Chronic consumption of fructose in combination with <Emphasis Type="Italic">trans</Emphasis> fatty acids but not with saturated fatty acids induces nonalcoholic steatohepatitis with fibrosis in rats

Purpose

Consumption of Western diet high in fat and fructose has been attributed to the recent epidemic of nonalcoholic fatty liver disease (NAFLD). However, the impact of specific fatty acids on the progression of NAFLD to nonalcoholic steatohepatitis (NASH) is poorly understood. In the present study, we investigated the chronic effects of consumption of fructose in combination with saturated fatty acids (SFA) or trans fatty acids (TFA) on the development of NAFLD.

Methods

Male Sprague–Dawley rats were randomly assigned to six isocaloric starch/high fructose (44% of calories), high fat (39% calories) diet containing either starch–peanut oil, fructose–peanut oil, fructose–palmolein, fructose–clarified butter, fructose–coconut oil or fructose–partially hydrogenated vegetable oil and fed for 24 weeks. Palmolein, clarified butter and coconut oil were used as the source of SFA whereas partially hydrogenated vegetable oil was used as the source of TFA. Peanut oil was used as the reference oil.

Results

Long-term feeding of fructose in combination with SFA or TFA induced hepatic steatosis of similar extent associated with upregulation of stearoyl CoA desaturase-1. In contrast, fructose in combination with TFA induced NASH with fibrosis as evidenced by upregulation of hepatic proinflammatory cytokine and fibrogenic gene expression, increased hepatic oxidative stress and adipocytokine imbalance. Histopathological analysis revealed the presence of NASH with fibrosis. Further, peanut oil prevented the development of NAFLD in fructose-fed rats.

Conclusion

Fructose in combination with TFA caused NASH with fibrosis by inducing oxidative stress and inflammation, whereas, fructose in combination with SFA caused simple steatosis, suggesting that the type of fatty acid is more important for the progression of NAFLD.

     

Burden of ocular morbidities and color blindness among school-attending children in a foothill town of Uttarakhand State

Purpose:To estimate prevalence of common ocular morbidities including color blindness among school-attending children of an urban foothill town of Uttarakhand State in Northern India.Methods:A cross-sectional study was conducted among school-going children of age group 6–16 years of standard I–XII. Schools were selected using population proportionate to the size sampling technique. Detailed ocular examination including color vision and unaided or aided visual acuity for various ocular morbidities was done. Data was entered into MS excel with statistical analysis using SPSS version 23 with significant P value <0.05.Results:In total, 13,492 students (mean age 10.9 ± 2.7 years) with almost equal male to female ratio were screened. Overall prevalence of ocular morbidity was 23.2%, with refractive error (18.5%) on top, followed by color blindness (2.2%). The later was observed more among males (3.0%) as compared to females (1.4%) with significantly higher odds, OR = 2.3 (1.7–2.9) (P < 0.001).Conclusion:Refractive error has been the most common ocular morbidity, followed by color blindness. Earliest detection can prevent permanent disability and disappointment among youngsters when rejected from entering certain professions due to color vision defect.     

A district-based audit of the causes and circumstances of maternal deaths in South Kalimantan, Indonesia

A district-based audit of maternal and perinatal mortality began during 1994 in three provinces of South Kalimantan, Indonesia. Both medical and non-medical factors were documented and an effort was made to progress from merely assessing substandard care to recommending improvements in access to care and the quality of care. Extensive discussions of cases of maternal death were held during regular meetings with providers, policy-makers and community members. The sources of information included verbal autopsies with family members and medical records. Between 1995 and 1999 the audit reviewed 130 maternal deaths. The leading causes of death were haemorrhage (41%) and hypertensive diseases (32%). Delays in decision-making and poor quality of care in health facilities were seen as contributory factors in 77% and 60% of the deaths, respectively. Economic constraints were believed to have contributed to 37% of the deaths. The distance between a patient's home and a health provider or facility did not appear to have a significant influence, nor did transport problems. The audit led to changes in the quality of obstetric care in the district. Its success was particularly attributable to the process of accountability of both health providers and policy-makers and to improved working relationships between health providers at different levels and between providers and the community. With a view to the continuation and further expansion of the audit it may be necessary to reconsider the role of the provincial team, the need of health providers for confidentiality, the added benefit of facility-based audits, the need to incorporate scientific evidence into the review process, and the possible consideration of severe complications as well as deaths. It may also be necessary to recognize that village midwives are not solely responsible for maternal deaths.     

Cocoa products decrease low density lipoprotein oxidative susceptibility but do not affect biomarkers of inflammation in humans

Flavonoids and related polyphenolics with antioxidant and anti-inflammatory activities may play a role in the prevention of cardiovascular disease by decreasing oxidative stress and inflammation. We wished to determine the effects of cocoa extract supplementation on markers of oxidative stress and inflammation. Healthy subjects (n = 25) were studied at baseline, after cocoa supplementation (36.9 g of dark chocolate bar and 30.95 g of cocoa powder drink) for 6 wk and after a 6-wk washout period. Fasting blood and early morning urine were collected at the three time points. Two indices of flavonoid intake, total phenols and oxygen radical absorbance capacity of plasma, were measured after an overnight fast. Neither was affected by supplementation. Measures of oxidative stress included copper-catalyzed LDL oxidation kinetics and urinary F(2) isoprostanes. LDL oxidizability was lower after chocolate supplementation as evidenced by a longer lag time (P < 0.05) of conjugated diene formation (101.0 +/- 20.7 min) compared with baseline (91.3 +/- 18.0 min) and washout (96.4 +/- 7.5 min) phases. There was no effect of chocolate on urinary F(2) isoprostane levels or on markers of inflammation including the whole-blood cytokines, interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha, high sensitivity C-reactive protein and P-selectin. In conclusion, cocoa products supplementation in humans affects LDL oxidizability, but not urinary F(2) isoprostanes or markers of inflammation.     

The effects of COX-1 and COX-2 inhibitors on prostaglandin synthesis and the formation of heterotopic bone in a rat model

Introduction Traumatic heterotopic ossification (HO) is a common clinical condition associated with various orthopedic procedures that involve injury to soft tissues near bone. In this study, we tested the hypothesis that the prophylactic effects of NSAID’s in the treatment of HO are mediated via inhibition of the COX-2 enzyme. Here we describe a rat model that simulates HO in the human that was used to test the above hypothesis. Materials and methods Heterotopic ossification was surgically induced in the quadriceps by injury to the muscle and femoral periosteum and transplantation of donor bone marrow cells containing osteoprogenitors into the site of injury. HO was imaged and quantified by micro-CT scanning of femurs removed from sacrificed animals at 6 weeks post-injury, three-dimensional computer reconstructions of the scanned bones and computer-assisted morphometric analysis. Prostaglandin E₂ (PGE₂) synthesis was quantified using an enzyme immunoassay system. The effects of a nonselective COX inhibitor or specific inhibitors of COX-1 or COX-2 following oral administration on the content of ectopic bone and PGE₂ were also measured. Results Micro-CT and histological analyses demonstrated that all of the femurs in operated limbs developed HO in the vastus lateralis muscle belly of the quadriceps close to the anterior femur. Only the COX-1,2 nonselective and COX-2 inhibitors significantly decreased HO formation (by about one-third in each case; P < 0.05). PGE₂ synthesis at the site of injury was increased 50- and 100-fold (to 25 ng/g tissue) within 1 and 7 days, respectively, post-injury with the levels declining to near baseline within 2 weeks of surgery. Both the COX-1,2 nonselective and COX-2 inhibitors significantly decreased PGE₂ levels to 25% of control HO levels within 24 h of the first administration, even at low dosages. The COX-1 inhibitor only produced the same effect after 1 week of administration. Conclusion These findings suggest that although inhibitors of COX-2 or COX-1 reduced PGE₂ synthesis, only the COX-2 enzyme plays a role in the mechanism of traumatic HO.     

Serum magnesium: an early predictor of course and complications of diabetes mellitus

The aim of this study was to evaluate relationship between serum magnesium and course of diabetes mellitus and also to find out, if there is any relation between serum magnesium and various complications of diabetes mellitus. A cross-sectional study was conducted to examine the relationship between serum magnesium in 50 type 1 and type 2 diabetic patients with or without complications and 40 normal healthy persons. Serum magneisum estimation was done using calmagite dye method using autoanalyser (Beckman DU clin systems). Serum magnesium levels in diabetic population was significantly low (1.93 +/- 0.282 meq/l) in comparison to control (2.25 +/- 0.429 meq/l). It was statistically significant (+3.84; p < 0.005). Serum magnesium was significantly low in diabetes with complication than without complications (p < 0.001). Duration of diabetes and serum magnesium were inversely related. Poor glycaemic control was associated with hypomagnesaemia (-2.623; p < 0.05). There was strong association between hypomagnesaemia and retinopathy (1.76 +/- 0.26), obesity (1.878 +/- 0.326) and hypertension (1.75 +/- 0.071) and it was statistically significantly (p < 0.005, 0.042, 0.000 respectively). Hence it is concluded that the change in serum magnesium level may have a bearing on the complication and morbidity in patients of diabetes mellitus.     

One-year-old male with accelerated growth and development

A 1-year-old male child with isosexual central (gonadotropin-dependent) precocious puberty caused by hypothalamic hamartoma is reported. Details of the diagnosis based solely on neuromaging characteristics, and satisfactory results of medical treatment with gonadotropin releasing hormone agonist analogues, are highlighted.     

Differential endocytosis of fluorescein iso-thiocyanate-concanavalin A by normal and chronic myeloid leukemic granulocytes

Summary Isolated granulocytes from normal individuals and patients suffering from chronic myeloid leukemia (CML) displayed different fluorescent patterns on treatment with fluorescein isothiocyanate concanavalin A (Fl-Con A). The ligand was internalized by 86% of the normal granulocytes, while 80% of the leukemic granulocytes exhibited Fl-Con A localized on the cell periphery. In further experiments, pretreatment of the normal granulocytes with cytochalasin B, iodoacetamide, 2-deoxyglucose and sodium fluoride (but not with sodium azide or dinitrophenol) was found to drastically inhibit internalization of the ligand. However, pretreatment of granulocytes from CML patients with cytochalasin B and 2-deoxyglucose, caused only a little alteration in the pattern of Fl-Con A labelling relative to untreated cells. These results indicate that CML granulocytes are defective in their ability to endocytose Fl-Con A. We suggest that this differential interaction between Fl-Con A and normal and leukemic granulocytes is a convenient system to study the initial steps in receptor mediated endocytosis of Concanavalin A.