Study of the characteristics of the inotropic effect of insulin in rabbit papillary muscle.

The effect of insulin was examined with emphasis on the alteration in the force-frequency relation. The results show that insulin does not change the time to peak tension nor the time of contraction. The inotropic effect was significant and did not depend upon the frequency of stimulation. However, there was a definite dependence of the magnitude of the inotropic effect on temperature. Previous studies have indicated that the inotropic effect is not a result of increased substrate availability or changes in cAMP phosphodiesterase activity. These results and those reported here are consistant with the hypothesis that insulin's inotropic effect is due to increases in intracellular Ca++.     

Study of the characteristics of the inotropic effect of insulin in rabbit papillary muscle

Summary The effect of insulin was examined with emphasis on the alteration in the force-frequency relation. The results show that insulin does not change the time to peak tension nor the time of contraction. The inotropic effect was significant and did not depend upon the frequency of stimulation. However, there was a definite dependence of the magnitude of the inotropic effect on temperature. Previous studies have indicated that the inotropic effect is not a result of increased substrate availability or changes in cAMP phosphodiesterase activity. These results and those reported here are consistant with the hypothesis that insulin's inotropic effect is due to increases in intracellular Ca⁺⁺.This work was supported by a grant from the U. S. Public Health Service HL-02285.     

Inhibition of saline-induced diuresis in the rat by sulpiride.

Sulpiride (120 mg/kg, i.p.) inhibited saline-induced diuresis in the rat, an effect not observed with haloperidol, clozapine, pimozide or chloromazine. The antidiuretic effect of sulpiride also occurred in hypophysectomized rats suggesting that the response was not prolactin-mediated.     

Corticotropin and nonshivering thermogenesis.

Chronic treatment with corticotropin led to reduced calorigenic effect of norepinephrine in cold acclimatized rats, but potentiated its effect in controls. This inhibitory effect was not due to the observed decrease in corticosterone plasma level, as it was shown by metopirone administration. It is concluded that corticotropin could have a competitive action on receptor sites mediating the calorigenic effect of norepinephrine in nonshivering thermogenesis.     

The effect of bisphosphonates on glycolysis in cultured calvaria cells and their homogenate

Rat calvaria cells previously cultured for 7 days in the presence of 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) or dichloromethylenebisphosphonate (Cl2MBP), showed a decrease in the glycolytic pathway. When glycolysis was analyzed under anaerobic conditions, this effect was not observed. The inhibition by the bisphosphonates occurred to a similar degree regardless of whether lactate production was measured in whole cells or in cell homogenates. Bisphosphonates added directly to the homogenate had no inhibitory effect. Thus, the effect is not a direct one and is unlikely to be due to a soluble mediator in the cytoplasm.     

Direct toxic effect of isoproterenol on cultured cardiac muscle cells

Summary Isoproterenol at relatively high doses (2.5 mg/ml) has a marked toxic effect on rat heart muscle cells cultivated in vitro. This effect is not prevented by propranolol and therefore is not mediated by beta adrenergic receptors.This work has been supported in part by a grant from the Muscular Dystrophy Association, Inc. to Prof. M. Aloisi.     

Effects of alpha- and beta-adrenergic blockers on the actions of noradrenaline on body temperature in the newborn guinea-pig.

The effect of NA injected into the lateral cerebral ventricle on Tc was blocked by alpha-adrenergic receptor blockers, but not by beta-receptor blockers, whereas the effect of systemically administered NA was blocked by i.p. administered beta-receptor blockers, but not by alpha-blockers.     

Absence of effects of dibutyryl cyclic guanosine 3',5'-monophosphate on release of alpha-amylase, 45Ca efflux, and protein synthesis in rat pancreas in vitro.

Dibutyryl cyclic GMP did not affect basal, or carbachol stimulated secretion of alpha-amylase from rat pancreas. The nucleotide did not have a significant effect on 45Ca release from the pancreas nor did it alter the response to carbachol. The dibutyryl analogue of cyclic GMP did not duplicate or alter the inhibitory effect of carbachol on 3H-leucine incorporation into pancreatic trichloroacetic acid-precipitable protein.     

Opposite effects of beta-adrenoceptor stimulation and 8-bromo-cyclic AMP on potassium efflux in mammalian heart muscle

beta-adrenoceptor stimulation by isoprenaline increases the potassium efflux in beating guinea-pig atria. This effect is not mimicked by 8-bromo-cyclic AMP, a cyclic AMP analogue which exerts a positive inotropic effect in this preparation.     

Corticotropin and nonshivering thermogenesis

Summary Chronic treatment with corticotropin led to reduced calorigenic effect of norepinephrine in cold acclimatized rats, but potentiated its effect in controls. This inhibitory effect was not due to the observed decrease in corticosterone plasma level, as it was shown by metopirone administration. It is concluded that corticotropin could have a competitive action on receptor sites mediating the calorigenic effect of norepinephrine in nonshivering thermogenesis.Grateful acknowledgment is expressed to Mrs M. Lopez for her technical assistance.     

Effect of testosterone on the hypothalamic-pituitary-gonadal axis of pinealectomized and pineal-intact male rats.

Previous studies indicate that steroid hormones alter pineal biochemistry, and it has been suggested that at least part of the negative feedback effect of steroid hormones on pituitary gonadotropin release may be mediated by the pineal gland. In this study, pinealectomy did not alter the inhibitory effect of testosterone on neuroendocine-gonadal activity in the male rat, suggesting that the pineal gland does not mediate the response of the rat hypothalamic-pituitary axis to testosterone.     

Trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid) inhibits the effect of androgens on the rat prostate.

Trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid, FA) antagonized the effect of exogenous androgens on the ventral prostate (VP) in castrated rats as well as the effect of endogenous androgens in intact rats. FA, however, had no effect on the seminal vesicles (SV) and levator ani muscle (LAM), nor oestrogenic effect in female rats and mice. FA did not antagonize the receptor binding of testosterone nor inhibit the conversion of testosterone into 5 alpha-dihydrotestosterone (DHT).     

Bacillus thuringiensis delta-endotoxin: evidence that toxin acts at the surface of susceptible cells

Enzymically activated delta-endotoxin of Bacillus thuringiensis covalently bound to Sephadex beads, has the same effect on insect cells in tissue culture as free toxin. The effect is prevented by antitoxin antibody and heat denaturation and is not due to a nonspecific protein effect, the beads, or toxin released from the beads. The toxin, therefore, probably acts at the cell surface.     

Hsp70: a carrier molecule with built-in adjuvanticity

One problem associated with the development of subunit vaccines is their limited immunogenicity, due to their physico-chemical structure, their inability to encounter the correct MHC restriction element, or the need for strong adjuvants to be delivered along with them. These problems are usually solved by conjugating target epitopes (peptides or oligosaccharides) with carrier proteins which provide a source of T-cell epitopes recognised by a large proportion of the vaccinated individuals. We have shown that mycobacterial hsp65 and hsp70 exert a strong helper effect in vivo when conjugated to synthetic peptides or oligosaccharides. Interestingly, this helper effect did not require the need for any adjuvant, either in mice or in monkeys. The helper effect mediated by the hsp65 required that animals were previously primed with either live BCG or the hsp65 alone; on the other hand, such a priming was not required when the hsp70 was used in the conjugates. Similar results were obtained with HSP molecules fromEscherichia coli. This may suggest that the adjuvant-free helper effect observed applies not only to mycobacterial HSP, but also to HSP from other prokaryotes. These findings suggest that microbial hsp70 could be considered for the design of conjugated vaccine constructs for eventual human use.     

Enclomiphene induces luteolysis in the nonpregnant guinea pig

The effect of two antiestrogens, enclomiphene and tamoxifen, on luteal function in the guinea pig was compared to that of estradiol, a known luteolysin. Enclomiphene caused premature luteolysis when administered during the early or mid-luteal phase of the cycle, but was not as potent as estradiol. Tamoxifen had no effect. The luteolytic effect of enclomiphene was mediated by the uterus, as has been shown for estradiol.     

Enclomiphene induces luteolysis in the nonpregnant guinea pig

Summary The effect of two antiestrogens, enclomiphene and tamoxifen, on luteal function in the guinea pig was compared to that of estradiol, a known luteolysin. Enclomiphene caused premature luteolysis when administered during the early or mid-luteal phase of the cycle, but was not as potent as estradiol. Tamoxifen had no effect. The luteolytic effect of enclomiphene was mediated by the uterus, as has been shown for estradiol.     

Inactivation of N-assimilating enzymes and proteolytic activities in wheat leaf extracts: Effect of pyridine nucleotides and of adenylates

Summary Nitrate reductase was protected from inactivation in wheat leaf extracts by NADH, while NADPH was less effective. NAD, NADP or adenylates did not affect nitrate reductase inactivation in vitro. Glutamine synthetase was more stable than nitrate reductase and was protected from inactivation by ATP. ADP, AMP or pyridine nucleotides had no or only a minor effect on the decrease of glutamine synthetase activity in extracts. The caseolytic activity extracted from senescing leaves was slightly decreased by NADH and NADPH but this effect was not sufficient to explain the stabilization of nitrate reductase by NADH. Oxidized pyridine nucleotides and adenylates had no major effect on the caseolytic activity under the conditions used.This work was supported by grant 3.067-0.81 from the Swiss National Science Foundation. Author for correspondence: U.F.     

混凝土材料非线性多轴动态强度准则

将广义非线性强度理论的4个材料参数转化为混凝土材料的基本强度参数,通过混凝土材料的基本强度特性,分析了4个材料参数的变化规律与取值范围.基于S准则建立了混凝土材料4个基本强度参数的率效应表达式,建立了混凝土材料的非线性多轴动态强度准则,分析了动态强度参数的率效应规律,结果表明,混凝土材料的强度特性随着应变率的提高,逐渐向金属材料的强度特性过渡,在应变率从-3~3,应变率对混凝土动态强度的影响较大,并且动强度不是随着应变率的提高无限增大的,而是存在动强度峰值.通过与3组双轴压-压和2组双轴拉-压动态加载时混凝土材料试验结果的比较,表明非线性多轴动态强度准则可较好地描述混凝土材料双轴动强度规律.在同一应变率下,可较好地描述强度的非线性特性;不同应变率下,动强度面互不相交,即应变率效应与多轴应力状态对强度规律不存在耦合影响.     

Is chemical memory transfer due to shock or behavior training?

A memory transfer experiment was performed to determine whether the transfer effect is due to stress associated with the foot shock or to the specific behavioral training. Recipient animals were significantly better in the 'jump-out' testing than either the shock-control recipients or the control recipients, but the shock-control recipients performed significantly better than the control recipients. Foot shock has an effect on the transfer phenomena but is not responsible for the entire effect.     

Some properties of external NADH oxidation by human placental mitochondria.

Isolated human term placenta mitochondria catalyse oxidation of external NADH in the presence of cytochrome c. This reaction is insensitive to the respiratory chain inhibitors such as rotenone and antimycin A, and is not coupled to phosphorylation. Comparison of the effect of Mg++ ion on NADH plus cytochrome c oxidation by human term placental, human skeletal muscle and rat skeletal mitochondria showed that Mg++ ion exerts an inhibitory effect in the case of human mitochondria and a stimulatory effect in the case of rat skeletal muscle mitochondria.