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Biomedical subjects

A Iso

Publications and source records attributed to A Iso.

At least 19 recordsLinked to original sources
PubMed1999

Enteral nutrition prevents bacterial translocation but does not improve survival during acute pancreatitis.

OBJECTIVE: To evaluate the effect of enteral nutrition (EN) in attenuating bacterial and/or endotoxin translocation, maintaining immune responsiveness, and improving outcome in early acute pancreatitis (AP) in Wistar male rats. DESIGN: Acute pancreatitis was induced in rats receiving total parenteral nutrition (TPN) (AP/TPN group) (n=34) and EN (AP/EN group) (n=35) by pressure injection of 1% deoxycholate into the biliopancreatic duct (0.6 mg/kg of body weight). Rats in the sham/TPN and sham/EN groups (n=10 each) underwent laparotomy without induction of AP. Catheters for TPN and EN were placed into the external jugular vein and jejunum, respectively. Rats were infused with Ringer lactate solution for 48 hours followed by TPN in the AP/TPN and sham/TPN groups, and EN in the AP/EN and sham/EN groups until day 7. The fluid volume and energy (calories) intake were similar in all groups. SETTING: Medical school research laboratory. MAIN OUTCOME MEASURES: Survival, blood endotoxin level, villus height, 5-bromo-2'-deoxyuridine (BrdU) uptake in the jejunum and ileum, bacterial culture of mesenteric lymph nodes, and CD4/CD8 ratio of T cells in mesenteric lymph nodes, spleen, and peripheral blood. RESULTS: There was no difference in survival and pancreatic healing between the AP/TPN and AP/EN groups. Colony-forming units of the mesenteric lymph nodes and the endotoxin level were significantly lower in the AP/EN group than in the AP/TPN group (P<.05). Villus height and BrdU intake was significantly higher in the AP/EN group than in the AP/TPN group (P<.05). The CD4/CD8 ratio of T cells in spleen and peripheral blood was higher in the AP/EN group than in the AP/TPN group (P<.05), whereas there was no difference in mesenteric lymph nodes. CONCLUSIONS: Jejunal administration of EN is well tolerated in early AP, maintains immune responsiveness and gut integrity, and reduces bacterial and/or endotoxin translocation. However, compared with TPN, EN does not improve outcome. These results suggest that factors other than bacterial and/or endotoxin translocation may be responsible for mortality in this rat model of early AP. However, additional studies of both early bacterial and/or endotoxin translocation and late assessment of outcome are indicated.

Acute Disease↗
PubMed1999

Role of gender in the toxicity of norcocaine.

Gender differences may significantly influence the toxicity of cocaine in mammals. In this study, the influence of gender on the toxicity of norcocaine, a pharmacologically active metabolite of cocaine, was compared with its parent compound in adult male and female rats. In addition, the plasma and tissue norcocaine concentrations were evaluated after the administration of norcocaine and cocaine. Norcocaine or cocaine was administered intravenously at a rate of 2 mg/kg/min until circulatory collapse. Arterial blood samples as well as heart, liver, and brain tissues were obtained at circulatory collapse for the measurement of concentrations of norcocaine as well as cocaine and its major metabolites. There were no gender-related differences in the doses of norcocaine required to produce circulatory collapse; however, there were significant gender-related differences in the norcocaine tissue-to-plasma concentration ratios (T:P ratios). After the administration of norcocaine, T:P ratios for heart, liver, and brain tissue were significantly greater in males. Furthermore, after cocaine administration, the hepatic norcocaine T:P ratio was approximately 3-fold greater in the male rats than in the female rats. In contrast, female rats had a greater percentage of norcocaine in the plasma at circulatory collapse after acute cocaine administration. Although no gender differences in the lethality of norcocaine were observed, it remains to be seen whether the gender differences in the distribution and uptake of norcocaine play a role in the hepatotoxicity of the drug, particularly after chronic exposure.

Animals↗
PubMed1999

The comparative toxicity of cocaine and its metabolites in conscious rats.

BACKGROUND: The metabolites of cocaine, benzoylecgonine and ecgonine methyl ester, have been considered pharmacologically inactive when administered systemically. However, recent in vitro studies suggest that this may not be true. The current study was designed to evaluate the systemic toxicity of cocaine and its metabolites when administered systemically to awake rats fitted with catheters for long-term monitoring. METHODS: Cocaine, norcocaine, cocaethylene, benzoylecgonine, and ecgonine methyl ester were infused intravenously to produce sequential behavioral alterations and central nervous system and cardiovascular toxic effects. Arterial blood pressure and heart rate were monitored continuously. Plasma and tissue samples were analyzed for all compounds by capillary gas chromatography-mass spectrometry. RESULTS: The dose of norcocaine necessary to produce toxic effects was smaller than that of cocaine and cocaethylene. Benzoylecgonine and ecgonine methyl ester did not produce toxic manifestations at infusion rates that produced toxicity in the cocaine, norcocaine, and cocaethylene groups. Furthermore, 30- and 60-fold higher doses of benzoylecgonine and ecgonine methyl ester, respectively, were necessary to produce only mild neurobehavioral changes. Benzoylecgonine was not lethal even at doses 100 times greater than cocaine. CONCLUSIONS: These results indicate that benzoylecgonine and ecgonine methyl ester are not as toxic as cocaine, norcocaine, or cocaethylene when administered intravenously to pharmacologically naive rats.

Animals↗
PubMed1998

Endothelin in liver cell injury and regeneration after 70% hepatectomy with portal ischemia.

Hepatic ischemia-reperfusion (IR) injury caused by portal vein clamping is a common problem in hepatobiliary surgery. Endothelin (ET) is a potent vasoconstrictor and is associated with IR injury. This study evaluated the effect of ET on liver cell injury and hepatic regeneration after hepatectomy with IR. The portal veins of rats were clamped for 20 min, then unclamped and a 70% partial hepatectomy was performed. TAK-044 (TAK), the nonselective ETA/ETB receptor antagonist, was administered s.c. 30 min before laparotomy [TAK(+)]. Portal blood ET-1, GOT levels, hepatic blood flow, histologic change, DNA synthesis of hepatocytes, and the relationship of Ito cells and perisinusoidal cells were evaluated. ET-1 concentration increased after IR and was significantly higher in the TAK(+) group owing to the blockade of ET receptors. Increased GOT levels and sinusoidal congestion were reduced, but DNA synthesis of hepatocytes and hepatic blood flow did not change in the TAK(+) group. Changes in desmin staining showed that Ito cells might be related to IR injury. In conclusion, ET-1 was associated with IR injury and TAK-044 reduced but did not affect hepatocyte DNA synthesis after partial hepatectomy.

Animals↗
PubMed1996

Pregnancy enhances cocaine-induced stimulation of uterine contractions in the chronically instrumented rat.

OBJECTIVE: Our purpose was to test whether cocaine stimulates uterine activity in nonpregnant and pregnant rats. STUDY DESIGN: The carotid artery and jugular vein were chronically catheterized, and a microballoon probe was inserted into the uterine cavity of 15 pregnant and 14 nonpregnant female rats. Conscious animals received a bolus dose of either cocaine or saline solution intravenously. Cardiovascular and uterine contractile responses were studied. RESULTS: Cocaine (2.5 mg/kg) induced a marked increase in uterine activity and arterial blood pressure in both pregnant and nonpregnant animals without producing systemic toxicity. The maximum change in uterine contractions was greater in the pregnant group than in the nonpregnant group, and blood pressure responses were transient in both. CONCLUSION: This study is the first demonstration that cocaine stimulates the rat uterus in vivo, with a greater increase in contractions in pregnant compared with nonpregnant animals. These differences are not related to the hemodynamic response or pharmacokinetic profile of cocaine.

Animals↗
PubMed1996

Effect of a parenteral nucleoside-nucleotide mixture on hepatic metabolism in partially hepatectomized cirrhotic rats.

After hepatectomy, purine and pyrimidine metabolism is a key process in synthesis of DNA and RNA and in energy metabolism. To supply nucleosides for salvage synthesis, nucleoside-nucleotide mixture solutions have been developed, and they have been found to improve protein metabolism and hepatic regeneration after partial hepatectomy in normal rats. However, the effect of the solution in cirrhotic liver, common in patients with hepatocellular carcinoma, has not been reported. The aim of this study was to evaluate the metabolic effect of the nucleoside-nucleotide mixture on cirrhotic rats after partial hepatectomy. Seventy percent partial hepatectomy was performed in thioacetamide-administered cirrhotic rats. The fractional protein synthetic rate, nitrogen balance, hepatic content of nucleic acid, and blood chemistry after the administration of the nucleoside-nucleotide mixture solution (OG-VI) with total parenteral nutrition was evaluated at 7 d after partial hepatectomy. OG-VI increased hepatic RNA level and hepatic fractional protein synthetic rate (p < 0.05). It is concluded that the nucleoside-nucleotide mixture solution is an effective nutritional supplement to the metabolism of cirrhotic rats after partial hepatectomy.

Animals↗
PubMed1996

[Bacterial translocation induces remnant liver injury after subtotal (90%) hepatectomy in rats--the effect of decontamination of gram-negative rods in digestive tract by oral polymyxin B treatment].

To clarify the relationship of bacterial translocation (BT) to remnant liver injury after subtotal (90%) hepatectomy, we compared orally polymyxin B treated rats (PL-B (+)), of which gram-negative rods (GNR) in digestive tract decreased, with control rats (PL-B (-)). The increase in intestinal permeability assessed by lactulose/mannitol ratio in urine, the increase in GNR positive in tissue culture including mesenteric lymphnode, liver, spleen, portal blood, and kidney, and the elevation of serum endotoxin levels showed BT after subtotal hepatectomy in PL-B (-) group. Liver injury was also observed by increased serum GPT levels and massive coagulative necrosis of hepatocytes with bleeding in the remnant liver. In PL-B (+) group rats, BT and liver injury decreased and hepatocyte DNA synthesis increased, while intestinal permeability was the same as PL-B (-) group. It is suggested that BT is the cause of remnant liver injury after subtotal hepatectomy, and oral PL-B treatment is effective in preventing liver injury.

Administration, Oral↗
PubMed1994

Effect of nucleosides and a nucleotide mixture on proliferation of human gastric cancer cells (KATO III).

The effect of the nucleotides and a nucleotide mixture (OG-VI), consisting of inosine, guanosine 5'-monophosphate (5'-GMP), cytidine, uridine, thymidine (TdR) (4:4:4:3:1 in molar ratio), and TdR co-administration on proliferation of KATO III human gastric cancer cells in culture was evaluated. Consumption of purine and pyrimidine by cancer cells and changes in cell number with OG-VI or TdR were compared with the control culture medium (Williams E) after 72 hour-culture. Addition of OG-VI or TdR did not enhance the cellular proliferation, but inhibited growth when given in higher concentrations (0.3-3 mM inosine, 0.3-3 mM 5'-GMP, 0.22-2.2 mM uridine, 74-740 microM TdR). Consumption rate of TdR in the medium was less in the TdR group, 33.7%, than in the OG-VI group, 72.2% (p < 0.05). This suggests that TdR metabolism is modulated by other nucleosides and nucleotide included in OG-VI. Under the coadministration of 5-fluorouracil (FUra), addition of OG-VI or TdR suppressed cellular proliferation (p < 0.05). The inhibition rate of cellular proliferation in the OG-VI group was slightly higher than the TdR group, but there was no statistically significant difference between the two groups. The combination of FUra with OG-VI or TdR enhances the antitumor effect of FUra. It is concluded that the OG-VI does not enhance the tumor cell proliferation and it is a potential biochemical modulator of FUra metabolism in human cancer cells.

Cell Division↗
PubMed1994

[The effect of cocaine on uterine contractions in the rat].

The abuse of cocaine during pregnancy has become a major problem in substance abuse in the U.S.A. Although cocaine often induces preterm labor, little is known about the effect of this drug on uterine contractions. In 23 pregnant (P) and 23 nonpregnant (NP) rats, a carotid artery and jugular vein were catheterized, and a balloon catheter was inserted into the uterine cavity 24 hrs prior to the study. Arterial blood pressure, heart rate, intrauterine pressure were recorded throughout the study. Uterine contractions were expressed in Montevideo Units (M.V.U.). Cocaine (1.25-20 mg/kg) or saline was administered intravenously to test its toxicity and the effect on uterine contractions. A 1.25 or 2.5 mg/kg dose of cocaine did not produce toxic symptoms, but 2.5 mg/kg resulted in a marked increase in M.V.U. in both P and NP. In P, the maximum change in M.V.U. was as high as 250% from the baseline value, twice as much as that observed in NP. Mean arterial blood pressure increased 15% on the average and heart rate decreased 10%. This study indicates that a non-toxic dosage of cocaine stimulates uterine contractions, and pregnancy enhances this effect.

Animals↗
PubMed1993

[Incidence rates of cerebral palsy, severe mental and motor retardation, and Down syndrome in the city of Kokubunji in suburban Tokyo].

We investigated the incidence rates of cerebral palsy, severe mental and motor retardation, and Down syndrome in the City of Kokubunji in suburban Tokyo with a total population of about 100,000. The number of liveborn babies during 1985-1989 was 5,475. The number of children with cerebral palsy (CP) was 11 and the incidence rate was 2.01/1,000, which was equal to the rates in reports from several countries and was higher than those of the previous reports from Japan. Two out of 10 patients with CP had mild motor handicaps and were expected to "outgrow" their handicaps. The number of children with "severe mental and motor retardation" (SMMR) was 6 and the incidence rate was 1.10/1,000. Prenatal brain damage played a major role in the pathogenesis of CP and SMMR. The number of children with Down syndrome (DS) was 11 and the incidence rate was 2.01/1,000 which was higher than the previous rates. Incidence rates of CP, SMMR, and DS still remain high and further strategy to prevent pediatric neurological diseases is necessary.

Cerebral Palsy↗
PubMed1992

[Incidence rates of cerebral palsy, severe mental and motor retardation, and Down syndrome in the city of Higashiyamato in suburban Tokyo].

We investigated the incidence rates of three neurological diseases in childhood in the City of Higashiyamato in suburban Tokyo with a total population of about 70,000. The number of liveborn babies during 1985-1989 was 3,958. The number of patients with cerebral palsy (CP) was 9 and the incidence rate was 2.2/1,000, which was equal to the reports from several countries. Four out of 9 patients with CP had mild motor handicaps and were expected to "outgrow" their handicaps. The number of patients with "severe mental and motor retardation" (SMMR) was 4 and the incidence rate was 1.0/1,000. Prenatal brain damage played a major role in the pathogenesis of CP and SMMR. The number of patients with Down syndrome (DS) was 7 and the incidence rate was 1.8/1,000. Incidence rates of CP, SMMR, and DS still remain high and further strategy to prevent pediatric neurological diseases is necessary.

Birth Rate↗