The efficacy of clofibrate (CPIB) and nicotinic acid (NA) in the treatment of type III hyperlipoproteinemia was evaluated in 5 male subjects in a randomized cross-over study with clofibrate 1 g b.i.d. and NA 3 g/day (given either b.i.d. or t.i.d.). Following a baseline period of 6 weeks, each drug was given for 12 weeks with samples for lipid and lipoprotein determinations obtained at 6, 9, and 12 weeks. Both clofibrate and NA resulted in a significant reduction from baseline of total cholesterol (23% and 28%), VLDL cholesterol (49% and 56%), total triglycerides (40% and 43%), and VLDL triglycerides (46% and 48%), as well as a significant increase in HDL cholesterol (22% and 28%) and HDL/LDL ratio (31% and 62%). The HDL/LDL ratio was higher on NA than clofibrate (0.47 +/- 0.19 vs. 0.38 +/- 0.09, P less than 0.05). Four subjects were continued in the study and treated sequentially with NA 3.0 g/day (alternate to the previous schedule) and gemfibrozil 1.2 g/d in divided doses. Each of the 4 regimens resulted in a significant change from baseline of each of the measured lipid and lipoprotein determinations except LDL cholesterol. Comparison among the treatment regimens revealed no differences except for significantly higher HDL cholesterol and HDL/LDL ratio with NA given t.i.d.

Adult↗

PubMedDate not supplied

Sustained rise in ACh sensitivity of a sympathetic ganglion cell induced by postsynaptic electrical activities.

Long-term alteration in synaptic efficacy found in several neurones of both vertebrates and invertebrates has been suggested as an important mechanism for learning and memory. In bullfrog sympathetic ganglia, acetylcholine (ACh) release from presynaptic nerve terminals is potentiated for a long time by adrenaline through a cyclic AMP system. We report here a new form of mechanism for long-term synaptic potentiation in sympathetic ganglia, which occurs postsynaptically in a Ca2+-dependent manner. Our results suggest that Ca2+ entry into a ganglion cell during repeated action potentials initiates a long-lasting mechanism for the enhancement of a nicotinic ACh action on the subsynaptic membrane. This, as well as the presynaptic mechanism, may contribute to neuronal plasticity in the peripheral autonomic nervous system.

Acetylcholine↗

PubMedDate not supplied

Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey.

The Minnesota Coronary Survey was a 4.5-year, open enrollment, single end-time double-blind, randomized clinical trial that was conducted in six Minnesota state mental hospitals and one nursing home. It involved 4393 institutionalized men and 4664 institutionalized women. The trial compared the effects of a 39% fat control diet (18% saturated fat, 5% polyunsaturated fat, 16% monounsaturated fat, 446 mg dietary cholesterol per day) with a 38% fat treatment diet (9% saturated fat, 15% polyunsaturated fat, 14% monounsaturated fat, 166 mg dietary cholesterol per day) on serum cholesterol levels and the incidence of myocardial infarctions, sudden deaths, and all-cause mortality. The mean duration of time on the diets was 384 days, with 1568 subjects consuming the diet for over 2 years. The mean serum cholesterol level in the pre-admission period was 207 mg/dl, falling to 175 mg/dl in the treatment group and 203 mg/dl in the control group. For the entire study population, no differences between the treatment and control groups were observed for cardiovascular events, cardiovascular deaths, or total mortality. A favorable trend for all these end-points occurred in some younger age groups.

Adult↗

PubMedDate not supplied

Stimulatory effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on cyclic AMP formation in the hypothalamus and cerebral cortex of four avians and rat.

PACAP38 and PACAP27, tested at 0.0001-1 microM, potently stimulated synthesis of cyclic AMP in the hypothalamus and cerebral cortex of chicks; the effects of vasoactive intestinal polypeptide (VIP) in the two brain regions were much weaker, reaching statistical significance only at 3 microM concentration. This characteristics suggests the existence in the bird's brain of adenylyl cyclase-linked PAC1 receptors. PACAP27 (0.001-1 microM) concentration-dependently stimulated cyclic AMP production in the hypothalamus and cerebral cortex of three other birds: duck, goose and turkey; the effects were, however, somewhat lower than those in chicks, but comparable to those found in rats. These data demonstrate PACAP to be capable of potently stimulating cyclic AMP generating system in the avian central nervous system.

Animals↗

PubMedDate not supplied

Effects of neuropeptides of the secretin/VIP/PACAP family on cyclic AMP formation in the chick hypothalamus and cerebral cortex.

Six neuropeptides: short and long form of the pituitary adenylate cyclase activating polypeptide (PACAP), i.e. PACAP27 and PACAP38, vasoactive intestinal peptide (VIP), peptide histidine-isoleucine (PHI), secretin and glucagon, members of the secretin/VIP/PACAP superfamily ofpolypeptides, were tested for their ability to stimulate cyclic AMP formation in [3H]adenine-prelabeled slices of the chick hypothalamus and cerebral cortex. Of the tested peptides, only PACAP evoked pronounced and significant responses in the two analyzed brain structures. Although magnitude of the responses varied in different experiments, the effects of both forms of PACAP were usually larger in the cerebral cortex than in the hypothalamus. Glucagon, PHI (both used at concentrations 0.01-1 microM) and VIP (0.1-3 microM) induced concentration-dependent yet comparatively small effects that did not reach statistical significance, while secretin (0.1-3 microM) had no effect.

Amino Acid Sequence↗