Liver fibrosis in guinea pigs experimentally induced by combined copper and aflatoxin application

Aflatoxin B1 alone (0.05 mg resp. 0.037 mg/kg/d), copper alone (6.6 mg/kg/d or 200 mg/l drinking water) or a combination of both was administrated orally for 6 months to young guinea pigs from the first/second day of life. In the copper group there were no pathomorphological changes. For the aflatoxin B1 group liver damage was established. In the combined group liver injury was more frequent and more severe compared to the aflatoxin B1 group. Compared with the copper group biliary copper excretion was diminished and the kidney copper content was elevated in the Afl. B1 + Cu group. While copper concentrations in bile and kidney correlated with other parameters, notably the pathological lesions of the liver, no such correlation was found for liver copper. Therefore in this experiment the degree of Cu accumulation was not decisive for the liver lesions. The livers' capacity for excreting Cu by bile seems to be a much more important factor. Histologically only the livers of the combined group exhibited degeneration, atrophy and steatosis of liver cells, and a fibrosis more or less pronounced. For childhood cirrhosis (ICC and ICT), a combined etiology--a liver damaging agent plus elevated alimentary copper--is a plausible hypothesis.     

Improvement in inner ear blood flow by nitric oxide following experimentally induced cochlear thrombosis in anesthetized guinea pigs

The nitric oxide (NO) donor sodium nitropruside (SNP) applied to the round window membrane has recently been found to increase cochlear blood flow (CoBF) in normal guinea pigs and in normal and presbyacusic mice. This study examined the effect of topical applications of SNP on experimentally impaired CoBF in anesthetized guinea pigs. Small (3 microliters) portions of 3% SNP were applied to the round window niche of both normal and thrombosed cochleas. Local vascular impairment was produced by ferromagnetic thrombosis of cochlear blood vessels and the microcirculation measured using laser Doppler flowmetry. Ferromagnetic thrombosis resulted in a mean decrease of CoBF to 52% of baseline. There was a clear improvement in mean CoBF to 84% of baseline by the topical application of SNP that depended on the degree of ischemic damage produced. Under neuroleptanalgesia and ketamine-xylazine anesthesia, significant increases in CoBF were measured in normal ears as well as in the thrombosed ones. However, several SNP applications were needed to improve the impaired CoBF, while a single portion was sufficient in the normal cochlea to cause a drastic increase in mean CoBF to 234% of baseline. In urethane-anesthetized animals, no flow increase was found despite repeated drug administration. Careful evaluation of the laser Doppler signals was necessary to accurately determine the concentrations of the moving blood cells and their mean velocities.     

Estimation of the mutagenic potential of the trematode Opisthorchis felineus in experimentally infected guinea pigs

We studied the mutagenic potential of the trematode Opisthorchis felineus in experimentally infected guinea pigs by chromosome analysis. The investigation was conducted on 30 treated (experimentally infected) and 20 normal (uninfected) guinea pigs (Cavia porcellus). A sample of living metacercariae of O. felineus was obtained from the muscle of naturally infected crucian carp captured in the Tom River, and 1 ml suspension containing approximately 50 metacercariae in 0.9% NaCl solution was individually given p.o. to guinea pigs that were used as treated specimens, whereas normal guinea pigs from the same stock were given 1 ml 0.9% NaCl solution per individual to serve as controls. The treated and control animals were killed by CO2 asphyxiation and decapitation at 7, 15, 30, 45, and 120 days after contamination. The smears of bone marrow cells for chromosome analysis were prepared by a standard method. Statistical analysis of the data was done using Student's t-test. We found that experimental infection of guinea pigs with O. felineus induced significantly high frequencies of hypoploid cells and, at the 120th day p.i., led to a considerable incidence of chromatid breaks and polyploidy in bone marrow cells.     

Histopathological lesions in lead intoxicated dogs

Epidermoid cysts (ECs) are rare developmental lesions occurring anywhere along the central nervous system. Usually affecting adult patients, the occurrence of supratentorial dorsal cistern ECs has been reported in only 1 certain case of pediatric age. An additional pediatric case is presented. An 11-year-old boy had an 8-year history of petit mal seizures. Neurologic examination on admission was negative. T1-weighted magnetic resonance images demonstrated homogenous, hypointense, intradural, extracerebral, right frontal, precentral, parasagittal mass with relatively high signal intensity on T2-weighted images. The lesion was completely removed using a microneurosurgical technique with special care taken with regard to the adjacent nervous and vascular structures. Histologically, an EC was diagnosed. The patient had no recurrence for 2 years and seizures were significantly reduced. This case suggests the need to include ECs in the differential diagnosis of intradural supratentorial extracerebral lesions in childhood.     

Suppression of somatotroph function induced by growth hormone treatment in neonatal pigs

The Her-2/neu protooncogene is associated with malignant transformation and aggressive disease. Because of its overexpression in tumor cells and because it has been shown to be immunogenic, this protein represents an excellent target for T-cell immunotherapy. By identifying potential HLA-A2.1-binding peptides from the Her-2/neu sequence, peptides were selected as candidate T-cell epitopes. The immunogenicity of each peptide was evaluated by priming double transgenic mice expressing both the human (hu) CD8 and HLA-A2.1 molecules with synthetic peptides corresponding to these sequences. Because of the lack of interaction between murine CD8 and HLA-A2.1, expression of huCD8 on murine cells facilitates recognition of HLA molecules on human tumor cell lines. This led to the identification of two peptides that elicit an A2-restricted CTL response, one of which has not been previously identified. Both peptide-specific CTL populations were able to specifically lyse A2.1 and Her-2/neu expressing human tumor cells originating from a variety of tissues, demonstrating the utility of this murine model in identifying peptides presented by human cells. However, several Her-2/neu peptides previously reported to be immunogenic for human CTL were found not to be immunogenic in transgenic mice. The basis for these discrepancies is discussed.     

Endometritis in cattle experimentally induced by Chlamydia psittaci

On the day of estrus, eight virgin heifers received intrauterine inoculations of yolk sac propagated Chlamydia psittaci strain BovEnd 11/88 isolated from the uterus of a slaughter cow. All heifers developed purulent vaginal discharge which persisted for 3 to 7 weeks. Chlamydiae or chlamydial antigen were detected in vaginal and uterine discharges of infected animals by culture or Capture ELISA, while other bacterial pathogens were not found. In sera of the chlamydia-infected heifers marked increases in antibody titres against the chlamydial genus-specific LPS-antigen were found by ELISA and complement fixation test. Six heifers were artificially inseminated in 5 successive cycles beginning at the first estrus following intrauterine inoculation. In two of the infected heifers spontaneous healing of endometritis occurred after 5 estrus cycles. Only these animals conceived after the 5th breeding, whereas in the remaining four animals a chlamydia-associated chronic endometritis was recognized as the cause of infertility in the 19th and 26th week p.i. at slaughter. Two control heifers which remained clinically normal after intrauterine exposure to sterile yolk sac-suspensions conceived at the 1st and 2nd service, respectively.     

Hypoxic protection in paraquat poisoning

Ingestion or injection of the herbicide paraquat (1,1'-dimethyl-4,4'-dipyridylium dichloride) has caused more than 120 deaths in humans. Most have been due to respiratory failure caused by pulmonary edema, hemorrhage, and atelectasis, or subsequent pulmonary fibrosis. Paraquat is concentrated in lung tissue and is believed to cause superoxide radical formation in the presence of oxygen and suitable electron donors. Exposure to increased concentrations of oxygen has been reported to accelerate the toxicity of paraquat. The therapeutic efficacy of a reduced oxygen environment was investigated by exposing paraquat-poisoned mice to 10% oxygen after stepwise drops from 14% oxygen. Sixty-one mice were given intraperitoneal injections of 27 mg. per kg. of paraquat. The 25 mice in hypoxia for 7 days had a 32% mortality rate versus a 78% mortality rate for the remainder of the mice in room air, p less than 0.01. After a dose of 20 mg. per kg. of paraquat administered intraperitoneally, 24 mice in hypoxia had a 25% mortality rate versus 51% for 35 animals in room air. Brief exposures of the hypoxic group to "normoxia" (room air) led to pulmonary edema and death. The continuous exposure of paraquat-poisoned animals to hypoxic environments was protective. This approach may be useful in other oxidant lung injuries.     

Protective role of thyroxine in methylparathion intoxicated chick embryos

Graded activity of the DPP signaling pathway is critical for specification of dorsal embryonic cell fates in Drosophila. We present evidence that a second BMP ligand, SCW, potentiates DPP activity. Using dominant-negative forms of the type I receptors SAX and TKV, we demonstrate that SAX mediates the SCW signal, while TKV is required for both DPP and SCW activity. We find that while DPP/TKV signaling is obligatorily required, SCW/SAX activity is necessary but not sufficient for dorsal patterning. SAX and TKV act synergistically, suggesting a mechanism for integration of the SCW and DPP signals. Further, we show that the extracellular protein SOG can antagonize SCW, thus limiting its ability to augment DPP signaling in a graded manner.     

Middle ear overpressure treatment of endolymphatic hydrops in guinea pigs

Changes in sleep state and night-time body temperature were studied in 13 healthy young men. Temperature data showed serial dependence that was removed when considering three main segments of the thermogram: an initial rapid drop between 60 and 140 min after lights off, followed by a slower decrease to the thermal minimum and a final temperature increase until waking. The first segment was fitted by a two-term function, while the other two segments were fitted by linear regression. Temperature data obtained after fitting these models were stationary and used to calculate the fast Fourier transformation and the cross-correlation functions between the hypnogram and the thermogram of each subject. Attaining stationarity has unmasked short oscillations during sleep and some temperature series showed the presence of ultradian oscillations with a period of 90-100 min. Significant cross-correlations between sleep stages and body temperature were found, and the parameters of the two-term function fitted to the first temperature drop were related to the sign of the correlation and to that time series (sleep or temperature) which preceded the other during the night.     

Current directions in research on understanding and preventing intoxicated aggression

The present paper describes promising research directions that emerged from a recent international conference on intoxication and aggression and from the scientific literature generally. In this overview, intoxicated aggression is seen as arising from an interactional process involving multiple contributing factors or causes. This model helps to define research directions that can further understanding and prevention. First, the societal/cultural framing of intoxication and aggression exerts a powerful influence on drinking behaviour and needs to be better understood. Another important area for research is the moderating role on alcohol-related aggression of personal factors such as predisposition to aggression and individual differences in expectations about alcohol and aggression. Research on the role of basic pharmacological effects of alcohol in increasing the likelihood of aggressive behaviour is also a critical aspect of understanding intoxicated aggression. Drinking contexts and environments play a considerable role in the relationship between intoxication and aggressive behaviour and need to be better understood. Another critical direction for future research is the study of intoxicated aggression as a process involving the interaction of the person, the situation and the effects of alcohol in natural and experimental settings. Finally, the paper highlights promising directions for research on interventions to prevent intoxicated aggression and violence.     

Transport of paraquat by isolated renal proximal tubular segments from rabbits

In order to evaluate somatostatin (SRIH) secretion in uremia, plasma SRIH concentrations were determined in basal conditions and after an oral glucose tolerance test (OGTT) in 14 non-dialysed patients with chronic renal failure (CRF), seven of whom had normal glucose tolerance (NGT) and seven impaired glucose tolerance (IGT). Plasma insulin, C-peptide and glucagon and blood glucose concentrations were also evaluated. The results were compared with those obtained in a group of age- and sex-matched normal subjects. In CRF patients, plasma SRIH fasting values (8.6 +/- 0.6 and 7.8 +/- 0.6 pmol/L in NGT and IGT patients, respectively) were comparable to those recorded in controls (7.7 +/- 0.5 pmol/L). SRIH response to OGTT, evaluated as area under curves (AUC) above basal, was similar in both groups of CRF patients (412.9 +/- 84.5 and 415.6 +/- 51.9 pmol/L per min), and significantly lower than in controls (660.1 +/- 58.5 pmol/L per min). Data indicate that chronic uremia induces a loss of SRIH secretory cell responsiveness to glucose. A possible effect of impaired SRIH secretion on glucose metabolism in CRF is discussed.     

Chicken egg yolk antibodies against F18ab fimbriae of Escherichia coli inhibit shedding of F18 positive E. coli by experimentally infected pigs

F18ab and F18ac are antigenic variants of a colonizing fimbria commonly found on E. coli associated with postweaning diarrhea and edema disease in pigs. Chicken F18ab antibodies were obtained by immunising hens with purified F18ab fimbriae. For their in vitro characterisation antibodies were isolated from diluted egg yolks by ammonium sulfate precipitation. In vitro adhesion tests demonstrated that the chicken F18ab antibodies inhibited attachment of F18ab positive E. coli bacteria to the intestinal mucosa. Just weaned piglets were experimentally infected with an F18ab positive edema disease strain of E. coli, or with an F18ac positive postweaning diarrhea E. coli strain. The animals were infected on the second day of a period during which chicken F18ab antibodies were added to their feed. During the same period, pigs of the control group received commercial eggs in which no F18 antibodies were detected. In both experimental infections the excretion of the F18 positive strain was reduced in pigs that received the F18ab antibodies as compared to the control animals. The F18ab antibodies diminished the cases of diarrhea and death in animals infected with F18ac positive E. coli.     

Polyamines and paraquat toxicity in Arabidopsis thaliana

The morbidly obese have a disproportionately greater risk of hypertension, diabetes, and coronary artery disease than their lean or less seriously obese counterparts. Roux-en-Y gastric bypass surgery has been found to be highly effective in inducing, and sustaining, weight loss in individuals with morbid obesity. The purpose of the present study was to examine the effects of weight loss with Roux-en-Y gastric bypass surgery (GBP) on blood pressure, fasting blood glucose, and the lipid/lipoprotein status of 61 morbidly obese women and 21 men. Anthropometric and blood pressure assessments and blood samples for glucose and lipid/lipoprotein analyses were obtained before surgery and at 6 to 12 months postoperatively. By this time, morbidly obese (MO) males and females had lost 33% and 30% of their initial body weight, respectively, along with significant reductions in fasting blood glucose (p < 0.01) and systemic blood pressure (p < 0.05). Weight loss with GBP was also associated with significant reductions in the apoprotein B-containing lipoproteins and the triglyceride and cholesterol composition of these particles. There was a trend (p < 0.10) toward increased serum levels of high density lipoprotein (HDL)-cholesterol following GBP, and significant (p < 0.05) improvement in HDL subfraction distribution and composition. These findings demonstrate the effectiveness of GBP in inducing metabolic changes in the MO population, which may reduce the risk of coronary artery disease, diabetes, and hypertension.     

Transport of paraquat by a renal epithelial cell line, MDCK

Transport of paraquat (PQ), a herbicidal cation, was previously investigated in a proximal (LLC-PK1), renal epithelial cell line using permeable collagen-coated filters. PQ was actively transported from the basolateral side via a cation transport system by the LLC-PK1 cells. In the present study, the transport of PQ was investigated in a distal renal epithelial cell line, MDCK. PQ was predominantly transported from the basolateral to apical (B to A) side. The basolateral transport of PQ in MDCK cells was not saturable with increasing concentrations and not energy dependent. The flux and uptake of PQ was much lower in the MDCK than LLC-PK1 cells. It is concluded that MDCK, a distal renal tubular cell line, does not have an active transport system for PQ.     

Metabolic alterations in hepatocytes promoted by the herbicides paraquat, dinoseb and 2,4-D

The cytotoxic effects of the herbicides paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride), dinoseb (2-sec-butyl-4,6-dinitrophenol) and 2,4-D (2,4-dichlorophenoxyacetic acid) on freshly isolated rat hepatocytes were investigated. Paraquat and 2,4-D (1-10 mM) caused a dose and time dependent cell death accompanied by depletion of intracellular glutathione (GSH) and mirroring increase of oxidized glutathione (GSSG). Dinoseb, the most effective cytotoxic compound under study (used in concentrations 1000 fold lower than paraquat and 2,4-D), exhibited moderate effects upon the level of GSH and GSSG. These limited effects are at variance with significant effects upon the adenine and pyridine nucleotide contents. ATP and NADH levels are rapidly depleted by herbicide metabolism. This depletion is observed in the millimolar range for paraquat and 2,4-D and in the micromolar range for dinoseb. 2,4-D completely depletes cellular ATP, with subsequent cell death, as detected by LDH leakage. Paraquat rapidly depletes NADH, according to the redox cycling of the herbicide metabolism. The most effective compound is dinoseb since it exerts similar effects as described for paraquat and 2,4-D at concentrations 1000 fold lower. Simultaneously with NADH and ATP depletion, the levels of ADP, AMP and NAD+ increase in hepatocytes incubated in the presence of the herbicides. In contrast to NADH, the time course and extent of ATP depletion and fall in energy charge correlate reasonably with the time of onset and rate of cell death. It is concluded that the herbicides, paraquat and 2,4-D are hepatotoxic and initiate the process of cell death by decreasing cellular GSH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Short-circuiting of threat by experimentally altering cognitive appraisal.

Previous research has shown that film-induced threat could be reduced by appropriately designed narratives or sound tracks based on ego-defense theory. This study demonstrated that such a narrative, based on the concepts of denial and reaction formation, is even more effective if presented as an introductory statement before the film begins. It significantly reduced both physiological and self-report evidence of stress reaction. Moreover, the amount of stress reaction and the capacity of the narrative to reduce stress reaction depended upon personality. Ss high in disposition to deny threat as measured by various MMPI scales did indeed deny affective disturbance more than low deniers, while showing greater autonomic evidence of stress reaction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enforcement of drunken driving laws in cases involving injured intoxicated drivers

The uptake of vitamin D3 by the liver cells and its hydroxylation in the hepatocytes of rats at experimental diabetes has been studied. It is proved that in this pathology the disturbances of vitamin D3 exchange in the rat liver take place. It is concluded that the lowering of the level of absorption of vitamin D3 by hepatocytes and its transportation to these cells from reticulocytes as well as the inhibition of vitamin D3-25-hydroxylase liver systems can be the most probable cause of these disturbances.     

The frequency of unsuspected minor illness or injury in intoxicated patients

OBJECTIVE: To determine the frequency of unsuspected minor illness or injury in a group of patients frequently seen in the ED for acute intoxication. METHODS: The medical records of the 20 patients seen most frequently in the ED for acute intoxication in 1993 were reviewed for the number of ED visits for intoxication, the number of associated documented episodes of minor trauma or illness, the extent of ED workup of discovered illness or injury, and patient disposition from the ED. RESULTS: The 20 study patients were evaluated in the ED 1,858 times in 1993 for acute intoxication, a mean of 92.5 visits/patient (+/- 26.6). The most frequent injury was minor trauma above the neck, occurring a mean of 9 times (+/- 3.6) in each of the study patients during 1993. Evaluation included repeated neurologic examinations and frequent radiography of the cervical spine (n = 80), skull (n = 5), facial bones (n = 6), and mandible (n = 5). A limited number of head CT scans also were done (n = 8). The most frequent minor illnesses were gastritis (n = 7), managed with hydration, and mild hypothermia (n = 6), managed with passive rewarming. CONCLUSIONS: The incidence of unsuspected minor illness or injury in this patient group was substantial. While most unsuspected medical problems had little clinical significance, some were potentially dangerous, and some necessitated hospitalization (e.g., hypothermia, hematemesis, and respiratory depression).