Open Access Review Article

Role of CaMK II α in the Injury of Dorsal Root Ganglion Neurons Induced by Ropivacaine Hydrochloride in the Dorsal Root Ganglion of Rats

Wu Zhaoxia, Chen Meixin, Li Yiqun, Yang Shuxuan, Wen Xianjie

Journal of Pharmaceutical Research International, Page 1-7
DOI: 10.9734/jpri/2020/v32i4731106

Objective: To investigate whether CaMKⅡα participates in the dorsal root ganglion neurotoxicity induced by ropivacaine hydrochloride.

Methods: DRG neurons were isolated from 1-day-old SD rats and cultured in vitro. pAd-shRNA-CaMKⅡα-DRG cells were constructed by RNA interference technique to inhibit the expression of CaMKⅡα. The experiment was divided into six groups: DRG group (DRG group), vector DRG group (vector group), pAd-shRNA- CaMKIIα-DRG group (pAd-shRNA group), DRG + ropivacaine group (DRG + R group), vector DRG + ropivacaine group (vector + R group), pAd-shRNA-CaMKII α - DRG + ropivacaine group (pAd-shRNA + R group), and the last three groups were treated with 3 mM ropivacaine hydrochloride for 4 hours. MTT assay was used to detect cell viability, flow cytometry was used to detect cell apoptosis rate, laser confocal microscopy was used to detect intracellular calcium level, and real-time PCR was used to detect the mRNA expression of CaMKⅡα, Cav3.2 and Cav3.3.

Results: The cell viability of DRG+R group, vector+R group and pAd-shRNA+R group decreased significantly after 3 mM ropivacaine hydrochloride treatment for 4 h. Compared with DRG+R group, the cell viability of pAd-shRNA+R group was significantly higher. After 3 mM ropivacaine hydrochloride treatment for 4 h, the apoptosis rate of DRG + R group, vector + R group and pAd-shRNA + R group increased significantly. Compared with DRG+R group, the apoptosis rate in pAd shRNA+R group was significantly lower. After 3 mM ropivacaine hydrochloride treatment for 4 h, the intracellular calcium levels in DRG + R group, vector + R group and pAd-shRNA + R group were significantly increased, and the intracellular calcium levels in pAd-shRNA + R group were significantly lower than those in DRG + R group. The mRNA expressions of CaMKⅡα, Cav3.2 and Cav3.3 were significantly decreased in pAd- shRNA group. The mRNA expressions of CaMK Ⅱ α, Cav3.2 and Cav3.3 were up-regulated in DRG + R group, vector + R group and pAd-shRNA + R group after 3 mm ropivacaine treatment for 4 h. The mRNA expressions of CaMKⅡα, Cav3.2 and Cav3.3 in pAd-shRNA + R group were significantly lower than those in DRG + R group.

Conclusion: Inhibition of CaMKⅡα expression can down regulate the expression of Cav3.2 and Cav3.3 mRNA, increase cell viability of DRG neurons, reduce the apoptosis rate, and improve the dorsal root ganglion neurotoxicity induced by ropivacaine hydrochloride.

Open Access Original Research Article

Effect of Dexamathasone in Surgical Extraction of Mandibular Impacted Third Molar

Abdul Hayee Shaikh, Kashif Ali Channar, Ajeet Kumar, Naveed Iqbal, Junaid Shakeel, Uzma Shahid, Shumaila Shaikh, Nayel Syed, Aisha Jabeen, Mirza Tasawer Baig, Imran Qureshi

Journal of Pharmaceutical Research International, Page 8-13
DOI: 10.9734/jpri/2020/v32i4731107

Objective: The objective of this study was to determine the role of dexamethasone in mandibular third molar surgical extraction.

Methodology: This cross sectional study was conducted in Oral & Maxillofacial surgery department, Liaquat University of Medical & Health sciences Hyderabad / Jamshoro. 50 cases were included in this study by using simple random sampling technique. All patients were divided into two groups. Patients in Group-A were given dexamethasone (DM)8 mg intramuscularly (IM) before surgery and 4 mg 24 hours after surgery and Augmentin tablet 625mg Q12 hrs. and Brufen 400 mg Q8 hrs. and patients in group-B were given Augmentin 625 mg BD and Brufen 400 mg  TDS post operatively only. The facial swelling was checked before and after surgery.All information was collected and entered in a proforma.

Results: The study sample was consisted of 62% men and 38% women. Mean age was 26.9±6.64.The mean preoperative swelling was 109.20 ± 1.190 mm in control group and 109.44 ± 1.083 in DM group. After 48 hours of surgery, post extraction swelling increased in both group with mean swelling 114.28± 1.242 mm in control group and 114.64± 1.350 in DM group, after a week of surgery more swelling was reduced in DM group as compared to control group.

Conclusion: It is found that Dexamethasone group showed decrease in swelling as compared to control group.

Open Access Original Research Article

Assessment of Perception, Awareness about Predictors of Colorectal Cancer of Hail Region Saudi Arabia population

Fahmida Khatoon, Madiha Rabie Mahmood, Sofian Talal Obeidat, Munirah Abdalmohsin Mohammad Alsatti, Reema Saleh Sulaiman Alanazi Alanazi, Razan Saud M. Abu Kabbos, Zahid Balouch, Shimaa M. H. Obelanga

Journal of Pharmaceutical Research International, Page 14-24
DOI: 10.9734/jpri/2020/v32i4731108

Colorectal cancer is one of the major malignancies world-wide, accounting for approximately 20% of incident cases. The incidence and mortality have dramatically increased over the past 10th decades in Saudi Arabia. It has been argued that the change in epidemiological pattern is due to the implementation of a way of life style, characterized by use of junk foods and lack somatic exercise. The pharmacokinetics (PK) and pharmacodyn amics (PD) of various drug are also under study for Colon cancer patients. It is remarkable that a lack of routine exercise or activity is supplementary evident for GIT cancer than any other cancer combined. Obesity has been reported to be associated with increased risk of colorectal cancer, and  closely associated with the level of physical activity in this study the effect of sociodemographic factor on biochemical aspects of Cancer is further analyzed. Aim of this study is to determine the awareness and perception of Colorectal cancer in Saudi Arabia and to find out the dietary habits and use of fiber diet among them in order to identify the subpopulation that can be recipients of awareness and screening programs. About 317 subjects was selected after taking written consent on a detailed prescribed questionnaire. Sociodemographic data and information about dietary habits was collected along with biophysical data. All information and the obtained results were analyzed by using SPSS 23. Results: Most of the respondents (51% and 71.9%) knew what is colon and its function. About 11.7%, 62.1% and 22.1% respectively answer high, moderate and low incidence of CRC in Saudi Arabia while 66.9% knew that bowel cancer is 90% curable if detected early. 42% respondent shoed that that there is a an association between IBD and CRC and 75% know the correct time of screening for CRC. Very few respondents know the correct symptoms, risks factors, and screening modalities of Colorectal cancer. Mass media and books are most common method to know about colorectal cancer.

Conclusions: Most of the respondent have enough knowledge about CRC although Screening awareness and modalities for screening of CRC need to be further acknowledged. Although they have enough awareness about CRC still most of the study population showed unhealthy life style and few of them use fiber diets and Vegetables and fruits as daily ingredient.

Open Access Original Research Article

Evaluation of Hepatoprotective and Antioxidant Activity of Ethanolic Extract of Artabotrys zeylanicus Stem against Various Hepatotoxins Induced Hepatotoxicity in Albino Wister Rats

K. Suresh, Hindustan Abdul Ahad, S. V. Satyanarayana

Journal of Pharmaceutical Research International, Page 25-37
DOI: 10.9734/jpri/2020/v32i4731110

The objective of the present study was to investigate the antioxidant and hepatoprotective activity of ethanolic stem extract of Artabotrys zeylanicus against paracetamol (PCT), Ethanol (ETN) and Isoniazid and Rifampicin (IR) induced hepatotoxicity in Albino wister rats.

Methodology: The material was dried in shade, they were powdered and extracted with ethanol. Preliminary Phytochemical tests were done. The hepatoprotective activity of the ethanol extract was assessed in Albino wister rats. PCT (3 g/kg), ETN (5 gm/kg) and IR (100 mg/kg) has enhanced the levels of various biochemical markers of hepatic damage like Serum Glutamic Oxaloacetic Trasaminase (SGOT), Serum Glutamic pyruvic transaminase (SGPT), Alkaline phosphatise (ALP), bilirubin. Antioxidant levels were tested in all the Hepatotoxins treated and untreated groups.

Results: The various biochemical and Histopathological investigations done were Serum Glutamic Oxaloacetic Trasaminase (SGOT), Serum Glutamic pyruvic transaminase (SGPT), Alkaline phosphatise (ALP), Bilirubin, antioxidant activity by 1,1-diphenyl 2-picryl hydrazyl (DPPH), Nitro Blue Tetrazolium (NBT), Hyderogen peroxide (H2O2), lipid perioxidation, hyderoxil radical and nitric oxide. Treatment of ethanolic extract of stem of A. zeylanicus (100mg/kg, 200mg/kg and 400mg/kg body weight) has brought back the altered levels of biochemical markers to the near normal levels in the dose dependent manner. Ethanolic extract of A. zeylanicus were observed to inhibit oxidant stress with the maximum value of 71% and 62% at the concentration of 100 µg/mL. The crude ethanolic extract of A. zeylanicus had a calculated IC50 value of 62.2 and 63.25 μg/mL, which is nearly similar to the calculated IC50 value of the known antioxidant, ascorbic acid, ie 65.3 μg/mL. While the rats treated with AZ extract (100, 200 and 400 mg/kg) which were shown as reduction/absence of inflammatory cells, vascular congestion, cellular degeneration, necrosis and vacuoles. In contrast, the lower doses (100 mg/kg) of ethanolic extract of AZ stem shown low protection than at higher dose 400 mg/kg.

Conclusion: Our findings suggested that A. zeylanicus ethanol stem extract possessed a potent antioxidant and hepatoprotective activity.

Open Access Original Research Article

Identification of Respiratory Syncytial Virus Fusion Protein Inhibitor: In silico Screening and Molecular Docking Approach

Khalid Alshaghdali

Journal of Pharmaceutical Research International, Page 41-48
DOI: 10.9734/jpri/2020/v32i4731112

In young children, immunocompromised individuals, and elderly people, the respiratory syncytial virus (RSV) is the primary source of acute lower respiratory tract infection. Intervention with RSV-specific small-molecule antivirals may provide significant therapeutic potential. For virus entry, the RSV fusion protein (F) is crucial as it facilitates viral and hosts membrane fusion. To date, no approved vaccine or drug molecule is available to treat RSV. With this purpose, in the present study, virtual screening of a library of natural compounds against the active site of F protein was performed, followed by an in-depth molecular docking study of top-scored compounds. Selected hits ZINC8740013, ZINC4029781 and ZINC898642were found to strongly bind with RSV F protein relative to the other compounds as well as the control. The binding energy (BE) and inhibition constant for ‘ZINC8740013-RSV F’, ‘ZINC4029781-RSV F’, and ‘ZINC898642-RSVF’ complexes were found as ‘-7.8 kcal/mol and 63.27 µM’, ‘-7.7 kcal/mol and 19.04 µM’, and ‘-7.5 kcal/mol and 3.31 µM’, respectively. However, BE and inhibition constant of control (JNJ-53718678) with RSV F protein was found as -6.1 kcal/mol and 563.26 µM, respectively. Phe140 and Phe488 are the main interacting residues of RSV F protein with JNJ-53718678 and selected hit compounds. The finding of this study suggests that these hits can be utilized as the RSV Fprotein inhibitor to prevent the fusion of the viral envelope with the host cells. Further, bench work experiments are required to optimize these hit compounds as RSV Fprotein inhibitors.

Open Access Original Research Article

In vitro: The Modulating Effect of Myricetin on the Atherosclerosis Related Processes in THP1 Macrophages

Rehab F. Almassabi, Etimad A. Huwait, Sanaa J. Almowallad, Salma Y. Saddeek, Kalamegam Gauthaman

Journal of Pharmaceutical Research International, Page 62-73
DOI: 10.9734/jpri/2020/v32i4731116

Aims: To assess the anti-atherosclerotic effects of Myricetin (pharmaceutical) in human THP-1 macrophages following IFN-γ or MCP-1 stimulation.

Study Design: The protective effects of myricetin against atherosclerosis was evaluated using the humanTHP-1 macrophages and studying the following parameters namely, cell viability, cell proliferation, cell migration, inflammation related gene expression and cholesterol efflux in vitro.

Place and Duration of Study: THP-1 cell line: Department of biochemistry (faculty of science), Cell Culture Unit, Experimental Biochemistry Unit (King Fahad Medical Research Centre), King Abdul Aziz University, between September 2019 and September 2020.

Methodology: The THP-1 cell lines were differentiated into macrophages by incubation with PMA (160 nM) for 24 hours. The viability percentage was determined using Pierce LDH cytotoxicity assay kit, the percentage change in macrophages proliferation was evaluated by crystal violet dye, the RNA was extracted then the cDNA was synthesized and the quantitative real time polymerase chain reaction (qRT-PCR) was done for inflammation-related genes, ICAM-1 and MCP-1. The percentage of monocyte migration and cholesterol efflux were also calculated.

Results: Cytotoxicity assays demonstrated no significant toxicity with myricetin at 25μM and 50 μM concentrations on THP-1 macrophages. The quantitative real-time RT-PCR (qRT-PCR) demonstrated a significant increase in interferon gamma (IFN-γ) mediated expression of both intercellular adhesion molecule (ICAM-1) and monocyte chemo-attractant protein-1 (MCP-1) by 2.1 and 7.1 fold respectively, compared to the control. Treatment with myricetin (25 μM and 50 μM) significantly inhibited the IFN-γ induced overexpression of ICAM-1 by 42.86% & 71.34% and MCP-1 by 53.52% & 87.32% respectively. Myricetin (25 μM) significantly reduced the migration of monocytes by 33.66% compared to MCP-1. The cholesterol efflux from THP-1 macrophages treated with myricetin was significantly increased by 47% and 57% in the absence and presence of IFN-γ, respectively compared to the control.

Conclusion: Myricetin has anti-inflammatory effects and supports cholesterol efflux, which can help in prevention of atherosclerosis. Furthermore, myricetin did not exhibit any cytotoxic effects and therefore is a safe phytochemical which can complement conventional therapeutics.

Open Access Original Research Article

Antimicrobial Activity of Coriander sativum

Samina Amin Qurban Ali, Arif Malik

Journal of Pharmaceutical Research International, Page 74-81
DOI: 10.9734/jpri/2020/v32i4731117

The increasing rate of drug-repellent pathogens and poisonousness of existing antiseptic compounds has strained attention toward activity of antimicrobial products which are natural. Main purpose of this research was to assess antimicrobial activity of seeds and leaves of Coriandrum sativum’s essential oil, antioxidant, antimicrobial activity and chemical composition of Coriandrum sativum’s ethanol extracts and essential oils. Numerous approaches were used in reviewing the antioxidant activity such as, p-anisidine test – malonaldhyde, DPPH and peroxide value. Antimicrobial activity of the extracts towards six microbial strains; two bacterial strains (Salmonella typhi and Staphylococcus aureus), one yeast (Candida tropicals) and three fungal strains (Aspergillus flavus, Mucor sp and Emericella nidulans) was assessed by determination of inhibition zone and count of bacteria, yeast and spares of fungus. The antimicrobial mechanisms found in these essential oils have been explained on the basis of their content in natural compounds such as carvacrol, thymol, p-cymene and c-terpinene, among others. Although these two essential oils have received much attention, scientists working in the fields of biomedicine and food science are paying increasing attention to a wider variety of aromatic natural oils in an effort to identify original and natural applications for the inhibition of microbial pathogens. In conclusion, utilization of coriander or their components as food additives will increase the antioxidant and the antimicrobial potential of the food which prevent food deterioration and improve the shelf-life of food beside its nutritional value. The results revealed that the leaves extracts have high levels of phenolics than the seeds extract. Concerning antioxidant activity, significant decreases (p>0.001) were observed in peroxide, P- anisidine and TBA values as compared to control oil. On the other hand, scavenging activity % of the four extracts on DPPH radical were higher than that of butylated hydroxyl toluene (BHT) especially with high concentration (1000 μg/ ml). Regarding antimicrobial activity, the results showed that the extract of coriander seeds has the highest reduction percent in growth of all the examined microorganisms. The result also revealed that Mucor sp was resistant to the action of parsley extracts while Aspergillus flavus has the highest resistance against coriander extracts.

Open Access Letter to the Editor

Should Travellers have Priorities for COVID 19 Vaccine?

Najim Z. Alshahrani, Sultan M. Alshahrani, Nada Fussi, Mohammed J. Alsheef

Journal of Pharmaceutical Research International, Page 38-40
DOI: 10.9734/jpri/2020/v32i4731111

The “Type of Article” of this paper is “Letter to the Editor”. This paper discuses about: “Should Travellers have Priorities for COVID 19 Vaccine?”. No formal abstract is available. Readers are requested to read the full article.

Open Access Systematic Review Article

A Systematic Review and Meta-Analysis of an Emerging Therapy against COVID-19: Is Convalescent Plasma a Hidden Gem Not Yet Optimized?

Azza Sarfraz, Zouina Sarfraz, Aminah Abdul Razzack, Donald Hathaway III, Sindhu Thevuthasan, Sarabjot Singh-Makkar, Trissa Paul, Gaurav Patel, Muhammad Khawar Sana, Muzna Sarfraz, Franz Richter, Marcos A. Sanchez Gonzalez

Journal of Pharmaceutical Research International, Page 49-61
DOI: 10.9734/jpri/2020/v32i4731113

Background: An unprecedented global effort in identifying potentially viable and emerging drugs for effective treatment of the novel coronavirus disease (2019) is being made. Of the most promising candidate therapies, convalescent plasma (CP), albeit controversial, is approved for emergency use authorization (EUA) by the U.S. Food and Drug Administration (FDA). The concept rests on passive immunity, achieved by administering plasma with high titers of neutralizing antibodies to reduce severity of SARS-CoV-2 infection and mortality. The aim of this paper is to assess the clinical improvement, patients’ discharge status and all-cause mortality in convalescent plasma versus standard of care COVID-19 patient groups.

Methods: Using PRISMA guidelines, a review was conducted from January, 2020, until October, 2020 employing keywords including “convalescent plasma”, “clinical improvement, “mortality”, “adverse events”, “viral load”, “dosing”, and survival.” Dichotomous data for all-cause mortality, patients’ discharge status, and clinical improvement at day 14 of treatment were meta-analyzed applying the Mantel-Haenszel (M-H) random effects model using Review Manager 5.4. 

Results: A total of 627 (23.9%) patients in the CP group and 1997 (76.1%) patients in the control group were pooled. The studies were conducted in the United States, China, Netherlands, and Iran. The CP group had a lower association to all-cause mortality as compared to the control group [OR: 0.69; CI: 0.50 to 0.96; P=0.03]. Patients who received CP had higher probability of discharge during the study course [OR: 1.87; CI: 1.1 to 3.18; P=0.02]. Bias was expected in the analysis due to the stratified of study designs included.

Conclusion: Convalescent plasma therapy may be an effective and vital tool with promising historical, current, and expected clinical trial evidence of metrics such as increased safety and reduction of all-cause mortality.

Open Access Minireview Article

Ayushman Bharat: An Ethical Analysis of the World’s Biggest Health Scheme

Rajesh Kumar Bhola, B. B. Pradhan

Journal of Pharmaceutical Research International, Page 82-88
DOI: 10.9734/jpri/2020/v32i4731118

An affordable health scheme has been always required by the Indian people. Even after passing74 years of Indian independence, quality healthcare has not been accessible to the Indian people. The data have shown out of the vast population of India only 25 percent of people are insured under the private and government insurance scheme. To overcome this problem Indian government has launched the Ayushman Bharat scheme on 25 December 2018 on the occasion of the birth anniversary of Pt. Deen Dayal Upadhyaya. The Ayushman Bharat is the Hindi translation of “India blessed with long life”. This scheme is the biggest health care scheme in the world which covers the huge population of India and the covered population under this scheme is more than 100 million. The scheme has categories into the primary, secondary, and tertiary care domain to address the health-related problems of the people and the most important and fascinating feature of the scheme is that a beneficiary avails the facilities in government hospital along with private hospitals. The present study reviews different aspects of the scheme in relevance to the helath sector to provide better perpective towards Indian health care systems.