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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the mechanisms mediating intracellular calcium transients involved in diabetic cardiac dysfunction, changes in intracellular calcium concentration ([Ca2+]i) in response to stimulation by caffeine, ouabain, KCl and ATP were studied in single cardiomyocytes (quiescent or electrically-stimulated) isolated from streptozotocin (STZ) diabetic rats. [Ca2+]i was measured by fluorescence microscopy using fura-2. Peak [Ca2+]i response to caffeine (20 mM) and decline of [Ca2+]i (-peak d[Ca2+]i/dt) were decreased in diabetic myocytes. Insulin treatment corrected these depressed [Ca2+]i responses. The data suggest a reduced sarcoplasmic reticulum (SR) calcium content and a depressed Na-Ca exchange activity in diabetic myocytes. Insulin deficiency may play a causal role in these changes. The maximum [Ca2+]i increase in response to ouabain was reduced in diabetic cells while the sensitivity of diabetic myocytes to ouabain was increased. This may be a result of depressed Na-K ATPase and elevated [Na+]i as previously reported. The KCl (12.5-50 mM)-induced [Ca2+]i increase was enhanced in diabetic cells. Caffeine (20 mM) and dichlorobenzamil (DCB, 10 microM) blocked this [Ca2+]i transient to a smaller degree in diabetic cells, but nitrendipine effects were similar in diabetic and control cells. These effects may be due to the increased L-channel activity and altered features, such as different responses to Ca-channel blockers, in diabetes which has previously been reported. The maximum response of [Ca2+]i to exogenous ATP was increased in diabetic cells while the sensitivity remained unchanged. The mechanisms underlying this enhanced response may be similar to the KCl-induced [Ca2+]i changes in diabetes.
Diabetes Res Clin Pract 1995 Oct
PMID:Altered [Ca2+]i mobilization in diabetic cardiomyocytes: responses to caffeine, KCl, ouabain, and ATP. 874 1

Malignant hyperthermia (MH) in humans is usually triggered by volatile anaesthetics and depolarizing muscle relaxants. However, other factors or drugs (e.g. cresol) are thought to induce MH. We report a case of fulminant MH associated with a ketoacidotic diabetic coma. After therapy for diabetic coma with insulin (containing the preservative cresol) and electrolyte solutions was started, the patient complained of increasing myalgia, developed a high fever and respiratory and metabolic acidosis and lost consciousness. MH was treated immediately with dantrolene; the patient recovered within 14 days. Five months later the patient was diagnosed as MH-susceptible by the in vitro caffeine and halothane contracture test. This case supports the assessment that MH and diabetes are associated diseases and that cresol could possibly trigger MH. Furthermore, therapy with dantrolene has been demonstrated to be beneficial in the treatment of MH associated with diabetic coma.
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PMID:Fulminant malignant hyperthermia associated with ketoacidotic diabetic coma. 888 Feb 51

It has been suggested that alterations in intracellular Ca2+ homeostasis may be responsible for the development of diabetic cardiomyopathy. We have studied the effects of streptozotocin-induced diabetes on intracellular Ca2+ concentration ([Ca2+]i) in enzymically isolated rat ventricular myocytes. [Ca2+]i was measured using indo 1 or fluo 3. Both diastolic and peak systolic [Ca2+]i were reduced in diabetic compared with normal myocytes (by 52 and 43%, respectively). The decay phase of the systolic [Ca2+]i transient was slower in the diabetic myocyte compared with normal (time constant = 89.6 +/- 3.4 ms, n = 23, normal vs. 105.2 +/- 4.05 ms, n = 20, diabetic; P < 0.01). This led to a significant prolongation of the [Ca2+]i transient duration in the diabetic myocyte. In both normal and diabetic myocytes, increasing the frequency of electrical stimulation decreased peak systolic [Ca2+]i. The relationship between stimulation frequency and normalized peak systolic [Ca2+]i was the same for both normal and diabetic myocytes. We also found that the caffeine-induced Ca2+ release [used as an index of sarcoplasmic reticulum (SR) Ca2+ content] was significantly reduced in diabetic myocytes. These data indicate that SR Ca2+ content is decreased by diabetes. In the presence of thapsigargin (2.5 microM, an inhibitor of SR Ca(2+)-adenosinetriphosphatase), the magnitude and time course of stimulus-evoked [Ca2+]i transients were identical in both groups of myocytes, suggesting that Ca2+ influx and/or efflux across the plasma membrane is not significantly affected in diabetes. We conclude that 1) diabetes is associated with significant alterations in [Ca2+]i homeostasis and 2) the decrease in systolic [Ca2+]i and lengthening of the systolic [Ca2+]i transient result primarily from dysfunction of the SR.
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PMID:Altered Ca2+ handling in ventricular myocytes isolated from diabetic rats. 892 57

The acceptance of medication as a legitimate adjunct to diet and behavior modification in the treatment for obesity is an emerging phenomenon spurred by advances in understanding the biologic basis of body weight regulation and by the demonstration of safe and effective chronic maintenance of weight loss using a pharmacobehavioral approach. The decision to medicate for obesity depends on good clinical judgment based on such considerations as body mass index; body composition; body fat dissociation; age; sex; and comorbid conditions, such as diabetes and hypertension. Several nonadrenergic agents and a serotonergic agent have FDA-approved indications for weight loss. Phenylpropanolamine is available over the counter. Clinical trials support the efficacy of fluoxetine and ephedrine or caffeine in producing weight loss, although these agents do not have FDA-approved indications for treatment for obesity. In addition, new agents are being developed or are anticipated for approval. The use of existing agents in combination and their use adjunctive to diet and behavioral approaches to obesity treatment are fertile areas for research. The expectant attention to this subject is demanded by the imperative that the health in one three people in the United States is adversely affected by obesity.
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PMID:Medicating the obese patient. 897 57

A cocktail of 4 substances (caffeine/CYP1A/CYP1A2, metamizol/CYP2B, debrisoquin/CYP2D6 and sulfamethazine/N-acetyltransferase) was administered to 15 maturity-onset diabetics before and 6 months after insulin therapy (IT) to examine changes in hepatic biotransformation capacity in humans under pathological conditions. Blood and urine samples were taken 6 h after oral administration of the drugs. There were no differences in acetylation- and hydroxylationsphenotyping before or during IT. However, a significant increase in concentration of free sulfamethazine during IT can be interpreted as induction of N-acetyltransferase by poor metabolic control. Comparison of caffeine-concentration showed no significant differences. Obviously in humans CYP1A2 is not influenced by type-II-diabetes mellitus. Concentration of 4-methyl-antityprine (4-MAA), a metabolite of metamizol, was significantly increased during IT. This results shows a possible induction of CYP2B by poor metabolic control.
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PMID:[Comparison of serum concentrations of caffeine, 4-methylaminoantipyrine, sulfamethazine and debrisoquin following oral administration of these substances as a cocktail in type II diabetics before and after insulin therapy]. 899 40

Currently available as a dietary supplement, the pineal hormone melatonin is portrayed by the media as a formidable weapon against disease and aging. Accordingly, primary health care providers should be cognizant of which of its proposed uses are supported by biomedical research and which are, as yet, unproven. Melatonin entrains circadian rhythms and, thus, can treat jet lag, delayed sleep phase syndrome, and sleep disorders in the blind and in some neurologically impaired children. By virtue of its hypnotic effect, melatonin can mitigate insomnia in the elderly. Reductions in melatonin secretion have been associated with many disorders, including cardiovascular disease, Alzheimer's, diabetes, SIDS, and aging; however, melatonin's role in their etiology and/or pathophysiology is unproven. Preliminary studies suggest a possible adjuvant therapeutic role for melatonin in cancer therapy. Melatonin secretion is reduced by alcohol, caffeine, and some commonly prescribed drugs. Since tolerance, fatigue, and other side effects have been reported, melatonin use on consecutive nights should be avoided and only the lowest effective hypnotic dose should be taken.
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PMID:Melatonin: media hype or therapeutic breakthrough? 905 17

Dexfenfluramine increases serotonergic activity by stimulating serotonin (5-hydroxytryptamine; 5-HT) release into brain synapses, inhibiting its reuptake into presynaptic neurons and by directly stimulating postsynaptic serotonin receptors. On the basis of the serotonin hypothesis of appetite control, these actions would be expected to reduce appetite and, consequently, bodyweight. Studies conducted in animals and in overweight patients with and without associated disorders have confirmed the weight-reducing efficacy and good tolerability of dexfenfluramine. In 3-month clinical studies in obese patients, weight reductions with dexfenfluramine 15mg twice daily combined with dietary support were significantly higher than those achieved with placebo and similar to those with ephedrine/caffeine 20/20mg 3 times daily, sibutramine 10mg once daily and fluoxetine 60 mg/day. Furthermore, dexfenfluramine recipients with non-insulin-dependent diabetes mellitus, hyperlipidaemia or hypertension consistently show improvements in glycaemic control, blood lipid profiles and blood pressure. 12-month trial results indicate that most weight loss occurs in the initial 6 months and appears to be maintained for a further 6 months. Weight regain after withdrawal of treatment in 12-month studies demonstrates that dexfenfluramine is effective in maintaining a stable bodyweight at a lower level than placebo and in limiting food intake over this time period. Commonly reported adverse events with dexfenfluramine include diarrhoea, tiredness, dry mouth and somnolence; these symptoms are generally mild and transient. Approximately 7 and 10% of dexfenfluramine recipients in short and long term studies withdrew because of adverse events. Dexfenfluramine was better tolerated than ephedrine/caffeine and fluoxetine in short term studies. Obesity is a chronic condition that is accompanied by a number of metabolic complications. It is a significant health problem in developed countries, and as a major risk factor for many chronic diseases, including diabetes and cardiovascular disease, the economic burden of this condition is considerable. As with other chronic conditions, there is a role for pharmacological intervention in patients with severe obesity. However, drugs should be considered as only one component of a weight-control programme, since additional lifestyle modification is required to maintain weight loss. The promising data on the long term efficacy and tolerability of dexfenfluramine as well as its favourable effects on risk factors associated with obesity requires confirmation in long term studies. In the meantime, dexfenfluramine should be considered a valuable adjunct to a reduced-calorie diet in the management of severe obesity, particularly in patients with associated disorders and those unsuccessful with conventional weight loss measures. Available data support the use of the drug for up to 1 year to maintain weight loss and thus dexfenfluramine should be considered for long term administration.
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PMID:Dexfenfluramine. An updated review of its therapeutic use in the management of obesity. 911 19

Urinary incontinence is common in the elderly, affecting 6-8% of people over 64 years in the community and up to 31% in hospital and long-term care. It is possible to establish the diagnosis clinically in most incontinent patients with the likelihood of improving symptoms in the majority. Treatment of patients with urinary incontinence requires attention to general and specific measures. General measures include moderation of fluid intake to about 1.5 litres/day, reduced intake of caffeine-rich drinks, treatment of aggravating conditions such as urinary infection, oestrogen deficiency, increased solute load as in diabetes mellitus and uraemia, and drugs like diuretics, sedatives and antidepressants. Specific measures include pelvic floor exercises, vaginal cones, interferential therapy and oestrogens for patients with stress incontinence. Bladder retraining and anticholinergic drugs are for patients with urge incontinence, and alpha-blockers and 5-alpha reductase inhibitors for patients with overflow incontinence due to prostatic hyperplasia.
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PMID:Management of urinary incontinence in the elderly. 914 9

The quality control indices of myocyte isolation (viability, yield, survival time, cell response, etc.) suggest that the adult rat myocyte model is stable and useful in [Ca2+]i measurements and functional studies at the cellular level. Moreover, diabetic cardiomyocytes are a valuable model for studying cellular functions of the diabetic heart as they retain most of the features of cardiac dysfunction of intact rat. Data from our studies indicate that the basal [Ca2+]i in both quiescent and electrically-stimulated cells is not changed. Thus, resting levels of [Ca2+]i and basal [Ca2+]i transients may not reflect the abnormalities observed in diabetes until the system is challenged by certain stimuli. [Ca2+]i responses to isoproterenol are depressed in both resting and stimulated diabetic cells. This suggests an alteration in the beta-adrenergic pathway, possibly related to the beta-adrenoceptor deficiency reported in the diabetic heart. SR Ca-ATPase is also involved in the isoproterenol-induced [Ca2+]i changes. Moreover, the decreased maximum response to 8-bromo-cAMP provides evidence of a post-receptor alteration in the pathway. Diabetic myocytes are more sensitive to ouabain, whereas the maximum response to ouabain was depressed. This may be the result of depressed Na-K ATPase and increased [Na+]i. In diabetic myocytes, rapid cooling contractures and caffeine contractures are depressed, whereas caffeine-induced Ca2+ transients are decreased. Ryanodine binding suggests a decreased number of high-affinity binding sites in the SR of diabetic myocytes. Additionally, there are indications that SR releasable calcium is reduced and that the major functions of SR, notably uptake, release and storage, may be depressed in diabetic myocytes. Finally, L-type Ca(2+)-channels are quantitatively and qualitatively altered in diabetes. Insulin treatment normalizes most of the diabetes-induced changes in cardiomyocytes, suggesting that metabolic alterations due to insulin deficiency play an important role in diabetic cardiomyopathy. Results from several studies show that in diabetes the function of major organelles which handle [Ca2+]i in myocytes is depressed, which in turn causes the alteration of [Ca2+]i mobilization in myocytes. Different second messenger systems involved in E-C coupling may also be altered due to the metabolic impairments. The rapid increase in our understanding of the pathophysiology of calcium homeostasis in cardiomyocytes will be forthcoming as the powerful new tools of molecular and structural biology are used to investigate the regulation of the Ca2+ transport system.
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PMID:Intracellular calcium levels are unchanged in the diabetic heart. 921 77

Although the Restless-Legs-Syndrome (RLS) is harmless, it can be considerably bothersome on occasions. It seems to affect 1-5% of the population. The minimal criteria for diagnosis are: Symmetric or asymmetric dysesthesias of the lower, sometimes also of the upper extremities, present at rest, especially at night. This induces a need to move. Moving gives always relief, but only for a few seconds. Occasionally, dysesthesia can be painful. Additional features are: Involuntary, rhythmic retraction movements occurring especially at night, during sleep stages I und II. Sleep is disrupted and superficial, followed by daytime fatigue. Aetiologically, it is a mostly primary or hereditary disease, but may go along with uremia, diabetes and rheumatoid arthritis. Pathophysiologically there seems to be a malfunction of dopamine and opiate receptors in the central nervous system. Recently, morphological modifications have been found in peripheral nerves. Coffeine has been claimed as causative factor, but its role remains questionable. Therapy shows a high success rate. Some patients may complain about some remaining symptoms even with high doses of medication. Although carbamazepine, clonazepam and clonidine showed satisfactory results in controlled studies, dopaminergic agents and opiates have many advantages. In contrast to the former compounds, the latter are also effective against periodic movements in sleep. Side effects will be discussed according to the literature. In the second part of this paper, practical aspects concerning the care of RLS patients are considered.
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PMID:[Restless legs syndrome--current aspects]. 924 61


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