Relationships of plasma viscosity, coagulation and fibrinolysis to coronary risk factors and angina

Plasma viscosity, molecular markers of activated coagulation and fibrinolysis (fibrinopeptides A and B beta 15-42), coagulation factors (fibrinogen and factor VII) and antiplasmins were measured in 529 men aged 35-54 years and related to new angina pectoris (n = 117) and to coronary risk factors in controls without angina (n = 412). Five major risk factors (cigarette-smoking, blood pressure, cholesterol, triglyceride and body mass index) were each associated with increases in plasma viscosity, coagulation factors, and imbalance of coagulation over fibrinolysis (increased ratio of fibrinopeptide A/fibrinopeptide B beta 15-42). Increased viscosity and fibrinogen in smokers were partly reversed in ex-smokers, but the imbalance of coagulation and fibrinolysis persisted. Cholesterol and triglyceride were also associated with increased antiplasmin activity. In men with angina, only fibrinogen was elevated compared to controls. We suggest that increased plasma viscosity and an imbalance of coagulation over fibrinolysis may be mechanisms by which known risk factors promote arterial thrombosis, but are not present in stable angina.     

Outcome and clinical course in inpatient bulimic women: a 2- to 9-year follow-up study

BACKGROUND: One previous follow-up study suggested that inpatient bulimic women do quite poorly; after an interval of 2 to 5 years, only 13% were recovered. To examine the course and outcome of a sample of patients with bulimia nervosa that was severe enough to require inpatient hospitalization, the authors conducted the following study. METHOD: Women (N = 52) with DSM-III-R bulimia nervosa were sought 2 to 9 years after hospitalization. Prior to contact, a retrospective chart review was conducted to determine global functioning and admission diagnoses. At follow-up, patients participated in a 4 to 6 hour interview that assessed current and lifetime Axis I disorders (SCID-I), current Axis II disorders (PDE), eating behaviors (EAT, BSQ, EDI, PSR), global functioning (GAF), social adjustment (SAS-SR), and treatment and medical problems experienced since discharge. To assess the significance of differences between the recovered and the currently bulimic women, Yates-corrected chi-square tests and two-tailed t tests were used. RESULTS: Of the 52 women, 46 were interviewed, 1 had died, and 5 could not be located. Of the 46 interviewed women, 39% had fully recovered, 20% had partially recovered, and 41% were currently bulimic. The likelihood of recovery increased with length of time since discharge. While medical problems related to the bulimia were few, treatment with phenelzine was associated with three reports of serious hypertensive episodes, one of which led to death. Global functioning before hospitalization, lifetime DSM-III-R Axis I diagnoses, and current Axis II diagnoses were not associated with outcome. CONCLUSIONS: These findings suggest that even severely ill bulimic patients have a significant chance of achieving full recovery.     

Treatment with methylazoxymethanol at different gestational days: physical, reflex development and spontaneous activity in the offspring

Pregnant rats were injected with a single dose of methylazoxymethanol (MAM, 25 mg/kg) on gestational day 14, 15, 16, 17, 18 or 19 and offspring were tested for their physical development, reflex development and spontaneous activity. MAM treatment did not affect gestational and litter parameters at any of the time of administration studied. Treatment at gestational day 14 (GD14) had the most severe effect on functional neurodevelopment until weaning: righting reflex at surface, chimney test, horizontal wire test resulted altered. Administration at GD15, 16, 18, 19 did not affect the performance in these tests. Offspring treated at GD17 showed a delayed eye opening and an impaired performance in the horizontal wire test. When tested at 50 days of age on the rotarod, all the treated groups performed worse than controls with the exception of GD19 treated offspring. Administration at GD14 and GD15 resulted in increased spontaneous activity of the offspring at 21 days but not at 60 days of age. Different degrees of microencephaly were observed for all treated groups. The results indicate that alterations of physical and behavioral development induced by MAM treatment are dependent on the time of MAM administration, and specific behavioral tests are able to detect different abnormalities and differentiate among treatment groups. Some alterations observed in MAM rats undergo to adaptive changes during maturation of the CNS.     

Dibutyryl-cAMP induces SNAP-25 translocation into the neurites in PC12.

SNAP-25 immunoreactivity was translocated into the endings of the processes induced in PC12 cells by dibutyryl-cAMP-treatment. Conversely, the protein was not present in the endings of the processes seen after NGF-treatment unless dibutyryl-cAMP was used simultaneously. This redistribution of SNAP-25 immunoreactivity appeared to be dependent upon new protein synthesis. Finally, dibutyryl-cAMP was capable of inducing SNAP-25 expression.     

Afterpotential characteristics and firing patterns in maturing rat hippocampal CA1 neurones in in vitro slices.

The postnatal evolution of depolarizing after-potentials (DAPs) and after-hyperpolarizations (AHPs) was studied in rat CA1 hippocampal neurones (5-68 days of age) using in vitro slices. Results were pooled into 4 age groups: P5-9, P10-16, P17-24 and P26-68. In P5-9 cells, DAPs were seen as passive signals, with a time constant similar to the time constant of the membrane. The evolution of the DAP was characterized by a decrease in amplitude, an increase in duration and a change in contour. In P10-16 and P17-24 cells, the DAPs often had a plateau or a hump-like shape which increased the probability of firing and the occurrence of spike doublets. The firing pattern and bursting behaviour of P10-16 CA1 neurones differed from the pattern typical of the adult. P5-9 and P10-16 cells had post-burst AHPs with a smaller amplitude and a more prolonged early phase than at late stages of development.     

Pharmacological modulation of neuropeptides in peripheral mononuclear cells.

The concentrations of beta-endorphin and cholecystokinin were measured in fresh resting peripheral mononuclear cells obtained from rats and human subjects in basal conditions and after different pharmacological treatments. Both in the human and the rat, beta-endorphin concentrations in mononuclear cells, increased after treatment with serotoninergic agonists, decreased after dopaminergic or GABAergic drugs, while the respective antagonists exerted the opposite effect. In vitro, serotoninergic and GABAergic compounds confirmed their roles in the modulation of beta-endorphin in mononuclear cells. Cholecystokinin was never affected by the pharmacological treatments.     

The identity of the calcium-storing, inositol 1,4,5-trisphosphate-sensitive organelle in non-muscle cells: calciosome, endoplasmic reticulum ... or both?

Although the initial phase of receptor-mediated Ca2+ signaling, involving Ca2+ release from intracellular stores by inositol 1,4,5-trisphosphate, is relatively well characterized, the nature of the organelle releasing Ca2+ is a controversial subject. At issue is the question of whether Ca2+ is released from the endoplasmic reticulum, or from a more specialized organelle called the 'calciosome'. In this review, we attempt to analyse the arguments for and against these two views, and attempt to reconcile some of the apparently conflicting findings by proposing a hypothetical model of the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool.     

Familial association of intracranial aneurysms and cervical artery dissections.

BACKGROUND AND PURPOSE: The familial occurrence of intracranial aneurysms and cervical artery dissections has been described in different families and supports the hypothesis that a primary arteriopathy may play a role in the pathogenesis of these disorders. Although the basis for this arteriopathy is generally not believed to be similar among cases of intracranial aneurysms and cervical artery dissections, several similarities exist in the epidemiology of these disorders and a common underlying arterial abnormality may be suspected. SUMMARY OF REPORTS: The medical records of all 175 patients with spontaneous dissections of the cervical arteries who were seen at the Mayo Clinic between 1970 and 1989 were reviewed to identify families in which intracranial aneurysms and cervical dissections coexisted. Three families were identified in which intracranial aneurysms and cervical artery dissections were observed among siblings. These families are described in detail. CONCLUSIONS: The familial occurrence of intracranial aneurysms and cervical artery dissections within the same families provides support to the importance of a common underlying arteriopathy in the pathogenesis of both these disorders. The underlying vascular defect may, at least in some cases, be inherited.     

Cerebral and peripheral neurotoxicity of chlorpromazine and ethanol interaction: implications for alcohol and aldehyde dehydrogenase.

The effects of certain experimental variables on rodents brain and liver alcohol--(ADH) and aldehyde-dehydrogenase (LALDH) were evaluated. The in vivo and in vitro effect of chlorpromazine on these enzymes was determined. Short-term housing under complete darkness differentially inhibited ADH and ALDH in distinct brain regions with ADH showing more sensitivity than ALDH. The hepatic enzymes studied were not affected by such housing conditions but a non-competitive inhibition of L-ALDH occurred as a consequence of exposure to UV lighting for 3 consecutive weeks. Short-term treatment with chlorpromazine inhibited striatal ADH which was not affected by experimentally-induced hypothermia. Likewise, both hepatic and testicular ADH were noncompetitively inhibited in vitro by chlorpromazine. The results suggest sensitivity of brain and hepatic ADH to environmental housing conditions and indicate a similarity between peripheral and cerebral ADH responses to chlorpromazine. The modulation of ADH and/or ALDH may facilitate the formation of endogenous biogenic amines derived alkaloids which have been implicated in alcohol and extrapyramidal side effects.