Guilherme da Silva Mazzini

Serum levels of S100B and NSE proteins in Alzheimer's disease patients

BackgroundAlzheimers disease is the most common dementia in the elderly, and the potential of peripheral biochemical markers as complementary tools in the neuropsychiatric evaluation of these patients has claimed further attention.MethodsWe evaluated serum levels of S100B and neuron-specific enolase (NSE) in 54 mild, moderate and severe Alzheimers disease (AD) patients and in 66 community-dwelling elderly. AD patients met the probable NINCDS-ADRDA criteria. Severity of dementia was ascertained by the Clinical Dementia Rating (CDR) scale, cognitive function by the Mini Mental State Examination (MMSE), and neuroimage findings with magnetic resonance imaging. Serum was obtained from all individuals and frozen at -70°C until analysis.ResultsBy comparing both groups, serum S100B levels were lower in AD group, while serum NSE levels were the same both groups. In AD patients, S100B levels were positively correlated with CDR scores (rho = 0.269; p = 0.049) and negatively correlated with MMSE scores (rho = -0.33; P = 0.048). NSE levels decreased in AD patients with higher levels of brain atrophy.ConclusionsThe findings suggest that serum levels of S100B may be a marker for brain functional condition and serum NSE levels may be a marker for morphological status in AD.

Impairment of the Organization of Locomotor and Exploratory Behaviors in Bile Duct-Ligated Rats

Hepatic encephalopathy (HE) arises from acute or chronic liver diseases and leads to several problems, including motor impairment. Animal models of chronic liver disease have extensively investigated the mechanisms of this disease. Impairment of locomotor activity has been described in different rat models. However, these studies are controversial and the majority has primarily analyzed activity parameters. Therefore, the aim of the present study was to evaluate locomotor and exploratory behavior in bile duct-ligated (BDL) rats to explore the spatial and temporal structure of behavior. Adult female Wistar rats underwent common bile duct ligation (BDL rats) or the manipulation of common bile duct without ligation (control rats). Six weeks after surgery, control and BDL rats underwent open-field, plus-maze and foot-fault behavioral tasks. The BDL rats developed chronic liver failure and exhibited a decrease in total distance traveled, increased total immobility time, smaller number of rearings, longer periods in the home base area and decreased percentage of time in the center zone of the arena, when compared to the control rats. Moreover, the performance of the BDL rats was not different from the control rats for the elevated plus-maze and foot-fault tasks. Therefore, the BDL rats demonstrated disturbed spontaneous locomotor and exploratory activities as a consequence of altered spatio-temporal organization of behavior.

The ischemic heart as an extracerebral source for S100B

S100B and neuron specific enolase (NSE) are proteins that have een extensively studied as biochemical markers for brain injury: ncreased concentrations in serum and/or cerebrospinal fluid are ssociated with the extent of brain damage, as well neurologial outcome after events such as cardiac arrest.1 Nevertheless, a tudy on postoperative neurological impairment following cardiac urgery, reported increased S100B serum values early after cariopulmonary bypass that did not differ between patients with or ithout neurological dysfunction, but correlated positively with ardiac Troponin I.2 Similarly, positive correlation between S100B nd creatine kinase–MB serum levels has been reported after cariac surgery with cardiopulmonary bypass.3 These previous studies ndicate an extracerebral source for S100B; possibly the heart. Thus, e read with great interest the very elegant study published in esuscitation by Pfeifer et al.4 They investigated the influence of hort-term left ventricular assist device (LVAD) support on serum oncentrations of NSE and S100B, in patients undergoing percutaeous coronary intervention (PCI) for acute myocardial infarction AMI). Eighty non-resuscitated AMI patients who received LVAD upport were compared with a reference group of 43 patients with ncomplicated AMI without LVAD support after PCI. The results emonstrated an increase in serum concentrations of S100B and SE in the LVAD support group, but also in the reference group, not upported with a LVAD. Besides the brain’s potential contribution o the increase in serum values of both proteins, the authors raised he possibility of a component caused by myocardial ischemia. lthough difficult to prove in human studies, this hypothesis has lready been tested experimentally by our group. Using an isolated at heart perfusion model, we demonstrated a time course release f S100B and cardiac Troponin T by the rat heart soon after an schemic insult.5 As the brain was ruled out as the source of S100B, e believe that these results may provide experimental support for d tion 80 (2009) 142–144

Impact of laparoscopic fundoplication for the treatment of laryngopharyngeal reflux: review of the literature.

Laryngopharyngeal reflux (LPR) is part of the so-called extraesophageal manifestations of gastroesophageal reflux disease (GERD). It is presented by unspecific symptoms and signs and is believed to be caused by the reflux of gastric content to the proximal esophagus and larynx. However, evidence considering the role of the antireflux surgery for LPR has failed to demonstrate results comparable to those for GERD. The aim of this paper is to review the current literature regarding the impact of laparoscopic fundoplication for the treatment of LPR.

Concurrent miR-21 suppression and FXR activation as a mechanism of improvement in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity, metabolic syndrome, and type 2 diabetes (T2DM), which is projected to become the leading cause of liver-related morbidity and mortality within 20 years. Nuclear receptor dysregulation contributes to the pathogenesis of NAFLD by impacting the energy and nutrient-integrated control of metabolism and inflammation, and ligand-activated nuclear receptors have been studied as targets for novel NAFLD therapies. Thus, we read with great interest the paper previously published in Cell Death & Disease, entitled “miR-21 Ablation and Obeticholic Acid Ameliorate Nonalcoholic Steatohepatitis in Mice”, by Rodrigues et al.. Liver miR-21 is one of the most upregulated microRNAs in nonalcoholic steatohepatitis (NASH) patients and is a potent inhibitor of peroxisome proliferator-activated receptor α (PPARα), a nuclear receptor, which expression in liver is decreased in NASH patients . The authors demonstrated that the wild-type (WT) mice fed a methionine and cholinedeficient (MCD) diet developed steatohepatitis, presenting moderate to severe vacuolation of hepatocytes, large lipid droplets, pronounced hepatocellular hypertrophy, and moderate to severe inflammation. These changes were almost abrogated in miR-21 knockout (KO) mice, which exhibited markedly reduced steatosis. miR-21 ablation led to increased liver PPARα, with miR-21 KO mice presenting mild to moderate hepatocellular vacuolation, smaller and scattered lipid droplets, as well as a robust decrease in cell hypertrophy. However, Loyer et al. previously demonstrated that either pharmacologic-inhibiting or knocking-out miR-21 reduced liver cell injury, inflammation and fibrosis in mice fed an MCD diet, but had no effect in steatosis. Liver lipid accumulation and liver expression of ß-oxidation-related genes were not different between miR-21 KO and WT mice. They also studied liver miR-21 cell localization in liver. In both mice and human patients with NASH, miR21 was primarily overexpressed in biliary (CK19+ ) and inflammatory (CD3+ ) cells, but not in hepatocytes. We encourage Rodrigues et al. to address this main difference between their results and the previous one from Loyer et al. regarding lipid accumulation, as they used a similar experimental model. Taking into account that Loyer et al. detected the overexpression of miR-21 mainly in biliary and inflammatory cells in liver, it is reasonable to expect the improvement in inflammation and fibrosis, but not in steatosis. Lipid accumulation is a consequence of hepatocyte metabolism impairment, and only the modulation of PPARα inside hepatocytes could lead to the improvement in steatosis. Diet-induced obese mice treated with a PPARα agonist improved hepatic steatosis accompanied by enhancement of the hepatocyte ultrastructure favoring β-oxidation and decrease in hepatic de novo lipogenesis, but no study has compared miR-21 KO to PPARα agonist treatment. Francque et al. first demonstrated that human liver PPARα gene expression negatively correlates with NASH severity and insulin resistance, and suggested PPARα as a potential therapeutic target in NASH. However, in our opinion, the role of miR21 inhibition in hepatocyte PPARα activation should be better investigated. Finally, in the same study, Rodrigues et al. also demonstrated that the simultaneous miR-21 suppression and Farnesoid X receptor (FXR) activation by obeticholic

Ki-67 Antigen Overexpression Is Associated with the Metaplasia-Adenocarcinoma Sequence in Barrett's Esophagus

Introduction. The objective of this study was to evaluate Ki-67 antigen expression in patients with Barretts esophagus and esophageal adenocarcinoma and to assess its correlation with the metaplasia-esophageal adenocarcinoma progression. Methods. Using immunohistochemistry we evaluated the Ki-67 index in patients with Barretts esophagus, esophageal adenocarcinoma, and controls. We included patients with endoscopically visible columnar mucosa of the distal esophagus (whose biopsies revealed specialized intestinal-type metaplasia), patients with esophageal and esophagogastric tumors types I and II, and patients with histologically normal gastric mucosa (control). Results. In the 57 patients studied there were no statistically significant differences between the groups with respect to age or race. Patients with cancer were predominantly men. The Ki-67 index averaged 10 ± 4 % in patients with normal gastric mucosa (n = 17), 21 ± 15 % in patients with Barretts esophagus (n = 21), and 38 ± 16 % in patients with cancer (n = 19). Ki-67 expression was significantly different between all groups (P < 0.05). There was a strong linear correlation between Ki-67 expression and the metaplasia-adenocarcinoma sequence (P < 0.01). In patients with cancer, Ki-67 was not associated with clinical or surgical staging. Conclusions. Ki-67 antigen has increased expression along the metaplasia-adenocarcinoma sequence. There is a strong linear correlation between Ki-67 proliferative activity and Barretts carcinogenesis.

High phosphate serum levels correlate with the severity of experimental severe acute pancreatitis: insight into the purinergic system.

Objectives Extracellular purines are a component of the systemic inflammatory response, and their levels are modulated by ectonucleotidases. In addition, nucleotide hydrolysis releases phosphate. We studied serum phosphate levels as a predictor of severity in acute pancreatitis (AP) and their correlation with extracellular purinergic metabolism. Methods Acute pancreatitis was induced by the retrograde injection of sodium taurocholate. The AP group was compared with animals submitted to a model of sepsis by cecal ligation and puncture. The sham group was submitted to laparotomy and closure. We measured the phosphate and purine levels in serum and the expression of 5′-nucleotidase (CD73) and the adenosine A2a receptor in pancreatic tissue by quantitative real-time polymerase chain reaction. Results Serum phosphate levels were higher in severe AP and correlated with severity. Severe AP led to increased serum levels of adenosine diphosphate, adenosine monophosphate, and adenosine. In addition, adenosine monophosphate conversion to adenosine in serum was accelerated in the AP groups. We found a positive correlation between serum adenosine and phosphate in the AP groups. The expression levels of CD73 and the adenosine A2a receptor in the pancreas were not altered. Conclusions Our study suggests that serum phosphate correlates with severity in AP and implicates extracellular purines in the systemic response to severe AP.