Biomedical subjects
Publications and source records attributed to G Zimmer.
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The release of .OH and alkyl free radicals into the coronary flow were compared in Langendorff perfused and working rat hearts during normoxia (30 min), hypoxia (30 min) and reoxygenation (60 min) by means of spin-trapping techniques using 5,5-dimethyl-1-pyrroline-1-oxide (DMPO). In Langendorff hearts, there was a small but steady increase in the radical concentration during the course of hypoxia and reoxygenation. At the start of reoxygenation, only small initial peaks of hydroxyl and alkyl radicals occurred. After a general decrease of free radical production during hypoxia, working hearts produced nearly double the amount of free radicals during reoxygenation as Langendorff hearts. After an initial large increase during early reoxygenation, the amount of free radicals produced fluctuated on a high level during the remaining reoxygenation period. Heart work is thus correlated with an increased production of free radicals, possibly due to an increase in oxygen consumption by the heart.
Stereological investigations on myocardial capillaries provided evidence that the common estimator of capillarity, the capillary density (i.e., number of capillary profiles per unit transverse sectional area), underestimates the true capillary supply since the capillary axes are not oriented perfectly in parallel to the myofiber axes. Recently, we studied the "true" capillarity, i.e., the length density of capillaries (LV = capillary length per capillary volume), in some experimental models of cardiac hypertrophy which have been published elsewhere. It has been shown that LV decreases in renovascular hypertension, but is maintained in physical exercise and after chronic thyroxin application. However, the growth pattern of capillaries in hypertrophic hearts has not yet been analyzed. In the present paper it is demonstrated that important information on the capillary network can be derived from the two-dimensional capillary-to-fiber ratios (2D CFR: capillary profiles per myofiber profiles in transverse sections) and from the three-dimensional capillary-to-fiber ratios (3D CFR: capillary length per unit myofiber length). Increase in both suggests neoformation of additional capillary branches in parallel connection. Retrospective analysis of the quantitative data indicates that in hypertrophy induced by physical exercise or by chronic thyroxin application capillary neoformation in parallel connection counterbalances increase of oxygen diffusion distance due to myofiber enlargement. In renovascular hypertension, capillary neoformation in parallel connection does not occur. Studies on normal growth indicated both a slight decrease of LV of capillaries, as well as a continuous neoformation of additional capillary branches.
In the working rat heart we investigated heart function (aortic and coronary flow) during a normoxic, a hypoxic, and a reoxygenation phase after hypoxia. A depressed heart function was obtained by limiting oxygen supply and reducing left ventricular filling pressure (preload). After hypoxic perfusion for about 90 min, reoxygenation resulted in a 50% decrease of aortic flow. Lactate production and release increased immediately after oxygen deprivation and reached a maximum after about 35 min of hypoxia. Following reoxygenation, lactate release decreased. Lactate dehydrogenase became significant after reoxygenation. After stabilization of aortic flow at 50% in the reoxygenation phase different reagents were examined for their influence on heart performance. 1.5 mM of 2-Mercaptopropionylglycine (MPG) significantly increased aortic flow by 40%. The oxidized form of MPG (ox-MPG) at a concentration of 0.6 mM increased aortic flow by 125%. A molecular mechanism is proposed involving reorientation of the ATPase molecules at their membrane sites.
In the isolated working rat heart, the damaging effect of 0.05-0.06 microM Carbonylcyanide-p-trifluoro-methoxyphenylhydrazone (FCCP) was reversible within 20 sec by perfusion with fresh buffer. Cysteine 3 mM restored the aortic flow to the initial value within an additional 15-20 sec. Thereafter, the FCCP effect became irreversible due to a progressive structural membrane change. The structural change by FCCP is probably brought about by 'internalization' of polar groups (R-SH; R-NH3+) of the mitochondrial (and other) membrane.
The cardioprotective concentration range of the thiol drug 2-mercaptopropionylglycine (MPG) was investigated during reoxygenation after 30 min of hypoxia. It was found that aortic flow and frequency were increased by 1 mM MPG. Coronary flow, systolic and diastolic pressure were not significantly influenced by the drug. Mitochondria, isolated from hearts after termination of the perfusion phases, revealed increased values of RCI, when MPG had been present in the previous reoxygenation phase at 1 mM concentration. 5 mM MPG no longer showed a protective influence on the above cardiac and mitochondrial parameters. ATPase activities were decreased at 1 mM MPG by 14% and at 5 mM MPG by 40% of the controls. The latter concentration of MPG also doubled the inhibitory action of carboxyatractyloside on ATPase activity, indicating a structural change of the adenine nucleotide carrier. 1 mM MPG is considered an optimal therapeutic range in this model. The mechanism of action most probably includes an SH/-S-S-interchange reaction as well as a free radical scavenging mechanism. For many thiols, the latter is known to occur in the presence of metal ions.
A mobile nuclear magnetic resonance (NMR) device similar to a bore-hole probe has been developed for applications in materials science and biomedicine. Inhomogeneous polarizing and radio-frequency (rf) magnetic fields are applied to arbitrarily large samples from one side. Different experimental techniques have been tested to measure transverse and longitudinal relaxation times and translational diffusion constants. Good contrast for discrimination of material properties is gained when the residual dipolar coupling is retained in soft matter by avoiding spinlock effects in multi-pulse techniques. Applications to characterization of products from technical elastomers, skin, and coatings on iron sheets are reported.
Determination of tumor cell maturity and induction of cell differentiation are significant issues in oncology. We studied here in vitro the effects of cyclic AMP and cyclic GMP on human cervix carcinoma cells (HeLa cells), using normal human cervix cells as controls. Relative plasma membrane fluidity (which corresponds with the adhesive power of the cell, membrane permeability, and the ability to maintain the ionic milieu), cell cycle characteristics, and protein kinase C activity (a regulator of the cell cycle) were determined. In the untreated HeLa cells, membrane fluidity and protein kinase C activity were increased versus the controls. Administration of dbcAMP decreased the membrane fluidity and the protein kinase C activity, prolonged the G0/G1 phase of the cell cycle and shortened the S + G2 + M phase; with dbcGMP, the opposite changes were recorded (all findings, p < 0.05). Findings from HeLa cells treated with dbcAMP approached those from the normal controls. Each of the parameter studied reflected the differentiation of the HeLa cells during dbcAMP treatment. They may be of potential use for the determination of tumor cell maturity in clinical oncology.
BACKGROUND: Pleomorphic adenoma (PA) arising in the external auditory canal (EAC) is a very rare neoplasm, thought to be derived from ceruminous glands. CASE: A 43-year-old male presented with a slowly growing mass in the right EAC. Clinical and radiologic examinations showed a well-circumscribed tumor limited to the EAC, without a connection to the parotid gland. Fine needle aspiration cytology (FNAC) revealed the typical cytologic findings of PA. The diagnosis was confirmed by histologic examination. CONCLUSION: This case illustrates that together with clinical and radiologic findings, primary PA of the EAC can confidently be diagnosed by FNAC.
OBJECTIVE: To apply basic benchmarking techniques to hospital antibiotic expenditures and clinical pharmacy personnel and their duties, to identify cost savings strategies for clinical pharmacy services. DESIGN: Prospective survey of 18 hospitals ranging in size from 201 to 942 beds. Each was asked to provide antibiotic expenditures, an overview of their clinical pharmacy services, and to describe the duties of clinical pharmacists involved in antibiotic management activities. Specific information was sought on the use of pharmacokinetic dosing services, antibiotic streamlining, and oral switch in each of the hospitals. RESULTS: Most smaller hospitals (< 300 beds) did not employ clinical pharmacists with the specific duties of antibiotic management or streamlining. At these institutions, antibiotic management services consisted of formulary enforcement and aminoglycoside and/or vancomycin dosing services. The larger hospitals we surveyed employed clinical pharmacists designated as antibiotic management specialists, but their usual activities were aminoglycoside and/or vancomycin dosing services and formulary enforcement. In virtually all hospitals, the yearly expenses for antibiotics exceeded those of Millard Fillmore Hospitals by $2,000-3,000 per occupied bed. In a 500-bed hospital, this difference in expenditures would exceed $1.5 million yearly. Millard Fillmore Health System has similar types of patients, but employs clinical pharmacists to perform streamlining and/or switch functions at days 2-4, when cultures come back from the laboratory. CONCLUSIONS: The antibiotic streamlining and oral switch duties of clinical pharmacy specialists are associated with the majority of cost savings in hospital antibiotic management programs. The savings are considerable to the extent that most hospitals with 200-300 beds could readily cost-justify a full-time clinical pharmacist to perform these activities on a daily basis. Expenses of the program would be offset entirely by the reduction in the actual pharmacy expenditures on antibiotics.
1-anilino-naphthalene-8-sulfonate (ANS) fluorescence measurements have revealed that red blood cell membrane of the Rhnull type undergoes a transition at about 16 degrees C. In contrast, viscosity measurements of the extracted membrane lipids showed the usually observed transition at about 18 degrees C. Lower values of titratable sulfhydryl (SH) groups were observed in Rhnull membrane using 5,5'-dithiobis-(2-nitro-benzoic-acid) (Nbs2). In contrast, disulfide bonds in Rhnull membrane were estimated to be about 3 times the value of the controls. Spin labeling experiments using 2-(3-carboxypropyl)-4, 4 dimethyl-2-tridecyl 3-oxazolidinyloxyl were carried out with phospholipase A2 modified membranes. The mobile part of the spectra was significantly increased on the Rhnull membrane. In the presence of D-glucose, infrared spectrometry showed a larger reduction of the intensity of the POO-band in Rhnull membrane. In contrast to controls, binding of the reagent diethylpyrocarbonate resulted in no significant changes of the Rhnull membrane as determined by electron spin resonance (ESR) measurements. D-glucose transport activity was found to be at the upper level of a group of Rh positive and Rh negative persons. It is suggested that the intensity of the polar protein-lipid interaction is reduced in Rhnull membrane.
The transport inhibitor phloretin was bound to human red cell membrane and the concomitant structural changes were observed by spectroscopic methods. By the spin labeling method a decrease in fluidity of the membrane was found at 1 and 10 microM concentrations of the reagent. This result was obtained with the 2-(3-Carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl, and the 2-4(14-Carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxyl lipid spin labels. Infrared spectroscopy of modified membranes revealed an intensity increase of the POO- band at about 1250 cm-1. Moreover, a shift of the peak at 1050 cm-1 to 1100 cm-1 was observed in the presence of phloretin. Raman spectroscopy of the membranes did not contradict the results found with infrared and ESR spectroscopy: In the phloretin modified membrane we observed a lack of the band at 1085 cm-1, which leads to suggest that the POO- and/or C-C regions are less fluid. Changes of the extracted red cell membrane lipids were less characteristic, and the results differed from those found in red cell membrane.