Search results for: herbal drug of depression

Authors: Zahra Dehghani, Hoda Dehghani, Elham Zarenezhad

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1,2,3-Triazole derivatives are important compounds in medicinal chemistry owing to their wide applications in drug discovery. They can readily associate with biologically targets through the hydrogen bonding and dipole interactions. The 1,2,3-triazole core is a key structural motif in many bioactive compounds, exhibiting a broad spectrum of biological activities, such as antiviral, anticancer, anti-HIV, antibiotic, antibacterial, and antimicrobial. Additionally, they have found significant industrial applications as dyes, agrochemicals, corrosion inhibitors, photo stabilizers, and photographic materials. we disclose the synthesis and characterization of 1-azido-3-(aryl-2-yloxy)propan-2-ol drivatives. The chemistry works well with various ß-azido alcohols involving aryloxy, alkoxy and alkyl residues, and also tolerates a wide spectrum of electron-donating and electron-withdrawing functional groups in both alkyne and azide molecules. Most of ß-azidoalcohols used in these experiments were pre-synthesized by the regioselective ring opening reaction of corresponded epoxides with sodium azide, whereas the majority of terminal alkynes were prepared via SN2-type reaction of propargyl bromide and corresponded nucleophiles. To evaluate the bioactivity of title compounds, the in vitro antifungal activity of all compound was investigated against several pathogenic fungi including Candida albicans, Candida krusei, Aspergillus niger, and Trichophyton rubrum , clotrimazole and fluconazole was used as standard antifungal drugs, also To understand the antibacterial activity of synthesized compounds, they were in vitro screened against E. coli and S. aureus as Gram-negative and Gram-positive bacteria, respectively. The in vitro tests have shown the promising antifungal but marginal antibacterial activity against tested fungi and bacteria.

Keywords: biological activities, antibacterial, antifungal, 1, 2, 3-Triazole

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Authors: Alene Toulany, Elizabeth Dettmer, Seena Grewal, Kaley Roosen, Andrea Regina, Cathleen Steinegger, Kate Stadelman, Melissa Chambers, Lindsay Lochhead, Kelsey Gallagher, Alissa Steinberg, Andrea Leyser, Allison Lougheed, Jill Hamilton

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Obesity and psychiatric disorders occur together so frequently that the combination has been coined an epidemic within an epidemic. Youth living with obesity are at increased risk for trauma, depression, anxiety and disordered eating. Although symptoms of binge eating disorder are common in paediatric obesity management programs, they are often not identified or addressed within treatment. At The Hospital for Sick Children (SickKids), a tertiary care paediatric hospital in Toronto, Canada, adolescents with obesity are treated in an interdisciplinary outpatient clinic (1-2 hours/week). This intensity of care is simply not enough to help these extremely complex patients. Existing day treatment programs for eating, and psychiatric disorders are not well suited for patients with obesity. In order to address this identified care gap, a unique collaboration was formed between the obesity, psychiatry, and eating disorder programs at SickKids in 2015. The aim of this collaboration was to provide an enhanced treatment arm to our general psychiatry day hospital program that addresses both the mental health issues and the lifestyle challenges common to youth with obesity and binge eating. The program is currently in year-one of a two-year pilot project and is designed for a length of stay of approximately 6 months. All youth participate in daily group therapy, academics, and structured mealtimes. The groups are primarily skills-based and are informed by cognitive/dialectical behavioural therapies. Weekly family therapy and individual therapy, as well as weekly medical appointments with a psychiatrist and a nurse, are provided. Youth in the enhanced treatment arm also receive regular sessions with a dietitian to establish normalized eating behaviours and monthly multifamily meal sessions to address challenges related to behaviour change and mealtimes in the home. Outcomes that will be evaluated include measures of mental health, anthropometrics, metabolic status, and healthcare satisfaction. At the end of the two years, it is expected that we will have had about 16 youth participants. This model of care delivery will be the first of its kind in Canada and is expected to inform future paediatric treatment practices.

Keywords: adolescent, binge eating, mental illness, obesity

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Authors: Tadesse Eguale, Ephrem Engdawork, Wondwossen Gebreyes, Dainel Asrat, Hile Alemayehu, John Gunn

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Salmonella is one of the major zoonotic pathogens affecting wide range of vertebrates and humans worldwide. Consumption of contaminated dairy products and contact with dairy cattle represent the common sources of non-typhoidal Salmonella infection in humans. Fecal samples were collected from 132 dairy herds in central Ethiopia and cultured for Salmonella to determine the prevalence, serotype distribution and antimicrobial susceptibility. Salmonella was recovered from the feces of at least one cattle in 10(7.6%) of the dairy farms. Out of 1193 fecal samples 30(2.5%) were positive for Salmonella. Large farm size, detection of diarrhea in one or more animals during sampling and keeping animals completely indoor compared to occasional grazing outside were associated with Salmonella positivity of the farms. Farm level prevalence of Salmonella was significantly higher in young animals below 6 months of age compared to other age groups(X2=10.24; p=0.04). Nine different serotypes were isolated. The four most frequently recovered serotypes were S. Typhimurium (23.3%),S. Saintpaul (20%) and S. Kentucky and S. Virchow (16.7%) each. All isolates were resistant or intermediately resistant to at least one of the 18 drugs tested. Twenty-six (86.7%), 20(66.7%), 18(60%), 16(53.3%) of the isolates were resistant to streptomycin, nitrofurantoin, sulfisoxazole and tetracycline respectively. Resistance to 2 drugs was detected in 93.3% of the isolates. Resistance to 3 or more drugs were detected in 21(70%) of the total isolates while multi-drug resistance (MDR) to 7 or more drugs were detected in 12 (40%) of the isolates. The rate of occurrence of MDR in Salmonella strains isolated from dairy farms in Addis Ababa was significantly higher than those isolated from farms outside of Addis Ababa((p= 0.009). The detection of high MDR in Salmonella isolates originating from dairy farms warrants the need for strict pathogen reduction strategy in dairy cattle and spread of these MDR strains to human population.

Keywords: salmonella, antimicrobial resistance, fecal prevalence

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Authors: Hui-Ling Yang, Kuei-Ru Chou

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Background: Studies show that cognitive training can effectively delay cognitive failure. However, there are several gaps in the previous studies of cognitive training in mild cognitive impairment: 1) previous studies enrolled mostly healthy older adults, with few recruiting older adults with cognitive impairment; 2) they also had limited generalizability and lacked long-term follow-up data and measurements of the activities of daily living functional impact. Moreover, only 37% were randomized controlled trials (RCT). 3) Limited cognitive training has been specifically developed for mild cognitive impairment. Objective: This study sought to investigate the changes in cognitive function, activities of daily living and degree of depressive symptoms in older adults with mild cognitive impairment after cognitive training. Methods: This double-blind randomized controlled study has a 2-arm parallel group design. Study subjects are older adults diagnosed with mild cognitive impairment in residential care facilities. 124 subjects will be randomized by the permuted block randomization, into intervention group (Cognitive training, CT), or active control group (Passive information activities, PIA). Therapeutic adherence, sample attrition rate, medication compliance and adverse events will be monitored during the study period, and missing data analyzed using intent-to-treat analysis (ITT). Results: Training sessions of the CT group are 45 minutes/day, 3 days/week, for 12 weeks (36 sessions each). The training of active control group is the same as CT group (45min/day, 3days/week, for 12 weeks, for a total of 36 sessions). The primary outcome is cognitive function, using the Mini-Mental Status Examination (MMSE); the secondary outcome indicators are: 1) activities of daily living, using the Lawton’s Instrumental Activities of Daily Living (IADLs) and 2) degree of depressive symptoms, using the Geriatric Depression Scale-Short form (GDS-SF). Latent growth curve modeling will be used in the repeated measures statistical analysis to estimate the trajectory of improvement by examining the rate and pattern of change in cognitive functions, activities of daily living and degree of depressive symptoms for intervention efficacy over time, and the effects will be evaluated immediate post-test, 3 months, 6 months and one year after the last session. Conclusions: We constructed a rigorous CT program adhering to the Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines. We expect to determine the improvement in cognitive function, activities of daily living and degree of depressive symptoms of older adults with mild cognitive impairment after using the CT.

Keywords: mild cognitive impairment, cognitive training, randomized controlled study

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Authors: Ronel Solis, Leonardo Collado

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Migration law in the Republic of Panama has been regulated mainly by the executive branch. This has created a crisis not only institutional but also social because the evolution of these norms has rested greatly from the discretion of the government in office. This has created instability in immigration regulation and more now, with the migration crisis of which Panama is also part. Different migration policies have been established. The most recent is that of the controlled migration flow, in which, for humanitarian reasons, migrants move from the border with Colombia to the border with Costa Rica. Unfortunately, such control is not enough, and in some cases, unprotected migrants have been confined for months, their passports have been withheld, and no recognition of their rights is offered. The Inter-American Court of Human Rights has condemned Panama for the unfair detention of an irregular migrant, who was detained for two years in Panamanian prisons, without having committed a crime and without accessing a just defense. This is the case Vélez Loor vs. the Republic of Panama. Uncontrollable migration has been putting pressure on Panamanian public health services. The recent denunciation of HIV-related NGOs that warns that there are hundreds of foreigners who receive expensive antiretroviral therapy in Panama is serious, and several of them are irregular migrants. On the other hand, there are no border control posts with the Republic of Colombia, because it is a jungle area and migrants are exposed to arms and drug trafficking, and unfortunately, also to prostitution. Government entities such as the border police service have provided humanitarian support to migrants on the border with Colombia, although it is not their administrative function, and various entities discuss who should address this crisis. However, few economic resources are allocated by the government to solve this problem, especially with the recent mass migration of Venezuelans who have fled their country. The establishment of a migratory normative code is necessary to establish uniformity in the recognition and application of migratory rights. In this way, dependence on the changing migration policies of the different Panamanian governments would be eliminated, and the rights of migrants and nationals would be guaranteed.

Keywords: executive branch, irregular migration, migration code, Republic of Panama

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Authors: Manisha Singh, Padam Simkhada

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Background: Although mental health policy has been adapted in Nepal since 1997, the implementation of the policy framework is yet to happen. The fact that mental health services are largely concentrated in urban areas more specific to treatment only provides a clear picture of the scarcity of mental health services in the country. The shreds of evidence from around the world, along with WHO’s (World Health Organization) Mental Health Gap Action Program (mhGAP) suggest that effective mental health services can be provided from Primary Health Care (PHC) centers through community-based programs without having to place a specialized health worker. However, the country is still facing the same challenges to date with very few psychiatrists and psychologists, but they are largely based in cities. Objectives: The main objectives of this study are; (a) to understand the perception of health workers at PHC on maternal mental health, and (b) to assess the availability of the mental health services at PHC to address maternal mental health. Methods: This study used a qualitative approach where an in-depth interview was conducted with the health workers at the primary level. “Mayadevi” rural municipality in Rupendehi District that comprised of 13 small villages, was chosen as the study site. A total 8 health institutions which covered all 13 sites were included where either the health post in- charge or health worker working in maternal and child health care was interviewed for the study. All the health posts in the study area were included in the study. The interviews were conducted in Nepali; later, they were translated in English, transcribed, and triangulated. NViVO was used for the analysis. Results: The findings show that most of the health workers understood what maternal mental health was and deemed it as a public health issue. They could explain the symptoms and knew what medication to prescribe if need be. However, the majority of them failed to name the screening tools in place for maternal mental health. Moreover, they hadn’t even seen one. None of the health care centers had any provision for screening mental health status. However, one of the centers prescribed medication when the patients displayed symptoms of depression. But they believed there were a significant number of hidden cases in the community due to the stigma around mental health and being a woman with mental health problem makes the situation even difficult. Nonetheless, the health workers understood the importance of having screening tools and acknowledged the need of training and support in order to provide the services from PHC. Conclusion: Community health workers can identify cases with mental health problems and prevent them from deteriorating further. But there is a need for robust training and support to build the capacity of the health workers. The screening tools on mental health needs to be encouraged to be used in the PHC levels. Furthermore, community-based culture-sensitive programs need to be initiated and implemented to mitigate the stigma related issues around mental health.

Keywords: maternal mental health, health care providers, screening, Nepal

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Authors: Sree Sanyal

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Research in ageing often highlights the age-related health dimension more than the psycho-social characteristics of the elderly, which also influences and challenges the health outcomes. Multimorbidity is defined as the person having more than one chronic non-communicable diseases and their prevalence increases with ageing. The study aims to evaluate the influence of social ties on self-reported prevalence of multimorbidity (selected chronic non-communicable diseases) among the selected states of elderly population in India. The data is accessed from Building Knowledge Base on Population Ageing in India (BKPAI), collected in 2011 covering the self-reported chronic non-communicable diseases like arthritis, heart disease, diabetes, lung disease with asthma, hypertension, cataract, depression, dementia, Alzheimer’s disease, and cancer. The data of the above diseases were taken together and categorized as: ‘no disease’, ‘one disease’ and ‘multimorbidity’. The predicted variables were demographic, socio-economic, residential types, and the variable of social ties includes social support, social engagement, perceived support, connectedness, and importance of the elderly. Predicted probability for multiple logistic regression was used to determine the background characteristics of the old in association with chronic morbidities showing multimorbidity. The finding suggests that 24.35% of the elderly are suffering from multimorbidity. Research shows that with reference to ‘no disease’, according to the socio-economic characteristics of the old, the female oldest old (80+) from others in caste and religion, widowed, never had any formal education, ever worked in their life, coming from the second wealth quintile standard, from rural Maharashtra are more prone with ‘one disease’. From the social ties background, the elderly who perceives they are important to the family, after getting older their decision-making status has been changed, prefer to stay with son and spouse only, satisfied with the communication from their children are more likely to have less single morbidity and the results are significant. Again, with respect to ‘no disease’, the female oldest old (80+), who are others in caste, Christian in religion, widowed, having less than 5 years of education completed, ever worked, from highest wealth quintile, residing in urban Kerala are more associated with multimorbidity. The elderly population who are more socially connected through family visits, public gatherings, gets support in decision making, who prefers to spend their later years with son and spouse only but stays alone shows lesser prevalence of multimorbidity. In conclusion, received and perceived social integration and support from associated neighborhood in the older days, knowing about their own needs in life facilitates better health and wellbeing of the elderly population in selected states of India.

Keywords: morbidity, multi-morbidity, prevalence, social ties

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Authors: Naveeda Akhtar Qureshi, Wajiha

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Coccidiosis is a protozoan parasitic disease of genus Eimeria. It is an avian infection causing a great economic loss of 3 billion USD per year globally. A number of anticoccidial drugs are in use however many of them have side effects and cost effective. With increase in poultry demand throughout the world there is a need of more drugs and vaccines against coccidiosis. The present study is based upon the use of F. racemosa a medicinal plant to be a potential source of anticoccidial agents. The methanolic leaves extract was fractionated by column and thin layer chromatography and got nineteen fractions. Each fraction different concentrations was evaluated for its anticoccidial properties in an invitro experiment against E. tenella, E. necatrix and E. mitis. The anticoccidial active fractions were further characterized by spectroscopy (UV-Vis, FTIR) and GC-MS analysis. The in silico molecular docking of active fractions identified compounds were carried out. Among all fractions significantly maximum sporulation inhibition efficacy was shown by F-19 (67.11±2.18) followed by F-15 (65.21±1.34) at concentration of 30mg/ml against E. tenella. The significantly highest sporozoites viability inhibition was shown by F-19 (69.23±2.11) followed by F-15 (67.14±1.52) against E. necatrix at concentration 30mg/ml. Anticoccidial active fractions 15 and 19 showed peak spectrum at 207 and 202nm respectively by UV analysis. Their FTIR analysis confirmed the presence of carboxylic acid, amines, phenols, etc. Anticoccidial active compounds like Cyclododecane methanol, oleic acid, Octadecanoic acid, etc were identified by GC-MS analysis. Identified compounds in silico molecular docking study showed that cyclododecane methanol of F-19 and oleic acid of F-15 showed highest binding affinity with target S-Adenosylmethionine synthase. Hence for further authentication in vivo anticoccidial studies are recommended.

Keywords: ficus racemosa, cluster fig, column chromatography, anticoccidial fractions, GC-MS, molecular docking., s-adenosylmethionine synthase

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Authors: Abbas Pourreza

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MicroRNAs (miRNAs) are small single-stranded non-coding RNAs. They are almost 18-25 nucleotides long and very conservative through evolution. They are involved in adjusting the expression of numerous genes due to the existence of a complementary region, generally in the 3' untranslated regions (UTR) of target genes, against particular mRNAs in the cell. Also, miRNAs have been proven to be involved in cell development, differentiation, proliferation, and apoptosis. More than 2000 miRNAs have been recognized in human cells, and these miRNAs adjust approximately one-third of all genes in human cells. Dysregulation of miRNA originated from abnormal DNA methylation patterns of the locus, cause to down-regulated or overexpression of miRNAs, and it may affect tumor formation or development of it. Breast cancer (BC) is the most commonly identified cancer, the most prevalent cancer (23%), and the second-leading (14%) mortality in all types of cancer in females. BC can be classified based on the status (+/−) of the hormone receptors, including estrogen receptor (ER), progesterone receptor (PR), and the Receptor tyrosine-protein kinase erbB-2 (ERBB2 or HER2). Currently, there are four main molecular subtypes of BC: luminal A, approximately 50–60 % of BCs; luminal B, 10–20 %; HER2 positive, 15–20 %, and 10–20 % considered Basal (triple-negative breast cancer (TNBC)) subtype. Aberrant expression of miR-145, miR-21, miR-10b, miR-125a, and miR-206 was detected by Stem-loop real-time RT-PCR in BC cases. Breast tumor formation and development may result from down-regulation of a tumor suppressor miRNA such as miR-145, miR-125a, and miR-206 and/or overexpression of an oncogenic miRNA such as miR-21 and miR-10b. MiR-125a, miR-206, miR-145, miR-21, and miR-10b are hugely predicted to be new tumor markers for the diagnosis and prognosis of BC. MiR-21 and miR-125a could play a part in the treatment of HER-2-positive breast cancer cells, while miR-145 and miR-206 could speed up the evolution of cure techniques for TNBC. To conclude, miRNAs will be presented as hopeful molecules to be used in the primary diagnosis, prognosis, and treatment of BC and battle as opposed to its developed drug resistance.

Keywords: breast cancer, HER2 positive, miRNA, TNBC

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Authors: Oluyomi Stephen Adeyemi, Kentaro Kato

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Toxoplasma gondii is the etiological agent of toxoplasmosis, a common parasitic disease capable of infecting a range of hosts, including nearly one-third of the human population. Current treatment options for toxoplasmosis patients are limited. In consequence, toxoplasmosis represents a large global burden that is further enhanced by the shortcomings of the current therapeutic options. These factors underscore the need for better anti-T. gondii agents and/or new treatment approach. In the present study, we sought to find out whether preparing and capping nanoparticles (NPs) in amino acids, would enhance specificity toward the parasite versus the host cell. The selection of amino acids was premised on the fact that T. gondii is auxotrophic for some amino acids. The amino acid-nanoparticles (amino-NPs) were synthesized, purified and characterized following established protocols. Next, we tested to determine the anti-T. gondii activity of the amino-NPs using in vitro experimental model of infection. Overall, our data show evidence that supports enhanced and excellent selective action against the parasite versus the host cells by amino-NPs. The findings are promising and provide additional support that warrants exploring the prospects of NPs as alternative anti-parasite agents. In addition, the anti-parasite action by amino-NPs indicates that nutritional requirement of parasite may represent a viable target in the development of better alternative anti-parasite agents. Furthermore, data suggest the anti-parasite mechanism of the amino-NPs involves multiple cellular processes including the production of reactive oxygen species (ROS), modulation of hypoxia-inducing factor-1 alpha (HIF-1α) as well as the activation of kynurenine pathway. Taken together, findings highlight further, the prospects of NPs as alternative source of anti-parasite agents.

Keywords: drug discovery, infectious diseases, mode of action, nanomedicine

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Authors: Santhani M. Selveindran

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Background: Natural disasters are traumatic global events that are becoming increasing more common, with significant psychosocial impact on survivors. This impact results not only in psychosocial distress but, for many, can lead to psychosocial disorders and chronic psychopathology. While there are currently available interventions that seek to prevent and treat these psychosocial sequelae, their effectiveness is uncertain. The evidence-base is emerging with more primary studies evaluating the effectiveness of various psychosocial interventions for survivors of natural disasters, which remains to be synthesized. Aim of Review: To identify, critically appraise and synthesize the current evidence-base on the effectiveness of psychosocial interventions in preventing or treating Post-Traumatic Stress Disorder (PTSD), Major Depressive Disorder (MDD) and/or Generalized Anxiety Disorder (GAD) in adults and children who are survivors of natural disasters. Methods: A protocol was developed as a guide to carry out this review. A systematic search was conducted in eight international electronic databases, three grey literature databases, one dissertation and thesis repository, websites of six humanitarian and non-governmental organizations renowned for their work on natural disasters, as well as bibliographic and citation searching for eligible articles. Papers meeting the specific inclusion criteria underwent quality assessment using the Downs and Black checklist. Data were extracted from the included papers and analysed by way of narrative synthesis. Results: Database and website searching returned 3777 papers where 31 met the criteria for inclusion. Additional 2 papers were obtained through bibliographic and citation searching. Methodological quality of most papers was fair. Twenty-five studies evaluated psychological interventions, five, social interventions whereas three studies evaluated ‘mixed’ psychological and social interventions. All studies, irrespective of methodological quality, reported post-intervention reductions in symptom scores for PTSD, depression and/or anxiety and where assessed, reduced diagnosis of PTSD and MDD, and produced improvements in self-efficacy and quality of life. Statistically significant results were seen in 27 studies. However, three studies demonstrated that the evaluated interventions may not have been very beneficial. Conclusions: The overall positive results suggest that any psychosocial interventions are favourable and should be delivered to all natural disaster survivors, irrespective of age, country, and phase of disaster. Yet, heterogeneity and methodological shortcomings of the current evidence-base makes it difficult to draw definite conclusions needed to formulate categorical guidance or frameworks. Further, rigorously conducted research is needed in this area, although the feasibility of such, given the context and nature of the problem, is also recognized.

Keywords: psychosocial interventions, natural disasters, survivors, effectiveness

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Authors: Kang-Hyun Leem, Myung-Gyou Kim, Hye Kyung Kim

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Deer antler, traditionally used as a tonic and valuable drug in oriental medicine, has been considered to possess bone-strengthening activity. The upper section, mid section, and base of the antler has been known to exhibit different biological properties. Present study was performed to examine the effects of different parts of deer antler extract (DH) on osteogenic gene expressions in MG-63 cells and longitudinal bone growth in adolescent male rats. The expressions of osteogenic genes, collagen, alkaline phosphatase, osteocalcin, and osteopontin, were measured by quantitative real-time PCR. Longitudinal bone growth was measured in 3-week-old male Sprague-Dawley rats using fluorescence microscopy. To examine the effects on the growth plate metabolism, the total height of growth plate and bone morphogenetic protein-2 (BMP-2) were measured. Collagen and osteocalcin mRNA expressions were increased by all three parts of the DH treatment while osteopontin gene expression was not affected by any of the DH treatment. Alkaline phosphatase gene expression was increased by upper and mid part of DH while base part of DH fails to affect alkaline phosphatase gene expression. The upper and mid parts of the DH treatment enhanced longitudinal bone growth and total height of growth plate. The induction of BMP-2 protein expression in growth plate assessed by immunostaining was also promoted by upper and mid parts of the DH treatment. These results suggest that DH, especially upper and mid parts, stimulate osteogenic gene expressions and have the effect on bone growth in adolescent rats and might be used for the growth delayed adolescent and inherent growth failure patient.

Keywords: bone morphogenetic protein-2, deer antler, longitudinal bone growth, osteogenic genes

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Authors: Faisal A. Salih

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Vinpocetine (Vin) is an ethyl ester of apovincamic acid and is a semisynthetic derivative of vincamine, an alkaloid from plants of the genus Periwinkle (plant) vinca minor. It was found that this compound stimulates cerebral metabolism: it increases the uptake of glucose and oxygen, as well as the consumption of these substances by the brain tissue. Vinpocetine enhances the flow of blood in the brain and has a vasodilating, antihypertensive, and antiplatelet effect. Vinpocetine seems to improve the human ability to acquire new memories and restore memories that have been lost. This drug has been clinically used for the treatment of cerebrovascular disorders such as stroke and dementia memory disorders, as well as in ophthalmology and otorhinolaryngology. It has no side effects, and no toxicity has been reported when using vinpocetine for a long time. For the quantitative determination of Vin in dosage forms, the HPLC methods are generally used. A promising alternative is potentiometry with Vin- selective electrode, which does not require expensive equipment and materials. Another advantage of the potentiometric method is that the pills and solutions for injections can be used directly without separation from matrix components, which reduces both analysis time and cost. In this study, it was found that the choice of a good plasticizer an electrode with the following membrane composition: PVC (32.8 wt.%), ortho-nitrophenyl octyl ether (66.6 wt.%), tetrakis-4-chlorophenyl borate (0.6 wt.%) exhibits excellent analytical performance: lower detection limit (LDL) 1.2•10⁻⁷ M, linear response range (LRR) 1∙10⁻³–3.9∙10⁻⁶ M, the slope of the electrode function 56.2±0.2 mV/decade). Vin masses per average tablet weight determined by direct potentiometry (DP) and potentiometric titration (PT) methods for the two different sets of 10 tablets were (100.35±0.2–100.36±0.1) mg for two sets of blister packs. The mass fraction of Vin in individual tablets, determined using DP, was (9.87 ± 0.02–10.16 ±0.02) mg, while the RSD was (0.13–0.35%). The procedure has very good reproducibility, and excellent compliance with the declared amounts was observed.

Keywords: vinpocetine, potentiometry, ion selective electrode, pharmaceutical analysis

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Authors: Amira Abdelrasoul

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This study aimed to ascertain the controlled permeability of biomimetic cellulose triacetate (CTA) membranes by investigating the electrical oscillatory behavior across impregnated membranes (IM). The biomimetic CTA membranes were infused with a fatty acid to induce electrical oscillatory behavior and, hence, to ensure controlled permeability. In situ synchrotron radiation micro-computed tomography (SR-μCT) at the BioMedical Imaging and Therapy (BMIT) Beamline at the Canadian Light Source (CLS) was used to evaluate the main morphology of IMs compared to neat CTA membranes to ensure fatty acid impregnation inside the pores of the membrane matrices. A monochromatic beam at 20 keV was used for the visualization of the morphology of the membrane. The X-ray radiographs were recorded by means of a beam monitor AA-40 (500 μm LuAG scintillator, Hamamatsu, Japan) coupled with a high-resolution camera, providing a pixel size of 5.5 μm and a field of view (FOV) of 4.4 mm × 2.2 mm. Changes were evident in the phase transition temperatures of the impregnated CTA membrane at the melting temperature of the fatty acid. The pulsations of measured voltages were related to changes in the salt concentration of KCl in the vicinity of the electrode. Amplitudes and frequencies of voltage pulsations were dependent on the temperature and concentration of the KCl solution, which controlled the permeability of the biomimetic membranes. The presented smart biomimetic membrane successfully combined porous polymer support and impregnating liquid not only imitate the main barrier properties of the biological membranes but could be easily modified to achieve some new properties, such as facilitated and active transport, regulation by chemical, physical and pharmaceutical factors. These results open new frontiers for the facilitation and regulation of active transport and permeability through biomimetic smart membranes for a variety of biomedical and drug delivery applications.

Keywords: biomimetic, membrane, synchrotron, permeability, morphology

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Authors: Nassima Elyebdri, Asma Boumediou, Soumia Addoun

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Traditional medicine has been part of the Algerian culture for decades. In particular, the city of Tlemcen still retains practices based on phytotherapy to the present day, as this kind of medicine fulfills the needs of its followers among the local population. The toxic plants contain diverse natural substances which supplied a lot of medicine in the pharmaceutical industry. In order to explore new medicinal sources among toxic plants, an ethnobotanical study was carried out on the use of these plants by the population, at Emir Abdelkader Square of the city of Tlemcen, a rather busy place with a high number of traditional health practitioners and herbalists. This is a descriptive and transversal study aimed at estimating the frequency of using toxic plants among the studied population, for a period of 4 months. The information was collected, using self-anonymous questionnaires, and analyzed by the IBM SPSS Statistics software used for statistical analysis. A sample of 200 people, including 120 women and 80 men, were interviewed. The mean age was 41 ± 16 years. Among those questioned, 83.5% used plants; 8% of them used toxic plants and 35% used plants that can be toxic under certain conditions. Some improvements were observed in 88% of the cases where toxic plants were used. 80 medicinal plants, belonging to 36 botanical families, were listed, identified and classified. The most frequent indications for these plants were for respiratory diseases in 64.7% of cases, and for digestive disorders in 51.5% of cases. 11% of these plants are toxic, 26% could be toxic under certain conditions. Among toxics plants, the most common ones are Berberis vulgaris with 5.4%, indicated in the treatment of uterine fibroids and thyroid, Rhamnus alaternus with 4.8% for hepatic jaundice, Nerium oleander with 3% for hemorrhoids, Ruta chalepensis with 1.2%, indicated for digestive disorders and dysmenorrhea, and Viscum album with 1.2%, indicated for respiratory diseases. The most common plants that could be toxic are Mentha pulegium (15.6%), Eucalyptus globulus (11.4%), and Pimpinella anisum (10.2%). This study revealed interesting results on the use of toxic plants, which are likely to serve as a basis for further ethno-pharmacological investigations in order to get new drug sources.

Keywords: ethnobotany, phytotherapy, Tlemcen, toxic plants

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Authors: Neelima Rashmi Lakra

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India was among one of the highly developed economy up to 1850 due to its cottage industries. During the end of the 18th century, modern industrial enterprises began with the first cotton mill in Bombay, the jute mill near Calcutta and the coal mine in Raniganj. This was counted as the real beginning of industry in 1854 in India. Prior to this period people concentrated only to agriculture, menial service or handicraft, and the introduction of industries exposed them to the disciplines of factory which was very tedious for them. With increasing number of factories been setup adding on to mining and introduction of railway, World War Period (1914-19), Second World War Period (1939-45) and the Great Depression (1929-33) there were visible change in the nature of work for the people, which resulted in outburst of strike for various reasons in these factories. Here, with India’s independence there was emergence of public sector industries and labour legislations were introduced. Meanwhile, trade unions came to notice to the rescue of the oppressed but failed to continue till long. Soon after, with the New Economic Policy organisations came across to face challenges to perform their best, where social justice for the workmen was in question. On these backdrops, studies were found discussing the central human capabilities which could be addressed through Social Security schemes. Therefore, this study was taken up to look at the reforms and legislations mainly meant for the welfare of the labour. This paper will contribute to the large number of Indian population who are serving in public sectors in India since the introduction of industries and will complement the issue of social justice through social security measures among this huge crowd serving the nation. The objectives of the study include; to find out what labour Legislations have already been existing in India, the role of Trade Union Movement, to look at the effects of New Economic Policy on these reforms and its effects and measures taken for the workforce employed in the public sectors and finally, if these measures fulfil the social justice aspects for the larger society on whole. The methodology followed collection of data from books, journal articles, reports, company reports and manuals focusing mainly on Indian studies and the data was analysed following content analysis method. The findings showed the measures taken for Social Security, but there were also reflections of very few particular additions or amendments to these Acts and provisions with the onset of New Liberalisation Policy. Therefore, the study concluded examining the social justice aspects in the context of a developing economy and discussing the recommendations.

Keywords: public sectors, social justice, social security schemes, trade union movement

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Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

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Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

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Authors: Fitsumbrhan Tajebe, Fadil Murad, Mitikie Tigabie, Mareye Abebaw, Tadele Alemu, Sefanit Abate, Rezika Mohammedw, Arega Yeshanew, Elias Shiferaw

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Background: Visceral leshimaniasis is a parasitic disease characterized by a systemic infection of phagocytic cells. Hematological parameters of these patients may be affected by the progress of the disease or treatment. Thus, the current study aimed to assess the hematological profiles of visceral leishmaniasis patients before and after treatment. Method: An institutional based retrospective cohort study was conducted among visceral leishmaniasis patients at University of Gondar Comprehensive Specialized Referral Hospital Leishmaniasis Research and Treatment Center from 2013 to 2018. Hematological profiles before initiation and after completion of treatment were extracted from registration book. Descriptive statics was presented using frequency and percentage. Paired t-test and Wilcoxon Signed rank test were used for comparing mean difference for normally and non- normally distributed data, respectively. Spearman and Pearson correlation analysis was used to describe the correlation of hematological parameters with different variables. P value < 0.05 was considered as statistically significant. Result: Except absolute nerutrophil count, post treatment hematological parameters show a significant increment compared to pretreatment one. The prevalence of anemia, leucopenia and thrombocytopenia was 85.5%, 83.4% and 75.8% prior to treatment and it was 58.3%, 38.2% and 19.2% after treatment, respectively. Moreover, parasite load of the disease showed statistically significant negative correlation with hematological profiles mainly with white blood cell and red blood cell. Conclusion: Majority of hematological profiles of patients with active VL have been restored after treatment, which might be associated with treatment effect on parasite proliferation and concentration of parasite in visceral organ, which directly affect hematological profiles.

Keywords: visceral leshimaniasis, hematological profile, anti-leshimanial drug, Gondar

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Authors: Vladimir Zobov, Nail Nazarov, Alexandra Vyshtakalyuk, Vyacheslav Semenov, Irina Galyametdinova, Vladimir Reznik

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The aim of this study was to investigate hepatoprotective properties of the Xymedon derivative L-ascorbate 1- (2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropyrimidine-2-one (XD), which exhibits high efficiency as actoprotector. The study was carried out on 68 male albino rats weighing 250-400 g using preventive exposure to the test preparation. Effectiveness of XD win comparison with effectiveness of Xymedon (original substance) after administration of the compounds in identical doses. Maximum dose was 20 mg/kg. The animals orally received Xymedon or its derivative in doses of 10 and 20 mg/kg over 4 days. In 1-1.5 h after drug administration, CCl4 in vegetable oil (1:1) in a dose of 2 ml/kg. Controls received CCl4 but without hepatoprotectors. Intact control group consisted of rats, not receiving CCl4 or other compounds. The next day after the last administration of CCl4 and compounds under study animals were dehematized under ether anesthesia, blood and liver samples were taken for biochemical and histological analysis. Xymedon and XD administered according to the preventice scheme, exerted hepatoprotective effects: Xymedon — in the dose of 20 mg/kg, XD — in doses of 10 and 20 mg/kg. The drugs under study had different effects on liver condition, affected by induction with CCl4. Xymedon had a more pronounced effect both on the ALT level, which can be elevated not only due to destructive changes in hepatocytes, but also as a cholestasis manifestation, and on the serum total protein level, which reflects protein synthesis in liver. XD had a more pronounced effect on AST level, which is one of the markers of hepatocyte damage. Lower effective dose of XD — 10 mg/kg, compared to Xymedon effective according to, and its pronounced effect on AST, the hepatocyte cytolysis marker, is indicative of its higher preventive effectiveness, compared to Xymedon. This work was performed with the financial support of Russian Science Foundation (grant No: 14-50-00014).

Keywords: hepatoprotectors, pyrimidine derivatives, toxic liver damage, xymedon

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Authors: Lakmali Anthony, Madeline Gillies

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Background: Colorectal cancer (CRC) is usually managed with surgical resection. Many of the outcomes traditionally used to define successful operative management, such as resection margin, do not adequately reflect patients’ experience. Patient-reported outcomes (PRO), such as Health-Related Quality of life (HRQoL), provide a means by which the impact of surgery for cancer can be reported in a patient-centered way. HRQoL has previously been shown to be impacted by psychosocial, behavioral and disease-specific characteristics. This exploratory cross-sectional study aims to; (1) describe postoperative HRQoL in patients who underwent primary resection in a regional Australian hospital; (2) describe the prevalence of anxiety, depression and clinically significant fear of cancer recurrence (FCR) in this population; and (3) identify demographic, psychosocial, disease and treatment factors associated with poorer self-reported HRQoL. Methods: Consecutive patients who had resection of colorectal cancer in a single regional Australian hospital between 2015 and 2022 were eligible. Participants were asked to complete a survey instrument designed to assess HRQoL, as well as validated instruments that assess several other psychosocial PROs hypothesized to be associated with HRQoL; emotional distress, fear of cancer recurrence, social support, dispositional optimism, body image and spirituality. Demographic and disease-specific data were also collected via medical record review. Results: Forty-six patients completed the survey. Clinically significant levels of fear of recurrence as well as emotional distress, were present in this group. Many domains of HRQoL were significantly worse than an Australian reference population for CRC. Demographic and disease factors associated with poor HRQoL included smoking and ongoing adjuvant systemic therapy. The primary operation was not associated with HRQoL; however, the operative approach (laparoscopic vs. open) was associated with HRQoL for these patients. All psychosocial factors measured were associated with HRQoL, including cancer worry, emotional distress, body image and dispositional optimism. Conclusion: HRQoL is an important outcome in surgery for both research and clinical practice. This study provides an overview of the quality of life in a regional Australian population of postoperative colorectal cancer patients and the factors that affect it. Understanding HRQoL and awareness of patients particularly vulnerable to poor outcomes should be used to aid the informed consent and shared decision-making process between surgeon and patient.

Keywords: surgery, colorectal, cancer, PRO, HRQoL

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Authors: Nitin Kumar

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Purpose: The current research work focuses mainly on evolving a delivery system for ginseng extract (GE), which in turn will ameliorate the neuroprotective potential by means of enhancing the ginsenoside (Rb1) bio-availability (BA). For more noteworthy enhancement in oral bioavailability (OBA) along with pharmacological properties, the drug carriers’ performance can be strengthened by utilizing phytosomes-loaded microspheres (PM) delivery system. Methods: For preparing the disparate phytosome complexes (F1, F2, and F3), an aqueous extract of ginseng roots (GR) along with phospholipids were reacted in disparate ratio. Considering the outcomes, F3 formulation (spray-dried) was chosen for preparing the phytosomes powder (PP), PM, and extract microspheres (EM). PM was made by means of loading of F3 into Gum Arabic (GA) in addition to maltodextrin polymer mixture, whereas EM was prepared by means of the addition of extract directly into the same polymer mixture. For investigating the neuroprotective effect (NPE) in addition to their pharmacokinetic (PK) properties, PP, PM, and EM formulations were assessed. Results: F3 formulation gave enhanced entrapment efficiency (EE) (i.e., 50.61%) along with good homogeneity of spherical shaped particle size (PS) (42.58 ± 1.4 nm) with least polydispersity index (PDI) (i.e., 0.193 ± 0.01). The sustained release (up to 24 h) of ginsenoside Rb1 (GRb1) is revealed by the dissolution study of PM. A significantly (p < 0.05) greater anti-oxidant (AO) potential of PM can well be perceived as of the diminution in the lipid peroxidase level in addition to the rise in the glutathione superoxide dismutase (SOD) in addition to catalase levels. It also showed a greater neuroprotective potential exhibiting significant (p < 0.05) augmentation in the nociceptive threshold together with the diminution in damage to nerves. A noteworthy enhancement in the relative BA (157.94%) of GRb1 through the PM formulation can well be seen in the PK studies. Conclusion: It is exhibited that the PM system is an optimistic and feasible strategy to enhance the delivery of GE for the effectual treatment of neuropathic pain.

Keywords: ginseng, neuropathic, phytosome, pain

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Authors: Abdorrasoul Malekpour, Mohammad Ghorbani Mojtaba Mortazavi, Mohammadreza Fattahi, Mohammad Hassan Meshkibaf, Ali Fakhrzad, Saeid Salehi, Saeideh Zahedi, Amir Ahmadimoghaddam, Parviz Farzadnia Dr., Mohammadreza Hajyani Asl Bs

Abstract:

Hepatitis B as an infectious disease has eight main genotypes (A–H). The aim of this study is to Bioinformatically identify Rare Codon Clusters (RCC) in proteins structure of HBV. For detection of protein family accession numbers (Pfam) of HBV proteins; used of uni-prot database and Pfam search tool were used. Obtained Pfam IDs were analyzed in Sherlocc program and RCCs in HBV proteins were detected. In further, the structures of TrEMBL entries proteins studied in PDB database and 3D structures of the HBV proteins and locations of RCCs were visualized and studied using Swiss PDB Viewer software. Pfam search tool have found nine significant hits and 0 insignificant hits in 3 frames. Results of Pfams studied in the Sherlocc program show this program not identified RCCs in the external core antigen (PF08290) and truncated HBeAg protein (PF08290). By contrast the RCCs become identified in Hepatitis core antigen (PF00906) Large envelope protein S (PF00695), X protein (PF00739), DNA polymerase (viral) N-terminal domain (PF00242) and Protein P (Pf00336). In HBV genome, seven RCC identified that found in hepatitis core antigen, large envelope protein S and DNA polymerase proteins and proteins structures of TrEMBL entries sequences that reported in Sherlocc program outputs are not complete. Based on situation of RCC in structure of HBV proteins, it suggested those RCCs are important in HBV life cycle. We hoped that this study provide a new and deep perspective in protein research and drug design for treatment of HBV.

Keywords: rare codon clusters, hepatitis B virus, bioinformatic study, infectious disease

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Authors: Christine Ysabelle G. Roman, Pauline Torres

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Background: Hypertrophic cardiomyopathy is a disease of marked heterogeneity. It is a genetically determined heart disease characterized by significant myocardium hypertrophy that results in diastolic dysfunction, left ventricular outflow tract obstruction, and an increased risk of arrhythmias. The primary treatment in patients with such conditions is negative inotropic drugs, such as beta-blockers, calcium channel antagonists, and disopyramide. However, for those who remain symptomatic and need septal reduction therapy, surgical septal myectomy or alcohol septal ablation are options. Case Summary: A 19 – year old female presented in the authors’ institution with easy fatigability. The consult was done a year prior, and 2D echocardiography was requested which showed concentric left ventricular hypertrophy, asymmetrically hypertrophied interventricular septum (IVS) with the largest diameter of 3.3cm & subaortic dynamic obstruction with a maximum gradient of 47 mmHg. A repeat echo a year later showed asymmetric septal hypertrophy (IVS measuring at 3cm) with the systolic anterior motion of anterior mitral valve leaflet and left ventricular outflow tract obstruction (peak gradient of 50mmHg). The patient then underwent alcohol septal ablation and was discharged stable after four days of admission. Conclusion: Hypertrophic obstructive cardiomyopathy, a cardiovascular genetic disease, results in various patterns of left ventricular hypertrophy and abnormality of mitral valve apparatus. The patient is managed medically initially. However, despite optimal drug therapy and significant left ventricular outflow tract obstruction, significant heart failure symptoms or syncope require invasive treatment.

Keywords: hypertrophic obstructive cardiomyopathy, left ventricular outflow tract obstruction, alcohol septal ablation, alcohol

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

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

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

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Authors: M. Ardelean, F. Manea, A. Pop, J. Schoonman

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The presence of pharmaceuticals in the environment and especially in water has gained increasing attention. They are included in emerging class of pollutants, and for most of them, legal limits have not been set-up due to their impact on human health and ecosystem was not determined and/or there is not the advanced analytical method for their quantification. In this context, the development of various advanced analytical methods for the quantification of pharmaceuticals in water is required. The electrochemical methods are known to exhibit the great potential for high-performance analytical methods but their performance is in direct relation to the electrode material and the operating techniques. In this study, two types of carbon-based electrodes materials, i.e., boron-doped diamond (BDD) and carbon nanofiber (CNF)-epoxy composite electrodes have been investigated through voltammetric techniques for the detection of naproxen in water. The comparative electrochemical behavior of naproxen (NPX) on both BDD and CNF electrodes was studied by cyclic voltammetry, and the well-defined peak corresponding to NPX oxidation was found for each electrode. NPX oxidation occurred on BDD electrode at the potential value of about +1.4 V/SCE (saturated calomel electrode) and at about +1.2 V/SCE for CNF electrode. The sensitivities for NPX detection were similar for both carbon-based electrode and thus, CNF electrode exhibited superiority in relation to the detection potential. Differential-pulsed voltammetry (DPV) and square-wave voltammetry (SWV) techniques were exploited to improve the electroanalytical performance for the NPX detection, and the best results related to the sensitivity of 9.959 µA·µM^-1 were achieved using DPV. In addition, the simultaneous detection of NPX and fluoxetine -a very common antidepressive drug, also present in water, was studied using CNF electrode and very good results were obtained. The detection potential values that allowed a good separation of the detection signals together with the good sensitivities were appropriate for the simultaneous detection of both tested pharmaceuticals. These results reclaim CNF electrode as a valuable tool for the individual/simultaneous detection of pharmaceuticals in water.

Keywords: boron-doped diamond electrode, carbon nanofiber-epoxy composite electrode, emerging pollutans, pharmaceuticals

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Authors: Zinhle Cindi, Collet Dandara, Mpiko Ntsekhe, Edson Makambwa, Miguel Larceda

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Background: Warfarin is the most commonly used drug in the management of thromboembolic disease. However, there is a huge variability in the time, number of doses or starting doses for patients to achieve the required international normalised ratio (INR) which is compounded by a narrow therapeutic index. Many genetic-association studies have reported on European and Asian populations which have led to the designing of specific algorithms that are now being used to assist in warfarin dosing. However, very few or no studies have looked at the pharmacogenetics of warfarin in African populations, yet, huge differences in dosage requirements to reach the same INR have been observed. Objective: We set out to investigate the distribution of 3 SNPs CYP4F2 c.1347C > T, VKORC1 g.-1639G > A and VKORC1 c.1173C > T among South African Mixed Ancestry (MA) and Black African patients. Methods: DNA was extracted from 383 participants and subsequently genotyped using PCR/RFLP for the CYP4F2 c.1347 (V433M) (rs2108622), VKORC1 g.-1639 (rs9923231) and VKORC1 c.1173 (rs9934438) SNPs. Results: Comparing the Black and MA groups, significant differences were observed in the distribution of the following genotypes; CYP4F2 c.1347C/T (23% vs. 39% p=0.03). All VKORC1 g.-1639G > A genotypes (p < 0.006) and all VKORC1 c.1173C > T genotypes (p < 0.007). Conclusion: CYP4F2 c.1347T (V433M) reduces CYP4F2 protein levels and therefore expected to affect the amount of warfarin needed to block vitamin k recycling. The VKORC1 g-1639A variant alters transcriptional regulation therefore affecting the function of vitamin k epoxide reductase in vitamin k production. The VKORC1 c.1173T variant reduces the enzyme activity of VKORC1 consequently enhancing the effectiveness of warfarin. These are preliminary results; more genetic characterization is required to understand all the genetic determinants affecting how patients respond to warfarin.

Keywords: algorithms, pharmacogenetics, thromboembolic disease, warfarin

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Authors: Ziyad S. Haidar

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Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

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Authors: Tamer M. Shehata

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Objective: Currently, mucoadhesive microparticles acquired a high interest in both research and pharmaceutical technology fields. Recently, BÜCHI lunched its latest fourth generation nano spray dryer B-90 used for nanoparticle production. B-90 offers an elegant technology combined particle engineering and drying in one step. In our laboratory, we successfully developed a new formulation for metformin hydrochloride, mucoadhesive microparticles utilizing B-90 technology for treatment of type 2-diabetis. Method: Gelatin or sodium alginate, natural occurring polymers with mucoadhesive properties, solely or in combination was used in our formulation trials. Preformulation studies (atomization head mesh size, flow rate, head temperature, polymer solution viscosity and surface tension) and postformulation characters (particle size, flowability, surface scan and dissolution profile) were evaluated. Finally, hypoglycemic effect of the selected formula was evaluated in streptozotocin-induced diabetic rats. Spray head with 7 µm hole, flow rate of 3.5 mL/min and head temperature 120 ºC were selected. Polymer viscosity was less than 11.5 cP with surface tension less than 70.1 dyne/cm. Result: Discrete, non aggregated particles and free flowing powders with particle size was less than 2000 nm were obtained. Gelatin and sodium alginate combination in ratio 1:3 were successfully sustained the in vitro release profile of the drug. Hypoglycemic evaluation of the previous formula, showed a significant reduction of blood glucose level over 24 h. Conclusion: B-90 technology can open a new era of , mucoadhesive microparticles preparation offering convenient dosage form that can enhance compliance of type 2 diabetic patients.

Keywords: mucoadhesive, microparticles, technology, diabetis

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Authors: Shahnaz Haque, Anand Shukla, Sunita Singh, Anil Kem

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Introduction: Diabetes Mellitus is a chronic metabolic disease affecting millions worldwide. Metformin is the most commonly prescribed first line oral hypoglycemic drug for type 2 diabetes mellitus, but due to progressive worsening of blood glucose control during the natural history of type 2 diabetes, combination therapy usually becomes necessary. Objective: This study was designed to assess the treatment satisfaction between Sitagliptin versus Pioglitazone added to Metformin in patients with type 2 diabetes mellitus (T2DM). Methods: We conducted a prospective, open label, randomized, parallel group study in SIMS, Hapur, U.P. Eligible patients fulfilling inclusion criteria were randomized into two groups having 25 patients in each group using tab Sitagliptin 100mg, tab Pioglitazone 30mg added to ongoing tab Metformin (500mg) therapy for 16 weeks. The follow-up visits were on weeks 4,12 and 16. Result: 16 weeks later, addition of Sitagliptin 100mg compared to that of Pioglitazone 30 mg to ongoing Metformin therapy provided similar glycosylated hemoglobin (HbA1c) lowering efficacy in patients with T2DM with inadequate glycemic control on metformin monotherapy. Change in HbA1c in group1 was -0.656±0.21%(p<0.0001) whereas in group2 was -0.748±0.35%(p<0.0001). Hence decrease in HbA1c from baseline was more in group2. Both treatments were well tolerated with negligible risk of hypoglycaemia. Weight loss was observed with Sitagliptin in contrast to weight gain seen in Pioglitazone. Conclusion: In this study, Sitagliptin 100 mg along with metformin therapy in comparison to pioglitazone 30 mg plus metformin therapy was both effective, well-tolerated and improved glycemic control in both the groups. Addition of pioglitazone had cause oedema and weight gain to the patients whereas sitagliptin caused weight loss in its patients.

Keywords: sitagliptin, pioglitazone, metformin, type 2 diabetes mellitus

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Authors: S. B. Otieno1, F. Were, A. Afullo, K. Waza

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Background: Multi drug resistance HIV has emerged rendering the current conventional treatment of HIV ineffective. There is a need for new treatment regime which is cheap, effective and not prone to resistance development by HIV. Methods: In randomized clinical study of 68 HIV positive children 3 – 15 years to asses the efficacy of yeast selenium in HIV/AIDS patients, 50μ yeast selenium was administered to 34 children while in matched control of 34 were put on placebo. Blood samples and weight of the both groups which were taken every 3 months intervals up to 6 months, were analyzed by ELIZA for CD4T cells, the data was analyzed by SPSS version 16, WAZ scores were analyzed by Epi Info version 6. Results: No significant difference in age { χ2 (1, 62) =0.03, p =0.853}, cause of morbidity between test and controls {χ2 (1, 65) = 5.87, p= 0.015} and on condition of foster parents {χ2 ( 1,63) = 5.57, p= 0.0172} was observed. Children on selenium showed progressive improvement of WAZ and significant difference at six months {F (5,12) = =5.758, P=0.006}, and weight gain of up to 4.1 kilograms in six months, and significant CD4 T cell count increase t= -2.943, p<0.05 compared to matched controls t = -1.258 p> 0.05. CD4 T cell count increased among all age groups on test 3-5 years (+ 267.1),5-8 years (+200.3) 9-15 years (+71.2) cells/mm3 and in matched controls a decrease 3-5 years (-71), 5-8 years (-125) and 9-13 years (-10.1) cells/mm3 . No significant difference inCD4 T cell count between boys {F (2, 32) = 1.531 p= 0.232} and between boys {F (2, 49) = 1.040, p= 0.361} on test and between boys and girls {F (5, 81) = 1.379, p= 0.241} on test. Similarly no significant difference between boys and girls were observed {F (5, 86) = 1.168, p= 0.332}.In the test group there was significant positive correlation β =252.23 between weight for age (WAZ), and CD4 T Cell Count p=0.007, R2= 0.252, F< 0.05. In matched controls no significant correlation between weight gain and CD4 T cell count change was observed at six months p > 0.05. No positive correlation β =-138.23 was observed between CD4T Cell count, WAZ, p=0.934, R2 =0.0337 F >0.05. Majority (96.78%) of children on test either remained or progressed to WHO immunological stage I. Conclusion: From this study it can be concluded that yeast Selenium is effective in slowing the progress of HIV 1 in children from WHO clinical stage I by improving CD4 T cell count and hence the immunity.

Keywords: selenium, HIV, AIDS, WAZ

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