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The effect of verapamil on the action of parathyroid hormone on embryonic bone in vitro.

Short term in vitro experiments showed that, added alone, verapamil inhibited both glycolysis and Ca uptake in embryonic chicken and rat bone cells. Added together with PTH, verapamil (0.02 MM) enhanced cAMP production, had no effect on lactate production, but significantly inhibited citrate, calcium and phosphate release from embryonic rat and mouse calvaria incubated under hypocalcemic conditions. The depression by verapamil of PTH-stimulated demineralization was confirmed histologically. It is concluded that in addition to cAMP, Ca plays a key role in the action of PTH on bone.

Animals↗

Effect of temperature on the salt balance of milk studied by capillary ion electrophoresis.

Many inorganic species, such as calcium, phosphate and magnesium, are in equilibrium between the liquid and colloidal phases of milk and hence are of importance with respect to the coagulation properties of milk. Capillary ion electrophoresis makes possible the determination of anions and cations in less than 6 min. The soluble phase of milk was obtained by ultrafiltration and samples had to be diluted 250-fold before analysis. Cold storage increased soluble calcium and phosphate concentrations, and warm-up of the milk restored the initial ionic equilibria. More drastic heat treatments (80-90 degrees C) caused precipitation of tricalcium phosphate and calcium citrate.

Animals↗

Lack of deleterious effect of slow-release sodium fluoride treatment on cortical bone histology and quality in osteoporotic patients.

We evaluated the effects of intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate therapy on cortical bone histology, reflection ultrasound velocity (material strength) and back-scattered electron image analysis (BEI) in 26 osteoporotic patients before and following therapy. All measurements were made on transiliac crest bone biopsies obtained before and following 2 years of therapy in each patient. For all 26 patients there were no significant changes in cortical bone histomorphometric parameters. In 15 patients in whom bone material quality was assessed by reflection ultrasound, there was no change in velocity (4000 +/- 227 SD to 4013 +/- 240 m/s). BEI disclosed no mineralization defects or the presence of woven bone. Mean atomic number (density) of bone increased slightly, but significantly (9.261 +/- 0.311 to 9.457 +/- 0.223, P = 0.031). While these changes are less marked than those observed for cancellous bone, they indicate that this form of therapy does not adversely affect cortical bone remodelling.

Adult↗

Effect of slow-release sodium fluoride on cancellous bone histology and connectivity in osteoporosis.

We have previously demonstrated that a treatment regimen of slow-release sodium fluoride (SRNaF) and continuous calcium citrate increases lumbar bone mass, improves cancellous bone material quality, and significantly reduces vertebral fracture rate in osteoporotic patients. In order to assess whether such treatment also improves trabecular structure, we quantitated cancellous bone connectivity before and following 2 years of therapy with SRNaF in 23 patients with osteoporosis and vertebral fractures. In addition, we performed bone histomorphometry on the same sections used for connectivity measurements. There was a significant increase in L2-L4 bone mineral density during therapy (0.827 +/- 0.176 g/cm2 SD to 0.872 +/- 0.166, p = 0.0004). Significant histomorphometric changes were represented by increases in mineral apposition rate (0.6 +/- 0.4 microns/d to 1.1 +/- 0.7, p = 0.0078) and adjusted apposition rate (0.4 +/- 0.3 microns/d to 0.6 +/- 0.4, p = 0.016). On the other hand, trabecular spacing significantly declined (from 1375 +/- 878 microns to 1052 +/- 541, p = 0.05). Two-dimensional quantitation of trabecular struts on iliac crest histological sections disclosed significant increases in mean node number per mm2 of cancellous tissue area (0.22 +/- 0.12 vs. 0.39 +/- 0.27, p = 0.0077), the mean node to free-end ratio (0.23 +/- 0.21 vs. 0.41 +/- 0.46, p < 0.05), and in the mean node to node strut length per mm2 of cancellous area (0.098 +/- 0.101 vs. 0.212 +/- 0.183, p < 0.01). There were no significant changes in any of the measurements associated with free-end number or free-end to free-end strut length.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Treatment of endometriosis and chronic pelvic pain with letrozole and norethindrone acetate: a pilot study.

OBJECTIVE: To determine the role of an aromatase inhibitor, letrozole, in the treatment of reproductive-age women with endometriosis and associated chronic pelvic pain. DESIGN: Phase 2, open-label, nonrandomized proof-of-concept study. SETTING: Outpatient tertiary-care center. PATIENT(S): Ten patients with endometriosis, all previously treated both medically and surgically, with unsatisfactory results. INTERVENTION(S): Endometriosis was diagnosed by biopsy and scored from an initial diagnostic laparoscopy performed within 1 month before treatment was begun. Oral administration of letrozole (2.5 mg), the progestin norethindrone acetate (2.5 mg), calcium citrate (1,250 mg), and vitamin D (800 IU) was done daily for 6 months. Within 1-2 months after completion of the treatment, a second-look laparoscopy was performed to score and biopsy endometriosis. MAIN OUTCOME MEASURE(S): Changes in American Society for Reproductive Medicine (ASRM) scores for endometriosis, pelvic pain assessed by visual analog scale, serum hormone levels (FSH, LH, E(2), and estrone [E(1)]), and bone density (DEXA scan). RESULT(S): No histologically demonstrable endometriosis was present in any patient during the second-look laparoscopy. ASRM and pelvic pain scores decreased significantly in response to treatment. Overall, no significant change in bone density was detected. Gonadotropin levels were not significantly altered by treatment, and although circulating E(2) and E(1) levels were reduced, the decrease was not statistically significant. CONCLUSION(S): The combination of letrozole and norethindrone acetate achieved marked reduction of laparoscopically visible and histologically confirmed endometriosis in all 10 patients and significant pain relief in nine out of 10 patients who had not responded previously to currently available treatments. On this basis, letrozole should be a candidate for the medical management of endometriosis.

Adult↗

Urinary oxalate excretion and its role in vulvar pain syndrome.

OBJECTIVE: This study was undertaken to determine the urinary oxalate excretion patterns in patients with vulvodynia compared with controls and to evaluate antioxalate therapy in women with vulvar pain syndrome (vulvodynia). STUDY DESIGN: A total of 130 consecutive patients with vulvar pain syndrome and 23 volunteers without symptoms collected urine specimens for 24 hours; each voiding was saved in individual labeled containers and refrigerated. The specimens were analyzed individually for oxalate and calculated according to 24-hour concentration, volume, and peak oxalate by hour. A total of 59 patients were treated with low-oxalate diets and calcium citrate for 3 months and evaluated for objective relief of vulvar pain. RESULTS: The 24-hour excretion of oxalate was almost identical in controls and vulvodynia patients. The total 24-hour excretion was directly proportional to the volume of urine excreted (p < 0.001). No significant differences were found in peak oxalate excretion (95% confidence intervals). The number of voidings was higher in the vulvodynia cohort (p < 0.02). The 59 women with elevated oxalate concentrations (> 1 mg/40 dl) were treated with an antioxalate regimen. Fourteen (24%) demonstrated an objective response, but only 6 (10%) could have pain-free sexual intercourse. CONCLUSIONS: Urinary oxalates may be nonspecific irritants that aggravate vulvodynia; however, the role of oxalates as instigators is doubtful.

Circadian Rhythm↗

Gahat: a Napalese cure for urolithiasis?

OBJECTIVES: Gahat (Vigna unguiculata) is a legume used for centuries in Nepal and Pakistan to treat the symptoms associated with urinary calculi. We prospectively evaluated the effect of Gahat consumption on 24-hour urine parameters in an attempt to assess its in vivo effect in normal volunteers. METHODS: Eight non-stone-forming volunteers collected 24-hour urine specimens while on their routine diets for baseline data. Urine was analyzed for pH, volume, calcium, citrate, phosphate, sodium, magnesium, uric acid, and oxalate. The Gahat was prepared according to local custom. No additives were used to enhance flavor. The pureed mixture (8 ounces) was ingested three times daily for 2 days. Subjects were instructed to maintain their normal diet, including fluid intake and activity during the study period. Twenty-four hours after the start of Gahat intake, a second 24-hour urine collection was initiated while volunteers continued the Gahat. Results of the urine samples before and after Gahat intake were analyzed, using the paired Student t test. RESULTS: There were no significant differences in urinary electrolytes between the urine samples before and after Gahat intake. Magnesium, urine volume, and uric acid differences approached clinical significance. CONCLUSIONS: Gahat increased urinary magnesium through an unknown mechanism and had no effect on other routine 24-hour urine electrolytes. The increase in urinary volume is attributed to the increase in fluid consumption by the subjects. If this legume is effective in preventing or dissolving urinary calculi, it may act through mechanisms not identified in 24-hour urine electrolytes.

Citrates↗

Impact of renal cryoablation on urine composition.

OBJECTIVES: To examine prospectively serial urine biochemical parameters in 14 patients (9 men, 5 women) undergoing laparoscopic cryoablation of a small, exophytic solid renal mass. Prior studies have shown that various types of renal injury may predispose to the formation of urinary calculi. The metabolic effects of cryoenergy on the surrounding normal renal parenchyma are unknown. METHODS: Timed 24-hour urine collections were obtained preoperatively and postoperatively on days 1, 30, and 60 to evaluate the following parameters: light microscopic findings, volume, pH, creatinine, protein, beta(2)-microglobulin, calcium, citrate, oxalate, phosphate, uric acid, sodium, and potassium. RESULTS: Urinary beta(2)-microglobulin excretion increased from a preoperative baseline value of 114.8 to 1931.2 microg/L on postoperative day 1, an increase of more than 15-fold (P = 0.05), thus confirming major renal injury. These values sharply decreased at 30 days and returned to near-baseline levels at 60 days postoperatively (P = 0.76). Nevertheless, all lithogenic parameters remained within the normal range throughout the follow-up period, with no significant change in any value. CONCLUSIONS: Our findings suggest that renal cryoablation does not adversely alter urine composition with respect to lithogenic parameters for up to 2 months after surgery. Elevated beta(2)-microglobulin levels indicating significant renal injury immediately postoperatively spontaneously revert to baseline levels within 2 months.

Adult↗

Daidzin suppresses ethanol consumption by Syrian golden hamsters without blocking acetaldehyde metabolism.

Daidzin is a potent, selective, and reversible inhibitor of human mitochondrial aldehyde dehydrogenase (ALDH) that suppresses free-choice ethanol intake by Syrian golden hamsters. Other ALDH inhibitors, such as disulfiram (Antabuse) and calcium citrate carbimide (Temposil), have also been shown to suppress ethanol intake of laboratory animals and are thought to act by inhibiting the metabolism of acetaldehyde produced from ingested ethanol. To determine whether or not daidzin inhibits acetaldehyde metabolism in vivo, plasma acetaldehyde in daidzin-treated hamsters was measured after the administration of a test dose of ethanol. Daidzin treatment (150 mg/kg per day i.p. for 6 days) significantly suppresses (> 70%) hamster ethanol intake but does not affect overall acetaldehyde metabolism. In contrast, after administration of the same ethanol dose, plasma acetaldehyde concentration in disulfiram-treated hamsters reaches 0.9 mM, 70 times higher than that of the control. In vitro, daidzin suppresses hamster liver mitochondria-catalyzed acetaldehyde oxidation very potently with an IC50 value of 0.4 microM, which is substantially lower than the daidzin concentration (70 microM) found in the liver mitochondria of daidzin-treated hamsters. These results indicate that (i) the action of daidzin differs from that proposed for the classic, broad-acting ALDH inhibitors (e.g., disulfiram), and (ii) the daidzin-sensitive mitochondrial ALDH is not the one and only enzyme that is essential for acetaldehyde metabolism in golden hamsters.

Acetaldehyde↗

The role of indigenous yeasts in traditional Irish cider fermentations.

AIMS: To study the role of the indigenous yeast flora in traditional Irish cider fermentations. METHODS AND RESULTS: Wallerstein laboratory nutrient agar supplemented with biotin, ferric ammonium citrate, calcium carbonate and ethanol was employed together with PCR-restriction fragment length polymorphism analysis of the region spanning the internal transcribed spacers (ITS1 and ITS2) and the 5.8S rRNA gene in the identification of indigenous yeasts at the species level, from traditional Irish cider fermentations. By combining the molecular approach and the presumptive media it was possible to distinguish between a large number of yeast species, and to track them within cider fermentations. The Irish cider fermentation process can be divided into three sequential phases based on the predominant yeast type present. Kloeckera/Hanseniaspora uvarum type yeasts predominate in the initial 'fruit yeast phase'. Thereafter Saccharomyces cerevisiae type yeast dominate in the 'fermentation phase', where the alcoholic fermentation takes place. Finally the 'maturation phase' which follows, is dominated by Dekkera and Brettanomyces type yeasts. H. uvarum type yeast were found to have originated from the fruit. Brettanomyces type yeast could be traced back to the press house, and also to the fruit. The press house was identified as having high levels of S. cerevisiae type yeast. A strong link was noted between the temperature profile of the cider fermentations, which ranged from 22 to 35 degrees C and the yeast strain population dynamics. CONCLUSIONS: Many different indigenous yeast species were identified. The mycology of Irish cider fermentations appears to be very similar to that which has previously been reported in the wine industry. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has allowed us to gain a better understanding of the role of indigenous yeast species in 'Natural' Irish cider fermentations.

Alcoholic Beverages↗

A reinvestigation of the usefulness of breath analysis in the determination of blood acetaldehyde concentrations.

Human volunteers were given ethanol (0.4 g/kg) either intravenous or per os. They were also given ethanol (0.2 g/kg) intravenous 4 hr after receiving a dose of 50 mg citrated calcium carbimide, an aldehyde dehydrogenase inhibitor. During the first hour after starting the administration of ethanol, ethanol and acetaldehyde concentrations were determined in expired air, blood from the right atrium, arterial blood, and venous blood. In the absence of calcium carbimide treatment, the respective maximal blood acetaldehyde concentrations were (range): 6-30 microM (calculated from breath analysis using a blood:breath partition ratio of 190 for acetaldehyde); 0-3.5 microM (right atrium blood); and 0 microM (arterial and venous blood). After calcium carbimide treatment, the maximal blood acetaldehyde concentrations were 10-220 microM (calculated from concentrations in expired air), 38-280 microM (right atrium), 31-250 microM (arterial blood), and 7-186 microM (venous blood). With aldehyde dehydrogenase inhibition, a clear correlation existed between breath concentrations and blood concentrations. Without this inhibition, no such correlation was found. A clear arterio-venous difference was seen for acetaldehyde concentrations while they were artificially elevated by calcium carbimide. Our study suggests that factors other than the equilibration of acetaldehyde between alveolar air and pulmonary blood are of great importance in determining the concentration of acetaldehyde in expired air.

Acetaldehyde↗

Feed-back control of milk secretion in the goat by a chemical in milk.

In order to investigate the nature of the inhibition of milk secretion during a long milking interval, goats were treated in three possible ways: (i) milked twice daily at 08.00 h and 16.00 h or (ii) milked thrice daily at 00.00 h, 08.00 h and 16.00 h, or (iii) milked thrice daily at 00.00 h, 08.00 h and 16.00 h, but at 00.00 h the milk removed was replaced with an equal volume of isosmotic sucrose solution. The latter treatment was carried out in order to subject the gland to a degree of physical distension equivalent to that on treatment (i). On either thrice-daily milking or thrice-daily milking with sucrose replacement, milk secretion rate over the 16.00-08.00 h period was significantly higher (by about 10% in both cases) than on twice-daily milking. Secretion rates of lactose, milk protein, citrate and calcium during the 00.00-08.00 h period were similar on either thrice-daily milking or thrice-daily milking with sucrose replacement; the secretion rate of fat was significantly higher on thrice-daily milking with sucrose replacement. Secretion rates of Na+, K+ and Cl- were significantly higher on thrice-daily milking with sucrose replacement. In the case of Na+, the increased Na+ secretion rate was sufficient to create a normal Na+ concentration in the milk/sucrose mixture removed at the next milking. In the cases of K+ and Cl-, their secretion rates were not sufficient to restore their concentrations to normal by the next milking.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Transport of milk constituents by the mammary gland.

This review deals with the cellular mechanisms that transport milk constituents or the precursors of milk constituents into, out of, and across the mammary secretory cell. The various milk constituents are secreted by different intracellular routes, and these are outlined, including the paracellular pathway between interstitial fluid and milk that is present in some physiological states and in some species throughout lactation. Also considered are the in vivo and in vitro methods used to study mammary transport and secretory mechanisms. The main part of the review addresses the mechanisms responsible for uptake across the basolateral cell membrane and, in some cases, for transport into the Golgi apparatus and for movement across the apical membrane of sodium, potassium, chloride, water, phosphate, calcium, citrate, iodide, choline, carnitine, glucose, amino acids and peptides, and fatty acids. Recent work on the control of these processes, by volume-sensitive mechanisms for example, is emphasized. The review points out where future work is needed to gain an overall view of milk secretion, for example, in marsupials where milk composition changes markedly during development of the young, and particularly on the intracellular coordination of the transport processes that result in the production of milk of relatively constant composition at a particular stage of lactation in both placental and marsupial mammals.

Amino Acids↗

Treatment of uremic hyperphosphatemia--is there still a need for aluminum salts?

Aluminum-containing phosphate binders have been widely employed in the past in the management of uremic hyperphosphatemia. However, an increasing number of reports on aluminum toxicity has stimulated efforts to replace this therapy by safer methods. The aim of the present review is to critically evaluate other treatment strategies. It appears that aluminum-containing phosphate binders should no longer be considered the treatment of choice for controlling uremic hyperphosphatemia. Calcium carbonate, calcium citrate, magnesium carbonate and a mixture of ketoanalogues and amino acids present important therapeutical alternatives which could replace aluminum-containing phosphate binders in the majority of patients. However, it is mandatory, as these therapies also carry some risks, that side effects are detected early.

Alum Compounds↗

Urinary glycosaminoglycan excretion in normal and stone-forming subjects: significant disturbance in recurrent stone formers.

The overnight (12 h) urinary excretion of glycosaminoglycans, citrate, magnesium, calcium and uric acid were measured in 82 normal subjects and 63 outpatients who had formed at least one urinary stone. No significant difference could be found between the two groups of unselected subjects with respect to any of the urinary parameters. Nonetheless, recurrent stone formers had significantly lower glycosaminoglycans and predictive risk index than normal controls.

Adult↗

Adhesion to and decalcification of hydroxyapatite by carboxylic acids.

Fundamental to the processes of decalcification of or adhesion to mineralized tissues is the molecular interaction of acids with hydroxyapatite. This study was undertaken to chemically analyze the interaction of 1 mono-, 2 di-, 1 tri-, and 2 polycarboxylic acids with hydroxyapatite in an attempt to elucidate the underlying mechanism. Maleic, citric, and lactic acid decalcified hydroxyapatite, in contrast to oxalic acid and the two polycarboxylic acids that were chemically bonded to hydroxyapatite. Solubility tests showed that the calcium salts of the former were very soluble, whereas those of the latter could hardly be dissolved in the respective acid solutions. Based on these data, an adhesion/decalcification concept was advanced that predicts that carboxylic acids, regardless of concentration/pH, either adhere to or decalcify hydroxyapatite, depending on the dissolution rate of the respective calcium salts in the acid solution. This contrasting behavior of organic acids most likely results from their differential structural conformations.

Acrylic Resins↗

Calcium as a treatment of osteoporosis.

The role of calcium in bone metabolism, optimal calcium intake, the use of calcium as monotherapy for osteoporosis or in combination with other drugs and the differences between various calcium salts are reviewed. Calcium is an essential element in bone mineralization and formation. There are sufficient data supporting the use of calcium in the prevention and treatment of osteoporosis and calcium in combination with vitamin D is widely used in the prevention and treatment of osteoporosis mainly in elderly patients, although its indication in postmenopausal osteoporosis is not yet clear. Numerous calcium preparations are available on the market and differ only in regard to their bioavailability. However, this difference has very little clinical significance except in patients with achlorhydria or elderly persons with low gastric secretion, in which cases pidolate and calcium citrate can be used since they are more efficiently absorbed.

Journal Article↗