Vitamin D Intoxication and Nephrocalcinosis in a Young Breastfed Infant.

Numerous studies were performed assessing the benefits and side effects of vitamin D. Vitamin D helps in regulating the calcium and phosphate metabolism leading to a healthy mineral and bone development. Vitamin D intoxication is an uncommon event that leads to hypercalcemia which can be associated with both immediate and late morbidities that can cause severe renal complications. Here, we present a case of a 4-month-old girl with a history of decreased feed and activity due hypercalcemia and high vitamin D level, which led to nephrocalcinosis. The patient received IV fluids, IV diuretics, methylprednisolone, and bisphosphonate in order to normalize the calcium level in blood. With clear verbal and written instructions for the dosage and administration of vitamin D supplements, as well as clear warnings of the potential risks of overdose, vitamin D intoxication could be an easily avoidable condition.

Phytanic acid attenuates insulin-like growth factor-1 activity via nitric oxide-mediated γ-secretase activation in rat aortic smooth muscle cells: possible implications for pathogenesis of infantile Refsum disease.

BACKGROUND: Infantile Refsum disease (IRD), a peroxisomal disease with defective phytanic acid oxidation, causes neurological impairment and development delay. Insulin-like growth factor-1 (IGF-1) regulates child development and to understand molecular mechanism(s) of IRD, we examined the effect of phytanic acid (PA) on IGF-1 activity. METHODS: Bromodeoxyuridine (BrdU) incorporation was measured in rat aortic smooth muscle cell (SMC) cultures following treatment with fetal bovine serum (FBS), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) or IGF-1 in the absence or presence of PA. Gene expression and protein contents of IGF-1 receptor (IGF-1R) and PDGF receptor (PDGFR) were examined using quantitative PCR and western blotting. RESULTS: PA inhibited mitogenic activities of FBS, PDGF and IGF-1 with more pronounced effect on IGF-1-induced bromodeoxyuridine (BrdU) incorporation. Palmitic acid or lignoceric acids did not inhibit IGF-1 activity. PA had no effect on PDGFR mRNA/protein levels but markedly increased IGF-1R mRNA levels. PA and nitric oxide (NO) markedly decreased IGF-1R protein. L-NAME, a NO synthase inhibitor and DAPT, a γ-secretase inhibitor, alleviated PA-induced decrease in IGF-1R protein. Both PA and NO donor increased γ-secretase activity which was alleviated by L-NAME. CONCLUSION: This study demonstrates that PA attenuates IGF-1 activity possibly through IGF-1R impairment and NO-mediated modulation of γ-secretase activity.

Phytanic acid activates NADPH oxidase through transactivation of epidermal growth factor receptor in vascular smooth muscle cells.

BACKGROUND: Phytanic acid (PA) has been implicated in development of cancer and its defective metabolism is known to cause life-threatening conditions, such as Refsum disease, in children. To explore molecular mechanisms of phytanic acid-induced cellular pathology, we investigated its effect on NADPH oxidase (NOX) and epidermal growth factor receptor (EGFR) in rat aortic smooth muscle cells (RASMC). METHODS: Smooth muscle cells were isolated from rat aortae using enzymic digestion with collagenase and elastase. Cultured RASMC were treated with varying concentrations (0.5-10 µg/ml) of phytanic acid in the presence/absence of fetal bovine serum (FBS) and/or EGFR inhibitor, AG1478. Following treatment with experimental agents, NOX activity was assayed in RASMC cultures by luminescence method. Gene expression of NOX-1 and p47phox was assessed using RT-PCR. NOX-1, p47phox and, total EGFR protein and its phosphorylated form were measured by Western blotting. RESULTS: Treatment of RASMC with supraphysiological concentrations (>2.5 µg/ml) of PA significantly (p < 0.01) increased the NOX activity. PA also significantly increased gene/protein expression of NOX-1 and p47phox whereas p22phox and p67phox remained unaffected. Interestingly, PA (2.5-10 µg/ml) markedly (2-3 folds) increased the total and phosphorylated EGFR. Treatment of cells with EGFR inhibitor, AG1478, significantly blocked the PA-induced enhancement of NOX activity. CONCLUSIONS: Our findings that PA transactivates EGFR and induces NOX activity in vascular smooth muscle cells provide new insights into molecular mechanisms of PA's role in cancer and Refsum disease.

Prevalence of type 2 diabetes mellitus among Kuwaiti children and adolescents.

OBJECTIVES: To determine the prevalence of type 2 diabetes among 6- to 18-year-old Kuwaiti children. SUBJECTS AND METHODS: Children with type 2 diabetes were identified at 182 schools (50 primary, 63 intermediate, and 69 secondary) randomly selected using the 2000/2001 educational districts' registers as a sampling frame. Prevalence rates were adjusted to the 2002 Kuwaiti population. Diagnosis of type 2 diabetes was based on the World Health Organization and the American Diabetes Association criteria. RESULTS: Type 2 diabetes was identified in 45 of the 128,918 children surveyed, thereby giving an overall prevalence of 34.9 per 100,000 [95% confidence interval (CI) 24.7-45.1]. There was a significant difference in prevalence between males (47.3, 95% CI 28.7-65.8) and females (26.3, 95% CI 14.8-37.8) at p = 0.05 and a significant trend for an increase in prevalence of type 2 diabetes with age (p = 0.026). The overall age-adjusted prevalence rate in the 2002 Kuwaiti population was 33.2 (95% CI 26.6-39.9), 41.6 (95% CI 31.2-52.0) in male and 24.6 (95% CI 16.4-32.7) in female children; the difference was significant at p = 0.013. There was no significant difference in prevalence between regions. Children with type 2 diabetes had a significantly higher frequency (51.1%) of a positive family history of diabetes than children of a similar age without type 2 diabetes (22.2%) (p = 0.004). CONCLUSION: The prevalence of type 2 diabetes in adult Kuwaitis is spreading to children and adolescents, making it an emergency public health problem. Efforts need to be initiated to address prevention strategies of type 2 diabetes in youth.

Prevalence of type 1 diabetes among 6- to 18-year-old Kuwaiti children.

OBJECTIVES: To determine the prevalence of type 1 diabetes among 6- to 18-year-old Kuwaiti children according to gender, age, and region. SUBJECTS AND METHODS: Children with type 1 diabetes aged 6-18 years were identified at 182 schools (50 primary, 63 intermediate, and 69 secondary) in Kuwait during the study period October 2000 to September 2002. Schools were randomly selected using the 2000/01 educational districts' registers as sampling frame proportional to the number of schools in each district. Prevalence rates were adjusted to the 2002 Kuwaiti population. Diagnosis of type 1 diabetes was based on the World Health Organization, and the American Diabetes Association criteria. RESULTS: Prevalence of type 1 diabetes was 269.9 per 100,000 (95% confidence interval, CI 241.6-298.3). There was no significant difference in prevalence between male (247.6, 95% CI 205.2-290.0) and female (285.5, 95% CI 247.5-323.5). Type 1 diabetes was more prevalent in the age group 10-13 years (347.3), and lowest in the age group 6-9 years (182.6) per 100,000; the difference was significant at p < 0.001. The overall age-adjusted prevalence rate was 252.9 (95% CI 234.6-271.2), 229.1 (95% CI 204.6-253.6) in male and 277.4 (95% CI 250.0-304.7) in female children in the 2002 Kuwaiti population. The mean age at onset was 9.2, and 8.1 years in male and female children, respectively (p = 0.018). There was no significant difference in prevalence between regions. CONCLUSION: Type 1 diabetes is a common chronic disease in Kuwaiti children.

Association of serum sialic acid with cardiovascular metabolic risk factors in Kuwaiti children and adolescents with type 1 diabetes.

The aim of the present study was to investigate the relation of serum total sialic acid (TSA) concentrations with cardiovascular metabolic risk factors in Kuwaiti children and adolescents with uncomplicated type 1 diabetes. This case-control study included 150 (57 males and 93 females) type 1 diabetic children aged 6 to 18 years matched by age and sex to 150 nondiabetic children as controls. Measured variables included weight, height, systolic, diastolic blood pressure, and biochemical variables: blood glucose, glycated hemoglobin (HbA(1C)), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), apolipoproteins (apo) A1 and B, and urine microalbumin. There was no significant difference between mean serum TSA of the type 1 diabetic children (671.0 mg/L) and their controls (663.7 mg/L). In diabetic children, mean serum TSA was significantly higher in females (699.1 mg/L) than in males (625.2 mg/L) (P =.003). Significant correlations were found between serum TSA and the cardiovascular risk factors TC (P =.002), TG (P <.001), and apo B (P =.008). TSA mean level was significantly higher in diabetic children with poor glycemic control (HbA(1C) > 9.0%; P =.015), raised TC (P =.013), raised TG (P =.014), and in children with family history of cardiovascular disease (CVD; P =.02). In conclusion, the study suggests that serum TSA levels were not elevated in young type 1 diabetic children as compared with controls. The study also confirmed significant correlation of TSA concentrations with CVD risk factors TC, TG, and apo B, and as such serum TSA may be considered as a marker for CVD risk, especially in diabetic patients. A long-term prospective study is recommended to ascertain the longitudinal relationship of serum TSA with the adverse metabolic changes in type 1 diabetic children as complications prevail.