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The removal of regular weight-bearing activity generates a skeletal adaptive response in both humans and animals, resulting in a loss of bone mineral. Human models of disuse osteoporosis, namely bed rest, spinal cord injury and exposure to micro-gravity demonstrate the negative calcium balance, alterations in biochemical markers of bone turnover and resultant loss of bone mineral in the lower limbs that occurs with reduced weight-bearing loading. The site-specific nature of the bone response is consistent in all models of disuse; however, the magnitude of the skeletal adaptive response may differ across models. It is important to understand the various manifestations of disuse osteoporosis, particularly when extrapolating knowledge gained from research using one model and applying it to another. In rats, hindlimb unloading and exposure to micro-gravity also result in a significant bone response. Bone mineral is lost, and changes in calcium metabolism and biochemical markers of bone turnover similar to humans are noted. Restoration of bone mineral that has been lost because of a period of reduced weight bearing may be restored upon return to normal activity; however, the recovery may not be complete and/or may take longer than the time course of the original bone loss. Fluid shear stress and altered cytokine activity may be mechanistic features of disuse osteoporosis. Current literature for the most common human and animal models of disuse osteoporosis has been reviewed, and the bone responses across models compared. [ABSTRACT FROM AUTHOR]

: Smoking has been associated with low bone density, fractures and poor intestinal calcium absorption. Calcium absorption is a critical factor in calcium balance in postmenopausal women but the mechanisms causing decreased absorption efficiency in postmenopausal smokers are controversial and poorly defined. We performed a cross-sectional study of 405 postmenopausal women attending a clinic for the management of osteoporosis to compare intestinal calcium absorption efficiency, serum vitamin D metabolites and parathyroid hormone levels in postmenopausal women who had never smoked, who were smokers previously or who were current smokers, to examine the relationships between these variables in smokers. Two hundred and fifty-two of the women had never smoked, 79 had smoked previously and 74 were current smokers. The hourly fractional rate of calcium absorption was similar in non-smokers and those who had previously smoked. Radiocalcium absorption was less in the 74 smokers compared with the 331 non-smokers [0.60 (0.29 SD) vs 0.71 (0.27); p= 0.004], as were serum calcitriol (p<0.001) and parathyroid hormone (PTH) (p<0.01). There was no difference in the relationship between calcium absorption and serum calcitriol between smokers (r= 0.38) and non-smokers (r= 0.28); hence the impaired calcium absorption in the smokers was almost entirely attributable to suppression of the PTH–calcitriol endocrine axis. In postmenopausal women smoking is associated with a reduction in calcium absorption efficiency due to suppression of the PTH–calcitriol axis. This impairment of calcium absorption could lead to accelerated bone loss and limit the usefulness of dietary calcium supplementation. [ABSTRACT FROM AUTHOR]

: Vertebral fractures due to osteoporosis are a common but frequently unrecognized complication of ankylosing spondylitis (AS) and various factors may contribute to the development of osteoporosis in AS. It is known that inflammatory activity in rheumatic disease (i.e., proinflammatory cytokines) itself plays a possible role in the pathophysiology of bone loss. 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) seems to be another possible candidate for mediatory function in regulating both the inflammatory process and bone turnover. The aim of this study was to evaluate the relation between disease activity, bone turnover and calciotropic hormones. In 70 patients with established AS and an age- and sex-matched control group, the relation between disease activity (erythrocyte sedimentation rate, C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index), and serum levels of vitamin D metabolites, parathyroid hormone (PTH), bone alkaline phosphatase (bAP) and urinary pyridinium crosslinks were determined. Serum levels of 1,25(OH)2D3 (p<0.01) and PTH (p<0.01) were negatively correlated with disease activity, the excretion of urinary pyridinium crosslinks showed a positive correlation with disease activity (p<0.01), and 1,25(OH)2D3 and PTH were positively correlated with bAP (p<0.01). These results indicate that high disease activity in AS is associated with an alteration in vitamin D metabolism and increased bone resorption. Furthermore, the decreased levels of 1,25(OH)2D3 may contribute to a negative calcium balance and inhibition of bone formation. Our results suggest further research is necessary to determine whether low levels of 1,25(OH)2D3 as an endogenous immune modulator suppressing activated T cells and cell proliferation may accelerate the inflammation process in AS. [ABSTRACT FROM AUTHOR]

The development of pharmacological counter-measures to the adverse effects of physiological adaptation to microgravity has received relatively more attention than alternatives such as dietary management. The manipulation of dietary cation-anion balance, and its subsequent effects on acid–base metabolism, have been routinely used for some time in managing domestic animal health. More recently, dietary intake by humans of alkalinizing potassium salts has been demonstrated to exert profound beneficial effects on calcium balance, bone mineralization, predisposition to calcium oxalate nephrolithiasis, and overall nitrogen balance. Dietary sodium restriction has also been shown to improve calcium balance, bone mineralization, and the effectiveness of neurohumoral defenses against orthostatic hypotension. It is proposed that these simple alterations in the astronauts' diets may be easily implemented to lessen the adverse effects of physiological adaptations to space flight, and to enhance or even replace prescribed pharmacological counter-measures. [ABSTRACT FROM AUTHOR]

Restriction fragment length polymorphisms of the vitamin D receptor gene have recently been reported to be associated with changes in bone mineral density. Alterations in systemic calcium balance and Ca-regulating hormones such as 1,25(OH)2 vitamin D3 and parathyroid hormone have been demonstrated in essential hypertension. We investigated the relationship between polymorphisms of the vitamin D receptor gene and systemic Ca metabolism in patients with essential hypertension and in normotensives. We compared 147 subjects with essential hypertension and 100 normotensive control subjects. The genotype distribution and derived allele frequencies for the vitamin D receptor gene were similar in the two groups (genotype bb/Bb/BB and allele B/b: 60.1/32.6/7.2 and 0.24/0.76 in hypertensives vs. 56.0/36.0/8.0 and 0.26/0.74 in normotensive subjects). Serum concentrations of total Ca in the bb, Bb, and BB groups were, respectively, 4.5±0.3 vs. 4.5±0.4 vs. 4.4±0.5 mmol/l in normotensives and 4.6±0.3 vs. 4.6±0.4 vs. 4.4±0.5 mmol/l in hypertensives. Ionized Ca levels were 1.17±0.04 vs. 1.16±0.04 vs. 1.15±0.04 mmol/l in normotensives and 1.16±0.04 vs. 1.16±0.04 vs. 1.14±0.05 mmol/l in hypertensives, respectively. These results indicate that the BB genotype of the vitamin D receptor gene is associated with lower serum Ca levels but is not a useful predictive marker for the development of essential hypertension in Japanese subjects. [ABSTRACT FROM AUTHOR]

A high sucrose diet reduces dentin apposition of growing rats. The mechanisms of reduction are unclear, but disturbances in calcium balance or in mineralization of predentin may explain them. In this experiment, 29 Sprague-Dawley rats, 21 days old, were weaned and randomized into calcium-deficient, high-sucrose or standard-diet groups for 3 weeks. They were given food and water ad libitum. During the experiment, animals were individually housed in metabolic cages where urine samples were collected. At ages of 21 and 40 days mineralizing dentin was marked using I.P. injections of oxytetracycline hydrochloride. At 42 days of age, the animals were anesthetized and their blood was collected by cardiac puncture. Right hemimandibles were sectioned sagittally and left hemimandibles were fixed, decalcified, and cut into histological sections. Dentin appositions were measured planimetrically, predentin width, from histological sections. Ca, K, and Na levels of serum and urine were measured flame photimetrically and P levels were measured by the UV method. Statistical analyses were done using one-way analysis of variation (ANOVA) Tuckey's HSD t test. In the calcium-deficient group, hypocalcemia, reduced dentin apposition, and increased predentin width were noticed when compared with the control group (P<0.05). Also, the increase in predentin width, caused by calcium deficiency, was significant compared with sucrose-fed animals (P<0.05). Sucrose diet reduced dentinogenesis, increased Ca excretion to urine, but also reduced urinary levels of P, K, and Na, and the differences were significant for the controls (P<0.05). In conclusion, despite the same kind of reduced dentinogenesis in calcium-deficient and high-sucrose groups, calcium imbalance or reduced mineralization of predentin does not explain reduced dentinogenesis in sucrose-fed animals. [ABSTRACT FROM AUTHOR]

Renal ischemia/reperfusion (I/R) injury, which leads to acute kidney injury (AKI), is a major cause of morbidity and mortality in a variety of clinical situations. This study aimed to investigate the protective role of Mfn2 during renal I/R injury. Overexpression of Mfn2 in NRK-52E rat renal tubular epithelial cells and rats, then we constructed hypoxia reoxygenation (H/R) cells and I/R rat model. Apoptosis, ROS, ATP, Ca2+ levels in cells and rats, as well as renal tissue and functional injury in rats were detected respectively. Endoplasmic reticulum (ER) stress was further examined in cells and rats. The morphological changes of mitochondria-associated ER membranes (MAMs) were also detected. Mfn2 expression is reduced in H/R-treated NRK-52E cells and renal tissue of I/R rats. At the cellular level, overexpression of Mfn2 promoted cell proliferation, inhibited cell apoptosis, attenuated mitochondrial damage and Ca2+ overload, and ER stress. In addition, Mfn2 also restored the MAMs structure. In vivo experiments found that overexpression of Mfn2 could improve renal function and alleviate tissue injury. Concomitant with elevated Mfn2 expression in the kidney, reduced renal cell apoptosis, restored mitochondrial function, and reduced calcium overload. Finally, ER stress in rat kidney tissue was alleviated after overexpression of Mfn2. These results reveal that Mfn2 contributes to ER stress, mitochondrial function, and cell death in I/R injury, which provides a novel therapeutic target for AKI. [ABSTRACT FROM AUTHOR]

Peritoneal calcification is a prominent feature of the later stage of encapsulating peritoneal sclerosis (EPS) in patients undergoing long-term peritoneal dialysis (PD). However, the pathogenesis and preventive strategy for peritoneal calcification remain unclear. Peritoneum samples from EPS patients were examined histologically. Peritoneal calcification was induced in mice by feeding with an adenine-containing diet combined with intraperitoneal administration of lipopolysaccharide and a calcifying solution containing high calcium and phosphate. Excised mouse peritoneum, human mesothelial cells (MeT5A), and mouse embryonic fibroblasts (MEFs) were cultured in calcifying medium. Immunohistochemistry confirmed the appearance of osteoblastic differentiation-marker-positive cells in the visceral peritoneum from EPS patients. Intraperitoneal administration of magnesium suppressed peritoneal fibrosis and calcification in mice. Calcifying medium increased the calcification of cultured mouse peritoneum, which was prevented by magnesium. Calcification of the extracellular matrix was accelerated in Met5A cells and MEFs treated with calcification medium. Calcifying medium also upregulated osteoblastic differentiation markers in MeT5A cells and induced apoptosis in MEFs. Conversely, magnesium supplementation mitigated extracellular matrix calcification and phenotypic transdifferentiation and apoptosis caused by calcifying conditions in cultured MeT5A cells and MEFs. Phosphate loading contributes to the progression of EPS through peritoneal calcification and fibrosis, which can be prevented by magnesium supplementation. [ABSTRACT FROM AUTHOR]

The stable calcium (Ca) isotopes offer a minimally invasive method for assessing Ca balance in the body, providing a new avenue for research and clinical applications. In this study, we measured the Ca isotopic composition of soft tissues (brain, muscle, liver, and kidney), mineralized tissue (bone), and blood (plasma) from 10 mice (5 females and 5 males) with three different genetic backgrounds and same age (3 months old). The results reveal a distinctive Ca isotopic composition in different body compartments of mice, primally controlled by each compartment's unique Ca metabolism and genetic background, independent of sex. The bones are enriched in the lighter Ca isotopes (δ44/40Cabone = − 0.10 ± 0.55 ‰) compared to blood and other soft tissues, reflecting the preferential incorporation of lighter Ca isotopes through bone formation, while heavier Ca isotopes remain preferentially in blood. The brain and muscle are enriched in lighter Ca isotopes (δ44/40Cabrain = − 0.10 ± 0.53 ‰; δ44/40Camuscle = 0.19 ± 0.41 ‰) relative to blood and other soft tissues, making the brain the isotopically lightest soft tissues of the mouse body. In contrast, the kidney is enriched in heavier isotopes (δ44/40Cakidney = 0.86 ± 0.31 ‰) reflecting filtration and reabsorption by the kidney. This study provides important insight into the Ca isotopic composition of various body compartments and fluids. [ABSTRACT FROM AUTHOR]

Components of the renin–angiotensin–aldosterone system (RAAS) are present on bone cells. One measure of RAAS activity, the aldosterone-renin-ratio (ARR), is used to screen for primary aldosteronism. Associations between ARR and bone mineral density are conflicting. This study investigated associations between ARR and peripheral quantitative computed tomography (pQCT) and impact microindentation (IMI). Male participants (n = 431) were from the Geelong Osteoporosis Study. "Likely" primary aldosteronism was defined as ARR ≥ 70 pmol/mIU. Another group, "possible" primary aldosteronism, was defined as either ARR ≥ 70 pmol/mIU or taking a medication that affects the RAAS, but not a beta blocker, and renin < 15 mU/L. Using pQCT, images at 4% and 66% of radial (n = 365) and tibial (n = 356) length were obtained. Using IMI measurements, bone material strength index (BMSi; n = 332) was determined. Associations between ARR or likely/possible primary aldosteronism and IMI or pQCT-derived bone parameters were tested using median regression. ARR and aldosterone values were not associated with any of the pQCT-derived bone variables in either unadjusted or adjusted analyses. Men with likely primary aldosteronism (n = 16), had lower adjusted total bone area (radial 66% site, − 12.5%). No associations were observed for men with possible primary aldosteronism (unadjusted or adjusted). No associations with BMSi were observed (p > 0.05). There were no associations between ARR or aldosterone and pQCT-derived bone parameters. Men with likely primary aldosteronism had lower bone area, suggesting clinically high levels of ARR may have a negative impact on bone health. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism in pregnancy is a rare disease that can have detrimental effects on both maternal and fetal/neonatal outcomes. The physiological changes that occur during pregnancy can complicate the diagnosis, imaging examinations, and treatment of this disorder. To enhance our understanding and management of primary hyperparathyroidism in pregnancy, experts from various fields, including endocrinology, obstetrics, surgery, ultrasonography, nuclear medicine, pediatrics, nephrology, and general practice in China, collaborated to develop a consensus addressing the critical aspects of the diagnosis and treatment of primary hyperparathyroidism in pregnancy with a multidisciplinary team approach. This consensus provides valuable guidance for healthcare professionals in managing this condition, ultimately improving outcomes for both mothers and their babies. [ABSTRACT FROM AUTHOR]

One of the most important features of innate immunity is the presence of a special group of pattern recognition receptors (PRRs) called toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), resulting in a quick and effective immune response to them. Glomerulonephritis (GN) is one of the most important categories of renal disorders characterized by destructive responses of the immune system to the glomerulus. To date, the association of TLRs as important innate immune system members with GN has been one of the topics that attracted the attention of researchers in this field. However, the exact role of these receptors in the immunopathogenesis of GN has not yet been fully discussed. Therefore, this study aims to overview the role of TLRs in GN and the possibility of using them as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Few studies are available on associations between metal mixture exposures and disrupted thyroid hormone homeostasis; particularly, the role of iodine status was ignored. Here, we aimed to explore the cross-sectional relationship of blood cell metals with thyroid homeostasis and explore the potential modifying effect of iodine status. Among 328 workers from the manganese-exposed workers healthy cohort (MEWHC), we detected thyroid function parameters: thyroid stimulating hormone (TSH), total triiodothyronine (TT3), free triiodothyronine (FT3), total tetraiodothyronine (TT4), free tetraiodothyronine (FT4) as well as calculated sum activity of peripheral deiodinases (GD) and thyroid's secretory capacity (GT). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure 22 metal concentrations in blood cells. Based on the consistent results of least absolute shrinkage and selection operator (LASSO) and Bayesian kernel machine regression (BKMR) analyses, there were significant positive associations between copper and TSH (β = 2.016), iron and FT4 (β = 0.403), titanium and GD (β = 0.142), nickel and GD (β = 0.057), and negative associations between copper and FT4 (β = − 0.226), selenium and GD (β = − 0.332), among the participants. Interestingly, we observed an inverted-U shape relationship between magnesium and FT4. Furthermore, we found a synergistic effect between arsenic and copper on the TSH level, while antagonistic effects between nickel and copper as well as nickel and selenium on the TSH level. We observed a modified effect of iodine status on association between strontium and GD (Pinteraction = 0.026). It suggests metal mixture exposures can alter thyroid homeostasis among the occupational population, and deiodinase activity had a modified effect on association between strontium and GD. Validation of these associations and elucidation of underlying mechanisms require further researches in the future. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX), which is used to treat various cancers and hematological malignancies, has limited therapeutic application due to its toxicity in tissues and organs. These toxic effects occur through alterations in intracellular calcium regulation, elevated cell stress and oxidative damage, and increased apoptosis. Lercanidipine (LRD) is a long-acting antihypertensive calcium channel blocker with anti-inflammatory, anti-apoptotic, and antioxidant effects. The aim of this study was to investigate the effect of LRD on DOX-induced lung toxicity. Four groups (control, DOX, DOX + 0.5 LRD, and DOX + 2 LRD) totaling 32 rats were established. TNF-α levels in the lung tissues were detected by immunohistochemistry, and the tissues were subjected to histopathological examination. In determining oxidative stress, total antioxidant status (TAS) and total oxidative stress (TOS) were determined using spectrophotometry, and the oxidative stress index (OSI) value was calculated. The mRNA relative expression levels of the genes were evaluated by RT-qPCR. It was determined that inflammatory and oxidative stress markers and pro-apoptotic gene levels were increased and anti-apoptotic gene levels were decreased in the lung tissues of the DOX-administered group. In addition, histopathological changes were significantly increased. Although it was not statistically significant, inflammation, oxidative stress, and apoptosis were reduced, as were other histopathological indicators, in the group that received LRD (0.5 mg/kg). Inflammation, oxidative stress, and apoptosis were found to be statistically reduced and corroborated by histological findings in the group given LRD (2 mg/kg). In conclusion, it was determined that LRD had an ameliorative effect on DOX-induced lung toxicity in an experimental animal model. [ABSTRACT FROM AUTHOR]

Objective: Population studies have shown that vitamin D (VitD) deficiency is associated with an increased incidence of type 2 diabetes mellitus (T2DM), VitD deficiency is a potential risk factor for T2DM, and the proportion of M1-type macrophages and M2-type macrophages in T2DM patients is imbalanced. Another study reported that VitD can affect the differentiation of macrophages into M1 and M2 types. However, there is no definitive result about the correlation between plasma VitD levels and macrophage typing in patients with T2DM. Whether VitD affects the progression of T2DM by regulating the polarization type of macrophages and the specific regulatory mechanism is not very clear. Therefore, we carried out the following research. Methods: We first used flow cytometry to detect the proportions of M1 and M2 macrophages in peripheral blood of T2DM patients with different VitD levels. Furthermore, we used ELISA to detect the inflammatory factors affecting macrophage differentiation in patients' plasma, including IL-6 secreted by M1-type macrophages and TGF-β secreted by M2-type macrophages. Mononuclear cells were separated from human peripheral blood with immunomagnetic beads, cultured in vitro, and treated with different concentrations of VitD, and the ratio of differentiation into M1 and M2 macrophages was detected by flow cytometry. Results: With the increase of serum 25(OH)D levels in patients with T2DM, the proportion of M1 and M2 macrophages in peripheral blood decreased, that is, the polarized phenotype of macrophages was more inclined to M2 type, while plasma IL-6 gradually decreased, and TGF-β gradually increased. In addition, VitD can promote the differentiation of CD14-positive monocytes cultured in vitro into M2 macrophages. Conclusions: When the level of VitD in T2DM patients is low, there are more M1-type macrophages in peripheral blood, and when the level of VitD is increased, M2-type macrophages are increased. Changes in related inflammatory factors were also consistent. In vitro culture of monocytes further confirmed that VitD can promote the differentiation of macrophages to M2 type in T2DM patients. [ABSTRACT FROM AUTHOR]

Objectives: Evaluate mandibular cortical bone in childhood cancer survivors (CCS) and correlate findings with disease and treatment characteristics. Methods: Dental panoramic radiographs of 60 CCS and of 120 age and gender-matched healthy individuals were assessed by two independent observers. Bone was categorized as normal, moderately or severely eroded and its width was calculated at four sites bilaterally. Significant differences were tested using Chi-square and Pearson correlation co-efficient. Possible risk factors were detected by multivariate regression analysis. Results: Forty five percent of CCS had moderately eroded bone, while 67% of healthy individuals normal bone. Mean width was 3.9 mm in CCS (1.9 mm–6.4 mm) and 2.7 mm in healthy controls (1.4 mm–6 mm). None of the above differences were significant. Survivors diagnosed at a younger age had a five times greater probability of presenting mildly eroded bone. Conclusions: No direct effect of antineoplastic treatment on cortical bone could be demonstrated in the current study, underlying the need for more well-designed studies. [ABSTRACT FROM AUTHOR]

This study investigated the acute effects of dibutyl phthalate (DBP) exposure on energy metabolism and gill histology in zebrafish (Danio rerio). The in vitro incubation of gill tissue with 10 μM DBP for 60 min altered tissue energy supply, as shown by decreased lactate content and lactate dehydrogenase (LDH) activity. Higher concentrations of DBP (100 μM and 1 mM) increased lactate content and LDH activity; however, they blocked glucose uptake, depleted the glycogen content in cellular stores, and induced injury to the gills, as measured by LDH release to the extracellular medium. In addition, in vivo exposure of fish to 1 pM DBP for 12 h induced liver damage by increasing alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) activities. Gill histology indicated hyperemia, lamellar fusion, lamellar telangiectasis, and necrosis. Data indicate that acute exposure of zebrafish gills to the higher DBP concentrations studied induces anaerobic cellular activity and high lactate production, causing gill damage, diminishing cell viability, and incurring liver dysfunction. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of different non-osteoporotic drugs on the increase or decrease in the risk of incident fragility fractures (vertebral, humerus or hip) in a cohort of patients diagnosed with osteoporosis on active anti-osteoporotic therapy. Methods: For this retrospective longitudinal study, baseline and follow-up data on prescribed non-osteoporotic treatments and the occurrence of vertebral, humerus or hip fractures in 993 patients from the OSTEOMED registry were analyzed using logistic regression models. The drugs evaluated with a possible beneficial effect were thiazides and statins, while the drugs evaluated with a possible harmful effect were antiandrogens, aromatase inhibitors, proton pump inhibitors, selective serotonin reuptake inhibitors, benzodiazepines, GnRH agonists, thyroid hormones, and oral and inhaled corticosteroids. Results: Logistic regression analyses indicated that no treatment significantly improved fracture risk, with the only treatments that significantly worsened fracture risk being letrozole (OR = 0.18, p-value = 0.03) and oral corticosteroids at doses ≤ 5 mg/day (OR = 0.16, p-value = 0.03) and > 5 mg/day (OR = 0.27, p-value = 0.04). Conclusion: The potential beneficial or detrimental effects of the different drugs evaluated on fracture risk are masked by treatment with anabolic or antiresorptive drugs that have a more potent action on bone metabolism, with two exceptions: letrozole and oral corticosteroids. These findings may have important clinical implications, as patients receiving these treatments are not fully protected by bisphosphonates, which may imply the need for more potent anti-osteoporotic drugs such as denosumab or teriparatide. [ABSTRACT FROM AUTHOR]

Caspases are proteolytic enzymes that belong to the cysteine protease family and play a crucial role in homeostasis and programmed cell death. Caspases have been broadly classified by their known roles in apoptosis (caspase-3, caspase-6, caspase-7, caspase-8, and caspase-9 in mammals) and in inflammation (caspase-1, caspase-4, caspase-5, and caspase-12 in humans, and caspase-1, caspase-11, and caspase-12 in mice). Caspases involved in apoptosis have been subclassified by their mechanism of action as either initiator caspases (caspase-8 and caspase-9) or executioner caspases (caspase-3, caspase-6, and caspase-7). Caspases that participate in apoptosis are inhibited by proteins known as inhibitors of apoptosis (IAPs). In addition to apoptosis, caspases play a role in necroptosis, pyroptosis, and autophagy, which are non-apoptotic cell death processes. Dysregulation of caspases features prominently in many human diseases, including cancer, autoimmunity, and neurodegenerative disorders, and increasing evidence shows that altering caspase activity can confer therapeutic benefits. This review covers the different types of caspases, their functions, and their physiological and biological activities and roles in different organisms. [ABSTRACT FROM AUTHOR]

Background: This is a phase II clinical trial to investigate the immunotherapeutic effect of Curcumin, Piperine, and Taurine (CPT) combination in hepatocellular carcinoma (HCC). Methods: Twenty-six HCC patients aged (50–80 years) were recruited for administration of a daily dose of 5 g of curcumin, 50 mg of piperine, and 500 mg of taurine divided into three doses for successive 3 months. The three components (CPT) were prepared in one capsule. Patients were assessed after each month (cycle) for the plasma levels of CD4, CD8, CD25, Interleukins-2 (IL-2), IL-6, IL-12, Interferon-gamma (IFN- γ), Lactate dehydrogenase (LDH), and Vascular endothelial growth factor (VEGF), FOXP3 mRNA, and miRNA 21. Results: There was a significant increase in the plasma levels of CD4 and CD8, while a significant decrease in the CD25 level after the second and third cycles compared to the baseline level [P < 0.001 for both]. Also, there was a significant increase in the plasma levels of IL-2, IL-12, and IFN-γ [ P = 0.001, P = 0.006, and P = 0.029; respectively], while there was a significant decrease in IL-6, VEGF-α, LDH, and Alpha-fetoprotein (AFP) after CPT administration compared to the baseline levels [P < 0.001, P < 0.001, P = 0.020, and P = 0.004; respectively]. The expression level of miRNA-21 was significantly decreased after CPT administration compared to the baseline level [5.5±0.88, 4.1±0.78, 3±0.75, and 2.5±0.76; respectively, P<0.001]. Though there was a noticeable decrease in the FOXP3 expression after each cycle, however, it didn't reach a significant level [5.3±0.8, 4.2±0.76, 3.2±0.67, and 2.5±0.79; respectively, P=0.184]. Conclusion: CPT could exhibit a potential immune-stimulating effect in HCC patients. The current trial had been registered at the National Hepatology and Tropical Medicine Research Institute (NHTMRI), with a registration number of NHTMRI-IRB 2-21 on 5th January 2021. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the association between soft drinks, tea and coffee consumption, and risk of fracture in the China Health and Nutrition Survey. Materials and methods: A cross-sectional study with multi-stage random cluster sampling was conducted in nine Chinese provinces in 2004, 2006, 2009 and 2011. A total of 36,740 participants were included the data analyses. Self-administered questionnaires and physical examinations provided data on beverages consumption, fracture history, and other potential risk factors. Binary logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for potentially confounding variables. Results: The prevalence of fracture increased over the 7-year period of the surveys, with 1833 (5.3%) participants reporting a fracture history. Soft drink consumption increased over this time period, and tea consumption was relatively stable, whereas coffee consumption tended to increase sharply. Consumers of soft drinks ≥ 3 times/week (versus never) had a higher risk of fracture (OR = 1.86, 95% CI = 1.43–2.32, p < 0.001, p for trend = 0.039). Consumers of tea ≥ 5 cups/day (versus never) also had a higher risk of fracture (OR = 1.21, 95% CI = 1.09–1.45, p = 0.028, p for trend < 0.001). Similarly, consumers of coffee ≥ 2 cups/day (versus never) had a higher risk of fracture (OR = 1.84, 95% CI = 1.01–3.34, p = 0.045, p for trend = 0.002). Subgroup analyses by gender suggested that coffee consumption increased risk of fracture in females (OR = 1.84, 95% CI = 1.32–2.63, p = 0.001). Conclusion: Our findings suggest that high consumption of soft drinks, tea and coffee is associated with an increased risk of fracture in the Chinese population. Which has important public health implications given the widespread consumption of these beverages. [ABSTRACT FROM AUTHOR]

Organophosphates (OP) are one of the most common neurotoxic xenobiotics. In acute OP poisoning, as a result of suppression of synaptic acetylcholinesterase (AChE) activity, a cholinergic syndrome develops, which can transform into status epilepticus. Within a few days after acute poisoning, the so-called an intermediate syndrome can develop, which is associated with prolonged inhibition of AChE, desensitization of nicotinic receptors, and functional degradation of synapses and muscle fibers. In 10–20 days after a single acute or repeated subacute poisoning, OP-induced delayed polyneuropathy (OPIDN) can develop—a neurodegenerative disease, the signs of which are ataxia, loss of function of the distal sensory and motor axons of peripheral nerves. The occurrence of a neuropsychiatric disorder (NPD) caused by chronic exposure to relatively low-toxicity organophosphorus compounds is usually not associated with acute poisoning; symptoms include cognitive impairment, chronic fatigue, and extrapyramidal symptoms. The list of possible diseases or pathological conditions (syndromes) that develop as a result of acute, subacute or chronic effects of OP on the human body has expanded in recent years due a number of known neurodegenerative diseases (Alzheimer's, Parkinson's, multiple sclerosis, etc.). The aging of the body in general and the aging of the brain in particular are considered in the review from the point of view of the consequences of OP poisoning, which can serve as a nonspecific trigger of aging and related neurodegenerative diseases. Gulf syndrome is not a consequence of OP intoxication, but is also of interest and is considered in the context of OP-induced pathology, since its etiology and pathogenesis are associated with the exposure to cholinesterase inhibitors. The review presents data indicating the important role of the vascular endothelium in the development of OP-induced pathology; The first suggestions were made by clinicians in the late 1980s, and the first experimental data were obtained in the early 2000s. The principles of therapy for acute poisoning are outlined, taking into account experimental data from recent years. Some methods for studying OP in experiments in vitro, ex vivo and in vivo with laboratory animals, including the use of carboxylesterase inhibitors, are presented. The most important part of in vivo investigations has been and remains the search for new biomarkers to assess the effectiveness of adjuvant and regenerative therapies. [ABSTRACT FROM AUTHOR]

In the present study we aim to evaluate serum vitamin D levels in participants having tinnitus with normal audiometric findings. Total 98 participants in the age range 20–70 year were included in the study. Participants underwent detail case history, ear examination, pure tone audiometry and impedance audiometry. 68 participants with subjective tinnitus for more than 3 months and with normal audiometric thresholds and "A" type tympanogram were included in study group and 30 participants without tinnitus in the control group. The participants fullfillng the inclusion criteria underwent thorough tinnitus evaluation which included administration of tinnitus severity index tinnitus handicap inventory, psychophysical evaluation of tinnitus (pitch matching, loudness matching) and assessment of Vitamin D levels. It was seen that the mean Vitamin D levels were significantly lower in study group, and out of 68 participants only 11 had optimal Vitamin D levels, 57 (83%) had Vitamin D levels less that 30 mg/dl. In the control group 20 (66%) had vitamin D deficiency. The difference came out to be statistically significant. Our study suggests that there is a link between vitamin D and tinnitus, in view of these findings we recommend evaluating serum Vitamin D levels in patients of chronic idiopathic tinnitus, especially in adults with normal hearing. Our study suggests vitamin D deficiency may be one of the risk factor for tinnitus in people with normal hearing in the absence of other manifestations. [ABSTRACT FROM AUTHOR]

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and an important cause of short-term and long-term disability. Recommended physiotherapy activity programs are essential for controlling JIA associated complications such as stiffness, deformity, muscle contractures, and cramps. It is uncertain if physiotherapy (PT) can significantly enhance prognosis and quality of life (QOL). In this review we focused on the specific effects of various PT on JIA manifestations. To conduct a literature review, the databases PubMed, Scopus, and DOAJ (last access in June 2023) were searched. The PubMed search returned a total of 952 articles, Scopus returned 108, and DOAJ returned no results. After screening, the final list included 18 papers on PT treatment for JIA patients. In children with JIA, targeted PT exercise may have the ability to improve strength, posture, aerobic conditioning, gait, functional mobility, and reduce pain. [ABSTRACT FROM AUTHOR]

Background: Infants with chronic kidney disease (CKD) form a vulnerable population who are highly prone to mineral and bone disorders (MBD) including biochemical abnormalities, growth retardation, bone deformities, and fractures. We present a position paper on the diagnosis and management of CKD-MBD in infants based on available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce. Methods: PICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and relevant literature searches performed covering a population of infants below 2 years of age with CKD stages 2–5 or on dialysis. Clinical practice points (CPPs) were developed and leveled using the American Academy of Pediatrics grading matrix. A Delphi consensus approach was followed. Results: We present 34 CPPs for diagnosis and management of CKD-MBD in infants, including dietary control of calcium and phosphate, and medications to prevent and treat CKD-MBD (native and active vitamin D, calcium supplementation, phosphate binders). Conclusion: As there are few high-quality studies in this field, the strength of most statements is weak to moderate, and may need to be adapted to individual patient needs by the treating physician. Research recommendations to study key outcome measures in this unique population are suggested. [ABSTRACT FROM AUTHOR]

Desert-living Cistanche herb (DC), as a traditional Chinese medicine for tonifying kidney yang, is often used to treat postmenopausal osteoporosis (PMOP). Total phenylethanoid glycosides are instruction ingredients for discrimination and assay according to the China pharmacopoeia for DC. This research aimed to reveal the anti-osteoporosis mechanism of total phenylethanoid glycosides of DC (PGC) by transcriptomic analysis of ovariectomized rats. Serum levels of BGP were evaluated by ELISA, the bone weight was measured, and transmission electron microscopy was used to examine the ultrastructure of osteoblasts in rats. In addition, micro-CT was used to detect the bone volume (Tb.BS/BV), bone mineral density (Tb.BMD), and bone mineral content (Tb.BMC) in trabecular bone, and the ratio of cortical bone area to total area (Ct.ar/Tt.ar), and the level of bone mineral content (Ct.BMC) in cortical bone. Differential expressed genes (DEGs) after PGC treatment were analyzed by transcriptomics. Then, a bioinformatics analysis of DEGs was carried out through GO enrichment, KEGG enrichment, and selection of the nucleus gene through the protein-protein interaction network. Through qRT-PCR analysis, the DEGs were verified. The analysis results indicated that PGC increased the secretion of osteogenic markers, and ultrastructural characterization of osteoblasts and bone morphology were improved in ovariectomized rats. A total of 269 genes were differentially expressed, including 201 genes that were downregulated and 68 genes that were upregulated between the model group and the PGC group. Bioinformation analysis results prompt the conclusion that PGC could promote the bone metabolism by muscle cell development, myofibril assembly, etc. In addition, our study also found that PGC has a good effect on osteoporosis complicated with cardiomyopathy, and it also provided evidence for the correlation between sarcopenia and osteoporosis. [ABSTRACT FROM AUTHOR]

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Purpose of Review: Consumption of high-protein diets is increasingly popular due to the benefits of protein on preserving lean mass and controlling appetite and satiety. The paper is to review recent clinical research assessing dietary protein on calcium metabolism and bone health. Recent Findings: Epidemiological studies show that long-term, high-protein intake is positively associated with bone mineral density and reduced risk of bone fracture incidence. Short-term interventional studies demonstrate that a high-protein diet does not negatively affect calcium homeostasis. Existing evidence supports that the negative effects of the acid load of protein on urinary calcium excretion are offset by the beneficial skeletal effects of high-protein intake. Summary: Future research should focus on the role and the degree of contribution of other dietary and physiological factors, such as intake of fruits and vegetables, in reducing the acid load and further enhancing the anabolic effects of protein on the musculoskeletal system. [ABSTRACT FROM AUTHOR]

The therapeutic profile on bone of nandrolone decanoate is that of inhibitor of bone resorption with temporary increase in bone formation, followed by an absence of suppression of bone formation, indicating uncoupling of bone resorption and formation. This results is an increase in bone mineral content at the proximal and distal radius, and in some patients at the lumbar spine. Furthermore, nandrolone decanoate increases calcium balance and muscle mass, diminishes vertebral pain and increases the mobility of the spine. Virilization occurred in around 50% of the patients (mainly hoarseness and/or hirsutism), and 9% of the patients dropped out because of this reason. A dose of 50 mg every 3 to 4 weeks is indicated in the treatment of osteoporosis in women, especially when they have low muscle mass, associated debilitating disease, and in patients with corticosteroid induced osteoporosis. It should only be prescribed after the age of 65 to 75 years to minimize the occurrence of clinical adverse effects and to increase its tolerability, which is higher in this group. Although some effects are reported on fracture rate, insufficient prospective data are available. [ABSTRACT FROM AUTHOR]

Calcitonin (CT) constitutes one of the major choices for the pharmacologic treatment of postmenopausal and senile osteoporosis. In postmenopausal osteoporosis, CT, analogous to estrogens, determines increase of bone mass, improvement of intestinal calcium absorption and a positivization of calcium balance. Patients treated with CT can also benefit from the analgesic effect of the hormone. Unlike estrogens, these beneficial effects of CT occur with minimal risk and require no routine gynecological monitoring. In addition, CT is completely devoid of toxicity. The only limitations to the use of CT are linked to the frequent parenteral injections and the occurrence of side effects. These limitations can now be overcome by the availability of the new nasal spray preparation, which has been developed for synthetic salmon calcitonin (sCT). The introduction of this new form increases the patients' compliance, and the different pharmacokinetic curtails the side effects, compared to the parenteral administration. At present, one-year controlled studies have been reported, showing a beneficial effect of sCT on bone mass in patients with established osteoporosis. Also, shorter studies demonstrate the analgesic activity of sCT treatment in patients with vertebral crush fractures and bone pain. The improvement in the patients' compliance and the reduction of side effects allow this new CT preparation to be used in the prevention of post-menopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Radiological and clinical features are presented in 14 patients with idiopathic juvenile osteoporosis. The disease shows a characteristic pattern with onset before puberty, a limited course, and usually ends in remission with or without residual deformity, depending on the severity. In contrast to osteogenesis imperfecta, which is the main differential diagnosis, a familial history is absent in these patients. Haematological and biochemical analyses are usually normal in idiopathic juvenile osteoporosis, apart from a negative calcium balance in some severely affected patients. [ABSTRACT FROM AUTHOR]

Disorders of bone metabolism caused by resection of three quarters of the small bowel in rats were investigated biochemically and histomorphologically. Metabolic bone disorders developing 90 days after in 75%-distal-small-bowel resected rats were characterized by reduction in ash content of the femur and by the disappearance of the trabecular bone in tibial metaphysis. Biochemical studies showed significant decrease in serum Ca and 1,25-dihydroxyvitamin D concentrations in 75% distal small bowel resected rats. These data suggest that 75% distal small bowel resection impairs intestinal absorption of calcium and results in a negative calcium balance, which may contribute to the development of bone metabolic disorder in rats. On the other hand, 75% proximal small bowel resection causes no obvious metabolic bone disorders in rats, possibly because of the adaptation by the remaining part of the intestine. [ABSTRACT FROM AUTHOR]

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The two main determinants of hip fractures are falls and bone loss leading to an intrinsic femoral fragility. Substantial femoral bone loss continues throughout old age, with a continuous and exponential increase in the risk of hip fracture; thus any reduction or arrest of this loss will induce an important reduction in the incidence of hip fracture. Preventive measures may be achieved during childhood by increasing peak bone mass with calcium and exercise, by using long-term estrogen replacement therapy after menopause, but also by using vitamin D and calcium supplements for late prevention in the elderly. Vitamin D insufficiency and a deficit in calcium intake are very common in the elderly living either in institutions or at home and the cumulative response to these deficits is a negative calcium balance which stimulates parathyroid hormone secretion. This senile secondary hyperparathyroidism is one of the determinants of femoral bone loss and can be reversed by calcium and vitamin D supplements. We have shown in a 3-year controlled prospective study that the daily use of supplements (1.2 g calcium and 800 IU vitamin D) given in a large population of 3270 elderly ambulatory women living in nursing homes reduced the number of hip fractures by 23% (intention-to-treat analysis). In parallel, serum parathyroid hormone concentrations were reduced by 28% and low baseline serum 25-hydroxy vitamin D concentration returned to normal values. After 18 months of treatment the bone density of the total proximal femoral region had increased by 2.7% in the vitamin D-calcium group and decreased by 4.6% in the placebo group (p<0.001). This prevention is safe and can be recommended for people living in institutions. It could also be useful in other elderly subjects at particular risk due to a low calcium intake, an absence of solar exposure, a low femoral bone density, a high serum parathyroid hormone concentration, a low serum 25-hydroxyvitamin D concentration and a previous history of falls. Prospective studies are needed for further evaluation of these risk factors. [ABSTRACT FROM AUTHOR]

In several studies on patients with rheumatoid arthritis, an association of bone loss with a persistently high disease activity has been found. The aim of our study was to investigate the relation between disease activity and serum levels of vitamin D metabolites, parathyroid hormone (PTH), and parameters of bone turnover in patients with rheumatoid arthritis. A total of 96 patients (83 women and 13 men) were divided into three groups according to disease activity measured by serum levels of C-reactive protein (CRP). In the whole group, serum levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (P < 0.001) and PTH (P < 0.05) were negatively correlated to disease activity. The urinary excretion of collagen crosslinks--pyridinoline (Pyd) (P < 0.001) and deoxypyridinoline (Dpd) (P < 0.05)--showed a positive correlation with disease activity. The inverse correlation between serum 1,25(OH)2D3 and disease activity was separately evident in patients with (P < 0.001) and without (P < 0.01) glucocorticoid treatment, in pre- (P < 0.01) and postmenopausal (P < 0.001) women, and in men (P < 0.01). 1,25(OH)2D3 and PTH serum levels were positively correlated to serum bone alkaline phosphatase (ALP) (P < 0.01). The results indicate that high disease activity in patients with rheumatoid arthritis is associated with an alteration in vitamin D metabolism and increased bone resorption. The decrease of 1,25(OH)2D3 levels in these patients may contribute to a negative calcium balance and inhibition of bone formation. Furthermore, low levels of 1,25(OH)2D3 as an endogenous immunomodulator suppressing activated T cells and the proliferation of cells may accelerate the arthritic process in rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Calcitriol is used in the treatment of osteoporosis but the indications for its use have not been clearly defined. Because it stimulates calcium absorption, we have tended to select osteoporotic patients with low calcium absorption for this therapy and now report the results. We measured the hourly fractional rate of calcium absorption (alpha) with 45Ca and fasting urinary calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (OHPr/Cr) in 103 postmenopausal women aged 68 (0.67SE) years with vertebral compression fractures (77) or forearm or vertebral bone density below the young normal range (26). They were given 0.25 microg daily of calcitriol (Rocaltrol, Roche, Basle, Switzerland) with a 1 g calcium supplement daily for 6-12 weeks, when the biochemical tests were repeated. Initial OHPr/Cr was inversely related to initial alpha (P = 0.001) and positively to initial Ca/Cr (P < 0.001). alpha rose on therapy from 0.47 (0.018) to 0.59 (0.018) per hour (P < 0. 001) and OHPr/Cr fell in the whole group from 19.1 (0.83) to 13.8 (0. 58) (P < 0.001). The change in alpha on therapy (corrected for the "regression to the mean effect") was inversely related to initial alpha (P < 0.001) as was the change in OHPr/Cr (P = 0.001). There was no relationship, however, between initial Ca/Cr and either the rise in alpha or the fall in OHPr/Cr on therapy. The data support the concept that low calcium absorption is a cause of negative calcium balance in postmenopausal osteoporosis and that the effectiveness of calcitriol therapy is inversely related to the initial rate of calcium absorption. [ABSTRACT FROM AUTHOR]

Metabolic bone disorders caused by resection of the distal three quarters of the small bowel and the effects of 1α-hydroxyvitamin D (1 α(OH)D) on the rats were investigated biochemically and histomorphologically. 1α(OH)D was administered orally to the rats for 13 weeks. A group of ' sham operation' animals and the 75%-distal-small-bowel-resected control animals received only the vehicle. Bone changes developed 13 weeks after the partial bowel resection. The disorder was characterized by reductions in ash content of the femur and by the disappearance of the trabecular bone in tibial metaphysis. Decreased Ca absorption from the intestines was demonstrated by a radiotracer technique, and biochemical studies showed significant decreases in serum Ca and 1,25(OH)D concentrations in the bowel-resected rats. These findings suggest that 75% distal small bowel resection impairs intestinal absorption of calcium and results in a negative calcium balance, which may contribute to the development of bone metabolic disorder in rats. This disorder was demonstrated as high bone turnover via urinalysis and by a radiotracer technique. Administration of 1α(OH)D increased dose-dependent Ca absorption from the intestine and the serum Ca, normalized the bone turnover rate and prevented the development of bone metabolic disorder. [ABSTRACT FROM AUTHOR]

The effect of 1 α-hydroxyvitamin D (1 α(OH)D) on the metabolic bone disorders developed in gastrectomized rats were investigated biochemically and histomorphologically. 1α(OH)D was suspended in 0.2 % Triton-X-100 aqueous solution after dissolving in a very small amount of ethanol, was given orally to the rats for 10 weeks. The sham operated animals and the gastrectomy control animals received the vehicle alone. Gastrectomy was followed by the development of the metabolic bone disorders after 10 weeks of observation. This was characterized by reduction in ash content of the femur and histologically by a disappearance of the trabecular bone in tibial metaphysis. Decrease Ca absorption from the intestines was demonstrated by a radiotracer technique. Biochemical studies showed significant decreases in serum 25(OH)D concentration in gastrectomized rats. These findings suggest that gastrectomy partially impairs intestinal absorption of calcium and results in a negative calcium balance, which may contribute to the development of bone metabolic disorders in rats. The administration of 1α(OH)D increased dose-dependently serum calcium and Ca absorption from the intestine and prevented the development of bone metabolic disorders histomorphologically. [ABSTRACT FROM AUTHOR]

Conventional glucocorticoids exert a negative influence on calcium balance, and long-term treatment with these agents leads to osteopenia. Deflazacort is an oxazoline derivative of prednisolone with documented calcium-sparing properties when compared to prednisone on a weight basis. The purpose of the present study was to determine the relative antiinflammatory potency of deflazacort and prednisone. In a randomized, cross-over, double-blind trial, 11 patients, all suffering from polymyalgia rheumatica, and all on a stable maintenance dose of prednisone, were treated with equimolar doses of prednisone and deflazacort (i.e., weight ratio 1:1.2) for two consecutive 2-week periods. Following deflazacort treatment, significant rises compared with initial values were seen in erythrocyte sedimentation rate (ESR), plasma fibrinogen, serum alkaline phosphatase, and general pain and tenderness. No changes were seen following prednisone treatment. Subsequently, in a similar regimen, prednisone was compared with deflazacort at a weight ratio of 1:1.2 in 10 patients, 1:1.5 in another 10 patients, and 1:1.8 in still another 10 patients for purposes of dose titration. Again, significant rises were seen in ESR, plasma fibrinogen, and serum alkaline phosphatase following the lowest dose of deflazacort, whereas no changes were seen following the higher doses of deflazacort or prednisone. In conclusion, the relative antiinflammatory potency of deflazacort and prednisone lies between 0.83 and 0.66 on a weight basis (1.02 and 0.82 on a molar basis) as evaluated by clinical and biochemical parameters reflecting disease activity in polymyalgia. This disease appears to represent a sensitive, reliable and reproducible clinical model for assessment of the relative antiinflammatory potency of glucocorticoids. [ABSTRACT FROM AUTHOR]

Chronic diabetes mellitus in the rat is attended by a reduced bone turnover and growth arrest, decreased circulating immunoreactive parathyroid hormone (iPTH), and hypercorticosteronism. Since chronic insulin deficiency in the rat is associated with intestinal hyperabsorption of calcium and a positive calcium balance that may account for the decreased iPTH, as well as other hormonal alterations observed in these animals, we studied the effect of long-term (5 week) dietary calcium restriction (0.1% Ca, 0.8% P) in control and streptozotocin-induced diabetic rats. Chronic diabetic rats reared on a normal calcium (1.2% Ca) diet had increased serum calcium and phosphate (Pi) concentrations and were markedly hypercalciuric and phosphaturic compared with controls. Serum corticosterone was increased and iPTH markedly decreased in the diabetic animals. Dietary Ca restriction (0.1% Ca) decreased urinary calcium excretion and resulted in a comparable phosphaturic response in both control and diabetic rats. Moreover, although Ca restriction in diabetic animals had no appreciable effect on serum insulin, serum glucose, or urinary glucose excretion, it was associated with a marked increase in circulating iPTH; this resulted in serum concentrations comparable with that observed in control animals reared on the low Ca diet. These results support the hypothesis that the decreased circulating iPTH observed in chronic diabetic rats results predominantly from their intestinal hyperabsorption of Ca. In contrast to control animals, diabetic rats reared on a low Ca diet failed to maintain their serum Ca despite the marked increase in serum iPTH and striking decrease in calciuria, thus underscoring the reliance of these animals on intestinal hyperabsorption of Ca to maintain Ca balance under conditions of adequate Ca intake. Serum corticosterone was insignificantly altered by dietary Ca restriction in control rats; hypercorticosteronism, characteristically observed in diabetic rats, was normalized by Ca restriction. We conclude that a primary disturbance in Ca homeostasis may contribute, in part, to hormonal alterations observed in chronic experimental diabetes. [ABSTRACT FROM AUTHOR]

Prolonged therapeutic administration of prednisone or other corticosteroids frequently produces severe osteopenia with an increased incidence of bone fractures. Recent efforts to decrease the severity of corticosteroid-induced osteopenia have included the development of corticosteroid analogues designed to possess diminished bone-wasting effects relative to their anti-inflammatory activity. We compared the effects of an oxazoline derivative of prednisolone, oxazacort (azacortinol), with those of prednisone on mineral metabolism in man. After a 12-day equilibration period on a 600 mg/day calcium diet, normal volunteers were studied for 15 days during treatment with either prednisone (20 mg/day, 12 subjects) or oxazacort (25 mg/day, 10 subjects). There was no difference between the two groups with regard to the effects of each corticosteroid on serum ionized calcium, phosphate, alkaline phosphatase, immunoreactive parathyroid hormone (iPTH), and 25-hydroxyvitamin D (25OHD) concentrations. Both corticosteroids suppressed intestinalCa absorption to a similar degree after 15 days of treatment (prednisone: −28.5±7.5, oxazacort: −30.2±4.4% of initial values). Although both corticosteroids increased 24-h urinary calcium excretion significantly above pretreatment values, this effect was less marked in the oxazacort-treated subjects. The mean cumulative 15-day increase in urinary calcium excretion in the prednisone-treated group (+326 ± 54 mg/g creatinine/24 h) was more than twice as great as that in the oxazacort-treated group (+146 ± 48 mg/g creatinine/24 h), a difference significant at P<0.001. It is concluded that the increase in urinary calcium excretion, and presumably the negative calcium balance, produced by a 2-week administration of oxazacort is significantly less pronounced than that produced by an equivalent dose of prednisone. [ABSTRACT FROM AUTHOR]

We have examined the effects of H, CO, and HCO concentrations during metabolic and respiratory acidosis and alkalosis on bone resorption in vitro. Rat fetal bones prelabeled withCaCl were cultured at 2%, 5%, and 10% CO for up to 120 h, and the release ofCa was measured in devitalized bones (non-cell-mediatedCa release) and in live bones (cell-mediatedCa release) cultured with or without PTH and 1,25(OH)D. Non-cell-mediated mineral loss was linearly related to H concentration but not to CO or HCO concentration. This effect was observed on both labeled and stable calcium. Over a wide pH range (6.9-7.5) H, CO, or HCO concentrations did not influence cell-mediated bone resorption in control or in PTH-and 1,25(OH)D-stimulated cultures. However, inhibition of cell-mediated bone resorption was observed at higher or lower pH irrespective of CO or HCO concentrations. These observations demonstrate that the bone mineral mobilizing effect of acidosis in vitro is mainly due to the effect of changing H concentration on devitalized bone. Effects on cell-mediated bone resorption and hormonal response were observed only at extremes of pH. The effects of H were independent of changes in CO or HCO concentration and could be responsible for the negative calcium balance and increased urinary loss observed in metabolic acidosis in vivo, but do not explain the reported differences in effects on calcium metabolism between respiratory and metabolic acidosis. [ABSTRACT FROM AUTHOR]

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Vitamin D3 is generated in skin by UV irradiation of 7-dehydrocholesterol (7-DEHC). Whether the 7-DEHC amount in skin affects vitamin D3 formation, and thereby the plasma level of 25-hydroxyvitamin D3 (25[OH]D3) is not known. In the present work we report on the influence on vitamin D and Ca metabolism of a new hypocholesterolemic agent, HCG-917 (0-2-[hydroxy-3-]N′-(2-chlorophenyl)-N-piperazinyl-1-[propyl]-4-chloro-benz-aldoxim-hydrochloride) which inhibits 7-DEHC reductase and thereby increases skin 7-DEHC. Rats were treated with HCG 917 (0.3 and 5.0 mg/kg, orally) for 13 days. HCG 917 caused a dose-dependent decrease in cholesterol and concomitant accumulation of 7-DEHC in plasma and skin. In skin, 7-DEHC was: control: 1.05±0.20; HCG 917, 0.3 mg/kg: 1.41±0.22; HCG 917, 5.0 mg/kg: 2.35±0.35 mg/g. At a dose of 0.3 mg/kg, HCG 917 had no significant influence on the plasma level of neither 25(OH)D3 nor 1,25(OH)2D3. However, at a dose of 5.0 mg/kg, HCG 917 induced a significant increase in plasma 25(OH)D3 (control: 36.2±2.2; HCG 917 5.0 mg/kg: 57.6±6.5 nmol/l) and a slight but not significant rise in 1,25(OH)2D3. Calcium balance studies indicated that HCG 917 did not influence intestinal Ca absorption nor urinary Ca excretion. At a dose of 5.0 mg/kg HCG 917 slightly induced a decrease in total plasma Ca. In conclusion, HCG 917 treatment can induce a significant rise in skin 7-DEHC with an increase in plasma 25(OH)D3. These results suggest that variation in the skin level of 7-DEHC can directly influence the cutaneous production of vitamin D3 and thereby the vitamin D status of the organism. [ABSTRACT FROM AUTHOR]

Tilapia larvae were exposed to 0 (control), 50 (50-Cd) or 100 (100-Cd) µg l-1 cadmium for 4 days and then transferred to cadmium-free fresh water for 3 days of detoxification. Total length and weight, calcium influx and total body calcium and cadmium content were examined at various times during detoxification. All the groups grew normally with regards to total length and body weight. Within the first 12h of detoxification the 50- and 100-Cd exposed groups released cadmium at the similar rate of about 24 ng mg-1 h-1 (or 140 ng larva-1 h-1). Later, however, this rate declined to only 4–16% of the initial level. Calcium influx in the control group showed a 10–26% increase during the detoxification period. Calcium influx in the 50-Cd group increased by about 280% and reached it peak at 12h. Calcium influx in the 100-Cd group increased by 440% and did not peak until 24h after transfer. After peaking, the influxes in both 50- and 100-Cd groups declined to the level of control at the end of the experiment. Calcium contents in 50- and 100-Cd groups increased more rapidly than that in control group within first 24h of the detoxification period. However the rate of increase in calcium content in three groups was the same after 24h. The changes in calcium influx appeared to be correlated with those in calcium content, and these suggested that tilapia larvae regulate the mechanism of calcium balance to compensate for the reduced calcium level in the body. [ABSTRACT FROM AUTHOR]