PubMed Health⌕ Search

Biomedical subjects

C F Cobb

Publications and source records attributed to C F Cobb.

At least 19 recordsLinked to original sources
PubMed1994

Serum D(-)-lactate levels as an aid to diagnosing acute intestinal ischemia.

No serum marker has consistently proved helpful in diagnosing early acute mesenteric ischemia. D(-)-lactate is a product of bacterial metabolism and was found to be elevated in peripheral blood in a rat model of intestinal ischemia. We conducted a prospective study to evaluate preoperative D(-)-lactate levels in 31 patients undergoing laparotomy for acute abdominal emergencies, including suspected acute mesenteric ischemia. The serum was deproteinated and D(-)-lactate concentration was determined by a spectrophotometric assay. A control group was composed of patients with a benign abdominal examination who were operated on for central venous line placement. We found significant elevations in D(-)-lactate levels in patients with mesenteric ischemia compared with controls (P < 0.00005), as well as in patients with other forms of abdominal catastrophes (P < 0.00005) and with bowel obstruction (P < 0.0005). Sensitivity and specificity were 90% and 87%, respectively. The negative predictive value was 96%, and the positive predictive value was 70%. We have found that D(-)-lactate serum levels can aid in diagnosing acute mesenteric ischemia.

Acute Disease↗
PubMed1993

Serum D(-)-lactate levels as a predictor of acute intestinal ischemia in a rat model.

Currently there exists no reliable serum marker for the early diagnosis of acute mesenteric ischemia. We investigated D(-)-lactate as a marker of acute mesenteric ischemia in a rat model. D(-)-Lactate is a byproduct of bacterial metabolism; it is neither produced nor metabolized by mammalian cells. In an ischemic segment of bowel the resident microflora rapidly proliferate and soon overgrow the affected intestinal segment. Additionally, the mucosal barrier of the gut begins to break down. Under these conditions we hypothesize that D(-)-lactate should cross the mucosal barrier in large quantities. To determine if this rapid bacterial proliferation and mucosal leakage produces D(-)-lactate concentrations in quantities sufficient to elevate peripheral blood levels, two models of acute intestinal ischemia and one model of simple obstruction were developed in rats. The three models included: strangulation obstruction of terminal ileum, superior mesenteric artery ligation, and simple intestinal obstruction of the ileum. Controls were divided into two groups: sham-operated controls and unoperated controls. Serum samples were collected via an internal jugular catheter at 5 min, 2 hr, and 4 hr after surgery. These samples were then assayed for D(-)-lactate using an enzymatic-spectrophotometric assay. Data was analyzed by repeated measures analysis of variance and where applicable the Student t test was used to determine statistical significance. We found statistically significant elevations in D(-)-lactate concentrations as early as t = 5 min in the strangulation obstruction model and SMA ligation model compared to unoperated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1987

Direct stimulation of the adrenal cortex by interleukin-1.

The impact of human recombinant beta-interleukin-1 (IL-1) on adrenocortical stimulation was investigated. This study asked three questions: Does IL-1 increase the corticosterone levels of rat serum? Is there a direct effect on the adrenal cortex? What is the mechanism of this effect? The intraperitoneal injection of IL-1 (70 micrograms) in anesthetized male Fisher rats resulted in elevated corticosterone levels at 30 minutes and reached a maximum at 180 minutes (94 +/- 12 versus 34 +/- 4 micrograms/dl, p less than 0.01). Next, the adrenal glands from separate animals were perfused in situ. Corticosterone secretion was significantly increased (p less than 0.01) 90 minutes after a single arterial bolus of 35 micrograms of IL-1. The response to IL-1 was dose dependent, beginning at 3.5 micrograms and reaching a maximum at 35 micrograms. The addition of indomethacin (3 mumol/L) completely abolished the stimulatory effect of IL-1. This study demonstrates that IL-1 increases rat serum corticosterone levels, IL-1 directly stimulates the adrenal cortex, and the stimulation may be mediated through prostaglandin synthesis. This is the first evidence that IL-1 has a direct stimulatory effect on the adrenal cortex.

Adrenal Cortex↗
PubMed1985

Consequences of complete bile-duct ligation on the pubertal process in the male rat.

Prepubertal male rats underwent bile-duct ligation or a sham operation. Sham-operated animals were divided into two groups: isocalorically-fed (matched to the bile-duct-ligated animals) and ad-libitum-fed animals. At 60 days of age (after puberty in a male rat) all animals were killed. Bile-duct-ligated animals had larger livers, greater bilirubin, greater bile acid, greater aspartate transaminase, and greater alkaline phosphatase levels and lower testosterone and luteinizing hormone levels in their serum than did the controls. Moreover, the testes and seminal vesicles were smaller in the bile-duct-ligated animals than in the controls. These data suggest that chronic cholestasis contributes, at least in part, to the pubertal and maturational failure that occurs with the chronic cholestatic diseases of childhood.

Animals↗
PubMed1983

Ethanol, a Leydig cell toxin: evidence obtained in vivo and in vitro.

The available evidence which suggests that ethanol is a Leydig cell toxin is presented. Both in vivo and in vitro data are reviewed. The minor differences obtained in vitro as compared to those obtained in vivo are discussed. As a result of information obtained during the last decade, there can be little doubt that ethanol and possibly acetaldehyde are clinically important environmental Leydig cell toxins.

Alcohol Drinking↗
PubMed1983

Ethanol inhibition of glucose absorption in isolated, perfused small bowel of rats.

There is evidence for both humans and rats that malnutrition frequently occurs when ethanol is chronically ingested. Small bowel 14C-labelled glucose absorption was measured with an ex vivo system in which the small bowel of the rat was surgically removed and then arterially perfused with an artificial medium. Glucose absorption for a control group of seven rats was 248 +/- 8 microM/min/gm dry weight of small bowel (mean +/- SEM). This was significantly greater than the value 112 +/- 12 microM/min/gm dry weight (P less than 0.005) for a group of five rats in which a competitive inhibitor of glucose absorption, phlorizin (0.2 mM), was added to the bowel lumen. In the presence of 3% ethanol within the gut lumen of five rats, glucose absorption was also reduced (to 131 +/- 12 microM/min/gm dry weight) compared to absorption in the control group (P less than 0.005). The calculated amount of glucose absorbed was corrected for metabolism to lactate and carbon dioxide. We conclude that both phlorizin and ethanol inhibit glucose absorption in the isolated and perfused small bowel of rats and that probably at least part of the malnutrition in ethanol-fed rats is due to glucose malabsorption.

Animals↗
PubMed1983

An evaluation of the respective roles of portosystemic shunting and portal hypertension in rats upon the production of gonadal dysfunction in cirrhosis.

To evaluate the differential effects of portal hypertension and portosystemic shunting upon the endocrine changes that occur in men with advanced chronic liver disease, male rats underwent either partial portal vein ligation or direct portocaval anastomosis. Testicular mass was found to be reduced in both models (p less than 0.05). Similarly, estradiol levels were found to be increased (p less than 0.05) in both models when compared with sham-operated controls. The increase in estradiol levels was greater in the animals with a complete shunt than in those animals with incomplete shunts developed as a consequence of portal hypertension (p less than 0.05). Luteinizing hormone levels were reduced (p less than 0.01) in the animals with the greater estradiol levels. As expected, testosterone levels were reduced (p less than 0.01) only in the animals with reduced luteinizing hormone levels. These data suggest that portosystemic shunting, and not portal hypertension per se, is responsible, at least in part, for the gonadal injury that occurs with advanced liver disease.

Animals↗
PubMed1982

Mechanism of ethanol-induced adrenal stimulation.

A historical review of studies addressing the adrenal cortical response to ethanol and the mechanisms thought to contribute to such responses is presented. Studies reviewed range from the earliest based upon crude bioassay techniques to more modern papers which have utilized highly specific radioimmunoassay techniques and isolated perfused rat adrenal glands. Evidence for both hypothalamic-pituitary as well as direct adrenal stimulation is presented. Available evidence, however, would suggest that acetaldehyde rather than ethanol per se, is responsible for direct adrenal stimulation when it occurs.

Adrenal Cortex Hormones↗
PubMed1981

Effects of ethanol and acetaldehyde on the rat adrenal.

A pseudoCushing syndrome, indistinguishable from true Cushing syndrome except that it disappears with abstinence from alcohol, is known to occur in alcoholics. An animal model was used to study this syndrome in vitro, as earlier studies have shown that ethanol administration to animals increases corticosterone secretion. Such secretion appears to be the result of ethanol-induced ACTH secretion. We have examined the effects of ethanol and acetaldehyde on the production of three steroids: corticosterone, progesterone, and androstenedione in the isolated perfused rat adrenal. The adrenal glands and left kidney of rats were perfused with medium and one of the following additions: ethanol, acetaldehyde, ACTH or ACTH with either ethanol or acetaldehyde. The amount of the three steroids in the adrenal and the perfusion effluent was determined and compared to that of nonperfused adrenal glands. We found that perfusion with medium alone increased the production of each steroid (p less than 0.05) in the presence of ethanol or acetaldehyde. Assay of the medium before and after perfusion showed no ACTH, so that the increased steroid production cannot be ascribed to ACTH contamination. Furthermore, the addition of ACTH to perfusion medium which contained ethanol or acetaldehyde did not further enhance the responses.

Acetaldehyde↗
PubMed1981

Is ethanol a testicular toxin?

A method is described by which the testis of the rat can be isolated and selectively perfused in vitro to examine the effect of potential gonadal toxins. Using this system, the effect of ethanol at levels commonly found in the plasma of nonalcoholic men who drink alcohol was evaluated. Ethanol was found to significantly reduce (p less than 0.01) testosterone production and secretion by the isolated perfused testis. The advantage of such a system is that it permits examination of the effect of specific testicular toxins, such as alcohol, independent of hepatic metabolism and/or hypothalamic-pituitary suppression by such substances. These results suggest that ethanol, independent of hepatic metabolism and/or hypothalamic-pituitary suppression, is a direct testicular toxin.

Animals↗
PubMed1980

Isolated testes perfusion: a method using a cell- and protein-free perfusate useful for the evaluation of potential drug and/or metabolic injury.

A method is described by which the testes and left kidney of the rat can be isolated, maintained, and selectively perfused in vitro to examine the effect of potential gonadal toxins. The integrity of the system was confirmed by demonstrating appropriate increases in steroid (testosterone and estradiol) production and secretion in response to stimulation with chorionic gonadotropin; maintenance of testicular ATP levels; and failure to observe an increase in perfusate concentration of transaminase and lactic dehydrogenase over 2 hr of perfusion. After such confirmation, the effect of two potential gonadal toxins, ethanol and acetaldehyde, at levels commonly found in the plasma of men who abuse alcohol, was evaluated using the system. Both of these substances significantly (p less than 0.01) reduced the testosterone production and secretory response of the isolated perfused testes. The advantages of such a system are that the effect of specific potential toxins independent of hepatic metabolism and/or hypothalamic-pituitary suppression by such substances can be identified and examined in a system free of extragonadal metabolism.

Acetaldehyde↗
PubMed1980

Alcohol and sexual function.

The pathophysiologic factors which either document or which have been shown to be responsible for not only the hypogonadism and feminization of chronic alcoholic men but also the loss of gonadal function with resultant defeminization of chronic alcoholic women are reviewed. Evidence is presented which suggests that alcohol abuse is associated with the production of a primary form of hypogonadism characterized by loss of endocrine and reproductive function of the gonads. Moreover, evidence is presented which suggests that alcohol abuse is associated with the production of an associated hypothalamic-pituitary defect in gonadotropin secretion which prevents appropriate enhancement of gonadotropin secretion in response to the primary gonadal injury. Finally, the factors which have been found to partially explain the feminization often seen in chronic alcoholic men with advanced liver disease are discussed individually and a composite mechanism incorporating each is presented.

Alcoholism↗