Search results for: drug release.

Authors: Aneena Suresh, C. S. Sidharth

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Drug related problems (DRPs) are common in chronic kidney disease (CKD) patients and end stage patients undergoing hemodialysis. To treat the co-morbid conditions of the patients, more complex therapeutic regimen is required, and it leads to development of DRPs. So, this calls for frequent monitoring of the patients. Due to the busy work schedules, physicians are unable to deliver optimal care to these patients. Addition of a clinical pharmacist in the team will improve the standard of care offered to CKD patients by minimizing DRPs. In India, the role of clinical pharmacists in the improving the health outcomes in CKD patients is poorly recognized. Therefore, this study is conducted to put an insight on the role of clinical pharmacist in improving Drug Related Problems in patients with chronic kidney disease, thereby helping them to achieve desired therapeutic outcomes in the patients. A prospective interventional study was conducted for a year in a 620 bedded tertiary care hospital in India. Data was collected using an unstructured questionnaire, medication charts, etc. DRPs were categorized using Hepler and Strand classification. Relationships between the age, weight, GFR, average no of medication taken, average no of comorbidities, and average length of hospital days with the DRPs were identified using Mann Whitney U test. The study population primarily constituted of patients above the age of 50 years with a mean age of 59.91±13.59. Our study showed that 25% of the population presented with DRPs. On an average, CKD patients are prescribed at least 8 medications for the treatment in our study. This explains the high incidence of drug interactions in patients suffering from CKD (45.65%). The least common DRPs in our study were found to be sub therapeutic dose (2%) and adverse drug reactions (2%). Out of this, 60 % of the DRPs were addressed successfully. In our study, there is an association between the DRPs with the average number of medications prescribed, the average number of comorbidities, and the length of the hospital days with p value of 0.022, 0.004, and 0.000, respectively. In the current study, 86% of the proposed interventions were accepted, and 41 % were implemented by the physician, and only 14% were rejected. Hence, it is evident that clinical pharmacist interventions will contribute significantly to diminish the DRPs in CKD patients, thereby decreasing the economic burden of healthcare costs and improving patient’s quality of life.

Keywords: chronic kidney disease, clinical pharmacist, drug related problem, intervention

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Authors: Leslie Raphael de M. Ferraz, Salvana Priscylla M. Costa, Tarcyla de A. Gomes, Giovanna Christinne R. M. Schver, Cristóvão R. da Silva, Magaly Andreza M. de Lyra, Danilo Augusto F. Fontes, Larissa A. Rolim, Amanda Carla Q. M. Vieira, Miracy M. de Albuquerque, Pedro J. Rolim-Neto

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Efavirenz (EFV) is a drug used as first-line treatment of AIDS. However, it has poor aqueous solubility and wettability, presenting problems in the gastrointestinal tract absorption and bioavailability. One of the most promising strategies to improve the solubility is the use of solid dispersions (SD). Therefore, this study aimed to characterize SD EFZ with the polymers: PVP-K30, PVPVA 64 and SOLUPLUS in order to find an optimal formulation to compose a future pharmaceutical product for AIDS therapy. Initially, Physical Mixtures (PM) and SD with the polymers were obtained containing 10, 20, 50 and 80% of drug (w/w) by the solvent method. The best formulation obtained between the SD was selected by in vitro dissolution test. Finally, the drug-carrier system chosen, in all ratios obtained, were analyzed by the following techniques: Differential Scanning Calorimetry (DSC), polarization microscopy, Scanning Electron Microscopy (SEM) and spectrophotometry of absorption in the region of infrared (IR). From the dissolution profiles of EFV, PM and SD, the values of area Under The Curve (AUC) were calculated. The data showed that the AUC of all PM is greater than the isolated EFV, this result is derived from the hydrophilic properties of the polymers thus favoring a decrease in surface tension between the drug and the dissolution medium. In adittion, this ensures an increasing of wettability of the drug. In parallel, it was found that SD whom had higher AUC values, were those who have the greatest amount of polymer (with only 10% drug). As the amount of drug increases, it was noticed that these results either decrease or are statistically similar. The AUC values of the SD using the three different polymers, followed this decreasing order: SD PVPVA 64-EFV 10% > SD PVP-K30-EFV 10% > SD Soluplus®-EFV 10%. The DSC curves of SD’s did not show the characteristic endothermic event of drug melt process, suggesting that the EFV was converted to its amorphous state. The analysis of polarized light microscopy showed significant birefringence of the PM’s, but this was not observed in films of SD’s, thus suggesting the conversion of the drug from the crystalline to the amorphous state. In electron micrographs of all PM, independently of the percentage of the drug, the crystal structure of EFV was clearly detectable. Moreover, electron micrographs of the SD with the two polymers in different ratios investigated, we observed the presence of particles with irregular size and morphology, also occurring an extensive change in the appearance of the polymer, not being possible to differentiate the two components. IR spectra of PM corresponds to the overlapping of polymer and EFV bands indicating thereby that there is no interaction between them, unlike the spectra of all SD that showed complete disappearance of the band related to the axial deformation of the NH group of EFV. Therefore, this study was able to obtain a suitable formulation to overcome the solubility limitations of the EFV, since SD PVPVA 64-EFZ 10% was chosen as the best system in delay crystallization of the prototype, reaching higher levels of super saturation.

Keywords: characterization, dissolution, Efavirenz, solid dispersions

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Authors: Ikram Elsiddig, Yacouba Djamila, Amna Hamad

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Abstract—The worldwide increasing of using herbs in form of medicine with or without prescription medications potentiates the interactions between herbal products and conventional medicines; due to more research for herb-drug interactions are needed. for a long time hyperglycemia had been treated with several medicinal plants. A. sativum, belonging to the Liliaceae family is well known for its medicinal uses in African traditional medicine, it used for treating of many human diseases mainly diabetes, high cholesterol and high blood pressure. The purpose of this study is to determine the interaction effect between A. sativum bulb extracts and metformin drug used in diabetes treatment. The in vitro and in vivo evaluation were conducted by glucose reuptake using isolated rats hemidiaphgrams tissue and by estimate glucose tolerance in glucose-loaded wistar albino rats. The results showed that, petroleum ether, chloroform and ethyl acetate extracts were found to have activity of glucose uptake in isolated rats hemidiaphgrams of 24.11 mg/g, 19.07 mg/g and 15.66 mg/g compared to metformin drug of 17 mg/g. These activity were reducded to 17.8 mg/g, 13.59 mg/g and 14.46 mg/g after combination with metformin, metformin itself reduced to 13.59 mg/g, 14.46 mg/g and 12.71 mg/g in comination with chloroform and ethyl acetate. These decrease in activity could be due to herbal–drug interaction between the extracts of A. sativum bulb and metformin drug. The interaction between A. sativum extract and metformin was also shown by in vivo study on the induced hyperglycemic rats. The glucose level after administered of 200 mg/kg was found to be increase with 47.2 % and 17.7% at first and second hour compared to the increase of blood glucose in the control group of 82.6% and76.7%.. At fourth hour the glucose level was became less than normal with 3.4% compared to control which continue to increase with 68.2%. Dose of 400 mg/kg at first hour showed increase in blood glucose of 31.5 %, at second and fourth hours the glucose level was became less than normal with decrease of 3.2 % and 30.4%. After combination the activity was found to be less than that of extract at both high and low dose, whereas, at first and second hour, the glucose level was found to be increase with 50.4% and 21.2%, at fourth hour the glucose level was became less than normal with 14%. Therefore A. sativum could be a potential source for anti-diabetic when it used alone, and it is significant important to use the garlic extract alone instead of combined with Metformin drug in diabetes- treatment.

Keywords: Antagonistic, Garlic, Metformin, Synergistic

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Authors: Sunil Kumar

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For many years, small organic molecules derived naturally from microbes and plants have delivered a number of expedient therapeutic drug agents. The search for naturally occurring lead compounds has continued in recent years as well, with the constituents of marine flora and fauna along with those of telluric microorganisms and plants being investigated for their anti-bacterial and anti-cancer activities. It has been observed that such promising lead molecules incline to promptly generate substantial attention among scientists like synthetic organic chemists and biologists. Subsequently, the availability of a given precious natural product sample may be enriched, and it may be possible to determine a preliminary idea of structure-activity relationships to develop synthetic analogues. For instance, anti-tumor drug topotecan is a synthetic chemical compound similar in chemical structure to camptothecin which is found in extracts of Camptotheca acuminate. Similarly, researchers at AstraZeneca discovered anti-biotic pyrrolamide through a fragment-based lead generation approach from kibdelomycin, which is isolated from Staphylococcus aureuss.

Keywords: anticancer, antibiotic, lead molecule, natural product, synthetic analogues

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Authors: Natida Thongsima, Patompong Satapornpong

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Introduction: Lamotrigine is widely used in the treatment of epilepsy and bipolar disorder. However, lamotrigine leads to adverse drug reactions (ADRs) consist of severe cutaneous adverse reactions (SCARs) include Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug rash with eosinophilia and systemic symptoms (DRESS). Moreover, lamotrigine-induced SCARs are usually manifested between 2 and 8 weeks after treatment initiation. According to a previous study, the association between HLA-B*15:02 and lamotrigine-induced cutaneous adverse drug reactions in the Thai population (odds ratio 4.89; 95% CI 1.28–18.66; p-value = 0.014) was found. Therefore, the distribution of pharmacogenetics markers a major role in predicting the culprit drugs for SCARs in many populations. Objective: In this study, we want to investigate the prevalence of HLA-B allele, which correlates with lamotrigine-induced SCARs in the healthy Thai population. Materials and Methods: We enrolled 350 healthy Thai individuals and were approved by the ethics committee of Rangsit University. HLA-B alleles were genotyped by the Lifecodes HLA SSO typing kits (Immucor, West Avenue, Stamford, USA). Results: The results presented HLA-B allele frequency in healthy Thai population were 14.71% (HLA-B*46:01), 8.57% (HLA-B*15:02), 6.71% (HLA-B*40:01), 5.86% (HLA-B*13:01), 5.71% (HLA-B*58:01), 5.14% (HLA-B*38:02), 4.86% (HLA-B*18:01), 4.86% (HLA-B*51:01), 3.86% (HLA-B*44:03) and 2.71% (HLA-B*07:05). Especially, HLA-B*15:02 allele was the high frequency in the Thais (8.57%), Han Chinese (7.30%), Vietnamese (13.50%), Malaysian (6.06%) and Indonesian (11.60%). Nevertheless, this allele was much lower in other populations, namely, Africans, Caucasians, and Japanese. Conclusions: Although the sample size of the healthy Thai population in this research was limited, there were found the frequency of the HLA-B*15:02 allele could predispose them toward to lamotrigine-induced SCARs in Thailand.

Keywords: lamotrigine, cutaneous adverse drug reactions, HLA-B, Thai population

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Authors: Smita Lakhotia, C. Kew, S. H. M. Siraj, B. Chern

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Up to 50% of those with endometriosis may suffer from infertility due to either distorted pelvic anatomy/impaired oocyte release or inhibit ovum pickup and transport, altered peritoneal function, endocrine and anovulatory disorders, including LUF, impaired implantation, progesterone resistance or decreased levels of cellular immunity. The dilemma continues as to whether the surgery or IVF is the optimal management for such recurrent endometriomas. The core question is whether surgery adds anything of value for infertile women with recurrent endometriosis or not. Complete and detailed information on risks and benefits of treatment alternatives must be offered to patients, giving a realistic estimate of chances of success of repetitive surgery and of multiple IVF cycles in order to allow unbiased choices between different possible optionsAn individualized treatment plan should be developed taking into account patient age, duration of infertility, previous pregnancies and specific clinical conditions and wish.

Keywords: recurrent endometriosis, infertility, oocyte release, pregnancy

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Authors: Kazem Shakouri, Alireza Pishgahi, Homayoun Sadeghi-bBazargani, Shahla Dareshiri

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Introduction: Carpal Tunnel Syndrome has numerous nonsurgical treatments including splint, physical therapy and corticosteroid injections. Aim: The purpose of this study was to evaluate the effectiveness of an ultrasound guided treatment procedure, for individuals with severe carpal tunnel syndrome. Materials and Method: 20 patients with an electrodiagnostic evidence of severe carpal tunnel syndrome were treated by an office-based ultrasound guided procedure (combination of percutaneous needle release of carpal tunnel and corticosteroid injection). Electrodiagnostic (nerve conduction study), clinical (Boston Carpal Tunnel Questionnaire, grip strength) and ultrasonic (median nerve and carpal tunnel cross-sectional area) measurements were recorded at baseline and one month after intervention. Results: Our preliminary data analysis showed that in one month follow up, patients had a significantly smaller cross-sectional area of the median nerve compared to pretreatment values (mean difference 0.06; 95%CI: 0.02-0.1; p < 0.001). In addition, patients had significantly less functional impairment (mean difference 35; 95% CI:28.7-43.4 ; p < 0.001), and an improved hand grip strength in one month follow up (mean difference 5.4; 95%CI: 3.1-7.8; p < 0.001;). There were no significant complications. Conclusion: Patients with severe carpal tunnel syndrome, who are candidates for surgical intervention, can consider office-based ultrasound guided needle release of carpal tunnel as an alternative safe treatment.

Keywords: Carpal Tunnel Syndrome, needle release, pain, ultrasound

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Authors: Neslihan Demirci, Serdar Durdağı

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Mycobacterium tuberculosis is still a worldwide disease-causing agent that, according to WHO, led to the death of 1.5 million people from tuberculosis (TB) in 2020. The bacteria reside in macrophages located specifically in the lung. There is a known quadruple drug therapy regimen for TB consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Over the past 60 years, there have been great contributions to treatment options, such as recently approved delamanid (OPC67683) and bedaquiline (TMC207/R207910), targeting mycolic acid and ATP synthesis, respectively. Also, there are natural compounds that can block the tryptophanyl-tRNA synthetase (TrpRS) enzyme, chuangxinmycin, and indolmycin. Yet, already the drug resistance is reported for those agents. In this study, the newly released TrpRS enzyme structure is investigated for potential inhibitor drugs from already synthesized molecules to help the treatment of resistant cases and to propose an alternative drug for the quadruple drug therapy of tuberculosis. Maestro, Schrodinger is used for docking and molecular dynamic simulations. In-house library containing ~8000 compounds among FDA-approved indole-containing compounds, a total of 57 obtained from the ChemBL were used for both ATP and tryptophan binding pocket docking. Best of indole-containing 57 compounds were subjected to hit expansion and compared later with virtual screening workflow (VSW) results. After docking, VSW was done. Glide-XP docking algorithm was chosen. When compared, VSW alone performed better than the hit expansion module. Best scored compounds were kept for ten ns molecular dynamic simulations by Desmond. Further, 100 ns molecular dynamic simulation was performed for elected molecules according to Z-score. The top three MMGBSA-scored compounds were subjected to steered molecular dynamic (SMD) simulations by Gromacs. While SMD simulations are still being conducted, ponesimod (for multiple sclerosis), vilanterol (β₂ adrenoreceptor agonist), and silodosin (for benign prostatic hyperplasia) were found to have a significant affinity for tuberculosis TrpRS, which is the propulsive force for the urge to expand the research with in vitro studies. Interestingly, top-scored ponesimod has been reported to have a side effect that makes the patient prone to upper respiratory tract infections.

Keywords: drug repurposing, molecular dynamics, tryptophanyl-tRNA synthetase, tuberculosis

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Authors: Rostyslav Horbay, Nick Korolis, Vahid Anvari, Rostyslav Stoika

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Introduction: Giant cancer cells (GCC) are common in all types of cancer, especially after poor therapy. Some specific features of such cells include ~10-fold enlargement, drug resistance, and the ability to propagate similar daughter cells. We used murine NK/Ly lymphoma, an aggressive and fast growing lymphoma model that has already shown drastic changes in GCC comparing to parental cells (chromatin condensation, nuclear fragmentation, tighter OXPHOS/cellular respiration coupling, multidrug resistance). Materials and methods: In this study, we compared morpho-functional changes of GCC that predominantly show either a cytostatic or a cytotoxic effect after treatment with drugs. We studied the effect of a combined cytostatic/cytotoxic drug treatment to determine the correlation of drug efficiency and GCC formation. Doses of G1/S-specific drug paclitaxel/PTX (G2/M-specific, 50 mg/mouse), vinblastine/VBL (50 mg/mouse), and DNA-targeting agents doxorubicin/DOX (125 ng/mouse) and cisplatin/CP (225 ng/mouse) on C57 black mice. Several tests were chosen to estimate morphological and physiological state (propidium iodide, Rhodamine-123, DAPI, JC-1, Janus Green, Giemsa staining and other), which included cell integrity, nuclear fragmentation and chromatin condensation, mitochondrial activity, and others. A single and double factor ANOVA analysis were performed to determine correlation between the criteria of applied drugs and cytomorphological changes. Results: In all cases of treatment, several morphological changes were observed (intracellular vacuolization, membrane blebbing, and interconnected mitochondrial network). A lower gain in ascites (49.97% comparing to control group) and longest lifespan (22+9 days) after tumor injection was obtained with single VBL and single DOX injections. Such ascites contained the highest number of GCC (83.7%+9.2%), lowest cell count number (72.7+31.0 mln/ml), and a strong correlation coefficient between increased mitochondrial activity and percentage of giant NK/Ly cells. A high number of viable GCC (82.1+9.2%) was observed compared to the parental forms (15.4+11.9%) indicating that GCC are more drug resistant than the parental cells. All this indicates that the giant cell formation and its ability to obtain drug resistance is an expanding field in cancer research.

Keywords: ANOVA, cisplatin, doxorubicin, drug resistance, giant cancer cells, NK/Ly lymphoma, paclitaxel, vinblastine

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Authors: G. R. Khan, Sadia Mahjabin, A. S. Mollah, M. R. Mawla

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Atmospheric dispersion modeling is significant for any nuclear facilities in the country to predict the impact of radiological doses on environment as well as human health. That is why to ensure safety of workers and population at plant site; Atmospheric dispersion modeling and radiation dose calculations were carried out for a hypothetical accidental release of airborne radionuclide from the 3 MW TRIGA research reactor of Savar, Bangladesh. It is designed with reactor core which consists of 100 fuel elements(1.82245 cm in diameter and 38.1 cm in length), arranged in an annular corefor steady-state and square wave power level of 3 MW (thermal) and for pulsing with maximum power level of 860MWth.The fuel is in the form of a uniform mixture of 20% uranium and 80% zirconium hydride. Total effective doses (TEDs) to the public at various downwind distances were evaluated with a health physics computer code “HotSpot” developed by Lawrence Livermore National Laboratory, USA. The doses were estimated at different Pasquill stability classes (categories A-F) with site-specific averaged meteorological conditions. The meteorological data, such as, average wind speed, frequency distribution of wind direction, etc. have also been analyzed based on the data collected near the reactor site. The results of effective doses obtained remain within the recommended maximum effective dose.

Keywords: accidental release, dispersion modeling, total effective dose, TRIGA

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Authors: Shuye Jiang, Ali Ma, Srinivasan Ramachandran

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Indoor air quality could be improved through traditional air purifiers. However, they may not be environmental products. Here, a bio-based method was employed to improve indoor air quality by increasing negative air ion (NAI) release from ornamental plants. A total of 60 plant species has been screened by evaluating their ability to release NAIs, from which four candidates were selected to further study. All of them are from the Dracaena or fabids clade. These four candidates were then subjected to survey their ability to reduce the concentration of particulate matter with diameter of 2.5 or 10 microns (PM2.5 and PM10) in the growth chamber. High concentrations of PM2.5 and PM10 were artificially generated by burning a stick of incense for 2 minutes in the closed growth chamber (80cm length × 80cm width × 80cm height), in which the PM2.5 and PM10 concentration were generally around 500 µg/m3 and 1500 µg/m3, respectively. Both PM2.5 and PM10 were naturally reduced to 410 and 670, respectively after two hours in case that no plants were placed inside the chamber. Interestingly, these two sizes of particulars were reduced to 170 µg/m3 and 210 µg/m3, respectively after two hours when plants were placed to the chamber. It took 4 hours for the plants to reduce particular concentration to acceptable level at less than 55 µg/m3 for both PM2.5 and PM10, respectively. However, the PM2.5 and PM10 concentration were still above 200 µg/m3 and 300 µg/m3, respectively after 4 hours in the growth chamber without any plants. These results suggest the contribution of plants to the particulate deposition. However, all of these data are preliminary and the results may be updated by further studies. In addition, the roles of plants in absorbing indoor formaldehyde have also been explored and their absorbing ability is being improved by optimizing their growth conditions and treating with various exogenous agents. Thus, our preliminary studies provide an alternative strategy to improve indoor air quality.

Keywords: bio-based method, indoor air, negative air ion, particulate matter

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Authors: Sivakumar Singaravelu, Giriprasath Ramanathan, M. D. Raja, Uma Tirichurapalli Sivagnanam

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The goal of the present study was to develop and evaluate composite film for tissue engineering application. The keratin was extracted from bovine horn and used for preparation of keratin (HK), physiologically clotted fibrin (PCF) and gelatin (G) blend films in different stoichiometric ratios (1:1:1, 1:1:2 and 1:1:3) by using solvent casting method. The composite films (HK-PCF-G) were characterized physiochemically using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA) and Scanning Electron Microscopy (SEM). The mechanical properties of the composite films were analyzed. The results of tensile strength show that ultimate strength and elongation were 10.72 Mpa and 4.83 MPA respectively for 1:1:3 ratio combination. The SEM image showed a slight smooth surface for 1:1:3 ratio combination compared to other films. In order to impart antibacterial activities, the composite films were loaded with Mupirocin (MP) to act against infection. The composite films acted as a suitable carrier to protect and release the drug in a controlled manner. This developed composite film would be a suitable alternative material for tissue engineering application.

Keywords: bovine horn, keratin, fibrin, gelatin, tensile strength

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Authors: Mahdi Akhbardeh

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St John's wort plant can help to treat depression disease through decreasing this disease symptom, due to having some similar features of Prozac (Fluoxetine Hcl) pill. People suffering from slight depression who have fear of using antidepressants side effects can use St John's wort drops under doctor observation. This method of treatment is proposed specially to those women who are spending menopause or depression resulted from this period. St John's wort plant have proposed traditional and plant medicine as newest researches in treating mood disorders compared to Prozac (Fluoxetine Hcl) drug in treating depression disease which is being administrated in clinic research center of Washington. Objective: the aim of this study is to find an alternative treatment method in people suffering from depression which are treated with Prozac (Fluoxetine Hcl). Almost 70 percent of treatment failures with Prozac (Fluoxetine Hcl) drug in patients suffering from slight to normal depression is due to intensive side effects including: decrease in blood pressure, reduce in sexual desire and 30 percent of it is due to this drug affectless in treatment procedure which leads to leaving treatment. Results of Hypercuim plant function are exactly similar to antidepressants. Increase in serotonin amount in brain synopsis terminal end causes increase in existence time of this material in this part. In fact these two drugs have similar function. Though side effects of Hypercuim plant(St John's wort) including headache and slight nausea tolerable. Results: St John's wort plant can be used lonely in slight to normal depressions in which patients are avoiding Prozac (Fluoxetine Hcl) drug due to it's side effects. In intensive depressions through which general patients don’t indicate positive response to drug, it is probably expected relative or even complete treatment through combining antidepressants drugs with this plant. This treatment method has been investigated and confirmed in clinical tests and researches.

Keywords: depression, St John's wort, Prozac, antidepressant

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Authors: Michelle V. Tomczak, Reyhaneh Bakhtiari, Aaron Granley, Anthony Singhal

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Objective: Cannabis and cocaine are associated with a range of mental and physical effects that can impair aspects of human behavior. Driving is a complex cognitive behavior that is an essential part of everyday life and can be broken down into many subcomponents, each of which can uniquely impact road safety. With the growing movement of jurisdictions to legalize cannabis, there is an increased focus on impairment and driving. The purpose of this study was to identify driving-related cognitive-performance deficits that are impacted by recreational drug use. Design and Methods: With the assistance of law enforcement agencies, we recruited over 300 participants under the influence of various drugs including cannabis and cocaine. These individuals performed a battery of computer-based tasks scientifically proven to be re-lated to on-road driving performance and designed to test response-speed, memory processes, perceptual-motor skills, and decision making. Data from a control group with healthy non-drug using adults was collected as well. Results: Compared to controls, the drug group showed def-icits in all tasks. The data also showed clear differences between the cannabis and cocaine groups where cannabis users were faster, and performed better on some aspects of the decision-making and perceptual-motor tasks. Memory performance was better in the cocaine group for simple tasks but not more complex tasks. Finally, the participants who consumed both drugs performed most similarly to the cannabis group. Conclusions: Our results show distinct and combined effects of cannabis and cocaine on human performance relating to driving. These dif-ferential effects are likely related to the unique effects of each drug on the human brain and how they distinctly contribute to mental states. Our results have important implications for road safety associated with driver impairment.

Keywords: driving, cognitive impairment, recreational drug use, cannabis and cocaine

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Authors: Bahiru Tsegaye, Chandrajit Balomajumder, Partha Roy

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The limited supply and related negative environmental consequence of fossil fuels are driving researcher for finding sustainable sources of energy. Lignocellulose biomass like sorghum straw is considered as among cheap, renewable and abundantly available sources of energy. However, lignocellulose biomass conversion to bioenergy like bioethanol is hindered due to the reluctant nature of lignin in the biomass. Therefore, removal of lignin is a vital step for lignocellulose conversion to renewable energy. The aim of this study is to optimize microwave pretreatment conditions using design expert software to remove lignin and to release maximum possible polysaccharides from sorghum straw for efficient hydrolysis and fermentation process. Sodium hydroxide concentration between 0.5-1.5%, v/v, pretreatment time from 5-25 minutes and pretreatment temperature from 120-2000C were considered to depolymerize sorghum straw. The effect of pretreatment was studied by analyzing the compositional changes before and after pretreatments following renewable energy laboratory procedure. Analysis of variance (ANOVA) was used to test the significance of the model used for optimization. About 32.8%-48.27% of hemicellulose solubilization, 53% -82.62% of cellulose release, and 49.25% to 78.29% lignin solubilization were observed during microwave pretreatment. Pretreatment for 10 minutes with alkali concentration of 1.5% and temperature of 1400C released maximum cellulose and lignin. At this optimal condition, maximum of 82.62% of cellulose release and 78.29% of lignin removal was achieved. Sorghum straw at optimal pretreatment condition was subjected to enzymatic hydrolysis and fermentation. The efficiency of hydrolysis was measured by analyzing reducing sugars by 3, 5 dinitrisylicylic acid method. Reducing sugars of about 619 mg/g of sorghum straw were obtained after enzymatic hydrolysis. This study showed a significant amount of lignin removal and cellulose release at optimal condition. This enhances the yield of reducing sugars as well as ethanol yield. The study demonstrates the potential of microwave pretreatments for enhancing bioethanol yield from sorghum straw.

Keywords: cellulose, hydrolysis, lignocellulose, optimization

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Authors: Hu-Jiang Shi, Li-Juan Zhu

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The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in affective behaviors is a topic of debate, and the underlying mechanisms remain largely unclear. Here, we elucidate that the interaction between hippocampal neuronal nitric oxide synthase (nNOS) and carboxy-terminal PDZ ligand of nNOS (CAPON) contributes to the disruption of hippocampal excitation-inhibition (E/I) balance, which is responsible for the anxiety- and depressive-like behaviors caused by chronic stress-related 5-HT2CR signaling deficiency. In detail, activation or inhibition of 5-HT2CR by CP809101 or SB242084 modulates nNOS-CAPON interaction by influencing intracellular Ca²⁺ release. Notably, the dissociation of nNOS-CAPON abolishes SB242084-induced anxiety- and depressive-like behaviors, as well as the reduction in extracellular signal-regulated kinase (ERK)/cAMP-response element binding protein (CREB)/synapsin signaling and SNARE complex assembly. Furthermore, nNOS-CAPON blockers restore the impairments caused by SB242084, including the reduction in SNARE assembly-mediated γ-aminobutyric acid (GABA) vesicle release and a consequent shift of the E/I balance toward excitation in CA3 pyramidal neurons. Conclusively, our findings disclose the regulatory role of 5-HT2CR in anxiety- and depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.

Keywords: 5-HT2CR, anxiety, depression, nNOS-CAPON coupling, excitation-inhibition balance, neurotransmitter release

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Authors: Rosa L. Figueroa, Joselyn A. Hernández

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During the last couple of years, the Ministry of Health have been developing new health policies in order to regulate and improve in benefit of the patient the pharmaceutical system in our country. However, there are still some deficiencies in how medicines have been accessed, distributed, and sold. Therefore, it is necessary to empower the patient by offering new instances to improve access to drug information. This work introduces ‘the bioequivalent’ a medical drug search tool created to increase both diffusion and getting information about the therapeutic equivalence of medicines for the patient. The development of the search tool started with a study on the availability of sources of drug information accessible to the patient where advantages and disadvantages were analyzed. The information obtained was used to feed the functional design of the new tool. The design of the new tool shows an external interface that includes a header, body, sidebar and footer. The header has a menu containing ‘Home,’ ‘Who we are,’ and ‘Mission and vision.’ The Body contains the medical drug search tool, and the Sidebar is for the user logging in. It could be anonym, registered user, as well as, administrator. Anonym user could only use the tool. Registered users could add some information on existing medicines in the database; however, adding information will be restricted and limited to specific items and subject to administrator approval because the information added must be endorsed by the Chilean Public Health Institute. On the other hand, the administrator will have all the privileges, including creating or deleting drugs or information about them. The Bioequivalent was tested on different mobile devices, and no fails have been found. Moreover, a small survey was answered by ten people who tested the tool, and all of them agree that the tool was useful to get information about bioequivalent drugs, and they would recommend the tool to others. Nevertheless, an 80% of people who tested the tool says it was easy to use, and a 70% indicates that additional help is not required. These results are evidence that ‘the Bioequivalent’ may contribute to the knowledge about the therapeutic bioequivalence and bioequivalent drugs existing in Chile. As future work, the tool will be developed to make it available to the public for a first testing stage in a more massive scenario.

Keywords: collaborative database, bioequivalent drugs, search tool, web platform

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Authors: Prateek Singh, Arun Kumar Pandey, C. Raghu Kumar, M. R. Rath, A. S. Reddy

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Drum scrubber is widely used equipment in the washing of Iron ore. The purpose of the scrubber is to release the adhered fine clayey particles from the iron-bearing particles. Presently, the iron ore wash plants in the Eastern region of India consist of the scrubber, double deck screen followed by screw classifier as the main unit operations. Hence, scrubber performance efficiency has a huge impact on the downstream product quality. This paper illustrates the effect of scrubber feed % solids on scrubber performance and alumina distribution on downstream equipment. Further, it was established that scrubber performance efficiency could be defined as the ratio of the adhered particles (-0.15mm) released from scrubber feed during scrubbing operation with respect to the maximum possible release of -0.15mm (%) particles.

Keywords: scrubber, adhered particles, feed % solids, efficiency

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Authors: Kyou Hee Shim, Hwa Sung Shin

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When a thrombolysis agent is administered to treat ischemic stroke, excessive reactive oxygen species are generated due to a sudden provision of oxygen and occurs secondary damage cell necrosis. Thus, it is necessary to administrate adjuvant as well as thrombolysis agent to protect and reduce damaged tissue. As cerebral blood vessels have specific structure called blood-brain barrier (BBB), it is not easy to transfer substances from blood to tissue. Therefore, development of a drug carrier is required to increase drug delivery efficiency to brain tissue. In this study, cyanobacterial pigment from the blue-green algae known for having neuroprotective effect as well as antioxidant effect was nasally administrated for bypassing BBB. In order to deliver cyanobacterial pigment efficiently, the nano-sized liposome was used as a carrier. Liposomes were coated with a positive charge of chitosan since negative residues are present at the nasal mucosa the first gateway of nasal administration. Characteristics of liposome including morphology, size and zeta potential were analyzed by transmission electron microscope (TEM) and zeta analyzer. As a result of cytotoxic test, the liposomes were not harmful. Also, being administered a drug to the ischemic stroke animal model, we could confirm that the pharmacological effect of the pigment delivered by chitosan coated liposome was enhanced compared to that of non-coated liposome. Consequently, chitosan coated liposome could be considered as an optimized drug delivery system for the treatment of acute ischemic stroke.

Keywords: ischemic stroke, cyanobacterial pigment, liposome, chitosan, nasal administration

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Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

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Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

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Authors: Bouami Hind, Millot Patrick

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The implementation of automated devices in life-critical systems such as hospitals can bring a new set of challenges related to automation malfunctions. While automation has been identified as great leverage for the medication dispensing system’s security and efficiency, it also increases the complexity of the organization. In particular, the installation and operation stage of automated devices can be complex when malfunctions related to automated systems occur. This paper aims to document operators’ situation awareness about the malfunctions of automated drug delivery systems (ADCs) during their implementation through Saint Brieuc hospital’s feedback. Our evaluation approach has been deployed in Saint Brieuc hospital center’s pharmacy, which has been equipped with automated nominative drug dispensing systems since January of 2021. The analysis of Saint Brieuc hospital center pharmacy’s automation revealed numerous malfunctions related to the implementation of Automated Delivery Cabinets. It appears that the targeted performance is not reached in the first year of implementation in this case study. Also, errors have been collected in patients' automated treatments’ production such as lack of drugs in pill boxes or nominative carnets, excess of drugs, wrong location of the drug, drug blister damaged, non-compliant sachet, or ticket errors. Saint Brieuc hospital center’s pharmacy is doing a tremendous job of setting up and monitoring performance indicators from the beginning of automation and throughout ADC’s operation to control ADC’s malfunctions and meet the performance targeted by the hospital. Health professionals, including pharmacists, biomedical engineers and directors of work, technical services and safety, are heavily involved in an automation project. This study highlights the importance of the evaluation of ADCs’ performance throughout the implementation process and the hospital’s team involvement in automation supervision and management.

Keywords: life-critical systems, situation awareness, automated delivery cabinets, implementation, risks and malfunctions

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Authors: H. Aksas, S. Boughrara, K. Louhab

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The goal of this study was the use of life cycle assessment (LCA) methodology to assess the environmental impact of pharmaceutical product (four kinds of syrup form and tree kinds of pomade form), which are produced in one leader manufactory in Algeria town that is SAIDAL Company. The impacts generated have evaluated using SimpaPro7.1 with CML92 Method for syrup form and EPD 2007 for pomade form. All impacts evaluated have compared between them, with determination of the compound contributing to each impacts in each case. Data needed to conduct Life Cycle Inventory (LCI) came from this factory, by the collection of theoretical data near the responsible technicians and engineers of the company, the practical data are resulting from the assay of pharmaceutical liquid, obtained at the laboratories of the university. This data represent different raw material imported from European and Asian country necessarily to formulate the drug. Energy used is coming from Algerian resource for the input. Outputs are the result of effluent analysis of this factory with different form (liquid, solid and gas form). All this data (input and output) represent the ecobalance.

Keywords: pharmaceutical product, drug residues, LCA methodology, environmental impacts

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Authors: Mewa Singh

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Nanomedicine, a fusion of nanotechnology and medicine, is an emerging technology ideally suited to the targeted therapies. Nanoparticles overcome the low selectivity of anti-cancer drugs toward the tumor as compared to normal tissue and hence result-in less severe side-effects. Our new technology, HYBRID-NANOENGINEERING™, uses a new molecule (MR007) in the creation of nanoparticles that not only helps in nanonizing the medicine but also provides synergy to the medicine. The simplified manufacturing process will result in reduced manufacturing costs. Treatment is made more convenient because hybrid nanomedicines can be produced in oral, injectable or transdermal formulations. The manufacturing process uses no protein, oil or detergents. The particle size is below 180 nm with a narrow distribution of size. Importantly, these properties confer great stability of the structure. The formulation does not aggregate in plasma and is stable over a wide range of pH. The final hybrid formulation is stable for at least 18 months as a powder. More than 97 drugs, including paclitaxel, docetaxel, tamoxifen, doxorubicinm prednisone, and artemisinin have been nanonized in water soluble formulations. Preclinical studies on cell cultures of tumors show promising results. Our HYBRID-NANOENGINEERING™ platform enables the design and development of hybrid nano-pharmaceuticals that combine efficacy with tolerability, giving patients hope for both extended overall survival and improved quality of life. This study would discuss or present this new discovery of HYBRID-NANOENGINEERING™ which targets drug delivery, synergistic, and potentiating effects, and barriers of drug delivery and advanced drug delivery systems.

Keywords: nano-medicine, nano-particles, drug delivery system, pharmaceuticals

Procedia PDF Downloads 484

Authors: Daria Zabolotnaya, Svetlana Degtyareva, Veronika Kanestri, Danila Konnov

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An adequate choice of the initial antiretroviral treatment determines the treatment efficacy. In the clinical guidelines in Russia non-nucleoside reverse transcriptase inhibitors (NNRTIs) are still considered to be an option for first-line treatment while pretreatment drug resistance (PDR) testing is not routinely performed. We conducted a cohort retrospective study in HIV-positive treatment naïve patients of the H-clinic (Moscow, Russia) who performed PDR testing from July 2017 to November 2021. All the information was obtained from the medical records anonymously. We analyzed the mutations in reverse transcriptase and protease genes. RT-sequences were obtained by AmpliSens HIV-Resist-Seq kit. Drug resistance was defined using the HIVdb Program v. 8.9-1. PDR was estimated using the Stanford algorithm. Descriptive statistics were performed in Excel (Microsoft Office, 2019). A total of 261 HIV-1 infected patients were enrolled in the study including 197 (75.5%) male and 64 (24.5%) female. The mean age was 34.6±8.3 years. The median CD4 count – 521 cells/µl (IQR 367-687 cells/µl). Data on risk factors of HIV-infection were scarce. The total quantity of strains containing mutations in the reverse transcriptase gene was 75 (28.7%). From these 5 (1.9%) mutations were associated with PDR to nucleoside reverse transcriptase inhibitors (NRTIs) and 30 (11.5%) – with PDR to NNRTIs. The number of strains with mutations in protease gene was 43 (16.5%), from these only 3 (1.1%) mutations were associated with resistance to protease inhibitors. For NNRTIs the most prevalent PDR mutations were E138A, V106I. Most of the HIV variants exhibited a single PDR mutation, 2 were found in 3 samples. Most of HIV variants with PDR mutation displayed a single drug class resistance mutation. 2/37 (5.4%) strains had both NRTIs and NNRTIs mutations. There were no strains identified with PDR mutations to all three drug classes. Though earlier data demonstrated a lower level of PDR in HIV treatment naïve population in Russia and our cohort can be not fully representative as it is taken from the private clinic, it reflects the trend of increasing PDR especially to NNRTIs. Therefore, we consider either pretreatment testing or giving the priority to other drugs as first-line treatment necessary.

Keywords: HIV, resistance, mutations, treatment

Procedia PDF Downloads 91

Authors: Jianuo Sun, Jinghan Wang, Sirui Zhang, Chenhan Xu, Hongxia Hao, Hong Zhou

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In recent years, the diversification and industrialization of drug-related crimes have posed significant threats to public health and safety globally. The widespread and increasingly younger demographics of drug users and the persistence of drug-impaired driving incidents underscore the urgency of this issue. Drug detection, a specialized forensic activity, is pivotal in identifying and analyzing substances involved in drug crimes. It relies on pharmacological and chemical knowledge and employs analytical chemistry and modern detection techniques. However, current drug detection methods are limited by their inability to perform semi-quantitative, real-time field analyses. They require extensive, complex laboratory-based preprocessing, expensive equipment, and specialized personnel and are hindered by long processing times. This study introduces an alternative approach using nucleic acid aptamers and Aggregation-Induced Emission (AIE) technology. Nucleic acid aptamers, selected artificially for their specific binding to target molecules and stable spatial structures, represent a new generation of biosensors following antibodies. Rapid advancements in AIE technology, particularly in tetraphenyl ethene-based luminous, offer simplicity in synthesis and versatility in modifications, making them ideal for fluorescence analysis. This work successfully synthesized, isolated, and purified an AIE molecule and constructed a probe comprising the AIE molecule, nucleic acid aptamers, and exonuclease for cocaine detection. The probe demonstrated significant relative fluorescence intensity changes and selectivity towards cocaine over other drugs. Using 4-Butoxytriethylammonium Bromide Tetraphenylethene (TPE-TTA) as the fluorescent probe, the aptamer as the recognition unit, and Exo I as an auxiliary, the system achieved rapid detection of cocaine within 5 mins in aqueous and urine, with detection limits of 1.0 and 5.0 µmol/L respectively. The probe-maintained stability and interference resistance in urine, enabling quantitative cocaine detection within a certain concentration range. This fluorescent sensor significantly reduces sample preprocessing time, offers a basis for rapid onsite cocaine detection, and promises potential for miniaturized testing setups.

Keywords: drug detection, aggregation-induced emission (AIE), nucleic acid aptamer, exonuclease, cocaine

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Authors: Mohamed I. D. Helal, Mohamed M. El-Mogy, Hassan A. Khater, Muhammad A. Fathy, Fatma E. Ibrahim, Yuncong C. Li, Zhaohui Tong, Karima F. Abdelgawad

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Minimizing the consumption of agrochemicals, particularly nitrogen, is the ultimate goal for achieving sustainable agricultural production with low cost and high economic and environmental returns. The use of biopolymers instead of petroleum-based synthetic polymers for CRFs can significantly improve the sustainability of crop production since biopolymers are biodegradable and not harmful to soil quality. Lignin is one of the most abundant biopolymers that naturally exist. In this study, controlled-release fertilizers were developed using a biobased nanocomposite of lignin and bentonite clay mineral as a coating material for urea to increase nitrogen use efficiency. Five types of controlled-release urea (CRU) were prepared using two ratios of modified bentonite as well as techniques. The efficiency of the five controlled-release nano-urea (CRU) fertilizers in improving the growth of tomato plants was studied under field conditions. The CRU was applied to the tomato plants at three N levels representing 100, 50, and 25% of the recommended dose of conventional urea. The results showed that all CRU treatments at the three N levels significantly enhanced plant growth parameters, including plant height, number of leaves, fresh weight, and dry weight, compared to the control. Additionally, most CRU fertilizers increased total yield and fruit characteristics (weight, length, and diameter) compared to the control. Additionally, marketable yield was improved by CRU fertilizers. Fruit firmness and acidity of CRU treatments at 25 and 50% N levels were much higher than both the 100% CRU treatment and the control. The vitamin C values of all CRU treatments were lower than the control. Nitrogen uptake efficiencies (NUpE) of CRU treatments were 47–88%, which is significantly higher than that of the control (33%). In conclusion, all CRU treatments at an N level of 25% of the recommended dose showed better plant growth, yield, and fruit quality of tomatoes than the conventional fertilizer.

Keywords: nitrogen use efficiency, quality, urea, nano particles, ecofriendly

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Authors: Vatsal M. Patel, Navin B. Patel

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The present studies deal with the developing a series bearing a diphenyl ethers nucleus using structure-based drug design concept. A newer series of diphenyl ether based azetidinone namely N-(3-chloro-2-oxo-4-(3-phenoxyphenyl)azetidin-1-yl)-2-(substituted amino)acetamide (2a-j) have been synthesized by condensation of m-phenoxybenzaldehyde with 2-(substituted-phenylamino)acetohydrazide followed by the cyclisation of resulting Schiff base (1a-j) by conventional method as well as microwave heating approach as a part of an environmentally benign synthetic protocol. All the synthesized compounds were characterized by spectral analysis and were screened for in vitro antimicrobial, antitubercular and antiprotozoal activity. The compound 2f was found to be most active M. tuberculosis (6.25 µM) MIC value in the primary screening as well as this same derivative has been found potency against L. mexicana and T. cruzi with MIC value 2.09 and 6.69 µM comparable to the reference drug Miltefosina and Nifurtimox. To provide understandable evidence to predict binding mode and approximate binding energy of a compound to a target in the terms of ligand-protein interaction, all synthesized compounds were docked against an enoyl-[acyl-carrier-protein] reductase of M. tuberculosis (PDB ID: 4u0j). The computational studies revealed that azetidinone derivatives have a high affinity for the active site of enzyme which provides a strong platform for new structure-based design efforts. The Lipinski’s parameters showed good drug-like properties and can be developed as an oral drug candidate.

Keywords: antimycobacterial, antiprotozoal, azetidinone, diphenylether, docking, microwave

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Authors: Maki Mizogami, Hironori Tsuchiya, Yoshiroh Hayabuchi, Kenji Shigemi

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Since drugs exhibit significant structure-dependent differences in activity and toxicity, their differentiation based on the mechanism of action should have implications for comparative drug efficacy and safety. We aimed to differentiate drug stereoisomers by their stereostructure-selective membrane interactions underlying pharmacological and toxicological effects. Biomimetic lipid bilayer membranes were prepared with phospholipids and sterols (either cholesterol or epicholesterol) to mimic the lipid compositions of neuronal and cardiomyocyte membranes and to provide these membranes with the chirality. The membrane preparations were treated with different classes of stereoisomers at clinically- and pharmacologically-relevant concentrations (25-200 μM), followed by measuring fluorescence polarization to determine the membrane interactivity of drugs to change the physicochemical property of membranes. All the tested drugs acted on lipid bilayers to increase or decrease the membrane fluidity. Drug stereoisomers could not be differentiated when interacting with the membranes consisting of phospholipids alone. However, they stereostructure-selectively interacted with neuro-mimetic and cardio-mimetic membranes containing 40 mol% cholesterol ((3β)-cholest-5-en-3-ol) to show the relative potencies being local anesthetic R(+)-bupivacaine > rac-bupivacaine > S(‒)-bupivacaine, α2-adrenergic agonistic D-medetomidine > rac-medetomidine > L-medetomidine, β-adrenergic antagonistic R(+)-propranolol > rac-propranolol > S(–)-propranolol, NMDA receptor antagonistic S(+)-ketamine > rac-ketamine, analgesic monoterpenoid (+)-menthol > (‒)-menthol, non-steroidal anti-inflammatory S(+)-ibuprofen > rac-ibuprofen > R(‒)-ibuprofen, and bioactive flavonoid (+)-epicatechin > (‒)-epicatechin. All of the order of membrane interactivity were correlated to those of beneficial and adverse effects of the tested stereoisomers. In contrast, the membranes prepared with epicholesterol ((3α)-chotest-5-en-3-ol), an epimeric form of cholesterol, reversed the rank order of membrane interactivity to be S(‒)-enantiomeric > racemic > R(+)-enantiomeric bupivacaine, L-enantiomeric > racemic > D-enantiomeric medetomidine, S(–)-enantiomeric > racemic > R(+)-enantiomeric propranolol, racemic > S(+)-enantiomeric ketamine, (‒)-enantiomeric > (+)-enantiomeric menthol, R(‒)-enantiomeric > racemic > S(+)-enantiomeric ibuprofen, and (‒)-enantiomeric > (+)-enantiomeric epicatechin. The opposite configuration allows drug molecules to interact with chiral sterol membranes enantiomer-selectively. From the comparative results, it is speculated that a 3β-hydroxyl group in cholesterol is responsible for the enantioselective interactions of drugs. In conclusion, the differentiation of drug stereoisomers by their stereostructure-selective membrane interactions would be useful for designing and predicting drugs with higher activity and/or lower toxicity.

Keywords: chiral membrane, differentiation, drug stereoisomer, enantioselective membrane interaction

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Authors: Mohamed A. Etman, Mona G. Abd-Elnasser, Mohamed A. Shams-Eldin, Aly H. Nada

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Orally disintegrating tablets (ODTs) are gaining importance as new drug delivery systems and emerged as one of the popular and widely accepted dosage forms, especially for the pediatric and geriatric patients. Their advantages such as administration without water, anywhere, anytime lead to their suitability to geriatric and pediatric patients. They are also suitable for the mentally ill, the bed-ridden and patients who do not have easy access to water. The benefits, in terms of patient compliance, rapid onset of action, increased bioavailability, and good stability make these tablets popular as a dosage form of choice in the current market. These dosage forms dissolve or disintegrate in the oral cavity within a matter of seconds without the need of water or chewing. Desloratadine is a tricyclic antihistaminic, which has a selective and peripheral H1-antagonist action. It is an antagonist at histamine H1 receptors, and an antagonist at all subtypes of the muscarinic acetylcholine receptor. Desloratadine is the major metabolite of loratadine. Twelve different placebos ODT were prepared (F1-F12) using different functional excipients. They were evaluated for their compressibility, hardness and disintegration time. All formulations were non sticky except four formulations; namely (F8, F9, F10, F11). All formulations were compressible with the exception of (F2). Variable disintegration times were found ranging between 20 and 120 seconds. It was found that (F12) showed the least disintegration time (20 secs) without showing any sticking which could be due to the use of high percentage of superdisintegrants. Desloratadine showed bitter taste when formulated as ODT without any treatment. Therefore, different techniques were tried in order to mask its bitter taste. Using Eudragit EPO resulted in complete masking of the bitter taste of the drug and increased the acceptability to volunteers. The compressible non sticky formulations (F1, F3, F4, F5, F6, F7 and F12) were subjected to further evaluation tests after addition of coated desloratadine, including weight uniformity, wetting time, and friability testing.. Fairly good weight uniformity values were observed in all the tested formulations. F12 exhibiting the shortest wetting time (14.7 seconds) and consequently the lowest (20 seconds) disintegration time. Dissolution profile showed that 100% desloratadine release was attained after only 2.5 minutes from the prepared ODT (F12) with dissolution efficiency of 95%.

Keywords: Desloratadine, orally disintegrating tablets (ODTs), formulations, taste masking

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Authors: Bharti Jain, Rajeev Jain, Abuzar Kabir, Torki Zughaibi, Shweta Sharma

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Drug-facilitated crimes (DFCs) entail the use of a single drug or a mixture of drugs to render a victim unable. Traditionally, biological samples have been gathered from victims and conducted analysis to establish evidence of drug administration. Nevertheless, the rapid metabolism of various drugs and delays in analysis can impede the identification of such substances. For this, the present article describes a rapid, sustainable, highly efficient and miniaturized protocol for the identification and quantification of three sedative-hypnotic drugs, namely diazepam, chlordiazepoxide and ketamine in alcoholic beverages and complex food samples (cream of biscuit, flavored milk, juice, cake, tea, sweets and chocolate). The methodology involves utilizing fabric phase sorptive extraction (FPSE) to extract diazepam (DZ), chlordiazepoxide (CDP), and ketamine (KET). Subsequently, the extracted samples are subjected to analysis using gas chromatography-mass spectrometry (GC-MS). Several parameters, including the type of membrane, pH, agitation time and speed, ionic strength, sample volume, elution volume and time, and type of elution solvent, were screened and thoroughly optimized. Sol-gel Carbowax 20M (CW-20M) has demonstrated the most effective extraction efficiency for the target analytes among all evaluated membranes. Under optimal conditions, the method displayed linearity within the range of 0.3–10 µg mL–¹ (or µg g–¹), exhibiting a coefficient of determination (R2) ranging from 0.996–0.999. The limits of detection (LODs) and limits of quantification (LOQs) for liquid samples range between 0.020-0.069 µg mL-¹ and 0.066-0.22 µg mL-¹, respectively. Correspondingly, the LODs for solid samples ranged from 0.056-0.090 µg g-¹, while the LOQs ranged from 0.18-0.29 µg g-¹. Notably, the method showcased better precision, with repeatability and reproducibility both below 5% and 10%, respectively. Furthermore, the FPSE-GC-MS method proved effective in determining diazepam (DZ) in forensic food samples connected to drug-facilitated crimes (DFCs). Additionally, the proposed method underwent evaluation for its whiteness using the RGB12 algorithm.

Keywords: drug facilitated crime, fabric phase sorptive extraction, food forensics, white analytical chemistry

Procedia PDF Downloads 65