat hepatocytes. Hepatocytes incubated either in the presence or absence of 2.5 mM Ca2+ were injured by 10 mM methylglyoxal to a similar extent, while 1 mM of the alpha-oxoaldehyde caused a moderate damage only in the absence of Ca2+. In the absence of Ca2+, however, hepatocytes were already injured, even without the presence of methylglyoxal hepatotoxicity proceeds independently of the Ca2+ influx.


Primary malignant tumours associated with thyroid carcinoma in autopsy material. In our Department 37,504 autopsies were performed in the last 30 years. Double multiple primary malignant tumours were found in 385 cases (4.2% of the cases with malignant tumours). In thyroid cancer cases, tumours of other organs were more frequent (20 cases, 22.7%), and these tumour associations were observed mainly simultaneously; there were no significant sex differences. In the more frequent synchronous cases, the thyroid cancer was a tumour only accessory to other malignancies; in the rarer metachronous cases, the thyroid cancer was secondary to postoperative irradiation of the first tumour (4 of 5 cases). Thyroid cancers were seen most frequently together with lung, breast and digestive system tumours; there was no special association recognizable to certain other malignancies. Follicular carcinoma was more frequent among the cancers associated with another tumour (12 of 20 cases), while in general the papillary was the most frequent type (48 of 88 cases).


[Treatment of crural varicose with topical dressings of "synthetic skin"]. In Dermatological Department of the Lublin Medical Academy 22 patients with crural varicose ulcerations have been treated with topical Codogard dressings. Before this treatment the patients were given some antiinflammatory and vasodilatatory drugs. The treatment lasted from 4 to 12 weeks (mean 6). In 9 patients complete healing was reported (they had small ulcerations). In 10 cases the improvement was evident, in 2 cases the treatment was discontinued. The obtained results point to clinical usefulness of Codogard, as the drug is easy to be applied and it may play a significant role to outpatients.


[Studies of susceptibility to antibiotics in strains of E. coli isolated from urine in the years 1986-1990]. From 1986 to 1990 research was conducted on E. coli strains isolated from patients with clinical symptoms of urinary tract infection. The paper-disk-plate technique was applied to determine their susceptibility to ampicillin, carbenicillin, azlocillin, cefamandole, cefotaxime, ceftriaxone, ceftazidime, cefoperazone, amikacin, netilmicin, gentamycin, vibramycin, and colistin. According to the authors' results the efficacy of ampicillin against the examined strains is as low as 3.4%. Aminoglycosides were traditionally recommended in therapy of urinary tract infections. Our research proves amikacin and netilmicin to be more effective against E. coli than gentamycin. The third-generation cephalosporins are recommended as alternative to aminoglycosides, especially since they are proved to be non-nephrotoxic. According to the results of the authors' research ceftazidime, cefotaxime and particularly ceftriaxone show the highest activity against the used strains of E. coli.


[Susceptibility to nitrofurantoin, biseptol and nalidixic acid of E. coli strains isolated from urine in the years 1983-1990]. The group of microorganisms causing urinary tract infections includes the Enterobacteriaceae family, particularly E. coli, being the most commonly detected etiologic factor of the above infections. Research was conducted from 1983 to 1990 on 1102 E. coli strains isolated from patients with clinical diagnosis of urinary tract infection. Susceptibility of the bacteria to nitrofurantoin, Biseptol and nalidixic acid was determined by application of the paper-disk- plate technique. The percentage of nitrofurantoin susceptible strains during the time period of research remained on the low level of 6-20%. The susceptibility of the strains isolated from 1983 to 1987 to Biseptol was also low, 0-11%, however, in later years (1988-1990) the gradual increase of susceptibility was observed, reaching the level of 35% in 1990. The most active of the used chemotherapeutics turned out to be nalidixic acid proven to be effective against 34.3-56.3% of E. coli strains.


[Dr. Piotr Borsukiewicz--one of the pleiad of physicians in Lublin (the 75th anniversary of his death)]. Seventy years have passed since the death of dr Piotr Borsukiewicz. He spent 9 out of his 22 years of work in Lublin (1909-1918) being the head of the paediatric hospital (1911-1918), the member of the Lublin Medical Society, the president and vice president of some other public service organizations and inscribed himself in letters of gold in the history of medicine and people of Lublin. He worked and lived in the difficult years of two wars (1904-1905 and 1914-1918), the rapid development of medical sciences and the separation of medical specialties. His diligence, loyalty to the Hippocratic code and the instructions of dr W. Biegański as well as to the patriotic dictates resulted in the union of the meaning of his own existence with the deep belief in man and the favourite work as a physician. Helping the poor and those in need he contracted spotted fever but belittled his complaints and died on April 12, 1918 in Lublin. He left us the special patterns of the ideal medical care which are still alive today, so non omnis moriar.


[Examination of gastric juice in animals fed with fodder containing power plant ashes and loess dusts]. Normal metabolism, regulation of stimulation and checking of electrolyte secretion in the gastric juice depend on the way of feeding and its nutritional ingredients. Feeding experimental animals with fodder containing power plant ashes or loess dusts causes a change in the gastric juice reaction, thus resulting in a different assimilation of elements contained in the fodder. There was shown an increase of some elements content (Mg, Na, Cu, Fe), a decrease in the content of some others (Pb,Zn) in the gastric juice and a positive tendency for blocking by calcium ions of heavy metals contained in the fodder by the mucous membrane of the stomach.


Thirty years after the creation of cryoophthalmology. Low temperatures in ophthalmology were first applied in the end of the previous century. However, those experiments were not sufficiently documented and were not widely used. So the report concerning the Krwawicz (6) method of the cataract cryoextraction published in 1960 is commonly treated as the beginning of the modern cryoophthalmology. This extremely effective and simple method very quickly met with approbation and became commonly applied. After the surgical exposure of the opacificated lens the copper cryoextractor frozen to about -72 degrees C was applied to it. The deep lens freezing to the apparatus occurred enclosing the subcapsular masses. Then the fibres of Zinn ligament were broken and the cataract was gently removed. Due to its safety and the lack of complications the above technique led the real revolution in the cataract surgery. Its was compared to the epochal contribution of Daviel who was the first to remove the lens in 1774. Its importance however, was not just limited to the improvement of the surgical technique. Thanks to the cryoextraction the possibilities of the low temperature application in medicine were noticed. In a short period of time low temperatures began to be used in some other specialties: laryngology, neurosurgery, oncology, etc. It was found out that great number of the eye diseases could be treated in that way, including viral keratitis, haemorrhages to the vitreous, glaucoma, etc. The gradually gained experience gave rise to the new branch of ophthalmology called cryoophthalmology.


[The lateral root of the median nerve and its fascicles in the human]. The studies were carried out bilaterally on bodies of 51 males and 52 females who died at the age from 1 day to 87 years. There was shown a great individual variability and asymmetry regarding both the thickness of the lateral root of the median nerve, the number of fascicles, the size of the cross-section area of fascicles and the index of the fascicles area.


[Acid-base equilibrium of hydrazone derivatives 4-R-3R1-thazol-2-one. I. Ionization constants of alpha-methyl-beta-(4-R-thiazol-2-yl)- and alpha-methyl-beta-(4-R-3-R1-thiazol-2-ylidene)-hydrazides of benzoic acid]. The ionization constants of the following compounds have been determined spectrophotometrically in aqueous solution: [table: see text] The comparison of absorption spectra in UV and pK values of the compounds being described in this work and of the derivatives having a thiazole or thiazoline structure which were studied previously let us suggest that in the II-H neutral molecule and the I-H and II-H mono-anion the thiazole form prevails while in the case of the I-H neutral molecule the thiazoline form is more probable.


[Fascicular structure of the root of the brachial plexus from C7 in post-fetal life in man]. The thickness of the root of the brachial plexus coming from C7, the number of its fascicles, the size and the index of their cross-section area have been examined bilaterally on the bodies of 69 dead men of both sexes. During the postnatal life there increased: thickness of the root--over 3.4 times, the cross-section area of root's fascicles--2.9 times, the number of fascicles--by about 60%. In the same time the index of fascicles cross-section area decreased over 18%. The above changes took place mostly up to 22nd year of life.


The evaluation of medical college students' preparation to propagate health education. The propagation of health education is within the range of nurses' professional duties. It necessitates the use of specific methods and techniques of work. "Inasmuch as the doctor treats, it is the nurse who creates best possible conditions for recovering and keeping health conditions permitting treatment or prevention" (3, 12). The increased level of general education among people and changes in modern nursing make the nurse face new tasks in her work. Nurse must be qualified in the field of health education if she works in the out-patient medical service as well as in hospital. She must be able to convince people about the necessity of changing life style, harmful and improper habits. The fulfillment of this difficult, yet important task may change patient's and his family's health habits and behaviour. So, nowadays the nurse must combine two functions: health-nursing called health-missioner's work with sick-nursing (1, 4, 9). Work in the field of health education requires high level of professional knowledge, skills, methods, recognition of educational and sanitary needs of a social group, personal direct influence based on proper social attitude, which is very important (10, 11). Health education is best and most effectively propagated in situations of individual contact with the patient (7). Patients seeking help in medical service institutions are interested in their health and want to do something in the field (8). The analysis of nurse's and midwife's positions shows that work in out-patient health service and in hospital offers a close contact with the patient and his environment.(ABSTRACT TRUNCATED AT 250 WORDS)


[Examination of the pancreas using various imaging methods]. After presenting contemporary employed various imaging methods, the comparative evaluation of Ultrasonography and CT in examination of pancreas lesions is discussed. It was stressed that techniques mentioned above give comparable good results and that they are complementary. The authors pointed out that US is the first technique of examination of the gland and in many cases it enables the proper diagnosis, whereas CT is used when the result of US examination is doubtful. Standard scans were performed and interpreted in each patient before using US and CT examination. In cases still obscure a biopsy is indicated. The frequency of pancreas visualization is dependent not only on the quality of the equipment used, training of the investigator, correct determination of the pancreatic field, but also on the experience and cooperation of the team performing the investigation.


Propositional reasoning by model.

Propositional reasoning by model. This article describes a new theory of propositional reasoning, that is, deductions depending on if, or, and, and not. The theory proposes that reasoning is a semantic process based on mental models. It assumes that people are able to maintain models of only a limited number of alternative states of affairs, and they accordingly use models representing as much information as possible in an implicit way. They represent a disjunctive proposition, such as "There is a circle or there is a triangle," by imagining initially 2 alternative possibilities: one in which there is a circle and the other in which there is a triangle. This representation can, if necessary, be fleshed out to yield an explicit representation of an exclusive or an inclusive disjunction. The theory elucidates all the robust phenomena of propositional reasoning. It also makes several novel predictions, which were corroborated by the results of 4 experiments.


DNA cleavage by hydroxyl radicals generated in a vanadyl ion-hydrogen peroxide system. Vanadyl ion (+4 oxidation state) has been shown to be an effective agent for chemoprotection of cancers in animals. For understanding the mechanism, distribution of vanadium was studied. More vanadium was found to accumulate in the nuclei of the liver of rats when it was given as vanadyl sulfate than when it was given as sodium vanadate (+5 oxidation state). The reactivity of vanadyl ion with DNA was investigated by the DNA cleavage technique and the reaction mechanism by ESR spectroscopy. Incubation of double-strand DNA with vanadyl ion and hydrogen peroxide resulted in marked concentration- and pH-dependent DNA cleavage. Studies by the ESR spin-trap method demonstrated that hydroxyl radicals are generated during the reactions of vanadyl ion with hydrogen peroxide. Thus the antineoplastic action of vanadyl ion is proposed to be due to DNA cleavage by hydroxyl radicals generated in the cells.


Study of the conformational stability of 7S globulin from french beans (phaseolin) using high-sensitivity differential scanning microcalorimetry. The change of the conformational stability and quaternary structure of the 7S globulin from french beans (phaseolin) has been investigated in the pH range 2.0-11.0 using the high-sensitivity differential scanning microcalorimetry technique. It has been established that each polypeptide chain of phaseolin consists of two thermodynamically unequivalent cooperative domains. The number and type of the side-chain hydrogen bonds which participate in the stabilization of the folded structure of each domain have been determined. The more stable domain contains six side-chain hydrogen bonds: four of the carboxylate-tyrosyl type and two of the carboxylate-histidyl type. The less stable domain contains four side-chain hydrogen bonds: two of the carboxylate-tyrosyl type and two of the carboxylate-histidyl type. All these side-chain hydrogen bonds appear to be localized within the hydrophobic interior of the domains. It has been found that the 3S form of phaseolin that is a product of the complete phaseolin dissociation at extreme pH values does not undergo any cooperative transition at heating. Consequently, this form probably has a conformation of 'molten globule' type.


Selective inhibition of arthropod-borne and arenaviruses in vitro by 3'-fluoro-3'-deoxyadenosine. A novel nucleoside analog, 3'-fluoro-3'-deoxyadenosine (3'F3'dAdo), was evaluated for antiviral activity against several arthropod-borne and arenaviruses in Vero cell culture. The following 50% inhibitory concentrations (EC50) of virus plaque formation were obtained against the test viruses: Semliki Forest (10.3 microM) and Venezuelan equine encephalitis (5.3 microM) alphaviruses, lymphocytic choriomeningitis (7.7 microM) and Pichinde (greater than 32 microM) arenaviruses, Punta Toro (greater than 32 microM) and San Angelo (1.6 microM) bunyaviruses, banzi flavivirus (4.0 microM), and Colorado tick fever orbivirus (0.6 microM). By comparison, the broad-spectrum antiviral agent ribavirin was active against lymphocytic choriomeningitis (18 microM), Pichinde (24 microM), Punta Toro (114 microM), and San Angelo (99 microM) viruses, but was less active against the other 4 viruses (greater than 200 microM). Vero cell proliferation and thymidine and uridine incorporation into replicating Vero cells were inhibited by 50% with 3'F3'dAdo concentrations of 36, 45, and 32 microM, respectively. In virus yield reduction assays, increasing the multiplicity of infections of Semliki Forest and Venezuelan equine encephalitis viruses reduced the inhibitory activity of 3'F3'dAdo. Using the same assay, 3'F3'dAdo was found to enhance Punta Toro virus replication up to 5-fold relative to the untreated control. By adding the nucleoside transport inhibitor nitrobenzylthioinosine (100 microM) to the culture medium, antiviral activity against the two alphaviruses was eliminated, indicating that 3'F3'dAdo uses the nucleoside transport system for cell entry. When actinomycin D (5 microM) was used to greatly suppress cellular RNA synthesis in Semliki Forest virus-infected and uninfected cells, 3'F3'dAdo preferentially inhibited viral RNA synthesis. The results of these studies indicate 3'F3'dAdo is a selective inhibitor of most of the viruses tested and should be a promising candidate for in vivo evaluations.


[Contraception using a subcutaneous implant, Norplant]. The contraceptive device Norplant, not yet commercialized in Belgium, has been studied prospectively on 198 women, which were followed for up to 42 months per patient. All together, 2,643 months of use were surveyed. Norplant consists of 6 silastic capsules, liberating levonorgestrel, a synthetic progestagen. The pregnancy protection lasts for 5 years. Insertion site is the inner part of the upper arm. The Pearl Index was 0.46% women-years (only one pregnancy occurred); the continuity rate was high (86% after 1 year and 60% after 2 years). The main side effects were menstrual disturbances and abnormal intermenstrual blood loss. No other important side effects have been found. There is no absolute contra-indication to the use of Norplant.


Free levonorgestrel index and its relationship with luteal activity during long-term use of Norplant implants. Levonorgestrel serum levels and sex hormone binding globulin (SHBG) were measured in 82 women during different years of use of Norplant implants. The ratio between levonorgestrel and SHBG was calculated as an indicator of the free biologically active fraction of levonorgestrel (free levonorgestrel index, FLI). These parameters were then correlated with the presence of luteal activity, as determined by progesterone levels above 9.6 nmol/L, in a sampling run of 10 samples taken twice a week for five consecutive weeks. Levonorgestrel serum levels remained constant around 1.0 nmol/L during the five-year period. SHBG levels were below normal for the first 18 months of use, returning to normal levels during the last three years of use. The FLI in the first two years was significantly higher than that observed in the later years. The frequency of cycles with luteal activity was 12% during the first 2 years, increasing to 44% in the latter years, when FLI levels were lower. Our results suggest that the changes in SHBG and consequently in the free biologically active fraction of levonorgestrel may largely account for the differences in degree of ovarian suppression observed between the first two years of use of Norplant implants and the latter three, even in the absence of a significant variation in total levonorgestrel concentrations.


The acceptability of Norplant in Egypt.

The acceptability of Norplant in Egypt. Currently, the pill and IUD account for 83% of contraceptive use in Egypt; Norplant will be an important complement to those methods of family planning. In Egypt where childbearing begins early, and closely spaced pregnancies are the norm, the long duration of Norplant's effectiveness and its relative ease of use should be appealing. The Egyptian Fertility Care Society (EFCS) initiated a study in 1988 on the acceptability of Norplant in Egypt to study the clientele of the EFCS clinical trial in the five university teaching hospitals. The clinical trial participants were women in their thirties who had an average of four children. Most had used a method of family planning before Norplant, and were anxious to maintain contraceptive protection as most wanted no more children. Satisfaction with Norplant among users was high. In the survey, 93% of the women expressed satisfaction with the method. More than half (67%) of the women said they would consider using Norplant again in the future, and another 22% were undecided. Eighty-seven percent of the women who had not discontinued were planning to continue with their current Norplant set for the full five years. Egyptian women like Norplant because of its long duration of effectiveness, the site of insertion, its ease of use, and its relative lack of perceived side-effects compared to the pill and IUD. In Egypt where a reliable, long-term, but not permanent method of contraception is badly needed, Norplant should become a popular method of family planning.


Hypertension and kidney transplantation. Hypertension in kidney transplant patients is a common complication that affects long-term patient and allograft survival. Although multifactorial in nature, at least two causes can be corrected by surgical or radiologic intervention--stenosis and native kidney-associated hypertension. Unfortunately, the current immunosuppressive agents have added to the problem of hypertension. Both prednisone and cyclosporine appear to aggravate posttransplant hypertension. Newer agents are on the horizon that may address this problem. Currently, physicians should consider the possibilities of correctable forms of hypertension. If none are indicated, medical therapy with renal vasodilating drugs such as calcium channel blockers or converting enzyme inhibitors or both along with diuretics are usually effective.


Management of renal disease and hypertension in insulin-dependent diabetes, with an emphasis on early nephropathy. In the follow-up of insulin-dependent diabetes mellitus patients with renal disease, a decline in glomerular filtration rate measured by an exact technique is the major primary end point in evaluating the progress of the disease. Abnormal albuminuria is considered an intermediate or secondary end point. All studies suggest that an increase in albuminuria indicates a decline or a risk of future decline in glomerular filtration rate. The main risk factor for progression appears to be the elevated blood pressure (which in itself may be a pathogenetic factor) that is associated with abnormal albumiuria from the microalbuminuric level. Abnormal albuminuria seems to always be associated with the risk of progression, and a reversal of abnormal albuminuria suggests a beneficial prognosis. Abnormal albuminuria is easily monitored by immunochemical procedures, including semiquantitative dipstick tests that may be important in renal screening procedures. Elevated blood pressure is important for the progression of abnormal albuminuria, but poor metabolic control seems to be the major initiating factor (although the mechanisms at a molecular biologic level are less clear). New studies confirm the strong predictive value of microalbuminuria for overt renal disease. At the same time, it is clear that microalbuminuria is associated with many cardiovascular abnormalities that cluster in some patients and is clearly associated with a poor prognosis. An intervention strategy is to achieve the best possible metabolic control without creating hypoglycemic problems or too difficult a lifestyle. Increasingly, studies underscore the value of early antihypertensive therapy, especially with angiotensin-converting enzyme inhibitors, in patients with microalbuminuria. This scenario of earlier and earlier antihypertensive treatment for microalbuminuric patients is evolving. Numerous studies indicate that microalbuminuria is stabilized or reversed by this treatment, and some new evidence suggests better preservation of glomerular filtration rate by this intervention program. Accumulating results also suggest considerable improvement in survival rate with this program in proteinuric insulin-dependent diabetes mellitus patients.


Management of chronic renal failure.

Management of chronic renal failure. There is growing evidence that treatment of patients with renal function impairment will undergo a major shift within the next few years. Along with more or less successful attempts to alleviate the signs and symptoms of reduced renal function, new insights into renal pathophysiology as well as new therapeutic modalities have given rise to the notion that we may be able to retard the naturally occurring decline in renal function in patients with diabetic and nondiabetic nephropathy.


The molecular biology of mammalian glucose transporters. Recent advances concerning the function and regulation of the facilitative and sodium-dependent glucose transport proteins are discussed. Physiologic roles have been proposed for GLUT3 and GLUT5 in the brain and intestine, respectively. Cell biologists are beginning to elucidate the subcellular trafficking pathways of GLUT4 in insulin-responsive cells. New members of the SGLT family, including a sodium-nucleoside cotransporter, have been identified.


Management of glomerular diseases of primary and secondary origin. Most recent information on the management of glomerular diseases is clustered in three areas. In nephrotic syndrome, interest has focused on the use of cyclosporine in steroid-resistant patients, treatment of progressive membranous nephropathy with alkylating agents, and symptomatic management of unresponsive cases with angiotensin-converting enzyme inhibitors. The most recent data on lupus nephritis establish the efficacy of intravenous cyclophosphamide in the long-term preservation of renal function and the lack of benefit of plasmapheresis in patients with severe disease. In rapidly progressive glomerulonephritis, the discovery of circulating antibodies to neutrophil cytoplasmic antigens has proved valuable in diagnosing certain forms of renal vasculitis. A rational approach to treating such patients is beginning to crystallize.


Prevention and attenuation of acute renal failure. Recent progress in our understanding of the pathogenetic processes involved in ischemic acute renal failure is considerable. Blockade of the production of endothelium-derived relaxing factor may markedly improve survival in patients with septic shock. Atrial natriuretic peptide and growth factors enhance renal recovery in animal models of acute renal failure, even when administered well after the ischemic insult. Aminoglycosides and radiocontrast agents are the most common causes of drug-induced acute renal failure. Once-daily administration of aminoglycosides is an effective treatment modality that may limit the occurrence of nephrotoxicity. Awareness of the patient's volume status has decreased the incidence of radiocontrast-induced acute renal failure. The new, expensive, nonionic, low-osmolar radiocontrast agents do not offer apparent benefits in patients with normal or slightly decreased renal function. However, use of such agents may decrease the incidence of radiocontrast-induced renal failure in diabetic patients with severe renal failure. The prognosis for patients with renal vasculitis has improved greatly in the past decade. The discovery of antibodies directed against antigenic targets in the cytoplasm of neutrophils has facilitated the diagnosis of renal vasculitides, has improved our knowledge of the pathogenesis of these diseases, and may guide rational treatment.


ATP-sensitive potassium channels in physiology, pathophysiology, and pharmacology. Potassium-selective ion channels, whose activity is inhibited by micromolar to millimolar concentrations of ATP presented at the cytoplasmic ATP-sensitive K+ (K+[ATP]) surface, have been found in a variety of cell types. These "K+(ATP) channels" have emerged as significant targets for physiologic as well as pharmacologic modulation of cell processes. In insulin-secreting beta cells of the pancreatic islet, closure of these channels on presentation of a metabolite secretogogue, such as glucose, or an oral hypoglycemic sulfonylurea, results in cell depolarization and triggers electrical activity. Ultimately, this results in Ca2+ entry and Ca(2+)-dependent exocytosis of insulin granules. In myocytes, opening of K+(ATP) channels during hypoxia or metabolite deprivation or with exposure to a new class of K+ channel opener drugs results in cell hyperpolarization and myocyte relaxation. This contributes to vasodilation. In renal tubule cells, K+(ATP) channels contribute to cell potassium balance during vectorial bulk solute transfer by the proximal tubule as well as net urinary potassium secretion by the distal nephron. Agents that modulate the activity of these K+(ATP) channels in epithelial cells may prove to be useful as K(+)-sparing diuretics. in epithelial cells may prove to be useful as K(+)-sparing diuretics.


The molecular biology of chloride channels. The molecular biology of chloride channels is a new field, having begun only 5 years ago with the cloning, on the basis of partial amino acid sequence information, of complementary DNAs for subunits of the neuronal glycine and gamma-aminobutyric acid-receptor channels. The sequences of these subunits that form heterooligomeric channels revealed a general similarity with the structural motif employed by the well-studied and previously cloned nicotinic acetylcholine-receptor subunits. The principal distinguishing feature was the rings of positively charged residues within the loops separating the putative transmembrane helices of the new chloride selective channels. A great diversity of subunit types with specific functional and pharmacologic properties as well as localizations within the central nervous system have been identified and cloned. Chloride channels are known to play an important role in both secretion and reabsorption of salt and fluid across wet epithelia, and the cystic fibrosis transmembrane conductance regulator, cloned by genetic means, has been shown to be centrally involved in both of these processes. It is regulated by a complex mechanism involving both ATP binding and phosphorylation at multiple sites. Expression cloning techniques have yielded a voltage-gated family of channels with a large number of potential membrane spanning segments; one member is responsible for the resting potential of skeletal muscle. An entirely different low molecular weight-voltage-gated channel, possibly regulated by osmolarity changes, is the most recent chloride channel to be cloned. It almost certainly will not be the last.


Osmolytes.

Osmolytes. The cells of the renal medulla osmotically adapt to chronic alterations in extracellular tonicity by appropriate changes in the intracellular contents of organic osmoeffectors. The major organic osmolytes are glycerophosphorylcholine, betaine, myo-inositol, sorbitol, and, possibly, taurine. When the concentrations of poorly permeant external solutes are acutely reduced, cells that have been adapted to high tonicities rapidly release organic osmolytes via specific transmembrane transport pathways. In contrast, when medullary cells are depleted of organic osmolytes, osmolyte accumulation on acute elevation of external tonicity is slow and involves stimulation of uptake, intracellular de novo synthesis, or inhibition of intracellular degradation, and is preceded by increased intracellular electrolyte concentrations. The available evidence suggests that this rise in intracellular ionic strength plays an important role in the initiation of those processes responsible for full adaptation of renal medullary cells to high tonicities. Recently, complementary DNAs encoding a myo-inositol and a betaine transporter have been isolated.


Cellular and molecular mechanisms of renal development and tubulogenesis. Recent advances in the basic mechanisms of developmental biology have started to shed new light on the mechanisms of nephrogenesis. The kidney is the only epithelial organ that starts as mesenchyme and converts to epithelium. It appears that the mesenchyme is composed of stem cells that are able to form glomeruli and proximal and distal tubules under the inductive influences of the ureteric bud. Epithelial cells cultured in a three-dimensional matrix could be induced to form tubules under the influence of a soluble factor from fibroblasts. This factor was identified as scatter factor or hepatocyte growth factor. Polycystic kidney disease appears to be a developmental renal disease in which a basolateral protein, the Na/K ATPase, is mistargeted to the apical and lateral membranes.


Renal epithelial cell polarity.

Renal epithelial cell polarity. Recent cell biologic studies of protein trafficking, sorting, and distribution in polarized renal epithelial cells have begun to provide important new insights into the mechanisms involved in generating and maintaining cell surface polarity. Advances in this field have been rapid in the last year, due in part to the development of new approaches to analyzing protein delivery and distribution in polarized renal cells grown in vitro. Sorting signals within apical and basal-lateral membrane proteins have been described that may be involved in the segregation of proteins into different populations of transport vesicles in the trans-Golgi network; the nature of these signals has provided insight into the mechanisms involved. Elements of the cytoskeleton appear to be involved in the delivery of these transport vesicles to the appropriate membrane domain (microtubules) and in the retention of specific proteins in the correct membrane domain (membrane skeleton). Finally, detailed analysis of two prominent renal diseases, ischemia and polycystic kidney disease, indicates that abnormalities in the regulation of membrane protein distribution may be a contributing factor in generating the disease state.


Defects in membrane transport of ions as possible pathogenic factors in hypertension. Although abnormalities in cellular ion transport have been shown in a variety of cells of essential hypertensives, the mechanistic link between these abnormalities and elevated blood pressure is poorly understood. Reduced sodium-potassium ATPase activity, with and without elevated levels of a circulating inhibitor of this transport system, has been reported by a number of studies. The recent characterization of the endogenous ouabain or its isomer will facilitate the testing of the hypothesis that salt-sensitive essential hypertension relates to higher levels of this factor. The erythrocyte sodium-lithium countertransport may serve as a marker for a subpopulation of essential hypertensives. However, this transport system has no physiologic counterpart and thus does not provide insight into mechanisms associated with altered cellular ionic homeostasis in essential hypertension. Increased activity of the sodium-hydrogen antiport in essential hypertension relates to an alkaline shift in the cytosolic pH set-point for activation of this transport system. This process may reflect increased cytosolic free calcium concentration with or without augmented protein kinase C activity.


The phosphoinositide signaling system and hypertension. The phosphoinositide signaling system is common to many vasoconstrictor agents and as such is influential in the regulation of blood pressure. Recently, there have been major advances in our understanding of these lipids and their metabolism. Characterization of the phospholipase C isozymes and protein kinase C isozymes involved in transmembrane signaling has progressed rapidly. The role of diacylglycerol kinase as a regulator of protein kinase C activity has been established, and phosphatidic acid has been recognized as a cellular messenger. Studies in the spontaneously hypertensive rat have shown abnormalities of phospholipase C that could result in enhanced activity and explain changes in sensitivity reported in rats with this disease. During agonist activation of inositol lipid hydrolysis, levels of inositol 1,4,5-trisphosphate and 1,2-diacylglycerol are elevated in spontaneously hypertensive rats compared with Wistar-Kyoto control rats. These changes are observed early, prior to blood pressure stabilization, and may be downregulated once hypertension is established. In addition, there is evidence for reduced diacylglycerol kinase activity and enhanced protein kinase C activity in the spontaneously hypertensive rat. These data provide evidence for hyperresponsiveness of the phosphoinositide signaling system in the developmental stages of hypertension. However, confirmatory experiments in nongenetic animal models of hypertension and in human tissues are needed to establish that this is not just a phenotypic phenomenon of the spontaneously hypertensive rat.


Nonpharmacologic treatment of hypertension. A variety of lifestyle modifications will lower both the blood pressure and various other cardiovascular risk factors that are frequently present in patients with hypertension. Numerous recent studies document the overall efficacy of some (weight reduction, sodium restriction, physical activity, moderation of alcohol) and the relative lack of effect of others (stress management and calcium, magnesium, and fish oil supplements). In particular, the Trials of Hypertension Prevention, Phase I (a control trial funded by the National Heart, Lung, and Blood Institute) provides important new data on the ability of these various modalities to prevent the development of hypertension, an equally or even more important goal than the reduction of already-established disease.


New classes of antihypertensive drugs and new findings with established agents. Research on antihypertensive drugs not only provides new information on presently used agents but also leads to the introduction of exciting new compounds. Several important clinical trials involving currently available drugs have been published recently. Angiotensin-converting enzyme inhibitors improved survival in patients with milder degrees of congestive heart failure, which indicates that they have become the cornerstone of treatment for this condition. Angiotensin-converting enzyme inhibitors delayed or prevented the development of diabetic proteinuria (> 200 micrograms/min) in a placebo-controlled randomized trial. Further, enalapril was more effective than metoprolol in reducing the rate of decline in renal function in patients with type I diabetes. Calcium channel blockers protected against acute renal failure in patients after renal transplantation in two separate studies. Calcium channel blockers were shown to promote natriuresis, with negative sodium balance the same as that associated with thiazide diuretics. The voltage-dependent calcium channel has been cloned, and the binding sites of the three classes of calcium channel blockers are now known. beta-Blockers and thiazide diuretics were the drug treatments in the Systolic Hypertension in the Elderly Program trial and in the Swedish Trial in Old Patients with Hypertension study (patients 65 to 85 years). In both investigations, stroke and cardiovascular events were significantly reduced by these conventional inexpensive agents. Clonidine was found to lower blood pressure primarily by its interaction with the imidazole receptor rather than the alpha 2 receptor. Elucidation of the imidazole receptor promises to shed light on physiologic mechanisms as well as lead to the introduction of new agents, such as moxonidine.(ABSTRACT TRUNCATED AT 250 WORDS)


Detection and serotyping of rotaviruses in stool specimens by using reverse transcription and polymerase chain reaction amplification. Direct rotavirus serotyping (VP7, G type) in stool specimens was carried out by reverse transcription and polymerase chain reaction amplification (RT-PCR) and compared to serotyping by enzyme immunoassay with monoclonal antibodies (EIA-MAb). The methods used for double-stranded (ds) RNA extraction, RT-PCR amplification, and the primers used were modified from previous reports [Gouvea et al.: Journal of Clinical Microbiology 29:519-523, 1990; Gentsch et al.: Journal of Clinical Microbiology, 1992]. For samples that were positive by both methods, the serotypes obtained were identical, however RT-PCR typing was found to be considerably more sensitive (70.4% samples serotyped) than EIA-MAb (35.6% of samples serotyped). The overall sensitivities for detection of rotavirus in stool samples by latex agglutination, enzyme immunoassay, electron microscopy, polyacrylamide gel electrophoresis, and RT-PCR were essentially the same. The results confirm that RT-PCR typing (genotyping) is extremely valuable for G typing of samples which cannot be typed by EIA-MAb. We also developed a PCR confirmation technique for serotypes 1, 2, and 4.


Alzheimer skin fibroblasts show increased susceptibility to free radicals. We have studied the response to toxic oxygen metabolites of fibroblasts derived from skin biopsies of 5 patients with familial (FAD) and 4 with sporadic (AD) Alzheimer's disease compared with those derived from 4 normal controls. Fibroblasts were damaged by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde by 50 munits of xanthine-oxidase (Xo). To quantify cell damage we measured lactate dehydrogenase (LDH) activity in the culture medium and cell viability in fibroblast cultures. We found a significant increase in LDH activity in the FAD vs. controls and also in the AD vs. controls.


Age-related excretion of six glycosidases in rat urine. The activity of beta-N-acetylglucosaminidase (NAG), beta-galactosidase, alpha-L-fucosidase, beta-glucuronidase, beta-glucosidase and alpha-mannosidase was determined in the urine of rats at progressive ages from newborn to old animals. The age-dependence of urinary creatinine, protein and pH values was also studied. Enzyme activity, related to urinary creatinine, was significantly higher in the newborn group than other ages. The excretion of NAG increased significantly in adult rats (3-6 months old) compared to young rats (1 month old). Most of the enzyme activities were diminished in old rats (25 months old). Increased proteinuria and creatinine excretion were observed in rats since 3 months of age. Age-related differences among enzyme activities therefore should be considered when these urinary glycosidases are to be studied in rats.


Effects of aging on exocrine immune responses to Mycoplasma pulmonis. Formalinized Mycoplasma pulmonis was used to immunize 3 different age groups of Fischer 344 rats. A specific antibody to this antigen was detected in both saliva and lung lavage fluids and differences were noted in the elicitation of secretory antibody between the different ages of the animals. Few statistical differences were noted between the three age groups for salivary IgG responses to M. pulmonis, regardless of the dosage given, even though all responses were greater than their respective control groups. The principal differences among the three age groups were noted in the kinetics of the response, that is, the amount of time that was necessary to produce a peak response. The younger group of animals took less time to produce a peak response than the older two groups, even though the magnitude of the response was lower. Salivary IgA responses to M. pulmonis appeared predominantly as a primary response, particularly in the senescent animals. Secondary salivary IgA responses were not significantly greater than their respective primary responses, suggesting that secretory IgA did not display classic anamnestic responses that were observed with salivary IgG. As with IgG responses, the senescent animals took longer to produce a peak salivary IgA response when compared to the other age groups. Lung lavage IgG responses, normalized to total protein, were greatest in the youngest group of animals and appeared to diminish as the age of the animal increased. In contrast, lung lavage IgA responses to M. pulmonis were of a greater magnitude in the senescent animals. These studies suggest that senescent animals are capable of eliciting a humoral immune response in mucosal secretions to Mycoplasma pulmonis. However, differences noted with regard to disease severity and mortality to respiratory mycoplasmosis in senescent animals may result from intrinsic defects in the quality of the humoral response or as a consequence of deficient cellular responses to this pathogen.


Effect of aging on macrophage adherence to extracellular matrix proteins. Fibronectin, type I, type IV and type V collagens were compared for their abilities to promote mouse peritoneal resident macrophage adherence and the effect of aging on macrophage adhesion to these matrix proteins was examined. Adherence of macrophages to fibronectin was remarkable and more than 5-fold compared to type I, type IV or type V collagens. Adherence of macrophages to fibronectin and type I collagen increased during aging. However, no age-related changes were observed in macrophage adherence to type IV and type V collagens. The percent of inhibition of macrophage adherence to fibronectin by arginine-glycine-aspartic acid-serine (RGDS) peptide (58.1 +/- 2.7%) was significantly (P < 0.01) higher than that in cells from young mice (23.1 +/- 5.7%). These data suggest that macrophage attach preferentially to fibronectin and that the ability of macrophage to attach to fibronectin increases during aging. The age-related increase in macrophage attachment to fibronectin is related to the concentration of cell surface receptors of macrophage which recognize RGDS sequence within fibronectin during aging. Adherence of macrophage to fibronectin implies retention of macrophages in subendothelial space. Age-related increase in macrophage ability to attach to fibronectin may be related to atherogenesis during aging.


Heavy metals and lipofuscinogenesis. A study on myocardial cells cultured under varying oxidative stress. The aim of this study was to examine the influence on lipofuscinogenesis of a number of transition and non-transition heavy metals in cultured post-mitotic cells (neonatal rat myocytes) at varying oxidative stress. The effects of Al, Cd, Cr, Cu, Hg, Pb and Zn, added to the medium as chlorides, were examined after 14 days in culture under 5, 20 and 40% ambient oxygen. Lipofuscin was quantified by microspectrofluorometry of individual cells. The addition of Al (40 microM), Cd (40 nM), Hg (30 microM) and Pb (40 microM) to the culture growth medium markedly increased the amount of intracellular lipofuscin, whereas Cr (40 microM), Cu (40 microM) and Zn (40 microM) had the opposite effect. Transmission electron microscopic examination of the myocytes showed greatly increased numbers of autophagic vacuoles in cells exposed to those heavy metals that increased lipofuscin formation. This effect was most pronounced when cells were grown at high (40%) oxygen tension. Possible explanations for the metal augmented pigment formation may be (i) inhibition of lysosomal enzymes, (ii) catalytic interference with peroxidative reactions, or (iii) general toxicity with unspecifically increased autophagocytosis. The decreased pigment accumulation after the addition of Zn, Cr and Cu may, at least partly, be related to the replacement of iron, which has catalytic activity in Fenton reactions.