On the mechanism of increased potassium conductance by the potassium channel opener BRL 34915 in Isolated ventricular myocytes

The potassium conductance increased by BRL 34915 (BRL, cromakalim) was studied in single guinea pig ventricular myocytes by using a whole cell voltage-clamp technique. In control voltage-clamp recordings, the late current-voltage relation showed a distinct inward rectification. BRL (1–100 μM) shortened the action potential and diminished or abolished inward rectification but had no effect on the slope conductance and currents flowing during hyperpolarizing clamp steps. BRL did not decrease the slow inward current but accelerated the time constant of activation and amplitude of the outward current. Cd markedly decreased (0.2 mM) or abolished (0.4–0.6 mM) the slow inward current and BRL induced a faster outward shift of late current to a greater value. Glybenclamide (10 μM), a blocker of ATP-sensitive K⁺ channels, had little effect of its own on action potential, membrane currents, and I-V relation. However, in the presence of BRL, glybenclamide abolished BRL effects on action potential and currents and restored inward rectification. It is concluded that the mechanism by which BRL shortens the action potential is a faster growth of an outward current due to the reduction or abolition of the inward rectification of an ATP-dependent potassium channel. The reduction in force in non-isolated tissues appears to be an indirect result of the action potential shortening and not of a decreased slow inward current.     

EFFECTS OF STROPHANTHIDIN ON THE SLOW INWARD CURRENT IN GUINEA-PIG ISOLATED VENTRICULAR MYOCYTES

1. The effect of strophanthidin on the slow inward current (Isi) and on contractile force were studied in guinea-pig isolated ventricular myocytes and intact papillary muscles, respectively. In myocytes, both low (10 nmol/L) and high (1-10 mumols/L) concentrations had small or no effects in either direction on Isi whereas norepinephrine (10-100 nmol/L) increased it. To determine whether the same results are obtained after decreasing or increasing intracellular calcium or sodium, the same concentrations of strophanthidin were tested in different procedures that are known to (i) increase [Ca]i and decrease [Na]i (high [Ca]o, 3.6-5.4 mmol/L; low [Na]o, 112 mmol/L; (ii) decrease [Ca]i and increase [Na]i (low [Ca]o, 0.45-1 mmol/L; Sr, 1 mmol/L; (iii) decrease [Ca]i and [Na]i (Cd, 0.1-0.2 mmol/L); and (iv) increase [Ca]i and [Na]i (veratridine, 0.2 mumol/L). High [Ca]o and veratridine increased whereas low [Ca]o and Cd decreased Isi. In contrast, during these various procedures, strophanthidin had small and inconsistent effects at a low or high concentration. In intact papillary muscles, low strophanthidin decreased whereas high strophanthidin increased contractile force. It is concluded that strophanthidin has little direct or indirect effect on Isi and that the decrease in force by low and increase in force by high concentrations in intact muscle are probably related to demonstrated decrease and increase, respectively, in intracellular sodium activity.     

Ultrastructure of a two-cell human embryo

Summary A two-cell human embryo recovered from the Fallopian tube 82 h following the LH peak in plasma and 37 h after a single episode of intercourse was examined by transmission electron microscopy. At the time of recovery the embryo was denuded of cumulus cells, and both the zona pellucida and the two adjoining blastomeres were intact. The finding of two polar bodies in the perivitelline space, two nucleated blastomeres and remnants of the fertilizing sperm tail within the cytoplasm of one of them, were considered as evidences that the embryo was normally fertilized. Among the most compicuous features found were the presence of very distinct desmosome-like structure between blastomeres, and the cytoplasmic cell organelles distribution in three areas referred as: a sub-cortical, a middle and a perinuclear bands. An outstanding feature was the extensive blebbing of the nuclear envelope. In general, the features seem to correspond to a normally developing two-cell embryo undergoing cleavage at a normal rate.     

Comparatice effects of loratadine and selected antihistamines on sleep-waking patterns in the cat

The central effects of the new antihistamine loratadine and three reference antihistamine agents were studied in the cat. As a sensitive measure of drug action on the central nervous system (CNS) we evaluated changes in sleep-waking patterns. For comparison, diphenhydramine was studied as an example of an antihistamine having potent central effects; astemizole and terfennadine were used as examples of new agents claimed to be free of CNS effects. Diphenhydramine, given at 3 mg/kg p.o., increased spindle sleep, i.e., the electrophysiological correlate of drowsiness, and suppressed rapid eye movement (REM) sleep. In addition, cats displayed unusual sleep postures during the various sleep stages. Loratadine had little or no effect on the various features of sleep-waking patterns over a broad dose range (3 and 30 mg/kg p.o.). Astemizole, at 30 mg/kg p.p., significantly increased wakefulness and reduced both slow-wave sleep and REM. No significant changes of the sleep patterns occurred after the low dose of 3 mg/kg. Terfenadine reduced REM duration at 30 mg/kg p.o. but had no effects on sleep patterns at 3 mg/kg. The cat appeared to be a sensitive animal model to the central action of antihistamines since the reference drug diphenhydramine affected sleep-waking patterns at a dose that closely approximates the dose requirements for adverse CNS effects in man. Under the same conditions, loratadine was free of central actions at a dose range far above that effective either therapeutically or in standard tests in other animal species. Astemizole and terfenadine seemed to be devoid of CNS effects at doses similar to those effective as antihistamines in man, but they produced some central actions at higher doses. Comparing the clinically effective doses of the antihistamines examined, loratadine appears to be the least liable to produce adverse effects on the CNS function.     

Idiopathic normal pressure hydrocephalus associated with empty sella

A 70-year-old female presented with the clinical triad of normal pressure hydrocephalus (NPH) and senile tremor. Neuroimaging disclosed findings of both NPH and empty sella (ES). A ventriculoperitoneal shunt did not modify the clinical course except for a mild and transient improvement, and shunt malfunction occured later on. The association of NPH and ES may result from a common underlying mechanism such as transient increases in intracranial pressure.     

Laparoscopic Treatment of Gallbladder and Common Bile Duct Stones: A Prospective Study

n = 2), port site infection ( n = 2), and subumbilical hematoma ( n = 1). Major morbidity was bile leakage from the cystic duct stump in two cases due to clips or transcystic duct drainage displacement, respectively. One elderly, high risk patient died after being referred for several failed attempts of endoscopic clearance; she died from cardiogenic shock 3 days after successful laparoscopic treatment. Laparoscopic CBD exploration is feasible and safe in most patients, with short-term results that compare favorably with the results of sequential ES/LC reported in the literature.     

A preliminary study into the dental health status of multiple sclerosis patients

Multiple sclerosis (MS) is an inflammatory disease of unknown etiology involving the central nervous system. Since MS affects the whole body, orofacial aspects of the disease must be expected, particularly since loss of muscular coordination may result in a diminished ability to maintain oral hygiene. This preliminary study examined the dental health status of 22 volunteer MS patients. A questionnaire collected data regarding medical and dental histories and socieo-demographic information. Extra- and intra-oral examinations were carried out on all subjects to determine the particular dental treatment needs of this special group. The DMFT and CPITN scores for this group did not indicate that MS patients were more susceptible to dental caries or periodontal disease. However, the prevalence of trigeminal neuralgia and symptoms of TMJ dysfunction in the group studied indicated that these conditions may be manifest in MS patients and warrant further investigations.     

Interaction between Marihuana and Ethanol: Effects on Psychomotor Performance

This is a report of the results of a placebo-controlled study in which the effects of the interaction between ethanol and marihuana on drug plasma concentrations, subjective ratings of intoxication, heart rate acceleration, and psychomotor performance were investigated. Six healthy, male, paid volunteers, moderate users of ethanol and marihuana, participated in the study. Ethanol (0.42 g/kg, 0.85 g/kg, or placebo) was administered over a 30-min interval. Fifteen minutes later the subjects smoked, in their customary manner, NIDA cigarettes containing 2.4% or 0.0004% (placebo) delta-9-tetrahydrocannabinol (THC). Each subject was tested in a single-blind, latin-square crossover design with the following six conditions: placebo ethanol/placebo marihuana; low dose ethanol/placebo marihuana; high dose ethanol/placebo marihuana; placebo ethanol/marihuana; low dose ethanol/marihuana; and high dose ethanol/marihuana. The variables measured in the study were: (a) subjective rating of ethanol and/or marihuana intoxication; (b) heart rate; (c) accuracy and latency of response in the Simulator Evaluation of Drug Impairment (SEDI) task; (d) blood ethanol concentration by gas chromatography; and (e) plasma concentration of THC by radioimmunoassay. The results indicate that the decrements due to ethanol in performance of skills necessary to drive an automobile were significantly enhanced by marihuana in an additive and perhaps synergistic manner. The administration of ethanol prior to marihuana smoking did not produce significant effects on the subjective rating of "high," heart rate acceleration, or THC plasma concentration.