Purification of a 5-HT uptake inhibitor from the venom of Cerastes vipera

Heart rate (HR) and heart rate variability (HRV) are risk markers in cardiac disease. HRV is also an index of the sympathovagal modulation of heart rate. Their relations have been rarely analyzed. We aimed to study such relations in normal adult conscious rats by using a novel bradycardic agent, a sinus node inhibitor, S-16257. Placebo-drug crossover designs were used while monitoring HR with telemetry and analyzing HRV in both time and frequency domains. S-16257 (2 mg/kg; n = 10) decreased HR by 29% and markedly increased HRV in parallel. By using various combinations of S-16257, atropine (2 mg/kg), and propranolol (4 mg/kg), a positive relation was shown between RR interval and various indexes of HRV: the slower the HR, the greater the HRV. Nevertheless, there is one exception to this correlation. When S-16257 was associated with both atropine and propranolol, the deep bradycardia was accompanied by a reduction of HRV, which indicates that the physiologic negative correlation between HR and HRV is not an intrinsic property of the pacemaker but is highly dependent on the two components of the autonomic system.     

Low-frequency vibrations in the treatment of patients with acute maxillary sinusitis and ethmoiditis. Non-specific resistance and immunity

Effect of sodium hypochlorite disinfection of impressions on the size and quality of plaster models is studied. Twenty-minute submerging of silicone impressions in 0.5% sodium hypochlorite solution did not change their size and did not deteriorate the quality of surface and hardness of plaster models. Stomalgin impressions cannot be disinfected by sodium hypochlorite solution because of expressed destructive effect of this disinfectant on the impressions.     

Age-associated alterations in calcium current and its modulation in cardiac myocytes

Stimulatory effects of several types of adjuvants on secondary antibody response to inactivated Newcastle disease virus (iNDV) were examined in chickens. For this purpose, animals were primed with iNDV without adjuvant resulting in a low but significant antibody response, boosted with iNDV plus adjuvant 3 weeks later, and analysed for specific antibody titres in serum 3 weeks after the booster. Water-in-mineral oil emulsion (W/O) caused significant increase in antibody titres measured in an indirect enzyme-linked immunosorbent (ELISA), haemagglutination inhibition (HI), and virus neutralisation (VN) assay. The adjuvants tested included three oil-in-water emulsions (i.e. mineral oil-in-water, sulpholipo(SL)-Ficoll400/squalane-in-water and sulpholipo-cyclodextrin/squalane-in-water), three negatively-charged polymers with high molecular weight (i.e. polyacrylate, polystyrenesulphonate and sulpho(S)-Ficoll400) and two surface-active agents (i.e. dimethyldioctadecylammonium bromide (DDA) and Quil A). These adjuvants enhanced significantly the secondary immune response but none reached the titre obtained with W/O. Combinations of adjuvants with distinct physicochemical properties, i.e. polyacrylate and DDA revealed only slight, beneficial effects. We concluded that the various types of adjuvants tested can stimulate secondary immune responses in primed animals but that W/O is superior.     

Multicenter prospective study of the current status of treatment for bleeding ulcer in Germany

The current state of ulcer treatment in Germany was analysed in a prospective multi-centre study. It was based on 1139 consecutive patients admitted to the participating hospitals because of upper gastrointestinal bleeding. The source of the bleeding was identified by diagnostic endoscopy in 1075 patients (94%), from a gastric and/or duodenal ulcer in 546 of them (mean age 62 +/- 18 years). Using Forrest's classification, 4% of patients were in bleeding stage Ia, 17% in stage Ib, 16% stage IIa, 30% stage IIb and 33% stage III. An attempt to arrest bleeding through the endoscope was made in 233 patients (43%): more often with tissue-preserving substances (epinephrine +/- NaCl in 36%, fibrin glue +/- epinephrine in 24%) than with tissue-damaging procedures (epinephrine + polidocanol +/- NaCl in 26%, epinephrine + thermocoagulation in 7%). Primary haemostasis was achieved in 219 patients (94%). There was a total of 66 recurrences of bleeding (12%), but the rate was 18% after endoscopic haemostasis. 64 patients (12%) required operative intervention, including initial emergency operations. Severe complications (infections, organic failure) occurred in 82 patients (16%). 114 of the 546 patients were in the high risk group (older than 60 years; high amount of bleeding). Their bleeding recurrence and mortality rates (27 and 22%, respectively) were significantly higher (P < 0.01) than those of the total group. Overall mortality rate was 11% (58 patients). The mortality rate depended on the severity of initial bleeding (26% for Forrest group Ia). After recurrent bleeding the mortality rate was 34% with conservative and 33% with operative treatment. 7% of all deaths were the direct result of bleeding. The following factors prognostically closely correlated with mortality rate: age of patient (P < 0.01); haemoglobin < 8 g/dl on admission (P < 0.05); initial severity of bleeding (Forrest group I; P < 0.05); and recurrence of bleeding (P < 0.001).     

Synthesis and structure elucidation of estrogen quinones conjugated with cysteine, N-acetylcysteine, and glutathione

A micromechanical model for predicting the densification of particulate matter under hydrostatic loading was developed to account for the time-dependent response of materials to applied loads. Viscoelastic material response used in the analysis was based upon a standard three-parameter rheological model. Compaction data under closed die conditions were collected using an Instron analyzer for different rates of applied load. Densification during the loading phase of PMMA/coMMA powder, a pharmaceutical polymeric coating material, was well predicted by the proposed algorithm, which contrasts with the prediction implied through a static indentation model. Secondary factors which affect compaction such as die-wall friction are also briefly discussed.     

Vitamin E modifies neither fructosamine nor HbA1c levels in poorly controlled diabetes

OBJECTIVE: To examine the effects of vitamin E on total serum protein glycation (fructosamine), hemoglobin glycation (HbA1c), and serum levels of glucose, total cholesterol, triglycerides, LDL-C, HDL-C, apolipoprotein A1 and apolipoprotein B. MATERIAL AND METHODS: Sixty poorly controlled diabetic patients were randomly assigned to receive either 1200 mg/day of vitamin E or identical placebo capsules during a two month period following a double blind cross-over design with a four week wash-out period between regimens. RESULTS: Seven patients were excluded from the study because of reasons not related to the medication. In the remaining 53 patients, the levels of serum glucose, fructosamine, HbA1c, total cholesterol, HDL-C, LDL-C, Apo A1 and Apo B did not vary significantly with vitamin E as compared with placebo. CONCLUSIONS: No significant effects of vitamin E on any of the parameters evaluated were observed in poorly controlled diabetic patients.     

Prodrugs of nitroxyl and nitrosobenzene as cascade latentiated inhibitors of aldehyde dehydrogenase

The prototypic aromatic C-nitroso compound, nitrosobenzene (NB), was shown previously to mimic the effect of nitroxyl (HN=O), the putative active metabolite of cyanamide, in inhibiting aldehyde dehydrogenase (AlDH). To minimize the toxicity of NB in vivo, pro-prodrug forms of NB, which were designed to be bioactivated either by an esterase intrinsic to AlDH or the mixed function oxidase enzymes of liver microsomes, were prepared. Accordingly, the prodrug N-benzenesulfonyl-N-phenylhydroxylamine (3) was further latentiated by conversion to its O-acetyl (1a), O-methoxycarbonyl (1b), O-ethoxycarbonyl (1c), and O-methyl (2) derivatives. Similarly, pro-prodrug forms of nitroxyl were prepared by derivatization of the hydroxylamino moiety of methanesulfohydroxamic acid with N, O-bis-acetyl (7a), N,O-bis-methoxycarbonyl (7b), N, O-bis-ethoxycarbonyl (7c), and N-methoxycarbonyl-O-methyl (7d) groups. It was expected that the bioactivation of these prodrugs would initiate a cascade of nonenzymatic reactions leading to the ultimate liberation of NB or nitroxyl, thereby inhibiting AlDH. Indeed, the ester pro-prodrugs of both series were highly active in inhibiting yeast AlDH in vitro with IC50 values ranging from 21 to 64 microM. However, only 7d significantly raised ethanol-derived blood acetaldehyde levels when administered to rats, a reflection of the inhibition of hepatic mitochondrial AlDH-2.     

Comparison of a functional obstacle course with an index of clinical gait and balance and postural sway

BACKGROUND: Older adults commonly experience falls because of balance and mobility problems. Better assessment methods are needed to understand and correct balance and mobility disorders. METHODS: We used a low technology, functional obstacle course (FOC) to measure balance and mobility in 352 community-dwelling elderly participants. To establish concurrent validity of the FOC, we compared performance on the FOC with two established measures of balance and mobility: performance on the Tinetti Index (TI) and postural sway area measured on a force platform. RESULTS: Bivariate correlation analyses revealed significant inverse correlations between FOC completion time, the TI balance and gait subscores, and the TI total score (r = -.73 to -.78). The FOC quality scores and TI balance and subscores gait and TI total scores (r = .76 to .82) were significantly positively correlated. FOC time had significant, but small, positive correlations with sway area with eyes open (r = .18) and closed (r = .17) and nonsignificant correlation with sway area with visual feedback. FOC quality also had significant, but smaller, inverse correlations with sway area with eyes open (r = -.024) and closed (r = -.015), and nonsignificant correlation with sway area with visual feedback. Regression analysis showed that TI gait and balance measures accounted for most of the variance found in FOC performance. CONCLUSIONS: Our findings support the position that the FOC and the TI measure dynamic balance, whereas postural sway measures a different aspect of balance. Advantages of the FOC include the evaluation of environmentally influenced falls and balance problems.