Recent studies have revealed a significant relationship between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS), both of which commonly affect middle-aged and older men. These conditions share underlying causes, particularly endothelial dysfunction, atherosclerosis, and chronic pelvic ischemia (CPI). This study investigated the therapeutic potential of LDD175, a large-conductance Ca 2+ -activated K + channel (BKCa channel) opener, in simultaneously treating both conditions using a CPI animal model of male Sprague Dawley rats. Our study investigated the induction of CPI through surgical endothelial damage combined with a high-cholesterol diet. We assessed erectile and voiding functions by measuring intracavernosal pressure (ICP) and intraurethral pressure (IUP), respectively, after nerve stimulation. We performed histological examinations of vascular changes and western blot analyses of cavernous and prostate tissues to understand the underlying mechanisms. This study evaluated the effectiveness of LDD175 compared to standard treatments, such as sildenafil for ED and tamsulosin for LUTS. Therefore, the CPI model successfully demonstrated ED and LUTS symptoms with decreased ICP and increased IUP. Analysis revealed elevated levels of hypoxia-inducible factor-1α, transforming growth factor-β1 and β2 in cavernous tissue, and increased α1A-adrenoceptor expression in prostate tissue. LDD175 administration showed promising results, with dose-dependent improvements in ICP and IUP, and therapeutic effects comparable to those of established treatments. Our findings suggest a novel therapeutic approach that can simultaneously address ED and LUTS, opening new possibilities for clinical application in the treatment of these interconnected conditions.
Male ; Animals ; Erectile Dysfunction/etiology* ; Rats, Sprague-Dawley ; Lower Urinary Tract Symptoms/etiology* ; Ischemia/drug therapy* ; Rats ; Tamsulosin ; Hypoxia-Inducible Factor 1, alpha Subunit/drug effects* ; Sildenafil Citrate/therapeutic use* ; Penis/blood supply* ; Disease Models, Animal ; Transforming Growth Factor beta1/metabolism* ; Pelvis/blood supply* ; Prostate/metabolism* ; Sulfonamides/therapeutic use* ; Large-Conductance Calcium-Activated Potassium Channels/agonists*

Calreticulin (CALR), a multifunctional protein thoroughly researched in mammals, comprises N-, P-, and C-domain and has roles in calcium homeostasis, chaperoning, clearance of apoptotic cells, cell adhesion, and also angiogenesis. In this study, the spatial and temporal expression patterns of the Opisthorchis viverrini CALR gene were analyzed, and calcium-binding and chaperoning properties of recombinant O. viverrini CALR (OvCALR) investigated. OvCALR mRNA was detected from the newly excysted juvenile to the mature parasite by RT-PCR while specific antibodies showed a wide distribution of the protein. OvCALR was localized in tegumental cell bodies, testes, ovary, eggs, Mehlis’ gland, prostate gland, and vitelline cells of the mature parasite. Recombinant OvCALR showed an in vitro suppressive effect on the thermal aggregation of citrate synthase. The recombinant OvCALR C-domain showed a mobility shift in native gel electrophoresis in the presence of calcium. The results imply that OvCALR has comparable function to the mammalian homolog as a calcium-binding molecular chaperone. Inferred from the observed strong immunostaining of the reproductive tissues, OvCALR should be important for reproduction and might be an interesting target to disrupt parasite fecundity. Transacetylase activity of OvCALR as reported for calreticulin of Haemonchus contortus could not be observed.
Antibodies ; Calcium ; Calreticulin* ; Cell Adhesion ; Cell Body ; Citrate (si)-Synthase ; Eggs ; Electrophoresis ; Female ; Fertility ; Haemonchus ; Homeostasis ; In Vitro Techniques ; Mammals ; Molecular Chaperones ; Opisthorchis* ; Ovary ; Ovum ; Parasites ; Prostate ; Reproduction ; RNA, Messenger ; Testis ; Vitellins

Milk-alkali syndrome (MAS), a triad of hypercalcemia, metabolic alkalosis, and renal failure, is associated with ingestion of large amounts of calcium and absorbable alkali. MAS is the third most common cause of hypercalcemia in hospital, after primary hyperparathyroidism and malignant neoplasm. MAS is not often reported in the Korean literature. We describe MAS secondary to intake of calcium citrate for the treatment of osteoporosis with thoracic spine compression fracture. A 70-year-old man presented to our hospital with a 1-week history of general weakness and lethargy. He was found with acute kidney injury (serum creatinine, 4.6 mg/dL), hypercalcemia (total calcium, 14.8 mg/dL), and alkalosis. Laboratory evaluation excluded both hyperparathyroidism and malignancy. Mental status and serum calcium level was normalized within a week after proper hydration and intravenous administration of furosemide. However, he developed aspiration pneumonia, pseudomembranous colitis, and sepsis with multi-organ failure. Despite intensive treatment including inotropics, mechanical ventilation, and renal replacement therapy, he expired with no signs of renal recovery on the 28th hospital day.
Acute Kidney Injury ; Administration, Intravenous ; Aged ; Alkalies ; Alkalosis ; Calcium Citrate ; Calcium* ; Creatinine ; Eating ; Enterocolitis, Pseudomembranous ; Fractures, Compression ; Furosemide ; Humans ; Hypercalcemia* ; Hyperparathyroidism ; Hyperparathyroidism, Primary ; Lethargy ; Osteoporosis ; Pneumonia, Aspiration ; Renal Insufficiency ; Renal Replacement Therapy ; Respiration, Artificial ; Sepsis ; Spine

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: 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*

The prevalence of kidney stone disease is increasing, and newer research is finding that stones are associated with several serious morbidities. These facts suggest that emphasis needs to be placed not only on stone treatment but also stone prevention. However, there is a relative dearth of information on dietary and medical therapies to treat and avoid nephrolithiasis. In addition, studies have shown that there are many misconceptions among both the general community and physicians about how stones should be managed. This article is meant to serve as a review of the current literature on dietary and drug therapies for stone prevention.
Allopurinol/therapeutic use ; Calcium Oxalate/analysis ; Cystine/analysis ; *Diet ; Humans ; Kidney Calculi/chemistry/*prevention & control ; Potassium Citrate/therapeutic use ; Sodium Chloride Symporter Inhibitors/therapeutic use ; Uric Acid/analysis ; Urological Agents/*therapeutic use

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.

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

Adult Fanconi syndrome is characterized by variable abnormalities caused by renal proximal transport defects, resulting in glycosuria, aminoaciduria, bicarbonaturia, uricosuria and phosphaturia. A 57-year-old man with kappa-light chain multiple myeloma, undergoing chemotherapy with prednisolone and melphalan for 17 month, was admitted with spontaneous femoral neck fracture and was consulted due to polyuria and refractory metabolic acidosis immediately after hemiarthroplasty. The laboratory values showed normal anion gap metabolic acidosis with normal urinary anion gap, hypokalemia, hypouricemia, hypophosphatemia at the time of consultation. After partial correction of acidemia, the fractional excretion of HCO3- was 11.9%, it was interpreted as proximal renal tubular acidosis. 24-hour urine collection showed increased level of excretion for most aminoacids. Diffuse osteopenia and multiple compression fractures on spine were detected on radiological examinations. Also, osteoporosis and osteomalacia was suggested during his clinical course. After the diagnosis of Fanconi syndrome was made, treatment was started with sodium bicarbonate, potassium citrate, calcitriol, calcium carbonate along with phosphate rich diet. Laboratory abnormalities were corrected and refractory multiple bone pain was ameliorated with these treatment.
Acid-Base Equilibrium ; Acidosis ; Acidosis, Renal Tubular ; Adult ; Bone Diseases, Metabolic ; Calcitriol ; Calcium Carbonate ; Diet ; Fanconi Syndrome ; Femoral Neck Fractures ; Fractures, Compression ; Glycosuria ; Hemiarthroplasty ; Humans ; Hypokalemia ; Hypophosphatemia ; Hypophosphatemia, Familial ; Melphalan ; Middle Aged ; Multiple Myeloma ; Osteomalacia ; Osteoporosis ; Polyuria ; Potassium Citrate ; Prednisolone ; Sodium Bicarbonate ; Spine ; Urine Specimen Collection

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*