A Novel cause of Massive Hepatosplenomegaly with Fibrosis in two children: Transient Infantile Hypertriglyceridemia.

Background: Transient infantile hypertriglyceridemia (TIH) is a syndrome of hypertriglyceridemia, fatty liver, and deranged liver functions with progression to fibrosis and cirrhosis. It is an autosomal recessive disorder caused by mutations in Glycerol-3-phosphate dehydrogenase 1 gene present on Chromosome 12q12-q13, and has been reported in Israeli Arab families with high consanguinity. TIH is suspected by high serum triglyceride levels and steatosis on liver biopsy; however, diagnosis is confirmed on clinical exome sequencing. Clinical description: We present two cases of TIH belonging to the indigenous Hindu, hilly population of Himachal Pradesh in North India with no history of either consanguinity or family history. Management and outcome: The parents of both the cases were counselled regarding the disease and importance of growth and lipid level monitoring. Conclusion: Though TIH is an extremely rare entity, awareness about it is required as it is a contributor to non-alcoholic fatty liver disease (NAFLD) in children. Any child presenting with hepatomegaly and elevated fasting triglyceride levels should be further investigated for TIH.

Pathological involvement of apoptotic and inflammatory molecules in cardiovascular remodeling in rats on high fructose diet-induced metabolic syndrome.

Fructose consumption has been linked to manifestation of metabolic syndrome (MS); an emerging epidemic. The current study attempts to demonstrate fructose overconsumption-mediated cardiovascular disease (CVD) remodeling in Wistar rats. Rats were randomly segregated into control (CON) and high fructose diet (FFR) groups and received customized diets for 20 weeks. Levels of diabetic, lipid, antioxidant, markers, mRNA levels of inflammatory, apoptotic markers, and histopathological changes were assessed in excised hearts of both groups. Significant increase in uric acid, pro-oxidants diabetic, lipid, inflammatory markers, cytosolic cytochrome C, nuclear NF-кB-p65, and decrease in antioxidants was observed in FFR group. Abnormal myocardial architecture was observed in the FFR group along with elevated mRNA levels of inflammatory, apoptotic markers, and MMP-9, -2. The outcomes of the study are suggestive of role of aforementioned molecules in high fructose intake-mediated pathological deterioration of heart and development of MS-associated CVD progression. PRACTICAL APPLICATIONS: Excessive fructose consumption in the form of high fructose corn syrup, sugary drinks, and commonly available fast foods has been shown to be linked with many diseases such as liver malfunction, metabolic syndrome diabetes, and cardiovascular diseases. However, delineated pathways and clear mechanisms and their role in cardiovascular remodeling due to excessive fructose consumption are yet to be established. The present study establishes the deleterious effects of foods with high sugar content on progression toward metabolic syndrome and cardiovascular remodeling. It further investigates the role of different pathways involved in the development of high fructose-induced diet-induced metabolic syndrome, and thereby leading to harmful effects on the hearts of rats consuming high fructose diet leading to cardiovascular in Wistar rats. The study suggests the role of immunomodulation and oxidative stress in the remodeling of cardiac muscles and in turn progression toward metabolic syndrome and cardiovascular remodeling. The study, therefore, throws light on the deleterious effects of consumption of foods and easily available fast foods on progression toward numerous non-communicable diseases.

Low serum PON1 activity: an independent risk factor for coronary artery disease in North-West Indian type 2 diabetics.

The paraoxonase (PON1) gene polymorphisms are known to affect the PON1 activity and coronary artery disease (CAD) risk. Studies done so far have given conflicting results. In the present study, we determined the role of PON1 genetic variants and PON1 activity in the development of CAD in North-West Indian Punjabis, a distinct ethnic group, having high incidence of both CAD and type 2 diabetes. 300 angiographically proven CAD with type 2 diabetics and 250 type 2 diabetics with no clinically evident CAD were enrolled. Serum PON1 activity and genotyping of coding (Q192R, L55M) and promoter (-909G/C, -162A/G, -108C/T) region polymorphisms were carried out and haplotypes were determined using PHASE software. The serum PON1 activity was significantly lower in CAD with type 2 diabetics as compared to diabetics alone (51.0 vs. 114.2nmol/min/ml). In logistic regression model after adjusting for confounding variables, lower PON1 activity was found to be significantly associated with CAD risk in type 2 diabetics with OR being 16.8 (95% CI: 10.2-27.7). The lower serum PON1 activity, irrespective of genotypes and haplotypes is a risk factor for development of CAD in North-West Indian Punjabis with type 2 diabetics.