Study of discrepancies in ABO blood grouping: experience of a tertiary health-care center

Background: An accurate ABO grouping is the most important test which is done in the blood bank. Mistyping can lead to transfusion with ABO incompatible blood which results in severe intravascular haemolysis and may even result in the death of the recipient. An ABO discrepancy implies that the forward or red cell ABO grouping does not agree with the reverse or serum ABO grouping. The study was conducted to evaluate the frequency of ABO blood group discrepancies, to identified main causes of discrepancies, to avoid chances of wrong interpretation of blood group and to mitigate clinical impact associated with mismatch ABO transfusion.Methods: A prospective study of ABO discrepancies and their causes was performed on 25,129 samples of the patients and 13,251 samples of blood donors at the red cell serology laboratory in tertiary care teaching hospital and blood bank over the period from February 2017 to July 2018.Results: ABO group discrepancies were mainly divided in 4 different groups. Out of 51 discrepancies 32 (62.74%) were found in group-IV category, being highest amongst all; 10 (19.60%) in group-II which was second highest; other were 8 (15.69%) in group-I and 1 (1.96%) in group-III category.Conclusions: All discrepancies reported on ABO cell and serum grouping must be investigated further, so that correct blood group is reported, minimizing the chances of transfusion reaction. A note of caution should be mentioned on the blood group card to prevent ABO incompatibility in case of transfusion

Transfusion effect of random donor platelet and single donor platelet in thrombocytopenic patients at tertiary care hospital of South Gujarat

Background: Platelet transfusion plays a key role in therapy for the patients with thrombocytopenia. Superiority of Single donor platelet (SDP) over Random donor platelet (RDP) transfusions is largely assumed, but unproven. Platelet Rich Plasma-Platelet concentrate (PRP-PC) and Apheresis-PC were prepared and their therapeutic efficacy were assessed in thrombocytopenic patients.Methods: This study included 60 transfusion episodes consisting of 30 SDP and 30 RDP (147units of RDP). The post transfusion efficacy of transfused platelets was assessed at 1 hour and 24 hours by corrected count increment (CCI) and percentage recovery (PR). Paired ‘t’-test was used for statistical analysis and a probability of p<0.05 was used to reject null hypothesis.Results: The mean platelet dose of SDP (n=30) and RDP (n=30) was 2.86±1.05 x 1011 and 2.36±0.54 x 1011 respectively. The mean platelet increments of SDP at 1 hour and 24 hours were 38±18.1 x 103/μl and 37.3±20.7x 103/μl. The mean platelet increments of RDP at 1 hour and 24 hours were 28.5±11.4 x 103/μl and 26 ±11.6 x 103/μl. The mean CCI of SDP at 1hour and 24 hours were 21.4 ±7.3 x 103/μl and 20.8±7.4 x 103/μl respectively. The mean CCI of RDP at 1hour and 24 hours were 18.5±6.3x 103/μl and 17.4±7.6 x 103/μl respectively.Conclusions: Post-transfusion increments were significantly higher in patients who received SDP as compared to RDP, but the CCI and PR were comparable in both groups of patients

Dupilumab provides favourable long‐term safety and efficacy in children aged ≥ 6 to < 12 years with uncontrolled, severe atopic dermatitis: results from an open‐label phase IIa study and subsequent phase III open‐label extension study

Background Children aged ≥ 6 to < 12 years with severe atopic dermatitis (AD) have limited treatment options. In a 16‐week, randomized, placebo‐controlled, phase III trial in children, dupilumab, a monoclonal antibody inhibiting interleukin (IL)‐4/IL‐13 signalling, significantly improved signs and symptoms with acceptable safety; longer‐term safety and efficacy data are lacking. Objectives To report the pharmacokinetic profile and long‐term safety and efficacy of dupilumab in children (aged ≥ 6 to < 12 years) with severe AD. Methods Children (aged ≥ 6 to < 12 years) with severe AD were enrolled in a global, multicentre, phase IIa, open‐label, ascending‐dose, sequential cohort study and subsequent open‐label extension (OLE) study. Patients received single‐dose dupilumab 2 or 4 mg kg−1 followed by 8‐week pharmacokinetic sampling, then 2 or 4 mg kg−1 weekly for 4 weeks (phase IIa), followed by the same weekly regimen (OLE). Primary endpoints were dupilumab concentration–time profile and treatment‐emergent adverse events (TEAEs); secondary assessments included Eczema Area and Severity Index (EASI) and Peak Pruritus Numeric Rating Scale (PP‐NRS) score. Results Of 38 children enrolled, 37 completed phase IIa and 33 continued to the OLE. Nonlinear, target‐mediated pharmacokinetics characterized dupilumab concentrations (week 24–48 mean serum concentrations: 2 mg kg−1, 61–77 mg L−1; 4 mg kg−1, 143–181 mg L−1). TEAEs were mostly mild to moderate and transient; none led to treatment discontinuation. The most commonly reported TEAEs were nasopharyngitis (2 mg kg−1, 47%; 4 mg kg−1, 56%) and AD exacerbation (29% and 13%, respectively). Single‐dose dupilumab rapidly improved AD with further improvements through week 52. Mean EASI and PP‐NRS improved by −37%/−33% and −17%/−20% at week 2 (phase IIa) and −92%/−84% and −70%/−58% at week 52 (OLE), respectively. Conclusions These safety and efficacy results support the use of dupilumab as a continuous long‐term treatment for children aged ≥ 6 to < 12 years with severe AD

Interaction of Pyrrolobenzodiazepine (PBD) Ligands with Parallel Intermolecular G-Quadruplex Complex Using Spectroscopy and ESI-MS

Studies on ligand interaction with quadruplex DNA, and their role in stabilizing the complex at concentration prevailing under physiological condition, has attained high interest. Electrospray ionization mass spectrometry (ESI-MS) and spectroscopic studies in solution were used to evaluate the interaction of PBD and TMPyP4 ligands, stoichiometry and selectivity to G-quadruplex DNA. Two synthetic ligands from PBD family, namely pyrene-linked pyrrolo[2,1-c][1,4]benzodiazepine hybrid (PBD1), mixed imine-amide pyrrolobenzodiazepine dimer (PBD2) and 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4) were studied. G-rich single-stranded oligonucleotide d(5′GGGGTTGGGG3′) designated as d(T2G8), from the telomeric region of Tetrahymena Glaucoma, was considered for the interaction with ligands. ESI-MS and spectroscopic methods viz., circular dichroism (CD), UV-Visible, and fluorescence were employed to investigate the G-quadruplex structures formed by d(T2G8) sequence and its interaction with PBD and TMPyP4 ligands. From ESI-MS spectra, it is evident that the majority of quadruplexes exist as d(T2G8)2 and d(T2G8)4 forms possessing two to ten cations in the centre, thereby stabilizing the complex. CD band of PBD1 and PBD2 showed hypo and hyperchromicity, on interaction with quadruplex DNA, indicating unfolding and stabilization of quadruplex DNA complex, respectively. UV-Visible and fluorescence experiments suggest that PBD1 bind externally where as PBD2 intercalate moderately and bind externally to G-quadruplex DNA. Further, melting experiments using SYBR Green indicate that PBD1 unfolds and PBD2 stabilizes the G-quadruplex complex. ITC experiments using d(T2G8) quadruplex with PBD ligands reveal that PBD1 and PBD2 prefer external/loop binding and external/intercalative binding to quadruplex DNA, respectively. From experimental results it is clear that the interaction of PBD2 and TMPyP4 impart higher stability to the quadruplex complex

Design, Synthesis and Biological Evaluation of Syn and Anti-like Double Warhead Quinolinones Bearing Dihydroxy Naphthalene Moiety as Epidermal Growth Factor Receptor Inhibitors with Potential Apoptotic Antiproliferative Action

Our investigation includes the synthesis of new naphthalene-bis-triazole-bis-quinolin-2(1H)-ones 4a–e and 7a–e via Cu-catalyzed [3 + 2] cycloadditions of 4-azidoquinolin-2(1H)-ones 3a–e with 1,5-/or 1,8-bis(prop-2-yn-1-yloxy)naphthalene (2) or (6). All structures of the obtained products have been confirmed with different spectroscopic analyses. Additionally, a mild and versatile method based on copper-catalyzed [3 + 2] cycloaddition (Meldal–Sharpless reaction) was developed to tether quinolinones to O-atoms of 1,5- or 1,8-dinaphthols. The triazolo linkers could be considered as anti and syn products, which are interesting precursors for functionalized epidermal growth factor receptor (EGFR) inhibitors with potential apoptotic antiproliferative action. The antiproliferative activities of the 4a–e and 7a–e were evaluated. Compounds 4a–e and 7a–e demonstrated strong antiproliferative activity against the four tested cancer cell lines, with mean GI50 ranging from 34 nM to 134 nM compared to the reference erlotinib, which had a GI50 of 33 nM. The most potent derivatives as antiproliferative agents, compounds 4a, 4b, and 7d, were investigated for their efficacy as EGFR inhibitors, with IC50 values ranging from 64 nM to 97 nM. Compounds 4a, 4b, and 7d demonstrated potent apoptotic effects via their effects on caspases 3, 8, 9, Cytochrome C, Bax, and Bcl2. Finally, docking studies show the relevance of the free amino group of the quinoline moiety for antiproliferative action via hydrogen bond formation with essential amino acids

Carcass traits of crossbred (Landrace × Desi) barrows reared with different floor space allowances under intensive system

Present study assessed the effect of floor space allowances on carcass traits of crossbred (Landrace × Desi) barrows in Indian conditions. Crossbred barrows (36) were reared with 3 different floor space allowances (12 each) having group size of 4 pigs/pen. One group (TIS) was provided floor space as per Indian Standards (0.9, 1.35 and 1.8 m2/pig for weaner, grower and finisher stages, respectively) specifications, while other two groups with 33% (T2/3) and 50% (T1/2) reduced floor space allowances. Pigs were reared up to 29 weeks of age. Final weight of pigs did not differ significantly among the groups. Six animals from each group were slaughtered. None of the major economic carcass traits, viz. carcass weight, dressing %, back fat thickness (BFT), loin eye area (LEA), estimated lean meat percentage etc. was adversely affected. Major cut-up parts, share of edible as well as inedible offal and composition of pork (moisture, CP and EE) also did not differ among groups. It indicates scope of 50 % reduction in floor space allowance for pig production in India without affecting final body weight and major carcass characteristics

Assay strategies for the discovery and validation of therapeutics targeting <i>Brugia pahangi</i> Hsp90

The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target