Exercise intensity, training, diet, and lactate concentration in muscle and blood

With some, but not all, types and intensities of exercise, lactate accumulates in the blood and in the muscles engaged in the exercise. A great deal of attention has been directed towards attempting to understand the dynamics of lactate production and removal at the onset of exercise, during exercise, and during the recovery process following exercise. It has been hoped that an unravelling of these events would provide a key to understanding cellular metabolism and its regulation during exercise. The purpose of this introductory paper to a symposium on lactate is to present a brief overview of some of the conditions that influence the rate and magnitude of lactate accumulation during exercise. It is pointed out that many conditions influence the rate and magnitude of the accumulation of lactate in blood and muscles. Included are diet, state of physical fitness, and the type and duration of the exercise. We have cautioned against trying to evaluate the state of oxygen delivery to muscle and the state of tissue oxygenation from the appearance of lactate in blood. We have pointed out the positive aspects of lactate production based on how it augments the cellular supply of ATP, thereby allowing for high intensity exercise, and also the negative aspects that develop as a result the reduction in pH which adversely influences many cellular processes essential for muscular activity.     

Rapid desensitization of the acute stimulatory effects of nicotine on rat plasma adrenocorticotropin and prolactin

The dose of nicotine and the frequency of its administration appear to be essential determinants of its action on multiple systems including the neuroendocrine regulation of the adrenocorticotropin (ACTH)-corticosterone and prolactin (PRL) axes in the rat. Because desensitization to the acute depressive effects of nicotine has been observed after both acute and chronic administration, these investigations assessed whether desensitization to the stimulative effects of nicotine on ACTH and PRL secretion occurs with repetitive dosing. Extensive dose and time course experiments showed that nicotine rapidly elevates rat plasma ACTH and PRL levels with a threshold dose between 0.1 to 0.25 mg/kg b.wt. i.p. After the stimulation of PRL, levels became significantly depressed. Desensitization to the acute stimulatory effects of nicotine on both hormones was induced by a single dose of nicotine (0.5 mg/kg). One hour later nicotine (1.0 mg/kg) failed to significantly stimulate PRL levels and resulted in a modest increase of ACTH. Desensitization was maximal by 1 hr after the first dose and persisted for at least 6 hr. Adrenalectomy, performed to eliminate corticosterone-induced negative feedback, did not enhance PRL responsiveness to a second dose of nicotine but it partially restored the ACTH response. Pretreatment with corticosterone also failed to modify the PRL response to a single dose of nicotine whereas it partially suppressed the ACTH response. Rapid desensitization to the acute stimulatory effects of nicotine on plasma PRL is independent of glucocorticoid negative-feedback whereas desensitization of the ACTH response is modestly dependent.     

The cytochromes P-450 concentrations in microsomes of liver, kidney and duodenal mucosa of the camel, sheep and goat

The concentration of microsomal cytochromes P-450, and of protein in the homogenate, cytosol and microsomes were measured in the liver, kidney and duodenal mucosa of healthy well-fed male and female camels, sheep and goats. For comparison, data from the liver of male and female rats were also obtained. The protein concentrations in the tissues of adult animals were broadly similar in the four species. The concentration of cytochromes P-450 was highest in the liver, followed by the kidney, then the duodenal mucosa in all the species. No cytochromes P-450 were detected in the tissues of immature (less than 1 mo) male goats, whereas the female goat had the highest concentrations of these enzymes in the liver and kidney when compared with the respective tissues in the other species studied. Males had higher activity of cytochromes P-450 than females in the three tissues, except in the duodenal mucosa of sheep, where males had lower activity than females. In camel liver and sheep kidney, the amount of cytochromes P-450 were similar in the two sexes. The present results suggest that the mature female goat is the species best equipped to handle xenobiotics which are detoxified by the cytochromes P-450 and other drug metabolizing enzymes in diseased or malnourished animals is suggested as these two conditions are known to modify drug metabolizing enzymes.     

Syrup of ipecac availability: before and after a poisoning

A retrospective review was conducted of 1,230 human poison exposures in which syrup of ipecac was administered to determine the availability of this emetic. Ipecac was available in 41.1% of the homes, while 42.5% obtained it from the pharmacy. Eight and two tenths percent were referred to a health care facility, 2.9% obtained ipecac from a neighbor, 2.3% went to an emergency room prior to calling the poison center, and 3% obtained ipecac from other sources. A randomly selected sample of 150 of these 1,230 cases were contacted 6 months after their initial call to the poison center to determine any changes in the availability of syrup of ipecac in the home. Although almost 30% more homes had syrup of ipecac than previously, 22.2% of homes still did not have ipecac available, despite the previous poisoning experience. Greater effort should be made during follow-up to educate the public regarding ipecac and its use.     

Affinity purification of a high molecular weight human breast cancer-associated antigen identified by the BCD-B4 monoclonal antibody

This study reports the purification and characterization of a high molecular weight human breast cancer-associated antigen identified by a previously described (1,2) murine monoclonal antibody, BCD-B4. Immunohistochemical analysis indicated that BCD-B4 recognizes an antigen expressed in an altered form on the human breast carcinoma cell line, BT-20, compared to the non-malignant human mammary epithelial cell line, HBL-100. Chemical treatments and enzymatic digestions suggested that the recognized moiety was a protein. The antigenic determinant was resistant to neuraminidase and periodate treatments but was sensitive to trypsin and proteinase K. The antigen was purified by affinity chromatography and its molecular weight, determined by SDS-PAGE analysis under non-reducing conditions, was proven to be 250 Kd. Under reducing conditions, the molecule dissociated into two polypeptides of 125 and 45 Kd, respectively. Both subunits could be isolated from normal HBL-100 and neoplastic BT-20 cellular protein extracts by affinity chromatography. The higher molecular weight subunit showed; however, qualitative and quantitative differences between the two cell lines: it was expressed in greater quantity on BT-20 cells and its molecular weight was 15 Kd higher. Both subunits could also be identified by immunoblots of BT-20 cells.     

Bovine cumulus-oocyte disconnection in vitro

Summary Cumulus-oocyte complexes were obtained from cows by aspiration of small (1–6 mm in diameter) antral follicles after slaughter. Complexes with a compact multilayered cumulus investment were cultured and processed for transmission electron microscopy after different periods of culture including a 0 h control group. In 0 h control oocytes the cumulus cells had numerous projections which penetrated the zona pellucida and established gap junctions with the oolemma. A partial loss of these junctions was noticed as an early event of oocyte maturation occurring within the first 3 h of culture. A low frequency of gap junctions was maintained until 12–18 h of culture where the junctional contact was completely disrupted. This decrease in intercellular communication was parallelled by resumption of oocyte meiosis.     

The proapoptotic 9-2 isozyme of 2-5 (A) synthetase cannot substitute for the sperm functions of the proapoptotic protein, Bax.

The 9-2 isozyme of 2-5 (A) synthetase has cellular proapoptotic functions that are mediated not by enzyme activity but by the Bcl-2 homology domain 3 present in its unique carboxyl-terminal region. Another proapoptotic cellular protein is Bax, whose absence in the Bax(-/-) mice causes male sterility due to abnormal sperm differentiation. In this study, we examined whether transgenic 9-2 expression can substitute for the in vivo reproductive function of Bax. To achieve this goal, a sperm-specific promoter was used to drive the expression of 9-2 in the sperm of transgenic mice. By selective cross-breeding, the transgene was transferred to Bax(-/-) mice to generate the experimental mouse line (Bax(-/-), 9-2(+/+)). The male experimental mice were sterile, and their testes maintained the structural abnormality found in Bax(-/-) mice. Thus, the male reproduction functions of Bax could not be replaced by the 9-2 isozyme of 2-5 (A) synthetase.