SNAKE BITE PRESENTING AS INTRACRANIAL BLEED WITH NORMAL COAGULATION PARAMETERS

Snakebite being commonly encountered emergency in our country and most dreaded one too. It has been estimated that as many as 2.8 million people are bitten by snakes, and 45 900 people die from snakebite every year in India1. The most common coagulopathy associated with snake-bite envenoming is Venom Induced Consumptive Coagulopathy. Venom contain enzymes like proteases, phospholipase A2, hyaluronidase and arginine ester hydrolase. Phospholipase A2 is the factor responsible for hemolysis secondary to the esterlytic effect on the red cell membranes The hyaluronidase causes spread of the venom in the subcutaneous tissue by disrupting mucopolysaccharides. In majority of cases there is disruption in coagulation profile causing increase in PT, INR, aPTT, thrombocytopenia and increase in FDP, which suggests DIC as the probable cause for intracerebral hemorrhage . But always it is not true there are some cases in which there is hemorrhagic risk without alteration in coagulation profile. All my 3 cases present to us with normal coagulation profile , One 26 year old male present within one hour of snake bite and died within 3 days of the bite, while other two presented lately that is 2and 6 day of the snake bite ,of which both survived and had no residual focal deficit at time of discharge. This delayed clinical, laboratory manifestation of vasculotoxic snake due to the delayed seepage of venom from deeper reservoirs in the bite site or due to disassembly of the antigen-antibody complex with reinstitution of circulating unbound venom constituents. Intracranial hemorrhages are poorly understood in case of snake bite and can occur later complication also even after treatment with ASV. Still use of FFP is not advocated in much studies, there is immense need to investigate this area. Use of ASV and FFP without increased WBCT to avoid later complication is to be studied.

Diabetic Ketoacidosis, Hypertriglyceridemia and Abdominal Pain due to Acute Pancreatitis Complicated by Non-immune Haemolytic Anaemia

The triad of diabetic ketoacidosis, acute pancreatitis and hypertriglyceridemia is a rare phenomenon, with mortality rates of up to 80%. A unique characteristic of the described case is the co-occurrence of non-immune haemolytic anaemia (NIHA) with the complex triad. It is suggested that this presentation is secondary to hyperlipidemia which leads to increased fragility of erythrocytes due to destabilization of red cell membranes. Supportive treatment with intravenous insulin and blood transfusions is the cornerstone of treatment.

Orally Administered Fumonisins Affect Porcine Red Cell Membrane Sodium Pump Activity and Lipid Profile without Apparent Oxidative Damage

Weaned piglets (n = 3 × 6) were fed 0, 15 and 30 mg/kg diet fumonisin (FB1, FB2 and FB3, i.e., FBs, a sphinganine analogue mycotoxin), from the age of 35 days for 21 days, to assess mycotoxin induced, dose-dependent changes in the red cells’ membrane. Ouabain sensitive Na+/K+ ATPase activity was determined from lysed red cell membranes, membrane fatty acid (FA) profile was analysed, as well as antioxidant and lipid peroxidation endpoints. Final body weight was higher in the 30 mg/kg group (vs. control), even besides identical cumulative feed intake. After 3 weeks, there was a difference between control and the 30 mg/kg group in red cell membrane sodium pump activity; this change was dose-dependent (sig.: 0.036; R2 = 0.58). Membrane FA profile was strongly saturated with non-systematic inter-group differences; pooled data provided negative correlation with sodium pump activity (all individual membrane n6 FAs). Intracellular antioxidants (reduced glutathione and glutathione peroxidase) and lipid peroxidation indicators (conj. dienes, trienes and malondialdehyde) were non-responsive. We suppose a ceramide synthesis inhibitor (FB1) effect exerted onto the cell membrane, proven to be toxin dose-dependent and increasing sodium pump activity, with only indirect FA compositional correlations and lack of lipid peroxidation.

The common hereditary elliptocytosis-associated α-spectrin L260P mutation perturbs erythrocyte membranes by stabilizing spectrin in the closed dimer conformation

Key Points The common HE mutation αL260P reduces spectrin tetramer links between junctional complexes in red cell membranes by favoring closed dimers. Favoring closed spectrin dimer formation is a new mechanism of red cell membrane destabilization by hereditary anemia mutations.

Crystal structure and functional interpretation of the erythrocyte spectrin tetramerization domain complex

As the principal component of the membrane skeleton, spectrin confers integrity and flexibility to red cell membranes. Although this network involves many interactions, the most common hemolytic anemia mutations that disrupt erythrocyte morphology affect the spectrin tetramerization domains. Although much is known clinically about the resulting conditions (hereditary elliptocytosis and pyropoikilocytosis), the detailed structural basis for spectrin tetramerization and its disruption by hereditary anemia mutations remains elusive. Thus, to provide further insights into spectrin assembly and tetramer site mutations, a crystal structure of the spectrin tetramerization domain complex has been determined. Architecturally, this complex shows striking resemblance to multirepeat spectrin fragments, with the interacting tetramer site region forming a central, composite repeat. This structure identifies conformational changes in α-spectrin that occur upon binding to β-spectrin, and it reports the first structure of the β-spectrin tetramerization domain. Analysis of the interaction surfaces indicates an extensive interface dominated by hydrophobic contacts and supplemented by electrostatic complementarity. Analysis of evolutionarily conserved residues suggests additional surfaces that may form important interactions. Finally, mapping of hereditary anemia-related mutations onto the structure demonstrate that most, but not all, local hereditary anemia mutations map to the interacting domains. The potential molecular effects of these mutations are described.

MULTISCALE MODELING OF FLUID AND SOLUTE TRANSPORT IN SOFT TISSUES AND MICROVESSELS

This study focuses on the movement of particles and extracellular fluid in soft tissues and microvessels. It analyzes modeling applications in biological and physiological fluids at a range of different length scales: from between a few tens to several hundred nanometers, on the endothelial glycocalyx and its effects on interactions between blood and the vessel wall; to a few micrometers, on movement of blood cells in capillaries and transcapillary exchange; to a few millimetres and centimetres, on extracellular matrix deformation and interstitial fluid movement in soft tissues. Interactions between blood cells and capillary wall are discussed when the sizes of the two are of the same order of magnitude, with the glycocalyx on the endothelial and red cell membranes being considered. Exchange of fluid, solutes, and gases by microvessels are highlighted when capillaries have counter-current arrangements. This anatomical feature exists in a number of tissues and is the key in the renal medulla on the urinary concentrating mechanism. The paper also addresses an important phenomenon on the transport of macromolecules. Concentration polarization of hyaluronan on the synovial lining of joint cavities is presented to demonstrate how the mechanism works in principle and how model predictions agree to experimental observations quantitatively.