Search results for: anti diabetic

Authors: Tanima Chatterjee, Maitree Bhattacharyya

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The global challenge of type 2 diabetes mellitus is a major health concern in this millennium, and researchers are continuously exploring new targets to develop a novel therapeutic strategy. Type 2 diabetes mellitus (T2DM) is often coupled with dyslipidemia increasing the risks for cardiovascular (CVD) complications. Enhanced oxidative and nitrosative stresses appear to be the major risk factors underlying insulin resistance, dyslipidemia, β-cell dysfunction, and T2DM pathogenesis. Autophagy emerges to be a promising defense mechanism against stress-mediated cell damage regulating tissue homeostasis, cellular quality control, and energy production, promoting cell survival. In this study, we have attempted to explore the pivotal role of autophagy in T2DM subjects with or without dyslipidemia in peripheral blood mononuclear cells and insulin-resistant HepG2 cells utilizing flow cytometric platform, confocal microscopy, and molecular biology techniques like western blotting, immunofluorescence, and real-time polymerase chain reaction. In the case of T2DM with dyslipidemia higher population of autophagy, positive cells were detected compared to patients with the only T2DM, which might have resulted due to higher stress. Autophagy was observed to be triggered both by oxidative and nitrosative stress revealing a novel finding of our research. LC3 puncta was observed in peripheral blood mononuclear cells and periphery of HepG2 cells in the case of the diabetic and diabetic-dyslipidemic conditions. Increased expression of ATG5, LC3B, and Beclin supports the autophagic pathway in both PBMC and insulin-resistant Hep G2 cells. Upon blocking autophagy by 3-methyl adenine (3MA), the apoptotic cell population increased significantly, as observed by caspase‐3 cleavage and reduced expression of Bcl2. Autophagy has also been evidenced to control oxidative stress-mediated up-regulation of inflammatory markers like IL-6 and TNF-α. To conclude, this study elucidates autophagy to play a protective role in the case of diabetes mellitus with dyslipidemia. In the present scenario, this study demands to have a significant impact on developing a new therapeutic strategy for diabetic dyslipidemic subjects by enhancing autophagic activity.

Keywords: autophagy, apoptosis, dyslipidemia, reactive oxygen species, reactive nitrogen species, Type 2 diabetes

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Authors: I. L. Ibrahim, A. Mann, B. A. Adam

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This project involved screening for antibacterial activity, phytochemical and mineral properties of Leptadenia hastata by flame photometry. The result of phytochemical screening reveals that the presence of flavonoids, tannins, saponins, alkaloids, steroidal, and anthraquinones while the cardiac glycoside was absent. This justifies the plant been used as anti-bleeding and anti-inflammatory agents. The result of flame photometry revealed that 1.85 % (Na), 0.65% (K) and 1.85 % (Ca) which indicates the safe nature of the plant extract as such could be used to lower high blood pressure. The antibacterial properties of both the aqueous and ethanolic extract were studied against some bacteria, Escherichia coli, Bacillus Cercus, Pseudomonas aeruginas, and Enterobacter aerogegens, by disc diffusion method and the result reveals that there are very good activities against the organism while the ethanolic extract at concentration 1.0 – 1.2 mg/ml. the ethanolic extract showed in considerable zone inhibition against bacteria’s; Escherichia coli, Bacillus Cercus, pseudomonas aeruginosa andklebsellapnemuoniae. Minimum inhibitory concentration (MIC) and minimum Bacterial concentration (MBC) were conducted with fairly good significant effect of inhibition on the organism, therefore, plant extract could be a potential source of antibacterial agent.

Keywords: antibacterial activity, Leptadenia hastata, infectious diseases, phytochemical screening

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Authors: Farah Nameni, Hamidreza Poursadra, Maasumeh Nurani Pilehrud

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Exercise training induced Inflammation and stress. Antioxidant, for example L- Carnitine has beneficial effects in immune system and increased antioxidant enzymes activity. L- Carnitine protects the tissue against the oxidative side effect and helps the body to protect against stress during and after acute exercise. The aim of this study was to determine the effect of L-Carnitine on the blood enzymes: GPX SOD, CAT and GR response. In this study, 20 basketball players girls participated. Subjects were randomly assigned into two groups; placebo and supplementation. Antioxidadision enzymes (Superoxide Dismutase, Catalase, Glutathione Reductase, Glutathione Peroxidase) evaluated. L-Carnitine supplement group orally daily received 3000 mg powder for 14 dys. Then all participates trained basketball exercise acute. Blood samples were drawn vein before and immediately after exercise. Superoxide Dismutase, Catalase, Glutathione Reductase, Glutathione Peroxidase were measured, and data was analyzed using repeated measure ANOVA, Bonferroni and t-test. Our results showed: SOD, GPX and GPX (P < 0.05) have a significant increase. These results suggest L-Carnitine supplementation may increase GPX SOD, CAT, and basal anti oxidative capacity. L-Carnitine can modulate the alterations of exercise oxidative damage in girl basketball players.

Keywords: l-carnitine, GPX, SOD, CAT, exercise, GR, anti-oxidant

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Authors: Amnah M. A. Alsuhaibani, Amal N. Al-Kuraieef

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Introduction: In the recent decades, production of low-calorie jams is needed for diabetics that comprise low calorie fruits and low calorie sweeteners. Object: the research aimed to prepare low calorie formulated pumpkin jams (fructose, stevia and aspartame) incorporated with soy bean and evaluate the jams through chemical analysis and sensory evaluation after storage for six month. Moreover, the possible effect of consumption of low calorie jams on diabetic rats was investigated. Methods: Five formulas of pumpkin jam with different sucrose, fructose, stevia and aspartame sweeteners and soy bean were prepared and stored at 10 oC for six month compared to ordinary pumpkin jam. Chemical composition and sensory evaluation of formulated jams were evaluated at zero time, 3 month and 6 month of storage. The best three acceptable pumpkin jams were taken for biological study on diabetic rats. Rats divided into group (1) served as negative control and streptozotocin induce diabetes four rat groups that were positive diabetic control (group2), rats fed on standard diet with 10% sucrose soybean jam, fructose soybean jam and stevia soybean jam (group 3, 4&5), respectively. Results: The content of protein, fat, ash and fiber were increased but carbohydrate was decreased in low calorie formulated pumpkin jams compared to ordinary jam. Production of aspartame soybean pumpkin jam had lower score of all sensory attributes compared to other jam then followed by stevia soybean Pumpkin jam. Using non nutritive sweeteners (stevia & aspartame) with soybean in processing jam could lower the score of the sensory attributes after storage for 3 and 6 months. The highest score was recorded for sucrose and fructose soybean jams followed by stevia soybean jam while aspartame soybean jam recorded the lowest score significantly. The biological evaluation showed a significant improvement in body weight and FER of rats after six weeks of consumption of standard diet with jams (Group 3,4&5) compared to Group1. Rats consumed 10% low calorie jam with nutrient sweetener (fructose) and non nutrient sweetener (stevia) soybean jam (group 4& 5) showed significant decrease in glucose level, liver function enzymes activity, and liver cholesterol & total lipids in addition of significant increase of insulin and glycogen compared to the levels of group 2. Conclusion: low calorie pumpkin jams can be prepared by low calorie sweeteners and soybean and also storage for 3 months at 10oC without change sensory attributes. Consumption of stevia pumpkin jam fortified with soybean had positive health effects on streptozoticin induced diabetes in rats.

Keywords: pumpkin jam, HFCS, aspartame, stevia, storage

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Authors: William Creighton, Jan Smitheram

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Queer discourse has been tied to a middle-class, urban-centric, white approach to the discussion of queerness. In doing so, the multilayeredness of queer existence has been washed away in favour of palatable queer occupation. This paper uses design to explore a queer anti-urbanist approach to facilitate a more egalitarian architectural occupancy. Scott Herring’s work on queer anti-urbanism is key to this approach. Herring redeploys anti-urbanism from its historical understanding of open hostility, rejection and desire to destroy the city towards a mode of queer critique that counters normative ideals of homonormative metronormative gay lifestyles. He questions how queer identity has been closed down into a more diminutive frame where those who do not fit within this frame are subjected to persecution or silenced through their absence. We extend these ideas through design to ask how a queer anti-urbanist approach facilitates a more egalitarian architectural occupancy. Following a “design as research” methodology, the design outputs allow a vehicle to ask how we might live, otherwise, in architectural space. A design as research methodologically is a process of questioning, designing and reflecting – in a non-linear, iterative approach – establishes itself through three projects, each increasing in scale and complexity. Each of the three scales tackled a different body relationship. The project began exploring the relations between body to body, body to known others, and body to unknown others. Moving through increasing scales was not to privilege the objective, the public and the large scale; instead, ‘intra-scaling’ acts as a tool to re-think how scale reproduces normative ideas of the identity of space. There was a queering of scale. Through this approach, the results were an installation that brings two people together to co-author space where the installation distorts the sensory experience and forces a more intimate and interconnected experience challenging our socialized proxemics: knees might touch. To queer the home, the installation was used as a drawing device, a tool to study and challenge spatial perception, drawing convention, and as a way to process practical information about the site and existing house – the device became a tool to embrace the spontaneous. The final design proposal operates as a multi-scalar boundary-crossing through “private” and “public” to support kinship through communal labour, queer relationality and mooring. The resulting design works to set adrift bodies in a sea of sensations through a mix of pleasure programmes. To conclude, through three design proposals, this design research creates a relationship between queer anti-urbanism and design. It asserts that queering the design process and outcome allows a more inclusive way to consider place, space and belonging. The projects lend to a queer relationality and interdependence by making spaces that support the unsettled, out-of-place, but is it queer enough?

Keywords: queer, queer anti-urbanism, design as research, design

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Authors: Dina Atmani-Kilani, Farah Yous, Djebbar Atmani

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The etiology of peptic ulcer is closely related to stress, excessive consumption of nonsteroidal anti-inflammatory drugs, or ethanol. Clematis flammula (Ranunculaceae) is a medicinal plant widely used by rural populations to treat inflammatory disorders. This study was designed to assess the gastroprotective potential of C. flammula extracts. Gastric ulcer was induced by stress, indomethacin, HCl / ethanol, and absolute ethanol on NMRI-type mice. The antioxidant potency of the ethanolic extract of Clematis flammula (EECF) was evaluated on catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities. Glutathione (GSH) and malonaldehyde (MDA) levels were also quantified. The anti-inflammatory potential was evaluated through the effect of EECF on myeloperoxidase activity (MPO) and vascular permeability. Complementary tests concerning the quantification of mucus levels, gastric motility, inhibition of ATPase H+/K+activity, as well as a histopathological study were also undertaken to explore the mechanism of action of the EECF. The EECF exhibited a significant (p <0.001) and optimal (100 mg/kg) gastroprotective effect by elevating SOD, CAT, and GSH levels, thereby minimizing the production of MDA and lowering the activity of MPO and vascular permeability. EECF also increased the rate of mucus production, decreased gastric motility, and completely suppressed the H+/K+ ATPase activity. Histopathological study confirmed the effectiveness of the extract in the prevention of peptic ulcer. The results obtained in this study demonstrated the gastro-protective effect of EECF via acidic antioxidant, anti-inflammatory, cytoprotective and anti-secretory mechanisms, which may justify its use as a substitute in peptic ulcer treatment.

Keywords: clematis flammula, superoxide dismutase, myeloperoxidase, ATPase, pump

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Authors: Faizan Ali, Dayu Zhou, Xiaohua Liu, Tony Schenk, Johannes Muller, Uwe Schroeder

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Recently, the ferroelectricity (FE) and anti-ferroelectricity (AFE) introduced in so-called 'high-k dielectric' HfO₂ material incorporated with various dopants (Si, Gd, Y, Sr, Gd, Al, and La, etc.), HfO₂-ZrO₂ solid-solution, Al or Si-doped Hf₀.₅Zr₀.₅O₂ and even undoped HfO₂ thin films. The origin of FE property was attributed to the formation of a non-centrosymmetric orthorhombic (o) phase of space group Pbc2₁. To the author’s best knowledge, AFE property was observed only in HfO₂ doped with a certain amount of Si, Al, HfₓZr₁₋ₓO₂ (0 ≤ x < 0.5), and in Si or Al-doped Hf₀.₅Zr₀.₅O₂. The origin of the anti-ferroelectric behavior is an electric field induced phase transition between the non-polar tetragonal (t) and the polar ferroelectric orthorhombic (o) phase. Compared with the significant amount of studies for the FE properties in the context of non-volatile memories, AFE properties of HfO₂-based and HfₓZr₁₋ₓO₂ (HZO) thin films have just received attention recently for energy-related applications such as electrocaloric cooling, pyroelectric energy harvesting, and electrostatic energy storage. In this work, energy storage and solid state cooling properties of Si-doped HfO₂ AFE thin films are investigated. Owing to the high field-induced polarization and slim double hysteresis, an extremely large Energy storage density (ESD) value of 61.2 J cm⁻³ is achieved at 4.5 MV cm⁻¹ with high efficiency of ~65%. In addition, the ESD and efficiency exhibit robust thermal stability in 210-400 K temperature range and excellent endurance up to 10⁹ times of charge/discharge cycling at a very high electric field of 4.0 MV cm⁻¹. Similarly, for solid-state cooling, the maximum adiabatic temperature change (

Keywords: thin films, energy storage, endurance, solid state cooling, anti-ferroelectric

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Authors: Ghibeche Abderrahmane

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To examine whether genes associated with cellular defense against oxidative stress are associated with insulin sensitivity, patients with type 2 diabetes (n=7) and age-matched (n=5) and young (n=9) control subjects underwent a euglycemic-hyperinsulinemic clamp for 120 min. Muscle samples were obtained before and after the clamp and analyzed for heat shock protein (HSP)72 and heme oxygenase (HO)-1 mRNA, intramuscular triglyceride content, and the maximal activities of β-hyroxyacyl-CoA dehydrogenase (β-HAD) and citrate synthase (CS). Basal expression of both HSP72 and HO-1 mRNA were lower (P < 0.05) by 33 and 55%, respectively, when comparing diabetic patients with age-matched and young control subjects, with no differences between the latter groups. Both basal HSP72 (r = 0.75, P < 0.001) and HO-1 (r = 0.50,P < 0.05) mRNA expression correlated with the glucose infusion rate during the clamp. Significant correlations were also observed between HSP72 mRNA and both β-HAD (r = 0.61, P < 0.01) and CS (r = 0.65, P < 0.01). HSP72 mRNA was induced (P < 0.05) by the clamp in all groups. Although HO-1 mRNA was unaffected by the clamp in both the young and age-matched control subjects, it was increased (P < 0.05) ∼70-fold in the diabetic patients after the clamp. These data demonstrate that genes involved in providing cellular protection against oxidative stress are defective in patients with type 2 diabetes and correlate with insulin-stimulated glucose disposal and markers of muscle oxidative capacity. The data provide new evidence that the pathogenesis of type 2 diabetes involves perturbations to the antioxidant defense mechanism within skeletal muscle.

Keywords: euglycemic-hyperinsulinemic, HSP72, mRNA, diabete

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Authors: Hamidreza Saberkari, Mousa Shamsi, Hossein Ahmadi, Saeed Vaali, , MohammadHossein Sedaaghi

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In the recent years, using signal processing tools for accurate identification of the protein coding regions has become a challenge in bioinformatics. Most of the genomic signal processing methods is based on the period-3 characteristics of the nucleoids in DNA strands and consequently, spectral analysis is applied to the numerical sequences of DNA to find the location of periodical components. In this paper, a novel ensemble algorithm for gene selection in DNA sequences has been presented which is based on the combination of Goertzel algorithm and anti-notch filter (ANF). The proposed algorithm has many advantages when compared to other conventional methods. Firstly, it leads to identify the coding protein regions more accurate due to using the Goertzel algorithm which is tuned at the desired frequency. Secondly, faster detection time is achieved. The proposed algorithm is applied on several genes, including genes available in databases BG570 and HMR195 and their results are compared to other methods based on the nucleotide level evaluation criteria. Implementation results show the excellent performance of the proposed algorithm in identifying protein coding regions, specifically in identification of small-scale gene areas.

Keywords: protein coding regions, period-3, anti-notch filter, Goertzel algorithm

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Authors: Mohamed A. Hammad, Dzul Azri Mohamed Noor, Syed Azhar Syed Sulaiman, Majed Ahmed Al-Mansoub, Muhammad Qamar

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There is a progressive increase in the prevalence of early onset Type 2 diabetes mellitus. Early detection of Type 2 diabetes enhances the length and/or quality of life which might result from a reduction in the severity, frequency or prevent or delay of its long-term complications. The study aims to determine the onset age for the first diagnosis of Type 2 diabetes mellitus. A retrospective study conducted in the endocrine clinic at Hospital Pulau Pinang in Penang, Malaysia, January- December 2016. Records of 519 patients with Type 2 diabetes mellitus were screened to collect demographic data and determine the age of first-time diabetes mellitus diagnosis. Patients classified according to the age of diagnosis, gender, and ethnicity. The study included 519 patients with age (55.6±13.7) years, female 265 (51.1%) and male 254 (48.9%). The ethnicity distribution was Malay 191 (36.8%), Chinese 189 (36.4%) and Indian 139 (26.8%). The age of Type 2 diabetes diagnosis was (42±14.8) years. The female onset of diabetes mellitus was at age (41.5±13.7) years, while male (42.6±13.7) years. Distribution of diabetic onset by ethnicity was Malay at age (40.7±13.7) years, Chinese (43.2±13.7) years and Indian (42.3±13.7) years. Diabetic onset was classified by age as follow; ≤20 years’ cohort was 33 (6.4%) cases. Group >20- ≤40 years was 190 (36.6%) patients, and category >40- ≤60 years was 270 (52%) subjects. On the other hand, the group >60 years was 22 (4.2%) patients. The range of diagnosis was between 10 and 73 years old. Conclusion: Malay and female have an earlier onset of diabetes than Indian, Chinese and male. More than half of the patients had diabetes between 40 and 60 years old. Diabetes mellitus is becoming more common in younger age <40 years. The age at diagnosis of Type 2 diabetes mellitus has decreased with time.

Keywords: age of onset, diabetes diagnosis, diabetes mellitus, Malaysia, outpatients, type 2 diabetes, retrospective study

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Authors: T. Mahesh, M. K. Samanta

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Antibody dug conjugate (ADC’s) concept is a less explored and more trustable for the treatment of Type 1 diabetes (T1D). T1D is thought to arise from selective immunologically mediated destruction of the insulin- producing β-cells in the pancreatic islets of Langerhans with consequent insulin deficiency. It is evident that type 1 diabetes can be conquered, by 1) to stop immune destruction of βcells, 2) to replace or regenerate β-cells, and 3) to preserve β-cell function and mass. Many studies found that the regulatory T cells (Tregs) are crucial for the maintenance of immunological tolerance. Immune tolerance is liable for the activation of the Th1 response. The important role of Th1 response in pathology of T1D entails the depletion of CD4+ T cells, which initiated the use of anti-CD4 monoclonal antibodies (mAbs) against CD4+ T cells to interfere with induction of T1D.Insulin is regulated by Glucagon-Like Peptide-1 hormone (GLP-1) which also stimulates β-cells proliferation as the half-life of GLP-1 harmone is less due to rapid degradation by DPP-IV enzyme an alternative DPP-IV-inhibitors can increase the half-life of GLP-1 through which it conquers the replacement and reserve β-cells mass. Thus in the present study Anti-CD4 mAb was conjugated with Sitagliptin which is a DPP-IV inhibitor Drug loaded in Nanoparticles through Sulfo-MBS cross-linkers. The above study can be an effective approach for treatment to overcome the Passive subcutaneous insulin therapy.

Keywords: antibody drug conjugates, anti-CD4 Mab, DPP IV inhibitors, GLP-1

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Authors: Tamphasana Wairokpam

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Inflammatory myopathies (IMs) have long been recognised as a heterogenous family of myopathies with acute, subacute, and sometimes chronic presentation and are potentially treatable. Necrotizing autoimmune myopathies (NAM) are a relatively new subset of myopathies. Patients generally present with subacute onset of proximal myopathy and significantly elevated creatinine kinase (CK) levels. It is being increasingly recognised that there are limitations to the independent diagnostic utility of muscle biopsy. Immunohistochemistry tests may reveal important information in these cases. The traditional classification of IMs failed to recognise NAM as a separate entity and did not adequately emphasize the diversity of IMs. This review and case report on NAM aims to highlight the heterogeneity of this entity and focus on the distinct clinical presentation, biopsy findings, specific auto-antibodies implicated, and available treatment options with prognosis. This article is a meta-analysis of literatures on NAM and a case report illustrating the clinical course, investigation and biopsy findings, antibodies implicated, and management of a patient with NAM. The main databases used for the search were Pubmed, Google Scholar, and Cochrane Library. Altogether, 67 publications have been taken as references. Two biomarkers, anti-signal recognition protein (SRP) and anti- hydroxyl methylglutaryl-coenzyme A reductase (HMGCR) Abs, have been found to have an association with NAM in about 2/3rd of cases. Interestingly, anti-SRP associated NAM appears to be more aggressive in its clinical course when compared to its anti-HMGCR associated counterpart. Biopsy shows muscle fibre necrosis without inflammation. There are reports of statin-induced NAM where progression of myopathy has been seen even after discontinuation of statins, pointing towards an underlying immune mechanism. Diagnosisng NAM is essential as it requires more aggressive immunotherapy than other types of IMs. Most cases are refractory to corticosteroid monotherapy. Immunosuppressive therapy with other immunotherapeutic agents such as IVIg, rituximab, mycophenolate mofetil, azathioprine has been explored and found to have a role in the treatment of NAM. In conclusion,given the heterogeneity of NAM, it appears that NAM is not just a single entity but consists of many different forms, despite the similarities in presentation and its classification remains an evolving field. A thorough understanding of underlying mechanism and the clinical correlation with antibodies associated with NAM is essential for efficacious management and disease prognostication.

Keywords: inflammatory myopathies, necrotising autoimmune myopathies, anti-SRP antibody, anti-HMGCR antibody, statin induced myopathy

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Authors: S. N. T. I. Sampath, J. M. S. Jayasinghe, A. P. Attanayake, V. Karunaratne

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Diabetes mellitus is one of the major public health posers throughout the world today that incidence and associated with increasing mortality. Insufficient regulation of the blood glucose level might be serious effects for health and its necessity to identify new therapeutics that have ability to reduce hyperglycaemic condition in the human body. Even though synthetic antidiabetic drugs are more effective to control diabetes mellitus, there are considerable side effects have been reported. Thus, there is an increasing demand for searching new natural products having high antidiabetic activity with lesser side effects. The purposes of the present study were to evaluate different physical parameters and in-vitro and in-vivo antidiabetic potential of the selected combined medicinal plant extracts mixture composed of leaves of Murraya koenigii, cloves of Allium sativum, fruits of Garcinia queasita and seeds of Piper nigrum. The selected plants parts were mixed and ground together and extracted sequentially into the hexane, ethyl acetate and methanol. Solvents were evaporated and they were further dried by freeze-drying to obtain a fine powder of each extract. Various physical parameters such as moisture, total ash, acid insoluble ash and water soluble ash were evaluated using standard test procedures. In-vitro antidiabetic activity of combined plant extracts mixture was screened using enzyme assays such as α-amylase inhibition assay and α-glucosidase inhibition assay. The acute anti-hyperglycaemic activity was performed using oral glucose tolerance test for the streptozotocin induced diabetic Wistar rats to find out in-vivo antidiabetic activity of combined plant extracts mixture and it was assessed through total oral glucose tolerance curve (TAUC) values. The percentage of moisture content, total ash content, acid insoluble ash content and water soluble ash content were ranged of 7.6-17.8, 8.1-11.78, 0.019-0.134 and 6.2-9.2 respectively for the plant extracts and those values were less than standard values except the methanol extract. The hexane and ethyl acetate extracts exhibited highest α-amylase (IC50 = 25.7 ±0.6; 27.1 ±1.2 ppm) and α-glucosidase (IC50 = 22.4 ±0.1; 33.7 ±0.2 ppm) inhibitory activities than methanol extract (IC50 = 360.2 ±0.6; 179.6 ±0.9 ppm) when compared with the acarbose positive control (IC50 = 5.7 ±0.4; 17.1 ±0.6 ppm). The TAUC values for hexane, ethyl acetate, and methanol extracts and glibenclamide (positive control) treated rats were 8.01 ±0.66; 8.05 ±1.07; 8.40±0.50; 5.87 ±0.93 mmol/L.h respectively, whereas in diabetic control rats the TAUC value was 13.22 ±1.07 mmol/L.h. Administration of plant extracts treated rats significantly suppressed (p<0.05) the rise in plasma blood glucose levels compared to control rats but less significant than glibenclamide. The obtained results from in-vivo and in-vitro antidiabetic study showed that the hexane and ethyl acetate extracts of selected combined plant mixture might be considered as a potential source to isolate natural antidiabetic agents and physical parameters of hexane and ethyl acetate extracts will helpful to develop antidiabetic drug with further standardize properties.

Keywords: diabetes mellitus, in-vitro antidiabetic assays, medicinal plants, standardization

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Authors: Carolyne Ndungu, Wesley Too, Diana Kassaman

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Diabetes is a global public health problem with an increasing morbidity and mortality rate across the globe. It is reported that 422 million people worldwide have diabetes with type 2 diabetes more common in people of African descent. Whilst prevalence of diabetes is four times more than it was in the last three decades, making it the world's ninth greatest cause of mortality, treatment of complications resulting from poor glycemic control is still high, contributing to poverty level in sub-Saharan. Poor treatment adherence has also been identified as a major contributing factor poor glycemic control among diabetic patients and still remains a significant challenge especially among patients living in rural Kenya. This study therefore seeks to identify gaps, barriers and challenges towards medication non-adherence among diabetic patients on follow-up at Kiambu County Referral Hospital, Kenya. Methods: A cross- sectional descriptive study was carried out at Gatundu Level five Hospital in Kiambu County. The study population consisted of adult patients with type two diabetes mellitus (T2DM) on follow up, at the Diabetes clinic between the month of June to July 2022. Systematic sampling of 200 participants was carried out. Ethical approvals from relevant authorities were done and ethical aspects of the study were also observed. Data analysis is ongoing using logistic regression analysis. Results, recommendations -contribution of this study will be highlighted within the next one month.

Keywords: adherence, diabetes, medication, Kenya

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Authors: Munmunlisa Mohanty, K. D. Raju

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Rail industry is one of the model employers in India has separate national legislation (Railways Act 1989) to regulate its vast employment structure, functioning across the country. Indian Railway is not only the premier transport industry of the country; indeed, it is Asia’s most extensive rail network organisation and the world’s second-largest industry functioning under one management. With the growth of globalization of industrial products, the scope of anti-employment discrimination is no more confined to gender aspect only; instead, it extended to the unregularized classification of labour force applicable in the various industrial establishments in India. And the Indian Rail Industry inadvertently enhanced such discriminatory employment trends by engaging contractual labour in an unprecedented manner. The engagement of contractual labour by rail industry vanished the core “Employer-Employee” relationship between rail management and contractual labour who employed through the contractor. This employment trend reduces the cost of production and supervision, discourages the contractual labour from forming unions, and reduces its collective bargaining capacity. So, the primary intention of this paper is to highlight the increasing discriminatory employment scope for contractual labour engaged by Indian Railways. This paper critically analyses the diminishing perspective of anti-employment opportunity practiced by Indian Railways towards contractual labour and demands an urgent outlook on the probable scope of anti-employment discrimination against contractual labour engaged by Indian Railways. The researcher used doctrinal methodology where primary materials (Railways Act, Contract Labour Act and Occupational, health and Safety Code, 2020) and secondary data (CAG Report 2018, Railways Employment Regulation Rules, ILO Report etc.) are used for the paper.

Keywords: anti-employment, CAG Report, contractual labour, discrimination, Indian Railway, principal employer

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Authors: Lydia Foucan, Christine Rambhojan, Rachel Billy, Christophe Armand, Carl-Thony Michel, Jean-Marc Lacorte, Laurent Larifla

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Leptin, an adipocyte-derived hormone, modulates insulin secretion and action via the leptin receptor (LEPR) that is expressed in pancreatic beta cells, adipose tissue, and muscle. Several polymorphisms have been described in the human LEPR gene including p.K109R (rs1137100), p.Q223R (rs1137101) and p.K656N (rs1805094) polymorphisms. The role of these polymorphisms is not yet studied in Guadeloupian population. Our aim was to explore the association of LEPR polymorphisms (K109R, Q223R and K656N) with leptin levels and obesity in non-diabetic Afro-Caribbean subjects. Genotypic analysis of the three polymorphisms was performed in 425 subjects using TaqMan and KASPar Assays. Serum leptin was measured with ELISA kits Biovendor® (RD191001100). Logistic regressions were used for assessment of statistical associations. Mean age was 47.6 ± 12.7 years. Among the participants, 238 (56 %) were women, 124 (30%) were obese and 155 (36.5%) had abdominal obesity. Carriers of LEPR K656N rs1805094 rare allele had significant higher frequencies of obesity (P = 0.007), abdominal obesity (P = 0.004) and metabolic syndrome (P = 0.021) but mean leptin level was not significantly different between both groups (P = 0.075). Odds ratios, adjusted for age and sex associated with presence of rs1805094 rare allele were 1.8 (1.1-2.9), P = 0.012 for obesity, 2.0 (1.2-3.3), P = 0.008 for abdominal obesity and 1.8 (1.1-3.0), P = 0.031 for MetS. No significant association was found with K109R, Q223R. These findings suggest that the K656N polymorphism (but not the K109R or Q223R polymorphism) of LEPR is associated with obesity, abdominal obesity and metabolic syndrome in this Afro-Caribbean non-diabetic population.

Keywords: Afro-Caribbean, leptin levels, leptin receptor gene polymorphisms, obesity

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Authors: Raham El-Kahlout, Hadi Yassin, Asmaa Athani, Marwan Abou Madi, Gheyath Nasrallah

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Background: Since its first isolation in September 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has diffused across 27 countries infecting more than two thousand individuals with a high case fatality rate. MERS-CoV–specific antibodies are widely found in Dromedary camel along with viral shedding of similar viruses detected in human at same region, suggesting that MERS epidemiology may be central role by camel. Interestingly, MERS-CoV has also been also reported to be asymptomatic or to cause influenza-like mild illnesses. Therefore, in a country like Qatar (bordered Saudi Arabia), where camels are widely spread, serological surveys are important to explore the role of camels in MERS-CoV transmission. However, widespread strategic serological surveillances of MERS-CoV among populations, particularly in endemic country, are infrequent. In the absence of clear epidemiological view, cross-sectional MERS antibody surveillances in human populations are of global concern. Method: We performed a comparative serological screening of 4719 healthy blood donors, 135 baseline case contacts (high risk individual), and four MERS confirmed patients (by PCR) for the presence of anti-MERS IgG. Initially, samples were screened using Euroimmune anti- MERS-CoV IgG ELISA kit, the only commercial kit available in the market and recommended by the CDC as a screening kit. To confirm ELISA test results, farther serological testing was performed for all borderline and positive samples using two assays; the anti MERS-CoV IgG and IgM Euroimmune indirect immunofluorescent test (IIFT) and pseudoviral particle neutralizing assay (PPNA). Additionally, to test cross reactivity of anti-MERS-CoV antibody with other family members of coronavirus, borderline and positive samples were tested for the presence of the of IgG antibody of the following viruses; SARS, HCoV-229E, HKU1 using the Euroimmune IIFT for SARS and HCoV-229E and ELISA for HKU1. Results: In all of 4858 screened 15 samples [10 donors (0.21%, 10/4719), 1 case contact (0.77 %, 1/130), 3 patients (75%, 3/4)] anti-MERS IgG reactive/borderline samples were seen in ELISA. However, only 7 (0.14%) of them gave positive with in IIFT and only 3 (0.06%) was confirmed by the specific anti-MERS PPNA. One of the interesting findings was, a donor, who was selected in the control group as a negative anti-MERS IgG ELISA, yield reactive for anti-MERS IgM IIFT and was confirmed with the PPNA. Further, our preliminary results showed that there was a strong cross reactivity between anti- MERS-COV IgG with both HCoV-229E or anti-HKU1 IgG, yet, no cross reactivity of SARS were found. Conclusions: Our findings suggest that MERS-CoV is not heavily circulated among the population of Qatar and this is also indicated by low number of confirmed cases (only 18) since 2012. Additionally, the presence of antibody of other pathogenic human coronavirus may cause false positive results of both ELISA and IIFT, which stress the need for more evaluation studies for the available serological assays. Conclusion: this study provides an insight about the epidemiological view for MERS-CoV in Qatar population. It also provides a performance evaluation for the available serologic tests for MERS-CoV in a view of serologic status to other human coronaviruses.

Keywords: seroprevalence, MERS-CoV, healthy individuals, Qatar

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Authors: Mohammad Soltani, Ayoub Saeidi, Nikoo Khosravi, Hanieh Nohbaradar, Seyedeh Parya Barzanjeh, Hassane Zouhal

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Exercise training and herbs supplement represent have role in the treatment for patients with type 2 diabetes (T2D). However, it is unclear combined effects of exercise training and herbs supplements on diabetic risk markers. This study aimed to determine the effect of 12 weeks of combined exercise and broccoli supplementation on decitin-1 and insulin resistance in men with type 2 diabetes. Forty-four type 2 diabetes men (age, 48.52 ± 4.36) were randomly allocated to training -supplement (TS, n = 11), training- placebo (TP, n = 11), supplement (S, n = 11) and control- placebo (CP, n = 11) groups. The combined exercise program included 12 weeks, three sessions per week, that each session contained 45 minutes of resistance training with intensity 60-70% of one maximal repetition and 30 minutes aerobic training (running) with intensity 60-70% of maximum heart rate. In addition supplement groups consumed 10 grams of Broccoli per day for 12 weeks. Plasma Decitin-1, HOMA-IR, Insulin, glucose and body composition were assessed before and after training. Plasma Dectin-1, HOMA-IR, glucose and BMI significantly decreased in TS, TP and S groups compared with CP group (P < .05). In addition Insulin and skeletal muscles mass showed significant increase in TS and TP groups compared with S and CP groups (P < .05). It is concluded that both combined exercise training (aerobic-resistance) or broccoli supplement can improve plasma Decitin-1 and insulin resistance in two diabetic patients however combine of exercise training and broccoli supplement have more effective on these markers.

Keywords: broccoli supplements, combined training, decitin-1, insulin resistance, type 2 diabetes

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Authors: Mohammed Khalil Ur Rahman, Pradnya Chigle, Bushra Farhen

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Indian mythology believes that Vedas are eternal treatises. Vedas are categorized into four divisions viz., Rigveda, Yajurveda, Samveda, Atharveda. All these spiritual classics not only deal with rituals and customs but also consist of inclusion of many references related to health. Out of these four, Atharveda deals with maximum principles pertaining to health sciences. Therefore, it is said that the science and the art of Ayurveda has developed from Atharveda. Ayurveda deals with many medicinal plants either as a single therapeutic use or in combination. One such medicinal plant is Snuhi (Euphorbia neriifolia Linn.) which finds its extensive importance along with Haridra and Apamargakshar, in the preparation of Ksharsutra which in turn is used for the treatment of Fistula in Ano. It is interesting to note that this plant Snuhi is also referred in Holy Quran as the Tree of Zaqqum advocated as the food for the sinners as a part of torment. The reference in Surat Ad-Dukhan is as follows: - 44:43-46. “Verily, the tree of Zaqqum will be the food of the sinners, Like boiling oil, it will boil in the bellies, like the boiling of scalding water.” The above verse implies that plant Snuhi/Zaqqum due to irritant property acts as a drastic purgative but at the same time it also possesses anti inflammatory properties in order to relieve the irritation. These properties of Zaqqum has been unfolded in the modern research which states that, Diterpene polycyclic esters are responsible for its toxic and irritant nature whereas; triterpenes are responsible for its anti inflammatory property. Present work will be an effort to review the concept of Quran about latex of the Tree of Zaqqum in terms of its phytochemistry and its therapeutic use in Ksharsutra pertaining to irritant and anti inflammatory property.

Keywords: ayurveda, Quran, zaqqum, ksharsutra, latex piles, inflammation

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Authors: Sabrina Sebbane, Alina Elena Parvu

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Introduction: Santolina rosmarinifolia is a plant of the Santolina genus, a family made of medicinal plants widely used. Some of the Santolina species have been proven to have potent anti-inflammatory and anti-oxidant effects. However, no in vivo study has been made to demonstrate this in Santolina rosmarinifolia. The aim of our study is to experimentally evaluate the potential anti-inflammatory and anti-oxidant effects of Santolina rosmarinifolia plant extracts on acute inflammation in rats. These effects are defined by measuring the modifications on nitric oxide, reactive oxygen species and anti-oxidant response in serum. Materials and Methods: Rats were divided into 5 groups (n=6). Three groups were given Santolina rosmarinifolia extract by gavage in different concentrations(100%, 50%, 25%) for a week. Inflammation was induced by i.m injection of turpentine oil on the 8th day. One group was only given turpentine oil and the fifth group acted as control and was given only saline solution. Blood was collected and serum separated. Global tests were used to measure the oxidative stress, total oxidative status (TOS), total antioxidant reactivity (TAR) and the modified method of Griess assay to measure NO synthesis. Malondilaldehyde (MDA) and thiols levels were also assessed. Results: Santolina rosmarinifolia did not significantly change the TOS levels (p > 0.05). Santolina rosmarinifolia 25% and 50% decreased significantly the TAR levels (p < 0.001). Santolina 100% didn't have a significant effect on TAR (p > 0.05). All concentrations of Santolina rosmarinifolia increased the oxidative stress index (OSI) significantly(p < 0.05). Santolina rosmarinifolia 100% significantly decreased NO synthesis (p value < 0.05). In the diluted Santolina groups, no significant effect on NO synthesis was observed. In the groups treated with Santolina 100% and Santolina rosmarinifolia 50%, thiols concentration were significantly higher compared to the inflammation group (p < 0.02). A higher stimulatory effect was found in the Santolina 25% group (p value < 0.05). MDA levels were not significantly modified by the administration of Santolina rosmarinifolia (p > 0.05). Conclusion: All three solutions of Santolina rosmarinifolia had no important effect on oxidant production. However, Santolina rosmarinifolia solutions had a positive effect by increasing the thiols concentration in the serum of the models. The sum of all the effects produced by the administration of Santolina did not show a significant decrease of nitro-oxidative stress. Further experiments including smaller concentrations of Santolina rosmarinifolia will be made. Santolina rosmarinifolia should also be tested as a curative treatment.

Keywords: inflammation, MDA, nitric oxide, santolina rosmarinifolia, thiols, TAR, TOS

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Authors: Tahira Hyder, Saima Quraeshi, Zohaib Akram

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Salvadora Persica (SP) is known to have anti-inflammatory, antioxidant, anti-coagulant and anti-bacterial properties that may provide therapeutic benefits in the treatment of chronic periodontitis (CP). The current clinical trial was designed to investigate the clinical and anti-microbial effects of SP gel as an adjunct to scaling and root planning (SRP) in subjects with generalized CP. Sixty-six subjects with CP were randomized allocated into two groups: SRP + SP gel (test group) and SRP only (control group). Clinical parameters (periodontal pocket depth, gingival recession, clinical attachment level, bleeding score and plaque score) were recorded at baseline before SRP and at 6 weeks. At baseline and 6 weeks subgingival plaque samples were collected and periodontopathogen Porphyromonas Gingivalis (Pg) quantified using Real-time Polymerase Chain Reaction (RT-PCR). Both therapies reduced the mean periodontal pocket depth (PPD), plaque score (PS) and bleeding score (BOP) and improved the mean clinical attachment level (CAL) between baseline and 6 weeks. In subjects receiving adjunctive SP gel a statistically significant improvement was observed in BOP at follow-up compared to control group (15.01±3.47% and 22.81±6.81% respectively, p=0.001), while there was no statistically significant difference in periodontal pocket depth, gingival recession, clinical attachment level and plaque score between both groups. The test group displayed significantly greater Pg reduction compared to the control group after 6 weeks. The current study establishes that local delivery of SP gel into periodontal pocket in CP stimulated a significant reduction in bacteria Pg level and an improvement in gingival health, as evident from a reduced bleeding score, when used as an adjunct to SRP.

Keywords: miswak, scaling and root planing, porphyromonas gingivalis, chronic periodontitis

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Authors: Thomas Compton

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As Decolonialism becomes an important topic in Political Theory, the rupture between the colonized and the colonist relation has lost attention. Focusing on the anti-colonial activist Madhi Amel, we shall consider his attention to the permanence of the colonial relation and how it preempts Frank Wilderson’s formulation of (white) culturally necessary Anti-Black violence. Both projects draw attention away from empirical accounts of oppression, instead focusing on the structural relation which precipitates them. As Amel says that we should stop thinking of the ‘underdeveloped’ as beyond the colonial relation, Wilderson says we should stop think of the Black rights that have surpassed the role of the slave. However, Amel moves beyond his idol Althusser’s Structuralism toward a formulation of the colonial relation as source of domination. Our analysis will take a Lacanian turn in considering how this non-relation was formulated as a relation how this space of negativity became a ideological opportunity for Colonial domination. Wilderson’s work shall problematise this as we conclude with his criticisms of Structural accounts for the failure to consider how Black social death exists as more than necessity but a cite of white desire. Amel, a Lebanese activist and scholar (re)discovered by Hicham Safieddine, argues colonialism is more than the theft of land, but instead a privatization of collective property and form of investment which (re)produces the status of the capitalist in spaces ‘outside’ the market. Although Amel was a true Marxist-Leninsist, who exposited the economic determinacy of the Colonial Mode of Production, we are reading this account through Alenka Zupančič’s reformulation of the ‘invisible hand job of the market’. Amel points to the signifier ‘underdeveloped’ as buttressed on a pre-colonial epistemic break, as the Western investor (debt collector) sees the (post?) colony narcissistic image. However, the colony can never become site of class conflict, as the workers are not unified but existing between two countries. In industry, they are paid in Colonial subjectivisation, the promise of market (self)pleasure, at home, they are refugees. They are not, as Wilderson states, in the permanent social death of the slave, but they are less than the white worker. This is formulated as citizen (white), non-citizen (colonized), anti-citizen (Black/slave). Here we may also think of how indentured Indians were used as instruments of colonial violence. Wilderson’s aphorism “there is no analogy to anti-Black violence” lays bare his fundamental opposition between colonial and specifically anti-Black violence. It is not only that the debt collector, landowner, or other owners of production pleasures themselves as if their hand is invisible. The absolute negativity between colony and colonized provides a new frontier for desire, the development of a colonial mode of production. An invention inside the colonial structure that is generative of class substitution. We shall explore how Amel ignores the role of the slave but how Wilderson forecloses the history African anti-colonial.

Keywords: afropessimism, fanon, marxism, postcolonialism

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Authors: Abeer Y. Ibrahim, Faten M. Ibrahim, Samah A. El-Newary, Saber F. Hendawy

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Objective: Appreciation of in-vitro anti-inflammatory and antioxidant characters of Vitex agnus-castus berries alcoholic extract and fractions, as well as in-vivo antitumor ability of alcoholic extract and chloroform fraction against Ehrlich ascites carcinoma is the aim of this study. Material and methods: Antioxidant properties of crude alcoholic extract of vitex berries as well as petroleum ether, chloroform, ethyl acetate and butanol fractions were evaluated, in-vitro assessments, as compared with standard materials, l-ascorbic acid (vitamin C) and butylated hydroxyl toluene(BHT). The anti-inflammatory activity was investigated in cyclooxygenase (COX)-1 and COX-2 inhibition assays. Moreover, in-vivo antitumor effect of vitex berries alcoholic and chloroform extracts were evaluated using Ehrlich ascites carcinoma model. Data were presented as mean±SE, and data were analyzed by one-way analysis of variance test. Results and conclusion: Berries crude extract showed potent antioxidant activity followed with its fractions ethyl acetate and chloroform as compared with standard (V.C and BHT). Ethyl acetate fraction showed good reduction capability, metal ion chelation, hydrogen peroxide scavenging, nitric oxide scavenging and superoxide anion scavenging. Meanwhile, chloroform fraction produced the highest free radical scavenging activity and total antioxidant capacity. In respectable of lipid peroxidation inhibition, crude alcoholic extract and its fractions cleared weak inhibition in comparing with standard materials. Anti-inflammatory activity of V. agnus-castus berries chloroform fraction of vitex was best COX-2 inhibitor (IC₅₀, 135.41 µg/ ml) as compared to vitex alcoholic extract or ethyl acetate fraction with weak inhibitory effect on COX-1 (IC50, 778.432 µg/ ml), where the lowest effect on COX-1 was recorded with alcoholic extract. Alcoholic extract and its fractions showed weak COX-1 inhibition activity, whereas COX-2 was inhibited (100%), compared with celecoxib drug (72% at 1000ppm). The crude alcoholic and chloroform extracts of V. agnus-castus barries significantly reduced the viable Ehrlich cell count and increased nonviable count with amelioration of all hematological parameters. This amelioration was reflected on increasing median survival time and significant increase (P < 0.05) in lifespan.

Keywords: anti-inflammatory, antioxidants, ehrlich ascites carcinoma, Vitex agnus-castus

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Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.

Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin

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Authors: Salma A. El-Marasy, Reham M. Abd-Elsalam, Omar A. Ahmed-Farid

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Dementia is characterized by impairments in memory and other cognitive abilities. This study aims to elucidate the possible ameliorative effect of silymarin on scopolamine-induced dementia using the object recognition test (ORT). The study was extended to demonstrate the role of cholinergic activity, oxidative stress, neuroinflammation, brain neurotransmitters and histopathological changes in the anti-amnestic effect of silymarin in demented rats. Wistar rats were pretreated with silymarin (200, 400, 800 mg/kg) or donepezil (10 mg/kg) orally for 14 consecutive days. Dementia was induced after the last drug administration by a single intraperitoneal dose of scopolamine (16 mg/kg). Then behavioral, biochemical, histopathological, and immunohistochemical analyses were then performed. Rats pretreated with silymarin counteracted scopolamine-induced non-spatial working memory impairment in the ORT and decreased acetylcholinesterase (AChE) activity, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), restored gamma-aminobutyric acid (GABA) and dopamine (DA) contents in the cortical and hippocampal brain homogenates. Silymarin dose-dependently reversed scopolamine-induced histopathological changes. Immunohistochemical analysis showed that silymarin dose-dependently mitigated protein expression of a glial fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NF-κB) in the brain cortex and hippocampus. All these effects of silymarin were similar to that of the standard anti-amnestic drug, donepezil. This study reveals that the ameliorative effect of silymarin on scopolamine-induced dementia in rats using the ORT maybe in part mediated by, enhancement of cholinergic activity, anti-oxidant and anti-inflammatory activities as well as mitigation in brain neurotransmitters and histopathological changes.

Keywords: dementia, donepezil, object recognition test, rats, silymarin, scopolamine

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Authors: Gauri Shankar Shah

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Objectives: The Type I diabetes mellitus in children is frequently a missed diagnosis and children presents in emergency with diabetic ketoacidosis having significant morbidity and mortality. The present study was done to find out the clinical presentation and outcome at a tertiary-care centre. Methods: This was retrospective analysis of data of Type I diabetes mellitus reporting to our centre during last one year (2012-2013). Results: There were 12 patients (8 males) and the age group was 4-14 years (mean ± 3.7). The presenting symptoms were fever, vomiting, altered sensorium and fast breathing in 8 (66.6%), 6 (50%), 4 (33.3%), and 4 (33.3%) cases, respectively. The classical triad of polyuria, polydypsia, and polyphagia were present only in two patients (33.2%). Seizures and epigastric pain were found in two cases each (33.2%). The four cases (33.3%) presented with diabetic ketoacidosis due to discontinuation of insulin doses, while 2 had hyperglycemia alone. The hemogram revealed mean hemoglobin of 12.1± 1.6 g/dL and total leukocyte count was 22,883.3 ± 10,345.9 per mm3, with polymorphs percentage of 73.1 ± 9.0%. The mean blood sugar at presentation was 740 ± 277 mg/ dl (544–1240). HbA1c ranged between 7.1-8.8 with mean of 8.1±0.6 %. The mean sodium, potassium, blood ph, pCO2, pO2 and bicarbonate were 140.8 ± 6.9 mEq/L, 4.4 ± 1.8mEq/L, 7.0 ± 0.2, 20.2 ± 10.8 mmHg, 112.6 ± 46.5 mmHg and 9.2 ± 8.8 mEq/L, respectively. All the patients were managed in pediatric intensive care unit as per our protocol, recovered and discharged on intermediate insulin given twice daily. Conclusions: Thus, it shows that these patients have uncontrolled hyperglycemia and often presents in emergency with ketoacidosis and deranged biochemical profile. The regular administration of insulin, frequent monitoring of blood sugar and health education are required to have better metabolic control and good quality of life.

Keywords: type I diabetes mellitus, hyperglycemia, outcome, glycemic control

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Authors: Paul J Yazaki, Michael Bouvet, John Shively

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Surgery for solid gastrointestinal (GI) cancers such as pancreatic, colorectal, and gastric adenocarcinoma remains the mainstay of curative therapy. Complete resection of the primary tumor with negative margins (R0 resection), its draining lymph nodes, and distant metastases offers the optimal surgical benefit. Real-time fluorescence guided surgery (FGS) promises to improve GI cancer outcomes and is rapidly advancing with tumor-specific antibody conjugated fluorophores that can be imaged using near infrared (NIR) technology. Carcinoembryonic Antigen (CEA) is a non-internalizing tumor antigen validated as a surface tumor marker expressed in >95% of colorectal, 80% of gastric, and 60% of pancreatic adenocarcinomas. Our humanized anti-CEA hT84.66-M5A (M5A) monoclonal antibody (mAb)was conjugated with the NHS-IRDye800CW fluorophore and shown it can rapidly and effectively NIRoptical imageorthotopically implanted human colon and pancreatic cancer in mouse models. A limitation observed is that these NIR-800 dye conjugated mAbs have a rapid clearance from the blood, leading to a narrow timeframe for FGS and requiring high doses for effective optical imaging. We developed a novel antibody-fluorophore conjugate by incorporating a PEGylated sidearm linker to shield or mask the IR800 dye’s hydrophobicity which effectively extended the agent’s blood circulation half-life leading to increased tumor sensitivity and lowered normal hepatic uptake. We hypothesized that our unique anti-CEA linked to the fluorophore, IR800 by PEGylated sidewinder, M5A-SW-IR800 will become the next generation optical imaging agent, safe, effective, and widely applicable for intraoperative image guided surgery in CEA expressing GI cancers.

Keywords: optical imaging, anti-CEA, cancer, fluorescence-guided surgery

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Authors: Anjali Verma, Mahesh Pal, Veena Pande, Dalip Kumar Upreti

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The present study is carried out to explore the anti-hyperglycemic activity of Leucas cephalotes plant parts. A fruit, leaves, stems, and roots part of the Leucas cephalotes has been extracted in ethanol and have been evaluated for anti-hyperglycemic activity. The present study indicated that, ethanolic extract of fruit and leaves have shown significant α- amylase inhibitory activity with IC50 value of 92.86 ± 0.89 μg/mL and 98.09 ± 0.69 μg/mL respectively. Two known compounds β-sitosterol and lupeol were isolated from ethanolic extract of L. cephalotes leaves and were subjected to anti-hyperglycemic activity. Lupeol shows the best activity with IC50 55.73 ± 0.47 μg/mL and the results were verified by docking study of these compounds with mammalian α-amylase was carried out on its active site. It was concluded from the study that β-sitosterol and lupeol form one H-bond interactions with the active site residues either Asp212 or Thr21. The estimated free energy binding of β-sitosterol was found to be -9.47 kcal mol-1 with an estimated inhibition constant (Ki) of 558.94 nmol whereas the estimated free energy binding of lupeol was -11.73 kcal mol-1 with an estimated inhibition constant (Ki) of 476.71pmmol. The present study clearly showed that lupeol is more potent in comparison to β-sitosterol. The study indicates that L. cephalotes have significant potential to inhibit α-amylase enzyme.

Keywords: alpha-amylase, beta-sitosterol, hyperglycemia, lupeol

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Authors: Sharif Abdelghany

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Polymeric nanoparticles have been widely investigated as a controlled release drug delivery platform for the treatment of tuberculosis (TB). These nanoparticles were also readily internalised into macrophages, leading to high intracellular drug concentration. In this study two anti-TB drugs, amikacin and moxifloxacin were encapsulated into PLGA nanoparticles. The novelty of this work appears in: (1) the efficient encapsulation of two hydrophilic second-line anti-TB drugs, and (2) intramacrophage delivery of this synergistic combination potentially for rapid treatment of multi-drug resistant TB (MDR-TB). Two water-oil-water (w/o/w) emulsion strategies were employed in this study: (1) alginate coated PLGA nanoparticles, and (2) alginate entrapped PLGA nanoparticles. The average particle size and polydispersity index (PDI) of the alginate coated PLGA nanoparticles were found to be unfavourably high with values of 640 ± 32 nm and 0.63 ± 0.09, respectively. In contrast, the alginate entrapped PLGA nanoparticles were within the desirable particle size range of 282 - 315 nm and the PDI was 0.08 - 0.16, and therefore were chosen for subsequent studies. Alginate entrapped PLGA nanoparticles yielded a drug loading of over 10 µg/mg powder for amikacin, and more than 5 µg/mg for moxifloxacin and entrapment efficiencies range of approximately 25-31% for moxifloxacin and 51-59% for amikacin. To study macrophage uptake efficiency, the nanoparticles of alginate entrapped nanoparticle formulation were loaded with acridine orange as a marker, seeded to THP-1 derived macrophages and viewed under confocal microscopy. The particles were readily internalised into the macrophages and highly concentrated in the nucleus region. Furthermore, the anti-mycobacterial activity of the drug-loaded particles was evaluated using M. tuberculosis-infected macrophages, which revealed a significant reduction (4 log reduction) of viable bacterial count compared to the untreated group. In conclusion, the amikacin-moxifloxacin alginate entrapped PLGA nanoparticles are promising for further in vivo studies.

Keywords: moxifloxacin and amikacin, nanoparticles, multidrug resistant TB, PLGA

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Authors: Abdul Salam Turkmani

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The Lower Cretaceous rocks are exposed only in the mountains regions of Syria, such as the Anti- Lebanon mountain on the western side of Damascus. The lower cretaceous sequences are made up of different rocks. The upper and middle parts of the section are composed mainly of carbonate sediments and, less frequently, gypsum and anhydrite. The lower beds are mainly composed of sandstone, conglomerate and clay. Clay samples were collected from the study area, which is located about 45 km west of the city of Damascus, near the border village of Kfer Yabous and to the left of the Damascus -Beirut International Road, within the lower Cretaceous upper Aptian deposits. The properties of clay were carried out by X-ray diffraction (XRD) and, X-ray fluorescence (XRF) and Thermal Analysis (DTA-TG-DSC) techniques. The studied samples of clay were mainly composed of kaolinite, quartz, illite. Chemical analysis shows the content of SiO₂ varied between 46.06 to 73 % Al₂O₃ 14.55-26.56%, about the staining oxides (Fe₂O₃ + TiO₂), the total content is about 4.3 to 12.5%. The physical properties were determined by studying the behavior of the body before and after firing, showed low bending strength values (22.5 kg/cm²) after drying, and (about 247 kg/cm²) after firing at 1180°C, water absorption value was about 10%. The cubic thermal expansion coefficient at 1140°C is 213.77 x 10-7 /°C. All of the presented results confirm the suitability of this clay for the ceramic industry.

Keywords: anti-Lebanon, Damascus, ceramic, clay, thermal analysis, thermal expansion coefficient

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