Current Drug Research Reviews - Volume 11, Issue 2, 2019

In recent years, there has been a significant increase in the number of scientific publications. The h-index offers a consistent estimation method about a researcher’s overall scientific achievements since it combines the total number of publications (i.e., productivity) and the number of citations (i.e., quality of those publications). In other words, the h-index is intended to measure simultaneously the quality and quantity of scientific output in a cumulative approach and does not provide data regarding the recent productivity. This editorial presents advantages and limitations of h-index that all researchers in health sciences need to be aware of, especially if this metric is used for professional progression, and discusses the simple modification indexed to “academic/scientific age”. It is obvious that no single metric is perfect, and the use of two or more metrics is more prone to success.

Background: The effectiveness of lithium salts in neuropsychiatric disorders such as bipolar disorder, Alzheimer’s disease, and treatment-resistant depression has been documented in an extensive scientific literature. Lithium inhibits inositol monophosphatase, inositol polyphosphate 1- phosphatase, and glycogen synthase kinase-3 and decreases expression level of tryptophan hydroxylase 2, conceivably underlying the mood stabilizing effects of lithium, as well as procognitive and neuroprotective effects. However, the exact molecular mechanisms of action of lithium on mood stabilizing and pro-cognitive effects in humans are still largely unknown. Objective: On the basis of the known aspects of lithium pharmacology, this review will discuss the possible mechanisms underlying the therapeutic effects of lithium on positive symptoms of methamphetamine abuse and dependence. Conclusion: It is possible that lithium treatment reduces the amount of newly synthesized phosphatidylinositol, potentially preventing or reversing neuroadaptations contributing to behavioral sensitization induced by methamphetamine. In addition, it is suggested that exposure to repeated doses of methamphetamine induces hyperactivation of glycogen synthase kinase-3β in the nucleus accumbens and in dorsal hippocampus, resulting in a long-term alterations in synaptic plasticity underlying behavioral sensitization as well as other behavioral deficits in memory-related behavior. Therefore it is clear that glycogen synthase kinase-3β inhibitors can be considered as a potential candidate for the treatment of methamphetamine abuse and dependence.

Background: Alcohol consumption is associated with risky sex, which increases the risk of acquiring and transmitting HIV. Objective: To examine the prevalence of, and associations among alcohol, risky sex, and HIV, in Nigeria. Methods: We searched electronic databases and reviewed reference sections of relevant papers to locate studies that sampled people living in Nigeria and assessed both alcohol and sexual risk behavior. We calculated effect sizes to determine (a) prevalence of alcohol and sex behaviors and (b) associations between alcohol consumption and risky sex, and examined moderators to determine if sample characteristics predicted behavioral or biological outcomes. Results: Of the 696 unique records identified, 35 manuscripts reporting on 42 separate studies met the inclusion criteria. Participants in these studies (N = 83,350; M age = 26 years; 48% women; 10% HIV-infected) reported high rates of heavy drinking (63%) and low rates of consistent condom use (24%). One-third of participants (30%) also reported using alcohol before sexual activity. Participants who consumed alcohol were more likely to report sexual activity (OR = 3.66, 95% CI = 3.09, 4.33), multiple partners (OR = 3.22, 95% CI = 2.38, 4.36), and condomless sex or inconsistent use of condoms (OR = 2.30, 95% CI = 1.54, 3.43). Conclusion: High rates of heavy drinking and low rates of condom use have been well-documented in Nigeria. Results from this meta-analysis can be used to inform critically needed alcohol-related HIV interventions.

Background: Radiation-induced pneumonitis and fibrosis are the most common side effects of chest radiotherapy. They result from massive and chronic production of Reactive Oxygen Species (ROS), inhibition of antioxidant enzymes as well as the release of several inflammatory mediators. In this study, we aimed to detect the radioprotective effects of metformin (as inhibitor of mitochondrial ROS), resveratrol (as stimulator of antioxidant defense enzymes) and alpha-lipoic acid (as direct antioxidant) for alleviating radiation-induced pneumonitis and fibrosis. Methods: 80 Male Mice were randomly allotted to eight groups which include G1: control; G2: resveratrol; G3: alpha-lipoic acid; G4: metformin; G5: radiation; G6: radiation plus resveratrol; G7: radiation plus alpha-lipoic acid; G8: radiation plus metformin. Drugs’ doses were as follows: 100 mg/kg metformin, 200 mg/kg resveratrol and 200 mg/kg alpha-lipoic acid. Irradiation with a single radiation dose of 18 Gy was performed using a cobalt-60 (60Co) gamma-ray source. After 80 days, all mice were sacrificed and their lung tissues evaluated for morphological changes using histopathological markers. Results: Irradiation led to acute pneumonitis including infiltration of inflammatory cells and damages to alveolar and vascular, as well as mild fibrosis. Metformin, alpha-lipoic acid and resveratrol were able to reduce pneumonitis and overcome radiation-induced fibrosis. Conclusion: All agents could protect against radiation-induced lung injury moderately. It is possible that administering higher doses of these drugs over a long period of time could give better radioprotection of the lung.

Background: Human Epidermal development factor Receptor-2 (HER2) is a membrane tyrosine kinase which is overexpressed and gene amplified in human breast cancers. HER2 amplification and overexpression have been linked to important tumor cell proliferation and survival pathways for 20% of instances of breast cancer. 9-aminoacridines are significant DNA-intercalating agents because of their antiproliferative properties. Objective: Some novel isoxazole substituted 9-anilinoacridines(1a-z) were designed by in-silico technique for their HER2 inhibitory activity. Docking investigations of compounds 1a-z are performed against HER2 (PDB id-3PP0) by using Schrodinger suit 2016-2. Methods: Molecular docking study for the designed molecules 1a-z are performed by Glide module, in-silico ADMET screening by QikProp module and binding free energy by Prime-MMGBSA module of Schrodinger suit. The binding affinity of designed molecules 1a-z towards HER2 was chosen based on GLIDE score. Results: Many compounds showed good hydrophobic communications and hydrogen bonding associations to hinder HER2. The compounds 1a-z, aside from 1z have significant Glide scores in the scope of - 4.91 to - 10.59 when compared with the standard Ethacridine (- 4.23) and Tamoxifen (- 3.78). The in-silico ADMET properties are inside the suggested about drug likeness. MM-GBSA binding of the most intense inhibitor is positive. Conclusion: The outcomes reveal that this study provides evidence for the consideration of isoxazole substituted 9-aminoacridine derivatives as potential HER2 inhibitors. The compounds, 1s,x,v,a,j,r with significant Glide scores may produce significant anti breast cancer activity and further in vitro and in vivo investigations may prove their therapeutic potential.

Background: Effects of substance abuse frequently expand beyond the nuclear family. Extended family members can experience feelings of abandonment, anxiety, fear, anger, concern, embarrassment, or guilt. Thus, they may wish to ignore or cut ties with the person involved in substance abuse. The aim of this study was to compare the mental health status of families with and without substance abusers. Methods: This cross sectional study was conducted among 114 family members with substance abusers (case group) and 114 without substance abusers (control group) in Hamadan city of Iran, in a time period from October to December 2016. Data collection tools included demographic and SCL-90-R questionnaires. Data were analyzed by t- test using SPSS software version 16. The significance level was considered less than 0.05. Results: The mean age of participants in the case and control groups was 33±4.7 and 35±5.2 years. There was a significant difference in the mean of subscales which included somatization, interpersonal sensitivity, depression, anxiety and phobia in families with and without substance abusers (p< 0.001). In other words, the mental health status of family members with a substance abuser was lower than in the control group. Overall, 29.4% of family members with substance abusers and 16% without substance abusers were suspected to have mental disorders. Conclusion: Substance abuse is a disorder that can impact families in countless ways. Therefore, it is recommended that more attention should be given to this group toward planning mental health programs. Also, families should be screened by health professionals in regard to psychological needs and improvement of their mental health conditions.

Background: Cyclin-Dependent Kinases-6 (CDK-6) is a serine/threonine protein kinase with regular activity in the cell cycle. Some inhibitors, such as abemaciclib, hymenialdisine, and indirubin, cause cell arrest by decreasing its activity. Objectives: The purpose of this study was to evaluate the Molecular Dynamic (MD) effects of abemaciclib, hymenialdisine, and indirubin on the structure of CDK-6. Methods: The PDB file of CDK-6 was obtained from the Protein Data Bank (http://www.rcsb.org). After the simulation of CDK-6 in the Gromacs software, 200 stages of molecular docking were run on CDK-6 in the presence of the inhibitors using AutoDock 4.2. The simulation of CDK-6 in the presence of inhibitors was performed after docking. Results: Abemaciclib showed the greatest tendency to bind CDK-6 via binding 16 residues in the binding site with hydrogen bonds and hydrophobic bonding. CDK-6 docked to hymenialdisine and indirubin increased the Total Energy (TE) and decreased the radius of gyration (Rg). CDK-6 docked to hymenialdisine significantly decreased the coil secondary structure. Conclusion: CDK-6 is inhibited via high binding affinity to abemaciclib, hymenialdisine, and indirubin inhibitors and induces variation in the secondary structure and Rg in the CDK-6 docked to the three inhibitors. It seems that developing a drug with a binding tendency to CDK6 that is similar to those of abemaciclib, indirubin, and hymenialdisine can change the secondary structure of CDK6, possibly more potently, and can be used to develop anticancer drugs. However, additional studies are needed to confirm this argument.

Background: Cocaine is one of the most widely used illicit drugs, and it is the most common cause of drug-related death. The association of cocaine use with acute heart failure is a rare occurrence. Case Report: We report the case of a 31 years-old woman who presented Takotsubo cardiomyopathy with severe cardiogenic shock after cocaine abuse. That required the use of high doses of positive inotropic amines and mechanical ventilation. The evolution was quickly favorable after the cessation of cocaine. Discussion: Takotsubo cardiomyopathy is often related to a stressful trigger, and several cases have been described with the use of several psychostimulants. As such, it is not surprising that cocaine use can be associated with the development of Takotsubo cardiomyopathy when it results in excess release of catecholamines and excitation of adrenergic receptors. Conclusion: In critical care unit, Takotsubo cardiomyopathy is a rare complication of cocaine abuse. This etiological diagnosis can be difficult especially in the absence of the concept of toxic intake as it was initially the case for our patient, but the treatment does not differ from other causes of cardiomyopathy and Cessation of cocaine use has been associated with improvement in cardiac function.

Background: Carbon monoxide (CO) is a major and ubiquitous component of fire atmospheres produced when organic matter is burned in an inadequate supply of oxygen. Accidental poisoning by CO is common in cold climates where fireplaces, a gas, electric or kerosene heaters or grills are used inside ill-ventilated buildings. In the Brazilian Amazon, with its hot and humid climate, there is no need for the use of heaters and accidents may occur in cases of residential fires or burning of the forests for land use in agriculture. Objective: We present a case of CO suicide of twenty-six-year-old men. Methods: A forensic autopsy was performed to evaluate the circumstances, cause and medio-legal death etiology. Results: Autopsy evidenced the typical but also not commonly published cherry-red color of the hypostasis, lungs and other organs, and the very fluid cherry-red blood. The cause of death was due to a massive CO inhalation. Conclusion: While these poisonings are well recognized, and a vast number of publications on CO toxicity exist, both in an environmental and industrial context, suicide is infrequently encountered in forensic practice and the typical signs are rarely seen in the literature.