Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

Foxp3 and IL-10 Expression Correlates with Parasite Burden in Lesional Tissues of Post Kala Azar Dermal Leishmaniasis (PKDL) Patients

Post kala azar dermal leishamniasis (PKDL), an unusual dermatosis develops in 5–15% of apparently cured visceral leishmaniasis cases in India and in about 60% of cases in Sudan. PKDL cases assume importance since they constitute a major human reservoir for the parasite. Inadequate treatment of VL, genetics, nutrition and immunological mechanisms that allow renewed multiplication of latent parasites or reinfection predispose to PKDL. Immunopathogenesis of PKDL is poorly understood. IL-10 is widely accepted as an immuno-suppressive cytokine and produced by diverse cell populations including, B cells, macrophages and CD4+ T cells. Natural T regulatory (nTreg) cells are subpopulation of CD4+ T cells that inhibit the response of other T cells. In this study we reported the accumulation of nTreg cells in lesion tissues of PKDL patients. Further correlation of Treg markers and IL-10 with parasite load in lesion tissues suggested a role of IL-10 and Treg in parasite establishment or persistence. Further studies are warranted to explore antigen specific IL-10 source in lesion tissues and unravel the concerted induction or accumulation of Treg in PKDL

Evidence for Involvement of Th17 Type Responses in Post Kala Azar Dermal Leishmaniasis (PKDL)

Post kala azar dermal leishamniasis (PKDL), an unusual dermatosis, develops in 5–15% of apparently cured visceral leishmaniasis cases in India and in about 60% of cases in Sudan. PKDL cases assume importance since they constitute an important human reservoir for the parasite. Host immunological responses, considered as major factors in PKDL development, are poorly understood. Limited studies have been performed to explore the host immune responses and that too, restricted to a few immune parameters. The present study employed cDNA array technique that identified various host immuno-determinants including cytokines, chemokines, apoptotic and signaling molecules which were not reported previously in PKDL. In addition, we showed for the first time that Th17 responses are present during L. donovani infection in PKDL which possibly contributes significantly to disease pathogenesis by inducing TNF-α and nitric oxide production. Our findings lead to improved understanding of the host parasite interaction in terms of immune responses and pathology in tissue lesions of PKDL

Breakage of fascial closure device during laparoscopic surgery

Breakage of instruments during laparoscopic surgery is rare. However, when it does occur, locating and retrieving the broken part of the instrument can be cumbersome. Moreover, inability to do so may carry serious medicolegal implications. We report a patient in whom the tip of a fascial closure device broke during laparoscopic surgery. This was located by intraoperative fluoroscopy and retrieved from the extraperitoneal plane via a small incision. The paper discusses the probable factors responsible for breakage of the fascial closure device in our patient and reviews the previously reported cases of the rare complication of breakage of instruments during laparoscopic surgery

Filtering test models to support incremental testing

Model-based testing can be hampered by the fact that a model depicting the system as designed does not necessarily correspond to the product as it is during development. Tests generated from such a model may be impossible to execute due to unimplemented features and already known errors. This paper presents a solution in which parts of the model can be filtered out and the remainder used to generate tests for the implemented portion of the product. In this way model-based testing can be used to gradually test the implementation as it becomes available. This is particularly important in incremental testing commonly used in industry.Peer reviewe

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Not AvailableAerobic rice is grown in well-drained, non-puddled and non-saturated soils without ponded water. It is rice growing in aerobic soil, with the use of external inputs such as supplementary irrigation, fertilizers & aiming at high yields. Main driving force behind aerobic rice is economic water use. Aerobic rice is better remedy for future climate change under drought condition with lesser green house gas (GHG) emission.ICA

Laparoscopic biopsy in patients with abdominal lymphadenopathy

Background: Abdominal lymphadenopathy (AL) - a common clinical scenario faced by clinicians - often poses a diagnostic challenge. In the absence of palpable peripheral nodes, tissue has to be obtained from the abdominal nodes by image-guided biopsy or surgery. In this context a laparoscopic biopsy avoids the morbidity of a laparotomy. Aim: This retrospective analysis of prospectively collected data represents our experience with laparoscopic biopsy of abdominal lymph nodes. Materials and Methods: Between October 2000 and November 2005, 28 patients with AL underwent laparoscopic biopsy. Pre-operative radiological imaging studies had identified a nodal mass in 20, a solitary node in 1, a cold abscess in 1 and a mesenteric cystic lesion in 1 patient. In five patients with chronic right lower abdominal pain and normal ultra-sonographic findings mesenteric nodes were identified and biopsied during diagnostic laparoscopy. Results: The sites of biopsied lymph nodes included para-aortic (10), mesenteric (8), external iliac (3), left gastric (2), obturator (1), aorto-caval (1) and porta hepatis (1). One patient with enlarged peripancreatic nodes mass and another with a mesenteric cystic mass had cold abscesses drained in addition to biopsy. There were no perioperative complications and the median postoperative stay was 2 days (range 1-4 days). Histopathology revealed tuberculosis in 23 patients, reactive adenitis in 2, lymphoma in 1 metastatic carcinoma in 1, and a retroperitoneal sarcoma in 1. Conclusions: In patients with AL, laparoscopy provides a safe and effective means of obtaining biopsy. It is of particular value in patients in whom (a) the nodes are small or present in locations unsuitable for image-guided biopsy, (b) adequate tissue cannot be obtained by image-guided biopsy or (c) previously undiagnosed lymphadenopathy is encountered during diagnostic laparoscopy