Compartmental aspects of Na+ saturation kinetics in prog skina

Epithelial membranes are multicompartment structures of microscopic and submicroscopic dimensions. Therefore, interpretations of kinetic data on solute fluxes, based on the standard three compartment model are open to criticism. We have obtained an integrated view of the kinetics of Na⁺ transport in frog skin epidermis by application of the computer simulation method. Epidermis and whole skin models were designed which resemble photomicrographs of these tissues. Justification is given for the way in which internal and external chamber compartments are connected (topology). The epidermis model has eight passive, and two active transfer sites. Our primary aims were 1) simulation of the transepidermal Na⁺ influx and the concomitant Na⁺ backflux saturation kinetics, and 2) localization of the so-called “outer” and “inner” Na⁺ responsive borders in epidermis. The analysis, based on methodical variations of transfer coefficients, suggests involvement of the “composite desmosomes” and the transepithelial Na⁺-pump leak pathway. These are located in the outer and the inner region of the epidermis, respectively. Reasonable functional agreement between epidermis and model was also seen in 1) Na⁺ saturation kinetics in ouabain, poisoned system, 2) relative independence of the two borders to the “trans” [Na⁺] in the external solutions, and 3) equal energy requirement, for the transmembrane Na⁺ pump, Na⁺/O₂∼-20. This work was supported by NIH Grant GM 03545-23     

Diabetes, erectile dysfunction, and sleep-related erections

Sleep-related erections were assessed in conjunction with polysomnography in 100 diabetic and 400 nondiabetic men with complaints of erectile problems. We also measured bulbocavernosus reflex latency, heart rate response to deep breathing, postural-related blood pressure changes, penile arterial sufficiency, and brachial blood pressures. To investigate the relationship between diabetes and erectile capacity, the results obtained from men with and without diabetes were compared. Men with diabetes had fewer sleep-related erections, less tumescence time, diminished penile circumference increase, and lower penile rigidity than nondiabetic men. These diabetes-related differences were found regardless of the maximum penile rigidity observed. The diabetic group had less heart rate response to deep breathing and lower penile blood pressures than the nondiabetic group, but only among men with maximum penile rigidity less than 500 g. These data indicate that both neurological and vascular mechanisms are involved to a greater degree in organic diabetic impotence than in the organic erectile dysfunction that occurs in nondiabetic men. Finally, the pattern of lower values for measures of nocturnal tumescence among diabetic men, compared to nondiabetic men, occurred in all age groups, except the oldest. Among impotent men, age 65 years or older, no difference was found between men with and without diabetes. This suggests that diabetes may foreshadow some of the age-related pathophysiological processes associated with erectile dysfunction.     

Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype

Inhibitory neurotransmission in the brain is largely mediated by GABA(A) receptors. Potentiation of GABA receptor activation through an allosteric benzodiazepine (BZ) site produces the sedative, anxiolytic, muscle relaxant, anticonvulsant and cognition-impairing effects of clinically used BZs such as diazepam. We created genetically modified mice (alpha1 H101R) with a diazepam-insensitive alpha1 subtype and a selective BZ site ligand, L-838,417, to explore GABA(A) receptor subtypes mediating specific physiological effects. These two complimentary approaches revealed that the alpha1 subtype mediated the sedative, but not the anxiolytic effects of benzodiazepines. This finding suggests ways to improve anxiolytics and to develop drugs for other neurological disorders based on their specificity for GABA(A) receptor subtypes in distinct neuronal circuits.     

Acute non-lymphocytic leukemia with t(16;21)

A patient with ANLL FAB subtype M1 was found to possess a t(16;21)(p11;q22) and trisomy 10. The 16;21 translocation has been reported in 12 other cases of ANLL, of various subtypes, and its relationship to the disease profile is discussed.     

Treatment of chlordecone (Kepone) toxicity with cholestyramine. Results of a controlled clinical trial.

Industrial workers exposed to the organochlorine pesticide, chlordecone (Kepone), had signs of toxicity in several organs. The extent of toxicity was proportional to the levels of this chemical in the tissues. In 22 patients, chlordecone was eliminated slowly from blood (half time of 165 +/- 27 days--mean +/- S.E.M.) and fat (half time of 125 days, with a range of 97 to 177), chiefly in the stool. Output of chlordecone in bile was 10 to 20 times greater than in stool, suggesting that chlordecone is reabsorbed in the "ntestine. Cholestyramine, an anion-exchange resin that binds chlordecone, increased its fecal excretion by seven times. In a five-month trial, cholestyramine significantly accelerated elimination of chlordecone from blood, with a half life of 80 +/- 4 days (S.E.M.) (P less than 0.005) and fat (half life of 64 days, with a range of 52 to 85) (P less than 0.05). Cholestyramine offers a practical means for detoxification of persons exposed to chlordecone and possibly to other lipophilic toxins.