Actions of phencyclidine on the action potential and membrane currents of single guinea-pig myocytes

The direct actions of phencyclidine (PCP) on mammalian sarcolemma were examined by determination of the drug's effects on the action potentials of isolated guinea-pig ventricular cells, and on the underlying ionic currents. PCP (10(-6) to 10(-4) M) did not alter the resting membrane potential but produced a dose-dependent prolongation of the duration of the action potential, and a reduction of the rate of depolarization of phase 0 (Vmax) of the action potential. Voltage clamp experiments revealed that PCP blocks both myocardial Ca++ channels and myocardial time-dependent K+ channels. The K+ channel blockade was shown to exhibit an apparent voltage-dependence. The effects of PCP on these ionic channels could explain previous reports of it prolonging myocardial action potentials and conflicting reports of positive and negative inotropism.     

The Effect of High-Dose Ascorbate Supplementation on Plasma Lipoprotein(a) Levels in Patients With Premature Coronary Heart Disease

Study Objective . To determine the efficacy of high-dose ascorbate supplementation in lowering lipoprotein(a) [Lp(a)] levels in patients with premature coronary heart disease (CHD). Design . Randomized, double-blind, placebo-controlled trial. Setting . Outpatient clinic. Patients . Forty-four patients with documented premature CHD. defined as confirmed myocardial infarction and/or angiographically determined stenosis of 50% or greater in at least one major coronary artery before age 60 years. Interventions . Patients were block randomized on the basis of age, gender, and screening Lp(a) concentrations to receive ascorbate 4.5 g/day or placebo for 12 weeks. Measurements and Main Results . High-dose ascorbate was well tolerated and produced a marked elevation in mean plasma ascorbate levels (+1.2 mg/dl; p<0.001). Multiple linear regression analysis revealed no significant effect of supplementation on postintervention Lp(a) levels (p=0.39) in a model that included treatment group assignment, and baseline Lp(a) levels. Conclusions . Our findings do not support a clinically important lowering effect of high-dose ascorbate on plasma Lp(a) in patients with premature CHD.     

DNA-ploidy studies in a keratocyst undergoing subsequent malignant transformation

Using techniques that allow flow cytometry to be performed on tissue stored in paraffin wax, we have examined the DNA content of cells from an odontogenic keratocyst which underwent malignant transformation. On histological examination, the primary lesion was an odontogenic keratocyst showing dysplastic changes within the squamous epithelium. Flow cytometry revealed a prominent, abnormal DNA stemline, which was also present in the subsequent squamous cell carcinoma.     

Successful Treatment of Kasabach-Merritt Syndrome with Prednisone and Epsilon-Aminocaproic Acid

The Kasabach-Merritt syndrome is characterized by thrombocytopenia and localized coagulopathy associated with a hemangioma. Most techniques applied to eradicate the tumor or accelerate its involution (surgery, radiation therapy, embolization) are invasive and require transfusion of large amounts of blood products. In some cases, medical treatment is the only alternative. Efficacy of steroids and antifibronolytic agents has already been described, but even this approach is associated with the administration of blood products. We report two cases of infants with Kasabach-Merritt syndrome associated with cardiac and hepatic hemangiomas. At admission, both had signs of cardiac failure. They were successfully treated with prednisone and epsilon-aminocaproic acid (EACA). Blood products were not required once the diagnosis was made. These observations have important implications for the management of patients with Kasabach-Merritt syndrome because they show that even in severe cases blood transfusions can be avoided by the use of prednisone and EACA.     

Swallowing food without chewing; a simple way to reduce postprandial glycaemia

1. The degree to which disruption by mastication affects the glycaemic response to four different carbohydrate foods was investigated in healthy human volunteers; each food was eaten by six subjects. 2. Subjects ate meals of sweetcorn, white rice, diced apple or potato on two occasions; on one occasion they chewed the food thoroughly, on the other occasion they swallowed each mouthful without chewing it. 3. When the foods were chewed the postprandial blood glucose levels rose to levels which varied according to the food ingested. 4. Swallowing without chewing reduced the glycaemic response to each food, achieving a similar effect as administration of viscous polysaccharides or 'slow-release' carbohydrates.     

Calcium channel antagonist properties of Bay K 8644 in single guinea pig ventricular cells

The effects of Bay K 8644 on the high-threshold calcium channel was investigated by means of the whole-cell patch-clamp technique in single guinea pig ventricular myocytes. The goal of the experiments was to characterize the inhibitory effects of Bay K 8644 on the calcium channel, and identify the factors that influence the inhibition. Bay K 8644 was found to have strong calcium channel antagonist properties, which were both dose- and voltage-dependent. Channel block by Bay K 8644 had both a tonic and a use-dependent component. The stimulatory effect of the drug was found to have little obvious dependence on the holding potential. The accumulation of use-dependent block during trains of pulses was facilitated by faster rates of stimulation, longer pulse durations, and more positive holding potentials. Application of the drug induced the appearance of a second, slow component of calcium channel recovery. Both the time-constant and relative proportion of the slow component of recovery were found to be voltage-dependent. Bay K 8644 was also found to cause a hyperpolarizing shift of the inactivation curve for the calcium current, suggesting that it has strong interactions with the inactivated state of the calcium channel. Thus, Bay K 8644 has, along with its stimulatory effects, inhibitory effects that strongly resemble those of typical calcium channel antagonists.