Search results for: antibiotic drugs

Authors: Oktira Roka Aji, Maelita R. Moeis, Ihsanawati, Ernawati A. Giri-Rachman

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Globally, tuberculosis (TB) remains a leading cause of death. The emergence of multidrug-resistant strains and extensively drug-resistant strains have become a major public concern. One of the potential candidates for drug target is the cytoplasmic domain of PhoR Histidine Kinase, a part of the Two Component System (TCS) PhoR-PhoP in Mycobacterium tuberculosis (Mtb). TCS PhoR-PhoP relay extracellular signal to control the expression of 114 virulent associated genes in Mtb. The 3D structure of PhoR cytoplasmic domain is needed to screen novel drugs using structure based drug discovery. The PhoR cytoplasmic domain from Mtb H37Rv was overexpressed in E. coli BL21(DE3), then purified using IMAC Ni-NTA Agarose his-tag affinity column and DEAE-ion exchange column chromatography. The molecular weight of the purified protein was estimated to be 37 kDa after SDS-PAGE analysis. This sample was used for pre-crystallization screening by applying sitting drop vapor diffusion method using Natrix (HR2-116) 48 solutions crystal screen kit at 25ºC. Needle-like crystals were observed after the seventh day of incubation in test solution No.47 (0.1 M KCl, 0.01 M MgCl2.6H2O, 0.05 M Tris-Cl pH 8.5, 30% v/v PEG 4000). Further testing is required for confirming the crystal.

Keywords: tuberculosis, two component system, histidine kinase, needle-like crystals

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Authors: Fateme Nokhodchi Bonab

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Studies related to magnetic resonance imaging (MRI) and drug delivery are reviewed in this study to demonstrate the role of transport theory in porous media in facilitating advances in biomedical applications. Diffusion processes are believed to be important in many therapeutic modalities such as: B. Delivery of drugs to the brain. We analyse the progress in the development of diffusion equations using the local volume average method and the evaluation of applications related to diffusion equations. Torsion and porosity have significant effects on diffusive transport. In this study, various relevant models of torsion are presented and mathematical modeling of drug release from biodegradable delivery systems is analysed. In this study, a new model of drug release kinetics from porous biodegradable polymeric microspheres under bulk and surface erosion of the polymer matrix is presented. Solute drug diffusion, drug dissolution from the solid phase, and polymer matrix erosion have been found to play a central role in controlling the overall drug release process. This work paves the way for MRI and drug delivery researchers to develop comprehensive models based on porous media theory that use fewer assumptions compared to other approaches.

Keywords: MRI, porous media, drug delivery, biomedical applications

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Authors: Swati Kapoor, Rajeev Upreti, Monica Mahajan, Abhaya Indrayan, Dinesh Srivastava

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Enteric Fever is caused by gram negative bacilli Salmonella typhi and paratyphi. It is associated with high morbidity and mortality worldwide. Timely initiation of treatment is a crucial step for prevention of any complications. Cultures of body fluids are diagnostic, but not always conclusive or practically feasible in most centers. Moreover, the results of cultures delay the treatment initiation. Serological tests lack diagnostic value. The blood counts can offer a promising option in diagnosis. A retrospective study to find out the relevance of leucopenia and eosinopenia was conducted on 203 culture proven enteric fever patients and 159 culture proven non-enteric fever patients in a tertiary care hospital in New Delhi. The patient details were retrieved from the electronic medical records section of the hospital. Absolute eosinopenia was considered as absolute eosinophil count (AEC) of less than 40/mm³ (normal level: 40-400/mm³) using LH-750 Beckman Coulter Automated machine. Leucopoenia was defined as total leucocyte count (TLC) of less than 4 X 10⁹/l. Blood cultures were done using BacT/ALERT FA plus automated blood culture system before first antibiotic dose was given. Case and control groups were compared using Pearson Chi square test. It was observed that absolute eosinophil count (AEC) of 0-19/mm³ was a significant finding (p < 0.001) in enteric fever patients, whereas leucopenia was not a significant finding (p=0.096). Using Receiving Operating Characteristic (ROC) curves, it was observed that patients with both AEC < 14/mm³ and TCL < 8 x 10⁹/l had 95.6% chance of being diagnosed as enteric fever and only 4.4% chance of being diagnosed as non-enteric fever. This result was highly significant with p < 0.001. This is a very useful association of AEC and TLC found in enteric fever patients of this study which can be used for the early initiation of treatment in clinically suspected enteric fever patients.

Keywords: absolute eosinopenia, absolute eosinophil count, enteric fever, leucopenia, total leucocyte count

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Authors: M. Umar Hafeez, Furqan Khursheed Hashmi, Nadeem Irfan Bukhari, Shahzad Ali, Muzammil Ali

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The trend of self-medication is increasing due to various factors and is associated with a large number of complications. A cross-sectional study was aimed to investigate self-medication trend in an urban community and its correlates such as level of education, gender and behavior of using psychoactive medicines. A validated questionnaire was used to collect the data from different locations of Lahore, provincial capital of Punjab, Pakistan. The trend of self-medication was noted in reference to difference in educational level and in gender. This study showed that total 110 respondents, all literate,were found to be self-medicating, and their educational status was as 73.13% primary, 63.15% secondary, 61.12% higher secondary and 62.15% university going. In this sample 74.99% were males and 48.00%were females. Twenty nine (26.36%) of the total sample were found to be using psychoactive agents without consulting the physician. The trend of self-medication was 10% higher in individuals having primary level education, whereas there was not much difference of self-medication trend in other levels of education. The main reasons involved in self-medication trend were socio-economic status, medicine accessibility, religious and cultural beliefs, lack of awareness about risks associated with medicine, non-prescription sale of medicines and previous medication experience. The trend of self-medication of psychotropic agents is quite significant.

Keywords: self-medication, educated community, psychotropic drugs, education levels

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Authors: Sertac Arslan, Guven Guney, Ayse Ipek Akyuz Unsal, Emre Demir, Buket Demirci

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Purpose: There is little histologic data concerning effects of nasal decongestants on the respiratory tract. We aimed to put forth the effects of nasal decongestants on the trachea and lower airways of rats. Materials and Methods: Four to six months old 60 male rats were randomly categorized into 6 groups. Experimental drugs were applied to the same nostril of rats twice daily for 8 weeks (Xylometazolin, Benzalkolyum, EDTA, Sorbitol and combined drug solutions). We applied normal saline solution (NaCl %0.9) for the control group. In the end, trachea and both lungs were dissected and kept in formaldehyde for histopathologic evaluation. Results: Inflammation and bronchial edema were most common findings. While all rats in sorbitol group had increased numbers of type 2 pneumocytes; 80% of BAC group had increased numbers of type 2 pneumocytes. Spillover of tracheal epithelium was seen mostly in sorbitol, EDTA and combined drug groups (60%, 87.5%, 50% respectively). Bronchial smooth muscle hypertrophy was seen mostly in BAC and EDTA group (70%, 62.5% respectively). The number of goblet cells showed the significant difference between control-combined drug (p=0.025) and control-BAC (p=0.001) groups. Conclusions: Nasal decongestants can cause permanent changes at lower respiratory tract in addition to changes in upper respiratory tract.

Keywords: decongestive agents, xylometazoline, lung, trachea

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Authors: Feras Darwish Elhajji, Alberto Berardi, Manal Ayyash, Iman Basheti

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The concept of the use of probiotics for humans now has been known for decades however, their intake by the Jordanian population seems to be less common when compared to population in the developed countries. Community pharmacy is the main supplier of probiotics, however, after conducting an extensive literature review, not any published research article could be found talking about the role, knowledge, and practice of the pharmacists in the area of probiotics. The main aim of this study was to evaluate the level of knowledge about probiotics and their dispensing practice in community pharmacies in Jordan. Community pharmacy staff (pharmacists and technicians) in Amman and north of Jordan were randomly selected to complete an anonymous questionnaire that had been pre-tested and validated. Ethical approval was obtained from the university ethics committee. The questionnaire included the following sections: demographics, knowledge and perceptions about probiotics, and role of the pharmacist Pharmacists and technicians were visited and interviewed in 281 community pharmacies. Asking about probiotics, 90.4% of them said that they know what probiotics are, although only 29.5% agreed that pharmacy staff in Jordan have good knowledge about probiotics, and 88.3% agreed that pharmacy staff in Jordan need more training and knowledge about probiotics. Variables that were significantly related to knowledge about probiotics were being a pharmacist (ρ= 0.012), area of the community pharmacy (ρ= 0.019), and female staff (ρ= 0.031) after conducting logistic regression statistical analysis. More than two-thirds of the participants thought that probiotics are classified as dietary supplements by Jordan Food and Drug Administration (JFDA). Of those who knew probiotics, the majority of them – 76.8% and 91.7% – agreed that probiotics are effective and safe, respectively. Believing in efficacy of the probiotics was significantly associated with answering their use to be with or after antibiotic administration and to increase normal flora gut population (ρ= 0.007). Efficacy was also significantly associated with recommending probiotics to consumers by the pharmacist (ρ< 0.001) and by the doctor (ρ= 0.041). At the same time, the concept of safety was mainly associated with their use for flatulence and gases (ρ= 0.048). Level of knowledge about probiotics and their uses, efficacy and safety amongst community pharmacy staff in Jordan is found to be good. However, this level can be raised in the future, especially knowledge about uses of probiotics.

Keywords: community pharmacy, Jordan, prebiotics, probiotics

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Authors: Syeda Fahria Hoque Mimmi

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Many new and promising treatments for reducing or diminishing the adverse effects of microorganisms are being discovered day by day. On the other hand, the dairy industry is accelerating the economic wheel of Bangladesh. Considering all these facts, new thoughts were developed to isolate milk proteins by the present experiment for opening up a new era of developing natural antibiotics from milk. Lactoferrin, an iron-binding glycoprotein with multifunctional properties, is crucial to strengthening the immune system and also useful for commercial applications. The protein’s iron-binding capacity makes it undoubtedly advantageous to immune system modulation and different bacterial strains. For fulfilling the purpose, 4 of raw and 17 of commercially available milk samples were collected from different farms and stores in Bangladesh (Dhaka, Chittagong, and Cox’s Bazar). Protein quantification by nanodrop technology has confirmed that raw milk samples have better quantities of protein than the commercial ones. All the samples were tested for their antimicrobial activity against 18 pathogens, where raw milk samples showed a higher percentage of antibacterial activity. In addition to this, SDS-PAGE (Sodium Dodecyl Sulfate–Polyacrylamide Gel Electrophoresis) was performed to identify lactoferrin in the milk samples. Lactoferrin was detected in 9 samples from which 4 were raw milk samples. Interestingly, Streptococcus pyogenes, Klebsiella pneumoniae, Bacillus cereus, Pseudomonas aeruginosa, Vibrio cholera, Staphylococcus aureus, and enterotoxigenic E. coli significantly displayed sensitivity against lactoferrin collected from raw milk. Only Bacillus cereus, Pseudomonas aeruginosa, Streptococcus pneumonia, Enterococcus faecalis, and ETEC (Enterotoxigenic Escherichia coli) were susceptible to lactoferrin obtained from a commercial one. This study suggested that lactoferrin might be used as the potential alternative of antibiotics for many diseases and also can be used to reduce microbial deterioration in the food and feed industry.

Keywords: alternative of antibiotics, commercially available milk, lactoferrin, nanodrop technology, pathogens, raw milk

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Authors: Lichung Jen, Yi Chun Liu, Kuan-Wei Lee

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Fruitful data has been accumulated in database nowadays and is commonly used as support for decision-making. In the healthcare industry, hospital, for instance, ordering pharmacy inventory is one of the key decision. With large drug inventory, the current cost increases and its expiration dates might lead to future issue, such as drug disposal and recycle. In contrast, underestimating demand of the pharmacy inventory, particularly standing drugs, affects the medical treatment and possibly hospital reputation. Prescription behaviour of hospital physicians is one of the critical factor influencing this decision, particularly irregular prescription behaviour. If a drug’s usage amount in the month is irregular and less than the regular usage, it may cause the trend of subsequent stockpiling. On the contrary, if a drug has been prescribed often than expected, it may result in insufficient inventory. We proposed a hierarchical Bayesian mixture model with two components to identify physicians’ regular/irregular prescription patterns with probabilities. Heterogeneity of hospital is considered in our proposed hierarchical Bayes model. The result suggested that modeling the prescription patterns of physician is beneficial for estimating the order quantity of medication and pharmacy inventory management of the hospital. Managerial implication and future research are discussed.

Keywords: hierarchical Bayesian model, poission mixture model, medicines prescription behavior, irregular behavior

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Authors: Calvin A. Omolo, Rahul S. Kalhapure, Mahantesh Jadhav, Sanjeev Rambharose, Chunderika Mocktar, Thirumala Govender

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Treatment of infections is compromised by limitations of conventional dosage forms and drug resistance. Nanocarrier system is a strategy to overcome these challenges and improve therapy. Thus, the development of novel materials for drug delivery via nanocarriers is essential. The aim of the study was to synthesize a multi-arm polymer (6-mPEPEA) for enhanced activity of vancomycin (VM) against susceptible and resistant Staphylococcus aureus (MRSA). The synthesis steps of the star polymer followed reported procedures. The synthesized 6-mPEPEA was characterized by FTIR, ¹H and ¹³CNMR and MTT assays. VM loaded micelles were prepared from 6-mPEPEA and characterized for size, polydispersity index (PI) and surface charge (ZP) (Dynamic Light Scattering), morphology by TEM, drug loading (UV Spectrophotometry), drug release (dialysis bag), in vitro and in vivo efficacy against sensitive and resistant S. aureus. 6-mPEPEA was synthesized, and its structure was confirmed. MTT assays confirmed its nontoxic nature with a high cell viability (77%-85%). Unimolecular spherical micelles were prepared. Size, PI, and ZP was 52.48 ± 2.6 nm, 0.103 ± 0.047, -7.3 ± 1.3 mV, respectively and drug loading was 62.24 ± 3.8%. There was a 91% drug release from VCM-6-mPEPEA after 72 hours. In vitro antibacterial test revealed that VM-6-mPEPEA had 8 and 16-fold greater activity against S. aureus and MRSA when compared to bare VM. Further investigations using flow cytometry showed that VM-6-mPEPEA had 99.5% killing rate of MRSA at the MIC concentration. In vivo antibacterial activity revealed that treatment with VM-6-mPEPEA had a 190 and a 15-fold reduction in the MRSA load in untreated and VM treated respectively. These findings confirmed the potential of 6-mPEPEA as a promising bio-degradable nanocarrier for antibiotic delivery to improve treatment of bacterial infections.

Keywords: biosafe, MRSA, nanocarrier, resistance, unimolecular-micelles

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Authors: A. Lubis, R. Widayanti, Z. Hikmah, A. Endaryanto, A. Harsono, A. Harianto, R. Etika, D. K. Handayani, M. Sampurna

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Neonatal lupus erythematous (NLE) is a rare disease marked by clinical characteristic and specific maternal autoantibody. Many cutaneous, cardiac, liver, and hematological manifestations could happen with affect of one organ or multiple. In this case, both babies were premature, low birth weight (LBW), small for gestational age (SGA) and born through caesarean section from a systemic lupus erythematous (SLE) mother. In the first case, we found a baby girl with dyspnea and grunting. Chest X ray showed respiratory distress syndrome (RDS) great I and echocardiography showed small atrial septal defect (ASD) and ventricular septal defect (VSD). She also developed anemia, thrombocytopenia, elevated C-reactive protein, hypoalbuminemia, increasing coagulation factors, hyperbilirubinemia, and positive blood culture of Klebsiella pneumonia. Anti-Ro/SSA and Anti-nRNP/sm were positive. Intravenous fluid, antibiotic, transfusion of blood, thrombocyte concentrate, and fresh frozen plasma were given. The second baby, male presented with necrotic tissue on the left ear and skin rashes, erythematous macula, athropic scarring, hyperpigmentation on all of his body with various size and facial haemorrhage. He also suffered from thrombocytopenia, mild elevated transaminase enzyme, hyperbilirubinemia, anti-Ro/SSA was positive. Intravenous fluid, methyprednisolone, intravenous immunoglobulin (IVIG), blood, and thrombocyte concentrate transfution were given. Two cases of neonatal lupus erythematous had been presented. Diagnosis based on clinical presentation and maternal auto antibody on neonate. Organ involvement in NLE can occur as single or multiple manifestations.

Keywords: neonatus lupus erythematous, maternal autoantibody, clinical characteristic, multiple organ manifestation

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Authors: Lokesh Bhatt, Jayesh Rathod

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Hypertension is one of the most prevalent cardiovascular disorder. It is responsible for several other cardiovascular disorders. Although many drugs are available for the treatment of hypertension, still a large population has uncontrolled blood pressure. Thus there is an unmet need for new therapeutic approaches for the same. Fruit juice of Citrus paradise contains several flavonoids with vasodilatory activity. We hypothesized that alcoholic extract of Citrus paradise, which contains flavonoids, might attenuate hypertension. The objective of the present study was to evaluate the antihypertensive activity of alcoholic extract of Citrus paradise fruit juice in rats. Hypertension was induced using one clip one kidney model in rats. The renal artery was occluded for 4 h after removal of one kidney. Once stabilized, the ganglionic blockade was performed followed by removal of the arterial clip from the kidney. Removal of clip resulted in an increase in blood pressure which is due to release of renin from the kidney. Alcoholic extract of Citrus paradise fruit juice was then administered at 50 mg/kg and 100 mg/kg dose by intravenous injection. Blood pressure was monitored continuously. Alcoholic extract of Citrus paradise fruit juice reduced hypertension in dose-dependent manner. Antihypertensive activity was found to be associated with vasodilation. The results of the present study showed antihypertensive potential of alcoholic extract of Citrus paradise fruit juice.

Keywords: citrus paradise, alcoholic extract, one clip one kidney model, vasodilation

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Authors: Ahmed A. Abd El Rahim, Andrew Anis Fakhrey Mosaad

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Background: An important psychological issue that has an impact on both mental and physical function is anxiety disorders. The general consensus is that aerobic exercise and physical activity are good for lowering anxiety and mood. Purpose: This study's goal was to look into how patients with anxiety disorders responded to aerobic exercise. Subjects: Anxiety disorders were identified in 30 individuals from the psychiatric hospital at Sohag University who were chosen based on inclusive criteria and had ages ranging from 25 to 45. Methods: Patients were split into two equal groups at random: For four weeks, three sessions per week, fifteen patients in group A (the study group), seven men and eight women, underwent medication therapy and aerobic exercise. Age (28.4 ± 2.11 years), weight (72.5 ± 10.06 kg), height (164.8 ± 9.64 cm), and BMI (26.65 ± 2.68 kg/m2) were all mean SD values. And in Group B (Control Group), only medication therapy was administered to 15 patients (9 males and 6 females). Age (29.6 ± 3.68), weight (75 ± 7.07 kg), height (166.9 ± 6.75) cm, and BMI (26.87 ± 1.11) kg/m2 were the mean SD values. Before and after the treatment, the Hamilton Anxiety Scale was used to gauge the patient's degree of anxiety. Results: Within the two groups, there were significant differences both before and after the treatment. Following therapy, there was a significant difference between the two groups; the study group displayed better improvement on the Hamilton Anxiety Scale. Conclusion: Patients with anxiety problems can benefit from aerobic activities and antianxiety drugs as effective treatments for lowering anxiety levels.

Keywords: aerobic exercises, anxiety disorders, antianxiety medications, Hamilton anxiety scale

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Authors: Mohamed Mahdi Alshahni, Takashi Tamura, Koichi Makimura

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Objective: The objective of this study is to evaluate roles of ABC-type efflux transporters in the resistance of Candida auris against common antifungal agents. Material and Methods: A wild-type C. auris strain and its antifungal resistant derivative strain that is generated through induction by antifungal agents were used in this study. The strains were cultured onto media containing beauvericin alone or in combination with azole agents. Moreover, expression levels of four ABC-type transporter’s homologs in those strains were analyzed by real time PCR with or without antifungal stress by fluconazole or voriconazole. Results: Addition of beauvericin helped to partially restore the susceptibility of the resistant strain against fluconazole, suggesting participation of ABC-type transporters in the resistance mechanism. Real time PCR results showed that mRNA levels of three out of the four analyzed transporters in the resistant strain were more than 2-fold higher than their counterparts in the wild-type strain under negative control and antifungal agent-containing conditions. Conclusion: C. auris is an emerging multidrug-resistant pathogen causing human mortality worldwide. Providing effective treatment has been hampered by the resistance to antifungal drugs, demanding understanding the resistance mechanism in order to devise new therapeutic strategies. Our data suggest a partial contribution of ABC-type transporters to the resistance of this pathogen.

Keywords: resistance, C. auris, transporters, antifungi

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Authors: Li-Yu Lee, Yu-Shuan Chen, Jun Sheng Wang, I-Ming Chu

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Microneedle patch is a painless transdermal drug delivery method, It could solve some problems in traditional drug delivery such as digestive system causing drug metabolism and subcutaneous injection causing some side effects. Coating drug on or loading drug in microneedle can carry active ingredient through stratum corneum, also can control dose well when microneedle patch apply on localized topical area. We used hyaluronic acid to fabricate dissolvable microneedle patch and encapsulated minoxidil into microneedles. Minoxdil is a drug for exterior use that can be used to treat Androgenetic alopecia, but related commercial products have some shortcomings, for example, propylene glycol which is used to soften stratum corneum cause skin allergic reaction, comparing chemical promotion, microneedle patch provide physical way to make drugs through nature barrier of skin. In this research, we designed a two-step process to fabricate microneedle patch, that can effectively reduce drug waste, and gentle production process could maintain drug activity well. We also do in vitro test on cadaver to make sure patch has enough mechanical strength to penetrate stratum corneum. In the release test and animal test, we found microneedle patch has higher delivery efficiency than tradition way. In this study, we may determine that germinal MNs patch is a potential commodity.

Keywords: dissolving microneedles, androgenetic alopecia, minoxidil, transdermal drug delivery

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Authors: Reza Ferdousi, Reza Safdari, Yadollah Omidi

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Drug-drug interactions (DDIs) are main cause of the adverse drug reactions and nature of the functional and molecular complexity of drugs behavior in human body make them hard to prevent and treat. With the aid of new technologies derived from mathematical and computational science the DDIs problems can be addressed with minimum cost and efforts. Market basket analysis is known as powerful method to identify co-occurrence of thing to discover patterns and frequency of the elements. In this research, we used market basket analysis to identify important bio-elements in DDIs occurrence. For this, we collected all known DDIs from DrugBank. The obtained data were analyzed by market basket analysis method. We investigated all drug-enzyme, drug-carrier, drug-transporter and drug-target associations. To determine the importance of the extracted bio-elements, extracted rules were evaluated in terms of confidence and support. Market basket analysis of the over 45,000 known DDIs reveals more than 300 important rules that can be used to identify DDIs, CYP 450 family were the most frequent shared bio-elements. We applied extracted rules over 2,000,000 unknown drug pairs that lead to discovery of more than 200,000 potential DDIs. Analysis of the underlying reason behind the DDI phenomena can help to predict and prevent DDI occurrence. Ranking of the extracted rules based on strangeness of them can be a supportive tool to predict the outcome of an unknown DDI.

Keywords: drug-drug interaction, market basket analysis, rule discovery, important bio-elements

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Authors: Emad Heydarnia, Aref Sepasi, Nika Asefi, Sara Khakshournia, Javad Mohammadnejad

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Background: Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and Sorafenib are well-known therapeutic in breast cancer. In the present study, we combined Sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. Methods: The MCF-7 cells were treated with Metformin, Sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by Real-time PCR. Results: The results showed that MCF-7 cells treated with Metformin/Sorafenib and PCL-sorafenib/Metformin co-treatment contributed to 50% viability compared to untreated group. Moreover, PI and Annexin V staining tests showed that the cells viability for Metformin/Sorafenib and PCL-sorafenib/Metformin was 38% and 17%, respectively. Furthermore, Sorafenib/Metformin and PCL-sorafenib/Metformin leads to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2, and BAX genes and altered the cell cycle. Conclusion: Together, the combination of PCL-sorafenib/Metformin and Sorafenib/Metformin increased Sorafenib absorption at lower doses and also leads to apoptosis and oxidative stress increases in MCF-7 cells.

Keywords: breast cancer, metformin, nanotechnology, sorafenib

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Authors: Katharigatta N. Venugopala, Melendhran Pillay, Bander E. Al-Dhubiab

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Tuberculosis (TB) infection is caused mainly by Mycobacterium tuberculosis (MTB) and it is one of the most threatening and wide spread infectious diseases in the world. Benzothiazole derivatives are found to have diverse chemical reactivity and broad spectrum of pharmacological activity. Some of the important pharmacological activities shown by the benzothiazole analogues are antitumor, anti-inflammatory, antimicrobial, anti-tubercular, anti-leishmanial, anticonvulsant and anti-HIV properties. Keeping all these facts in mind in the present investigation it was envisaged to synthesize a series of novel {2-(benzo[d]-thiazol-2-yl-methoxy)-substitutedaryl}-(substitutedaryl)-methanones (4a-f) and characterize by IR, NMR (1H and 13C), HRMS and single crystal x-ray studies. The title compounds are investigated for in vitro anti-tubercular activity against two TB strains such as H37Rv (ATCC 25177) and MDR-MTB (multi drug resistant MTB resistant to Isoniazid, Rifampicin and Ethambutol) by agar diffusion method. Among the synthesized compounds in the series, test compound {2-(benzo[d]thiazol-2-yl-methoxy)-5-fluorophenyl}-(4-chlorophenyl)-methanone (2c) was found to exhibit significant activity with MICs of 1 µg/mL and 2 µg/mL against H37Rv and MDR-MTB, respectively when compared to standard drugs. Single crystal x-ray studies was used to study intra and intermolecular interactions, including polymorphism behavior of the test compounds, but none of the compounds exhibited polymorphism behavior.

Keywords: benzothiazole analogues, characterization, crystallography, anti-TB activity

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Authors: Adnan Lanjawi

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This paper is carried out to investigate the management of hazardous waste in the chemistry section which belongs to Dubai Police forensic laboratory. The chemicals are the main contributor toward the accumulation of hazardous waste in the section. This is due to the requirement to use it in analysis, such as of explosives, drugs, inorganic and fire debris cases. This leads to negative effects on the environment and to the employees’ health and safety. The research investigates the quantity of chemicals there, the labels, the storage room and equipment used. The target is to reduce the need for disposal by looking at alternative options, such as elimination, substitution and recycling. The data was collected by interviewing the top managers there who have been working in the lab more than 20 years. Also, data was collected by observing employees and how they carry out experiments. Therefore, a survey was made to assess their knowledge about the hazardous waste. The management of hazardous chemicals in the chemistry section needs to be improved. The main findings illustrate that about 110 bottles of reference substances were going to be disposed of in 2014. These bottles were bought for about 100,000 UAE Dirhams (£17,600). This means that the management of substances purchase is not organised. There is no categorisation programme in place, which makes the waste control very difficult. In addition, the findings show that chemical are segregated according to alphabetical order, whereas the efficient way is to separate them according to their nature and property. In addition, the research suggested technology and experiments to follow to reduce the need for using solvents and chemicals in the sample preparation.

Keywords: control, hazard, laboratories, waste,

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Authors: Fariha Akhter Chowdhury, Sabrina Mahboob, Anamika Saha, Afrin Jahan, Mohammad Nurul Islam

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Urinary tract infection (UTI) is frequently experienced by the female population where the prevalence increases with aging. Escherichia coli, one of the most common UTI causing organisms, retains glutathione defense mechanism that aids the organism to withstand the harsh physiological environment of urinary tract, host oxidative immune response and even to affect antibiotic-mediated cell death and the emergence of resistance. In this study, we aimed to investigate the glutathione reductase activity of uropathogenic E. coli (UPEC) by observing the reduced glutathione (GSH) level alteration under stressful condition. Urine samples of 58 patients with UTI were collected. Upon isolation and identification, 88% of the samples presented E. coli as UTI causing organism among which randomly selected isolates (n=9), obtained from urine samples of female patients, were considered for this study. E. coli isolates were grown under normal and stressful conditions where H₂O₂ was used as the stress-inducing agent. GSH level estimation of the isolates in both conditions was carried out based on the colorimetric measurement of 5,5'-dithio-bis (2-nitrobenzoic acid) (DTNB) and GSH reaction product using microplate reader assay. The GSH level of isolated E. coli sampled from adult patients decreased under stress compared to normal condition (p = 0.011). On the other hand, GSH production increased markedly in samples that were collected from elderly subjects (p = 0.024). A significant partial correlation between age and change of GSH level was found as well (p = 0.007). This study may help to reveal ways for better understanding of E. coli pathogenesis of UTI prevalence in elderly patients.

Keywords: Escherichia coli, glutathione reductase activity, oxidative stress, reduced glutathione (GSH), urinary tract infection (UTI)

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Authors: H. Tayefih, F. farajzade ahari, F. Zarghami, V. Zeighamian, N. Zarghami, Y. Pilehvar-soltanahmadi

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Breast cancer is the most frequently occurring cancer among women throughout the world. Natural compounds such as curcumin hold promise to treat a variety of cancers including breast cancer. However, curcumin's therapeutic application is limited, due to its rapid degradation and poor aqueous solubility. On the other hand, previous studies have stated that drug delivery using nanoparticles might improve the therapeutic response to anticancer drugs. Poly (N-isopropylacrylamide-co-methacrylic acid) (PNIPAAm–MAA) is one of the hydrogel copolymers utilized in the drug delivery system for cancer therapy. The aim of this study was to examine the cytotoxic potential of curcumin encapsulated within the NIPAAm-MAA nanoparticle, on the MCF-7 breast cancer cell line. In this work, polymeric nanoparticles were synthesized through the free radical mechanism, and curcumin was encapsulated into NIPAAm-MAA nanoparticles. Then, the cytotoxic effect of curcumin-loaded NIPAAm-MAA on the MCF-7 breast cancer cell line was measured by MTT assays. The evaluation of the results showed that curcumin-loaded NIPAAm-MAA has more cytotoxic effect on the MCF-7 cell line and efficiently inhibited the growth of the breast cancer cell population, compared with free curcumin. In conclusion, this study indicates that curcumin-loaded NIPAAm-MAA suppresses the growth of the MCF-7 cell line. Overall, it is concluded that encapsulating curcumin into the NIPAAm-MAA copolymer could open up new avenues for breast cancer treatment.

Keywords: PNIPAAm-MAA, breast cancer, curcumin, drug delivery

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Authors: Md. Danish Eqbal, Venkat Gundabala

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Microparticles and microcapsules are basically used as a carrier for cells, tissues, drugs, and chemicals. Due to its biocompatibility, non-toxicity and biodegradability, alginate based microparticles have numerous applications in drug delivery, tissue engineering, organ repair and transplantation, etc. The production of uniform monodispersed microparticles was a challenge for the past few decades. However, emergence of microfluidics has provided controlled methods for the generation of the uniform monodispersed microparticles. In this work, we present a successful method for the generation of both microparticles and microcapsules (single and double core) using merging approach of two droplets, completely inside the microfluidic device. We have fabricated hybrid glass- PDMS (polydimethylsiloxane) based microfluidic device which has coflow geometry as well as the T junction channel. Coflow is used to generate the single as well as double oil-alginate emulsion in oil and T junction helps to form the calcium chloride droplets in oil. The basic idea is to match the frequency of the alginate droplets and calcium chloride droplets perfectly for controlled generation. Using the merging of droplets technique, we have successfully generated the microparticles and the microcapsules having single core as well as double and multiple cores. The cores in the microcapsules are very stable, well separated from each other and very intact as seen through cross-sectional confocal images. The size and the number of the cores along with the thickness of the shell can be easily controlled by controlling the flowrate of the liquids.

Keywords: double-core, droplets, microcapsules, microparticles

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Authors: Soo Hong Da, Ng Zheng Yao, Burra Venkata Durga Kumar

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The Healthcare sector is a business that consists of providing medical services, manufacturing medical equipment and drugs as well as providing medical insurance to the public. Most of the time, the data stored in the healthcare database is to be related to patient’s information which is required to be accurate when it is accessed by authorized stakeholders. In distributed systems, one important issue is concurrency in the system as it ensures the shared resources to be synchronized and remains consistent through multiple read and write operations by multiple clients. The problems of concurrency in the healthcare sector are who gets the access and how the shared data is synchronized and remains consistent when there are two or more stakeholders attempting to the shared data simultaneously. In this paper, a framework that is beneficial to distributed healthcare sector concurrent environment is proposed. In the proposed framework, four different level nodes of the database, which are national center, regional center, referral center, and local center are explained. Moreover, the frame synchronization is not symmetrical. There are two synchronization techniques, which are complete and partial synchronization operation are explained. Furthermore, when there are multiple clients accessed at the same time, synchronization types are also discussed with cases at different levels and priorities to ensure data is synchronized throughout the processes.

Keywords: resources, healthcare, concurrency, synchronization, stakeholders, database

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Authors: Prasanthi Malapati, R. Reshma, Vijay Soni, Perumal Yogeeswari, Dharmarajan Sriram

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In the present study, we attempted to develop Mycobacterium tuberculosis (Mtb) inhibitors by exploring the pharmaceutically underexploited enzyme targets which are majorly involved in cell wall biosynthesis of mycobacteria. For this purpose, glutamate racemase (coded by MurI gene) was selected. This enzyme racemize L-glutamate to D-glutamate required for the construction of peptidoglycan in the bacterial cell wall synthesis process. Furthermore this enzyme is neither expressed nor its product, D-glutamate is normally found in mammals, and hence designing inhibitors against this enzyme will not affect the host system as well act as potential antitubercular drugs. A library of BITS in house compounds were screened against Mtb MurI enzyme. Based on docking score, interactions and synthetic feasibility one hit lead was identified. Further optimization of lead was attempted and its derivatives were synthesized. Forty eight derivatives of 2-phenylbenzo[d]oxazole and 2-phenylbenzo[d]thiazole were synthesized and evaluated for Mtb MurI inhibition study, in vitro activities against Mtb, cytotoxicity against RAW 264.7 cell line. Chemical derivatization of the lead resulted in compounds NR-1213 AND NR-1124 as the potent M. tuberculosis glutamate racemase inhibitors with IC50 of 4-5µM which are remarkable and were found to be non-cytotoxic. Molecular dynamics, dormant models and cardiotoxicity studies of the most active molecules are in process.

Keywords: cell wall biosynthesis, dormancy, glutamate racemase, tuberculosis

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Authors: Hosein Alimadadi, Fatemeh Farahmand, Ali Jafarian, Nasir Fakhar, Mohammad Hassan Sohouli, Neda Raeesi

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Backgroundsː Regarding the important role of liver transplantation as the only treatment in many cases of end-stage liver disease in children, the aim of this study is to investigate the complications of liver transplantation and their management in children referred to the Children's Medical Center. Methods: This study is a cross-sectional study on pediatric patients who have undergone liver transplants in the years 2016 to 2021. The indication for liver transplantation in this population was confirmed by a pediatric gastroenterologist, and a liver transplant was performed by a transplant surgeon. Finally, information about the patient before and after the transplantation was collected and recorded. Results: A total of 53 patients participated in this study, including 25 (47.2%) boys and 28 (52.8%) girls. The most common causes of liver transplantation were cholestatic and metabolic diseases. The most common early complication of liver transplantation in children was acute cellular rejection (ACR) and anastomotic biliary stricture. The most common late complication in these patients was an infection which was observed in 56.6% of patients. Among the drug side effects, neurotoxicity (convulsions) was seen more in patients, and 15.1% of the transplanted patients died. Conclusion: In this study, the most common early complication of liver transplantation in children was ACR and biliary stricture, and the most common late complication was infection. Neurotoxicity (convulsions) was the most common side effect of drugs.

Keywords: liver transplantation, complication, infection, survival rate

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Authors: Lamees A. Ben Saad, Kah Hwi Kim, Chin Chew Quah, Mustafa Shahimi

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Background: Punica granatum (pomegranate) was used as a traditional medicine in different parts of the world. It has been used in the treatment of pain and inflammatory conditions such as peptic ulcer. The numerous risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of pain and inflammation give rise to using medicinal herbs as alternative therapies. This study aimed to evaluate the anti-inflammatory effect of the ethyl acetate pomegranate fraction (EtOAc) by determination of its inhibitory effects on lipopolysaccharide (LPS), stimulated nitric oxide (NO), prostaglandin E2 (PGE-2), interleukin-6 (IL-6) and cyclooxxgenase-2 (COX2) release from RAW264.7cells. Methods: The inhibitory effect of EtOAc was evaluated on (LPS) induced NO production, PGE2, and IL-6 quantified by immunoassay kit and prostaglandin E2 competitive ELISA kit. COX2 production is an in vitro indication of possible anti-inflammatory activity and was estimated by Western blotting. Results: EtOAc potentially inhibited LPS-induced nitric oxide, prostaglandin, and IL-6 production. With these findings, it was evident that the EtOAc could reduce the LPS-induced cyclooxygenase-2 (COX-2) at the protein level in a dose-dependent manner as determined by Western blotting. Conclusion: The results emphasize potential therapeutic applications of Punica granatum in the treatment of inflammation.

Keywords: inflammation, Punica granatum, cytotoxicity, cytokines

Procedia PDF Downloads 648

Authors: Jawad Alzeer

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Natural products are well recognized as sources of drugs in several human ailments. To investigate the impact of variable extraction techniques on the cytotoxic effects of medicinal plant extracts, 5 well-known medicinal plants from Palestine were extracted with 90% ethanol, 80% methanol, acetone, coconut water, apple vinegar, grape vinegar or 5% acetic acid. The resulting extracts were screened for cytotoxic activities against three different cancer cell lines (B16F10, MCF-7, and HeLa) using a standard resazurin-based cytotoxicity assay and Nile Blue A as the positive control. Highly variable toxicities and tissue sensitivity were observed, depending upon the solvent used for extraction. Acetone consistently gave lower extraction yields but higher cytotoxicity, whereas other solvent systems gave much higher extraction yields with lower cytotoxicity. Interestingly, coconut water was found to offer a potential alternative to classical organic solvents; it gave consistently highest extraction yields, and in the case of S. officinalis L., highly toxic extracts towards MCF-7 cells derived from human breast cancer. These results demonstrate how the cytotoxicity of plant extracts can be inversely proportional to the yield, and that solvent selection plays an important role in both factors.

Keywords: plant extract, natural products, anti cancer drug, cytotoxicity

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Authors: Mona Mahmoud Abou Samra, Alaa Hamed Salama, Ghada Awad, Soheir Said Mansy

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Proniosomes are well documented for topical drug delivery and preferred over other vesicular systems because they are biodegradable, biocompatible, non-toxic, possess skin penetration ability and prolong the release of drugs by acting as depot in deeper layers of skin. Proniosome drug delivery was preferred due to improved stability of the system than niosomes. The present investigation aimed at formulation development and performance evaluation of proniosomal gel as a vesicular drug carrier system for antifungal drug tolnaftate. Proniosomes was developed using different nonionic surfactants such as span 60 and span 65 with cholesterol in different molar ratios by the Coacervation phase separation method in presence or absence of either lecithin or phospholipon 80 H. Proniosomal gel formulations of tolnaftate were characterized for vesicular shape & size, entrapment efficiency, rheological properties and release study. The effect of surfactants and additives on the entrapment efficiency, particle size and percent of drug released was studied. The selected proniosomal formulations for topical delivery of tolnaftate was subjected to a microbiological study in male rats infected with Trichophyton rubrum; the main cause of Tinea Pedis compared to the free drug and a market product and the results was recorded.

Keywords: fungal infection, proniosome, tolnaftate, trichophyton rubrum

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Authors: Yulistiani Yulistiani, Zamrotul Izzah, Lintang Bismantara, Wenny Putri Nilamsari, Arif Bachtiar, Budi Suprapti

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Interferon-gamma (IFN-γ) and interleukin-6 (IL-6) are pro-inflammatory cytokines, which have the protective immune response against Tuberculosis (TB). Indeed, pro-inflammatory cytokines Mycobacterium tuberculosis antigen-specific CD4+ and CD8+ T cells and NK cells increase the level of production of IFN-γ, a cytokine critical for augmenting the microbicidal activity of phagocytes. On the other hand, M. tuberculosis reduces the effects of IFN-γ by inhibiting the transcription of IFN-γ- responsive genes and by inducing the secretion of IL-6, which inhibits IFN-γ signaling. Probiotics Lactobacillus sp. and Bifidobacterium sp. were known to increase IFN-γ production in vivo, while vitamin B1, B6, and B12 worked on macrophages and releasing cytokines. Therefore, the present study was to evaluate the effect of probiotics and vitamin B supplement on changes of plasma cytokine levels in active pulmonary TB. From October to November 2016, twelve M. tuberculosis-infected patients starting anti-TB drugs were recruited, then divided into two groups. Seven patients were given a combination of probiotics and vitamin B, while five patients were in the control group. Plasma IFN-γ and IL-6 levels were measured by the ELISA kit before and a month after treatment. IFN-γ levels raised in four patients receiving the supplement (P = 0.743), while IL-6 increased in three patients in this group until day 30 of treatment (P = 0.298). Taken together, these results show the promising effect of probiotics and vitamin B on stimulation of IFN-γ and IL-6 production during intensive therapy of TB.

Keywords: interferon-gamma, interleukin-6, probiotic, tuberculosis

Procedia PDF Downloads 337

Authors: Checkfaith I. Aizebeoje, Temitope O. Lawal, Bolanle A. Adeniyi

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The overuse and abuse of antibiotics in treating zoonotic infections in humans and opportunistic infections in rabbit has contributed to the increase in antimicrobial drug resistance, therefore, an alternative to antibiotics is needed in treating these infections. The study was carried out to determine the antimicrobial activity of lactic acid bacteria (LAB) isolated from rabbit’s faeces against multidrug-resistant (MDR) pathogens isolated from the same rabbit. Twelve faecal samples and twelve swabs from fur samples were randomly collected aseptically from apparently healthy rabbits from Ajibode, Ibadan and University of Ibadan research farm in Ibadan, Oyo state, Nigeria. Lactic acid bacteria and multidrug-resistant pathogens were isolated using appropriate agar media and identified by partial sequencing of the 16SrRNA gene. Antibiotic susceptibility pattern of isolated bacteria and LAB were determined by the agar diffusion method. The antibacterial activity of the LAB against the test pathogens was determined using the agar overlay and agar diffusion methods. The pathogens Myroides gitamensis, Citrobacter rodentium, Acinetobacter johnsonii, Enterobacter oryzendophyticus and Serratia marcescens as well as twenty-eight (28) species of LAB belonging to Acetobacter and Lactobacillus genera were identified and characterized. Lactobacillus plantarum had the highest (60.71%) occurrence of the LAB. Viable cells and cell free supernatant (CFS) of isolated LAB inhibited the growth of the test organisms with the largest zone of inhibition (40 mm) produced by Lactobacillus plantarum against Citrobacter rodentium. This study showed that LAB from rabbit possess considerable antibacterial activity against multidrug-resistant bacteria from the same environment.

Keywords: antibacterial activities, cell-free supernatant, lactic acid bacteria; multidrug-resistant pathogens, rabbits’ faeces

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Authors: L. Kloetzer, M. Poştaru, A. I. Galaction, D. Caşcaval

Abstract:

Gentamicin is an aminoglycoside antibiotic industrially obtained by biosynthesis of Micromonospora purpurea or echinospora, the product being a complex mixture of components with very similar structures. Among them, three exhibit the most important biological activity: gentamicins C1, C1a, C2, and C2a. The separation of gentamicin from the fermentation broths at industrial scale is rather difficult and it does not allow the fractionation of the complex mixture of gentamicins in order to increase the therapeutic activity of the product. The aim of our experiments is to analyze the possibility to selectively separate the less active gentamicin, namely gentamicin C1, from the biosynthetic mixture by reactive extraction with di-(2-ethylhexyl) phosphoric acid (D2EHPA) dissolved in dichloromethane, followed selective re-extraction of the most active gentamicins C1a, C2, and C2a. The experiments on the reactive extraction of gentamicins indicated the possibility to separate selectively the gentamicin C1 from the mixture obtained by biosynthesis. The extraction selectivity is positively influenced by increasing the pH-value of an aqueous solution and by using a D2EHPA concentration in organic phase closer to the value needed for an equimolecular ratio between the extractant and this gentamicin. For quantifying the selectivity of separation, the selectivity factor, calculated as the ratio between the degree of reactive extraction of gentamicin C1 and the overall extraction degree of gentamicins were used. The possibility to remove the gentamicin C1 at an extractant concentration of 10 g l-1 and pH = 8 is presented. In these conditions, it was obtained the maximum value of the selectivity factor of 2.14, which corresponds to the modification of the gentamicin C1 concentration from 31.92% in the biosynthetic mixture to 72% in the extract. The re-extraction of gentamicins C1, C1a, C2, and C2a with sulfuric acid from the extract previously obtained by reactive extraction (mixture A – extract obtained by non-selective reactive extraction; mixture B – extract obtained by selective reactive extraction) allows for separating selectively the most active gentamicins C1a, C2, and C2a. For recovering only the active gentamicins C1a, C2, and C2a, the re-extraction must be carried out at very low acid concentrations, far below those corresponding to the stoichiometry of its chemical reactions with these gentamicins. Therefore, the mixture resulted by re-extraction contained 92.6% gentamicins C1a, C2, and C2a. By bringing together the aqueous solutions obtained by reactive extraction and re-extraction, the overall content of the active gentamicins in the final product becomes 89%, their loss reaching 0.3% related to the initial biosynthetic product.

Keywords: di-(2-ethylhexyl) phosphoric acid, gentamicin, reactive extraction, selectivity factor

Procedia PDF Downloads 309