Herbal antioxidant in clinical practice: A review

Antioxidant-the word itself is magic. Using the antioxidant concept as a spearhead in proposed mechanisms for staving off so-called "free-radical" reactions, the rush is on to mine claims for the latest and most effective combination of free-radical scavenging compounds. We must acknowledge that such "radicals" have definitively been shown to damage all biochemical components such as DNA/RNA, carbohydrates, unsaturated lipids, proteins, and micronutrients such as carotenoids (alpha and beta carotene, lycopene), vitamins A, B₆, B₁₂, and folate. Defense strategies against such aggressive radical species include enzymes, antioxidants that occur naturally in the body (glutathione, uric acid, ubiquinol-10, and others) and radical scavenging nutrients, such as vitamins A, C, and E, and carotenoids. This paper will present a brief discussion of some well- and little-known herbs that may add to the optimization of antioxidant status and therefore offer added preventive values for overall health. It is important to state at the outset that antioxidants vary widely in their free-radical quenching effects and each may be individually attracted to specific cell sites. Further evidence of the specialized nature of the carotenoids is demonstrated by the appearance of two carotenoids in the macula region of the retina where beta-carotene is totally absent.     

Novel investigational therapies for treating pulmonary arterial hypertension

Introduction: Despite the development of new therapies, pulmonary arterial hypertension (PAH) has a median survival of 6 – 7 years. This is likely because the currently approved therapies affect predominantly pulmonary vasoconstriction. The past two decades have witnessed greater insights into the pathogenesis of PAH, from the role of inflammation to molecular signaling and epigenetics. Multiple pharmacological agents targeting these newly identified pathways are currently being investigated in preclinical and early clinical studies.

Areas covered: Herein, the authors review the modalities targeting recently identified molecular targets in PAH. These include: prostaglandin receptor agonists, agents that alter the cyclic adenosine monophosphate and cyclic guanosine monophosphate pathways, vasoactive peptides, receptor tyrosine kinase inhibitors, Rho-kinase inhibitors, serotonin pathway inhibitors, anti-inflammatory agents, antioxidants, agents that alter nitric oxide signaling, various cardiac medications, mitochondrial metabolism modifying agents, epigenetic agents and cell-based therapies. The authors also address the gaps in the knowledge and explain why certain agents may or may not be promising PAH pharmacotherapeutics.

Expert opinion: Newer agents target multiple pathways including vasoconstriction, cellular proliferation and inflammatory response. And while only a few of the current investigational drugs will likely be further developed, the authors expect that the next two decades will bring some major breakthroughs in PAH management.     

Effectiveness of m-learning on knowledge and attitude of nurses about the prevention and control of MDR TB: A quasi-randomized study

BackgroundMultidrug-Resistant Tuberculosis is a fatal form because of high morbidity and poor recovery. Improper use of first line medicines and default treatment are the prime reasons of developing resistance of mycobacterium towards conventional anti- TB drugs. Nurses with refined knowledge, current evidence and positive attitude can prevent arising of MDR TB cases by ensuring adequate treatment, promoting treatment adherence and real time case monitoring. Because of paucity of data, present study was aimed to assess efficacy of m-learning in improving knowledge and attitude of nurses about the prevention and control of MDR-TB.MethodsIn this Quasi-randomized study, nurses working in the unit of pulmonary, emergency, respiratory ICU, general medicine of AIIMS Rishikesh during the months of August–October 2019 were involved. The number of participation was 190 (95 in each group; experimental and control) where m-learning intervention was available only for experimental group. There were structured questionnaire to measure knowledge and dichotomous checklist to evaluate attitude of nurses of both group before and one week after the provision of m-learning module.ResultsBoth the group was homogeneous and m-learning intervention was effective to improve knowledge, when compared post-test knowledge score between experimental and control group (18.2 ± 5.4 vs 12.4 ± 4.4; P < 0.001); however, this one-time social media based intervention could not improve attitude of participants (10.3 ± 1.8 vs. 9.9 ± 1.8; P = 0.175).ConclusionHence, m-learning is useful for knowledge development among large number of nurses within limited resource setting but frequent provision of technology based module is recommended to acquire positive attitude among nurses.     

A survey of gastroenterologists' perceptions and practices related to Helicobacter pylori infection

OBJECTIVE: The aim of this study was to assess the current practice of gastroenterologists in the United States concerning Helicobacter pylori (H. pylori) infection. METHODS: We mailed a structured questionnaire to 1000 gastroenterologists chosen at random from a national database. We asked about personal and practice demographics and practices relating to testing for, and treating, H. pylori infection. RESULTS: A total of 922 questionnaires were delivered, from which we received 286 responses (31%). Respondents used many different tests for H. pylori infection, but only 10% each had used either the 13C- or 14C-urea breath test. Testing for H. pylori infection was usually for appropriate reasons, although 21% indicated that they might not treat a patient with a positive test result. Different multiple treatment regimens were used; the most frequent were combinations of a proton pump inhibitor, clarithromycin, and either amoxicillin or metronidazole. Estimates of the prevalence of antibiotic resistance were highly variable and often inaccurate. Most respondents would not check asymptomatic individuals for the infection; however, in the absence of symptoms, 38% would personally undergo testing and treatment if positive. CONCLUSIONS: Gastroenterologists usually test for H. pylori infection in appropriate conditions, but may not always treat the infection based on a positive test result. Most use efficacious regimens to treat the infection although many have inaccurate information on resistance rates, which may adversely influence prescribing. Many would have testing and, if positive, treatment in the absence of symptoms or a specific diagnosis, but do not recommend this for their patients.     

Reporter Assay for Endo/Lysosomal Escape of Toxin-Based Therapeutics

Protein-based therapeutics with cytosolic targets are capable of exhibiting their therapeutic effect once they have escaped from the endosomes or lysosomes. In this study, the reporters—horseradish peroxidase (HRP), Alexa Fluor 488 (^Alexa) and ricin A-chain (RTA)—were investigated for their capacity to monitor the endo/lysosomal escape of the ribosome-inactivating protein, saporin. The conjugates—saporin-HRP, ^Alexasaporin and saporin-KQ-RTA—were constructed, and the endo/lysosomal escape of these conjugates alone (lack of endo/lysosomal release) or in combination with certain structurally-specific triterpenoidal saponins (efficient endo/lysosomal escape) was characterized. HRP failed in reporting the endo/lysosomal escape of saporin. Contrastingly, Alexa Fluor 488 successfully allowed the report of the process at a toxin concentration of 1000 nM. In addition, single endo/lysosome analysis facilitated the determination of the amount of ^Alexasaporin released from each vesicle. RTA was also successful in reporting the endo/lysosomal escape of the enzymatically inactive mutant, saporin-KQ, but in this case, the sensitivity of the method reached a toxin concentration of 10 nM. In conclusion, the simultaneous usage of Alexa Fluor 488 and RTA as reporters may provide the possibility of monitoring the endo/lysosomal escape of protein-based therapeutics in the concentration range of 10–1000 nM.     

Basal lower esophageal sphincter pressure in gastroesophageal reflux disease: An ignored metric in high-resolution esophageal manometry

Manometry and 24-h pH interpretation have seldom been studied. Our aim was to study these parameters as gold standard in reflux disease and to identify predictors of pathological acid reflux. Retrospective case record review of all patients with reflux disease evaluated using endoscopy, manometry, and 24-h pH testing from 2010 to 2016. Patients were categorized using Johnson-DeMeester score into two groups—group I (score > 14.7, normal study) and group II (< 14.7, normal study). These groups were compared for the above-mentioned parameters. Appropriate statistical tests were applied. P-value < 0.05 was considered significant. The study group includes 94 patients (median age 44 years, 63.8% males). Sixty (63.8%) and 34 patients belonged to groups I and II, respectively, 76.6% patients had normal endoscopy while the remaining had mild esophagitis. Peristalsis was normal in 66%, followed by ineffective esophageal motility (19.1%) and fragmented peristalsis (14.9%). Demography, symptoms, endoscopy findings, and peristalsis characteristics were similar between the two groups. Group II patients had significantly lower basal lower esophageal sphincter (LES) pressure (11.9 vs. 16.6; p < 0.02), lower integrated relaxation pressure (5.7 vs. 7.4; p < 0.01), and larger separation between LES and crural diaphragm (1.7 vs. 1.4 cm; p < 0.003). Basal LES pressure < 10 mmHg had the highest likelihood ratio (2.2) to predict an abnormal pH study. Basal LES pressure, integrated relaxation pressure, and hiatus size correlated with pathological acid reflux. Hypotensive basal lower esophageal sphincter pressure was the best predictor of an abnormal pH study but with negative linear correlation.     

Degradation kinetics of high molecular weight poly(L-lactide) microspheres and release mechanism of lipid:DNA complexes

Plasmid DNA encoding the green lantern protein was ion-paired with 1,2-dioleoyl, 3-trimethylammonium propane (DOTAP) at a (+/-) charge ratio of (1:1) to form a hydrophobic ion-pair (HIP) complex using the Bligh and Dyer method, and transferred into methylene chloride. Precipitation with a compressed antisolvent (PCA) was then employed to encapsulate plasmid DNA into poly(L-lactide) (PLLA) microspheres. The hydrophobicity of DOTAP:DNA complexes allowed consistently high encapsulation efficiencies (>70%) to be achieved. Release of the DOTAP:DNA complex from PLLA microspheres exhibited minimal burst and a short (ca. 1 week) lag phase, followed by sustained release over a 20 week period. Release kinetics were consistent with a simple Fickian diffusion model. No correlation was identified between release rate of soluble poly(L-lactide) species (< or =10 lactate units) from PLLA and the DNA release kinetics. Only approximately 12% of the polymer was degraded into soluble poly(L-lactide) over the time frame where approximately 90% of the plasmid load had been released.