Lack of galectin-3 alters the balance of innate immune cytokines and confers resistance to Rhodococcus equi infection

Galectin-3 is a p-galactoside-binding lectin implicated in the fine-tuning of innate immunity. Rhodococcus equi, a facultative intracellular bacterium of macrophages, causes severe granulomatous bronchopneumonia in young horses and immunocompromised humans. The aim of this study is to investigate the role of galectin-3 in the innate resistance mechanism against R. equi infection. The bacterial challenge of galectin-3-deficient mice (gal3(-/-)) and their wild-type counterpart (gal3(+/+)) revealed that the LD50 for the gal3(-/-) mice was about seven times higher than that for the gal3(+/+) mice. When challenged with a sublethal dose, gal3(-/-) mice showed lower bacteria counts and higher production of IL-12 and IFN-gamma production, besides exhibiting a delayed although increased inflammatory reaction. Gal3(-/-) macrophages exhibited a decreased frequency of bacterial replication and survival, and higher transcript levels of IL-1 beta, IL-6, IL-10, TLR2 and MyD88. R. equi-infected gal3(+/+) macrophages showed decreased expression of TLR2, whereas R. equi-infected gal3(-/-) macrophages showed enhanced expression of this receptor. Furthermore, galectin-3 deficiency in macrophages may be responsible for the higher IL-1 beta serum levels detected in infected gal3(-/-) mice. Therefore galectin-3 may exert a regulatory role in innate immunity by diminishing IL-1 beta production and thus affecting resistance to R. equi infection.

Leprosy in transplant recipients: report of a case after liver transplantation and review of the literature

P>Leprosy still is an important public health problem in several parts of the world including Brazil. Unlike the diseases caused by other mycobacteria, the incidence and clinical presentation of leprosy seems little affected in immunosuppressed patients. We report the first case, to our knowledge, of a liver transplant patient who developed multi-bacillary leprosy. The patient presented with papules and infiltrated plaques with loss of sensation suggestive of leprosy 3.5 years after living-related liver transplantation for autoimmune hepatitis. A skin biopsy showing non-caseating macrophagic granulomas, neuritis, and intact acid-fast bacilli on Fite-Faraco stain, confirmed the diagnosis of borderline lepromatous leprosy. The donor of the liver did not show any evidence of leprosy. During follow-up, the patient presented 2 episodes of upgrading leprosy type I reactions, 1 mild before leprosy treatment, and 1 moderate 3 months after receiving standard multi-drug treatment (rifampicin, clofazimine, and dapsone). These reactions were accompanied by increase in liver function tests, especially of canalicular enzymes. This reaction occurred despite the patient`s triple immunosuppression regimen. The moderate reaction was successfully treated with further immunosuppression (prednisone, 0.5 mg/kg). Currently, the patient is asymptomatic, off leprosy medication, with routine liver transplant follow-up. The dilemmas in diagnosis and management of such a case are discussed and the literature on leprosy in transplant recipients is reviewed.

Accuracy of store-and-forward diagnosis in leproy

Telemedicine might increase the speed of diagnosis for leprosy and reduce the development of disabilities. We compared the accuracy of diagnosis made by telemedicine with that made by in-person examination. The cases were patients with suspected leprosy at eight public health clinics in outlying areas of the city of Sao Paulo. The case history and clinical examination data, and at least two clinical images for each patient, were stored in a web-based system developed for teledermatology. After the examination in the public clinic, patients then attended a teaching hospital for an in-person examination. The benchmark was the clinical examination of two dermatologists at the university hospital. From August 2005 to April 2006, 142 suspected cases of leprosy were forwarded to the website by the doctors at the clinics. Of these, 36 cases were excluded. There was overall agreement in the diagnosis of leprosy in 74% of the 106 remaining cases. The sensitivity was 78% and the specificity was 31%. Although the specificity was low, the study suggests that telemedicine may be a useful low-cost method for obtaining second opinions in programmes to control leprosy.

Endemic and opportunistic infections in Brazilian solid organ transplant recipients

OBJECTIVE To evaluate the frequency and clinical features of endemic and other opportunistic infections in liver or kidney transplant recipients in four transplant centres in different geographical areas of Brazil. METHODS Retrospective analysis of medical and laboratory records of four transplant centres on endemic and other opportunistic infections in liver or kidney transplant recipients. Analyses were performed with spss statistical software. RESULTS From 2001 to 2006, 1046 kidney and 708 liver transplants were registered in all centres. The average age was 42 years. Among 82 (4.7%) cases with infections, the most frequent was tuberculosis (2.0%), followed by systemic protozoal infections (0.7%), toxoplasmosis (0.4%) and visceral leishmaniasis (0.3%). Systemic fungal infections occurred in 0.6%, of which 0.4% were cryptococcosis and 0.2% were histoplasmosis. Dengue was the only systemic viral infection and was registered in two cases (0.1%), of which one was classified as the classic form and the other as dengue haemorrhagic fever. Nocardiosis was described in one case (0.05%). The infectious agents most frequently associated with diarrhoea were Blastocystis sp., Schistosoma mansoni and Strongyloides stercoralis. CONCLUSIONS Opportunistic Infections in transplant patients have a wide spectrum and may vary from asymptomatic to severe infections with high mortality. A better understanding of the epidemiology of endemic pathogens and clinical manifestations can contribute to the establishment of an early diagnosis as well as correct treatment aimed at decreasing morbidity and mortality.

Molecular Characterization, Distribution, and Dynamics of Hepatitis C Virus Genotypes in Blood Donors in Colombia

Hepatitis C virus (HCV) is a frequent cause of acute and chronic hepatitis and a leading cause for cirrhosis of the liver and hepatocellular carcinoma. HCV is classified in six major genotypes and more than 70 subtypes. In Colombian blood banks, serum samples were tested for anti-HCV antibodies using a third-generation ELISA. The aim of this study was to characterize the viral sequences in plasma of 184 volunteer blood donors who attended the ""Banco Nacional de Sangre de la Cruz Roja Colombiana,`` Bogota, Colombia. Three different HCV genomic regions were amplified by nested PCR. The first of these was a segment of 180 bp of the 5`UTR region to confirm the previous diagnosis by ELISA. From those that were positive to the 5`UTR region, two further segments were amplified for genotyping and subtyping by phylogenetic analysis: a segment of 380 bp from the NS5B region; and a segment of 391 bp from the E1 region. The distribution of HCV subtypes was: 1b (82.8%), 1a (5.7%), 2a (5.7%), 2b (2.8%), and 3a (2.8%). By applying Bayesian Markov chain Monte Carlo simulation, it was estimated that HCV-1b was introduced into Bogota around 1950. Also, this subtype spread at an exponential rate between about 1970 to about 1990, after which transmission of HCV was reduced by anti-HCV testing of this population. Among Colombian blood donors, HCV genotype 1b is the most frequent genotype, especially in large urban conglomerates such as Bogota, as is the case in other South American countries. J. Med. Virol. 82: 1889-1898, 2010. (C) 2010 Wiley-Liss, Inc.

Breast cancer in Western Australia in 1989 .5. Outcome at 5 years after diagnosis

Background: A follow-up study was undertaken of all Western Australian women who had a new diagnosis of boast cancer during 1989. The aims were to determine survival, frequency of recurrence and quality of life (QoL) of Western Australian women 5 years after a diagnosis of breast cancer; to determine reasons for choice ol rejection of reconstructive surgery in those women treated by mastectomy, and to determine if the choice of lumpectomy or mastectomy affects subsequent QoL. Methods: The vital status as at Ist June 1994 of all 692 women who had a new diagnosis of breast cancer in 1989 was ascertained by electronic linkage to official mortality registrations. A subsample of 215 survivors who had originally been treated by the nine surgeons who had managed 20 or more cases each was sent a reply-paid postal questionnaire asking about follow-up treatment since diagnosis, recurrence of disease, current QoL and attitudes to, and use of, reconstructive surgery. Results: The overall survival rate at 5 years was 80.8% (85.9% and 78.8% for Stage I and II, respectively). Cumulative mortality was 35% lower among the third of patients treated by the nine most active surgeons (14% vs 22%, P < 0.02), but this may be subject to referral bias. The subsample was representative of all surviving cases except for being an average of 2.7 years younger at diagnosis (mean ages 55.2 and 57.9 years). The response rate of the subsample to the postal questionnaire was 78%. Of women who had had a mastectomy. 40% had considered having a reconstruction, but only nine (78%) had undergone this operation. Median QoL on the Rosser scale (maximum = 1.0) was 0.9. QoL was worse for the 23% of patients with a recurrence of breast cancer. Patients treated by breast-conserving surgery showed a trend toward a better QoL compared with those treated by mastectomy. Conclusion: At 5 years after the diagnosis of breast cancer, one in five women had died and an estimated one in four of the survivors had recurrent disease. Quality of life in the remaining patients, half of whom had undergone adjuvant treatment, was very good. These are important baseline data against which to judge the impact of mammographic screening.

Phylogenetic Analysis of Hepatitis B Virus Genotype F Complete Genome Sequences From Chilean Patients With Chronic Infection

Molecular epidemiological data concerning the hepatitis B virus (HBV) in Chile are not known completely. Since the HBV genotype F is the most prevalent in the country, the goal of this study was to obtain full HBV genome sequences from patients infected chronically in order to determine their subgenotypes and the occurrence of resistance-associated mutations. Twenty-one serum samples from antiviral drug-naive patients with chronic hepatitis B were subjected to full-length PCR amplification, and both strands of the whole genomes were fully sequenced. Phylogenetic analyses were performed along with reference sequences available from GenBank (n = 290). The sequences were aligned using Clustal X and edited in the SE-AL software. Bayesian phylogenetic analyses were conducted by Markov Chain Monte Carlo simulations (MCMC) for 10 million generations in order to obtain the substitution tree using BEAST. The sequences were also analyzed for the presence of primary drug resistance mutations using CodonCode Aligner Software. The phylogenetic analyses indicated that all sequences were found to be the HBV subgenotype F1b, clustered into four different groups, suggesting that diverse lineages of this subgenotype may be circulating within this population of Chilean patients. J. Med. Virol. 83: 1530-1536, 2011. (C) 2011 Wiley-Liss, Inc.

Adult starvation and disease-related malnutrition: A proposal for etiology-based diagnosis in the clinical practice setting from the International Consensus Guideline Committee

Background & aims: Multiple definitions for malnutrition syndromes are found in the literature resulting in confusion. Recent evidence suggests that varying degrees of acute or chronic inflammation are key contributing factors in the pathophysiology of malnutrition that is associated with disease or injury. Methods: An International Guideline Committee was constituted to develop a consensus approach to defining malnutrition syndromes for adults in the clinical setting. Consensus was achieved through a series of meetings held at the ASPEN and ESPEN Congresses. Results: It was agreed that an etiology-based approach that incorporates a current understanding of inflammatory response would be most appropriate. The Committee proposes the following nomenclature for nutrition diagnosis in adults in the clinical practice setting. ""Starvation-related malnutrition"", when there is chronic starvation without inflammation, ""chronic disease-related malnutrition"", when inflammation is chronic and of mild to moderate degree, and ""acute disease or injury-related malnutrition"", when inflammation is acute and of severe degree. Conclusions: This commentary is intended to present a simple etiology-based construct for the diagnosis of adult malnutrition in the clinical setting. Development of associated laboratory, functional, food intake, and body weight criteria and their application to routine clinical practice will require validation. (C) 2009 European Society for Clinical Nutrition and Metabolism and ASPEN American Society for Parenteral and Enteral Nutrition. Published by Elsevier Ltd. All rights reserved.

Adult Starvation and Disease-Related Malnutrition: A Proposal for Etiology-Based Diagnosis in the Clinical Practice Setting From the International Consensus Guideline Committee

Background & Aims: Multiple definitions for malnutrition syndromes are found in the literature resulting in confusion. Recent evidence suggests that varying degrees of acute or chronic inflammation are key contributing factors in the pathophysiology of malnutrition that is associated with disease or injury. Methods: An International Guideline Committee was constituted to develop a consensus approach to defining malnutrition syndromes for adults in the clinical setting. Consensus was achieved through a series of meetings held at the ASPEN. and ESPEN Congresses. Results: It was agreed that an etiology-based approach that incorporates a current understanding of inflammatory response would be most appropriate. The Committee proposes the following nomenclature for nutrition diagnosis in adults in the clinical practice setting. ""Starvation-related malnutrition,"" when there is chronic starvation without inflammation, ""chronic disease-related malnutrition"", when inflammation is chronic and of mild to moderate degree, and ""acute disease or injury-related malnutrition"", when inflammation is acute and of severe degree. Conclusions: This commentary is intended to present a simple etiology-based construct for the diagnosis of adult malnutrition in the clinical setting. Development of associated laboratory, functional, food intake, and body weight criteria and their application to routine clinical practice will require validation. (JPEN J Parenter Enteral Mar. 2010;34:156-159)

Solid pseudopapillary neoplasm of the pancreas: distinct patterns of onset, diagnosis, and prognosis for male versus female patients

Background. Solid pseudopapillary neoplasm of the pancreas is a distinctive pancreatic neoplasm with low metastatic potential. This study examines clinical differences and prognosis between male and female Patients. Methods. The medical records of 34 consecutive patients with pancreatic solid pseudopapillaly neoplasms between 1990 and 2006 were reviewed. Whenever feasible, organ-preserving operation was performed. Statistical analysis was performed using chi-square and Student t test. Results. There were 27 women (79%) and seven men (21%) with median age of 23 years. Mean diameter of the tumor was 7 cm. Tumor size tended to be smaller in patients treated in more recent years. Conservative surgery was possible in I I patients including spleen-preserving distal pancreatectomy in 3, central pancreatectomy in 5, and enucleation in 3 patients. Median hospital stay was 11 days, morbidity rate was 62%, including 17 patients with grade A pancreatic fistula, and there was no operative mortality. Mean follow-up time was 84 months. Tumor recurred in 2 patients (6%). Overall late morbidity rate was 12%. At the time of diagnosis, age was ((x) over bar +/- SD) higher among male patients (25 +/- 2 years vs 37 +/- 7 years, P < .05) with no difference in tumor size. The neoplasms were more aggressive in male Patients; therefore, conservative surgery was less likely. There was no correlation between tumor aggressiveness and age of the patient or size of tumor. Conclusion. This is the first single center study to demonstrate that solid pseudopapillary neoplasms in male patients have distinct Patterns Of onset and aggressiveness when compared with female patients. Although valid prognostic criteria are still lacking, it appears that male patients may be best treated by more radical operation and should be observed more closely during follow-up.

Immunohistochemistry and polymerase chain reaction on paraffin-embedded material improve the diagnosis of cutaneous leishmaniasis in the Amazon region

Background Recently, there has been an increase in the incidence of cutaneous leishmaniasis (CL), which represents an important health problem. This increase may be related to the epidemiologic expansion of the infective agent and the increase in tourism in tropical areas. The difficulty in clinical diagnosis, mainly in areas in which CL is not the first consideration of local physicians, has intensified efforts to describe diagnostic tests, which should be specific, sensitive, and practical. Amongst the new tests described are those including nucleic acid amplification (polymerase chain reaction, PCR) and immunohistochemistry (IHC). Methods In this study, we evaluated the sensitivity of a PCR based on small subunit (SSU) ribosomal DNA, in comparison with IHC using Leishmania spp. antibodies, in biopsies embedded in paraffin. Result The results indicated a total sensitivity of 96% (90.9% with PCR and 68.8% with IHC), showing the possibility of using paraffin-embedded biopsies to diagnose CL. Conclusion We propose the use of the two tests together as a routine protocol for diagnosis. This would require the provision of local medical services to perform molecular biology techniques and adequate Leishmania antibodies.

Molecular evidence of human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2) infections in HTLV seroindeterminate individuals from Sao Paulo, Brazil

Background: Using enzyme immunoassays and Western blot (Wb) tests, HTLV serodiagnosis yields indeterminate results in a significant number of cases. Objective: To determine the prevalence of HTLV infection among HTLV-seroindeterminate individuals. Study design: We studied peripheral blood mononuclear cells from 65 anti-HTLV Wb-seroindeterminate individuals by attempting to amplify proviral DNA sequences (tax and pot) to identify HTLV-I and HTLV-2 infections. Results: These 65 specimens exhibited predominantly (43%) anti-HTLV antibodies to gag-coded antigens in the absence of anti-p24 on Wb analysis. Tax proviral sequences were detected in 6 (9.2%) samples. According to restricted fragment polymorphism analysis (RFLP), we identified HTLV-1 proviral DNA in 4 samples. HTLV-2 in one and sequences from both in another. Nested PCR for the pot region was positive in 3 (4.6%) specimens, which were also positive for tax sequences. After hybridization HTLV-1 infection was confirmed in 2 samples (3.1%) and HTLV-2 in another (1.5%). Detection of a single HTLV DNA sequence may be due to infection by defective provirus, but its significance remains undefined. In this cohort, no Wb reactivity pattern was predictive of proviral detection. HTLV-I infection was demonstrated in an individual who had Wb reactivity to gag-coded antigens only. Conclusions: This emphasizes the importance of clinical and laboratory follow-up of HTLV-seroindeterminate individuals from endemic areas. (c) 2009 Elsevier B.V. All rights reserved.

In vivo effects of chicken interferon-gamma during infection with Eimeria

Newly hatched chickens are highly susceptible to infection by opportunistic pathogens during the first 1 or 2 weeks of life, The use of cytokines as therapeutic agents has been studied in animal models as well as in immunosuppressed patients, This approach has become more feasible in livestock animals, in particular poultry, with the recent cloning of cytokine genes and the development of new technologies, such as live delivery vectors, We have recently cloned the gene for chicken interferon-gamma (Ch-IFN-gamma), Poly-HIS-tagged recombinant Ch-IFN-gamma was expressed in Escherichia coil, was purified by Ni chromatography, and was found to be stable at 4 degrees C and an ambient temperature for at least several months and Several weeks, respectively, Ch-IFN-gamma was capable of protecting chick fibroblasts from undergoing virus-mediated lysis, induced nitrite secretion from chicken macrophages in vitro, and enhanced MHC class II expression on macrophages, Administration of recombinant Ch-IFN-gamma to chickens resulted in enhanced weight gain over a 12-day period, Furthermore, the therapeutic potential of Ch-IFN-gamma was assessed using a coccidial challenge model, Birds were treated with Ch-IFN-gamma or a diluent control and then infected with Eimeria acervulina. Infected birds treated with Ch-IFN-gamma showed improved weight gain relative to noninfected birds, The ability of Ch-IFN-gamma to enhance weight gain in the face of coccidial infection makes it an excellent candidate as a therapeutic agent.