Water Quality Interaction with Alkaline Phosphatase in the Ganga River: Implications for River Health

Carbon, nitrogen and phosphorus inputs through atmospheric deposition, surface runoff and point sources were measured in the Ganga River along a gradient of increasing human pressure. Productivity variables (chlorophyll a, gross primary productivity, biogenic silica and autotrophic index) and heterotrophy (respiration, substrate induced respiration, biological oxygen demand and fluorescein diacetate hydrolysis) showed positive relationships with these inputs. Alkaline phosphatase (AP), however, showed an opposite trend. Because AP is negatively influenced by available P, and eutrophy generates a feedback on P fertilization, the study implies that the alkaline phosphatase can be used as a high quality criterion for assessing river health.     

Hydrotalcite catalyzed N-alkylation: A practical greener approach towards Carbon-Nitrogen bond formation

Main driving force of this research work is to focus 9th principle (Catalysis) out of 12 principles of green chemistry so as to protect environment concerned with the reduction in generation of carbon dioxide, one of the green house gas. An innovative development of chemical pathway regarding N-alkylation reaction carried out by adding and recycling only catalytic amount of Hydrotalcite as solid base instead of stoichiometric amount, as per prior art techniques, has attempted. Synthesis of 3° amines, important Active Pharmaceutical Ingredients (APIs) and their intermediates, maintaining the same quality attributes resulting in to minimum generation of carbon dioxide are described. These concept is designed, synthesized, characterized, quantified and compared using “Carbon Efficiency”, a Green Chemistry Metrics, with already reported work to prove its sustainability. It is industrially advantageous by getting improvement in carbon efficiency and yield as outcome. Here we show a practical greener approach towards Carbon – Nitrogen bond formation with the help of calculation of Carbon efficiency and rate of reaction for first time.     

SIRT1 Promotes Neuronal Fortification in Neurodegenerative Diseases through Attenuation of Pathological Hallmarks and Enhancement of Cellular Lifespan

Neurodegeneration is a complex neurological phenomenon characterized by disturbed coherence in neuronal efflux. Progressive neuronal loss and brain damage due to various age-related pathological hallmarks perturb the behavioral balance and quality of life. Sirtuins have been widely investigated for their neuroprotective role, with SIRT1 being the most contemplated member of the family. SIRT1 exhibits significant capabilities to enhance neurogenesis and cellular lifespan by regulating various pathways, which makes it an exciting therapeutic target to inhibit neurodegenerative disease progression. SIRT1 mediated neuronal fortification involves modulation of molecular co-factors and biochemical pathways responsible for the induction and sustenance of pro-inflammatory and pro-oxidative environment in the cellular milieu. In this review, we present the major role played by SIRT1 in maintaining cellular strength through the regulation of genomic stability, neuronal growth, energy metabolism, oxidative stress, inhibiting mechanisms and anti-inflammatory responses. The therapeutic significance of SIRT1 has been put into perspective through a comprehensive discussion about its ameliorating potential against neurodegenerative stimuli in a variety of diseases that characteristically impair cognition, memory and motor coordination. This review enhances the acquaintance concerned with the neuroprotective potential of SIRT1 and thus promotes the development of novel SIRT1 regulating therapeutic agents and strategies.     

Effect of complicated ocular surgery in stress-related parameters: A novel outlook into surgeon’s health

Purpose:To assess the stress-related physiological parameters of ophthalmic surgeons during complicated cataract surgery and compare them with uncomplicated routine cataract surgery.Methods:In this cross-sectional observational study, 110 patients of various types of cataract were divided into two groups: Group 1 included 55 patients with simple cataract (Grade ≤3) with no ocular or systemic comorbidities, whereas Group 2 included 55 patients with complicated cataracts (Grade >3) and ocular/systemic comorbidities. All patients underwent phacoemulsification with intraocular lens implantation in the right eye only. The outcome measures were systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), and saturation of peripheral oxygen (SpO₂).Results:The average SBP, DBP, MAP, and HR were significantly higher in the surgeon operating Group 2 (complicated cataract) compared with Group 1 (uncomplicated cataract; P < 0.05). The average SBP of the surgeon while operating Group 1 patients preoperatively and postoperatively was 125.42 ± 2.49 mmHg and 122.45 ± 2.10 mmHg, respectively, whereas in Group 2, the average SBP of the surgeon taken preoperatively and postoperatively was 145.98 ± 3.80 mmHg and 137.44 ± 3.45 mmHg, respectively (P < 0.05). The surgeon’s SpO₂ showed no significant difference between the two groups.Conclusion:There is a significant level of increase in stress-related parameters of operating surgeons while doing complicated cataract surgery.     

Lactoferrin-conjugated dendritic nanoconstructs for lung targeting of methotrexate

The present investigation was aimed at developing and exploring the potential of lactoferrin (Lf)-conjugated dendritic nanocomposite for lung targeting of methotrexate (MTX). The 5.0 G poly(propylene imine) (PPI) dendrimer and Lf-conjugated 5.0 G PPI dendrimer were synthesized and characterized by Fourier-transform infrared spectroscopy, nuclear magnetic resonance, and transmission electron microscopy. The entrapment efficiency, in vitro release, and hemolytic toxicity were assessed. Pharmacokinetic and organ distribution studies were carried out to evaluate in vivo targeting potential of developed system. The pharmacokinetic studies showed that elimination half-life of MTX-loaded plain PPI dendrimer (10.41 ± 2.12 h, p < 0.05) and MTX-loaded Lf-conjugated PPI dendrimer (12.23 ± 1.53 h, p < 0.01) was significantly higher than the free drug (5.85 ± 1.19 h). Organ distribution assessment of different formulations displayed significant (p <0.05) higher accumulation of drug in lungs by MTX-Lf-PPI (1329 ± 26.7 ng/g of tissue) as compared with MTX-PPI (721 ± 23.4 ng/g of tissue) and free MTX (575 ± 19.7 ng/g of tissue) after 6 h of administration. The result suggested that Lf-conjugated 5.0 G PPI dendrimer-based formulations to be approximately 1.5 times and 2.5 times superior to plain 5.0 G PPI dendrimer as well as pure MTX, respectively, for lung targeting of anticancer drugs.     

Dose escalation pharmacokinetics and lipid lowering activity of a novel farnesoid X receptor modulator: 16-Dehydropregnenolone

Objectives:

To study the dose escalation pharmacokinetics and lipid lowering activity of a novel FXR modulator, 16-Dehydropregnenolone (DHP).

Materials and Methods:

The disposition of DHP following oral (36, 72, 100 and 150 mg/kg) and intravenous (1, 5 and 10 mg/kg) administration and its dose-response relationship were carried out in Sprague–Dawley rats. DHP and its metabolite 5-pregnene-3β-ol-16, 17-epoxy-20-one (M1) were analyzed by a validated LC-MS/MS method in plasma after intravenous and oral administration. Dose escalation lipid lowering activities were carried out by triton-induced hyperlipidemic model.

Results:

Oral administration resulted in higher amount of M1 formation as compared to intravenous administration. Dose escalation intravenous administration (1, 5 and 10 mg/kg) resulted in nonlinear increase in AUC of DHP. This was due to saturation of metabolism. On the contrary, systemic AUC and C_max after oral administration show non-linear pharmacokinetics where saturated systemic DHP and M1 pharmacokinetics was observed above 72 mg/kg, indicating saturated oral absorption. Lipid lowering activity by its oral route of administration was in accordance with its pharmacokinetic profile and reached saturation above 72 mg/kg.

Conclusion:

DHP exhibits route and dose-dependent pharmacokinetics. Pharmacokinetic and lipid lowering activity by oral route indicate saturation of oral absorption at higher doses. The study contributes to the understanding of the plasma disposition pharmacokinetics of DHP and its metabolite in rats by oral and intravenous route of administration.KEY WORDS: Dose-escalation pharmacokinetics, lipid-lowering activity, 80/574     

Comparison of sensory attributes and immediate efficacy of intranasal ciclesonide and fluticasone propionate in allergic rhinitis: A randomized controlled trial

Objectives:

Intranasal corticosteroids (INCs) are the most effective modality for treating allergic rhinitis and their sensory attributes are important in patient compliance. This study aimed to compare the sensory attributes (scent, immediate taste, aftertaste, run down to throat, nose run off, soothing feel, nasal irritation, and urge to sneeze) and immediate response to the new intranasal steroid, ciclesonide (CIC), with fluticasone propionate (FLP) in allergic rhinitis.

Materials and Methods:

A randomized, double blind, single dose, crossover study was done with 74 patients presenting with acute allergic rhinitis. Eligible subjects were randomized in 1:1 ratio to one of the two treatment sequences – CIC followed by FLP or vice versa. Sensory attributes were assessed using a questionnaire to score each item on a seven-point Likert scale, immediately and 2 min after dosing. Total nasal symptom score (TNSS) was calculated to evaluate immediate efficacy 10 min after first drug administration. Overall preference was recorded 10 min after the second drug administration. Patients were queried about treatment emergent adverse events following study drug administration and also 24 h later over the phone.

Results:

Patients (58% males; pooled median age 32 years [Interquartile range, IQR, 25–41]; pooled median symptom duration 24 months [IQR 12–72]) preferred FLP over CIC nasal spray overall (55.41% vs. 25.68%, P = 0.007) and also with respect to attributes of scent, soothing feel, and nasal irritation. There was no statistically significant difference in immediate efficacy. Two patients reported mild headache following CIC first, while three felt mild headache, one dizziness, and one nasal congestion following FLP first administration. There were no delayed adverse events.

Conclusions:

There was no difference in immediate outcome following use of either of the two INCs. FLP was preferred over CIC with respect to scent, soothing feel and nasal irritation, and also overall. There were no significant adverse events.KEY WORDS: Allergic rhinitis, ciclesonide, fluticasone propionate, intranasal corticosteroid