The gut-brain and gut-macrophage contribution to gastrointestinal dysfunction with systemic inflammation.

The gastrointestinal tract is one of the main organs affected during systemic inflammation and disrupted gastrointestinal motility is a major clinical manifestation. Many studies have investigated the involvement of neuroimmune interactions in regulating colonic motility during localized colonic inflammation, i.e., colitis. However, little is known about how the enteric nervous system and intestinal macrophages contribute to dysregulated motility during systemic inflammation. Given that systemic inflammation commonly results from the innate immune response against bacterial infection, we mimicked bacterial infection by administering lipopolysaccharide (LPS) to rats and assessed colonic motility using ex vivo video imaging techniques. We utilized the Cx3cr1-Dtr rat model of transient depletion of macrophages to investigate the role of intestinal macrophages in regulating colonic motility during LPS infection. To investigate the role of inhibitory enteric neurotransmission on colonic motility following LPS, we applied the nitric oxide synthase inhibitor, Nω-nitro-L-arginine (NOLA). Our results confirmed an increase in colonic contraction frequency during LPS-induced systemic inflammation. However, neither the depletion of intestinal macrophages, nor the suppression of inhibitory enteric nervous system activity impacted colonic motility disruption during inflammation. This implies that the interplay between the enteric nervous system and intestinal macrophages is nuanced, and complex, and further investigation is needed to clarify their joint roles in colonic motility.

Facile synthesis of N-(α-furanyl) alkyl sulfoximines via gold catalyzed Michael addition/cyclization of enynones and sulfoximines.

Herein, we prepare a new array of N-(α-furanyl) alkyl sulfoximines via a gold catalyzed reaction of enynone with sulfoximine in moderate to very good yields. The reaction involves Michael addition of sulfoximine to enynone, followed by intramolecular cyclization. The presence of two chiral centres led to the formation of a mixture of diastereomers approximately in a 1 : 1 ratio. The salient features of the protocol include broad substrate scope, high efficiency and high yields. The synthetic utility of the protocol is explored using Suzuki-Miyaura cross-coupling and mild, metal-free opening of the furan ring.

Faster Gastrointestinal Transit, Reduced Small Intestinal Smooth Muscle Tone and Dysmotility in the Nlgn3R451C Mouse Model of Autism.

Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein Neuroligin-3 was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction. Mice expressing this mutation (Nlgn3R451C mice) are a well-studied preclinical model of autism and show autism-relevant characteristics, including impaired social interaction and communication, as well as repetitive behaviour. We previously showed colonic dysmotility in response to GABAergic inhibition and increased myenteric neuronal numbers in the small intestine in Nlgn3R451C mice bred on a mixed genetic background. Here, we show that gut dysfunction is a persistent phenotype of the Nlgn3 R451C mutation in mice backcrossed onto a C57BL/6 background. We report that Nlgn3R451C mice show a 30.9% faster gastrointestinal transit (p = 0.0004) in vivo and have 6% longer small intestines (p = 0.04) compared to wild-types due to a reduction in smooth muscle tone. In Nlgn3R451C mice, we observed a decrease in resting jejunal diameter (proximal jejunum: 10.6% decrease, p = 0.02; mid: 9.8%, p = 0.04; distal: 11.5%, p = 0.009) and neurally regulated dysmotility as well as shorter durations of contractile complexes (mid: 25.6% reduction in duration, p = 0.009; distal: 30.5%, p = 0.004) in the ileum. In Nlgn3R451C mouse colons, short contractions were inhibited to a greater extent (57.2% by the GABAA antagonist, gabazine, compared to 40.6% in wild-type mice (p = 0.007). The inhibition of nitric oxide synthesis decreased the frequency of contractile complexes in the jejunum (WT p = 0.0006, Nlgn3R451C p = 0.002), but not the ileum, in both wild-type and Nlgn3R451C mice. These findings demonstrate that changes in enteric nervous system function contribute to gastrointestinal dysmotility in mice expressing the autism-associated R451C missense mutation in the Neuroligin-3 protein.

Hyperimmune bovine colostrum containing lipopolysaccharide antibodies (IMM124-E) has a nondetrimental effect on gut microbial communities in unchallenged mice.

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of bacterial diarrhea with the potential to cause long-term gastrointestinal (GI) dysfunction. Preventative treatments for ETEC-induced diarrhea exist, yet the effects of these treatments on GI commensals in healthy individuals are unclear. Whether administration of a prophylactic preventative treatment for ETEC-induced diarrhea causes specific shifts in gut microbial populations in controlled environments is also unknown. Here, we studied the effects of a hyperimmune bovine colostrum (IMM-124E) used in the manufacture of Travelan (AUST L 106709) on GI bacteria in healthy C57BL/6 mice. Using next-generation sequencing, we aimed to test the onset and magnitude of potential changes to the mouse gut microbiome in response to the antidiarrheagenic hyperimmune bovine colostrum product, rich in immunoglobulins against select ETEC strains (Travelan, Immuron Ltd). We show that in mice administered colostrum containing lipopolysaccharide (LPS) antibodies, there was an increased abundance of potentially gut-beneficial bacteria, such as Akkermansia and Desulfovibrio, without disrupting the underlying ecology of the GI tract. Compared to controls, there was no difference in overall weight gain, body or cecal weights, or small intestine length following LPS antibody colostrum supplementation. Overall, dietary supplementation with colostrum containing LPS antibodies produced subtle alterations in the gut bacterial composition of mice. Primarily, Travelan LPS antibody treatment decreased the ratio of Firmicutes/Bacteroidetes in gut microbial populations in unchallenged healthy mice. Further studies are required to examine the effect of Travelan LPS antibody treatment to engineer the microbiome in a diseased state and during recovery.

Rhizobium mayense sp. Nov., an efficient plant growth-promoting nitrogen-fixing bacteria isolated from rhizosphere soil.

The nitrogen-fixing bacterium has great prospects in replacing synthetic fertilizers with biofertilizers for plant growth. It would be a useful tool in eradicating chemical fertilizers from use. Five nitrogen-fixing bacteria were isolated from the Tea and Groundnut rhizosphere soil out of which RSKVG 02 proved to be the best. The optimized condition of RSKVG 02 was found to be pH 7 at 30 °C utilizing 1% glucose and 0.05% ammonium sulfate as the sole carbon and nitrogen source. Plant growth-promoting traits such as IAA and ammonia were estimated to be 82.97 ± 0.01254a µg/ml and 80.49 ± 0.23699a mg/ml respectively. Additionally, their phosphate and potassium solubilization efficiency were evaluated to be 46.69 ± 0.00125 b mg/ml and 50.29 ± 0.000266 mg/ml. Morphological, and biochemical methods characterized the isolated bacterial culture, and molecularly identified by 16 S rRNA sequencing as Rhizobium mayense. The isolate was further tested for its effects on the growth of Finger millet (Eleusine coracana) and Green gram (Vigna radiata) under pot conditions. The pot study experiments indicated that the bacterial isolates used as bio inoculants increased the total plant growth compared to the control and their dry weight showed similar results. The chlorophyll content of Green gram and Finger millet was estimated to be 19.54 ± 0.2784a mg/L and 15.3 ± 0.0035 mg/L which suggested that Rhizobium sp. Possesses high nitrogenase activity. The enzyme activity proved to use this bacterium as a biofertilizer property to enhance soil fertility, efficient farming, and an alternative chemical fertilizer. Therefore, Rhizobium mayense can be potentially used as an efficient biofertilizer for crop production and increase yield and soil fertility.

Mixed polyaromatic hydrocarbon degradation by halotolerant bacterial strains from marine environment and its metabolic pathway.

Accidents involving diesel oil spills are prevalent in sea- and coastal regions. Polycyclic aromatic hydrocarbons (PAHs) can be adsorbed in soil and constitute a persistent contaminant due to their poor water solubility and complex breakdown. PAHs pollution is a pervasive environmental concern that poses serious risks to human life and ecosystems. Thus, it is the need of the hour to degrade and decontaminate the toxic pollutant to save the environment. Among all the available techniques, microbial degradation of the PAHs is proving to be greatly beneficial and effective. Bioremediation overcomes the drawbacks of most physicochemical procedures by eliminating numerous organic pollutants at a lower cost in ambient circumstances and has therefore become a prominent remedial option for pollutant removal, including PAHs. In the present study, we have studied the degradation of Low molecular Weight and High Molecular Weight PAH in combination by bacterial strains isolated from a marine environment. Optimum pH, temperature, carbon, and nitrogen sources, NaCl concentrations were found for efficient degradation using the isolated bacterial strains. At 250 mg/L concentration of the PAH mixture an 89.5% degradation was observed. Vibrio algiolytcus strains were found to be potent halotolerant bacteria to degrade complex PAH into less toxic simple molecules. GC-MS and FTIR data were used to probe the pathway of degradation of PAH.

Examining enteric nervous system function in rat and mouse: an interspecies comparison of colonic motility.

Gastrointestinal motility is crucial to gut health and has been associated with different disorders such as inflammatory bowel diseases and postoperative ileus. Despite rat and mouse being the two animal models most widely used in gastrointestinal research, minimal studies in rats have investigated gastrointestinal motility. Therefore, our study provides a comparison of colonic motility in the mouse and rat to clarify species differences and assess the relative effectiveness of each animal model for colonic motility research. We describe the protocol modifications and optimization undertaken to enable video imaging of colonic motility in the rat. Apart from the broad difference in terms of gastrointestinal diameter and length, we identified differences in the fundamental histology of the proximal colon such that the rat had larger villus height-to-width and villus height-to-crypt depth ratios compared with mouse. Since gut motility is tightly regulated by the enteric nervous system (ENS), we investigated how colonic contractile activity within each rodent species responds to modulation of the ENS inhibitory neuronal network. Here we used Nω-nitro-l-arginine (l-NNA), an inhibitor of nitric oxide synthase (NOS) to assess proximal colon responses to the stimulatory effect of blocking the major inhibitory neurotransmitter, nitric oxide (NO). In rats, the frequency of proximal colonic contractions increased in the presence of l-NNA (vs. control levels) to a greater extent than in mice. This is despite a similar number of NOS-expressing neurons in the myenteric plexus across species. Given this increase in colonic contraction frequency, the rat represents another relevant animal model for investigating how gastrointestinal motility is regulated by the inhibitory neuronal network of the ENS.NEW & NOTEWORTHY Mice and rats are widely used in gastrointestinal research but have fundamental differences that make them important as different models for different questions. We found that mice have a higher villi length-to-width and villi length-to-crypt depth ratio than rat in proximal colon. Using the ex vivo video imaging technique, we observed that rat colon has more prominent response to blockade of major inhibitory neurotransmitter (nitric oxide) in myenteric plexus than mouse colon.

Community voices around COVID-19 vaccine in Chennai, India: A qualitative exploration during early phase of vaccine rollout.

Background & objectives: Globally, vaccination is considered as an important public health strategy to mitigate the impact of the COVID-19 pandemic. The purpose of the current study was to conduct an in-depth inquiry to explore perceptions of community members around COVID-19 vaccines in the southern city of Chennai, Tamil Nadu. This was conducted during the early phase of the vaccine rollout programme in India. Methods: A qualitative investigation was conducted between January-February 2021 through in-depth interviews. Healthcare workers, religious leaders, community influencers, local administrators and representatives of marginalized communities were included. The key informant interview guides and probes explored five domains; (i) vaccine availability, (ii) trust in COVID-19 vaccines, (iii) vaccine-related concerns, (iv) health/risk balance and (v) vaccine prioritization. Transcripted interviews were coded using a thematic approach and analyzed manually as well as with the help of ATLAS.ti 9 software. Results: Eagerness to receive COVID-19 vaccines amongst some of the respondents was linked with freedom from fear, possible restoration of normalcy, protection of family and ability to travel and work abroad. Concerns around threat of emergence of new variants, damage caused by such viral mutants and trust in policymakers were other facilitatory influencers for vaccine uptake. On the other hand, doubts surrounding safety and fear of side effects of COVID-19 vaccine were the feeders to vaccine hesitancy. Lack of accurate information, sensational media reports and rumours exacerbated this fear and provoked anxiety among people. Apprehensions around COVID-19 vaccine in the wake of its rapid development and approval for use and reluctance to take it during the declining phase of the epidemic were identified as other inhibitory factors. Participants underlined the importance of having responsive communication strategies in place focussing on vaccine safety. Making vaccines available to people free of cost and ensuring wider access were other programmatic suggestions. Interpretation & conclusions: In conclusion, our study findings suggest that it is essential to remain engaged with communities and execute evidence-based information dissemination strategy about the safety and efficacy of the vaccines. We identified that it is also imperative to sensitize and train media professionals on how to report side effects related to vaccines. Responsive communication strategies will thus have the potential to serve as a key public health approach pertaining to future pandemic preparedness as well as to manage the demands of clinical and public health issues in an ongoing pandemic situation.

Metabolic and molecular modelling of zebrafish gut biome to unravel antimicrobial peptides through metagenomics.

Recently efforts have been taken for unravelling mysteries between host-microbe interactions in gut microbiome studies of model organisms through metagenomics. Co-existence and the co-evolution of the microorganisms is the significant cause of the growing antimicrobial menace. There needs a novel approach to develop potential antimicrobials with capabilities to act directly on the resistant microbes with reduced side effects. One such is to tap them from the natural resources, preferably the gut of the most closely related animal model. In this study, we employed metagenomics approaches to identify the large taxonomic genomes of the zebra fish gut. About 256 antimicrobial peptides were identified using gene ontology predictions from Macrel and Pubseed servers. Upon the property predictions, the top 10 antimicrobial peptides were screened based on their action against many resistant bacterial species, including Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, E. coli, and Bacillus cereus. Metabolic modelling and flux balance analysis (FBA) were computed to conclude the antibiotic such as tetracycline, cephalosporins, puromycin, neomycin biosynthesis pathways were adopted by the microbiome as protection strategies. Molecular modelling strategies, including molecular docking and dynamics, were performed to estimate the antimicrobial peptides' binding against the target-putative nucleic acid binding lipoprotein and confirm stable binding. One specific antimicrobial peptide with the sequence "MPPYLHEIQPHTASNCQTELVIKL" showed promising results with 53% hydrophobic residues and a net charge +2.5, significant for the development of antimicrobial peptides. The said peptide also showed promising interactions with the target protein and expressed stable binding with docking energy of -429.34 kcal/mol and the average root mean square deviation of 1 A0. The study is a novel approach focusing on tapping out potential antimicrobial peptides to be developed against most resistant bacterial species.

Structural, functional, resistome and pathogenicity profiling of the Cooum river.

The microbial community's structure and functions determine the health, quality, and anthropogenic conditions of the river ecosystems. The presence of Bacteria such as Arcobacter spp, Escherichia spp, and Campylobacters spp, have been shown to reflect the poor water quality of rivers. Apprehension of the microbial community in polluted water bodies is significant because it affects human health and the environment. Culture-independent metagenomic and metatranscriptomic approaches employed in the current study of the Cooum river unraveled the taxonomic classification of diverse microbes, including archaea, bacteria, viruses, and phages. The presence of abundant Macellibacteroides fermentans, Arcobacter bivolvorium, Arcobacter butzleri, Methanothrix soenhngeii, and Bacteroides graminisolvens were noted. Viruses and phages like Caudovirales, Human mastadenovirus C, Siphoviridae, Escherichia phage, Erwinia phage, Synechoccus phage, and Vibrio phage were relatively predominant. Various metabolic pathways like methane, sulfur, and nitrogen metabolism adopted by the microbiome confer dangerous gases. Mechanisms such as secretory systems, signal transduction, Chemotaxis, quorum sensing, transportation of chemicals and ions were significantly enriched. The microbes expressed antimicrobial resistance mechanisms as identified from the genes encoding beta-lactamase enzymes and aminoglycoside phosphotransferase enzymes. Metal resistance mechanisms against copper, tellurium, chromium, and cadmium were plentiful. Presence of human pathogens interactions with Yersinia pestis, Campylobacter jejuni, Escherichia coli, Helicobacter pylori, and Francisella tularensis subsp. tularensis suggested the possibilities of transmission of pathogenesis to humans. The current study is the first to apprehend the detailed microbiome composition of one of the highly polluted rivers in South India. The study elaborated the microbiome's structure, functions, and metabolic potential at a specific site of the polluted river.

Mixed azo dyes degradation by an intracellular azoreductase enzyme from alkaliphilic Bacillus subtilis: a molecular docking study.

The rise of pollution due to the dye industries and textile wastes are evolving rapidly every day. The dyes are used in different trade names by the textile industries. The actual chemistry of dye is vague and difficult to understand even today though we are equipped technically. The toxic effects of the dyes and the reasons behind the acute toxicity are also an undiscovered mystery; therefore, no effective measures can be employed to degrade dyes. Deploying physical or chemical methods to pre-treat the azo dyes are expensive, extremely energy-consuming, and are not environment friendly. Hence, the use of microbes for textile dye degradation will be eco-friendly and is probably a cost-effective alternative to physicochemical methods. The present study was conducted to investigate the degradation of azo dyes isolated from textile effluent contaminated soil by employing the bacterial strains for degradation. The bacterial strains could degrade the optimum concentration of mixed azo dyes (200 mg/L) with an incubation up to 5 days. The decolourization of the dyes was expressed in terms of percentage of decolourization, and was found that about 87.35% of degradation by Bacillus subtilis strain. The enzyme responsible was analyzed as intracellular azoreductase involved in the degradation of mixed azo dyes. The enzymatic pathway and 1-phenyl-2-4(4-methyl phenyl)-diazene 1-oxide was observed as the major metabolite by GC-MS analysis. The in silico study determined the binding of mixed azo dye with azoreductase and hypothesized that their linking could be the main reason for the degradation of mixed azo dye.

Ebselen prevents cigarette smoke-induced gastrointestinal dysfunction in mice.

Gastrointestinal (GI) dysfunction is a common comorbidity of chronic obstructive pulmonary disease (COPD) for which a major cause is cigarette smoking (CS). The underlying mechanisms and precise effects of CS on gut contractility, however, are not fully characterised. Therefore, the aim of the present study was to investigate whether CS impacts GI function and structure in a mouse model of CS-induced COPD. We also aimed to investigate GI function in the presence of ebselen, an antioxidant that has shown beneficial effects on lung inflammation resulting from CS exposure. Mice were exposed to CS for 2 or 6 months. GI structure was analysed by histology and immunofluorescence. After 2 months of CS exposure, ex vivo gut motility was analysed using video-imaging techniques to examine changes in colonic migrating motor complexes (CMMCs). CS decreased colon length in mice. Mice exposed to CS for 2 months had a higher frequency of CMMCs and a reduced resting colonic diameter but no change in enteric neuron numbers. Ten days cessation after 2 months CS reversed CMMC frequency changes but not the reduced colonic diameter phenotype. Ebselen treatment reversed the CS-induced reduction in colonic diameter. After 6 months CS, the number of myenteric nitric-oxide producing neurons was significantly reduced. This is the first evidence of colonic dysmotility in a mouse model of CS-induced COPD. Dysmotility after 2 months CS is not due to altered neuron numbers; however, prolonged CS-exposure significantly reduced enteric neuron numbers in mice. Further research is needed to assess potential therapeutic applications of ebselen in GI dysfunction in COPD.

The multitasking organ: recent insights into skin immune function.

The skin provides the first line defense of the human body against injury and infection. By integrating recent findings in cutaneous immunology with fundamental concepts of skin biology, we portray the skin as a multitasking organ ensuring body homeostasis. Crosstalk between the skin and its microbial environment is also highlighted as influencing the response to injury, infection, and autoimmunity. The importance of the skin immune network is emphasized by the identification of several skin-resident cell subsets, each with its unique functions. Lessons learned from targeted therapy in inflammatory skin conditions, such as psoriasis, provide further insights into skin immune function. Finally, we look at the skin as an interacting network of immune signaling pathways exemplified by the development of a disease interactome for psoriasis.

HLA-C*06:02 genotype is a predictive biomarker of biologic treatment response in psoriasis.

BACKGROUND: Biologic therapies can be highly effective for the treatment of severe psoriasis, but response for individual patients can vary according to drug. Predictive biomarkers to guide treatment selection could improve patient outcomes and treatment cost-effectiveness. OBJECTIVE: We sought to test whether HLA-C*06:02, the primary genetic susceptibility allele for psoriasis, predisposes patients to respond differently to the 2 most commonly prescribed biologics for psoriasis: adalimumab (anti-TNF-α) and ustekinumab (anti-IL-12/23). METHODS: This study uses a national psoriasis registry that includes longitudinal treatment and response observations and detailed clinical data. HLA alleles were imputed from genome-wide genotype data for 1326 patients for whom 90% reduction in Psoriasis Area and Severity Index score (PASI90) response status was observed after 3, 6, or 12 months of treatment. We developed regression models of PASI90 response, examining the interaction between HLA-C*06:02 and drug type (adalimumab or ustekinumab) while accounting for potentially confounding clinical variables. RESULTS: HLA-C*06:02-negative patients were significantly more likely to respond to adalimumab than ustekinumab at all time points (most strongly at 6 months: odds ratio [OR], 2.95; P = 5.85 × 10-7), and the difference was greater in HLA-C*06:02-negative patients with psoriatic arthritis (OR, 5.98; P = 6.89 × 10-5). Biologic-naive patients who were HLA-C*06:02 positive and psoriatic arthritis negative demonstrated significantly poorer response to adalimumab at 12 months (OR, 0.31; P = 3.42 × 10-4). Results from HLA-wide analyses were consistent with HLA-C*06:02 itself being the primary effect allele. We found no evidence for genetic interaction between HLA-C*06:02 and ERAP1. CONCLUSION: This large observational study suggests that reference to HLA-C*06:02 status could offer substantial clinical benefit when selecting treatments for severe psoriasis.

A sexually dimorphic effect of cholera toxin: rapid changes in colonic motility mediated via a 5-HT3 receptor-dependent pathway in female C57Bl/6 mice.

KEY POINTS: Cholera causes more than 100,000 deaths each year as a result of severe diarrhoea, vomiting and dehydration due to the actions of cholera toxin; more females than males are affected. Cholera toxin induces hypersecretion via release of mucosal serotonin and over-activation of enteric neurons, but its effects on gastrointestinal motility are not well characterized. We found that cholera toxin rapidly and reversibly reduces colonic motility in female mice in oestrus, but not in males or females in prooestrus, an effect mediated by 5-HT in the colonic mucosa and by 5-HT3 receptors. We show that the number of mucosal enterochromaffin cells containing 5-HT changes with the oestrous cycle in mice. These findings indicate that cholera toxin's effects on motility are rapid and depend on the oestrous cycle and therefore can help us better understand differences in responses in males and female patients. ABSTRACT: Extensive studies of the mechanisms responsible for the hypersecretion produced by cholera toxin (CT) have shown that this toxin produces a massive over-activation of enteric neural secretomotor circuits. The effects of CT on gastrointestinal motility, however, have not been adequately characterized. We investigated effects of luminal CT on neurally mediated motor activity in ex vivo male and female mouse full length colon preparations. We used video recording and spatiotemporal maps of contractile activity to quantify colonic migrating motor complexes (CMMCs) and resting colonic diameter. We compared effects of CT in female colon from wild-type and mice lacking tryptophan hydroxylase (TPH1KO). We also compared CMMCs in colons of female mice in oestrus with those in prooestrus. In female (but not male) colon, CT rapidly, reversibly and concentration-dependently inhibits CMMC frequency and induces a tonic constriction. These effects were blocked by granisetron (5-HT3 antagonist) and were absent from TPH1KO females. CT effects were prominent at oestrus but absent at prooestrus. The number of EC cells containing immunohistochemically demonstrable serotonin (5-HT) was 30% greater in female mice during oestrus than during prooestrus or in males. We conclude that CT inhibits CMMCs via release of mucosal 5-HT, which activates an inhibitory pathway involving 5-HT3 receptors. This effect is sex- and oestrous cycle-dependent and is probably due to an oestrous cycle-dependent change in the number of 5-HT-containing EC cells in the colonic mucosa.

S100A8/A9 (calprotectin) is critical for development of glomerulonephritis and promotes inflammatory leukocyte-renal cell interactions.

Glomerulonephritis is a common cause of end-stage renal disease. Infiltrating leukocytes interacting with renal cells play a critical role during the initiation and progression of glomerulonephritis, but the exact mechanisms are not clearly defined. By using the murine model of nephrotoxic nephritis, we investigated the role of S100A8/A9 [myeloid-related protein (MRP) 8/14, calprotectin] in promoting glomerulonephritis. In nephrotoxic nephritis, wild-type (WT) mice with glomerulonephritis have elevated serum levels of S100A8/A9, whereas mice deficient in MRP14 (S100a9(-/-)), and hence S100A8/A9, are significantly protected from disease. By using bone marrow transplants, we showed that MRP14 deficiency is required in both the hemopoietic and intrinsic cells for the protective effect. In vitro, both the WT bone marrow-derived macrophages and renal mesangial cells stimulated with S100A8/A9 secrete IL-6, CXCL1, and tumor necrosis factor α; however, Mrp14(-/-) cells exhibit significantly blunted proinflammatory responses. The interaction of WT bone marrow-derived macrophages with renal microvascular endothelial cells results in increased levels of monocyte chemotactic protein 1, IL-8, and IL-6 cytokines, which is attenuated in Mrp14(-/-) bone marrow-derived macrophages. Data shows that S100A8/A9 plays a critical role during glomerulonephritis, exerting and amplifying autocrine and paracrine proinflammatory effects on bone marrow-derived macrophages, renal endothelial cells, and mesangial cells. Therefore, complete S100A8/A9 blockade may be a new therapeutic target in glomerulonephritis.

Lipemia Retinalis due to Secondary Hyperlipidemia in Type 1 Diabetes Mellitus.

Lipemia retinalis is a rare and asymptomatic condition which occurs when high levels of triglycerides and chylomicrons are present in blood. We report a rare case of secondary hyperlipoproteinemia in a 27 year old type 1 diabetes patient who presented with diabetic ketoacidosis and this peculiar ocular manifestation. The fundoscopic abnormality and creamy white serum cleared as the level of chylomicrons in the plasma dropped with intensive insulin therapy.

Wilson's Disease with Systemic Lupus Erythematosus.

Case reports of Wilson's disease occurring in combination with SLE are rarely reported in literature. Drug induced lupus have been observed in patients taking D-penicillamine for Wilson's disease. Here we report a case from Coimbatore Medical College hospital, who presented with fever and neuropsychiatric symptoms as the initial manifestation and found to have both SLE and Wilson's disease on subsequent evaluation.

Cerebral Sinus Venous Thrombosis as a Rare Complication of Primary Varicella Zoster Virus Infection.

We present the case of a 23 year old with acute onset left hemiparesis and meningeal irritation, associated with recent history of chickenpox 15 days prior. Varicella-IgG and IgM was positive in the CSF and blood along with reduced serum/CSF ratios of VZV immunoglobulins. MRV showed thrombosis (CVT) of superior sagittal, transverse, right sigmoid sinuses with haemorrhagic infarct in right frontoparietal region. Patient responded well to intravenous heparin, Acyclovir and oral anticoagulant therapy.