Recovery of free ADP, Pi, and free energy of ATP hydrolysis in human skeletal muscle

BACKGROUND: Recent studies have demonstrated that a high concentration of phosphate directly stimulates parathyroid hormone (PTH) secretion. High serum levels of phosphate are usually observed in patients with end-stage renal disease. The aim of the present study was to evaluate whether serum phosphate concentration had an acute effect on PTH secretion in hemodialysis patients. The levels of serum phosphate were manipulated during the hemodialysis session by using a phosphate free dialysate or a dialysate with a high content of phosphate. METHODS: Ten stable hemodialysis patients with PTH values above 300 pg/ml were included in the study. A PTH-calcium curve was obtained during both high phosphate and phosphate free hemodialysis. RESULTS: The serum phosphate concentration remained high (2.17 +/- 0.18 mM) throughout the high phosphate hemodialysis and decreased progressively to normal levels (1.02 +/- 0.06 mM) during the phosphate free hemodialysis. The serum PTH levels at maximal inhibition by hypercalcemia (minimal PTH) were greater during the high phosphate than the phosphate free hemodialysis (413 +/- 79 vs. 318 +/- 76 pg/ml, P < 0.003). In all patients the values of minimum PTH were greater during the high phosphorus than the phosphorus free hemodialysis. The values of maximally stimulated PTH during hypocalcemia and the set point of the PTH-calcium curve were similar during the high phosphate and the phosphate free hemodialysis. CONCLUSION: The maintenance of high serum phosphorus levels during hemodialysis prevented, in part, the inhibition of PTH secretion by calcium, which strongly suggests that in hemodialysis patients high serum phosphate contributes directly to the elevation of PTH levels despite normal or high serum calcium concentration.     

Elevation of serum phosphate affects parathyroid hormone levels in only 50% of hemodialysis patients, which is unrelated to changes in serum calcium

Hyperphosphatemia is said to cause hyperparathyroidism either by depressing the plasma levels of ionized calcium and/or by affecting serum 1,25(OH)2 vitamin D3 levels. Direct evidence that hyperphosphatemia contributes to hyperparathyroidism in hemodialysis patients is unclear because previous published data are with older parathyroid hormone (PTH) assays. Phosphate was added to the dialysate of 15 patients for 12 wk whose predialysis serum phosphates were between 1.5 and 1.9 mM (4.7 to 5.9 mg/dL) in order to further increase their serum phosphate by 0.75 mM (2.4 mg/dL) without adjustments in other medications. No patient was on vitamin D therapy. In half of the patients, PTH levels remained unchanged (nonresponders; 214 +/- 64 versus 219 +/- 60 ng/L), whereas in the other patients, PTH rose from 204 +/- 53 to 338 +/- 60 ng/L (P < 0.05; responders). The degree of induced hyperphosphatemia was virtually identical in both groups, 1.7 mM increasing to 2.4 mM. Ionized calcium was unchanged in both groups after phosphate. Plasma 1,25(OH)2 vitamin D3 levels were low to start with and remained low throughout. Nonresponders had been on dialysis twice as long as responders and had consumed over seven times more aluminum salts. Nonresponders had higher postdeferoxamine increments in plasma aluminum (3,588 +/- 1,466 versus 603 +/- 390; P < 0.05), although neither these amounts nor plasma levels were in the toxic range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum vanadium levels in chronic hemodialysis patients

Serum vanadium, aluminum, silicon and beta 2-microglobulin levels as well as the red cell count, hemoglobin and systolic blood pressure were simultaneously measured in 80 chronic hemodialysis patients. The serum vanadium level was positively correlated with the serum levels of aluminum, silicon and beta 2-microglobulin as well as the systolic blood pressure, and was inversely correlated with the red cell count and hemoglobin. The mean serum vanadium level was 18.4 +/- 7.6 ng/ml before hemodialysis and decreased to 13.0 +/- 5.30 ng/ml at the completion of dialysis. The dialysate vanadium level increased from 0.4 +/- 0.2 (inflow) to 1.0 +/- 0.4 ng/ml (outflow). It was concluded that vanadium was transferred from blood to dialysate when purified water was used in the preparation of the dialysate.     

Mutation (677 C to T) in the methylenetetrahydrofolate reductase gene aggravates hyperhomocysteinemia in hemodialysis patients

Hyperhomocysteinemia is frequent in hemodialysis patients and represents an independent risk factor for vascular disease in these patients. Elevated total homocysteine (tHcy) plasma levels can results from defective remethylation of Hcy to methionine due to decreased activity of the enzyme methylenetetrahydrofolate reductase (MTHFR). A genetic aberration in the MTHFR gene (677 C to T substitution) has been shown to result in reduced MTHFR activity. We tested the hypothesis that elevation of tHcy plasma levels in hemodialysis patients is influenced by the 677 C to T mutation of the MTHFR gene and examined the relation of the genotype with tHcy, folate and vitamin B12 plasma levels in these patients. The allelic frequency of the MTHFR mutation was evaluated in 203 patients maintained on chronic hemodialysis treatment. Total Hcy, folate, vitamin B12 levels and the MTHFR mutation were analyzed in 69 of the 203 patients and in 69 age- and sex-matched healthy control subjects. The allelic frequency of the 677 C to T transition in the MTHFR gene in hemodialysis patients was 34.7% versus 35.5% in healthy controls. Of 203 patients 26 (12.8%) were homozygous for the mutation (+/+) versus 10.2% in healthy subjects. The heterozygous (+/-) genotype was identified in 43.8% of patients versus 50.7% in controls. The mean tHcy level in hemodialysis patients was 28.7 +/- 11.0 mumol/liter versus 10.0 +/- 3.0 mumol/liter in control subjects. The mean tHcy levels were 36.4 +/- 13.4 mumol/liter in (+/+) patients and 12.2 +/- 4.5 mumol/liter in (+/+) controls, 28.7 +/- 10.8 mumol/liter in (+/-) patients and 9.9 +/- 2.7 mumol/liter in (+/-) controls and 25.4 +/- 8.5 mumol/liter in (-/-) hemodialysis patients versus 9.7 +/- 2.8 mumol/liter in (-/-) controls: There was no significant difference of folate and vitamin B12 concentrations in patients and controls with different MTHFR genotypes. Analysis of covariance including age, gender, folate concentrations, vitamin B12 levels, albumin and creatinine as covariables revealed a significant influence of the (+/+) genotype, albumin and folate status on tHcy levels in hemodialysis patients. Together, our data demonstrate that the extent of hyperhomocysteinemia in hemodialysis patients is not only the result of uremia or folate status, but is also genetically determined by the (+/+) MTHFR genotype. The presence of the 677 C to T mutation in the MTHFR gene does not appear to represent a risk factor for development of end-stage renal disease.     

Ab initio electronic structure calculation of a new gene system using the negative factor counting method

It has been reported that cumulative carnitine losses through dialysis membranes may worsen hyperlipidemia during long-term hemodialysis. However, carnitine supplementation has not shown a consistent beneficial response. We undertook the present study to determine if there is any hypolipidemic effect of L-carnitine on Greek dialysis patients in concert with the dialysate buffer composition (acetate or bicarbonate). A total of 28 patients (16 male, 12 female), mean age 43 years (range 21-61), with end-stage renal disease on maintenance hemodialysis for a mean period of 25 months (range 7-84) were studied. The dialysis schedule was 4 h, 3 times/week using cuprophane hollow-fiber dialyzers and acetate (n = 14) or bicarbonate (n = 14) dialysate. In all patients L-carnitine (5 mg/kg body weight) was infused intravenously 3 times/week at the end of each hemodialysis session. Blood samples for carnitine and lipid determinations were obtained before treatment, and 3 and 6 months following treatment. Even though L-carnitine did not modify most of the serum lipid levels, a significant decrease in serum triglycerides was evident in the whole group of patients (from 225 +/- 76 to 201 +/- 75 mg/dl, p = 0.03). Furthermore, L-carnitine could decrease serum triglycerides only in hypertriglyceridemic patients (from 260 +/- 64 to 226 +/- 82 mg/dl, p < 0.05). L-Carnitine resulted in a reduction of serum triglycerides in both patients on bicarbonate and on acetate dialysis, while there were no significant differences in the changes of lipid parameters after L-carnitine between the two groups of hemodialysis patients. We conclude that relatively low doses of L-carnitine supplementation could contribute to the management of some hypertriglyceridemic hemodialysis patients.     

Safety and efficacy of pulse and daily calcitriol in patients on CAPD: a randomized trial

BACKGROUND: Calcitriol therapy is the mainstay of therapy for the treatment of secondary hyperparathyroidism. Oral administration of calcitriol is necessary in CAPD patients, but no studies have directly compared different routes of administration in this patient population. METHODS: To determine if the peak serum calcitriol level (pulse therapy) is more important than the total delivered dose, we randomized CAPD patients with mild to moderate secondary hyperparathyroidism to receive either pulse (3.0 microg twice a week, n = 10) or daily (0.75 microg a day, n = 8) oral calcitriol in comparable weekly doses. The main comparison was the rate of decline of serum intact parathyroid hormone (PTH) levels to reach the desired end-point of 100 pg/ml. The patients were dialysed with low-calcium dialysate and received only calcium-containing phosphate binders. RESULTS: Pharmacokinetic analysis after a single dose of 3.0 microg (pulse) vs 0.75 microg (daily) revealed 1,25(OH)2-vitamin D levels to be higher in the pulse group at 3 and 6 h, but equivalent by 12 h. The area under the curve for 1 week of daily and 1 week of pulse therapy was equal. The patients in the 2 arms had equivalent basal serum levels of PTH (pulse = 562 +/- 291 vs daily = 454 +/- 113 pg/ml), calcium (pulse = 2.32 +/- 0.20 vs daily = 2.32 +/- 0.12 mmol/l) and phosphorus (pulse = 1.32 +/- 0.52 vs daily = 1.35 +/- 0.26 mmol/l). The time required for the PTH to decrease to 100 pg/ml and the rate of decline in PTH were similar (time: pulse = 14.2 +/- 6.8 weeks, daily = 12.2 +/- 7 weeks; rate: pulse = 7.4 +/- 4.2 vs daily = 8.4 +/- 4.2% PTH/week; P = NS). The serum calcium increased similarly in both groups. Hypercalcaemia (> 2.9 mmol/l) was rare (pulse = 3, daily = 2 episodes). CONCLUSIONS: This study demonstrates that pulse and daily calcitriol are similarly effective and safe for the treatment of mild to moderate secondary hyperparathyroidism in CAPD patients despite higher peak levels of 1,25(OH)2-vitamin D with pulse therapy.     

Residual urine in 75-year-old men and women. A normative population study

To evaluate the therapeutic effects of high dose pulse oral calcitrol, 3.5 micrograms calcitrol three times a week and calcium carbonate were administered to 13 patients with end-stage renal disease on chronic hemodialysis with hyperparathyroidism refractory to conventional calcitrol therapy. Serum parathyroid hormone and osteocalcin were detected by radioimmunoassay. Serum parathyroid hormone level of the patients decreased from 1111 +/- 344 ng/L to 492 +/- 218 ng/L by 57.5 +/- 11.5 percent (P < 0.01) in 6 months after the beginning of treatment. Both serum alkaline phosphatase and osteocalcin levels declined markedly, and correlated positively with that of parathyroid hormone. Plasma calcium concentration was markedly elevated, but no obvious increase of plasma phosphate was found. High dose pulse oral calcitrol was effective on secondary hyperparathyroidism. During the course of treatment timely and individual adjustment of calcitrol dose and dialysate calcium concentration is essential.     

Low-dose intravenous calcitriol treatment of secondary hyperparathyroidism in hemodialysis patients. Italian Group for the Study of Intravenous Calcitriol

Intravenous calcitriol is known to directly suppress PTH secretion and release. We evaluated the effect of four months of treatment with low-dose intravenous calcitriol on PTH levels in 83 hemodialysis patients. The criteria for including patients in the study were a serum PTH levels at least four times the normal limit, a serum total calcium less than 10 mg/dl and good control of the serum phosphorus level. All patients underwent standard bicarbonate or acetate dialysis; dialysate calcium level was maintained at the usual 3.5 mEq/liter concentration. Initial calcitriol dose was 0.87 +/- 0.02 (SEM) micrograms (0.015 micrograms/kg body wt) thrice weekly at the end of dialysis, and it was reduced in case of hypercalcemia or elevated calcium-phosphate product. Seven out of 83 patients dropped out during treatment. Among the 76 patients who completed the study, 58 (76%) showed a highly significant decrease of intact PTH levels (average reduction 48%) and of alkaline phosphatase levels after four months of therapy. Total serum calcium increased slightly but significantly in the responder group but remained unchanged in the non-responders. No significant changes in ionized calcium levels could be detected, even in responders. Treatment was well tolerated by patients, but 60% of them had transient episodes of hyperphosphatemia. Mean serum phosphate was 4.95 mg/dl at the beginning of the study. It increased significantly after four months of treatment in patients who showed a decrease of PTH levels, although it remained within acceptable limits, below 5.5 mg/dl. Twenty-eight of 76 patients (37%) reduced the dose of calcitriol because their calcium-phosphate products exceeded 60.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calcium alpha-ketoglutarate administration to malnourished hemodialysis patients improves plasma arginine concentrations

Calcium alpha-ketoglutarate administration to 24 malnourished hemodialysis patients for 1 year leads to a significant increase in plasma concentrations of L-arginine from 53.6 +/- 18.3 (compared to a healthy control group: 87.5 +/- 27.3) to 71.1 +/- 15.9 mumol/l (p < 0.05). Furthermore, concentrations in plasma of proline and histidine, precursors of glutamate biosynthesis, are increased; inorganic phosphate and urea are significantly decreased in hemodialysis patients after 1 year of calcium alpha-ketoglutarate administration.     

Substitution of acetic acid for hydrochloric acid in the bicarbonate buffered dialysate

In a multicenter study including 5 dialysis units, blood acetate changes during 4 h dialysis sessions in 141 patients treated with a 4 mM acetate-containing bicarbonate dialysate (ABD) were evaluated and compared to the values of 114 patients using an acetate-free bicarbonate dialysate (AFD). Acetate-free bicarbonate dialysate was delivered by a dialysis machine from the mixing with water for dialysis of a 1/26.2 bicarbonate concentrate, and a 1/35 acid-concentrate in which acetic acid was substituted for hydrochloric acid (Soludia, Fourquevaux, France). This new type of dialysate was routinely in use for 3 years on average (range, from 2 to 5 years). All patients fasted before and during dialysis. Blood samples were withdrawn at the start and at the end of dialysis sessions. The acetate plasma concentration was determined using the acetyl-CoA synthetase enzymatic method (Boehringer, Manheim, Germany). In patients treated with ABD whose predialysis blood acetate levels were in the physiologic range of < or = 100 microM (n = 113), the acetate plasma concentration increased from a predialysis mean value of 22+/-3 microM to a postdialysis mean value of 222+/-11 microM in 88 patients (78% of patients) whereas the acetate plasma concentration changes remained in the range of physiologic values from 21+/-6 to 58+/-7 microM in the other 25 patients. In contrast, patients treated with AFD whose predialysis blood acetate levels were in the physiologic range (n = 108), acetate plasma concentration increased from a predialysis mean value of 49+/-6 microM to 160+/-19 microM in only 13 patients (12% of patients) whereas acetate plasma concentration changes remained in the range of physiologic values of 23+/-2 to 41+/-3 microM in most of the patients of this group. In this study, a significant number of patients, whether receiving standard or acetate-free bicarbonate dialysates, exhibited an extremely high acetate plasma concentration at the start of the dialysis session. Hyperacetatemia was controlled with AFD in patients whose predialysis acetate plasma concentration of 316+/-82 decreased to 55 +/-23 microM (n = 6) at the end of the dialysis session whereas the acetate plasma concentration remained high when the predialysis concentration was 580+/-76 microM, with a postdialysis concentration of 233+/-39 microM (n = 28). It is concluded that in patients whose predialysis blood acetate levels were in the physiologic range, acetate-containing bicarbonate dialysate induces hyperacetatemia whereas postdialysis blood acetate remains in the normal range in such dialysis patients treated with acetate-free dialysate. Chronic hyperacetatemia, which could be found in dialysis patients, is well controlled by dialysis using an acetate-free dialysate.     

Effects of hindlimb contraction on pressor and muscle interstitial metabolite responses in the cat

We used the microdialysis technique to measure the interstitial concentration of several putative metabolic stimulants of the exercise pressor reflex during 3- and 5-Hz twitch contractions in the decerebrate cat. The peak increases in heart rate and mean arterial pressure during contraction were 20 +/- 5 beats/min and 21 +/- 8 mmHg and 27 +/- 9 beats/min and 37 +/- 12 mmHg for the 3- and 5-Hz stimulation protocols, respectively. All variables returned to baseline after 10 min of recovery. Interstitial lactate rose (P < 0. 05) by 0.41 +/- 0.15 and 0.56 +/- 0.16 mM for the 3- and 5-Hz stimulation protocols, respectively, and were not statistically different from one another. Interstitial lactate levels remained above (P < 0.05) baseline during recovery in the 5-Hz group. Dialysate phosphate concentrations (corrected for shifts in probe recovery) rose with stimulation (P < 0.05) by 0.19 +/- 0.08 and 0.11 +/- 0.03 mM for the 3- and 5-Hz protocols. There were no differences between groups. The resting dialysate K+ concentrations for the 3- and 5-Hz conditions were 4.0 +/- 0.1 and 3.9 +/- 0.1 meq/l, respectively. During stimulation the dialysate K+ concentrations rose steadily for both conditions, and the increase from rest to stimulation (P < 0.05) was 0.57 +/- 0.19 and 0.81 +/- 0.06 meq/l for the 3- and 5-Hz conditions, respectively, with no differences between groups. Resting dialysate pH was 6.915 +/- 0.055 and 6.981 +/- 0.032 and rose to 7.013 (P < 0.05) and 7.053 (P < 0.05) for the 3- and 5-Hz conditions, respectively, and then became acidotic (6. 905, P < 0.05) during recovery (5 Hz only). This study represents the first time simultaneous measurements of multiple skeletal muscle interstitial metabolites and pressor responses to twitch contractions have been made in the cat. These data suggest that interstitial K+ and phosphate, but not lactate and H+, may contribute to the stimulation of thin fiber muscle afferents during contraction.     

The motor organization of the sense of rhythm

Serum inorganic fluoride levels in obese versus control patients were compared during and after sevoflurane anesthesia. Mean serum inorganic fluoride levels in the obese group increased more rapidly and were significantly higher than in the control group at each sampling time (P < 0.01). The area under the curve of fluoride concentration, versus time up to 24 h and 48 h in the obese patients, was significantly greater than that in the nonobese patients (P < 0.001). Peak serum fluoride level in the obese patients was 51.7 +/- 2.5 mumol/L and exceeded 50 mumol/L for nearly 2 h. Our study showed that serum fluoride concentrations between mildly obese and nonobese patients differed during and after sevoflurane anesthesia.     

A study of cis-diamminedichloroplatinum(II) suppositories for the treatment of rabbit uterine endometrial carcinoma

OBJECTIVE: To determine the effects of continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) on endothelin-1 (ET-1) levels in patients with end-stage renal disease (ESRD) and to assess the relationship between plasma ET-1 levels and selected patient parameters. DESIGN: Prospective, nonrandomized comparison study. SETTING: Outpatient CAPD and HD units of a university medical center. PARTICIPANTS: Twelve ESRD patients (6 on CAPD and 6 on HD) and 5 healthy normotensive subjects. INTERVENTIONS: CAPD patients had blood and peritoneal dialysate samples collected and measurements made following an overnight exchange. HD patients had blood collected and measurements made at 0 hours (basal) and again at 3 hours during a midweek HD session. Blood samples were also collected from normal subjects and served as ET-1 controls. MEASUREMENTS: ET-1 and patient parameters (creatinine, peritoneal dialysate volume, blood pressure, body weight, age, and treatment duration) were determined. Data are reported as the mean +/- one standard deviation. RESULTS: Plasma and dialysate ET-1 levels in the CAPD group were 19.5 +/- 4.2 pg/mL and 9.2 +/- 4.2 pg/mL, respectively. The control group plasma and unused dialysate contained no detectable ET-1 (< 3.0 pg/mL, the limit of detection). The peritoneal clearance of ET-1 was less than that of creatinine (2.29 +/- 0.69 mL/minute vs 4.22 +/- 0.66 mL/minute, p = 0.005). The basal (0 hour) plasma ET-1 level in the HD group (16.5 +/- 7.8 pg/mL) did not differ from that of the CAPD group, p = 0.423. Furthermore, no differences in patient parameters were detected between the CAPD and basal HD groups. Although the mean arterial pressure (MAP) decreased during HD, the plasma ET-1 level at 3 hours (13.5 +/- 5.4 pg/mL) remained unchanged from the basal level, p = 0.307. An analysis of pooled data from the CAPD and HD groups revealed no significant correlation between plasma ET-1 and MAP, body weight, creatinine, or treatment duration. There was, however, a positive correlation between plasma ET-1 and age (r = 0.643, p = 0.024).     

Intermittent intraperitoneal ceftazidime dosing in end-stage renal disease

Infections are a common problem in dialysis patients. As hospital stay shortens, many require outpatient antibiotic therapy. Parenteral administration may pose considerable logistic and financial burdens, whereas daily intraperitoneal dosing increases the risk of contamination. Ceftazidime, with its long half-life, may provide adequate dosing when administered intraperitoneally thrice weekly. The authors therefore studied the kinetics of a 2 g loading dose followed by a 1.5 g dose every 48 hr in seven stable chronic peritoneal dialysis patients. In vitro stability at 4 degrees C (measured by high performance liquid chromatography) was 91% at 120 hr. Peak serum concentration (60 +/- 22 microg/ml) was reached at 4.9 +/- 2.2 hr. Serum values were 25 +/- 9 and 8 +/- 3 microg/ml at 24 and 48 hr, respectively. However, median trough levels at 48 hr in dialysate were significantly lower than in serum (2.8 vs 8.5 microg/ml, respectively; p = 0.0425). Pharmacokinetic parameters were as follows: bioavailability (F), 88% +/- 8%; volume of distribution at steady state (VDss), 20 +/- 8 L; absorption half-life (T1/2(abs)), 1.8 +/- 1.3 hr; elimination half-life (T1/2(el)), 11.4 +/- 4.5 hr; and clearance (CL), 22 +/- 10 ml/min. Intraperitoneal ceftazidime every 48 hr is a practical alternative to parenteral therapy of nonperitoneal infections. In peritonitis, whether increased permeability results in improved dialysate levels remains to be defined.     

Three cases of near-tetraploid acute myeloid leukemias originating in pluripotent myeloid progenitors

The kinetics of peritoneal transport of insulin-like growth factor (IGF) system-related proteins during dialysis is not well characterized. We studied temporal changes in dialysate and serum concentrations of IGF-I and IGF-II as well as IGF binding protein (BP)-1, -2, and -3 in ten children with end-stage renal disease (ESRD) undergoing continuous cycling peritoneal dialysis (CCPD) during a 4-h peritoneal equilibration test (PET). Dialysate concentrations of IGF-I, IGF-II, and all three IGFBPs demonstrated a time-dependent increase during PET. Despite their transport, the serum concentrations of these proteins did not change significantly during the PET. Dialysate/serum ratios for IGF-I, IGF-II, and IGFBP-1, -2, and -3 were significantly increased at 2 h and increased further at 4 h, at which time values averaged 1.3+/-0.2%, 3.1+/-0.5%, 6.2+/-1.0%, 2.4+/-0.2%, and 1.3+/-0.2% of serum levels, respectively. The transperitoneal clearance (microl/min per 1.73 m2) of the three IGFBPs was inversely related to both their molecular weight and plasma concentration. However, peritoneal clearance of IGF-I and -II was similar to that of the larger and more-abundant IGFBP-3. Mass transfer rates (microg/h per 1.73 m2) for the IGFs and their binding proteins were directly proportional to their prevailing plasma concentration. Based on estimates of mass transfer, only a small molar excess of IGFBPs was removed from the circulation relative to the combined molar concentration of IGF-I and IGF-II. Hence, it seems unlikely that any beneficial effect of CCPD on growth in children with ESRD is mediated via a preferential loss of IGFBPs into the dialysate fluid.     

Fracture strength of type IV and type V die stone as a function of time

OBJECTIVE: To evaluate risk/benefit of various continuous ambulatory peritoneal dialysis (CAPD) dialysate calcium concentrations. DATA SOURCES: A review of the literature on the effects of various CAPD dialysate Ca concentrations on plasma Ca, plasma phosphate, plasma parathyroid hormone (PTH), doses of calcium carbonate, doses of vitamin D analogs, and requirements of aluminum-containing phosphate binders. STUDY SELECTION: Eleven studies of nonselected CAPD patients, and 13 studies of CAPD patients with hypercalcemia were reviewed. RESULTS:In nonselected CAPD patients, treatment with a reduced dialysate Ca concentration (1.00, 1.25, or 1.35 mmol/L) improved the tolerance to calcium carbonate and/or vitamin D metabolites and reduced the need for Al-containing phosphate binders. When using dialysate Ca 1.25 or 1.35 mmol/L, the initial decrease of plasma Ca and increase of PTH could easily be reversed with an immediate adjustment of the treatment. After 3 months, stable plasma Ca and PTH levels could be maintained using only monthly investigations. In patients with hypercalcemia and elevated PTH levels, treatment with dialysate Ca concentrations below 1.25 mmol/L implied a considerable risk for the progression of secondary hyperparathyroidism. When hypercalcemia was present in combination with suppressed PTH levels, a controlled increase of PTH could be obtained with a temporary discontinuation of vitamin D and/or a reduction of calcium carbonate treatment in combination with a dialysate Ca concentration of 1.25 or 1.35 mmol/L. CONCLUSION: Most CAPD patients can be treated effectively and safely with a reduced dialysate Ca concentration of 1.35 or 1.25 mmol/L. Treatment with dialysate Ca concentrations below 1.25 mmol/L should not be used. A small fraction of patients with persistent hypocalcemia need treatment with high dialysate Ca, such as 1.75 mmol/L.     

Extracellular serotonin is decreased in the nucleus accumbens during withdrawal from cocaine self-administration

Many of the withdrawal symptoms reported by human cocaine users are thought to be correlated with serotonergic dysfunction. To explore the neurochemical basis for this hypothesis, we used in vivo microdialysis to monitor extracellular serotonin (5-HT) in the nucleus accumbens of the rat both during and for several hours after unlimited-access intravenous cocaine self-administration. Self-administration of cocaine produced an increase of approx. 340% of baseline in the dialysate concentration of 5-HT that persisted for the entire 12 h session. During the first 6 h after self-administration, dialysate 5-HT levels were significantly decreased to 41% of pre-session levels and 25% of the levels in drug-naive control animals. The effects of cocaine exposure on basal extracellular 5-HT concentrations were also examined using a quantitative microdialysis method (Difference Method). Rats withdrawing from extended-access cocaine self-administration displayed significantly lower extracellular 5-HT levels (0.6 +/- 0.3 nM) than either drug-naive control animals (2.0 +/- 0.5 nM) or animals which received daily 3-h self-administration training sessions only (limited-access; 1.4 +/- 0.2 nM). Together these results indicate that extracellular 5-HT is significantly decreased in the nucleus accumbens during withdrawal from cocaine self-administration. The severity of this decrease is contingent on the length of time cocaine is self-administered.     

Enzymatic assay of D-mannose in serum

We describe a new and improved enzymatic assay for determining the concentration of D-mannose in sera. Serum D-glucose is selectively converted to glucose-6 phosphate with the highly specific thermostable glucokinase (EC 2.7.1.2) from Bacillus stearothermophilus. The anionic reaction products and excess substrates are removed by a rapid and simple anion-exchange chromatography step in microcentrifuge spin columns. D-Mannose in the glucose-depleted sample is then assayed spectrophotometrically by using coupled enzymatic reactions. The quantitative elimination of glucose from the serum samples allowed the accurate and reproducible assay of serum mannose in the 0-200 mumol/L range. Recovery of mannose added to serum (5-200 mumol/L) was 94% +/- 4.4%. The intraassay CV was 6.7% at 40 mumol/L mannose (n = 5; 39.6 +/- 1.6 mumol/L) and 4.4% at 80 mumol/L (n = 11; 75.0 +/- 1.8 mumol/L); the interassay CV at these concentrations was 12.2% (n = 7; 36.9 +/- 2.1 mumol/L) and 9.8% (n = 7; 74.2 +/- 2.7 mumol/L), respectively. Sera from 11 healthy human volunteers contained an average of 54.1 +/- 11.9 mumol/L mannose (range 36-81 mumol/L).     

Temperature/light dependent development of selective resistance to photoinhibition of photosystem I

BACKGROUND: Circulating magnesium exists in the ionized state and in the undissociated form, either bound to albumin, or complexed to various anions. Until recently, only the measurement of total plasma magnesium has been possible. Now circulating ionized magnesium can be assessed as well. METHODS: Total and ionized plasma magnesium were determined in 43 patients on maintenance hemodialysis (dialysate composition: calcium 1.75 mmol/l, magnesium 0.75 mmol/l) before a dialysis session and in a group of 23 healthy subjects. RESULTS: The total (1.16 [1.03-1.31] versus 0.81 [0.78-0.89] mmol/l; median and interquartile range) and the ionized (0.71 [0.66-0.78] versus 0.54 [0.53-0.59] mmol/l) plasma magnesium levels were significantly higher (p < 0.01) and the ionized plasma magnesium fraction lower (0.61 [0.58-0.65] versus 0.67 [0.64-0.70]; p < 0.02) in patients than in controls. CONCLUSION: The determination of circulating ionized magnesium using selective electrodes is an attractive method to evaluate extracellular magnesium in kidney disease.     

High phosphate level directly stimulates parathyroid hormone secretion and synthesis by human parathyroid tissue in vitro

Phosphate retention plays an important role in the pathogenesis of secondary hyperparathyroidism in patients with renal failure. In in vitro studies, high extracellular phosphate levels directly stimulate PTH secretion in rat and bovine parathyroid tissue. The present study evaluates the effect of high phosphate levels on the secretion of PTH and the production of prepro PTH mRNA in human hyperplastic parathyroid glands. The study includes parathyroid glands obtained from patients with primary adenomas and from hemodialysis and kidney-transplant patients with diffuse and nodular secondary hyperplasia. The experiments were performed in vitro using small pieces of parathyroid tissue. The ability of high calcium levels to decrease PTH secretion was less in adenomas than in secondary hyperplasia; among the secondary hyperplasia, nodular was less responsive to an increase in calcium than diffuse hyperplasia. In diffuse hyperplasia, PTH secretion was increased in response to 3 and 4 mM phosphate compared with 2 mM phosphate, despite a high calcium concentration in the medium; prepro PTH mRNA levels increased after incubation in 4 mM phosphate. Similar results were obtained with nodular hyperplasia, except that the elevation of PTH secretion in response to 3 mM phosphate did not attain statistical significance. In adenomas, high calcium concentrations (1.5 mM) did not result in inhibition of PTH secretion, independent of the phosphate concentration, and the prepro PTH mRNA was not significantly increased by high phosphate levels. In conclusion, first, the PTH secretory response to an increase in calcium concentration is less in nodular than diffuse hyperplasia; second, high phosphate levels directly affect PTH secretion and gene expression in patients with advanced secondary hyperparathyroidism.