Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- Parathyroid hormone levels 1 hour after thyroidectomy: an early predictor of postoperative hypocalcemia. [JOURNAL ARTICLE]
- Can J Surg 2014 Aug; 57(4):237-240.
Parathyroid dysfunction leading to symptomatic hypocalcemia is not uncommon following a total or completion thyroidectomy and is often associated with significant patient morbidity and a prolonged hospital stay. A simple, reliable indicator to identify patients at risk would permit earlier pharmacologic prophylaxis to avoid these adverse outcomes. We examined the role of intact parathormone (PTH) levels 1 hour after surgery as a predictor of post-thyroidectomy hypocalcemia.We prospectively reviewed the cases of consecutive patients undergoing total or completion thyroidectomy. Ionized calcium (Ca(2+)) and intact PTH levels were measured preoperatively and at 1-, 6- and 24-hour intervals postoperatively. The specificity, sensitivity, negative and positive predictive values of the 1-hour PTH serum levels (PTH-1) in predicting 24-hour post-thyroidectomy hypocalcemia and eucalcemia were determined.We reviewed the cases of 149 patients. Biochemical hypocalcaemia (Ca(2+) < 1.1 mmol/L) developed in 38 of 149 (25.7%) patients 24 hours after thyroidectomy. The sensitivity, specificity, positive and negative predictive values of a low PTH-1 were 89%, 100%, 97% and 100%, respectively.We found that PTH-1 levels were predictive of symptomatic hypocalcemia 24 hours after thyroidectomy. Routine use of this assay should be considered, as it could prompt the early administration of calcitriol in patients at risk of hypocalcemia and allow for the safe and timely discharge of patients expected to remain eucalcemic.
- 1,25-dyhydroxyvitamin D3 attenuates rotenone-induced neurotoxicity in SH-SY5Y cells through induction of autophagy. [JOURNAL ARTICLE]
- Biochem Biophys Res Commun 2014 Jul 28.
Dysregulation of the autophagy pathway has been suggested as an important mechanism in the pathogenesis of Parkinson's disease (PD). Therefore, modulation of autophagy may be a novel strategy for the treatment of PD. Recently, an active form of vitamin D3 has been reported to have neuroprotective properties. Therefore, we investigated the protective, autophagy-modulating effects of 1,25-dyhydroxyvitamin D3 (calcitriol) in an in vitro model of Parkinson's disease.An in vitro model of Parkinson's disease, the rotenone-induced neurotoxicity model in SH-SY5Y cells was adapted. We measured cell viability using an MTT assay, Annexin V/propidium iodide assay, and intracellular reactive oxygen species levels and analyzed autophagy-associated intracellular signaling proteins by Western blotting.Rotenone treatment of SH-SY5Y cells reduced their viability. This treatment also increased reactive oxygen species levels and decreased levels of intracellular signaling proteins associated with cell survival; simultaneous exposure to calcitriol significantly reversed these effects. Additionally, calcitriol increased levels of autophagy markers, including LC3, beclin-1, and AMPK. Rotenone inhibited autophagy, as indicated by decreased beclin-1 levels and increased mTOR levels, and this effect was reversed by calcitriol treatment.Calcitriol protects against rotenone-induced neurotoxicity in SH-SY5Y cells by enhancing autophagy signaling pathways such as those involving LC3 and beclin-1. These neuroprotective effects of calcitriol against rotenone-induced dopaminergic neurotoxicity provide an experimental basis for its clinical use in the treatment of PD.
- The Glyceraldehyde 3-Phosphate Dehydrogenase Gene (GAPDH) is Regulated by Myeloid Zinc Finger 1 (MZF-1) and Is Induced by Calcitriol. [JOURNAL ARTICLE]
- Biochem Biophys Res Commun 2014 Jul 24.
Recently, new tissue-specific functions for Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) have been discovered, aside from its archetypal function in glycolysis. This casts doubt on the legitimacy of using GAPDH as a normalization control for gene expression analysis. We report the binding of the Myeloid Zinc Finger-1 (MZF-1) transcription factor to the human GAPDH promoter. Furthermore, we show that up-regulation of MZF-1 by 1,25-dideoxyvitamin D3 (calcitriol) induces GAPDH in HS-5 stromal fibroblasts, while knockdown of MZF1 by shRNA leads to a concomitant reduction in GAPDH expression. This argues that MZF-1 regulates GAPDH, indicating a role for GAPDH in calcitriol-mediated signaling.
- A Single Parathyroid Hormone Level Obtained 4 Hours after Total Thyroidectomy Predicts the Need for Postoperative Calcium Supplementation. [JOURNAL ARTICLE]
- J Am Coll Surg 2014 Jun 18.
Parathyroid hormone (PTH) levels after total thyroidectomy have been shown to predict the development of symptomatic hypocalcemia and the need for calcium supplementation. This study aimed to determine whether a PTH level drawn 4 hours postoperatively is as effective as a level drawn on postoperative day 1 (POD1) in predicting this need.This is a single-institution retrospective review of 4-hour and POD1 PTH levels in patients who underwent total thyroidectomy from January 2012 to September 2012. If POD1 PTH was ≥10 pg/mL, patients did not routinely receive supplementation; if PTH was <10 pg/mL, patients received oral calcium with or without calcitriol.Of 77 patients, 20 (26%) had a 4-hour PTH <10 pg/mL; 18 (90%) of these patients had a POD1 PTH <10 pg/mL. No patient with a 4-hour PTH ≥10 pg/mL had a POD1 PTH <10 pg/mL. All 18 patients with POD1 PTH <10 pg/mL received calcium supplementation. Three additional patients received supplementation due to reported symptoms or surgeon preference. A 4-hour PTH ≥10 pg/mL compared with a POD1 PTH had a similar ability to predict which patients would not need calcium supplementation; sensitivity was 98% vs 98%, specificity was 90% vs 86%, and and negative predictive value was 95% vs 95%. Of 21 patients who received supplementation, 13 (62%) also received calcitriol, including 9 patients (69%) with a 4-hour PTH <6 pg/mL.A single PTH level obtained 4 hours after total thyroidectomy that is ≥10 pg/mL accurately identifies patients who do not need calcium supplementation or additional monitoring of serum calcium levels. Same-day discharge, if deemed safe, can be accomplished with or without calcium supplementation based on the 4-hour PTH level. Greater consideration should be given to calcitriol supplementation in patients with a 4-hour PTH <6 pg/mL.
- Effects of calcitriol on bone mineral density in patients treated with esomeprazole. [JOURNAL ARTICLE]
- Pharm Biol 2014 Jul 21.:1-4.
Abstract Context: Proton pump inhibitor (PPI) increases the risk of decrease in bone mineral density (BMD). However, whether calcitrol improves this situation is unknown. Objective: The current study investigates the effects of calcitriol on BMD in patients with esomeprazole therapy. Materials and methods: Three hundred and eighty-six participants with gastrointestinal ulcerations were enrolled and randomly assigned into controlled and supplemented groups. Participants in the controlled group were prescribed esomeprazole (20 mg/qd), while the supplemented group was prescribed esomeprazole (20 mg/qd) and calcitriol (2.5 μg/qd). BMD, serum levels of calcium, carboxy-terminal collagen crosslinks (CTX), and alkaline-phosphatase (ALP) were assessed. Results: (1) No significant between-group difference of age, gender, smoking, previous glucocorticoid use and hemoglobin level was found; (2) after 10.6 ± 0.8 d of PPI therapy, BMD T score in the controlled group was slightly increased compared with initial (-1.25 ± 0.08 versus -1.28 ± 0.06, p = 0.084), while there was no change in the supplemented group (-1.25 ± 0.05 versus -1.26 ± 0.03, p = 0.308); (3) during study termination, calcium level in the supplemented group was slightly higher than the controlled group (2.05 ± 0.03 mmol/L versus 2.01 ± 0.05 mmol/L, p = 0.073), while no significant differences of CTX (366.57 ± 43.71 pg/mL versus 373.15 ± 50.23 pg/mL, p = 0.036) and ALP were found among these two groups (50.47 ± 9.32 U/L versus 52.23 ± 10.45 U/L, p = 0.075). Conclusion: Patients with gastrointestinal ulcerations with esomeprazole therapy, calcitriol supplement showed no efficacy on BMD changes.
- The PI3K/p-Akt signaling pathway participates in calcitriol ameliorating podocyte injury in DN rats. [JOURNAL ARTICLE]
- Metabolism 2014 Jun 20.
The present study aimed to investigate the relationship between PI3K/p-Akt signaling pathway and podocyte impairment in DN rats as well as the protective effect of calcitriol.SD rats were randomly divided into four groups: normal control (NC), normal treated with calcitriol (NC+VD), diabetic nephropathy (DN) and DN treated with calcitriol (DN+VD); all VD rats were treated with 0.1μg/kg/d calcitriol by gavage. DN model rats were established by intraperitoneal injections of streptozotocin (STZ). Rats were sacrificed after 18weeks of treatments.In the present study, increased albuminuria was observed as early as 3weeks of diabetes and continued to increase more than six-fold throughout the length of the study (18weeks). Expectedly, animals receiving the treatment with calcitriol was protected from this increase, lower about one third. Meanwhile, the expression of podocyte specific markers, including nephrin and podocin, together with PI3K/p-Akt was significantly decreased in DN rats, whereas calcitriol reversed these above changes accompanied by elevated the expression levels of VDR. Additionally, a positive correlation was observed between the expression levels of nephrin and VDR (r=0.776, P<0.05). Likewise, the expression of nephrin was positively correlated with both PI3K-p85 and p-Akt (r=0.736, P<0.05; r=0.855, P<0.05, respectively).PI3K/p-Akt signaling pathway participates in calcitriol ameliorating podocyte injury in DN rats. The manipulation of calcitriol might act as a promising therapeutic intervention for diabetic nephropathy.
- Bone Geometry, Volumetric Density, Microarchitecture and Estimated Bone Strength Assessed by HR-pQCT in Adult Patients with Hypophosphatemic Rickets. [JOURNAL ARTICLE]
- J Bone Miner Res 2014 Jul 10.
Hypophosphatemic rickets (HR) is characterized by a generalized mineralization defect. While densitometric studies have found the patients to have an elevated bone mineral density (BMD), data on bone geometry and microstructure are scarce. The aim of this cross-sectional in-vivo study was to assess bone geometry, volumetric BMD (vBMD), microarchitecture and estimated bone strength in adult patients with HR using high-resolution peripheral quantitative computed tomography (HR-pQCT). Twenty-nine patients (aged 19 to 79 years; 21 female, 8 male patients), 26 of whom had genetically proven X-linked HR, were matched with respect to age and sex with 29 healthy subjects. Eleven patients were currently receiving therapy with calcitriol and phosphate for a median duration of 29.1 years (12.0 to 43.0 years). Due to the disproportionate short-stature in HR, the region of interest in HR-pQCT images at the distal radius and tibia were placed in a constant proportion to the entire length of the bone in both patients and healthy volunteers. In age and weight adjusted models, HR patients had a significantly higher total bone cross-sectional areas (radius 36%, tibia 20%; both p < 0.001) with significantly higher trabecular bone areas (radius 49%, tibia 14%; both p < 0.001) compared with controls. In addition, HR patients had lower total vBMD (radius -20%, tibia -14%; both p < 0.01), cortical vBMD (radius -5%, p < 0.001), trabecular number (radius -13%, tibia -14%; both p < 0.01) and cortical thickness (radius -19%; p < 0.01) compared with controls, while trabecular spacing (radius 18%, tibia 23%; p < 0.01) and trabecular network inhomogeneity (radius 29%, tibia 40%; both p < 0.01) were higher. Estimated bone strength was similar between the groups. In conclusion, in patients with HR, the negative impact of lower vBMD and trabecular number on bone strength seems to be compensated by an increase in bone diameter resulting in HR patients having normal estimates of bone strength. © 2014 American Society for Bone and Mineral Research.
- Low serum level of 1,25(OH)2 D is associated with chronic periodontitis. [JOURNAL ARTICLE]
- J Periodontal Res 2014 Jul 7.
Vitamin D has been studied primarily for its involvement in calcium and phosphate absorption and bone metabolism. The active form of vitamin D-1,25(OH)2 D-has also been investigated for its immune modulatory properties. We explored associations between serum levels of 25(OH)D and 1,25(OH)2 D and periodontal health.This case-control study included 55 subjects with chronic periodontitis (cases) and 30 periodontally healthy subjects (controls). Their serum levels of 25(OH)D, 1,25(OH)2 D, ultrasensitive C-reactive protein and high-density lipoprotein cholesterol were determined. Associations between vitamin D and periodontal health status were studied using logistic regression analysis.A statistically significant association was found between serum 1,25(OH)2 D level and periodontal health status; in that subjects with a low 1,25(OH)2 D were more likely to belong to the periodontitis group (OR = 0.97, 95% CI = 0.95-1.00). There was practically no association between 25(OH)D level and periodontal health status.In this case-control study low serum 1,25(OH)2 D level appeared to be associated with periodontitis, which was in line with the previously reported associations between serum 1,25(OH)2 D levels and other inflammatory diseases. Whether this association is causal in nature, remains to be confirmed in future studies.
- During the pre-dialysis stage of chronic kidney disease, which treatment is associated with better survival in dialysis? [JOURNAL ARTICLE]
- Nefrologia 2014 Jul 14; 34(4):469-476.
Introduction: Specialised care of patients in advanced stages of chronic kidney disease (CKD) is associated with better survival in dialysis, but it is not known which treatments specifically favour this outcome. Objectives: To analyse normal treatment in advanced stages of CKD and establish which treatments are associated with better survival in dialysis as well as their relationship with causes of death. Material and method: Cohort, prospective observational study of 591 patients who started dialysis (491 haemodialysis and 100 peritoneal dialysis), who had previously been monitored in the CKD clinic. The treatments analysed were: antihypertensive treatments, statins, antiplatelet drugs, xanthine oxidase inhibitors, correction of metabolic acidosis, treatment with (calcium or non-calcium) phosphate binders, vitamin D (calcitriol or paricalcitol), erythropoietin and the availability of an internal arteriovenous fistula (IAVF). The independent association of each of these treatments with mortality in dialysis was analysed using Cox regression models adjusted for age, sex, pre-dialysis monitoring time, renal function at the start of dialysis, comorbidity, serum albumin and C-reactive protein, and with stratification of the type of dialysis. Results: With a median follow-up period of 28 months, the total number of patients who died was 191 (32%). In the multivariate models, we observed that, in addition to age, the comorbidity index, serum albumin, pre-dialysis treatment with angiotensin-converting-enzyme inhibitors and/or angiotensin receptor blockers, correction of acidosis with sodium bicarbonate and IAVF at the start of haemodialysis were significantly associated with better survival in dialysis. We did not observe differences in causes of death between the different treatments analysed. Conclusion: These results suggest a potential delayed benefit of some treatments in pre-dialysis stages on the outcome of dialysis. Furthermore, beginning dialysis without an IAVF, resulting in the need for intravenous catheters, worsens prognosis in these patients.
- The Role of Iex-1 in the Pathogenesis of Venous Neointimal Hyperplasia Associated with Hemodialysis Arteriovenous Fistula. [JOURNAL ARTICLE]
- PLoS One 2014; 9(7):e102542.
Arteriovenous fistulas (AVFs) used for hemodialysis fail because of venous neointimal hyperplasia (VNH). There are 1,500,000 patients that have end stage renal disease worldwide and the majority requires hemodialysis. In the present study, the role of the intermediate early response gene X-1 (IEX-1), also known as IER-3 in the pathogenesis of VNH was evaluated. In human samples removed from failed AVF, there was a significant increase in IEX-1 expression localized to the adventitia. In Iex-1-/- mice and wild type (WT) controls, chronic kidney disease was induced and an AVF placed 28 days later by connecting the carotid artery to jugular vein. The outflow vein was removed three days following the creation of the AVF and gene expression analysis demonstrated a significant decrease in vascular endothelial growth factor-A (Vegf-A) and monocyte chemoattractant protein-1 (Mcp-1) gene expression in Iex-1-/- mice when compared to WT mice (P<0.05). At 28 days after AVF placement, histomorphometric and immune-histochemical analyses of the outflow vein demonstrated a significant decrease in neointimal hyperplasia with an increase in average lumen vessel area associated with a decrease in fibroblast, myofibroblast, and Ly6C staining. There was a decrease in proliferation (Ki-67) and an increase in the TUNEL staining in Iex-1 KO mice compared to WT. In addition, there was a decrease in Vegf-A, Mcp-1, and matrix metalloproteiniase-9 (Mmp-9) staining. Iex-1 expression was reduced in vivo and in vitro using nanoparticles coated with calcitriol, an inhibitor of Iex-1 that demonstrated that Iex-1 reduction results in decrease in Vegf-A. In aggregate, these results indicate that the absence of IEX-1 gene results in reduced VNH accompanied with a decrease in proliferation, reduced fibroblast, myofibroblast, and Ly6C staining accompanied with increased apoptosis mediated through a reduction in Vegf-A/Mcp-1 axis and Mmp-9. Adventitial delivery of nanoparticles coated with calcitriol reduced Iex-1 and VNH.