The effect of cholinergic drugs on [3H]acetylcholine release from slices of rat hippocampus, striatum and cortex

Slices from rat hippocampus, striatum or cortex were incubated with l mum [3H] choline and following 75 min superfusion with Krebs solution the efflux of radioactivity was measured. The slices were stimulated either electrically (1 Hz) or with 25 mM potassium and the rate constant of the evoked release and the size of the releasable pool were estimated. The spontaneous efflux of radioactivity and the releasable pool but not the rate of evoked release correlated with the reported endogenous ACh content of the 3 areas. Raised potassium released radioactivity at a lower rate but from a larger pool than electrical stimulation from all 3 areas. In all 3 areas atropine alone potentiated while physostigmine, oxotremorine and carbamylcholine decreased the rate of evoked release. This depression was fully antagonized by atropine. The drugs had no effect on the size of the releasable pool. Findings suggest that muscarinic receptors located on cholinergic axons or terminals have a physiological role in the autoregulation of ACh release from these 3 areas.     

The influence of sex hormones on obesity across the female life span

Women have a higher prevalence of obesity than men in most developed countries. Obesity affects many aspects of women's health by increasing risk for heart disease, diabetes, breast cancer, and infertility. One reason for the gender difference in obesity may be that fluctuations in reproductive hormone concentrations throughout women's lives uniquely predispose them to excess weight gain. Studies in experimental animals and women have shown that hormonal changes across the menstrual cycle affect calorie and macronutrient intake and alter 24-hour energy expenditure. Pregnancy is a significant factor in the development of obesity for many women. Various factors are associated with excess weight retention following pregnancy, including weight gain during pregnancy, ethnicity, dietary patterns, and interval between pregnancies. There is a need to tailor recommendations for energy intake during pregnancy to individual women, and recent evidence also suggests that the timing of weight gain during pregnancy is a critical factor. Menopause is also a high-risk time for weight gain in women. Although the average woman gains 2-5 pounds during menopausal transition, some women are at risk for greater weight gains. There is also a hormonally driven shift in body fat distribution from peripheral to abdominal at menopause, which may increase health risks in older women. Hormone therapies have varying impacts on body weight and fat distribution. In summary, hormonal fluctuations across the female life span may explain the increased risk for obesity in women. Awareness of these factors allows development of targets for prevention and early intervention.     

Variation in growth form and precocity at birth in eutherian mammals

Using the flexible Chapman-Richards model for describing the growth curves from birth to adulthood of 69 species of eutherian mammals, we demonstrate that growth form differs among eutherian mammals. Thereby the commonly used Gompertz model can no longer be considered as the general model for describing mammalian growth. Precocial mammals have their peak growth rate earlier in the growth process than altricial mammals. However, the position on the altricial-precocial continuum accounts for most growth-form differences only between mammalian lineages. Within mammalian genera differences in growth form are not related to precocity at birth. This indicates that growth form may have been associated with precocity at birth early in mammalian evolution, when broad patterns of body development radiated. We discuss four non-exclusive interpretations to account for the role of precocity at birth on the observed variation in growth form among mammals. Precocial and altricial mammals could differ according to (i) the distribution of energy output by the mother, (ii) the ability of the young to assimilate the milk yield, (iii) the allocation of energy by the young between competing functions and (iv) the position of birth between conception and attainment of physical maturity.     

Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy

Sporadic persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or nesidioblastosis is a heterogeneous disorder characterized by profound hypoglycemia due to inappropriate hypersecretion of insulin. An important diagnostic goal is to distinguish patients with a focal hyperplasia of islet cells of the pancreas (FoPHHI) from those with a diffuse abnormality of islets (DiPHHI) because management strategies differ significantly. 16 infants with sporadic PHHI resistant to diazoxide and who underwent pancreatectomy were investigated. Selective pancreatic venous sampling coupled with peroperative surgical examination and analysis of extemporaneous frozen sections allowed us to identify 10 cases with FoPHHI and 6 cases with DiPHHI. We show here that in cases of FoPHHI, but not those of DiPHHI, there was specific loss of maternal alleles of the imprinted chromosome region 11p15 in cells of the hyperplastic area of the pancreas but not in normal pancreatic cells. This somatic event is consistent with a proliferative monoclonal lesion. It involves disruption of the balance between monoallelic expression of several maternally and paternally expressed genes. Thus, we provide the first molecular explanation of the heterogeneity of sporadic forms of PHHI such that it is possible to perform only partial pancreatectomy, limited to the focal somatic lesion, so as to avoid iatrogenic diabetes in patients with focal adenomatous hyperplasia.     

A comparison of thromboelastography with heparinase or protamine sulfate added in vitro during heparinized cardiopulmonary bypass

Thromboelastography (TEG) has been used after cardiopulmonary bypass (CPB) to diagnose excessive postoperative hemorrhage. Conventional TEG during CPB is not possible due to the sensitivity of the TEG to even small amounts of heparin, which produces a nondiagnostic tracing. The purpose of this study was to compare heparin neutralization using heparinase or protamine in TEG blood samples obtained during CPB. TEG testing was performed on 48 patients before, during and after CPB. Tissue plasminogen activator activity and antigen were measured on a subset of 32 patients. We found: 1) heparinase neutralized at least 10 IU/ml heparin while 1.6 ug/ml protamine neutralized up to 7 IU/ml heparin, 2) in samples with complete heparin neutralization by both methods, there was no significant difference in the R values, 3) while there was good correlation for other TEG parameters between heparinase and protamine treated samples, heparinase treatment produced shorter K values and higher angle, MA and A60, 4) while fibrinolysis was detected using both methods, heparinase treatment suppressed fibrinolysis in the TEG in both samples from patients and after in vitro addition of tissue plasminogen activator, 5) TEG was not a sensitive indicator of t-PA activity, detecting only 21% of samples with increased t-PA activity during bypass, and 5) heparinase was at least 100 times more expensive than protamine. We conclude that while both heparinase and protamine can be used to neutralize heparin in TEG samples obtained during CPB, protamine neutralization is more sensitive to fibrinolysis and less expensive, but the protamine dose must be carefully selected to match the heparin level used at individual institutions.     

KCNE1 mutations cause jervell and Lange-Nielsen syndrome

The third reported case of pelvic gliomatosis found within foci of endometriosis is documented 16 years after the removal of a benign cystic teratoma. Grossly at laparoscopy the lesions appear as typical deep fibrotic endometriotic implants.