OBJECTIVETo investigate the effect of a new biomaterial combining calcium citrate and recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone regeneration in a bone defect rabbit model.

METHODSTotally 30 male New Zealand white rabbits were randomly and equally divided into calcium citrate-rhBMP-2 (CC-rhBMP-2) group and rhBMP-2 only group. Two 10 mm-long and 5 mm-deep bone defects were respectively created in the left and right femoral condyles of the rabbits. Subsequently 5 pellets of calcium citrate (10 mg) combined with rhBMP-2 (2 mg) or rhBMP-2 alone were implanted into the bone defects and compressed with cotton swab. Bone granules were obtained at 2, 4 and 6 weeks after procedure and received histological analysis. LSD t-test and a subsequent t-test were adopted for statistical analysis.

RESULTSHistomorphometric analysis revealed newly formed bones, and calcium citrate has been absorbed in the treatment group. The percent of newly formed bone area in femoral condyle in control group and CC-rhBMP-2 group was respectively 31.73%+/-1.26% vs 48.21%+/-2.37% at 2 weeks; 43.40%+/-1.65% vs 57.32%+/-1.47% at 4 weeks, and 51.32%+/-7.80% vs 66.74%+/-4.05% at 6 weeks (P less than 0.05 for all). At 2 weeks, mature cancellous bone was observed to be already formed in the treatment group.

CONCLUSIONFrom this study, it can be concluded that calcium citrate combined with rhBMP-2 signifcantly enhances bone regeneration in bone defects. This synthetic gelatin matrix stimulates formation of new bone and bone marrow in the defect areas by releasing calcium ions.

Eleven patients with uric acid nephrolithiasis(Five with uric acid stones alone and six with both uric acid and calcium stone) underwent long-term treatment(0.5 to 3.75 years, mean of 2.33 years) with potassium citrate(30 to 80 mEq/day. usually 60mEq/day). Urinary pH increased from low(5.0-6.0) to normal(6.5-7.0) during treatment. Urinary content of uric acid which was 584+/-150 mg, day. slightly increased to 595+/-163 mg/day following treatment. Serum content of uric acid which was 6.45+/-0.9 mg%, slightly decreased to 6.1+/-0.8 mg%. The protein matrix was round in all 11 cases. And 4 types of nucleus were found. which were ca. oxalate, ca. phosphate, dried blood and suture material During the period' (Jan. 1987-Mar. 1990) of preventive management(enough fluid intake. restiction of animal protein and Polycitra-K), no new stones were found.
Animals ; Calcium ; Humans ; Hydrogen-Ion Concentration ; Nephrolithiasis* ; Potassium Citrate* ; Potassium* ; Sutures ; Uric Acid*

We report the case of a female patient with incomplete distal renal tubular acidosis with nephrocalcinosis. She was admitted to the hospital because of acute pyelonephritis. Imaging studies showed dual medullary nephrocalcinosis. Subsequent evaluations revealed hypokalemia, hypocalcemia, hypercalciuria, and hypocitraturia with normal acid-base status. A modified tubular acidification test with NH4Cl confirmed a defect of urine acidification, which is compatible with incomplete distal tubular acidosis. We treated our patient with potassium citrate, which corrects hypokalemia and prevents further deposition of calcium salts.
Acidosis ; Acidosis, Renal Tubular ; Calcium ; Female ; Humans ; Hypercalciuria ; Hypocalcemia ; Hypokalemia ; Kidney ; Nephrocalcinosis ; Potassium Citrate ; Pyelonephritis ; Salts

OBJECTIVE: To assess the effect of vitamin K2 in addition to risedronate on postmenopausal osteoporosis METHOD: We enrolled 21 postmenopausal osteoporosis women (age: 65.2+/-7.8 years). Ten subjects received risedronate (35 mg, weekly) and vitamin K2 (45 mg, daily) and eleven subjects only received risedronate. They all received calcium citrate 2,130 mg and vitamin D 600 IU daily. The duration of treatment was 7.7+/-1.4 months. Bone mineral density (BMD) of lumbar spine and both femurs, serum osteocalcin and urine deoxypyridinoline were examined at baseline and after treatment. RESULTS: After treatment, BMD, serum osteocalcin and urine deoxypyridinoline were improved in each group but there was no statistical difference between the groups. CONCLUSION: There was no evidence of the benefit of vitamin K2 in addition to risedronate in bone metabolism on postmenopausal osteoporosis.
Bone Density ; Calcium Citrate ; Female ; Femur ; Humans ; Metabolism ; Osteocalcin ; Osteoporosis, Postmenopausal* ; Risedronate Sodium ; Spine ; Vitamin D ; Vitamin K 2* ; Vitamins*

PURPOSE: Citrate is a well recognized inhibitor of the formation of calcium oxalate and calcium phosphate stones. Hypocitraturia is a common etiology of recurrent calcium nephrolithiasis, with an incidence of 19 to 63%. Potassium citrate therapy can be a useful therapeutic approach for the management of calcium nephrolithiasis. But pharmacological treatment of hypocitraturic calcium nephrolithiasis requires taking too many tablets, or numerous crystal package or liquid supplements throughout the day. This cumbersome regimen often decreases patient compliance. We administered dietary citrate via lemon juice to stone former and evaluated the change of citrate levels. MATERIALS AND METHODS: The prospective study included 7 women and 8 men with documented recurrent or multiple urinary stone disease. None of the subjects suffered from renal impairment, urinary tract infection and other metabolic disorder. Controls comprised 6 voluntary men. They had no previous stone history and no evidence of stone. Patients ingested total 1 liter of lemon juice(containing 4.0gm/L.citrate) divided at 6 hours interval without strict diet restriction. Urine specimens were obtained for urinary citrate levels after 2-3days of lemon juice therapy and compared to pre-lemon juice baseline values. RESULTS: All 15 patient showed increased urinary citrate levels during lemon juice therapy. Average urinary citrate levels increased from 146+/-109mg/day at baseline to 453+/-226mg/day during treatment(p<0.05). Urinary citrate levels during treatment increased up to those of control group(351+/-265mg/day) and did not show significant difference (p>0.05). Urinary pH increased from 5.9+/-0.4 at baseline to 6.8+/-0.6 during treatment(p<0.05). No patient complained of gastrointestinal discomforts. CONCLUSIONS: Citrate supplementation with lemon juice increased urinary citrate levels and urinary pH. Lemon juice is well tolerated dietary source of citrate and would be beneficial in the control of calcium urolithiasis.
Calcium ; Calcium Oxalate ; Citric Acid* ; Diet ; Female ; Humans ; Hydrogen-Ion Concentration ; Incidence ; Male ; Nephrolithiasis ; Patient Compliance ; Potassium Citrate ; Prospective Studies ; Tablets ; Urinary Calculi ; Urinary Tract Infections ; Urolithiasis*

Potassium citrate therapy caused a sustained increase in urinary pH and potassium, and restored urinary citrate to normal levels. No significant changes occurred in urinary uric acid, oxalate, sodium or phosphorus levels. Owing to these physiological changes, uric acid solubility increased, urinary saturation of calcium oxalate decreased and the propensity for spontaneous nucleation of calcium oxalate was reduced to normal. Therefore, the Physicochemical environment of urine following treatment become less conductive to the crystallization of calcium oxalate or uric acid. Twenty six patients with uric acid nephrolithiasis with or without calcium nephrolithiasis underwent treatment and long-term preventive management (mean of 20.8 months) with potassium citrate. Urinary pH increased from acid (5.0-5.5) to normal (6.5-7.0) during treatment. During the period of preventive management, stones were not developed.
Calcium ; Calcium Oxalate ; Citric Acid ; Crystallization ; Humans ; Hydrogen-Ion Concentration ; Nephrolithiasis ; Oxalic Acid ; Phosphorus ; Potassium Citrate* ; Potassium* ; Solubility ; Uric Acid ; Urinary Calculi*

PURPOSE: To study the effects of long-term treatment with potassium magnesium citrate and vitamin B-6 prophylaxis (Urikind-KM6; 1,100-mg potassium citrate, 375-mg magnesium citrate, and 20-mg pyridoxine hydrochloride/5 mL) every 8 hours over 3 years. MATERIALS AND METHODS: A total of 247 patients with recurrent idiopathic hypocitraturia with or without hyperuricosuria and randomized controls were studied prospectively for 3 years. The total patients were divided into three groups. Control group 1 consisted of 61 patients (24.7%) who had moderate to severe hypocitraturia with or without hyperuricosuria and were recurrent stone formers but discontinued prophylaxis because of drug intolerance within 1 month of therapy. Control group 2 constituted 53 patients (21.5%) who were first-time stone formers and who had mild hypocitraturia with or without hyperuricosuria and were not put on prophylactic therapy and were followed for 3.16+/-0.08 years. Control group 3 constituted 133 patients (54.8%) who were recurrent stone formers who had moderate to severe hypocitraturia with or without hyperuricosuria and were put on prophylaxis therapy and were followed for 3.16+/-0.08 years. All patients were followed up at 6-month intervals. RESULTS: Potassium magnesium citrate prophylaxis produced a sustained increase in 24-hour urinary citrate excretion from initially low values (221.79+/-13.39 mg/dL) to within normal to high limits (604.04+/-5.00 mg/dL) at the 6-month follow-up. Urinary pH rose significantly from 5.62+/-0.2 to 6.87+/-0.01 and was maintained at 6.87+/-0.01. The stone recurrence rate declined from 3.23+/-1.04 per patient per year to 0.35+/-0.47 per patient per year. CONCLUSIONS: Potassium magnesium citrate prophylaxis was effective in reducing the recurrence of calcium oxalate and phosphate urolithiasis.
Calcium Oxalate* ; Citric Acid* ; Follow-Up Studies ; Humans ; Hydrogen-Ion Concentration ; Magnesium* ; Potassium Citrate ; Potassium* ; Prospective Studies ; Pyridoxine ; Recurrence ; Urolithiasis* ; Vitamins*

PURPOSE: We compared the biochemical and clinical presentation of gouty diathesis in patients with uric acid and calcium nephrolithiasis MATERIALS AND METHODS: We retrospectively reviewed biochemical and clinical data from 69 gouty diathesis patients(48 with uric acid stones and 21 with calcium stones) and 57 normal subjects were performed at our institution. RESULTS: Demographic similarity between two groups was a male predominance. Gouty diathesis patients in both groups showed abnormally low urinary pH(<5.5) and propensity for hyperuricemia and hypertriglyceridemia. Gouty arthritis and hyperuricemia was found in 31% and 44% of those with uric acid stones whereas 9.5% and 23.8% in those with calcium stone respectively. In control group, 1 case presented with hyperuricemia and urinary pH at 6.3. Both urinary pH and citrate increased after potassium citrate treatment in both groups. CONCLUSIONS: The two groups of gouty diathesis with either uric acid stone or calcium stones have similar biochemical and clinical features that are characteristic of primary gout. Calcium stone formation in patients with hyperuricemia or persistent acidic urine may represent a latent form of gout. Patients with calcium stones and biochemical feature of gouty diathesis may manifest primary gouty. Both groups are responsive to potassium citrate treatment.
Arthritis, Gouty ; Calcium* ; Citric Acid ; Disease Susceptibility* ; Gout ; Humans ; Hydrogen-Ion Concentration ; Hypertriglyceridemia ; Hyperuricemia ; Male ; Nephrolithiasis ; Potassium Citrate ; Retrospective Studies ; Uric Acid*

Sildenafil relaxes vascular smooth muscle cells and is used to treat pulmonary artery hypertension as well as erectile dysfunction. However, the effectiveness of sildenafil on skeletal muscle and the benefit of its clinical use have been controversial, and most studies focus primarily on tissues and organs from disease models without cellular examination. Here, the effects of sildenafil on skeletal muscle at the cellular level were examined using mouse primary skeletal myoblasts (the proliferative form of skeletal muscle stem cells) and myotubes, along with single-cell Ca2+ imaging experiments and cellular and biochemical studies. The proliferation of skeletal myoblasts was enhanced by sildenafil in a dose-independent manner. In skeletal myotubes, sildenafil enhanced the activity of ryanodine receptor 1, an internal Ca2+ channel, and Ca2+ movement that promotes skeletal muscle contraction, possibly due to an increase in the resting cytosolic Ca2+ level and a unique microscopic shape in the myotube membranes. Therefore, these results suggest that the maintenance ability of skeletal muscle mass and the contractility of skeletal muscle could be improved by sildenafil by enhancing the proliferation of skeletal myoblasts and increasing the Ca2+ availability of skeletal myotubes, respectively.
Animals ; Cytosol ; Erectile Dysfunction ; Hypertension ; Maintenance* ; Male ; Membranes ; Mice ; Muscle Fibers, Skeletal ; Muscle, Skeletal* ; Muscle, Smooth, Vascular ; Myoblasts, Skeletal ; Pulmonary Artery ; Ryanodine Receptor Calcium Release Channel ; Sildenafil Citrate*

PURPOSE: It has previously been reported that citrate, thiazide, allopurinol and magnesium (CTAM) have inhibitory effects on calcium oxalate crystallization, but the effects of CTAM on the matrix proteins of stones in vivo has not been studied. Using an ethylene glycol-induced urolithiasis model, we investigated the effects of CTAM on renal crystallization and the expression of osteopontin (OPN), which is an important stone matrix protein. MATERIALS AND METHODS: Adult Sprague-Dawley rats (200-250gm) were divided randomly into 6 groups of 10 rats. Group 1 was left untreated, and served as a control. Group 2 (CID group) was fed 0.8% ethylene glycol and 1% ammonium chloride (crystal-inducing diet, CID) in drinking water for 4 weeks. Groups 3, 4, 5 and 6 (CTAM groups) were fed the same CID as group 2, but were also treated with either potassium citrate or hydrochlorothiazide or allopurinol or magnesium hydroxide, for 4 weeks, respectively. We biochemically analyzed the 24-hour urine and serum samples. The renal calcium content was measured by atomic absorption. The kidneys were histologically examined for crystal deposit with HandE staining, and for OPN expression with immunohistochemical staining. RESULTS: The grade of calcium oxalate crystal deposits, and renal calcium content, were significantly decreased in the CTAM groups compared to the CID group, which also correlated with the decreased expression of OPN proteins in the kidneys of the CTAM-treated rats. CTAM were all effective in preventing calcium oxalate crystal formation, and decreasing the expression of OPN in rat kidneys. CONCLUSIONS: Our results suggest that CTAM are effective in preventing calcium oxalate stone formation, and that OPN plays an important role in calcium oxalate nephrolithiasis.
Absorption ; Administration, Oral* ; Adult ; Allopurinol* ; Ammonium Chloride ; Animals ; Calcium Oxalate* ; Calcium* ; Citric Acid* ; Crystallization ; Diet ; Drinking Water ; Ethylene Glycol ; Hand ; Humans ; Hydrochlorothiazide ; Kidney ; Magnesium Hydroxide ; Magnesium* ; Nephrolithiasis ; Osteopontin* ; Potassium Citrate ; Rats* ; Rats, Sprague-Dawley ; Urolithiasis*