Hygeia journal for drugs and medicines

1-2

Authors: Prof.M K. Unnikrishnan

The other day, I was invited to participate in the National convention on Medicine and Law at Mumbai to deliberate on violence against doctors. The brochure ominously asserted that “75% of doctors have faced violence at work” Why has this antipathy towards doctors become so commonplace? Is it from the seeds of suspicion planted by Google-driven health information systems retrieved from the internet? Or is it the mounting expectations of the‘informed’ patient with insurance cover and cash? Could it be the corporatization of healthcare that places profit before patient care? Or is it lack of personalized attention? Or a sense of being swindled by unnecessary diagnostic tests and avoidable hospital admissions? Must be a combination of all of the above, in addition to even more reasons peculiar to India. The healthcare system is particularly vulnerable to exploitation because of ‘knowledge asymmetry.’ When we want to buy a car, we decide what car we need, what additional fittings it should adorn, and when we should take delivery. No such freedom exists when it comes to our own health. We have no idea what vaccinations or diagnostic tests we need, what medicines we should buy or what surgeries we have to go through.The knowledge intensive nature of healthcare typically creates a conflict of interest between the ignorant patients and well-informed, profit-seeking health care providers. Trust alone can bridge this divide.

16-26

Authors: Manjula Devi A.S*, Senthilvel. N, Dhanu Josey, Divya Ann Jetto, Evelyn Harold, Mabel Elizabeth V.K.

Plan: To assess the incidence of inappropriate dosing of drugs having side effects like hepatotoxicity in hospitalized patients with hepatic impairment. Preface: Inappropriate dosing in patients with liver dysfunction can cause toxicity or ineffective therapy. Method: The degree of hepatic impairment was calculated using Child-Pugh classification which incorporates five variables to assess the severity of liver disease: total bilirubin, serum albumin, prothrombin time, the presence of encephalopathy and the presence of ascites. The dose of all drugs with potential hepatotoxicity was evaluated using the published drug dosing guidelines and the dosing interval was increased or the total dose was reduced when necessary. Outcome: Four hundred and twenty nine drugs in 50 patients were evaluated, of which, most of the drugs requiring dose adjustment were anti hypertensives followed by anti diabetics. Major type of error identified was under dosing followed by overdosing and contraindications.About 27.58% of the drugs were to be avoided in hepatic impairment as per the available evidences. Conclusion: Drug dosing evaluation and concurrent feedback mechanism by the pharmacist can improve drug safety in patients with hepatic impairment.

35-43

Authors: Honey Jose, Arya KR, Sindhu TJ, Syamjith P, Vinod KR*, Sandhya S

Nutmeg and mace are the two spices derived from several tree species in genus Myristica. They contain essential oil and is used therapeutically cosmetic and culinary preparations. Several value addition products widens the commercial value of this herb. Although fifty percent shade is recommended in the initial levels,as the tree grows it can be reduced. It is better to adopt budding or grafting as there are possibility of plants seedlings to grow into male and female plants, resulting in the production of 50% unproductive male plants. The female trees start fruiting from 6 years old even though peak period is 20 years. Overdose of essential oils of nutmeg is having hallucination effects

1-2

Authors: Dr.D.Suresh Kumar

The lifestyles of people worldwide have changed in the last century due to a rise in income, increased leisure time, and reduced physical activity. These new lifestyles have a considerable impact on health. Consequently, there is a global rise in the incidence of diseases such as obesity, cardiovascular diseases, diabetes mellitus, and rheumatoid arthritis. The medical world is therefore looking for better strategies to contain this trend. As a parallel development, there is a worldwide increase in health awareness and interest in herbal alternatives. Nowadays, elderly people worldwide are more concerned about the quality of the food and beverages that they consume. Functional foods have therefore emerged as an effective means for the prevention of diseases. This change in consumer outlook has encouraged the food and beverage industry to apply modern manufacturing technology in food fortification. A reduction in weight, a reduction of cholesterol, the promotion of bone health, an increase in energy, the enhancement of disease resistance through the immune system, and the improvement of digestive functions are the major health concerns that influence the purchase of functional foods.....

9-17

Authors: Sandhya S*, Venkata Ramana K,Vinod K.R

Plan: The methanol extracts of Tephrosia calophylla and Tephrosia maxima (Fabaceae) roots were assessed for the antacid activity by using self-fabricated modified artificial stomach model. Preface: Tephrosia calophylla and Tephrosia maxima are two medicinal plants prevalent to AndhraPradesh, Karnataka and Tamil Nadu. These two plants are used widely in folklore medicine for their antiulcer activity. Methodology: The preliminary chemical tests performed for the extracts showed the presence of tannins, flavonoids, glycosides, saponins and carbohydrates. Then they were evaluated for the antacid potencies by working on the parameters like determination of pH of the prepared extracts, neutralizing effects on artificial gastric acids, duration of consistent neutralization effect on artificial gastric acids and neutralization capacity. Two commercially available antacids were used as the standard. Outcome: The methanolic extract T.maxima showed potent antacid activity when compared to T.calophylla and the two standards. Hence T.maxima can be considered as a potent substitute for the synthetic antacids that are well reputed for unwanted side effects. Further investigations on in vivo preclinical and clinical studies are yet to be performed.

28-33

Authors: Siji MP, K. Krishna Kumar, K. Jayapraksah, L. Panayappan*

Plan: Antiplatelet drugs are the cornerstone in the treatment of cardiovascular disease. They remain the mainstay in preventing aberrant platelet activation in pathophysiological conditions like myocardial infarction, ischemia and stroke. Preface: According to consensus guidelines, early revascularization and intensive antiplatelet therapy are keyto reducing the complication that arises from myocardial ischemia and the recurrence of cardiovascular events. The different anti-platelets are aspirin,clopidogrel, ticagrelor, elinogrel, ticlopidine. Effective antagonism of the P2Y12 platelet receptor is central to the treatment of acutecoronary syndrome. Limitations in safety, efficacy and tolerability haveprecluded many of the antiplatelet inhibitors from use in patients. Unforeseen incidences of increased bleeding risk andrecurrent arterial thrombosis observed in patients have hampered thedevelopment of superior next generation antiplatelet therapies. Outcome: The effective antiplatelettherapy is important for the acute and secondary prevention of cardiovasculardisease. The newer antiplatelet agents will reduce the limitation of thecurrent therapy.

42-50

Authors: Preeti Garg and Akashdeep

Diabetes mellitus is a common and very prevalent disease affecting the citizens of both developed and developing countries. It is estimated that 25% of the world population is affected by this disease. Diabetes mellitus is caused by the abnormality of carbohydrate metabolism which is linked to low blood insulin level or insensitivity of target organs to insulin. In the present review we discussed about Herbal medicinal plants for the treatment of Diabetes mellitus.Herbs are used to manage Type 1 and Type II diabetes and their complications. This study may be useful to the health professionals, scientists and scholars working in the field of pharmacology and therapeutics to develop antidiabetic drugs.

1-2

Authors: Prof. Dr. Annie Shirwaikar

The use of herbal medicine has increased worldwide in recent years as they are believed to be safer with fewer adverse effects as compared to conventional medicines. Growing evidence points out that many current conventional drug therapies suppress the symptoms of disease while really ignoring the underlying processes , in contrariety to natural products which demonstrate better clinical results as they address the root cause more effectively. The full therapeutic potential of the herb is often,however, not realized because of unsuitable molecular size and/or poor lipid solubility,which in turn results in low absorption with reduced bioavailability. The poor progress in herbal medicine development has prompted the need for a multidisciplinary approach to drug delivery. For a long time a lack of scientific evidence,coupled with manufacturing problems like isolation and identification of individual pure phytocomponents and standardization deterred the development of herbal drugs and poly herbals as novel formulations. The need to increase patient compliance and to avert recurrent administration has necessitated a scientific approach in the development of these formulations. The novel drug delivery system technology has been useful in enhancing the bioavailability of herbal drug delivery systems. Novel carriers viz. liposomes, niosomes, nano-particles,lipid based systems etc. have been documented for successful modified herbal drug delivery.Some noteworthy advantages over the conventional herbal formulations include enhanced stability, solubility, bioavailability,pharmacological activity, sustained delivery etc.

10-17

Authors: P. Ragavendran, Radha A., Mariya Paul and D. Suresh Kumar*

Plan: Careya arborea is a medicinal plant used in Ayurveda and Chinese medicine. The bark, leaves and fruits are used in these systems for the treatment of ulcers, haemorrhoids and tumours. Several reports are available on the pharmacognosy of the leaf and bark of this medicinal tree. However, there is complete lack of information on the pharmacognosy of the fruit. The present paper is the first report on this subject. Methodology: Histology of the fruit and microscopy of the fruit powder were studied. Tests for identification of phytochemical compound classes were carried out on methanol extract of the fresh fruit. The chemical constitution of the fruits was studied using HPTLC and HPLC. Outcome: Phytochemical screening revealed the presence of alkaloids, flavonoids, phenols, tannins, sterols and fixed oils. The fruit contains high amount of phenols, of which, gallic acid is present at the rate of 0.92 ± 0.03%. The high content of gallic acid and reported antibacterial activities of the extract quality the fruit for further investigations.

28-37

Authors: Bandita Sarma1, Shamanna Mohan1, JanardhanSaravanan, Satyendra Deka*, Pallab Kalita, Nayan Talukdar, Bhargav Nimavat

Plan: Present work aims to synthesize a series of new benimidazoles (SBS-a-m) with various substitutions at 2-o-amino phenyl position and to evaluate their in-vitro antibacterial and anti-fungal activity. Prologue: Benzimidazole containing organic compounds forms a significant group of drugs which exhibit an array of biological activities ranging from antibacterial, antifungal, anti-inflammatory, analgesic, anthelmintic activities and so on. Methodology: The starting material SBS was synthesized by microwave irradiation of o-phenylenediamine and anthranilic acid mixture in presence of polyphosphoric acid. SBS was further derivatized to Schiff bases (SBS-a-m) by reacting with various substituted aromatic aldehydes. The in-vitro antibacterial and anti-fungal activity was carried out by the agar diffusion method using Ampicillin and Miconazole nitrate respectively as standards at a concentration of 50µg/0.1ml. Outcome: SBS-k was found to be most active on all the bacteria used and SBS-e showed good activity against both Gram-positive bacteria and moderate activity against both Gram-negative bacteria. No compound showed significant antifungal activity.

46-56

Authors: Francis M Saleshier*, Sajna Hameed, Jubina Karim, and Mythri.M

Plan: The present study focuses on the structure based drug design approach for anticancer activity of various substituted benzothiazoles whether as an EGFR TK inhibitor or as topoisomerase inhibitor. Preface: The development of novel therapeutic agents for the treatment of cancer is of vital importance since the currently available chemotherapeutic agents only provide palliative care. Benzothiazoles are multitarget agents with broad spectrum of biological activity. Topoisomerase II inhibitors are in clinical use as anticancer therapy for decades and works by stabilizing the enzyme induced DNA breaks. Methodology: Computer aided drug design brings out the molecular study of the enzymes and the various other targets, it opens the new world of drug discovery into a target specific path of a drug towards disease. The Insilico method mainly includes the target selection, selection of lead and the lead optimization. Outcome: Docking results confirmed the possibility of benzothiazole moiety possessing the anticancer activity. The structure was finally characterized by UV, IR, NMR and Mass spectra. In the present work the tumorigenic cell line activity of the substituted benzothiazole is compared with the two standard drugs Gefitinib and Doxorubicin by an Invitro assay against Dalton’s Lymphoma Ascites cell using trypan blue dye and percentage inhibition was calculated.

1-2

Authors: Shirley Samson Varghese

Pharmacovigilance (PV) is the science and activities relating to the detection, assessment,understanding and prevention of adverse effects or any other drug-related problem. WHO established its Programme for International Drug Monitoring in response to the thalidomide disaster detected in 1961 The aims of PV are to enhance patient care and patient safety in relation to the use of medicines;and to support public health programs by providing reliable, balanced information for the effective assessment of the risk-benefit profile of medicines. Though it was set in motion several decades ago, some countries still look upon PV as a ritual or a copycat strategy to comply with the International bodies. PV is not yet felt as an intrinsic need.......

5-16

Authors: A. Premkumar , T. Muthukumaran,V. Ganesan , Shanmugam R, Priyanka D.L

Plan: The main aim of our research was to develop a novel cream formulation consisting of combination of Miconazole nitrate, Mupirocin and Hydrocortisone for the treatment of secondary skin infections. Prologue: Topical route is most suitable route for skin infections. The development of topical drug delivery systems designed to have systemic effects appears to be beneficial for a number of drugs on account of the several advantages over conventional routes of drug administration. Methodology: A novel cream formulation consisting of combination of Miconazole nitrate, Mupirocin and Hydrocortisone was prepared. The formulation was subjected to in-vitro diffusion studies. Microbiological studies and in-vivo skin irritation studies were performed to find out the safety of materials used in the formulation. Outcome: The developed cream consisting of combination of Miconazole nitrate, Mupirocin, and Hydrocortisone was found to be safe and effective for the treatment of skin infections.

25-35

Authors: Manjula Devi A. S, Bittu Thomas, Annu Joseph, Kavuri Sravani.

Plan: To assess the incidence of inappropriate dosing of renally excreted drugs in hospitalized patients with renal impairment. Preface: Inappropriate dosing in patients with renal dysfunction can cause drug accumulation and toxicity. Method: Creatinine clearance or estimated glomerular filtration rate of patients with serum creatinine greater than 1.7 mg% was calculated using Cockroft-Gault equation and Modified Diet in Renal Disease equation respectively. Dose of all potentially nephrotoxic drugs was evaluated using the published drug dosing guidelines and the new dose or dosing interval was recommended based on the patient’s individual degree of renal impairment. Outcome: Five hundred and six drugs in 50 patients were evaluated of which the dosages of 88 (17.39%) drugs were not adjusted at the time of prescribing. Most of the drugs requiring dose adjustment were antibiotics (39.77%) and antihypertensives (14.77%). About 27% of the drugs were to be avoided strictly. Conclusion: Drug dosing evaluation and concurrent feedback mechanism by the pharmacist improve drug safety in patients with renal impairment.

45-56

Authors: Srinivasan.N and Sathyanarayana.D

Plan: A preliminary Pharmacognostical study on the leaves and stems of Indigofera barberi Gamble Methodology: The Indigofera barberi Gamble leaves and stems were collected, in the forest regions of Thalakona (Nelakona regions) of Chittoor district, Andhra Pradesh, India in the month of November. The collected drug were dried and studied to determine various Pharmacognostical parameters such as macroscopy, microscopical characters of leaf and stems including its powder microscopical characters. The shade dried powder and various solvent extracts (viz., petroleum ether, chloroform, dichloromethane ethanol and water) have been analysed for their phytochemicals, behaviour of powder with different chemical reagents and fluorescence characters. Outcome: The data generated for the Pharmacognostical evaluation on Indigofera barberi Gamble leaves and stems. The results may be useful as a reference material in the preparation of standard monograph.

71-91

Authors: Mohannad A. Elkhider and Bob Chaudhuri

Plan: This review focus on the role of autophagy, in up regulation, in the innate and adaptive immune response, in controlling carcinogenesis, and in supporting neuronal cell growth, development & remodeling. Also the review covers the therapeutic interventions involved in the cancer management through autophagy modulations. Preface: Autophagy is a cellular degradative pathway where un wanted and weary cytosolic components are recycled. Any defects interfering with theintegrity of the autophagic machinery would compromises the cells defensesleaving the cell susceptible to infection by circulating pathogens. Currentliterature points out that the dysregulation of autophagy may be associatedwith the genesis of cancer. Accumulation of aberrant organelles and proteinsincreases the chances of triggering an inflammatory microenvironment favoringchromosomal instability and mutagenesis. The aggregation of certain proteinsyields cellular toxicity which eventually leads to cell death andneurodegeneration. Therefore, the autophagic duty of continuously monitoringand clearing out aggregated proteins isindispensable in neuronal cells. Outcome: The accumulation of autophagosomes is an established assurance in a number of neuro degenerative diseases. However, this observation has triggered controversy whereas one opinion considers the activated autophagic pathway to act as an executioner by initiating neuronal cell death while the other explains the presence of autophagosomes as a final attempt by the cell to sustain viability against the increasing amount of stress.

1-3

Authors: Prof.Dr.MK.Unnikrishnan

There was a time when fairly descriptive accounts were considered good enough to evaluate people, situations and outcomes. But not anymore! The clamour for transparency, accountability and equal opportunity have increased the democratic burden in the dispensation of justice. In India,for instance, it has become essential to rank a candidate’s entrance examination scores down to the second or third decimal for allotting a medical seat. Such absurd demands for accuracy in day to day transactions brings to my mind a good friend of mine, back home in my village, who depended on agriculture for his livelihood. He used to sport a curious vintage HMT watch, (analog of course)with only the hour hand. For some reason, he had not bothered to replace the broken minute hand. When I asked him why, he said that minutes do not matter to a farmer. “We think in seasons... I do not even need a watch. A calendar is more than enough to work in the farm. “

6-11

Authors: Shini Dominic * and V. Padmaja

Plan: To verify the effect of Amlodipine on 3 β HSD gene expression in rat testis and its modification upon stopping the drug / co administration of Astercantha longifolia seed extract. Preface: Though a few data are available on the potential of Amlodipine to adversely affect and that of Astercantha longifolia seeds to potentiate the male reproductive parameters, no studies are available on the effect of these on gene expression. Methodology: Different groups of rat were treated orally with Amlodipine and Amlodipine plus Astercantha longifolia seed extract. After treatment the Amlodipine treated group was kept untreated for recovery. Finally total RNA from all groups were extracted and PCR for 3 β HSD gene was performed and products were analyzed by gel electrophoresis. Outcome: Amlodipine treated groups showed down regulation of 3 β HSD expression but the same could be reversed after the recovery period of about 67 days. In groups treated with Amlodipine and Astercantha longifolia seed extract, 3 β HSD expression was up regulated in a dose dependent manner. It may be concluded that as 3 β HSD is involved in the conversion of cholesterol to testosterone, the decrease / increase in testosterone level may be due to the down / up regulation of 3 β HSD expression .

20-24

Authors: Manjima Prabhakaran, Bincy Reejo, D. Suresh Kumar*

Plan: The present study was planned to investigate the antibacterial activity of ethyl acetate,ethanol and hexane extracts of the fruits of Careya arborea Roxb. Methodology: Agar diffusion assay was carried out using the extracts. Outcome: All the tested bacterial strains viz., Escherichia Coli, Salmonella typhimurium, Listeria monocytogenes, Staphylococcus aureus and Staphylococcus epidermis) were found to be sensitive to all the 3 concentrations of ethyl acetate and methanolic extracts of fresh and dry fruit, in ascending order.

31-39

Authors: M.Nithya*V. , Ambikapathy and A.Panneerselvam.

Plan: In this study 10 strains of mushroom Ganoderma lucidum were collected from various places and decided to screen their phytotoxicity activity and phytochemical constitution. Preface: The popular mushroom Ganoderma lucidum (Reishi) was a bracket fungus and has been widely used for the promotion of health and longevity in Asian countries. The Dried powder of G.lucidum was popular as a cancer chemotherapy agent in ancient China. G.lucidum clearly demonstrated anticancer activity in experiments with cancer cells and has possible therapeutic potential as a dietary supplement or alternative therapy for breast and prostate cancer. And also the fruiting bodies of Ganoderma lucidum (Polyporaceae) are a well known Chinese crude drugs identified as a phytotoxic agent. However, since G.lucidum was available from different sources, it is advisable to test its biological activity. Methodology: G.lucidum strains collected was isolated and identified with potato dextrose agar medium. Then The secondary metabolites were qualitatively studied through phytochemical analysis. Outcome: Significant root length inhibition was observed at 100 ppm and 200 ppm. Similarly seed germination was also significantly inhibited at the concentration 100 ppm and 200 ppm extracts. The mean data of root length inhibition by ethanol extract in 100 ppm was 0.393 and 0.208 in 200ppm. Likewise the mean data of seed germination inhibition by ethanol extract in 100 ppm was 15 and 0.208 in200ppm. Overall Results supported that Ganoderma lucidum clearly supported the wider medicinal uses and established its anticancer activity.

48-62

Authors: J.Jayapal , A.C.Tangavelou , and A.Panneerselvam

Plan: Muniandavar Sacred Groves from Vaduvakudi at Thiruvaiyaru Taluk, Thanjavur district of Tamil Naduwas selected for floristic exploration to know the plant diversity of the vegetation,the availability of rare and endangered floras, the ecological significance,regeneration status and the anthropogenic pressures, to document the religiousbeliefs and spirituality and the participation of locals on conservation. Outcome : In the present study, theflora of Muniandavar Sacred Groves comprises about 180 plant species belongingto 158 genera and 75 plant families, Key stone species available in the Sacredgroves includes Anacardium occidentale, Borassus flabellifer, Ficusbenghalensis that harbors a number of birds and other survival of many otherspecies. Muniandavar sacred grove is in good vegetation status and theconservationists should take necessary action to protect this grove fromplastic pollution. An environmental awareness programme is planned to conductfor the local people in order to safeguard this sacred grove from pollution.

74-80

Authors: A.Radha, Jessy Sebastian, Manjima Prabhakaran and D. Suresh Kumar*

Plan: Ayurveda makes use of many Kvatha or hot infusions. In olden days the physician provided a handwritten recipe of the Kvatha in question and patients prepared these medicines at home. However, this tradition ended with the advent of commercial manufacture of Ayurvedic medicines in Kerala since 1902.Considering the growing popularity of Ayurveda, an attempt was made tocompare the quality of seven brands of Maharasnadi Kvatha, a formulation that is widely recommended by physicians. Methodology: Seven brands of MaharasnadiKvatha available in the local market were procured. Their pH, total dissolved solids, sodium benzoate content, HPTLC profiles and microbial load were measured. Additionally, the presence of alkaloids, tannins, phenols, and sterols was detected qualitatively. Total tannins, alkaloids, phenols and sterols were estimated. Outcome: The colour of the seven brands,their pH, total dissolved solids, sodium benzoate content, HPTLC profiles,microbial load and content of compound classes showed wide variation. HPTLC fingerprinting can serve as a useful technique to assess the quality of Ayurvedic medicines. The number of bands and their area percentages can serve as quality indices. Such methods can be used for improving the quality of Ayurvedic medicines.

95-105

Authors: S. Lakshmi Devi * and Madhu.C.Divakar

Plan:The present study aims to facilitate an updated phytochemical and pharmacological activity study reports of various researchers pertaining to the plant Wrightia tinctoria. Preface:Wrightia tinctoria (Roxb.) R. Br (Apocynaceae) is widely distributed in the plains and slopes of Shevaroy hills of Yercaud Town, situated in Salem district, Tamilnadu. Wrightia tinctoria is extensively used in a number of traditional medicines. Outcome:Chemical constituents isolated from different parts ofthe plant W. tinctoria and their biological activities reported are summarized in this review.

111-121

Authors: Konstantinos M. Kasiotis

Plan:This study includes the characteristics and variation of non volatile constituents in propolis samples collected from different regions of the world. The review covers the research activities after 2010 on propolis constituents. Outcome: Propolis constitutes a complex resinous material collected by honeybees serving as a defense system for their hives. Apart from this evident natural use, propolis is marketed by the pharmaceutical industry due to its claimed beneficial effects on human health such as antioxidant,antibacterial, antiviral and anticancer activities. These properties are attributed to the chemical compounds that are found in propolis mainly phenolic compounds and terpenes. In this review article the analysis of non-volatile compounds of propolis performed by high performance liquid chromatography (HPLC) coupled with various detectors, will be presented. Future trends and further insights are quoted and commented.