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Biomedical subjects

R S Goldstein

Publications and source records attributed to R S Goldstein.

At least 127 records · Page 7Linked to original sources
PubMed1985

Cephaloridine nephrotoxicity: strain and sex differences in mice.

Marked species and sex differences have been observed in the nephrotoxicity to the cephalosporin antibiotic cephaloridine (CPH). Preliminary studies have also indicated significant strain differences in mice to CPH nephrotoxicity. To investigate these findings further, male and female C57BL, BALB/c, CD-1, CFW, CBA/J, and DBA/2 mice were given either 4000 or 6000 mg/kg of CPH, sc. Renal function was assessed 48 hr later by the ability of renal cortical slices to accumulate the organic ions p-aminohippurate (PAH) and tetraethylammonium (TEA), changes in blood urea nitrogen (BUN) and kidney-to-body wt ratios. CPH produced dose-dependent nephrotoxicity in C57BL female mice. After 6000 mg/kg, PAH and TEA slice-to-medium (S/M) ratios were reduced by 70 and 49%, respectively; BUN was elevated 10-fold. The same dose given to CFW females had no effect. BALB/c, CD-1, CBA/J, and DBA/2 females showed intermediate signs of toxicity. Male mice of all strains tested exhibited no nephrotoxicity. CPH nephrotoxicity has been correlated with the concentration of CPH within the tubular cell; and C57BL female mice had relatively greater intracellular accumulation of CPH than C57BL male mice and CFW female mice in vitro and in vivo. Thus, differences in net renal cortical accumulation of CPH suggest possible differences in transport, binding, and/or metabolism of CPH may exist among strains and between sexes of mice.

Animals↗
PubMed1985

Effects of gentamicin on renal function in isolated perfused kidneys from male and female rats.

The isolated perfused rat kidney was used to determine whether sex differences in gentamicin nephrotoxicity are related to intrinsic differences in renal response to gentamicin. Acute exposure to gentamicin decreased fractional reabsorption of water and electrolytes without changes in glomerular filtration rate in both sexes. Gentamicin decreased the tubular reabsorption of lysozyme but not glomerular permeability to lysozyme. No sex differences in renal responses were observed following in vitro exposures to gentamicin, suggesting that sex differences in susceptibility to gentamicin in vivo may be attributable to extrarenal factors, such as pharmacokinetics.

Absorption↗
PubMed1984

Influence of dietary pectin on intestinal microfloral metabolism and toxicity of nitrobenzene.

Intestinal microfloral metabolism of nitrobenzene is essential for the production of methemoglobin. Since dietary pectin alters intestinal microflora, these studies were designed to examine the effects of dietary pectin on nitrobenzene-induced methemoglobinemia. Male Fischer-344 rats were fed either AIN-76A (purified diet containing 5% cellulose), AIN-76A with 5% pectin replacing the cellulose, or NIH-07 (cereal-based diet containing 8.4% pectin) for 28 days. Following this period, nitrobenzene (200 mg/kg) was administered by gastric intubation, and methemoglobin concentrations were determined after 1, 2, 4, 8, and 24 hr. Nitrobenzene-induced methemoglobinemia was evident as early as 1 hr, peaked at 4 hr, and diminished thereafter in rats fed NIH-07 diet. In contrast, nitrobenzene-induced methemoglobinemia was not detectable in rats fed AIN-76A; however, inclusion of 5% pectin in this diet resulted in methemoglobinemia comparable to that of NIH-07-fed animals at 4, 8, and 24 hr. Administration of 400 or 600 mg/kg nitrobenzene resulted in significant diet-related differences in methemoglobinemia. Administration of 600 mg/kg nitrobenzene to animals fed NIH-07 resulted in the highest methemoglobin concentrations (64 +/- 1%); those fed AIN-76A had the lowest (20 +/- 5%), and those fed AIN-76A containing pectin had intermediate methemoglobin concentrations (44 +/- 6%). No diet-related differences in the microbial population of the stomach or small intestine were observed. However, the number of anaerobes present in the ceca of rats fed AIN-76A containing pectin was 2 to 2.5 times greater than that of rats fed AIN-76A. In vitro reductive metabolism of [14C]nitrobenzene was significantly greater in the cecal contents of rats fed NIH-07 than that in the cecal contents of either of the groups fed the AIN-76A-based diets. These studies indicate that intestinal microfloral metabolism and red blood cell toxicity of nitrobenzene is markedly different in animals fed cereal-based versus purified diets. Furthermore, since inclusion of pectin into the purified diet diminishes the magnitude of these effects, differences in dietary composition of fermentable carbohydrates in cereal-based and purified diets may mediate differences in metabolism and toxicity of nitrobenzene.

Animals↗
PubMed1984

Effect of supplemental nocturnal oxygen on gas exchange in patients with severe obstructive lung disease.

We studied the effect of supplemental nocturnal oxygen on blood gases in 15 patients with severe but stable chronic obstructive lung disease (ratio of forced expired volume in one second to forced vital capacity, 37.2 +/- 1.8 [mean +/- S.E.] per cent of predicted; arterial oxygen tension, 50.7 +/- 1.4 mm Hg; and arterial carbon dioxide tension [PCO2], 53.1 +/- 1.5 mm Hg). Sleep variables and measures of gas exchange were determined on two consecutive nights; on the first night the subjects breathed supplemental oxygen, and on the second they breathed room air. Transcutaneous PCO2 was measured with an infrared sensor, and arterial oxygen saturation with an ear oximeter. Breathing of supplemental oxygen sufficient to keep oxygen saturation at or above 90 per cent was associated with only small increases (less than 6 mm Hg) in PCO2 throughout sleep, as compared with values while subjects were breathing room air. The increase in PCO2 occurred early in the night and was not progressive. Only three patients, who were found to have obstructive sleep apnea in addition to obstructive lung disease, had larger increases in PCO2 during sleep and reported morning headaches. We conclude that nocturnal oxygen does not induce clinically important increases in PCO2 during sleep in patients with stable obstructive lung disease and therefore can safely be used to prevent the dangerous consequences of hypoxia.

Aged↗
PubMed1984

Tuberous sclerosis with pulmonary involvement.

Pulmonary tuberous sclerosis produced interstitial disease in a woman with normal-sized lungs; numerous hemosiderin-laden macrophages were found in the fluid obtained through bronchoalveolar lavage. The pathological changes seen in the lungs were identical to those of pulmonary lymphangiomyomatosis, in which the constellation of clinical signs usually found in tuberous sclerosis is absent. The two conditions are sufficiently similar in clinical presentation, pathological changes and prognosis to be considered variants of the same disease. The recent findings of progestin receptors in lung tissue from patients with pulmonary lymphangiomyomatosis will likely direct future management towards hormonal manipulation.

Adenoma↗
PubMed1984

Macromolecular covalent binding of [14C]nitrobenzene in the erythrocyte and spleen of rats and mice.

Nitrobenzene exposure is known to produce red blood cell damage as well as engorgement and sinusoidal congestion of the spleen in male Fischer-344 (F-344) rats but not in male B6C3F1 mice. These studies were conducted to investigate the species differences in the covalent binding of [14C]nitrobenzene in the erythrocyte and spleen and to assess the contribution of nitrobenzene-induced erythrocytic damage to the splenic effects. Total and covalently bound 14C concentrations in erythrocytes of rats were 6-13 times greater than those of mice following a single oral dose of 75, 150, 200 or 300 mg/kg [14C]nitrobenzene, suggesting that species differences in nitrobenzene-induced red blood cell toxicity may be related to differences in erythrocytic accumulation of nitrobenzene and its metabolites. Covalently bound 14C in erythrocytes of rats peaked 24 h following administration of 200 mg [14C]nitrobenzene/kg; in contrast, bound radiolabel in erythrocytes from mice plateaued at 10 h. Splenic engorgement increased in a time-related manner in treated rats but not in mice. Species specificity was also observed in the accumulation of bound radiolabel in the spleen. Gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of lysed, dialyzed erythrocytes from treated rats revealed that hemoglobin was the primary, if not the exclusive, site of macromolecular covalent binding following nitrobenzene treatment. SDS-PAGE of dialyzed rat spleens revealed that 82% of total bound 14C migrated identically to hemoglobin. These data indicate that covalent binding of [14C]nitrobenzene and its metabolites in the spleen is primarily derived from bound 14C from scavenged erythrocytes. Therefore, the species differences in splenic engorgement and accumulation of [14C]nitrobenzene may be related to differences in susceptibility to nitrobenzene-induced red blood cell damage.

Animals↗
PubMed1983

Minireview. The nephrotoxicity of cisplatin.

Cisplatin is a cancer chemotherapeutic agent whose clinical use is complicated by its dose related kidney toxicity. Since the histopathological profile of cisplatin nephrotoxicity appears similar to that of other heavy metals, it has been commonly presumed that cisplatin nephrotoxicity is related to the platinum moiety. However, the delayed time course and development of cisplatin nephrotoxicity is not characteristic of heavy metal nephropathy. Furthermore, cisplatin nephrotoxicity is stereospecific to the cis and not the trans isomer, indicating that the platinum atom is not the proximate nephrotoxicant. It is likely that a metabolite of cisplatin, possibly an aquated and/or hydroxylated complex, mediates the nephrotoxicity of cisplatin.

Acute Kidney Injury↗
PubMed1983

Lesion of a serotonergic modulatory neuron in Aplysia produces a specific defect in feeding behavior.

The serotonergic metacerebral cells (MCCs) of Aplysia were destroyed by intracellular injection of proteolytic enzyme. MCC-lesioned animals showed alterations of biting responses compared to MCC-sham and B-cell-lesioned control animals, as well as to their own preoperative behavior. The alterations of biting responses included a prolongation of the duration of radula protraction and a lengthening of interbite interval. No changes were observed in non-biting feeding responses and in behaviors unrelated to feeding.

Animals↗
PubMed1983

Hyperglucagonemia following cisplatin treatment.

These studies were initiated to determine (1) if cisplatin (cis-DDP)-induced hyperglucagonemia is related to decreased hormone degradation, (2) the relationship between impaired kidney function associated with cis-DDP nephrotoxicity and hyperglucagonemia, and (3) the contribution of cis-DDP-induced hyperglucagonemia to disturbances in glucose metabolism in male F-344 rats. Administration of 5 or 7.5, but not 2.5, mg/kg cis-DDP iv increased fasting plasma immunoreactive glucagon (IRG) concentrations. Hyperglucagonemia following cis-DDP treatment was characterized by an increase in the biologically active or true pancreatic form of IRG as well as an increase in an extrapancreatic component. cis-DDP treatment (5 mg/kg) resulted in a prolonged half-life and a reduced rate of plasma disappearance of exogenous glucagon. Reducing cis-DDP nephrotoxicity, via mannitol pretreatment, resulted in a significant reduction in total, true pancreatic, and extrapancreatic plasma IRG. Other nephrotoxicants, such as glycerol or gentamicin, also resulted in hyperglucagonemia, indicating that the effects of cis-DDP on glucagon metabolism are also characteristic of other nephrotoxicants and, therefore, may be secondary to kidney toxicity. Despite marked hyperglucagonemia following cis-DDP treatment, neither severe fasting hyperglycemia nor increased hepatic and renal gluconeogenic enzyme activity was apparent in treated animals. This apparent discrepancy cannot be attributed to glucagon resistance at the target tissue level since cis-DDP-treated animals responded appropriately to exogenous glucagon. These results indicate that hyperglucagonemia following cis-DDP treatment (1) may be related to decreased glucagon degradation associated with impaired renal function and (2) does not markedly disrupt glucose homeostasis.

Animals↗
PubMed1983

The effects of cisplatin and other divalent platinum compounds on glucose metabolism and pancreatic endocrine function.

Three divalent platinum compounds, cis-dichlorodiammineplatinum (cis-DDP), trans-dichlorodiammineplatinum (trans-DDP), and ammonium tetrachloroplatinate, were examined for their effects on glucose metabolism in male F-344 rats. Rats were treated with a single iv dose of cis-DDP (0, 2.5, or 5 mg/kg), trans-DDP (0, 5, 7.5, or 15 mg/kg) or tetrachloroplatinate (0, 6, or 18 mg/kg). Glucose tolerance was evaluated 2, 4, 7, and 14 days following platinum treatment by serially measuring plasma glucose before and following an ip glucose load. Administration of 5 mg/kg cis-DDP impaired glucose tolerance on Days 2 and 4, but not on Days 7 and 14. Plasma immunoreactive glucagon (IRG) was elevated at all times following cis-DDP treatment and thus was not correlated with the transient impairment in glucose tolerance. Plasma immunoreactive insulin (IRI) response to a glucose load was deficient relative to the degree of hyperglycemia in cis-DDP-treated (5 mg/kg) animals on Days 2 and 4. However, neither histopathological damage of the pancreas nor pancreatic stores of IRI were affected by cis-DDP treatment. In contrast to cis-DDP, equimolar or greater than equimolar doses of trans-DDP or tetrachloroplatinate did not significantly affect glucose tolerance at any time examined. These results indicate that cis-DDP-mediated glucose intolerance is unique to the geometry of the complex and is related to properties other than the presence of a divalent platinum atom. Furthermore, glucose intolerance following cis-DDP treatment appears to be related to a relative deficiency in insulin secretion.

Animals↗
PubMed1982

Effect of breathing pattern on oxygen concentration received from standard face masks.

Standard face masks are widely used for patients who require high oxygen concentrations. A mechanical model was designed to reproduce various respiratory manoeuvres while oxygen was delivered through a standard variable-performance face mask. Over a range of tidal volumes from 300 to 1200 ml and of frequencies from 10 to 30 breaths/min, the received oxygen concentration was lower than the delivered concentration. The disparity between delivered and received oxygen increased with increasing rate and depth of simulated breathing but could be reduced by increasing the flow rate up to 60 l/min. When a turbulent environment was created, the difference between delivered and received oxygen concentrations was exaggerated. Disparities between delivered and received concentrations can be lessened by increasing the flow rate.

Humans↗
PubMed1982

Tuberculosis--a review of 498 recent admissions to hospital.

To document the changing clinical spectrum of tuberculosis among inpatients, 498 consecutive admissions to the tuberculosis unit of West Park Hospital, Toronto between January 1977 and March 1980 were reviewed. The results were compared with those of a study at this hospital two decades earlier. The recent patients were older, had a shorter stay in hospital, were more often alcoholic and more often had nontuberculous mycobacterial pulmonary disease.

Aged↗
PubMed1982

Glucose intolerance following cis-platinum treatment in rats.

cis-Dichlorodiammineplatinum (cis-Pt) is a heavy metal complex used in cancer chemotherapy. Since this drug has been shown to induce hyperglycemia in rats, these studies were initiated to elucidate the effects of cis-Pt on carbohydrate tolerance and insulin and glucagon secretion. Two days following i.v. cis-Pt (2.5 or 7.5 mg/kg, 5 ml/kg) or vehicle administration to male F-344 rats, plasma glucose, immunoreactive insulin (IRI) and glucagon (IRG) concentrations were determined in the basal state and serially following a glucose load (2 g/kg, i.p.). Since cis-Pt induces a dose-related anorexia, a pair-fed control group was also studied. Administration of 7.5 mg/kg cis-Pt was associated with plasma glucose concentrations 2.5-5 times greater than ad-libitum and pair-fed controls at every time point during the 2-h glucose tolerance test. Although basal plasma IRI concentrations of the 7.5-mg/kg group were comparable to ad-libitum fed controls, they were significantly greater than those of pair-fed partners. Furthermore, the appropriate IRI response to a glucose stimulus observed in both controls and the 2.5-mg/kg group was absent in the 7.5-mg/kg group. Basal plasma IRG concentrations of the 7.5-mg/kg group were approximately 3-4 times greater than ad-libitum and pair-fed controls and were not suppressed following a glucose load. These results suggest that cis-Pt induces marked glucose intolerance in association with an impaired IRI response and abnormal glucagon response to a glucose stimulus.

Animals↗
PubMed1982

Intraneuronal injection of horseradish peroxidase labels glial cells associated with the axons of the giant metacerebral neuron of Aplysia.

After injecting the cell body of the giant serotonergic neuron (GCN) in the cerebral ganglion of Aplysia with horseradish peroxidase (HRP), we found that some glial cells were labeled along the cerebrobuccal connective and posterior lip nerve, the two nerves that contain the major axon branches of the injected neuron. Starting at a distance of about 3 mm from the site of the injection, only glial cells in the nerve that are close to an axon branch of the GCN contained HRP. Labeling appears to be selective because, at most, only one out of three glial cells was labeled within an area of 20 micrometer of the axon. Moreover, no HRP was detected in any of the many glial cells within the cerebral ganglion. Reaction product diffusely labeled the cytoplasm of glial cell bodies and processes after intraneuronal injection of HRP. This distribution was markedly different from that observed in glial cells after the uptake of HRP from the extracellular space; HRP, presumed to be taken up by endocytosis, was found to be localized to vesicles, tubules, and multivesicular bodies.

Animals↗