Non-alcoholic Steatohepatitis (NASH) and Hepatocellular Carcinoma

Non-alcoholic fatty liver disease (NAFLD) is characterized by an excessive accumulation of fatty acids and triglycerides within the cytoplasm of the hepatocytes of non-alcohol users. The natural history varies according to the initial histological diagnosis. A current consideration is that cryptogenic cirrhosis may be representative of a late stage of non-alcoholic steatohepatitis (NASH), which has lost its features of necroinflammatory activity and steatosis in up to 80% of patients. Since NASH is able to progress to cirrhosis, hepatocellular carcinoma (HCC) development may be an end-stage of this disease. We report below two clinical cases of patients diagnosed with NASH who developed HCC. The relationship between NAFLD and HCC is reviewed.     

Therapeutic capacity of the synthetic peptide-based vaccine against Taenia solium cysticercosis in pigs

The S3Pvac synthetic vaccine composed of three peptides (GK1, KETc1 and KETc12) effectively protect against pig cysticercosis. Preliminary results point to an additional cysticidal capacity induced by S3Pvac or GK1 immunization. Herein, clear evidences of the cysticidal effect of S3Pvac but not of GK1 are presented. S3Pvac immunization of already experimentally infected pigs induced a reduction in the parasite load, in the vesicular cysticerci and in their viability. It also substantially increases the percent of histological damaged cysticerci more importantly in muscles than in brains, with a concomitant reduction in the antibody levels. Thus, S3Pvac represents a powerful means of controlling cysticercosis infection in pigs.     

Paradoxical effect of body mass index on survival in rheumatoid arthritis: role of comorbidity and systemic inflammation

BACKGROUND: Despite high cardiovascular mortality in rheumatoid arthritis (RA), few studies of body mass index (BMI) and obesity as risk factors for death in RA have been published. METHODS: We estimated the effect of BMI on survival in a cohort of 779 patients with RA adjusting for comorbidity, RA disease severity, erythrocyte sedimentation rate (ESR), and other potential confounders. RESULTS: The cohort accrued 123 deaths in 3460 person-years (3.6 deaths per 100 person-years; 95% confidence interval [CI], 3.0-4.2). The BMI was inversely associated with mortality. Patients with BMIs of 30 or higher had the lowest mortality, 1.7 deaths per 100 person-years (95% CI, 1.1-2.5). Mortality was higher in each lower BMI category, reaching its highest rate among patients with BMIs lower than 20 with 15.0 deaths per 100 person-years (95% CI, 9.9-23.0). The survival advantage of high BMI was independent of RA onset age, RA duration, sex, ethnic group, socioeconomic status, smoking status, and use of methotrexate but was lost on adjusting for comorbidity and RA severity. We observed an interaction between BMI and ESR, where the BMI protective influence occurred only if the ESR was low. The BMI x ESR interaction was independent of all covariates, including comorbidity and RA severity. CONCLUSIONS: Body mass has a paradoxical effect on mortality in RA. Patients with high BMI have lower mortality than thinner patients. This effect is mediated in part by comorbidity. The effect of body mass on survival seems to be modified by the level of systemic inflammation.     

Relative contribution of cardiovascular risk factors and rheumatoid arthritis clinical manifestations to atherosclerosis

OBJECTIVE: To estimate the contribution of cardiovascular (CV) risk factors and rheumatoid arthritis (RA) disease manifestations to atherosclerosis in RA. METHODS: We used high-resolution carotid ultrasound to measure the carotid intima-media thickness (IMT) and plaque in 631 RA patients. Using R(2) measures from multivariable models, we estimated the contribution of demographic characteristics (age, sex, and ethnic group), CV risk factors (diabetes mellitus, hypercholesterolemia, cigarette smoking, hypertension, and body mass index, and RA manifestations (joint tenderness, swelling, and deformity, nodules, erythrocyte sedimentation rate [ESR], C-reactive protein, rheumatoid factor, the HLA-DRB1 shared epitope, and cumulative glucocorticoid dose) to each of the outcomes. Estimates were obtained in the full sample, and within strata defined by age, sex, and ethnic group. We tested for interaction between CV risk factors and RA manifestations. RESULTS: The contribution of demographic factors, CV risk factors, and RA manifestations to IMT and plaque R(2) varied depending on the patients' age stratum. Demographic features explained 11-16% of IMT variance, CV risk factors explained 4%-12%, and RA manifestations explained 1-6%. The greatest contribution of RA manifestations occurred in the youngest age group, while that of CV risk factors occurred in the older age groups. Results for carotid plaque were similar. There was a significant interaction between the number of CV risk factors present and the ESR, suggesting that the ESR's effect on IMT varied according to the number of CV risk factors. CONCLUSION: Both established CV risk factors and manifestations of RA inflammation contribute significantly to carotid atherosclerosis in RA, and may modify one another's effects. These findings may have implications regarding the prevention of atherosclerosis in RA.     

Neuropeptide Y and leptin in patients with obstructive sleep apnea syndrome: role of obesity

Neuropeptide Y (NPY) and leptin are two peptides involved in the regulation of body weight, energy balance, and sympathetic tone. This study investigates the independent role of apneas and obesity on NPY and leptin plasma levels in patients with obstructive sleep apnea syndrome (OSAS). To this end we compared their values in 23 obese (body mass index > 30 kg/m2) and 24 nonobese (body mass index < 27 kg/m2) patients with OSAS, and in 19 obese and 18 nonobese control subjects without OSAS. Patients who used continuous positive airway pressure for more than 4 hours/night were reexamined 3 and 12 months later. We found that NPY levels were increased (p < 0.01) in patients with OSAS independently of obesity. Leptin levels were also increased in OSAS but this was mostly associated to obesity. Continuous positive airway pressure treatment reduced NPY levels in all patients and leptin levels only in nonobese patients (p < 0.01). We concluded that NPY and leptin plasma levels are increased in patients with OSAS. Yet, whereas the former appear independent of obesity, the latter are mostly associated with obesity.     

Choline acetyltransferase expression does not identify early pathogenic events in fetal SMA spinal cord

We investigated the expression of choline acetyltransferase, a specific marker for cholinergic neurons, in control and spinal muscular atrophy fetuses and newborns. By immunoblot we observed at 12 and 15 weeks a similar pattern of choline acetyltransferase expression in spinal muscular atrophy with respect to controls, although at 22 weeks this expression was reduced, probably due to a smaller number of motor neurons in the spinal muscular atrophy spinal cord. By immunohistochemistry, the counting of positive and negative motor neurons for choline acetyltransferase immunostaining in control and spinal muscular atrophy fetuses showed a similar proportion at all stages analyzed. The choline acetyltransferase-negative motor neurons were of similar appearance in both groups. After birth, chromatolytic motor neurons were detected in spinal muscular atrophy, all of which were choline acetyltransferase-negative. Our results in spinal muscular atrophy fetuses indicate that choline acetyltransferase immunostaining does not identify early events in neuronal pathogenesis and suggest that the spinal muscular atrophy surviving motor neurons may not be dysfunctional during this period. Furthermore, spinal muscular atrophy choline acetyltransferase-negative motor neurons showed detectable pathological changes only after birth, indicating that choline acetyltransferase is a late marker for motor neuron degeneration and not a primary contributing factor in this process.     

Increased occipital delta dipole density in major depressive disorder determined by magnetoencephalography

OBJECTIVE: To test the hypothesis that there is increased low-frequency activity located predominantly in the frontal lobe in patients with major depressive disorder using magnetoencephalography. METHODS: We carried out an unmatched or separate sampling case-control study of 31 medication-free patients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), criteria for major depressive disorder and were outpatients of the Hospital Central de la Defensa, Madrid, and 22 healthy control subjects with no history of mental illness. A logistic regression analysis was employed to examine the predictive value of magnetoencephalography dipole density scores in the diagnosis of depression. We attempted to locate generators of focal magnetic slow waves by employing a single moving dipole model and by calculating dipole densities in prefrontal, frontal, parietal, temporal and occipital areas. The study lasted from February 2001 to January 2003. RESULTS: Only 2 dipole density scores, right occipital delta and left temporal delta, were significantly related to depression. According to the comparison of univariate and multivariate models and odds ratios, the right occipital delta dipole density is the factor with the greatest predictive power for depression, and the only one to show a significant correlation with severity of depression. CONCLUSIONS: We did not find any frontal lobe functional alteration. Our study provides, to the best of our knowledge, the first evidence of abnormal focal magnetic low-frequency activity in the occipital lobe of untreated patients with depression. Increased occipital lobe delta dipole density seems to be a reliable risk factor for depression, which correlates with disease severity according to the Hamilton Rating Scale for Depression.     

Update of tnf-alpha antagonists and cardiovascular disease in rheumatoid arthritis

Tumor necrosis factor-á (TNF-á) antagonists were unexpectedly found to have no beneficial effects in moderate-to-severe heart failure in two large randomized clinical trials. In certain doses, the agents were found to be harmful. These results have important implications for rheumatoid arthritis (RA). Patients with the disease have an increased risk for developing cardiovascular co-morbidity, including heart failure. Because of the beneficial effect of the TNF-á antagonists in the management of RA, these agents have gained widespread use. Rheumatologists and other physicians who provide care for RA are thus likely to encounter candidates for anti-TNF-á therapy who have overt or subclinical heart failure. Although data are currently not sufficient to support evidence-based recommendations, it is possible to make reasonable suggestions to guide clinical practice.     

Systemic effects of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) affects various structural and functional domains in the lungs. It also has significant extrapulmonary effects, the so-called systemic effects of COPD. Weight loss, nutritional abnormalities, and skeletal muscle dysfunction are well-recognized systemic effects of COPD. Other less well-known but potentially important systemic effects include an increased risk of cardiovascular disease and several neurologic and skeletal defects. The mechanisms underlying these systemic effects are unclear, but they are probably interrelated and multifactorial, including inactivity, systemic inflammation, tissue hypoxia and oxidative stress among others. These systemic effects add to the respiratory morbidity produced by the underlying pulmonary disease and should be considered in the clinical assessment as well as the treatment of affected patients.