Current Drug Research Reviews - Volume 12, Issue 2, 2020

Objective: Dithranol (DTH) is a well-known moiety that has long been used promisingly to impede and treat skin disorders, particularly psoriasis. Nowadays, a rekindled interest in the use of DTH for this disorder has been observed. Side effects associated with conventional topical formulations of this moiety have aroused the interest of the scientific community in investigating novel cargos of DTH for psoriasis management. Results: Previous research has evidenced the anti-inflammatory and anti-proliferating potential of DTH. Numerous studies have indicated that DTH inhibits polymorphonuclear (PMN) leucocyte, modulates epidermal cell receptors and promotes anti-psoriatic action. However, some deterrent factors like poor solubility, stability, toxicity, staining and skin irritation hamper its use as a potential therapeutic agent. With the adoption of novel drug delivery technologies, the above mentioned inherent limitations of DTH have been compensated to reestablish this drug moiety. Conclusion: This article reviews novel drug delivery aspects, safety concerns, clinical evidence, current status, and future opportunities of DTH in the management of psoriasis. Further, it will update researchers on this promising drug moiety, which is free from systemic adverse responses in comparison to other therapeutic molecules like steroids, for psoriasis treatment.

Background: The interactions between Alzheimer’s Disease (AD) and major depression can be translated into clinical data showing that depressive patients have had an enhanced risk for developing AD (later in life). The cellular mechanisms involved in these interactions remain under intensive debate in the literature. In addition, the role of a Ca²⁺ homeostasis dysregulation in the pathogenesis of neurodegenerative diseases, like AD, and major depression has been under intensive discussion. Objective: Thus, revealing the interplay between AD and major depression may provide novel insights into the pathogenesis of these diseases. Methods: Publications involving Ca²⁺ signalling pathways, AD, and major depression (alone or combined) were collected by searching multiple databases to find the maximum number of relevant citations (using a search strategy with high sensitivity for studies of etiology). Results: CaCa²⁺ Channel Blockers (CCBs), classically prescribed for hypertensive patients, have been demonstrating neuroprotective effects, such as decreasing the incidence of AD in hypertensive patients, including alleviating major depression symptoms. A mechanism under debate is focused on the restoration of the Ca²⁺ homeostasis. Indeed, previous studies of our own have correlated Ca²⁺ and cAMP signalling pathways (Ca²⁺/cAMP signalling) in controlling both the neurotransmitter release and neuronal death. These studies also observed that CCBs can affect Ca²⁺/cAMP signalling. Conclusion: This review discussed the plausible role of Ca²⁺/cAMP signalling in the neuroprotective effects of CCBs, including the participation of Ca²⁺/cAMP signalling in the interactions between major depression and AD. Considering both AD and major depression have become highly prevalent medical problems in the world, the comprehension of the interactions between these diseases could improve drug development.

Objective: Imidazole is a heterocyclic moiety having immense biological importance. Since ancient times, the imidazole nucleus is considered to be a promising moiety in the field of chemistry. Preliminary in vitro and in vivo studies have provided valuable scientific evidence for its use. Subsequently, imidazole constitutes a new class of compounds for new drug development as the presence of this nucleus in diverse therapeutic categories viz; antimicrobial, anti-inflammatory, anticancer, immunomodulator, antiviral etc. has made it an interesting moiety for the design and development of new pharmacological agents. Thus, this review aims to summarize the reported molecular entities which were synthesized by using conventional as well as microwave processes, chemistry and biological potential of imidazole containing heterocyclic molecules while identifying potential areas of further research on imidazole. Results: The review comprises literature pertaining to the evidence-based pharmacological or therapeutic potential of imidazole using published articles and worldwide databases. Various pharmacological experiments using different models exclusively proved the potential of imidazole. Summary: Focusing on the discovery and development of new imidazole nucleus based molecules at a faster rate, there is a need to search previous information available in the market in the field of medicinal chemistry. Therefore, the present review aims to elaborate the therapeutic worth of imidazole and its analogs.

Background: Pharmacobezoars are specific types of bezoars formed when medicines, such as tablets, suspensions, and/or drug delivery systems, aggregate and may cause death by occluding airways with tenacious material or by eluting drugs resulting in toxic or lethal blood concentrations. Objective: This work aims to fully review the state-of-the-art regarding pathophysiology, diagnosis, treatment, and other relevant clinical and forensic features of pharmacobezoars. Results: Patients of a wide range of ages and of both sexes present with signs and symptoms of intoxications or more commonly gastrointestinal obstructions. The exact mechanisms of pharmacobezoar formation are unknown but are likely multifactorial. The diagnosis and treatment depend on the gastrointestinal segment affected and should be personalized to the medication and the underlying factor. A good and complete history, physical examination, image tests, upper endoscopy, and surgery through laparotomy of the lower tract are useful for diagnosis and treatment. Conclusion: Pharmacobezoars are rarely seen in clinical and forensic practice. They are related to controlled or immediate-release formulations, liquid, or non-digestible substances, in normal or altered digestive motility/anatomy tract, and in overdoses or therapeutic doses, and should be suspected in the presence of risk factors or patients taking drugs which may form pharmacobezoars.

Background: Resistance to glucocorticoid (GC)-induced apoptosis in Acute Lymphoblastic Leukemia (ALL), is considered one of the major prognostic factors for the disease. Prednisolone is a corticosteroid and one of the most important agents in the treatment of acute lymphoblastic leukemia. The mechanics of GC resistance are largely unknown and intense ongoing research focuses on this topic. Aim: The aim of the present study is to review some aspects of GC resistance in ALL, and in particular of Prednisolone, with emphasis on previous and present knowledge on gene expression and signaling pathways playing a role in the phenomenon. Methods: An electronic literature search was conducted by the authors from 1994 to June 2019. Original articles and systematic reviews selected, and the titles and abstracts of papers screened to determine whether they met the eligibility criteria, and full texts of the selected articles were retrieved. Results: Identification of gene targets responsible for glucocorticoid resistance may allow discovery of drugs, which in combination with glucocorticoids may increase the effectiveness of anti-leukemia therapies. The inherent plasticity of clinically evolving cancer justifies approaches to characterize and prevent undesirable activation of early oncogenic pathways. Conclusion: Study of the pattern of intracellular signal pathway activation by anticancer drugs can lead to development of efficient treatment strategies by reducing detrimental secondary effects.

Background: Postpartum Hemorrhage (PPH) is one of the primary causes of maternal mortality and morbidity during the third stage of labor. Oxytocin is the gold standard uterotonic agent for the prevention of PPH. Objective: We aimed to compare the efficacy of oxytocin administered Intramuscularly (IM) or Intravenously (IV) for the preventive management of PPH. Methods: We searched six databases for relevant clinical trials evaluating the administration of oxytocin for the prevention against PPH through July 2019. Data on blood loss, PPH (≥500 ml), severe PPH (≥1000 ml), blood transfusion, the change in hemoglobin, the use of additional uterotonics, and the incidence of retained placenta were extracted and pooled in a meta-analysis model using RevMan version 5.3. Results: Seven studies with a total of 6996 participants were included. IM oxytocin group was associated with higher incidence rates of PPH (≥500 ml) (RR=1.35; p=0.003), severe PPH (≥1000 ml) (RR=1.58; p=0.04), and blood transfusion (RR=2.43; p=0.005). In terms of blood loss, the IV route was superior to the IM route (SMD= 0.15; p=0.00001). However, we observed no statistically significant difference between the two routes regarding the change in Hb (SMD=-0.02; p=0.72) and the use of additional uterotonics (RR=0.96, p= 0.94). Conclusion: IV oxytocin infusion is maybe superior to IM injection for the management of PPH. Further studies with larger sample sizes are still needed to support these findings.

Background: The average age of using illicit drugs for the first time in adolescents has decreased in Iran over the past years. Studies show that family and environment play a notable role in keeping adolescents away from substances. Aims: The present study is an attempt to develop and validate a model-based questionnaire to measure parental factors related to substance use prevention in adolescents. Methods: This methodological study was carried out on 336 parents of high school students in Sabzevar- Iran, in 2018. The first draft of the questionnaire, including 136 items, was developed based on the constructs of the Health Promotion Model (HPM) using similar questionnaires, literature review, and interviewing 9 qualified experts. The validity of the questionnaire was measured through face validity (qualitative and quantitative), content validity (qualitative and quantitative), and construct validity (confirmatory factor analysis). The reliability of the questionnaire was measured by internal consistency and test-retest reliability. SPSS ver. 16 and LISREL ver. 8.2 software was used for statistical analysis. Results: Throughout the validation process, 35 items were omitted, and the final version of the questionnaire consisting of 101 items was developed. The overall content validity ratio was 0.81, which indicates the proper and understandable content of the items. The overall content validity index was 0.96, which indicates excellent expert validity. The Cronbach’s alpha coefficient of the questionnaire was 0.85 (constructs range= 0.73-0.96), and the intraclass correlation coefficient of the questionnaire was 0.78 (constructs range= 0.46-0.91), which indicates that the questionnaire has good internal consistency and test-retest reliability. Further, the confirmatory factor analysis yielded an appropriate fit for the model (RMSEA= 0.069, χ2/df= 2.77, GFI= 0.60, AGFI= 0.83, CFI= 0.83, NNFI= 0.83). Conclusion: The validity and reliability of the HPM-based questionnaire were supported. Therefore, the questionnaire can be used by health educators and health policymakers in empowerment programs for parents to improve their behavioral skills concerning the prevention of substance use in their adolescents.

Background: Substance use is becoming a global health problem that concerns health professionals and decision makers. Studies showed that teens are at higher risk for substance use. Purpose: the purpose of this study was to examine the prediction power of the selected sociodemographic and psychological factors on substance use among high school students in Jordan. Specific aims were; 1) to explore substance use among high school students in Jordan, and 2) to examine the prediction power of sociodemographic and psychological factors on substance use among high school students in Jordan. Methods: This is a predictive cross-sectional study where data was collected using self-administered questionnaires from a convenience sample of 1497 high school students in the central district of Jordan. Results: Students who reported that they have never used stimulant agent were 91.5%, tranquilizer sedative 87.2%, hypnotic agent 85.8% and antidepressant agent 94.5%, while those never used nicotine were 81.7%. Coping efficacy (crude OR = 1.07, CI 95% = 1.03 - 1.12), psychological distress (crude OR = 1.07, CI 95% = 1.03 - 1.11), and perceived social support from family (crude OR = 1.20, CI 95% = 0.95 - 1.24) were significantly associated with substance use. While perceived social support from friends was not. Conclusion: High school students are at risk for the use of various forms of substances and mainly the over counter ones. Legitimate rules of screening and using substance prevention programs at high schools considering the psychological factors is a priority for school health professionals and policy makers.

Background: Despite many successes in the discovery of numerous cancer chemotherapeutic agents from natural sources, some of the moieties were dropped because of its inefficiency or serious toxicity. Mitosis is an ordered series of fundamentally mechanical events in which identical copies of the genome are moved to two discrete locations within the dividing cell. The crucial role of the mitotic spindle in cell division has identified, which is an important target in cancer chemotherapy. In the present study, we are reporting molecular docking studies and In silico pharmacokinetic profiles of selected phytoconstituents obtained from Amyris pinnata. Methods: Molecular docking studies of selected phytoconstituents were performed using iGEMDOCK. The crystal structure of the protein was exported from the protein data bank (PDB id: 4C4H). In silico pharmacokinetic profile of selected phytoconstituents was performed using the SWISSADME server. Results: Compound AMNP6 showed higher binding affinity as compared to the standard ligand. All the selected phytoconstituents have passed the Lipinski rule of five and shown no violations. Conclusion: Good binding affinity and drug likeliness of the AMNP6 suggest that it can be further investigated and explored as mitotic spindle kinase inhibitor in cancer disease.