Effect of bovine colostrum-based food supplement in the treatment of HIV-associated diarrhea in Northern Uganda: a randomized controlled trial.

AIM: HIV-associated diarrhea is common in HIV/AIDS patients in developing countries. An earlier uncontrolled study showed that a nutritional product made from bovine colostrum (ColoPlus®) alleviates HIV-associated diarrhea. We performed a randomized single-blind controlled trial of addition of colostrum-based supplement (ColoPlus®) to standard anti-diarrhea treatment in HIV/AIDS patients with diarrhea. METHODS: Eighty-seven adult patients with HIV-associated diarrhea were recruited at Gulu Hospital and four community clinics in Northern Uganda. Forty-five patients were randomized to receive 50 g of colostrum-based supplement twice a day for 4 weeks in addition to standard anti-diarrhea treatment, and 42 patients received standard anti-diarrhea treatment alone. Patients were followed up for 9 weeks. Daily stool frequency was recorded, and body weight and body mass index were evaluated at weeks 1, 4 and 9. Baseline CD4+ count was measured at baseline and at week 9. RESULTS: Mean daily stool frequency decreased by 79% from 7.5 to 1.3 motions over the study period in patients on colostrum-based supplement, compared to a 58% reduction in controls (p < 0.001). Self-reported fatigue was reduced by 85% in patients on colostrum-based supplement by week 9 compared to 43% reduction amongst controls (p < 0.001). Patients on colostrum-based supplement had 11% increase (p < 0,001) in mean body weight and body mass index by week 9, but no changes were observed in control subjects. Mean CD4+ count increased by 14% for patients on colostrum-based supplement, in contrast to 12% decrease in controls (p < 0.001). CONCLUSIONS: This study shows that addition of colostrum-based supplement to standard therapy is effective in treatment of HIV-associated diarrhea.

Unique patient with cerebrotendinous xanthomatosis. Evidence for presence of a defect in a gene that is not identical to sterol 27-hydroxylase.

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder believed to be exclusively caused by mutations in the CYP27A1 gene coding for the enzyme sterol 27-hydroxylase. Common findings in CTX are tendon xanthomas, cataracts and progressive neurological dysfunction. Here, we characterize an adult female patient with tendon xanthomas and classic biochemical findings of CTX (i.e. high levels of bile alcohols and cholestanol and extremely low levels of 27-hydroxycholesterol in plasma). Additionally, sterol 27-hydroxylase activity in cultured monocyte-derived macrophages from this patient was <5% of normal. Sequencing the CYP27A1 gene uncovered that the patient is heterozygous for two previously undescribed base substitutions in exon 8, C478A and C479A, which are expected to affect the haeme-binding domain of the enzyme. When expressed in HEK293 cells, the corresponding protein had only 8% of normal enzymatic activity. No other mutation was found in the open reading frame of the CYP27A1 gene, intron-exon boundaries or in the 5'-untranslated region up to 5000 bp distal to the translational start site. Sequencing mRNA isolated from leucocytes from the patient revealed a 1 : 1 ratio of mutated and nonmutated species, with total mRNA levels that were not significantly different from the controls. It is concluded that the patient is heterozygous for two mutations affecting one allele of the CYP27A1 gene and with at least one additional yet undefined gene that is of critical importance for the activity of sterol 27-hydroxylase.

Tobacco smoking increases the risk for gastric adenocarcinoma among Helicobacter pylori-infected individuals.

BACKGROUND: The importance of tobacco smoking and Helicobacter pylori infection as risk factors in the development of gastric carcinoma was investigated through multivariate conditional logistic regression analysis in a nested case-control study. METHODS: Blood samples and a questionnaire on smoking habits were collected from a cohort of 32,906 city residents during a health screening programme from 1974 to 1992. Fifty-six cases of gastric cancer and 224 matched controls were selected. The mean interval between screening and cancer diagnosis was 5.7 years. H. pylori infection was determined by IgG-serology. Occupation categorized into blue-collar workers, white-collar workers, self-employed and unknown occupation was included in the statistical analysis as an indicator of socio-economic status. RESULTS: The proportion of current smokers was 61% among gastric cancer cases, versus 41% among controls. H. pylori seropositivity was present in 82% of the cases and 49% of the controls. In a multivariate model current smokers had an odds ratio (OR) of 2.2 (95% confidence interval (CI): 1.2-4.2). With different levels of tobacco consumption, smoking less than 20 g tobacco each day gave the OR of 2.1 (95% CI: 0.98-4.4), and the OR when smoking more than 20 g tobacco per day was 2.5 (95% CI: 1.1-5.6). The OR of H. pylori infection was 5.0 (95% CI: 2.2-11.2). Among H. pylori-seropositive citizens, current smoking was associated with an increased risk of 2.3 (95% CI: 1.1-4.7) compared with non-smoking H. pylori-positive persons. CONCLUSIONS: Tobacco smoking and H. pylori are both risk factors in the development of gastric cancer, and tobacco smoking is still a risk factor among H. pylori-infected individuals. The risk of gastric cancer among H. pylori-infected current smokers is 11 times that of non-infected individuals not currently smoking.

Helicobacter pylori infection is associated with a decreased risk of developing oesophageal neoplasms.

BACKGROUND: The role of Helicobacter pylori infection in the development of oesophageal malignancies was investigated through a multivariate conditional logistic regression analysis in a nested case-control study. METHODS: Blood samples and a questionnaire on smoking and alcohol habits were collected from a cohort of 32,906 city residents during a health-screening programme between 1974 and 1992. Forty-four cases of oesophageal cancer and 149 matched controls were selected. The mean interval between screening and cancer diagnosis was 11.9 years. H. pylori seropositivity was determined by an enzyme-linked immunosorbant assay measuring IgG. Occupation was included in the statistical analysis as an indicator of socio-economic status. RESULTS: Helicobacter pylori seropositivity was present in 10 of the cases (22.7%) and 67 of the controls (45.0%). In a multivariate model, with adjustment for occupation, tobacco and alcohol consumption, the odds ratio for developing an oesophageal malignancy when infected with H. pylori was 0.29 (95% confidence interval (CI): 0.12-0.67). Current smokers had an odds ratio of 17.3 (95% CI: 3.0-99.4) and the odds ratio for ex-smokers was 5.9 (95% CI: 1.15-29.9). High alcohol consumption was no longer significantly associated with oesophageal neoplasms after tobacco smoking was included into the model, odds ratio 1.22 (95% CI: 0.46-3.2). The protective effect of H. pylori was more pronounced for oesophageal adenocarcinoma (seven cases, odds ratio 0.16, 95% CI: 0.00-1.06) than for squamous-cell carcinoma (29 cases, odds ratio 0.41, 95% CI: 0.14-1.2). CONCLUSIONS: Helicobacter pylori infection is associated with a decreased risk of developing an oesophageal malignancy. Current smokers and ex-smokers have instead a definite increased risk of oesophageal neoplasms.

Alpha1-antitrypsin deficiency may be a risk factor for duodenal ulcer in patients with Helicobacter pylori infection.

BACKGROUND: Most individuals with Helicobacter pylori infection in Western countries have no evidence of peptic ulcer disease (PUD). We therefore assessed the PiZ deficiency variant of the major plasma protease inhibitor alpha1-antitrypsin (alpha1AT) as a risk factor for PUD in H. pylori-infected individuals. METHODS: The cohort comprised 100 patients with endoscopically or surgically proven PUD (30 patients with duodenal ulcer (DU) and 70 patients with gastric ulcer (GU)) and 162 age- and sex-matched controls with PUD-negative endoscopic findings and no history of PUD. Plasma samples were screened for alpha1AT deficiency (PiZ) with an enzyme-linked immunosorbent assay (ELISA) and phenotyped by isoelectric focusing. H. pylori infection was evaluated with an IgG ELISA technique. RESULTS: Among the 262 patients 17 (6.5%) were positive for the PiZ alpha1AT deficiency, a frequency of the same magnitude as in the Swedish general population (4.7%). Of the PiZ carriers 76% (13 of 17) had H. pylori antibodies compared with 61% (151 of 245) of the non-PiZ carriers (NS). The prevalence of DU tended to be higher in H. pylori-positive PiZ carriers than in non-PiZ carriers (15.4%, 4 of 26 versus 0 of 4). Furthermore, among patients with DU a high PiZ allele frequency (13.3%, 4 of 30) was found compared with the general population (4.7%) (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.09-8.94; P = 0.02). All DU patients carrying the PiZ allele were positive for H. pylori. In addition, four of five PiZ carriers with H. pylori infection and PUD had DU. CONCLUSIONS: The PiZ allele may be a contributing factor in the development of DU in H. pylori-positive individuals.

An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation (C240F).

Familial hypercholesterolemia (FH) is caused by a defect in the function of the low density lipoprotein (LDL) receptor and inherited in an autosomal, codominant way. In this study we present a 13-year-old girl, compound heterozygote for the LDL receptor mutations C240F and Y167X. Fibroblasts from the patient showed very low cholesterol esterification rate, LDL uptake, and degradation compared to normal fibroblasts (< 2%, 8%, and < 2%, respectively). The C240F mutant was expressed in LDL receptor deficient CHOMldlA7 cells. Analysis of cell extracts by immunoblotting demonstrated delayed processing of the mutated LDL receptor, which was accumulated as a precursor protein of normal size. A high molecular weight form of the receptor was also detectable in these cells, which probably reflects cross-linking through the unpaired cysteine residue in the binding domain. Cells expressing the C240F mutant protein were unable to mediate uptake and degradation of LDL. The two siblings of the index case also carried the C240F mutation, but surprisingly one of them (a 17-year-old brother) showed no signs of hypercholesterolemia. This observation is consistent with the view that there may be cholesterol lowering mechanisms that can be activated, perhaps by mutations in known or hitherto unknown genes.

Enhancement of low density lipoprotein catabolism by non-steroidal anti-inflammatory drugs in cultured HepG2 cells.

Several clinical studies have shown that different types of non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the cholesterol content of atherosclerotic blood vessels. The mechanism of this reduction is not established. One possibility is that NSAIDs affect low density lipoprotein (LDL) catabolism. In this study, we investigated the effect of the NSAIDs, indomethacin, flufenamic acid, ibuprofen, acetaminophen, and also acetylsalicylic acid on LDL binding, cell-association and degradation in cultured hepatoma HepG2 cells. LDL was labelled with 125I to study LDL catabolism. Furthermore, dextran sulphate, a substance that is known to release bound LDL from its receptors, was used to study LDL receptor activity. Reverse transcription-polymerase chain reaction was used to study the messenger RNA (mRNA) of LDL receptor. Our results show that flufenamic acid, indomethacin, and to a lesser extent ibuprofen, and acetaminophen increase LDL binding, cell-association, and degradation. Flufenamic acid was most potent and increased LDL catabolism by 50-70%, whereas acetylsalicylic acid had only a modest effect. Also, flufenamic acid and indomethacin were both found to increase the synthesis of mRNA of the LDL receptor with a subsequent increase of LDL receptor protein. We also investigated the effect of indomethacin on LDL binding in the presence of the 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase inhibitor, fluvastatin. We found that both indomethacin and fluvastatin had an additive up-regulatory effect on LDL receptor activity. In addition the effect of flufenamic acid on cell-associated LDL was examined in the presence of cyclosporine, which is known to decrease LDL catabolism. The results show that flufenamic acid can restore the inhibitory effect of cyclosporine. The study thus shows that NSAIDs enhance LDL catabolism due to increased synthesis of the mRNA for LDL receptor protein. This action might contribute to the lipid-lowering effect of NSAIDs.

[Enteroscopy valuable in obscure small bowel disease. Chances are good to discover curable conditions]. / Enteroskopi av värde vid oklar tunntarmssjukdom. Chansen stor att hitta behandlingsbara tillstånd.

Indications for enteroscopic examination of the proximal small bowel are expanding, above all in cases of gastro-intestinal bleeding of obscure origin. Of 66 patients examined enteroscopy revealed new and unforeseen diagnoses in about half of them, such as angiodysplasia and erosions (15 per cent of cases each). Former as well as ongoing bleeding was treated with electro cautery, bicap. In four cases the need for blood transfusion ceased. Ulcers, neoplasia and varices were also diagnosed. 16 out of 36 pathologic lesions were located within reach of an ordinary gastroscope, in spite of the patients being selected through repeated normal upper and lower endoscopic examinations. This emphasises the need for better quality assurance in routine endoscopic examinations.

Mutations in the low-density lipoprotein receptor gene in Swedish familial hypercholesterolaemia patients: clinical expression and treatment response.

BACKGROUND: Familial hypercholesterolaemia, an autosomal co-dominant disorder caused by defects in the low-density lipoprotein receptor gene, is strongly associated with premature development of cardiovascular disease. METHODS: In this study, we have applied a gene screening method in a population of familial hypercholesterolaemia patients in order to describe the genetic background of the disease in southern Sweden. These patients were studied with the aim of relating the presence of the different mutations to the clinical expression of the disease and to the response to pharmacological treatment. RESULTS: In 16 out of 21 patients, potentially disease-causing low-density lipoprotein receptor gene defects were found, including five not previously described alterations (C240-->F, C122-->stop, C356-->Y, 785insG, 165delG). No defects in apolipoprotein B were found. One group of patients (n = 4) carried the mutation C122-->stop and another group of patients (n = 4) a mutation causing the substitution W66-->G. Patients in the two genotype subgroups were very similar with respect to lipid levels before treatment. CONCLUSION: A tendency towards differential susceptibility to treatment with statins was observed for the patient groups, encouraging further comparative studies of heterozygous FH patients.

Troglitazone upregulates LDL receptor activity in HepG2 cells.

The aim of this in vitro study was to investigate the effect of troglitazone, a new oral antidiabetic agent, on LDL catabolism. HepG2 cells, which are cells from a well-differentiated cell line of hepatoma cells, were cultured and used to study LDL catabolism. Different concentrations of troglitazone, all within the therapeutic range for humans, were incubated in culture medium with 125I-labeled LDL to measure cell-associated and degraded 125I-LDL. Troglitazone increased cell-associated and degraded 125I-LDL by approximately 30%. We also investigated if this effect occurred through a LDL receptor-mediated pathway or a non-LDL receptor pathway. By using dextran sulfate, a substance known to release bound LDL from its receptor, we found that troglitazone upregulated LDL receptor activity by approximately 35%. In addition, we found that troglitazone increased the expression of the LDL receptor mRNA. The effect of troglitazone was comparable with that of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin, with troglitazone having an upregulatory effect similar to that of fluvastatin. Insulin within human physiological concentrations also increased LDL receptor activity. We found that troglitazone and insulin had an additive effect on LDL catabolism. Also, the effect of troglitazone on LDL catabolism was studied in the presence of cyclosporine, an immunosuppressant drug that reduces LDL catabolism mainly by decreasing LDL receptor activity. The results showed that troglitazone can compensate for the reduced LDL receptor activity induced by cyclosporine, but that cyclosporine had a residual effect on the action of troglitazone. Thus troglitazone enhanced LDL binding, cell association, and degradation by increasing LDL receptor mRNA expression, with a subsequent increase in LDL receptor activity.

Bone mineral density in patients with Crohn's disease during long-term treatment with azathioprine.

OBJECTIVES: To ascertain whether patients with Crohn's disease treated with azathioprine maintained bone mineral mass better than patients treated with steroids alone. DESIGN: Retrospective study. SETTING: University Hospital of Malmö, Sweden. SUBJECTS: A total of 59 patients with ileocolonic, ileocaecal or colonic Crohn's disease. METHODS: Bone mass was assessed by dual photon X-ray absorptiometry at the level of L2-L4. RESULTS: Patients treated with a high lifetime dose of steroids (> 5 g prednisolone) had significantly (P = 0.011) lower Z-score of L2-L4 (-0.87 +/- 1.11; 11 SD) than steroid-treated patients, who had received a low dose of prednisolone (< 5 g) (0.08 +/- 1.16 SD). Azathioprine did not negatively influence the steroid effect on bone mineral density. CONCLUSIONS: Azathioprine does not seem to affect bone mineral density by itself. However, by being steroid-saving, it seems to conserve bone mineral mass in patients with Crohn's disease.

Cost-Effectiveness of Budesonide Controlled Ileal Release (CIR) Capsules as Maintenance Therapy versus No Maintenance Therapy for Ileocaecal Crohn's Disease in Sweden.

A decision-analytic model was designed to estimate the associated costs and outcomes of maintenance therapy for Crohn's disease with budesonide controlled ileal release (CIR) capsules (Entocort((R)) capsules, Astra Draco, Lund, Sweden) versus no maintenance therapy. A third-party payer perspective was adopted to compare the direct costs associated with the medication and healthcare resource use for each therapy over a period of 12 four-week cycles. The costs of routine patient care and the consequences of failure, in terms of relapses, acute therapies, hospitalisations and surgery, were included. The outcome was measured as the average number of days in remission per patient per 12-cycle period. Based on the assumptions in the model, the results show that budesonide CIR capsules are associated with a reduction of 16.6 (26%) days in relapse, i.e. a 6% increase in days in remission, over a one-year period compared with no maintenance therapy. Direct healthcare costs are increased by 6% or Swedish kronor (SEK) 1673 ($US1 ~ SEK7.60). Overall, the model shows that there are substantial (non-drug associated) cost offsets from using budesonide CIR capsules as maintenance therapy in Crohn's disease. These cost offsets, in addition to improvements in patients' well-being and quality of life, indicate that maintenance therapy is cost effective compared with no maintenance therapy. The cost per added day in remission is relatively modest (SEK101 ~ $US13). If indirect costs are added to the calculation, it is realistic to argue that a net saving to society would be most likely.

Additive inhibitory effect of hydrocortisone and cyclosporine on low-density lipoprotein receptor activity in cultured HepG2 cells.

Both glucocorticoids and cyclosporine are used to prevent rejection in organ transplant recipients. However, long-term treatment with these drugs is known to induce hyperlipidemia and premature development of atherosclerosis. In previous studies, we have shown that the immunosuppressive drug cyclosporine inhibits catabolism of low-density lipoproteins (LDL) mainly by reducing the expression of LDL-receptor messenger RNA (mRNA), thus explaining the increased plasma levels of LDL cholesterol observed in patients treated with cyclosporine. In the present study, our objective was to investigate the mechanism by which glucocorticoids increase plasma levels of LDL cholesterol. We studied the catabolism of LDL in the human hepatoma cell line HepG2. Our results show that hydrocortisone at physiologically relevant concentrations inhibits LDL binding, uptake, and degradation in a dose-dependent way. Moreover, hydrocortisone also reduces the expression of LDL-receptor mRNA in a dose-dependent way. Cyclosporine also has an additive inhibitory effect on hydrocortisone in the catabolism of LDL. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin reverses the inhibitory effect of both hydrocortisone and cyclosporine. We conclude that treatment with hydrocortisone and/or cyclosporine induces increased plasma levels of LDL cholesterol because of reduced hepatic LDL receptor activity. HMG-CoA reductase inhibitors reverse this undesirable effect and thus reduce the risk of the development of atherosclerosis in patients subjected to immunosuppressive treatment.

Bambuterol raises high-density lipoprotein levels in patients with hyperlipidaemia.

OBJECTIVE: The objective of this study was to investigate the effects of bambuterol (a prodrug of the beta 2-agonist terbutaline) on lipid and lipoprotein levels in patients with hyperlipidaemia. Both these drugs are extensively used in the treatment of patients with bronchial asthma. Earlier studies in healthy volunteers and in patients with noninsulin dependent diabetes mellitus have shown that terbutaline and bambuterol increase HDL cholesterol levels, and therefore bambuterol might have beneficial effects on HDL levels in patients with hyperlipidaemia. DESIGN: The present study was a randomized, double-blind, crossover study, comparing 20 mg of bambuterol with placebo, each one given for 6-8 weeks with a 3-4 week washout period in between. SETTING: The study was performed in an out-patient lipid clinic at Malmö University Hospital. SUBJECTS: Thirty-one patients with hyperlipidaemia (S-cholesterol > 6.5 mmol L-1 and S-triglycerides > 2.0 mmol L-1) were included. MAIN OUTCOME MEASUREMENTS AND RESULTS: The results showed that bambuterol increased S-HDL cholesterol levels by 7% (P = 0.012). Increases were 23% for P-HDL2 and 7% for P-HDL3 fractions, but no effect was apparent on S-apolipoprotein A-1 levels. CONCLUSION: This study suggests that the beta 2-agonist bambuterol might be used as an alternative or as a complement in the treatment of dyslipidemic patients, when an increase in HDL cholesterol is desired.

Low density lipoprotein catabolism is enhanced by the cleaved form of alpha-1-antitrypsin.

The frequent occurrence of hypocholesterolaemia following inflammatory processes is well known but unexplained. Elevated plasma levels of serine proteinase inhibitors (serpins) and their complexes with target enzymes have been demonstrated in inflammatory, malignant and infectious diseases which are also often accompanied by low plasma cholesterol levels. Under inflammatory conditions, uncomplexed, but cleaved inactive serpins arising from slow deacylation of the serpin-proteinase complex may be present in the circulation. To determine the influence of native and cleaved forms of serpins, such as alpha-1-antitrypsin (AAT), on lipoprotein metabolism, we investigated the effect of these forms on low density lipoprotein (LDL) catabolism in human HepG2 cell line. We have found that the cleaved form of AAT in concentrations from 125 to 2000 nmol l-1 stimulates LDL binding to the HepG2 cells, by up to 49% with a subsequent increase in LDL uptake and degradation of up to 79 and 65% respectively. Native AAT was also found to increase LDL binding and internalization by 20-25%, independently of the amount of AAT added, an effect most probably due to the cleaved form of AAT produced by local proteolysis of native AAT incubated in the cell culture. Moreover we have shown that the cleaved form of AAT interacts with LDL in vitro, and that such an interaction abolishes AAT ability to stimulate LDL binding and internalization. This study for the first time describes the ability of the cleaved form of AAT to stimulate LDL binding and internalization in HepG2 cell culture, and provides evidence that hypocholesterolaemia occurring during inflammatory processes may be mediated by cleaved forms of serpins.

Reversal of cyclosporine-inhibited low-density lipoprotein receptor activity in HepG2 cells by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

Previously we have shown that cyclosporine inhibits low-density lipoprotein (LDL) catabolism in HepG2 cells. This inhibition mainly occurs through reduced LDL-receptor activity. 3-Hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase inhibitors up-regulate LDL receptor activity with a subsequent increase in LDL uptake and degradation. In this study, in HepG2 cells, we investigated the effects of HMG-CoA reductase inhibitors on cellular LDL catabolism in the presence of cyclosporine. Different concentrations of cyclosporine and HMG-CoA reductase inhibitors, which were within the range of therapeutic concentrations used in humans, were added to the culture medium and the cellular LDL receptor activity was then measured. The results show that HMG-CoA reductase inhibitors reverse the down-regulatory effect of cyclosporine on LDL receptor activity, thus further supporting our previous findings and also providing a rationale for the already established treatment in cyclosporine-induced hypercholesterolemia with HMG-CoA reductase inhibitors.

Association between Helicobacter pylori and gastric carcinoma in the city of Malmö, Sweden. A prospective study.

BACKGROUND: We have investigated the association between Helicobacter pylori and gastric carcinoma through a nested case-control study in a single city. METHODS: From a cohort of 32,906 residents recruited from 1974 through 1992, 56 cases of gastric adenocarcinoma and 224 matched controls were selected. The mean interval between serum collection and diagnosis was 5.7 years. Frozen serum or plasma samples were analysed for IgG antibodies against H. pylori with an enzyme-linked immunosorbent assay. RESULTS: The overall seropositivity prevalence in gastric cancer cases was 82%, compared with 49% in controls, giving an odds ratio (OR) of 5.0 (95% confidence interval (CI), 2.2-11.5). Partial gastrectomy because of peptic ulcer 5 to 36 year before diagnosis of gastric cancer could be a confounding factor. With exclusion of 10 such cases, H. pylori seropositivity among cases was 78%, as compared with 50% in matched controls (OR, 3.9; 95% CI, 1.7-9.2). Tumours of the cardia were not associated with H. pylori (OR, 0.92; 95% CI, 0.23-3.7), which is in contrast to tumours of the fundus, corpus, and antrum, which were significantly associated (OR, 11.1; 95% CI, 2.4-71.8). This difference in location was significant (P < 0.01). CONCLUSION: There is a significant association between prior infection with H. pylori and later development of gastric carcinoma, and the association is related to noncardia gastric cancer.

Cyclosporine inhibits catabolism of low-density lipoproteins in HepG2 cells by about 25%.

The aim of this study was to elucidate the possible causes of elevated low-density lipoprotein (LDL)-cholesterol levels in transplanted patients treated with the immunosuppressant drug, cyclosporine. HepG2 cells, from a well-differentiated cell-line of hepatoma cells, were cultured and used as a model for in vitro hepatocytic LDL uptake. Different concentrations of cyclosporine, which were within the range of concentrations found in humans treated with cyclosporine, were added to tissue culture medium together with 125I-LDL. The results showed that cyclosporine reduced LDL uptake and degradation in HepG2 cells by about 25%. The cells were also pretreated with cyclosporine for 1 to 24 hours and then incubated with new medium containing labeled LDL for 2 hours at 4 degrees C in an LDL-binding assay. The data showed that cyclosporine reduced the subsequent LDL binding. Cyclosporine has no toxic effects on HepG2 cells, as shown by unchanged growth capacity of the cells. By means of a 50-fold excess of unlabeled LDL, a monoclonal anti-LDL receptor antibody, and dextran sulfate, we also evaluated if this inhibition of LDL binding occurred through the LDL receptor-mediated pathway, through non-LDL receptor-mediated pathways, or through both. The results show that cyclosporine reduces LDL binding and uptake by mainly inhibiting the LDL receptor-mediated pathway. We also studied the effect of the LDL-cyclosporine complex on the binding of labelled LDL. The presence of cyclosporine in the LDL particle does not influence the binding behaviour of LDL to its receptor. We also found that cyclosporine reduces the expression of the LDL receptor messenger RNA (mRNA) by about 40%. Thus, the interpretation of this study is that cyclosporine can cause an increase in LDL-cholesterol in the plasma of transplantation patients by reducing the catabolism of LDL in the liver by inhibiting mainly the LDL receptor-mediated catabolism through an effect on LDL receptor synthesis.