Biomedical subjects

S A Katz

Publications and source records attributed to S A Katz.

At least 19 recordsLinked to original sources

PubMed1992

Use of hair analysis for evaluating mercury intoxication of the human body: a review.

Relationships have been established between the concentrations of mercury in human scalp hair and environmental or dietary mercury exposures. For chronic exposures, the hair/blood ratio for mercury is in the range 200:1-300:1, and scalp hair mercury concentrations of greater than 5 ppm are indicative of mercury intoxication. These observations, coupled with the ease by which samples may be collected, transported and stored, support the use of hair analysis for evaluating mercury intoxication of the human body.

Environmental Exposure↗

PubMed1992

Renal injury in obese Zucker rats: glomerular hemodynamic alterations and effects of enalapril.

Angiotensin-converting enzyme inhibitors may ameliorate experimental glomerular injury by either hemodynamic or nonhemodynamic mechanisms. In a long-term study, we examined the effects of 30 wk of enalapril treatment on the development of glomerular disease in obese Zucker rats (OZR). Enalapril significantly (P less than 0.05) lowered blood pressure, fasting serum cholesterol, and urine albumin excretion in OZR throughout the experimental period. At 38 wk of age, enalapril-treated OZR had a sixfold reduction in the percent glomeruli exhibiting focal glomerulosclerosis and a 20-30% reduction in kidney weight and glomerular area. A separate micropuncture study in 22- to 26-wk-old rats revealed that untreated OZR with albuminuria and increased blood pressure had elevated glomerular capillary pressure (Pgc). Enalapril-treated OZR had less albuminuria and lower blood pressure, but Pgc was not reduced. The value of the transcapillary hydraulic pressure difference (delta P) in enalapril-treated OZR was intermediate between values in untreated OZR and lean Zucker rats. Thus enalapril markedly attenuated the development of glomerular injury in OZR. The salutary effects of enalapril may have involved a reduction in delta P coupled to a nonhemodynamic action, possibly restriction of glomerular growth or lowering of serum cholesterol.

Albuminuria↗

PubMed1992

Lovastatin but not enalapril reduces glomerular injury in Dahl salt-sensitive rats.

Dahl salt-sensitive (S) rats fed a high salt diet develop hypertension, hyperlipidemia, and progressive renal disease. Previous studies have suggested that lipids may be important in the pathogenesis of glomerulosclerosis in Dahl S rats. To investigate this possibility, Dahl S rats fed 4% NaCl chow were treated chronically with the cholesterol synthesis inhibitor lovastatin. After 22 weeks, lovastatin-treated rats had a 38% reduction in serum cholesterol, a 76% reduction in urine albumin excretion, and one-sixth the incidence of focal glomerulosclerosis compared with vehicle-treated control rats. Blood pressure in lovastatin-treated rats was significantly (p < 0.05) lower than that in vehicle-treated rats both early in the study (4 weeks of treatment) and at the end of the protocol. Lovastatin had no effect on glomerular filtration rate or glomerular ultrafiltration dynamics. The efficacy of angiotensin converting enzyme inhibitors in attenuating proteinuria and experimental glomerular disease may be dependent on sodium intake. Thus, we also investigated the effects of long-term enalapril treatment on glomerular injury in Dahl S rats fed high salt chow. Enalapril treatment (50 or 200 mg/l drinking water) significantly lowered blood pressure in Dahl S rats, but did not significantly affect albuminuria or glomerulosclerosis. Enalapril also had no effect on glomerular hemodynamics. These results suggest that lipids may be important in the development of both glomerular disease and hypertension in Dahl S rats and that angiotensin converting enzyme inhibition may not affect the course of renal disease in a setting of high salt intake.

Albuminuria↗

PubMed1991

Comparative pharmacokinetics and pharmacodynamics of epoetin alfa and epoetin beta.

Different recombinant human erythropoietin products have been developed. Although they appear to have similar pharmacokinetics and function, these have not been directly compared. This randomized, double-blind, four-period crossover study compared the pharmacokinetics and pharmacodynamics of intravenous and subcutaneous epoetin alfa and epoetin beta in 18 normal male volunteers. As a control, three subjects received placebo treatment. After intravenous administration, the steady-state volume of distribution and beta-phase volume of distribution of epoetin beta were 7.7% and 16.9% larger than for epoetin alfa (p less than 0.05). The terminal elimination half-life after intravenous administration of epoetin beta was 20% longer than the terminal elimination half-life of epoetin alfa. After subcutaneous administration there was a delayed drug absorption with epoetin beta compared with epoetin alfa (p less than 0.05). There was a small but significantly greater absolute reticulocyte response after subcutaneous epoetin beta compared with subcutaneous epoetin alfa. The findings support differences in the pharmacokinetics and function of epoetin alfa and beta that are possibly caused by differences in their glycosylation.

Adolescent↗

PubMed1991

Acute stimulation of renin secretion changes the multiple form profile of active plasma renin.

Active renin is composed of multiple forms with variable isoelectric points. In this study, the relative proportions of five major active renin forms in human peripheral venous plasma were compared before and 2 h after stimulation of renin secretion with both converting enzyme inhibition (quinapril) and upright posture in five patients with essential hypertension. The five major active renin forms were separated by shallow gradient isoelectric focusing and quantitated by radioimmunoassay of generated angiotensin I. Plasma renin activity increased from 1.2 to 5.1 ng AI/mL/h (P less than .05). This was accompanied by a significant increase in the proportions of the two most basic renin forms and a significant decrease in the proportion of the most acidic form in venous plasma. Although the mechanism cannot be determined from this study, the altered renin form profile observed could have resulted from preferential renal secretion and/or altered hepatic extraction of the more basic forms. An altered renin form profile in response to acute stimulation has important physiologic implications. Since the relatively basic renin forms are preferentially degraded they possess shorter half-lives. Additionally, the multiple forms of active renin may be functionally heterogenous. Thus, acute stimulation of renin secretion may result in circulating renin with a shorter duration of action and different functional effects than renin released under steady state conditions.

Antihypertensive Agents↗

PubMed1991

Functional evidence for sympathetic nerve activity in conscious cervical spinal rats.

Experiments in anesthetized animals have demonstrated sympathetic nerve activity after cervical spinal cord transection (CST), yet little evidence exists for sympathetic nerve activity in conscious spinal animals. We determined the effect of CST on mean arterial pressure (MAP), heart rate (HR), and plasma renin activity (PRA) in conscious rats. Next, we tested for the presence of functionally significant sympathetic nerve activity 24 h after CST by measuring MAP, HR, urine flow, urinary sodium excretion (UNaV), urinary potassium excretion (UKV), and PRA before and for 2 h during administration of adrenergic antagonists (propranolol + phentolamine) or vehicle. CST resulted in significant decreases in MAP (100.0 +/- 1.6 to 75.0 +/- 1.4 mmHg), HR (353 +/- 7.5 to 315 +/- 6.6 beats/min), and PRA (2.2 +/- 0.3 to 1.2 +/- 0.2 ng angiotensin I.ml-1.h-1). Subsequent adrenergic blockade resulted in a further drop in HR (-52 +/- 21 beats/min), as well as two- to threefold increases in UNaV and UKV. We conclude that CST causes an overall decrease in sympathetic drive. However, sympathetic nerve activity to the heart and kidney remains after CST and is responsible for support of HR and retention of sodium and potassium.

Animals↗

PubMed1991

The analytical biochemistry of chromium.

The essentiality and carcinogenicity of chromium depend on its chemical form. Oxidation state and solubility are particularly important in determining the biological effects of chromium compounds. For this reason, total chromium measurements are of little value in assessing its nutritional benefits or its toxicological hazards. Aqueous sodium carbonate-sodium hydroxide solutions have been successfully used for extracting hexavalent chromium from a variety of environmental and biological matrices while preserving its oxidation state. Typical recoveries are 90 to 105% in samples spiked with both trivalent and hexavalent chromium. Determination of hexavalent chromium after extraction with sodium carbonate-sodium hydroxide solution, coupled with the determination of total chromium after nitric acid-hydrogen peroxide digestion, has been applied to the evaluation of chromium speciation in airborne particulates, sludges, and biological tissues.

Carcinogens, Environmental↗

PubMed1991

Analysis of active renin heterogeneity.

Active renin is a heterogeneous enzyme that can be separated into multiple forms with high-resolution isoelectric focusing. The isoelectric heterogeneity may result from differences in glycosylation between the different forms. In order to determine the relationship between active renin heterogeneity and differences in composition or attachment of oligosaccharides, two separate experiments were performed: (i) Tunicamycin, which interferes with normal glycosylation processing, increased the proportion of relatively basic renin forms secreted into the incubation media by rat renal cortical slices. (ii) Endoglycosidase F, which enzymatically removes carbohydrate from some classes of glycoprotein, similarly increased the proportion of relatively basic forms when incubated with active human recombinant renin. In addition, further studies with inhibitors of human renin activity revealed that the heterogeneous renin forms were similarly inhibited by two separate renin inhibitors. These results are consistent with the hypothesis that renin isoelectric heterogeneity is due in part to differences in carbohydrate moiety attachment and that the heterogeneity of renin does not influence access of direct renin inhibitors to the active site of renin.

Animals↗

PubMed1991

Evidence for the functional significance of multiple renin forms.

Our laboratory demonstrated the existence of 6 forms of renin, (F1-F6) each with a unique isoelectric point (pI). We ascribe the heterogeneity to differences in glycosylation. This heterogeneity has been demonstrated to exist in all animals studied in our laboratory, across a wide evolutionary scale. Multiple forms have been found in fish, amphibians, birds and mammals, including humans. We have been able to demonstrate that hepatic inactivation of the renin forms in humans is different for each form. Isolation and purification of the forms allowed injection of a single form into rats. IV infusion of F4 resulted in a significant natriuresis and diuresis, while the other forms had no significant renal effects. However, if the same forms were infused into the cerebroventricles at a much lower dose, F6 caused a natriuresis. Pretreatment with converting enzyme inhibitor abolished that effect. We were able to show that Spontaneously Hypertensive Rats (SHR) exhibited a renin profile that was altered in a predictable way and was significantly correlated with their blood pressure. The hepatic clearance of each form was also different, so that the forms have different half lives. These data support the hypothesis that renin heterogeneity is dependent upon glycosylation and is functionally significant.

Ambystoma↗

PubMed1990

Effect of acute stimulation of renin secretion on renal renin content in vivo.

Acute stimulation of renal renin secretion has been reported to increase, not change, or decrease intra-renal renin (IRR) content. However, these effects and the potential mechanisms for acute changes in IRR content have not been studied directly. In this study, the effect of acute stimulation of renin secretion on IRR content was studied directly using a new in vivo blood perfused rabbit kidney preparation. Following removal of the right kidney for determination of IRR content (N = 7) the left kidney was cannulated and perfused for an average of 55 minutes (baseline) at mean arterial blood pressure. Renin secretion by the left kidney was subsequently stimulated by reducing renal perfusion pressure to 60 mm Hg and administering enalapril, 1 mg/kg intravenously. After 38 to 140 minutes (mean 90 min) of stimulation, the left kidney was also removed and IRR content assessed. Renal blood flow and renin secretory rate (RSR) were determined frequently at baseline and following stimulation of renin secretion. The total amount of renin secreted in response to acute stimulation was calculated by integrating the RSR response over time. RSR from the left kidney increased by 515% during acute stimulation. IRR content in the left kidney also increased and averaged 16% greater than the right kidney from the same animal. In order to account for all of the renin secreted as well as the increase in IRR content following acute stimulation, it was calculated that the renin synthesis rate would have been required to increase over 26-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Renal secretion and hepatic clearance of human multiple renin forms.

Human active renin can be separated into at least five forms by isoelectric focusing. The present study assessed the preferential renal secretion and hepatic degradation of renin forms in humans. The renin form profile of secreted renal renin was determined before transplant in an ex vivo kidney donor perfusion system and compared with the peripheral plasma multiple renin form profile of normal subjects. The effect of hepatic degradation on renin forms was assessed in hepatic vein plasma in comparison with infrarenal vena cava plasma in hypertensive patients during renal vein renin studies. The results revealed a significantly greater proportion of the more basic forms in the perfusate of donor kidneys compared with normal plasma. In hypertensive patients the proportion of the more basic renin forms in the hepatic vein was significantly decreased in comparison with the infrarenal vena cava. Thus, the human kidney may preferentially secrete the more basic renin forms. In contrast, the liver preferentially degrades the more basic forms, giving these forms a shorter plasma half-life. The preferential secretion and clearance of the more basic forms of renin may contribute to short-term control of human renin-angiotensin system activity.

Adult↗

PubMed1989

Inorganic chemistry of chromium and its speciation in Whetlerite.

Chromium compounds are among the impregnants that enhance the ability of carbon air filters to absorb and destroy toxic agents such as CK and AC. The possibility of inhaling chromium-containing carbon dust from such filters has caused concern because, in addition to being an essential nutrient, chromium has been identified as a chemical carcinogen in humans. The essentiality or carcinogenicity of chromium depends upon its chemical speciation. Solubility and oxidation state are particularly important factors in assessing the potential hazards associated with the possible inhalation of chromium-containing dusts from these impregnated carbons or Whetlerites. The chemical speciation of the chromium in Whetlerite was found to be: from 0.6 to 1.3% insoluble trivalent chromium; from 1.0 to 1.3% insoluble hexavalent chromium; and from 0.7 to 0.9% soluble hexavalent chromium. The impregnation process, and the resulting speciation of chromium in Whetlerite, is consistent with the inorganic chemistry of chromium.

Air Pollutants, Occupational↗

PubMed1989

Speciation, bioavailability, and systemic distribution of chromium from Whetlerite dust.

Exploratory studies were conducted to determine if chromium from Whetlerite dust is bioavailable when administered intratracheally to rats, and if so, to determine its speciation. These studies indicated that chromium in this form and by this route of administration was bioavailable and was found in the trivalent state only. Less than 25% of the administered dose was recovered after 4 h, suggesting that most of the chromium was rapidly absorbed, distributed, and eliminated. Most of the chromium was found in the lungs and kidneys. The time course in the kidney suggests that this organ may be involved in the metabolism and elimination of trivalent chromium. Unexpected mortality in the experimental group of rats may have been due to the copper content of the Whetlerite, which exceeded the LD50 in the dose administered.

Animals↗

PubMed1989

Mathematical model of edema in the isolated rabbit lung perfused with oleic acid.

The development of edema by the isolated, perfused rabbit lung in response to oleic acid was analyzed with the equations of Kedem and Katchalsky (Biochim. Biophys. Acta 27: 229-246, 1958). A perfused cylinder and annulus surround was chosen as a model. Isolated lungs, perfused with an isosmotic solution containing dextran as an oncotic agent, received a bolus injection of oleic acid into the pulmonary artery, resulting in marked edema without a rise in mean pulmonary arterial pressure. Hydrostatic pressure was kept constant and in the model was converted to its equivalent concentration of osmotically active impermeant solute, with a reflection coefficient (sigma) of 1. Fluid changes could be analyzed with three principal components as follows: the capillary permeability to solute (Pk), the hydraulic coefficient (Lp), and sigma. The equations were solved using Euler's method for integration, and the values for the three coefficients were adjusted to fit the data. The analysis indicated that the edema measured experimentally could be simulated by a progressive increase in Lp at constant or increasing values of Pk and decreasing values for sigma but not after selective increases in Pk and/or decreases in sigma alone. The analysis suggests that an expanding hydraulic conductivity may be the rate-limiting factor in oleic acid-induced pulmonary edema in the isolated, perfused rabbit lung.

Animals↗

PubMed1988

Blood oxygen content estimated from PO2, PCO2, and pH.

Oxygen content of blood (265 samples, 25 dogs) from two experimental groups was estimated from measurements of blood PO2, PCO2, pH, hemoglobin, and body temperature with the computational subroutines of Olszowka and Farhi (6). Each computed value was compared with the corresponding oxygen content measured directly by a galvanometric oxygen fuel cell (Lex-O2-Con analyzer). The computed values had consistent errors when compared with the corresponding fuel cell determinations. Linear regression of fuel cell determinations on the corresponding computed values was used to obtain a corrected estimate of oxygen content. When the linear regression correction procedure was performed within each of 25 dogs, the resultant estimates were substantially improved over a lumped correction. The mean absolute value of the difference between the corrected calculated value within an individual dog and the corresponding oxygen fuel cell content determination was 0.38 +/- 0.28 (6 anesthetized dogs, 76 samples) and 0.17 +/- 0.15 (19 awake dogs, 189 samples) (SD) vol% for the two experimental groups. It is concluded that blood oxygen content may be accurately estimated from PO2, PCO2, and pH when appropriately corrected. The advantage is that only a small subset of the total number of blood samples needs to be analyzed with the oxygen fuel cell.

Animals↗

PubMed1988

Human platelets attenuate oxidant injury in isolated rabbit lungs.

Because platelets contain active antioxidant systems, the capacity of platelets to attenuate oxidant lung injury was investigated. Purine and xanthine oxidase were infused into isolated perfused rabbit lungs (IPL) to generate H2O2, thereby causing increased membrane permeability edema. The coinfusion of washed human platelets (1.20 +/- 0.07 x 10(10) cells) attenuated the degree of edema formation as measured by lung weight gain and lung lavage albumin concentration. Electron microscopy of lung preparations demonstrated platelet adherence to capillary endothelial luminal surfaces of oxidant-injured lungs, but there was no evidence of vascular plugging with platelet macroaggregates. The platelet glutathione redox cycle or platelet catalase were inhibited before infusion of platelets into the IPL with purine and xanthine oxidase. Inhibition of the glutathione redox cycle with 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-chloro-2,4-dinitrobenzene, or buthionine sulfoximine prevented platelet attenuation of lung injury. Inactivation of platelet catalase with 3-amino-1,2,4-triazole, however, did not significantly reduce the platelet-induced lung protection. We conclude that the platelet glutathione redox cycle plays a major role in reducing enzymatically generated toxic O2 metabolites and attenuating lung injury.

Animals↗

PubMed1988

Catalase pretreatment attenuates oleic acid-induced edema in isolated rabbit lung.

Because reactive O2 metabolites have been demonstrated to be potent mediators of vascular dysfunction and are synthesized by lung tissue, their involvement as mediators of oleic acid (OA)-induced pulmonary edema in the isolated Krebs-perfused rabbit lung was assessed. Injection of OA (0.1 ml) into the pulmonary artery after vehicle pretreatment induced marked increases in lung weight [50.4 +/- 13.9 vs. 4.2 +/- 2.0 (SE) g 45 min after OA or vehicle, respectively, P less than 0.05], an index of pulmonary edema, and airway pressure. OA also caused a significant though minimal increase in pulmonary arterial pressure. Pretreatment with catalase (1,000 U/ml), a scavenger of H2O2, significantly (P less than 0.05, Friedman's) attenuated the increases in lung weight (50.4 +/- 13.9 vs. 15.1 +/- 4.9 g), airway pressure, and pulmonary arterial pressure. In contrast to catalase, pretreatment with Cu-tryptophan (40 microM), a lipid-soluble scavenger of superoxide, provided no protective effect by itself, nor was there any potentiation of protection when combined with catalase. Further evidence implicating O2 metabolites in OA-induced edema was obtained by electron paramagnetic resonance (EPR) spectroscopy of perfusate samples to which the spin trap, sodium 3,5-dibromo-4-nitrosobenzenesulfonate (10 mM), was added. Analysis of these samples revealed the presence of free radicals after OA. Pretreatment with catalase (1,000 U/ml) and superoxide dismutase (250 U/ml) attenuated the EPR signal, indicating that proximal formation of O2 free radicals was in part responsible for the signal. These results suggest that reactive O2 metabolites are mediators of OA-induced pulmonary edema in the isolated perfused rabbit lung.

Animals↗

PubMed1988

Systole has little effect on diastolic coronary artery blood flow.

The hypothesis that myocardial systolic contraction attenuates diastolic coronary flow was tested by comparing flow during diastole to flow during a prolonged asystole. The circumflex coronary artery was cannulated and perfused at constant pressure in closed-chest, morphine- and alpha-chloralose-anesthetized dogs. The heart was paced at 80, 120, 160, or 200 beats/min after atrioventricular heart block under control, intracoronary adenosine, and intravenous norepinephrine treatment conditions. Cessation of pacing while holding coronary pressure constant at the previous diastolic pressure resulted in asystolic circumflex flow that initially equaled the previous diastolic flow during heart rates of 80, 120, and 160 in all treatment groups. Initial asystolic circumflex flow was approximately 5% higher than the previous diastolic flow at a heart rate of 200 beats/min, but this was probably due to an artifact. It is concluded that systolic contraction does not limit diastolic coronary flow at heart rates less than 160 beats/min and probably does not at higher heart rates.

Animals↗