Ethanol-induced hypothermia. Cross tolerance with morphine

The development of tolerance to ethanol-induced hypothermia and hypnosis, and cross-tolerance with morphine was studied in mice and rats. Ethanol significantly decreased the body temperature in rats (3.0 and 3.2 g/kg) and in mice (3.5 and 4.0 g/kg). Chronic administration of ethanol resulted in the tolerance not only to ethanol hypothermia but also to hypothermic effects of morphine in examined animals. Implantation of morphine pellets caused the development of cross tolerance to ethanol-induced hypothermia in rats but not in mice. The hypnotic effect of ethanol was significantly shorter in chronic alcoholized rats but not in morphine-implanted rats. Neither chronic ethanol administration nor implantation of morphine pellets changed the duration of ethanol-induced hypnosis in mice. These results seem to support the hypothesis on the opiate-like mechanism of ethanol action.     

Differences between the tolerance characteristics of two anticonvulsant benzodiazepines

Clobazam (10 mg/kg) and clonazepam (0.25 mg/kg) were administered to mice twice daily by the intraperitoneal route. The development of tolerance to their anticonvulsant effect was compared using a slow intravenous infusion of pentylenetetrazole as the convulsant stimulus. Tolerance to clonazepam developed gradually throughout a 72 h study and did not become significant until the fifth dose. In contrast, tolerance to clobazam occurred extremely rapidly, after only one dose; it was manifested as a single step and no further significant change in protection was observed. Recovery from benzodiazepine tolerance was also studied and seen to occur rapidly with both these compounds; following cessation of dosing, protection was restored to initial levels within 36-48 h.     

Effect of proteolytic enzymes on antibiotic distribution when the preparations are administered by different routes]

The effect of proteolytic enzymes, such as terrilitine and chymotripsin on pharmacokinetics of morphocycline and streptomycin in rats after their administration by various routes was studied comparatively. The oral use of the enzymes or their introduction directly into the duodenum simultaneously or 30 minutes before the antibiotic administration did not increase the morphocycline and streptomycin levels in the biosubstrates tested. A tendency to a decrease in the serum and organ levels of the antibiotics in animals when used orally in combination with the enzymes was noted. When the drugs were administered intramuscularly, the morphocycline serum and organ levels in the rats increased insignificantly, while the streptomycin levels increased significantly. Administration of formalin as a stressor had an analogous effect which provided a supposition of a possibility of non-specific effect of the enzymes of distribution of the antibiotics on intramuscular injection of the enzymes in large doses having a local irritating effect.     

Development of clonidine-tolerance in the rat vas deferens: Cross tolerance to other presynaptic inhibitory agents

Possibility of the development of clonidine-tolerance in the peripheral nervous tissue was examined using vas deferens isolated from rats chronically treated with clonidine. Rats were treated with clonidine for 10 days by adding the drug to drinking water (10 μg/ml). For the control rats, drug-free tap water was provided. Electrically evoked twitch response of vas deferens was suppressed by adenosine, β-endorphine and α₂-adrenergic agonists, such as clonidine and B-HT 933, both in control and clonidine-treated groups. Vas deferens isolated from clonidine-treated rats showed significantly lower responsiveness to the inhibitory effects of clonidine and B-HT 933 compared to those from control rats. Vas deferens from clonidine-treated rats also was less responsive to adenosine and β-endorphin, both of which interact with presynaptic inhibitory receptors other than α₂-adrenergic and muscarinic cholinergic stimulation responsiveness of the postsynaptic smooth muscle to both α-adrenergic and muscarinic cholinergic stimulation did not change after 10 days of treatment with clonidine. These results suggest that clonidinetolerance can be induced in the peripheral nervous system by chronic treatment of this drug and that the tolerance is not specific to α₂-adrenergic agonists. Some common pathway in the inhibitory mechanisms of various agents or possible interactions between the different types of presynaptic inhibitory receptors may be involved in this phenomenon.     

IC-tagged proteins are able to interact with each other and perform complex reactions when integrated into muNS-derived inclusions

We have recently developed a versatile tagging system (IC-tagging) that causes relocation of the tagged proteins to ARV muNS-derived intracellular globular inclusions. In the present study we demonstrate (i) that the IC-tag can be successfully fused either to the amino or carboxyl terminus of the protein to be tagged and (ii) that IC-tagged proteins are able to interact between them and perform complex reactions that require such interactions while integrated into muNS inclusions, increasing the versatility of the IC-tagging system. Also, our studies with the DsRed protein add some light on the structure/function relationship of the evolution of DsRed chromophore.     

Radioprotective action of GHM-10 when administered with dextran sulfate and heparin

A single administration of dextransulfate (40 mg/kg, 1-3 days before irradiation), or a double injection of heparin (250 units/kg, 24 hr and 15 min before irradiation) potentiated a weak radioprotective effect of gas hypoxic mixture (GHM-10) on animals exposed to absolutely lethal doses.     

In contrast to other Xenopus genes the estrogen-inducible vitellogenin genes are expressed when totally methylated

The methylation-sensitive restriction enzymes Hha I and Hpa II were used to analyze the methylation pattern of four Xenopus laevis genes in DNA of embryos, of erythrocytes, and of untreated and estrogen-treated hepatocytes. Within these four genes all sites tested are fully modified in embryonic DNA. However, the adult β1-globin gene is unmethylated in DNA of erythrocytes, where it is expressed, and the 68 kd albumin gene, active only in hepatocytes, is specifically hypomethylated in hepatic DNA. The vitellogenin genes A1 and A2, in hepatocytes simultaneously expressed upon estrogen treatment, are heavily methylated in all adult tissues, irrespective of expression. Our results reveal that specific genes can be actively transcribed even when they are fully methylated and that changes in the methylation pattern are not a general prerequisite for gene activation.     

Repeated probit regression when covariates are measured with error

This paper develops a model for repeated binary regression when a covariate is measured with error. The model allows for estimating the effect of the true value of the covariate on a repeated binary response. The choice of a probit link for the effect of the error-free covariate, coupled with normal measurement error for the error-free covariate, results in a probit model after integrating over the measurement error distribution. We propose a two-stage estimation procedure where, in the first stage, a linear mixed model is used to fit the repeated covariate. In the second stage, a model for the correlated binary responses conditional on the linear mixed model estimates is fit to the repeated binary data using generalized estimating equations. The approach is demonstrated using nutrient safety data from the Diet Intervention of School Age Children (DISC) study.     

Predators are rare even when they are small

A recent review of published studies revealed that predators generally have lower population densities than non-predators in a variety of communities. We report here similar results for a highly replicated study of macroinvertebrates that colonized very uniform detrital microcosms in an old field. This pattern persisted even though predators usually were smaller than non-predators, as determined by body length and volume.     

Organic substances responsible for salt tolerance inEruca sativa

Responses of a salt tolerant and a normal population of an oilseed crop,Eruca sativa Mill. were assessed after four weeks growth in sand culture salinized with 0 (control), 100, 200, or 300 mol m^?3 NaCl. The salt tolerant plants produced significantly greater dry biomass than the normal population. The populations did not differ significantly in leaf osmotic potential, relative water content and leaf soluble proteins. However, the tolerant population accumulated significantly greater amounts of soluble sugars, proline and free amino acids in the leaves compared with the non-tolerant population. It is established that leaf soluble sugars, proline, and free amino acids are important components of salt tolerance inEruca sativa.     

The fitness of chemotrophs increases when their catabolic by‐products are consumed by other species

Chemotrophic microorganisms synthesise biomass by utilising energy obtained from a set of chemical reactions that convert resources to by‐products, forming catabolic interactions. The amount of energy obtained per catabolic reaction decreases with the abundance of the by‐product named as the ‘abundant resource premium’. Consider two species, Species 1 and 2, Species 1 obtains energy from a reaction that converts resource A to by‐product B. Species 2 then utilises B as its resource, extracting energy from a reaction that converts B to C. Thus, the presence of Species 2 reduces the abundance of B, which improves the fitness of Species 1 by increasing the energy acquisition per reaction of A to B. We discuss the population dynamic implication of this effect and its importance in expanding a realised niche, boosting material flow through the ecosystem and providing mutualistic interactions among species linked by the material flow. Introducing thermodynamics into population ecology could offer us fundamental ecological insights into understanding the ecology of chemotrophic microorganisms dominating the subsurface realm.     

Differences between the tolerance characteristics of two anticonvulsant benzodiazepines in the amygdaloid-kindled rat

The characteristics of the development of tolerance to the anticonvulsant effects of chronic treatment by dipotassium clorazepate and diazepam using amygdaloid-kindled rats were investigated. Dipotassium clorazepate (5 mg/kg) or diazepam (5 mg/kg) were intraperitoneally administered for 10 consecutive days. Tolerance to the anticonvulsant effect of dipotassium clorazepate developed in seizure stage on day 6, after-discharge duration on day 7 and seizure latency on day 4. In contrast, tolerance to the effects of diazepam developed more rapidly in seizure stage on day 4, after-discharge duration on day 4 and seizure latency on day 3. Thus tolerance to the anticonvulsive effect of dipotassium clorazepate developed relatively slower than that to diazepam. All rats had stage 5 convulsions 24 hr after cessation of the administration of dipotassium clorazepate and diazepam. Concomitant determinations of plasma concentrations of the main metabolite of dipotassium clorazepate and diazepam, desmethyldiazepam, showed no statistical difference during treatment, suggesting that the developed tolerance was not metabolic but functional.     

Removing Cancer when it is Correlated with other Causes of Death

This paper presents an identifiability theorem in the theory of dependent competing risks and it applies the result by examining the effect of removing cancer from the United States population when cancer is correlated with the other causes of death. The paper shows how dependence can be modeled with copula functions and it shows that calculating the survival probabilities after cancer is removed is equivalent to solving a system of nonlinear differential equations.