Partial identification of the fibrinolytic activators in onion.

A steam-distilled and an ether extract of onion have both been found to enhance blood fibrinolysis without depressing fibrinogen content in groups of human volunteers. Chemical analysis has shown which sulphur-containing compounds were in highest concentration and common to both and thus likely to carry this property, but their very intense and prolonged flavour precludes their clinical use. One sulphur containing but nearly odourless compound has been identified as having indirect fibrinolytic potential. A species difference in respect of fibrinolysis has been found between English and Spanish onion but is of little importance.

Stress versus depression.

1. Exhaustive evidence is quoted showing that uncontrollable (uncoping) stress provoked in experimental mammals leads to depletion of central noradrenergic activity+ adrenomedullary-cortical gland hyperactivity. These physiological disorders cause the typical neuroendocrine peripheral profile: a) raised catecholamines (CA) in plasma [noradrenaline (NA)+adrenaline (Ad)+dopamine (DA), b) reduced NA/Ad ratio in plasma and c) raised plasma cortisol. 2. Exhaustive evidence is quoted which indicates that severely ill humans show peripheral neuroendocrine profile similar to that found in mammals submitted to uncontrollable stress situation. Further, the NA/Ad ratio does not increase but decreases during orthostasis and exercise stress challenges, as well as oral glucose stress (tolerance) test. 3. Exhaustive evidence is quoted which indicates that endogenous depressed subjects show a neuroendocrine profile opposite to that observed in stressed mammals and severely ill humans. This profile consists of central NA (neural sympathetic) hyperactivity+ adrenomedullary glands hyporresponsivity. These disorders are reflected in a three to ten fold increase of the NA/Ad ratio in plasma. 4. Exhaustive evidence is also quoted showing that dysthymic depressed patients show low plasma catecholamines+low NA/Ad plasma ratio (< 2) during supine-resting condition, it is normalized at orthostasis and exercise periods. 5. It is quoted evidence showing that whereas platelet serotonin is increased in dysthymics, the same is reduced in both endogenous depressed and stressed mammals as well as severely ill humans. 6. It is quoted evidence showing that free serotonin in plasma is greatly raised in uncoping stressed mammals and severely ill humans. The same parameter is normal or slightly increased in dysthymic and endogenous depressed humans. These findings are consistent with the increased platelet aggregability observed in "uncontrollable" stressed mammals and in severely ill, but not depressed patients. 7. It is also quoted evidence showing that whereas parasympathetic activity is absent in uncontrollable stressed mammals and severely ill humans, the same is increased in both types of depressed humans. 8. According to the above, the authors postulate the existence of 3 distinct central+ peripheral neuroendocrine profiles for endogenous depression, dysthymic depression and maladaptation to stress syndrome. These different profiles should lead researchers to attempt different therapeutical approach. 9. In view of the fact that the authors found much clinical overlap among the three syndromes (endogenous depression, dysthymic depression and severely ill patients), they believe that a differential diagnosis should be based on neurochemical, neuroendocrine, physiologic, metabolic and neuropharmacological grounds. 10. The experimentally induced uncontrollable stress (behavioral despair) syndrome in mammals should not be used as a valid model of human depressive syndrome.

Effect of essential oil of onion (allyl propyl disulphide) on blood glucose, free fatty acid and insulin levels of normal subjects.

The administration of allyl propyl disulphide (APDS), a volatile substance contained in onion, to six normal volunteers after a 12 hour fast caused a significant fall in the blood glucose levels and a significant rise in the serum insulin levels during the subsequent 4 hours. It is argued that this effect is due to an insulin sparing action. The expected rise of serum free fatty acid levels after fasting did not occur after APDS administration and this effect is probably related to the simultaneous rise in the insulin levels.

The evaluation of eye patching in the treatment of traumatic corneal epithelial defects.

The objective of this study was to compare the rates of healing for patched and non-patched traumatic corneal epithelial defects (CEDs) after 1 day of treatment. To achieve this we initiated a randomized, controlled, prospective, clinical investigation comparing patching vs. non-patching of CEDs. Patients were evaluated initially and at 24 h using slit lamp biomicroscopy, and each corneal epithelial defect was documented on standardized initial and follow-up grid sheets. Percentage of healing and healing rates were determined by comparing the grid sheets. Our results found no significant difference in abrasion size between the two groups, but there was found to be a significantly improved rate of healing at follow-up in non-patched patients. This study demonstrates a significant improvement in the healing rate of traumatic CEDs in the non-patched group as compared to the patched group; therefore, the use of eye patching is not mandatory for corneal epithelial healing to occur.

Effect of nifedipine on carbohydrate metabolism and serum lipoproteins in hypertensive patients with and without diabetes mellitus.

Newly diagnosed hypertensive patients, and patients with hypertension which was not controlled by their existing therapy, were studied in a single-blind, placebo-controlled trial. Criteria for inclusion in the study were a systolic blood pressure less than 160 mmHg and a diastolic blood pressure greater than 95 mmHg. The study group was composed of 15 non-diabetic patients, 14 patients with non-insulin dependent diabetes mellitus (NIDDM) and 13 patients with insulin-dependent diabetes mellitus (IDDM). Mean supine and erect, systolic and diastolic blood pressure were reduced in all three groups after 2 and 14-16 weeks of nifedipine therapy (P less than 0.001). Mean fasting blood glucose, mean haemoglobin A1, mean total serum cholesterol, mean high density lipoprotein (HDL) cholesterol and mean serum triglycerides were not affected by nifedipine in any of the three groups over the 14-16 weeks' treatment. Forty out of the 42 patients entering, completed the study. One patient with NIDDM and angina died from a myocardial infarction in the final 4 weeks of the study, and one non-diabetic patient was unable to tolerate nifedipine after two weeks of treatment and was withdrawn from the study. No patients were withdrawn due to treatment failure.

Benzodiazepines: tolerability in elderly patients.

Aging is a physiological process that shares many behavioral, biochemical and neuroendocrine phenomena with the pathophysiological situation of unresolved stress, as well as with a pharmacologically induced syndrome resulting from chronic benzodiazepine (BZ) consumption. Behavioral findings include symptoms such as drowsiness, ataxia, fatigue, confusion, weakness, dizziness, vertigo, syncope, reversible dementia, depression, impairment of intellectual, psychomotor and sexual function, agitation, auditory and visual hallucinations, paranoid ideation, panic, delirium, depersonalization, sleepwalking, aggressivity, orthostatic hypotension, and insomnia. Neuroendocrine findings include: central depletion of noradrenaline (NA), dopamine, adrenaline (AD), and serotonin (5-HT); reduction in the ratio of circulating NA/AD as well as platelet 5-HT and increase of AD, plasma free 5-HT and cortisol. These disturbances together with the increased platelet aggregability observed in the three groups are typical of unresolved-stress situations. Immunological findings include significant reduction of peripheral T lymphocytes (CD3, CD4, CD8) and the CD4/CD8 ratio, CD16 and gamma-delta cells. On the other hand, the three groups (elderly subjects, subjects faced with unresolved stress, and BZ consumers) show increase of the CD57 lymphocyte subset as well as natural killer cytotoxicity. Alterations of several biological markers have also been found, specifically in the oral glucose tolerance test, the intramuscular clonidine test, and the supine/orthostasis/exercise test. From a clinical point of view, the three groups appear to be more susceptible to the appearance and progression of many acute and chronic diseases (infectious and malignant diseases). As a result, chronic consumption of BZs should be avoided in both the elderly and subjects in unresolved-stress situations.

Treatment of Cushing's disease with adrenal blocking drugs and megavoltage therapy to the pituitary.

Eighteen patients with Cushing's disease were seen over a 40-month period and considered for treatment by pituitary irradiation and adrenal blocking drugs. Fourteen patients entered the study and each received megavoltage therapy to give a mean dose of 4600 rad to the pituitary over 31 days. Each patient was treated for one (two patients) or two (12 patients) years with one or both of the adrenocortical enzyme inhibitors, metyrapone or aminoglutethmide to suppress cortisol secretion. Doses were adjusted to maintain urinary free cortisol secretion below 300 nmol/24 h. One patient failed to complete the trial. Normal urinary free cortisol excretion and plasma cortisol concentration were maintained after treatment in eight of the remaining 13 patients after therapy. Only one patient required cortisol replacement and normal menstrual function was restored in five of the six women. The remaining five patients relapsed and four were subsequently treated by total adrenalectomy. It was noted that the patients who responded to treatment were substantially younger than the therapeutic failures. It is suggested that this treatment is most useful in the management of younger patients.

Effects of buspirone on plasma neurotransmitters in healthy subjects.

Buspirone is an anxiolytic drug which exerts several central effects. It antagonizes presynaptic inhibitory DA2 autoreceptors at dopaminergic neurons and acts as an agonist for 5-HT1A inhibitor autoreceptors at serotonergic cells. Thus, buspirone respectively enhances and depresses the firing rates of both type of neurons. At doses which correlate with dopaminergic stimulation, but not 5-HT inhibition, buspirone also increases the firing rates of the central noradrenergic cells. We measured levels of circulating neurotransmitters before and up to 240 minutes after the oral administration of 20 mg of buspirone in 32 healthy volunteers. Buspirone significantly increased levels of noradrenaline, dopamine, and free serotonin but did not affect levels of adrenaline, tryptophane, or platelet serotonin. Small but significant drops in systolic blood pressure and heart rate were observed after buspirone ingestion. Atropine administration before buspirone ingestion annulled the free serotonin increase as well as systolic blood pressure-heart rate decrease. We found significant positive correlations between noradrenaline and dopamine levels. The strength and significance of these correlations were increased by using the noradrenaline/adrenaline ratio instead of noradrenaline absolute values. This finding indicates that increases in both noradrenaline and dopamine arise from sympathetic nerves rather than the adrenal glands. We also found significant negative correlations between free serotonin increases and systolic blood pressure-heart rate decreases. Our results indicate that buspirone stimulates central sympathetic activity. These acute effects of buspirone are reflected in an increased peripheral neural sympathetic activity, but not adrenal sympathetic activity in healthy individuals. In addition, buspirone increases free serotonin plasma concentrations and decreases systolic blood pressure plus heart rate levels through mechanisms associated with parasympathetic activation.

Plasma neurotransmitters, blood pressure and heart rate during supine resting, orthostasis and moderate exercise in severely ill patients: a model of failing to cope with stress.

BACKGROUND: Previous clinical research has shown that severely ill (somatic) as well as many psychosomatic patients show raised noradrenaline (NA), adrenaline (AD), cortisol, free serotonin (f5HT) and platelet aggregability. Conversely, they show reduced NA/AD plasma ratio and platelet serotonin (p5HT). They also show adrenal hyperresponsiveness to an oral glucose load. These findings are opposed to those observed in depressed patients who show adrenal gland sympathetic hyporesponsiveness and neural sympathetic hyperactivity. OBJECTIVE: To investigate adrenal gland and neural sympathetic systems as well as the other parameters in nondrepressed severely ill patients through the orthostasis exercise stress test which in normals triggers NA but no AD rise. METHODS: We investigated 35 severely ill patients and their age- and sex-paired controls. Systolic, diastolic pulse pressure (PP), heart rate and neuroendocrine parameters were measured supine (0 min), at orthostasis (1 min) and exercise (5 min). A second test was performed 2 weeks later, after atropine injection. Multivariate analysis of variance, paired t test and Pearson product-moment test were employed. RESULTS: The normal PP orthostasis fall was not observed in patients. At this period, an abnormal AD peak substituted the normal NA peak. The normal p5HT-f5HT orthostasis-exercise peaks were absent in patients. Cortisol and platelet aggregability were raised in patients. CONCLUSIONS: Severely ill (somatic) patients responded to the orthostasis-exercise stress test with adrenal and corticosuprarenal but not neural sympathetic activity. They did not show the normal parasympathetic activity at orthostasis. This adrenal gland sympathetic hyperactivity registered in somatic patients is similar to that observed in mammals which fail to cope with stress and contrary to the profile registered in depressed subjects who show NA but not AD rise.