Amastigotes forms of Trypanosoma cruzi detected in a renal allograft

Trypanosoma cruzi, the causative agent of Chagas’disease assumes two distinct forms in vertebrate hosts: circulating trypomastigote and tissular amastigote. This latter form infects predominantly the myocardium, smooth and skeletal muscle, and central nervous system. The present work describes for the first time the detection of amastigote forms of T. cruzi in the renal parenchyma of a kidney graft recipient one month after transplantation. The patient was serologically negative for Chagas’disease and received no blood transfusion prior to transplant. The cadaver donor was from an endemic area for Chagas’disease. The recipient developed the acute form of the disease with detection of amastigote forms of T. cruzi in the renal allograft biopsy and circulating trypomastigote forms. The present report demonstrates that T. cruzi can infect the renal parenchyma. This mode of transmission warrants in endemic areas of Chagas’disease

Serological markers and risk factors for hepatitis B and C viruses in patients infected with human immunodeficiency virus

Both hepatitis B and hepatitis C viruses (HBV and HCV) infection are common in HIV-infected individuals as a result of shared risk factors for acquisition. A serological study for HBV and HCV was performed in 251 HIV-positive individuals from Medellín, Colombia. A qualitative RT-PCR for HCV was done in 90 patients with CD4+ T-cell count < 150 per mm³. Serological markers for HBV infection were present in 97 (38.6%) patients. Thirty six of them (37.1%) had isolated anti-HBc. A multivariate analysis indicated that the following risk factors were significantly associated with the presence of these markers: age (OR = 1.05, 95% CI: 1.01-1.08), pediculosis pubis (OR = 1.83, 95% CI: 1.01-3.33), men who have sex with men and women (OR = 3.23, 95% CI: 1.46-7.13) and men who have sex only with men (OR = 3.73, 95% CI: 1.58-8.78). The same analysis restricted to women showed syphilis as the only significant risk factor. Thus, HBV infection was considerably associated with high risk sexual behavior. HCV was present in only two (0.8%) of HIV patients. Both of them were positive by RT-PCR and anti-HCV. This low frequency of HIV/HCV coinfection was probably due to the uncommon intravenous drug abuse in this population. The frequent finding of isolated anti-HBc warrants molecular approaches to rule out the presence of cryptic HBV infection.

The use of long acting sulfonamides, alone or with pyrimethamine, in malaria (with special reference to sulformetoxine)

Review of the early literature as well as more recent results show that sulfonamides possess a distinct antimalarial activity. However, when give alone, their action is less marked and slower than that of the antimalarials commonly used in the treatment of the acute attack. Combinations with pyrimethamine provide better results, even in cases of pyrimethamine and chloroquine resistance. This warrants further investigations in an attempt to develop a therapeutic agent suitable for the treatment of such resistant cases. It may also be possible with an appropriate combination of pyrimethamine with a sulfonamide to achieve a satisfactory method for suppressive treatment both in areas with and without pyrimethamine resistance. Three main points must still be carefully studied: 1) the risk of developing malaria resistance against one or both of the components of the combination. 2) The risk of developing bacterial resistance to sulfonamides if these substances are used on a large scale in too low doses. It seems indeed that antimalarial effect with the combination of sufonamides + pyrimethamine can be obtained with doses of sulfonamides which are below those usually employed in bacterial diseases. Since the range of the ratios providing potentiation is rather large, only ratios of the combination sulfonamides: pyrimethamine should be chosen in which an antfbacterial sulfonamidemia is guaranteed. 3) It goes without sayinq that, although both pyrimethamine and modem sulfonamides, when given by themselves, have proved tc possess a large margin of safety, long term administration of their combination should be careful studied from the point of view of possible side effects. Substantial evidence has already been produced to show that the long acting sulfonamide Fanasil (Ro 4-4393) given once or once weekly possesses marked schizonticidal activity against P. falciparum. Although its action is slower than that of 4-aminoquinolines, it may be useful as a second choice drug in semi-immune subjects for the therapy of falciparum malaria. Preliminary results show that, when combined with pyrimethamine, Fanasil is highly effective in suppressing fever and asexual parasitemia due to P. falciparum. Single doses of 1 g Fanasil together with 50 mg pyrimethamine seem to be adequate for the treatment of acute falciparum malaria in semi-immune patients. The onset of action of the combination is much more rapid than that of the single components. Weekly doses of 500 mg Fanasil and 25 mg pyrimeihamine appear to provide satisfactory suppressive effects against P. falciparum at least in East Africa. This combination is active on strains which do not respond satisfactorily to the standard doses of pyrimethamine and/or chloroquine and seems to have a satisfactory sporontocidal effect. Preliminary results indicate that Fanasil alone cannot be recommended for use against the other human malaria parasites. The combination with pyrimethamine appears to be much more effective. East African strains of P. malariae seem to respond better to the combination than do Malayan strains of P. vivax but further trials are required before definite assessment can be made. Fanasil by itself has no gametocytoddal or sporontocidal action but seems to potentiate the effect of pyrimethamine at least on sporogony of P. falciparum.

Gene Expression Profiling and Association Studies Implicate the Neuregulin Signaling Pathway in Behçet's Disease Susceptibility

Behçet's disease (BD) is a complex disease with genetic and environmental risk factors implicated in its etiology; however, its pathophysiology is poorly understood. To decipher BD's genetic underpinnings, we combined gene expression profiling with pathway analysis and association studies. We compared the gene expression profiles in peripheral blood mononuclear cells (PBMCs) of 15 patients and 14 matched controls using Affymetrix microarrays and found that the neuregulin signaling pathway was over-represented among the differentially expressed genes. The Epiregulin (EREG), Amphiregulin (AREG), and Neuregulin-1 (NRG1) genes of this pathway stand out as they are also among the top differentially expressed genes. Twelve haplotype tagging SNPs at the EREG-AREG locus and 15 SNPs in NRG1 found associated in at least one published BD genome-wide association study were tested for association with BD in a dataset of 976 Iranian patients and 839 controls. We found a novel association with BD for the rs6845297 SNP located downstream of EREG, and replicated three associations at NRG1 (rs4489285, rs383632, and rs1462891). Multifactor dimensionality reduction analysis indicated the existence of epistatic interactions between EREG and NRG1 variants. EREG-AREG and NRG1, which are members of the epidermal growth factor (EGF) family, seem to modulate BD susceptibility through main effects and gene–gene interactions. These association findings support a role for the EGF/ErbB signaling pathway inBD pathogenesis that warrants further investigation and highlight the importance of combining genetic and genomic approaches to dissect the genetic architecture of complex diseases.

A abolição da dupla incriminação no mandado de detenção europeu

This essay presents the European Arrest Warrant and its relationship with the principle of double criminality, which was abolished in 2002 with the new Framework Decision (FD). This instrument was essential to implement the principle of mutual recognition and strengthen the police and judicial cooperation in criminal matters in the newly created space of freedom, security and justice. It was urgent to create mechanisms to combat cross-border crime, that alone States have struggled to counter. An analysis of the FD No 2002/584/JHA is made. The execution of warrants and the non-mandatory and optional grounds of refusal are studied in detail. As it is the implementation issue. The role of mutual recognition in practice is studied as well. The procedure is to introduce the principle of double criminality, to explain the concept and its abolition, warning for the consequences derived from them, related to the principle of legality and fundamental rights. The analysis of the European Arrest Warrant in practice in Portugal and in comparison with other Member States allows the measurement of the consequences from the abolition of dual criminality and the position of States on this measure. With the abolition of double criminality, the cooperation in judicial and criminal matters departs from what was intended by the European Council of Tampere. And without cooperation, fundamental rights of citizens are unprotected, so the states have to adopt measures to remedy the "failures" of the European Law.

Laboratory diagnosis of amebiasis in a sample of students from southeastern Brazil and a comparison of microscopy with enzyme-linked immunosorbent assay for screening of infections with Entamoeba sp.

Introduction: Epidemiological studies on amebiasis have been reassessed since Entamoeba histolytica and E. dispar were first recognized as distinct species. Because the morphological similarity of these species renders microscopic diagnosis unreliable, additional tools are required to discriminate between Entamoeba species. The objectives of our study were to compare microscopy with ELISA kit (IVD®) results, to diagnose E. histolytica infection, and to determine the prevalence of amebiasis in a sample of students from southeastern Brazil. Methods: In this study, diagnosis was based on microscopy due to its capacity for revealing potential cysts/trophozoites and on two commercial kits for antigen detection in stool samples. Results: For 1,403 samples collected from students aged 6 to 14 years who were living in Divinópolis, Minas Gerais, Brazil, microscopy underestimated the number of individuals infected with E. histolytica/E. dispar (5.7% prevalence) compared with the ELISA kit (IVD®)-based diagnoses (15.7% for E. histolytica/E. dispar). A comparison of the ELISA (IVD®) and light microscopy results returned a 20% sensitivity, 97% specificity, low positive predictive value, and high negative predictive value for microscopy. An ELISA kit (TechLab®) that was specific for E. histolytica detected a 3.1% (43/1403) prevalence for E. histolytica infection. Conclusions: The ELISA kit (IVD®) can be used as an alternative screening tool. The high prevalence of E. histolytica infection detected in this study warrants the implementation of actions directed toward health promotion and preventive measures.

Relatório de estágio no departamento central de investigação e acção penal

The means of obtaining evidence, the amount of evidence obtained, the number of defendants related to each criminal case and the gravity of the crimes for which the magistrates of the Department are holders of penal action, define its real importance to the Rule of Law. I have deeply studied the subject of the institution of hierarchical intervention required by the assistant and the application of an opening statement by the defendant, starting from a hypothetical case, provided when the query of an investigation with the subject of the crime of active corruption, where this institution was called as a reaction to the archiving dispatch delivered by the Public Ministry. I have study about the implementation of the institution of provisional suspension of the process, specifically in the scope of fiscal criminality, analyzing the effective satisfaction of the purposes of the sentences in two slopes: general prevention and special prevention. I went for my first time to a Central Court of Criminal Instruction, where I attended the measures of inquiry and instructive debate of a process that culminated with the prosecution and pronunciation of the defendants. In addition to this criminal experience, I have deepened and consolidated the academic knowledge with the study of various criminal cases from various fields in the scope of criminality investigated by the Department. I could therefore check the basis of procedural delays, regarding to our legal system, especially in this type of crime, raising issues that I analyzed and discussed, always in a critical and academic way. I had the opportunity to attend and witness a seminar in the Lisbon Directorate of Finance as well of entering the Centre for Judicial Studies to attend a conference on the International Anti-Corruption Day. Focus on the investigatory importance of the international judicial cooperation, through the various organs, with special interest to EUROJUST. I comprehended the organization and functioning of these communitarian organs and means of communication of procedural acts, in particular, the rogatory letters and european arrest warrants. This involvement is motivated by the moratorium factor of the investigations where rogatory letters are necessary for the acquisition of evidence or information relevant to the good continuation of the process. For this reason the judicial cooperation through the relevant communitarian organs, translates a streamlined response between the competent judicial authorities of the Member States, through the National Member that integrates EUROJUST. This report aims to highlight some of the difficulties and procedural issues that Public Prosecutors of DCIAP and criminal police bodies that assist them, face in combating violent and organized crime, of national and transnational nature, of particular complexity, according to the specifics of criminal types.

A abolição da dupla incriminação no mandado de detenção europeu

This essay presents the European Arrest Warrant and its relationship with the principle of double criminality, which was abolished in 2002 with the new Framework Decision (FD). This instrument was essential to implement the principle of mutual recognition and strengthen the police and judicial cooperation in criminal matters in the newly created space of freedom, security and justice. It was urgent to create mechanisms to combat cross-border crime, that alone States have struggled to counter. An analysis of the FD No 2002/584/JHA is made. The execution of warrants and the non-mandatory and optional grounds of refusal are studied in detail. As it is the implementation issue. The role of mutual recognition in practice is studied as well. The procedure is to introduce the principle of double criminality, to explain the concept and its abolition, warning for the consequences derived from them, related to the principle of legality and fundamental rights. The analysis of the European Arrest Warrant in practice in Portugal and in comparison with other Member States allows the measurement of the consequences from the abolition of dual criminality and the position of States on this measure. With the abolition of double criminality, the cooperation in judicial and criminal matters departs from what was intended by the European Council of Tampere. And without cooperation, fundamental rights of citizens are unprotected, so the states have to adopt measures to remedy the "failures" of the European Law.

Analysis of haemochromatosis mutations in the North West population

Background: Hereditary haemochromatosis is a heritable disorder caused by an inborn error in the metabolism of iron. It results in over absorption of iron by the body, which can manifest clinically as fatigue, arthritis, diabetes and cardiovascular problems. The highest prevalence for the genetic mutations that cause hereditary haemochromatosis can be found in the Irish population. Individuals with diabetes may also have haemochromatosis (and vice versa), due to the bi-directional relationship between iron metabolism and glucose metabolism. Objectives: To determine the incidence of the three haemochromatosis mutations C282Y, H63D & S65C, in a population from the North West of Ireland and to investigate whether there is an increased frequency of these three mutations in a diabetic population from the same region. Method: DNA was extracted from 500 whole blood samples (250 diabetic samples and 250 ‘control’ samples) using a Wizard™ kit. PCR was conducted utilising specific primers for each mutation and in accordance with a set protocol. Following amplification, PCR product was subjected to restriction endonuclease digestion, where different restriction enzymes (Rsa I, Nde II & Hinf I) were employed to determine the HFE genotype status of samples. Results: The incidence of C282Y homozygosity (1/83) and C282Y heterozygosity (1/6) in the ‘control’ group was similar to those reported for the general Irish population (1/83 and 1/5, respectively). Incidences of H63D homozygotes and H63D heterozygotes or ‘carriers’ in the diabetic population were greater than that of the ‘control’ population. A significant finding of this study was that of an incidence of 1/32 S65C carriers in the control population. This is, to our knowledge, the highest incidence of the genotype reported to date in the general Irish population. Statistical analysis showed that there was no significant differences between the HFE genotype frequencies in the Diabetic and Control Populations. Conclusion: Results of the study concord with published literature in terms of C282Y homozygosity and C282Y heterozygosity in the general Irish population. An increased frequency of the H63D mutation in diabetic individuals was also found but was not statistically significant. The biochemical effect of the H63D mutation is still unknown. The significance of such a high incidence of S65C carriers in the ‘control’ population warrants further investigation.

Anxiety, Depression, and General Psychological Distress in Patients with Coronary Slow Flow

AbstractBackground:The relationship between psychiatric illness and heart disease has been frequently discussed in the literature. The aim of the present study was to investigate the relationship between anxiety, depression and overall psychological distress, and coronary slow flow (CSF).Methods:In total, 44 patients with CSF and a control group of 50 patients with normal coronary arteries (NCA) were prospectively recruited. Clinical data, admission laboratory parameters, and echocardiographic and angiographic characteristics were recorded. Symptom Checklist 90 Revised (SCL-90-R), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) scales were administered to each patient.Results:The groups were comparable with respect to age, sex, and atherosclerotic risk factors. In the CSF group, BAI score, BDI score, and general symptom index were significantly higher than controls (13 [18.7] vs. 7.5 [7], p = 0.01; 11 [14.7] vs. 6.5 [7], p = 0.01; 1.76 [0.81] vs. 1.1[0.24], p = 0.01; respectively). Patients with CSF in more than one vessel had the highest test scores. In univariate correlation analysis, mean thrombolysis in myocardial infarction (TIMI) frame counts were positively correlated with BAI (r = 0.56, p = 0.01), BDI (r = 0.47, p = 0.01), and general symptom index (r = 0.65, p = 0.01). The psychiatric tests were not correlated with risk factors for atherosclerosis.Conclusion:Our study revealed higher rates of depression, anxiety, and overall psychological distress in patients with CSF. This conclusion warrants further studies.

Identification of schistosome-infected snails by detecting schistosomal antigens and DNA sequences

Cercarial shedding tests do not provide species identification of the shistosomes concerned and cannot detect prepatent schistosomal infections. We have demonstrated that both immunodetection by ELISA of schistosomal antigens in snail hemophlymph, and dot hybridization of snail extracts by DNA probe representing highly repeated sequences, proved suitable for detecting infected snails during prepatnecy as well as patency. A group-specific monoclonal antibody was found to be suitable for detecting Schistosoma mansoni infection in Biomphalaria sp., but not for positive identification of S. haematobium in Blulinus sp. Comparative evaluation of the diagnostic qualities, and technical aspects and cost of these tests, point to the superiority of the immunodetection approach for large scale detection of snails prepatently infected with S. mansoni. This approach is potentially useful for providing extended information on schistosome-snail epidemiology that may facilitate rapid evaluation of the danger of post-control reinfection, and help make decisions on the time and place of supplementary control measures. In this context the potential usefulness of the immunodetection or DNA probing approach for facilitating catalytic model representation of schistosome-snail epidemiology warrants further evaluation. Specific identification of S. haematobium in Bulinus by either of these approaches may be possible depending on the development of suitable antibodies or DNA probes.

Altered expression of CD44 and DKK1 in the progression of Barrett's esophagus to esophageal adenocarcinoma.

Barrett's esophagus (BE) is an acquired condition in which the normal lining of the esophagus is replaced by intestinal metaplastic epithelium. BE can evolve to esophageal adenocarcinoma (EAC) through low-grade dysplasia (LGD) and high-grade dysplasia (HGD). The only generally accepted marker for increased risk of EAC is the presence of HGD, diagnosed on endoscopic biopsies. More specific markers for the prediction of EAC risk are needed. A tissue microarray was constructed comprising tissue samples from BE, LGD, HGD, and EAC. Marker expression was studied by immunohistochemistry using antibodies against CD44, DKK1, CDX2, COX2, SOX9, OCT1, E-cadherin, and beta-catenin. Immunostaining was evaluated semi-quantitatively. CD44 expression decreased in HGD and EAC relative to BE and LGD. DKK1 expression increased in HGD and EAC relative to BE and LDG. CDX2 expression increased in HGD but decreased in EAC. COX2 expression decreased in EAC, and SOX9 expression increased only in the upper crypt epithelial cells in HGD. E-cadherin expression decreased in EAC. Nuclear beta-catenin was not significantly different between BE, LGD, and HGD. Loss of CD44 and gain of DKK1 expression characterizes progression from BE and LGD to HGD and EAC, and their altered expression might indicate an increased risk for developing an EAC. This observation warrants inclusion of these immunohistochemically detectable markers in a study with a long patient follow-up.

Genital manifestations of schistosomiasis mansoni in women: important but neglected

Egg-induced lesions in the upper and the lower female reproductive tract are important complications of the infection with Schistosoma mansoni. The understanding of the pathophysiology and pathology of genital lesions is only rudimentary, simple and reliable diagnostic tools are not at hand, epidemiological data do not exist and how to treat best the women affected, is not known. In view of recent advances in the understanding of genital lesions induced by S. haematobium the existing literature is critically analysized and possible consequences of female genital schistosomiasis are outlined. We estimate that 6 to 27 % girls and women with intestinal schistosomiasis, at least temporarily, suffer from pathology induced by eggs sequestered somewhere in their genital organs. This is a mattern of concern and warrants more research into the epidemiology, pathology, diagnosis and therapy of this disease entity.

Liver kidney microsomes type 1 antibodies are associated with 80% reduction of the CYP2D6 activity in patients with chronic hepatitis C

Introduction Liver kidney microsomal type 1 (LKM-1) antibodies have been shown to decrease CYP2D6 activity in vitro. We investigated whether LKM-1 antibodies might reduce CYP2D6 activity also in vivo.Materials and Methods All patients with chronic hepatitis C and LKM-1 antibodies enrolled in the Swiss Hepatitis C Cohort Study (SCCS) were assessed: ten were eligible and fi tted to patients without LKM-1 antibodies. Patients were genotyped for CYP2D6 variants to exclude individuals with a poor metabolizer genotype. CYP2D6 activity was measured by a specifi c substrate using the dextromethorphan/dextrorphan (DEM/DOR) metabolic ratio to classify patients into four activity phenotypes (i.e. ultrarapid, extensive, intermediate and poor metabolizers). The concordance between phenotype based on DEM/DOR ratio and phenotype expected from genotype was examined in LKM-1 positive and negative patients. Groups were compared with respect to the DEM/DOR metabolic ratio.Results All patients had a CYP2D6 extensive metabolizer genotype. The observed phenotype was concordant with CYP2D6 genotype in most LKM-negative patients, whereas only three (30%) LKM-1 positive patients had a concordant phenotype (six presented an intermediate and one a poor metabolizer phenotype). The median DEM/DOR ratio was six-fold higher in LKM-1 positive than in LKM-1 negative patients (0.096 vs. 0.016, p = 0.004), indicating that CYP2D6 metabolic function was significantly reduced in the presence of LKM-1 antibodies.Conclusion In chronic hepatitis C patients with LKM-1 antibodies, the CYP2D6 metabolic activity was on average reduced by 80%. The impact of LKM-1 antibodies on CYP2D6-mediated drug metabolism pathways warrants further translational studies in the setting of new protease inhibitor therapies

Multilevel oblique corpectomy for cervical spondylotic myelopathy preserves segmental motion.

PURPOSE: To document the neurological outcome, spinal alignment and segmental range of movement after oblique cervical corpectomy (OCC) for cervical compressive myelopathy. METHODS: This retrospective study included 109 patients--93 with cervical spondylotic myelopathy and 16 with ossified posterior longitudinal ligament in whom spinal curvature and range of segmental movements were assessed on neutral and dynamic cervical radiographs. Neurological function was measured by Nurick's grade and modified Japanese Orthopedic Association (JOA) scores. Eighty-eight patients (81%) underwent either a single- or two-level corpectomy; the remaining (19%) undergoing three- or four-level corpectomies. The average duration of follow-up was 30.52 months. RESULTS: The Nurick's grade and the JOA scores showed statistically significant improvements after surgery (p < 0.001). The mean postoperative segmental angle in the neutral position straightened by 4.7 ± 6.5°. The residual segmental range of movement for a single-level corpectomy was 16.7° (59.7% of the preoperative value), for two-level corpectomy it was 20.0° (67.2%) and for three-level corpectomies it was 22.9° (74.3%). 63% of patients with lordotic spines continued to have lordosis postoperatively while only one became kyphotic without clinical worsening. Four patients with preoperative kyphotic spines showed no change in spine curvature. None developed spinal instability. CONCLUSIONS: The OCC preserves segmental motion in the short-term, however, the tendency towards straightening of the spine, albeit without clinical worsening, warrants serial follow-up imaging to determine whether this motion preservation is long lasting.