Search results for: drug promiscuity

Authors: Suzanne Ahmed

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Nanomotors, also commonly referred to as nanorobotics or nanomachines, have garnered considerable research attention due to their numerous potential applications in biomedicine, including drug delivery and microsurgery. Nanomotors typically consist of inorganic or polymeric particles that are powered to undergo motion. These artificial, man-made nanoscale motors operate in the low Reynolds number regime and typically have no moving parts. Several methods have been developed to actuate the motion of nanomotors including magnetic fields, electrical fields, electromagnetic waves, and chemical fuel. Since their introduction in 2012, ultrasonically powered nanomotors have been explored in biocompatible fluids and even within living cells. Due to the common use of ultrasound within the biomedical community for both imaging and therapeutics, the introduction of ultrasonically propelled nanomotors holds significant potential for biomedical applications. In this work, metallic nanomotors are electrochemically plated within porous anodic alumina templates to have a diameter of 300 nm and a length that is 2-4 µm. Nanomotors are placed within an acoustic chamber capable of producing bulk acoustic waves in the ultrasonic range. The motion of nanomotors within biomimetic confines is explored. The control over nanomotor motion is exerted by virtue of the properties of the acoustic signal within these biomimetic confines to control speed, modes of motion and directionality of motion. To expand the range of control over nanorod motion within biomimetic confines, external forces from biocompatible magnetic fields, are exerted onto the acoustically propelled nanomotors.

Keywords: nanomotors, nanomachines, nanorobots, ultrasound

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Authors: Madhavi S. Apte, Milind Bhitre

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In pharmaceutical research and new drug development, medicinal plants have important roles. Similarly, Indian dhak tree belonging to family Fabaceae has been widely used in the traditional Indian medical system of ‘Ayurveda’ for the treatment of a variety of ailments. Hence the cell viability study was undertaken to evaluate and compare the activity of extracts of various parts like flower, bark, leaf, seed by conducting MTT assay method along with other pharmacognostical studies. The methanolic extracts of bark, flowers, leaves, and seeds were used for the study. The cell viability MTT assay was performed using the standard operating procedures. The extracts were dissolved in DMSO and serially diluted with complete medium to get the concentrations range of test concentration. DMSO concentration was kept < 0.1% in all the samples. HUVEC cells maintained in appropriate conditions were seeded in 96 well plates and treated with different concentrations of the test samples and incubated at 37°C, 5% CO₂ for 96 hours. MTT reagent was added to the wells and incubated for 4 hours; the dark blue formazan product formed by the cells was dissolved in DMSO under a safety cabinet and read at 550nm. Percentage inhibitions were calculated and plotted with the concentrations used to calculate the IC50 values. The bark, flower, leaves and seed extracts have shown the cytotoxicity activity and can be further studied for antiangiogenesis activity.

Keywords: pharmacognosy, Cell viability, MTT assay, anti-angiogenesis

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Authors: Shradha S. Binani, P. S. Bodke, R. V. Joat

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Recent decades have witnessed an exponential growth in the field of acoustical parameters and ultrasound on solid, liquid and gases. Ultrasonic propagation parameters yield valuable information regarding the behavior of liquid systems because intra and intermolecular association, dipolar interaction, complex formation and related structural changes affecting the compressibility of the system which in turn produces variations in the ultrasonic velocity. The acoustic and thermo dynamical parameters obtained in ultrasonic study show that ion-solvation is accompanied by the destruction or enhancement of the solvent structure. In the present paper the ultrasonic velocity (v), density (ρ), viscosity(η) have been measured for the pharmacological important compound 2-hydroxy substituted phenyl pyrimidine derivative (2-hydroxy-4-(4’-methoxy phenyl)-6-(2’-hydroxy-4’-methyl-5’-chlorophenyl)pyrimidine) in ethanol as a solvent by using different concentration at constant room temperature. These experimental data have been used to estimate physical parameter like adiabatic compressibility, intermolecular free length, relaxation time, free volume, specific acoustic impedance, relative association, Wada’s constant, Rao’s constant etc. The above parameters provide information in understanding the structural and molecular interaction between solute-solvent in the drug solution with respect to change in concentration.

Keywords: acoustical parameters, ultrasonic velocity, density, viscosity, 2-hydroxy substituted phenyl pyrimidine derivative

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Authors: Wan Azuati Wan Omar, Selva Rani John Jasudass, Siti Rohaiza Md. Saad

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Introduction & objective: The objectives of this study were to assess patient’s knowledge of appropriate sublingual glyceryl trinitrate (GTN) use as well as to investigate how patients commonly store and carry their sublingual GTN tablets. Methodology: This was a cross-sectional survey, using a validated researcher-administered questionnaire. The study involved cardiac patients receiving sublingual GTN attending the outpatient and inpatient departments of Taiping Hospital, a non-academic public care hospital. The minimum calculated sample size was 92, but 100 patients were conveniently sampled. Respondents were interviewed on 3 areas, including demographic data, knowledge and use of sublingual GTN. Eight items were used to calculate each subject’s knowledge score and six items were used to calculate use score. Results: Of the 96 patients who consented to participate, majority (96.9%) were well aware of the indication of sublingual GTN. With regards to the mechanism of action of sublingual GTN, 73 (76%) patients did not know how the medication works. Majority of the patients (66.7%) knew about the proper storage of the tablet. In relation to the maximum number of sublingual GTN tablets that can be taken during each angina episode, 36.5% did not know that up to 3 tablets of sublingual GTN can be taken during each episode of angina. Fifty four (56.2%) patients were not aware that they need to replace sublingual GTN every 8 weeks after receiving the tablets. Majority (69.8%) of the patients demonstrated lack of knowledge with regards to the use of sublingual GTN as prevention of chest pain. Conclusion: Overall, patients’ knowledge regarding the self administration of sublingual GTN is still inadequate. The findings support the need for more frequent reinforcement of patient education, especially in the areas of preventive use, storage and drug stability.

Keywords: glyceryl trinitrate, knowledge, adherence, patient education

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Authors: Soham Das

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Oedipus in Oedipus Rex is necessarily a victim of fate and his own psychology. His curiosity brings about his downfall. Ancient Greek plays weren't just portrayals of some obscure tale but were insights into human nature. Oedipus, although a victim of circumstances, digs his own grave by curiously unravelling his past. Jocasta foresees his doom and begs him to stop, but to no avail. The curiosity of Oedipus forces him, almost like a drug, to explore the mystery regarding his birth. This curiosity is not something extraordinary in Oedipus - it is an intrinsic attribute of human nature. Knowledge is not always desired - whether it is Adam or Oedipus, their curiosity caused their eventual downfall. Oedipus was ill-fated since birth. He did not know that Laius was his biological father and therefore killed him. He arrived at Thebes, solved the riddle of the Sphinx, and married Jocasta without knowing that she, in fact, was his biological mother. He begot children and was living happily with his family when a sudden calamity struck Thebes. The calamity, though at first seemed public in nature, but later proved to be very personal for Oedipus. It drives home the fundamental truth about uncertainty of human life. That Laius was slayed by his own son, even after many precautions, proves the helplessness of humans in front of the designs of fate. Oedipus's mutilation of his eyes is also fated. It was committed by him in the heat of the moment and was certainly not a rational decision. It is evident to any modern reader that Oedipus does not have justice. Destiny treats him unfairly. Oedipus, in fact, defends his actions in Oedipus Rex in its sequel Oedipus At Colonus. The research paper discusses the unhappy fate of Oedipus and the role of destiny and his own curiosity in achieving it.

Keywords: ancient Greek drama, Oedipus Rex, Sophocles, destiny

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Authors: N. Dlamini, Mpumelelo G. Ndlela, Philisiwe Dlamini, Nicholus Kisyeri, Bhekizitha Sithole

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Accessing health services during the COVID-19 pandemic have exacerbated scarcity to routine medication. To ensure continuous accessibility to services, Eswatini launched Community Health Commodities Distribution (CHCD). Eligible Antiretroviral Therapy(ART) stable clients (VL<1,000) and patients on Non-Communicable Disease (NCD) medications were attended at community pick up points (PUP) based on distance between clients’ residence and the public health facility. Services provided includes ART and Pre-Exposure prophylaxis (PrEP) refills and NCD drug refills). The number of community PUP was 14% higher than health facility visits. Among all medications and commodities distributed between April and October 2020 at the PUP, 64% were HIV-related (HIV rapid test, HIVST, VL test, PrEP meds), and 36% were NCD related. The rapid roll out of CHCD during COVID-19 pandemic reduced the risk of COVID-19 transmission to clients as travel to health facilities was eliminated. It Additionally increased access to commodities during COVID-19-driven lockdown, decongested health facilities, integrated model of care, and increase service coverage. It was also noted that CHCD added different curative and HIV related services based on client specific needs and availability of the commodities.

Keywords: community health commodities distribution, pick up points, antiretroviral therapy, pre-exposure prophylaxis

Procedia PDF Downloads 134

Authors: Mae Genevieve G. Cheung, Michael G. Cuevas, Lovely Fe L. Cuison, Elijin P. Dai, Katrina Marie S. Duron, Azalea Damaris E. Encarnacion, May T. Magtoto, Gina C. Castro

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The present study aims to evaluate the effectiveness of aqueous and ethanolic leaf extracts of Blumea balsamifera in reducing obesity on diet-induced obese Sprague-Dawley rats. Aqueous and ethanolic leaf extracts were obtained by maceration and percolation, respectively, of air-dried, grinded leaves. The test animals were given a high fat diet (HFD) for 21 days, except for one negative control group fed with a standard diet (SD). The Blumea balsamifera extracts were given at doses of 300 mg/Kg and 600 mg/Kg for BBAE and BBEE groups, and the positive control group, Orlistat, was given at 21.6 mg/Kg dose. After 24 days of treatment, the statistical difference of parameters such as Lee’s index and lipid profile of each group before and after the treatment period were determined separately using Tukey’s test of two-way Analysis of Variance (ANOVA). The statistical results showed that the600mg/kg dose of BBAE and BBEE had greatly lowered the Lee’s index among the other doses while the 300 mg/Kg dose BBEE, 600 mg/Kg BBAE, and 300 mg/kg BBAE lowered the total cholesterol level, LDL level, and VLDL and total triglyceride level respectively. The extracts, however, lowered the HDL level which was also exhibited by the standard drug, Orlistat.

Keywords: adipocytes, adipogenesis, Blumea balsamifera, Lee’s index, obesity, Sambong

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Authors: Lu Yang, Keng Po Lai

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Metformin, a well-known clinical drug against diabetes, is found with potential anti-diabetic and anti-obese benefits, as reported in increasing evidences. However, the current clinical and experimental investigations are not to reveal the detailed mechanisms of metformin-anti-obesity/hypertension. We have used the bioinformatics strategy, including network pharmacology and molecular docking methodology, to uncover the key targets and pathways of bioactive compounds against clinical disorders, such as cancers, coronavirus disease. Thus, in this report, the in-silico approach was utilized to identify the hug targets, pharmacological function, and mechanism of metformin against obesity and hypertension. The networking analysis identified 154 differentially expressed genes of obesity and hypertension, 21 interaction genes, and 6 hug genes of metformin treating hypertensive obesity. As a result, the molecular docking findings indicated the potent binding capability of metformin with the key proteins, including interleukin 6 (IL-6) and chemokine (C-C motif) Ligand 2 (CCL2), in hypertensive obesity. The metformin-exerted anti-hypertensive obesity action involved in metabolic regulation, inflammatory reaction. And the anti-hypertensive obesity mechanisms of metformin were revealed, including regulation of inflammatory and immunological signaling pathways for metabolic homeostasis in tissue and microenvironmental melioration in blood pressure. In conclusion, our identified findings with bioinformatics analysis have demonstrated the detailed hug and pharmacological targets, biological functions, and signaling pathways of metformin treating hypertensive obesity.

Keywords: metformin, obesity, hypertension, bioinformatics findings

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Authors: Z. S. Haidar

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Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease, or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture, or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL); alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise, and risk of immune reactions. For cases of dry socket, specifically, the commercially available and often-prescribed home remedies are highly-lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Herein, SockGEL/PLUG (patent pending), an innovative, all-natural, drug-free, and injectable thermo-responsive hydrogel, was designed, formulated, characterized, and evaluated as an osteogenic, angiogenic, anti-microbial, and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in fresh extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (1) prevent the on-set of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (2) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physical-chemical-mechanically for safety (cell viability), viscosity, rheology, bio-distribution, and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The proposed animal model of cranial critical-sized and non-vascularized bone defects shall provide new and critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease, and speed in producing stable, biodegradable, and sterilizable thermo-sensitive matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for the intra-socket application. Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the innovation before engaging the market for feasibility, acceptance, and cost-effectiveness studies.

Keywords: hydrogel, nanotechnology, bioengineering, bone regeneration, nanogel, drug delivery

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Authors: Konesh Navsaria, Itumeleng Ramodumo

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The study explored university students’ perceptions of cannabis use on academic life at a higher education institution (HEI) in Nelson Mandela Bay, South Africa. Cannabis is described as the most commonly-used drug by youth, especially those who are in tertiary institutions. The use of cannabis has both negative and positive effects; this is evident in different areas of human functioning. Cannabis usage has been debated upon in courts regarding its legalization and decriminalization, and on the 18th of September 2018, the South African High Court decriminalized cannabis for personal use. Cannabis use has increased in academic settings, and this has raised concerns about how it affects the mental health of students. A qualitative approach was used for the study with an explorative, descriptive design. Purposive sampling was used to select 15 participants for the study. Data were collected using focused-group interviews, following ethical clearance from the HEI. The collected data were analyzed and interpreted using thematic analysis, and cognitive behavioural theory was used as the theoretical framework. The research findings indicated both positive and negative influences of cannabis use on mental health. Most participants who expressed positive effects have used cannabis before, whereas most participants with negative perspectives of cannabis use on mental health are non-cannabis users. The findings revealed that participants perceived that the quantity of cannabis smoked determined whether there was a positive or negative effect on mental health; that is, large doses of cannabis were perceived as having negative effects. The research findings also revealed that the legalization of cannabis is very likely to increase its use and also highlighted precautionary measures users take to avoid the substance’s negative effects on mental health.

Keywords: cannabis use, mental health, university students, legalization

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Authors: Ghazal Zahed, Leila Tabatabaee, Amirhossein Hosseini, Somaye Fatahi

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Functional retentive overflow incontinence (Retentive FI) is the most common cause of fecal soiling in children. Affected patients may have more problems with their parents and peer group, self-esteem issues, and more psychiatric comorbidities than the general population. Therapeutic interventions for Retentive FI and related problems and comorbid conditions are needed at the same time. Based on the clinical experiences, patients with retentive FI and comorbid psychiatric disorders, were accelerated in their treatment of fecal incontinence when they were being treated with Risperidone for their psychiatric comorbidities, therefore this study was conducted to evaluate the effect of Risperidone in the treatment of Retentive FI in children and adolescents. In this double-blind randomized clinical trial, 136 patients aged 4-18 years eligible for the study were randomly divided into two groups receiving Risperidone and placebo. About half of these patients had newly diagnosed psychiatric disorders and were drug naïve, this was considered in their division. In addition to polyethylene glycol, all the participants received family counseling and education for withholding behaviors and related behavioral interventions, and nonpharmacological interventions for psychiatric comorbidities. A significant correlation was observed between the duration of treatment with risperidone and the presence of psychiatric comorbidities (P <0.001) for diurnal fecal incontinence. Based on our findings in this study, Risperidone, used commonly for psychiatric disorders in children and adolescents, may be useful in the treatment of retentive fecal incontinence in the presence of psychiatric comorbidities, and along with other interventions.

Keywords: Retentive Fecal Incontinence, Risperidone, Treatment, Pediatric, Encopresis, Atypical Antipsychotics, Fecal Soiling

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Authors: Zakia Belhadj, Bing He, Hua Zhang, Xueqing Wang, Wenbing Dai, Qiang Zhang

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Mononuclear phagocyte system (MPS) forms an abominable obstacle hampering the tumor delivery efficiency of nanoparticles. Passively targeted nanocarriers have received clinical approval over the past 20 years. However, none of the actively targeted nanocarriers have entered clinical trials. Thus it is important to endue effective targeting ability to actively targeted approaches by overcoming biological barriers to nanoparticle drug delivery. Here, it presents that an Esomeprazole-based preconditioning strategy for regulating nanocarrier-MPS interaction to substantially prolong circulation time and enhance tumor targeting of nanoparticles. In vitro, the clinically approved proton pump inhibitor Esomeprazole “ESO” was demonstrated to reduce interactions between macrophages and subsequently injected targeted vesicles by interfering with their lysosomal trafficking. Of note, in vivo studies demonstrated that ESO pretreatment greatly decreased the liver and spleen uptake of c(RGDm7)-modified vesicles, highly enhanced their tumor accumulation, thereby provided superior therapeutic efficacy of c(RGDm7)-modified vesicles co-loaded with Doxorubicin (DOX) and Gefitinib (GE). This MPS-preconditioning strategy using ESO provides deeper insights into regulating nanoparticles interaction with the phagocytic system and enhancing their cancer cells' accessibility for anticancer therapy.

Keywords: esomeprazole (ESO), mononuclear phagocyte system (MPS), preconditioning strategy, targeted lipid vesicles

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Authors: Marwa T. Badawy, Alaa F. Bakr, Nesrine Hegazi, Mohamed A. Farag, Ahmed Abdellatif

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Diabetes Mellitus (DM) is a chronic disease affecting a large population worldwide. Africa is rich in native medicinal plants with myriad health benefits, though less explored towards the development of specific drug therapy as in diabetes. This study aims to determine the in vivo antidiabetic potential of the well-reported and traditionally used fruits of Baobab (Adansonia digitata L.) using STZ induced diabetic model. The in-vitro cytotoxic and antioxidant properties were examined using MTT assay on L-929 fibroblast cells and DPPH antioxidant assays, respectively. The extract showed minimal cytotoxicity with an IC50 value of 105.7 µg/mL. Histopathological and immunohistochemical investigations showed the hepatoprotective and the renoprotective effects of A. digitata fruits’ extract, implying its protective effects against diabetes complications. These findings were further supported by biochemical assays, which showed that i.p., injection of a low dose (150 mg/kg) of A. digitata twice a week lowered the fasting blood glucose levels, lipid profile, hepatic and renal markers. For a comprehensive overview of extract metabolites composition, ultrahigh performance (UHPLC) analysis coupled to high-resolution tandem mass spectrometry (HRMS/MS) in synchronization with molecular networks led to the annotation of 77 metabolites, among which 50% are reported for the first time in A. digitata fruits.

Keywords: adansonia digital, diabetes mellitus, metabolomics, streptozotocin, Sprague, dawley rats

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Authors: Funmilola O. Omoya, Abdul O. Momoh

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Malaria constitutes one of the major health problems in Nigeria. One of the reasons attributed for the upsurge was the development of resistance of Plasmodium falciparum and the emergence of multi-resistant strains of the parasite to anti-malaria drugs. A continued search for other effective, safe and cheap plant-based anti-malaria agents thus becomes imperative in the face of these difficulties. The objective of this study is therefore to evaluate the in vivo anti-malarial efficacy of ethanolic extracts of Chromolaena odorata and Androgaphis paniculata leaves. The two plants were evaluated for their anti-malaria efficacy in vivo in a 4-day curative test assay against Plasmodium berghei strain in mice. The group treated with 500mg/ml dose of ethanolic extract of A. paniculata plant showed parasite suppression with increase in Packed Cell Volume (PCV) value except day 3 which showed a slight decrease in PCV value. During the 4-day curative test, an increase in the PCV values, weight measurement and zero count of Plasmodium berghei parasite values was recorded after day 3 of drug administration. These results obtained in group treated with A. paniculata extract showed anti-malarial efficacy with higher mortality rate in parasitaemia count when compared with Chromolaena odorata group. These results justify the use of ethanolic extracts of A. paniculata plant as medicinal herb used in folklore medicine in the treatment of malaria.

Keywords: anti-malaria, curative, plant-based anti-malaria agents, biology

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Authors: Nouf Al Harthi

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Venous thromboembolism (VTE) is one of the most common causes of hospital-related deaths in critically ill patients. Guidelines recommended VTE prophylaxis with standardized, fixed doses for most patients. The underweight population has limited data to guide the appropriate drug and dosing regimen. The aim of this study was to describe the pattern of VTE prophylaxis dose regimens for underweighted critically ill adult patients and the prevalence of associated VTE and bleeding. This study is a retrospective cohort study, conducted in King Abdulaziz Medical City, Saudi Arabia. It included all critical patients admitted to the intensive care units and were above 14 years old with weight less than 50 kg or BMI of 18.5 kg/m2 or less and were on heparin as VTE prophylaxis for more than 72 hours from January 2016 until January 2020. After screening 270 patients, only 40 patients were included in this study according to our inclusion and exclusion criteria. Only 6 patients (15%) received VTE prophylaxis as an adjusted dose of heparin 2500 U Q12, while the rest of the patients were taking standard dosing of heparin, 5000 U Q12 was given to 21 (52.50%) patients and 5000 U Q8 was given to 13 (32.50%) patients. None of the adjusted doses developed any complications such as VTE or bleeding. There was no significant difference compared with the standard dose group. This study focused on describing the pattern of heparin doses as VTE prophylaxis in underweight patients. We also compared the standard dosing and adjusted dosage of VTE prophylaxis on underweight patients and any complications. There was no significant difference in the complication’s outcome or benefits between the two groups.

Keywords: venous thromboembolism prophylaxis, heparin, underweight patients, adult, critical care units

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Authors: Ogunniran Kehinde Olurotimi, Adekoya Joseph, Ehi-Eromosele Cyril, Mehdi Shihab, Mesubi Adediran, Tadigoppula Narender

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Nicotinic acid hydrazide and 2,4-dihydoxylbenzaldehyde were condensed at 20°C to form an acylhydrazone (H3L) with ONO coordination pattern. The structure of the acylhydrazone was elucidated by using CHN analyzer, ESI mass spectrometry, IR, 1H NMR, 13C NMR and 2D NMR such as COSY and HSQC. Thereafter, five novel metal complexes [Mn(II), Fe(II), Pt(II) Zn(II) and Pd(II)] of the hydrazone ligand were synthesized and their structural characterization were achieved by several physicochemical methods, namely elemental analysis, electronic spectra, infrared, EPR, molar conductivity and powder X-ray diffraction studies. Structural geometries of some of the compounds were supported by using Hyper Chem-8 program for the molecular mechanics and semi-empirical calculations. The stability energy (E) and electron potentials (eV) for the frontier molecules were calculated by using PM3 method. An octahedral geometry was suggested for both Pd(II) and Zn(II) complexes while both Mn(II) and Fe(II) complexes conformed with tetrahedral pyramidal. However, Pt(II) complex agreed with tetrahedral geometry. In vitro antitubercular activity study of the ligand and the metal complexes were evaluated against Mycobacterium tuberculosis, H37Rv, by using micro-diluted method. The results obtained revealed that (PtL1) (MIC = 0.56 µg/mL), (ZnL1) (MIC = 0.61 µg/mL), (MnL1) (MIC = 0.71 µg/mL) and (FeL1) (MIC = 0.82 µg/mL), exhibited a significant activity when compared with first line drugs such as isoniazid (INH) (MIC = 0.9 µg/mL). H3L1 exhibited lesser antitubercular activity with MIC value of 1.02 µg/mL. However, the metal complexes displayed higher cytoxicity but were found to be non-significant different (P ˂ 0.05) to isoniazid drug.

Keywords: hydrazones, electron spin resonance, thermogravimetric, powder X-ray diffraction, antitubercular agents

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Authors: Prabhavathi Sundaram, Heidi Abrahamse

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In recent years, nanotechnology coupled with photodynamic therapy (PDT) has received considerable attention in terms of improving the effectiveness of drug delivery in cancer therapeutics. The development of functionalized single-walled carbon nanotubes (SWCNTs) has become revolutionary in targeted photosensitizers delivery since it improves the therapeutic index of drugs. The objective of this study was to prepare, characterize and evaluate the potential of functionalized SWCNTs using hyaluronic acid and loading it with photosensitizer and to effectively target colon cancer cells. The single-walled carbon nanotubes were covalently functionalized with hyaluronic acid and the loaded photosensitizer by non-covalent interaction. The photodynamic effect of SWCNTs is detected under laser irradiation in vitro. The hyaluronic acid-functionalized nanocomposites had a good affinity with CD44 receptors, and it avidly binds on to the surface of CACO-2 cells. The cellular uptake of nanocomposites was studied using fluorescence microscopy using lyso tracker. The anticancer activity of nanocomposites was analyzed in CACO-2 cells using different studies such as cell morphology, cell apoptosis, and nuclear morphology. The combined effect of nanocomposites and PDT improved the therapeutic effect of cancer treatment. The study suggested that the nanocomposites and PDT have great potential in the treatment of colon cancer.

Keywords: colon cancer, hyaluronic acid, single walled carbon nanotubes, photosensitizers, photodynamic therapy

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Authors: Kouorsh Zarea, Fatemeh Hassani, Samira Beiranvand, Akram Mohamadi

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Background and Objectives: Medication error in hospitals is a major cause of the errors which disrupt the health care system. The aim of this study was to assess the nurses’ medication errors and related factors. Material and methods: This was a descriptive study on 225 nurses in various hospitals, selected through multistage random sampling. Data was collected by three researcher made tools; demographic, medication error and related factors questionnaires. Data was analyzed by descriptive statistics, Chi-square, Kruskal-Wallis, One-way analysis of variance. Results: Based on the results obtained, the type of medication errors giving drugs to patients later or earlier (55.6%), multiple oral medication together regardless of their interactions (36%) and the postoperative analgesic without a prescription (34.2%), respectively. In addition, factors such as the shortage of nurses to patients’ ratio (57.3%), high load functions (51.1%) and fatigue caused by the extra work (40.4%), were the most important factors affecting the incidence of medication errors. The fear of legal issues (40%) are the most important factor is the lack of reported medication errors. Conclusions: Based on the results, effective management and promotion motivate nurses. Therefore, increasing scientific and clinical expertise in the field of nursing medication orders is recommended to prevent medication errors in various states of nursing intervention. Employing experienced staff in areas with high risk of medication errors and also supervising less-experienced staff through competent personnel are also suggested.

Keywords: medication error, nurse, clinical care, drug errors

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Authors: Yagahira E. Castro-Sesquen, Chloe Kim, Robert H. Gilman, David J. Sullivan, Peter C. Searson

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Diagnosis of severe malaria is particularly important in highly endemic regions since most patients are positive for parasitemia and treatment differs from non-severe malaria. Diagnosis can be challenging due to the prevalence of diseases with similar symptoms. Accurate diagnosis is increasingly important to avoid overprescribing antimalarial drugs, minimize drug resistance, and minimize costs. A nanoparticle-based assay for detection and quantification of Plasmodium falciparum histidine-rich protein 2 (HRP2) in urine and serum is reported. The assay uses magnetic beads conjugated with anti-HRP2 antibody for protein capture and concentration, and antibody-conjugated quantum dots for optical detection. Western Blot analysis demonstrated that magnetic beads allows the concentration of HRP2 protein in urine by 20-fold. The concentration effect was achieved because large volume of urine can be incubated with beads, and magnetic separation can be easily performed in minutes to isolate beads containing HRP2 protein. Magnetic beads and Quantum Dots 525 conjugated to anti-HRP2 antibodies allows the detection of low concentration of HRP2 protein (0.5 ng mL-1), and quantification in the range of 33 to 2,000 ng mL-1 corresponding to the range associated with non-severe to severe malaria. This assay can be easily adapted to a non-invasive point-of-care test for classification of severe malaria.

Keywords: HRP2 protein, malaria, magnetic beads, Quantum dots

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Authors: Alba Luna Jimenez, Maria Dolores Hernando

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The administration of veterinary treatments at higher doses than the recommended Varroa mite control in beehive matrices has the potential to generate residues in the honeybee colony and in the derived products for consumption. Honeybee colonies can also be indirectly exposed to residues of plant protection products when foraging in crops, wildflowers near the crops, or in urban gardens just after spraying. The study evaluates the presence of both types of residues, veterinary treatments, and pesticides in beeswax, bee bread, and honey. The study was carried out in apiaries located in agricultural zones and forest areas in Andalusia, Spain. Up to nineteen residues were identified above LOQ using gas chromatography-triple quadrupole-mass spectrometry analysis (GC-MS/MS). Samples were extracted by a modified QuEChERs method. Chlorfenvinphos was detected in beeswax and bee bread despite its use is not authorized for Varroa mite control. Residues of fluvalinate-tau, authorized as veterinary treatment, were detected in most of the samples of beeswax and bee bread, presumably due to overdose or also to its potential for accumulation associated with its marked liposolubility. Residues of plant protection products were also detected in samples of beeswax and bee bread. Pesticide residues were detected above the LOQ that was established at 5 µg.kg⁻¹, which is the minimum concentration that can be quantified with acceptable accuracy and precision, as described in the European guidelines for pesticide residue analysis SANTE/11945/2015. No residues of phytosanitary treatments used in agriculture were detected in honey.

Keywords: honeybee colony, mass spectrometry analysis, pesticide residues, Varroa destructor, veterinary treatment

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Authors: Jarel Elgin Tolentino, Arby Denise Nera, Mary Rose Roco, Angela Vianca Aspa, Nikko Beltran, Else Dapat

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Drug resistance by cells has been the problem in the medical field for decades now. The use of medicinal plants as a source of creating powerful drugs has been nowadays recognized worldwide to treat such resistant diseases. In the present study, the potential for Diospyros philippinensis A. DC. to inhibit growth of both bacteria and cancer cell line was conducted. The leaf crude extracts were screened for the presence of phytochemicals and examined for potential bioactivities by employing several assays like Kirby-Bauer disc diffusion method, DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium assay for the antibacterial, antioxidant and cytotoxic activities of the extract, respectively. Phytochemical test results of the extracts revealed the presence of alkaloids, flavonoids, saponins, phenols, quinones, cardiac glycosides, phlobatannins, carbohydrate, cardenolides and proteins. The leaf extracts were found to exhibit antibacterial activity against gram-positive bacteria, high antioxidant activity (99.22% ± 0.005) but did not show any sign of cytotoxicity towards HCT116 (ATCC CCL-247). The study therefore concludes that D. philippinensis A. DC. leaf extract can be a source of antibacterial and chemopreventive agents. This claim may be used as basis for future investigation.

Keywords: bioassay, medicinal plants, plant crude extracts, phytochemical screening

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Authors: Shiva Rezaei, Seyed Jalal Hosseinimehr, Abbasali Karimpour Malekshah, Mansooreh Mirzaei, Fereshteh Talebpour Amiri, Mehryar Zargari

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Objective(s): Cyclophosphamide (CP), as an antineoplastic drug, is widely used in cancer patients, and liver toxicity is one of its complications. Sinapic acid (SA), as a natural phenylpropanoid, has antioxidant, anti-inflammatory, and anti-cancer properties. Materials and Methods: The purpose of the current study was to determine the protective effect of SA versus CP-induced liver toxicity. In this research, BALB/c mice were treated with SA (5 and 10 mg/kg) orally for one week, and CP (200 mg/kg) was injected on day 3 of the study. Oxidative stress markers, serum liver-specific enzymes, histopathological features, caspase-3, and nuclear factor kappa-B cells were then checked. Results: CP induced hepatotoxicity in mice and showed structural changes in liver tissue. CP significantly increased liver enzymes and lipid peroxidation and decreased glutathione. The immunoreactivity of caspase-3 and nuclear factor kappa-B cells was significantly increased. Administration of SA significantly maintained histochemical parameters and liver function enzymes in mice treated with CP. Immunohistochemical examination showed SA reduced apoptosis and inflammation. Conclusion: The data confirmed that SA with anti-apoptotic, anti-oxidative, and anti-inflammatory activities was able to preserve CP-induced liver injury in mice.

Keywords: apoptosis, cyclophosphamide, liver injury, inflammation, oxidative stress, sinapic acid

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Authors: Juan Antonio Mondragon Sanchez, Ruben Santamaria

Abstract:

The DNA G-quadruplex is a four-stranded DNA structure conformed by stacked planes of four base paired guanines (G-quartet). The guanine rich DNA sequences are present in many sites of genomic DNA and can potentially lead to the formation of G-quadruplexes, especially at the 3'-terminus of the human telomeric DNA with many TTAGGG repeats. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to regulate oncogene expression making the G-quadruplex an attractive target for anticancer therapy. Clearly, the G-quadruplex structured in the telomeric DNA is of fundamental importance for rational drug design. In this context, we investigate two G-quadruplex structures, the first follows from the sequence TTAGGG(TTAGGG)3TT (HUT1), and the second from AAAGGG(TTAGGG)3AA (HUT2), both in a K+ solution. We determine the free energy surfaces of the HUT1 and HUT2 structures and investigate their conformations using replica-exchange metadynamics simulations. The carbonyl-carbonyl distances belonging to different guanines residues are selected as the main collective variables to determine the free energy surfaces. The surfaces exhibit two main local minima, compatible with experiments on the conformational transformations of HUT1 and HUT2 under substitution of the K+ ions by the Na+ ions. The conformational transitions are not observed in short MD simulations without the use of the metadynamics approach. The results of this work should be of help to understand the formation and stability of human telomeric G-quadruplex in environments including the presence of K+ and Na+ ions.

Keywords: g-quadruplex, metadynamics, molecular dynamics, replica-exchange

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Authors: Merzak Siham, Benguerine Zohra, Si Tayeb Fatima, Bouzian Chaimaa Affaf, Jou Siham, Belkessam Nafissa

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Introduction: Medicinal plants, particularly spices, are essential for pharmacological research due to their health benefits. This study focuses on Curcuma longa, a spice recognized for its therapeutic properties. Materials and Methods: This study is based on a thorough search conducted on Google Scholar, PubMed, and ScienceDirect. From an initial selection of 25 articles, five were chosen to extract relevant information on Curcuma longa. Results and Discussions: Clinical studies have indicated that curcumin is well tolerated at doses up to 12 g/day. Its anti-rheumatic efficacy was compared to phenylbutazone in 18 individuals. Each participant received a daily dose of either 1200 mg of curcumin or 300 mg of phenylbutazone for 2 weeks. Curcumin was well tolerated at this dose and demonstrated activity comparable to phenylbutazone. Additionally, a study on 62 patients showed that curcumin sustainably relieved symptoms without toxicity. Its effects included reduced itching, lesions, and pain. In ten volunteers, administering 500 mg of curcumin for seven days resulted in a 33% decrease in lipid peroxidation, a 29% increase in HDL cholesterol, and a 12% decrease in total cholesterol. It is important to note that curcumin is a potent, selective inhibitor of phosphorylase kinase, an increased marker in psoriasis. Conclusion: Curcumin is promising as a future drug for various diseases, but its bioavailability must be improved through techniques such as nano encapsulation. Additionally, exploring chemical derivatives of curcumin could lead to more potent and targeted molecules.

Keywords: turmeric, spice, medicinal plants, pharmacological activities.

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Authors: Bhavana V. Mohite, Satish V. Patil

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Bacterial cellulose (BC) is an alternative for plant cellulose (PC) that prevents global warming leads to preservation of nature. Although PC and BC have the same chemical structure, BC is superior with its properties like its size, purity, porosity, degree of polymerization, crystallinity and water holding capacity, thermal stability etc. On this background the present study focus production and applications of BC as antimicrobial wound dressing material. BC was produced by Gluconoacetobacter hansenii (strain NCIM 2529) under shaking condition and statistically enhanced upto 7.2 g/l from 3.0 g/l. BC was analyzed for its physico mechanical, structural and thermal characteristics. BC produced at shaking condition exhibits more suitable properties in support to its high performance applications. The potential of nano silver impregnated BC was determined for sustained release modern antimicrobial wound dressing material by swelling ratio, mechanical properties and antimicrobial activity against Staphylococcus aureus. BC in nanocomposite form with other synthetic polymer like PVA shows improvement in its properties such as swelling ratio (757% to 979%) and sustainable release of antibacterial agent. The high drug loading and release potential of BC was evidenced in support to its nature as antimicrobial wound dressing material. The nontoxic biocompatible nature of BC was confirmed by MTT assay on human epidermal cells with 90% cell viability that allows its application as a regenerative biomaterial. Thus, BC as a promising new generation antimicrobial wound dressing material was projected.

Keywords: agitated culture, biopolymer, gluconoacetobacter hansenii, nanocomposite

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Authors: Rajesh Kumar G

Abstract:

A challenging aspect of any clinical trial is to carefully plan the study design to meet the study objective in optimum way and to validate the assumptions made during protocol designing. And when it is a pediatric study, there is the added challenge of stringent guidelines and difficulty in recruiting the necessary subjects. Unlike adult trials, there is not much historical data available for pediatrics, which is required to validate assumptions for planning pediatric trials. Typically, pediatric studies are initiated as soon as approval is obtained for a drug to be marketed for adults, so with the adult study historical information and with the available pediatric pilot study data or simulated pediatric data, the pediatric study can be well planned. Generalizing the historical adult study for new pediatric study is a tedious task; however, it is possible by integrating various statistical techniques and utilizing the advantage of hybrid study design, which will help to achieve the study objective in a smoother way even with the presence of many constraints. This research paper will explain how well the hybrid study design can be planned along with integrated technique (SEV) to plan the pediatric study; In brief the SEV technique (Simulation, Estimation (using borrowed adult data and applying Bayesian methods)) incorporates the use of simulating the planned study data and getting the desired estimates to Validate the assumptions.This method of validation can be used to improve the accuracy of data analysis, ensuring that results are as valid and reliable as possible, which allow us to make informed decisions well ahead of study initiation. With professional precision, this technique based on the collected data allows to gain insight into best practices when using data from historical study and simulated data alike.

Keywords: adaptive design, simulation, borrowing data, bayesian model

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Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia AbdulMajid, Maryam Zahedifard

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Colon cancer is one of the most prevalent cancers in the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. New schiff based compounds are reported to exhibit a wide spectrum of biological activities of therapeutic importance. To evaluate inhibitory properties of CdCl2(C14H21N3O2) complex on colonic aberrant crypt foci, five groups of 7-week-old male rats were used. Control group was fed with 10% Tween 20 once a day, cancer control group was intra-peritoneally injected with 15 mg/kg Azoxymethan, drug control group was injected with 15 mg/kg azoxymethan and 5-Flourouracil, experimental groups were fed with 2.5 and 5 mg/kg CdCl2(C14H21N3O2) compound each once a day. Administration of compound were found to be effectively chemoprotective. Andrographolide suppressed total colonic ACF formation up to 72% to 74%, respectively, when compared with control group. The results also showed a significant increase in glutathione peroxidase, superoxide dismutase, catalase activities and a decrease in malondialdehyde level. Immunohistochemical staining demonstrated down-regulation of PCNA protein. According to the Western blot comparison analysis, COX-2 and Bcl2 is up-regulated whilst the Bax is down-regulated. according to these data, this compound plays promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, Schiff based compound, aberrant crypt foci (ACF), immunohistochemical staining

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Authors: Zafar Iqbal, Sana Irshad Khan

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Organic extract from newly isolated plant growth promoting fungus (PGPF) Penicillium sp EU0013 was subjected to bioassays including anti fungal (disc diffusion) cytotoxicity (brine shrimp lethality), herbicidal (Lemna minor) and nematicidal activities. Metabolite profile of the extract was also assessed using HPLC analysis with the aim to identify bioactive natural products in the extract as new drug candidate(s). The extract showed anti fungal potential against tested fungal pathogens. Growth of the Wilt pathogen Fusarium oxyosproum was inhibited up to 63% when compared to negative reference. Activity against brine shrimps was weak and mortality up to 10% was observed at concentration of 200 µg. mL-1. The extract exhibited no toxicity against Lemna minor frond at 200 µg. mL-1. Nematicidal activity was observed very potent against root knot nematode and LC50 value was calculated as 52.5 ug. mL-1 using probit analysis. Methodically assessment of metabolites profile by HPLC showed the presence of kojic acid (Rt 1.4 min) and aflatoxin B1 (Rt 5.9 min) in the mycellial extract as compared with standards. The major unidentified metabolite was eluted at Rt 8.6 along with other minor peaks. The observed high toxicity against root knot nematode was attributed to the unidentified compounds that make fungal extract worthy of further exploration for isolation and structural characterization studies for development of future commercial nematicidal compound(s).

Keywords: penicillium, nematicidal activity, metabolites, HPLC

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Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Mehboob Alam

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The development of efficient delivery systems remains a major concern in cancer chemotherapy as many efficacious anticancer drugs are hydrophobic and difficult to formulate. Nanomedicines based on drug-loaded amphiphilic glycol chitosan micelles offer potential advantages for the formulation of drugs such as etoposide that may improve the pharmacokinetics and reduce the formulation-related adverse effects observed with current formulations. Amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxysuccinimide and quaternization to glycol chitosan backbone. To this end, a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternization, yielding a 13 kDa amphiphilic polymer. Micelles prepared from this amphiphilic polymer had a size of 162nm and were able to encapsulate up to 3 mg/ml etoposide. Pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drugs after intravenous administration. AUC 0.5-24h showed statistically significant difference in ETP-GCPQ vs. Commercial preparation in liver (25 vs.70, p<0.001), spleen (27 vs.36, p<0.05), lungs (42 vs.136,p<0.001),kidneys(25 vs.70,p< 0.05),and brain(19 vs.9,p<0.001). ETP-GCPQ crossed the blood-brain barrier, and 4, 3.5, 2.6, 1.8, 1.7, 1.5, and 2.5 fold higher levels of etoposide were observed at 0.5, 1, 2, 4, 6, 12, and 24hrs; respectively suggesting these systems could deliver hydrophobic anticancer drugs such as etoposide to tumors but also increased their transport through the biological barriers, thus making it a good delivery system

Keywords: glycol chitosan, micelles, pharmacokinetics, tissue distribution

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Authors: Md. Shadab, Mariyam N. Nashid, Venkata Srikanth Meka, Thiagarajan Madheswaran

Abstract:

Naringenin (NAR), is a naturally occurring plant flavonoid, found predominantly in citrus fruits, that possesses a wide range of pharmacological properties including anti-oxidant, anti-inflammatory behaviour, cholesterol-lowering and anticarcinogenic activities. However, despite the therapeutic potential of naringenin shown in a number of animal models, its clinical development has been hindered due to its low aqueous solubility, slow dissolution rate and inefficient transport across biological membranes resulting in low bioavailability. Naringenin nanosuspension were produced using stabilizers Tween® 80 by high pressure homogenization techniques. The nanosuspensions were characterized with regard to size (photon correlation spectroscopy (PCS), size distribution, charge (zeta potential measurements), morphology, short term physical stability, dissolution profile and antioxidant potential. A nanocrystal PCS size of about 500 nm was obtained after 20 homogenization cycles at 1500 bar. The short-term stability was assessed by storage of the nanosuspensions at 4 ◦C, room temperature and 40 ◦C. Result showed that naringenin nanosuspension was physically unstable due to large fluctuations in the particle size and zeta potential after 30 days. Naringenin nanosuspension demonstrated higher drug dissolution (97.90%) compared to naringenin powder (62.76%) after 120 minutes of testing. Naringenin nanosuspension showed increased antioxidant activity compared to naringenin powder with a percentage DPPH radical scavenging activity of 49.17% and 31.45% respectively at the lowest DPPH concentration.

Keywords: bioavailability, naringenin, nanosuspension, oral delivery

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