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.

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.

Effect of prolactin and estrogen on the serum level of 1,25-dihydroxy vitamin D and FGF23 in female rats.

INTRODUCTION: Estrogen and prolactin affect vitamin D metabolism. In conditions such as pregnancy and lactation, their interaction in regulating vitamin D metabolism and circulating FGF23 is not clearly defined. The aim of this study is to investigate this interaction in female rats. METHOD: This study was performed on 50 female adult rats, which were divided into five groups of Sham, ovariectomized rats (O), and three groups of ovariectomized rats were indicated with prolactin alone (OP), estradiol alone (OE), and a combination of estradiol and prolactin (OEP). Serum levels of 25(OH)D, 1,25(OH)2D3, FGF23, PTH, vitamin D-binding protein, calcium, and phosphorous were evaluated. RESULTS: Serum 1,25(OH)2D3 and PTH in OE were higher than the O group (P < 0.001 and P = 0.003, respectively). Serum FGF23 in the OE group was lower than the O group (P = 0.016). Serum 1,25(OH)2D3 increased in OP compared to the O group (P < 0.001) and OE group (P < 0.001). Serum FGF23 in OP was lower than the O group (P = 0.04). Furthermore, combining estradiol and prolactin showed no extra effect on increasing serum 1,25(OH)2D3. Serum 1,25(OH)2D3 was positively correlated with serum prolactin levels (r = 0.318, P = 0.017) in all five groups. CONCLUSION: It is suggested that estradiol could increase 1,25(OH)2D3 by elevating PTH and decreasing serum FGF23; however, prolactin was able to increase 1,25(OH)2D3 by lowering serum FGF23. Moreover, prolactin was shown to be more potent in augmenting serum 1,25(OH)2D3 than estrogen itself, which is important in maternal and fetal calcium supply during late pregnancy and lactation.

Human herpesvirus 6A active infection in patients with autoimmune Hashimoto's thyroiditis

ABSTRACT Background: Hypothyroidism due to Hashimoto's thyroiditis (HT) is the commonest autoimmune endocrine illness in which antibodies against thyroid organ result in inflammation. The disease has a complex etiology that involves genetic and environmental influences. Viral infections may be involved in triggering of the disease as their molecular mimicry enhance autoimmune responses. Human herpesvirus-6 (HHV-6) is recognized for its contribution to some autoimmune diseases. Objective: In the current study, the prevalence of HHV-6 active infection in patients with HT and with non-autoimmune thyroid disorders were compared with patients with euthyroidism. In addition, a correlation between presence of HHV-6 infections and HT was investigated. Methods: A total of 151 patients with clinically and laboratory confirmed HT, 59 patients with non-autoimmune thyroid disorders, and 32 patients with normal thyroid function were included in the study. For further confirmation of HT disease, all the precipitants were tested for anti-thyroid peroxidase (TPO), and anti-thyroglobulin (TG) antibodies. For detection of both HHV-6 types A and B, nested PCR and restriction enzyme digestion were used. HHV-6 DNA positive samples were further investigated by DNA sequencing analysis. Results: HHV-6A DNA was found in serum sample of 57 out of 151 patients (38%) with HT, which was significantly more often than in patients with non-autoimmune thyroid disorders (p = 0.001). However, HHV-6 DNA was not detected in serum samples of euthyroid subjects. Conclusions: The results support a possible role for active HHV-6A infection, demonstrated by the presence of HHV-6 DNA in sera, in the development of HT.

Effect of different iron chelation regimens on bone mass in transfusion-dependent thalassemia patients.

Objectives: Iron overload might lead to bone loss in transfusion-dependent beta-thalassemia (TDT) patients. To investigate the role of iron chelation therapy (ICT) on bone mineral density (BMD) of TDT patients suffering from iron overload, the authors compared the efficacy of five different iron chelation regimens through assessing serum ferritin and BMD.Methods: In 256 consecutive TDT patients, BMD was measured by dual-energy X-ray absorptiometry in lumbar spine and femoral neck regions. Treatment outcome of five iron chelation regimens including Deferoxamine (DFO), Deferiprone (DFP), Deferasirox (DFX), and combination therapy was evaluated to compare the mean differences of serum ferritin and BMD indices pre- and post-treatment during 12-months follow-up period.Results: No significant difference was observed in DXA characteristics and serum ferritin level changes between ICT groups, but combination of DFO and DFX had the best outcome in improving bone mass through assessing each group individually.Conclusion: Combination therapy with DFX and DFO had the highest impact on reducing serum ferritin, however insignificant, and improving bone loss in both lumbar spine and femoral neck in comparison with other regimens. A randomized prospective clinical trial is advised to accurately assess the efficacy of iron chelation regimens on BMD measurements of TDT patients.

The Effect of Aromatherapy by Lavender Oil on Infant Vaccination Pain: a Double Blind Randomized Controlled Trial.

Introduction: Exposure to noxious stimuli can cause pain in infants. This study was conducted to evaluate the effects of the lavender oil inhalation on the pain resulting from the pentavalent vaccination. Methods: This clinical trial consisted of two groups: the lavender oil group with 42 infants and the placebo group with 57 infants. The healthy infants without congenital abnormalities in need of pentavalent vaccine also participated in our study. The infants started the lavender oil or placebo aromatherapy one minute before injection. The pain was assessed three times, using the Neonatal Infant pain Scale (NIPS): before vaccination, 15 s, and 5 min after vaccination. Also, the duration of crying was measured in both groups. Results: At baseline, the two groups were similar in relation to the NIPS scores. While, after 5 minutes, the NIPS score was significantly lower in the lavender group. Based on the repeated measures analysis, the NIPS score changed over time totally. However, the two groups were significantly different in relation to the NIPS score over time. The duration of crying was 75.47 (60.675) second in the lavender group and 105.22 (75.739) s in the control group. The statistical test showed a significant difference between the two groups. Conclusion: A low concentration of the lavender oil inhalation can reduce the pain and improve soothing in the infants with the pentavalent vaccine injection.

The effect of prolactin itself and in combination with estrogen on bone mineral density in female rats.

Estrogen deficiency induced by hyperprolactinemia can reduce bone mineral density. Hyperprolactinemia through other mechanisms other than estrogen deficiency, with direct effect on the bone might cause bone loss in women. The present study evaluated the effect of prolactin itself and in combination with estrogen on bone mineral density of female rats. This study was performed on 50 adult female rats divided into five groups; included (a) Sham, (b) Ovariectomized rats; and (c-e) included ovariectomized rats were given prolactin alone, prolactin + estradiol and estradiol, respectively. Bone mineral density (BMD) and vitamin D metabolism parameters were checked in all groups before and after the study. There was no significant difference in baseline values of these parameters. Estradiol could increase 1,25(OH)2D3 and PTH levels and decrease serum ALP level. In addition, Prolactin could increase serum 1,25(OH)2D3 and ALP levels and decrease tibia BMD significantly without any change in PTH level. Combination of estradiol and prolactin could increase serum 1,25(OH)2D3 and PTH and tibia BMD compared with OVX group. Combination of estradiol and prolactin could significantly increase tibia BMD, in ovariectomized rats. We hypothesized that this combination could improve bone loss secondary to hyperprolactinemia by elevated PTH.

An ICET-A survey on occult and emerging endocrine complications in patients with ß-thalassemia major: Conclusions and recommendations.

In adult thalassemia major (TM) patients, a number of occult and emerging endocrine complications, such as: central hypothyroidism (CH), thyroid cancer, latent hypocortisolism, and growth hormone deficiency (GHD) have emerged and been reported. As the early detection of these complications is essential for appropriate treatment and follow-up, the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) promoted a survey on these complications in adult TM patients, among physicians (pediatricians, hematologists and endocrinologists) caring for TM patients in different countries. The data reported by 15 countries are presented.The commonest endocrine complications registered in 3.114 TM adults are CH and GHD (4.6 % and 3.0 %, respectively), followed by latent hypocortisolism (1.2%). In 13 patients (0.41%) a cytological papillary or follicular thyroid carcinoma was diagnosed in 11 and 2 patients, respectively, and a lobectomy or thyroidectomy was carried out. Of 202 TM patients below the age of 18 years, the  reported endocrine complications were: GHD in 4.5%, latent hypocortisolism in 4.4% and central hypothyrodisim in 0.5%. Transition phase was an area of interest for many clinicians, especially as patients with complex chronic health conditions are responding to new treatments extending their lifespan beyond imagination.. In conclusion, our survey provides a better understanding of  physicians' current clinical practices and beliefs in the detection, prevention and treatment of some endocrine complications prevailing in adult TM patients. Regular surveillance, early diagnosis, treatment and follow-up in a multi-disciplinary specialized setting are recommended.

Investigating the bone mineral density in children with solid tumors in southern Iran: a case-control study.

Along with increasing childhood cancer survival, there is increasing concern about its chronic complications. We showed that 20.5 and 45.9% of children with solid tumors in southern Iran had low bone mass for chronological age in lumbar and femoral area, which was associated with serum ferritin and hemoglobin. 52.4% of these children had vitamin D deficiency, as well. PURPOSE/INTRODUCTION: Along with increasing the childhood cancer survival, there is increasing concern about the chronic complications of the disease and the related therapies. This study aims to compare the vitamin D status and bone mineral apparent density (BMAD) of these children with healthy ones and assess some possible associated factors. METHOD: This case-control study enrolled 50 children with solid tumors and their age- and sex-matched controls. Dual-energy X-ray absorptiometry was used to assess bone mineral density. Body mass index, puberty, physical activity, sun exposure, and biochemical data were assessed. RESULTS: 52.4% of children with solid tumors had vitamin D deficiency, and there was no significant difference between the prevalence of vitamin D deficiency in patients and controls (P = 0.285). The prevalence of low bone mass for chronological age in lumbar area was 20.5 and 12.5% in patients and controls, respectively (P = 0.399). Lumbar spine BMD was associated with hemoglobin level (r = 0.468, P = 0.049), while low bone mass in femoral neck was associated with serum ferritin (859 ± 1037 in low bone mass vs. 178 ± 264 in without low bone mass, P = 0.039). CONCLUSION: Vitamin D deficiency and low bone mass are prevalent among Iranian children with solid tumors. Future studies are warranted to investigate the best strategies to prevent and treat vitamin D deficiency and low bone mass in children surviving cancer.

Bone mineral density in children with acute leukemia and its associated factors in Iran: a case-control study.

Acute leukemia is the most common malignancy in children. We showed that low bone mass is prevalent among children with leukemia, especially in femur. Serum calcium, exercise, chemotherapy protocol, and radiotherapy are the main contributing factors. We suggest that early diagnosis and treatment of this problem could improve bone health in them. INTRODUCTION: Acute leukemia is the most common malignancy in children and has been reported to be associated with low bone mass. Due to lack of sufficient data about the bone mineral density of children with leukemia in the Middle East, and inconsistencies between possible associated factors contributing to decreasing bone density in these children, we aimed to conduct a case-control study in Iran. MATERIALS AND METHODS: This case-control study was conducted on 60 children with acute leukemia and 60 age- and sex-matched healthy controls. Anthropometric data, sun exposure, puberty, physical activity, and mineral biochemical parameters were assessed. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA). Data analysis was done by SPSS software v. 21. RESULTS: Serum calcium was higher in the control group (P = 0.012) while serum phosphorous, alkaline phosphatase, and serum 25(OH)D3 were higher in children with leukemia with P values of 0.04, 0.002, and 0.036, respectively. Sun exposure and physical activity were more in healthy controls (P values <0.001 and 0.003, respectively). Prevalence of vitamin D deficiency in case and control groups was 57.8 and 79.4 %, respectively. This prevalence was higher in healthy controls (P value = 0.007). Both lumbar and femoral neck bone mineral apparent density (BMAD) were higher in the control group (P value <0.001). Serum calcium, physical activity, and radiotherapy were the most relevant factors associated with lumbar BMAD. Femoral neck BMAD was associated with chemotherapy protocol. CONCLUSION: Low bone mass for chronological age is prevalent among children with leukemia, especially in the femoral neck. Serum calcium, physical activity, chemotherapy protocol, and radiotherapy are the main contributing factors.

DIAGNOSTIC ACCURACY OF UREA BREATH TEST FOR HELICOBACTER PYLORI INFECTION IN CHILDREN WITH DYSPEPSIA IN COMPARISON TO HISTOPATHOLOGY.

BACKGROUND: Helicobacter pylori infection is the gram negative bacillus with the close association with chronic antral gastritis. OBJECTIVE: In this study, we evaluate the accuracy of urea breath test (UBT) with carbon isotope 13 in comparison with histopathology of gastric antrum for detection of H. pylori infection in children with dyspepsia. METHODS: This cross-sectional study was performed at specialized laboratory of Shiraz Gastroenterohepatology Research Center and Nemazee Hospital, Iran, during a 12-months period. This study investigated the sensitivity, specificity, and positive and negative predictive values of UBT in comparison with biopsy-based tests. We included a consecutive selection of 60 children who fulfilled Rome III criteria for dyspepsia. All children were referred for performing UBT with carbon isotope 13 (C13) as well as endoscopy. Biopsies were taken from antrum of stomach and duodenum. The pathologic diagnosis was considered as the standard test. RESULTS: The mean age of the participants was 10.1±2.6 (range 7-17 years). From our total 60 patients, 28 (46.7%) had positive UBT results and 32 (53.3%) had negative UBT results. Pathologic report of 16 (57.1%) out of 28 patients who had positive UBT were positive for H. pylori and 12 (42.9%) ones were negative. Sensitivity and specificity of C13-UBT for detection of H. pylori infection were 76.2% and 69.2% respectively. CONCLUSION: Sensitivity and specificity of C13-UBT for detection of H. pylori infection were 76.2% and 69.2% respectively. Another multicenter study from our country is recommended.

Diagnostic accuracy of urea breath test for helicobacter pylori infection in children with dyspepsia in comparison to histopathology

ABSTRACT Background - Helicobacter pylori infection is the gram negative bacillus with the close association with chronic antral gastritis. Objective - In this study, we evaluate the accuracy of urea breath test (UBT) with carbon isotope 13 in comparison with histopathology of gastric antrum for detection of H. pylori infection in children with dyspepsia. Methods - This cross-sectional study was performed at specialized laboratory of Shiraz Gastroenterohepatology Research Center and Nemazee Hospital, Iran, during a 12-months period. This study investigated the sensitivity, specificity, and positive and negative predictive values of UBT in comparison with biopsy-based tests. We included a consecutive selection of 60 children who fulfilled Rome III criteria for dyspepsia. All children were referred for performing UBT with carbon isotope 13 (C13) as well as endoscopy. Biopsies were taken from antrum of stomach and duodenum. The pathologic diagnosis was considered as the standard test. Results - The mean age of the participants was 10.1±2.6 (range 7-17 years). From our total 60 patients, 28 (46.7%) had positive UBT results and 32 (53.3%) had negative UBT results. Pathologic report of 16 (57.1%) out of 28 patients who had positive UBT were positive for H. pylori and 12 (42.9%) ones were negative. Sensitivity and specificity of C13-UBT for detection of H. pylori infection were 76.2% and 69.2% respectively. Conclusion - Sensitivity and specificity of C13-UBT for detection of H. pylori infection were 76.2% and 69.2% respectively. Another multicenter study from our country is recommended.

RESUMO Contexto - A infecção por Helicobacter pylori, bacilo gram negativo, tem estreita associação com gastrite antral crônica. Objetivo - Neste estudo, avaliou-se a precisão do teste respiratório da urease (UBT) com isótopos de carbono 13 em comparação com a histopatologia do antro gástrico para detecção da infecção por H. pylori em crianças com dispepsia. Métodos - Estudo transversal realizado no laboratório especializado no Centro de Pesquisa Gastroenterológica de Shiraz e do Hospital de Nemazee, Iran, durante um período de 12 meses. Este estudo investigou a sensibilidade, a especificidade e valores preditivos positivos e negativos da UBT em comparação com testes baseados em biópsia. Incluímos uma seleção consecutiva de 60 crianças que preencheram os critérios de Roma III para dispepsia. Todas as crianças foram encaminhadas para a realização de UBT com isótopos de carbono 13 (C13) assim como endoscopia. Biópsias foram tiradas do antro do estômago e duodeno. O diagnóstico patológico era considerado o teste padrão. Resultados - A idade média dos participantes foi 10.1±2.6 (intervalo de 7 a 17 anos). Do nosso total de 60 pacientes, 28 (46,7%) tiveram resultados positivos UBT e 32 (53,3%) tiveram resultados negativos de UBT. Dezesseis (57,1%) de 28 pacientes que tiveram UBT positiva foram H. pylori positivo e 12 (42,9%) foram negativos. A sensibilidade e especificidade do C13-UBT para detecção da infecção por H. pylori foi de 76,2% e 69,2%, respectivamente. Conclusão - A sensibilidade e especificidade do C13-UBT para detecção da infecção por H. pylori foi de 76,2% e 69,2%, respectivamente. Recomenda-se outro estudo multicêntrico de nosso país.

Diffuse hepatic calcifications in a transfusion-dependent patient with Beta-thalassemia: a case report.

Hepatic calcification is usually associated with infectious, vascular, or neoplastic processes in the liver. We report the first case of beta-thalassemia major with isolated diffuse hepatic calcification in a 23 year old woman, who had been transfusion-dependent since the age of 6 months. She was referred to our center with a chief complaint of abdominal pain. Computed tomography scan of the abdomen revealed diffuse hepatic calcification in the right, left, and caudate lobes of the liver. Her medical history disclosed hypoparathyroidism as well as chronic hepatitis C virus infection, which was successfully treated but led to early micronodular cirrhosis on liver biopsy. Other studies done to search for the cause of hepatic calcification failed to reveal any abnormalities. We suspect that hypoparathyroidism caused liver calcification, and should be, therefore, considered in the differential diagnosis of hepatic calcification if other causative factors have been ruled out.

Prevalence of celiac disease in patients with type 1 diabetes mellitus in the south of Iran.

BACKGROUND/AIMS: Celiac disease is a chronic enteropathy caused by hypersensitivity to gluten. An increased prevalence of celiac disease has been found in children with diabetes mellitus type 1. The large differences in the frequency of celiac disease in different countries show a great regional variability. Our aim was to detect the prevalence of celiac disease in diabetes mellitus type 1 children among southern Iranians. MATERIALS AND METHODS: A prospective study was conducted on 83 diabetes mellitus type 1 children from the south of Iran. They were tested for the presence of anti-tissue transglutaminase immunoglobulin A antibody and total immunoglobulin A level. The patients testing immunoglobulin A anti-tissue transglutaminase-positive were offered small bowel biopsy. RESULTS: Eighty-three children with diabetes mellitus type 1 (49 females, 34 males) aged 10.38±4.7 years were enrolled. None of the patients was immunoglobulin A deficient. Twelve diabetic children had a high titer of anti-tissue transglutaminase immunoglobulin A (14.4%). In four patients, biopsy was in favor of celiac disease (4.8%). CONCLUSIONS: Our study showed that the prevalence of celiac disease in diabetes mellitus type 1 children in Iran is more than in America and Europe but similar to that observed in Turkey. The age of the patient and duration of disease had an effect on this prevalence, and more studies should be done to determine the effects of ethnic, genetic and environmental factors such as diet to identify the reasons for these differences.

Clinical and genetic features in patients with cystic fibrosis in southwestern iran.

OBJECTIVE: Cystic fibrosis (CF) is a common autosomal recessive genetic disease caused by a mutation in the CF transmembrane conductance regulatory (CFTR) gene. This study attempted to identify the most common CFTR mutations and any correlations between certain mutations and the clinical presentation of the disease in CF patients in southwestern Iran. METHODS: Twenty nine common CFTR gene mutations were examined in 45 CF patients. FINDINGS: Chronic cough, intestinal obstruction, dehydration, heat exhaustion and steatorrhea were the most common early clinical symptoms among our patients. The most common mutation was ΔF508, with an allele frequency of 21%. The homozygous ΔF508 mutation was observed in eight patients (18%), and three patients (7%) were ΔF508 carriers. The 2183AA > G mutation was observed in four patients, one of whom was also a ΔF508 carrier. The R1162X mutation was detected in two patients. The G542X, R334W and N1303K mutations were detected each in one patient, the first of whom was also a ΔF508 carrier. CONCLUSION: Out of 45 patients, 27 (60%) had none of the CFTR gene mutations we tested for. The most frequent mutations in southwestern Iranian patients with CF should be identified by sequencing the entire CFTR gene in order to optimize the design of a diagnostic kit for common regional mutations.

The side effects of gonadotropin releasing hormone analog (diphereline) in treatment of idiopathic central precocious puberty.

Treatment of central precocious puberty (CPP) is the administration of GnRH analogs. Metabolic syndrome comprised metabolic disturbances that confer increased risk of (CVD) diabetes mellitus (DM) and cardiovascular disease. This study is a longitudinal prospective study in pediatric endocrinology clinic. 30 non-obese children with idiopathic CPP were involved. Total body weight, height, blood pressure, BMI and waist circumference of the patients along with their triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), fasting plasma sugar (FPS) were evaluated at the beginning and during 3 and 6 months GnRH analog therapy. All of the patients involved in this study were female with age 9.5±1.02 years. Waist circumference, weight and BMI were 69.3 cm, 37.21 kg, and 19.13 kg/cm(2) before therapy and 72.25 cm, 40.11 kg, and 19.54 kg/m(2) 6 months after therapy respectively. Mean systolic and diastolic blood pressure of the patients before therapy was 96.83 mmHg, 66mmHg and after 6 months therapy was 98.66 mmHg, 89.63 mmHg respectively. Mean TG, LDL, HDL and FPS were 90.06 mg/dl, 91.6 mg/dl, 43.7 mg/dl and 89.6 mg/dl before therapy and 96.4 mg/dl, 93.1 mg/dl, 44.7 mg/dl and 91.36 after 6 months therapy respectively. GnRH analog therapy doesn't cause metabolic syndrome after 3 and 6 month therapy but it may cause hyperlipidemia and central obesity.

Juvenile paget's disease in an Iranian kindred with vitamin D deficiency and novel homozygous TNFRSF11B mutation.

Juvenile Paget's disease (JPD) is a rare heritable osteopathy characterized biochemically by markedly increased serum alkaline phosphatase (ALP) activity emanating from generalized acceleration of skeletal turnover. Affected infants and children typically suffer bone pain and fractures and deformities, become deaf, and have macrocranium. Some who survive to young adult life develop blindness from retinopathy engendered by vascular microcalcification. Most cases of JPD are caused by osteoprotegerin (OPG) deficiency due to homozygous loss-of-function mutations within the TNFRSF11B gene that encodes OPG. We report a 3-year-old Iranian girl with JPD and craniosynostosis who had vitamin D deficiency in infancy. She presented with fractures during the first year-of-life followed by bone deformities, delayed development, failure-to-thrive, and pneumonias. At 1 year-of-age, biochemical studies of serum revealed marked hyperphosphatasemia together with low-normal calcium and low inorganic phosphate and 25-hydroxyvitamin D levels. Several family members in previous generations of this consanguineous kindred may also have had JPD and vitamin D deficiency. Mutation analysis showed homozygosity for a unique missense change (c.130T>C, p.Cys44Arg) in TNFRSF11B that would compromise the cysteine-rich domain of OPG that binds receptor activator of NF-κB ligand (RANKL). Both parents were heterozygous for this mutation. The patient's serum OPG level was extremely low and RANKL level markedly elevated. She responded well to rapid oral vitamin D repletion followed by pamidronate treatment given intravenously. Our patient is the first Iranian reported with JPD. Her novel mutation in TNFRSF11B plus vitamin D deficiency in infancy was associated with severe JPD uniquely complicated by craniosynostosis. Pamidronate treatment with vitamin D sufficiency can be effective therapy for the skeletal disease caused by the OPG deficiency form of JPD.