Polymorphisms in the activin A receptor type 2A gene affect the onset time and severity of preeclampsia in the Turkish population.

AIM: To investigate the possible roles of selected single nucleotide gene polymorphisms (SNPs) of the activin A receptor type 2A (ACVR2A) gene in the pathogenesis of preeclampsia. METHODS: Ninety-four patients with preeclampsia and 166 healthy pregnant women were included in this study. Genomic DNA was extracted from venous blood and were stored at -80°C before the analysis. Selected ACVR2A SNPs (rs10497025, rs1128919, rs13430086) were determined in an ABI 7900 HT Real-Time PCR instrument. RESULTS: For all three SNPs, no statistically significant difference was found between preeclampsia and control groups in terms of genotype and allele frequencies. In the late preeclampsia group, with regard to the rs1128919 SNP, the frequency of GG genotype was found to be significantly lower (P=0.02). Although the frequency of "A" allele was found to be higher (P=0.05; OR=1.54), and the "G" allele was found to be lower (P=0.05; OR=0.65), the results did not reach statistical significance in late preeclamptic patients. For the rs1128919 SNP, the frequency of the AA genotype was found to be significantly higher in both mild (P=0.004) and severe (P=0.0001) preeclampsia groups, whereas the frequency of GG genotype was found to be significantly lower (P=0.008, and P=0.0001, respectively). For the rs13430086 SNP, while the frequency of the AA genotype was found to be significantly lower in both mild (P=0.02) and severe (P=0.0001) preeclamptic patients, the frequency of TT genotype was found to be significantly higher in only severe preeclampsia group (P=0.0001). CONCLUSION: ACVR2A gene polymorphisms may play a role in the development of preeclampsia.

Determination of the effects of alcohol dehydrogenase (ADH) 1B and ADH1C polymorphisms on alcohol dependence in Turkey.

Alcoholism is a complex genetically influenced disorder which refers to alcohol abuse and alcohol dependence. There are controversial results on the role of gene polymorphisms in alcohol dependence in the literature. Differences in population groups and selective inclusion criteria for alcohol dependence may affect results. In this study, we investigated the role of ADH1B Arg48His (rs1229984) and, ADH1C Ile350Val (rs698) gene polymorphisms in Turkish population. 100 healthy volunteers and 75 patients who were admitted to Ege University Alcohol Dependence Unit enrolled in the study. We found significant increase both in ADH1B (Arg48His) polymorphism Arg allele and Arg/Arg genotype frequency in patients. No profound connection between alcohol dependence and ADH1C Ile350Val gene polymorphism was detected. Alcohol dependence is an important health problem that depends on many genetic and environmental factors but we think that it is possible to interpret genetic risk for developing early diagnostic methods and treatment strategies by comprehensive linkage and association studies.

The interaction between antioxidant status and cervical cancer: a case control study.

AIMS AND BACKGROUND: To compare the antioxidant status of cervical cancer patients with healthy controls and to assess the antioxidant levels before and after radiotherapy or radiochemotherapy. METHODS AND STUDY DESIGN: Antioxidant levels (glutathione, glutathione peroxidase, superoxide dismutase, and malondialdehyde) were measured in 35 patients with cervical cancer and 35 age-matched healthy controls. Blood samples were collected twice (before and after treatment) from cervical cancer patients and once from healthy control subjects. RESULTS: In the patient group, pre-radiotherapy glutathione and glutathione peroxidase levels were significantly lower (P <0.01 and P <0.0001, respectively) than the control group. Pre-radiotherapy levels of superoxide dismutase were significantly higher in cancer patients (P <0.01). In general, no difference was observed between pre- and post-radiotherapy antioxidant levels in cancer patients. However, when post-radiotherapy glutathione levels were analyzed, patients who did not respond to treatment had significantly higher levels than those who did respond (P <0.01). CONCLUSIONS: Levels of antioxidants significantly differed between the patients with cervical cancer and the controls, and no change in antioxidant levels was observed after treatment. Moreover, further studies evaluating the predictive value of glutathione levels on treatment response are warranted.

Potential involvement of serine/threonine protein phosphatases in apoptosis of HepG2 cells during selenite treatment.

Selenium, an essential biological trace element present in both prokaryotic and eukaryotic cells, exerts its regulatory effect in a variety of cellular events, including cell growth, survival, and death. Selenium compounds have been shown in different cell lines to inhibit apoptosis by several mechanisms. Serine/threonine phosphatases (STPs) are potentially important in selenite-induced apoptosis because of their role in regulation of diverse set of cellular processes. In this study, the regulatory role of STPs in selenite-induced apoptosis has been implied by the use of two specific inhibitors: ocadaic acid and calyculin A. Our results show a decrease in cell density in HepG2 cells under selenite treatment. Resulting specific enzyme activities showed a concentration-dependent increase in all three phosphatase activities after 24 h in cells treated with 5 microM selenite and these activities decreased at 48 and 72 h. However, in cells treated with 10 microM selenite, PP2A and PP2B decreased at 48 h, whereas PP2C activity did not change at this dose. In cells treated with 25 microM, there was not a significant change in PP2C activity. These data suggest that the most specific response to selenite treatment was in PP2A and PP2B activities in a dose-dependent manner. Our results with OA and Cal-A further support the view that PP1 and PP2A might act as negative regulators of growth. With these data, we have first demonstrated the role of serine/threonine protein phosphatases in the signaling pathway of selenite-induced apoptosis and resulting cytotoxicity.

TLR-2 gene Arg753Gln polymorphism is strongly associated with acute rheumatic fever in children.

The recently described family of toll-like receptors (TLRs) is a key player in host immunity by mediating inflammatory reactions against a wide range of pathogens. Mutations and polymorphisms in TLRs have revealed the importance of TLRs in human defence against diseases. TLR-2 is reported to interact with different bacterial structures, including lipoproteins, peptidoglycan and lipoteichoic acid. To assess the role of TLR-2 gene polymorphism in acute rheumatic fever (ARF) etiopathology, 61 independent Caucasian Turkish patients and 91 child and 116 adult controls were studied. Antistreptolycin O, C-reactive protein, sedimentation and white blood cell counts were studied to evaluate the clinical characteristics of the patients. Genomic DNA was extracted from peripheral blood using a standard column extraction technique. The Arg753Gln and Arg677Trp polymorphisms were genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism. The PCR products for the TLR-2 gene were analysed on 1.5% agarose gel pre-stained with ethidium bromide. Compared with healthy adult controls, the Arg753Arg genotype was significantly decreased in the entire group of ARF cases [odds ratio (OR) 0.01, 95% confidence interval (95% CI) 0.0034-0.031, p<0.0001]. Significantly, ARF patients were just 16 times more frequent with Gln allele (OR 15.6, 95% CI 7.87-30.8, p<0.0001). Moreover, evidence for an intensifying effect of the Gln allele was noteworthy when patients with Arg753Gln genotype were compared with healthy controls (OR 97.1, 95% CI 32.5-290, p<0.0001). However, no Arg677Trp polymorphism was detected in either patients or controls. Our data suggest that there is strong evidence for the biological role of TLR-2 in ARF. The common TLR-2 Arg to Gln polymorphism at position 753 significantly contributes to the pathogenesis of ARF. These results will allow the construction of a profile of individuals prone to ARF and may assist in developing new therapies.

Thrombin activatable fibrinolysis inhibitor in Behçet's disease.

INTRODUCTION: Thrombin activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase downregulating plasmin formation, thereby causing a tendency for thrombosis development. Since, Behçet's disease (BD) is a systemic vasculitis, which is commonly complicated by arterial and venous thrombosis, we aimed to find out plasma TAFI levels in BD, compared with healthy controls. We also searched whether plasma TAFI levels were significantly different between Behçet's subgroups with and without thrombosis. MATERIALS AND METHODS: In this study, 105 BD patients (M/F: 64/41; mean age 36+/-1 years), followed up by Ege University Rheumatology Department were enrolled. The exclusion criteria were hemophilia, hyperlipidemia, diabetes mellitus, hepatic diseases renal failure, antiphospholipid positivity, oral contraceptive use and pregnancy. Age-and sex-matched healthy controls (n=53) were also included. Plasma TAFI levels were measured by ELISA. Since TAFI is also an acute-phase reactant, we also measured other inflammatory markers such as C-reactive protein (CRP). RESULTS: Plasma TAFI levels were significantly higher in Behçet's patients (91.1+/-7.4 ng/ml) compared with healthy controls (14.3+/-4.5 ng/ml) (P<0.001), but there were no significant difference between the subgroups with and without thrombosis. In BD, there was no correlation between plasma TAFI levels and CRP. CONCLUSIONS: Regardless of manifest thrombosis, plasma TAFI levels in BD were significantly higher than in healthy controls. High TAFI levels might possibly contribute to the thrombotic tendency in BD. Future studies investigating TAFI gene polymorphism and functional activity are clearly needed, to clarify the exact role of TAFI in Behçet's thrombosis.

Induction of apoptosis by fatty acid ethyl esters in HepG2 cells.

Fatty acid ethyl esters (FAEEs) are esterification products of ethanol and fatty acids which have been found particularly in the organ damaged by ethanol abuse. To evaluate any effect of FAEEs on HepG2 cells, we added FAEEs to cell culture medium. Electrophoresis of DNA from HepG2 cells exposed to 18.5 microM ethyl palmitate (EP) and 10.6 microM ethyl stearate (ES) for 24 h revealed a smear which is typical of non-specific degradation by DNA ladder assay. Apoptosis was characterized by electron microscopy, flow cytometry revealed that the cell cycle of HepG2 cells was perturbed by exposure to FAEEs. In the present study we demonstrate that treatment of HepG2 cells with EP and ES induces apoptosis, as well as perturbing the cell cycle as the number of cells in the G(2)/M and S phases decreased.

Involvement of immunoglobulin FcgammaRIIA and FcgammaRIIIB gene polymorphisms in susceptibility to rheumatic fever.

OBJECTIVES: To assess the impact of the human FcgammaRIIA and FcgammaRIIIB gene polymorphisms on the risk of rheumatic fever (RF). DESIGNS AND METHODS: FcgammaRIIA-R/H-131 and FcgammaRIIIB-NA1/NA2 genotypes were determined using polymerase chain reaction in 66 RF cases and 117 healthy controls in this case control study. RESULTS: Compared with healthy controls, the RR genotype was enriched in the entire group of RF cases (odds ratio [OR] 4.98, 95% confidence interval [95% CI] 1.81-13.70). RF patients were more frequently HR heterozygotes rather than HH homozygotes (OR 3.09 vs. 0.11). The results of this study show that patients who have RF are more likely to have the RR and HR genotypes than control children. These probabilities show that RR is associated with the greatest risk for rheumatic fever and HR is associated with an intermediate risk. For the distribution of FcgammaRIIIB NA2 genotypes, a nonsignificant increase was found in RF patients (39.31% vs. 51.51%; OR 1.64, P = 0.1226). CONCLUSION: The FcgammaRIIA-R/H-131 polymorphism may be an important marker in determining predisposition to RF.

Trace elements analysis of ascitic fluid in benign and malignant diseases.

OBJECTIVES: To evaluate differences in ascitic fluid trace element concentrations which might be useful in discrimination between benign and malignant ascites. DESIGN AND METHODS: The concentrations of copper, zinc, magnesium and iron in ascitic fluid and venous blood in 17 patients were investigated. The relationship between these trace elements and type of disease were examined. Investigations were carried out in a group of 5 males and 5 females aged 54 to 77 yr who had cirrhosis ascites and in a group of 7 females aged 41 to 76 yr with ascites due to gynecologic neoplasms. RESULTS: The mean ascitic fluid and serum concentrations of copper were significantly higher in neoplastic diseases compared to benign disease states (118,43 vs. 97,50, 91,14 vs. 26.90) (p < 0,05 and p < 0,01 respectively). The zinc levels in ascitic fluid and serum were significantly different between the groups (p < 0,01). Neoplastic patients had significantly higher ascitic fluid magnesium levels than the benign disease group (2,17 vs. 1,55, p < 0,001). The serum levels of iron were significantly lower in the neoplastic diseases group (92, 28 vs. 255, p < 0, 01). In benign diseases the concentration of zinc in ascitic fluid correlated positively with ascitic fluid copper concentrations. The concentrations of zinc and iron in malignant ascites correlate positively with the magnesium concentrations. Statistically significant negative correlations were found between ascites zinc and magnesium and magnesium and copper in cirrhotic patients and magnesium and copper in malignant diseases. CONCLUSIONS: The results showed that zinc, magnesium and iron levels were significantly different between cirrhotic and neoplastic illness. Analysis of serum and ascitic fluid trace element composition may be helpful in identifying and distinguishing the malignant and nonmalignant ascites and provides useful information on processes regulating passage of blood components into the peritoneal cavity.

Leukotriene receptor antagonism in experimental acute pancreatitis in rats.

OBJECTIVES: Acute pancreatitis is a multifactorial disease caused by activation of several inflammatory mediators. Leukotrienes, beside other mediators, may be involved in acute pancreatitis. The aim of this study was to investigate the effects of 'zafirlukast', a leukotriene receptor antagonist, in acute pancreatitis and its relation with prostaglandin synthesis. METHODS: Eighty rats were randomly divided into eight groups. Acute pancreatitis was induced by subcutaneous injection of cerulein (20 microg/kg), four times at 1-h intervals. Zafirlukast (20 mg/kg) was applied intraperitoneally as a pretreatment. Prostaglandin synthesis was inhibited by low-dose indomethacin (5 mg/kg subcutaneously). Pancreatic histopathology, serum amylase activity and pancreatic myeloperoxidase activity were determined to assess the severity of pancreatitis. RESULTS: Zafirlukast pretreatment alone did not induce any inflammation and fatty necrosis in pancreatic tissue. However, it increased the histopathological score from 3.70 +/- 0.57 to 6.62 +/- 0.53 in rats with acute pancreatitis (P < 0.001). Fatty necrosis was especially prominent in the zafirlukast-treated acute pancreatitis group compared with the untreated group (2.62 +/- 0.26 versus 0.40 +/- 0.22, respectively; P < 0.001). Inhibition of prostaglandin synthesis by indomethacin partially suppressed the harmful effects of zafirlukast in acute pancreatitis. It decreased the pathological score (4.62 +/- 0.73) and fatty necrosis (1.50 +/- 0.32) in that group. CONCLUSION: Interestingly, leukotriene receptor antagonism by zafirlukast increased the pancreatic histopathological score and fatty necrosis in rats with acute pancreatitis. Blocking of cysteinyl leukotriene receptors might cause an induction of mediator synthesis via other pathways. Effects of leukotriene receptor antagonism on the pancreas must be evaluated extensively in further studies.

Role of thiocyanate ion in metallothionein induction and in endogenous distribution of essential elements in the rat liver.

Thiocyanate is the major toxic metabolite of hydrogen cyanide, a toxic substance the organism may be exposed to as a result of cigarette smoking or industrial pollution. The complex interactions existing between metals and metallothionein induction are well known. However, the possible role of thiocyanate, which is also an anion, has not been established yet. Considering the interactions between metals and the metallothioneins, in this study the relationship between thiocyanate and the in vivo distribution of hepatic metallothionein and zinc, copper, iron, calcium, magnesium, and manganese are investigated in rats. This study implies that thiocyanate has, to some extent, an effect on the in vivo expression of metallothionein and endogenous distribution of essential elements in rat liver. Elevated levels of metallothionein and changes in hepatic concentrations of essential elements have suggested a role for thiocyanate in cellular metabolism and it might reflect a direct role of thiocyanate on alteration of cellular functional activities.

Characterization of the cellular response during apoptosis induction in cadmium-treated Hep G2 human hepatoma cells.

Cadmium is a toxic transition heavy metal of continuing occupational and environmental concern, with a wide variety of adverse effects on regulation of gene expression and cellular signal transduction pathways. Injury to cells by cadmium leads to a complex series of events that can culminate in the death of the cell. It has been reported that cadmium induces apoptosis in many cell lines. However, the morphological characteristics leading to apoptosis or subsequent regeneration in cells exposed to cadmium have not been clarified. We evaluated whether human hepatoma cells maintained in culture undergo apoptosis when exposed to cadmium. Cytotoxic activity of cadmium on Hep G2 cells determined using 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide assay. A DNA ladder assay was performed by electrophoresis. Cell cycle analysis was quantified by flow cytometry. Nuclear morphology was studied by fluorescence microscopy after staining with propidium iodide and Hoechst 33342. Morphologic alterations in culture hepatocytes treated with CdCl2 were observed by transmission electron microscopy. We have demonstrated that apoptosis is a major mode of elimination of damaged HepG2 cells in cadmium toxicity and it precedes necrosis.

Biochemical and morphological characteristics of selenite-induced apoptosis in human hepatoma Hep G2 cells.

Selenium is a cellular growth inhibitor in many mammary tumor cells. To comprehend the mechanism for the selenium-induced cell death, we examined the effects of sodium selenite, which has been one of the most extensively investigated selenium compounds, in human hepatoma Hep G2 cells.Cell viability gradually decreased after treatment with sodium selenite within the concentration range of 10-50 microM. Low (10 mM) selenite has shown a high-percentage laddering pattern compared to the high (25 microM) cytotoxic selenium concentration in agarose gel electrophoresis. G2/M-phase enrichment was also concentration dependent. The most consistent transmission electron microscopic finding was the existence of large lysosomes. Based on these data, we hypothesize that sodium selenite predominantly shows its apoptotic effect over hydrogen selenite accumulation.

Effect of omeprazole on plasma zinc levels after oral zinc administration.

BACKGROUND: The intestines are the major site of zinc absorption and excretion. Reduced gastric acid secretion and elevated gastric pH is an important factor affecting intestinal mineral absorption. METHODS: Gastric pH and volume, and basal and maximal acid outputs were measured in 14 healthy volunteers. Plasma zinc levels were then measured at baseline and 1, 2, 3 and 4 hours after oral administration of 300 mg zinc sulfate. The experiment was repeated after omeprazole administration (60 mg/day orally) for 7 days. RESULTS: Omeprazole administration significantly increased fasting gastric pH (5.5 versus 2.4; p < 0.001). Mean basal gastric acid output (1.6 vs 8.0 mEq/h; p < 0.001) and maximal acid output (20.6 vs 106.6 mEq/h; p < 0.001) decreased after omeprazole administration. Zinc absorption decreased after omeprazole administration (141 [34] mg/dL/h) compared with pre-omeprazole values (245 [35]; p < 0.01). CONCLUSION: Suppression of gastric acid secretion by omeprazole reduces intestinal absorption of zinc.

Calcineurin inhibitor-based and free regimens have distinct gene expression patterns in subclinical graft fibrosis.

BACKGROUND: Chronic nephrotoxic effects of calcineurin inhibitors may be responsible for late allograft dysfunction and reduced allograft half-life. Mammalian target of rapamycin inhibitors (mTOR-i's), a newer class of immunosuppressant, do not have the chronic nephrotoxic effects shown with calcineurin inhibitors (CNI). Whether these drug classes have distinct features at the molecular level is not clear. MATERIAL/METHODS: Difference in gene expression profiles of kidney graft protocol biopsies from patients treated with CNI or mTOR-i's were investigated. Biopsies from patients using CNI (n=4) and mTOR-i-based treatments (n=4) were analyzed. The control group consisted of 5 biopsies obtained at the time of implantation (zero hour). Microarray hybridization was performed using the Affymetrix® GeneChip U133 plus 2.0 Array. RESULTS: In the CNI and mTOR-i groups, 64 up-regulated and 119 down-regulated genes were found compared to control subjects. A total of 29 genes in the CNI group and 101 genes in the mTOR-i group were up-regulated compared to each other. CONCLUSIONS: Despite similar clinical courses and histopathological appearances, different treatment strategies cause different gene expression profiles in kidney transplantation.

Clostridial collagenase aggravates the systemic inflammatory response in rats with partial-thickness burns.

AIM: Clostridial collagenase A (CCA) has been shown effective in degrading collagen in eschar tissue and promoting healing in partial-thickness burns. As there are also reports of fever, leukocytosis, increased C-reactive protein (CRP) levels and septic complications during treatment with CCA, we aimed to determine in rats whether CCA aggravates the systemic inflammatory response. METHODS: Rats with partial-thickness burns were randomly divided into groups with either no dressing (ND), povidone-iodine dressing (PID) or CCA dressing (CCAD). Body weights and temperatures, blood leukocyte counts, and serum levels of CRP, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), were measured at 0, 3, and 24h and days 3 and 7 from burn. Wounds were cultured on days 1, 3 and 7 and burn depth was evaluated on day 1. RESULTS: Body weights for all groups were significantly lower after burn, with highest loss (25.5%) in the CCAD group. At 3h a significant drop in rectal temperature was noted in all groups. The CCAD group had higher rectal temperature levels than the PID group on days 3 and 7 (p<0.05). Changes in serum levels of CRP, IL-1 beta, IL-6 and TNF-alpha were not significant in the ND and PID groups; the CCAD group showed a significant rise in serum levels of CRP on day 1, of IL-6 on day 3 and of TNF-alpha on day 7. Wound infection was more common in CCAD group and increased on days 3 and 7, but this was insignificant. CONCLUSION: CCA aggravated the systemic inflammatory response in rats with partial-thickness burns, which is accompanied by a higher risk of infection.

The interaction between taxoids and serine/threonine protein phosphatase activities during taxan-induced apoptosis of HL 60 leukemic cells.

Paclitaxel and docetaxel (taxoids) are chemotherapy agents whose mode of action is through an effect on cellular microtubules. Several studies have investigated their potential in the treatment of myeloid malignancies. The aim of our study was to investigate the potential role of the serine/threonine protein phosphatase system in docetaxel/paclitaxel induced cytotoxicity on HL 60 cells. The IC50 dose of paclitaxel and docetaxel were found as 20 and 5 nM respectively using trypan blue dye exclusion and XTT assays. Treating HL 60 cells with docetaxel and paclitaxel resulted in dose and time dependent cytotoxicity. Docetaxel induced the decrease in the activity of protein phosphatase 1 (PP1) and increase in the activity of PP2 subgroups, while paclitaxel induced the increase in the activity of PP1 and decrease in the activity of PP2 subgroups. Potential use of specific protein phosphatase inhibitors or activators in combination with taxoids will open new windows in the treatment of myeloid leukemias.

Sodium selenite protects against diabetes-induced alterations in the antioxidant defense system of the liver.

BACKGROUND: Free radical genesis of disorder is one of the major subjects of discussion in the explanation of pathological conditions. In this study, the effects of micro molar quantities of sodium selenite treatment on diabetes-induced alterations in the antioxidant defense system were investigated. METHODS: Diabetes was induced by administration of streptozotocin (STZ, 50 mg/kg body weight) and both diabetic and control animals were treated with sodium selenite (5 micromol/kg/day) for 4 weeks. RESULTS: Our results have shown that induction of diabetes in the liver tissue of animals for 5 weeks resulted in decreased superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GSHPx) activities and concomitantly increased lipid peroxidation (LPO). CONCLUSION: Sodium selenite treatment of the diabetic rats resulted in almost full restoration of all the parameters mentioned above. Metallothionein, which is known to be one of the major antioxidants and a central protein in heavy metal regulation, is altered by diabetes, and sodium selenite treatment restored this alteration as well.

Infliximab: a new therapeutic agent in acute pancreatitis?

PURPOSE: Tumor necrosis factor alpha (TNF-alpha) has a central role in the pathogenesis of acute pancreatitis and related systemic complications. The aim of this study is to investigate the therapeutic effectiveness of monoclonal TNF antibody (infliximab) in acute edematous and severe necrotizing pancreatitis models in rats. METHODS: One hundred rats were randomly divided into 10 groups. Acute edematous pancreatitis (AEP) was induced by injection of cerulein 20 microg/kg 4 times subcutaneously at hourly intervals. Severe necrotizing pancreatitis (SNP) was induced by retrograde injection of 3% taurocholate into the common biliopancreatic duct. Infliximab 8 mg/kg was given via intravenous infusion. Serum amylase activity, pancreatic histopathology, myeloperoxidase enzyme activity (MPO), and pulmonary changes were assessed. RESULTS: Infliximab treatment significantly decreased serum amylase activity (11939 +/- 1914 U/L versus 3458 +/- 915 U/L, P < 0.001) and histopathologic score (4.1 +/- 0.5 versus 1.5 +/- 0.3, P < 0.001) in AEP. It also suppressed neutrophil infiltration and MPO activity of the pancreatic tissue. In SNP, infliximab treatment was found to decrease pathologic score (9.4 +/- 1.2 versus 3.6 +/- 0.8, P < 0.001) and serum amylase activity (20442 +/- 2375 versus 8990 +/- 1730, P < 0.01). It ameliorated both parenchymal and fatty tissue necrosis of the pancreas. Infliximab also alleviated alveolar edema and acute respiratory distress syndrome like pulmonary complications, but the difference was not significant. CONCLUSIONS: Chimeric TNF antibody, infliximab, should be evaluated for treatment of acute pancreatitis.

Effect of omeprazole on plasma zinc levels after oral zinc administration.

BACKGROUND: The intestines are the major site of zinc absorption and excretion. Reduced gastric acid secretion and elevated gastric pH is an important factor affecting intestinal mineral absorption. METHODS: Gastric pH and volume, and basal and maximal acid outputs were measured in 14 healthy volunteers. Plasma zinc levels were then measured at baseline and 1, 2, 3 and 4 hours after oral administration of 300 mg zinc sulfate. The experiment was repeated after omeprazole administration (60 mg/day orally) for 7 days. RESULTS: Omeprazole administration significantly increased fasting gastric pH (5.5 versus 2.4; p < 0.001). Mean basal gastric acid output (1.6 vs 8.0 mEq/h; p < 0.001) and maximal acid output (20.6 vs 106.6 mEq/h; p < 0.001) decreased after omeprazole administration. Zinc absorption decreased after omeprazole administration (141 [34] mg/dL/h) compared with pre-omeprazole values (245 [35]; p < 0.01). CONCLUSION: Suppression of gastric acid secretion by omeprazole reduces intestinal absorption of zinc.