Gastrointestinal and systemic uptake of bismuth in mice after oral exposure

Bismuth compounds have been used in medicine for more than 200 years. In recent years, bismuth has gained renewed interest as a remedy for eradication of gastrointestinal pathogens, especially Helicobacter pylori. In this study we describe the anatomical distribution of bismuth in the gastrointestinal tract and other organs after oral exposure in a mouse model. After exposure of the experimental animals to ranitidine bismuth citrate or bismuth citrate, we used the autometallographic silver enhancement technique to demonstrate the presence of bismuth in tissue samples from the gastrointestinal tract, liver, spleen, thymus, kidney and lymph nodes. We exposed cultured murine peritoneal macrophages to bismuth citrate and examined the bismuth accumulation over time. We found that in the mouse bismuth is absorbed systemically after a single dose of either compound, ranitidine bismuth more easily than bismuth citrate. Uptake could be shown in the stomach, duodenum, ileum and kidney for hours after exposure. Weeks after the exposure, deposits of bismuth were found in lymph nodes, liver, spleen and kidney as well as in macrophages in the gastrointestinal lamina propria. At the subcellular level, bismuth was found exclusively in lysosomes, primarily in macrophages and dendritic cells. Subsequent analyses of macrophage cultures showed lysosomal accumulations to be time and dose dependent.     

No increased risk of hypoglycaemic episodes during 48 h of subcutaneous glucagon-like-peptide-1 administration in fasting healthy subjects

Objective  It is uncertain whether the ability to avoid hypoglycaemia during fasting is preserved, and the risk of reactive hypoglycaemia after an oral glucose stimulus following a prolonged fasting period is increased at augmented glucagon-like peptide-1 (GLP-1) levels.
Design  A randomized, double-blind placebo-controlled cross-over study in eight healthy men to assess the safety, in terms of hypoglycaemia, of a continuously infused pharmacological dose of native GLP-1 during long-term fasting. After an overnight fast the fasting period continued for 48 h and was followed by a 3-h oral glucose tolerance test (OGTT). GLP-1(7-36 amide) or placebo was continuously infused subcutaneously and titrated to a dose of 4·8 pmol/kg per min.
Results  Two subjects in the GLP-1 group and one subject in the placebo group were withdrawn due to protocol specified plasma glucose (PG) ≤ 2·8 m m and neuroglycopaenic symptoms.
The infusion of GLP-1 resulted in pharmacological levels of intact GLP-1. During the fasting period PG, insulin and C-peptide levels declined and glucagon, GH and free fatty acid (FFA) levels increased with no differences between GLP-1 and placebo. During OGTT circulating levels of insulin and C-peptide were higher with GLP-1 infusion. However, PG was similar during GLP-1 vs. placebo infusions. GLP-1 infusion increased norepinephrine and cortisol levels during OGTT.
Conclusion  The counter-regulatory response during 48 h of subcutaneous GLP-1 infusion was preserved despite long-term fasting with no apparent increased risk of hypoglycaemic episodes. No reactive hypoglycaemia was observed when the fast was followed by an OGTT. Thus use of long-acting GLP-1 analogues may not increase the risk of hypoglycaemia.     

Tonsillectomy: assessment of quality by consultation rate after discharge.

The aim of this prospective study was to establish a measure of short-term quality of treatment after tonsillectomy/adenotonsillectomy. One hundred and thirty-four questionnaires, returned after 14 days, from 41 children and 93 adults were analysed. Forty-seven per cent had one or more consultations with health-care professionals. Eighty-three consultations by telephone and 33 consultations in person were made. Two recent studies reported higher consultation rates in person to doctors compared to this study. The predominant reason for consulting health-care professionals was pain. Maximum pain scores were significantly higher among those with consultations vs. no consultations (p = 0.0001). Additionally, the intensity as well as the duration of maximal pain increased with the number of contacts per patient (p = 0.0001, p = 0.0045). Sixty-four per cent felt relieved after consultation by telephone and 83 per cent felt relieved after consultation in person. The present study suggests consultation rate as a parameter of quality of treatment and quality of information.     

Zinc-transporter genes in human visceral and subcutaneous adipocytes: lean versus obese

Zinc ions influence adipose tissue metabolism by regulating leptin secretion and by promoting free fatty acid release and glucose uptake. The mechanisms controlling zinc metabolism in adipose tissue are unknown. We therefore examined the gene-expression levels of a number of zinc-transporting proteins in adipose tissue, comparing subcutaneous fat with visceral fat from lean and obese humans. Both ZnT-proteins responsible for zinc transport from cytosol to extracellular compartments and intracellular vesicles and Zip-proteins responsible for zinc transport to the cytoplasm were expressed in all samples. This suggests that zinc metabolism in adipocytes is actively controlled by zinc-transporters. The expression levels were different in lean and obese subjects suggesting a role for these proteins in obesity. Furthermore, the expression levels were different from subcutaneous fat to intra-abdominal fat suggesting that the metabolic activity in adipocytes is to some extent dependent upon zinc and the activity of zinc-transporting proteins or vice versa.     

No association of seropositivity for anti-Borrelia IgG antibody with mental and physical complaints

Undiagnosed chronic Lyme disease caused by Borrelia burgdorferi is considered a differential diagnoses in medically unexplained symptoms like arthralgias, distal paresthesias, depressive symptoms, lack of concentration and fatigue. The aims of the study were to assess the association of mental and physical complaints with seropositivity for anti-Borrelia IgG in a general population sample. Seropositivity indicated an infection with Borrelia in the past. The Study of Health in Pomerania was conducted in a community living in a region with endemic Lyme disease. Mental and physical complaints were assessed on 38 items with the von Zerssen's complaint scale. IgG antibodies to Borrelia were determined by ELISA in 4264 individuals. Seropositivity was analyzed applying two cut-off scores (>5 and >10 IU/ml). IgG antibodies to Borrelia were found positive in 388 subjects (9.1%) applying the >5 IU/ml cut-off and in 130 subjects (3.0%) applying the >10 IU/ml cut-off. In multivariate analyses (MANCOVA), both definitions of seropositivity were not associated with increased mental or physical complaints while adjusting for gender, age, employment status, rural residency, physical activity, diabetes mellitus and number of chronic diseases. In the general population, seropositivity for anti-Borrelia IgG antibodies was not associated with an increase of self-rated mental or physical complaints or impairments. Therefore, clinicians should not overvalue seropositivity for anti-Borrelia IgG as a medical cause for unexplained mental or physical complaints.     

Experimentally induced lipid peroxidation after exposure to chromium, mercury or silver: interactions with carbon tetrachloride.

Chromium, along with other heavy metals, induces an increased production of malondialdehyde (MDA), an indicator of lipid peroxidation, in liver and kidney tissue of NMRI male mice. After acute intoxications MDA levels remain high for 60 min. and thereafter return to normal in the kidney whereas MDA levels in liver are still increased 48 hr after exposure. Exposure of mice to chromium, mercury, or silver and another stimulator of lipid peroxidation, carbon tetrachloride, showed synergism between inorganic mercury and CCl4. Pre-exposure to chromium, organic mercury, or silver at selected doses did not enhance CCl4-toxicity as measured by organ content of MDA.     

Non-steady State Analysis of the Pharmacokinetic Interaction between Propofol and Remifentanil

Background: The pharmacokinetics of both propofol and remifentanil have been described extensively. Although they are commonly administered together for clinical anesthesia, their pharmacokinetic interaction has not been investigated so far. The purpose of the current investigation was to elucidate the nature and extent of pharmacokinetic interactions between propofol and remifentanil.

Methods: Twenty healthy volunteers aged 20-43 yr initially received either propofol or remifentanil alone in a stepwise incremental and decremental fashion via a target controlled infusion. Thereafter, the respective second drug was infused to a fixed target concentration in the clinical range (0-4 [mu]g/ml and 0-4 ng/ml for propofol and remifentanil, respectively) and the stepwise incremental pattern repeated. Frequent blood samples were drawn for up to 6 h for propofol and 40 min for remifentanil after the end of administration and assayed for the respective drug concentrations with gas chromatography-mass spectrometry. The time courses of the measured concentrations were fitted to standard compartmental models. Calculations were performed with NONMEM. After having established the individual population models for both drugs and an exploratory analysis for hypothesis generation, pharmacokinetic interaction was identified by including an interaction term into the population model and comparing the value of the objective function in the presence and absence of the respective term.

Results: The concentration-time courses of propofol and remifentanil were described best by a three- and two-compartment model, respectively. In the concentration range examined, remifentanil does not alter propofol pharmacokinetics. Coadministration of propofol decreases the central volume of distribution and distributional clearance of remifentanil by 41% and elimination clearance by 15%. This effect was not concentration-dependent in the examined concentration range of propofol.