Copper pumping ATPases: Common concepts in bacteria and man

AbstractRecently, four genes encoding putative copper pumping ATPases have been cloned from widely different sources: two genes from Enterococcus hirae that are involved in copper metabolism and two human genes that are defective in the copper-related Wilson and Menkes disease. The predicted gene products are P-type ATPases. They exhibit extensive sequence similarity and appear to be members of a new class of ATP driven copper pumps involved in the regulation of cellular copper

A Controlled Increase in Dietary Phosphate Elevates BP in Healthy Human Subjects.

Background Despite epidemiologic evidence for increased cardiovascular morbidity and mortality associated with both high dietary and serum phosphate in humans with normal renal function, no controlled phosphate intervention studies of systemic hemodynamics have been reported. Higher serum 25(OH) vitamin D levels are associated with better cardiovascular outcomes, but vitamin D increases intestinal phosphate absorption.Methods We conducted a prospective outpatient study with blinded assessment in 20 young adults with normal renal function randomized to high phosphate (regular diet plus 1 mmol/kg body wt per day of Na as neutral sodium phosphate) or low phosphate (regular diet plus lanthanum, 750 mg thrice/day, plus 0.7 mmol/kg body wt per day of Na as NaCl) for 11 weeks. After 6 weeks, all subjects received vitamin D3 (600,000 U) by intramuscular injection. Outcome parameters were 24-hour ambulatory systolic and diastolic BP (SBP and DBP), pulse rate (PR), biomarkers, and measures of endothelial and arterial function.Results Compared with the low-phosphate diet group, the high-phosphate diet group had a significant increase in mean±SEM fasting plasma phosphate concentration (0.23±0.11 mmol/L); 24-hour SBP and DBP (+4.1; 95% confidence interval [95% CI], 2.1 to 6.1; and +3.2; 95% CI, 1.2 to 5.2 mm Hg, respectively); mean 24-hour PR (+4.0; 95% CI, 2.0 to 6.0 beats/min); and urinary metanephrine and normetanephrine excretion (54; 95% CI, 50 to 70; and 122; 95% CI, 85 to 159 µg/24 hr, respectively). Vitamin D had no effect on any of these parameters. Neither high- nor low-phosphate diet nor vitamin D affected endothelial function or arterial elasticity.Conclusions Increased phosphate intake (controlled for sodium) significantly increases SBP, DBP, and PR in humans with normal renal function, in part, by increasing sympathoadrenergic activity

Correction of metabolic acidosis improves thyroid and growth hormone axes in haemodialysis patients

Background. Chronic metabolic acidosis (CMA) in normal adults results in complex endocrine and metabolic alterations including growth hormone (GH) insensitivity, hypothyroidism, hyperglucocorticoidism, hypoalbuminaemia and loss of protein stores. Similar alterations occur in chronic renal failure, a prototypical state of CMA. We evaluated whether metabolic acidosis contributes to the endocrine and metabolic alterations characteristic of end-stage renal disease. Methods. We treated 14 chronic haemodialysis patients with daily oral Na-citrate for 4 weeks, yielding a steady-state pre-dialytic plasma bicarbonate concentration of 26.7 mmol/l, followed by 4 weeks of equimolar Na-chloride, yielding a steady-state pre-dialytic plasma bicarbonate of 20.2 mmol/l. Results. Blood pressure, body weight and dialysis adequacy were equivalent in the two protocols. Na-citrate treatment corrected CMA, improved GH insensitivity, increased and normalized plasma free T3 concentration, and improved plasma albumin. Correction of CMA had no significant effect on measured cytokines (interleukin-1β and -6, tumour necrosis factor-α) or acute phase reactants (C-reactive protein, serum amyloid A, α2-macroglobulin). Conclusion. CMA contributes to the derangements of the growth and thyroid hormone axes and to hypoalbuminaemia, but is not a modulator of systemic inflammation in dialysis patients. Correcting CMA may improve nutritional and metabolic parameters and thus lower morbidity and mortalit

Correction of metabolic acidosis improves thyroid and growth hormone axes in haemodialysis patients

Background. Chronic metabolic acidosis (CMA) in normal adults results in complex endocrine and metabolic alterations including growth hormone (GH) insensitivity, hypothyroidism, hyperglucocorticoidism, hypoalbuminaemia and loss of protein stores. Similar alterations occur in chronic renal failure, a prototypical state of CMA. We evaluated whether metabolic acidosis contributes to the endocrine and metabolic alterations characteristic of end-stage renal disease. Methods. We treated 14 chronic haemodialysis patients with daily oral Na-citrate for 4 weeks, yielding a steady-state pre-dialytic plasma bicarbonate concentration of 26.7 mmol/l, followed by 4 weeks of equimolar Na-chloride, yielding a steady-state pre-dialytic plasma bicarbonate of 20.2 mmol/l. Results. Blood pressure, body weight and dialysis adequacy were equivalent in the two protocols. Na-citrate treatment corrected CMA, improved GH insensitivity, increased and normalized plasma free T3 concentration, and improved plasma albumin. Correction of CMA had no significant effect on measured cytokines (interleukin-1β and -6, tumour necrosis factor-α) or acute phase reactants (C-reactive protein, serum amyloid A, α2-macroglobulin). Conclusion. CMA contributes to the derangements of the growth and thyroid hormone axes and to hypoalbuminaemia, but is not a modulator of systemic inflammation in dialysis patients. Correcting CMA may improve nutritional and metabolic parameters and thus lower morbidity and mortalit

Chronic respiratory alkalosis induces renal PTH-resistance, hyperphosphatemia and hypocalcemia in humans

Chronic respiratory alkalosis induces renal hyperphosphatemia and hypocalcemia in humans. The effects of chronic respiratory alkalosis on divalent ion homeostasis have not been reported in any species. We studied four normal male subjects during a four-day control period (residence at 500 m), during six days of chronic respiratory alkalosis induced by hypobaric hypoxia (residence at 3450 m), followed by a six-day eucapnic recovery period (500 m) under metabolic balance conditions. Chronic respiratory alkalosis (ΔPaCO2, -8.4mm Hg, Δ[H+] -3.2 nmol/liter) resulted in a sustained decrement in plasma ionized calcium concentration (Δ[IoCa++]p, -0.10 mmol/liter, P < 0.05) and a sustained increment in plasma phosphate concentration (Δ[PO4]p, +0.14 mmol/liter, P < 0.005) associated with increased fractional excretion of Ca++ (+0.5%, P < 0.005), decreased phosphate clearance (-6.1 ml/min, P < 0.025) and decreased excretion of nephrogenous cAMP (-1.5 nmol/100 ml GFR, P < 0.0025). Urinary phosphate excretion decreased by 15.4 mmol/24 hr on day 1 of chronic respiratory alkalosis (P < 0.0025), but returned to control values by day 6 despite hyperphosphatemia. Serum intact [PTH] did not change. Sustained hypomagnesuria (-0.8 mmol/24 hr, P < 0.05) occurred during chronic respiratory alkalosis and was accounted for, at least in part, by decreased fractional excretion of Mg++ (-0.7%, P < 0.05) in the absence of change in plasma magnesium concentration. Serum 1,25(OH)2D levels were unchanged by chronic respiratory alkalosis. In conclusion, the decrease in nephrogenous cAMP generation despite unchanged serum intact PTH concentration suggests that chronic respiratory alkalosis results in impaired renal responsiveness to PTH as manifested by alterations in PTH-dependent renal calcium and phosphate transport. Hypomagnesuria in chronic respiratory alkalosis may be due, at least in part, to hypocalcemia-induced enhancement of renal magnesium reabsorption. The failure of [PTH] to increase during hypocalcemia may reflect defective PTH secretion

The Swiss Kidney Stone Cohort (SKSC), a longitudinal, multi-centric, observational cohort to study course and causes of kidney stone disease in Switzerland

Kidney stone disease has a high prevalence worldwide of approximately 10 % of the population and is characterized by a high recurrence rate Kidney stone disease results from a combination of genetic, environmental, and life-style risk factors, and the dissection of these factors is complex. The Swiss Kidney Stone Cohort (SKSC) is an investigator-initiated prospective, multi-centric longitudinal, observational study in patients with kidney stones followed with regular visits over a period of 3 years after inclusion. Ongoing follow-ups by biannual telephone interviews will provide long-term outcome data up to 10 years. SKSC comprises 782 adult patients (age &gt; 18 yrs) with either recurrent stones or a single stone event with at least one risk factor for recurrence. In addition, a control cohort of 207 individuals without kidney stone history and absence of kidney stones on a low-dose CT-scan at enrolment has also been recruited. SKSC includes extensive collections of clinical data, biochemical data in blood and 24 hr urine samples, and genetic data. Biosamples are stored at a dedicated biobank. Information on diet and dietary habits were collected through food frequency questionnaires and standardized recall interviews by trained dieticians with the Globodiet software. SKSC provides an unique opportunity and resource to further study cause and course of kidney disease in a large population with data and samples collected of a homogenous collective of patients throughout the whole Swiss population

[It is more difficult to smash a prejudice than an atom]

The death of a 17-year-old patient caused by hypokalemia-induced arrhythmia illustrates the tragic dangers of the current paranoid preoccupation, particularly of young women, with physical beauty and low body weight. This case also reminds the reader that modern textbooks are not always sufficiently reliable. An intellectual approach how to circumvent diagnostic misinterpretation even in the context of misleading textbook information is proposed

Kurz und bündig - Fokus auf ... Gesund essen: Parallele zu erfolgreicher ­Aktieninvestition

Zentral und überlebenswichtig ist bei beidem: Diversifikation! ; Der sogenannten Weisheit der Märkte* entspricht: Die Gesundheitsfolgen der Diät sind unter anderem unsere Langlebigkeit (also machen wir nicht alles falsch). ; Wir verstehen aber die Folgen individueller Komponenten nicht oder schlecht (und signifikante Korrelationen werden auffällig häufig wieder relativiert). ; Ein weiteres Beispiel: Milchkonsum und Gesundheit! kein Effekt auf Frakturraten beim Erwachsenen; keine eindeutigen Folgen auf Gewichtskontrolle, Diabeteshäufigkeit und kardiovaskuläre Morbidität; angeblich erhöhtes Risiko für Prostata- und Endometriumkarzinome, aber tieferes Risiko für kolorektale Karzinome ; Im Aktienkurs sind die Folgen aller kursrelevanten Informationen bereits enthalten. Stimmt meist, aber eben nicht immer ..

Effects of acidogenic diet forms on musculoskeletal function

Chronic metabolic acidosis exerts well-characterized consequences on musculoskeletal function, including physicochemical dissolution of bone with calcium loss from bone, cellular effects on osteoblasts and osteoclasts and disturbed bone matrix mineralization. These mechanisms are responsible for the acidotic bone phenotype with features of both osteoporosis and osteomalacia. In addition, loss of muscle mass, sarcopenia and negative nitrogen balance are consequences of metabolic acidosis. It is becoming increasingly clear that these effects also occur as a consequence of the diet-induced acid loads characteristic of modern diets. Interventional, short- and long-term studies suggest that the result of neutralizing the diet-induced acid loads is skeletal calcium retention, decreased bone resorption and increases in bone mineral density, suggesting that such an intervention may have an important potential to prevent osteoporosis