Retracted: Micro-computed tomography evaluation of apical transportation and centring ability of Reciproc and WaveOne systems in severely curved root canals.

The following article from International Endodontic Journal, 'Micro-computed tomography evaluation of apical transportation and centring ability of Reciproc and WaveOne systems in severely curved root canals' by D. A. de Meireles, T. C. C. A. de Brito, A. A. F. Marques, A. D. B. Garrido, L. F. R. Garcia & E. C. Sponchiado Jr, published online on 5 February 2015 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, Prof. Paul Dummer, and John Wiley & Sons Ltd. The retraction has been agreed due to the use of techniques for crucial measurements in canal shaping and a lack of clarity regarding the measuring methodology. The use of inadequate measuring methodologies makes the findings of the paper invalid.

Metabolic Syndrome and Positive Frailty Screening: A Cross-Sectional Study with Community-Dwelling Older Adults.

Background: Metabolic Syndrome is a set of disorders that characterized by the association of three or more risk factors, like the obesity central, dyslipidemia, borderline blood pressure, hyperglycemia, and the increase of triglycerides. However, these factors also can be associated with pathophysiology of frailty. Objectives: verifying whether the metabolic syndrome is associated to the positive frailty screening in the older people. Design: Cross-sectional study. Participants: 443 older people living in Rio Branco, Brazil. Setting: Data collection was carried out in two stages: a personal interview and blood collection. Measurements: The diagnosis of metabolic syndrome was based on the criteria of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. The frailty screening was performed using subjective questions validated in a previous study. Descriptive statistics and multinomial logistic regression were used for data analyses. Results: There was a predominance of female older people (69.07%), aged between 60 and 79 years (87.13%), with an income greater than or equal to one minimum wage (72.09%), no cognitive decline (75.94%) and depressive symptoms (63.31%), independent for BADL (86.46%) and dependent for IADL (51.69%). From the total sample, 56.88% of the older people were identified as frail, 34.09% pre-frail and 9.03% non frail. The prevalence of metabolic syndrome was 51.69%. After adjusting by the independent variables, an association between metabolic syndrome and pre-frailty was observed, and older people with metabolic syndrome were more likely to be prefrail (RRR=2.36; 95%CI=1.08-5.18). Conclusion: The metabolic syndrome was associated to the increase chance of screening for prefrailty in the older people evaluated, which reinforces the needy to establish preventive measures in relation to the metabolic syndrome to avoid frailty in the older people.

Association of slow N-acetyltransferase 2 profile and anti-TB drug-induced hepatotoxicity in patients from Southern Brazil.

PURPOSE: To determine the frequency of N-acetyltransferase 2 (NAT2) polymorphisms, the NAT2 acetylation profile and its relation to the incidence of gastrointestinal adverse drug reactions (ADRs), anti-tuberculosis (TB) drug-induced hepatotoxicity, and the clinical risk factors for hepatotoxicity in a population from Brazil. METHODS: Two hundred and fifty-four Brazilian TB patients using isoniazid (INH), rifampicin (RMP), and pirazinamide (PZA) were tested in a prospective cohort study. NAT2 genotyping was performed by direct PCR sequencing. The association between gastrointestinal ADRs/hepatotoxicity and the NAT2 profile genotype was evaluated by univariate analysis and multiple logistic regression. RESULTS: Of the 254 patients analyzed, 69 (27.2%) were slow acetylators and 185 (72.8%) were fast acetylators. Sixty-five (25.6%) patients were human immunodeficiency virus (HIV)-positive. Thirty-three (13%) and 14 (5.5%) patients developed gastrointestinal ADR and hepatotoxicity, respectively. Of the 14 hepatotoxicity patients, nine (64.3%) were slow acetylators and five (35.7%) were fast acetylators. Sex, age, presence of hepatitis C virus, alcohol abuse, and baseline aminotransferases were not found to be risk factors for hepatotoxicity. However, logistic regression analysis revealed that slow acetylator status and the presence of HIV (p < 0.05) were independent risk factors for hepatotoxicity. CONCLUSIONS: Our findings show that HIV-positive patients that have the slow acetylation profile are significantly associated with a higher risk of developing hepatotoxicity due to anti-TB drugs.

Immunohistochemical and in situ hybridization studies of the liver and kidney in human leptospirosis.

An in situ hybridization (ISH) assay for the detection of leptospiral DNA in tissues was described and its diagnostic and pathogenetic usefulness in combination with immunohistochemistry (IHC) was evaluated in formalin-fixed, paraffin-embedded liver and kidney samples from human fatal cases of leptospirosis. IHC assays with anti-E-cadherin antibodies assessed the liver-plate disarray frequently observed in leptospirosis. Immunohistochemistry detected leptospiral antigen (LAg) in macrophages, both in human liver and kidney. In guinea pigs, in addition to these findings, staining on cell membranes of hepatocytes and, occasionally, in apical membrane of kidney tubular cells was demonstrated. Positive ISH signal was observed chiefly in the nuclei of human hepatocytes and in the cytoplasm and nuclei of liver cells of experimentally infected guinea pigs. Loss of E-cadherin membrane expression is associated with liver-plate disarray. These findings were discussed in the contention that, in leptospirosis, cell membrane damage might be important for the pathogenesis of the disease. Finally, it was suggested that both IHC and/or ISH might be used for both diagnostic and research purposes.

Correlation between Trypanosoma cruzi parasitism and myocardial inflammatory infiltrate in human chronic chagasic myocarditis: Light microscopy and immunohistochemical findings.

Trypanosoma cruzi parasites are only rarely identified in conventional histological sections of hearts from chronic chagasic patients. This finding suggests that T. cruzi plays no important direct role in the chronic myocarditis that accordingly has been considered mainly an autoimmune process. We reinvestigated this issue using a polyclonal anti-T. cruzi antibody serum to map immunohistochemically the T. cruzi antigen(s) in 9 different regions of 8 necropsy hearts and 24 septal fragments from 24 hearts from chronic chagasic patients. T. cruzi antigen(s) were identified in 7 (87%) of the 8 mapped hearts and in 14 (58%) of the 24 septal fragments. There was a statistically significant correlation between the presence of T. cruzi antigen(s) and moderate or severe inflammatory infiltrate (p = 0.005). When staining revealed amastigotes within intact myocardial fibers, there was no surrounding inflammatory infiltrate. However, when T. cruzi antigen(s) were found in macrophages either as amastigotes, diffusely in the macrophages cytoplasm, or free in the interstitium as round structures similar to amastigotes, there was a heavy inflammatory infiltrate. In the case in which no parasite was detected, a mild inflammatory infiltrate was present in the myocardium. Foci of fibrosis did not stain for T. cruzi antigen. These findings do not exclude a role of autoimmunity in chronic chagasic cardiopathy. However, the striking correlation between the presence of T. cruzi antigen(s) with the severity of site of the inflammatory infiltrate supports a direct role for the parasite in the perpetuation of myocardial inflammation in Chagas' disease. The destruction of microvessels and occasional endothelial cells with parasitism among dense inflammatory infiltrate favors the concept that microcirculatory injury, induced by T. cruzi, also contributes to the lesions of chronic Chagas' disease.

Glomerular involvement in human kala-azar. A light, immunofluorescent, and electron microscopic study based on kidney biopsies.

Glomerular involvement characterized by mesangial cell proliferation with fibrillar thickening of the axial region and deposits of immune complexes is reported in three human cases of kala-azar. IgG was seen in all 3 and Igm in 2 patients. Complement (C3) was detected in the glomeruli in all cases and fibrinogen in the only case in which it was tested for. The deposits appeared mainly along the mesangium and their staining was particularly strong for complement and IgG. Electron microscopy detected granular electron dense deposits mainly close to mesangial cells. In one case clumps made us of electron dense lamellae were seen in the glomerular basal membrane interpreted as evidence of focal membranolysis. No granulocytes were seen in the glomeruli. Attempts to demonstrate antigen were unsuccessful. The pattern of the lesion resembles that described in the kidney of human cases of hepatosplenic schistosomiasis, and the distribution of the deposits suggests that relatively large, poorly soluble complexes formed either in the presence of excess antigen or, under certain circumstances, in the presence of excess antibody, are trapped in the glomerular capillaries. The aggregates are partially shunted to the mesangial cells, which enlarge and proliferate.

Human schistosomiasis: Schistosoma mansoni antigen detection in renal glomeruli.

Twelve kidney, five biopsy and seven necropsy specimens, all from schistosomiasis mansoni patients were studied by light and immunoflurescent microscopy in an attempt to detect antigen in the glomerular walls. Deposits of IgM, IgG,I gA, IgE, complement C3 and fibrinogen were observered in most cases. Antigen was successfully detected in two cases(one biopsy and one necropsy specimen), both exhibiting proliferative glomerulonephritis. The only clinical manifestation was a slight proteinuria. IgG antibodies eluted from the sutopsy kidney homogenates showed specific binding mostly to Schistosoma mansoni gut, thus spggesting that the fixed antibodies (eluates) are, at least partially, consituted by antibodies similar to the anti-circulating antigen. These data reinfroce the hypothesis that renal injury in schistosomiasis is mediated through an immune complex disease.

Cutaneous leishmaniasis of the New World: diagnostic immunopathology and antigen pathways in skin and mucosa.

Non-specific chronic inflammation and/or granulomatous reaction are the main histopathological manifestations of cutaneous and mucocutaneous leishmaniasis of the New World. Plasma cell infiltration associated with collagen and vascular changes are data suggestive but not diagnostic of the disease. Specific diagnosis is only possible through demonstration of the parasite in the tissue examined. It is noteworthy that the parasites are usually scanty and difficult to demonstrate in the lesions. Biopsies from 40 patients with cutaneous or mucocutaneous leishmaniasis were examined using the immunofluorescence and immunoperoxidase techniques in order to demonstrate the parasite and/or antigen in the tissues. Nineteen biopsies showed non-specific chronic inflammation and 21 a granulomatous reaction. Parasites were found in 20% of the routine biopsies. The positivity through indirect immunofluorescence was 88.46% in frozen sections of fresh material and 89.28% in paraffin embedded tissue. The antigen positivity with the immunoperoxidase technique was 64.51%. Antigen was detected as amastigotes and also as diffuse material in the macrophage cytoplasm and adsorbed in the epithelial basement membrane and vessel walls. There was no difference in the positivity of antigen according to the type of inflammatory reaction.

Human fatal yellow fever. Immunohistochemical detection of viral antigens in the liver, kidney and heart.

An immunohistochemical method to detect yellow fever antigen was developed using immune sera from rabbits and hamsters and hyperimmune ascitic fluid from mice. A search for the antigen was carried out in liver, kidney and heart in three fatal cases of yellow fever. In the liver it was present in the cytoplasm of hepatocytes, Councilman bodies and Kupffer cells. Yellow fever antigen was also detected in renal tubular epithelium and in groups of myocardial fibers. These findings suggest that viral replication occurs at sites other than the liver. Since yellow fever shares many features with other haemorrhagic fevers the use of immunohistochemistry can impart a significant improvement in the accuracy of its histopathological diagnosis.

Leptospiral antigens in the liver of experimentally infected guinea pig and their relation to the morphogenesis of liver damage.

In order to investigate the morphogenes of experimental leptospirosis by morphologic and immunohistologic methods, 24 guinea-pigs were inoculated intraperitoneally with L. interrogans serogroup Icterohaemorrhagiae. They were divided in 6 groups, sacrificed from the 1st to the 6th day of infection. Semiquantitative analyses of histopathological liver lesions were performed in 1 micron sections of tissue embedded in glycol-methacrylate. The distribution of leptospiral antigen (L. Ag) and its glycolipoprotein (GLP) was demonstrated by peroxidase-antiperoxidase on paraffin embedded tissue. Significant lesions appeared at the 4th day of infection, progressing to a peak on the 6th day. Inflammation was associated with injury of the portal triad. Liver cells showed either swelling or acidophilic degeneration and necrosis, together with loss of cell cohesion, leading to disarray of liver cell plates. Mitochondria were found progressively enlarged and irregularly distributed. L. Ag expression was parallel to the morphological changes. Portal distribution was significant at the 4th day and on later stages centrilobular localization became predominant. Spiral forms suggestive of intact leptospires were initially found but, chiefly at the 6th day, L. Ag was seen in granules, probably resulting from phagocytosis. GLP staining was similar to granular L. Ag in morphology, and distribution. Cytokeratin condensation was seen in liver cells with acidophilic necrosis and was marked in areas of disorganization of cell plates. Our findings lead us to hypothesize a direct leptospiral cytotoxic effect on endothelial and on liver-cell membranes. At first, leptospires themselves would induce subcellular changes acting mainly on membrane permeability. Afterwards, their granular forms, including GLP, would act as adjuvant factors. These findings demonstrate that the disarray of liver cell plates at the late phase of the disease is genuine.

Intestinal spirochetosis: first cases reported in Brazil and the use of immunohistochemistry as an aid in histopathological diagnosis.

Colonization of the colon and rectum by intestinal spirochetes is detected for the first time in Brazil in 4 of 282 (1.41%) patients who had undergone sigmoidoscopy and/or colonoscopy with a histopathological diagnosis of chronic non specific-colitis. This frequency is probably underestimated, since surgically obtained specimens were not considered in the present study. Histopathological diagnosis was performed using routine stains like hematoxylin-eosin which showed the typical, of 3-microns thick hematoxyphilic fringe on the brush border of the surface epithelium, and by silver stains like the Warthin-Starry stain. Immunohistochemical procedures using two, polyclonal, primary antibodies, one against Treponema pallidum and the other against Leptospira interrogans serovar copenhageni serogroup Icterohaemorrhagiae cross-reacted with spirochetal antigen/s producing a marked contrast of the fringe over the colonic epithelium, preserving the spiral-shaped morphology of the parasite. In one case with marked diarrhea, immunohistochemistry detected spirochetal antigen/s within a cell in an intestinal crypt, thus demonstrating that the infection can be more widely disseminated than suspected using routine stains. Immunohistochemical procedures, thus, greatly facilitate the histological diagnosis of intestinal spirochetosis and may contribute to a better understanding of the pathogenesis of the disease. Transmission and scanning electron microscopy performed in one case showed that the spirochete closely resembled the species designated as Brachyspira aalborgi.

Schistosoma mansoni circulating polysaccharide and protein antigens recognized by sheep antisera in patients with different clinical forms of schistosomiasis before and after treatment.

Two sheep antisera, one of which raised against polysaccharide (Po) and other against protein (Pt) components of Schistosoma mansoni adult worms, were assessed by ELISA for their ability to detect circulating parasite antigens in patients with different clinical forms of chronic schistosomiasis mansoni. The former antiserum detected parasite antigens in liver granulomata and the latter in renal glomeruli from schistosomiasis patients and mice experimentally infected with S. mansoni. In general, the levels and/or positivity rate of circulating antigens and specific IgG antibodies were significantly higher in patients with hepatointestinal (HI) and hepatosplenic (HS) forms than in mild intestinal (I) forms. An association between Po antigens and clinical features of the disease was observed, as the level of these antigens was low (137 ng/ml) as well as the positivity rate (7.9%) in patients with I forms; values that were intermediate (593 ng/ml and 33.3%) in those with HI forms, and high (1.563 ng/ml and 50.0%) in more severe HS forms. The Pt antigens were detected in the studied clinical forms not differing statistically but, the positivity rate was significantly higher in HS forms comparatively to I forms. The antisera studied revealed distinct circulating antigen profiles, and the prognostic value of Po and Pt antigens was suggested.

Liver morphology with emphasis on bile ducts changes and survival analysis in mice submitted to multiple Schistosoma mansoni infections and chemotherapy.

In an attempt to be as close as possible to the infected and treated patients of the endemic areas of schistosomiasis (S. mansoni) and in order to achieve a long period of follow-up, mice were repeatedly infected with a low number of cercariae. Survival data and histological variables such as schistosomal granuloma, portal changes, hepatocellular necrosis, hepatocellular regeneration, schistosomotic pigment, periductal fibrosis and chiefly bile ducts changes were analysed in the infected treated and non treated mice. Oxamniquine chemotherapy in repeatedly infected mice prolonged survival significantly when compared to non-treated animals (chi-square 9.24, p = 0.0024), thus confirming previous results with a similar experimental model but with a shorter term follow-up. Furthermore, mortality decreased rapidly after treatment suggesting an abrupt reduction in the severity of hepatic lesions. A morphological and immunohistochemical study of the liver was carried out. Portal fibrosis, with a pattern resembling human Symmers fibrosis was present at a late phase in the infected animals. Bile duct lesions were quite close to those described in human Mansonian schistosomiasis. Schistosomal antigen was observed in one isolated altered bile duct cell. The pathogenesis of the bile duct changes and its relation to the parasite infection and/or their antigens are discussed.

Effects of pine processionary caterpillar Thaumetopoea pityocampa contact in dogs: 41 cases (2002-2006).

The pine processionary caterpillar, Thaumetopoea pityocampa, is considered an emerging pine pest in Mediterranean countries, with high medical relevance. In recent years, adverse reactions reports in humans following contact with T. pityocampa have been increasingly reported. Dogs living in pinewood areas are also frequently exposed to the caterpillar. This work consisted on a retrospective study of 41 cases of lepidopterism. All dogs presented drooling, dysphagia, submandibular lymphadenomegaly and clinical signs of pain. The animals were distributed in three groups, according to the time span from exposure to the caterpillar until presentation: up to 2 h (group 1), 2-5 h (group 2) and more than 5 h (group 3). All animals from groups 2 (n = 5) and 3 (n = 9), and eight dogs from group 1 (n = 27) developed lingual necrosis. Lepidopterism coursed through a predictable clinical pattern. The evolution was mainly dependent on the time span between exposure to the caterpillar and medical intervention, which should take place earlier than 2 h from exposure.

Cytokine gene expression in the tissues of dogs infected by Leishmania infantum.

Canine leishmaniosis (CanL) caused by the protozoan parasite Leishmania infantum is a chronic systemic disease that is endemic in certain parts of the world. The domestic dog is the most important reservoir of L. infantum and is the main source of infection for other animals and for the human population. The aim of this study was to evaluate and compare the level of expression of genes encoding particular cytokines (interleukin [IL]-12, interferon [IFN]-γ, IL-2 and IL-4) in different tissues and organs of 53 adult dogs with or without clinical signs of leishmaniosis and after treatment for the disease. Asymptomatic dogs showed high expression of genes encoding IL-4 in blood leucocytes and of genes encoding IL-12 and IL-2 in lymph nodes. Blood leucocytes from symptomatic dogs had a mixed Th1 and Th2 cytokine gene expression profile, but lymph nodes from these animals had dominant IL-2 and IFN-γ gene expression, while bone marrow appeared to be unresponsive. The predominance of IL-4 gene expression in the blood of asymptomatic dogs may favour parasite replication, while the balance between Th1 and Th2 cytokine gene expression in the blood of symptomatic dogs may be important in reducing parasite replication and delaying the dissemination of Leishmania to other organs. The drugs used to treat CanL do not completely eliminate the parasite, so the high expression of the gene encoding IL-4 in blood leucocytes and the high expression of IL-12 and IL-4 mRNA in lymph nodes may reflect the persistence of residual Leishmania amastigotes. L. infantum appears able to regulate the host immune response in order to ensure its survival, but also to prevent the host from succumbing to infection. This guarantees its transmission and the completion of its life cycle.