The ethics and practice of authorship and peer review

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Bentonite toxicology and epidemiology – a review

Bentonite, a clay with numerous industrial and consumer applications, is mined and processed in many countries of the world. Its many beneficial uses also create the potential for widespread occupational and consumer exposure. The available studies on toxicity and epidemiology indicate that the principal exposure pathway of concern is inhalation of respirable dust by occupationally exposed cohorts. Bentonite itself is probably not more toxic than any other particulate not otherwise regulated and is not classified as a carcinogen by any regulatory or advisory body, but some bentonite may contain variable amounts of respirable crystalline silica, a recognized human carcinogen. Therefore, prudent management and adherence to occupational exposure limits is appropriate. This review summarizes the literature available on production, applications, exposure, toxicity, and epidemiology of bentonite and identifies data gaps and limitations.     

Digoxin: Pharmacology and toxicology—A review

Digoxin is a cardiac glycoside used as drug in case of heart problems, including congestive heart failure, atrial fibrillation or flutter, and certain cardiac arrhythmias. It has a very narrow therapeutic window of the medication. Digoxin is toxic substance with well known cardiotoxic effect. In this work, pharmacology and toxicology of digoxin are summarized; Its pharmacokinetics, pharmacodynamics, available acute toxicity data (different species, different administration routes) are summarized in this article. Moreover, its treatment side effect and human poisonings are thoroughly discussed. Finally, appropriate therapy regimen is proposed.     

Diabetes mellitus and oxidative stress—A concise review

Human body is continuously exposed to different types of agents that results in the production of reactive species called as free radicals (ROS/RNS) which by the transfer of their free unpaired electron causes the oxidation of cellular machinery. In order to encounter the deleterious effects of such species, body has got endogenous antioxidant systems or it obtains exogenous antioxidants from diet that neutralizes such species and keeps the homeostasis of body. Any imbalance between the RS and antioxidants leads to produce a condition known as “oxidative stress” that results in the development of pathological condition among which one is diabetes. Most of the studies reveal the inference of oxidative stress in diabetes pathogenesis by the alteration in enzymatic systems, lipid peroxidation, impaired Glutathione metabolism and decreased Vitamin C levels. Lipids, proteins, DNA damage, Glutathione, catalane and superoxide dismutase are various biomarkers of oxidative stress in diabetes mellitus. Oxidative stress induced complications of diabetes may include stroke, neuropathy, retinopathy and nephropathy. The basic aim of this review was to summarize the basics of oxidative stress in diabetes mellitus.     

Fluorine—A current literature review. An NRC and ATSDR based review of safety standards for exposure to fluorine and fluorides

Background: A review of the literature of the element fluorine and its bonded-form, fluoride, was undertaken. Generally regarded as safe, an expanding body of literature reveals that fluoride’s toxicity has been unappreciated, un-scrutinized, and hidden for over 70 years. The context for the literature search and review was an environmental climate-change study, which demonstrated widespread fluoride contamination by smokestack emissions from coal-fired electricity-generating plants. The objective of this review is to educate and inform regarding the ubiquitous presence and harmful nature of this now ever-present corrosive and reactive toxin.

Methods: Methods include examination of national health agency reviews, primarily the National Research Council (NRC), Agency for Toxic Substances & Disease Registry (ATSDR), standard medical toxicology references, text books, as well as reports and documents from both private and public research as well as consumer-based NGOs. Study criteria were chosen for relevancy to the subject of the toxicity of fluoride.

Results: Fluoride is the extreme electron scavenger, the most corrosive of all elements, as well as the most-reactive. Fluoride appears to attack living tissues, via several mechanisms. Fluoride renders strong evidence that it is a non-biological chemical, demonstrating no observed beneficial function or role in organic chemistry, beyond use as a pesticide or insecticide. Fluorine has a strong role to play in industry, having been utilized extensively in metals, plastics, paints, aluminium, steel, and uranium production.

Conclusion: Due to its insatiable appetite for calcium, fluorine and fluorides likely represent a form of chemistry that is incompatible with biological tissues and organ system functions. Based on an analysis of the affects of fluoride demonstrated consistently in the literature, safe levels have not been determined nor standardized. Mounting evidence presents conflicting value to its presence in biological settings and applications. Evidence examined in this review of the literature, and specifically the recent report by the National Research Council (NRC), offer strong support for an immediate reconsideration concerning risk vs benefit. Consensus recommendations from several sources are presented.     

A systematic review on pharmacists’ turnover and turnover intention

BackgroundTurnover is an important issue in all healthcare professions including pharmacy practice settings. A high turnover rate of pharmacists, not only has negative financial impact, but also reduces quality of care and patient safety. The high turnover also increases workload and job stress which can increase job errors and decrease job efficiency and performance in pharmacy practices.ObjectivesTo systematically review the extent of pharmacists' turnover and their intention to leave their jobs or the pharmacy profession.MethodsAn electronic search was performed from database inception to December 19, 2020 using the following 6 databases; PubMed, Scopus, ScienceDirect, ProQuest, ERIC, and ERIC-EBSCO. Articles were included if they were relevant to reports of pharmacist turnover or turnover intention. Only research studies were included, but not editorials, letters, or review articles.ResultsTwenty-eight studies were contained within this systematic review. Using the QualSyst assessment tool to assess the included article qualities, all studies demonstrated good quality with quality assessment score of 0.75. Fifteen studies (53.6%) were conducted from the US, 3 studies (10.7%) from Taiwan, 2 studies (7.1%) from the UK, and the remaining studies from Lithuania, Australia, New Zealand, Malaysia, Saudi Arabia, and Jamaica. The turnover of the pharmacists from their jobs ranged from 8.6 to 17%, and the turnover from the pharmacy profession was in the range of 6–9%. The turnover intention of the pharmacists in their jobs was from 13% to 61.2%, and the turnover intention in the pharmacy profession was 6.5%–18.8%. Hospital pharmacists had significantly higher turnover intentions than community ones. The turnover intention rates of both hospital and community pharmacists have gradually increased over time in both European countries and Asian countries.ConclusionBased on the included articles, pharmacists' turnover rate appeared to increase over time. However, based on the heterogeneity of studies, further research is warranted to confirm this and to help to identify the potential causes of turnover intention since intention was related to behavior.     

Paraquat and Parkinson’s disease: a systematic review and meta-analysis of observational studies

This investigation aimed to conduct a systematic review of the literature and meta-analysis to determine whether exposure to the herbicide paraquat was associated with the development of Parkinson’s disease (PD). Observational studies that enrolled adults exposed to paraquat with PD as the outcome of interest were searched in the PubMed, Embase, LILACS, TOXNET, and Web of Science databases up to May 2019. Two authors independently selected relevant studies, extracted data, and assessed methodological quality. The evidence certainty was assessed by the GRADE approach, which served as basis for a tentative causality assessment, supplemented by the Bradford Hill criteria when necessary. Results from nine case–control studies indicated that PD occurrence was 25% higher in participants exposed to paraquat. The only cohort investigation included demonstrated a non-significant OR of 1.08. Results from subgroup analyses also indicated higher PD frequency in participants that were exposed to paraquat for longer periods or individuals co-exposed with paraquat and any other dithiocarbamate. Data indicate apositive association between exposure to paraquat and PD occurrence, but the weight-of-evidence does not enable one to assume an indisputable cause–effect relationship between these two conditions. Better designed studies are needed to increase confidence in results.

Systematic Review Registration: PROSPERO CRD42017069994.     

A patent review of butyrylcholinesterase inhibitors and reactivators 2010–2017

Introduction: Butyrylcholinesterase (BuChE) has obtained a renewed interest as therapeutic target in Alzheimer’s disease (AD), when changes in BuChE activity and expression along disease progression were highlighted as well as correlation between BuChE levels and cognitive function.

Areas covered: During the last eight years, fourteen patents on BuChE inhibitors (BuChEI) have been submitted. Only three of them relate to BuChE selective inhibitors, while four of them focus on multitarget inhibitors which address different key pathological factors other than BuChE. Two patents report on non-selective acetylcholinesterase (AChE)/BuChE inhibitors, while four patents deal with natural compounds and their derivatives. One patent relates to antitoxic agents to treat exposure to ChEI pesticides and nerve agents.

Expert opinion: Increasing evidence supports BuChE as a more beneficial target in moderate-to-severe forms of AD in comparison to the well-known AChE. However, hitting a single pathological target is likely not sufficient to halt the disease progression. Therefore, patented BuChE inhibitors with a multifunctional profile may open new therapeutic avenues, since the additional activities could reinforce the therapeutic effects. Unfortunately, in vivo studies are limited and key parameters, such as ADMET data, are missing. This lack of information makes difficult to forecast the development of patented BuChEIs into effective drug candidates.     

Plants and plant products with potential antipsoriatic activity – a review

Context: Psoriasis vulgaris is a hyper proliferative, autoimmune skin disorder affecting 1–3% of the world’s population. The prescribed synthetic drugs for the treatment of psoriasis are associated with severe side effects, thus, researchers around the globe are searching for new, effective, and safer drugs from natural resources.

Objective: The present review has been prepared with an objective to compile exhaustive literature on pharmacological reports on antipsoriatic plants, plant products, and formulations. An attempt has been made to incorporate chemical constituents (with structures) isolated from different plants responsible for antipsoriatic activity and their possible mechanism of actions in this review.

Materials and methods: The review has been compiled using references from major databases like Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, PubMed, Scirus, Google scholar, Open J Gate, Scopus, Science Direct and Online Journals, and includes 127 references.

Results: A survey of literature revealed that extracts/fractions/isolates from 18 plants, 23 chemical constituents of plant origin and 40 plant-based formulations from various systems of medicine have been reported to possess antipsoriatic activity, and 37 antipsoriatic formulations containing plants have been patented.

Conclusion: Preliminary antipsoriatic activity studies have been carried out on crude extracts of traditionally used and medicinally promising plants. Such plants need to be explored properly with a view to isolate antipsoriatic constituents, and to evaluate their possible mode of actions so that these plant drugs could be exploited properly as potential antipsoriatic drugs.     

Post-herpetic neuralgia – a review of current management and future directions

Introduction: Post-herpetic neuralgia (PHN) is common and treatment is often suboptimal with less than half of patients achieving adequate 50% pain relief. As an area of unmet clinical need and as an archetype of neuropathic pain, it deserves the attention of clinicians and researchers.

Areas covered: This review summarises the epidemiology, pathophysiology, risk factors and clinical features of varicella infection. It describes the current and possible future management strategies for preventing varicella infection and reactivation and for treating PHN.

Expert opinion: A highly successful Varicella Zoster (VZV) vaccine has not been universally adopted due to fears that it may increase Herpes Zoster (HZ) incidence – and thus PHN – in older, unvaccinated generations. This is a controversial theory but advances in the efficacy of vaccines against HZ may allay these fears and encourage more widespread adoption of the VZV vaccine.

Treatment of PHN, as for any neuropathic pain, must be multidisciplinary and multimodal. Advances in sensory phenotyping technology and genomics may allow more individualised treatment. Traditional research methodologies are ill-suited to assess the kind of complex interventions that are necessary to achieve better clinical outcomes in this challenging field.     

Enhanced analgesic activity by cyclodextrins – a systematic review and meta-analysis

Introduction: Analgesics can be ineffective in treating some types of pain, hence, improved drug delivery systems could optimize their efficacy.

Area covered: The authors conducted a systematic review to evaluate the analgesic activity of compounds complexed in cyclodextrins, analyzing whether these complexes improved analgesic efficacy. The search terms ‘analgesics’, ‘cyclodextrins’ and ‘drug effects’ were used to retrieve articles in SCOPUS, PUBMED and EMBASE. A total of 22 papers were identified. In the clinical studies, there was greater efficacy in the complexed drug when compared with control groups, with differences ranging from 25 to 83%. Through a meta-analysis, the preclinical studies showed that the complexed drug had a significantly (p < 0.01) greater effect than the non-complexed drug.

Expert opinion: The use of cyclodextrins can improve the efficacy of analgesic compounds, and they are an important tool in the search for greater analgesic effect. They may also be a way to reduce the therapeutic doses, and hence increasing the potential of the drug.     

Speed freaks? A literature review detailing the nature and prevalence of dance drugs and driving

Considerable interest has lately been expressed in motor car driving whilst under the influence of drugs. Unlike depressant drugs (e.g. alcohol) dance drugs are often perceived to enhance driving skills. The physical effects and the current lack of police roadside testing are possible contributing reasons for dance drug driving. This paper aims to show through a literature review on the subject, the demographics of those involved in dance drug driving and the extent to which certain dance drugs are implicated in drug driving incidents. Drug driving is found to be highest amongst the 18-35 year age group and more prevalent amongst adult males. Prevalence figures for driving under the influence of individual drugs are also given. The numbers of people involved in accidents/fatalities and testing positive for amphetamine, cocaine and other dance drugs is small. Although self-reporting especially of illegal activities is difficult to accurately evaluate, most of the reported studies use actual blood/urine samples and so can be considered accurate. The literature does not highlight any real concerns regarding dance drug driving in terms of prevalence although it does highlight the paucity of research in this area, in particular 'Culture E and driving'.     

Postoperative nausea and vomiting – a narrative review of pathophysiology,pharmacotherapy and clinical management strategies

Introduction: Postoperative nausea and vomiting (PONV) are common complications concerning patients undergoing general anesthesia. Intensive research was performed during the last two decades in order to develop therapeutic and prophylactic strategies to prevent this complication.

Areas covered: This article reviews the pathophysiology as well as pharmacological aspects of PONV prophylaxis and treatment. Relevant strategic aspects for pharmacological prophylaxis of PONV are discussed and clinical standard operating procedures are presented.

Expert opinion: The expert opinion focuses on poor implementation of actual PONV guidelines and future considerations.     

Can formulation and drug delivery reduce attrition during drug discovery and development—review of feasibility,benefits and challenges

Drug discovery and development has become longer and costlier process. The fear of failure and stringent regulatory review process is driving pharmaceutical companies towards “me too” drugs and improved generics (505(b) (2)) fillings. The discontinuance of molecules at late stage clinical trials is common these years. The molecules are withdrawn at various stages of discovery and development process for reasons such as poor ADME properties, lack of efficacy and safety reasons. Hence this review focuses on possible applications of formulation and drug delivery to salvage molecules and improve the drugability. The formulation and drug delivery technologies are suitable for addressing various issues contributing to attrition are discussed in detail.KEY WORDS: Drug discovery and development, Drugability, Formulation, Drug delivery technology     

Synthesis,biosynthesis and biological activities of galbanic acid – A review

Context: Galbanic acid (GA) is a biologically active sesquiterpene coumarin from Ferula species (Apiaceae). This compound showed various biological properties including anticancer, cancer chemopreventive, anticoagulant, antiviral, and antileishmanial activities.

Objectives: This article is a review on the synthesis, biosynthesis, and biological activities of GA. In addition, we discussed gaps in our knowledge about GA that deserve future research. In this article, we also evaluated the drug-likeness of GA in silico.

Methods: All relevant databases were searched for the terms “galbanic acid”, “methyl galbanate”, “Ferula” and “sesquiterpene coumarin” without limitation, up to May 2013. Information on GA was collected via electronic search using Pubmed, Scopus, Web of Science, and Sciencedirect. All physicochemical parameters used for the prediction of drug-likeness were calculated using MarvinSketch (version 5.11, academic package, ChemAxon).

Results: This compound showed various biological properties including anticancer, cancer chemopreventive, anticoagulant, antiviral and antileishmanial activities. GA can inhibit the growth of prostate cancer cells via decreasing androgen receptor abundance. In silico physicochemical studies on GA showed that this compound has drug-like properties, the parameters that are important to predict potential of a compound for being a future drug.

Conclusion: GA is a valuable natural product with various biological activities. New discoveries with GA are to be expected.     

Acid–base properties of penicillins and cephalosporins (a review)

Published data on the acid–base properties of penicillin and cephalosporin antibiotics are summarized and systematized. It is suggested to classify penicillins and cephalosporins with respect to the acid–base type. The influence of the structure of antibiotics and the conditions and method used for determining the ionization constants of proton-donor groups in antibiotics are considered.