Therapeutic Role of Punica Granatum (Pomegranate) Seed Oil Extract on Bone Turnover and Resorption Induced in Ovariectomized Rats.

CONTEXT: Postmenopausal osteoporosis is mostly caused by increased bone remodeling resulting from estrogen deficiency. Hormone replacement therapy (HRT) is used to prevent osteoporosis, but it increases the risk for breast cancer, thromboembolism, strokes, and heart attacks. Pomegranate seed oil extract (SOE) is rich in phytoestrogen and antioxidant compounds. OBJECTIVES: To evaluate the therapeutic role of SOE against bone turnover, resorption and osteoporosis induced in ovariectomized rats as a postmenopausal model and comparing the results with those from Generic CycloProgynova drug (D). DESIGN: The study used western albino rats undergo bilaterally ovariectomization as a model for postmenopausal. SETTING: The study took part in a laboratory setting. ANIMALS: Forty female western albino rats (age: 3-4 months) weighing 150-180 gm. MEASUREMENTS: Rats were divided into four groups, 10 rats each; SC-group: Sham control = untreated and unovariectomized rats; OVX-group = ovariectomized rats; (OVX-SOE) and (OVX-D) groups = OVX rats were treated with SOE and D, respectively. Bone markers (BMs) especially osteocalcin (BGP), alkaline phosphatase (ALP), tartarate resistance acid phosphatase (TRAcP), bone weight, bone calcium concentration, serum electrolytes (calcium, sodium and potassium) and serum estradiol (E2) level and histopathological examination of bones were determined. Also lipid profile, uric acid, prothrombin time (INR) and liver and kidney functions were measured to evaluate the adverse effects of SOE and D. RESULTS: In OVX group the activities of ALP and TRAcP and the levels of BGP, serum calcium, sodium and body weight were significantly higher (p≤0.05) than SC-group, while bone calcium concentration, bone mass, serum E2 and potassium level as well as uterus mass were significantly lower (p≤0.05). Also histopathological results revealed that the outer cortical bone became thinner, while the cancellous bone trabeculae lost their normal architecture. Moreover in OVX group lipid profile and uric acid levels were significantly higher (p≤0.05) than SC group, but there were no significant changes (p≤0.05) in INR level, liver and kidney functions. Treatment of OVX rats with SOE or D for 12 weeks improved both the architecture of bones as shown from the histopathological results and BMs, serum electrolytes and E2 levels (p≤0.05) which approached SC-group. Moreover after treatment of OVX rats with SOE the levels of lipid profile and uric acid were improved and approached SC-group, while liver function became significant lower (p≤0.05) than SC-group. Also there were no significant changes (p≤0.05) in kidney functions and INR of (OVX-SOE), OVX and SC groups. In contrast in (OVX-D) group the levels of lipid profile, liver and kidney functions, uric acid and INR were significantly higher (p≤0.05) than those of OVX and SC groups. CONCLUSION: The results of this study show that SOE has therapeutic effects on osteoporosis, while it has no adverse effects on lipid profile, uric acid, liver and kidney functions when compared to HRT. SOE offers a promising alternative in the design of new strategies in nutritional management of age-related bone complications.

Association between type 1, type 2 cytokines, diabetic autoantibodies and 25-hydroxyvitamin D in children with type 1 diabetes.

PURPOSE: Vitamin D may play a role in the pathogenesis of type 1 diabetes (T1D). The aim of the current study was to determine the possible association between 25-hydroxyvitamin D [25(OH)D] levels and circulating levels of type 1 and type 2 cytokines, as well as the pathophysiology of T1D in children. METHODS: A total of 250 T1D patients and 250 sex- and age-matched T1D-free controls were screened for 25(OH)D, hemoglobin A1c (HbA1c), type 1 and type 2 cytokines, C-reactive protein (CRP) and bone mineral metabolism, as well as antibodies against insulin, glutamic acid decarboxylase (anti-GAD 65) and islet cells. RESULTS: Our data showed that the plasma level of 25(OH)D was significantly lower in T1D patients and that there was a significant negative correlation between 25(OH)D levels and HbA1c values. There was a significant association between deficient levels of 25(OH)D and higher levels of cytokines (IFN-γ, TNF-α, IL-6, IL-1ß, IL-4 and IL-10) and CRP. Total blood hemoglobin, the hematocrit percentage, body mass index SDS values, phosphate and magnesium levels were significantly lower in T1D patients than in T1D-free subjects. The levels of parathyroid hormone and alkaline phosphatase were significantly higher in T1D patients. Higher levels of cytokines were significantly associated with deficient levels of 25(OH)D. Moreover, in T1D patients, higher levels of islet antibodies, anti-GAD antibodies and anti-insulin antibodies were significantly associated with deficient levels of 25(OH)D. CONCLUSIONS: In type 1 diabetic children, deficient levels of 25(OH)D are associated with high levels of HbA1c, circulatory cytokines and antibody markers.

SOS1: a new player in the Noonan-like/multiple giant cell lesion syndrome.

Noonan-like/multiple giant cell lesion syndrome is a rare condition with phenotypic overlap with Noonan syndrome (NS) and cherubism. PTPN11 gene mutations were described in several individuals with this phenotype, and it is recently considered as a variant phenotype of NS. Gain-of-function mutations in the SOS1 gene were recently described as the second major cause of NS. Here, we report for the first time the involvement of SOS1 gene in a family with the Noonan-like/multiple giant cell lesion phenotype.