Food preservatives sodium sulfite and sorbic acid suppress mitogen-stimulated peripheral blood mononuclear cells

Antioxidant preservatives prolong the quality of food and ensure the nutritional adequacy, palatability and safety of many processed foods and beverages. Effects of sodium sulfite (E221) and sorbic acid (E200) were investigated in human peripheral blood mononuclear cells (PBMC) which were purified from blood of healthy donors. Cells were stimulated with the mitogen phytohaemagglutinin in vitro, which induces proliferation of T-cells and the production of Th1-type cytokines like interferon-γ. The latter triggers enzyme indoleamine (2,3)-dioxygenase, which degrades tryptophan, and GTP cyclohydrolase I, which leads to increased neopterin production, in monocyte-derived macrophages. Sodium sulfite and sorbic acid suppressed both these biochemical changes in a dose-dependent way (P < 0.01 at 1 mM sodium sulfite and 50 mM sorbic acid). Data demonstrate a suppressive influence of sodium sulfite and sorbic acid on the activated Th1-type immune response.     

Modulation of ryanodine-induced contractures in human skeletal muscle pretreated with dantrolene

Dantrolene seems to be the causal therapy in malignant hyperthermia (MH) crisis but the complex mechanisms of MH and dantrolene therapy are still not fully understood. The influence of dantrolene on ryanodine-induced contractures has been reported in animal studies only. In the present study 20 patients from] 7 families were tested for MH using the protocol of the European Malignant Hyperthermia Group. In addition ryanodine-induced contractures were evaluated following bolus application of 10.0 μmol · 1^-1 ryanodine. After pretreatment with 1 μimol · 1^-1 dantrolene ryanodine-provoked contractures developed significantly later in MHS (15.8±1.8 min) and MHN (46.0±4.2 min) muscle specimens than after ryanodine alone (MHS 4.8±0.7 min), (MHN 13.7±0.9 min). They were no longer observed in either group after pretreatment with 5 μimol · 1^-1 dantrolene. We conclude that dantrolene is able to attenuate ryanodine-induced contractures dose-dependendy, and therefore it is speculated that dantrolene could specifically act at the ryanodine receptor binding site.     

Literaturübersicht

Ohne Zusammenfassung     

Vergiftungen durch Trinitrotoluol und durch Tetranitromethylanilin

Ohne Zusammenfassung     

Amnesic Concentrations of the Nonimmobilizer 1,2-Dichlorohexafluorocyclobutane (F6, 2N) and Isoflurane Alter Hippocampal θ Oscillations In Vivo

Background: Drug-induced temporary amnesia is one of the principal goals of general anesthesia. The nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, also termed 2N) impairs hippocampus-dependent learning at relative, i.e., lipophilicity-corrected, concentrations similar to isoflurane. Hippocampal [theta] oscillations facilitate mnemonic processes in vivo and synaptic plasticity (a cellular model of memory) in vitro and are thought to represent a circuit level phenomenon that supports memory encoding. Therefore, the authors investigated the effects of F6 and isoflurane on [theta] oscillations (4-12 Hz).

Methods: Thirteen adult rats were implanted with multichannel depth electrodes to measure the microelectroencephalogram and were exposed to a range of concentrations of isoflurane and F6 spanning the concentrations that produce amnesia. Five of these animals also underwent control experiments without drug injection. The authors recorded the behavioral state and hippocampal field potentials. They confirmed the electrode location postmortem by histology.

Results: The tested concentrations for isoflurane and F6 ranged from 0.035% to 0.77% and from 0.5% to 3.6%, respectively. Isoflurane increased the fraction of time that the animals remained immobile, consistent with sedation, whereas F6 had the opposite effect. Electroencephalographic power in the [theta] band was less when the animals were immobile than when they explored their environment. F6 suppressed the power of oscillations in the [theta] band. Isoflurane slowed [theta] oscillations without reducing total power in the [theta] band.     

Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures.

Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR-based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis. INTRODUCTION: Lactase deficiency is a common autosomal recessive condition resulting in decreased intestinal lactose degradation. A -13910 T/C dimorphism (LCT) near the lactase phlorizin hydrolase gene, reported to be strongly associated with adult lactase nonpersistence, may have an impact on calcium supply, bone density, and osteoporotic fractures in the elderly. MATERIALS AND METHODS: We determined LCT genotypes TT, TC, and CC in 258 postmenopausal women using a polymerase chain reaction-based assay. Genotypes were related to milk intolerance, nutritional calcium intake, intestinal calcium absorption, bone mineral density (BMD), and nonvertebral fractures. RESULTS: Twenty-four percent of all women were found to have CC genotypes and genetic lactase deficiency. Age-adjusted BMD at the hip in CC genotypes and at the spine in CC and TC genotypes was reduced by -7% to -11% depending on the site measured (p = 0.04). LCT(T/C-13910) polymorphisms alone accounted for 2-4% of BMD in a multiple regression model. Bone fracture incidence was significantly associated with CC genotypes (p = 0.001). Milk calcium intake was significantly lower (-55%, p = 0.004) and aversion to milk consumption was significantly higher (+166%, p = 0.01) in women with the CC genotype, but there were no differences in overall dietary calcium intake or in intestinal calcium absorption test values. CONCLUSION: The LCT(T/C-13910) polymorphism is associated with subjective milk intolerance, reduced milk calcium intake, and reduced BMD at the hip and the lumbar spine and may predispose to bone fractures. Genetic testing for lactase deficiency may complement indirect methods in the detection of individuals at risk for both lactose malabsorption and osteoporosis.     

Ileal release of glucagon-like peptide-1 (GLP-1)

There is evidence that the distal intestine participates in the regulation of gastric motor and secretory function. It was the aim of this study to examine in greater detail the effects of ileal nutrient exposure on human gastric acid secretion and to investigate potential intermediary mechanisms. Twelve normal subjects were intubated with an oroileal multilumen tube assembly for gastric, duodenal, and ileal perfusion of marker and test solutions, aspiration, and intestinal manometry. We studied ileal effects on gastric acid output in the unstimulated, interdigestive state (during early phase II,N=6), and during endogenous stimulation by intraduodenal essential amino acid perfusion,N=6) and on release of candidate humoral mediators, peptide YY (PYY) and glucagonlike peptide-1 (GLP-1), both known inhibitors of human gastric acid secretion. Compared with ileal saline perfusion, ileal carbohydrate (total caloric load: 60 kcal) decreased interdigestive gastric acid output by 64% (P<0.01), and endogenously stimulated output by 68%, respectively (P<0.005). Under all experimental conditions, ileal carbohydrate increased plasma GLP-1 by 80–100% (allP<0.005). Ileal lipid perfusion had similar inhibitory effects on gastric acid output and stimulatory effects on GLP-1 release as had ileal carbohydrate. By contrast, ileal perfusion with peptone had no or only weak effects on either acid output or plasma GLP-1. Plasma PYY concentrations and suppression of gastric secretion in response to ileal perfusions were not correlated. In humans, both interdigestive and endogenously stimulated gastric acid output are inhibited in response to intraileal carbohydrate or lipids, but not protein, Decreased acid output is associated with release of GLP-1, but not PYY. These findings support the hypothesis that the distal small intestine may participate in the late postprandial inhibitory regulation of gastric secretory function in humans and that GLP-1 may be an intermediary factor.     

Klinische Wertigkeit einer dermatoskopischen Klassifikation von Clark‐Nävi

Background and objectives: The aim of this study was to evaluate the practical value of the dermatoscopic classification of Clark nevi Patients and methods: Dermatoscopic images of 268 lesions clinically and dermatoscopically diagnosed as Clark nevi were presented to 2 dermatologists without knowledge of the histological diagnosis. The dermatologists evaluated the lesions according to a simplified version of the classification scheme for Clark nevi proposed by Hofmann‐Wellenhof and differentiated between 12 different types of Clark nevi. Results: The most common type of Clark nevus was the reticular‐homogenous type (n = 64, 23,9 %), followed by the globular‐homogeneous type (n = 32, 12 %) and by the homogenous type (n = 30, 11,2 %). The overall inter‐rater agreement between the examiners was moderate to good (kappa = 0,58). The highest level of agreement was found for the peripheral hyperpigmented type (kappa = 0,83). Histologically, 17 lesions (6,3 %) were diagnosed as melanomas. The frequency of melanoma was highest among the peripheral‐hyperpigmented type for one observer and among the homogenous type for the other observer. No melanoma was found among the globular, reticular‐globular, and the central‐hyperpigmented types. Conclusions: A dermatoscopic classification of Clark nevi is practically feasible and allows – to some extent – a risk stratification of Clark nevi, which could be useful for clinical management.