Extrapancreatic insulin effect of glibenclamide

In eight patients with uncomplicated non insulin dependent diabetes mellitus, serum insulin levels, serum C-peptide levels and blood glucose levels were measured before and after oral administration of glibenclamide 0.1 mg/kg body weight and a test meal, or after a test meal alone. The rise in serum insulin levels persisted longer after glibenclamide. The initial rise in serum insulin was of the same magnitude in both situations, as was the rise in serum C-peptide levels during the entire 5 h study. It is concluded that glibenclamide is able to maintain a more protonged increase in serum insulin levels by inhibiting the degradation of insulin in the vascular endothelial cells of the liver. The inhibition contributes to the blood glucose lowering effect of glibenclamide

RNAi in the regulation of mammalian viral infections

Although RNA interference (RNAi) is known to play an important part in defense against viruses of invertebrates, its contribution to mammalian anti-viral defense has been a matter of dispute. This is surprising because all components of the RNAi machinery necessary for robust RNAi-mediated restriction of viruses are conserved in mammals, and the introduction of synthetic small interfering RNAs (siRNAs) into cells efficiently silences the replication of viruses that contain siRNA complementary sequences in those cells. Here, I discuss the reasons for the dispute, and review the evidence that RNAi is a part of the physiological defense of mammalian cells against viral infections

RNA interference approaches for treatment of HIV-1 infection

HIV/AIDS is a chronic and debilitating disease that cannot be cured with current antiretroviral drugs. While combinatorial antiretroviral therapy (cART) can potently suppress HIV-1 replication and delay the onset of AIDS, viral mutagenesis often leads to viral escape from multiple drugs. In addition to the pharmacological agents that comprise cART drug cocktails, new biological therapeutics are reaching the clinic. These include gene-based therapies that utilize RNA interference (RNAi) to silence the expression of viral or host mRNA targets that are required for HIV-1 infection and/or replication. RNAi allows sequence-specific design to compensate for viral mutants and natural variants, thereby drastically expanding the number of therapeutic targets beyond the capabilities of cART. Recent advances in clinical and preclinical studies have demonstrated the promise of RNAi therapeutics, reinforcing the concept that RNAi-based agents might offer a safe, effective, and more durable approach for the treatment of HIV/AIDS. Nevertheless, there are challenges that must be overcome in order for RNAi therapeutics to reach their clinical potential. These include the refinement of strategies for delivery and to reduce the risk of mutational escape. In this review, we provide an overview of RNAi-based therapies for HIV-1, examine a variety of combinatorial RNAi strategies, and discuss approaches for ex vivo delivery and in vivo delivery

Screening for congenital hypothyroidism, first trimester 1990

In the first trimester of 1990, 49601 newborn babies were screened for congenital hypothyroidism. In 695 cases (1.40%) a second heel card was requested. In this group 103 babies were pre- or dysmature. For 50 children no data on birth weight or duration of pregnancy were provided. 391 children were screened according to the so called modified procedure. Of the 1187 samples mentioned in Table 2 in 52 cases the date of sampling and in 3 cases the date of birth was deleted. There is some variation between the laboratories with respect to the T4-level (Tables 3 and 4). The daily means in this trimester range from 122-146 pg/punch. In contrast the results obtained with the external quality control samples show a smaller range. After 37 trimesters of screening the general conclusion is that the program functions well.RIV

Distribution of extracellular potassium and electrophysiologic changes during two-stage coronary ligation in the isolated, perfused canine heart

We studied the relation between [K+]o and the electrophysiologic changes during a "Harris two-stage ligation," which is an occlusion of a coronary artery, preceded by a 30-minute period of 50% reduction of flow through the artery. This two-stage ligation has been reported to be antiarrhythmic. Local direct current electrograms and [K+]o signals from up to 48 intramural sites were simultaneously recorded in isolated, perfused dog hearts. A second period of one-stage ligation was compared with a consecutive two-stage ligation because reproducibility in [K+]o and electrophysiologic changes are established only after the first period of ischemia. In control experiments, no difference was found between the second and third period of one-stage ligation in the electrophysiologic changes and in increases in [K+]o. After complete occlusion during two-stage ligation, activation block in the ischemic tissue occurred about 6 minutes earlier than during one-stage ligation, but the average potassium concentration at which block occurred was identical. This [K+]o during total ischemia was achieved earlier during two-stage ligation than during one-stage ligation. No indication was found for a large decrease of intracellular potassium content during the period of low flow perfusion. Early activation block may explain the previously reported reduced incidence of ventricular fibrillation during two-stage ligatio