Search results for: drug affordability

Authors: Feng-Sheng Wang, Chao-Ting Cheng

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Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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Authors: Gaweł Magdalena, Lipkowska Anna, Olbert Magdalena, Frąckiewicz Ewelina, Librowski Tadeusz, Nowak Gabriel, Pilc Andrzej

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Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (HSP32), has been shown to be implicated in cytoprotection in various organs. Its activation plays a significant role in acute and chronic inflammation, protecting cells from oxidative injury and apoptosis. This inducible isoform of HO catalyzes the first and rate-limiting step in heme degradation to produce equimolar quantities of biologically active products: carbon monoxide (CO), free iron and biliverdin. CO has been reported to possess anti-apoptotic properties. Moreover, it inhibits the production of proinflammatory cytokines and stimulates the synthesis of the anti-inflammatory interleukin-10 (IL-10), as well as promotes vasodilatation at sites of inflammation. The second product of catalytic HO-1 activity, free cytotoxic iron, is promptly sequestered into the iron storage protein ferritin, which lowers the pro-oxidant state of the cell. The third product, biliverdin, is subsequently converted by biliverdin reductase into the bile pigment bilirubin, the most potent endogenous antioxidant among the constituents of human serum, which modulates immune effector functions and suppresses inflammatory response. Furthermore, being one of the so-called stress proteins, HO-1 adaptively responds to different stressors, such as reactive oxygen species (ROS), inflammatory cytokines and heavy metals and thus protects cells against such conditions as ischemia, hemorrhagic shock, heat shock or hypoxia. It is suggested that pharmacologic modulation of HO-1 may represent an effective strategy for prevention of stress and drug-induced gastrointestinal toxicity. HO-1 is constitutively expressed in normal gastric, intestinal and colonic mucosa and up-regulated during inflammation. It has been proven that HO-1 up-regulated by hemin, heme and cobalt-protoporphyrin ameliorates experimental colitis. In addition, the up-regulation of HO-1 partially explains the mechanism of action of 5-aminosalicylic acid (5-ASA), which is used clinically as an anti-colitis agent. In 2009 Ueda et al. has reported for the first time that mucosal protection by Polaprezinc, a chelate compound of zinc and L-carnosine used as an anti-ulcer drug in Japan, is also attributed to induction of HO-1 in the stomach. Since then, inducers of HO-1 are desired subject of research, as they may constitute therapeutically effective anti-ulcer drugs.

Keywords: heme oxygenase-1, gastric lesions, gastroprotection, Polaprezinc

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Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

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Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

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Authors: Taissir Fekih Romdhane

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This paper proposes a mobile web application named Pharmacy-Station that sells medicines and permits user to search for medications based on their symptoms, making it is easy to locate a specific drug online without the need to visit a pharmacy where it may be out of stock. This application is developed using the jQuery Mobile framework, which uses many web technologies and languages such as HTML5, PHP, JavaScript and CSS3. To test the proposed application, we used data from popular pharmacies in Saudi Arabia that included important information such as location, contact, and medicines in stock, etc. This document describes the different steps followed to create the Pharmacy-Station application along with screenshots. Finally, based on the results, the paper concludes with recommendations and further works planned to improve the Pharmacy-Station mobile application.

Keywords: pharmacy, mobile application, jquery mobile framework, search, medicine

Procedia PDF Downloads 159

Authors: Gaironeesa Hendricks, Shazly Savahl, Maria Florence

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The aim of the study is to determine whether peer pressure and leisure boredom influence substance use among adolescents in low-income communities in Cape Town. Non-probability sampling was used to select 296 adolescents between the ages of 16–18 from schools located in two low-income communities. The measurement tools included the Drug Use Disorders Identification Test, the Resistance to Peer Influence and Leisure Boredom Scales. Multiple regression revealed that the combined influence of peer pressure and leisure boredom predicted substance use, while peer pressure emerged as a stronger predictor than leisure boredom on substance use among adolescents.

Keywords: substance use, peer pressure, leisure boredom, adolescents, multiple regression

Procedia PDF Downloads 598

Authors: J. O. Ezekwesili-Ofili, L. I. Okorafor, S. C. Nsofor

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Diabetes mellitus is a carbohydrate metabolism disorder due to an absolute or relative deficiency of insulin secretion, action or both. Many known hypoglycaemic drugs are known to produce serious side effects. However, the search for safer and more effective agents has shifted to plant products, including foods and spices. One of such is the rhizome of Curcuma longa or turmeric, which is a spice with high medicinal value. A drawback in the use of C. longa is the poor bioavailability of curcumin, the active ingredient. It has been reported that piperine, an alkaloid present in peppers increases the bioavailability of curcumin. This work therefore investigated the hypoglycaemic and antioxidant effects of ethanolic extract of C. longa rhizomes, alone and with two pepper adjuvants in alloxan-induced diabetic rats. A total of 48 rats were divided into 6 groups of 8 rats each. Groups A–E were induced with diabetes using 150mg/kg body weight of alloxan monohydrate, while group F was normoglycaemic: Group A: Diabetic; fed with 400 mg/g body weight of turmeric extract; group B: Diabetic, fed with 400 mg/kg b. w. and 200mg/kg b. w of ethanolic extract of seeds of Piper guinensee; group C: Diabetic, fed with 400 mg/kg b. w. and 200 mg /kg b. w. of ethanolic extract of seeds of Capsicum annum var cameroun, group D: Diabetic, treated with standard drug, glibenclamide (0.3mg/kg body weight), group E: Diabetic; no treatment i.e. Positive control and group F: non diabetic, no treatment i.e. Negative control. Blood glucose levels were monitored for 14 days using a glucometer. The levels of the antioxidant enzymes; glutathione peroxidase, catalase and superoxide dismutase were also assayed in serum. The ethanolic extracts of C. longa rhizomes at the dose given (400 mg/kg b. w) significantly reduced the blood glucose levels of the diabetic rats (p<0.05) comparable to the standard drug. Co administration of extract of the peppers did not significantly increase the efficiency of the extract, although C. annum var cameroun showed greater effect, though not significantly. The antioxidant effect of the extract was significant in diabetic rats. The use of piperine-containing peppers enhanced the antioxidant effect. Phytochemical analyses of the ethanolic extract of C. longa showed the presence of alkaloids, flavonoids, steroids, saponins, tannins, glycosides, and terpenoids. These results suggest that the ethanolic extract of C. longa had antidiabetic with antioxidant effects and could thus be of benefit in the treatment and management of diabetes as well as ameliorate pro-oxidant effects that may lead to diabetic complications. However, while the addition of piperine did not affect the antidiabetic effect of C. longa, the antioxidant effect was greatly enhanced.

Keywords: antioxidant, Curcuma longa rhizome, hypoglycaemic, pepper adjuvants, piperine

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Authors: H. Al-Khalaifa, A. Al-Nasser

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The viewpoint towards the use of drugs or vaccines against avian parasitic diseases is one of the most striking challenges in avian medical parasitology. This includes many difficulties associated with drug resistance and in developing prophylactic vaccines. In many instances, the potential success of a vaccination in controlling parasitic diseases in poultry is well-documented. However, some medical, technical and financial limitations are still paramount. On the other hand, chemotherapy is not very well-recommended due to a number of medical limitations. But in the absence of an effective vaccine, drugs are used against parasitic diseases. This paper sheds light on some the advantages and disadvantages of using vaccination and drugs in controlling parasitic diseases in poultry species. The usage of chemotherapeutic drugs is discussed with some examples. Then, more light will be shed on using vaccines as a potentially effective and promising control tool.

Keywords: drugs, parasitology, poultry, vaccines

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Authors: Mariya Yeldhos, G. Hema, Sowmya Narayanan, L. Dhiviyalakshmi

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Insomnia is one of the most prevalent psychological disorders worldwide. Some of the deficiencies of the current treatments of insomnia are: side effects in the case of sleeping pills and high costs in the case of psychotherapeutic treatment. In this paper, we propose a device which provides a combination of audio visual entrainment and acupressure based compression therapy for insomnia. This device provides drug-free treatment of insomnia through a user friendly and portable device that enables relaxation of brain and muscles, with certain advantages such as low cost, and wide accessibility to a large number of people. Tools adapted towards the treatment of insomnia: -Audio -Continuous exposure to binaural beats of a particular frequency of audible range -Visual -Flash of LED light -Acupressure points -GB-20 -GV-16 -B-10

Keywords: insomnia, acupressure, entrainment, audio-visual entrainment

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Authors: Eliane G. Tótoli, Hérida Regina N. Salgado

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Daptomycin is an important antimicrobial agent used in clinical practice nowadays, since it is very active against some Gram-positive bacteria that are particularly challenges for the medicine, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). The importance of environmental preservation has receiving special attention since last years. Considering the evident need to protect the natural environment and the introduction of strict quality requirements regarding analytical procedures used in pharmaceutical analysis, the industries must seek environmentally friendly alternatives in relation to the analytical methods and other processes that they follow in their routine. In view of these factors, green analytical chemistry is prevalent and encouraged nowadays. In this context, infrared spectroscopy stands out. This is a method that does not use organic solvents and, although it is formally accepted for the identification of individual compounds, also allows the quantitation of substances. Considering that there are few green analytical methods described in literature for the analysis of daptomycin, the aim of this work was the development and validation of a green analytical method for the quantification of this drug in lyophilized powder for injectable solution, by Fourier-transform infrared spectroscopy (FT-IR). Method: Translucent potassium bromide pellets containing predetermined amounts of the drug were prepared and subjected to spectrophotometric analysis in the mid-infrared region. After obtaining the infrared spectrum and with the assistance of the IR Solution software, quantitative analysis was carried out in the spectral region between 1575 and 1700 cm-1, related to a carbonyl band of the daptomycin molecule, and this band had its height analyzed in terms of absorbance. The method was validated according to ICH guidelines regarding linearity, precision (repeatability and intermediate precision), accuracy and robustness. Results and discussion: The method showed to be linear (r = 0.9999), precise (RSD% < 2.0), accurate and robust, over a concentration range from 0.2 to 0.6 mg/pellet. In addition, this technique does not use organic solvents, which is one great advantage over the most common analytical methods. This fact contributes to minimize the generation of organic solvent waste by the industry and thereby reduces the impact of its activities on the environment. Conclusion: The validated method proved to be adequate to quantify daptomycin in lyophilized powder for injectable solution and can be used for its routine analysis in quality control. In addition, the proposed method is environmentally friendly, which is in line with the global trend.

Keywords: daptomycin, Fourier-transform infrared spectroscopy, green analytical chemistry, quality control, spectrometry in IR region

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Authors: Preet Shah, Om Shrivastav

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Introduction : In India, Leishmania donovani is the only parasite causing Leishmaniasis. The parasite infects the reticuloendothelial system and is found in the bone marrow, spleen and liver. Treatment of choice is amphotericin-B with sodium stibogluconate being an alternative. Miltefosine is useful in refractory cases. In our case, Leishmaniasis occurred in a person residing in western India (which is quite rare) and it failed to respond to two different drugs (again an uncommon feature) before it finally responded to a third one. Description: A 50 year old lady, a resident of western India, with no history of recent travel, presented with an ulcer on the left side of the nose since 8 months. She was apparently alright 8 months back, when she noticed a small ulcerated lesion on the left ala of the nose which was immediately biopsied. The biopsy revealed amastigotes of Leishmania for which she was administered intra-lesional sodium stibogluconate for 1 month (4 doses every 8 days).Despite this, there was no regression of the ulcer and hence she presented to us for further management. On examination, her vital parameters were normal. Barring an ulcer on the left side of the nose, rest of the examination findings were unremarkable. Complete blood count was normal. Ultrasound abdomen showed hepatomegaly. PET-CT scan showed increased metabolic activity in left ala of nose, hepatosplenomegaly and increased metabolic activity in spleen and bone marrow. Bone marrow biopsy was done which showed hypercellular marrow with erythroid preponderance. Considering a diagnosis of leishmaniasis which had so far been unresponsive to sodium stibogluconate, she was started on liposomal amphotericin-B. At the time of admission, her creatinine level was normal, but it started rising with the administration of liposomal amphotericin-B, hence the dose was reduced. Despite this, creatinine levels did not improve, and she started developing hypokalemia and hypomagnesemia as side effects of the drug, hence further reductions in the dosage were made. Despite a total of 3 weeks of liposomal amphotericin-B, there was no improvement in the ulcer. As had so far failed to respond to sodium stibogluconate and liposomal amphotericin-B, it was decided to start her on miltefosine. She received the miltefosine for a total of 12 weeks. At the end of this duration, there was a marked regression of the cutaneous lesion. Conclusion: Refractoriness to amphotericin-B in leishmaniasis may be seen in up to 5 % cases. Here, an alternative drug such as miltefosine is useful and hence we decided to use it, to which she responded adequately. Furthermore, although leishmaniasis is common in the eastern part of India, it is a relatively unknown entity in the western part of the country with the occurrence being very rare. Because of these 2 reasons, we consider our case to be a unique one.

Keywords: amphotericin-b, leishmaniasis, miltefosine, tropical diseases

Procedia PDF Downloads 139

Authors: Despina Yiakoumi, Agathe Rouaix

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Laboratory experiments were run to investigate the impact of different design characteristics of the auctions, which have been implemented to procure capacity in the UK’s reformed electricity markets. The experiment studies competition among bidders in procurement multi-unit discrete descending clock auctions under different feedback policies and pricing rules. Theory indicates that feedback policy in combination with the two common pricing rules; last-accepted bid (LAB) and first-rejected bid (FRB), could affect significantly the auction outcome. Two information feedback policies regarding the bidding prices of the participants are considered; with feedback and without feedback. With feedback, after each round participants are informed of the number of items still in the auction and without feedback, after each round participants have no information about the aggregate supply. Under LAB, winning bidders receive the amount of the highest successful bid and under the FRB the winning bidders receive the lowest unsuccessful bid. Based on the theoretical predictions of the alternative auction designs, it was decided to run three treatments. First treatment considers LAB with feedback; second treatment studies LAB without feedback; third treatment investigates FRB without feedback. Theoretical predictions of the game showed that under FRB, the alternative feedback policies are indifferent to the auction outcome. Preliminary results indicate that LAB with feedback and FRB without feedback achieve on average higher clearing prices in comparison to the LAB treatment without feedback. However, the clearing prices under LAB with feedback and FRB without feedback are on average lower compared to the theoretical predictions. Although under LAB without feedback theory predicts the clearing price will drop to the competitive equilibrium, experimental results indicate that participants could still engage in cooperative behavior and drive up the price of the auction. It is showed, both theoretically and experimentally, that the pricing rules and the feedback policy, affect the bidding competitiveness of the auction by providing opportunities to participants to engage in cooperative behavior and exercise market power. LAB without feedback seems to be less vulnerable to market power opportunities compared to the alternative auction designs. This could be an argument for the use of LAB pricing rule in combination with limited feedback in the UK capacity market in an attempt to improve affordability for consumers.

Keywords: descending clock auctions, experiments, feedback policy, market design, multi-unit auctions, pricing rules, procurement auctions

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Authors: Esra Yuce, Isil D. S. Yamaner, Murude Yazan

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Aims and objective: Antiresorptive agents including bisphosphonates and denosumab as strong suppressors of osteoclasts are the most commonly used antiresorptive medications for the treatment of osteoporosis which counteract the negative quantitative alteration of trabecular and cortical bone by inhibition of bone turnover. Oral bisphosphonate therapy for the treatment of osteopenia, osteoporosis or Paget's disease is associated with the low-grade risk of osteonecrosis of the jaw, while higher-grade risk is associated with receiving intravenous bisphosphonates therapy in the treatment of multiple myeloma and bone metastases. On the other hand, there has been a remarkable increase in incidences of antiresorptive related osteonecrosis of the jaw (ARONJ) in oral bisphosphonate users. This clinical presentation will evaluate the healing outcomes via piezoelectric bone surgery under the irrigation of PVP-I solution irrigation in patients received bisphosphonate therapy. Material-Method: The study involved 8 female and 5 male patients that have been treated for ARONJ. Among 13 necrotic sites, 9 were in the mandible and 4 were in the maxilla. All of these 13 patients treated with surgical debridement via piezoelectric bone surgery under irrigation by solution with 3% PVP-I concentration in combination with long-term antibiotic therapy and 5 also underwent removal of mobile segments of bony sequestrum. All removable prosthesis in 8 patients were relined with soft liners during the healing periods in order to eliminate chronic minor traumas. Results: All patients were on oral bisphosphonate therapy for at least 2 years and 5 of which had received intravenous bisphosphonates up to 1 year before therapy with oral bisphosphonates was started. According to the AAOMS staging system, four cases were stage II, eight cases were stage I, and one case was stage III. The majority of lesions were identified at sites of dental prostheses (38%) and dental extractions (62%). All patients diagnosed with ARONJ stage I had used unadjusted removable prostheses. No recurrence of the symptoms was observed during the present follow-up (9–37 months). Conclusion: Despite their confirmed effectiveness, the prevention and treatment of osteonecrosis of the jaw secondary to oral bisphosphonate therapy remain major medical challenges. Treatment with piezoelectric bone surgery with irrigation of povidone-iodine solution was effective for management of bisphosphonate-related osteonecrosis of the jaw. Taking precautions for patients treated with oral bisphosphonates, especially also denture users, may allow for a reduction in the rate of developing osteonecrosis of the maxillofacial region.

Keywords: antiresorptive drug related osteonecrosis, bisphosphonate therapy, piezoelectric bone surgery, povidone iodine

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Authors: Josiah Damisa, Michelle Louise Richardson, Morenike Adewuyi

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Lower back pain is a significant cause of disability worldwide and associated with great implications in terms of the well-being of affected individuals and society as a whole due to its undeniable socio-economic impact. With its prevalence on the increase as a result of an aging global population, the need for novel forms of pain management is ever paramount. This review aims to provide further insight into current research regarding a role for the endocannabinoid signaling pathway as a target in the treatment of chronic pain, with particular emphasis on its potential use as part of the treatment of lower back pain. Potential advantages and limitations of cannabis-based medicines over other forms of analgesia currently licensed for medical use are discussed in addition to areas that require ongoing consideration and research. To evaluate the efficacy of cannabis-based medicines in chronic pain, studies pertaining to the role of medical cannabis in chronic disease were reviewed. Standard searches of PubMed, Google Scholar and Web of Science databases were undertaken with peer-reviewed journal articles reviewed based on the indication for pain management, cannabis treatment modality used and study outcomes. Multiple studies suggest an emerging role for cannabis-based medicines as therapeutic agents in the treatment of chronic back pain. A potential synergistic effect has also been purported if these medicines are co-administered with opiate analgesia due to the similarity of the opiate and endocannabinoid signaling pathways. However, whilst recent changes to legislation in the United Kingdom mean that cannabis is now licensed for medicinal use on NHS prescription for a number of chronic health conditions, concerns remain as to the efficacy and safety of cannabis-based medicines. Research is lacking into both their side effect profiles and the long-term effects of cannabis use. Legal and ethical considerations to the use of these products in standardized medical practice also persist due to the notoriety of cannabis as a drug of abuse. Despite this, cannabis is beginning to gain traction as an alternative or even complementary drug to opiates, with some preclinical studies showing opiate-sparing effects. Whilst there is a paucity of clinical trials in this field, there is scope for cannabinoids to be successful anti-nociceptive agents in managing chronic back pain. The ultimate aim would be to utilize cannabis-based medicines as alternative or complementary therapies, thereby reducing opiate over-reliance and providing hope to individuals who have exhausted all other forms of standard treatment.

Keywords: endocannabinoids, cannabis-based medicines, chronic pain, lower back pain

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Authors: Robin Anderson, Elizabeth Latham, David Nisbet

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Propagation and dissemination of antimicrobial resistant and pathogenic microbes from spoiled silages and composts represents a serious public health threat to humans and animals. In the present study, the antimicrobial activity of the short chain nitro-compound, 2-nitro-1-propanol (9 mM) as well as the medium chain fatty acid, lauric acid, and its glycerol monoester, monolaurin, (each at 25 and 17 µmol/mL, respectfully) were investigated against select pathogenic and multi-drug resistant antimicrobial resistant Gram-positive bacteria common to spoiled silages and composts. In an initial study, we found that growth rates of a multi-resistant Enterococcus faecalis (expressing resistance against erythromycin, quinupristin/dalfopristin and tetracycline) and Staphylococcus aureus strain 12600 (expressing resistance against erythromycin, linezolid, penicillin, quinupristin/dalfopristin and vancomycin) were more than 78% slower (P < 0.05) by 2-nitro-1-propanol treatment during culture (n = 3/treatment) in anaerobically prepared ½ strength Brain Heart Infusion broth at 37oC when compared to untreated controls (0.332 ± 0.04 and 0.108 ± 0.03 h-1, respectively). The growth rate of 2-nitro-1-propanol-treated Listeria monocytogenes was also decreased by 96% (P < 0.05) when compared to untreated controls cultured similarly (0.171 ± 0.01 h-1). Maximum optical densities measured at 600 nm were lower (P < 0.05) in 2-nitro-1-propanol-treated cultures (0.053 ± 0.01, 0.205 ± 0.02 and 0.041 ± 0.01, respectively) than in untreated controls (0.483 ± 0.02, 0.523 ± 0.01 and 0.427 ± 0.01, respectively) for E. faecalis, S. aureus and L. monocytogenes, respectively. When tested against mixed microbial populations during anaerobic 24 h incubation of spoiled silage, significant effects of treatment with 1 mg 2-nitro-1-propanol (approximately 9.5 µmol/g) or 5 mg lauric acid/g (approximately 25 µmol/g) on populations of wildtype Enterococcus and Listeria were not observed. Mixed populations treated with 5 mg monolaurin/g (approximately 17 µmol/g) had lower (P < 0.05) viable cell counts of wildtype enterococci than untreated controls after 6 h incubation (2.87 ± 1.03 versus 5.20 ± 0.25 log10 colony forming units/g, respectively) but otherwise significant effects of monolaurin were not observed. These results reveal differential susceptibility of multi-drug resistant enterococci and staphylococci as well as L. monocytogenes to the inhibitory activity of 2-nitro-1-propanol and the medium chain fatty acid, lauric acid and its glycerol monoester, monolaurin. Ultimately, these results may lead to improved treatment technologies to preserve the microbiological safety of silages and composts.

Keywords: 2-nitro-1-propanol, lauric acid, monolaurin, gram positive bacteria

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Authors: Haile Nega Mulata, Seifu Daniel, Umeta Melaku, Wendwesson Ergete, Natesan Gnanasekaran

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Background: In Ethiopia, medicinal plants have been used for various human and animal diseases. In this study, we have examined the potential effect of hydroethanolic extract of Calpurnia aurea seed against hepatotoxicity and haematotoxicity induced by Highly Active Antiretroviral Therapy (HAART) drugs in Albino Wistar rats. Methods: We collected Matured dried seeds of Calpurnia aurea from northern Ethiopia (south Tigray and south Gondar) in June 2013. The powder of the dried seed sample was macerated with 70% ethanol and dried using rotavapor. We have investigated the Preliminary phytochemical tests and in-vitro antioxidant properties. Then, we induced toxicity with HAART drugs and gave the experimental animals different doses of the crude extract orally for thirty-five days. On the 35th day, the animals were fasted overnight and sacrificed by cervical dislocation. We collected the blood samples by cardiac puncture. We excised the liver and brain tissues for further histopathological studies. Subsequently, we analysed serum levels of the liver enzymes- Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Total Bilirubin, and Serum Albumin, using commercial kits in Cobas Integra 400 Plus Roche Analyzer Germany. We have also assessed the haematological profile using an automated haematology Analyser (Sysmex KX-2IN). Results: A significant (P<0.05) decrease in serum enzymes (ALT and AST) and total bilirubin were observed in groups that received the highest dose (300mg/kg) of the seed extract. And significant (P<0.05) elevation of total red blood cell count, haemoglobin, and hematocrit percentage was observed in the groups that received the seed extract compared to the HAART-treated groups. The WBC count mean values showed a statistically significant increase (p<0.05) in groups that received HAART and 200 and 300mg/kg extract, respectively. The histopathological observations also showed that the oral administration of varying doses of the crude extract of the seed reversed to a normal state. Conclusion: The hydroethanolic extract of the Calpurnia aurea seed lowered the hepatotoxicity and haematotoxicity in a dose-dependent manner. The antioxidant properties of the Calpurnia aurea seed extract may have possible protective effects against the drug's toxicity.

Keywords: calpurnia aurea, hepatotoxicity, haematotoxicity, antioxidant, histopathology, HAART

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Authors: Somayeh Nezami

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The management of financial and human resources of police in metropolitans requires many information and exact plans to reduce a rate of crime and increase the safety of the society. Geographical Information Systems have an important role in providing crime maps and their analysis. By using them and identification of crime hot spots along with spatial presentation of the results, it is possible to allocate optimum resources while presenting effective methods for decision making and preventive solutions. In this paper, we try to explain and compare between some of the methods of hot spots analysis such as Mode, Fuzzy Mode and Nearest Neighbour Hierarchical spatial clustering (NNH). Then the spots with the highest crime rates of drug smuggling for one province in Iran with borderline with Afghanistan are obtained. We will show that among these three methods NNH leads to the best result.

Keywords: GIS, Hot spots, nearest neighbor hierarchical spatial clustering, NNH, spatial analysis of crime

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Authors: Akinyemi Olufunminiyi Akinbobola

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This paper analytically discusses the disciplinary problems among Adeyemi College of Education Students in the Ondo State of Nigeria. The paper posits that the causes and types of disciplinary problems experienced by the students are determinacy of disciplinary measures to be taken. The study used a questionnaire titled: Disciplinary Problem Questionnaire (DPQ) to collect data. Five hundred (500) students were randomly sampled in the five schools in the college. The results showed that drug addiction, school curriculum, cultism, peer group influence, overcrowded classroom, political, social, and economic among others are disciplinary problems experienced in the study area. The study made recommendations on how to improve the situation.

Keywords: challenges in higher institutions, disciplinary problems, social vices, students’ indiscipline

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Authors: Anandkumar Rshindhe

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Patents are considered as good monopoly in India. It is a mechanism by which the inventor is encouraged to do invention and also to make available to the society at large with a new useful technology. Patent system does not provide any protection to the invention itself but to the claims (rights) which the patentee has identified in relation to his invention. Thus the patentee is granted monopoly to the extent of his recognition of his own rights in the form of utilities and all other utilities of invention are for the public. Thus we find both benefit to the inventor and the public at large that is the ultimate consumer. But developing any such technology is not free of cost. Inventors do a lot of investment in the coming out with a new technologies. One such example if of Pharmaceutical industries. These pharmaceutical Industries do lot of research and invest lot of money, time and labour in coming out with these invention. Once invention is done or process identified, in order to protect it, inventors approach Patent system to protect their rights in the form of claim over invention. The patent system takes its own time in giving recognition to the invention as patent. Even after the grant of patent the pharmaceutical companies need to comply with many other legal formalities to launch it as a drug (medicine) in market. Thus major portion in patent term is unproductive to patentee and whatever limited period the patentee gets would be not sufficient to recover the cost involved in invention and as a result price of patented product is raised very much, just to recover the cost of invent. This is ultimately a burden on consumer who is paying more only because the legislature has failed to provide for the delay and loss caused to patentee. This problem can be effectively remedied if Patent Term extension is done. Due to patent term extension, the inventor gets some more time in recovering the cost of invention. Thus the end product is much more cheaper compared to non patent term extension.The basic question here arises is that when the patent period granted to a patentee is only 20 years and out of which a major portion is spent in complying with necessary legal formalities before making the medicine available in market, does the company with the limited period of monopoly recover its investment made for doing research. Further the Indian patent Act has certain provisions making it mandatory on the part of patentee to make its patented invention at reasonable affordable price in India. In the light of above questions whether extending the term of patent would be a proper solution and a necessary requirement to protect the interest of patentee as well as the ultimate consumer. The basic objective of this paper would be to check the implications of Extending the Patent term on Indian Consumers. Whether it provides the benefits to the patentee, consumer or a hardship to the Generic industry and consumer.

Keywords: patent term extention, consumer interest, generic drug industry, pharmaceutical industries

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Authors: S. Ivanova, K. Ivanov

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Bemitil (2-ethylthiobenzimidazole hydrobromide) is a synthetic adaptogen and actoprotector, with wide-ranging pharmacological activities such as nootropic, antihypoxic, antioxidant, immunostimulant. The intake of Bemitil increases mental and physical performance and could be applied under either normal or extreme conditions. Until 2017 Bemitil was not considered as doping and was used by professional athletes more than 30 years because of its high efficiency and safety. The drug was included in WADA monitoring programme for 2018, and most likely it would be included in WADA Prohibited List for 2019. Usually, a substance/method is included in WADA Prohibited List if it meets any two of the following three criteria: the potential to enhance or enhances sports performance/ potential health risk to the athlete/ violates the spirit of sport. Bemitil has high performance-enhancing potential, but it is also safe- it is controversial whether it should be considered as doping.

Keywords: doping, bemitil, sport, actoprotector

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Authors: Philip Robert Alldritt

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The continuing increase in human migration is at crisis levels in all areas of the planet. The causes are varied, and the risks are high for the migrants. Migration has been ongoing since the beginning of human emergence on the planet, but for the first time in our historic memory has the, migration reached this level of critical mass. The causes are many. Climate collapse, economic opportunity, drug cartel activity, political upheaval, and gang wars. Many locations are seemingly “within reach” of the migrants, and the push factors are so loaded with hopelessness that almost anyone would be willing to risk anything to improve their conditions. There is no argument about that mass migrations are occurring and will increase in the future. The solutions to this increase are complex. This paper will examine the causes of migration and attempt to provide some reasonable solutions to mitigate the migrations with equitable outcomes that may guide immigration policy in impacted areas.

Keywords: immigration, crisis, climate, cartels

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Authors: Nikhil Agrawal, Adam A. Skelton

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Alzheimer’s disease (AD) is one of the most common forms of dementia, which is caused by misfolding and aggregation of amyloid beta (Aβ) peptides into amyloid-β fibrils (Aβ fibrils). To disrupt the remodeling of Aβ fibrils, a number of candidate molecules have been proposed. To study the molecular mechanisms of Aβ fibrils remodeling we performed a series of all-atom molecular dynamics simulations, a total time of 3µs, in explicit solvent. Several previously undiscovered candidate molecule-Aβ fibrils binding modes are unraveled; one of which shows the direct conformational change of the Aβ fibril by understanding the physicochemical factors responsible for binding and subsequent remodeling of Aβ fibrils by the candidate molecule, open avenues into structure-based drug design for AD can be opened.

Keywords: alzheimer’s disease, amyloid, MD simulations, misfolded protein

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Authors: Ming-Dong Wang, Abigail F. Ruby, Michelle E. Ross

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Methylphenidate is a first-line treatment drug for attention deficit hyperactivity disorder (ADHD), a common mental health disorder in children and adolescents. Over the last several decades, the rate of children and adolescents using ADHD medication has been increasing in many countries. A recent study found that the prevalence of ADHD medication use among children aged 3-18 years increased in 13 different world regions between 2001 and 2015, where the absolute increase ranged from 0.02 to 0.26% per year. The goal of this study was to examine the use of methylphenidate in Canadian children and its associated adverse reactions. Methylphenidate use information among young Canadians aged 0-14 years was extracted from IQVIA data on prescriptions dispensed by pharmacies between April 2014 and June 2020. The adverse reaction information associated with methylphenidate use was extracted from the Canada Vigilance database for the same time period. Methylphenidate use trends were analyzed based on sex, age group (0-4 years, 5-9 years, and 10-14 years), and geographical location (province). The common classes of adverse reactions associated with methylphenidate use were sorted, and the relative risks associated with methylphenidate use as compared with two second-line amphetamine medications for ADHD were estimated. This study revealed that among Canadians aged 0-14 years, every 100 people used about 25 prescriptions (or 23,000 mg) of methylphenidate per year during the study period, and the use increased with time. Boys used almost three times more methylphenidate than girls. The amount of drug used was inversely associated with age: Canadians aged 10-14 years used nearly three times as many drugs compared to those aged 5-9 years. Seasonal methylphenidate use patterns were apparent among young Canadians, but the seasonal trends differed among the three age groups. Methylphenidate use varied from region to region, and the highest methylphenidate use was observed in Quebec, where the use of methylphenidate was at least double that of any other province. During the study period, Health Canada received 304 adverse reaction reports associated with the use of methylphenidate for Canadians aged 0-14 years. The number of adverse reaction reports received for boys was 3.5 times higher than that for girls. The three most common adverse reaction classes were psychiatric disorders, nervous system disorders and injury, poisoning procedural complications. The number one commonly reported adverse reaction for boys was aggression (11.2%), while for girls, it was a tremor (9.6%). The safety profile in terms of adverse reaction classes associated with methylphenidate use was similar to that of the selected control products. Methylphenidate is a commonly used pharmaceutical product in young Canadians, particularly in the province of Quebec. Boys used approximately three times more of this product as compared to girls. Future investigation is needed to determine what factors are associated with the observed geographic variations in Canada.

Keywords: adverse reaction risk, methylphenidate, prescription trend, use variation

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Authors: Adebayo-Victoria Tobi Dada, Dada Emmanuel

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This study assessed households’ food security and hunger levels among different communities with varying educational and economic background in Ile-Ife, Nigeria, and its environment. It also examined the impacts of varying demography on the household food security level in the area. This was with a view to providing information on the food security status of the subjects within the study area. Ten different communities with varying demography (Parakin, Mokuro, Ilare, Obafemi Awolowo University (OAU) Staff Quarters, Ibadan Road, Aba-Iya Gani, Eleweran, Iraye, Boosa, and Eku-Isobo) were identified within the study area. Fieldwork was then carried out from 7th to 14th of March, 2016 in each of these communities through survey of market prices of food stuff, diet, and nutrition, social well-being, food accessibility and affordability as well as price fluctuation and variation in household’s social background. Selection of households for the survey was done using stratified random sampling method. Key informants included community heads, landlords, tenants, and household heads. Similarly, information on food security levels with respect to demographic backgrounds was obtained from the use of modified Food and Hunger Insecurity Module (FHIM) structured questionnaire. The questionnaire was administered to one percent of the households’ population per community. The results showed that communities such as Parakin and OAU Senior Staff Quarters were dominated by civil servants, while community such as Boosa was dominated by artisans. Respondents earning between ₦11,000 and ₦20,000 per month, during the study period, had the highest percentage across the selected communities. The household food security indices showed that about 41% of the investigated respondents could not guarantee their household food for a month, while 18% reduced or skipped meals. There were positive significant relationships between monthly income (F-value = 132.04), educational status (F-value = 102.30), occupation (F-value = 104.05) and food budget (F-value = 122.09), all at p < 0.05. However, there was no significant relationship between the monthly food budget and household sizes (t-value = -1.4074, p > 0.05). Food secured households’ had the household heads with a higher level of educational attainment. The study concluded that large variations which existed between socio-economic and educational background among the communities had significant effects on households’ food security level in the study area.

Keywords: food security, households, hunger level, market prices

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Authors: Mridula Devi

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Trafficking of women is a slur on human dignity and a shameful act to human civilization and development. Trafficking of women is one of worst brazen abuses which violate the women’s human rights. In India, more particularly in Assam, human trafficking and infringement of human rights of individual includes mainly the women and girl child of the State. Trafficking in North East region of India, more particularly in Assam occurs in two different ways – one is the internal trafficking of women and girl child from conflict affected rural areas of Assam for domestic work and prostitution. Secondly, there is trafficking of women to other south-East Asiatic countries like Bangladesh, Bhutan, Bangkok, Myanmar (Burma) for various purposes such as drug trafficking, labor, bar girl and prostitution.Historically, trafficking in human beings is associated with slavery and bonded or forced labor. Since the period of Roman Civilization, there was the practice of traffic in persons in the form of slave trade among the nations. With the rise of new imperialism, slavery had become an integral part of the colonial system of European Countries. With time, it almost became synonymous with prostitution or commercial sexual exploitation. Finally, the United Nation adopted the Convention for the Suppression of the Traffic in Persons and of the Prostitution of others, 1949 by the G.A.Res.No.-317(iv). The Convention totally denounces the traffic in persons for the purpose of prostitution. However, it is important to note that, now a days trafficking is not confined to commercial sexual exploitation of women and children alone. It has myriad forms and the number of victims has been steadily on the rise over the past few decades. In Assam, it takes place through and for marriage, sexual exploitation, begging, organ trading, militancy conflicts, drug padding and smuggling, labour, adoption, entertainment, and sports. In this paper, empirical methodology has been used. The study is based on primary and secondary sources. Data’s are collected from different books, publications, newspaper, journals etc. For empirical analysis, some random samples are collected and systematized for better result. India suffers from the ignominy of being one of the biggest hubs of women trafficking in the world. Over the years, Assam: the north east part of India has been bearing the brunt of the rapidly rising evil of trafficking of women which threaten the life, dignity and human rights of women. Though different laws are adopted at international and national level to restore trafficking, still the menace of trafficking of women in Assam is not decreased, rather it increased. This causes a serious violation of women’s human right in Assam. Human trafficking or women’s trafficking is a serious crime against society. To curb this in Assam it is required to take some effective and dedicated measure at state level as well as national and international level.

Keywords: Assam, human trafficking, sexual exploitation, India

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Authors: Natalia Espinosa, Arthur Amorim, Rudolf Huebner

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Epilepsy is a chronic neural disease and around 50 million people in the world suffer from this disease, however, in many cases, the individual acquires resistance to the medication, which is known as drug-resistant epilepsy, where a detection system is necessary. This paper showed the development of an automatic system for seizure detection based on artificial neural networks (ANN), which are common techniques of machine learning. Discrete Wavelet Transform (DWT) is used for decomposing electroencephalogram (EEG) signal into main brain waves, with these frequency bands is extracted features for training a feedforward neural network with backpropagation, finally made a pattern classification, seizure or non-seizure. Obtaining 95% accuracy in epileptic EEG and 100% in normal EEG.

Keywords: Artificial Neural Network (ANN), Discrete Wavelet Transform (DWT), Epilepsy Detection , Seizure.

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Authors: Nancy Wilson

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In utero, fetal drug exposure is prevalent amongst birthing facilities. Assessment tools for neonatal abstinence syndrome (NAS) are often cumbersome and ill-fitting, harboring immense subjectivity. This paradox often leads the clinical assessor to be hypervigilant when assessing the newborn for subtle symptoms of NAS, often mistaken for normal newborn behaviors. As a quality improvement initiative, this project led to a more adaptable NAS tool termed eat, sleep, console (ESC). This function-based NAS assessment scores the infant based on the ability to accomplish three basic newborn necessities- to sleep, to eat, and to be consoled. Literature supports that ESC methodology improves patient and family outcomes while providing more cost-effective care.

Keywords: neonatal abstinence syndrome, neonatal opioid withdrawal, maternal substance abuse, pregnancy, and addiction, Finnegan neonatal abstinence syndrome tool, eat, sleep, console

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Authors: Rashmi Shukla, Yamini Bhusan Tripathi

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Diabetic nephropathy (DN) is characterized as diabetic kidney disease which involves many pathways e.g. hyperactivated protein kinase c (PKC), polyol pathway, excess production of advanced glycation end product (AGEs) & free radical accumulation etc. All of them results to hypoxia followed by apoptosis of podocytes, glomerulosclerosis, extracellular matrix (ECM) accumulation and fibrosis resulting to irreversible changes in kidney. This is continuously rising worldwide and there are not enough specific drugs, to retard its progress. Due to increasing side effects of allopathic drugs, interest in herbal remedies is growing. Earlier, we have reported that PTY-2 (a phytomedicine, derived from Pueraria tuberosa Linn.) inhibits the accumulation of extracellular matrix (ECM) through activation of MMP-9. Present study exhibited the therapeutic potential of Pueraria tuberosa in the prevention of podocytes apoptosis and modulation of nephrin expression in streptozotocin (STZ) induced DN rats. DN rats were produced by maintaining persistent hyperglycemia for 8 weeks by intra-peritoneal injection of 55 mg/kg streptozotocin (STZ). These rats were randomly divided in 2 groups, i.e. DN control, and DN+ water extract of Pueraria tuberosa (PTW). One group of age-matched normal rats served as non-diabetic control (group-1), The STZ induced DN rats (group-2) and DN+PTW treated rats (group-3). The PTW was orally administered (0.3g/kg) daily to group-2 rats and drug vector (1 ml of 10% tween 20) in control rats. The treatments were continued for 20 days and blood and urine samples were collected. Rats were then sacrificed to investigate the expression Bcl2, Bax and nephroprotective protein i.e. nephrin in kidney glomerulus. The effect of PTW was evaluated, we have found that the PTW significantly(p < .001) reversed the raised serum urea, serum creatinine, urine protein and improved the creatinine clearance in STZ induce diabetic nephropathy in rats and also significantly(p < .001) prevented the rise in urine albumin excretion. The Western blot analysis of kidney tissue homogenate showed increased expression of Bcl2 in PTW treated rats. The RT-PCR showed the increased expression and accumulation of nephrin mRNA. The confocal photomicrographs also supported the reduction of Bax and a simultaneous increase in Bcl2 and nephrin in glomerular podocytes. Hence, our finding suggests that the nephroprotective role of PTW is mediated via restoration of nephrin thus prevents the podocytes apoptosis and ameliorates diabetic nephropathy. The clinical trial of PTW would prove to be a potential food supplement/ drug of alternative medicine for patients with diabetic nephropathy in early stage.

Keywords: Pueraria tuberosa, diabetic nephropathy, anti-apoptosis, nephrin

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Authors: Sanjay Shukla, A. Nayak, R. K. Sharma, A. P. Singh, S. P. Tiwari

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Excessive use of antibiotics is a major problem in the treatment of wounds and other chronic infections, and antibiotic treatment is frequently non-curative, thus alternative treatment is necessary. Phage therapy is considered one of the most promising approaches to treat multi-drug resistant bacterial pathogens. Infections caused by Staphylococcus aureus are very efficiently controlled with phage cocktails, containing a different individual phages lysate infecting a majority of known pathogenic S. aureus strains. The aim of the present study was to evaluate the efficacy of a purified phage cocktail for prophylactic as well as therapeutic application in mouse model and in large animals with chronic septic infection of wounds. A total of 150 sewage samples were collected from various livestock farms. These samples were subjected for the isolation of bacteriophage by the double agar layer method. A total of 27 sewage samples showed plaque formation by producing lytic activity against S. aureus in the double agar overlay method out of 150 sewage samples. In TEM, recovered isolates of bacteriophages showed hexagonal structure with tail fiber. In the bacteriophage (ØVS) had an icosahedral symmetry with the head size 52.20 nm in diameter and long tail of 109 nm. Head and tail were held together by connector and can be classified as a member of the Myoviridae family under the order of Caudovirale. Recovered bacteriophage had shown the antibacterial activity against the S. aureus in vitro. Cocktail (ØVS1, ØVS5, ØVS9, and ØVS 27) of phage lysate were tested to know in vivo antibacterial activity as well as the safety profile. Result of mice experiment indicated that the bacteriophage lysate were very safe, did not show any appearance of abscess formation, which indicates its safety in living system. The mice were also prophylactically protected against S. aureus when administered with cocktail of bacteriophage lysate just before the administration of S. aureuswhich indicates that they are good prophylactic agent. The S. aureusinoculated mice were completely recovered by bacteriophage administration with 100% recovery, which was very good as compere to conventional therapy. In the present study, ten chronic cases of the wound were treated with phage lysate, and follow up of these cases was done regularly up to ten days (at 0, 5, and 10 d). The result indicated that the six cases out of ten showed complete recovery of wounds within 10 d. The efficacy of bacteriophage therapy was found to be 60% which was very good as compared to the conventional antibiotic therapy in chronic septic wounds infections. Thus, the application of lytic phage in single dose proved to be innovative and effective therapy for the treatment of septic chronic wounds.

Keywords: phage therapy, S aureus, antimicrobial resistance, lytic phage, and bacteriophage

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Authors: Krittapast Dara-Opast, Sureeporn Ruengsangtongkul, Jumreang Tummatorn, Kittipong Chainok, Onrapak Reamtong, Somsak Ruchirawat, Charnsak Thongsornkleeb

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Selective synthesis of gem-dihalo spiroisobenzofuran and spiroisocoumarin can be performed via halogenative double cyclization of methyl 2-(hydroxyalk-1-yn-1-yl) benzoates in the presence of either N-chlorosuccinimide (NCS) or N-bromosuccinimide (NBS) and chlorotrimethylsilane (TMSCl). The combination of NCS and TMSCl led to the generation of electrophilic chlorine in situ, which activated the alkyne functional group of the substrate leading to the cyclization via either 5-exo-dig or 6-endo-dig mode of cyclization to produce the target compounds in moderate yields. The protocol could be carried on a broad scope of substrates under mild conditions (0 °C to rt). The parent compounds showed good antiparasitic activity compared to standard drug albendazole. Further investigation of the scope of the reaction and their antiparasitic activities is underway.

Keywords: antiparasitic activities, halogenative annulation, spirocycles, spirocyclization

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Authors: Sperisa Distantina, Fadilah, Mujtahid Kaavessina

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Crosslinked konjac glucomannan and kappa carrageenan film were prepared by chemical crosslinking using glutaraldehyde (GA) as the crosslinking agent. The effect crosslinking on the swelling degree was investigated. Konjac glucomanan and its mixture with kappa carragenan film was immersed in GA solution and then thermally cured. The obtained crosslinked film was washed and soaked in the ethanol to remove the unreacted GA. The obtained film was air dried at room temperature to a constant weight. The infrared spectra and the value of swelling degree of obtained crosslinked film showed that glucomannan and kappa carrageenan was able to be crosslinked using glutaraldehyde by film immersion and curing method without catalyst. The crosslinked films were found to be pH sensitive, indicating a potential to be used in drug delivery polymer system.

Keywords: crosslinking, glucomannan, carrageenan, swelling

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