Melatonin has profound effects on mitochondrial dynamics in myocardial ischaemia/reperfusion.

Research focus recently shifted to mitochondrial dynamics and the role of fusion and fission in cardioprotection. The aim of this study was to evaluate (i) the function and dynamics of mitochondria isolated from hearts exposed to ischaemia/reperfusion (I/R) (ii) the effects of melatonin, a powerful cardioprotectant, on mitochondrial dynamics in I/R. Isolated perfused rat hearts were stabilized for 30 min, subjected to 20 min global ischaemia, followed by 30 min reperfusion. Tissue was collected, mitochondria isolated for measurement of mitochondrial oxidative function and lysates from mitochondrial and cytosolic fractions prepared for western blotting. Melatonin (0.3 or 50 µM) was administered for 10 min immediately before the onset of ischaemia and for 10 min at the onset of reperfusion. Infarct size was assessed after 35 min regional ischaemia/60 min reperfusion using triphenyltetrazolium staining. The results show that reperfusion significantly reduced mitochondrial QO2 (states 3 and 4), with minor effects by melatonin. Cytosolic Beclin 1 and the LC3 II/I ratio were reduced by ischaemia and increased by reperfusion. Both ischaemia and reperfusion reduced mitochondrial PINK1 and Parkin levels, while reperfusion increased p62. An alternative mitophagy pathway mediated by Rab9 is activated during myocardial ischaemia/reperfusion. Ischaemia reduced and reperfusion increased cytosolic ULK1 expression, associated with redistribution of Rab9 and Drp1 between the cytosol and mitochondria. Melatonin significantly reduced mitochondrial p62 expression upon reperfusion. Throughout the protocol, melatonin significantly (i) increased cytosolic total (t) and phospho (p) ULK1, and Rab9 levels (ii) increased the cytosolic and reduced the mitochondrial pDrp1 levels and p/t Drp1 ratio, suggesting inhibition of mitochondrial fission. Fusion was affected to a lesser extent. Cardioprotection by melatonin is associated with substantial effects on mitophagy, the significance thereof remains to be established.

Cardiac manifestations of digoxin intoxication. (Clinical correlations with serum levels).

Clinical, electrocardiographic and laboratory data were found out in 52 patients with cardiac arrhythmias and conduction defects due to digoxin intoxication. Forty six nontoxic patients were also studied for comparison. Blood urea concentration was significantly higher in toxic patients as compared to nontoxic ones (P less than 0-01). Ventricular bigeminy and trigeminy (38.6%), multifocal ventricular premature beats (25%) and second or third degree A-V blocks (25%) were very much prevalent. Fairly good correlations have been observed between different cardiac arrhythmias and serum digoxin levels. Significantly higher mean serum digoxin levels were observed in patients with A-V block and multifocal ventricular premature beats as compared to patients with supraventricular arrhythmias.

Serum magnesium concentrations in atrial fibrillation.

Serum magnesium and digoxin levels were obtained in 13 nontoxic patients with atrial fibrillation due to chronic rheumatic heart disease receiving digoxin for the control of ventricular rate and heart failure. Fairly good correlations were made between serum digoxin levels and ventricular rates. Hypomagnesemia was quite common (7 out of 13) and mean magnesium serum levels were significantly lowered in total as well in 7 hypomagnesemic patients, as compared to in healthy controls. Magnesium sulphate was successfully used in patients with magnesium deficiency to control the ventricular rates.

Personality types in Ayurveda.

The basis of human personality as given in ancient Hindu Ayurvedan literature is reviewed and interpreted in the light of current knowledge and understanding. The structure of mind expounded in Sankhyan philosophy is explained and its parallelism with the Freudian approach is brought out. The formative influences in the development of the mental constitution of an individual are described. An attempt is made to demonstrate close similarity between Ayurvedan and Lewin's field (Gestalt) theories. Significance of Tridosh (Vet, Pitta and Kaf), by vitiating the chemical balance, as etiological factors of mental illness is described. Sixteen personality types and their correspondence with 16 types of mental disorders are mentioned.

Psychiatric training and therapies in Ayurved.

This paper describes the selection and training procedures, ethical codes, metaphysical theories and principles of psychiatric treatments as practiced in Ayurved. Three treatment approaches for psychological disorders are: Ministered therapies (psychotherapies), Performance therapies (rituals), Auto therapies. Other forms of therapies mentioned are herbal, physical and natural. Treatments were administered with benediction. Man was treated as a whole with a psychosomatic approach. Ayurved is still a living science, though much of its knowledge has passed into oblivion. Resurrection of the lost treasure is advocated if the objective of 'Health for All by 2000 A.D.' is to be achieved for countries like India.

Severe depression in different cultures.

The observations on 99 cases of psychotic depression as per I.C.D.--8 categories 296.0, 296.2, 298.0 (WHO 1967) which were included and studied during the course of the 'International Pilot Study of Schizophrenia' carried out in nine field research centres in different countries are reported. An attempt is made to high-light and discuss in cross-cultural perspective: (i) the psychopathological similarities and differences among psychotic depressives, and (ii) similarities and differences of psychotic depressives with clinically diagnosed schizophrenics and with corcordant and discrepant groups (WHO 1973) of schizophrenia.

"Makings of a dacoit".

A study of the dacoits of the Chambal River valley was undertaken to determine what special circumstances exist to make them to take to dacoity, or whether these outlaws had a psychopathic disposition. The study sample consisted of 50 dacoits, compared with 50 aggressive criminals and 50 normals (non-criminals) from the same region. Among the most important factors contributing to their choosing this particular criminal career were: insecure childhood, enemity, psychopathic or wayward tendencies, belonging to a family of outlaws, rejection by society, extremely discordant family conditions, and the influence of operating dacoits.

Per rectal diazepam therapy in convulsive disorders.

One hundred and twenty children with persistent convulsions (lasting > or = 10 min) were treated with per rectal diazepam (dosage: 0.2 to 0.7 mg/kg/dose). Another group of 100 age matched children with convulsions, along with those who did not respond to rectal therapy were given intravenous diazepam in a dosage of 0.2 to 0.3 mg/kg/dose. Rectal treatment was effective in 80.83% cases while intravenous diazepam was effective in 90% cases which is statistically just significant (p < 0.05). No significant difference was observed in the efficacy of two routes of administration in controlling convulsions of different clinical types and various etiological groups (p < 0.05), except for primary generalized type where intravenous route was more effective than the rectal one (p < 0.05). No significant side-effect was observed with rectal therapy. Among the 23 (19.17%) children in whom rectal therapy failed, 12 (10%) responded to intravenous diazepam while the remaining 11 (9.17%) cases were resistant to both routes of administration.

PUFA and LC-PUFA intake during the first year of life: can dietary practice achieve a guideline diet?

BACKGROUND: An appropriate supply of n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) during early childhood may enhance cognitive development. Little attention is paid to the fatty acid (FA) supply during the complementary feeding period. We examined the polyunsaturated fatty acids (PUFAs) and LC-PUFAs pattern in dietary practice of two study groups and evaluated the results against the present Dietary Guidelines in Germany. METHODS: The food consumption and FA pattern of dietary practice in subjects from two prospective studies (n=102 and n=184, respectively) at the age of 3, 6 and 9 months was assessed by weighed diet records, and changes during the first year of life were compared with the food-based dietary guidelines for the first year of life. RESULTS: Dietary practice in the complementary feeding period was clearly dominated by commercial food products. The FA composition in dietary practice was different from the Guideline Diet and the ratio of n-6/n-3 PUFAs was less favorable. Consumption of breast milk or formula was still of major importance for the intake of LC-PUFAs in the complementary feeding period. CONCLUSION: LC-PUFAs are predominantly provided by breast milk and formula during the first year of life and consequently decrease when milk consumption decreases. For compensation, commercial complementary food might come closer to the Guideline Diet by lowering the n-6/n-3 PUFA ratio through appropriate vegetable oil along with an increase in total fat content up to the legal limit.

Modification of dietary polyunsaturated fatty acids via complementary food enhances n-3 long-chain polyunsaturated fatty acid synthesis in healthy infants: a double blinded randomised controlled trial.

OBJECTIVE: To study the effect of modified polyunsaturated fatty acid (PUFA) profiles of complementary food on long-chain (LC) PUFA composition in healthy infants. DESIGN: Double blinded, randomised, controlled intervention trial. SETTING: Dortmund, Germany. PATIENTS: Free-living sample of healthy term infants. METHODS: Participants were randomly assigned within the first 2 months of life. During the intervention period from 4 to 10 months, the control group (n = 53) received commercial complementary meals with corn oil (3.4 g/meal) rich in n-6 linoleic acid (LA), the intervention group (n = 49) received the same meals with rapeseed oil (1.6 g/meal) rich in n-3 alpha-linolenic acid (ALA). Fatty acid intake was assessed from dietary records throughout the intervention period. Fatty acid proportions (% of total fatty acid) in total plasma were analysed before and after the intervention. RESULTS: Plasma fatty acid profiles did not differ between the intervention and control groups before the intervention. During the intervention, the only difference in fatty acid intake between the intervention and control groups was a higher intake of ALA in the intervention group, 21% deriving from study food and a lower ratio of LA/ALA (10.7 vs 14.8). At the end of the intervention, the plasma proportions of total n-3 fatty acids and of n-3 LC-PUFA, but not of ALA, were higher and the ratios of n-6/n-3 fatty acids were lower in the intervention group. CONCLUSIONS: Feasible dietary modifications of the precursor fatty acid profile via n-3 PUFA-rich vegetable oil favoured n-3 LC-PUFA synthesis in the complementary feeding period when LC-PUFA intake from breast milk and formula is decreasing.

Analysis of factors influencing the rate of germination of spores of Bacillus subtilis by very high pressure.

AIMS: To elucidate the factors that determine the rate of germination of Bacillus subtilis spores with very high pressure (VHP) and the mechanism of VHP germination. METHODS AND RESULTS: Spores of B. subtilis were germinated rapidly with a VHP of 500 MPa at 50 degrees C. This VHP germination did not require the spore's nutrient-germinant receptors, as found previously, and did not require diacylglycerylation of membrane proteins. However, the spore's pool of dipicolinic acid (DPA) was essential. Either of the two redundant enzymes that degrade the spore's peptidoglycan cortex, and thus allow completion of spore germination, was essential for completion of VHP germination. However, neither of these enzymes was needed for DPA release triggered by VHP treatment. Completion of spore germination as well as DPA release with VHP had an optimum temperature of approx. 60 degrees C, in contrast to an optimum temperature of 40 degrees C for germination with the moderately high pressure of 150 MPa. The rate of spore germination by VHP decreased approx. fourfold when the sporulation temperature increased from 23 degrees C to 44 degrees C, and decreased twofold when 1 mol l(-1) salt was present in sporulation. However, large variations in levels of unsaturated fatty acids in the spore's inner membranes did not affect rates of VHP germination. Complete germination of spores by VHP was not inhibited significantly by killing of spores with several oxidizing agents, and was not inhibited by ethanol, octanol or o-chlorophenol at concentrations that abolish nutrient germination. Completion of spore germination by VHP was also inhibited by Hg(2+), but this ion did not inhibit DPA release caused by VHP. In contrast, dodecylamine, a surfactant that can trigger spore germination, strongly inhibited DPA release caused by VHP treatment. CONCLUSIONS: VHP does not cause spore germination by acting upon the spore's nutrient-germinant receptors, but by directly causing DPA release. This DPA release then leads to subsequent completion of germination. VHP likely acts on the spore's inner membrane to cause DPA release, targeting either a membrane protein or the membrane itself. However, the precise identity of this target is not yet clear. SIGNIFICANCE AND IMPACT OF THE STUDY: There is significant interest in the use of VHP to eliminate or reduce levels of bacterial spores in foods. As at least partial spore germination by pressure is almost certainly essential for subsequent spore killing, knowledge of factors involved and the mechanism of VHP germination are crucial to the understanding of spore killing by VHP. This work provides new insight into factors that can affect the rate of B. subtilis spore germination by VHP, and into the mechanism of VHP germination itself.

Nosology and therapy of mental illness in Ayurveda.

Ayurveda, the ancient Indian system of medicine, is described in Atharva Veda and in subsequent treatises by Charak, Susrut, and Vagbhatt, containing the details of etiology, symptoms, diagnosis, and therapy of afflictions in humans and animals. The science of mental disorders (Bhoot-Vidya) describes extensively conditions from mild anger and greed to severe psychoses. This paper presents a synoptic overview comparing the clinical conditions described in Ayurveda with clinical conditions described in the Internationl Classification of Diseases. The symbiotic relationship between 'psyche' and 'soma' was recognised in Ayurveda, attributing the highest importance to psychic energy as the propulsive power of creation--the original force. According to Vedic concepts, personality is composed of three elements (gunas): i. Satva (pure qualities), ii. Rajas (pleasure-seeking propensities and emotions), iii. Tamas (animal-like behavioural tendencies leading to deterioration). Abnormalities result from the excess of Tomas and Rajas. The main therapies are i. suggestion, auto-suggestion, hynotism, assurance, persuasion, and ritualistic therapy; ii. transferring of symptoms; iii. confession, penance, and sacrifice; iv. use of natural elements; v. medicine and endocrine therapies; and vi. tantic and yogic practices.

Long term course and outcome of the Agra cases in the International Pilot Study of Schizophrenia.

The course and outcome at a 13-14-year follow-up of the Agra cases in the International Pilot Study of Schizophrenia (IPSS) was observed by two methods: i) through a mailed questionnaire to assess the key respondents own perception of their state, ii) by a thorough clinical examination and assessment using standard instruments. The results of these two methods were compared and no significant difference found. Based on the second method it was found that 46% of schizophrenics and 43% of manic-depressives had one or two episodes during the first 5 years after inclusion and none in the subsequent period of 8 to 9 years (up to the present follow-up). The results indicate that the illness loses its intensity over a period of years. Mortality among schizophrenics was higher than the expected rate in a general population. The suicide rate was similar to that reported in other studies.

Hypomagnesemia in relation to digoxin intoxication in children.

Serum magnesium estimation was done in 19 children who had heart failure of varied etiology. Five of nine toxic patients and three of 10 nontoxic ones had magnesium deficiency (serum magnesium less than 1.5 mEq. per liter). Mean serum magnesium level was significantly lowered (P less than 0.01) in 19 children and it was further lowered in nine toxic patients (P less than 0.001) as well as in eight hypomagnesemic patients (P less than 0.001) than in healthy control subjects. Mean serum digoxin level in toxic patients was significantly higher than in nontoxic ones (P less than 0.05). In three cases magnesium sulfate was successfully used for the management of cardiac arrhythmias.

Calcium homeostasis in larval and adult Drosophila melanogaster.

Calcium homeostasis in Drosophila melanogaster was examined in response to the challenges imposed by growth, reproduction and variations in dietary calcium content. Turnover time for calcium, calculated as the time for (45)Ca(2+)to accumulate to half the steady state value of 3.46 nmol/fly, was 3.3 days. Although larvae weighed 2x as much as adults, they contained 3-4x as much calcium. Anterior Malpighian tubules (Mts) contain much more calcium than posterior Mts, accounting for 25-30% of the calcium content of the whole fly. In response to a 6.2-fold increase in dietary calcium level, calcium content of whole flies increased only 10%. Hemolymph calcium concentration ( approximately 0.5 mM) was similar in males and females and in animals raised on diets differing in calcium content. Fluid secretion rate, secreted fluid calcium concentration, and transepithelial calcium flux in tubules isolated from flies raised on high and low calcium diets did not differ significantly. Malpighian tubules secrete calcium at rates sufficient to eliminate whole body calcium content in 0.5 and 3 days for tubules secreting fluid at basal and maximal rates, respectively. It is suggested that flies absorb high quantities of calcium from the diet and maintain homeostasis through the combined effects of elimination of calcium in fluid secreted by the Malpighian tubules and the sequestration of calcium in granules, especially within the distal segment of the anterior pair of Malpighian tubules.

Drug use among college students--an interim report.

A survey was conducted at Agra (India) to study the extent and pattern of the non-medical use of dependence producing drugs among the post-graduate students of the local colleges and a number of medical students of other colleges of the state of Uttar Pradesh who were posted for training at the Mental Hospital. The study was confined to the academic year 1975-76 and covered 1,200 students. The present interim report is based on a sample of 564 students covered during 1975 (1st stage). The data on the total sample of 1200 (2nd and the final stage) are still being analysed. The results reveal that 73.88 per cent male, and 25.96 per cent female students had a drug experience at some time or another. Drug use was highest (80.66 per cent) among male medical students. The substances commonly used by males were: alcohol, barbiturates, Mandrax (methaqualone diphenhydramine hydrochloride). Vesparax (hydroxyzine hydrochloride), Equanil (meprobamate). Librium (chlordiazeproxide), pain killers (minor analgesics such as aspirin, and cannabis (bhang, ganja, and charas). The female students mainly used Equanil and pain killers. Among the 23 reasons offered for the use of drugs, the majority of students (50-59 per cent) stated that their main reason for drug use was "to relieve tension and facilitate relaxation". The next motivating factor for indulgence was "for the sake of fun" (30-39 per cent). The student drug users reported a number of effects produced by various substances. The most commonly mentioned effects were: excessive sleepiness, sluggishness, giddiness, inability to concentrate on studies, poor physical co-ordination. They expressed their opinion on various aspects of the drug use problem and favoured stringent measures to curb it.