Evaluation of vitamin D deficiency and low bone mass in children with asthma in fars province: A case-control study.

Background and Aims: Asthma is a chronic inflammatory pulmonary disease which affects 10%-20% of children and adolescents. Inhaled corticosteroids (ICS) is one of its most effective therapies. The effect of systemic corticosteroids on decreasing bone mineral density (BMD) was investigated and proved in children; however, the influence of ICSs on bone density has still remained unclear. This study evaluates the bone mineral density of children and adolescents with asthma in southern Iran and the associated factors, for example, amount of used inhaled steroid. Method: This case-control study enrolled 41 children and adolescents (aged 8-18 years) with asthma and their age and gender-matched controls in 2019-2020. Serum Calcium, phosphate, vitamin D, and bone mineral density were measured. Their physical activity, sun exposure, and fracture history were evaluated subjectively. Results: Lumbar BMD and BMD Z-score in patients showed no significant difference with controls (p = 0.23, p = 0.73). Also, it showed that there was no significant difference in biochemical studies, growth, and bone densitometry parameters between patients who used ICSs for less than 3 months/year corticosteroid therapy compared to those with equal or more than 3 months/year usage. Prevalence of vitamin D deficiency was 28% and 8% in the controls and patients, respectively (p = 0.005). Conclusion: The present study showed that 9.46% of children and adolescents with asthma had low bone mass for chronological age, and it is not significantly higher than normal population. Dosage of inhaled steroid did not associate with osteoporosis in these patients. Prevalence of vitamin D deficiency in patients was lower than normal population, probably due to receiving vitamin D in their routine follow-ups.

Vitamin D supplementation affects bone marrow-derived mesenchymal stem cells differentiation into insulin-producing cells.

Background this study was conducted to assess the effects of vitamin D on differentiation of bone marrow- derived mesenchymal stem cells (BM-MSCs) into insulin producing cells (IPCs). Method BM-MSCs were isolated from femur and tibia of rats and incubated in low (LG) or high glucose (HG) (5mM or 25mM), or high glucose DMEM media supplemented with vitamin D (0.2nM) (HGD) for 14 days. Cells viability was analysis by MTT assay. Differentiation of SCs was confirmed using measuring genes expression level of pdx1 and insulin, and insulin secretion, glucose stimulated insulin secretion, and insulin content by ELISA method. Results Cell viability was significantly higher in HGD than LG (p < 0.05) in day 3, also, in HG and HGD than LG (p < 0.001), and HGD vs. HG (p < 0.001) in day 7. Pdx1 and insulin level was markedly higher in HGD than LG (p < 0.05 and p < 0.01). pdx1 expression was markedly higher in HGD (p < 0.05) than LG, also insulin expression the HG (p < 0.05), and HGD (p < 0.01) groups compared to the LG group. Insulin release at 5mM glucose was notably higher in the HGD group compared to LG (p < 0.05), and at 25mM glucose, both HG and HGD showed significant increases vs. LG (p < 0.05 and p < 0.01, respectively). Insulin content was significantly higher in both 5mM and 25mM glucose for HG and HGD vs. LG (p < 0.01 and p < 0.001, respectively). In conclusion, treatment BM-MSCs with vitamin D could increase their differentiation into IPCs and it can be considered as a potential supplementary agent in enhancing differentiation SCs into insulin generating cells.

A prospective guide for clinical implementation of selected OGTT- derived surrogate indices for the evaluation of ß- cell function and insulin sensitivity in patients with transfusion-dependent ß- thalassaemia.

The gold standard for the measurement of insulin secretion is the hyperglycemic clamp and for insulin sensitivity the hyperinsulinemic euglycemic clamp, respectively. A number of surrogate indices, derived from plasma glucose and insulin levels at a fasting state or after oral glucose load, have been proposed to estimate ß-cell response, and the ability of ß-cells to compensate for changes of insulin sensitivity by modulating insulin secretion (disposition index). Starting from the current recommendations for the annual screening of glucose dysregulation in patients with transfusion dependent ß-thalassemia (ß-TDT), this article summarizes the most frequently used indirect indices of insulin secretion and resistance derived from the oral glucose tolerance test (OGTT) and discusses the strengths and weaknesses of selected indices and the basic concepts underlying each method for the appropriate evaluation of glucose regulation. Basal indices for ß-cell function and insulin sensitivity, albeit simple and cheap, have limited usefulness due to a high coefficient variation and the lack of data about response to glucose load. Therefore, measurement of indices during an OGTT, despite being costly and time-consuming, is suggested since it can detect, even subtle, dynamic changes in insulin secretion and glucose handling. In patients with ß-TDT, the indices derived from OGTT may offer an additional factor to evaluate the efficiency of iron chelation therapy and detect patients who may need intensification of iron chelation therapy and/or pharmacological intervention.

Pantoprazole-Induced Bone Loss through Gastrin Secretion: A Stereological Study.

Background: Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the goal of this study was to see if it caused bone loss through gastrin secretion. Methods: Forty male rats were divided into control, octreotide (Oct), pantoprazole (Pan), and pantoprazole plus octreotide (Pan+Oct) groups. Serum calcium, phosphorous, alkaline phosphatase, parathyroid hormone, and gastrin were measured before and three months after the treatment, and bone densitometry was examined. The rats' femoral bones were examined stereologically at the end of the investigation. Results: The Pan group had considerably greater levels of serum alkaline phosphatase, parathyroid hormone (PTH), and gastrin, but this was prevented in the presence of Oct, a gastrin secretion inhibitor. All parameters of femoral bone densitometry in the Pan group were significantly lower than the control after treatment which was considerably inhibited in the presence of Oct. Furthermore, when compared to the control and Oct groups, the rats in the Pan group had a lower trabecular volume, femur bone weight, and volume, as well lower number of osteocytes. The amount of osteoclasts, on the other hand, was much higher in the Pan group than in the other groups. Conclusion: Overall findings revealed that pantoprazole caused bone loss, which could be prevented by adding octreotide. Because these detrimental effects were not detected in rats given both Oct and Pan, it was suggested that the effect of Pan on bone was produced by a hypergastrinemic condition.

New concepts in regulation and function of the FGF23.

In comparison to the regulation of calcium homeostasis, which has been widely studied over the last several decades, phosphate homeostasis is little understood. The parathyroid hormone (PTH)/vitamin D axis has traditionally been used as a conceptual framework for understanding mineral metabolism. Recently, the fundamental regulator of phosphate homeostasis, fibroblast growth factor 23 (FGF23), which is produced by osteocytes and is involved in the hormonal bone-parathyroid-kidney axis, has attracted more attention. The secretion of FGF23 is controlled by diet, serum phosphate levels, PTH, and 1,25(OH)2 vitamin D. FGF-23, the FGF receptors and the obligate co-receptor α-Klotho work in concert to affect FGF-23 actions on targeted organs. Despite all efforts to investigate pleotropic effects of FGF23 in various endocrine organs, many aspects of the regulation and functions of FGF23 and the exact crosstalk among FGF23, serum phosphate, calcium, PTH, and vitamin D in the regulation of mineral homeostasis remain unclear; much efforts need to be established before it can be moved toward therapeutic applications. In this regard, we provide a brief overview of the novel findings in the regulation and function of FGF23 and refer to related questions and hypotheses not answered yet, which can be a window for future projects. We also focus on the current knowledge about the role of FGF23 obtained from our researches in recent years.

Prevalence of Hypothyroidism in Children and Adolescents of Fars Province (Southern Iran): A Nationwide Prescription Study, 2018-2019.

BACKGROUND: Hypothyroidism is the most common hormonal deficiency worldwide; however, there is limited data about its prevalence in the children and adolescents of the Middle East. METHODS: The prevalence of hypothyroidism were calculated by dividing the number of patients purchasing levothyroxine in 1397 Solar-Hijri year (Correlate with March 2018-February 2019) by the population at risk (per 10000 persons). Data were collected from the Iran health insurance organization registration records and family physician databases of health vice-chancellor of Shiraz University of Medical Sciences. RESULTS: The present study shows that the prevalence of levothyroxine treated population aged under 18 years is 13 in 10000 in the Fars province and it is more common in females (17 in 10000 in females versus 9 in 10000 in males). This study also revealed that the prevalence of hypothyroidism was different in various age groups and increased in older children and adolescents after pubertal ages. Also, an increase in the female: male ratio of prevalence was more obvious during and after puberty. CONCLUSION: Our study showed that the prevalence of congenital hypothyroidism was 3/10000 in southern Iran. Also, the prevalence of hypothyroidism in children and adolescents was totally 13/10000 population, and this prevalence increased in older age and female gender. This prevalence was close to the data from iodine sufficient areas in Europe and the United States.

Ellagic acid effects on testis, sex hormones, oxidative stress, and apoptosis in the relative sterility rat model following busulfan administration.

BACKGROUND: Busulfan is an antineoplastic medication that is broadly utilized for cancer treatment. It affects the testicular function and leads to sterility. The present study aimed to evaluate the effects of ellagic acid on testicular tissue changes, sexual hormones, antioxidant defense system, and caspase-9 and Bcl2 gene expression in the busulfan-induced relative sterile rat model. METHODS: This is an interventional-experimental animal study that was performed on 65 Adult male rats; they were randomly divided into five groups including control (1 ml of 0.9% normal saline), ellagic acid (50 mg/kg); busulfan (10 mg/kg); and busulfan plus ellagic acid (10 mg/kg and 50 mg/kg). At the end of the experiment, blood samples were collected, and plasma levels of sex hormones, antioxidant system, apoptosis-related genes, and testis histology were assessed. RESULTS: Busulfan reduced the levels of serum testosterone, total antioxidant capacity, gene expression of Bcl2, testicular volume, seminiferous tubule, germinal epithelium, interstitial tissue volume, and the number of spermatogonia, spermatocyte, round spermatid, elongated spermatid, Sertoli cells and Leydig cells (p < 0.05). Busulfan administration resulted in a significant increase (p < 0.05) in the level of LH, FSH, malondialdehyde, and caspase 9. Busulfan + ellagic acid (50 mg/kg) showed higher serum levels of testosterone, gene expression of Bcl-2 and antioxidant markers, and lower LH, FSH levels, and gene expression of caspase 9 compared to the Busulfan-treated rats (p < 0.05). Stereological parameters were also ameliorated in the group treated with Busulfan+ 50 mg/kg ellagic acid (p < 0.05). CONCLUSION: In conclusion, the consumption of ellagic acid may have beneficial effects on the antioxidant defense system, sexual hormone abnormality, and testicular tissue damage induced by busulfan.

The The use of oral glucose-lowering agents (GLAs) in ß-thalassemia patients with diabetes: Preliminary data from a retrospective study of ICET-A Network.

OBJECTIVE: The management of prediabetes and hyperglycemia is an increasingly important aspect of care in patients with thalassemia. In light of the limited evidence about the management of GD (glucose dysregulation) with glucose-lowering agents (GLAs), we have conducted a retrospective survey in TDT and NTDT patients with diabetes mellitus to collect more detailed information on GLA use in order to make preliminary recommendations. STUDY DESIGN AND METHOD: A questionnaire was prepared and distributed to the tertiary thalassemia care Centers of ICET-A Network. RESULTS: Eight  thalassemia care Centers [Bulgaria, Greece, Iran, Italy (4 Centers) and Qatar], following 1.554 with transfusion-dependent thalassemia (TDT), 132 (8.4%) with diabetes and 687 with non-transfusion-dependent thalassemia (NTDT), 27 (3.9%) with diabetes, participated in the retrospective survey. The records of 117 TDT patients and 9 NTDT patients with diabetes treated with GLAs were analyzed. Metformin, a biguanide, was the most frequently used drug (47.6 %), followed by alpha-glucosidase inhibitors (5.5 %), incretins (4.7%) and insulin secretagogues (3.1%).  In 68 (61.2) patients  GLAs was prescribed as monotherapy, while the remaining  49  (38.8%), who had inadequate glucose control with metformin, were treated with combination treatment. Fifty-one patients  of 126 (40.4%) initially treated with oral GLA, for a mean duration of 61.0 ± 35.6 months (range: 12- 120 months), required insulin therapy for better metabolic control. CONCLUSION: This retrospective study covers an unexplored area of research in patients with thalassemia and GD. Oral GLAs appear to be safe and effective for the treatment of diabetes mellitus in patients with thalassemia, and can achieve adequate glycemic control for a substantial period of time.

Effects of Paricalcitol on Body Composition in Vitamin D-Deficient Rats.

Background: Paricalcitol has been proposed for the treatment of secondary hyperparathyroidism in patients with renal failure and vitamin D deficiency (VDD); however, VDD is related to a range of clinical complaints. We aimed to investigate the effects of paricalcitol on body composition in VDD rats. Methods: Thirty adult male rats aged 10 weeks were randomly divided into three groups of 10, comprising control, VDD, and VDD plus paricalcitol (32 ng/rat intraperitoneal injection) (VDD+P), at the Animal Lab of the Endocrinology and Metabolism Research Center, Shiraz, Iran, in 2020. Body composition was assessed after three weeks via serum biochemical tests and dual-energy X-ray absorptiometry. Finally, the data were analyzed by using the paired-sample t test, the one-way ANOVA, and the Tukey post hoc test. Results: Global lean mass and fat mass were lower in the VDD and VDD+P groups than in the controls (P<0.001). Global fat percentage was reduced significantly in the VDD+P group (P=0.029). Conclusion: Paricalcitol reduced global fat mass and fat percentage in a rat model with VDD. Evaluation of insulin and adiponectin levels is suggested to clarify the physiology of paricalcitol in VDD states.

The Prevalence of glucose dysregulations (GDs) in patients with ß-thalassemias in different countries: A preliminary ICET-A survey.

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Detection of Human Papillomavirus in Papillary Thyroid Carcinoma and its Association with Tumor Staging and Pathologic Features.

Background: The role of human papillomavirus (HPV), as a common infection, has been evaluated in many cancers such as the cervix and squamous cell carcinoma of the head and neck. To the best of our knowledge, for the first time, the association of HPV with papillary thyroid carcinoma (PTC) and its pathologic features are investigated. Methods: A retrospective cross-sectional study was conducted from May 2014 to January 2018 in several hospitals affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. Thyroid tissue specimens of patients diagnosed with PTC (n=82) and benign thyroid nodules (n=77) were collected using the consecutive sampling method. The presence of HPV in PTC, adjacent normal tissue, and benign thyroid nodules was evaluated using the polymerase chain reaction (PCR) method. The frequency of HPV positivity in PTC tissues was compared with benign thyroid nodules and adjacent normal tissue. Association of pathologic features of PTC with HPV positivity was also investigated. Data were analyzed using SPSS version 21.0, and P values less than 0.05 were considered statistically significant. Results: HPV PCR positivity was observed in 3.8% of benign thyroid nodules and 13.4% of PTC samples but in none of the adjacent normal tissues. After adjustment for age and sex, the prevalence of HPV PCR positivity in the PTC tissues was significantly more than the benign thyroid nodules (P=0.015). The prevalence was also significantly higher than the adjacent normal tissues (P<0.001). Conclusion: There was a significant association between PTC and HPV positivity. Further studies are required to determine the cause and effect of the association between these two conditions.

The effects of L-carnitine on renal function and gene expression of caspase-9 and Bcl-2 in monosodium glutamate-induced rats.

BACKGROUND: Monosodium glutamate (MSG) is frequently consumed as a flavor enhancer or food additive. Possible damages induced by MSG effects on some organs have been stated in experimental animal models. The aim of the present study was to evaluate the protective effects of L-carnitine (L-ca) on the renal tissue in MSG-Induced Rats. METHODS: In this regard, 60 male rats were randomly divided into six groups (n = 10/each): 1 (Control); 2 (sham); 3 (L-carnitine 200 mg/kg b.w); 4 (MSG 3 g/kg b.w); 5 (MSG + L-carnitine 100 mg/kg); and 6 (MSG + L-carnitine 200 mg/kg). After 6 months, the rats were sacrificed, the blood sample collected and the kidneys harvested for evaluation of biochemical analytes, genes expression, and histopathological changes. RESULTS: MSG significantly increased the serum level of MDA, BUN, creatinine, uric acid and renal Caspase-9, NGAL and KIM-1 expression, but it decreased the serum activity also renal expression of SOD, catalase, GPX, and Bcl-2 expression compared to the control group. Treatment with L-ca significantly reduced the serum BUN, creatinine, uric acid and MDA level and increased catalase, GPX and SOD compared to the MSG group. However, only administration of L-ca 200 significantly decreased the caspase-9, NGAL and KIM-1; also, it increased the Bcl-2 expression in the kidney compared to the MSG group. CONCLUSIONS: Our findings indicated that L-carnitine had a major impact on the cell protection and might be an effective therapy in ameliorating the complications of the kidney induced by MSG via its antioxidant and anti-apoptotic properties.

Bone density, fractures and the associated factors in iranian children and adolescent with Osteogenesis Imperfecta.

BACKROUND: Osteogenesis imperfecta(OI) is a frequent bone fragility disorder in children. The purpose of this study was to assess the BMD and Vitamin D level in children with OI in southern Iran. METHOD: This case-control study was conducted on 23 children, clinically diagnosed as osteogenesis imperfecta and 23 age- and gender-matched healthy controls. Demographic and anthropometric data, biochemical parameters, puberty, sun exposure and physical activity were assessed. Bone mineral density (BMD) was measured by Dual-energy X-ray absorptiometry (DXA). Data analysis was done by SPSS22. RESULTS: Forty-three point four percent of OI patients and fifty-six point five percent of control group had vitamin D deficiency (P = 0.376). Thirteen OI patients (56%) had low bone mass for chronological age in lumbar area (P < 0.001). Fracture episodes during treatment was significantly influenced by time of Pamidronate start, courses of Pamidronate injection, puberty and sun exposure (P values = 0.015, 0.030, 0.044 and 0.032, respectively). Fracture episodes during treatment had significantly increased in patients who had received Pamidronate more than 3 years compared with those received less than 3 years(P values = 0.047). CONCLUSIONS: This study showed that vitamin D deficiency is prevalent amongst OI children in southern Iran. More than half of the OI children had low bone mass for chronological age in lumbar area, despite receiving bisphosphonate therapy. The present results revealed that early initiation of Pamidronate and number of Pamidronate courses are associated with lower fracture rate. However, treatment period more than 3 years can have adverse effect on fracture rates.

Association of vitamin D and FGF23 with serum ferritin in hypoparathyroid thalassemia: a case control study.

BACKGROUND: FGF23 controls serum l,25(OH)2D3 levels and phosphate homeostasis. This study evaluates the effects of ferritin on intact PTH, FGF23, and l,25(OH)2D3 in patients with major thalassemia. It also evaluates FGF23 changes in patients with hypoparathyroidism to clarify the interaction between FGF23 and PTH in the absence of proper PTH functioning in human. METHODS: In this case-control study, 25 major-beta thalassemia patients with hypoparathyroidism were age- and gender-matched with major-beta thalassemia patients having normal parathyroid function. Biochemical studies assessed the serum calcium, albumin, phosphorus, alkaline phosphatase, PTH, FGF23, 25(OH) D, 1,25(OH)2D3, ferritin, and the fractional excretion of phosphorous. RESULTS: FGF23 was higher in the patients with hypoparathyroidism than the controls (P = 0.002). The fractional excretion of phosphorous was lower in patients with hypoparathyroidism, despite the high level of FGF23 (P = 0.001). There was a correlation between serum 1,25(OH)2D3 and FGF23 with ferritin in the controls (P = < 0.001and P = < 0.001, respectively). CONCLUSIONS: The present study showed a strong positive correlation between serum ferritin and levels of FGF23 and 1,25(OH)2D3. We hypothesized that ferritin could have a stimulatory effect on the production of 1,25(OH)2D3. Moreover, a rise in FGF23 in patients with thalassemia, might be either associated with the stimulating effect of PTH and 1,25(OH)2D3, or directly related to the stimulating effect of ferritin.

Stereological assessment of the effects of vitamin D deficiency on the rat testis.

BACKGROUND: Accumulating evidence suggests that low vitamin D status may affect male gonadal structure. This study was undertaken to reveal whether vitamin D-deficient rats have demonstrable changes in the quantitative histomorphometric properties of the testis. METHODS: In the present investigation, adult male Sprague-Dawley rats were divided into four groups and received: group 1) conventional diet; group 2) vitamin D-deficient diet; group 3) vitamin D-deficient diet and paricalcitol and group 4) conventional diet plus paricalcitol. After 3 months, serum levels of vitamin D metabolites, Ca, P, LH, FSH, testosterone, and epididymal sperm quality were evaluated. Moreover, the morphometric characteristics of testis were assessed via stereological methods. RESULTS: Rats fed a vitamin D-deficient diet (groups 2 and 3) were normocalcemic and had 25-hydroxyvitamin D3 level below 10 ng/mL. A significant reduction in serum testosterone and comparable gonadotropin levels were seen in vitamin D-deficient groups compared to controls. The concentration, morphology, and motility of sperm cells were profoundly disturbed in animals raised on the vitamin D-deficient diet. There was a significant decline in the population of different germ cells, the volume of interstitial tissue and germinal epithelium in group 2 and 3 rats, which were placed on the vitamin D-deficient diet. No appreciable difference in the estimates of the Leydig or Sertoli cell numbers were observed between groups. CONCLUSIONS: The depletion of vitamin D stores and induction of moderate grades of vitamin D deficiency by dietary measures led to remarkable impairment of spermatogenesis and microscopic architecture of rat testis. These findings can be attributed, at least in part, to decreased androgen production.

Evaluation of The Metabolic Syndrome Criteria And Body Composition in Ambulatory Children with Epilepsy UsingSodium Valproate and Carbamazepine In Southern Iran: A Case-Control Study.

OBJECTIVES: Previous studies in adults with epilepsy revealed a higher prevalence of metabolic syndrome, resulting in cerebrovascular and cardiovascular events. However, there is insufficient data about body composition and metabolic syndrome in children, especially in the Middle Eastern region. We aimed to investigate metabolic syndrome criteria and body composition in ambulatory children with Epilepsy in Southern Iran. MATERIAL & METHODS: Seventy seven epileptic children with an average age of 11.4 ± 3.2 years and their age-gender-matched controls were included in this study. Anthropometric data, lipid profile, blood glucose, and blood pressure were checked. Body composition was also evaluated by Hologic system dual-energy X-ray absorptiometry. RESULTS: The prevalence of metabolic syndrome as well as the fat mass index in patients were higher than the controls, and p values are 0.032 and 0.012, respectively. Moreover, the lean mass with Bone Mineral Content (BMC) index was detected lower than the controls (P= 0.017).Regarding drugs consumption, serum triglyceride and the blood pressure in patients who receiving carbamazepine was higher than the control individuals with P = 0.019, Beta = 0.379 and P = 0.016, Beta = -0.26, respectively. Fat mass index was also higher in patients using sodium valproate (P = 0.031, Beta = 0.238). CONCLUSION: Our study revealed that children with epilepsy are more prone to metabolic syndrome and higher body fat mass. Therefore, early diagnosis and prevention of metabolic syndrome criteria in patients with epilepsy, With performing regular exercise and having a healthy diet should be encouraged in these children.

Bone mineral density in transfusion-dependent thalassemia patients and its associated factors in Southern Iran.

Despite the significant improvements in the management of thalassemia, there are growing concerns regarding their long-term complications. We showed that low bone mass is one of the most prevalent complications among these patients. Insufficient physical activity and hypogonadism are the main possible associated factors followed by DM and insufficient sun exposure. PURPOSE: Despite the significant improvements in the management of transfusion-dependent thalassemia (TDT), there are growing concerns regarding their long-term complications. METHODS: This cross-sectional study included 615 TDT patients who were registered and followed in a comprehensive thalassemia clinic in Southern Iran. We measured serum biochemical tests and bone mineral density in all patients. We recorded physical activity and sun exposure subjectively, and an endocrinologist visited and examined all the patients. A group of age- and gender-matched healthy volunteers participated in the study as the control group. RESULTS: The mean age of the studied population was 28.4 ± 7.7 years, and 55.8% were female. The prevalence of vitamin D deficiency was 45.6% and 54.4% in TDT patients and the control group. A portion of TDT patients suffered from different endocrinopathies, which included hypogonadism (49.8%), diabetes mellitus (17.2%), hypoparathyroidism (14.6%), and hypothyroidism (6.3%). The prevalence of low bone mass in patients with TDT was 48.3 and 74.6% in the femoral and lumbar bones, respectively. Low physical activity, insufficient sun exposure, diabetes mellitus, and hypogonadism were associated with low bone mass. CONCLUSION: Low bone mass is highly prevalent among TDT patients in Southern Iran. Insufficient physical activity and hypogonadism are the main possible associated factors, followed by DM and insufficient sun exposure.

The effect of human wharton's jelly-derived mesenchymal stem cells on MC4R, NPY, and LEPR gene expression levels in rats with streptozotocin-induced diabetes.

OBJECTIVES: Type 1 diabetes (T1D) is an autoimmune disease resulting from inflammatory destruction of islets ß-cells. Nowadays, progress in cell therapy, especially mesenchymal stem cells (MSCs) proposes numerous potential remedies for T1D. We aimed to investigate the combination therapeutic effect of these cells with insulin and metformin on neuropeptide Y, melanocortin-4 receptor, and leptin receptor genes expression in TID. MATERIALS AND METHODS: One hundreds male rats were randomly divided into seven groups: the control, diabetes, insulin (Ins.), insulin+metformin (Ins.Met.), Wharton's Jelly-derived MSCs (WJ-MSCs), insulin+metformin+WJ-MSCs (Ins.Met.MSCs), and insulin+WJ-MSCs (Ins.MSCs). Treatment was performed from the first day after diagnosis as diabetes. Groups of the recipient WJ-MSCs were intraportally injected with 2× 106 MSCs/kg at the 7th and 28th days of study. Fasting blood sugar was monitored and tissues and genes analysis were performed. RESULTS: The blood glucose levels were slightly decreased in all treatment groups within 20th and 45th days compared to the diabetic group. The C-peptide level enhanced in these groups compared to the diabetic group, but this increment in Ins.MSCs group on the 45th days was higher than other groups. The expression level of melanocortin-4 receptor and leptin receptor genes meaningfully up-regulated in the treatment groups, while the expression of neuropeptide Y significantly down-regulated in the treatment group on both times of study. CONCLUSION: Our data exhibit that infusion of MSCs and its combination therapy with insulin might ameliorate diabetes signs by changing the amount of leptin and subsequent changes in the expression of neuropeptide Y and melanocortin-4 receptor.

Interaction between serum FGF-23 and PTH in renal phosphate excretion, a case-control study in hypoparathyroid patients.

BACKGROUND: phosphate homeostasis is mediated through complex counter regulatory feed-back balance between parathyroid hormone, FGF-23 and 1,25(OH)2D. Both parathyroid hormone and FGF-23 regulate proximal tubular phosphate excretion through signaling on sodium- phosphate cotransporters IIa and IIc. However, the interaction between these hormones on phosphate excretion is not clearly understood. We performed the present study to evaluate whether the existence of sufficient parathyroid hormone is necessary for full phosphaturic function of FGF-23 or not. METHODS: In this case-control study, 19 patients with hypoparathyroidism and their age- and gender-matched normal population were enrolled. Serum calcium, phosphate, alkaline phosphatase,parathyroid hormone, FGF-23, 25(OH)D, 1,25(OH)2D and Fractional excretion of phosphorous were assessed and compared between the two groups, using SPSS software. RESULTS: The mean serum calcium and parathyroid hormone level was significantly lower in hypoparathyroid patients in comparison with the control group (P < 0.001 and P < 0.001, respectively). We found high serum level of phosphate and FGF-23 in hypoparathyroid patients compared to the control group (P < 0.001 and P < 0.001, respectively). However, there was no significant difference in Fractional excretion of phosphorous or 1,25OH2D level between the two groups. There was a positive correlation between serum FGF-23 and Fractional excretion of phosphorous just in the normal individuals (P < 0.001, r = 0.79). CONCLUSIONS: Although the FGF-23 is a main regulator of urinary phosphate excretion but the existence of sufficient parathyroid hormone is necessary for the full phosphaturic effect of FGF-23.

Clinical manifestations and associated disorders in children with celiac disease in southern Iran.

BACKGROUND: Celiac disease (CD) is an immune mediated inflammatory enteropathy, triggered by gluten exposure in HLA-DQ2 and/or -DQ8 genetics. The presentation of celiac disease in children is changing, with increase in non-classical symptoms. We aim to evaluate the clinical presentations of celiac disease amongst children, diagnosed with CD. METHODS: In this cross sectional study, we investigated the clinical features of 130 celiac patients at hospitals affiliated with Shiraz University of Medical Sciences. We used their hospital charts and conducted an interview with patients and their parents to find out demographic data, symptoms, laboratory, and histopathology findings for Marsh grading. RESULTS: Celiac disease was detected more amongst females (63.8%). We found that 5.4% of the patients had BMI more than 95th percentile. The most common GI symptoms were abdominal pain, flatulence and constipation. Also, the most common extra intestinal manifestation included bone pain, long term fatigue and anemia. Flatulence, chronic diarrhea, and paresthesia were observed more amongst male participants. The most common comorbidities were type 1 diabetes mellitus and hypothyroidism. CONCLUSION: The most common gastrointestinal symptoms amongst our patients were abdominal pain, flatulence and constipation. Furthermore, the most common extra intestinal manifestations included bone pain, long term fatigue and anemia. The most associated comorbidities with CD in our children were type 1 diabetes mellitus and hypothyroidism.