Coinfection of Sarcina ventriculi and Candida in a patient of gastric outlet obstruction: An overloaded pyloric antrum.

Sarcina ventriculi is a rare gram-positive, anaerobic bacteria, associated with delayed gastric emptying. We report a case of a 45-year-old lady, who presented with features of gastric outlet obstruction, and coinfection of S. ventriculi and Candida was detected on examining gastric brushings and biopsy. S. ventriculi is identified by its peculiar configuration in the form of tetrads and octets. Coexistence of S. ventriculi with other organisms is highly unusual.

Patterns of Adverse Transfusion Reactions in a Tertiary Care Centre of North India: A Step Towards Hemovigilance.

Transfusion of blood and blood products is a double edged sword, so it should be used judiciously. The primary aim of the centralized Haemovigilance Program is to improve transfusion safety. To determine the incidence of adverse transfusion reactions (ATRs) in recipients of blood and blood components. Prospective study from January 2014 till April 2015 was done. ATRs reported to the Department of Transfusion Medicine were recorded and analyzed on the basis of their clinical features and lab tests. During the study period 25,099 units of blood and blood components were transfused and 100 ATRs (0.40 %) were reported. The incidence of febrile nonhemolytic transfusion reactions (FNHTR) was maximum (73 %) followed by allergic reactions (24 %), bacterial sepsis (1 %), hypotension due to ACE inhibitors (1 %) and acute hemolytic transfusion reaction (AHTR) (1 %). Of all the reported ATRs, 76 % occurred with packed red cells, 15 % occurred with whole blood, while platelets and Fresh Frozen Plasma transfusions were responsible for 8 % and 1 %, respectively. The majority of the reactions were FNHTRs followed by allergic reactions. Reporting of all adverse events and continuous medical education to medical and paramedical staff will help in strengthening hemovigilance system.

A longitudinal analysis of angiotensin II type 1 receptor antibody and angiogenic markers in pregnancy.

BACKGROUND: Preeclampsia can be caused by shallow trophoblast invasion and results in endothelial dysfunction. Angiotensin II type 1 receptor antibodies may have a role in both processes. Other angiogenic markers (placental growth factor, soluble fms-like tyrosine kinase-1, and soluble endoglin) have been shown to alter before clinically evident preeclampsia. OBJECTIVE: The aim of this study is to assess the longitudinal changes and utility of biomarker angiotensin II type 1 receptor antibodies and angiogenic markers in hypertensive disorders of pregnancy, gestational hypertension, and preeclampsia. STUDY DESIGN: A longitudinal prospective cohort observational study of angiogenic markers and a secondary retrospective case-control study of angiotensin II type 1 receptor antibody changes were conducted. The studies were conducted in a large tertiary metropolitan teaching hospital (Sydney, Australia). Sequential recruitment of women with a singleton pregnancy (N = 351) was undertaken. Plasma concentrations of angiotensin II type 1 receptor antibodies, placental growth factor, soluble fms-like tyrosine kinase-1, and soluble endoglin were measured using validated enzyme-linked immunosorbent assays at 12, 18, 28, 36, and 40 weeks' gestation and 6 weeks' postpartum. Clinical, demographic, and pregnancy data were prospectively collected. Pregnancy outcomes were classified as normotensive, gestational hypertension, or preeclampsia. Analyses were carried out using software and significance set at P < .05. RESULTS: In all, 351 women were recruited, 17 developed gestational hypertension, and 18 developed preeclampsia. Women with preeclampsia at baseline were heavier (P = .015), were taller (P = .046), and had higher systolic (P = .029) and diastolic (P = .006) blood pressure. The preeclampsia group had higher soluble fms-like tyrosine kinase-1 from ≥28 weeks (P = .003) and lower placental growth factor from 18 weeks (P = .004). Soluble endoglin and angiotensin II type 1 receptor antibodies did not vary over time or between groups. Angiotensin II type 1 receptor antibody (12 weeks) was positively correlated with serum pregnancy associated plasma protein A (P = .008) and human chorionic gonadotrophin (P = .04). CONCLUSION: Angiogenic markers vary longitudinally during pregnancy and placental growth factor and soluble fms-like tyrosine kinase-1 have a role for predicting and diagnosing preeclampsia later in disease. Our data show that angiotensin II type 1 receptor antibodies are not sensitive for disease and hence not useful as a biomarker. Larger studies are required to describe the role and functionality of angiotensin II type 1 receptor antibodies in preeclampsia.

In silico selection of an aptamer to estrogen receptor alpha using computational docking employing estrogen response elements as aptamer-alike molecules.

Aptamers, the chemical-antibody substitute to conventional antibodies, are primarily discovered through SELEX technology involving multi-round selections and enrichment. Circumventing conventional methodology, here we report an in silico selection of aptamers to estrogen receptor alpha (ERα) using RNA analogs of human estrogen response elements (EREs). The inverted repeat nature of ERE and the ability to form stable hairpins were used as criteria to obtain aptamer-alike sequences. Near-native RNA analogs of selected single stranded EREs were modelled and their likelihood to emerge as ERα aptamer was examined using AutoDock Vina, HADDOCK and PatchDock docking. These in silico predictions were validated by measuring the thermodynamic parameters of ERα -RNA interactions using isothermal titration calorimetry. Based on the in silico and in vitro results, we selected a candidate RNA (ERaptR4; 5'-GGGGUCAAGGUGACCCC-3') having a binding constant (Ka) of 1.02 ± 0.1 × 10(8) M(-1) as an ERα-aptamer. Target-specificity of the selected ERaptR4 aptamer was confirmed through cytochemistry and solid-phase immunoassays. Furthermore, stability analyses identified ERaptR4 resistant to serum and RNase A degradation in presence of ERα. Taken together, an efficient ERα-RNA aptamer is identified using a non-SELEX procedure of aptamer selection. The high-affinity and specificity can be utilized in detection of ERα in breast cancer and related diseases.

Snake venoms are integrated systems, but abundant venom proteins evolve more rapidly.

BACKGROUND: While many studies have shown that extracellular proteins evolve rapidly, how selection acts on them remains poorly understood. We used snake venoms to understand the interaction between ecology, expression level, and evolutionary rate in secreted protein systems. Venomous snakes employ well-integrated systems of proteins and organic constituents to immobilize prey. Venoms are generally optimized to subdue preferred prey more effectively than non-prey, and many venom protein families manifest positive selection and rapid gene family diversification. Although previous studies have illuminated how individual venom protein families evolve, how selection acts on venoms as integrated systems, is unknown. RESULTS: Using next-generation transcriptome sequencing and mass spectrometry, we examined microevolution in two pitvipers, allopatrically separated for at least 1.6 million years, and their hybrids. Transcriptomes of parental species had generally similar compositions in regard to protein families, but for a given protein family, the homologs present and concentrations thereof sometimes differed dramatically. For instance, a phospholipase A2 transcript comprising 73.4 % of the Protobothrops elegans transcriptome, was barely present in the P. flavoviridis transcriptome (<0.05 %). Hybrids produced most proteins found in both parental venoms. Protein evolutionary rates were positively correlated with transcriptomic and proteomic abundances, and the most abundant proteins showed positive selection. This pattern holds with the addition of four other published crotaline transcriptomes, from two more genera, and also for the recently published king cobra genome, suggesting that rapid evolution of abundant proteins may be generally true for snake venoms. Looking more broadly at Protobothrops, we show that rapid evolution of the most abundant components is due to positive selection, suggesting an interplay between abundance and adaptation. CONCLUSIONS: Given log-scale differences in toxin abundance, which are likely correlated with biosynthetic costs, we hypothesize that as a result of natural selection, snakes optimize return on energetic investment by producing more of venom proteins that increase their fitness. Natural selection then acts on the additive genetic variance of these components, in proportion to their contributions to overall fitness. Adaptive evolution of venoms may occur most rapidly through changes in expression levels that alter fitness contributions, and thus the strength of selection acting on specific secretome components.

Linking the old and new -- do angiotensin II type 1 receptor antibodies provide the missing link in the pathophysiology of preeclampsia?

Preeclampsia remains a leading cause of maternal and neonatal morbidity and mortality. The pathophysiology of preeclampsia remains poorly understood with various pathological mechanisms being implicated including the renin angiotensin system (RAAS), angiogenic pathways and various components of the immune system. Recently a pathogenic autoimmune factor has been identified in the form of auto-agonistic angiotensin II type 1 receptor antibodies (AT1-AA). AT1-AA have been studied in vitro and in vivo in various human and animal models and these data have provided compelling evidence for their role in preeclampsia. This review summarises the current literature surrounding the role of AT1-AA in preeclampsia and draws links between this relatively novel antibody to well-established pathological mechanisms including the immune system, the RAAS, angiogenic pathways and placental ischaemia.

Mucoadhesive polymeric platform for drug delivery; a comprehensive review.

Mucoadhesion can be defined as adhesion in biological setting. Process of mucoadhesion takes place in 3 stages- the first stage being that of wetting or swelling of mucoadhesive polymer. Second stage involves interpenetration of the chains of mucoadhesive polymer and the third stage involves formation of chemical bonds between entangled chains. Several polymer related factors like molecular weight, chain length, degree of cross-linking, hydration, functional groups, charge, polymer concentration and several environmental and physiological factors like contact time, mucin turnover rate and mucus viscosity affect the degree of mucoadhesion. Formulation scientists have structured and engineered several mucoadhesive polymers for their usefulness in enhancement of bioavailability, controlled and targeted drug delivery. Mucoadhesive polymers can be classified as non-specific first generation polymers and novel second generation polymers based on the mechanism of mucoadhesion. Mucoadhesive drug delivery systems have been applied to buccal cavity, oesophagus, gastrointestinal tract, eye, nasal cavity, vagina and rectal cavity. Several in vitro/ex vivo and in vivo evaluation techniques have evolved for the evaluation of mucoadhesive strength of these polymers. This review provides historical perspective on mucoadhesive polymers and an understanding of the phenomenon of mucoadhesion, factors affecting mucoadhesion, types of mucoadhesive polymers, their practical applications and the various evaluation techniques for determination of mucoadhesive strength.

Dangers of broth after transplantation.

Serum creatinine is routinely used to monitor renal function in transplant recipients. External factors including diet, exercise and hydration status can also influence serum creatinine concentration on a day-to-day basis. We describe a case of a patient whose serum creatinine increased from 128 to 171 µmol/L after ingestion of creatinine-rich (3098 µmol/L) soup. A renal biopsy was performed but revealed no cause for the rise in creatinine and by the next day, serum creatinine had returned to baseline. We conducted two experiments to examine the effect of soup ingestion by healthy volunteers. We measured the creatinine concentration of various store-bought stock preparations and found creatinine concentrations less than one-quarter of that contained in our patient's homemade soup. A creatinine-rich soup (4334 µmol/L) was ingested by six healthy volunteers age 33 (± 6.5) years with baseline normal serum creatinine 68 (± 14) µmol/L. Mean (standard deviation) serum creatinine increased to 77 (± 11) µmol/L 4 hours after soup ingestion (P = 0.0015, paired t-test). Mean (standard deviation) creatinine clearance, extrapolated from the 4 hour urine collection following soup ingestion, was high (267 ± 198 mL/min) exhibiting a supra-normal creatinine clearance. The rate of serum creatinine rise was lower in volunteers compared with the transplant patient, consistent with the concept of renal functional reserve. Our case highlights the importance of taking dietary changes into account when interpreting serum creatinine as a measure of allograft function.

Anticedants and natural prevention of environmental toxicants induced accelerated aging of skin.

Skin is frequently exposed to a variety of environmental and chemical agents that accelerate ageing. External stress such as UV radiations (UVR) and environmental pollutants majorly deteriorate the skin morphology, by activating certain intrinsic factors such as Reactive Oxygen Species (ROS) which trigger the activation of Matrix Metalloproteinases (MMPs) and inflammatory responses hence damaging the extracellular matrix (ECM) components. To counter this, an exogenous supply of anti-oxidants, is required since the endogenous anti-oxidant system cannot alone suffice the need. Bio-prospecting of natural resources for anti-oxidants has hence been intensified. Immense research is being carried out to identify potential plants with potent anti-oxidant activity against skin ageing. This review summarizes the major factors responsible for premature skin ageing and the plants being targeted to lessen the impact of those.