Impact of a program for the prevention of traffic accidents in a Southern Brazilian city: a model for implementation in a developing country

Background: Traffic accidents constitute the main cause of death in the first decades of life. Traumatic brain injury is the event most responsible for the severity of these accidents. The SBN started an educational program for the prevention of traffic accidents, adapted from the American model ""Think First"" to the Brazilian environment, since 1995, with special effort devoted to the prevention of TBI by using seat belts and motorcycle helmets. The objective of the present study was to set up a traffic accident prevention program based on the adapted Think First and to evaluate its impact by comparing epidemiological variables before and after the beginning of the program. Methods: The program was executed in Maringa city, from September 2004 to August 2005, with educational actions targeting the entire population, especially teenagers and young adults. The program was implemented by building a network of information facilitators and multipliers inside the organized civil society, with widespread population dissemination. To measure the impact of the program, a specific software was developed for the storage and processing of the epidemiological variables. Results: The results showed a reduction of trauma severity due to traffic accidents after the execution of the program, mainly TBI. Conclusions: The adapted Think First was systematically implemented and its impact measured for the first time in Brazil, revealing the usefulness of the program for reducing trauma and TBI severity in traffic accidents through public education and representing a standardized model of implementation in a developing country. (C) 2009 Elsevier Inc. All rights reserved.

Liver HLA-G expression is associated with multiple clinical and histopathological forms of chronic hepatitis B virus infection

As the mechanisms leading to the persistence of hepatitis B virus (HBV) infection are poorly understood and as the histocompatibility leucocyte antigen (HLA)-G is well described as a tolerogenic molecule, we evaluated HLA-G expression in 74 specimens of HBV liver biopsies and in 10 specimens obtained from previously healthy cadaver liver donors. HBV specimens were reviewed and classified by the METAVIR score, and HLA-G expression was assessed by immunohistochemistry. No HLA-G expression was observed in control hepatocytes. In contrast, 57 (77%) of 74 HBV specimens showed soluble and membrane-bound HLA-G expression in hepatocytes, biliary epithelial cells or both. No associations between the intensity of HLA-G expression and patient age or gender, HBeAg status, severity of liver fibrosis, and grade of histological findings were observed. Although significance was not reached (P = 0.180), patients exhibiting HLA-G expression presented a higher median HBV DNA viral load (105 copies/mL) than those who did not express HLA-G (103.7 copies/mL). These results indicate that HLA-G is expressed in most cases of chronic HBV infection in all stages and may play a role in the persistency of HBV infection.

A single nucleotide deletion at the C1 inhibitor gene as the cause of hereditary angioedema: insights from a Brazilian family

Background: Hereditary angioedema is an autosomal dominant disease characterized by episodes of subcutaneous and submucosal edema. It is caused by deficiency of the C1 inhibitor protein, leading to elevated levels of bradykinin. More than 200 mutations in C1 inhibitor gene have been reported. The aim of this study was to analyze clinical features of a large family with an index case of hereditary angioedema and to determine the disease-causing mutation in this family. Methods: Family pedigree was constructed with 275 individuals distributed in five generations. One hundred and sixty-five subjects were interviewed and investigated for mutation at the C1 inhibitor gene. Subjects reporting a history of recurrent episodes of angioedema and/or abdominal pain attacks underwent evaluation for hereditary angioedema. Results: We have identified a novel mutation at the C1 inhibitor gene, c.351delC, which is a single-nucleotide deletion of a cytosine on exon 3, resulting in frameshift with premature stop codon. Sequencing analysis of the hypothetical truncated C1 inhibitor protein allowed us to conclude that, if transcription occurs, this protein has no biological activity. Twenty-eight members of the family fulfilled diagnostic criteria for hereditary angioedema and all of them presented the c.351delC mutation. Variation in clinical presentation and severity of disease was observed among these patients. One hundred and thirty-seven subjects without hereditary angioedema did not have the c.351delC mutation. Conclusion: The present study provides definitive evidence to link a novel genetic mutation to the development of hereditary angioedema in patients from a Brazilian family.

Perception of dysphagia: lack of correlation with objective measurements of esophageal function

Background The mechanism underlying increased perception of food bolus passage in the absence of esophageal mechanical obstruction has not been completely elucidated. A correlation between the intensity of the symptom and the severity of esophageal dysfunction, either motility (manometry) or bolus transit (impedance) has not been clearly demonstrated. The aim of this study was to analyze the correlation between objective esophageal function assessment (with manometry and impedance) and perception of bolus passage in healthy volunteers (HV) with normal and pharmacologically-induced esophageal hypocontractility, and in patients with gastro-esophageal reflux disease (GERD) with and without ineffective esophageal motility (IEM). Methods Combined manometry-impedance was performed in 10 HV, 19 GERD patients without IEM and nine patients with IEM. Additionally, nine HV were studied after 50 mg sildenafil, which induced esophageal peristaltic failure. Perception of each 5 mL viscous swallow was evaluated using a 5-point scale. Manometry identified hypocontractility (contractions lower than 30 mmHg) and impedance identified incomplete bolus clearance. Key Results In HV and in GERD patients with and without IEM, there was no association between either manometry or impedance and perception on per swallow analysis (OR: 0.842 and OR: 2.017, respectively), as well as on per subject analysis (P = 0.44 and P = 0.16, respectively). Lack of correlation was also found in HV with esophageal hypocontractility induced by sildenafil. Conclusions & Inferences There is no agreement between objective measurements of esophageal function and subjective perception of bolus passage. These results suggest that increased bolus passage perception in patients without mechanical obstruction might be due to esophageal hypersensitivity.

The H63D genetic variant of the HFE gene is independently associated with the virological response to interferon and ribavirin therapy in chronic hepatitis C

Background Conflicting results have been reported in studies evaluating the relationship between serum markers of iron overload, liver iron deposits, and HFE mutations (C282Y and H63D) in chronic hepatitis C patients, and also their impact on the response to therapy in these patients. Aim To evaluate the role of HFE mutations in the severity of liver disease and in the response to therapy in chronic hepatitis C. Methods Two hundred and sixty-four hepatitis C patients treated with standard interferon and ribavirin were divided into two groups according to type of antiviral response: sustained virological response (SVR) and nonresponse or relapse. We evaluated the relationship between HFE mutation and the type of antiviral response, clinical data, biochemical tests, liver histopathology, virological data, and HFE mutations. Results Of the 264 patients, 88 (32.1%) had SVR whereas 67.9% had nonresponse or relapse. Liver iron deposits were observed in 49.2% of the patients. The factors associated with SVR were hepatitis C virus genotype 2 or 3, transferrin saturation value of 45% or less, and detection of the H63D mutation. HFE mutation was more frequent in patients with iron deposits, but without association with serum iron biochemistry or severity of liver disease. Steatosis was more frequent in patients with liver iron deposits. Conclusion The H63D mutation was an independent factor associated with SVR in chronic hepatitis C patients, as also were hepatitis C virus genotype 2 or 3 and transferrin saturation value of 45% or less. Moreover, the H63D mutation was associated with liver iron deposits. Eur J Gastroenterol Hepatol 22: 1204-1210 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Expression of human leucocyte antigen-G primarily targets affected skin of patients with psoriasis

P>Background The nonclassical human leucocyte antigen (HLA)-G molecule has been well recognized as a tolerogenic molecule and few studies have evaluated the role of the molecule in inflammatory cutaneous autoimmune diseases. Objectives To evaluate the expression of HLA-G in skin specimens of patients with psoriasis and to analyse its correlation with epidemiological and clinical variables. Methods Thirty untreated patients with psoriasis and 32 healthy individuals were enrolled. Immunohistochemistry was applied to identify HLA-G expression in formalin-fixed paraffin-embedded cutaneous skin biopsies. Results Soluble and membrane-bound HLA-G expression was detected in 30 (90%) of the skin specimens from patients presenting clinical and histopathological features of psoriasis. Although infiltrating lymphomononuclear cells of the dermis exhibited HLA-G expression, the epidermis was primarily targeted. HLA-G expression was also observed in 27% (three of 11) of the specimens that exhibited no clinical and histopathological features of psoriasis (nonaffected areas). In contrast, skin specimens obtained from healthy individuals exhibited no HLA-G expression (P < 0 center dot 0001). The intensity of HLA-G expression was not associated with type I/II psoriasis, Psoriasis Area and Severity Index score or clinical forms. Conclusions As the HLA-G molecule was consistently expressed in affected and, to a lesser extent, in nonaffected areas of untreated patients with psoriasis, irrespective of the severity of the clinical variants, one may hypothesize that the presence of HLA-G may be responsible, at least in part, for the regulation of autoimmune effector cells.

Protective Effect of RC-3095, an Antagonist of the Gastrin-Releasing Peptide Receptor, in Experimental Arthritis

Objective. To evaluate the antiinflammatory effects of RC-3095 in 2 experimental models of arthritis, collagen-induced arthritis (CIA) and antigen-induced arthritis (AIA), and to determine the mechanisms of action involved. Methods. RC-3095 was administered daily to mice with CIA and mice with AIA, after induction of disease with methylated bovine serum albumin. Disease incidence and severity were assessed using a clinical index and evaluation of histologic features, respectively. In mice with CIA, gastrin-releasing peptide receptor (GRPR) was detected by immunohistochemical analysis, while in mice with AIA, migration of neutrophils, presence of glycosaminoglycans, and lymphocyte proliferation, determined using the MTT assay, were assessed. Expression of cytokines interleukin-17 (IL-17), IL-1 beta, and tumor necrosis factor alpha (TNF alpha) was evaluated in all mouse knees using enzyme-linked immunosorbent assay. Treg cell production was assessed by flow cytometry in the joints of mice with AIA. Results. In mice with AIA, administration of RC-3095 reduced neutrophil migration, mechanical hypernociception, and proteoglycan loss. These findings were associated with inhibition of the levels of all 3 proinflammatory cytokines, decreased lymphocyte proliferation, and increased Treg cell numbers. In the CIA model, treatment with RC-3095 led to a significant reduction in arthritis clinical scores and the severity of disease determined histologically. Synovial inflammation, synovial hyperplasia, pannus formation, and extensive erosive changes were all dramatically reduced in the arthritic mice treated with RC-3095. Furthermore, arthritic mice treated with RC-3095 showed a significant reduction in the concentrations of IL-17, IL-1 beta, and TNF alpha, and showed a diminished expression of GRPR. Conclusion. These findings suggest that the GRP pathway has a significant role in chronic arthritis, and its inhibition can be explored as a possible therapeutic strategy in rheumatoid arthritis.

Role of cytokines (TNF-alpha, IL-1 beta and KC) in the pathogenesis of CPT-11-induced intestinal mucositis in mice: effect of pentoxifylline and thalidomide

Introduction Irinotecan (CPT-11) is an inhibitor of DNA topoisomerase I and is clinically effective against several cancers. A major toxic effect of CPT-11 is delayed diarrhea; however, the exact mechanism by which the drug induces diarrhea has not been established. Purpose Elucidate the mechanisms of induction of delayed diarrhea and determine the effects of the cytokine production inhibitor pentoxifylline (PTX) and thalidomide (TLD) in the experimental model of intestinal mucositis, induced by CPT-11. Materials and methods Intestinal mucositis was induced in male Swiss mice by intraperitoneal administration of CPT-11 (75 mg/kg) daily for 4 days. Animals received subcutaneous PTX (1.7, 5 and 15 mg/kg) or TLD (15, 30, 60 mg/kg) or 0.5 ml of saline daily for 5 and 7 days, starting 1 day before the first CPT-11 injection. The incidence of delayed diarrhea was monitored by scores and the animals were sacrificed on the 5th and 7th experimental day for histological analysis, immunohistochemistry for TNF-alpha and assay of myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and KC ELISA. Results CPT-11 caused significant diarrhea, histopathological alterations (inflammatory cell infiltration, loss of crypt architecture and villus shortening) and increased intestinal tissue MPO activity, TNF-alpha, IL-1 beta and KC level and TNF-alpha immuno-staining. PTX inhibited delayed diarrhea of mice submitted to intestinal mucositis and reduced histopathological damage, intestinal MPO activity, tissue level of TNF-alpha, IL-1 beta and KC and TNF-alpha immuno-staining. TLD significantly reduced the lesions induced by CPT-11 in intestinal mucosa, decreased MPO activity, TNF-alpha tissue level and TNF-alpha immuno-staining, but did not reduce the severity of diarrhea. Conclusion These results suggest an important role of TNF-alpha, IL-1 beta and KC in the pathogenesis of intestinal mucositis induced by CPT-11.

Severity dependent increases in circulating cardiac troponin I and MMP-9 concentrations after experimental acute pulmonary thromboembolism

Background: Making the diagnosis of acute pulmonary thromboembolism (APT) and assessing its severity is very challenging, While cardiac troponin I (cTnI) concentrations are promising in risk stratification, no previous study has examined whether there is a linear relation between cTnI concentrations and the severity of APT. Moreover, matrix metalloprotemases (MMPs) are involved in the pathophysiology of APT. However, it is unknown whether the increases in MMP concentrations after APT reflect the severity of this condition. We examined whether the circulating concentrations of these biomarkers increase in proportion to the severity of experimental APT induced in anesthetized dogs. Methods: APT was induced with autologous blood clots (saline, 1, 3, or 5 ml/kg) injected into the right atrium. Hemodynamic evaluations were carried out for 120 min. Gelatin zymography of MMP-2 and MMP-9 from plasma samples were performed and serum cTnI concentrations were determined at baseline and 120 min after APT. Results: While no significant increases in pro-MMP-2 concentrations were found after APT, pro-MMP-9 concentrations increased by 80% only after 5 ml/kg of clot embolization. Serum cTnI and plasma pro-MMP-9 concentrations correlated positively with pulmonary vascular resistance (P=0.007 and rs=0.833 for troponin 1, and P=0.034 and rs=0.684 for pro-MMP-9) and with pulmonary artery pressure (P=0.005 and rs=0.610 for troponin 1, and P=0.022 and rs=0.720 for pro-MMP-9). Conclusions: Circulating cTnI and pro-MMP-9 increase in proportion to the severity of APT, although the increases in plasma pro-MMP-9 are less clear with less severe APT. These findings may be relevant for clinical APT. (C) 2007 Elsevier B.V. All rights reserved.

5-Lipoxygenase is a key determinant of acute myocardial inflammation and mortality during Trypanosoma cruzi infection

This study provides evidence supporting the idea that although inflammatory cells migration to the cardiac tissue is necessary to control the growth of Trypanosoma cruzi, the excessive influx of such cells during acute myocarditis may be deleterious to the host. Production of lipid mediators of inflammation like leukotrienes (LTs) along with cytokines and chemokines largely influences the severity of inflammatory injury in response to tissue parasitism. T cruzi infection in mice deficient in 5-lipoxygenase (5-LO), the enzyme responsible for the synthesis of LTs and other lipid inflammatory mediators, resulted in transiently increased parasitemia, and improved survival rate compared with WT mice. Myocardia from 5-LO(-/-) mice exhibited reduced inflammation, collagen deposition, and migration of CD4(+), CD8(+), and IFN-gamma-producer cells compared with WT littermates. Moreover, decreased amounts of TNF-alpha, IFN-gamma, and nitric oxide synthase were found in the hearts of 5-LO(-/-) mice. Interestingly, despite of early higher parasitic load, 5-LO(-/-) mice survived, and controlled T cruzi infection. These results show that efficient parasite clearance is possible in a context of moderate inflammatory response, as occurred in 5-LO(-/-) mice, in which reduced myocarditis protects the animals during T cruzi infection. (c) 2010 Elsevier Masson SAS. All rights reserved.

Effects of Lidocaine Infusion during Experimental Endotoxemia in Horses

Background The clinical efficacy of IV infusion of lidocaine for treatment of equine endotoxemia has not been studied. Hypothesis Lidocaine infusion after exposure to lipopolysaccharide (LPS) will inhibit the inflammatory response and have inhibitory effects on the hemodynamic and cytokine responses to endotoxemia. Animals Twelve horses. Methods Two equal groups (n = 6): saline (GI) and lidocaine (GII). In all animals, endotoxin (500 ng/kg body weight [BW]) was injected intraperitoneally over 5 minutes. Twenty minutes later, animals received a bolus of GI or GII (1.3 mg/kg BW) over 5 minutes, followed by a 6-hour continuous rate infusion of GI or GII (0.05 mg/kg BW/min). Treatment efficacy was judged from change in arterial blood pressure, peripheral blood and peritoneal fluid (PF) variables (total and differential cell counts, enzyme activities, and cytokine concentrations), and clinical scores (CS) for behavioral evidence of abdominal pain or discomfort during the study. Results Compared with the control group, horses treated with lidocaine had significantly lower CS and serum and PF tumor necrosis factor-alpha (TNF-alpha) activity. At several time points in both groups, total and differential cell counts, glucose, total protein and fibrinogen concentrations, and alkaline phosphatase, creatine kinase, and TNF-alpha activities were significantly different from baseline values both in peripheral blood and in PF. Conclusions and Clinical Importance Lidocaine significantly decreased severity of CS and inhibited TNF-alpha activity in PF.

Comparative neuroanatomical and temporal characterization of FluoroJade-positive neurodegeneration after status epilepticus induced by systemic and intrahippocampal pilocarpine in Wistar rats

The aims of this study were to characterize the spatial distribution of neurodegeneration after status epilepticus (SE) induced by either systemic (S) or intrahippocampal (H) injection of pilocarpine (PILO), two models of temporal lobe epilepsy (TLE), using FluoroJade (FJ) histochemistry, and to evaluate the kinetics of FJ staining in the H-PILO model. Therefore, we measured the severity of behavioral seizures during both types of SE and also evaluated the FJ staining pattern at 12, 24, and 168 h (7 days) after the H-PILO insult. We found that the amount of FJ-positive (FJ+) area was greater in SE induced by S-PILO as compared to SE induced by H-PILO. After SE induced by H-PILO, we found more FJ+ cells in the hilus of the dentate gyrus (DG) at 12 h, in CA3 at 24 h, and in CA1 at 168 h. We found also no correlation between seizure severity and the number of FJ+ cells in the hippocampus. Co-localization studies of FJ+ cells with either neuronal-specific nuclear protein (NeuN) or glial fibrillary acidic protein (GFAP) labeling 24 h after H-PILO demonstrated spatially selective neurodegeneration. Double labeling with FJ and parvalbumin (PV) showed both FJ+/PV+ and FJ+/PV- cells in hippocampus and entorhinal cortex, among other areas. The current data indicate that FJ+ areas are differentially distributed in the two TLE models and that these areas are greater in the S-PILO than in the H-PILO model. There is also a selective kinetics of FJ+ cells in the hippocampus after SE induced by H-PILO, with no association with the severity of seizures, probably as a consequence of the extra-hippocampal damage. These data point to SE induced by H-PILO as a low-mortality model of TLE, with regional spatial and temporal patterns of FJ staining. (C) 2010 Elsevier B.V. All rights reserved.

ANXIETY, DYSPHORIA, AND DEPRESSION SYMPTOMS IN MOTHERS OF PRETERM INFANTS

To compare presence and severity of clinical symptoms of anxiety, dysphoria, and depression in mothers of preterm and of full-term infants and to observe changes in symptoms of mothers of preterm infants during hospitalization of the infants and after discharge, 50 mothers of preterm infants and 25 mothers of full-term infants completed the State-Trait Anxiety Inventory and the Beck Depression Inventory. The mothers with preterm infants had significantly higher clinical symptoms of State Anxiety during hospitalization than the group with full-term infants, but the clinical symptoms of anxiety in mothers of preterm infants decreased significantly after discharge. The health staff in a neonatal intensive care unit should not only be aware of infants` clinical status but also of the mothers` emotional state.

Histological effects of intratympanic gentamicin on the vestibular organ of guinea pigs

Background: Transtympanic administration of gentamicin may be suitable to achieve unilateral vestibular ablation, in order to control unilateral Meniere`s disease. In low doses, gentamicin appears to affect selectively the vestibular system, with relative sparing of the cochlea. An experimental study on guinea pigs was conducted to determine what single dose of gentamicin would produce a unilateral vestibular organ lesion when applied to the middle ear. Study design: Experimental and prospective. Methods: Four groups of guinea pigs received different gentamicin doses ( 1, 5, 10 and 25 mg) administered to the middle ear. The animals` vestibular organs were then assessed by scanning electron microscopy, in order to quantify the level of vestibular damage. Results: Study of the utricular macula and the ampullar crista of the lateral semicircular canal revealed vestibular neuroepithelial lesions in all infused ears. Conclusions: The severity of the vestibular neuroepithelial lesions was dose-dependent. Lower gentamicin doses were observed to damage vestibular structures more than cochlear structures.

Effects of Orofacial Myofunctional Therapy on Temporomandibular Disorders

The objectives of the current study were to analyze the effects of orofacial myofunctional therapy (OMT) on the treatment of subjects with associated articular and muscular temporomandibular disorders (TMD). Thirty subjects with associated articular and muscular TMD, according to the Research Diagnostic Criteria (RDCTTMD), were randomly divided into groups: 10 were treated with OMT (T group), 10 with an occlusal splint (OS group), and 10 untreated control group with TMD (SC). Ten subjects without TMD represented the asymptomatic group (AC). All subjects had a clinical examination and were interviewed to determine Helkimo`s Indexes (Di and Ai), the frequency and severity of signs and symptoms, and orofacial myofunctional evaluation. During the diagnostic phase, there were significant differences between groups T and AC. There were no significant differences between group T and OC and SC groups. During the final phase, groups T and OS presented significant improvement, however, the group T presented better results and differed significantly from group OS regarding the number of subjects classified as Aill; the severity of muscular pain and TMJ pain; the frequency of headache and the muscles and stomatognathic functions. The group T differed significantly from the SC group but no longer differed significantly from the AC group. OMT favored a significant reduction of pain sensitivity to palpation of all muscles studied but not for the TMJs; an increased measure of mandibular range of motion; reduced Helkimo`s Di and Ai scores; reduced frequency and severity of signs and symptoms; and increased scores for orofacial myofunctional conditions.