Burst on Hurst Algorithm for Detecting Activity Patterns in Networks of Cortical Neurons

Electrophysiological signals were recorded from primary cultures of dissociated rat cortical neurons coupled to Micro-Electrode Arrays (MEAs). The neuronal discharge patterns may change under varying physiological and pathological conditions. For this reason, we developed a new burst detection method able to identify bursts with peculiar features in different experimental conditions (i.e. spontaneous activity and under the effect of specific drugs). The main feature of our algorithm (i.e. Burst On Hurst), based on the auto-similarity or fractal property of the recorded signal, is the independence from the chosen spike detection method since it works directly on the raw data.

NFκB Pathway Modeling for Optimal Drug Combination Therapy on Multiple Myeloma

NFκB activation plays a crucial role in anti-apoptotic responses in response to the apoptotic signaling during tumor necrosis factor (TNFa) stimulation in Multiple Myeloma (MM). Although several drugs have been found effective for the treatment of MM by mainly inhibiting NFκB pathway, there are no any quantitative or qualitative results of comparison assessment on inhibition effect between different single drugs or drug combinations. Computational modeling is becoming increasingly indispensable for applied biological research mainly because it can provide strong quantitative predicting power. In this study, a novel computational pathway modeling approach is employed to comparably assess the inhibition effects of specific single drugs and drug combinations on the NFκB pathway in MM, especially the prediction of synergistic drug combinations.

Energy Fields as Alternative Cures for Viral Diseases

As days go by, we hear more and more about HIV, Ebola, Bird Flu and other dreadful viruses which were unknown a few decades ago. In both detecting and fighting viral diseases ordinary methods have come across some basic and important difficulties. Vaccination is by a sense introduction of the virus to the immune system before the occurrence of the real case infection. It is very successful against some viruses (e.g. Poliomyelitis), while totally ineffective against some others (e.g. HIV or Hepatitis-C). On the other hand, Anti-virus drugs are mostly some tools to control and not to cure a viral disease. This could be a good motivation to try alternative treatments. In this study, some key features of possible physical-based alternative treatments for viral diseases are presented. Electrification of body parts or fluids (especially blood) with micro electric signals with adjusted current or frequency is also studied. The main approach of this study is to find a suitable energy field, with appropriate parameters that are able to kill or deactivate viruses. This would be a lengthy, multi-disciplinary research which needs the contribution of virology, physics, and signal processing experts. It should be mentioned that all the claims made by alternative cures researchers must be tested carefully and are not advisable at the time being.

An Adaptive Memetic Algorithm With Dynamic Population Management for Designing HIV Multidrug Therapies

In this paper, a mathematical model of human immunodeficiency virus (HIV) is utilized and an optimization problem is proposed, with the final goal of implementing an optimal 900-day structured treatment interruption (STI) protocol. Two type of commonly used drugs in highly active antiretroviral therapy (HAART), reverse transcriptase inhibitors (RTI) and protease inhibitors (PI), are considered. In order to solving the proposed optimization problem an adaptive memetic algorithm with population management (AMAPM) is proposed. The AMAPM uses a distance measure to control the diversity of population in genotype space and thus preventing the stagnation and premature convergence. Moreover, the AMAPM uses diversity parameter in phenotype space to dynamically set the population size and the number of crossovers during the search process. Three crossover operators diversify the population, simultaneously. The progresses of crossover operators are utilized to set the number of each crossover per generation. In order to escaping the local optima and introducing the new search directions toward the global optima, two local searchers assist the evolutionary process. In contrast to traditional memetic algorithms, the activation of these local searchers is not random and depends on both the diversity parameters in genotype space and phenotype space. The capability of AMAPM in finding optimal solutions compared with three popular metaheurestics is introduced.

Drug Combinations with Steroid Dispensing in Drugstores: A Study in the Center Area of Bangkok, Thailand

The purposes of this research were 1) to survey the number of drugstores that unlawful dispense of asthma prescription drugs, in form of drug combinations in the Phaya Thai district of Bangkok, 2) to find the steroids contained in that drug combinations, 3) to find a means for informing general public about the dangers of drugs and for a campaign to stop dispensing them. Researcher collected drug combinations from 69 drugstores in Phaya Thai district from Feb 15, 2012 to Mar 15, 2012. The survey found 30.43%, 21, drug stores, sold asthma drug combinations to customers without a prescription. These collected samples were tested for steroid contamination by using Immunochromatography kits. Eleven samples, 52.38%, were found contaminated with steroids. In short, there should be control and inspection of drugstores in the distribution of steroid medications. To improve the knowledge of self health maintenance and drug usage among public, Thai Government and Department of Public Health should educate people about the side effects of using drug combinations and steroids.

Chemotherapy Safety Protocol for Oncology Nurses: It's Effect on Their Protective Measures Practices

Background: Widespread use of chemotherapeutic drugs in the treatment of cancer has lead to higher health hazards among employee who handle and administer such drugs, so nurses should know how to protect themselves, their patients and their work environment against toxic effects of chemotherapy. Aim of this study was carried out to examine the effect of chemotherapy safety protocol for oncology nurses on their protective measure practices. Design: A quasi experimental research design was utilized. Setting: The study was carried out in oncology department of Menoufia university hospital and Tanta oncology treatment center. Sample: A convenience sample of forty five nurses in Tanta oncology treatment center and eighteen nurses in Menoufiya oncology department. Tools: 1. an interviewing questionnaire that covering sociodemographic data, assessment of unit and nurses' knowledge about chemotherapy. II: Obeservational check list to assess nurses' actual practices of handling and adminestration of chemotherapy. A base line data were assessed before implementing Chemotherapy Safety protocol, then Chemotherapy Safety protocol was implemented, and after 2 monthes they were assessed again. Results: reveled that 88.9% of study group I and 55.6% of study group II improved to good total knowledge scores after educating on the safety protocol, also 95.6% of study group I and 88.9% of study group II had good total practice score after educating on the safety protocol. Moreover less than half of group I (44.4%) reported that heavy workload is the most barriers for them, while the majority of group II (94.4%) had many barriers for adhering to the safety protocol such as they didn’t know the protocol, the heavy work load and inadequate equipment. Conclusions: Safety protocol for Oncology Nurses seemed to have positive effect on improving nurses' knowledge and practice. Recommendation: chemotherapy safety protocol should be instituted for all oncology nurses who are working in any oncology unit and/ or center to enhance compliance, and this protocol should be done at frequent intervals.

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

Combining Gene and Chemo Therapy using Multifunctional Polymeric Micelles

Non-viral gene carriers composed of biodegradable polymers or lipids have been considered as a safer alternative for gene carriers over viral vectors. We have developed multi-functional nano-micelles for both drug and gene delivery application. Polyethyleneimine (PEI) was modified by grafting stearic acid (SA) and formulated to polymeric micelles (PEI-SA) with positive surface charge for gene and drug delivery. Our results showed that PEI-SA micelles provided high siRNA binding efficiency. In addition, siRNA delivered by PEI-SA carriers also demonstrated significantly high cellular uptake even in the presence of serum proteins. The post-transcriptional gene silencing efficiency was greatly improved by the polyplex formulated by 10k PEI-SA/siRNA. The amphiphilic structure of PEI-SA micelles provided advantages for multifunctional tasks; where the hydrophilic shell modified with cationic charges can electrostatically interact with DNA or siRNA, and the hydrophobic core can serve as payloads for hydrophobic drugs, making it a promising multifunctional vehicle for both genetic and chemotherapy application.

Knowledge Management Applied to Forensic Sciences

This paper presents initiatives of Knowledge Management (KM) applied to Forensic Sciences field, especially developed at the Forensic Science Institute of the Brazilian Federal Police. Successful projects, related to knowledge sharing, drugs analysis and environmental crimes, are reported in the KM perspective. The described results are related to: a) the importance of having an information repository, like a digital library, in such a multidisciplinary organization; b) the fight against drug dealing and environmental crimes, enabling the possibility to map the evolution of crimes, drug trafficking flows, and the advance of deforestation in Amazon rain forest. Perspectives of new KM projects under development and studies are also presented, tracing an evolution line of the KM view at the Forensic Science Institute.

Biorecognizable Nanoparticles Based On Hyaluronic Acid/Poly(ε-Caprolactone) Block Copolymer

Since hyaluronic acid (HA) receptor such as CD44 is over-expressed at sites of cancer cells, HA can be used as a targeting vehicles for anti-cancer drugs. The aim of this study is to synthesize block copolymer composed of hyaluronic acid and poly(ε-caprolactone) (HAPCL) and to fabricate polymeric micelles for anticancer drug targeting against CD44 receptor of tumor cells. Chemical composition of HAPCL was confirmed using 1H NMR spectroscopy. Doxorubicin (DOX) was incorporated into polymeric micelles of HAPCL. The diameters of HAPHS polymeric micelles were changed around 80nm and have spherical shapes. Targeting potential was investigated using CD44-overexpressing. When DOX-incorporated polymeric micelles was added to KB cells, they revealed strong red fluorescence color while blocking of CD44 receptor by pretreatment of free HA resulted in reduced intensity, indicating that HAPCL polymeric micelles have targetability against CD44 receptor.

How the Iranian Free-Style Wrestlers Know and Think about Doping? – A Knowledge and Attitude Study

Nowadays, doping is an intricate dilemma. Wrestling is the nationally popular sport in Iran. Also the prevalence of doping may be high, due to its power demanding characteristics. So, we aimed to assess the knowledge and attitudes toward doping among the club wrestlers. In a cross sectional study, 426 wrestlers were studied. For this reason, a researcher made questionnaire was used. In this study, researchers selected the clubs by randomized clustered sampling and distributed the questionnaire among wrestlers. Knowledge of wrestlers in three categories of doping definitions, recognition of prohibited drugs and side effects was poor or moderate in 70.8%, 95.8% and 99.5%, respectively. Wrestlers have poor knowledge in doping. Furthermore, they believe some myths which are unfavorable. It seems necessary to design a comprehensive educational program for all of the athletes and coaches.

Study of Encapsulation of Quantum Dots in Polystyrene and Poly (E-Caprolactone)Microreactors Prepared by Microvolcanic Eruption of Freeze Dried Microspheres

Polymeric microreactors have emerged as a new generation of carriers that hold tremendous promise in the areas of cancer therapy, controlled delivery of drugs, for removal of pollutants etc. Present work reports a simple and convenient methodology for synthesis of polystyrene and poly caprolactone microreactors. An aqueous suspension of carboxylated (1μm) polystyrene latex particles was mixed with toluene solution followed by freezing with liquid nitrogen. Freezed particles were incubated at -20°C and characterized for formation of voids on the surface of polymer microspheres by Field Emission Scanning Electron Microscope. The hollow particles were then overnight incubated at 40ºC with unfunctionalized quantum dots (QDs) in 5:1 ratio. QDs Encapsulated polystyrene microcapsules were characterized by fluorescence microscopy. Likewise Poly ε-caprolactone microreactors were prepared by micro-volcanic rupture of freeze dried microspheres synthesized using emulsification of polymer with aqueous Poly vinyl alcohol and freezed with liquid nitrogen. Microreactors were examined with Field Emission Scanning Electron Microscope for size and morphology. Current study is an attempt to create hollow polymer particles which can be employed for microencapsulation of nanoparticles and drug molecules.

Growth Effects of Caffeic Acid and Thioglycolic Acid Modified Chitosans in U937 Cells

Chitosan is a biopolymer composed of glucosamine and N-acetyl glucosamine. Solubility and viscosity pose problems in some applications. These problems can be overcome with unique modifications. In this study, firstly, chitosan was modified by caffeic acid and thioglycolic acid, separately. Then, growing effects of these modified polymers was observed in U937 cell line. Caffeic acid is a phenolic compound and its modifications act carcinogenic inhibitors in drugs. Thiolated chitosans are commonly being used for drugdelivery systems in various routes, because of enhancing mucoadhesiveness property. U937 cell line was used model cell for leukaemia. Modifications were achieved by 1 – 15 % binding range. Increasing binding ratios showed higher radical-scavenging activity and reducing cell growth, in compared to native chitosan. Caffeic acid modifications showed higher radical-scavenging activity than thiolated chitosans at the same concentrations. Caffeic acid and thioglycolic acid modifications inhibited growth of U937, effectively.

Pharmacology Applied Learning Program in Preclinical Years – Student Perspectives

Pharmacology curriculum plays an integral role in medical education. Learning pharmacology to choose and prescribe drugs is a major challenge encountered by students. We developed pharmacology applied learning activities for first year medical students that included realistic clinical situations with escalating complications which required the students to analyze the situation and think critically to choose a safe drug. Tutor feedback was provided at the end of session. Evaluation was done to assess the students- level of interest and usefulness of the sessions in rational selection of drugs. Majority (98 %) of the students agreed that the session was an extremely useful learning exercise and agreed that similar sessions would help in rational selection of drugs. Applied learning sessions in the early years of medical program may promote deep learning and bridge the gap between pharmacology theory and clinical practice. Besides, it may also enhance safe prescribing skills.

Using Data Mining Techniques for Finding Cardiac Outlier Patients

In this paper we used data mining techniques to identify outlier patients who are using large amount of drugs over a long period of time. Any healthcare or health insurance system should deal with the quantities of drugs utilized by chronic diseases patients. In Kingdom of Bahrain, about 20% of health budget is spent on medications. For the managers of healthcare systems, there is no enough information about the ways of drug utilization by chronic diseases patients, is there any misuse or is there outliers patients. In this work, which has been done in cooperation with information department in the Bahrain Defence Force hospital; we select the data for Cardiac patients in the period starting from 1/1/2008 to December 31/12/2008 to be the data for the model in this paper. We used three techniques for finding the drug utilization for cardiac patients. First we applied a clustering technique, followed by measuring of clustering validity, and finally we applied a decision tree as classification algorithm. The clustering results is divided into three clusters according to the drug utilization, for 1603 patients, who received 15,806 prescriptions during this period can be partitioned into three groups, where 23 patients (2.59%) who received 1316 prescriptions (8.32%) are classified to be outliers. The classification algorithm shows that the use of average drug utilization and the age, and the gender of the patient can be considered to be the main predictive factors in the induced model.

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.

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.

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.

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.

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.