A Native American community initiative to prevent diabetes.

The increasing prevalence of obesity and diabetes in the Mohawk Community of Akwesasne led to the formation of an advisory group who's mission was to increase community awareness and strengthen the infrastructure necessary to create a community coalition to promote healthy lifestyles. The methodology used to reach these goals included: obtaining an understanding of the community's knowledge, attitudes and behaviors about diabetes, diet and exercise using semi-structured interviews and focus groups; analyzing data from a case control study of diabetes and it complications using a medical record review; exploring methods for evaluating energy expenditure in children; and identifying influential community members and organizations. In the last 50 years people had become less physically active and high fat, high caloric foods were more available. Community members were concerned about health and the well-being of their children, had knowledge about healthy lifestyles but lacked confidence and social support for bringing about desired changes. A strong association was documented between diabetes, smoking cigarettes, high blood cholesterol and vascular disease in this community. Approximately 100 persons participated, several hundred received the results in presentations to 17 community organizations, two public fora, letters to participants and articles in local newspapers. Fifty persons and 29 businesses or organizations regarded as strong advocates of healthy lifestyles were identified. From these a community coalition was formed and has initiated programs to reduce dietary fat and increase physical activity in young children.

End-stage renal disease. Measures to prevent it or slow its progression.

Studies conducted over the past 10 years have indicated that end-stage renal disease can be prevented or its progression slowed in many cases. Although prevention involves lifestyle changes, which many patients find difficult to make, strategies must be developed to help patients achieve the changes. Tight glycemic control in diabetic patients, control of blood pressure, and use of angiotensin-converting enzyme inhibitors are the essential features of the care needed to prevent renal failure.

Systemic pH modifies ketone body production rates and lipolysis in humans.

To investigate whether changes in systemic pH influence ketone body production or utilization, total ketone body (TK) kinetics were measured with [3-14C]acetoacetate and D-beta-[1,3-13C2]hydroxybutyrate tracers in overnight fasted subjects during metabolic alkalosis (NaHCO3 infusion) or acidosis [NH4Cl ingestion or arginine (Arg)-HCl infusion]. Somatostatin, with insulin, glucagon, and growth hormone replacement, was infused in all studies. Blood pH and HCO3- (mM) increased from baseline (0-30 min) to 180-210 min by 0.08 +/- 0.02 and 7 +/- 1 with NaHCO3 and decreased by 0.08 +/- 0.2 and 7 +/- 1 or 5 +/- 1 with NH4Cl or Arg-HCl (all P less than 0.005). Over this period blood TK (microM) differed between the NaHCO3 (+198 +/- 65) and both NH4Cl (-90 +/- 53) and Arg-HCl (-154 +/- 55) (P less than 0.05). These changes resulted from parallel alterations in TK production rate of appearance (Ra TK, mumol.kg-1.min-1), because changes from baseline in Ra 14C TK also differed between NaHCO3 (+1.9 +/- 0.8) and NH4Cl (-1.0 +/- 0.6) and Arg-HCl (-2.0 +/- 0.5) (P less than 0.05). Ra TK calculated with single- or dual-tracer techniques were similar. Blood free fatty acids (FFA) increased with NaHCO3, and FFA and glycerol decreased with NH4Cl and Arg-HCl, suggesting that FFA availability mediated the pH effects on hepatic ketogenesis. These results demonstrate that modest changes in systemic pH modify FFA availability and TK production rates.

Ketoacid production in acute respiratory and metabolic acidosis and alkalosis in rats.

Metabolic acidosis inhibits and alkalosis enhances ketoacid production in ketotic humans and animals. To compare these effects with those of superimposed respiratory acid-base disturbances, ketone output was evaluated in awake ketotic rats during metabolic (intravenous infusions of HCl or NaHCO3) or respiratory (hyper or hypocapnia) disorders. With decreases in blood pH of 0.1-0.2 units over 3 h, blood ketone concentrations significantly decreased an average of 1.9 mM (metabolic) and 1.1 mM (respiratory) and urinary ketone excretion rates significantly decreased by 1.3 mumol/min (metabolic). With increases in systemic pH, blood ketone concentrations and urinary ketone excretion rates were significantly increased. Changes in blood pH correlated with changes in urinary ketone excretion rates in both metabolic (r = 0.87) and respiratory (r = 0.67) acid-base disturbances. The alterations occurred promptly and were rapidly reversible. These findings indicate that modest changes in systemic pH from metabolic or respiratory acid-base disturbances modify net ketoacid production in ketotic rats, confirm pH control of endogenous acid output as an acid-base regulator, and show that systemic pH, not bicarbonate concentration, mediates the process.

Effect of systemic pH on pHi and lactic acid generation in exhaustive forearm exercise.

To investigate whether changes in systemic pH affect intracellular pH (pHi), energy-rich phosphates, and lactic acid generation in muscle, eight normal volunteers performed exhaustive forearm exercise with arterial blood flow occluded for 2 min on three occasions. Subjects ingested 4 mmol/kg NH4Cl (acidosis; A) or NaHCO3 (alkalosis; B) or nothing (control; C) 3 h before the exercise. Muscle pHi and phosphocreatine (PCr) content were measured with 31P-nuclear magnetic resonance (31P-NMR) spectroscopy during exercise and recovery. Lactate output during 0.5-7 min of recovery was calculated as deep venous-arterial concentration differences times forearm blood flow. Before exercise, blood pH and bicarbonate were lower in acidosis (7.303 +/- 0.009, 18.6 +/- 0.5 meq/l) than alkalosis (7.457 +/- 0.010, 32.2 +/- 0.7 meq/l) and intermediate in control (7.389 +/- 0.007, 25.3 +/- 0.6 meq/l). Lactic acid output during recovery was less with A (245 +/- 39 mumol/100 ml) than B (340 +/- 55 mumol/100 ml) (P less than 0.05) and intermediate in C (293 +/- 31 mumol/100 ml). PCr utilization and resynthesis were not affected by extracellular pH changes. pHi did not differ before exercise (A, 7.04 +/- 0.01; B, 7.09 +/- 0.01; C, 7.06 +/- 0.01) or at its end (A, 6.28 +/- 0.07; B, 6.28 +/- 0.11; C, 6.31 +/- 0.09). Hence systemic acidosis inhibited and alkalosis stimulated lactic acid output. These findings suggest that systemic pH regulates cellular acid production, protecting muscle pH, at the expense of energy availability.

Impact of methionine on net ketoacid production in humans.

An exogenous acid load (NH4Cl) inhibits net ketoacid production in the first week of starvation and the fourth to eighth weeks of ketogenic dieting. To determine whether an acid load produced by amino acid metabolism can similarly modify ketosis, five overweight volunteers ingested methionine (H2SO4), NH4Cl, and NaCl (control), in varying order, each day for seven days during weeks 5 to 8 of hypocaloric ketogenic dieting. During days 5 to 7 of each phase, blood pH, bicarbonate, and pCO2 were stable but lower in the NH4Cl phase (7.32 +/- 0.02, 18.1 +/- 1.2 mmol/L, 35.8 +/- 1.4 mmHg) and the methionine phase (7.33 +/- 0.01, 17.1 +/- 0.9 mmol/L, 34.0 +/- 2.0 mmHg) than in the NaCl phase (7.38 +/- 0.01, 22.3 +/- 0.2 mmol/L, 37.6 +/- 1.6 mmHg), P less than .05. Over this period, blood acetoacetate concentration was lower during the methionine and NH4Cl phases than during NaCl, P less than .05. In addition blood beta-hydroxybutyrate and total ketone-body concentrations were lower in the methionine than NaCl phases, P less than .05. Urinary acetoacetate and beta-hydroxybutyrate excretion fell with both acid loads, P less than .05. Compared with control values, urinary total ketone excretion was suppressed by 67 +/- 10% in the NH4Cl and 89 +/- 3% in the methionine periods. When NaCl was ingested after either of the acid loads, urinary ketone excretion increased by 300% to 700%. Thus, methionine ingestion, which results in an acid challenge equivalent to that of a large protein load, has an impact on net ketoacid production similar to that of NH4Cl.(ABSTRACT TRUNCATED AT 250 WORDS)

pH regulation of endogenous acid production in subjects with chronic ketoacidosis.

In a previous study of starvation-induced acute ketoacidosis, net ketoacid production was inhibited by acid and facilitated by base ingestion. To determine whether hydrogen ion modifies net ketoacid production during chronic ketoacidosis, six over-weight volunteers ingested NaHCO3, NaCl, or NH4Cl (2 mmol X kg-1 X day-1), each for 7 days, during weeks 6-8 of ketogenic dieting. During days 4-7 of each phase, blood bicarbonate was stable but lower in the NH4Cl (19.6 +/- 0.7 mM) than the NaHCO3 (23.7 +/- 0.7 mM) phases. Throughout these periods, acid intake differed by 216 mmol/day, whereas acid output differed by 129 mmol/day between the NaHCO3 and the NH4Cl phases. The major contribution to this difference in acid balance was a difference in net organic acid (ketoacid) production. Although blood ketones were stable, ketoacid excretion, reflecting net ketoacid production, was decreased by 59% with acid and increased by 66% with base compared with NaCl (control) ingestion. Thus, in this state of chronic ketoacidosis, challenges to acid-base balance were countered by a rapidly occurring, sustained, reversible, and quantitatively significant modification of net acid production which acted as an effective mechanism for acid-base regulation.

Impact of hydrogen ion on fasting ketogenesis: feedback regulation of acid production.

To determine whether acid-base balance regulates hydrogen ion production, seven obese volunteers were given NaHCO3 and NH4Cl (2 mmol.kg-1.day-1) during two separate 7-day fasts. On days 5-7 plasma bicarbonate was lower in the NH4Cl fasts (14.0 +/- 1.4 mM) than in the NaHCO3 fasts (18.3 +/- 1.1 mM), while urine pH and net acid excretion did not differ. Acid production (acid excretion minus intake) was greater by 204 mmol/day in the NaHCO3 fasts (274 +/- 16 mmol/day) than in the NH4Cl fasts (70 +/- 19 mmol/day). Ketoacid excretion, which reflected net ketoacid production, paralleled acid production, decreasing from 213 +/- 24 mmol/day in the NaHCO3 fasts to 67 +/- 18 mmol/day in the NH4Cl fasts. Thus, during starvation, alterations in hydrogen ion intake and the associated changes in acid-base balance modify the net production of endogenous acid by influencing the synthesis or utilization of ketoacids. Although the specific site of this metabolic regulation is undefined, these results indicate that systemic acid-base status can exert feedback control over hydrogen ion production.

The use of magnesium-containing phosphate binders in patients with end-stage renal disease on maintenance hemodialysis.

We investigated the safety and efficacy of magnesium hydroxide as a phosphate binder in patients with end-stage renal disease on maintenance hemodialysis, 9 volunteers participated in a four-phase study during which each ingested (1) no phosphate binders, (2) magnesium hydroxide (Mg(OH)2) alone, (3) Mg(OH)2 and aluminum hydroxide (A1(OH)3) together and (4) A1(OH)3 alone. Serum magnesium (SMg) concentrations were maintained at less than 4.5 mEq/1 (2.3 mmol/l) in all subjects while they were ingesting 0.75-3 g Mg(OH)2/day and no magnesium toxicity was noted. In individuals taking a constant daily dose, SMg remained stable over 8-12 weeks. Serum phosphorus (SP) decreased from 9.0 mg/dl (2.9 mmol/l)d during the control period to 8.1 mg/dl (2.6 mmol/l) during the Mg(OH)2 period (p less than 0.05) and increased from 6.1 mg/dl (2.0 mmol/l) during the Mg(OH)2 and A1(OH)3 period to 7.0 mg/dl (2.3 mmol/l) during the Al(OH)3 period (p less than 0.05) indicating that Mg(OH)2 could significantly lower SP. However, SP was best controlled (6.1 mg/dl; 2.0 mmol/l) when Al(OH)3 and Mg(OH)2 were used together and all participants preferred the combination therapy to either of the agents alone. These results indicate that Mg(OH)2 is a potentially useful adjunct to A1(OH)3 for managing hyperphosphatemia in patients on maintenance hemodialysis. In this short-term study Mg(OH)3 for managing hyperphosphatemia in patients on maintenance hemodialysis. In this short-term study Mg(OH)2 was well tolerated and with appropriate monitoring did not cause uncontrolled hypermagnesemia. Further studies are clearly required to determine whether long-term therapy with Mg-containing agents is safe in dialysis patients.

Trimethoprim/sulfamethoxazole and renal function in transplant patients.

Twenty-two patients with functioning renal allografts took part in a double-blind crossover trial during which placebo, sulfamethoxazole, and trimethoprim/sulfamethoxazole were given for periods of 14 days. The patients were divided into 2 groups. The first group consisting of 12 patients had serum creatinine levels less than 0.18 mmol/L and the second group of 10 patients had serum creatinine levels between 0.18 mmol/L and 0.35 mmol/L. Renal function at the end of each period was assessed by clearance of inulin (CIn), p-aminohippurate (CPAH) and endogenous creatinine (CCr). The second group also had a pitressin concentration test as a measure of distal tubule function. There was no change in inulin or creatinine clearance or in maximum concentration after pitressin in any of the patients in any of the phases. In the first group there was an increase in PAH clearance during the sulfonamide and trimethroprim/sulfamethoxazole phases. This change was not seen in the second group of patients with significantly impaired renal function.

Urinary excretion of prostaglandin E2 and prostaglandin F2alpha in potassium-deficient rats.

Potassium-deficiency was induced in rats by dietary deprivation of potassium. The animals became polyuric and urine osmolality decreased more then three-fold compared to controls. Urinary excretion of prostaglandin E2 (PGE2) and prostaglandin F2alpha (PGF2alpha) did not increase during 2 weeks of potassium depletion. Partial inhibition of renal prostaglandin synthesis by meclofenamate did not increase the urine osmolality after water deprivation. These results make unlikely the hypothesis that the polyuria of potassium-deficiency, is the result of enhanced renal synthesis of prostaglandins with subsequent antagonism of the hydro-osmotic effect of vasopressin. Male animals consistently excreted less PGE2 than female animals.

Prostaglandins and the kidney.

This review provides a summary and assessment of research involving renal prostaglandins. Arachidonic acid released from phospholipids is converted by prostaglandin cyclo-oxygenase in the kidney to PGF2, PGF2alpha, PGD2, and, possibly, to PGI2 and thromboxane A2. Production of PGE2 and PGF2alpha is predominately but not exclusively in the medulla, whereas degradative enzymes are present in both cortex and medulla. Prostaglandins enter the tubular lumen by facilitated transport and are partially reabsorbed from the urine in the distal nephron. Urine prostaglandins probably reflect renal synthesis. PGE2 and endoperoxides stimulate and PGF2alpha and indomethacin inhibit renal renin synthesis. In response to ischemia, vasoconstriction, or angiotensin II the kidney increases prostaglandin synthesis to modulate renal vascular resistance. In conscious animals or man no role has been established for prostaglandins in the maintenance of basal renal blood flow or renal sodium excretion. PGE influences renal water excretion by inhibiting the action vasopressin. Despite conflicting data there is evidence that renal prostaglandins are involved either primarily or secondarily in many types of hypertension. Inhibitors of prostaglandin cyclooxygenase have been used with success in Bartter's syndrome. Conflicting results in many areas of investigation may be resolved by the use of more accurate and reliable assays, careful handling of samples, and the use of urine to further investigate renal prostaglandin synthesis.

Acute renal failure with myoglobinuria after tiger snake bite.

This report concerns a cause of snake bite by a tiger snake (Notechis scutatus) in which the predominant pathological feature was acute massive rhabdomyolysis with myoglobinuria, hypocalcaemia and acute renal failure.