Search results for: urinary purine derivatives

Authors: Jana Tchekalarova, Stela Georgieva, Petia Peneva, Petar Todorov

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In the present study, a series of bioconjugates of N-modified hemorphine analogs containing second pharmacophore cinnamic acids (CA) or caffeic acid (KA) were synthesized by a traditional solid-phase Fmoc chemistry method for peptide synthesis. Electrochemical and fluorometric analysis and in vivo anticonvulsant activity in mice were conducted on the compounds. The three CA (H4-CA, H5-CA, and H7-CA) and three KA (H4-KA, H5-KA, and H7-KA)-conjugated hemorphine derivatives showed dose-dependent anticonvulsant activity in the maximal electroshock test (MES) in mice. The KA-conjugated H5-KA derivate was the only compound that suppressed clonic seizures at the lowest dose of 0.5 µg/mouse in the scPTZ test. The activity against the psychomotor seizures in the 6-Hz test was detected only for the H4-CA (0.5 µg) and H4-KA (0.5 µg and 1 µg), respectively. The peptide derivates did not exhibit neurotoxicity in the rotarod test. Our findings suggest that conjugated CA and KA hemorphine peptides can be used as a background for developing hemorphin-related analogs with anticonvulsant activity. Acknowledgments: This study is funded by the European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, project № BG-RRP-2.004-0002, "BiOrgaMCT".

Keywords: hemorphins, SPSS, caffeic/cinnamic acid, anticonvulsant activity, electrochemistry, fluorimetry

Procedia PDF Downloads 129

Authors: Birsel Canan Demirbag, Kıymet Yesilcicek Calik, Hacer Kobya Bulut

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Objective: This study was conducted to evaluate the problems of women over 65 with incontinence diagnosis. Methods: This descriptive study was conducted with women over 65 with incontinence diagnosis in four Family Health Centers in a city in Eastern Black Sea region between November 1, and December 20, 2015. 203, 107, 178, 180 women over 65 were registered in these centers and 262 had incontinence diagnosis at least once and had an ongoing complaint. 177 women were volunteers for the study. During home visits and using face-to-face survey methodology, participants were given socio-demographic characteristics survey, Sandvik severity scale, Incontinence Quality of Life Scale, Urogenital Distress Inventory and a questionnaire including challenges experienced due to incontinence developed by the researcher. Data were analyzed with SPSS program using percentages, numbers, Chi-square, Man-Whitney U and t test with 95% confidence interval and a significance level p <0.05. Findings: 67 ± 1.4 was the mean age, 2.05 ± 0.04 was parity, 44.5 ± 2.12 was menopause age, 66.3% were primary school graduates, 45.7% had deceased spouse, 44.4% lived in a large family, 67.2% had their own room, 77.8% had income, 89.2% could meet self- care, 73.2% had a diagnosis of mixed incontinence, 87.5% suffered for 6-20 years % 78.2 had diuretics, antidepressants and heart medicines, 20.5% had urinary fecal cases, 80.5% had bladder training at least once, 90.1% didn’t have bladder diary calendar/control training programs, 31.1% had hysterectomy for prolapse, 97.1'i% was treated with lower urinary tract infection at least once, 66.3% saw a doctor to get drug in the last three months, 76.2 could not go out alone, 99.2 % had at least one chronic disease, 87.6 % had constipation complain, 2.9% had chronic cough., 45.1% fell due to a sudden rise for toilet. Incontinence Impact Questionnaire Average score was (QOL) 54.3 ± 21.1, Sandvik score was 12.1 ± 2.5, Urogenital Distress Inventory was 47.7 ± 9.2. Difficulties experienced due to incontinence were 99.5% feeling of unhappiness, 67.1% constant feeling of urine smell due to failing to change briefs frequently, % 87.2 move away from social life, 89.7 unable to use pad, 99.2% feeling of disturbing households / other individuals, 87.5% feel dizziness/fall due to sudden rise, 87.4% feeling of others’ imperceptions about the situation, % 94.3 insomnia, 78.2 lack of assistance, 84.7% couldn’t afford urine protection briefs. Results: With this study, it was found out that there were a lot of unsolved issues at individual and community level affecting the life quality of women with incontinence. In accordance with this common problem in women, to facilitate daily life it is obvious that regular home care training programs at institutional level in our country will be effective.

Keywords: health problems, incontinence, incontinence quality of life questionnaire, old age, urinary urogenital distress inventory, Sandviken severity, women

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Authors: Alok Nahata

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Introduction: Nowadays, androgen-mediated diseases such as prostate cancer, hirsutism, acne, androgenic alopecia and benign prostatic hyperplasia (BPH) have become serious problems. The aim of the present study was to find out whether Ganoderma lucidum (GL) can be used as a clinically effective medicine for the management of prostatic hyperplasia. Methodology: In vitro studies were conducted to assess the 5α-reductase inhibitory potential of GL. Testosterone (3 mg/kg s.c.) was administered to the rats along with the test extracts (10, 20 and 50 mg/kg p.o for a period of 28 days. Finasteride was used as a positive control (1 mg/kg p.o.). Major Findings: GL extracts attenuated the increase in the prostate/body weight ratio (P/BW) induced by testosterone. Most of the values were significant when compared to testosterone-treated group and finasteride treated groups. Petroleum ether extract (50 mg/kg p.o.) exhibited the best activity (P < 0.01). Ethanolic extract (20 and 50 mg/kg p.o.) also exhibited significant activity (P < 0.01). The urine output also improved significantly (P < 0.01 in all groups as compared to standard finasteride), which emphasize the clinical implications of the study. Testosterone levels measured weekly and prostate-specific antigen (PSA) levels measured at the end of the study also support the findings. Histological studies suggested improvement in prostatic histoarchitecture in extract-treated groups as compared to the testosterone-treated group. Conclusion: Study clearly reflects the utility of extracts in BPH. Because of conversion of testosterone to dihydrotestosterone, the prostate size is increased, thereby causing obstruction in urinary output. The observed effect that extracts do not allow the increase as reflected by urinary output, P/BW ratios and histoarchitecture showed that activity of administered testosterone was blocked by the extract and resulted in recovery.

Keywords: benign prostatic hyperplasia, Ganoderma lucidum, prostate-specific antigen, 5α-reductase, testosterone

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Authors: Kalin Ivanov, Stanislava Ivanova

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Actoprotectors are substances with hight performance enchasing potential and hight antioxidant activity. Most of these drugs have been developed in USSR for military medicine purposes. Based on their chemical composition actoprotectors could be classified into three categories: benzimidazole derivatives (ethomersol, bemitil); adamantane derivatives (bromantane), other chemical classes. First data for intake of actoprotectors from professional athletes is from 1980. The daily intake of actoprotectors demonstrate many benefits for athletes like: positive effect on the efficiency of physical work, antihypoxic effects, antioxidant effects, nootropic effects, rapid recovery. Since 1997, bromantane is considered as doping. This is a result of Summer Olympic Games in Athlanta (1996) when several Russian athletes tested positive for bramantane. Even the drug is safe for athletes health its use is considered as violation of anti- doping rules. More than 37 years bemetil has been used by professional athletes with no risk but currently it is included in WADA monitoring programme for 2018. Current perspectives are that most used actoprotectors would be considered as doping. Many clinical studies have confirmed that intake of bemitil and bromantan demonstrate positive influence on the physical work capacity but data for other actoprotectors like chlodantane, ademol, ethomersol is limited.

Keywords: actoprotector, sport, doping, bemitil

Procedia PDF Downloads 287

Authors: Jana Tchekalarova, Stela Georgieva, Petia Peneva, Petar Todorov

Abstract:

In the present study, a series of bioconjugates of N-modified hemorphine analogs containing second pharmacophore cinnamic acids (CA) or caffeic (KA) were synthesized by a traditional solid-phase Fmoc chemistry method for peptide synthesis. Electrochemical and fluorimetrical analysis and in vivo anticonvulsant activity in mice were conducted on the compounds. The three CA acids (H4-CA, H5-CA, and H7-CA) and three KA acids (H4-KA, H5-KA, and H7-KA)-conjugated hemorphine derivatives showed dose-dependent anticonvulsant activity in the maximal electroshock test (MES) in mice. The KA-conjugated H5-KA derivate was the only compound that suppressed clonic seizures at the lowest dose of 0.5 µg/mouse in the scPTZ test. The activity against the psychomotor seizures in the 6-Hz test was detected only for the H4-CA (0.5 µg) and H4-KA (0.5 µg and 1 µg), respectively. The peptide derivates did not exhibit neurotoxicity in the rotarod test. Our findings suggest that conjugated CA and KA hemorphine peptides can be used as a background for developing hemorphin-related analogs with anticonvulsant activity. Acknowledgements: This study is funded by the European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, project № BG-RRP-2.004-0002, "BiOrgaMCT".

Keywords: hemorphins, caffeic/cinnamic acid, anticonvulsant activity, electrochemistry, fluorimetry

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Authors: Maryam Taheri, Mehdi Jahanfar, Kenji Ogino

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Fast drying traffic marking paint comprising a solvent-borne resin, a filler, a pigment and a solvent that is especially suitable for colder ambient (temperatures near freezing) applications, where waterborne traffic paint cannot be used. Acrylic resins based on methyl methacrylate, butyl acrylate, acrylic acid, and styrene were synthesized in different solvents using organic peroxide initiators such as peroxyester, peroxyketal, dialkylperoxide and azo. After polymerization, the molecular weight (Mw), polydispersity index= PDI (Mw/Mn), viscosity, total residual monomer and APHA color were evaluated and results of organic peroxide initiators (t- butyl and t-amyl derivatives) were also compared with the azo initiator. The Mw, PDI, viscosity, mass conversation and APHA color of resins with t-amyl derivatives of organic peroxide initiators are very proper. The results of the traffic marking paints test such as non-volatile matter, no- pick- up time, hiding power, resistance to wear and water resistance study that produced with these resins also confirm this.

Keywords: fast drying traffic marking paint, acrylic resin, organic peroxide initiator, peroxyester, peroxyketal, dialkylperoxide and azo initiator

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Authors: Sara El Mansouria Beghdadi

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Quantitative structure–activity relationship (QSAR) modelling is one of the main computer tools used in medicinal chemistry. Over the past two decades, the incidence of fungal infections has increased due to the development of resistance. In this study, the QSAR was performed on a series of esters of 2-carboxamido-3-(1H-imidazole-1-yl) propanoic acid derivatives. These compounds have showed moderate and very good antifungal activity. The multiple linear regression (MLR) was used to generate the linear 2d-QSAR models. The dataset consists of 115 compounds with their antifungal activity (log MIC) against «Candida albicans» (ATCC SC5314). Descriptors were calculated, and different models were generated using Chemoffice, Avogadro, GaussView software. The selected model was validated. The study suggests that the increase in lipophilicity and the reduction in the electronic character of the substituent in R1, as well as the reduction in the steric hindrance of the substituent in R2 and its aromatic character, supporting the potentiation of the antifungal effect. The results of QSAR could help scientists to propose new compounds with higher antifungal activities intended for immunocompromised patients susceptible to multi-resistant nosocomial infections.

Keywords: quantitative structure–activity relationship, imidazole, antifungal, candida albicans (ATCC SC5314)

Procedia PDF Downloads 53

Authors: M. Koksal, T. Ozyazici, E. Gurdal, M. Yarım, E. Demirpolat, M. B. Y. Aycan

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The discovery of new drugs in cancer chemotherapy is still a major topic because of severe side effects, selectivity problems and resistance development potential of existing drugs. In recent years, combined anticancer therapies or multi-acting drugs are clinically preferred over traditional cytotoxic treatment, with the aim of avoiding resistance and toxic side effects. Arrangement of multi-acting targets can be carried out either by combination of several drugs with different mechanisms or by usage of a single chemical compound capable of regulating several targets of a disease with multiple factors. In literature, several pyrimidine and piperazine derivatives have been involved in the structure of many compounds which have been used as chemotherapeutic agents along with wide clinical applications. The aim of this study is to combine pyrimidine and piperazine core structures to research and develop novel piperazinylpyrimidine derivatives with selective cytotoxicity over cancer cells. In this study, a group of novel 6-fluorophenyl-3-[2-(substitutedpiperazinyl)ethyl] hexahydropyrimidine-2,4-dione derivatives designed to observe the desired anticancer activity due to pyrimidine and piperazine based scaffolds. Target compounds were obtained by the reaction of appropriate piperazine derivatives and 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione. The synthetic pathway of 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione was started with Rodionov reaction using aldehyde, malonic acid and ammonium acetate in ethanol. Isolated β-fluorophenyl-β-amino acids were treated with 2-chloroethylisocyanate in the presence of an aqueous sodium hydroxide solution at room temperature to yield the sodium salts of the corresponding ureido acids. By addition of a mineral acid, ureido acids were precipitated. Later, these ureido acids were refluxed in thionyl chloride to give the 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-di-one which were furthermore treated with secondary amines. Structures of purified compounds were characterized with IR, 1H-NMR, 13C-NMR, mass spectroscopies and elemental analysis. All of the compounds gave satisfactory analytical and spectroscopic data, which were in full accordance with their depicted structures. In IR spectra of the compounds, N-H group was seen at 3230-3213 cm⁻¹. C-H was seen at 3100-2820 cm⁻¹ and C=O vibrational peaks were observed approximately at 1725 and 1665 cm⁻¹ in accordance with literature. In the NMR spectra of target compounds, the methylene protons of piperazine give two separate multiplet peaks around 3.5 and 4.5 ppm representing the successful N-alkylation of the structure. The cytotoxic activity of the synthesized compounds was investigated on human bronchial epithelial (BEAS 2B), lung (A549), colon adenocarcinoma (COLO205) and breast (MCF7) cell lines, by means of sulphorhodamine B (SRB) assays in triplicate. IC₅₀ values of the screened derivatives were found in range of 11.8-78 µM. This project was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 215S157).

Keywords: cytotoxicity, hexahydropyrimidine, piperazine, sulphorhodamine B assay

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Authors: Pierre Mintom, William Djeukeu Asongni, Michelle Moni, William Dakam, Christine Fernande Nyangono Biyegue.

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Background: In order to prevent congestive heart failure, control of hypertension and hypercholesterolemia is necessary because those risk factors frequently occur in combination. Objective: The aim of the study is to determine the prevalence and risk factors of hypertension, hypercholesterolemia and double burden HTA-Hypercholesterolemia in patients with congestive heart failure. Methodology: A database of 98 patients suffering from congestive heart failure was used. The latter were recruited from August 15, 2017, to March 5, 2018, in the Cardiology department of Deido District Hospital of Douala. This database provides information on sociodemographic parameters, biochemical examinations, characteristics of heart failure and food consumption. ESC/ESH and NCEP-ATPIII definitions were used to define Hypercholesterolemia (total cholesterol ≥200mg/dl), Hypertension (SBP≥140mmHg and/or DBP≥90mmHg). Double burden hypertension-hypercholesterolemia was defined as follows: total cholesterol (CT)≥200mg/dl, SBP≥140mmHg and DBP≥90mmHg. Results: The prevalence of hypertension (HTA), hypercholesterolemia (hyperchol) and double burden HTA-Hyperchol were 61.2%, 66.3% and 45.9%, respectively. No sociodemographic factor was associated with hypertension, hypercholesterolemia and double burden, but Male gender was significantly associated (p<0.05) with hypercholesterolemia. HypoHDLemia significantly increased hypercholesterolemia and the double burden by 19.664 times (p=0.001) and 14.968 times (p=0.021), respectively. Regarding dietary habits, the consumption of rice, peanuts and derivatives and cottonseed oil respectively significantly (p<0.05) exposed to the occurrence of hypertension. The consumption of tomatoes, green bananas, corn and derivatives, peanuts and derivatives and cottonseed oil significantly exposed (p<0.05) to the occurrence of hypercholesterolemia. The consumption of palm oil and cottonseed oil exposed the occurrence of the double burden of hypertension-hypercholesterolemia. Consumption of eggs protects against hypercholesterolemia, and consumption of peanuts and tomatoes protects against the double burden. Conclusion: hypercholesterolemia associated with hypertension appears as a complicating factor of congestive heart failure. Key risk factors are mainly diet-based, suggesting the importance of nutritional education for patients. New management protocols emphasizing diet should be considered.

Keywords: risk factors, hypertension, hypercholesterolemia, congestive heart failure

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Authors: Ning Li, Jiacheng Zhang, Zheng Yang, Sylvia Kang

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Introduction: Polycystic ovary syndrome (PCOS) is a common physiological symptom in women of reproductive age. Women with PCOS may have infrequent or prolonged menstrual periods and excess male hormone (androgen) levels. Mira analyzes the cycle profiles and the luteinizing hormone (LH) changes in urine, closely related to the fertility level of healthy women and PCOS women. From the difference between the two groups, Mira helps to understand the physiological state of PCOS women and their hormonal changes in the menstrual cycle. Methods: In this study, data from 1496 cycles and information from 342 women belonging to two groups (181 PCOS and 161 Healthy) were collected and analyzed. Women test their luteinizing hormone (LH) in urine daily with Mira fertility test wand and Mira analyzer, from the day after the menstruation to the starting day of the next menstruation. All the collected data meets Mira’s user agreement and users’ identification was removed. The cycle length, LH peak, and other cycle information of the PCOS group were compared with the Healthy group. Results: The average cycle length of PCOS women is 41 days and of the Healthy women is 33 days. 91.4% of cycle length is within 40 days for the Healthy group, while it decreases to 71.9% for the PCOS group. This means PCOS women have a longer menstrual cycle and more variation during the cycle. With more variation, the ovulation prediction becomes more difficult for the PCOS group. The deviation between the LH surge day and the predicted ovulation day, calculated by the starting day of the next menstruation minus 14 days, is greater in the PCOS group compared with the Healthy group. Also, 46.96% of PCOS women have an irregular cycle, and only 19.25% of healthy women show an irregular cycle. Conclusion: PCOS women have longer menstrual cycles and more variation during the menstrual cycles. The traditional ovulation prediction is not suitable for PCOS women.

Keywords: menstrual cycle, PCOS, urinary luteinizing hormone, Mira

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Authors: Hai Chi, Ibrahim Mehmeti, Kirill Ovchinnikov, Hegle Holo, Ingolf F. Nes, Dzung B. Diep

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By using a panel of multiple indicator strains of different bacterial species and genera, we screened a large collection of bacterial isolates (over 1800 isolates) derived from raw milk, for bacteriocin producers with broad inhibition spectra (BIS). Fourteen isolates with BIS were identified, and by 16S rDNA sequencing they were found to belong to Lactococcus garvieae (10 isolates) and Enterococcus feacalis (4 isolates). Further analysis of the ten L. garvieae isolates revealed that they were very similar, if not identical, to each other in metabolic and genetic terms: they had the same fermentation profile on different types of sugars, repetitive sequence-based PCR (rep-PCR) DNA pattern as well as they all had the same inhibition profile towards over 50 isolates of different species. The bacteriocin activity from one of the L. garvieae isolates was assessed further. The bacteriocin which was termed garvicin KS, was found to be heatstable and proteinase-labile and its inhibition spectrum contained many distantly related genera of Firmicutes, comprising most lactic acid bacteria (LAB) as well as problematic species of Bacillus, Listeria, Streptococcus and Staphylococcus and their antibiotic resistant derivatives (e.g. VRE, MRSA). Taken together, the results indicate that this is a potent bacteriocin from L. garvieae and that its very broad inhibition spectrum can be a very useful property for use in food preservation as well as in infection treatments caused by gram-positive pathogens and their antibiotic-derivatives.

Keywords: bacteriocin, lactic acid bacteria, Lactococcus garvieae, antibiotics resistance

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Authors: Ozlem Temiz-Arpaci, Meryem Tasci, Fatma Sezer Senol, İlkay Erdogan Orhan

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Alzheimer’s disease (AD), a neurodegenerative disorder characterized by a progressive deterioration of memory and cognition, occurs more frequently in elderly people. Current treatment approaches in this disease with the major therapeutic strategy are based on the AChE and BChE inhibition. On the other hand, tyrosinase inhibition has become a target for the treatment of Parkinson’s disease (PD) since this enzyme may play a role in neuromelanin formation in the human brain and could be critical in the formation of dopamine neurotoxicity associated with neurodegeneration linked to PD. Also benzoxazoles are structural isosteres of natural nucleotides that can interact with biopolymers so that benzoxazoles showed a lot of different biological activities. In this study, a series of 2,5-disubstituted-benzoxazole derivatives were synthesized and were evaluated as possible inhibitors of acetylcholinesterase (AChE) / butyrylcholinesterase (BChE) and tyrosinase. The results demonstrated that the compounds exhibited a weak spectrum of AChE / BChE inhibitory activity ranging between 3.92% - 54.32% except compound 8 which showed no activity against AChE and compound 4 which showed no activity against BChE at the specified molar concentrations. Also, the compounds indicated lower than tyrosinase inhibitory activity of ranging between 8.14% - 22.90% to that of reference (kojic acid).

Keywords: AChE and BChE inhibition, Alzheimer’s disease, benzoxazoles, tyrosinase inhibition

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Authors: Moulay Driss Mellaoui, Khadija Zaki, Khalid Abbiche, Abdallah Imjjad, Rachid Boutiddar, Abdelouahid Sbai, Aaziz Jmiai, Souad El Issami, Al Mokhtar Lamsabhi, Hanane Zejli

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This study presents a comprehensive analysis of six isoxazolidine and isoxazoline derivatives, leveraging a multifaceted approach that combines Density Functional Theory (DFT), AdmetSAR analysis, and molecular docking simulations to explore their electronic, pharmacokinetic, and anticancer properties. Through DFT analysis, using the B3LYP-D3BJ functional and the 6-311++G(d,p) basis set, we optimized molecular geometries, analyzed vibrational frequencies, and mapped Molecular Electrostatic Potentials (MEP), identifying key sites for electrophilic attacks and hydrogen bonding. Frontier Molecular Orbital (FMO) analysis and Density of States (DOS) plots revealed varying stability levels among the compounds, with 1b, 2b, and 3b showing slightly higher stability. Chemical potential assessments indicated differences in binding affinities, suggesting stronger potential interactions for compounds 1b and 2b. AdmetSAR analysis predicted favorable human intestinal absorption (HIA) rates for all compounds, highlighting compound 3b superior oral effectiveness. Molecular docking and molecular dynamics simulations were conducted on isoxazolidine and 4-isoxazoline derivatives targeting the EGFR receptor (PDB: 1JU6). Molecular docking simulations confirmed the high affinity of these compounds towards the target protein 1JU6, particularly compound 3b, among the isoxazolidine derivatives, compound 3b exhibited the most favorable binding energy, with a g score of -8.50 kcal/mol. Molecular dynamics simulations over 100 nanoseconds demonstrated the stability and potential of compound 3b as a superior candidate for anticancer applications, further supported by structural analyses including RMSD, RMSF, Rg, and SASA values. This study underscores the promising role of compound 3b in anticancer treatments, providing a solid foundation for future drug development and optimization efforts.

Keywords: isoxazolines, DFT, molecular docking, molecular dynamic, ADMET, drugs.

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Authors: F. Madani, M. Doudi, L. Rahimzadeh Torabi

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The irregular consumption of current antibiotics contributes to an escalation in antibiotic resistance among urinary pathogens on a global scale. The objective of this research was to investigate the process of biologically synthesized silver nanoparticles through the utilization of Zataria multiflora extract. Additionally, the study aimed to evaluate the efficacy of these synthesized nanoparticles in inhibiting the growth of multi-drug resistant negative bacillus bacteria, which commonly contribute to urinary tract infections. The botanical specimen utilized in the current research investigation was Z. multiflora, and its extract was produced employing the Soxhlet extraction technique. The study examined the green synthesis conditions of silver nanoparticles by considering three key parameters: the quantity of extract used, the concentration of silver nitrate salt, and the temperature. The particle dimensions were ascertained using the Zetasizer technique. In order to identify synthesized Silver nanoparticles TEM, XRD, and FTIR methods were used. For evaluating the antibacterial effects of nanoparticles synthesized through a biological method, different concentrations of silver nanoparticles were studied on 140 cases of Multiple drug resistance (MDR) bacteria strains Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus vulgaris,Citrobacter freundii, Acinetobacter bumanii and Pseudomonas aeruginosa, (each genus of bacteria, 20 samples), which all were MDR and cause urinary tract infections, for identification of bacteria were used of PCR test and laboratory methods (Agar well diffusion and Microdilution methods) to assess their sensitivity to Nanoparticles. The data were subjected to analysis using the statistical software SPSS, specifically employing nonparametric Kruskal-Wallis and Mann-Whitney tests. This study yielded noteworthy findings regarding the impacts of varying concentrations of silver nitrate, different quantities of Z. multiflora extract, and levels of temperature on nanoparticles. Specifically, it was observed that an increase in the concentration of silver nitrate, extract amount, and temperature resulted in a reduction in the size of the nanoparticles synthesized. However, the impact of the aforementioned factors on the index of particle diffusion was found to be statistically non-significant. According to the transmission electron microscopy (TEM) findings, the particles exhibited predominantly spherical morphology, with a diameter spanning from 25 to 50 nanometers. Nanoparticles in the examined sample. Nanocrystals of silver. FTIR method illustrated that the spectrums of Z. multiflora and synthesized nanoparticles had clear peaks in the ranges of 1500-2000, and 3500 - 4000. The obtained results of antibacterial effects of different concentrations of silver nanoparticles on according to agar well diffusion and microdilution method, biologically synthesized nanoparticles showed 1000 mg /ml highest and lowest mean inhibition zone diameter in E. coli, A. bumanii 23 and 15mm, respectively. MIC was observed for all of bacteria 125 mg/ml and for A. bumanii 250 mg/ml. Comparing the growth inhibitory effect of chemically synthesized the results obtained from the experiment indicated that both nanoparticles and biologically synthesized nanoparticles exhibit a notable growth inhibition effect. Specifically, the chemical method of synthesizing nanoparticles demonstrated the highest level of growth inhibition at a concentration of 62.5 mg/mL The present study demonstrated an inhibitory effect on bacterial growth, facilitating the causative factors of urine infection and multidrug resistance (MDR).

Keywords: multiple drug resistance, negative bacillus bacteria, urine infection, Zataria multiflora

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Authors: Manasi Roy, Raju Mondal

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During last two decades the synthesis and design of MOFs or novel coordination polymers (CPs) has flourished as an emerging area of research due to their role as functional materials. Accordingly, ten new cobalt-based MOFs have been synthesized using a simple bispyrazole ligand, 4,4′-methylene-bispyrazole (H2MBP), and isophthalic acid (H2IPA) and its four 5-substituted derivatives R-H2IPA (R = COOH, OH, tBu, NH2). The major aim of this study was to validate the mutual influence of temperature and substitutions on the final structural self-assembly. Five different isophthalic acid derivatives were used to study the influence of substituents while each reaction was carried out at two different temperatures to assess the temperature effect. A clear correlation was observed between the reaction temperature and the coordination number of the cobalt atoms which consequently changes the self assembly pattern. Another fact that the periodical change in coordination number did bring about some systematic changes in the structural network via secondary building unit selectivity. With the presence of a tunable cavity inside the network, and unsaturated metal centers, MOFs show highly encouraging photocatalytic degradation of toxic dye with a potential application in waste water purification. Another fascinating aspect of this work is the construction of magnetic coordination polymers with the occurrence of a not-so-common MCE behavior of cobalt-based MOF.

Keywords: MOFs, temperature effect, MCE, dye degradation

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Authors: Elena Ionescu, Elena Iacob, Marie-Louise Ionescu, Carmen Elena Tebrencu, Oana Teodora Ciuperca

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Echinacea species (Asteraceae) has received a global attention because it is widely used for treatment of cold, flu and upper respiratory tract infections. Echinacea species contain a great variety of chemical components that contribute to their activity. The most important components responsible for the biological activity are those with high molecular-weight such as polysaccharides, polyacetylenes, highly unsaturated alkamides and caffeic acid derivatives. The principal factors that may influence the chemical composition of Echinacea include the species and the part of plant used (aerial parts or roots ). In recent years the market for Echinacea has grown rapidly and also the cases of adultery/replacement especially for Echinacea root. The identification of presence or absence of same biomarkers provide information for safe use of Echinacea species in food supplements industry. The aim of the study was the preliminary evaluation and fingerprinting by UV-VISIBLE spectroscopy of biomarkers in terms of content in phenolic derivatives of some Echinacea species (E. purpurea, E. angustifolia and E. pallida) for identification and authentication of the species. The steps of the study were: (1) samples (extracts) preparation from Echinacea species (non-hydrolyzed and hydrolyzed ethanol extracts); (2) samples preparation of reference substances (polyphenol acids: caftaric acid, caffeic acid, chlorogenic acid, ferulic acid; flavonoids: rutoside, hyperoside, isoquercitrin and their aglycones: quercitri, quercetol, luteolin, kaempferol and apigenin); (3) identification of specific absorption at wavelengths between 700-200 nm; (4) identify the phenolic compounds from Echinacea species based on spectral characteristics and the specific absorption; each class of compounds corresponds to a maximum absorption in the UV spectrum. The phytochemical compounds were identified at specific wavelengths between 700-200 nm. The absorption intensities were measured. The obtained results proved that ethanolic extract showed absorption peaks attributed to: phenolic compounds (free phenolic acids and phenolic acids derivatives) registrated between 220-280 nm, unsymmetrical chemical structure compounds (caffeic acid, chlorogenic acid, ferulic acid) with maximum absorption peak and absorption "shoulder" that may be due to substitution of hydroxyl or methoxy group, flavonoid compounds (in free form or glycosides) between 330-360 nm, due to the double bond in position 2,3 and carbonyl group in position 4 flavonols. UV spectra showed two major peaks of absorption (quercetin glycoside, rutin, etc.). The results obtained by UV-VIS spectroscopy has revealed the presence of phenolic derivatives such as cicoric acid (240 nm), caftaric acid (329 nm), caffeic acid (240 nm), rutoside (205 nm), quercetin (255 nm), luteolin (235 nm) in all three species of Echinacea. The echinacoside is absent. This profile mentioned above and the absence of phenolic compound echinacoside leads to the conclusion that species harvested as Echinacea angustifolia and Echinacea pallida are Echinacea purpurea also; It can be said that preliminary fingerprinting of Echinacea species through correspondence with the phenolic derivatives profile can be achieved by UV-VIS spectroscopic investigation, which is an adequate technique for preliminary identification and authentication of Echinacea in medicinal herbs.

Keywords: Echinacea species, Fingerprinting, Phenolic compounds, UV-VIS spectroscopy

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Authors: Periklis Brakatsoulas

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Recent empirical research shows a growing interest in investment decision-making under market anomalies that contradict the rational paradigm. Momentum is undoubtedly one of the most robust anomalies in the empirical asset pricing research and remains surprisingly lucrative ever since first documented. Although predominantly phenomena identified across equities, momentum premia are now evident across various asset classes. Yet few many attempts are made so far to provide traders a diversified portfolio of strategies across different assets and markets. Moreover, literature focuses on patterns from past returns rather than mechanisms to signal future price directions prior to momentum runs. The aim of this paper is to develop a diversified portfolio approach to price distortion signals using daily position data on stocks, credit derivatives, and bonds. An algorithm allocates assets periodically, and new investment tactics take over upon price momentum signals and across different ranking groups. We focus on momentum life cycles, trend reversals, and price acceleration signals. The main effort here concentrates on the density, time span and maturity of momentum phenomena to identify consistent patterns over time and measure the predictive power of buy-sell signals generated by these anomalies. To tackle this, we propose a two-stage modelling process. First, we generate forecasts on core macroeconomic drivers. Secondly, satellite models generate market risk forecasts using the core driver projections generated at the first stage as input. Moreover, using a combination of the ARFIMA and FIGARCH models, we examine the dependence of consecutive observations across time and portfolio assets since long memory behavior in volatilities of one market appears to trigger persistent volatility patterns across other markets. We believe that this is the first work that employs evidence of volatility transmissions among derivatives, equities, and bonds to identify momentum life cycle patterns.

Keywords: forecasting, long memory, momentum, returns

Procedia PDF Downloads 81

Authors: Jyoti Singh, Ranju Bansal

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Fighting pain and inflammation is a common problem faced by physicians while dealing with a wide variety of diseases. Since ancient time nonsteroidal anti-inflammatory agents (NSAIDs) and opioids have been the cornerstone of treatment therapy, however, the usefulness of both these classes is limited due to severe side effects. NSAIDs, which are mainly used to treat mild to moderate inflammatory pain, induce gastric irritation and nephrotoxicity whereas opioids show an array of adverse reactions such as respiratory depression, sedation, and constipation. Moreover, repeated administration of these drugs induces tolerance to the analgesic effects and physical dependence. Further discovery of selective COX-2 inhibitors (coxibs) suggested safety without any ulcerogenic side effects; however, long-term use of these drugs resulted in kidney and hepatic toxicity along with an increased risk of secondary cardiovascular effects. The basic approaches towards inflammation and pain treatment are constantly changing, and researchers are continuously trying to develop safer and effective anti-inflammatory drug candidates for the treatment of different inflammatory conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriasis and multiple sclerosis. Synthetic 3(2H)-pyridazinones constitute an important scaffold for drug discovery. Structure-activity relationship studies on pyridazinones have shown that attachment of a lactam at N-2 of the pyridazinone ring through a methylene spacer results in significantly increased anti-inflammatory and analgesic properties of the derivatives. Further introduction of the heterocyclic ring at lactam nitrogen results in improvement of biological activities. Keeping in mind these SAR studies, a new series of compounds were synthesized as shown in scheme 1 and investigated for anti-inflammatory, analgesic, anti-platelet activities and docking studies. The structures of newly synthesized compounds have been established by various spectroscopic techniques. All the synthesized pyridazinone derivatives exhibited potent anti-inflammatory and analgesic activity. Homoveratryl substituted derivative was found to possess highest anti-inflammatory and analgesic activity displaying 73.60 % inhibition of edema at 40 mg/kg with no ulcerogenic activity when compared to standard drugs indomethacin. Moreover, 2-substituted-4-benzo[d][1,3]dioxole-6-phenylpyridazin-3(2H)-ones derivatives did not produce significant changes in bleeding time and emerged as safe agents. Molecular docking studies also illustrated good binding interactions at the active site of the cyclooxygenase-2 (hCox-2) enzyme.

Keywords: anti-inflammatory, analgesic, pyridazin-3(2H)-one, selective COX-2 inhibitors

Procedia PDF Downloads 175

Authors: Mahmoud Huleihel, George Abu-Aqil, Manal Suleiman, Klaris Riesenberg, Itshak Lapidot, Ahmad Salman

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Urinary tract infections (UTIs) are considered to be the most common bacterial infections worldwide, which are caused mainly by Escherichia (E.) coli (about 80%). Klebsiella pneumoniae (about 10%) and Pseudomonas aeruginosa (about 6%). Although antibiotics are considered as the most effective treatment for bacterial infectious diseases, unfortunately, most of the bacteria already have developed resistance to the majority of the commonly available antibiotics. Therefore, it is crucial to identify the infecting bacteria and to determine its susceptibility to antibiotics for prescribing effective treatment. Classical methods are time consuming, require ~48 hours for determining bacterial susceptibility. Thus, it is highly urgent to develop a new method that can significantly reduce the time required for determining both infecting bacterium at the species level and diagnose its susceptibility to antibiotics. Fourier-Transform Infrared (FTIR) spectroscopy is well known as a sensitive and rapid method, which can detect minor molecular changes in bacterial genome associated with the development of resistance to antibiotics. The main goal of this study is to examine the potential of FTIR spectroscopy, in tandem with machine learning algorithms, to identify the infected bacteria at the species level and to determine E. coli susceptibility to different antibiotics directly from patients' urine in about 30minutes. For this goal, 1600 different E. coli isolates were isolated for different patients' urine sample, measured by FTIR, and analyzed using different machine learning algorithm like Random Forest, XGBoost, and CNN. We achieved 98% success in isolate level identification and 89% accuracy in susceptibility determination.

Keywords: urinary tract infections (UTIs), E. coli, Klebsiella pneumonia, Pseudomonas aeruginosa, bacterial, susceptibility to antibiotics, infrared microscopy, machine learning

Procedia PDF Downloads 141

Authors: Jia H. Wong, Jingli Zhang, Habsah Mohamad, Iswatun H. Abdullah Ripain, Muhammad Bilal, Amelia J. Lloyd, Abdul A. Mohamed Yusoff, Jafri M. Abdullah

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Epilepsy is one of the most common neurological diseases affecting more than 50 million of people worldwide. Epilepsy is a state of recurrent, spontaneous seizures with multiple syndromes and symptoms of different causes of brain dysfunction, prognosis, and treatments; characterized by transient, occasional and stereotyped interruptions of behavior whereby the excitatory-inhibitory activities within the central nervous system (CNS) are thrown out of balance due to various kinds of interferences. The goal of antiepileptic treatment is to enable patients to be free from seizures or to achieve control of seizures through surgical treatment and/or pharmacotherapy. Pharmacotherapy through AED plays an important role especially in countries with epilepsy treatment gap due to costs and availability of health facilities, skills and resources, yet there are about one-third of the people with epilepsy have drug-resistant seizures. Hence, this poses considerable challenges to the healthcare system and the effort in providing cost-effective treatment as well as the search for alternatives to treatment and management of epilepsy. Enhancement of γ-aminobutyric acid (GABA)-mediated inhibitory neurotransmission is one of the key mechanisms of actions of antiepileptic drugs. GABA type > a receptors (GABAAR) are ligand-gated ion channels that mediate rapid inhibitory neurotransmission upon the binding of GABA with a heteropentameric structure forming a central pore that is permeable to the influx of chloride ions in its activated state. The major isoform of GABAA receptors consists of two α1, two β2, and one γ2 subunit. It is the most abundantly expressed combinations in the brain and the most commonly researched through Xenopus laevis oocytes. With the advancing studies on ethnomedicine and traditional treatments using medicinal plants, increasing evidence reveal that spice and herb plants with medicinal properties play an important role in the treatment of ailments within communities across different cultures. Capsaicin is the primary natural capsaicinoid in hot peppers of plant genus Capsicum, consist of an aromatic ring, an amide linkage and a hydrophobic side chain. The study showed that capsaicins conferred neuroprotection in status epilepticus mouse models through anti-ictogenic, hypothermic, antioxidative, anti-inflammatory, and anti-apoptotic actions in a dose-dependent manner. In this study, five capsaicin derivatives were tested for their ability to increase the GABA-induced chloride current on α1β2γ2S of GABAAR expressed on Xenopus laevis oocytes using the method of two-microelectrode voltage clamp. Two of the capsaicin derivatives, IS5 (N-(4-hydroxy-3-methoxybenzyl)-3-methylbutyramide) and IS10 (N-(4-hydroxy-3-methoxybenzyl)-decanamide) at a concentration of 30µM were able to significantly increase the GABA-induced chloride current with p=0.002 and p=0.026 respectively. This study were able to show the enhancement effect of two capsaicin derivatives with moderate length of hydrocarbon chain on this receptor subtype, revealing the promising inhibitory activity of capsaicin derivatives through enhancement of GABA-induced chloride current and further investigations should be carried out to verify its antiepileptic effects in animal models.

Keywords: α1β2γ2 GABAA receptors, α1β2γ2S, antiepileptic, capsaicin derivatives, two-microelectrode voltage clamp, Xenopus laevis oocytes

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Authors: Jeounghee Kim

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Objective: To describe the incidence of complication, according to the stage of Traumatic Spinal Cord Injury (TSCI) which was treated at Asan Medical Center (AMC), Korea. Hereafter, it should be developed in nursing management protocol of traumatic SCI. Methods. Retrospectively reviewed hospital records about the patients who were admitted AMC Patients with traumatic spinal cord injury until January 2005 and December 2016 were analyzed (n=97). AMC is a single institution of 2,700 beds where patients with trauma and severe trauma can be treated. Patients who were admitted to the emergency room due to spinal cord injury and who underwent intensive care unit, general ward, and rehabilitation ward. To identify long-term complications, we excluded patients who were operated on to other hospitals after surgery. Complications such as respiratory(pneumonia, atelectasis, pulmonary embolism, and others), cardiovascular (hypotension), urinary (autonomic dysreflexia, urinary tract infection (UTI), neurogenic bladder, and others), and skin systems (pressure ulcers) from the time of admission were examined through medical records and images. Results: SCI was graded according to ASIA scale. The initial grade was checked at admission. (grade A 55(56.7%), grade B 14(14.4)%, grade C 11(11.3%), grade D 15(15.5%), and grade E 2(2.1%). The grade was rechecked when the patient was discharged after treatment. (grade A 43(44.3%), grade B 15(15.5%), grade C 12(12.4%), grade D 21(21.6%), and grade E 6(6.2%). The most common complication after SCI was UTI 24cases (mean 36.5day), sore 24cases (40.5day), and Pneumonia which was 23 cases after 10days averagely. The other complications after SCI were neuropathic pain 19 cases, surgical site infection 4 cases. 53.6% of patient who had SCI were educated about intermittent catheterization at discharge from hospital. The mean hospital stay of all SCI patients was 61days. Conclusion: The Complications after traumatic SCI were developed at various stages from acute phase to chronic phase. Nurses need to understand fully the time-course of complication in traumatic SCI to provide evidence-based practice.

Keywords: spinal cord injury, complication, nursing, rehabilitation

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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

Procedia PDF Downloads 248

Authors: Syeda Sahra, Abdullah Jahangir, Rachelle Hamadi, Ahmad Jahangir, Allison Glaser

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Background: Antimicrobial resistance is on the rise. The use of redundant and inappropriate antibiotics is contributing to recurrent infections and resistance. Newer antibiotics with more robust coverage for gram-negative bacteria are in great demand for complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), hospital-acquired bacterial pneumonia (H.A.B.P.), and ventilator-associated bacterial pneumonia (V.A.B.P.). Objective: We performed this meta-analysis to evaluate the efficacy and safety profile of a new antibiotic, Imipenem/cilastatin/relebactam, compared to other broad-spectrum antibiotics for complicated infections. Search Strategy: We conducted a systemic review search on PubMed, Embase, and Central Cochrane Registry. Selection Criteria: We included randomized clinical trials (R.C.T.s) with the standard of care as comparator arm with Imipenem/cilastatin/relebactam as intervention arm. Analysis: For continuous variables, the mean difference was used. For discrete variables, we used the odds ratio. For effect sizes, we used a confidence interval of 95%. A p-value of less than 0.05 was used for statistical significance. Analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. Results: The authors observed similar efficacy at clinical and microbiologic response levels on early follow-up and late follow-up compared to the established standard of care. The incidence of drug-related adverse events, serious adverse events, and drug discontinuation due to adverse events were comparable across both groups. Conclusion: Imipenem/cilastatin/relebactam has a non-inferior safety and efficacy profile compared to peer antibiotics to treat severe bacterial infections (cUTIs, cIAIs, H.A.B.P., V.A.B.P.).

Keywords: bacterial pneumonia, complicated intra-abdominal infections, complicated urinary tract infection, Imipenem, cilastatin, relebactam

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Authors: Tunca Gul Altuntas, Aziz Baydar, Cemre Acar, Sezen Yılmaz, Tulay Coban

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Free radicals, which are generated in many bioorganic redox processes, play a role in the pathogenesis of several diseases including cancer, arthritis, hemorrhagic shock, inflammatory, cardiovascular, neurodegenerative diseases and age-related degenerative brain diseases. Exposures of normal cell to free radical damages several structures, oxidizes nucleic acids, proteins, lipids, or DNA. Compounds interfere with the action of reactive oxygen species might be useful in prevention and treatment of these pathologies. A series of indole compounds containing piperazine ring were synthesized. Coupling of indole-2-carboxylic acid with monosubstituted piperazines was accomplished with 1,1’-carbonyldiimidazole (CDI) in a good yield. The structures of prepared compounds were verified in good agreement with their 1H NMR (nuclear magnetic resonance), MS (mass spectrophotometry), and IR (infrared spectrophotometry) characteristics. In this work, all synthetized indole derivatives were screened in vitro for their antioxidative potential against vitamin E (α-tocopherol) using different antioxidant assays such as superoxide anion formation, lipid peroxidation levels in rat liver, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) stable radical scavenging activity. The synthesized compounds showed various levels of inhibition compared to vitamin E. This may give promising results for the development of new antioxidant agents.

Keywords: antioxidant, indoles, piperazines, reactive oxygen species

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Authors: Mostafa Shahriari, Sergio Rojas, David Pardo, Angel Rodriguez- Rozas, Shaaban A. Bakr, Victor M. Calo, Ignacio Muga

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Logging-While Drilling (LWD) is a technique to record down-hole logging measurements while drilling the well. Nowadays, LWD devices (e.g., nuclear, sonic, resistivity) are mostly used commercially for geo-steering applications. Modern borehole resistivity tools are able to measure all components of the magnetic field by incorporating tilted coils. The depth of investigation of LWD tools is limited compared to the thickness of the geological layers. Thus, it is a common practice to approximate the Earth’s subsurface with a sequence of 1D models. For a 1D model, we can reduce the dimensionality of the problem using a Hankel transform. We can solve the resulting system of ordinary differential equations (ODEs) either (a) analytically, which results in a so-called semi-analytic method after performing a numerical inverse Hankel transform, or (b) numerically. Semi-analytic methods are used by the industry due to their high performance. However, they have major limitations, namely: -The analytical solution of the aforementioned system of ODEs exists only for piecewise constant resistivity distributions. For arbitrary resistivity distributions, the solution of the system of ODEs is unknown by today’s knowledge. -In geo-steering, we need to solve inverse problems with respect to the inversion variables (e.g., the constant resistivity value of each layer and bed boundary positions) using a gradient-based inversion method. Thus, we need to compute the corresponding derivatives. However, the analytical derivatives of cross-bedded formation and the analytical derivatives with respect to the bed boundary positions have not been published to the best of our knowledge. The main contribution of this work is to overcome the aforementioned limitations of semi-analytic methods by solving each 1D model (associated with each Hankel mode) using an efficient multi-scale finite element method. The main idea is to divide our computations into two parts: (a) offline computations, which are independent of the tool positions and we precompute only once and use them for all logging positions, and (b) online computations, which depend upon the logging position. With the above method, (a) we can consider arbitrary resistivity distributions along the 1D model, and (b) we can easily and rapidly compute the derivatives with respect to any inversion variable at a negligible additional cost by using an adjoint state formulation. Although the proposed method is slower than semi-analytic methods, its computational efficiency is still high. In the presentation, we shall derive the mathematical variational formulation, describe the proposed multi-scale finite element method, and verify the accuracy and efficiency of our method by performing a wide range of numerical experiments and comparing the numerical solutions to semi-analytic ones when the latest are available.

Keywords: logging-While-Drilling, resistivity measurements, multi-scale finite elements, Hankel transform

Procedia PDF Downloads 361

Authors: Strahinja Kovačević, Lidija Jevrić, Miloš Kuzmanović, Sanja Podunavac-Kuzmanović

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In this paper, various derivatives of benzimidazole have been evaluated against Gram-negative bacteria Escherichia coli. For all investigated compounds the minimum inhibitory concentration (MIC) was determined. Quantitative structure-activity relationships (QSAR) attempts to find consistent relationships between the variations in the values of molecular properties and the biological activity for a series of compounds so that these rules can be used to evaluate new chemical entities. The correlation between MIC and some absorption, distribution, metabolism and excretion (ADME) parameters was investigated, and the mathematical models for predicting the antibacterial activity of this class of compounds were developed. The quality of the multiple linear regression (MLR) models was validated by the leave-one-out (LOO) technique, as well as by the calculation of the statistical parameters for the developed models and the results are discussed on the basis of the statistical data. The results of this study indicate that ADME parameters have a significant effect on the antibacterial activity of this class of compounds. Principal component analysis (PCA) and agglomerative hierarchical clustering algorithms (HCA) confirmed that the investigated molecules can be classified into groups on the basis of the ADME parameters: Madin-Darby Canine Kidney cell permeability (MDCK), Plasma protein binding (PPB%), human intestinal absorption (HIA%) and human colon carcinoma cell permeability (Caco-2).

Keywords: benzimidazoles, QSAR, ADME, in silico

Procedia PDF Downloads 349

Authors: Hari Bezwada, Michelle Cheon, Ryan Divan, Hannah Escritor, Michelle Kagramian, Isha Korgaonkar, Maya MacAdams, Udgita Pamidigantam, Richard Pilny, Eleanor Race, Angadh Singh, Nathan Zhang, LeeAnn Nguyen, Fina Liotta

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Malaria is a deadly disease caused by the Plasmodium parasite, which continues to develop resistance to current antimalarial drugs. In this research project, the effectiveness of numerous thiazole derivatives was explored in inhibiting the PfPKG, a crucial part of the Plasmodium life cycle. This study involved the synthesis of six thiazole-derived amides to inhibit the PfPKG pathway. Nuclear Magnetic Resonance (NMR) spectroscopy and Infrared (IR) spectroscopy were used to characterize these compounds. Furthermore, AutoDocking software was used to predict binding affinities of these thiazole-derived amides in silico. In silico, compound 6 exhibited the highest predicted binding affinity to PfPKG, while compound 5 had the lowest affinity. Compounds 1-4 displayed varying degrees of predicted binding affinity. In-vitro, it was found that compound 4 had the best percent inhibition, while compound 5 had the worst percent inhibition. Overall, all six compounds had weak inhibition (approximately 30-39% at 10 μM), but these results provide a foundation for future drug discovery experiments.

Keywords: Medicinal Chemistry, Malaria, drug discovery, PfPKG, Thiazole, Plasmodium

Procedia PDF Downloads 62

Authors: Lauren G. Coggins

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Catheter-associated urinary tract infections (CAUTI) and central line-associated bloodstream infections (CLABSI) are among the most common healthcare-associated infections (HAI), contributing to prolonged lengths of stay, greater costs of patient care, and increased patient mortality. Evidence-based preventative care bundles exist to establish consistent, safe patient-care practices throughout an entire organization, helping to ensure the collective application of care strategies that aim to improve patient outcomes and minimize complications. The cardiac intensive care unit at a nationally ranked teaching and research hospital in the United States exceeded its annual CAUTI and CLABSI targets in the fiscal year 2019, prompting examination into the unit’s infection prevention efforts that included preventative care bundles for both HAIs. Adherence to the CAUTI and CLABSI preventative care bundles was evaluated through frequent audits conducted over three months, using standards and resources from The Joint Commission, a globally recognized leader in quality improvement in healthcare and patient care safety. The bundle elements with the lowest scores were identified as the most commonly missed elements. Three elements from both bundles, six elements in total, served as key content areas for the educational interventions targeted to bedside nurses. The CAUTI elements included appropriate urinary catheter order, appropriate continuation criteria, and urinary catheter care. The CLABSI elements included primary tubing compliance, needleless connector compliance, and dressing change compliance. An integrated, multi-platform education campaign featured content on each CAUTI and CLABSI preventative care bundle in its entirety, with additional reinforcement focused on the lowest scoring elements. One-on-one educational materials included an informational pamphlet, badge buddy, a presentation to reinforce nursing care standards, and real-time application through case studies and electronic health record demonstrations. A digital hub was developed on the hospital’s Intranet for quick access to unit resources, and a bulletin board helped track the number of days since the last CAUTI and CLABSI incident. Audits continued to be conducted throughout the education campaign, and staff were given real-time feedback to address any gaps in adherence. Nearly every nurse in the cardiac intensive care unit received all educational materials, and adherence to all six key bundle elements increased after the implementation of educational interventions. Recommendations from this implementation include providing consistent, comprehensive education across multiple teaching tools and regular audits to track adherence. The multi-platform education campaign brought focus to the evidence-based CAUTI and CLABSI bundles, which in turn will help to reduce CAUTI and CLABSI rates in clinical practice.

Keywords: education, healthcare-associated infections, infection, nursing, prevention

Procedia PDF Downloads 88

Authors: Stelvin Sebastian, Andriya Annie Tom, Joyalanna Babu, Merin Joshy

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Introduction: The worldwide increase in the use of antibiotics in poultry and livestock industry to treat and prevent bacterial diseases and as growth promoters in feeds has led to the problem of development of antibiotic resistance both in animals and human population. Aim: To study the pattern of antibiotic use and prevalence of multidrug-resistant Escherichia coli in poultry chickens in selected farms in Muvattupuzha and to compare the spread of multidrug-resistant bacteria from poultry environment to UTI patients. Methodology: Two farms from each of 6 localities in Muvattupuzha were selected. A questionnaire on the pattern of antibiotic use and various farming practices were surveyed from farms. From each farm, 60samples of fresh fecal matter, litter from inside, litter from the outside shed, agricultural soil and control soil were collected, and antimicrobial susceptibility testing of E. coli was done. Antibiogram of UTI patients was collected from the secondary care hospital included in the study, and those were compared with resistance patterns of poultry samples. Results: From survey response antibiotics such as ofloxacin, enrofloxacin, levofloxacin, ciprofloxacin, colistin, ceftriaxone, neomycin, cephalexin, and oxytetracycline were used for treatment and prevention of infections in poultry. 31of 48 samples (51.66%) showed E. coli growth. 7 of 15 antibiotics (46.6%) showed resistance. Ampicillin, amoxicillin, meropenem, tetracycline showed 100% resistance to all samples. Statistical analysis confirmed similar resistance pattern in the poultry environment and UTI patients for antibiotics such as ampicillin, amoxicillin, amikacin, and ofloxacin. Conclusion: E. coli were resistant not only to extended-spectrum beta-lactams but also to carbapenems, which may be disseminated to the environment where litter was used as manure. This may due to irrational use of antibiotics in chicken or from their use in poultry feed as growth promoters. The study concludes the presence of multidrug-resistant E.coli in poultry and its spread to environment and humans, which may cause potentially serious implications for human health.

Keywords: multidrug resistance, escherichia coli, urinary tract infection, poultry

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Authors: Zohreh Bayat, Dariush Minai-Tehrani

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Pseudomonas aeruginosa is a Gram-negative, rode shape and aerobic bacterium that has shown to be resistance to many antibiotics. This resistance makes the bacterium very harmful in some diseases. It can also generate diseases in any part of the gastrointestinal tract from oropharynx to rectum. P. aeruginosa has become an important cause of infection, especially in patients with compromised host defense mechanisms. One of the most important reasons that make P. aeruginosa an emerging opportunistic pathogen in patients is its ability to use various compounds as carbon sources. Lipase is an enzyme that catalyzes the hydrolysis of lipids. Most lipases act at a specific position on the glycerol backbone of lipid substrate. Some lipases are expressed and secreted by pathogenic organisms during the infection. Muscarinic antagonist used as an antispasmodic and in urinary incontinence. The drug has little effect on glandular secretion or the cardiovascular system. It does have some local anesthetic properties and is used in gastrointestinal, biliary, and urinary tract spasms. Aim: In this study the inhibitory effect of a muscarinic antagonist on lipase of P. aeruginosa was investigated. Methods: P. aeruginosa was cultured in minimal salt medium with 1% olive oil as carbon source. The cells were harvested and the supernatant, which contained lipase, was used for enzyme assay. Results: Our results showed that the drug can inhibit P. aeruginosa lipase by competitive manner. In the presence of different concentrations of the drug, the Vmax (2 mmol/min/mg protein) of enzyme did not change, while the Km raised by increasing the drug concentration. The Ki (inhibition constant) and IC50 (the half maximal inhibitory concentration) value of drug was estimated to be about 30 uM and 60 uM which determined that the drug binds to enzyme with high affinity. Maximum activity of the enzyme was observed at pH 8 in the absence and presence of muscarinic antagonist, respectively. The maximum activity of lipase was observed at 600C and the enzyme became inactive at 900C. Conclusion: The muscarinic antagonist drug could inhibit lipase of P. aeruginosa and changed the kinetic parameters of the enzyme. The drug binded to enzyme with high affinity and did not chang the optimum pH of the enzyme. Temperature did not affect the binding of drug to musmuscarinic antagonist.

Keywords: Pseudomonas aeruginosa, drug, enzyme, inhibition

Procedia PDF Downloads 411