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Plasma carriers influence the uptake of cholecalciferol by human hepatoma-derived cells.

The uptake of [3H]cholecalciferol by the human hepatoma-derived cell lines Hep G2 and Hep 3B was examined as a function of the sterol's presentation on various plasma proteins at their native concentrations. Control cultures utilized devitalized cells cross-linked with glutaraldehyde and estimated nonspecific sterol adherence to cells. With both cell lines, neither albumin nor plasma vitamin D binding protein permitted cholecalciferol uptake above control values. With Hep G2 cells, only low-density lipoprotein presentation of the sterol resulted in significant cellular uptake that had features resembling a receptor-mediated process. With Hep 3B, only high-density lipoprotein presentation of the sterol resulted in a significant uptake that was cell, carrier, and time dependent. These results support the hypothesis that lipoprotein carriers could account for the efficient hepatic accumulation of cholecalciferol in vivo.

Carcinoma, Hepatocellular↗

Intrastriatal administration of human immunodeficiency virus-1 glycoprotein 120 reduces glial cell-line derived neurotrophic factor levels and causes apoptosis in the substantia nigra.

Uninfected neurons of the substantia nigra (SN) degenerate in human immunodeficiency virus (HIV)-positive patients through an unknown etiology. The HIV envelope glycoprotein 120 (gp120) causes apoptotic neuronal cell death in the rodent striatum, but its primary neurotoxic mechanism is still under investigation. Previous studies have shown that gp120 causes neurotoxicity in the rat striatum by reducing brain-derived neurotrophic factor (BDNF). Because glial cell line-derived neurotrophic factor (GDNF) and BDNF are neurotrophic factors crucial for the survival of dopaminergic neurons of the SN, we investigated whether gp120 reduces GDNF and BDNF levels concomitantly to induce apoptosis. Rats received a microinjection of gp120 or vehicle into the striatum and were sacrificed at various time intervals. GDNF but not BDNF immunoreactivity was decreased in the SN by 4 days in gp120-treated rats. In these animals, a significant increase in the number of caspase-3- positive neurons, both tyrosine hydroxylase (TH)-positive and -negative, was observed. Analysis of TH immunoreactivity revealed fewer TH-positive neurons and fibers in a medial and lateral portion of cell group A9 of the SN, an area that projects to the striatum, suggesting that gp120 induces retrograde degeneration of nigrostriatal neurons. We propose that dysfunction of the nigrostriatal dopaminergic system associated with HIV may be caused by a reduction of neurotrophic factor expression by gp120.

AIDS Dementia Complex↗

Field trial of the efficacy of a simplified and standard metrifonate treatments of Schistosoma haematobium.

In a randomized double-blind study, the percentage egg reduction and cure rate after the standard schedule of metrifonate treatment of Schistosoma haematobium (3 doses of 7.5 mg.kg-1 at two-weekly intervals; A) and an abbreviated regimen (3 doses of 5 mg.kg-1 in one day; B) were compared in five villages in Somalia. 300 patients who were excreting 20 or more eggs of S. haematobium in 10 ml urine were recruited. The patients were classified according to their home villages and were then, randomly allocated to treatment A or B. They had similar ages, weights and egg output. Each patient received 3 doses of metrifonate and 2 doses of identical appearing placebo. Group A received metrifonate on the 1st, 4th and 5th dosing occasions and placebo on the 2nd and 3rd times. Group B received metrifonate on the 1st, 2nd and 3rd dosing times and placebo on the 4th and 5th times. Two hundred and one patients were followed up from 1 to 6 months. The remaining 99 (33%) patients either did not complete treatment or were lost during follow up. Egg reduction in the groups 1, 2, 3 and 6 months after treatment were 97, 97, 95 and 93% in Group A and 96, 96, 94 and 92% in Group B (NS). Corresponding cure rates for Group A were 52, 50, 48 and 44%, and in Group B they were 47, 48, 43 and 40% (NS). Seven patients from Group A and 9 from Group B complained of minor side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Poor patient compliance reduces the efficacy of metrifonate treatment of Schistosoma haematobium in Somalia.

The degree of compliance during metrifonate therapy of Schistosoma haematobium infection has been evaluated together with its impact on drug efficacy in two rural villages in Somalia. Drug treatment was offered to all subjects with S. haematobium infection. 243 subjects were screened for the presence of eggs in the urine using a sensitive Nucleopore filtration method and 211 were positive. All infected patients were put on a treatment schedule of 3 doses of metrifonate 7.5 mg/kg at fortnightly intervals. Drug efficacy was evaluated 6, 12 and 32 weeks after treatment. Only 48% of the patients took all 3 doses, 15% took 2 doses and 37% only took 1 dose. The cure rate was maximal in Week 6 at 60, 44 and 30% in those who took 3, 2 and 1 dose, respectively. Corresponding egg reduction rates were 98, 90 and 84%, respectively. Drug efficacy throughout the follow up period was much greater in patients who complied with all 3 doses. It is unlikely that the goal of mass treatment programmes for endemic S. haematobium in villages in Africa will be realized due to poor compliance with the current dosage schedule for metrifonate of 3 doses of 7.5 mg/kg at fortnightly intervals.

Adolescent↗

A simplified dosage schedule of metrifonate in the treatment of Schistosoma haematobium infection in Somalia.

We have carried out an open clinical study in Somalia to evaluate the efficacy and safety of a simplified dosage schedule of metrifonate in the treatment of Schistosoma haematobium infection. The doses used were: I. 10 mg X kg-1 once daily for 3 days II. 5 mg X kg-1 thrice daily for one day III. 7.5 mg X kg-1 thrice daily for one day. We screened a total of 550 subjects in four villages for egg excretion in urine, and selected patients with more than 200 eggs per 10 ml of urine. In the initial phase of the study eight patients were assigned to each of the three dose schedules. In an extended study 38 additional patients were treated with regimen II which gave the best outcome in the initial study. Dosage Schedules I and III turned out to be toxic, and none of the patients was treated with all three doses. Adverse effects, such as abdominal colic, nausea, salivation, dizziness, and headache, were seen in almost all the patients in those two groups. Two patients from Group I reported that they fainted within 2 h after the second dose. None of the patients in Group II reported adverse effects. After 4-6 weeks follow-up, egg reduction was 96-100% for Groups I and II and the cure rate was around 60%. This study has shown that a shorter course of treatment with metrifonate might be equally effective and safer than the recommended dosage schedule with three doses of 7.5-10 mg X kg-1 fortnightly.

Colic↗

Heterotopic chondrogenesis and osteogenesis induced by transformed cells: use of nude mice as a model system.

A subline of HeLa cells was shown to induce cartilage and bone formation in congenitally athymic (nude) mice when injected intramuscularly. The chondrogenesis and osteogenesis observed was similar to that found when other inducing epithelia are injected intramuscularly into cortisone-treated mice. A tumorigenic SV40 T antigen-positive human-mouse somatic cell hybrid with human chromosomes C7 and C6 did not induce cartilage or bone formation under similar conditions. The nude mouse may thus provide a system in which to investigate experimental host-cell differentiation without the complications of immunosuppression.

Animals↗

A comparison of the Nigerian indigenous fowl with White Rock under conditions of disease and nutritional stress.

Equal numbers of day old White Rock and Nigerian indigenous male chicks were reared to 10 weeks of age under 4 variables consisting of 2 dietary regimes and 2 regimes of immunity (natural versus vaccinal) to Newcastle disease challenge. Although White Rock grew significantly faster, ate more food and tended to be more efficient in feed utilisation than the indigenous chicks, the mortality of the latter was significantly lower. Growth rate and feed intake were significantly greater, feed efficiency better and prechallenge mortality lower in birds fed on the higher crude protein diet. Prechallenge mortality was significantly lower in birds that had been vaccinated against Newcastle disease.

Animals↗

Counter immunoelectroosmophoresis in the diagnosis of infectious bursal disease of poultry.

Infectious bursal disease virus antigen was detected in the bursa of Fabricius of infected birds by the use of the counter immunoelectroosmophoresis technique. Eight suspected outbreaks were confirmed in this way and 82 out of 89 bursal samples submitted for laboratory confirmation were positive. The test was also suitable for the detection of antibody to infectious bursal disease virus in sera of infected birds. Precipitin lines were visible within 30 min as compared with 18 to 24 h with the Ouchterlony agar gel precipitation test. Counter immunoelectroosmophoresis is recommended for rapid confirmation of infectious bursal disease of poultry.

Animals↗

Site of synthesis and phylogenetic distribution of a hemolymph trophic factor of the tobacco hornworm, Manduca sexta.

Identification of fifth instar larval Manduca sexta fat body and epidermis as sites of synthesis of a hemolymph protein (hemolymph trophic factor or HTF) was achieved using in vitro 3H-leucine incorporation into protein and subsequent immunoprecipitation of tissue homogenates. Fat body is the primary site of HTF synthesis with a maximal rate on Day 1; epidermis is a secondary site with peak synthesis on Day 0. In vitro radiolabelling followed by TCA precipitation of general protein of fat body and epidermal homogenates suggest that fat body actively elaborates protein on Days 0-5 with peak rates on Days 1 and 4, while epidermis is active on Days 0-5 with a peak rate on Day 3. Based on Anti-HTF ELISA estimates, HTF [500 to 1000 micrograms/ml] was found in the hemolymph of representatives of the insect orders Blattodea, Hemiptera, Orthoptera, and Lepidoptera and in the class Crustacea, but not in the class Merostomata. These studies suggest a possible fundamental role for HTF among modern arthropods in cuticular deposition involving both epidermis and fat body. The physiological role of HTF is undetermined.

Animals↗

Chloroquine blood concentrations and malaria prophylaxis in Tanzanian women during the second and third trimesters of pregnancy.

OBJECTIVE: Routine malaria prophylaxis with chloroquine (CQ) is recommended to pregnant semi-immune women in several countries in Africa. The dosage is empirically based. We investigated whether blood CQ concentrations and apparent oral blood clearance (CL/F) change during the course of pregnancy. We also studied whether malaria parasites could be detected together with low CQ blood levels. METHODS: Forty nine semi-immune Tanzanian women were recruited in the 16th week of pregnancy. They were given 310 mg oral CQ base once per week as prophylaxis during the whole pregnancy. Capillary blood samples were taken for analysis of CQ before treatment and at weeks 26 and 36. Blood samples were dried on filter paper and analysed by HPLC. Blood was also drawn to detect occurrence of malaria parasites. RESULTS: A total of 25 women fulfilled the sampling schedule. CL/F increased significantly from 160 ml.min-1 at week 26 to 180 ml.min-1 at week 36. In 7 of 25 women, CL/F increased > 20%. Trough blood CQ concentrations, determined on four occasions at week 26 and at week 36 varied between 200 and 900 nmol.l-1. No statistically significant differences between occasions were seen. Malaria parasites were seen in two individuals early in pregnancy. CONCLUSION: Blood CQ CL/F showed a small increase during the course of pregnancy. The estimated mean blood CL/F values of 160 and 180 ml.min-1 (week 26 and 36, respectively) were higher than the mean CL/F of 125 ml.min-1 in non-pregnant individuals, published previously. Efficacy of higher dosages of CQ in malaria prophylaxis in pregnant women could, therefore, be evaluated in controlled trials in high-risk malaria areas.

Adult↗

Human corticosteroid binding globulin is secreted by a hepatoma-derived cell line.

We used a sensitive radioimmunoassay for corticosteroid-binding-globulin (CBG) to demonstrate that a human hepatoma-derived cell line secretes a protein which: (a) the radioimmunoassay cannot distinguish from CBG; (b) has the same Stokes' radius as CBG; (c) is absorbed by a steroid affinity column which is specific for CBG.

Carcinoma, Hepatocellular↗

Epidemiology of hepatitis B in Somalia: inference from a cross-sectional survey of serological markers.

Hepatitis B markers were determined by radioimmunoassay in 383 adults from different areas of Somalia and in 135 pregnant females and 428 children from Mogadishu. The highest incidence of HBsAg among adults was among nomadic males (20/85; 23%). The frequencies were lower in males from the agricultural and coastal area, i.e. 16/93 (17%) and 14/98 (14%) respectively. The lowest frequency of HBsAg was among women from the coastal area (6/72; 8%). Among the pregnant women 14 were positive for HBsAg, none of whom had HBeAg. Low levels of positivity for HBsAg were found both among children under 4 years and among those between 4 and 13 years of age - 3/94 (3%) and 5/128 (4%) respectively. In the age group 15-19 years, 50% showed seroconversion from HBeAg to anti-HBe. 7 out of 41 HBsAg carriers of ages over 20 had HBeAg. Early seroconversion from HBeAg to anti-HBe and a low level of HBsAg positivity in children indicate that vertical transmission is not important in Somalia. The low frequency of HBsAg in Mogadishu children may have one of the following explanations: (i) the infection occurs during adolescence, (ii) Mogadishu is a low-prevalence area and the examined adults were not born in Mogadishu, or (iii) a change in hepatitis B epidemiology has taken place in the area during the last 2 decades and the relatively higher prevalence of HBsAg in adults might reflect higher rates of infection in their childhood.

Adolescent↗

Minor role of hepatitis B virus in the causation of chronic liver disease in Somalia indicated by a case-control study.

Chronic liver disease (CLD) is frequent in Somalia. In a case-control study, 116 in-patients with CLD were compared with the same number of age and sex matched controls. Demographic variables, use of drugs, symptoms and signs, serological markers for hepatitis B virus (HBV) and serum alpha-foetoprotein (AFP) were assessed. Hepatitis B surface antigen (HBsAg) was found in 44 cases of which 17 had antibodies to hepatitis D virus (anti-HD) and 7 had hepatitis B e antigen (HBeAg). Twenty-three controls were HBsAg-positive, of whom 3 had anti-HD and one HBeAg. Increased relative risks (95% confidence intervals in parentheses) were 2.5 (1.3-4.5) for HBsAg, 6.5 (1.7-21.5) for anti-HD, and 7.4 (0.9-66.5) for HBeAg. Despite the association between the presence of HBV markers and CLD, 62% of the cases had no markers indicating current HBV infection. This was reflected in the low risk attributable to chronic HBV infection (22.6%), which was lower than that in patients with CLD in other African populations with a high HBsAg carrier rate. The prevalence of HBV markers did not differ between cases with AFP greater than 100 ng/ml and those with AFP less than 100 ng/ml. The former were characterized by male predominance, shorter duration of symptoms, and larger mean liver size, indicative of malignancy. The mean age of HBsAg-positive cases with AFP greater than 100 ng/ml was significantly lower (by 7.7 years) than that of HBsAg-negative cases with AFP greater than 100 ng/ml. Among the CLD patients with AFP less than 100 ng/ml, 48 were HBsAg-negative. These cases differed significantly from the other 68 cases in that more were females (35% against 16%), more originated from an agricultural area (56% against 30%), and more were regular consumers of drugs (48% against 28%). In conclusion, factors as yet undefined play a considerable role in the causation of CLD in Somalia. The possibility of determining the role of hepatitis C virus (HCV) awaits the development of more specific assays for anti-HCV antibodies.

Adolescent↗