SOLVENT-RESISTANT NANOFILTRATION MEMBRANES: SEPARATION STUDIES AND MODELING

The primary focus of the research is to extend the principles of Nanofiltration(NF) to non-aqueous systems using solvent-resistant NF membranes. Several differentlevels of interaction are introduced when organic solvents are used with polymericmembranes and thus quantification of polymer-solvent interactions is critical. Puresolvent permeation studies were conducted to understand the mechanism of solventtransport through polymeric membranes. Different membrane materials (hydrophilic andhydrophobic) as well as different solvents (polar and non-polar) were used for the study.For example, hexane flux at 13 bar through a hydrophobic silicone based NF membranewas ~ 0.6 x 10-4 cm3/cm2. s. and that through a hydrophilic aromatic polyamide based NFmembrane was ~ 6 x 10-4 cm3/cm2. s. A simple model based on a solution-diffusionapproach which uses solvent physical properties (molar volume, viscosity) andmembrane properties (surface energy, etc) is used for correlating the pure solventpermeation through hydrophobic polymeric membranes.Solute transport studies were performed using organic dyes and triglycerides inpolar and non-polar solvents. For example, the rejection of Sudan IV (384 MW organicdye) in n-hexane medium is about 25 % at 15 bar and that in methanol is about –10 % atabout 20 bar for a hydrophobic (PDMS-based) membrane. However, for a hydrophilicpolyamide based NF membrane, the direction of separation is reversed (86 % in methanoland 43 % in n-hexane). From our experimental data with two types of membranes it isclear that coupling of the solute and solvent fluxes cannot be neglected. Two traditionaltransport theories (Spiegler-Kedem and Surface Force-Pore Flow model) that considercoupling were evaluated with literature and our experimental solute permeation data. Amodel based on a fundamental chemical potential gradient approach has been proposedfor explaining solute separation. The model uses solute, solvent and membrane physicalproperties and uses the Flory-Huggins and UNIFAC theories as activity coefficientmodels. This model has been used to obtain a correlation for the diffusion coefficients ofsolutes in hexane through a hydrophobic membrane. This correlation along withconvective coupling can be used to predict separation behavior for different solutes and atdifferent temperatures

Frequency of fokI and taqI polymorphism of vitamin D receptor gene in Indian population and its association with 25-hydroxyvitamin D levels

Background: The VDR protein is at the centre of the vitamin D endocrine system, a complex physiological system with substantial feedback regulatory mechanisms involved in maintaining serum calcium and 1, 25 dihydroxy vitamin D3. Variations in VDR gene are shown to have implications in several diseases and have also been implicated as an important genetic factor affecting bone mass. Aim: To determine the frequency of Fok I and Taq I variants in healthy Indian individuals and its association with 25-OH-Vitamin D levels. Settings and Design: Blood samples were collected from 143 unrelated normal individuals (Male-84 and Female-59) and their genotypes determined. Materials and Methods: After amplification by polymerase chain reaction, each polymorphism was genotyped by restriction fragment length polymorphism. For 100 normal healthy individuals 25-hydroxyvitamin D estimation was done using DiaSorin kit method. Statistical Analysis: Graph pad software was used to calculate the P values from the Chi-square. Results: Out of 143 samples analyzed for FokI and TaqI polymorphisms the following genotypic frequency was obtained FF 59%, Ff 36%, ff 5% and TT 49%, Tt 43%, tt 8% respectively. Conclusions: Results indicate that the distribution of the polymorphic loci Fok I and Taq I vary considerably not only in different populations, but also within India. Furthermore, when the genotypes were analyzed with respect to 25-OH-Vitamin D levels, a significant association was seen for the Taq 1 SNP but not with the Fok I

Development of Monoclonal Antibodies Against Cry1Ac/Ab Protein for Designing of Sandwich ELISA to Detect BT Toxin from Cotton Seeds and Leaves

The design of the study is to develop monoclonal antibodies against Cry1Ac/Ab protein for designing os sandwich ELISA(hybridoma technology). Hybridoma technology was invented by Cesar Milstein and Georges J.F Kohler in the year 1975 and is an unique method used to produce identical antibodies in maximum quantities. Monoclonal antibodies were developed by immunization of Balb/C mice with Cry1Ac/Ab Protein. Titer values of mice tail bleeds were checked and the best mice with higher titer value was used for fusion. Immunized mice spleen cells were fused with Myeloma cells (SP2-O), using polyethylene glycol (PEG) and the fused cells were incubated with HAT medium for 12 days and initially 400 positive hybridoma clones were obtained, of which 13 potential clones were selected using indirect ELISA against Cry1Ac/Ab recombinant antigen. Cross reactivity was ruled out using indriet ELSA against cry proteins such as Cry2A, Cry1F and CP4EPSPS using. Cloning was carried out twice for all 13 clones by limiting dilution factor and pure single clones were selected. The class IgG/IgM/IgA and sub classes IgG1, IgG2, IgG3 antibodies are determined by isotyping. Determination of class and subclass of an antibody is very important for selecting proper purification methods. Commercially available rapid isotyping kits were used for isotyping which provides the information of 1) IgG, IgM, IgA, IgG2a, IgG2b or IgG3 2) Light chain identification as either kappa or lambda. All pure clones were preserved in Liquid Nitrogen for future use to develop immunological kits for detection of Cry1Ac/Ab present in the plant tissue.The design of the study is to develop monoclonal antibodies against Cry1Ac/Ab protein for designing os sandwich ELISA(hybridoma technology). Hybridoma technology was invented by Cesar Milstein and Georges J.F Kohler in the year 1975 and is an unique method used to produce identical antibodies in maximum quantities. Monoclonal antibodies were developed by immunization of Balb/C mice with Cry1Ac/Ab Protein. Titer values of mice tail bleeds were checked and the best mice with higher titer value was used for fusion. Immunized mice spleen cells were fused with Myeloma cells (SP2-O), using polyethylene glycol (PEG) and the fused cells were incubated with HAT medium for 12 days and initially 400 positive hybridoma clones were obtained, of which 13 potential clones were selected using indirect ELISA against Cry1Ac/Ab recombinant antigen. Cross reactivity was ruled out using indriet ELSA against cry proteins such as Cry2A, Cry1F and CP4EPSPS using. Cloning was carried out twice for all 13 clones by limiting dilution factor and pure single clones were selected. The class IgG/IgM/IgA and sub classes IgG1, IgG2, IgG3 antibodies are determined by isotyping. Determination of class and subclass of an antibody is very important for selecting proper purification methods. Commercially available rapid isotyping kits were used for isotyping which provides the information of 1) IgG, IgM, IgA, IgG2a, IgG2b or IgG3 2) Light chain identification as either kappa or lambda. All pure clones were preserved in Liquid Nitrogen for future use to develop immunological kits for detection of Cry1Ac/Ab present in the plant tissue

Antipsychotic dose escalation as a trigger for Neuroleptic Malignant Syndrome (NMS): literature review and case series report

Background: “Neuroleptic malignant syndrome” (NMS) is a potentially fatal idiosyncratic reaction to any medication which affects the central dopaminergic system. Between 0.5% and 1% of patients exposed to antipsychotics develop the condition. Mortality rates may be as high as 55% and many risk factors have been reported. Although rapid escalation of antipsychotic dose is thought to be an important risk factor, to date it has not been the focus of a published case series or scientifically defined. <p/>Aims: To identify cases of NMS and review risk factors for its development with a particular focus on rapid dose escalation in the 30 days prior to onset. <p/>Methodology: A review of the literature on rapid dose escalation was undertaken and a pragmatic definition of “rapid dose escalation” was made. NMS cases were defined using DSM-IV criteria and systematically identified within a secondary care mental health service. A ratio of titration rate was calculated for each NMS patient and “rapid escalators” and “non rapid escalators” were compared. <p/>Results: 13 cases of NMS were identified. A progressive mean dose increase 15 days prior to the confirmed episode of NMS was observed (241.7mg/day during days 1-15 to 346.9mg/day during days 16-30) and the mean ratio of dose escalation for NMS patients was 1.4. Rapid dose escalation was seen in 5/13 cases and non rapid escalators had markedly higher daily cumulative antipsychotic dose compared to rapid escalators. <p/>Conclusions: Rapid dose escalation occurred in less than half of this case series (n=5, 38.5%), although there is currently no consensus on the precise definition of rapid dose escalation. Cumulative antipsychotic dose – alongside other known risk factors - may also be important in the development of NMS

Bridging the gap from medical to psychological safety assessment: consensus study in a digital mental health context

Background: Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence. Aims: The aim of this study was to generate an experts’ consensus on how the medical regulatory method used for assessing safety could best be adapted for DMHIs. Method: An online Delphi study containing three rounds was conducted with an international panel of 20 experts with experience/knowledge in the field of UK digital mental health. Results: Sixty-four items were generated, of which 41 achieved consensus (64%). Consensus emerged around ten recommendations, falling into five main themes: Enhancing the quality of adverse events data in DMHIs; Re-defining serious adverse events for DMHIs; Reassessing short-term symptom deterioration in psychological interventions as a therapeutic risk; Maximising the benefit of the Yellow Card Scheme; and Developing a harmonised approach for assessing the safety of psychological interventions in general. Conclusion: The implementation of the recommendations provided by this consensus could improve the assessment of safety of DMHIs, making them more effective in detecting and mitigating risk

Quality of life in purely ocular myasthenia in Japan

Background: Since there has been no conclusive evidence regarding the treatment of ocular myasthenia, treatment guidelines were recently issued by the European Federation of Neurological Societies/European Neurological Society (EFNS/ENS). However, the therapeutic outcomes concerning the quality-of-life (QOL) of patients with ocular myasthenia are not yet fully understood.Methods: We investigated the therapeutic outcomes of patients with purely ocular myasthenia in a multicenter cross-sectional survey in Japan. To evaluate the severity of ocular symptoms, we used the ocular-quantitative MG (QMG) score advocated by Myasthenia Gravis Foundation of America. We used the Japanese translated version of the MG-QOL15, a self-appraised scoring system.Results: Of 607 myasthenia gravis (MG) patients with an observation-duration of illness ? 2 years, the cases of 123 patients (20%) were limited to ocular muscles (purely ocular myasthenia). During the entire clinical course, 81 patients experienced both ptosis and diplopia, 36 had ptosis alone, and six had diplopia alone. Acetyl-cholinesterase inhibitors and prednisolone were used in 98 and 52 patients, respectively. Treatment improved ocular symptoms, with the mean reduction in ocular-QMG score of 2.3 ± 1.8 points. However, 47 patients (38%) failed to gain minimal manifestation or a better status. Patients with unfavorable outcomes also self-reported severe QOL impairment. Multivariate analyses showed that the pretreatment ocular-QMG score was associated with unfavorable outcomes, but not associated with the patient\u27s QOL.Conclusion: A treatment strategy designed in accord with a patient\u27s ocular presentation must be considered in order to improve ocular symptoms and the patient\u27s QOL