Sleep duration, physical activity, and caloric intake are related to weight status in Mexican American children: a longitudinal analysis.

BACKGROUND: Obesity is a serious issue, spanning all ages, and, in the U.S., disproportionately affects Latinos and African Americans. Understanding sleep, physical activity and dietary behaviors that may predict childhood obesity can help identify behavioral intervention targets. METHODS: Data were drawn from a U.S. cohort study of 323 Mexican American 8-10-year-old children and their mothers, who participated in a longitudinal study over a 2-year period. Measures were collected at baseline (BL; child mean age = 8.87, SD = 0.83), year 1 (FU1) and year 2 (FU2). Mothers reported on household income and acculturation at BL. Child height and weight were collected and BMI z-scores (BMIz) were calculated for weight status at BL, FU1, and FU2. Accelerometer-estimated sleep duration (hours) and moderate-to-vigorous physical activity (MVPA; minutes) were collected across 3 days at BL, FU1, and FU2. Two 24-h dietary recalls were performed at each time point; from these, average energy intake (EI, kcals/day) was estimated. Cross-lagged panel analysis was used to examine behavioral predictors on BMIz at each time point and across time. RESULTS: At BL and FU1, longer sleep duration (ß = - 0.22, p < 0.001; ß = - 0.17, p < 0.05, respectively) and greater MVPA (ß = - 0.13, p < 0.05; ß = - 0.20, p < 0.01, respectively) were concurrently related to lower BMIz. At FU2, longer sleep duration (ß = - 0.18, p < 0.01) was concurrently related to lower BMIz, whereas greater EI (ß = 0.16, p < 0.01) was related to higher BMIz. Longer sleep duration at BL predicted lower BMIz at FU1 (ß = - 0.05, p < 0.01). CONCLUSIONS: Longer sleep duration was concurrently related to lower weight status at each time point from ages 8-10 to 10-12. Higher MVPA was concurrently related to lower weight status in earlier childhood (ages 8-10 and 9-11) and higher EI was concurrently related to higher weight status toward the end of childhood (ages 10-12 years). Furthermore, longer sleep in earlier childhood was protective of children's lower weight status 1 year later. These findings suggest that sleep duration plays a consistent and protective role against childhood obesity; in addition, MVPA and healthy EI remain important independent factors for obtaining a healthy weight.

Temporal associations between circadian sleep and activity patterns in Mexican American children.

OBJECTIVE: This study aimed to examine the relationship between circadian sleep and activity behaviors (sedentary time [SED], light-intensity physical activity [LPA], and moderate- to vigorous-intensity physical activity [MVPA]) across 3 consecutive days. METHODS: This study included 308 Mexican American children aged 8-10 years from the San Francisco Bay Area. Minutes of sleep duration, SED, LPA, and MVPA were estimated using hip-worn accelerometers from Wednesday night to Saturday night. A cross-lagged panel model was used to estimate paths between sleep duration the prior night and subsequent behaviors, and paths between behaviors to subsequent sleep duration across the 3 days. We adjusted for child age, sex, body mass index, and household income. RESULTS: Overall, children were 8.9 (SD 0.8) years old; the weighted average for weekday and weekend combined was 9.6 (SD 0.7) hours per night in sleep duration, 483 (SD 74) min/d SED, 288 (SD 61) min/d LPA, and 63 (SD 38) min/d MVPA. Cross-lagged panel analyses showed that, over 3 days, for every 1-hour increase in sleep duration, there were an expected 0.66-hour (40-minute) decrease in SED, 0.37-hour (22-minute) decrease in LPA, and 0.06-hour (4-minute) decrease in MVPA. For every 1-hour increase in LPA, there was an expected 0.25-hour (15-minute) decrease in sleep duration. CONCLUSION: An additional hour of sleep the night before corresponded to an hour decrease in combined SED and LPA the next day in Mexican American children. For every hour of LPA, there was an associated 15-minute decrease in sleep. Encouraging longer sleep may help to reduce SED and LPA, and help offset LPA's negative predictive effect on sleep.

Predicting the development of liver cirrhosis by simple modelling in patients with chronic hepatitis C.

BACKGROUND: Data are scarce on the natural history of chronic hepatitis C (CHC) in patients with mild hepatitis C who did not respond to anti-viral therapy. AIM: To predict the risk of progression to cirrhosis, identifying patients with the more urgent need for therapy with effective anti-virals. METHODS: A cohort of 1289 noncirrhotic CHC patients treated with interferon-based therapy between 1990 and 2004 in two referral hospitals were followed up for a median of 12 years. RESULTS: Overall, SVR was achieved in 46.6% of patients. Data from a randomly split sample (n = 832) was used to estimate a model to predict outcomes. Among nonresponders (n = 444), cirrhosis developed in 123 (28%) patients. In this group, the 3, 5 and 10-year cumulative probabilities of cirrhosis were 4%, 7% and 22%, respectively, compared to <1% in the SVR-group (P < 0.05). Baseline factors independently associated with progression to cirrhosis in nonresponders were: fibrosis ≥F2, age >40 years, AST >100 IU/L, GGT >40 IU/L. Three logistic regression models that combined these simple variables were highly accurate in predicting the individual risk of developing cirrhosis with areas under the receiving operating characteristic curves (AUC) at 5, 7 and 10 years of ~0.80. The reproducibility of the models in the validation cohort (n = 457, nonresponders = 244), was consistently high. CONCLUSIONS: Modelling based on simple laboratory and clinical data can accurately identify the individual risk of progression to cirrhosis in nonresponder patients with chronic hepatitis C, becoming a very helpful tool to prioritise the start of oral anti-viral therapy in clinical practice.

Satiety responsiveness and eating behavior among Chilean adolescents and the role of breastfeeding.

OBJECTIVE: To determine patterns of satiety responsiveness and its relationship to eating in the absence of hunger (EAH), in a cohort of adolescents. We also assessed whether sex, body mass index and duration of breastfeeding, during infancy, predicted satiety responsiveness and eating behavior at 16 years. METHODS: Adolescents (n=576) from a longitudinal cohort, which began as an iron deficiency anemia preventive trial, participated in an unlimited breakfast after an overnight fast, and reported satiety response on a visual analog scale after the meal, followed by an EAH procedure. Height, weight and body composition were measured before breakfast. Latent profile analysis generated profiles that captured individual differences in satiety responsiveness. Multivariable regressions, adjusted for potential confounders, evaluated the association between: (1) satiety responsiveness and EAH, and (2) breastfeeding in infancy, satiety responsiveness and EAH in adolescence. RESULTS: Participants were on average 16.7-year old, 48% female, 37% overweight/obese and 76% were breastfed as the sole source of milk for <6 months. We found three latent profiles of satiety responsiveness: 1: 'responsive' (49%); 2: 'not responsive' (41%); 3: 'still hungry' (10%). Participants in the 'not responsive' or 'still hungry' profile were more likely to eat during the EAH procedure (odds ratio (OR)=2.5, 95% confidence interval (CI)=1.8-3.6). Being breastfed for <6 months was related to higher odds of being in the 'not responsive' or 'still hungry' profile (OR=1.8, 95% CI=1.2-2.6) and EAH (OR=2.2, 95% CI=1.4-3.3). Satiety responsiveness was not influenced by sex and overweight/obesity. CONCLUSION: After an ad libitum meal, we found varied satiety responses, which related to EAH. Furthermore, shorter breastfeeding duration was associated with poorer satiety response and higher consumption during an EAH procedure. Understanding if breastfeeding influences the development of satiety responsiveness and eating behavior may be important in an era characterized by abundant calorie-dense foods and a plethora of environmental cues promoting consumption.

Progressive histopathological changes and ß-cell loss in the pancreas of a new spontaneous rat model of type 2 diabetes.

The eSMT rat is a new spontaneous model of type 2 diabetes that develops a progressive diabetic syndrome with a stronger incidence in males than in females. We decide to investigate the progression of the pancreatic histopathological changes during the lifespan of the eSMT rat, especially those associated with islet cell populations. Besides that, some plasmatic parameters were evaluated in order to correlate them with the morphological findings. Male eSMT and Sprague-Dawley control rats were used. The results showed a dramatic decrease of the volume density (VD) of endocrine tissue in the eSMT rats without evidence of insulitis. Islets became fragmented structures with strong presence of interstitial fibrosis. Consequently, plasma insulin levels showed a significant decrease, while plasma glucose, cholesterol and triglyceride levels were increased. Normal rats showed no significant changes in the VD of endocrine tissue, except for the older animals, where the VD of ß-cell population was increased. Early derangements observed in islets, together with the progressive decrease of endocrine tissue and the metabolic disorders described, would be responsible for an irreversible pathologic condition which avoids the animal survival beyond about 18 months of age. However, there is still a need to investigate the causes of endocrine tissue decrease and its possible association with an inflammatory process that it could be associated with the development and progression of fibrosis.

Donor and recipient IL28B polymorphisms in HCV-infected patients undergoing antiviral therapy before and after liver transplantation.

IL28B gene polymorphisms are associated with the response to antiviral therapy in hepatitis C patients. We investigated the influence of IL28B polymorphisms on the response to therapy before and after liver transplantation (LT). Genotyping of SNPs rs8099917 and rs12979860 was performed in 128 HCV-infected liver transplant recipients and in their donors; all patients underwent antiviral treatment after LT. The prevalence of genotypes rs12979860CC and rs8099917TT was higher in donors than in recipients (50% vs.19%, p < 0.001 and 67% vs. 38%, p < 0.001, respectively). Response to antiviral therapy was significantly higher for recipient genotype rs12979860CC as compared to rs12979860CT/TT both before (100% vs. 48% p = 0.013) and after LT (59% vs. 25% p = 0.002). The figures were almost identical for SNP rs8099917. Sustained virological response after LT was particularly high in patients with favorable recipient and donor genotypes (p < 0.01 for both SNPs). In a subgroup of 34 patients treated while awaiting LT, a favorable donor IL28B genotype was associated with an improved virological response after LT. Our results support a major role of recipient IL28B genotype in the response to antiviral treatment for hepatitis C recurrence. Interestingly, donor genotype also seems to influence the response pattern, especially in recipients who have a favorable IL28B genotype.

Assessment of liver fibrosis before and after antiviral therapy by different serum marker panels in patients with chronic hepatitis C.

BACKGROUND: Liver biopsy is the reference standard to assess liver fibrosis in chronic hepatitis C. AIM: To validate and compare the diagnostic performance of non-invasive tests for prediction of liver fibrosis severity and assessed changes in extracellular matrix markers after antiviral treatment. METHODS: The performances of Forns' score, AST to platelet ratio index (APRI), FIB-4 index and Enhanced Liver Fibrosis (ELF) score were validated in 340 patients who underwent antiviral therapy. These scores were determined 24 weeks after treatment in 161 patients. RESULTS: Forns' score, APRI, FIB-4 and ELF score showed comparable diagnostic accuracies for significant fibrosis [area under the receiver operating characteristic curve (AUROC) 0.83, 0.83, 0.85 and 0.81, respectively]. To identify cirrhosis, FIB-4 index showed a significantly better performance over APRI and ELF score (AUROC 0.89 vs. 0.83 and 0.82, respectively). ELF score decreased significantly in patients with sustained virological response (SVR) (P < 0.0001) but remained unchanged in nonresponders. Non-1 hepatitis C virus (HCV) genotype, baseline lower HCV RNA, glucose, hyaluronic acid and higher cholesterol levels were independently associated with SVR. CONCLUSIONS: Simple panel markers and ELF score are accurate at identifying significant fibrosis and cirrhosis in chronic hepatitis C. A decrease in ELF score after antiviral treatment reflects the impact of viral clearance in hepatic extracellular matrix and probably in the improvement of liver fibrosis.

Apoptotic volume decrease as a geometric determinant for cell dismantling into apoptotic bodies.

Apoptosis is a mode of cell death through which cells are dismantled and cell remains are packed into small, membrane-bound, sealed vesicles called apoptotic bodies, which are easy to erase by phagocytosis by neighbouring and immune system cells. The end point of the process is to cleanly eliminate damaged or unnecessary cells without disrupting the surrounding tissue or eliciting an inflammatory response. The apoptotic process involves a series of specific events including deoxyribonucleic acid and nuclear fragmentation, protease-driven cleavage of specific substrates, which inhibits key survival functions and reorganizes the cell's structure, externalization of molecules involved in phagocytosis, membrane blebbing and cell shrinkage. Apoptotic volume decrease (AVD) leading to cell shrinkage is a core event in the course of apoptosis, the biological meaning of which has not been clearly ascertained. In this article we argue that volume loss is a geometrical requisite for cell dismantling into apoptotic bodies. This is derived from the cell's volume-to-surface ratio. Indeed, package of the original cell volume into smaller membrane-sealed vesicles requires that either cell membrane surface increase or cell volume decrease. In this sense, AVD provides a reservoir of membrane surface for apoptotic body formation. The strategic situation of AVD in the time course of apoptosis is also discussed in the context of apoptotic body formation.

Treatment of neurocysticercosis: current status and future research needs.

Here we put forward a roadmap that summarizes important questions that need to be answered to determine more effective and safer treatments. A key concept in management of neurocysticercosis is the understanding that infection and disease due to neurocysticercosis are variable and thus different clinical approaches and treatments are required. Despite recent advances, treatments remain either suboptimal or based on poorly controlled or anecdotal experience. A better understanding of basic pathophysiologic mechanisms including parasite survival and evolution, nature of the inflammatory response, and the genesis of seizures, epilepsy, and mechanisms of anthelmintic action should lead to improved therapies.

Prospective histopathological analysis of hepatocellular carcinoma treated with percutaneous ethanol injection in patients on the waiting list for liver transplantation.

INTRODUCTION: Liver transplantation (LT) improves survival in selected patients suffering from hepatocellular carcinoma (HCC). Unfortunately, the long time lapse between indication and LT may cause tumor progression. Thus, percutaneous ethanol injection (PEI) has been proposed as adjuvant therapy of HCC in patients awaiting LT. The efficacy of PEI assessed using histopathological analysis of hepatectomy specimens has not been adequately evaluated. PATIENTS AND METHODS: Twenty-nine nodules of HCC in 27 patients (21 men; mean age, 58.1 +/- 7.3 years) listed for LT were treated with PEI. Pretreatment mean serum alpha-fetoprotein (AFP) was 11 +/- 13.4 ng/mL. Mean tumor diameter was 30.8 +/- 12.9 mm. Data from the explanted livers after transplantation included percentage tumor necrosis, presence of satellite and distant nodules, vascular invasion, tumor capsule, and grade of differentiation. RESULTS: Nineteen patients with 20 treated lesions underwent transplantation. The median interval PEI-LT was 3 months. Complete necrosis was observed in 13 nodules (65%). Satellite nodules were present in 10% of lesions. Previously unrecognized distant lesions were seen in 15.8% of patients. Only 1 nodule presented microscopic vascular invasion. Most HCC were well differentiated (90%), and completely encapsulated (80%). No tumor-related deaths occurred. Seventeen patients are alive and recurrence-free after a median follow-up of 15 months. CONCLUSIONS: PEI may achieve significant necrosis in cases of HCC awaiting LT. Nevertheless, previously unrecognized satellite and distant lesions may be observed. Further studies are needed to evaluate the influence of tumor necrosis on overall survival of these patients.

Doppler ultrasonography for the assessment of tumor necrosis after percutaneous ethanol injection prior to liver transplantation as adjuvant therapy of hepatocellular carcinoma.

INTRODUCTION: Percutaneous ethanol injection (PEI) is considered to be a curative treatment for hepatocellular carcinoma (HCC). The imaging technique of choice for the assessment of local response after PEI has not been well defined, but helical computerized tomography (hCT) has been recommended. The aim of this study was to assess the accuracy of Doppler ultrasonography (US) for evaluation of tumor necrosis after PEI. PATIENTS AND METHODS: Twenty-one patients with single HCC listed for liver transplantation underwent multisession US-guided PEI. Liver Doppler US was done at the 4th week after PEI. Complete response was defined as the absence of any intratumoral Doppler signal. The liver was analyzed in transplant recipients during the follow-up. Complete pathological response was defined as necrosis > or = 90% of total tumor volume. Histological and sonographic findings were compared. RESULTS: Twelve patients underwent transplantation (9 men, mean age 60 +/- 5.2 years). Nine of these (75%) showed a complete ultrasonographic response. In the explanted liver, complete necrosis was present in 6 nodules, and incomplete necrosis was seen in the remaining 6 cases. In comparison with histology, Doppler US showed values of sensitivity, specificity, positive predictive values, and negative predictive values of 50%, 100%, 100%, and 60%, respectively. Overall accuracy was 75%. CONCLUSIONS: In our series, Doppler US showed low sensitivity but high specificity in the assessment of HCC necrosis after PEI. The ultrasonographic finding of complete response requires hCT for confirmation, but the presence in Doppler US of neoplastic viable tissue is enough to indicate a further cycle of PEI.

Safety of percutaneous ethanol injection as neoadjuvant therapy for hepatocellular carcinoma in waiting list liver transplant candidates.

UNLABELLED: Orthotopic liver transplantation (OLT) as therapy of hepatocellular carcinoma (HCC) improves the survival of a selected group of patients. Unfortunately, the progressive increase in waiting time for OLT may allow tumor progression. Percutaneous ethanol injection (PEI) has been proposed as neoadjuvant therapy for HCC in patients awaiting OLT, but its safety has not been defined. PATIENTS AND METHODS: During a 60-month period, 34 patients (27 men, overall mean age of 58.5 years, range 41-67) with HCC, were listed for OLT. Ultrasonography-guided PEI was delivered into 39 nodules at 117 sessions on an inpatient basis. Written informed consent was obtained from all patients before PEI. Doppler-ultrasonography was done before PEI, immediately after, and 4 weeks later. Noninvasive monitoring of arterial pressure, cardiac rate, and temperature was performed during the procedure and during a 24-hour period after each session. Pain was considered significant if analgesia was required or discontinuation of PEI necessary. Fever was defined as a temperature > or =37.5 degrees C after PEI. RESULTS: Minor complications included pain in 45 sessions (38.5%), fever in 17 (14.5%), arterial hypertension in 14 (12%), hypotension in 7 (7%), and vomiting in 2 (1.7%). The major complications were segmental liver infarction (n = 3), portal branch venous thrombosis (n = 2), ascites (n = 2), and one case each of subcapsular hematoma, duodenal ulcer, pneumonia, hepatic encephalopathy, and hepatic artery thrombosis. In all cases, clinical outcomes were favorable with conservative treatment. No evidence of tumor seeding in the needle track was reported and no PEI-related mortality observed. CONCLUSIONS: PEI is a safe neoadjuvant therapy for HCC on waiting list liver transplant candidates. In our series, pain and self-limited fever were the most frequent complications. Clinically significant severe complications were uncommon, and nonconservative treatments were not required.

Azithromycin prophylaxis during a hospitalwide outbreak of a pertussis-like illness.

A questionnaire regarding tolerability and adherence was administered for 5 days to hospital employees who received azithromycin prophylaxis during a hospitalwide outbreak of a pertussis-like illness. Analysis of the 239 responses from those having received prophylactic azithromycin determined that it was well tolerated and accounted for a minimal loss of days worked; 81.5% were fully adherent with the regimen.

Onset and evolution of nephropathy in rats with spontaneous diabetes mellitus.

The occurrence of renal diabetic complications was studied in diabetic nonobese IIM/FmeSS (eSS) rats. The results were compared with eumetabolic Wistar rats paired by sex and age. Between 6 and 12 months of age, eSS male rats had higher fructosamine values and glucose intolerance as well as increasing proteinuria and uremia. Enhancement in water, calcium and phosphorus fractional excretion with a concomitant lower sodium excretion, was observed from 12 months of age on. 18- and 21-month-old eSS rats exhibited fasting hyperglycaemia and rising values of fructosamine, glucose intolerance and glycosuria. Simultaneously, a notorious worsening of proteinuria as well as alterations in glomerular filtration were verified. Optic microscopy of 12-month-old eSS rat kidneys showed areas of tubular dilatation with protein cylinders. In 21-month-old eSS animals, kidneys appeared overtly damaged. Increased capsular, glomerular and Henle's thin loop diameters were verified in 12- and 21-month-old eSS rats. Glomeruli showed diffuse hypertrophy of mesangial tissue and thickening of the basement membrane. Areas of markedly atrophic and dilated tubules containing acidophilic proteinaceous material were observed. At age of 21 months, kidneys of eumetabolic Wistar control rats presented foci of interstitial and pielic inflammatory infiltrates.

Serum antigen detection in the diagnosis, treatment, and follow-up of neurocysticercosis patients.

The efficacy of albendazole (ABZ) treatment for human neurocysticercosis (NCC) was assessed by using a monoclonal antibody-based parasite antigen detection ELISA which specifically detects the products of living cysticerci in human serum. The assay displayed 85% diagnostic sensitivity, detecting 39 of 46 NCC cases. Only patients with a single viable cyst or only enhancing lesions (degenerating parasites) were seronegative. Specificity of the assay was 92% (23/25) when tested in healthy Peruvian volunteers. In 'cured' patients, in whom all parasites died after ABZ therapy, parasite antigen levels fell sharply by 3 months post treatment. This pattern was not observed in patients refractory to treatment. The sensitivity of the assay with serum samples, and its ability to identify successfully treated patients, make this monoclonal antibody-based ELISA the test of choice for the follow-up of NCC cases.

A specific antigen-detection ELISA for the diagnosis of human neurocysticercosis. The Cysticercosis Working Group in Peru.

An enzyme-linked immunosorbent assay (ELISA) for the detection of antigen secreted by viable Taenia solium metacestodes (Ag-ELISA) was applied to 43 pre-treatment and 47 follow-up cerebrospinal fluid (CSF) samples from Peruvian patients with neurocysticercosis demonstrated by computed tomography and enzyme-linked immunoelectrotransfer blot assay. The sensitivity of the assay was 86%. Negative pre-treatment results in the Ag-ELISA test were restricted to patients with only a single live cyst or only enhancing lesions. Patients with hydrocephalus had higher levels of circulating antigen. There was no difference between antigen levels in CSF taken before and immediately after treatment (day 14). Levels of parasite antigen were significantly positively correlated with the number of live cysts detected by tomography and were also proportional to the number and intensity of antibody reactions recognized by the immunoblot diagnostic test. In contrast, there was a negative correlation with the number of enhancing lesions revealed by tomography, supporting the hypothesis that enhancing lesions correspond to a terminal, moribund stage of the parasite. The use of antigen-detection tests specific for viable metacestodes has immediate utility in the clinical context, not only providing important information on the viability of the parasites but also leading to an improved understanding of the pathogenesis of neurocysticercosis before and after drug treatment.

Early lipid alterations in spontaneously diabetic rats.

Human and experimental diabetes mellitus extensively alters lipid metabolism. The eSS is a rat strain that develops a spontaneous diabetes of slow evolution, resembling the non-insulin-dependent diabetes mellitus of young people. We report here disturbances in lipid metabolism of 5-month old eSS rats compared to age-matched alpha-controls. Normal plasmatic glucose levels were found in the fasted state, whereas a diabetic curve was evident for eSS rats after glucose load. Triglyceride content was elevated in plasma and in liver microsomal preparations of eSS animals, when compared to the controls. The diabetic strain revealed a significant fall in the amount of linoleic acid in liver and kidney microsomes and in erythrocyte membranes. In liver, an increase in 22:6 (n-3) was also noted. A depression in the content of linoleic acid as well as an enhancement of docosahexaenoic acid were detected in phosphatidylcholine and phosphatidylethanolamine fractions from liver microsomes of eSS rats. The fatty acid pattern of eSS rat testis showed a raise in the relative percentage of arachidonic and a decrease in 22:5 (n-6), 22:5 (n-3) and 22:6 (n-3) acids compared to their controls. Diabetic rats exhibited a significant increase in microsomal cholesterol content and cholesterol/phospholipid ratio in liver and testis. In the latter tissue, higher values of fluorescence anisotropy were also observed. The current observations indicate that in early stages of the diabetes onset, when eSS rats are still normoglycemic, severe alterations of lipid metabolism may contribute to the establishment and progression of the diabetic syndrome.

Early lipid alterations in spontaneously diabetic rats

Human and experimental diabetes mellitus extensively alters lipid metabolism. The eSS is a rat strain that develops a spontaneous diabetes of slow evolution, resembling the non-insulin-dependent diabetes mellitus of young people. We report here disturbances in lipid metabolism of 5-month old eSS rats compared to age-matched alpha-controls. Normal plasmatic glucose levels were found in the fasted state, whereas a diabetic curve was evident for eSS rats after glucose load. Triglyceride content was elevated in plasma and in liver microsomal preparations of eSS animals, when compared to the controls. The diabetic strain revealed a significant fall in the amount of linoleic acid in liver and kidney microsomes and in erythrocyte membranes. In liver, an increase in 22:6 (n-3) was also noted. A depression in the content of linoleic acid as well as an enhancement of docosahexaenoic acid were detected in phosphatidylcholine and phosphatidylethanolamine fractions from liver microsomes of eSS rats. The fatty acid pattern of eSS rat testis showed a raise in the relative percentage of arachidonic and a decrease in 22:5 (n-6), 22:5 (n-3) and 22:6 (n-3) acids compared to their controls. Diabetic rats exhibited a significant increase in microsomal cholesterol content and cholesterol/phospholipid ratio in liver and testis. In the latter tissue, higher values of fluorescence anisotropy were also observed. The current observations indicate that in early stages of the diabetes onset, when eSS rats are still normoglycemic, severe alterations of lipid metabolism may contribute to the establishment and progression of the diabetic syndrome.

Early lipid alterations in spontaneously diabetic rats

Human and experimental diabetes mellitus extensively alters lipid metabolism. The eSS is a rat strain that develops a spontaneous diabetes of slow evolution, resembling the non-insulin-dependent diabetes mellitus of young people. We report here disturbances in lipid metabolism of 5-month old eSS rats compared to age-matched alpha-controls. Normal plasmatic glucose levels were found in the fasted state, whereas a diabetic curve was evident for eSS rats after glucose load. Triglyceride content was elevated in plasma and in liver microsomal preparations of eSS animals, when compared to the controls. The diabetic strain revealed a significant fall in the amount of linoleic acid in liver and kidney microsomes and in erythrocyte membranes. In liver, an increase in 22:6 (n-3) was also noted. A depression in the content of linoleic acid as well as an enhancement of docosahexaenoic acid were detected in phosphatidylcholine and phosphatidylethanolamine fractions from liver microsomes of eSS rats. The fatty acid pattern of eSS rat testis showed a raise in the relative percentage of arachidonic and a decrease in 22:5 (n-6), 22:5 (n-3) and 22:6 (n-3) acids compared to their controls. Diabetic rats exhibited a significant increase in microsomal cholesterol content and cholesterol/phospholipid ratio in liver and testis. In the latter tissue, higher values of fluorescence anisotropy were also observed. The current observations indicate that in early stages of the diabetes onset, when eSS rats are still normoglycemic, severe alterations of lipid metabolism may contribute to the establishment and progression of the diabetic syndrome. (AU)

Influence of gonadectomy in eSS diabetic rats.

The influence of gonadectomy on some variables related to the diabetic syndrome was studied in the eSS line of rats, a nonobese model of spontaneous non-insulin-dependent diabetes, whose biochemical and histopathological manifestations are more severe in males than in females. Rats were gonadectomized at 90 days of age. Spayed animals showed higher body weight, impaired intolerance to glucose at 9 and 12 months of age, lower insulinemia and a decreased number of large pancreatic islets. Castrated rats revealed lower body weight when compared with controls. However, those males did not evidence impairment in the intolerance to glucose, changes insulinemia or remarkable modifications in endocrine pancreas histology. In kidneys, a lower cellular area in superficial proximal convoluted tubules was noticed. Despite the lower biomass registered in orchidectomized animals, their diabetic evolution was not modified. Conversely, ovariectomy appeared to be a worsening factor.