Weanling rats, divided into 3 groups were maintained for 15 days on a diet containing either 5 per cent casein fed ad libitum (Group 1), 20 per cent casein pair-fed to Group 1 (Group 2), or 20 per cent casein fed ad libitum (Group 3). Animals were injected with either 0.9 percent saline or phenobarbital. Phenobarbital increased microsomal protein, cytochrome P-450, and phosphatidylcholine in all dietary groups; however, in all groups the increase in P-450 was greater than for phosphatidylcholine. Protein deficiency (Groups 1 vs. 2) decreased P-450 and microsomal protein but had no effect on phosphatidylcholine contents. The fraction of phosphatidylcholine-associated sites relative to the total sites was greater during protein deficiency and was in agreement with a greater Δ A_max per nmole P-450 for ethylmorphine. Phenobarbital induction decreases the proposed fraction of phosphatidylcholine-associated P-450 sites relative to the total P-450 sites and results in a decrease in the Δ A_max per nmole P-450 for ethylmorphine. Phenobarbital increased the Δ A_max per mg of microsomal protein for aniline, which paralleled the increase in total P-450 indicating that the Type II site is independent of any association Of cytochrome P-450 with phosphatidylcholine. The V_max per mg of microsomal protein was 64-66 per cent lower in the protein deficient group. Equivalent reductions of cytochrome P-450 and activities of cytochrome P-450 and c reductases were observed. Phenobarbital induction increased enzyme activities (V_max per mg of microsomal protein) in all groups with greater percentage increases in the protein deficient animals. The data suggested that phosphatidylcholine and cytochrome P-450 play important roles in the kinetics of metabolism and binding determined after protein deficiency and/or phenobarbital induction. The dietary study was repeated using 3-methylcholanthrene as inducer. 3-methylcholanthrene produced results similar to phenobarbital in most cases; however, this inducer illicits the production of a form of P-450 termed P-448. Induction of the various parameters appears more dependent on P-448 production than phosphatidylcholine-P-450 interactions. In contrast to phenobarbital treatment, 3-methylcholanthrene treatment does not increase the specific activity for ethylmorphine metabolism and the activity of cytochrome P-450 and c reductase. Other studies indicated the K_m and V_max for ethylmorphine N-demethylation is dependent on the substrate concentration range used to determine them. The oxidase system appears to have two different activities, one involving low substrate concentrations; the other, high substrate concentrations. During induction by both phenobarbital and 3-methylcholanthrene, there is a depression in both K_m and V_max during the first few hours after injection of the inducer which corresponds to the time period when the inducer is in the greatest concentration in the cell. After this initial depression, there was an increase in both K_m and V_max , indicating induction had taken place. / Ph. D.

Many lipophilic pesticides are known to be transferred to offspring via the mother's milk. The present study was conducted to determine how much endrin was transferred from endrin resistant and susceptible dams to their suckling pups and to further characterize the effects that endrin may have on the hepatic mixed function oxidase (MFO) system in the pups. Dosing of the dams with endrin began one day after birth with either (l) oral doses of endrin in corn oil or (2) a mixture of endrin in ground feed. The total amount of endrin in the pup was determined by gas chromatography. MFO activity was determined in 2-1/2 week old pups and for adult animals using maximal activities for the demethylation of ethylmorphine and hydroxylation of aniline. No difference in the amount of endrin present in the pups was observed between strains provided both received equal amounts of endrin. MFO activity for endrin dosed mature animals and for 2-1/2 week old pups from endrin dosed dams exhibited a significant decrease from control activities. There was no difference in MFO activities between age groups. A significantly higher ethylmorphine demethylase activity was observed in comparing the resistant to the susceptible strain but there was no significant difference in aniline hydroxylase activity. / Master of Science

[Truncated abstract] The hepatitis C virus (HCV) is a significant human pathogen for which there are limited post-infection therapies and no effective vaccine. Research into HCV is notoriously difficult due to the absence of suitable in vitro and in vivo model systems with which to study the virus. Furthermore, our understanding of HCV host interaction is limited and the mechanisms by which it subverts the host immune system remains largely unknown. Due to the difficult nature associated with studying HCV, the work presented in this thesis was designed to addresses a broad range of issues relating to both clinical and molecular aspects of HCV. Chronic HCV infection is often associated with the development of cirrhosis, end stage liver disease and hepatocellular carcinoma. To date, histological examination of liver biopsies provides the only approved method with which to assess the level of liver damage. While clinically informative, liver biopsies are highly invasive and may be contraindicative for patients such as haemophiliacs. Cytokine specific ELISPOT assays were used to determine whether cytokine secretion from PBMCs isolated from chronically infected HCV patients could be used as a non-invasive method to assess liver damage. Chronically infected patients with sever liver fibrosis demonstrated a significantly reduced ability to produce IFN-γ in response to HCV Core, but not other unrelated antigens, indicating that decreased IFN-γ secretion by PBMCs in response to HCV antigen could be used as a non-invasive marker for the development of liver fibrosis ... A series of HCV expression vectors covering the full length of the HCV ORF were constructed and their expression extensively tested before being used to assess the ability of HCV proteins to interact with Jak/STAT mediated Type I IFN signalling. Additionally, an alternative set of HCV IRES-EGFP reporter vectors were developed and used to access HCV IRES functionality between different eukaryotic cell lines. HCV Core protein expressed alone or in concert with E1-P7 and non-structural protein NS5B were shown to significantly reduce Jak/STAT mediated IFN expression. While the influence of HCV Core on Type I IFN signalling is consistent with previous reports in the literature, these results identify a new role for NS5B as a possible candidate protein involved in inhibition of Type I IFN signalling.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

No description available.

A prospective study of two combined oral contraceptives was conducted in the Sudan. No pregnancies occurred. Overall incidence of side effects was low. Headache was most frequently reported. Elevations were observed for weight, systolic and diastolic blood pressures, and SGOT and SGPT values while a decrease was seen for hemoglobin levels. Menstrual irregularities were not a problem for the users. Total 6-month use discontinuation rates were low for both pill groups.

Eighteen healthy dogs were divided into three equal groups. All dogs were evaluated at the beginning of the experiment with complete physical examination, complete blood count, serum alanine aminotransferase, serum alkaline phosphatase, serum bilirubin, serum albumin, sulfobromophthalein. excretion test, ammonia tolerance test, glucagon response test, portal and intraparenchymal pressures, operative mesenteric portography, and histologic assessment of hepatic tissue. The left hepatic vein was ligated in the chronic and acute dogs. The dogs had a ligature placed loosely around the left hepatic vein. Acute and control dogs were evaluated 24 hours postoperatively with the hematologic and biochemical tests listed above. Acute dogs were evaluated with portal and intraparenchymal pressure, operative mesenteric portography and histologic evaluation of hepatic tissue at 48 hours postoperatively. Chronic and control dogs were evaluated at 4 weeks postoperatively with all of the tests listed above. The results of all tests performed supported a transient hepatic congestion which resolved bv the fourth postoperative week. No longstanding effect on hepatic function was found. The conclusion of this experiment was that, in normal dogs, left hepatic vein ligation does not cause severe or permanent liver damage. These findings support a clinical trial of this procedure in patients with patent ductus venosus. / Master of Science

This diploma thesis deals with home parenteral nutrition in the day and night regime and its effect on patients. Parenteral nutrition is usually administered at night so that patients can do normal daily activities and so that nutrition administered in this way has the least impact on their lives. Parenteral nutrition is not a physiological route of nutrient administration and it is not natural for the human body to process nutrients at night. The first part of the theoretical work presents parenteral nutrition and its composition, indications, contraindications and complications. The next part of the thesis describes home parenteral nutrition and its organisation which is necessary for this form of nutritional support to be implemented. It is necessary to monitor many laboratory values on parenteral nutrition, the theoretical part specifically mentions cholesterol, triacylglycerols, glycemia or liver function tests. One of the important parts is the chapter about circadian rhythms, hormones and metabolic changes in energy intake at night. Qualitative research was chosen for this work, which involved 17 patients on home parenteral nutrition. These patients were getting their nutrition during the night. Their laboratory values such as liver function tests, glycaemia and blood fats was evaluated and...

Devido a controvérsias sobre a freqüência, diagnóstico e possibilidade de progressão para doença crônica da degeneração gordurosa do fígado em portadores de obesidade mórbida, planejou-se uma investigação retrospectiva em pacientes candidatos à cirurgia bariátrica. Foram analisados 60 indivíduos com indicação de gastroplastia com derivação intestinal em Y de Roux. Os pacientes foram submetidos a questionário clínico, provas bioquímicas e posteriormente, à biópsia hepática intraoperatória. A freqüência de EHNA e esteatose hepática foi elevada, e detectou-se 5% de cirrose. Na análise univariada houve correlação de diversos testes bioquímicos com as enzimas hepáticas. Na análise multivariada a albumina foi a variável determinante; apesar de seu debilitado valor preditivo. Nestas condições, apenas a avaliação histológica configura-se como critério definitivo para diagnóstico e acompanhamento desta população / Because of controversies about frequency, diagnosis and possibility of progression toward chronic disease of fatty degeneration of the liver in morbidly obese patients, a retrospective study was done in patients who underwent bariatric surgery. Sixty individuals with indication for gastroplasty with Roux-en-Y jejunal bypass were enrolled. They were submitted to clinical questionnaire, biochemistry tests and subsequently, intraoperative liver biopsy. Frequency of NASH and steatosis was high, and 5.0% suffered from cirrhosis. In univariate analysis there was correlation between various biochemical measurements and liver enzymes. In multivariate analysis only serum albumin was a determinant variable, with low predictive value. The histological grading system remains the definitive criterion for diagnosis and follow-up of this population

Devido a controvérsias sobre a freqüência, diagnóstico e possibilidade de progressão para doença crônica da degeneração gordurosa do fígado em portadores de obesidade mórbida, planejou-se uma investigação retrospectiva em pacientes candidatos à cirurgia bariátrica. Foram analisados 60 indivíduos com indicação de gastroplastia com derivação intestinal em Y de Roux. Os pacientes foram submetidos a questionário clínico, provas bioquímicas e posteriormente, à biópsia hepática intraoperatória. A freqüência de EHNA e esteatose hepática foi elevada, e detectou-se 5% de cirrose. Na análise univariada houve correlação de diversos testes bioquímicos com as enzimas hepáticas. Na análise multivariada a albumina foi a variável determinante; apesar de seu debilitado valor preditivo. Nestas condições, apenas a avaliação histológica configura-se como critério definitivo para diagnóstico e acompanhamento desta população / Because of controversies about frequency, diagnosis and possibility of progression toward chronic disease of fatty degeneration of the liver in morbidly obese patients, a retrospective study was done in patients who underwent bariatric surgery. Sixty individuals with indication for gastroplasty with Roux-en-Y jejunal bypass were enrolled. They were submitted to clinical questionnaire, biochemistry tests and subsequently, intraoperative liver biopsy. Frequency of NASH and steatosis was high, and 5.0% suffered from cirrhosis. In univariate analysis there was correlation between various biochemical measurements and liver enzymes. In multivariate analysis only serum albumin was a determinant variable, with low predictive value. The histological grading system remains the definitive criterion for diagnosis and follow-up of this population