Exploring the Therapeutic Potential of Anti-VEGF Drugs for the Management of Diabetic Retinopathy: An Overview.

The discovery of antivascular endothelial growth factor medications has resulted in a substantial change in diabetic retinopathy treatment. The most common cause of diabetic retinopathy blindness is Diabetic Macular Edema. The pathophysiology of Diabetic Macular Edema is thought to include the well-known pro-angiogenic and pro-permeability factor vascular endothelial growth factor. Over the past decade, drugs that impede the functions of vascular endothelial growth factors have established themselves as a standard-of-care treatment for a range of ocular ailments and improved patients' clinical results with diabetic retinopathy and Diabetic Macular Edema, and their frequency has grown exponentially with the introduction of these agents Pegaptanib, Ranibizumab, and Aflibercept which are approved for ophthalmic indications, while Bevacizumab is used off-label. These medications delivered intravitreally have halted the vascular development of diabetic retinopathy. Various randomized trials have proven that antivascular endothelial growth factor medication is safe and effective in preserving vision. Following an extensive period of preclinical development aimed at enhancing and defining its biological impacts, these drugs were shown in clinical trials to be effective in treating diabetic retinopathy and other ophthalmic conditions. Data from various sources suggest that Pegaptanib, Ranibizumab, and Aflibercept are costly, while Bevacizumab is cost-effective, and in low and middle-income nations, it is thus a desirable therapy choice. However, issues with compounding, counterfeiting, and off-label usage restrict its availability in many nations. The pharmacology, pharmacokinetics, pharmacodynamics, adverse effects, and contraindications of antivascular endothelial growth factor agents are discussed, and the results of clinical trials evaluating their efficacy are summarized.

Impact of prediabetes education program on Knowledge, attitude and practice among prediabetic population of south India.

Education plays a vital role not only in the management of diabetes but also for the effective prevention of diabetes and its complications. Prediabetes awareness and knowledge is grossly inadequate in India and massive prediabetic screening and management programs are urgently needed. This study was an initiative to conduct education program among the prediabetic subjects after assessment of their knowledge attitude and practice using a newly developed and validated prediabetes questionnaire. A total of 308 prediabetic participants were recruited through prediabetes screening camps conducted in the selected districts of Kerala and Tamilnadu. A newly developed and validated KAP-PAQ Questionnaire was used to analyze the Knowledge Attitude and Practice among the prediabetic population. The impact of Prediabetes Education Program was assessed by administration of questionnaire before and after PEP with an interval period of 30 days. Baseline assessment of knowledge among prediabetics shown that 90% had poor knowledge but after PEP program 43% had average knowledge and 44% could score good knowledge. Baseline assessment of attitude exhibited 30% with negative attitude but after counseling 68% shown positive attitude. Regarding practice assessment 35% had very poor and 52% shown poor practice but after PEP 71% shown good practice and 15% shown very good practice. Baseline KAP survey shows the need for health literacy among the newly diagnosed prediabetics. Prediabetes education program could bring significant improvement in knowledge attitude and practice and KAP-PAQ was found to be an efficient tool to conduct survey among the newly diagnosed prediabetics of south India.

Assessment of Adverse Drug Reactions Based on Spontaneous Signals at Secondary Care Public Hospital.

Adverse drug reactions are considered to be among the leading causes of morbidity and mortality. Approximately 5-25% of hospital admissions are due to adverse drug reactions and 6-15% of hospitalized patients experience serious adverse drug reactions, causing significant prolongation of hospital stay. Thus this study was aimed at determining adverse drug reactions by conducting spontaneous reporting in secondary care Govt. District Head Quarters Hospital at Ooty. A prospective Spontaneous Adverse Drug Reaction reporting study was conducted over a period of 12 months from July 2012 to June 2013. The assessment, categorization, causality, severity and preventability were assessed using standard criteria. A total of 47 suspected adverse drug reactions were reported during the study period. Over all incidences was 1.29% among the study population. Antibiotics (31.91%) were the class of drug most commonly involved, while ciprofloxacin (14.89%) was the most frequently reported. Type H (Hypersensitivity) reactions (51.06%) accounted for majority of the reports and a greater share of the adverse drug reactions are probable (89.36%) based on causality assessment. Mild reactions accounted 82.97% based on modified Hartwig and Siegel severity scale. In 76.59% of the reports, the reaction was considered to be preventable based on Schumock and Thornton preventability scale. The implementation of monitoring based on spontaneous reporting will be useful for the detection and evaluation is associated with increase in morbidity and duration of hospitalization. This study also has established the vital role of clinical pharmacist in the adverse drug reaction monitoring program.

Toxicoepidemiology of acute poisoning cases in a secondary care hospital in rural South India: A five-year analysis.

OBJECTIVE: To ascertain the trend of poisoning cases admitted to the Government District Headquarters Hospital, a secondary care center in Udhagamandalam, Nilgiris District, Tamil Nadu, India, over a five-year period. MATERIALS AND METHODS: The number of cases that presented to the hospital annually (incidence, mortality, and case fatality rates), socio-demographic pattern, and the nature of the poison were noted. RESULTS: A total of 1860 poisoning cases (80 deaths) were reported during the period from October 2008 to September 2013. The incidence of poisoning was found to increase every year. The average incidence was 1.60 per 1000 population, while the average case fatality rate and mortality rates were 40.51 and 0.07, respectively. A total of 1148 (62%) were males. The majority of cases were seen in the 21-30 age group (41.24%). The poisonings were largely deliberate self-harm (n = 1,755; 94.35%), followed by accidental (n = 85; 4.57%). Agrochemicals were the main choice of poisoning agents and among these, organophosphates were the major cause. CONCLUSION: The data generated can help policy makers take decisions on the sale and availability of pesticides in this region.

Newer therapies for the treatment of metastatic breast cancer: a clinical update.

Breast cancer is the foremost common malignancy among the female population around the world. Female breast cancer incidence rates have increased since 1980, slowed in 1990, the rate of increase have leveled off since 2001. In spite of the advances in the early detection, treatment, surgery and radiation support, almost 70% of the patients develop metastasis and die of the disease. Around 10% of the patients when diagnosed with breast cancer have metastases. Survival among the breast cancer patients have increased due to the introduction of novel single agent, combination of chemotherapeutic agents and targeted biologic agents, which is breast cancer specific. The staging of tumor-node-metastasis is significant for the prognosis and treatment. Predominantly the combination of chemotherapeutic regimen is given to improve the rate of clinical benefit and the overall survival rate. Novel mono-therapeutic options are being used often in metastatic setting as they will not be able to endure the toxicity of the combination regimen. Usually, endocrine therapy is recommended for hormone-responsive breast cancer due to efficacy and favorable side effect profile but chemotherapy becomes an option when endocrine therapy fails. This review summarizes the newer therapeutic options for early breast cancer and advanced breast cancer that are pretreated heavily on other chemotherapeutic agents. Further it provides monotherapies and other emerging novel combination regime which can be opted for first line or second line setting.

Calotropis gigantiea (L.) R. Br (Apocynaceae): a phytochemical and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Calotropis gigantiea (L.) R. Br (Apocynaceae) commonly called as "crown flower" or "giant milk weed" is a well-known weed to many cultures for treating various disorders related to central nervous system, skin diseases, digestive system, respiratory system, reproductive system etc. Indigenous groups made the plant as a part of their lives since they use the fruit fibre to make ropes, household items, for weaving clothes and flowers for garlands apart from usage for various indications. The study aims at far-reaching review on phytochemistry, pharmacological activities, ethnopharmacology, intellectual property transfer on pharmacological therapies, toxicity which aids to provide scientific evidence for the ethnobotanical claims and to identify gaps required to be conducted as a future research prerequisite. MATERIALS AND METHODS: A systematic literature search was performed using different databases such as Scopus, Science direct, PubMed and Sciverse with no timeline limit set during the search. All the available abstracts and full text articles were included in the systematic review. RESULTS: Most of the folkloric uses were validated by the scientific studies such as analgesic, anti-arthritic, anti-asthmatic, anti-bacterial, anti-convulsant, anti-pyretic, central nervous system disorders, contraceptive, anti-ulcer and wound healing. In addition other studies such as anti-diabetic, anti-diarrhoeal, anti-helminthic, anti-histamine, anti-inflammatory, anti-microbial, anti-oxidant, cardio-protective studies, cytotoxicity, hepatoprotectivity, fibrinolytic, mosquitocidal, nerve muscle activity, vasodilation and skeletal muscle activities were also reported for the plant. Isolated compounds such as calotropin, frugoside and 4'-O-ß-D-glucopyranosyl frugoside were tested for the cytotoxicity efficacy against both human and rat cell lines out of which calotropin showed potent activity (IC50-15 ng/ml). However there were no clinical trials reported on the plant which is one of the major lacunas. CONCLUSIONS: This review article explores the ethnopharmacological, pharmacological activities phytochemistry and intellectual rights of Cg which gives the evidence of a potent and commercial drug which up on further research leads to the most viable drug for variety of treatments. However there is further need for in-vivo studies and clinical trials on isolated phytoconstituents which will help to commercialise.

Botanicals as medicinal food and their effects on drug metabolizing enzymes.

Botanicals fall under different regulations in different countries and are mostly consumed without the consultation of the healthcare professional. Over the last decade, utilization of herbal therapies has been extensively documented. The findings indicate the possibility of potential herb-drug interactions due to the concomitant administration of herbal extracts and prescription/over-the-counter drugs. Simultaneously, with the increasing public awareness and search for safer herbal remedies, the study on herbal-drug interactions has gained momentum through the study of drug metabolizing enzymes. Cytochrome P450 (CYP) inhibition or induction is probably the most common mechanism for the pharmacokinetic interactions of herbs and drugs. Any inhibition of CYP enzymes by herbal extracts may result in enhanced plasma and tissue concentration of drugs, leading to toxicity, while induction results in reduced drug concentration leading to decreased drug efficacy and treatment failure. Considering the rapidly growing herbal markets, these types of clinical interactions remain under-reported and unclear. With the increasing consumption of herbal extracts along with prescription medicines, the safety of herbs has become a concern. This article reviews the potential for drug interactions by herbal extracts through drug metabolizing enzymes.

RP-HPLC-DAD for simultaneous estimation of mahanine and mahanimbine in Murraya koenigii.

Murraya koenigii leaves (Rutaceae) are widely used as food condiments in various food preparations in India. They possess a wide range of biological activities including antioxidant, antibacterial, anticancer, hypoglycemic and hypolipidemic activity. A rapid reverse-phase high-performance liquid chromatography (RP-HPLC) method has been developed for quantitative estimation of mahanine and mahanimbine, two major bioactive alkaloids in this plant. The amounts of mahanine and mahanimbine were detected as 9.56 ± 1.04 and 4.32 ± 0.81% w/w in the extract, with the retention times of 6.26 ± 0.66 and 10.40 ± 0.95 minutes. The limits of detection and quantification were estimated to be 29.30 and 81.12 µg/mL and 1.67 and 6.31 µg/mL, respectively. This specific and precise validated method can be useful for the routine analysis and quantitative determination of mahanine and mahanimbine in this therapeutically potent medicinal plant.

Cytochrome P450 inhibitory potential of Triphala--a Rasayana from Ayurveda.

ETHNOPHARMACOLOGICAL RELEVANCE: 'Triphala' is one of the age-old, most commonly used polyherbal preparation from Ayurveda as Rasayana drug. AIM OF THE STUDY: This study was aimed at evaluating the effect of 'Triphala' on drug modulating enzymes to assess its safety through its potential to interact with co-administered drugs. MATERIALS AND METHODS: The cytochrome P450 inhibitory effect of 'triphala' formulation was investigated on rat liver microsomes using CYP450-CO complex assay and on individual isoform such as CYP3A4 and 2D6 using fluorescence screening. RP-HPLC method was developed to standardize 'triphala' and its individual components using gallic acid as analytical marker compound. RESULTS: RP-HPLC analysis demonstrated the presence of gallic acid (4.30±2.09 mg/g) in the formulation. The formulation showed 23% inhibition of the rat liver microsomes through CYP450-CO complex assay which is comparatively less when compared with the individual components. Further, the effect of standardized formulation dissolved in ethanol showed CYP3A4 and CYP2D6 inhibitory activity at the IC(50) values of 119.65±1.91 µg/ml and 105.03±0.98 µg/ml respectively. Gallic acid was also found to inhibit both the isoforms at the IC(50) values of 87.24±1.11 µg/ml and 92.03±0.38 µg/ml respectively. CONCLUSIONS: Various concentrations of the formulation and its individual components showed significantly less inhibitory activity (p<0.001) on individual isoforms when compared with the positive control. Assessment on the in vitro effect of 'triphala' on drug modulating enzymes has important implications for predicting the likelihood of herb-drug interactions if these are administered concomitantly.

Cytochrome P450 inhibition assay for standardized extract of Terminalia chebula Retz.

The hydroalcoholic extract of fruit pulp of Terminalia chebula Retz. was standardized and evaluated for its safety through cytochrome P450 (CYP 450) inhibition assay. Standardization was performed through high performance thin layer chromatography (HPTLC) using gallic acid (GA) standard. Cytochrome P450-CO complex microplate assay was performed using rat liver microsomes. The effect of standardized extract, its fraction and bioactive marker compound were comparatively evaluated for its effect on CYP P450 enzymes. The extract of fruit pulp was used for HPTLC, where the R(f) value of the marker was found to be 0.43. The calibration plot was linear in the range of 2-14 µg of GA and correlation co-efficient of 0.99965. The mean quantity of GA was found to be 2.5% w/w. The CYP P450 concentration of the rat liver microsome sample used in the study was found to be 0.417 nmol/mg protein. The in vitro effect of various concentrations of extracts and fractions showed a linear concentration-dependent inhibition of cytochrome P450 up to 60 µL. The study showed more inhibition of fraction when compared to the extract and GA. Still, the inhibition showed by fraction is less when compared with standard Ketoconazole. Thus, this study indicated the in vitro cytochrome P450 inhibition potential of T. Chebula.

Ethnopharmacology and integrative medicine - Let the history tell the future.

Traditional systems of medicines need more evidence-based studies on both crude drugs and purified phytomolecules. Utilization of natural products as pharmacological tools could lead to a number of new major therapeutically active metabolites. Lead molecules are further screened for their potential in terms of quality control, safety assessments, and studies about molecular pharmacology and their related properties. Identification, and quality and safety evaluation of natural products, is a fundamental requirement of industry and other organizations dealing with natural health products (NHPs). Marker analysis, based on chemo-profiling and development of characteristic fingerprints for individual plants, could help to develop uniform standardization tools. Beside such evaluations of clinical parameters, safety profiles as well as drug-herb and herb-herb interactions are the most important parameters for assessment and promotion. With the steady growth of the NHPs, advanced analytical- and mechanism-based screening should be considered for their promotion and value addition in every way for the betterment of healthcare. Thus, there is an urgent need for the development of international co-ordination to promote and develop NHPs, including their assessment, perspectives, pharmacovigilance, and potential harmonization of regulation, quality control and clinical uses.

Antioxidant activity of Hypericum hookerianum Wight and Arn.

Methanolic extracts of leaf, root, flower and aerial parts of Hypericum hookerianum were assessed for in vitro antioxidant activity using eight different models. Total antioxidant capacity, phenol and flavanol content of the extracts were determined to correlate between their antioxidant activity and constituents present therein. Results of in vitro antioxidant study suggest that extracts from leaf and flower have strong antioxidant potential. Leaf extract (100 & 200 mg kg(-1) b.w. p.o.) that showed maximum activity was selected for in vivo antioxidant studies using a CCl(4)-intoxicated rat model. The effects of extracts on lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) in serum and liver homogenate were analysed. CCl(4) treatment caused a significant increase in the level of CAT and SOD and a significant decrease in the level of LPO in a dose-dependent manner when compared to CCl(4) treated control. The results indicate the strong antioxidant nature of H. hookerianum leaf extract.

Lead finding from medicinal plants with hepatoprotective potentials.

BACKGROUND: Several lead compounds have been developed from natural resources as hepatoprotective. The hepatotoxic nature of the drugs, industrial toxins and drug-induced hepatotoxicity has been recognized as the major problem associated with liver diseases. Natural products including herbs have great potential in treating liver disorders. OBJECTIVE: Botanicals have been used traditionally by herbalists and indigenous healers worldwide for several years for the prevention and treatment of liver disease and clinical research in this century has confirmed the efficacy of several plants in the treatment of liver disease. Many herbs used in several systems of alternative medicines have a long history of traditional use in revitalizing the liver and treating liver dysfunction and disease. Many of these herbs have been evaluated in clinical studies and are now being investigated phytochemically to understand their actions in a better way. CONCLUSION: An attempt has been made through this article to review the most potential medicinal plants with pharmacologically established hepatoprotective activity. Further, this article highlights their phytochemical profile and finds the effective leads from natural resources for the desired therapeutic benefit.

A study on the preparation and anti-tumor efficacy of bovine serum albumin nanospheres containing 5-fluorouracil.

The therapeutic profile of many anti-cancer drugs has been improved by their modified distribution through a colloidal carrier system. Hence, bovine serum albumin nanospheres containing 5-fluorouracil were prepared by pH-coacervation methods. To select the most suitable cryoprotector for the formulated nanosphere system, a study on the effect of cryoprotectors in the prevention of particle agglomeration was done. Using glucose and mannitol at various concentrations during freeze drying, glucose at a concentration of 5% was observed to be relatively more effective in the prevention of particle agglomeration than the other cryoprotectors. The carrier capacity was determined through the drug-to-albumin ratio. The particle size of all the drug-loaded batches was analyzed before and after freeze drying. The batch of nanospheres with uniform size distribution, and highest drug loading, was used for other subsequent studies. The effect of surfactant in drug loading was estimated through various concentrations of sodium lauryl sulfate, and it was observed that the surfactant has no influence on drug loading at the selected concentrations. The batch of nanospheres with highest drug loading was evaluated for its in-vitro release, and the drug release was found to be in a bi-phasic pattern. To evaluate the efficacy of 5-fluorouracil-loaded nanospheres against cancer cells, an in vitro cytotoxicity study was carried out using HEp-2 cell lines. The nanosphere-bound drug was observed to produce a better cytotoxic effect than the free drug. The anti-tumor efficacy of drug-loaded nanosphere was investigated in DLA tumor-induced mice models, and the percentage tumor inhibition was relatively higher in animals treated with nanosphere-bound drug than with free drug.

Study of biodistribution of methotrexate-loaded bovine serum albumin nanospheres in mice.

Nanospheres made from natural hydrophilic polymers have been proved efficient in terms of better drug-loading capacity, biocompatibility, and possibility less opsonization by reticuloendothelial system (RES) through an aqueous stearic barrier. Hence, nanospheres containing methotrexate were prepared from bovine serum albumin (BSA) by a novel pH coacervation method. A drug-to-polymer ratio study was carried out to determine the carrier capacity. The batch with the highest drug loading was subjected to in vitro analysis. It was found to provide a slow release after an initial burst release. Biodistribution of nanosphere-bound drug was compared with that of free drug in mice. It was observed that the percentage increase in drug distribution to the lungs, liver, and spleen was markedly high from the nanosphere when compared to free drug.

Nonliposomal approach--a study of preparation of egg albumin nanospheres containing amphotericin-B.

The stability of liposomes after introduction into the body is presently being discussed and needs thorough understanding. Hence, as a nonliposomal approach, egg albumin nanospheres were prepared by the pH-coacervation method, and a preliminary study was carried out of the influence of process variables on the size and shape of nanospheres by changing the pH of the albumin solution, concentration of albumin solution, and volume of cross-linking agent. The batch prepared with an albumin medium of pH 9, 2% concentration, and 100 microliters of 4% glutaraldehyde-ethanol solution was found to have a spherical uniform shape with an average size of 497.6 nm. The ideal batch was loaded with the systemic antifungal drug amphotericin-B. Drug-loaded nanospheres were evaluated to study their in vitro release. They were found to exhibit a biphasic pattern with a cumulative percentage release of 97.7%.