COF-supported zirconium oxyhydroxide as a versatile heterogeneous catalyst for Knoevenagel condensation and nerve agent hydrolysis.

A composite of catalytic Lewis acidic zirconium oxyhydroxides (8 wt %) and a covalent organic framework (COF) was synthesized. X-ray diffraction and infrared (IR) spectroscopy reveal that COF's structure is preserved after loading with zirconium oxyhydroxides. Electron microscopy confirms a homogeneous distribution of nano- to sub-micron-sized zirconium clusters in the COF. 3D X-ray tomography captures the micron-sized channels connecting the well-dispersed zirconium clusters on the COF. The crystalline ZrOx(OH)y@COF's nanostructure was model-optimized via simulated annealing methods. Using 0.8 mol % of the catalyst yielded a turnover number of 100-120 and a turnover frequency of 160-360 h-1 for Knoevenagel condensation in aqueous medium. Additionally, 2.2 mol % of catalyst catalyzes the hydrolysis of dimethyl nitrophenyl phosphate, a simulant of nerve agent Soman, with a conversion rate of 37% in 180 min. The hydrolytic detoxification of the live agent Soman is also achieved. Our study unveils COF-stabilized ZrOx(OH)y as a new class of zirconium-based Lewis + Bronsted-acid catalysts.

Co prescription of anti-acid therapy reduces the bioavailability of mycophenolate mofetil in systemic sclerosis patients: A crossover trial.

OBJECTIVE: Mycophenolate mofetil (MMF) is an effective treatment option for interstitial lung disease (ILD) in systemic sclerosis (SSc). Many patients require co-administration of proton pump inhibitors (PPI) or H2 receptor blockers (HRB) because of various gastrointestinal (GI) manifestations in SSc. Co-treatment with PPI or HRB have shown to reduce serum drug levels in post-transplant patients. We wanted to see if there is a similar phenomenon for Mycophenolate in SSc. METHODS: Twenty SSc patients, who were on a stable dose of MMF (1.5-3 g) underwent a sequential cross over study with MMF alone in the first month, followed by co-treatment with Ranitidine and then Esomeprazole in the second and third month respectively. Estimation of 12-hour area under curve (AUC) of Mycophenolic Acid (MPA) levels and total GI score were calculated at the end of each month and compared between the treatment arms. [Trial registration: CTRI/2020/06/025,939] RESULTS: Co-administration of esomeprazole was associated with 32.7% (mean difference = 22.28 µg h ml-1) reduction in mean AUC MPA, whereas ranitidine caused a reduction of 21.97% (mean difference = 14.93 µg h ml-1) in MPA AUC when compared to MMF without anti-acid therapies. The addition of ranitidine or esomeprazole resulted in significant reduction in the total GI score. CONCLUSION: Co-administration of PPI or HRB can significantly reduce the bioavailability of MMF in patients with SSc. To avoid therapeutic failure of MMF drug level monitoring is essential when these agents are co-prescribed with MMF.

Efficacy and safety of curcumin in maintaining remission during disease-modifying antirheumatic drug withdrawal in rheumatoid arthritis at 52 weeks: a phase III double-blind, randomized placebo-controlled trial.

Curcumin has anti-inflammatory properties but current evidence is limited to advocate its use in rheumatoid arthritis (RA). We explored whether curcumin could maintain remission in patients with RA while tapering conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARD). In this patient-and investigator-blinded trial, adults with RA in sustained remission for more than six months were randomized to oral curcumin (1 g) with piperine (5 mg) twice daily or matching placebo. Patients who had received biological DMARDs or curcumin supplements in the last 6 months were excluded. csDMARD were tapered and stopped sequentially as per a fixed protocol. The primary outcome was flare-free survival at 52 weeks. The secondary outcomes were flare rate, correlation of serum curcuminoid levels with flares and safety. 200 patients (100 per arm) entered the trial with comparable baseline characteristics. Per protocol analysis included 92 and 93 participants in the curcumin and the placebo group, respectively. Flare-free survival at week 52 was similar between both groups (60% versus 64%; p = 0.76). The median time to flare was similar [Curcumin: 219 days (IQR: 123) versus placebo: 214 days (95.8); p = 0.067]. Cox proportionate regression modelling showed that the flare-free survival was independent of serum curcuminoid levels [adjusted HR = 0.99 (95% CI: 0.97-1.0)]. The model showed that flare-free survival was not associated with age, gender, seropositivity, or csDMARD used at baseline. No serious adverse effects were noted. Curcumin did not impact the flare-free survival in patients with RA in remission during the tapering of csDMARDs despite achieving adequate serum levels.Trial registration: CTRI/2018/04/013279.

Limited Impact of Fetal Sex and Maternal Body Mass Index on Fetal and Maternal Insulin Resistance and Lipid Metabolism: Findings from the PEARs Study.

The intrauterine environment can have a significant impact on fetal and maternal well-being, both during pregnancy and in later life. We aimed to identify how fetal sex and maternal body mass index (BMI) influence insulin resistance and metabolic function during pregnancy with maternal BMI > 25 kg/m2. This secondary analysis assessed data from the PEARS-randomized controlled trial that recruited pregnant women with body mass indexes 25-39.9 kg/m2. Longitudinal measurements of maternal and fetal insulin resistance and metabolic function were recorded throughout pregnancy. Regression models tested the effects of fetal sex and maternal BMI on markers of metabolic function and insulin regulation. A total of 484 women and their newborns (252 (52%) males vs. 232 (48%) females) were included in the analysis. A total of 333 (69%) women were overweight and 151 (31%) were obese. Male newborns were heavier and larger than females, and had a higher rate of instrumental delivery. Males had a lower LDL, but no other markers of insulin resistance or metabolic function were affected by fetal sex. Women with obesity had elevated markers of insulin resistance and metabolic dysfunction compared with women that were overweight, but maternal BMI did not impact these variables in the fetus. Fetal sex did not impact maternal and fetal metabolic parameters in women with BMI > 25 kg/m2. However, a higher BMI caused increasingly deranged maternal blood lipid concentrations and markers of insulin resistance as pregnancy progressed. Lipid monitoring and interventions to reduce lipids during pregnancy therefore require further evaluation.

Evaluation of Supportive Care Management Outcomes in Cancer Chemotherapy: A Prospective Observational Study in a Tertiary Care Teaching Hospital in South India.

AIMS: Evaluation of supportive care management of cancer patients experiencing drug-related problems (DRPs) is a challenge because it might increase the cost due to additional therapy. The main objectives of this study were to estimate chemotherapy-associated drug-related hospital admissions in the department of medical oncology and to estimate the cost of managing chemotherapy-associated DRPs. SETTINGS AND DESIGN: This study is a prospective observational study. SUBJECTS AND METHODS: Patients with chemotherapy-related DRPs were prospectively identified from the patient's medical records. The contribution of DRPs and cost incurred due to each hospitalization was assessed. STATISTICAL ANALYSIS USED: Data were analyzed using SPSS® 20.0 version. RESULTS: Out of 55 patients analyzed for DRPs, 25 (45.5%) patients in the age group of 51-60 years experienced DRPs most frequently. Most commonly occurring DRP was adverse drug reactions 42 (76.4%), which were more frequent in females. DRPs were maximum with alkylating agents 15 (27.3%) and the least with hormonal agents 1 (1.8%). The mean length of hospitalization was 9.6 ± 6.5 days. The total direct medical cost was Rs. 31,540 ± 42,476, of which medicine cost accounted for Rs. 16,550 ± 25,404, constituting a major share of the total medical costs. CONCLUSIONS: Pharmacists can provide better patient care by identifying and preventing DRPs and reducing drug-related morbidity and mortality.

Enhanced expression of tumour suppressor RAR-ß by DSPC nano-formulated lipo-ATRA in the lung of B16F10 cell-implanted C57BL6 mice and in A549 cells.

AIM: All Trans Retinoic acid (ATRA) is an efficient drug for leukemia, but is not efficient therapy for solid cancers. Hence we have used 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol lipo-ATRA to investigate its molecular therapeutic effect on lung cancer. The objective was to find whether it could enhance ATRA receptor, RAR-ß expression in lung cells as it was lost in majority of cancers including lung cancer. MATERIALS AND METHODS: The study was made in an experimental C57BL/6 mice model developed by tail vein injection of B16F10 cells and in A549 human lung cancer cells. The RAR-ß protein expression was studied by Immunohistochemistry/Immunocytochemistry and the mRNA expression was studied by RT-PCR and qPCR methods. KEY FINDINGS: Both free and lipo-ATRA treatments showed an enhancement of RAR-ß protein and gene expressions, indicating its induction on RAR ß. However, lipo-ATRA treatment has shown significant induction when compared with free ATRA treatment. SIGNIFICANCE: Our results implies that the DSPC lipo-ATRA treatment might have accumulated more ATRA in to the target cells which might have resulted in the induction of its receptor RAR-ß expression in a hypothesis of ligand induced receptor expression.

ATRA Entrapped in DSPC Liposome Enhances Anti-metastasis Effect on Lung and Liver During B16F10 Cell Line Metastasis in C57BL6 Mice.

BACKGROUND: The high mortality rate of lung cancer is highly associated with faster metastasis spread. All Trans Retinoic Acid (ATRA), being the first choice drug for leukemia therapy is now under intense study for its therapeutic efficiency in other solid cancers. OBJECTIVES: This study was aimed to investigate the anti-metastasis activity of free ATRA and liposome entrapped ATRA (5:4:1) in the experimental C57BL/6 mice model developed by the injection of B16F10 cell line into the tail vein. METHOD: The ATRA drug was given via i.p for 21 days. The visual lung and liver metastatic tumor nodules were noted. Various biochemical markers of cancer metastasis in the serum as well as tissues were also analyzed after sacrifice. RESULTS: Tumor nodules have significantly decreased in ATRA treatment groups (32.83 ± 1.83 for free ATRA, 23 ± 2.36 for DSPC Lipo-ATRA) when compared with metastasis control (63.16 ± 2.9) in the lungs. Among the treatment groups, the DSPC lipo-ATRA treated group showed a significant tumor growth inhibition (63.6%) than that of in the free ATRA treated groups (48%). Similar anti-metastatic effect was observed in liver also. Furthermore lipo-ATRA has shown a significant change in the levels of biochemical cancer markers analyzed in this study. CONCLUSION: Our results concluded that the liposome encapsulated ATRA has an enhanced anti-metastasis potency than the free ATRA during B16F10 metastatic cell line implantation.