Renal complications and quality of life in postsurgical hypoparathyroidism: a case-control study.

PURPOSE: Conventional therapy (calcium and activated vitamin D) does not restore calcium homeostasis in patients with chronic hypoparathyroidism (HypoPT) and is associated with renal complications and reduced quality of life (QoL). The aim of this study was to evaluate in a case-control, cross-sectional study, the rate of renal complications and QoL in two sex- and age-matched cohort of patients with differentiated thyroid cancer with (n = 89) and without (n = 89) chronic post-operative HypoPT (PoHypoPT) and their relationship with the biochemical control of the disease. METHODS: Serum and urinary parameters, renal ultrasound and QoL were assessed by SF-36 and WHO-5 questionnaires. RESULTS: Forty-three (48.3%) PoHypoPT patients reported symptoms of hypocalcemia. Twenty-six (29.2%) patients were at target for all 6 parameters, 46 (51.6%) for 5. The most frequently unmet targets were gender-specific 24-h urinary calcium (44.9%) and serum calcium (37.1%). Serum phosphate, magnesium and 25(OH)D were in the normal range in > 90% of patients. Renal calcifications were found in 26 (29.2%) patients, with no correlation with 24-h urinary calcium. eGFR did not differ between patients and controls. Conversely, patients had a significant higher rate of renal calcifications and a lower SF-36, but not WHO-5, scores. SF-36 scores did not differ between PoHypoPT patients who were, or not, hypocalcemic. CONCLUSIONS: Our study shows that the rate of renal calcifications was higher in patients with PoHypoPT than in those without. This finding, together with the reduced QoL and the presence of hypocalcemic symptoms in about half patients, underscores that the treatment of chronic HypoPT with conventional therapy is suboptimal.

Safety of calcitonin stimulation tests with calcium.

INTRODUCTION: Medullary thyroid carcinoma (MTC) is an aggressive form of thyroid cancer. Early detection is essential because only complete resection of the thyroid tumor and any local metastases can cure MTC. Calcitonin (CT) is a marker used for diagnosis of MTC. In controversial cases of slightly elevated CT levels, stimulation tests have shown their utility, but their safety should also be taken into account. OBJECTIVE: Our aim is to present our own experience regarding the safety of CT stimulating tests. MATERIALS AND METHODS: We applied a specific protocol of calcium stimulation test in 176 patients after informed consent (115 women with a median age of 46 years, range 21-79; 61 men with a median age of 54 years, range 22-78). We recorded the side effects and a further analysis was performed. RESULTS: The most frequent side effects noted were hot flashes in 159 out of 176 patients (90.34%), followed by dysgeusia (32/176) and bradycardia (10/176). Severe bradycardia was reported in only one patient (0.568%), which was rapidly reversible. There was no correlation between patients' age, weight, height, body mass index, basal CT or peak stimulated CT, and grade of severity, but men were more likely to develop cardiovascular side effects than women, namely, bradycardia, tachycardia, ventricular or atrial extrasystoles, hypertension, hypotension, or angina (p = 0.024), with an odds ratio of 2.94 (CI: 1.11-7.76). We recommend thyroid surgery in all women with sCT above 285 pg/ml. CONCLUSION: The calcium stimulation test is well tolerated, with few adverse reactions. The test should be performed with appropriate precautions (i.e., ECG monitoring during and after the test) to minimize the possibility of a serious event.

Effects of intravenous magnesium sulfate on serum calcium-regulating hormones and plasma and urinary electrolytes in healthy horses.

Intravenous magnesium sulfate (MgSO4) is used in equine practice to treat hypomagnesemia, dysrhythmias, neurological disorders, and calcium dysregulation. MgSO4 is also used as a calming agent in equestrian events. Hypercalcemia affects calcium-regulating hormones, as well as plasma and urinary electrolytes; however, the effect of hypermagnesemia on these variables is unknown. The goal of this study was to investigate the effect of hypermagnesemia on blood parathyroid hormone (PTH), calcitonin (CT), ionized calcium (Ca2+), ionized magnesium (Mg2+), sodium (Na+), potassium (K+), chloride (Cl-) and their urinary fractional excretion (F) after intravenous administration of MgSO4 in healthy horses. Twelve healthy female horses of 4-18 years of age and 432-600 kg of body weight received a single intravenous dose of MgSO4 (60 mg/kg) over 5 minutes, and blood and urine samples were collected at different time points over 360 minutes. Plasma Mg2+ concentrations increased 3.7-fold over baseline values at 5 minutes and remained elevated for 120 minutes (P < 0.05), Ca2+ concentrations decreased from 30-60 minutes (P < 0.05), but Na+, K+ and Cl- concentrations did not change. Serum PTH concentrations dropped initially to rebound and remain elevated from 30 to 60 minutes, while CT concentrations increased at 5 minutes to return to baseline by 10 minutes (P < 0.05). The FMg, FCa, FNa, FK, and FCl increased, while urine osmolality decreased from 30-60 minutes compared baseline (P < 0.05). Short-term experimental hypermagnesemia alters calcium-regulating hormones (PTH, CT), reduces plasma Ca2+ concentrations, and increases the urinary excretion of Mg2+, Ca2+, K+, Na+ and Cl- in healthy horses. This information has clinical implications for the short-term effects of hypermagnesemia on calcium-regulation, electrolytes, and neuromuscular activity, in particular with increasing use of Mg salts to treat horses with various acute and chronic conditions as well as a calming agent in equestrian events.

The Skeletal Consequences of Bariatric Surgery.

PURPOSE OF REVIEW: This review outlines the recent findings regarding the impact of bariatric surgery on bone. It explores potential mechanisms for skeletal changes following bariatric surgery and strategies for management. RECENT FINDINGS: Bone loss following bariatric surgery is multifactorial. Probable mechanisms include skeletal unloading, abnormalities in calciotropic hormones, and changes in gut hormones. Skeletal changes that occur after bariatric surgery are specific to procedure type and persist for several years post-operatively. Studies suggest that while bone loss begins early, fracture risk may be increased later in the post-operative course, particularly after Roux-en-Y gastric bypass (RYGB). Further research is needed to assess the extent to which skeletal changes following bariatric surgery result in fragility. Current management should be geared toward prevention of bone loss, correction of nutritional deficiencies, and incorporation of weight bearing exercise. Pharmacologic treatment should be considered for high-risk patients.

Salmon calcitonin distributes into the arcuate nucleus to a subset of NPY neurons in mice.

The amylin receptor (AMY) and calcitonin receptor (CTR) agonists induce acute suppression of food intake in rodents by binding to receptors in the area postrema (AP) and potentially by targeting arcuate (ARC) neurons directly. Salmon calcitonin (sCT) induces more potent, longer lasting anorectic effects compared to amylin. We thus aimed to investigate whether AMY/CTR agonists target key neuronal populations in the ARC, and whether differing brain distribution patterns could mediate the observed differences in efficacy with sCT and amylin treatment. Brains were examined by whole brain 3D imaging and confocal microscopy following subcutaneous administration of fluorescently labelled peptides to mice. We found that sCT, but not amylin, internalizes into a subset of ARC NPY neurons, along with an unknown subset of ARC, AP and dorsal vagal motor nucleus cells. ARC POMC neurons were not targeted. Furthermore, amylin and sCT displayed similar distribution patterns binding to receptors in the AP, the organum vasculosum of the lamina terminalis (OVLT) and the ARC. Amylin distributed within the median eminence with only specs of sCT being present in this region, however amylin was only detectable 10 minutes after injection while sCT displayed a residence time of up to 2 hours post injection. We conclude that AMY/CTR agonists bind to receptors in a subset of ARC NPY neurons and in circumventricular organs. Furthermore, the more sustained and greater anorectic efficacy of sCT compared to rat amylin is not attributable to differences in brain distribution patterns but may more likely be explained by greater potency at both the CTR and AMY.

Efficient biotransformation of vitamin D3 to 25-hydroxyvitamin D3 by a newly isolated Bacillus cereus strain.

25-hydroxyvitamin D3 has attracted considerable attention due to its great medical value and huge market demand in animal husbandry. Microbial production of 25-hydroxyvitamin D3 has been recognized as an alternative superior to traditional chemical synthesis. In this study, a Gram-positive bacteria zju 4-2 (CCTCC M 2019385) was isolated from the soil using vitamin D3 as the sole carbon source and was identified as Bacillus cereus according to its physiological characteristics and 16S rRNA analysis, which also showed a relatively high capacity for 25-hydroxyvitamin D3 production. Through systematic optimization of different catalytic conditions, the optimal solvent system of vitamin D3, vitamin D3 addition time and concentration, temperature, and pH were shown to be propylene glycol/ethanol (v/v = 9:1), early stationary phase, 2 g/L, 37 °C, and pH 7.2, respectively. With these optimal conditions, 796 mg/L of 25-hydroxyvitamin D3 was achieved after 48 h bioconversion with zju 4-2 at the shake flask level. Finally, up to 830 mg/L 25-hydroxyvitamin D3 with a yield of 41.5% was obtained in a 5 L fermentation tank. Our developed biotransformation process with this newly isolated strain provides a platform to produce 25-hydroxyvitamin D3 efficiently at industrialization scale.

An intact insect embryo for developmental neurotoxicity testing of directed axonal elongation.

Developmental neurotoxicity (DNT) of chemicals poses a serious threat to human health worldwide. Current in vivo test methods for assessing DNT require the use of high numbers of laboratory animals. Most alternative in vitro testing methods monitor rather simple toxicological endpoints, whereas the formation of a functional brain requires precisely timed navigation of axons within a complex tissue environment. We address this complexity by monitoring defects in axonal navigation of pioneer axons of intact locust embryos after exposure to chemicals. Embryos develop in serum-free culture with test chemicals, followed by immunolabeling of pioneer neurons. Defects in axon elongation of pioneer axons are quantified in concentration-response curves and compared to the general viability of the embryo, as measured by a resazurin assay. We show that selected chemical compounds interfering with calcium signaling, the cytoskeletal organization, and the reference developmental neurotoxicant rotenone, can be classified as DNT positive. The pesticide rotenone inhibits pioneer neuron elongation with a lower IC50 than the viability assay. The rho kinase inhibitor Y27632 can partially rescue outgrowth inhibition, supporting the classification of rotenone as a specific DNT positive compound. Since mechanisms of axonal guidance, such as growth cone navigation along molecular semaphorin gradients are conserved between locust and mammalian nervous systems, we will further explore the potential of this invertebrate preparation as an assay for testing the DNT potential of chemicals in humans.

A case of hypercalcemia in a heifer presumably due to mammary carcinoma bovine hypercalcemia of malignancy.

Mammary carcinoma is rare in cattle with only a handful of cases found in the literature, and none have reported an associated hypercalcemia. An 8-year-old Holstein-Friesian heifer was presented to the Purdue University Veterinary Teaching Hospital's Large Animal Hospital with a 3-month history of lethargy. Laboratory abnormalities included ionized hypercalcemia and hypophosphatemia (2.28 mmol/L and 1.8 mg/dL, respectively). Physical examination revealed a mammary mass that was cytologically described as a suspected mammary carcinoma, which was later confirmed by histologic evaluation. On surgical removal of the mass, calcium initially decreased rapidly, and within a few days was within the RI, further supporting a diagnosis of hypercalcemia of malignancy in a heifer. However, attempts to confirm this using hormone profiles (parathyroid hormone [PTH], parathyroid hormone-related protein [PTHrp], and calcitriol) were inconclusive due to the lack of validated assays and RIs for cattle. Immunohistochemical staining for PTHrP showed scattered cytoplasmic staining among the neoplastic cells, suggesting PTHrP production by these cells.

Role of vitamin D and vitamin D receptor (VDR) in oral cancer.

Oral cancer is known as one of the most common cancers, with a poor prognosis, related to delayed clinical diagnosis, either due to the lack of particular biomarkers related to the disease or costly therapeutic alternatives. Vitamin D executes its functions by interacting with the vitamin D receptor (VDR), both in healthy and diseased individuals, including oral cancer. This review discusses the role of vitamin D and VDR on tumorigenesis, emphasizing on oral cancer. Furthermore, regulation of VDR expression, mechanisms of anticancer effects of calcitriol, oral cancer chemoresistance and its relation with VDR and polymorphisms of VDR gene will be discussed. The manuscript is prepared mainly using the information collected from PubMed and MEDLINE.

The parathyroid hormone regulates skin tumour susceptibility in mice.

Using a forward genetics approach to map loci in a mouse skin cancer model, we previously identified a genetic locus, Skin tumour modifier of MSM 1 (Stmm1) on chromosome 7, conferring strong tumour resistance. Sub-congenic mapping localized Parathyroid hormone (Pth) in Stmm1b. Here, we report that serum intact-PTH (iPTH) and a genetic polymorphism in Pth are important for skin tumour resistance. We identified higher iPTH levels in sera from cancer-resistant MSM/Ms mice compared with susceptible FVB/NJ mice. Therefore, we performed skin carcinogenesis experiments with MSM-BAC transgenic mice (Pth MSM-Tg) and Pth knockout heterozygous mice (Pth +/-). As a result, the higher amounts of iPTH in sera conferred stronger resistance to skin tumours. Furthermore, we found that the coding SNP (rs51104087, Val28Met) localizes in the mouse Pro-PTH encoding region, which is linked to processing efficacy and increased PTH secretion. Finally, we report that PTH increases intracellular calcium in keratinocytes and promotes their terminal differentiation. Taken together, our data suggest that Pth is one of the genes responsible for Stmm1, and serum iPTH could serve as a prevention marker of skin cancer and a target for new therapies.