Simultaneous Quantification of an Enantiomer and the Racemic Compound of Ibuprofen by X-ray Powder Diffractometry

Purpose. An X-ray powder diffractometric method was developed for the simultaneous quantification of the relative amounts of the racemic compound (±) of ibuprofen (I) and S(+)-ibuprofen (II), when they occur as a mixture. Methods. The X-ray powder diffraction patterns of I and II show pronounced differences. This formed the basis for the determination of the relative amounts of I and II when they occur as a mixture. X-ray lines with d-spacings of 14.41 and 4.37 Å were unique to I and II, respectively. Mixtures containing different proportions of I and II were prepared which also contained lithium fluoride (III) as an internal standard. Results. A linear relationship was obtained when the intensity ratio (intensity of the 4.37 Å line of II/intensity of the 2.01 Å line of III) was plotted as a function of the weight fraction of II in the mixture. Similar results were obtained in the case of I. Using these standard curves, the weight fractions of I and II in 'unknown' mixtures were determined. The experimentally determined analyte concentration ranged between 98 and 104% of the true value. The relative error in the analyses of individual samples was < 10%. The minimum detectable weight fraction of I in II and II in I were 0.032 (3.2% w/w) and 0.034 (3.4% w/w), respectively. The minimum quantifiable weight fractions were 0.136 for I and 0.112 for II. Since the X-ray diffraction patterns of S(+)-ibuprofen and R(–)-ibuprofen are identical, the conclusions drawn regarding mixtures of I and II will also hold true in the quantitative analyses of mixtures of I and R(–)-ibuprofen.     

Intracerebroventricular passive immunization in transgenic mouse models of Alzheimer's disease

Since uncontrolled production of beta-amyloid (Abeta) is considered a key seeding event underlying progression of Alzheimer's disease (AD), elimination of excessive Abeta and preventing its reaccumulation constitute the primary therapeutic goal in preventing and treating AD. To date, immunoneutralization has been the most effective strategy in removing pre-existing cerebral Abeta. Both active and systemic passive immunizations are known to reduce cerebral Abeta and improve memory in transgenic murine models of AD. However, active immunization is associated with adverse effects such as encephalitis with perivascular inflammation and hemorrhage, while passive immunization has the potential to disrupt cerebral vasculature that is laden with amyloid and exposed to high levels of antibody in the blood. Intriguingly, intracerebroventricular passive immunization established in the authors' laboratory circumvented these problems. The authors demonstrated that a single intracerebroventricular injection of anti-Abeta antibody reduced the cerebral Abeta burden and Abeta-related astrocytosis, retarded reaccumulation of Abeta and restored Abeta-induced depletion of presynaptic SNAP-25, for at least 1 month and reduced inflammatory reactions for 1 week in AD murine models without producing inflammation, microhemorrhage or systemic histotoxicity. These facts suggest that intracerebroventricular anti-Abeta may be a safe method for the rapid clearance of pre-existing Abeta and retarding reaccumulation of Abeta in AD. Intracerebroventricular administration via a catheter and reservoir, may be combined with the development of humanized monoclonal antibody against Abeta. Intraventricular shunts and ventriculostomy are frequently employed with acceptable risk-to-benefit ratios in the treatment of various brain disorders, while humanized antibodies are currently used in clinical trials of brain diseases such as multiple sclerosis and lymphoma.     

Feasibility study for measuring patients’ visual acuity at home by their caregivers

Purpose:To assess the feasibility of measuring patients’ visual acuity (VA) in their homes by their caregivers.Methods:Patients consulting in a tertiary eye care institute were prospectively enrolled with informed consent. All underwent standard COMPlog distance VA testing. Patients and caregivers were oriented to test distance VA using the Peek Acuity app. The app was installed on the caregiver’s or patient’s smartphone. The patient’s VA was measured by the caregiver in the clinic (baseline value) under supervision. After 1 week, the caregivers recorded the patient’s VA with the Peek Acuity app at their home and reported the value in a telephone consultation. A questionnaire to assess the ease of using the app was administered at both the baseline visit and 1 week later.Results:A total of 100 patients (age group: 13 to 76 years) and 100 caregivers (age group: 17 to 65 years) participated. VA measurements with the Peek Acuity app were comparable with COMPlog (P > 0.1) both during the baseline and after 1-week measurement, regardless of the underlying ocular condition or educational level of the caregivers/patients. Most caregivers (95%) felt the app was easy to use.Conclusion:Though the Peek Acuity app was originally developed for health care workers to be used in field visits, we found that with proper orientation, the layperson can also use it. Such orientation can enable caregivers to effectively measure VA at home. Such a tool would enhance teleophthalmology consultations and can minimize the need for short follow-up visits.     

Proteomic profiling of forskolin-induced differentiated BeWo cells: an in-vitro model of cytotrophoblast differentiation

Placental trophoblastic differentiation is characterized by the fusion of monolayer cytotrophoblasts into syncytiotrophoblasts. During this process of differentiation, several morphological and biochemical changes are known to occur, and this model has been employed to investigate the changes that occur at the gene and protein level during differentiation. Using the sensitive technique of proteomics [two-dimensional gel electrophoresis (2DGE)], changes in protein profile were evaluated in the control and forskolin-induced differentiated cells of trophoblastic choriocarcinoma BeWo cell line. Several proteins were differentially expressed in control and differentiated cells. Four major proteins were up-regulated as assessed by silver staining, and were further characterized as c-h-ras p 21 (phosphorylated), retinoblastoma susceptibility protein 1 and integrase interactor protein 1. These proteins are known to play an important role in growth arrest of cells, and thus may play a role in initiating the process of differentiation.     

Migration,health, and socioenvironmental safety net among children of Dhaka,Bangladesh

This study quantifies the diarrhea burden among migrant children under age 5 (who have migrated due to environmental degradation) in Dhaka. We used a multifactor socioepidemiological as well as environmental approach with pretested questionnaires and observations. It was found that 52% of the children were affected by diarrhea. Disability-adjusted life years (DALYs) lost was reduced manifold with the increase of mothers' behavioral determinants. Health losses were 1,718 fold with significant coefficient (β) in the migrant group. DALYs lost were significantly associated with socioenvironmental factors such as mother's illiteracy (β = .18; p < .001), no hand wash before eating (β = .08; p = .004), and no hand wash after defecation (β = .10; p < .001). This puts emphasis clearly on the awareness at household level, especially of mothers and children under age 5 in Dhaka, Bangladesh, in formulating migration-related policies.     

Decrease in Antioxidant Status of Plasma and Erythrocytes from Geriatric Population

Background: Ageing is associated with an accumulation of free radical damage, which leads to physiological and clinical modifications. The study aims to find out the status of lipid profile, antioxidant enzymes, malondialdehyde in geriatric population. Patients/methods: The study was conducted on 150 subjects (75 healthy control between the ages of 20–30 years and 75 elderly subjects between ages of 50–70 years as cases). The following parameters were analyzed using the standard reference methods: lipid profile, reduced glutathione, glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase and malondialdehyde. Results: The present study was conducted to estimate the oxidative stress parameters in geriatric population. Highly significant increase in total cholesterol (TC), triglyceride (TG), LDL-cholesterol (LDL-C), VLDL-cholesterol (VLDL-C), malondialdehyde, catalase and decrease in high density lipoprotein cholesterol (HDL-C), reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase was observed in geriatrics when compared with their younger counterparts. Conclusion: This study concluded that there is enhanced oxidative stress and decreased antioxidant defence in geriatrics as compared to younger subjects which could play an important role in ageing. Dyslipidemia has become one of the important risk factors for the increasing prevalence of cardiovascular diseases. There is lack of awareness on the relationship between blood lipids and the risk of cardiovascular diseases in geriatric population. The strategy of early prevention should be adopted against dyslipidemia.     

Interventional Sialendoscopy for Parotid Ductal Calculi: Our Preliminary Experience

With this article we present our initial experience with interventional sialendoscopy of the parotid duct for the parotid calculi. We carried out a prospective study of patients of parotid calculi in a tertiary referral centre. Diagnostic and interventional sialendoscopy was performed in five cases of parotid calculi. The outcome was classified on the basis of clearance of the lumen of the duct and resolution of symptoms. Diagnostic sialendoscopy was able to diagnose the calculus in all cases. Interventional sialendoscopy was done under general anesthesia in all cases and calculus was successfully removed. The average size of sialolith was 8.2 mm. No complications occurred in any of the cases. Check sialendoscopy was done in all cases after a minimum follow up of 6 months, which showed the duct lumen to be free of stone with no stricture of the duct. Sialendoscopy is an optimal technique for removal of intraductal parotid calculi and avoids removal of the gland. In our series there was no associated morbidity and complication.     

Novel huperzine A based NMDA antagonists: insights from molecular docking,ADME/T and molecular dynamics simulation studies

Huperzine A (HupA) is an alkaloidal natural product and drug isolated from Chinese herb Huperzia serrata, which is a potent selective anticholinesterase inhibitor. HupA has symptomatic, cognitive-enhancing and protective effect on neurons against amyloid beta-induced oxidative injury and antagonizing N-methyl-d-aspartate receptors by blocking the ion channels. The present study aimed to identify the docking, ADME/T and molecular dynamics simulation parameters of a library of 40 analogues which can correlate the binding affinity, conformational stability and selectivity of the ligands towards NMDA receptor through in silico approach. Glide molecular docking analysis was performed for the designed analogues to understand the binding mode and interactions. MD simulations were performed to explain the conformational stability and natural dynamics of the interaction in physiological environmental condition of protein–ligand complex affording a better understanding of chemical-scale interactions between HupA and its analogues with NMDA channel that could potentially benefit the development of new drugs for neurodegenerative diseases involving NMDA receptors.

The in silico study explores the structural behavior and binding affinities of 40 novel analogues of huperzine A. Novel NMDA receptor antagonists have been virtually identified by molecular docking, ADME/T and molecular dynamics simulation studies.     

Surveillance of Artemisinin Resistance in Plasmodium falciparum in India Using the kelch13 Molecular Marker

Malaria treatment in Southeast Asia is threatened with the emergence of artemisinin-resistant Plasmodium falciparum. Genome association studies have strongly linked a locus on P. falciparum chromosome 13 to artemisinin resistance, and recently, mutations in the kelch13 propeller region (Pfk-13) were strongly linked to resistance. To date, this information has not been shown in Indian samples. Pfk-13 mutations were assessed in samples from efficacy studies of artemisinin combination treatments in India. Samples were PCR amplified and sequenced from codon 427 to 727. Out of 384 samples, nonsynonymous mutations in the propeller region were found in four patients from the northeastern states, but their presence did not correlate with ACT treatment failures. This is the first report of Pfk-13 point mutations from India. Further phenotyping and genotyping studies are required to assess the status of artemisinin resistance in this region.     

Phase I trial of a novel human monoclonal antibody mAb216 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia

Background

This phase I trial was conducted to determine the safety and pharmacokinetics of monoclonal antibody 216, a human monoclonal Immunoglobulin M antibody targeting a linear B-cell lactosamine antigen, administered alone and in combination with vincristine in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, and to preliminarily assess tumor targeting and efficacy.

Design and Methods

Three cohorts of patients received escalating doses of monoclonal antibody 216 administered as an intravenous infusion. In the case of poor response to the first dose of monoclonal antibody 216 alone, defined as less than 75% reduction in peripheral blood blast count, a second dose of the antibody with vincristine was given between days 4 and 7. Responses were assessed weekly until day 35. Serum concentration of monoclonal antibody 216 was measured before and after infusion. Monoclonal antibody 216 targeting was determined with an anti-idiotypic antibody to monoclonal antibody 216 and preliminary efficacy was analyzed by changes in peripheral blood blasts.

Results

Thirteen patients were enrolled. One episode of grade 3 epistaxis was the only dose-limiting toxicity observed. All patients showed a poor response to the first monoclonal antibody 216 infusion with a decrease in peripheral blasts from 6–65% in 9 patients. In 8 patients, addition of vincristine to monoclonal antibody 216 resulted in an average reduction of the peripheral blasts of 81%. One patient without peripheral blasts achieved a hypoplastic marrow without evidence of leukemia after one infusion of monoclonal antibody 216 and monoclonal antibody 216/vincristine each. Monoclonal antibody 216 was detected on peripheral blasts in all patients.

Conclusions

Treatment with monoclonal antibody 216 in combination with vincristine is feasible and well tolerated in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Binding of monoclonal antibody 216 to leukemic blasts was efficient, and favorable early responses were observed.