Impaired microvascular vasoconstrictive responses to vasopressin in septic rats

We have previously demonstrated that chronic alcohol consumption (8 to 10 weeks with ethanol as 36% of the caloric intake) does not exacerbate the effects of ischemia reperfusion injury on the heart. In those same studies, however, Gram-negative sepsis caused myocardial depression in both control and alcoholic rats, but also protected hearts from further damage due to ischemia-reperfusion. In the present study, we determined if preconditioning, a very short ischemia-reperfusion episode that protects the heart from more prolonged ischemia, would have similar effects on hearts from alcoholic and control rats with or without sepsis. Thus, rats were fed a liquid diet supplemented with ethanol or dextrin for 8 to 10 weeks. Some alcoholic and control rats were made septic with Escherichia coli injected into the subcutaneous space, whereas others received an injection of sterile saline. Isolated, isovolumically beating hearts were studied the following day. Hearts were made ischemic for 5 min, reperfused for 5 min, and then made ischemic for 35 min and reperfused for 25 min. Data from similar groups of hearts receiving only 35 min ischemia, and studied at the same time as the present groups, have been previously reported. The 5-min preconditioning episode was more effective in protecting hearts in the alcohol group than in the control group. Postischemic left ventricular developed pressure and +dP/dtmax were not significantly decreased from the preischemic values in the alcohol group, but were significantly decreased in the control group. The time to recovery of spontaneous contractions was decreased by preconditioning in the alcohol group but not in the control group, and the recovery of coronary flow was enhanced in the alcohol group, but not in the control group by pre-conditioning. Thus a single 5-min ischemic procedure was effective in protecting the heart from prolonged ischemia in the alcohol group, whereas it was not sufficient to elicit protection in the control group. Sepsis depressed preischemic function in both groups, but recovery from ischemia was complete.     

Attenuation of anticonvulsant effects of diazepam after chronic treatment with bicuculline

Changes in the GABAergic system after chronic treatment with bicuculline were examined in two strains of inbred rats, Fischer 344 (F344) and Lewis (LEW). Rats received an IP injection of either bicuculline (2 mg/kg) or vehicle once a day for 12 days. After this chronic treatment, the effects of diazepam (1 mg/kg, IP) and pentobarbital (20 mg/kg, IP) on bicuculline-induced convulsions were measured. Bicuculline was acutely infused into a tail vein at 0.0415 mg/min, and the infusion was terminated when rats showed seizure. Following the chronic bicuculline treatment, the anticonvulsant effect of diazepam, but not of pentobarbital, was significantly reduced as compared to its effect following chronic vehicle treatment in both strains. Both diazepam and pentobarbital showed a significant difference in anticonvulsant effects between strains (F344 > LEW). The hypnotic effects of muscimol, barbital, pentobarbital, and ethanol following chronic bicuculline treatment were examined. There was no significant difference in sleep time induced by these drugs between bicuculline- and vehicle-treated rats. These results suggest that the attenuation of diazepam's anticonvulsant effect after chronic bicuculline treatment may result from functional changes in benzodiazepine receptors and that the anticonvulsant effects of diazepam and pentobarbital may be influenced by genetic factors. Moreover, the hypnotic effects of several drugs tested are apparently not affected by chronic bicuculline treatment.     

Attenuation of gentamicin-induced nephrotoxicity in rats by fleroxacin

The effect of fleroxacin on gentamicin-induced nephrotoxicity was evaluated with female Sprague-Dawley rats. Animals were injected during 4 or 10 days with saline (NaCl; 0.9%), gentamicin alone at doses of 10 and 40 mg/kg of body weight/12 h (subcutaneously), fleroxacin alone at a dose of 25 mg/kg/12 h (intraperitoneally), or the combination gentamicin-fleroxacin in the same regimen. Gentamicin induced a dose- and time-dependent renal toxicity as evaluated by gentamicin cortical levels, sphingomyelinase activity in the renal cortex, histopathologic and morphometric analysis, blood urea nitrogen and serum creatinine levels, and cellular regeneration ([3H]thymidine incorporation into DNA of cortical cells). The extent of these changes was significantly reduced when gentamicin was given in combination with fleroxacin. Although the mechanisms by which fleroxacin reduces the nephrotoxic potential of gentamicin are unknown, we propose that the fleroxacin-gentamicin combination enhances exocytosis activity in proximal tubular cells, as suggested by the higher excretion of urinary enzymes and lower cortical levels of gentamicin observed in animals treated with the combination fleroxacin-gentamicin compared with those treated with gentamicin alone. The protective effect of fleroxacin on gentamicin nephrotoxicity should be investigated further.     

Viscosupplementation with hylan G-F 20: a 26-week controlled trial of efficacy and safety in the osteoarthritic knee

Cortical color blindness, or cerebral achromatopsia, has been likened by some authors to "blindsight" for color or an instance of "covert" processing of color. Recently, it has been shown that, although such patients are unable to identify or discriminate hue differences, they nevertheless show a striking ability to process wavelength differences, which can result in preserved sensitivity to chromatic contrast and motion in equiluminant displays. Moreover, visually evoked cortical potentials can still be elicited in response to chromatic stimuli. We suggest that these demonstrations reveal intact residual processes rather than the operation of covert processes, where proficient performance is accompanied by a denial of phenomenal awareness. We sought evidence for such covert processes by conducting appropriate tests on achromatopsic subject M.S. An "indirect" test entailing measurement of reaction times for letter identification failed to reveal covert color processes. In contrast, in a forced choice oddity task for color, M.S. was unable to verbally indicate the position of the different color, but was surprisingly adept at making an appropriate eye movement to its location. This "direct" test thus revealed the possible covert use of chromatic differences.     

Attenuation of salicylate-induced tinnitus by Ginkgo biloba extract in rats

The effects of an extract from Ginkgo biloba, EGb 761, on tinnitus were tested using an animal model of tinnitus. Daily oral administration of EGb 761 in doses from 10 to 100 mg/ kg/day began 2 weeks before behavioral procedures and continued until the end of the experiment. Tinnitus was induced by daily administration of 321 mg/kg sodium salicylate s.c. (corresponding to 275 mg/kg/day of salicylate acid) in fourteen groups of pigmented rats, 6 animals/group. The results from salicylate- and EGb-761-treated animals were compared to control groups receiving either salicylate, saline, or EGb 761 only in doses of 100 mg/kg. Administration of EGb 761 resulted in a statistically significant decrease of the behavioral manifestation of tinnitus for doses of 25, 50 and 100 mg/kg/ day.     

Attenuation of early hyperglycaemia induced by streptozocin in fasting rats

Early hyperglycaemia induced by streptozocin was studied in fasting rats. It was found that the early hyperglycaemia was attenuated, the hypoglycaemia was prolonged, and the initiation of the permanent hyperglycaemia was delayed. The early hyperglycaemia induced by streptozocin was further attenuated in carbon tetrachloride pretreated fasting rats. It was speculated that the appearance of the early hyperglycaemia was liver related.     

A 13-week subchronic toxicity study of josamycin in F344 rats

A 13-week subchronic toxicity study of josamycin was performed in male and female F344 rats to determine the maximum tolerable dose (MTD) for subsequent investigation of the carcinogenicity. As animals refused to take diet containing 5.0% josamycin in our preliminary study, dose levels in the present study were determined as 0, 0.16, 0.32, 0.63, 125 and 2.5% in diet. Rats were randomly allocated to 6 groups, each consisting of 10 males and 10 females. No animal died during the administration period and no group showed significant changes in body weight gain. Definite toxicity of josamycin was not noted in hematological and serum biochemical examinations. Histopathological examinations revealed no particular findings related to josamycin administration except cecal enlargement in the 1.25 and 2.5% groups. based on the results of the present study, it was concluded that the MTD of josamycin in 2.5% in diet, because the dietary dose level of 2.5% proved to exert no significant toxicological signs.     

A 13-week subacute oral toxicity study of pectin digests in rats

A 13-week subacute oral toxicity study of pectin digests was performed in both sexes of F344 rats. Water containing 0, 0.15, 0.5, 1.5 or 5% pectin digests was fed to 10 males and 10 females per group to detect its toxicity. No animals died during the administration period. Body weight gain was suppressed in male of the 5% group compared with the 0% group. Serum biochemistry analysis revealed a significant increase in BUN in male group treated with 5% and increases in CRN in male group treated with 1.5% or more. The weight of liver was significantly increased in female groups treated with 1.5% or more. Histopathologically, no treatment-related damage was observed in any dosed groups. Based on these results, the NOEL of pectin digests for both sexes in F344 rats was considered to be 0.5% in drinking water (male 545, female 657 mg/kg/day).     

Pharmacokinetics of fusidic acid after a single dose of a new paediatric suspension

Cell proliferation in response to growth factors is mediated by specific high affinity receptors. Ligand-binding by receptors of the protein tyrosine kinase family results in the stimulation of several intracellular signal transduction pathways. Key signalling enzymes are recruited to the plasma membrane through the formation of stable complexes with activated receptors. These interactions are mediated by the conserved, non-catalytic SH2 domains present in the signalling molecules, which bind with high affinity and specificity to tyrosine-phosphorylated sequences on the receptors. The assembly of enzyme complexes is emerging as a major mechanism of signal transduction and may regulate the pleiotropic effects of growth factors.     

13-week subchronic oral toxicity study of phaffia colour in F344 rats

A 13-week subchronic oral toxicity study of phaffia colour was performed in both sexes of F344 rats by feeding of CRF-1 powder diet containing 0, 0.2, 0.6, 1.7 and 5%. Rats were randomly divided into 5 groups, each consisting of 10 males and 10 females. No animals died during the administration period. There were no treatment-related changes in body weight gain, hematological and blood biochemical examination. No treatment-related histopathological changes were also observed in any dosed groups. These findings indicate that the treatment of 5% phaffia colour in diet for 13 weeks does not cause any toxicological changes in rats.     

Attenuation of gastric lesions by psychological aspects of aggression in rats.

In a study with 80 male albino rats, Ss that fought with each other in response to electric shock showed reduced gastric lesions in comparison with Ss that received the same shocks alone so that fighting behavior did not occur. Also, gastric lesions were similarly reduced in Ss that fought even though they could not physically contact one another because of a barrier between them. In this case, the "protective" effect of fighting derived from the release or display of fighting behavior and did not require physical combat. A 2nd experiment with 48 rats showed that Ss that received shock together but did not engage in fighting behavior showed no reduction of gastric lesions, so that the protective effect of fighting was not an artifact of Ss receiving shock together. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attenuation of alcohol intake by ibogaine in three strains of alcohol-preferring rats

Alcohol-preferring (P), Fawn-Hooded (FH) and alcohol-accepting (AA) rats were injected intraperitoneally (IP) or subcutaneously (SC) with different doses (10, 30, and 60 mg/kg) of Ibogaine or vehicle. In a separate experiment, FH rats were administered intragastrically (IG) with either 60 mg/kg of Ibogaine or vehicle for 5 days. In addition, the effects of Ibogaine on blood alcohol concentrations were measured. Our data show that, contrary to the SC administration of Ibogaine, IP administration of the agent significantly and dose-dependently reduced alcohol intake in these rats. Subchronic IG administration of 60 mg/kg of Ibogaine into FH rats significantly reduced alcohol intake without the development of tolerance or a significant effect on food or water intake. A single IP injection of 60 mg/kg Ibogaine into FH rats did not affect the blood alcohol levels. These results show that Ibogaine when injected IP or IG, but not SC, can significantly reduce alcohol intake without an effect on blood alcohol concentrations or food intake. These findings may suggest the involvement of Ibogaine's metabolite(s) in reducing alcohol intake. Although the neuronal mechanism(s) of action of Ibogaine on the regulation of alcohol intake is not fully understood, it is speculated that Ibogaine or its metabolite(s) exerts its attenuating effect on alcohol intake by modulating neurotransmitters/neuromodulators proposed to be involved in regulation of alcohol consumption.     

Decrease in effects of muscimol on the dorsal root after repeated administration of diazepam in rats

In in situ experiments on spinal rats transected at the C1 level and on non-spinal rats, muscimol (3 mg/kg, i.v.) depolarized the primary afferent fibers and diazepam (3 mg/kg, i.v.) potentiated this effect of muscimol. When diazepam was given for 14 days, the effect of muscimol was significantly reduced in non-spinal rats. These findings suggest that diazepam probably interacts with GABA-ergic mechanisms more closely in supraspinal regions of the rat.     

Endothelial changes following repeated effect of vasoconstrictive substances in vitro

A questionnaire containing 18 vignettes of common clinical educational situations with potentially abusive treatment of medical students and a 10-item attitude assessment about abusive behaviour were administered to the first- and fourth-year medical students at a mid-west US university medical school. The first- and fourth-year groups did not differ significantly on perceived abusiveness of most of the vignettes, although several of the individual vignettes were perceived significantly differently by the two groups. As hypothesized, the fourth-year students had experienced such situations more frequently. Attitudes towards abusive behaviour did not differ between the two groups. The authors contrast teaching interactions perceived as educationally useful and not abusive with those seen as abusive and not useful and offer explanations for the differences observed. Finally, the possible implications of the results for medical education are discussed.     

Fibrochondrogenesis in a 17-week fetus: a case expanding the phenotype

Four derivatives of 6-oxo-3,4,4a,5-tetrahydro-3-hydroxy-2,2-dimethylnaphtho-1,2-pyran (1), known as bactericidal, bacteriostatic, fungicidal, fungistatic agents, were synthesized to investigate the effect of substituents on the aromatic ring.     

Attenuation of alcohol consumption by a novel nontoxic ibogaine analogue (18-methoxycoronaridine) in alcohol-preferring rats

We previously reported that single administration of ibogaine, an indol alkaloid with antiaddictive properties, dose dependently reduced alcohol intake in three strains of alcohol-preferring rats. The present study examined the effect of different doses of a newly developed nontoxic ibogaine analogue, 18-methoxycoronaridine (18-MC), on alcohol intake. Selectively bred alcohol-preferring rats received a single intraperitoneal injection of vehicle or 5, 20 and 40 mg/kg of 18-MC at 9:30 AM, and their consumption of alcohol, water and food was measured for 24 h. Our results demonstrate that a single injection of 18-MC significantly and dose dependently attenuated alcohol consumption and preference and commensurately increased water intake. Only the highest dose of 18-MC significantly decreased food intake. Although the true mechanism of action of 18-MC in suppressing alcohol intake is not yet fully understood, it may, like ibogaine, exert its attenuating effects on alcohol consumption by modulating neurotransmitters believed to be involved in the regulation of alcohol intake.     

Attenuation of diabetic retinopathy by the molecular chaperone-inducer amino acid analogue canavanine in streptozotocin-diabetic rats

The effect of canavanine treatment on the electroretinograms of healthy and streptozotocin-diabetic rats was studied. The characteristic amplitudes of the a-wave, W2 and W3 oscillatory potentials were markedly diminished in the 2-week streptozotocin-diabetic rats compared with those of the control rats. In contrast, the amplitudes of all the responses of the canavanine-pretreated streptozotocin-diabetic rats were practically indistinguishable from those of the control animals. Our results prompt further investigations for the use of amino acid analogues and other inducers of molecular chaperones in easing the chronic consequences of diabetes such as retinopathy.     

Comparative hypocholesterolemic effects of six dietary oils in cholesterol-fed rats after long-term feeding

Rats (8 wk of age) fed a conventional diet were shifted to diets containing 10% Oenothera biennis Linn oil (OBLO, linoleic acid + gamma-linolenic acid) from a wild plant, evening primrose oil (EPO, linoleic acid + gamma-linolenic acid) from a cultivated plant, bio-gamma-linolenic acid oil from mold (BIO, palmitic acid + oleic acid + linoleic acid + gamma-linolenic acid), safflower oil (linoleic acid), palm oil (PLO, palmitic acid + oleic acid + linoleic acid), or soybean oil (linoleic acid + alpha-linolenic acid) with 0.5% cholesterol for 13 wk. Though there were no significant differences in the food intake among the groups, the body weight gain of the OBLO group was significantly lower than that of the other groups except for the BIO and PLO groups, and that of the EPO and SBO groups were the highest among the groups. The liver weight of the OBLO group was significantly lower than that of other groups, and that of the PLO group was the highest among the groups. The serum total cholesterol and very low density lipoprotein (VLDL) + intermediate density lipoprotein (IDL) + low density lipoprotein (LDL) cholesterol concentrations of the OBLO and EPO groups were consistently lower than those in the other groups. However, those of the BIO group were higher than those in the OBLO and EPO groups. The liver cholesterol concentration of the PLO group was the highest among all groups except for the EPO group. The fecal neutral sterol and bile acid extraction of the BIO group tended to increase compared to the other groups. The results of this study demonstrate that OBLO and EPO inhibit the increasing of serum total cholesterol and VLDL + IDL + LDL-cholesterol concentrations in the presence of excess cholesterol in the diet compared with the other dietary oils.     

Neuroprotective effects of NPS 846, a novel N-methyl-D-aspartate receptor antagonist, after closed head trauma in rats

OBJECT: The authors sought to determine whether 3,3-bis (3-fluorophenyl) propylamine (NPS 846), a novel noncompetitive N-methyl-D-aspartate receptor antagonist, alters outcome after closed head trauma in rats. METHODS: The experimental variables were: presence or absence of closed head trauma, treatment with NPS 846 or no treatment, and time at which the rats were killed (24 or 48 hours). The NPS 846 (1 mg/kg) was administered intraperitoneally at 1 and 3 hours after closed head trauma or sham operation. Outcome measures were the neurological severity score (NSS), ischemic tissue volume, hemorrhagic necrosis volume, and specific gravity, water content, and concentrations of calcium, sodium, potassium, and magnesium in brain tissue. The following closed head trauma-induced changes in the injured hemisphere (expressed as the mean +/- the standard deviation) were reversed by NPS 846: decreased specific gravity of 1.035 +/- 0.006 at 24 hours was increased to 1.042 +/- 0.004; the decreased potassium level of 0.583 +/- 0.231 mg/L at 48 hours and at 24 hours was increased to 2.442 +/- 0.860 mg/L; the increased water content of 84.7 +/- 2.6% at 24 hours was decreased to 79.8 +/- 2%; the increased calcium level of 0.592 +/- 0.210 mg/L at 24 hours was decreased to 0.048 +/- 0.029 mg/L; and the increased sodium level of 2.035 +/- 0.649 mg/L was decreased to 0.631 +/- 0.102 mg/L. Administration of NPS 846 also lowered the NSS (improved neurological status) at 48 hours (7 +/- 3) and caused no significant changes in ischemic tissue or hemorrhagic necrosis volumes in the injured hemisphere at 24 or 48 hours. CONCLUSIONS: In this model of closed head trauma, NPS 846 improved neurological outcome, delayed the onset of brain edema, and improved brain tissue ion homeostasis.     

Al（OH）3浮游物对氧化铝生产的影响及应对措施

本文分析了山西铝厂拜尔法种分母液浮游物高的原因、浮游物在蒸发过程中的返溶情况,指出了浮游物对氧化铝产出率及蒸发工序的影响,并提出了解决办法。