Der Einfluß des Jodes auf die Kohlensäureproduktion gärender Hefe.

Ohne Zusammenfassung     

Die Lichtempfindlichkeit Blinder Elritzen. (Untersuchungen Über das Zwischenhirn der Fische I.)

Ohne Zusammenfassung     

The histaminergic, but not the serotoninergic, system mediates amylin''s anorectic effect

In the present study, we investigated the influence of blockade of the serotoninergic and histaminergic neurotransmitter system on the anorectic effect of IP-injected amylin in rats. In 12- or 24-h food-deprived rats, blockade of central and peripheral serotonin (5-HT) receptors with the 5-HT₁ and 5-HT₂ receptor antagonist metergoline (0.5 or 0.05 mg/kg, IP, respectively) did not seem to influence the anorectic effect of IP injected amylin (1 μg/kg). Similarly, inhibition of 5-HT synthesis and release with the 5-HT_1A receptor agonist (±)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (200 μg/kg, IP) did not diminish amylin's (5 μg/kg, IP) anorectic effect in 24-h food-deprived rats whereas that of CCK (3 μg/kg, IP) was blocked under comparable conditions. Pretreatment of rats with the histamine H₃ receptor agonists R--methylhistamine (MH; 3 mg/kg, IP) and Imetit (3 mg/kg, IP), which block transmission in the histaminergic system by inhibiting release of endogenous histamine, attenuated amylin's (1 μg/kg) anorectic effect in 24-h food-deprived rats. These results suggest that the histaminergic system is involved in transduction of IP amylin's inhibitory effect on feeding in rats. In contrast, the serotoninergic system does not seem to be involved in mediating amylin's anorectic effect.     

Experimental Analysis of Tablet Properties for Discrete Element Modeling of an Active Coating Process

Coating of solid dosage forms is an important unit operation in the pharmaceutical industry. In recent years, numerical simulations of drug manufacturing processes have been gaining interest as process analytical technology tools. The discrete element method (DEM) in particular is suitable to model tablet-coating processes. For the development of accurate simulations, information on the material properties of the tablets is required. In this study, the mechanical parameters Young’s modulus, coefficient of restitution (CoR), and coefficients of friction (CoF) of gastrointestinal therapeutic systems (GITS) and of active-coated GITS were measured experimentally. The dynamic angle of repose of these tablets in a drum coater was investigated to revise the CoF. The resulting values were used as input data in DEM simulations to compare simulation and experiment. A mean value of Young’s modulus of 31.9 MPa was determined by the uniaxial compression test. The CoR was found to be 0.78. For both tablet–steel and tablet–tablet friction, active-coated GITS showed a higher CoF compared with GITS. According to the values of the dynamic angle of repose, the CoF was adjusted to obtain consistent tablet motion in the simulation and in the experiment. On the basis of this experimental characterization, mechanical parameters are integrated into DEM simulation programs to perform numerical analysis of coating processes.     

Histamine H1 receptors mediate the anorectic action of the pancreatic hormone amylin

We investigated the role of histamine H1 receptors in mediating the anorectic effect of intraperitoneally injected amylin (5 and 20 microg/kg), the amylin agonist salmon calcitonin (sCT; 10 microg/kg), leptin (1.3 mg/kg), and cholecystokinin (CCK; 20 microg/kg). The experiments were performed with mice lacking functional H1 receptors (H1Rko) and wild-type (WT) controls. The mice were also injected with the H3 antagonist thioperamide (20 mg/kg), which reduces feeding by enhancing the release of endogenous histamine through presynaptic H3 receptors. The feeding-suppressive effect of thioperamide was abolished in H1Rko mice. The anorectic effects of amylin and sCT were significantly reduced in 12-h food-deprived H1Rko mice compared with WT mice [1-h food intake: WT-NaCl 0.51 +/- 0.05 g vs. WT-amylin (5 microg/kg) 0.30 +/- 0.06 g (P < 0.01); H1Rko-NaCl 0.45 +/- 0.05 g vs. H1Rko-amylin 0.40 +/- 0.04 g; WT-NaCl 0.40 +/- 0.09 g vs. WT-sCT (10 microg/kg) 0.14 +/- 0.10 g (P < 0.05); H1Rko-NaCl 0.44 +/- 0.08 g vs. H1Rko-sCT 0.50 +/- 0.06 g]. The anorectic effect of leptin was absent in ad libitum-fed H1Rko mice, whereas CCK equally reduced feeding in WT and H1Rko animals. This suggests that the histaminergic system is involved in mediating the anorectic effects of peripheral amylin and sCT via histamine H1 receptors. The same applies to leptin but not to CCK. H1Rko mice showed significantly increased body weight gain compared with WT mice, supporting the role of endogenous histamine in the regulation of feeding and body weight.     

Depolarization of the liver cell membrane by metformin

Metformin (1,1-dimethylbiguanide; MET) is used in the treatment of type 2 diabetes mellitus. MET's antihyperglycemic action depends at least in part on its inhibitory effect on hepatic gluconeogenesis. As to gluconeogenesis from amino acids (e.g. L-alanine), this is associated with an inhibition of L-alanine uptake into hepatocytes. Since this uptake is mediated by an electrogenic transport mechanism, the aim of the present study was to investigate whether MET has an influence on the liver cell membrane potential which might explain its inhibitory effect on L-alanine uptake. The experiments were performed in vivo in anesthetized rats and in vitro using superfused mouse liver slices with the conventional microelectrode technique. In vivo, MET (160 mg/kg intraperitoneally (i.p.)) significantly depolarized (dV) the liver cell membrane by 6 mV. MET (1 mmol/l) also depolarized the liver cell membrane in vitro (e.g. 15 min after start of superfusion: dV=8 mV). MET's effect was at least partly reversible. Glucagon (10(-7) mol/l), which hyperpolarized the liver cell membrane, abolished MET's effect. Further, the MET-induced depolarization was completely absent during superfusion with low Cl(-) ([Cl(-)]=27 mmol/l) medium, and significantly attenuated by the Cl(-) channel blocker NPPB (25 micromol/l). While MET's effect was only somewhat attenuated by blockade of the Na(+)/K(+)/2Cl(-) cotransporter or by superfusion with (HCO(-)(3)-free) HEPES buffer, the carboanhydrase blocker acetazolamide (1 mmol/l) or blockade of the HCO(-)(3)/Cl(-) exchanger by DIDS (100 micromol/l), which, however, also blocks Cl(-) channels, abolished its effect. The depolarization of the liver cell membrane by MET was unaffected by a blockade of K(+) channels with Ba(2+), a blockade of the Na(+)/K(+) pump or superfusion with low Na(+) medium ([Na(+)]=26 mmol/l). According to these results, the MET-induced depolarization of the liver cell membrane could be due to an activation of the Cl(-)/HCO(-)(3) exchanger and thus depend on intracellular HCO(-)(3) formation. This activation could then lead to a disturbance of the equilibrium between intra- and extracellular Cl(-) and therefore to an enhanced Cl(-) efflux via Cl(-) channels. It is plausible that the depolarizing effect induced by MET is associated with its inhibitory effect on gluconeogenesis by inhibiting uptake of L-alanine and other amino acids into hepatocytes.     

Characteristics of Na(+)-dependent intestinal nucleoside transport in the pig

Since the capacity of nucleic acid digestion and absorption appears to be comparatively high in the pig, we investigated the properties of transport of (3)H-labelled nucleosides across the porcine intestinal brush border membrane (BBM) using BBM vesicles isolated from the small intestine of slaughter pigs. In the presence of a transmembrane Na(+) gradient, uridine, thymidine and guanosine transiently accumulated in the vesicular lumen beyond the equilibrium (60 min) value suggesting the presence of Na(+)/nucleoside cotransporters in the BBM. The findings of inhibitory studies are consistent with the presence of two Na(+)-dependent nucleoside transporters with overlapping substrate specificity, one for pyrimidine nucleosides (N2) and one for purine nucleosides (N1). Guanosine appeared to be a specific substrate for N1, while this applies to thymidine for N2. Transport of thymidine and guanosine were also inhibited by 2 mmol/l D-glucose and alpha-methyl-D-glucoside. The maximal transport capacity (V(max)) for Na(+)-dependent thymidine and guanosine transport were much higher than reported for other monogastric species. Unlike in other species tested, there was no proximal-to-distal gradient, neither in nucleoside transport activity nor in the inhibition of nucleoside transport by monosaccharides in the porcine small intestine. The high intestinal nucleoside transport activity may contribute to the high digestive capacity for nucleic acids in the pig.     

The Neuropeptide Saga

Neuropeptides are regulatory molecules produced by neural andnon-neural tissues. They are engaged in multiple forms of receptor-mediatedintercellular communication,ranging from hormonal (blood-borne)to close-range (synapse-like) signalling. In their neurohormonalcapacity, these peptides convey directives from the nervousto the endocrine system, as well as to terminal target tissues.As participants in interneuronal chemical communication, neuropeptidesmay act as neurotransmitters, or as modulators of signals exchangedbetween synaptically linked neurons. Outside the realms of neuroendocrinologyand neurobiology, peptidergic messenger substances carry outa variety of functions, including autoregulatory and integrativeactivities in the immune system     

Leukotriene and purinergic receptors are involved in the hyperpolarizing effect of glucagon in liver cells

The pancreatic hormone glucagon hyperpolarizes the liver cell membrane. In the present study, we investigated the cellular signalling pathway of glucagon-induced hyperpolarization of liver cells by using the conventional microelectrode method. The membrane potential was recorded in superficial liver cells of superfused mouse liver slices. In the presence of the K+ channel blockers tetraethylammonium (TEA, 1 mmol/l) and Ba2+ (BaCl2, 5 mmol/l) and the blocker of the Na+/K+ ATPase, ouabain (1 mmol/l), no glucagon-induced hyperpolarization was observed confirming previous findings. The hyperpolarizing effect of glucagon was abolished by the leukotriene B4 receptor antagonist CP 195543 (0.1 mmol/l) and the purinergic receptor antagonist PPADS (5 micromol/l). ATPgammaS (10 micromol/l), a non-hydrolyzable ATP analogue, induced a hyperpolarization of the liver cell membrane similar to glucagon. U 73122 (1 micromol/l), a blocker of phospholipase C, prevented both the glucagon- and ATPgammaS-induced hyperpolarization. These findings suggest that glucagon affects the hepatic membrane potential partly by inducing the formation and release of leukotrienes and release of ATP acting on purinergic receptors of the liver cell membrane.     

Reproduction in a female patient with Down's syndrome. Case report of a 46, XY child showing slight phenotypical anomalies, born to a 47, XX, + 21 mother.

A non-mongoloid boy born to a mongoloid mother is described. He showed aplasia of the left 5th finger and some clinical and dermatoglyphic features frequently found in Down's syndrome. Chromosome analysis revealed few hyperdiploid but no G-trisomic cells. An undetected G-trisomy mosaic, or a mechanism of extrachromosomal inheritance, and an embryonic development in a pathological milieu are discussed.