Search results for: anabolic steroids

Authors: Milica Ž. Karadžić, Lidija R. Jevrić, Sanja Podunavac-Kuzmanović, Strahinja Z. Kovačević, Anamarija I. Mandić, Katarina Penov-Gaši, Andrea R. Nikolić, Aleksandar M. Oklješa

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This study considered selection of the in silico molecular descriptors and the models for newly synthesized steroid derivatives description and their characterization using chemometric techniques. Multiple linear regression (MLR) models were established and gave the best molecular descriptors for quantitative structure-retention relationship (QSRR) modeling of the retention of the investigated molecules. MLR models were without multicollinearity among the selected molecular descriptors according to the variance inflation factor (VIF) values. Used molecular descriptors were ranked using generalized pair correlation method (GPCM). In this method, the significant difference between independent variables can be noticed regardless almost equal correlation between dependent variable. Generated MLR models were statistically and cross-validated and the best models were kept. Models were ranked using sum of ranking differences (SRD) method. According to this method, the most consistent QSRR model can be found and similarity or dissimilarity between the models could be noticed. In this study, SRD was performed using average values of experimentally observed data as a golden standard. Chemometric analysis was conducted in order to characterize newly synthesized steroid derivatives for further investigation regarding their potential biological activity and further synthesis. This article is based upon work from COST Action (CM1105), supported by COST (European Cooperation in Science and Technology).

Keywords: generalized pair correlation method, molecular descriptors, regression analysis, steroids, sum of ranking differences

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Authors: Supannika Klangphukhiew, Roongnapa Srichana, Rina Patramanon

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Cortisol has been used as a well-known commercial stress biomarker. A homeostasis response to psychological stress is indicated by an increased level of cortisol produced in hypothalamus-pituitary-adrenal (HPA) axis. Chronic psychological stress contributing to the high level of cortisol relates to several health problems. In this study, the cortisol biosensor was fabricated that mimicked the natural receptors. The artificial antibodies were prepared using molecular imprinted polymer technique that can imitate the performance of natural anti-cortisol antibody with high stability. Cortisol-molecular imprinted polymer (cortisol-MIP) was obtained using the multi-step swelling and polymerization protocol with cortisol as a target molecule combining methacrylic acid:acrylamide (2:1) with bisacryloyl-1,2-dihydroxy-1,2-ethylenediamine and ethylenedioxy-N-methylamphetamine as cross-linkers. Cortisol-MIP was integrated to the sensor. It was coated on the disposable screen-printed carbon electrode (SPCE) for portable electrochemical analysis. The physical properties of Cortisol-MIP were characterized by means of electron microscope techniques. The binding characteristics were evaluated via covalent patterns changing in FTIR spectra which were related to voltammetry response. The performance of cortisol-MIP modified SPCE was investigated in terms of detection range, high selectivity with a detection limit of 1.28 ng/ml. The disposable cortisol biosensor represented an application of MIP technique to recognize steroids according to their structures with feasibility and cost-effectiveness that can be developed to use in point-of-care.

Keywords: stress biomarker, cortisol, molecular imprinted polymer, screen-printed carbon electrode

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Authors: Tsige Reda

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Essential oil of Thymus vulgaris was extracted by means of hydro-distillation. This study was done to investigate the chemical composition, antibacterial and antioxidant activities. The chemical composition of the essential oils was determined using gas chromatography coupled to mass spectroscopy (GC-MS). Using disc diffusion assay the antibacterial activity was assessed on one Gram-positive bacteria and one Gram-negative bacteria. The percentage oil yield of the essential oil was found to be 0.97 ± 0.08% (w/w) with yellow color. The physicochemical constants of the oil were also noted. The phytochemical screening of the plant extract revealed the presence of tannins, saponins, phenol, flavonoids, terpenoids, steroids and alkaloids. A total of 18 chemical constituents were identified by Gas Chromatography-Mass Spectroscopy analysis representing 100% of the total essential oil of Thymus vulgaris, with thymol (31.977%), o-cymene (29.992%), and carvacrol (14.541%). Previous studies have revealed that the thymol, o-cymen and carvacrol components of Thymus vulgaris are responsible for their biological activities. Thymus vulgaris have been used traditionally to treat a wide variety of infections. Based on the extensive use and lack of scientific evidence, a study was embarked upon to determine its bioactivity. The essential oil of Thymus vulgaris leaves exhibited higher activity towards the Gram-positive bacteria (Staphylococcus aurous) than the Gram-negative bacteria (Escherichia coli) and also has good antioxidant activity, and can be used medicinal and therapeutic applications. This activity may be due to the high amount of thymol, o-cymen and carvacrol.

Keywords: hydro-distillation, Thymus vulgaris, essential oil composition, phytochemical screening, physicochemical constants, antioxidant activity, antibacterial activity

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Authors: Christianah Adebimpe Dare, Nelson Oghenebrorhie Elvis

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This study was aimed at analysing the phytochemicals in Chrysophyllum albidum cotyledon extract and their in vitro antioxidant and anti-inflammatory effects. The star apple fruit was bought at Igbona market Osogbo, Osun State, Nigeria. The seed from the fruit was removed and defatted. The residue was exhaustively extracted with methanol. The Chrysophyllum albidum cotyledon methanol extract (CCME) was phytochemically screened, flavonoids and phenol contents, antioxidant and anti-inflammatory assays were carried out on the extract using standard procedures. Phytochemicals analysis revealed the presence of steroids, tannins, flavonoid, saponin, triterpenes, and xanthoproteins. The phenolic concentration, total flavonoids concentration, and total sugar concentration were found to be 26.72 ± 0.048 µgTAE/mg, 23.12 ± 1.92µg of Rutin equivalent (RTE)/mg (10.49 ± 1.12µg of Quercetin equivalent (QE/mg) and 778.38 ± 12.82 µg of glucose/ml, respectively. The extract demonstrated significant inhibitory effect compared with the standards as potent antioxidant with percentage inhibition of DPPH as 38.10 %-39.51 %, lipid peroxidation as 45.85 %-65.85 %; ferric reducing power showed linear correlation to the standard and the anti-inflammatory potential with 22.06 %-26.37 % protection of the human red blood membrane and the percentage inhibition of denaturation of albumin 3.42 %-7.32 %. The study showed that C. albidum cotyledon methanol extract is a potent antioxidant and anti-inflammatory agent to combat oxidative stress and pathological diseases caused by reactive species.

Keywords: albumin denaturation, free radicals, lipid peroxidation, reactive species

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Authors: Oseni Margaret Oladunni, Ogundele Joan Olayinka, Olusanya Olalekan Samuel, Akinniyi Modupe Olakintan

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The world's growing population is pushing humans to look for alternative food sources among underutilised or wild plants. One of these food sources has been identified as Canavalia enisiformis, or jack beans. The only issue with using jack beans is that they contain anti-nutrient chemicals, which must be removed or diminished in order for them to be fit for human consumption. The objective of this study is to determine the nutritional and industrial utility of Canavalia enisiformis by analysing the anti-nutrient, phytochemical, and antioxidant composition of raw whole seed and soaking dehusked seeds using established procedures. Phytate (23.48±0.24, 15.24±0.41 and 14.83±0.00), oxalate (4.32±0.09, 3.96±0.09 and 2.88±0.09), tannins (22.77±0.73, 18.68±0.03 and 17.50±0.46), and lectins (6.67±0.04, 6.20±0.01 and 6.42±0.07) exhibited the highest anti-nutrient values in raw whole seed and, at the very least, in dehusked, soaked seeds. The samples were subjected to phytochemical screening, which detected the presence of cardiac glycosides as well as anthraquinones, alkaloids, tannins, saponins, steroids, flavonoids, terpenoids, phlobatannins, and flavonoids. Due to the reduction in phytochemical contents quantified as a result of dehusking and soaking, phenolbatannins and anthraquinones were not found in the samples. The research findings also demonstrated elevated concentrations of several plausible phytochemical components with potential medical value, with the raw whole seed exhibiting the greatest capacity to scavenge free radicals. Accordingly, the study's findings validate the seed's therapeutic applications and imply that it might be an inexpensive source of antioxidants for humans and animals alike.

Keywords: dehusking, soaking, anti-nutrients, antioxidants, jack bean

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Authors: Richard I. Licayan, Aisle Janne B. Dagpin, Romeo M. Del Rosario, Nenita D. Palmes

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Hiptage benghalensis, Antigonon leptopus, Macroptillium atropurpureum, and Dioscorea bulbifera L. are herbal weeds that have been used by traditional healers in rural communities in the Philippines as medicine. In this study, the basic pharmacological components of the crude secondary metabolites extracted from the four herbal weeds and their in vitro antioxidant properties was investigated to provide baseline data for the possible development of these metabolites in pharmaceutical products. Qualitative screening of the secondary metabolites showed that alkaloids, tannins, saponins, steroids, and flavonoids were present in their leaf extracts. All of the plant extracts showed varied antioxidant activity. The greatest DPPH radical scavenging activity was observed in H. begnhalensis (84.64%), followed by A. leptopus (68.21%), M. atropurpureum (26.62%), and D. bulbifera L. (19.04%). The FRAP assay revealed that H. benghalensis had the highest antioxidant activity (8.32 mg/g) while ABTS assay showed that M. atropurpureum had the strongest scavenging ability of free radicals (0.0842 mg Trolox/g). The total flavonoid content (TFC) analysis showed that D. bulbifera L. had the highest TFC (420.35 mg quercetin per gram-dried material). The total phenolic content (TPC) of the four herbal weeds showed large variations, between 26.56±0.160 and 55.91±0.087 mg GAE/g dried material. The plant leaf extracts arranged in increasing values of TPC are H. benghalensis (26.565) < A. leptopus (37.29) < D. bulbifera L. (46.81) < M. atropurpureum (55.91). The obtained results may support their use in herbal medicine and as baseline data for the development of new drugs and standardized phytomedicines.

Keywords: antioxidant properties, total flavonoids, total phenolics, creeping herbal weeds

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Authors: Himanshi Rathore, Shalinee Prasad, Satyawati Sharma, Ajay Singh Yadav

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Medicinal mushrooms are acceptable all over the world not only because they have a unique flavour and texture but also due to the presence of great nutritional, nutraceutical and functional properties. High content of physiologically active substances like ergosterol, vitamin D, phenolic compounds, triterpenoids and steroids make these medicinal mushrooms a key source of nutraceuticals. Calocybe indica is a popular medicinal mushroom of India which is known to possess high amount of secondary metabolites including ergosterol (vitamin D2). The ergosterol gets converted to vitamin D in the presence of UV rays by a photochemical reaction. In lieu of the above facts the present study was undertaken to investigate the effect of UV-B light treatment on the vitamin D2 concentration, phenolic content and non volatile compounds in Calocybe indica. For this study, UV-B light source of intensity 5.3w/m2 was used to expose mushrooms for the time period of 0min, 30min, 60min and 90 min. It was found that the vitamin D2 concentration increased with the time duration i.e. 85±0.15 (0 min), 182±1.6 (30 min), 187±0.4 (60 min) and 182 ±0.8 (90 min) μg/g (dry weight). Highest concentration of vitamin D2 was found at 60 min duration. No discoloration in sliced mushrooms was observed during the exposure time. The results revealed that the exposure of mushrooms for a minimum of 30 min duration under UVB source can be a novel, convenient and cheapest way to increase the vitamin D content in mushrooms. This can be one of richest source to fulfil the recommended dietary allowances of vitamin D in our daily diets. The paper provides information on the enhancement of vitamin D content by UV lights and its effects on the non volatile (soluble sugars, free amino acids, 5′-nucleotides and phenolics) compounds will also be presented.

Keywords: Calocybe indica, ergosterol, nutraceutical, phenolics

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Authors: K. M. Pratap Shankar, Dattatreya Rao, Sai Prasad

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Background: Skin diseases are among the most common health problems worldwide and are associated with a considerable burden. Eczema is such a skin ailment which cause psychological, social and financial burden on the patient and their families. Management of eczema with antibiotics, antihistamines, steroids etc., are available but even after their use relapses, recurrences and other complications are very common. Aim: The aim of this study was to assess the efficacy of leech application in the management of vicarcikā (Eczema) with Histopathological study. Methods: For the present study 10 patients having the classical symptoms of Vicarcikā, were randomly selected as per the inclusion and exclusion criteria from O.P.D. & I.P.D. sections of Śalya department, S.V. Āyurvedic Hospital, Tirupati. Minimum 4 sittings of Leech application was carried out with seven days interval. Total duration of treatment was 6 weeks. Biopsy samples were collected from the lesion site before and after treatment. Histopathological examination was done by the pathologist. Results: In eczema (dermatitis) the leech application therapy gives excellent response by reducing the inflammatory component, hyperkeratosis, spongiosis, irregular acanthosis and by evoking a granulation tissue response in the dermis and in most of the cases with complete recovery from the lesion. Most of the cases in the study were chronic dermatitis and sebhoric keratosis, almost all local/focal pigmented lesions is totally relieved by leech therapy especially in cases of sebhoric keratosis. Conclusion: In the present study it was found that, leech application evokes significant changes at histological level specifically in reduction of inflammatory component, hyperkeratosis, spongiosis and irregular acanthosis. It was also found that there was a considerable formation of granulation tissue, which helps in formation of healthy new tissues.

Keywords: acanthosis, eczema, hyperkeratosis, leech application, spongiosis

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Authors: Yasmin Sayed, Hala Hamdy, Hafez Bazaraa, Hanaa Rady, Sherif Elanwary

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Intravenous and inhaled magnesium sulfate (MgSO₄) had been recently used as an adjuvant therapy in cases suffering from the wheezy chest. Objective: We aimed to determine the possible change in the hemodynamic state in cases received intravenous or inhaled MgSO₄ in comparison to cases received standard treatment in critically ill infants and children with the wheezy chest. Methods: A randomized controlled trial comprised 81 patients suffering from wheezy chest divided into 3 groups. In addition to bronchodilators and systemic steroids, MgSO₄ was given by inhalation in group A, intravenously in group B, and group C didn't receive MgSO₄. The hemodynamic state was determined by assessment of blood pressure, heart rate, capillary refill time and the need for shock therapy or inotropic support just before and 24 hours after receiving treatment in 3 groups. Results: There was no significant difference in the hemodynamic state of the studied groups before and after treatment. Means of blood pressure were 102.2/63.2, 105.1/64.8 before and after inhaled MgSO₄; respectively. Means of blood pressure were 105.5/64.2, 104.1/64.9 before and after intravenous MgSO₄; respectively. Means of blood pressure were 107.4/62.8, 104.4/62.1 before and after standard treatment, respectively. There was a statistically insignificant reduction of the means of the heart rate in group A and group B after treatment rather than group C. There was no associated prolongation in capillary refill time and/or the need for inotropic support or shock therapy after treatment in the studied groups. Conclusion: MgSO₄ is a safe adjuvant therapy and not associated with significant alteration in the hemodynamic state in critically ill infants and children with the wheezy chest.

Keywords: critically ill infants and children, inhaled MgSO₄, intravenous MgSO₄, wheezy chest

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Authors: Nishtha, Richa, Anju Rao

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Plants are the source of herbal medicine and medicinal value of the plants lies in the bioactive phytochemical constituents that produce definite physiological effects on human body. Angiospermic families are known to produce such phytochemical constituents which are termed as secondary plant metabolites. These metabolites include alkaloids, saponins, phenolic compounds, flavonoids, tannins, terpenoids and so on. Solanaceae is one of the important families of Angiosperms known for medicinally important alkaloids such as hyoscyamine, scopolamine, solanine, nicotine, capsaicin etc. Medicinally important species of this family mostly belong to the genera of Datura,Atropa,Solanum,Withania and Nicotiana.Six species such as Datura metel, Solanum torvum, Physalis minima, Cestrum nocturnum, Cestrum diurnum and Nicotiana plumbaginifolia have been collected from different localities of Chandigarh and adjoining areas.Field and anatomical studies helped to identify the plants and their parts used for the study of secondary plant metabolites. Preliminary phytochemcial studies have been done on various parts of plants such as roots, stem and leaves by making aqueous and alcoholic extracts from their powdered forms which showed the presence of alkaloids in almost all the species followed by steroids, flavonoids, terpenoids, tannins etc. HPLC profiles of leaves of Datura metel showed the presence of active compounds such as scopalamine and hyoscyamine and Solanum torvum showed the presence of solanine and solasodine. These alkaloids are important source of drug based medicine used in pharmacognosy. The respective compounds help in treating vomiting, nausea, respiratory disorders, dizziness, asthma and many heart problems.

Keywords: alkaloids, flavanoids, phytochemical constituents, pharmacognosy, secondary metabolites

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Authors: Arun Jyothi Bheemagani, Chakrapani Pullagummi, Anupalli Roja Rani

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Exploration of the chemical constituents of the plants and pharmacological screening may provide us the basis for the development of novel agents. Plants have provided us some of the very important life saving drugs used in the modern medicine. The aim of our work was to screen the phytochemical constituents and antimicrobial and antioxidant activities of methanol extract of leaves of Annona cherimola Mill plant from Tirumala forest, Tirupathi. It was originally called Chirimuya by the Inca people who lived where it was growing in the Andes of South America, is an edible fruit-bearing species of the genus Annona from the family Annonaceae. Annona cherimola Mill is a multipurpose tree with edible fruits and is one of the sources of the medicinal products. The antibacterial activity was measured by agar well diffusion method; the diameter of the zone of bacterial growth inhibition was measured after incubation of plates. The inhibitory effect was studied against the pathogenic bacteria (Klebsiella pneumonia, Bacillus subtilis, Staphylococcus aureus and Escherichia coli (E. coli). Antioxidant assays were also performed for the same extracts by spectrophotometric methods using known standard antioxidants as reference. The studied plant extracts were found to be very effective against the pathogenic microorganisms tested. The methanolic extract of Annona cherimola Mill from showed maximum activity against Escherichia coli and Staphylococcus aureus and the least concentration required showing the activity was 0.5mg/ml. Phytochemical screening of the plants revealed the presence of flavonoids, alkaloids, steroids and carbohydrates. Good presence of antioxidants was also found in the methanolic extracts.

Keywords: annona cherimola, phytochemicals, antioxidant and antibacterial activity, methanol extract

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Authors: Hajar Hajmohammadi, Paul Pfeffer, Anna De Simoni, Jim Cole, Chris Griffiths, Sally Hull, Benjamin Heydecker

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Background: There is strong interest in the relationship between short-term air pollution exposure and human health. Most studies in this field focus on serious health effects such as death or hospital admission, but air pollution exposure affects many people with less severe impacts, such as exacerbations of respiratory conditions. A lack of quantitative analysis and inconsistent findings suggest improved methodology is needed to understand these effectsmore fully. Method: We developed a time series regression model to quantify the relationship between daily NOₓ concentration and Asthma exacerbations requiring oral steroids from primary care settings. Explanatory variables include daily NOₓ concentration measurements extracted from 8 available background and roadside monitoring stations in east London and daily ambient temperature extracted for London City Airport, located in east London. Lags of NOx concentrations up to 21 days (3 weeks) were used in the model. The dependent variable was the daily number of oral steroid courses prescribed for GP registered patients with asthma in east London. A mixed distribution model was then fitted to the significant lags of the regression model. Result: Results of the time series modelling showed a significant relationship between NOₓconcentrations on each day and the number of oral steroid courses prescribed in the following three weeks. In addition, the model using only roadside stations performs better than the model with a mixture of roadside and background stations.

Keywords: air pollution, time series modeling, public health, road transport

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Authors: Mariame Taibi, Marouane Aouiji, Rachid Bengueddour

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The Moroccan coastline is particularly rich in algae and constitutes a reserve of species with considerable economic, social and ecological potential. This work focuses on the research and characterization of algae bioactive compounds that can be used in pharmacology or phytopathology. The biochemical composition of the green alga Ulva lactuca (Ulvophyceae) was studied by determining the content of moisture, ash, phenols, flavonoids, total tannins, and chlorophyll. Seven solvents: distilled water, methanol, ethyl acetate, chloroform, benzene, petroleum ether, and hexane, were tested for their effectiveness in recovering chemical compounds. The identification of functional groupings, as well as the bioactive chemical compounds, was determined by FT-IR and GC-MS. The moisture content of the alga was 77%, while the ash content was 15%. Phenol content differed from one solvent studied to another, while chlorophyll a, b, and total chlorophyll were determined at 14%, 9.52%, and 25%, respectively. Carotenoid was present in a considerable amount (8.17%). The experimental results show that methanol is the most effective solvent for recovering bioactive compounds, followed by water. Moreover, the green alga Ulva lactuca is characterized by a high level of total polyphenols (45±3.24 mg GAE/gDM), average levels of total tannins and flavonoids (22.52±8.23 mg CE/gDM, 15.49±0.064 mg QE/gDM) respectively. The results of Fourier transform infrared spectroscopy (FT-IR) confirmed the presence of alcohol/phenol and amide functions in Ulva lactuca. The GC-MS analysis gave precisely the compounds contained in the various extracts, such as phenolic compounds, fatty acids, terpenoids, alcohols, alkanes, hydrocarbons, and steroids. All these results represent only a first step in the search for biologically active natural substances from seaweed. Additional tests are envisaged to confirm the bioactivity of seaweed.

Keywords: algae, Ulva lactuca, phenolic compounds, FTIR, GC-MS

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Authors: Hajir Abdllha, Alaa Mohamed, Khansa Almoniem, Naga Adam, Wdeea Alhaadi, Ahmed Elshikh, Ahmed Ali, Ismail Makuar, Anas Elnazeer, Nagat Elrofaei, Samir Abdoelftah, Monier Hemidan

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The present study was designed to investigate antimicrobial, and antioxidant activities of five species from Acacia (Acacia albidia, Acacia mellifera, Acacia nubica, Acacia seyal var. seyal and Acacia tortilis). Phytochemical study was piloted to detect the bioactive compounds, which have been responsible from the biological activities. The ethanol, chloroform and acetone plant extracts were seasoned against standard bacteria strains of gram +ve bacteria Staphylococcus aureus (ATCC 25923), Gram -ve bacteria Pseudomonas aeruginosa (ATCC 27853) and standard fungi Candida albicans (ATCC 90028), using cup-plate method. The antioxidant activities were conducted via DPPH radical scavenging and metal chelating assays. Prospective activity against the five species was observed in acetone extract. Ethanol extract showed highest activities against Staphylococcus aureus, and Candida albicans. Potential antioxidant activity was presented by ethanol. Cholorophorm and acetone extracts via DPPH, the radical scavenging activities were found to be 91±0.03, 88±0.01 and 85±0.04 respectively. The results of phytochemical screening showed that all extracts of studied plant contain flavonoids, saponins, terpenoids, steroids, alkaloids, phenols and tannins. This study gives rise to antioxidant, antimicrobial properties of studied plant, and showed interesting correlation with the phytochemical constituents and biological activities.

Keywords: antimicrobial, antioxidant, Acacia albidia, Acacia mellifera, Acacia nubica, Acacia seyal var. seyal, Acacia tortilis

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Authors: Hajir, B. Abdllha, , Alaa, I. Mohamed, Khansa, A. Almoniem, Naga, I. Adam, Wdeea, Alhaadi, Ahmed, A. Elshikh, Ahmed, J. Ali, Ismail, G. Makuar, Anas, M. Elnazeer, Nagat, A. Elrofaei, Samir, F. Abdoelftah, Monier, N. Hemidan

Abstract:

The present study was designed to investigate antimicrobial, and antioxidant activities of five species from Acacia (Acacia albidia, Acacia mellifera, Acacia nubica, Acacia seyal var.seyal and Acacia tortilis). Phytochemical study was piloted to detect the bioactive compounds, which have been responsible from the biological activities. The ethanol, chloroform and acetone plant extracts were seasoned against standard bacteria strains of gram +ve bacteria Staphylococcus aureus (ATCC 25923) ,Gram -ve bacteria Pseudomonas aeruginosa (ATCC 27853) and standard fungi Candida albicans (ATCC 90028), using cup-plate method. The antioxidant activities were conducted via DPPH radical scavenging and metal chelating assays. Prospective activity against the five species was observed in acetone extract. Ethanol extract showed highest activities against Staphylococcus aureus, and Candida albicans. Potential antioxidant activity was presented by ethanol. Cholorophorm and acetone extracts via DPPH, the radical scavenging activities were found to be 91±0.03, 88±0.01 and 85±0.04 respectively. The results of phytochemical screening showed that all extracts of studied plant contain flavonoids, saponins, terpenoids, steroids, alkaloids, phenols and tannins. This study give rise to antioxidant, antimicrobial properties of studied plant, and showed interesting correlation with the phytochemical constituents and biological activities.

Keywords: antimicrobial, Antioxidant, Acacia albidia, Acacia mellifera, acacia nubica, acacia seyal var.seyal, Acacia tortilis

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Authors: Antonia Harold-Barry, Eugene Dempsey

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Background: The objective is to examine the survival and outcome of infants born under 26 weeks gestation in an Irish tertiary maternity hospital from 2007-2016 and to describe the survival and neurodevelopmental outcomes of these extremely preterm infants. Method: The population is 132 infants born at 23, 24, and 25 weeks in Cork University Maternity Hospital from 2007 to 2016. Ethical approval was granted by the Cork Clinical Research Ethics Committee. Patient details were obtained from the Vermont Oxford and Badger Networks. Survival rates and Bayley scores were calculated to assess neurodevelopmental outcomes. Statistical analysis with SPSS included frequencies, distributions, and comparisons between data from 2007-2011 and 2012-2016. Results: Overall survival rate was 63%. Of the surviving babies, 61% had Bayley scores calculated. Survival stood at 39% for delivery at 23 weeks, 50% at 24 weeks, and 83% at 25 weeks. The 2012 to 2016 cohort has shown further increases in survival, with 50% of babies at 23 weeks, 58% at 24 weeks, and 89% at 25 weeks. Corresponding figures for 2007-2011 are 20%, 39%, and 75%. Gestational age and incidence of periventricular leukomalacia were statistically significant, with a p-value of 0.022. Gestational age and delivery room deaths had a p-value of 0.025, as did gestational age and birth weight. A comparison of the two cohorts (2007-2011 and 2012-2016) with the administration of antenatal steroids showed a statistically significant p-value of 0.044. Conclusion: There is less morbidity and mortality in infants born at 25 than at 23 or 24 weeks. Survival of extremely premature infants has increased significantly over the past ten years. Survival rates with normal neurodevelopmental outcomes are comparable with international standards and reflect positive changes in attitude and practices in neonatal intensive care. This study will inform parents about the potential outcomes of extreme prematurity and policy regarding the management of extreme prematurity.

Keywords: extreme of viability, neurodevelopmental outcome, periventricular leukomalacia, prematurity

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Authors: Rohit Kothari, Muneer Mohamed, Vivekanandh K., Sunmeet Sandhu, Preema Sinha, Anuj Bhatnagar

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Introduction: Hyper-IgE syndrome is a rare primary immunodeficiency syndrome characterised by triad of severe atopic dermatitis, recurrent pulmonary infections, and recurrent staphylococcal skin infections. The diagnosis requires a high degree of suspicion, typical clinical features, and not mere rise in serum-IgE levels, which may be seen in multiple conditions. Genetic studies are not always possible in a resource poor setting. This study highlights various presentations of Hyper-IgE syndrome in skin of color children. Case-series: Our study had six children of Hyper-IgE syndrome aged twomonths to tenyears. All had onset in first ten months of life except one with a late-onset at two years. All had recurrent eczematoid rash, which responded poorly to conventional treatment, secondary infection, multiple episodes of hospitalisation for pulmonary infection, and raised serum IgE levels. One case had occasional vesicles, bullae, and crusted plaques over both the extremities. Genetic study was possible in only one of them who was found to have pathogenic homozygous deletions of exon-15 to 18 in DOCK8 gene following which he underwent bone marrow transplant (BMT), however, succumbed to lower respiratory tract infection two months after BMT and rest of them received multiple courses of antibiotics, oral/ topical steroids, and cyclosporine intermittently with variable response. Discussion: Our study highlights various characteristics, presentation, and management of this rare syndrome in children. Knowledge of these manifestations in skin of color will facilitate early identification and contribute to optimal care of the patients as representative data on the same is limited in literature.

Keywords: absolute eosinophil count, atopic dermatitis, eczematous rash, hyper-immunoglobulin E syndrome, pulmonary infection, serum IgE, skin of color

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Authors: Saheed A. Adekola, Mabel A. Charles-Davies, Ridwan A. Adekola

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Background: Testosterone is a known androgenic and anabolic steroid, primarily secreted in the testes. It plays an important role in the development of testes and prostate and has a range of biological actions. There is evidence that exposure to mixed chemicals in the workplace leads to the generation of free radicals and inadequate antioxidants leading to oxidative stress, which may serve as an early indicator of a pathophysiologic state. Based on findings, testosterone shows direct antioxidant effects by increasing the activities of antioxidant enzymes like glutathione peroxidase, thus indirectly contributing to antioxidant capacity. Objective: To evaluate the antioxidant role of testosterone as well as the relationship between testosterone and oxidative stress biomarkers in males exposed to mixed chemicals in the automobile repair community. Methods: The study included 43 participants aged 22- 60years exposed to mixed chemicals (EMC) from the automobile repair community. Forty (40) apparently healthy, unexposed, age-matched controls were recruited after informed consent. Demographic, sexual and anthropometric characteristics were obtained from pre-test structured questionnaires using standard methods. Blood samples (10mls) were collected from each subject into plain bottles and sera obtained were used for biochemical analyses. Serum levels of testosterone and luteinizing hormone (LH) were determined by enzyme immunoassay method, EIA (Immunometrics UK.LTD). Levels of total antioxidant capacity (TAC), total plasma peroxide (TPP), Malondialdehyde (MDA), hydrogen peroxide (H2O2), glutathione peroxide (GPX), superoxide dismutase (SOD), glutathione-S-transferase (GST), and reduced glutathione (GSH) were determined using spectrophotometric methods respectively. Results obtained were analyzed using the Student’s t-test and Chi-square test for quantitative variables and qualitative variables respectively. Multiple regression was used to find associations and relationships between the variables. Results: Significant higher concentrations of TPP, MDA, OSI, H2O2 and GST were observed in EMC compared with controls (p < 0.001). Within EMC, significantly higher levels of testosterone, LH and TAC were observed in eugonadic when compared with hypogonadic participants (p < 0.001). Diastolic blood pressure, waist circumference, waist height ratio and waist hip ratio were significantly higher in participants EMC compared with the controls. Sexual history and dietary intake showed that the controls had normal erection during sex and took more vegetables in their diet which may therefore be beneficial. Conclusion: The significantly increased levels of total antioxidant capacity in males exposed to mixed chemicals despite their exposure may probably reflect the contributory antioxidant role testosterone that prevents oxidative stress.

Keywords: mixed chemicals, oxidative stress, antioxidant, hypogonadism testosterone

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Authors: Xiaoqing Liu, Kurt Friese, Karsten Rinke

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Lacustrine sediment archives rich paleoenvironmental information in lake and surrounding environment. Additionally, modern sediment is used as an effective medium for the monitoring of lake. Organic carbon in sediment is a heterogeneous mixture with varying turnover times and qualities which result from the different biogeochemical processes in the deposition of organic material. Therefore, the isolation of different carbon pools is important for the research of lacustrine condition in the lake. However, the numeric available fractionation procedures can hardly yield homogeneous carbon pools on terms of stability and age. In this work, a multi-step fractionation protocol that treated sediment with hot water, HCl, H2O2 and Na2S2O8 in sequence was adopted, the treated sediment from each step were analyzed for the isotopic and structural compositions with Isotope Ratio Mass Spectrometer coupled with element analyzer (IRMS-EA) and Solid-state 13C Nuclear Magnetic Resonance (NMR), respectively. The sequential extractions with hot-water, HCl, and H2O2 yielded a more homogeneous and C3 plant-originating OC fraction, which was characterized with an atomic C/N ratio shift from 12.0 to 20.8, and 13C and 15N isotopic signatures were 0.9‰ and 1.9‰ more depleted than the original bulk sediment, respectively. Additionally, the H2O2- resistant residue was dominated with stable components, such as the lignins, waxes, cutans, tannins, steroids and aliphatic proteins and complex carbohydrates. 6M HCl in the acid hydrolysis step was much more effective than 1M HCl to isolate a sedimentary OC fraction with higher degree of homogeneity. Owing to the extremely high removal rate of organic matter, the step of a Na2S2O8 oxidation is only suggested if the isolation of the most refractory OC pool is mandatory. We conclude that this multi-step chemical fractionation procedure is effective to isolate more homogeneous OC pools in terms of stability and functional structure, and it can be used as a promising method for OC pools fractionation of sediment or soil in future lake research.

Keywords: 13C-CPMAS-NMR, 13C signature, lake sediment, OC fractionation

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Authors: Simmi Chopra

Abstract:

In the last few years, there has been a surge of Autoimmune diseases that have become more like an epidemic all over the world. The reasons vary from stress, insufficient sleep, smoking, genetics, environmental pollution, adulterated foods, and a diet full of “the deadly white,” which is white sugar and white flour. Most of the people diagnosed with these diseases are given steroids, opioids, supplements, or elimination diets to manage their lives, but most of them continue suffering to varying degrees. On the other hand, Ayurveda can help manage autoimmune problems effectively. Ayurveda is a 5000 years old holistic medical system from India that has an individualistic approach where health problems are looked at from the lens of balancing body and mind and by targeting the root cause of the problem. A combination of diet and lifestyle according to Ayurvedic principles, Ayurvedic herbal formulations and Ayurvedic therapies can help in the management of autoimmune and other chronic diseases. Panchkarma, which is an intense six weeks detox method, helps balance our body and mind, and has been very effective in managing autoimmune problems. The paper will introduce the basic concepts of Ayurveda and describe the terminologies- doshas, agni and ama. The paper will discuss the importance of diet and lifestyle according to the individual’s imbalance in the three functional parameters - doshas, which govern every aspect of our body and mind, our cells and tissues. The significance of agni, which can be correlated to digestive strength and ama, which can be correlated to toxins that are formed in our body leading to health problems, will be outlined. The Ayurvedic pathophysiology of autoimmune diseases will be discussed with emphasis on Rheumatoid arthritis, Multiple sclerosis and Psoriasis. Ayurvedic management will be discussed for these autoimmune conditions. As Ayurveda is an individualistic system, one protocol will not work for everyone. Therefore, case studies with Ayurvedic protocols for the above autoimmune disease will be presented. Conclusion: Ayurveda can help in managing as well as arresting the progression of autoimmune problems. Ayurveda is an ancient medical system, is much more needed today than ever. It is a tried and tested holistic system which has been practiced for the past many generations in India.

Keywords: ayurveda, autoimmune, diseases, nutrition

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Authors: Noshaba Dilbar, Hina Ashraf

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Medicinal plants are considered as rich source of ingredients which can be used in drug development and synthesis. Moreover, these plants play a vital role in the development of human culture of using ayurvedic medicines around the whole world. Among all plants, dessert plants are being proved as effective source of ayurvedic medicines and remedy against many diseases. Considering the fact, two plant species Limium indicum and Euphorbia granulata were taken from Cholistan dessert of Bahawalpur, Pakistan. Firstly, phytochemical screening was done by making dry and fresh plant extracts in five different solvents i.e Petroleum ether, benzene, chloroform, ethanol and methanol. Standard confirmation tests for all compounds were applied for analysis. Results revealed the presence of high range of bioactive compounds such as alakaloids, terpenoids, glycosides, steroids, flavonoids, saponins, phytosterols, oxalic acid, anthocyanin and quinone in both plants. Best results were obtained by methanolic, chloroform and petroleum ether extracts and methanolic, ethanolic and benzene extracts of Limium indicum and Euphorbia granulate respectively. Considering the results, methanolic extracts of both plants were further analysed for antibacterial activity. Plants were analysed against four pathogens including Escherchia coli, Proteus vulgaris, Klebsiella pneumonia and Pseudomonas aruginosa using disc diffusion method. Limium indicum showed highly significant activity against all pathogens while Euphorbia granulata showed significant activity against Klebsiella pneumonia and Proteus vulgaris but lesser against Escherchia coli and Pseudomonas aruginosa. MIC of extracts against each positive bacterium was calculated and recorded. Present plants can be considered for making useful drugs but further studies are needed to isolate active agents from plant extracts for drug development.

Keywords: antibacterial activity, Euphorbia granulata, Limium indicum, medicinal plants, phytochemical screening

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Authors: Sodamade A., Bolaji K. A.

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Problems associated with protein malnutrition are still prevalent in third-world countries, leading to the constant search for plants that could serve as nutrients and medicinal purposes. Huckleberry is one of the plants that has been proven useful locally in the treatment of numerous ailments and diseases. A fresh sample of the plant (Vaccinium pavifolium) was collected from a vegetable garden situated near the Erelu dam of the Emmanuel Alayande College of Education Campus, Oyo. The sample was authenticated at the Forestry Research Institute of Nigeria (FRIN) Ibadan. The leaves of the plant were plucked and processed for leaf protein concentrates before proximate composition, mineral analysis phytochemical and antimicrobial properties were determined using a standard method of analysis. The results of proximate constituents showed; moisture content; 9.89±0.051g/100g, Ash; 3.23±0.12g/100g, crude fat; 3.96±0.11g/100g and 61.27±0.56g/100g of Nitrogen free extractive. The mineral analysis of the sample showed; Mg; 0.081±0.00mg/100g, Ca; 42.30±0.05mg/100g, Na; 27.57±0.09mg/100g, K; 6.81±0.01mg/100g, P; 8.90±0.03mg/100g, Fe; 0.51±0.00mg/100g, Zn; 0.021±0.00mg/100g, Cd; 0.04±0.04mg/100g, Pb; 0.002±0.00mg/100g, Cr; 0.041±0.00mg/100g Cadmium and Mercury were not detected in the sample. The result of phytochemical analysis of leaf protein concentrates of the Huckleberry showed the presence of Alkaloid, Saponin, Flavonoid, Tanin, Coumarin, Steroids, Terpenoids, Cardiac glycosides, Glycosides, Quinones, Anthocyanin, phytosterols, and phenols. Ethanolic extracts of the Vaccinium parvifolium L. leaf protein concentrates showed that it contains bioactive compounds that are capable of combating the following microorganisms; Staphylococcus aureus, Streptococcus pyogenes, Streptococcus faecalis, Pseudomonas aeruginosa, Klebisialae pneumonia and Proteus mirabilis. The results of the analysis of Vaccinium parvifolium L. leaf protein concentrates showed that the sample contains valuable nutrient and mineral constituents, and phytochemical compounds that could make the sample useful for medicinal activities.

Keywords: leaf protein concentrates, vaccinium parvifolium, nutritional characteristics, mineral composition, antimicrobial activity

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Authors: Elisabeth Louise Ndjengue Mindang, Charline Florence Awounfack, Derek Tantoh Ndinteh, Rui W. M. Krause, Dieudonne Njamen

Abstract:

The evolution of human fertility over the last 50 years has shown considerable problems due to a growing number of couples that find it difficult to procreate without medical assistance. In Africa, this inability to conceive affect 30 to 40% of couples. A number of contaminants in the environment are thought to contribute significantly to the observed infertility epidemic. Methods: On this basis, the impact of 40-days unique oral administration (between 9 and 10 am) of potassium sorbate (at of 12.5, 45, and 78 mg/kg BW doses) was evaluated on sexual maturation and hematologic parameters on immature Wistar rats (21-22 days of age). At the end of the treatment, animals were sacrificed. Vaginal opening was evaluated before the sacrifice. After the sacrifice, relative weight of reproductive organs, pituitary gonadotrophin level (LH and FSH), and sexuals steroids (estrogen and progesterone), cholesterol level in ovaries, folliculogenesis, and some hematological parameters were evaluated. Results: Compared to the control group, no significant variation was observed in the body weight of the animals treated with patassium sorbate. On the other hand, potassium sorbate, a significantly lower percentage (25%) of vaginal-opening in these rats, was observed from day 46 of age (p <0.01); likewise, a significant decrease was observed on the relative weight of the ovaries (p <0.01), number of primary follicles (p <0.01), and a significant increase of follicle number (p <0.001) at 78 mg/kg BW have been obseved. Potassium sorbate always decreased the number of white blood cells (p <0.05). Taken together, these results confirm the disturbing effects on the endocrine system, causing a decrease in fertility by increasing the number of follicles in atresia. A deleterious effect on the immune system was also observed. Overall, these results validate at least in part the global observations on the growing decline in fertility in populationsfeeding increasingly on industrial processed foods.

Keywords: potassium sorbate, early puberty, folliculogenesis, endocrine disruptor, immatur wistar rat

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Authors: Eitan Yefenof

Abstract:

Glucocorticoid (GC) hormones, e.g. Dexamethasone and Prednisone, are widely used in the therapy of leukemia and lymphoma owing to their apoptogenic effect on lymphoid cells. However, the emergence of GC resistant cells during therapy is a major cause for treatment failure, urging the need for novel strategies that maintain leukemia sensitivity to the pro-apoptotic activity of GCs. GCs act by binding to the GC receptor (GR), which, in its inactive state, is sequestered in the cytosol by a multi-subunit complex of heat shock proteins. Upon ligand binding, the complex dissociates, allowing GR activation and translocation to the nucleus, where it regulates transcription of multiple genes. We demonstrated that in addition to gene expression, GR also regulates microRNA (miR) expression. Deep-sequencing analysis revealed 14 miRs that are regulated in GC-sensitive but resistant leukemias upon treatment with GC. GC up-regulates miR-103, miR-15~16 and miR-30e/d, while down-regulates miR-17, mir-18a, miR-19a, miR-19b, miR-20a and miR-92a (members of the miR-17∼92a multi-cistron). Upon transfection, miR-103 confers GC apoptotic sensitivity to otherwise GC-resistant cell. Furthermore, knocking down miR-103 expression reduces the GC apoptotic response of sensitive cells. miR-103 abrogates c-Myc expression, an oncogenic transcription factor which is deregulated in many cancers. In addition, miR-103 up-regulates Bim, a pro-apoptotic protein crucial for GC-induced death. Activated glycogen synthase kinase 3 (GSK3) is also crucial for GC-induced apoptosis. GSK3 is active in GC-sensitive but not in GC-resistant cells. We found that GSK3 associates with the GR multi-subunit complex. Upon GC exposure, it dissociates from the GR and interacts with Bim to enable activation of the mitochondrial apoptosis pathway. miR-103 mediated c-Myc ablation is followed by down-regulation of the multi-cistron miR-17~92a, in particular miR-18a and miR-20a. miR-18a targets GR for degradation whereas miR-20a targets Bim degradation. Hence, miR-103 acts, in concert with Bim and GR, as a "tumor suppressor" that leads to reduced proliferation, cell-cycle arrest and cell death. We suggest that miR-103 can provide a diagnostic tool that predicts the sensitivity of leukemia to GC based therapy. Furthermore, exosomal delivery of miR-103 or up-regulation of the endogenous miR-103 could confer apoptotic sensitivity to resistant cells at the outset, thus becoming a useful therapeutic tool combined with GCs.

Keywords: apoptosis, leukemia, micro-RNA, steroids

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Authors: Shanza Akram, Samir Salah, Imran Saleem, Ashraf Alzaabi, Jassim Abdou

Abstract:

Introduction: 300 million people worldwide are affected by asthma .In UAE, prevalence is around 10% (900,000 people).Patients with persistent symptoms despite using high dose ICS plus a second controller +/- OCS are considered to have severe asthma. Omalizumab (Xolaire) an IgE monoclonal antibody is approved as add on therapy for severe allergic asthma. Objective: To determine the efficacy of omalizumab based on clinical outcomes in our cohort of patient pre and post 52 weeks of treatment to assess safety and tolerability of treatment. Methods: Medical records of patients receiving omalizumab therapy for asthma at ZMH ,Abu Dhabi were retrospectively analyzed.Patients fulfilling the criteria of severe allergic asthma as per GINA guidelines were included. Asthma control over 12 months prior to and 12 months after commencement of omalizumab therapy was analysed by taking into account the number of exacerbations and hospitalizations in addition to maintenance of medication dosages, need for rescue reliever therapy and pulmonary function testing. Results: Total cohort of 21 patient (5 females), average age 41 years and av length of therapy 22 months were included. Seven patients (total 11/52%) managed to stop steroids on treatment while four were able to decrease the dosage. Mean exacerbation rate decreased from five/ year pre treatment to 1.36 while on treatment. Number of hospitalizations decreased from mean of two per year to 0.9 per year. Rescue reliever inhaler usage decreased from mean of 40 puffs to 15 puffs per week. 2 patients discontinued therapy, 1 due to lack of benefit (2 doses) and 2nd due to severe persistent side effects including local irritation, severe limb and joint pains after 6 months. Conclusion: Treatment with omalizumab showed effect in terms of reduced number of exacerbations, maintenance therapy and reliever medications. However, no improvement was seen in PFTs.There is room for improved documentation in terms of symptom recording and use of rescue medicationas as well as for better patient education and counselling in order to improve compliance.

Keywords: asthma, omalizumab, severe allergic asthma, UAE

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Authors: Zahra Mohajer, Afsaneh Soltani

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Doping is a major issue in competitive sports and is favored by vast groups of athletes. The feeling of being higher-ranking than others and gaining fame has caused many athletes to misuse drugs. The definition of doping is to use prohibited substances and/or methods that help physical or mental performances or both. Doping counts as the illegal use of chemical substances or drugs, excessive amounts of physiological substances to increase the performance at or out of competition or even the use of inappropriate medications to treat an injury to gain the ability to participate in a competition. The International Olympic Committee (IOC) and World Anti-Doping Agency (WADA) have forbidden these substances to ensure fair and equal competition and also the health of the competitors. As of 2004 WADA has published an international list of illegal substances used for doping, which is updated annually. In the process of the Genome Project scientists have gained the ability to treat numerous diseases by gene therapy, which may result in bodily performance increase and therefore a potential opportunity to misuse by some athletes. Gene doping is defined as the non-therapeutic direct and indirect genetic modifications using genetic materials that can improve the performances in sports events. Biosynthetic drugs are a form of indirect genetic engineering. The method can be performed in three ways such as injecting the DNA directly into the muscle, inserting the genetically engineered cells, or transferring the DNA using a virus as a vector. Erythropoietin is a hormone majorly released by the kidney and in small amounts by the liver. Its function is to stimulate the erythropoiesis and therefore the more production of red blood cells (RBC) which causes an increase in Hemoglobin (Hb). During this process, the oxygen delivery to muscles will increase, which will improve athletic performance and postpone exhaustion. There are ways to increase the oxygen transferred to muscles such as blood transfusion, stimulating the production of red blood cells by using Erythropoietin (EPO), and also using allosteric effectors of Hemoglobin. EPO can either be injected as a protein or can be inserted into the cells as the gene which encodes EPO. Adeno-associated viruses have been employed to deliver the EPO gene to the cells. Employing the genes that naturally exist in the human body such as the EPO gene can reduce the risk of detecting gene doping. The first research about blood doping was conducted in 1947. The study has shown that an increase in hematocrit (HCT) up to 55% following homologous transfusion makes it more unchallenging for the body to perform the exercise at the altitude. Thereafter athletes’ attraction to blood infusion escalated. Also, a study has demonstrated that by reinfusing their own blood 4 weeks after being drawn, three men have shown a rise in Hb level which improved the oxygen uptake, and a delay in exhaustion. The list of performance-enhancing drugs is published by WADA annually and includes the following drugs: anabolic agents, hormones, Beta-2 agonists, Beta-blockers, Diuretics, Stimulants, narcotics, cannabinoids, and corticosteroids.

Keywords: doping, PEDs, sports, WADA

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Authors: S. Sreeja, Radhakrishnan R. Nair, Noble Gracious, Sreeja S. Nair, M. Radhakrishna Pillai

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Background: Tacrolimus is a potent immunosuppressant clinically used for the long term treatment of antirejection of transplanted organs in liver and kidney transplant recipients though dose optimization is poorly managed. However, So far no study has been carried out on the South Indian kidney transplant patients. The objective of this study is to evaluate the potential influence of a functional polymorphism in CYP3A5*3 gene on tacrolimus physiological availability/dose ratio in South Indian renal transplant patients. Materials and Methods: Twenty five renal transplant recipients receiving tacrolimus were enrolled in this study. Their body weight, drug dosage, and therapeutic concentration of Tacrolimus were observed. All patients were on standard immunosuppressive regime of Tacrolimus-Mycophenolate mofetil along with steroids on a starting dose of Tac 0.1 mg/kg/day. CYP3A5 genotyping was performed by PCR followed with RFLP. Conformation of RFLP analysis and variation in the nucleotide sequence of CYP3A5*3 gene were determined by direct sequencing using a validated automated generic analyzer. Results: A significant association was found between tacrolimus per dose/kg/d and CYP3A5 gene (A6986G) polymorphism in the study population. The CYP3A5 *1/*1, *1/*3 and *3/*3 genotypes were detected in 5 (20 %), 5 (20 %) and 15 (60 %) of the 25 graft recipients, respectively. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus Concentration/Dose ratio in kidney transplant recipients. Significantly higher L/D was observed among non-expressors 9.483 ng/mL(4.5- 14.1) as compared with the expressors 5.154 ng/mL (4.42-6.5 ) of CYP3A5. Acute rejection episodes were significantly higher for CYP3A5*1 homozygotes compared to patients with CYP3A5*1/*3 and CYP3A5*3/*3 genotypes (40 % versus 20 % and 13 %, respectively ). The dose normalized TAC concentration (ng/ml/mg/kg) was significantly lower in patients having CYP3A5*1/*3 polymorphism. Conclusion: This is the first study to extensively determine the effect of CYP3A5*3 genetic polymorphism on tacrolimus pharmacokinetics in South Indian renal transplant recipients and also shows that majority of our patients carry mutant allele A6986G in CYP3A5*3 gene. Identification of CYP3A5 polymorphism prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus for each patient.

Keywords: kidney transplant patients, CYP3A5 genotype, tacrolimus, RFLP

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Authors: Akanksha Agrawal, Richa Rathor, Geetha Suryakumar

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Muscle represents about ¾ of the body mass, and a healthy muscular system is required for human performance. A healthy muscular system is dynamically balanced via the catabolic and anabolic process. High altitude associated hypoxia altered this redox balance via producing reactive oxygen and nitrogen species that ultimately modulates protein structure and function, hence, disrupts proteostasis or protein homeostasis. The mechanism by which proteostasis is clinched includes regulated protein translation, protein folding, and protein degradation machinery. Perturbation in any of these mechanisms could increase proteome imbalance in the cellular processes. Altered proteostasis in skeletal muscle is likely to be responsible for contributing muscular atrophy in response to hypoxia. Therefore, we planned to elucidate the mechanism involving altered proteostasis leading to skeletal muscle atrophy under chronic hypobaric hypoxia. Material and Methods-Male Sprague Dawley rats weighing about 200-220 were divided into five groups - Control (Normoxic animals), 1d, 3d, 7d and 14d hypobaric hypoxia exposed animals. The animals were exposed to simulated hypoxia equivalent to 282 torr pressure (equivalent to an altitude of 7620m, 8% oxygen) at 25°C. On completion of chronic hypobaric hypoxia (CHH) exposure, rats were sacrificed, muscle was excised and biochemical, histopathological and protein synthesis signaling were studied. Results-A number of changes were observed with the CHH exposure time period. ROS was increased significantly on 07 and 14 days which were attributed to protein oxidation via damaging muscle protein structure by oxidation of amino acids moiety. The oxidative damage to the protein further enhanced the various protein degradation pathways. Calcium activated cysteine proteases and other intracellular proteases participate in protein turnover in muscles. Therefore, we analysed calpain and 20S proteosome activity which were noticeably increased at CHH exposure as compared to control group representing enhanced muscle protein catabolism. Since inflammatory markers (myokines) affect protein synthesis and triggers degradation machinery. So, we determined inflammatory pathway regulated under hypoxic environment. Other striking finding of the study was upregulation of Akt/PKB translational machinery that was increased on CHH exposure. Akt, p-Akt, p70 S6kinase, and GSK- 3β expression were upregulated till 7d of CHH exposure. Apoptosis related markers, caspase-3, caspase-9 and annexin V was also increased on CHH exposure. Conclusion: The present study provides evidence of disrupted proteostasis under chronic hypobaric hypoxia. A profound loss of muscle mass is accompanied by the muscle damage leading to apoptosis and cell death under CHH. These cellular stress response pathways may play a pivotal role in hypobaric hypoxia induced skeletal muscle atrophy. Further research in these signaling pathways will lead to development of therapeutic interventions for amelioration of hypoxia induced muscle atrophy.

Keywords: Akt/PKB translational machinery, chronic hypobaric hypoxia, muscle atrophy, protein degradation

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Authors: Nitin Rajan, Kashif Shakeel, Shashank Tiwari, Shachan Sagar

Abstract:

Background: - Aegle Marmelos (Bael) leaf extract is taken twice daily to treat ophthalmia, ulcers, and intestinal worms, among other ailments. Poultice made from bael leaf is used in the treatment of eye conditions. The leaf juice has a variety of therapeutic applications, with the most notable being the treatment of diabetes. Fenugreek is used to cure red spots around the eyes, as well as to soften the throat and chest and to give relief from coughing. The use of this plant in the form of infusion, powder, pomade, and decoction has been extremely popular in Iranian traditional medicine. The plant may be used to wash one's vaginal linings. This plant is used as an emollient in the lack of appetite, treatment of pellagra, and gastrointestinal problems, as well as a general tonic. Calendula officinalis leaves are used to treat varicose veins on the outside of the body by infusing them. In Europe, the leaves are diaphoretic and resolvent in nature, while the blooms are employed as an emmenagogue and antispasmodic stimulant in Canada and the United States. The flowers were decocted and served as a posset drink when smallpox and measles were common in England, and the fresh juice was used to treat jaundice. Objective: - This study is done to compare the physicochemical parameter of the alcoholic extract of the leaves of Aegle Marmelos, Calendula Officinalis, and Fenugreek. Materials and Methods: Extraction and Isolation of Aegle Marmelos, Calendula Officinalis, Fenugreek, were done. Preliminary phytochemical study for alkaloids, cardiac glycosides, flavonoids, glycosides, phenols, resins, saponins, steroids, tannins, terpenoids of the extract was done individual by using the standard procedure. Result: - The phytochemical screening of Aegle Marmelos, Calendula Officinalis, and Fenugreek shows the presence of alkaloids, carbohydrates, total phenolics, total flavonoids, tannins, saponins gum. Conclusion: - In this study, we have found that crude aqueous and organic solvent extracts of Aegle Marmelos, Calendula Officinalis, and Fenugreek leaves contain some important bioactive compounds and it justifies their use in the traditional medicines for the treatment of different diseases.

Keywords: Aegle Marmelos, Calendula Officinalis, Fenugreek, physiochemical parameter

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Authors: Mike T. Wei, Douglas N. Mintz, Lisa A. Mandl, Arielle W. Fein, Jayme C. Burket, Yuo-Yu Lee, Wei-Ti Huang, Vivian P. Bykerk, Mark P. Figgie, Edward F. Di Carlo, Bruce N. Cronstein, Susan M. Goodman

Abstract:

Background/Purpose: Rheumatoid arthritis (RA) patients have excellent total hip arthroplasty (THA) survival, and methotrexate (MTX), an anti-inflammatory disease modifying drug which may affect bone reabsorption, may play a role. The purpose of this study is to determine the diagnosis leading to revision THA (rTHA) in RA patients and to assess the association of radiographic lucency with MTX use. Methods: All patients with validated diagnosis of RA in the institution’s THA registry undergoing rTHA from May 2007 - February 2011 were eligible. Diagnosis leading to rTHA and medication use was determined by chart review. Osteolysis was evaluated on available radiographs by measuring maximum lucency in each Gruen zone. Differences within RA patients with/without MTX in osteolysis, demographics, and medications were assessed with chi-squared, Fisher's exact tests or Mann-Whitney U tests as appropriate. The error rate for multiple comparisons of lucency in the different Gruen zones was corrected via false discovery rate methods. A secondary analysis was performed to determine differences in diagnoses leading to revision between RA and matched OA controls (2:1 match by sex age +/- 5 years). OA exclusion criteria included presence of rheumatic diseases, use of MTX, and lack of records. Results: 51 RA rTHA were identified and compared with 103 OA. Mean age for RA was 57.7 v 59.4 years for OA (p = 0.240). 82.4% RA were female v 83.5% OA (p = 0.859). RA had lower BMI than OA (25.5 v 28.2; p = 0.166). There was no difference in diagnosis leading to rTHA, including infection (RA 3.9 v OA 6.8%; p = 0.719) or dislocation (RA 23.5 v OA 23.3%; p = 0.975). There was no significant difference in the length of time the implant was in before revision: RA 11.0 v OA 8.8 years (p = 0.060). Among RA with/without MTX, there was no difference in use of biologics (30.0 v 43.3%, p = 0.283), steroids (47.6 v 50.0%, p = 0.867) or bisphosphonates (23.8 v 33.3%, p = 0.543). There was no difference in rTHA diagnosis with/without MTX, including loosening (52.4 v 56.7%, p = 0.762). There was no significant difference in lucencies with MTX use in any Gruen zone. Patients with MTX had femoral stem subsidence of 3.7mm v no subsidence without MTX (p = 0.006). Conclusion: There was no difference in the diagnosis leading to rTHR in RA and OA, although RA trended longer prior to rTHA. In this small retrospective study, there were no significant differences associated with MTX exposure or radiographic lucency among RA patients. The significance of subsidence is not clear. Further study of arthroplasty survival in RA patients is warranted.

Keywords: hip arthroplasty, methotrexate, revision arthroplasty, rheumatoid arthritis

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