Effect of ondansetron on sensory level produced by intrathecal bupivacaine

Background: For spinal anesthesia there are drugs which can increase the level and quality of analgesia. Any drug which decreases sensory block level in spinal anesthesia is of great concern as it may need analgesic, sedative, supplement or even conversion to general anesthesia. Ondansetron is one such drug which has been reported to decrease the height of sensory block achieved after subarachnoid administration of bupivacaine. In this prospective observational study, we studied the effect of administration of ondansetron on the level of the sensory block achieved after subarachnoid blockade.Methods: In Group II, 4 mg ondansetron was given and 15 mins before giving spinal anesthesia Group II against control group receiving 2 ml saline intravenous (Group I). 15 mins before giving spinal anesthesia. Both groups received 3.5 ml of bupivacaine heavy was given intrathecally. Sensory and motor block was assessed 5, 15, and 30 mins. We analyzed both highest spinal block level achieved and time to regress to L1 level.Results: We found that in Group II both highest level of sensory block (T6 by median method) duration to regress to L1 level (1.43±0.22 hrs) was lesser as compared to group I and Group III T4 by median method and time to regress from T6 to L1 Group I 2.03±0.06 hrs Group III 1.84±0.27 hrs. Motor block did not differ between groups.Conclusions: We concluded that probably ondansetron was responsible for lower spinal block level and early recovery from spinal anesthesia after intrathecal bupivacaine and should not be given empirically for nausea and vomiting

Variable Immunogenic Potential of Wheat: Prospective for Selection of Innocuous Varieties for Celiac Disease Patients via in vitro Approach

Celiac Disease (CD) is a multifactorial, autoimmune enteropathy activated by cereal proteins in genetically predisposed individuals carrying HLA DQ2/8 genes. A heterogenous gene combination of the cereal prolamins is documented in different wheat genotypes, which is suggestive of their variable immunogenic potential. In the current study, four wheat varieties (C591, C273, 9D, and K78) identified via in silico analysis were analyzed for immunogenicity by measuring T-cell proliferation rate and levels of inflammatory cytokines (Interferon-γ and Tumor Necrosis Factor-α). Peripheral Blood Mononuclear Cells and biopsy derived T-cell lines isolated from four CD patients in complete remission and two controls were stimulated and cultured in the presence of tissue transglutaminase activated pepsin-trypsin (PT) digest of total gliadin extract from test varieties. The immunogenicity was compared with PBW 621, one of the widely cultivated wheat varieties. Phytohaemagglutinin-p was taken as positive control, along with unstimulated cells as negative control. Rate of cell proliferation (0.318, 0.482; 0.369, 0.337), concentration of IFN- γ (107.4, 99.2; 117.9, 99.7 pg/ml), and TNF- α (453.8, 514.2; 463.8, 514.2 pg/ml) was minimum in cultures supplemented with wheat antigen from C273, when compared with other test varieties and unstimulated cells. Significant difference in toxicity levels among different wheat genotypes to stimulate celiac mucosal T-cells and PBMC's was observed; where C273 manifested least immunogenic response amongst the test varieties analyzed

Regulatory mechanisms of plant rhizobacteria on plants to the adaptation of adverse agroclimatic variables

The mutualistic plant rhizobacteria which improve plant development and productivity are known as plant growth-promoting rhizobacteria (PGPR). It is more significant due to their ability to help the plants in different ways. The main physiological responses, such as malondialdehyde, membrane stability index, relative leaf water content, photosynthetic leaf gas exchange, chlorophyll fluorescence efficiency of photosystem-II, and photosynthetic pigments are observed in plants during unfavorable environmental conditions. Plant rhizobacteria are one of the more crucial chemical messengers that mediate plant development in response to stressed conditions. The interaction of plant rhizobacteria with essential plant nutrition can enhance the agricultural sustainability of various plant genotypes or cultivars. Rhizobacterial inoculated plants induce biochemical variations resulting in increased stress resistance efficiency, defined as induced systemic resistance. Omic strategies revealed plant rhizobacteria inoculation caused the upregulation of stress-responsive genes—numerous recent approaches have been developed to protect plants from unfavorable environmental threats. The plant microbes and compounds they secrete constitute valuable biostimulants and play significant roles in regulating plant stress mechanisms. The present review summarized the recent developments in the functional characteristics and action mechanisms of plant rhizobacteria in sustaining the development and production of plants under unfavorable environmental conditions, with special attention on plant rhizobacteria-mediated physiological and molecular responses associated with stress-induced responses

Targeting cancer addiction for SALL4 by shifting its transcriptome with a pharmacologic peptide

Sal-like 4 (SALL4) is a nuclear factor central to the maintenance of stem cell pluripotency and is a key component in hepatocellular carcinoma, a malignancy with no effective treatment. In cancer cells, SALL4 associates with nucleosome remodeling deacetylase (NuRD) to silence tumor-suppressor genes, such as PTEN. Here, we determined the crystal structure of an amino-terminal peptide of SALL4(1-12) complexed to RBBp4, the chaperone subunit of NuRD, at 2.7 Å, and subsequent design of a potent therapeutic SALL4 peptide (FFW) capable of antagonizing the SALL4-NURD interaction using systematic truncation and amino acid substitution studies. FFW peptide disruption of the SALL4-NuRD complex resulted in unidirectional up-regulation of transcripts, turning SALL4 from a dual transcription repressor-activator mode to singular transcription activator mode. We demonstrate that FFW has a target affinity of 23 nM, and displays significant antitumor effects, inhibiting tumor growth by 85% in xenograft mouse models. Using transcriptome and survival analysis, we discovered that the peptide inhibits the transcription-repressor function of SALL4 and causes massive up-regulation of transcripts that are beneficial to patient survival. This study supports the SALL4-NuRD complex as a drug target and FFW as a viable drug candidate, showcasing an effective strategy to accurately target oncogenes previously considered undruggable

AmBisome Monotherapy and Combination AmBisome-Miltefosine Therapy for the Treatment of Visceral Leishmaniasis in Patients Coinfected With Human Immunodeficiency Virus in India: A Randomized Open-Label, Parallel-Arm, Phase 3 Trial.

BACKGROUND: Visceral leishmaniasis (VL) in patients with human immunodeficiency virus (HIV) presents an increasingly important patient cohort in areas where both infections are endemic. Evidence for treatment is sparce, with no high-quality studies from the Indian subcontinent. METHODS: This is a randomized, open-label, parallel-arm, phase 3 trial conducted within a single hospital in Patna, India. One hundred and fifty patients aged ≥18 years with serologically confirmed HIV and parasitologically confirmed VL were randomly allocated to 1 of 2 treatment arms, either a total 40 mg/kg intravenous liposomal amphotericin B (AmBisome; Gilead Pharmaceuticals) administered in 8 equal doses over 24 days or a total 30 mg/kg intravenous AmBisome administered in 6 equal doses given concomitantly with a total 1.4 g oral miltefosine administered through 2 daily doses of 50 mg over 14 days. The primary outcome was intention-to-treat relapse-free survival at day 210, defined as absence of signs and symptoms of VL or, if symptomatic, negative parasitological investigations. RESULTS: Among 243 patients assessed for eligibility, 150 were recruited between 2 January 2017 and 5 April 2018, with no loss to follow-up. Relapse-free survival at day 210 was 85% (64/75; 95% CI, 77-100%) in the monotherapy arm, and 96%, (72/75; 90-100%) in the combination arm. Nineteen percent (28/150) were infected with concurrent tuberculosis, divided equally between arms. Excluding those with concurrent tuberculosis, relapse-free survival at day 210 was 90% (55/61; 82-100%) in the monotherapy and 97% (59/61; 91-100%) in the combination therapy arm. Serious adverse events were uncommon and similar in each arm. CONCLUSIONS: Combination therapy appears to be safe, well tolerated, and effective, and halves treatment duration of current recommendations. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry India (CTRI/2015/05/005807; the protocol is available online at https://osf.io/avz7r)

Patterned deposition of a mixed-coordination adenine-silver helicate, containing a π-stacked metallacycle, on a graphite surface

A novel mixed-valence silver complex with modified adenine and its adsorption behavior on different substrates was studied by atomic force microscopy, and selective patterning on a graphite surface is described in this report

A luminescent silver-adenine metallamacrocyclic quartet

This communication describes formation of a 3N-coordinated silver-modified adenine metallamacrocyclic quartet in solid state, its aggregative ordering on graphite surface, and luminescence

Mechanism of polyamine induced colistin resistance through electrostatic networks on bacterial outer membranes

Naturally occurring linear polyamines are known to enable bacteria to be resistant to cationic membrane active peptides. To understand this protective mechanism, molecular dynamics simulations are employed to probe their effect on a model bacterial outer membrane. Being protonated at physiological pH, the amine groups of the polyamine engage in favorable electrostatic interactions with the negatively charged phosphate groups of the membrane. Additionally, the amine groups form large number of hydrogen bonds with the phosphate groups. At high concentrations, these hydrogen bonds and the electrostatic network can non-covalently crosslink the lipid A molecules, resulting in stabilization of the outer membrane against membrane active antibiotics such as colistin and polymyxin B. Moreover, large polyamine molecules (e.g., spermidine) have a stronger stabilization effect than small polyamine molecules (e.g., ethylene diamine). The atomistic insights provide useful guidance for the design of next generation membrane active amine-rich antibiotics, especially to tackle the growing threat of multi-drug resistance of Gram negative bacteria.National Medical Research Council (NMRC)This work was supported by NMRC/TCR/002-SERI/2008/ R618, NMRC/TCR/R1018

Kinetic characterization of a bioinspired, heterogeneously active macromolecular catalyst for phenol oxidation and coupling reactions

We have synthesized and characterized a novel copper metalated polymeric matrix of modified nucleobase cytosine that catalyses oxidation of phenolic substrates. This metalated polymer is insoluble in common organic solvents, thus catalysis is heterogeneous in nature so that the material can be reused. The molecular structure of the monomer and the metalated monomer, a Michaelis-Menten kinetic analysis of oxidative transformations using different phenolic substrates and mechanistic investigations are presented in this paper

Contrasting crystallographic signatures of Ag(I)- and Cu(II)-N6,N6'- bisadenine complexes: extended vs. foldback geometries

We report crystallographic studies with N6,N6'-crosslinked bisadenine derivative, where complexation with Ag(I) exhibits a pentacoordination mode affording a molecular box, while interaction with Cu(II) results in an intramolecular complex