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Recent trials of the treatment of mild hypertension have suggested that there may be benefit from drug treatment of quite modest or borderline levels of pressure. Drug treatment of subjects with diastolic pressures over 95 mm Hg would pose a major problem in the efficient organization of such a long-term program and would also be costly. Perhaps about 350 patient years of treatment might be necessary to prolong one patient's life by 1 year. The side effects as well as the costs of such a program should make us cautious about offering such treatment solely on the results of measurement of arterial pressure. In people with diastolic pressures in the range of 90-100 mm Hg we should carefully consider several factors such as age, sex, cholesterol concentrations, diabetes, family history, and smoking habit which might also interact to identify particularly high risks and exclude those individuals with a particularly benign prognosis. The results of the more recent trials can give very little information about such subgroup analysis, which would be possible only with much larger samples. The untreated subjects with raised pressure should be carefully followed and offered advice on nondrug strategies such as weight reduction, treatment of lipid abnormalities, and reduction in dietary salt intake. This type of program demands careful, possibly computerized, records and follow-up.
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PMID:High blood pressure: what level to treat? 258 Jan 61

There is a growing evidence for that in modern societies the function of the cellular sodium-potassium pump (membrane-bound Na+ K+ ATPase) in several tissues in man cannot respond adequately to demands. This is not seen in any other free-living vertebrates on this earth. The clearly unphysiological very high intake of sodium-chloride (salt) and also alcohol is definitely playing an important role in the development of the common degenerating metabolic aberrations, e.g. essential hypertension, diabetes II and severe over-weight, in man. The special and overall important role of the sodium-potassium pump for optimal cellular function and regeneration with special reference to the vascular tissues is presented and discussed.
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PMID:The sodium pump and energy regulation: some new aspects for essential hypertension, diabetes II and severe overweight. 258 82

This study was conducted to investigate the relationship between life style factors and adult disease for Chinese living in Japan. The mortalities of major cancers and other major diseases of Chinese in Japan were compared with those of Japanese by calculating Standardized Mortality Ratios (SMR) for the Chinese using death rates in the Japanese population the standard. The life style data on smoking, drinking and dietary habits for Chinese in Japan were collected by self-administered questionnaire surveys, and age-adjusted proportions were calculated with the truncated world population as the standard. Then the corrected indexes on life style for Chinese in Japan were compared with those of Japanese. The results are summarized as follows: 1. The mortality rates of heart disease, diabetes mellitus, hypertensive disease, liver cirrhosis, rectum cancer, liver cancer (both sexes), lung cancer (females), breast cancer and cerebrovascular disease (females) for Chinese in Japan were higher than those for Japanese, but the rates of stomach cancer, pancreas cancer (both sexes), uterus cancer (females) and cerebrovascular disease (males) were lower than those for Japanese. 2. The prevalence of current smokers for Chinese males in Japan was lower than that of Japanese, and that of females was higher than that of Japanese. The prevalence of non-smokers for Chinese males was higher than that of Japanese, and that of females was lower than that of Japanese. 3. Although the prevalence of regular drinkers for Chinese of both sexes in Japan were lower than that of Japanese, the prevalence of heavy drinkers who drank over 80 ml of ethanol every day for Chinese males was higher than that of Japanese males. 4. Significant differences were not found in the prevalences of frequent consumers of meat, milk, eggs, fish, other vegetables and food using oil between cooks and non-cooks of Chinese of both sexes in Japan. 5. The age-adjusted prevalences of frequent meat and milk consumers for Chinese in Japan were higher than those of Japanese in both sexes, but those of frequent pickled vegetable and MISO soup consumers were lower than those of Japanese. The dietary pattern of Chinese in Japan was different from that of Japanese with intakes of much fat and less salt. 6. It is assumed that the mortalities due to adult disease for Chinese in Japan are related to their heavy drinking and to their dietary habits.
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PMID:[A socio-medical study of adult diseases related to the life style of Chinese in Japan]. 263 81

The injection of 25 mg/kg i.p. cyclosporin (CsA) for 3 wk caused marked functional and morphological deteriorations of pancreatic islet cells in Wistar rats that were prevented by the combined administration of p-aminobenzoic acid-N-D-mannoside sodium salt (K-MAP). In this article, the toxic effect of CsA on pancreatic islet cells and the preventive effect of K-MAP on CsA-associated islet cell toxicity were investigated. Prolonged hyperglycemia and depressed insulin secretion after the glucose challenge observed in CsA-treated rats could be prevented by the combined administration of 300 and 900 mg/kg K-MAP. Cytoplasmic vacuolizations and a decrease in the number of mitochondria, intact endoplasmic reticula, secretory granules, and insulin-positive cells, as revealed by peroxidase-antiperoxidase staining, could also be prevented by the administration of 900 mg/kg K-MAP. This preventive effect of K-MAP on CsA-associated islet cell toxicity may suggest the combined use of K-MAP with CsA in pancreas transplantation and treatment of insulin-dependent diabetes.
Diabetes 1989 Jan
PMID:Modulation of prostaglandin metabolism by K-MAP and prevention of toxic effect of cyclosporin on pancreatic islet cells. 264 33

Our ability to measure precisely the pressures and flows within the glomerular microcirculation has enabled us to begin to unravel the complex relationship between systemic hypertension and kidney disease. Although a number of factors have been implicated in the development of glomerular sclerosis, one consistent finding has been that glomerular injury occurs when elevated pressures are transmitted to the glomerular capillaries. Intrarenal hypertension, in conjunction with renal hypertrophy, and, possibly, disturbances in lipid metabolism and blood coagulation constitute secondary processes through which those nephrons not severely injured by the primary renal disease are eventually destroyed. Ultimately, all renal function is lost. Clinically, increased glomerular pressure is likely to contribute to glomerular injury in those patients in whom hypertension and renal insufficiency coexist. In patients with diabetes, as yet unidentified factors cause preglomerular resistance to fall so that glomerular hypertension develops even in the absence of elevation in systemic blood pressure. Although no therapy has been proven to slow the rate of progression to end stage renal failure in humans, a number of promising interventions have been identified. These include dietary protein or salt restriction, and medication, with either converting enzyme inhibitors or calcium channel blockers.
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PMID:Impact of antihypertensive therapy on progressive kidney damage. 266 87

Antihypertensive drugs have disparate effects on renal haemodynamics, tubular function, plasma electrolytes, and hormonal responses. Calcium entry blockers and angiotensin-converting enzyme (ACE) inhibitors are unique in that they may increase glomerular filtration rate (GFR) and renal blood flow in patients with hypertension. Both classes of drugs are distinctive in that they prevent salt retention because of their inhibitory effect on tubular sodium reabsorption. In addition to these attributes, which are desirable in terms of lowering systemic blood pressure, these 2 classes of drugs exert important intrarenal effects which may participate in limiting the progression of renal disease. ACE inhibitors have been shown to protect against the development of glomerulosclerosis in various experimental models of renal insufficiency. Importantly, there is emerging evidence from human studies supporting a distinctive beneficial effect of these agents on renal function in patients with hypertension, mild chronic renal insufficiency and diabetes mellitus. Calcium entry blockers have also been shown to exert some beneficial effect in limiting the progression of experimental kidney disease but neither an improvement in glomerular sclerosis nor a decrease in proteinuria have been clearly documented. At present ACE inhibitors appear the most attractive agents in terms of arresting the progression of renal disease. Acute deterioration in renal function may occur following the administration of ACE inhibitors, calcium entry blockers, and beta-blockers. This complication should be considered in every patient on antihypertensive therapy who suffers an unexplained deterioration in renal function. In particular, the sudden deterioration in renal function following initiation of therapy with an ACE inhibitor is a clue to the possible presence of bilateral renal artery stenosis or stenosis of a solitary functioning kidney. Renal damage may also occur in patients with unilateral renal artery stenosis even though total (2-kidney) GFR may not be appreciably reduced. In this setting, a captopril renal scan with hippuran and diethylenetriamine pentaacetic acid (DTPA) provides physiological information regarding the renal blood flow and GFR of each kidney. In patients with unilateral renal artery stenosis the impact of ACE inhibitor therapy on GFR may be discerned by the use of the DTPA scan, which may demonstrate a reduction in GFR in the stenotic kidney that is not apparent by evaluation of total kidney GFR. This suggests that despite adequate control of systemic blood pressure and unchanged plasma creatinine progressive kidney damage in the stenotic kidney ensues.
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PMID:Renal effects of antihypertensive drugs. 266 38

The chronic hyperglycemia in diabetes mellitus enhances the nonenzymic glycation of structural proteins possibly increasing the formation of highly reactive advanced glycation end products (AGE). These protein changes might be involved in tissue-damaging mechanisms leading to diabetic complications, including diabetic nephropathy. To simulate these events, an in vitro model, based on isolated human glomerular basement membrane (hGBM), has been developed. In this study we have investigated the extent of AGE formation and the binding changes induced by the nonenzymic glycation of hGBM. An enriched fraction of hGBM was isolated from normal human kidneys and glycated in vitro by incubation with glucose (500 mmol/l) at 37 degrees C for 10 days. The presence of AGE was investigated by two methods - spectrofluorescence and the diazonium salt reaction - both specific for this type of chemical entity. The binding capacity of glycated hGBM was tested by a 10-day incubation with human insulin, albumin, immunoglobulin G and fibrinogen. Higher relative spectrofluorescence values at 440 nm emission (20.0 +/- 2.0 vs. 12.5 +/- 5.0) and higher absorbance values at 492 nm (0.798 +/- 0.063 vs. 0.429 +/- 0.228) indicated the presence of increased levels of AGE in glycated vs. native hGBM. Insulin and the three proteins were bound to hGBM in increased amounts after its glycation (p less than 0.05). The results obtained in this in vitro model confirm that enhanced nonenzymic glycation of hGBM induces the formation of AGE and possibly, through these compounds, alters its physicochemical and binding properties. This reaction might contribute to the mechanisms eventually leading to diabetic nephropathy.
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PMID:Nonenzymic glycation of isolated human glomerular basement membrane changes its physicochemical characteristics and binding properties. 273 62

Blood pressure was studied in urban and rural samples of the Melanesian and Indian populations of Fiji during a National Cardiovascular Disease and Diabetes Survey in 1980. Mean blood pressures rose with age and tended to be higher in urban than in rural populations, particularly in the middle age range. There was no clear or significant difference between the ethnic groups. When the prevalence of hypertension was studied (using WHO criteria) similar age, geographic and ethnic differences were found. Comparisons with data from 1960 revealed no significant change in mean blood pressures during the 20-year interval. Rural populations were leaner and appeared to consume less salt than did urban groups. There were positive and significant correlations between blood pressure and triceps skinfold thickness in most subgroups.
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PMID:Blood pressure changes with age in two ethnic groups in Fiji. 277 34

Diet remains the cornerstone in the management of diabetes mellitus. A prudent nutrition plan reduces the exaggerated risk for atherosclerotic heart disease and metabolic complications of diabetes by improving lipid and glycemic control. The current consensus diabetes diet recommends 55 to 60 percent of energy as carbohydrate, 12 to 20 percent as protein, and less than 30 percent fat. Total cholesterol intake should be less than 300 mg per day. Fiber appears to have distinct benefits in improving glucose and lipid levels; therefore, an intake of up to 40 g per day or 15 to 25 g/1,000 kcal of food is recommended. Other considerations in meal planning for diabetes include alternative sweeteners, salt intake, alcohol consumption, and vitamin and mineral needs. Individualized and flexible nutrition plans, designed within established guidelines, promote adherence. Persons with diabetes can change their eating patterns and closely adhere to a diet plan if the entire health care team is enthusiastic, supportive, and instructive.
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PMID:New perspectives in nutrition management of diabetes mellitus. 284 14

BRL 26830, (R*,R*)-(+/-)-methyl-4-(2-[(2-hydroxy-2-phenylethyl)amino]propyl)-benzoa te, is a new type of beta-adrenoceptor receptor agonist that combines antihyperglycemic and thermogenic properties. In C57Bl/KsJ db/db mice, treatment with BRL 26830 (50 mg of the hemifumarate salt/kg diet) decreased blood glucose concentration and normalized water intake. As judged by the normalization of polydipsia, BRL 26830 was effective within 2 days and the effect was maintained throughout a treatment period of up to 11 wk. Treatment of db/db mice with BRL 26830 resulted in an increase in both plasma and pancreatic insulin concentrations and a partial restoration of first-phase insulin secretion by the isolated, perfused pancreas in response to a high (16.7 mM) glucose pulse. Given acutely, BRL 26830 increased energy expenditure in both fed and fasted db/db mice. When given chronically, BRL 26830 increased significantly the dietary and thermoregulatory component of metabolic rate. It is suggested that the antidiabetic and thermogenic properties of BRL 26830 are linked and that blood glucose acts either directly or indirectly as a substrate for thermogenesis.
Diabetes 1985 Nov
PMID:Improved glycemic control in C57Bl/KsJ (db/db) mice after treatment with the thermogenic beta-adrenoceptor agonist, BRL 26830. 286 98


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