Computer Modeling of Drug Distribution after Intravitreal Administration

Intravitreal injection (IVI) is the most common treatment for eye posterior segment diseases such as endopthalmitis, retinitis, age-related macular degeneration, diabetic retinopathy, uveitis, and retinal detachment. Most of the drugs used to treat vitreoretinal diseases, have a narrow concentration range in which they are effective, and may be toxic at higher concentrations. Therefore, it is critical to know the drug distribution within the eye following intravitreal injection. Having knowledge of drug distribution, ophthalmologists can decide on drug injection frequency while minimizing damage to tissues. The goal of this study was to develop a computer model to predict intraocular concentrations and pharmacokinetics of intravitreally injected drugs. A finite volume model was created to predict distribution of two drugs with different physiochemical properties in the rabbit eye. The model parameters were obtained from literature review. To validate this numeric model, the in vivo data of spatial concentration profile from the lens to the retina were compared with the numeric data. The difference was less than 5% between the numerical and experimental data. This validation provides strong support for the numerical methodology and associated assumptions of the current study.

Packaging the Alkaloids of Cinchona Bark in Combination with Etoposide in Polymeric Micelles Nanoparticles

Today, cancer remains one of the major diseases that lead to death. The main obstacle in chemotherapy as a main cancer treatment is the toxicity to normal cells due to Multidrug Resistance (MDR) after the use of anticancer drugs. Proposed solution to overcome this problem is the use of MDR efflux inhibitor of cinchona alkaloids which is delivered together with anticancer drugs encapsulated in the form of polymeric nanoparticles. The particles were prepared by the hydration method. The characterization of nanoparticles was particle size, zeta potential, entrapment efficiency and in vitro drug release. Combination nanoparticle size ranged 29-45 nm with a neutral surface charge. Entrapment efficiency was above 87% for the use quinine, quinidine or cinchonidine in combination with etoposide. The release test results exhibited that the cinchona alkaloids release released faster than that of etoposide. Collectively, cinchona alkaloids can be packaged along with etoposide in nanomicelles for better cancer therapy.

Proactive Identification of False Alert for Drug-Drug Interaction

Researchers of drug-drug interaction alert systems have often suggested that there were high overridden rate for alerts and also too false alerts. However, research about decreasing false alerts is scant. Therefore, the aim of this article attempts to proactive identification of false alert for drug-drug interaction and provide solution to decrease false alerts. This research involved retrospective analysis prescribing database and calculated false alert rate by using MYSQL and JAVA. Results of this study showed 17% of false alerts and the false alert rate in the hospitals (37%) was more than in the clinics. To conclude, this study described the importance that drug-drug interaction alert system should not only detect drug name but also detect frequency or route, as well as in providing solution to decrease false alerts.

Determination of in Vitro Susceptibility of the Typhoid Pathogens to Synergistic Action of Euphorbia Hirta, Euphorbia Heterophylla and Phyllanthus Niruri for Possible Development of Effective Anti-Typhoid Drugs

Studies were carried out to determine the in vitro susceptibility of the typhoid pathogens to combined action of Euphorbia hirta, Euphorbia heterophylla and Phyllanthus niruri. Clinical isolates of the typhoid bacilli were subjected to susceptibility testing using agar diffusion technique and the minimum inhibitory concentration (MIC) determined with tube dilution technique. These isolates, when challenged with doses of the extracts from the three medicinal plants showed zones of inhibition as wide as 26±0.2mm, 22±0.1mm and 18±0.0mm respectively. The minimum inhibitory concentration (MIC) revealed organisms inhibited at varying concentrations of extracts: E. hirta (S. typhi 0.250mg/ml, S. paratyphi A 0.125mg/ml, S. paratyphi B 0.185mg/ml and S. paratyphi C 0.225mg/ml), E. heterophylla (S. typhi 0.280mg/ml, S. paratyphi A 0.150mg/ml, S. paratyphi B 0.200mg/ml and S. paratyphi C 0.250mg/ml) and P. niruri (S. typhi 0.150mg/ml, S. paratyphi A 0.100mg/ml, S. paratyphi B 0.115mg/ml and S. paratyphi C 0.125mg/ml). The results of the synergy between the three plants in the ration of 1:1:1 showed very low MICs for the test pathogens as follows S. typhi 0.025mg/ml, S. paratyphi A 0.080mg/ml, S. paratyphi B 0.015mg/ml and S. paratyphi C 0.10mg/ml with the diameter zone of inhibition (DZI) ranging from 35±0.2mm, 28±0.4mm, 20±0.1mm and 32±0.3mm respectively. The secondary metabolites were identified using simple methods and HPLC. Organic components such as anthroquinones, different alkaloids, tannins, 6-ethoxy-1,2,3,4-tetrahydro-2,2,4-trimethyl and steroids were identified. The prevalence of Salmonellae, a deadly infectious disease, is still very high in parts of Nigeria. The synergistic action of these three plants is very high. It is concluded that pharmaceutical companies should take advantage of these findings to develop new anti-typhoid drugs from these plants.

A Comparison on Healing Effects of an Ayurvedic Preparation and Silver Sulfadiazine on Burn Wounds in Albino Rats

To compare Healing Effects of an Ayurvedic Preparation and Silver Sulfadiazine on burn wounds in Albino Rats. Methods: Albino rats– 30 male / female rats weighing between 150-200 g were used in the study. They were individually housed and maintained on normal diet and water ad libitum. Partial thickness burn wounds were inflicted, on overnight-starved animals under pentobarbitone (30mg/kg, i.p.) anaesthesia, by pouring hot molten wax at 80oC into a plastic cylinder of 300 mm2 circular openings placed on the shaven back of the animal. Apart from the drugs under investigation no local/ systemic chemotherapeutic cover will be provided to animals. All the animals were assessed for the percentage of wound contraction, signs of infection, scab formation and histopathological examination. Results: Percentage of wound healing was significantly better in the test ointment group compared to the standard. Signs of infection were observed in more animals in the test ointment group compared to the standard. Scab formation also took place earlier in the test ointment group compared to standard. Epithelial regeneration and healing profile was better in the test ointment compared to the standard. Moreover the test ointment group did not show any raised margins in the wound or blackish discoloration as was observed in silver sulfadiazine group. Conclusion: The burn wound healing effect of the ayurvedic ointment under study is better in comparison to standard therapy of silver sulfadiazine. The problem of infection encountered with the test ointment can be overcome by changing the concentrations and proportions of the ingredients in the test ointment which constitutes the further plan of the study.

Anti-microbial Activity of Aristolochic Acid from Root of Aristolochia bracteata Retz

The present research was designed to investigate the anti-microbial activity of aristolochic acid from the root of Aristolochia bracteata. From the methanolic & ethyl extract extracts of Aristolochia bracteata aristolochic acid I was isolated and conformed through IR, NMR & MS. The percentage purity of aristolochic acid I was determined by UV & HPLC method. Antibacterial activity of extracts of Aristolochia bracteata and the isolated compound was determined by disc diffusion method. The results reveled that the isolated aristolochic acid from methanolic extract was more pure than the compound from ethyl acetate extract. The various extracts (500μg/disc) of Aristolochia bracteata showed moderate antibacterial activity with the average zone of inhibition of 7-18 mm by disc diffusion method. Among the extracts, ethyl acetate & methanol extracts were shown good anti-microbial activity and the growth of E.coli (18 mm) was strongly inhibited. Microbial assay of isolated compound (Aristolochic acid I) from ethyl acetate & methanol extracts were shown good antimicrobial activity and the zone of inhibition of both at higher concentration 50 μg/ml was similar with the standard aristolochic acid. It may be concluded that the isolated compound of aristolochic acid I has good anti-bacterial activity.

An in Silico Approach for Prioritizing Drug Targets in Metabolic Pathway of Mycobacterium Tuberculosis

There is an urgent need to develop novel Mycobacterium tuberculosis (Mtb) drugs that are active against drug resistant bacteria but, more importantly, kill persistent bacteria. Our study structured based on integrated analysis of metabolic pathways, small molecule screening and similarity Search in PubChem Database. Metabolic analysis approaches based on Unified weighted used for potent target selection. Our results suggest that pantothenate synthetase (panC) and and 3-methyl-2-oxobutanoate hydroxymethyl transferase (panB) as a appropriate drug targets. In our study, we used pantothenate synthetase because of existence inhibitors. We have reported the discovery of new antitubercular compounds through ligand based approaches using computational tools.

Early Onset Neonatal Sepsis Pathogens in Malaysian Hospitals: Determining Empiric Antibiotic

Information regarding early onset neonatal sepsis (EONS) pathogens may vary between regions. Global perspectives showed Group B Streptococcal (GBS) as the most common causative pathogens, but the widespread use of intrapartum antibiotics has changed the pathogens pattern towards gram negative microorganisms, especially E. coli. Objective of this study is to describe the pathogens isolated, to assess current treatment and risk of EONS. Records of 899 neonates born in three General Hospitals between 2009 until 2012 were retrospectively reviewed. Proven was found in 22 (3%) neonates. The majority was isolated with gram positive organisms, 17 (2.3%). All grams positive and most gram negative organisms showed sensitivity to the tested antibiotics. Only two rare gram negative organisms showed total resistant. Male was possible risk of proven EONS. Although proven EONS remains uncommon in Malaysia, nonetheless, the effect of intrapartum antibiotics still required continuous surveillance.

Data Mining Classification Methods Applied in Drug Design

Data mining incorporates a group of statistical methods used to analyze a set of information, or a data set. It operates with models and algorithms, which are powerful tools with the great potential. They can help people to understand the patterns in certain chunk of information so it is obvious that the data mining tools have a wide area of applications. For example in the theoretical chemistry data mining tools can be used to predict moleculeproperties or improve computer-assisted drug design. Classification analysis is one of the major data mining methodologies. The aim of thecontribution is to create a classification model, which would be able to deal with a huge data set with high accuracy. For this purpose logistic regression, Bayesian logistic regression and random forest models were built using R software. TheBayesian logistic regression in Latent GOLD software was created as well. These classification methods belong to supervised learning methods. It was necessary to reduce data matrix dimension before construct models and thus the factor analysis (FA) was used. Those models were applied to predict the biological activity of molecules, potential new drug candidates.

Aqueous Extract of Flacourtia indica Prevents Carbon Tetrachloride Induced Hepatotoxicity in Rat

Carbon tetrachloride (CCl4) is a well-known hepatotoxin and exposure to this chemical is known to induce oxidative stress and causes liver injury by the formation of free radicals. Flacourtia indica commonly known as 'Baichi' has been reported as an effective remedy for the treatment of a variety of diseases. The objective of this study was to investigate the hepatoprotective activity of aqueous extract of leaves of Flacourtia indica against CCl4 induced hepatotoxicity. Animals were pretreated with the aqueous extract of Flacourtia indica (250 & 500 mg/kg body weight) for one week and then challenged with CCl4 (1.5 ml/kg bw) in olive oil (1:1, v/v) on 7th day. Serum marker enzymes (ALP, AST, ALT, Total Protein & Total Bilirubin) and TBARS level (Marker for oxidative stress) were estimated in all the study groups. Alteration in the levels of biochemical markers of hepatic damage like AST, ALT, ALP, Total Protein, Total Bilirubin and lipid peroxides (TBARS) were tested in both CCl4 treated and extract treated groups. CCl4 has enhanced the AST, ALT, ALP and the Lipid peroxides (TBARS) in liver. Treatment of aqueous extract of Flacourtia indica leaves (250 & 500 mg/kg) exhibited a significant protective effect by altering the serum levels of AST, ALT, ALP, Total Protein, Total Bilirubin and liver TBARS. These biochemical observations were supported by histopathological study of liver sections. From this preliminary study it has been concluded that the aqueous extract of the leaves of Flacourtia indica protects liver against oxidative damages and could be used as an effective protector against CCl4 induced hepatic damage. Our findings suggested that Flacourtia indica possessed good hepatoprotective activity

A Preliminary Study of Drug Perfusion Enhancement by Microstreaming Induced by an Oscillating Microbubble

Microbubbbles incorporating ultrasound have been used to increase the efficacy of targeted drug delivery, because microstreaming induced by cavitating bubbles affects the drug perfusion into the target cells and tissues. In order to clarify the physical effects of microstreaming on drug perfusion into tissues, a preliminary experimental study of perfusion enhancement by a stably oscillating microbubble was performed. Microstreaming was induced by an oscillating bubble at 15 kHz, and perfusion of dye into an agar phantom was optically measured by histology on agar phantom. Surface color intensity and the penetration length of dye in the agar phantom were increased more than 70% and 30%, respectively, due to the microstreaming induced by an oscillating bubble. The mass of dye perfused into a tissue phantom for 30 s was increased about 80% in the phantom with an oscillating bubble. This preliminary experiment shows the physical effects of steady streaming by an oscillating bubble can enhance the drug perfusion into the tissues while minimizing the biological effects.

Salbutamol Sulphate-Ethylcellulose Tabletted Microcapsules: Pharmacokinetic Study using Convolution Approach

The aim of this article is to narrate the utility of novel simulation approach i.e. convolution method to predict blood concentration of drug utilizing dissolution data of salbutamol sulphate microparticulate formulations with different release patterns (1:1, 1:2 and 1:3, drug:polymer). Dissolution apparatus II USP 2007 and 900 ml double distilled water stirrd at 50 rpm was employed for dissolution analysis. From dissolution data, blood drug concentration was determined, and in return predicted blood drug concentration data was used to calculate the pharmacokinetic parameters i.e. Cmax, Tmax, and AUC. Convolution is a good biwaiver technique; however its better utility needs it application in the conditions where biorelevant dissolution media are used.

Preparation and Characterization of M. × Piperita L. Oil Based Gel Formulation

The essential oil of M. × piperita L. was formulated into a topical gel. The prepared gel was characterized for its pH, viscosity, spreadiblity, consistency and extrudiblity, while its stability was evaluated under different temperature conditions. The prepared M. × piperita oil gel was clear and transparent. The pH value of developed gel was 6.6, while its viscosity was 1200 cP. Spreadability and consistency of the M. × piperita oil gel was 10.7 g.cm/sec and 7 mm, respectively. The prepared gel showed good extrudiblity. During the stability studies, no significant change in pH and viscosity as a function of time for gel was observed, indicating stability of prepared formulation. The gel developed in this study is expected to forward the usage of M. × piperita essential towards commercial application.

Antibacterial Activity of Ethanol Extract from Some Thai Medicinal Plants against Campylobacter Jejuni

In this study, the forty Thai medicinal plants were used to screen the antibacterial activity against Campylobacter jejuni. Crude 95% ethanolic extracts of each plant were prepared. Antibacterial activity was investigated by the disc diffusion assay, and MICs and MBCs were determined by broth microdilution. The results of antibacterial screening showed that five plants have activity against C.jejuni including Adenanthera pavonina L., Moringa oleifera Lam., Annona squamosa L., Hibiscus sabdariffa L. and Eupotorium odortum L. The extraction of A. pavonina L. and A. squamosa L. produced an outstanding against C. jejuni, inhibiting growth at 62.5-125 and 250-500 μg/mL, respectively. The MBCs of two extracts were just 4-fold higher than MICs against C. jejuni, suggesting the extracts are bactericidal against this species. These results indicate that A. pavonina and A. squamosa could potentially be used in modern applications aimed at treatment or prevention of foodborne disease from C. jejuni.

Study on Antioxidant and Antitumor Activities of Some Herbal Extracts

The potential of antioxidant activities of the plant extract Gynura procumbens, Achyranthes aspera and Polygenum tomentosum were studied by using 1, 1-diphenyl-2-picrylhydrazyl (DPPH) .Antioxidant activity was qualitatively and quantitatively determined. In this analysis , Ascorbic acid (Vitamin C) was used as the standard .The antioxidant activities were observed all three plant extracts and the EC50 values of G procumbens A.aspera and P.tomemtosum were 13.7 μg /ml,14.37 μg /ml and 14.35 μg /ml. Among these plants, G.procumbens is more potent antioxidant activity then others. Antitumor activities were found with A.aspera (s2) extracts in the dose of 100ppm in carrot disks and G.procumbens (s1) and P.tomentosum (s3) in the dose of 1000 ppm. Therefore, these herbal plants are used in traditional medicines.

Mass Casualty Acute Pepper Spray Inhalation Respiratory Effect Severity

Pepper spray use has gained momentum since 1992 and although the active ingredient is readily available, it is considered a weapon with restricted use in many regions, including The Bahamas. In light of controversy in the literature regarding the severity of presenting respiration complaints among individuals postacute exposure of pepper spray inhalation, this descriptive case series study was conducted to assess the respiratory status of persons evaluated during a mass casualty in The Bahamas. Parameters noted were patients- demographics and respiration severity determined via clinical examination findings, disposition and follow-up review of the 20 persons. Their most common complaint was difficulty breathing post exposure. Two required admission and stayed for

Pentachlorophenol Removal via Adsorption and Biodegradation

Removal of PCP by a system combining biodegradation by biofilm and adsorption was investigated here. Three studies were conducted employing batch tests, sequencing batch reactor (SBR) and continuous biofilm activated carbon column reactor (BACCOR). The combination of biofilm-GAC batch process removed about 30% more PCP than GAC adsorption alone. For the SBR processes, both the suspended and attached biomass could remove more than 90% of the PCP after acclimatisation. BACCOR was able to remove more than 98% of PCP-Na at concentrations ranging from 10 to 100 mg/L, at empty bed contact time (EBCT) ranging from 0.75 to 4 hours. Pure and mixed cultures from BACCOR were tested for use of PCP as sole carbon and energy source under aerobic conditions. The isolates were able to degrade up to 42% of PCP under aerobic conditions in pure cultures. However, mixed cultures were found able to degrade more than 99% PCP indicating interdependence of species.

Dextran/Poly(L-histidine) Graft Copolymer for pH-Responsive Drug Delivery

pH-sensitive drug targeting using nanoparticles for cancer chemotherapy have been spotlighted in recent decades. Graft copolymer composed of poly (L-histidine) (PHS) and dextran (DexPHS) was synthesized and pH-sensitive nanoparticles were fabricated for pH-responsive drug delivery of doxorubicin (DOX). Nanoparticles of DexPHS showed pH-sensitive changes in particle sizes and drug release behavior, i.e. particle sizes and drug release rate were increased at acidic pH, indicating that DexPHS nanoparticles have pH-sensitive drug delivery potentials. Antitumor activity of DOX-incorporated DexPHS nanoparticles were studied using CT26 colorectal carcinoma cells. Results indicated that fluorescence intensity was higher at acidic pH than basic pH. These results indicated that DexPHS nanoparticles have pH-responsive drug targeting.

Wound Healing Effect of Ocimum sanctum Leaves Extract in Diabetic Rats

Delayed wound healing in diabetes is primarily associated with hyperglycemia, over-expression of inflammatory marker, oxidative stress and delayed collagen synthesis. This unmanaged wound is producing high economic burden on the society. Thus research is required to develop new and effective treatment strategies to deal with this emerging issue. Our present study incorporates the evaluation of wound healing effects of 50% ethanol extract of Ocimum sanctum (OSE) in streptozotocin (45mg/kg)-induced diabetic rats with concurrent wound ulcer. The animals showing diabetes (Blood glucose level >140 and

Effects of a Methanol Fraction of the Leaves of Leonotis leonurus on the Blood Pressure and Heart Rate of Normotensive Male Wistar Rats

Leonotisleonurus a shrub indigenous to Southern Africa is widely used in traditional medicine to treat a variety of conditions ranging from skin diseases and cough to epileptic fits and ‘heart problems’. Studies on the aqueous extract of the leaves have indicated cycloxegenase enzyme inhibitory activity and an antihypertensive effect. Five methanol leaf extract fractions (MLEa - MLEe) of L. leonurus were tested on anaesthetized normotensive male Wistar rats (AWR) and isolated perfused working rat hearts (IWH). Fraction MLEc (0.01mg/kg – 0.05mg/kg) induced significant increases in BP and HR in AWR and positive chronotropic and inotropic effects in IWH (1.0mg/ml – 5.0mg/ml). Pre-administration of atenolol (2.0mg/kg) and prazosin (60μg/kg) significantly inhibited MLEc effect on HR and MAP respectively in vivo, while atenolol (7.0mg/ml) pre-perfusion significantly inhibited MLEc effect in vitro. The hypertensive effect of MLEc is probably via β1agonism. Results also indicate the presence of multiple cardioactive compounds in L. leonurus.