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July-August 2018
Volume 50 | Issue 4
Page Nos. 155-216
Online since Thursday, November 1, 2018
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EDITORIAL
Modulation of endocannabinoid system: Success lies in the failures
p. 155
Subodh Kumar, Phulen Sarma, Harish Kumar, Ajay Prakash, Bikash Medhi
DOI
:10.4103/ijp.IJP_541_18
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EDUCATIONAL FORUM
Evolution of pharmacology education in India: Past and future
p. 159
Dinesh K Badyal
DOI
:10.4103/ijp.IJP_239_18
Pharmacology education has passed through various stages in the evolution sequence due to ever-changing type and repository of drugs as well as technological advancements in the educational processes. This article reviews the journey of evolution of pharmacology education. Pharmacology is relevant component of various curricula in medical, dental, and paramedical courses. A huge number of students learn pharmacology as a subject. Important milestones in evolutionary sequence included revisions and updates in learning objectives, teaching-learning material/methods and assessment in undergraduate (UG) and postgraduate (PG) levels. During this period, a number of pharmacology organizations and associations were formed for the progress of the subject. The inception of Indian Pharmacological Society and International Union of Pharmacology is worth mentioning. There are standardization and unification efforts being done in pharmacology education at national and international levels. The era of animal experimentation is struggling to survive in the new era of animations and simulations. There is increasingly more emphasis on the relevant clinical pharmacy and clinical pharmacology components in the education. The past evolutionary sequences provide leads for future evolutions. New courses and innovations are being designed and implemented to make pharmacology education more meaningful and useful to the new technology-savvy students. A number of innovations in the form of case-based learning, objective-structured practical examination, small group learning, interactive, and integrated methods are being implemented. There is a lot of work being done to introduce a competency-based intergraded curriculum in medical UG and PG courses. All these evolutionary sequences require changing and evolving role of teachers as facilitators.
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RESEARCH ARTICLES
A big data approach with artificial neural network and molecular similarity for chemical data mining and endocrine disruption prediction
p. 169
Renjith Paulose, Kalirajan Jegatheesan, Gopal Samy Balakrishnan
DOI
:10.4103/ijp.IJP_304_17
CONTEXT:
Chemical toxicity prediction at early stage drug discovery phase has been researched for years, and newest methods are always investigated. Research data comprising chemical physicochemical properties, toxicity, assay, and activity details create massive data which are becoming difficult to manage. Identifying the desired featured chemical with the desired biological activity from millions of chemicals is a challenging task.
AIMS:
In this study, we investigate and explore big data technologies and machine learning approaches to do an efficient chemical data mining for endocrine receptor disruption prediction and virtual compound screening. The power of artificial neural network (ANN) in predicting chemicals' activity toward androgen receptor (AR) and estrogen receptor (ER) and thereby classifying into human endocrine disruptor or nondisruptor is investigated.
SUBJECTS AND METHODS:
Molecules are collected along with their Inhibitory Concentration (IC
50
) values toward AR and ER. Training and test datasets are created with active and inactive classes of molecules. Molecular fingerprints of Electro Topological State (E-State) are generated for describing every compound. ANN machine learning model is created using Apache Spark and implemented in Hadoop big data environment. Test chemical's structural similarity toward active class of training compounds is estimated and combined with ANN model for improving prediction accuracy.
RESULTS:
AR and ER predictive models applied on corresponding test datasets gave 86.31% and 89.57% accuracies, respectively, in correctly classifying molecules as disruptor or nondisruptor. Molecular fragments and functional groups are ranked based on their importance in forming ANN model and influence toward the AR and ER disruption behavior. Training molecules that are specific to the test molecules' endocrine disruption prediction are retrieved based on the structural similarity values.
CONCLUSIONS:
The current study demonstrates a new approach of chemical endocrine receptor disruption prediction combining ANN machine learning method and molecular similarity in a big data environment. This method of predictive modeling can be further tested with more receptors and hormones and predictive power can be examined.
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The effect of
Portulaca oleracea
and α-linolenic acid on oxidant/antioxidant biomarkers of human peripheral blood mononuclear cells
p. 177
Seydeh Negin Yahyazadeh Mashhadi, Vahid Reza Askari, Vahideh Ghorani, Gholam Ali Jelodar, Mohammad Hossein Boskabady
DOI
:10.4103/ijp.IJP_737_16
OBJECTIVES:
Various pharmacological effects including antioxidant property of
Portulaca oleracea L.
were reported previously. In the present study, the effect of the extract of the plant and its constituent, α-linolenic acid (ALA), on oxidant and antioxidant markers of PHA/non-stimulated human mononuclear cells was evaluated.
MATERIALS AND METHODS:
The effect of 10, 40, and 160 μg/ml of
P. oleracea
and 5, 15, and 45 μg/ml of ALA or dexamethasone (0.1 mM) on nitric oxide (NO), malondialdehyde (MDA), total thiol (SH), superoxide dismutase (SOD), and catalase (CAT) in the supernatant of phytohemagglutinin-A (PHA)- and nonstimulated lymphocytes was examined (
n
= 6 for each group).
RESULTS:
In nonstimulated cells, dexamethasone, high concentration of the extract (160 μg/ml), and ALA (45 μg/ml) significantly increased thiol, CAT, and SOD values. Dexamethasone and high concentration of ALA significantly reduced MDA value (
P
< 0.01 to
P
< 0.001). However, the levels of NO and MDA due to dexamethasone and 160 μg/ml of the extract and 15 and 45 μg/ml of ALA treatment were also reduced in PHA-stimulated cells (
P
< 0.001 for all cases). Treatment of stimulated lymphocyte by dexamethasone and two higher concentrations of the extract and ALA also leads to increased levels of thiol, CAT, and SOD (
P
< 0.05 to
P
< 0.001).
CONCLUSIONS:
P. oleracea
and ALA, as well as dexamethasone, decreased NO and MDA levels but increased antioxidant agents in human lymphocytes. These results suggest that
P. oleracea
and ALA may have therapeutic effect in diseases associated with enhancement of oxidation agents as an antioxidant agent.
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Subchronic hypoxia pretreatment on brain pathophysiology in unilateral common carotid artery occluded albino rats
p. 185
Kusal K Das, Saeed M Yendigeri, Bheemshetty S Patil, Ishwar B Bagoji, R Chandramouli Reddy, Shrilaxmi Bagali, MS Biradar, Sikha Saha
DOI
:10.4103/ijp.IJP_312_17
OBJECTIVE:
This study was aimed to assess the effect of unilateral common carotid artery occlusion on brain pathophysiology in rats pretreated with subchronic hypoxia.
MATERIALS AND METHODS:
Rats (200 ± 20 g) were randomized into three groups: Group 1 served as sham, Group 2 were normoxic (21% O
2
and 79% N
2
), and Group 3 were hypoxia preconditioned (10% O
2
and 90% N
2
) for 21 days before left common carotid artery occlusion (LCCAO). The LCCAO was done for 75 min followed by reperfusion for 12 h. Neurological scores were recorded. Serum malondialdehyde (MDA) and nitric oxide (NO) levels at pre- and 12 h post-LCCAO were measured. Brain histopathological assessments were also done.
RESULTS:
Higher neurological deficits scores in Group 2 as compared to Group 3 rats were noticed. Serum MDA and NO levels at 12 h post-LCCAO in Group 2 rats showed significant elevation as compared to preocclusion levels. Group 3 rats did not show such elevations. On histopathology of left and right cerebral hemispheres of Group 1 (sham) did not show any specific changes. In Group 2 rats, the right cerebral hemisphere (nonoccluded) showed no areas of ischemia-induced brain changes, but in the left side (occlusive), there were features of ischemic brain damage including cerebral edema. In the case of Group 3 rats, there were less ischemic damages in the left occluded side as compared to the left side of the Group 2 rats.
CONCLUSION:
This study clearly demonstrates that subchronic hypoxia pretreatment can reduce ischemic brain injury by unilateral common carotid artery occlusion in rats.
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Cutaneous adverse drug reactions with fixed-dose combinations: Special reference to self-medication and preventability
p. 192
Ratikanta Tripathy, Kali Prasad Pattnaik, Suhasini Dehury, Sibasis Patro, Prasanjeet Mohanty, Swayam Sourav Sahoo, Srikanta Mohanty
DOI
:10.4103/ijp.IJP_760_16
OBJECTIVES:
To identify the association of cutaneous adverse drug reactions (CADRs) with use of fixed-dose combinations (FDCs) and to compare the occurrence of preventable CADRs between self-medication and prescribed medication of FDCs.
PATIENTS AND METHODS:
All cases of suspected CADRs with the use of FDCs were collected, and causality assessment was carried out using the WHO UMC scale. The burden of CADRs on self-medication and prescribed medication was found out. Preventability status was analyzed by Schumock and Thornton Criteria and compared between self-medication and prescribed medication.
RESULTS:
A total of 74 CADRs were detected; 68.91% were detected with antimicrobial and 31.09% with nonsteroidal anti-inflammatory drug-based FDCs. Fluoroquinolones + nitroimidazole was the most commonly suspected medications. Majority of CADRs (44.59%) were fixed-drug eruptions, which was significantly higher than others (
P
= 0.002). Analysis of preventability showed that there was a significantly higher occurrence of definitely preventable CADRs in self-medication group (40%) in comparison to prescribed group (6.81%),
P
= 0.028.
CONCLUSIONS:
Self-medication with FDCs is quite common and associated with a higher rate of preventable CADRs in comparison to that in prescribed medication.
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SHORT COMMUNICATIONS
Comparative effect of manuka honey on anaerobic parasitic protozoans with standard drug therapy under
in vitro
conditions: A preliminary study
p. 197
Shweta Sinha, Ajay Prakash, Rakesh Sehgal, Bikash Medhi
DOI
:10.4103/ijp.IJP_227_18
BACKGROUND:
From the past five decades, metronidazole and tinidazole have been used for treating nonresistant and resistant giardiasis and trichomoniasis. However, due to the occurrence of drug resistance to standard therapy idealizes us to explore some additional therapies which is cost-effective, easy accessibility, and natural which has least side effects. Manuka honey obtained from
Leptospermum scoparium
is well known for its antibacterial and wound healing properties and is thought to be a better option as an additional therapy.
OBJECTIVE:
The present study was conducted to find out the effect of manuka honey on anaerobic protozoans that includes
Giardia
and
Trichomonas
under
in vitro
conditions in comparison to metronidazole and tinidazole.
MATERIALS AND METHODS:
Axenic culture of
Giardia lamblia
strain Portland 1 and
Trichomonas vaginalis
strain 413 was used for drug sensitivity assay to tinidazole, metronidazole, and manuka honey with the highest concentration of 17.1 μg/ml, 24.7 μg/ml, and 50%v/v by using (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole). For this, head-to-head comparison has been done and IC
50
of the standard drug as well as manuka honey was calculated.
RESULTS:
The result showed that percentage inhibition on the growth of both the parasites is dependent on concentration as well as exposure time of the drug. The calculated IC
50
was found to be 5.6%v/v and 1.5%v/v for manuka honey with respect to
G. lamblia
and
T. vaginalis
.
CONCLUSION:
The present study suggests that manuka honey can be used as an additional therapy for the patient with giardiasis or trichomoniasis. However,
in vivo
study in the near future will elucidate more about the effectiveness of honey in treating parasitic infections.
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Cefixime-associated acute generalized exanthematous pustulosis: Rare cases in India
p. 204
Vipin Kumar, Vivekanandan Kalaiselvan, A Pramod Kumar, Archana Saurabh, Prasad Thota, Shabir Sidhu, Bikash Medhi
DOI
:10.4103/ijp.IJP_673_17
BACKGROUND:
Cefixime is a widely used third-generation cephalosporin schedule H1 drug, which is prescribed for the treatment of otitis media, respiratory tract infections, and uncomplicated urinary tract infections and is effective against infections caused by
Enterobacteriaceae
and
Haemophilus influenzae
species in India. The National Coordination Centre (NCC)-Pharmacovigilance Programme of India (PvPI), Indian Pharmacopoeia Commission (IPC), has received rare individual case safety reports (ICSRs) for acute generalized exanthematous pustulosis (AGEP) associated with the use of cefixime.
MATERIALS AND METHODS:
IPC, NCC-PvPI also acts as a national collaborating center for pharmacovigilance activities under the aegis of Ministry of Health and Family Welfare, Government of India; moreover, it is a member country in global pharmacovigilance system, World Health Organization-Uppsala Monitoring Centre, Sweden. There are more than 250 government/corporate medical colleges and hospitals acting as regional adverse drug reaction monitoring centers, actively functioning under PvPI. Furthermore, various stakeholders including consumers and pharmaceutical industries also play a significant contribution. NCC-PvPI receives spontaneous ICSRs from various stakeholders.
RESULTS:
NCC-PvPI, IPC has received a total of four spontaneous ICSRs for cefixime-induced AGEP. After clinical evaluation of reported ICSRs, a strong causal relationship was established between AGEP and cefixime and was supported by published literature and histopathological examination of skin. Based on the statistics with positive information component (IC025 Value: 0.17) and proportionality relative risk (PRR:3.4), PvPI considered cefixime-associated AGEP may be a potential signal.
CONCLUSION:
Hence, initially, AEGP is considered by PvPI as drug safety alert in July 2016. Therefore, to enhance the safety of population in rational usage of medication, as a result, there is a need for physicians and health-care professionals to sensitize about serious adverse reaction while prescribing the cefixime as signal in India.
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Clinical Trials Registry – India: An overview and new developments
p. 208
M Vishnu Vardhana Rao, Mohua Maulik, Jyotsna Gupta, Yashmin Panchal, Atul Juneja, Tulsi Adhikari, Arvind Pandey
DOI
:10.4103/ijp.IJP_153_18
The Clinical Trials Registry – India (CTRI), launched over 10 years ago, is a free, searchable online platform for registration of clinical trials being conducted in India and as well as countries which do not have a Primary Registry of their own. The objective of the present article is to appraise the current status and the new developments of CTRI, which registers all types of clinical studies, including postgraduate theses. The CTRI which was until now allowing both prospective and retrospective registration is moving towards only prospective trial registration. From April 1, 2018, only those trials where the first patient enrollment has not yet commenced will be registered. Further, the CTRI is in the process of implementing structured summary results disclosure of all interventional clinical trials in the near future.
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DRUG WATCH
Zidovudine-induced lactic acidosis with acute pancreatitis and myopathy: Lethal and rare complications
p. 212
Subodh Kumar Mahto, Pulin Kumar Gupta, Rajesh Satyapal Taneja, Akanksha Singh
DOI
:10.4103/ijp.IJP_285_18
Highly active antiretroviral therapy (HAART) is nowadays universally available to patients with HIV/AIDS. This has led to increased longevity in people living with HIV/AIDS. However, these patients frequently face chronic and rarely acute life-threatening complications of HAART. Herein, we report the case of a patient who was on HAART and developed zidovudine-induced lactic acidosis, acute pancreatitis, and myopathy. Although these acute complications are rare, a high index of suspicion is required for early diagnosis and to reduce significant morbidity and mortality.
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LETTER TO THE EDITOR
Leprosy cases with respiratory infection – Rule out tuberculosis simultaneously with dapsone syndrome
p. 215
Pugazhenthan Thangaraju, Sajitha Venkatesan
DOI
:10.4103/ijp.IJP_164_18
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