Particle formation in emulsion polymerization, 1. Oligomers in emulsion polymerization of vinyl acetate

The oligomers formed in the beginning of the emulsion polymerization of vinyl acetate were characterized by surface tension measurements, analysis of molecular weight distribution and light scattering. The results indicate that primary particle formation in the emulsion polymerization of vinyl acetate is due to an oligomeric micellization. Additionally, these oligomers are strongly adsorbed onto highly dispersed silica particles in the aqueous phase. This effect leads to a disaggregation of the filler particles during the beginning of the emulsion polymerization.     

Hormonal effects on the immunocytochemical location of 3',5'-cyclic adenosine monophosphate-dependent protein kinase in rat tissues

Homogeneous preparations of type I and type II regulatory subunits (RI and RII, respectively) of cAMP-dependent protein kinase (cAMP kinase) were utilized as antigens to obtain isozyme specific antisera. Injections of pure catalytic subunit (C) from the type I isozyme resulted in antisera that reacted with C subunit obtained from either isozyme type. Cross-reactivity of the antisera raised against isolated subunits of the kinase was assessed by immunodiffusion analysis and by measuring the cAMP binding and phosphotransferase activities of the subunits after immunoprecipitation. These antisera were used to localize subunits of type I and type II cAMP kinases in rat skeletal muscle, liver, and adrenal by using indirect immunofluorescence and immunoperoxidase techniques. Specificity of the immunofluorescence was shown by absorption of the antisera with pure homologous antigens. In skeletal muscle, both R and C subunits of the type I and type II cAMP kinases were localized in the area of the sarcoplasmic reticulum and in periodic crossbands. Specific fluorescence for these components was observed in both isotropic and anisotropic band regions of the sarcomere. Densitometric determinations of immunoperoxidase staining revealed a larger amount of RI, RII, and C subunits in the isotropic band than in the anisotropic band regions. In liver, C, RI, and RII subunits were distributed both in cytoplasmic and nuclear areas and along plasma membranes of hepatocytes; however, there were qualitative differences observed among these various subcellular sites. With each antiserum, fluorescence was blocked by prior absorption with homologous antigen. After treatment of rats with glucagon, dramatic changes in the relative distribution patterns of C and RII were noted in the nucleus. In the adrenal gland, RI, RII, and C subunits were localized in both cytoplasmic and nuclear areas, and an apparent redistribution of these subunits occurred after treatment of (dexamethasone-suppressed) rats with ACTH. The application of this immunocytochemical approach provides a tool for examining and monitoring the subcellular distribution of these components of cAMP kinase in biological systems.     

New tetracyclic guanidine derivatives with H1-antihistaminic properties. Chemistry of epinastine

A series of new tetracyclic guanidines were synthesized by various methods. Specific binding of the described compounds to histamine-1 and histamine-2 receptors was determined. The compound 3-amino-9,13b-dihydro-1H-dibenz[c,flimidazo[1,5-a]azepine (epinastine, WAL 801, compound IIIa) combines high selectivity with high affinity for the H1 receptor and was selected from the compounds studied for further pharmacological and clinical investigations. Experimentally determined physicochemical parameters (pka-value, partition coefficient) and the hydrogen-bonding ability of epinastine are indications that this compound will not easily cross the blood-brain barrier. This explains the absence of CNS side-effects of epinastine in pharmacological and clinical studies.     

Blood level, metabolism and excretion of [14C]-brotizolam in mice

Blood level, metabolite pattern and excretion of [14C]-brotizolam, a hypnotic drug, were studied in mice following oral administration. [14C]-Brotizolam was rapidly absorbed which was indicated by a Tmax of the blood level of 0.5 h. Radioactive compounds were eliminated from the blood with a half-life of 5.6 h. Total excretion of radioactivity, the renal portion of which was 22.4%, was complete after 4 days. [14C]-Brotizolam was almost completely metabolized. Using TLC, HPLC and radioactivity measurement, the main metabolite in bile, urine and plasma was found to be brotizolam hydroxylated at the methyl group. Other major metabolites were brotizolam hydroxylated at the diazepine ring and a combination of both hydroxylations. In the bile, all metabolites were conjugated. The metabolism of brotizolam in mice is similar to that in dogs, monkeys and man but not in rats.     

Synthesis and antidepressant activity of 4-aryltetrahydrothieno[2,3-c]pyridine derivatives

A series of substituted 4-aryltetrahydrothieno[2,3-c]pyridines was prepared by acid-catalyzed cyclization of 1-aryl-2-[(2-thienylmethyl)amino]ethanol derivatives. The compounds were examined for their antidepressant activity, as demonstrated by their ability to inhibit the uptake of norepinephrine (NE) and serotonin (5-HT) and to prevent tetrabenazine-induced ptosis (TBZ) in mice. Significant inhibition of both neurotransmitters is observed for several of the tested compounds, while some of them are selective inhibitors of either NE or 5-HT uptake. Optimal activity is associated with the introduction of lipophilic substituents into the 4-position of the phenyl ring and less lipophilic substituents into the 2-position of the thiophene ring (11, 23). Compound 33 bearing substituents in positions 2 and 6 of the phenyl ring is inactive. This might be a consequence of an out of plane conformation of this compound.     

Bioavailability of zinc derived from beer and the effect of low dietary zinc intake on skeletal muscle zinc concentration

The bioavailability of zinc from freeze-dried cooked beef was determined using log total tibia zinc and body weight gain as the response criteria. Control diets consisted of different levels of zinc carbonate added to an egg-white protein source. Experimental diets were made by substituting various levels of freeze-dried beef as the zinc source. All diets were isocaloric and isonitrogenous. Zinc in the control diets was utilized as effectively as zinc in the experimental diets. The relative biological value (RBV) of zinc (ZnCO₃=100) in the experimental diet was 103 for 22-day weight gain, and 102 for total tibia zinc. These results indicate that zinc from cooked beef does not have an increased bioavailability over inorganic zinc added to an egg-white protein diet. Because a, large percentage of the total zinc in an animal is found in skeletal muscle, the content of zinc in two types of skeletal muscle was determined from animals fed different levels of dietary zinc. Animals consuming diets with zinc concentrations below their requirement had depressed growth rates; however, no significant differences were found in the zinc concentrations of either the soleus or plantaris muscle. The average zinc content of the soleus muscle (slow twitch oxidative fiber type) was 69 ppm and the plantaris muscle (fast twitch oxidative fiber type) was 15 ppm. These results indicate that the concentration of zinc in skeletal muscle is not significantly reduced in animals whose growth is restricted by low dietary zinc levels.     

Single-shot antithrombin in human pancreas-kidney transplantation: reduction of reperfusion pancreatitis and prevention of graft thrombosis.

Reperfusion pancreatitis and graft thrombosis often induce early graft loss in simultaneous pancreas-kidney (SPK) transplantation. Antithrombin (AT) is a coagulatory inhibitor with pleiotropic activities that reduces experimental ischemia/reperfusion injury. This study retrospectively analyses prophylactic high-dose AT application in patients with first SPK. In an university transplantation center, 53 consecutive patients with SPK were studied without randomization. In one group, 3000 IU of AT was given intravenously before pancreatic reperfusion (AT, n = 24). Patients receiving standard therapy including postoperative AT supplementation (controls, n = 29) served as controls. Daily blood sampling was performed as a part of the clinical routine during four postoperative days. There were no differences in demographic and laboratory parameters [donor/recipient age, ischemia time, perfusion solution, body weight, mismatches] between both groups. Baseline creatinine values were lower in the control group versus AT group (P < 0.05). Coagulatory parameters and bleeding incidence were not influenced by AT, while incidence of graft thrombosis was reduced (control: 7/29; AT: 4/24; relative reduction of risk: -33%; P < 0.05). Single-shot AT application during SPK modulated serum lipase activity on postoperative days 2 and 3, and minimized risk for graft thromboses without increasing perioperative bleeding. This new concept should deserve testing in a prospective clinical trial.     

Significant damage of the conduction system during cardioplegic arrest is due to necrosis not apoptosis.

OBJECTIVES: Ventricular conduction disturbances following cardioplegic arrest remains a serious, yet unsolved problem. In the present study we examined whether myocardial conduction cells (MCC, Purkinje fibers) are more vulnerable to ischemia/reperfusion injury than working myocardial cells and whether the damage is due to necrosis or apoptosis. METHODS: Mini-pigs were subjected to 60 min of crystalloid (St Thomas; n = 15 group I) or blood (Buckberg; n = 6 group II) cardioplegic arrest followed by 3 h of reperfusion. Animals not subjected to either procedures served as controls (n = 5). Ventricular myocardial specimens were investigated by hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining and immunohistochemical labeling of apoptosis-associated proteins (Bax, Bcl-2, Caspase-3). DNA-breaks were visualized by in situ end labeling (terminal deoxynucleotidyl transferase dUTP-biotin nick-end labeling, TUNEL). Electron microscopy confirmed apoptosis or necrosis. RESULTS: MCC of control hearts intrinsically expressed Bax, Bcl-2, and Caspase-3 without signs of either apoptotic or necrotic damage. Subendocardial Purkinje fibers of groups I and II hearts exhibited focal damage, with reduced labeling of apoptosis-associated proteins, glycogen loss, karyopycnosis and increased eosinophilia (15/21 hearts). The majority of damaged MCC displayed nuclear TUNEL-positivity (2.8+/-2.5% of MCC), whereas the average TUNEL-rate of the adjacent working myocardium was low (<0.1%). Electron microscopy demonstrated ischemic changes in MCC consistent with cellular necrosis. CONCLUSIONS: Ischemia/reperfusion injury due to cardioplegic arrest inflicts significant damage on subendocardial MCC, but not on working myocardium. Ultrastructural and light-microscopic findings are consistent with coagulation necrosis, rather than apoptosis.