In comparison: 1.064 μm-1.318 μm Nd-YAG continuous wave lasers. In vitro and in vivo experiments for endoscopic tumour therapy in the gastrointestinal tract

In in vitro and animal experiments the tissue effects of the 1.318m Nd-YAG laser were compared to those of the standard 1.064m Nd-YAG laser in order to evaluate the advantages of the new wavelength with a ten times higher absorption in water for gastroenterological tumour treatment. Under irradiation parameters related to clinical endoscopic practice, the laser of the wavelength 1.318m needs for both vaporization and coagulation significantly less energy than the 1.064m laser. Since vaporization at 1.318m is always accompanied by a higher coagulation effect compared to 1.064m the risk of late necrosis and resulting perforation appears to be increased.     

Cardiovascular effects of endothelin 1 in pithed spontaneously hypertensive rats: evaluation of its mechanism(s) of action

Summary The present experiments were carried out to investigate the cardiovascular effects of endothelin 1 (ET) in pithed spontaneously hypertensive (SH) rats and to evaluate its mechanism of action. The results show that ET (0.1 – 3 nmol/kg i.v.) is a powerful vasoconstrictor agent in the pithed rat. However, at a dose of 3 nmol/kg i.v. all the pithed animals died following a gradual decrease in mean arterial blood pressure and pulse pressure and changes in the form of the electrocardiogram (ECG). The predominant feature of the change in the ECG was a progressive decrease in the amplitude of the T wave resulting in a depression of the curve representing repolarization. Investigations in isolated perfused SH rat hearts showed that ET powerfully reduces coronary flow concentration-dependently (IC₅₀ 2.1 ±0.3 nM) an effect associated with sinus bradycardia and a decrease in coronary pressure amplitude. No overt ECG changes were seen. Control experiments with mechanical flow restriction suggest that bradycardia is a consequence of reduced coronary flow and that the ECG changes observed in vivo can be explained on the basis of coronary insufficiency and resulting myocardial hypoxia. Vasoconstrictor responses to angiotensin II (0.4 g/kg i.v.), phenylephrine (8 g/kg i.v.) and ET (0.5 nmol/kg i.v.) were antagonised by around 70% by isradipine (0.03 mg/kg i.a.). The results suggest that endothelin-induced vasoconstriction may involve receptor operated channel activation and opening of voltage sensitive Ca²⁺ channels.Send offprint requests to A. K. Mir at the above address     

Pharmacokinetics and tolerance of a new penem antibiotic,FCE 22101, in healthy volunteers after a single intravenous dose

Summary The clinical tolerance and pharmacokinetics of FCE 22101 (sodium (5R, 6S)-6-[(1R)-hydroxyethyl]-2-carbamoyloxymethyl-2-penem-3-carboxylate), a new penem antibiotic, have been studied after giving a single i.v. dose of 4 mg·kg^–1 to ten healthy male volunteers. The pharmacokinetics was estimated according to a two-compartment open model. The peak plasma concentration (C_max) was 15.5 (1.08) µg·ml^–1, mean (SEM). FCE 22101 was rapidly cleared from the systemic circulation [ =44.2 (4.2) min; CL=7.21 (0.47) ml·kg^–1·min^–1]. The mean apparent volume of distribution at steady-state was 246 (16.9) ml·kg^–1. The mean residence time relative to the 10 min infusion was 39.4 (1.5)min. Urinary recovery of FCE 22101 showed wide inter-subject variation, ranging from 10.2 to 53.6% of the dose. No subject complained of adverse effects.     

陡脉冲电场对荷瘤BALB/c小鼠癌细胞杀伤效应的实验研究

观测陡脉冲电场对荷瘤BALB/c小鼠癌细胞的杀伤效应。处理后的癌细胞在光镜下表现为细胞核固缩、核碎裂、核溶解;在电镜下表现为异染色质增加,边集,呈团块样改变,细胞质肿胀,脂滴数量增加,质膜破裂;核固缩,碎裂,线粒体肿胀。实验揭示了陡脉冲电场能有效地杀伤癌细胞,明显抑制了荷瘤小鼠恶性肿瘤的生长、增殖,有着良好的应用前景。     

The genetic fine structure of nonsense suppressors in Schizosaccharomyces pombe

Summary Meiotic fine-structure maps of two efficient UGA suppressors of Schizosaccharomyces pombe which are known (sup8-e) or inferred (sup10-e) to code for two leucine tRNAs carrying the mutant anticodon U^*CA (Kohli et al. 1979, 1980a, b; Wetzel et al. 1979; Mao et al. 1981) are presented. In both cases, the recombination frequencies given by the primary site of the anticodon mutation fitwell into the map defined by the sites of a number of inactivating secondary mutations. This contrasts the corresponding situation found in the serine tRNA genes sup3 and sup9 where the anticodon site exhibits a specific marker effect which strongly increases recombination frequencies in crosses with all revertant sites, due to a decrease in the efficiency of excision repair of base-pair mismatches whenever the anticodon site is included in hybrid-DNA (Hofer et al. 1979; Munz and Leupold 1979; Thuriaux et al. 1980). A pronounced specific marker effect which leads to a several fold increase of the recombination frequencies over those expected is observed, however, at one of the secondary inactivating sites mapping in the leucine tRNA gene sup8.     

Maternal effects in infant and adult phenotypes of 5HT1A and 5HT1B receptor knockout mice

The influence of the pre- and postweaning maternal environment on the offspring's phenotype was examined in 5-HT1A and 5-HT1B receptor knockout mice (KO1A and KO1B, respectively). We have previously shown that, when born to and raised by homozygous dams of the same genotype, adult KO1A are more anxious than wild-type (WT) mice, and adult KO1B are hyperactive and slightly less anxious than WT mice. We extend our studies here to the behavioral results of the offspring's own genotype, when the dam's genotype is constant, and the effects of the dam's genotype when the offspring's genotype is constant. In Experiments 1 and 2, KO1A-/- pups produced less ultrasonic vocalizations (USV) than controls in an isolation test on postnatal Day 7 when born to and reared by KO1A dams, either -/- or +/-. Heterozygous F1 pups reared by KO1A-/- dams produced more USV and were less anxious in the plus-maze at 2 to 3 months of age than F1 pups born to and reared by WT dams (Experiment 3). F1 pups reared by KO1B-/- dams produced less USV and were more anxious in the plus-maze than F1 pups reared by WT dams (Experiment 4). The results support a role for maternal effects that may comprise direct effects such as the dam's behavior and nutritional care of the pup, and possibly more complex indirect effects through the establishment of idiosyncratic dam-pup dyadic interactions. We recommend that breeding techniques that rely on same genotype (mutant-mutant or WT-WT) breeding pairs not be used to generate offspring when the focus of research is the study of gene function, but rather when familial effects need to be studied.     

Comparing non-hierarchical models: Application to non-linear mixed effects modeling

There is no method available to compare the fit of two non-hierarchical non-linear mixed effects models, although the common practice is to select the model with the lower objective function. Bootstrapping the log-likelihood differences (LLDs) of non-hierarchical models and constructing a bootstrap confidence interval on the LLDs is proposed for comparing the goodness-of-fit of such models. This is illustrated with different parameterizations of clearance models for an anti-infective agent in a longitudinal pharmacokinetic study which are compared. Additive and exponential models of creatinine clearance as a predictor of clearance are used as examples.     

Pressure-flow relationships of the canine iliac periphery and systemic hemodynamics: Effects of sodiumnitroprusside and adenosine

It has been reported that sodiumnitroprusside (SNP) decreases mean systemic pressure and simultaneously increases pressure pulse amplification towards the iliac periphery (Kenner and van Zwieten 1982). This unexpected finding was suggested to be due to a decrease in iliac peripheral resistance but an increase in iliac differential resistance. In order to investigate this apparent contradiction, the iliac periphery was hemodynamically isolated from the rest of the circulation and perfused with the dog's own blood by means of a pump. Perfusion pressure (P) and flow (F), femoral venous pressure (P_v), systemic pressure (P_s) and cardiac output (CO) were measured. Steady state pressure-flow relations of the isolated bed were obtained during control and during various i.v. infusion rates of SNP and adenosine (ADS) and were found to be straight (meanr=0.99). Their slope (P/F) was defined as differential resistance (R_d). Peripheral resistance (R_p) of the iliac bed was defined as R_p=(P-P_v)/F, calculated at the flow value where perfusion pressure equalled the prevailing systemic pressure. Total peripheral resistance (TPR) was defined as TPR=P_s/CO. The changes of R_d, R_p, P_s, CO and TPR with respect to control show that during low SNP infusion rates R_d and R_p were both increased while TPR was decreased. During all infusion rates of SNP CO did not change while P_s decreased. During low infusion rates of adenosine CO increased while P_s, R_d and R_p did not change and TPR decreased. During high infusion rates of ADS CO decreased again, R_d, R_p and P_s decreased, and TPR remained constant but at a decreased level.It is concluded that: (1) the suggestion of Kenner and van Zwieten is not supported, since SNP (as well as ADS) affects iliac peripheral and iliac differential resistance in a similar way; (2) SNP (as well as ADS) affects iliac peripheral resistance and total peripheral resistance in a differentiated way, and even in an opposite way during low infusion rates of SNP; (3) it is this opposite effect that explains the paradoxical observations of Kenner and van Zwieten; (4) for comparable reductions of TPR, CO is better maintained during infusion of SNP, while P_s is better maintained during infusion of ADS.     

Evening administration of melatonin and bright light: Interactions on the EEG during sleep and wakefulness

Both the pineal hormone melatonin and light exposure are considered to play a major role in the circadian regulation of sleep. In a placebo- controlled balanced cross-over design, we investigated the acute effects of exogenous melatonin (5 mg p.o. at 20.40 hours) with or without a 3-h bright light exposure (5000 lux from 21.00 hours–24.00 hours) on subjective sleepiness, internal sleep structure and EEG power density during sleep and wakefulness in healthy young men. The acute effects of melatonin, bright light and their interaction were measured on the first day (treatment day), possible circadian phase shifts were assessed on the post-treatment day. On the treatment day, the evening rise in subjective sleepiness was accelerated after melatonin and protracted during bright light exposure. These effects were also reflected in specific changes of EEG power density in the theta/alpha range during wakefulness. Melatonin shortened and bright light increased sleep latency. REMS latency was reduced after melatonin administration but bright light had no effect. Slow-wave sleep and slow-wave activity during the first non-rapid eye movement (NREMS) episode were suppressed after melatonin administration and rebounded in the second NREMS episode, independent of whether light was co-administered or not. Self rated sleep quality was better after melatonin administration whereas the awakening process was rated as more difficult after bright light. On the post-treatment day after evening bright light, the rise in sleepiness and the onset of sleep were delayed, independent of whether melatonin was co-administered or not. Thus, although acute bright light and melatonin administration affected subjective sleepiness, internal sleep structure and EEG power density during sleep and wakefulness in a additive manner, the phase shifting effect of a single evening bright light exposure could not be blocked by exogenous melatonin