On the role of CD4+ T cells and pathogenic mechanisms in HSV-1-induced ocular disease : herpetic stromal keratitis

Experimental infection of mice by scarification of cornea with HSV exhibits ocular disease pattem similar to the histopathological manifestations seen in man. An experiment in athymic mice that did not succumb to herpetic stromal keratitis (HSK) showed that HSK is an immunopathological manifestation of host T cell mediated immune response. It was confirmed later that following infection of corneas in the murine model with RE strain of HSV-1, the immunopathology is manifested by CD4+T lymphocytes that exhibit the Thl cytokine profile. A prominent cell type present in HSK lesions is the neutrophil (PMN), the infiltration of which is a biphasic event following HSV infection of immunocompetent mice, an initial transient infiltration appeared to be triggered by replicating virus and a second more intense invasion along with other inflammatory cells including CD4+ cells. This secondary PMN invasion episode, seemingly orchestrated by CD4+T cells, is called HSK and is not apparently triggered by replicating virus which remains undetectable at this stage. By taking advantage of cell depletion and adoptive transfer studies, the type of cells involved and sequence of cellular events in initiation and effector phase have been addressed. While some of these approaches could explain one facet of HSK immunopathology, identifying the antigen(s) (viral and/or host) to which T cells respond is another interesting field. Some of the recent observations lend credence to the growing notion that HSK represents an autoreactive inflammatory reaction set off by HSV that unmasks sequestered corneal antigens is normally accessible to the immune system. In this study, experiments were designed to address such issues and hence primarily focussed on elucidating the mechanisms which drive the inflammatory responses in HSV-infected murine cornea. Experiments described in this dissertation are aimed at T cell specificity, role of viral antigens in lesion development and mechanisms that drive the inflammatory response in the infected cornea. The series of experiments described here and their results indicate \u27nonspecific activation of CD4+T cells\u27 as a novel mechanism in herpes-induced stromal keratitis. Following an overview of herpes induced ocular disease in part 1, part 2 in addition to supporting HSK as a T cell-mediated immunoinflammatory disease, the results also show the potential for controlling the disease by coreceptor modulation. In part 3, characterization of a unique mouse model with skewed T cell repertoire (Tg- SCID) has been described which is useful for studying antigen specificity in T cell-mediated immunopathological disorders. Results of experiments described in part 4 propose nonspecific activation of T cells and hence the cytokine milieu by virus replication as a novel mechanism by which CD4+ T cells could orchestrate a virus induced ocular immunopathology. Finally, using adoptive transfer protocols, part 5 examines whether lesion development in Tg-SCID mice is virus replication, persistence and CD4+ T cell dependent. Additionally, in part 5, the differential role of HSV-specific antiserum and CD8+ T cells on virus dissemination was analyzed in the infected cornea

Community Assembly and Habitat Specialization of Tropical Tree Species along Moisture Gradients in the Western Ghats Biodiversity Hotspot in India

The interactions between ecological and evolutionary processes mediated through functional traits that confer habitat specialization have been proposed to explain the spatial assembly of plant communities both across space and in different habitats. However, the scale at which these mechanisms operate and their relative importance in dominance and assembly of tree communities in different habitat types distributed across spatially-varying environmental gradients in tropical forests have been rarely tested. Here, I elucidate patterns of functional trait and phylogenetic variation and evolutionary history of key functional traits conferring habitat specialization to understand community assembly mechanisms operating within in tropical tree communities distributed across spatially varying environmental gradients and in different habitat types in Western Ghats biodiversity hotspot, India. The chapter 2 focuses on patterns of functional trait and phylogenetic co-variation among a community of tropical canopy trees distributed across spatially varying moisture gradient. I find that tree communities in plots that experience lower precipitation and longer duration of dry period show clustering of both functional traits and phylogenetic relationship suggesting environmental filtering play a key role in the assembly of tree communities in these forests. The chapter 3 explores the relationship between key functional traits, phylogenetic relationship and abundance of 210 co-occurring tree species distributed across contrasting extremes of seasonal flooding gradient i.e. flooded forest and terra-firme forest (non-flooded). I found that repeated evolution of key functional traits together with strong environmental filtering play a key role in determining the ecological success (dominance) and assembly of tree communities in flooded habitat. The chapter 4 focuses on climatic niche evolution and evolutionary history of flooded habitat specialization in global and endemic Myristicaceae members in the Western Ghats. I found that, repeated gain of swamp habitat specialization and associated morphological traits in global and Western Ghats Myristicaceae implying seasonal flooding gradient is an important driver of ecological speciation. I also found that local habitat specialization promotes range-wide niche evolution among sister taxa. By elucidating the pattern functional traits and phylogenetic relationship across flooding and spatially varying moisture gradient and analysis of climatic niche evolution and habitat specialization among co-occurring sister taxa, this thesis contributes to our understanding of the determinants of assembly, dominance and diversification of tropical tree communities across diverse habitat types in tropical forest biomes

Ionic to electronic conductivity studies of lithium-​borate ruby-​glass-​ceramics containing gold nano particles

Glass-​ceramics contg. Au nanoparticles have been synthesized in the glass compn. 30Li2O-​70B2O3 with HAuCl4.3H2O as dopant. The characteristic ruby color has been obsd. which is attributed to the surface plasmon resonance of the Au nanoparticles, uniformly embedded in the glass matrix. The imparted red color due to the presence of gold nanoparticles has been confirmed by studying the optical absorption spectra using UV-​VIS spectrometer in the visible range (400-​1000 nm) which show a characteristic absorption peak at ∼560 nm. In order to check the crystn.​/amorphous nature, the samples were powd. and characterized using X-​ray diffraction (XRD)​. The microstructural modifications in the samples due to the addn. of Au have been recorded using SEM (SEM)​. Further, the ESR (ESR) studies reveal that the electronic state of gold is either Au0 or Au+. AC cond. studies have been performed at room temp. over a frequency range 100 to 10 MHz. The ac cond. data is fitted by Almond-​West law with power exponent "s". The dc cond. is found to be increasing with the increase of temp. for a typical ruby glass, but almost const. with dopant concn

Effect of pressure on the phase transition behavior of ammonium nitrate

Ammonium nitrate (AN) is used as oxidizer in solid propellants, explosives, gas generator systems and also as a fertilizer. AN crystallizes in five polymorphic phases that appear at different temperatures. Phase transition of AN from one polymorphic phase to another is very important as an oxidizer and also as fertilizer. During its use as an oxidizer, whether pressure plays any role in phase transition is described in this paper. High Pressure−Differential Thermal Analysis (HP−DTA) system is used for this study

Assessment of attitude and practice toward post-exposure prophylaxis for HIV among healthcare workers at a tertiary care hospital

Background: Prevention and control of AIDS are now a major problem as there is no vaccine or effective-curative treatment for this disease. Health care workers (HCWs) are at increased risk for HIV infection. There were inadequate studies about post-exposure prophylaxis (PEP) of HIV among HCWs in southern India. Hence, we are conducting this study to assess the attitude and practice of PEP toward HIV among HCWs.Methods: The cross-sectional study was done among HCWs (doctors, surgeons, nurses, and dentists). Pre-tested questionnaire was given and requested to fill it after explaining the purpose of the study. About 65% and above correct answers was considered as adequate response. Values expressed as mean, proportions and analyzed by SPSS version 17.Results: Overall 6 (66%) of the total 9 questions in attitude were answered satisfactorily, and thus can be said to have good attitude regarding PEP in HIV. Only 16 people (10%) of the participants had taken PEP regimen. Among those who took PEP, the responses for the questions about the time of initiation of regimen, completion of prescribed duration of therapy and checking of HIV status after completion of regimen were unsatisfactory. Among the professions, surgeons were exposed more compared to other professions.Conclusion: Overall attitude toward PEP was positive among all the HCWs. The practice of PEP was not satisfactory even after exposure to risks. Informing HCWs about completing treatment course and post-treatment testing is important to prevent HIV transmission. Awareness of PEP should be improved among health professionals, by regular training meetings and introducing the guidelines of the safe practices in the academic syllabus of all the professions

Assess the frequency and severity of adverse drug reactions due to errors in drug intake at a tertiary care hospital

Background: Drug-related problems are an important cause of morbidity and mortality and a significant burden on healthcare resources. There are few studies to account for errors in drug intake leading to adverse drug reactions (ADRs). This study was pursued with the objective of determining the frequency and severity of the ADRs resulting from erroneous drug intake, the expenses incurred in treating the same.Methods: The study was a prospective, cross-sectional, observational study. The study subjects were patients with ADRs due to errors in drug intake and from self-medication. All the information regarding the ADR were collected as per ADR reporting form issued by Central Drugs Standard Control Organization. Causality was assessed by both Naranjo and the WHO criteria for causality assessment. Direct cost of all the medications, hospital charges (admission, bed charges, consultations paid, treatment charges, investigations, and conveyance charges) were recorded to find the financial burden due to error in drug intake.Results: The study showed that nearly 30% of the ADRs were due to errors in drug intake and the major contributing factor is self-modification either by discontinuation or missed doses. Major drugs that are implicated in these ADRs were that of metformin and insulins among anti-diabetic drugs and amlodipine and atenolol among antihypertensives. These two groups contributed to 18 (62%) of the total 29 ADRs. Organ system commonly involved was central nervous system and that was followed by musculoskeletal system. The average direct cost incurred in the management of these ADRs was Rs. 5773 for non-serious adverse events (SAE’s) and Rs. 11,400 for SAE’s.Conclusion: Proper education about the importance of compliance and damaging consequences of self-modification of drug dosage in patients who are on treatment for chronic disorders like diabetes and hypertension will be an effective strategy to prevent many of these ADRs

Mid-esophageal diverticulum mimicking an aortic aneurysm on chest radiography

BACKGROUND: Mid-esophageal region is an uncommon location of esophageal diverticula, a condition usually diagnosed in elderly individuals. CASE REPORT: We report a case of an elderly male with incidental finding of mediastinal lesion, which was initially thought to be an aortic aneurysm. Further evaluation demonstrated a mid-esophageal diverticulum at the level of the carina. We present patient's medical history and imaging, followed by a discussion on symptoms and management. CONCLUSIONS: Knowledge of benign conditions that might mimic a mediastinal vascular pathology is important for therapeutic and prognostic reasons, as they are often managed conservatively