Search results for: Wistar rats

Authors: Benedict Ofori, Kwabena Sarpong, Stephen Antwi

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Background: Medicinal plants are utilized all around the world and are becoming increasingly important economically. The WHO notes that ‘inappropriate use of traditional medicines or practices can have negative or dangerous effects and that future research is needed to ascertain the efficacy and safety of such practices and medicinal plants used by traditional medicine systems. The poor around the world have limited access to palliative care or pain relief. Pharmacologists have been focused on developing safe and effective anti-inflammatory drugs. Most of the issues related to their use have been linked to the fact that numerous traditional and herbal treatments are classified in different nations as meals or dietary supplements. As a result, there is no need for evidence of the quality, efficacy, or safety of these herbal formulations before they are marketed. The fact that access to drugs meant for pain relief is limited in low-income countries means advanced studies should be done on home drugs meant for inflammation to close the gap. Methods: The ethanolic extracts of the plant were screened for the presence of 10 phytochemicals. The Pierce BCA Protein Assay Kit was used for the determination of the protein concentration of the egg white. The rats were randomly selected and put in 6 groups. The egg white was sub-plantar injected into the right-hand paws of the rats to induce inflammation. The animals were treated with the three plant extracts obtained from the root bark, stem, and leaves of the plant. The control groups were treated with normal saline, while the standard groups were treated with standard drugs indomethacin and celecoxib. Plethysmometer was used to measure the change in paw volume of the animals over the course of the experiment. Results: The results of the phytochemical screening revealed the presence of reducing sugars and saponins. Alkaloids were present in only R.L.S (1:1:1), and phytosterols were found in R.L(1:1) and R.L.S (1:1:1). The estimated protein concentration was found to be 103.75 mg/ml. The control group had an observable increase in paw volume, which indicated that inflammation was induced during the 5 hours. The increase in paw volume for the control group peaked at the 1st hour and decreased gradually throughout the experiment, with minimal changes in the paw volumes. The 2nd and 3rd groups were treated with 20 mg/kg of indomethacin and celecoxib. The anti-inflammatory activities of indomethacin and celecoxib were calculated to be 21.4% and 4.28%, respectively. The remaining 3 groups were treated with 2 dose levels of 200mg/kg plant extracts. R.L.S, R.L, and S.R.L had anti-inflammatory activities of 22.3%, 8.2%, and 12.07%, respectively. Conclusions: Egg albumin-induced paw model in rats can be used to evaluate the anti-inflammatory activity of herbs that might have potential anti-inflammatory activity. Herbal medications have potential anti-inflammatory activities and can be used to manage various inflammatory conditions if their efficacy and side effects are well studied. The three extracts all possessed anti-inflammatory activity, with R.L.S having the highest anti-inflammatory activity.

Keywords: inflammation, capparis erythrocarpos, anti-inflammatory activity, herbal medicine, paw volume, egg albumin

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Authors: Kinjal H. Shah, Piyush M. Patel

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Diabetes mellitus is considered to be a serious endocrine syndrome. Synthetic hypoglycemic agents can produce serious side effects including hematological effects, coma, and disturbances of the liver and kidney. In addition, they are not suitable for use during pregnancy. In recent years, there have been relatively few reports of short-term side effects or toxicity due to sulphonylureas. Published figures and frequency of side effects in large series of patient range from about 1 to 5%, with symptoms severe enough to lead to the withdrawal of the drug in less than 1 to 2%. Adverse effects, in general, have been of the following type: allergic skin reactions, gastrointestinal disturbances, blood dyscrasias, hepatic dysfunction, and hypoglycemia. The associated disadvantages with insulin and oral hypoglycemic agents have led to stimulation in the research for locating natural resources showing antidiabetic activity and to explore the possibilities of using traditional medicines with proper chemical and pharmacological profiles. Literature survey reveals that the inhabitants of Abbottabad district of Pakistan use the dried leaf powder along with table salt and water orally for treating diabetes, skin allergy, wounds and as a blood purifier, where they pronounced the plant locally as ‘Nem.' The detailed phytochemical investigation of the Cedrela toona Roxb. leaves for antidiabetic activity has not been documented. Hence, there is a need for phytochemical investigation of the leaves for antidiabetic activity. The collection of fresh leaves and authentification followed by successive extraction, phytochemical screening, and testing of antidiabetic activity. The blood glucose level was reduced maximum in ethanol extract at 5th and 7th h after treatment. Blood glucose was depressed by 8.2% and 10.06% in alloxan – induced diabetic rats after treatment which was comparable to the standard drug, Glibenclamide. This may be due to the activation of the existing pancreatic cells in diabetic rats by the ethanolic extract.

Keywords: antidiabetic, Cedrela toona Roxb., phytochemical screening, blood glucose

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Authors: Moetazza M. Alshafei, Ahmed M. Mabrouk, Emtenan M. Hanafi, Manal M. Ramadan, Reda M. S. Korany, Seham S. Kassem, Dina Mostafa Mohammed

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Metabolic syndrome (MeS) is a major health problem with a high incidence of obese individuals worldwide. Increased related morbidity of diabetes, hypertension and fatty liver disease, and complicated cardiovascular disease are inevitable. Boswellia serrata gum (Bos) is a promising traditional medicinal plant; it has several pharmacological properties, including anti-inflammatory, antioxidant, and antilipase activities. Probiotics (Bac) supplements have good benefits on health and MeS, whether it is supplemented in combination with prebiotics or alone. Microencapsulation helps to mask unpalatable taste and odor and deliver active ingredients to targeted organs. Methodology MeS rat model was produced by feeding rats with a high fat, high CHO diet (HFD). Bos was extracted, and both Bos and the probiotic were microencapsulated with a spray drier. Female rats were divided into 5 groups (N8). HFD control, control normal receiving basic diet, HFD treated, from the start of the experiment, either with encapsulated Bos, Bac and Bos or Bac only, all treatments were received for eight weeks (after approval from NRC animal ethical committee). Serum was collected to analyze lipid profile, blood sugar, liver and kidney functions, antioxidants, leptin, and progesterone. Rat's organs and body fat were weighed and collected for histopathology. Statistical analysis was done by use of one way Anova test in the SPSS program. Results showed control of elevated body weight, lipid profile, and glucose levels as well as decrease of body fat index and improvement of histopathology of liver and heart, especially in combination. Conclusion: We concluded that both microencapsulated Bos and probiotics have a controlling effect on MeS parameters.

Keywords: metabolic syndrome, Boswellia serata, probiotic, micro-encapsulation, histopathology, liver steatosis

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Authors: Ikram Mohamed Eltayeb, Ustina Saeed Barsoumbolice

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Cinnamomum zeylanicum belong to the family Lauraceae and Artemisia absinthium belong to the family Asteraceae. Both were traditionally used as antiemetic, anti-inflammatory and antidiabetic. In Sudan, the mixtures of the two plants were traditionally used for the treatment of diabetes. Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia. It is mainly classified into two major groups, type-1 and type-2. Type-2 is a combination of resistance to insulin action and an inadequate compensatory insulin secretory response. The treatment of type-2 diabetes mellitus (DM) with synthetic drugs have many side effects so many researches were conducted to overcome or reduce this side effects by using alternative medicine. The objective of this study is to investigate and compare the anti-diabetic activity of C. zeylanicum and A. absinthium and their combination with difference ratio. C. zeylanicum and A. absinthium were extracted by 96% ethanol using Soxhlet apparatus. Thirty-two rats were divided into eight groups; each group contains four rats. 1st group was administered with distilled water at dose of 10ml/kg, 2nd group had received glucose only at dose of 2g/kg intraperitoneal, the standard group (3rd group) had received Glibenclamide orally at dose of 0.45mg/kg, 4th group received 100 mg C. zeylanicum + 300 mg A. absinthium with a ratio of (25:75), 5th group received 300 mg C. zeylanicum + 100 mg A. absinthium with a ratio of (75:25), 6th group received 200 mg C. zeylanicum + 200 mg A. absinthiumwith a ratio of (50:50), 7th group received 400 mg of A. absinthium, 8th group received 400 mg of C. zeylanicum. Then the blood samples were taken Retro-orbitally at 0, 1, 2 and 4 hours and the glucose level was measured. Each plant alone and their combination with different ratios shows antidiabetic effect. The significant activity was shown by A. absinthium extract (400 mg/kg), combination of ratio of (75:25) A. absinthium: C. zeylanicum(400mg/kg) and then C. zeylanicum(400mg/kg) with p-value 0.001, 0.022, 0.030 respectively, the activity was found to be increased with time. The other combinations showed less activity with p-value > 0.05. The result concludes that the good antidiabetic activity was performed by A. absinthium alone and its activity decreased by increase combination ratio with C. zeylanicum. Which maybe explains by the antagonistic effect between the compounds of C. zeylanicum and A. absinthium.

Keywords: antidiabetic, Artemisia absinthium , cinnamomum zeylanicum, combination

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Authors: Bea Carmel H. Casiding, Charmaine A. Guy, Funny Jovis P. Malasan, Katrina Chelsea B. Manlutac, Danielle Ann N. Novilla, Marianne R. Oliveros, Magnolia C. Sibulo

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Moon jellyfish, Aurelia aurita, has become a popular research organism for diverse studies. Recent studies have verified the prevention of blood clotting properties of the moon jellyfish tentacle extract through in vitro methods. The purpose of this study was to validate the blood clotting ability of A. aurita tentacle extract using in vivo method of experimentation. The tentacles of A. aurita jellyfish were excised and filtered then centrifuged at 3000xg for 10 minutes. The crude nematocyst extract was suspended in 1:6 ratios with phosphate buffer solution and sonicated for three periods of 20 seconds each at 50 Hz. Protein concentration of the extract was determined using Bradford Assay. Bovine serum albumin was the standard solution used with the following concentrations: 35.0, 70.0, 105.0, 140.0, 175.0, 210.0, 245.0, and 280.0 µg/mL. The absorbance was read at 595 nm. Toxicity testing from OECD guidelines was adapted. The extract suspended in phosphate-buffered saline solution was arbitrarily set into three doses (0.1mg/kg, 0.3mg/kg, 0.5mg/kg) and were administered daily for five days to the experimental groups of five male Sprague-Dawley rats (one dose per group). Before and after the administration period, bleeding time and clotting time tests were performed. The One-way Analysis of Variance (ANOVA) was used to analyze the difference of before and after bleeding time and clotting time from the three treatment groups, time, positive and negative control groups. The average protein concentration of the sonicated crude tentacle extract was 206.5 µg/mL. The highest dose administered (0.5mg/kg) produced significant increase in the time for both bleeding and clotting tests. However, the preceding lower dose (0.3mg/kg) only was significantly effective for clotting time test. The protein contained in the tentacle extract with a concentration of 206.5 mcg/mL and dose of 0.3 mg/kg and 0.5 mg/kg of A. aurita elicited anticoagulating activity.

Keywords: anticoagulant, bleeding time test, clotting time test, moon jellyfish

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Authors: Mudrika Singhal

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The research paper is basically about how the genetically modified organisms evolved and their significance in today’s world. It also highlights about the various pros and cons of the genetically modified organisms and the progress of India in this field. A genetically modified organism is the one whose genetic material has been altered using genetic engineering techniques. They have a wide range of uses such as transgenic plants, genetically modified mammals such as mouse and also in insects and aquatic life. Their use is rooted back to the time around 12,000 B.C. when humans domesticated plants and animals. At that humans used genetically modified organisms produced by the procedure of selective breeding and not by genetic engineering techniques. Selective breeding is the procedure in which selective traits are bred in plants and animals and then are domesticated. Domestication of wild plants into a suitable cultigen is a well known example of this technique. GMOs have uses in varied fields ranging from biological and medical research, production of pharmaceutical drugs to agricultural fields. The first organisms to be genetically modified were the microbes because of their simpler genetics. At present the genetically modified protein insulin is used to treat diabetes. In the case of plants transgenic plants, genetically modified crops and cisgenic plants are the examples of genetic modification. In the case of mammals, transgenic animals such as mice, rats etc. serve various purposes such as researching human diseases, improvement in animal health etc. Now coming upon the pros and cons related to the genetically modified organisms, pros include crops with higher yield, less growth time and more predictable in comparison to traditional breeding. Cons include that they are dangerous to mammals such as rats, these products contain protein which would trigger allergic reactions. In India presently, group of GMOs include GM microorganisms, transgenic crops and animals. There are varied applications in the field of healthcare and agriculture. In the nutshell, the research paper is about the progress in the field of genetic modification, taking along the effects in today’s world.

Keywords: applications, mammals, transgenic, engineering and technology

Procedia PDF Downloads 579

Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

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Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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Authors: Rawia M. Khalil, Ahmed A. Abd El Rahman, Mahfouz A. Kassem, Mohamed S. El Ridi, Mona M. Abou Samra, Ghada E. A. Awad, Soheir S. Mansy

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Solid lipid nanoparticles (SLNs) have gained great attention for the topical treatment of skin associated fungal infection as they facilitate the skin penetration of loaded drugs. Our work deals with the preparation of nystatin loaded solid lipid nanoparticles (NystSLNs) using the hot homogenization and ultrasonication method. The prepared NystSLNs were characterized in terms of entrapment efficiency, particle size, zeta potential, transmission electron microscopy, differential scanning calorimetry, rheological behavior and in vitro drug release. A stability study for 6 months was performed. A microbiological study was conducted in male rats infected with Candida albicans, by counting the colonies and examining the histopathological changes induced on the skin of infected rats. The results showed that SLNs dispersions are spherical in shape with particle size ranging from 83.26±11.33 to 955.04±1.09 nm. The entrapment efficiencies are ranging from 19.73±1.21 to 72.46±0.66% with zeta potential ranging from -18.9 to -38.8 mV and shear-thinning rheological Behavior. The stability studies done for 6 months showed that nystatin (Nyst) is a good candidate for topical SLN formulations. A least number of colony forming unit/ ml (cfu/ml) was recorded for the selected NystSLN compared to the drug solution and the commercial Nystatin® cream present in the market. It can be fulfilled from this work that SLNs provide a good skin targeting effect and may represent promising carrier for topical delivery of Nyst offering the sustained release and maintaining the localized effect, resulting in an effective treatment of cutaneous fungal infection.

Keywords: candida infections, hot homogenization, nystatin, solid lipid nanoparticles, stability, topical delivery

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Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

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The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

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Authors: Sanjay Singh, Karunanithi Priyanka, Ramoji Kosuru, Raju Prasad Sharma

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Herbal drugs are well known for their mixed pharmacological activities with the benefit of no harmful side effects. The use of herbal drugs is limited because of their higher dose requirement, frequent drug administration, poor bioavailability of phytochemicals and delayed onset of action. Ficus religiosa, a potent anti-oxidant plant useful in the treatment of diabetes and cancer was selected for the study. Solid lipid nanoparticles (SLN) of Ficus religiosa extract was developed for the enhancement in oral bioavailability of stigmasterol and β-sitosterol-d-glucoside, principal components present in the extract. Hot homogenization followed by ultrasonication method was used to develop extract loaded SLN. Developed extract loaded SLN were characterized for particle size, PDI, zeta potential, entrapment efficiency, in vitro drug release and kinetics, fourier transform infra-red spectroscopy, differential scanning calorimetry, powder X-ray diffractrometry and stability studies. Entrapment efficiency of optimized extract loaded SLN was found to be 68.46 % (56.13 % of stigmasterol and 12.33 % of β-sitosteryl-d-glucoside, respectively). RP HPLC method development was done for simultaneous estimation of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract in rat plasma. Bioavailability studies were carried out for extract in suspension form and optimized extract loaded SLN. AUC of stigmasterol and β-sitosterol-d-glucoside were increased by 6.7-folds by 9.2-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Also, Cmax of stigmasterol and β-sitosterol-d-glucoside were increased by 4.3-folds by 3.9-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Mean residence times (MRT) for stigmasterol were found to be 12.3 ± 0.67 hours from extract and 7.4 ± 2.1 hours from SLN and for β-sitosterol-d-glucoside, 10.49 ± 2.9 hours from extract and 6.4 ± 0.3 hours from SLN. Hence, it was concluded that SLN enhanced the bioavailability and reduced the MRT of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract which in turn may lead to reduction in dose of Ficus religiosa extract, prolonged duration of action and also enhanced therapeutic efficacy.

Keywords: Ficus religiosa, phytosterolins, bioavailability, solid lipid nanoparticles, stigmasterol and β-sitosteryl-d-glucoside

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Authors: Konstantin Yu. Moiseev, Antonina F. Budnik, Andrey I. Emanuilov, Petr M. Masliukov

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The vast majority of sympathetic ganglionic neurons are catecholaminergic. Some sympathetic neurons lack catecholamines and mostly use acetylcholine as their main neurotransmitter. Some cholinergic postganglionic neurons also express neuronal nitric oxide synthase (nNOS). Preganglionic sympathetic neurons are cholinergic and most of them are also nNOS-immunoreactive (IR). The purpose of this study was to gain further insight into the neuroplasticity of sympathetic neurons during postnatal ontogenesis by comparing the development of pre- and postganglionic neurons expressing nNOS in different mammals. nNOS was investigated by immunohistochemistry in the sympathetic superior cervical ganglion (SCG), stellate ganglion (SG), celiac ganglion (CG) and spinal cord from rats, mice and cats of different ages (newborn, 10-day-old, 20-day-old, 30-day-old, 2-month-old and 2-year-old). In rats and mice, nNOS-positive neurons were not found in sympathetic ganglia from birth onwards. In cats, non-catecholaminergic nNOS-IR sympathetic ganglionic neurons are present from the moment of birth. In all studied age groups, substantial populations of nNOS-IR cells (up to 8.3%) was found in the SG, with a much smaller population found in the SCG (<1%) and only few cells observed in the CG. The percentage of nNOS-IR neurons in the CG and SCG did not significantly change during development. The proportion of nNOS-IR neuron profiles in the SG increased in first 20 days of life from 2.3±0.15% to 8.3±0.56%. In the SG, percentages of nNOS-IR sympathetic neurons colocalizing vasoactive intestinal peptide increased in the first 20 days of life. Choline acetyltransferase (ChAT)-IR and calcitonin gene-related peptide-IR neurons were not observed in the sympathetic ganglia of newborn animals and did not appear until 10 days after birth. In the SG of newborn and 10-day-old kittens, the majority of NOS-IR neurons were calbindin (CB)-IR, whereas in the SCG and CG of cats of all age groups and in the SG of 30-day-old and older kittens, the vast majority of NOS-IR neurons lacked CB. In newborn mammals, the most of sympathetic preganglionic neurons in the nucleus intermediolateralis thoracolumbalis pars principalis (nucl.ILp) were nNOS-IR. The percentage of nNOS-IR neurons decreased and the same parameter of ChAT-IR neurons increased during the development. We conclude that the development of nNOS-IR preganglionic and ganglionic sympathetic neurons in different mammals has time and species differences.

Keywords: sympathetic neuron, nitric oxide synthase, immunohistochemistry, development

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Authors: Vaibhav D. Bhatt, Anju P. Kunjadia, D. S. Nauriyal, Bhumika J. Joshi, Chaitanya G. Joshi

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Metagenomic analysis of milk samples collected from local cattle breed, kankrej (Bos indicus), Gir (Bos indicus) and Crossbred (Bos indicus X Bos taurus) cattle harbouring subclinical mastitis was carried out by next-generation sequencing (NGS) 454 GS-FLX technology. Around 56 different species including members of Enterobacteriales, Pseudomonadales, Bacillales and Lactobacillales with varying abundance were detected in infected milk. The interesting presence of bacteriophages against Staphylococcus aureus, Escherichia coli, Enterobacter and Yersinia species were observed, especially Enterobacteria and E. coli phages (0∙32%) in Kankrej, Enterobacteria and Staphylococcus phages (1∙05%) in Gir and Staphylococcus phages (2∙32%) in crossbred cattle. NGS findings suggest that phages may be involved in imparting natural resistance of the cattle against pathogens. Further infected milk samples were subjected for bacterial isolation. Fourteen different isolates were identified, and DNA was extracted. Genes (Tet-K, Msr-A, and Mec-A) providing antibiotic resistance to the bacteria were screened by Polymerase Chain Reaction and results were validated with traditional antibiotic assay. Total 3 bacteriophages were isolated from nearby environment of the cattle farm. The efficacy of phages was checked against multi-drug resistant bacteria, identified by PCR. In-vivo study was carried out for phage therapy in mammary glands of female rats “Wister albino”. Mammary glands were infused with MDR isolates for 3 consecutive days. Recovery was observed in infected rats after intramammary infusion of sterile phage suspension. From day 4th onwards, level of C-reactive protein was significant increases up to day 12th . However, significant reduction was observed between days 12th to 18th post treatment. Bacteriophages have significant potential as antibacterial agents and their ability to replicate exponentially within their hosts and their specificity, make them ideal candidates for more sustainable mastitis control.

Keywords: bacteriophages, c-reactive protein, mastitis, metagenomic analysis

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Authors: Maria Giovanna Lupo, Marina Camera, Marcello Rattazzi, Nicola Ferri

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A complex interplay among chronic kidney disease, lipid metabolism and aortic calcification has been recognized starting from results of many clinical and experimental studies. Here we investigated the influence of kidney function on PCSK9 levels, both in uremic rats and in clinical observation study, and its potential direct action on cultured smooth muscle cells (SMCs) calcification. In a cohort of 594 subjects enrolled in a single centre, observational, cross-sectional and longitudinal study, a negative association between GFR and plasma PCSK9 was found. Atherosclerotic cardiovascular disease (ASCVD), as co-morbidity, further increased PCSK9 plasma levels. Diet-induced uremic condition in rats, induced aortic calcification and increased total cholesterol and PCSK9 levels in plasma, livers and kidneys. Immunohistochemical analysis confirmed PCSK9 expression in aortic SMCs. SMCs overexpressing PCSK9 (SMCsPCSK9), cultured for 7-days in a pro-calcification environment (2.0mM or 2.4mM inorganic phosphate, Pi) showed a significantly higher extracellular calcium (Ca2+) deposition compared to mocked SMCs. Under the same experimental conditions, the addition of exogenous recombinant PCSK9 did not increase the extracellular calcification of SMCs. By flow cytometry analysis we showed that SMCsPCSK9, in response to 2.4mM Pi, released higher number of extracellular vesicles (EVs) positive for three tetraspanin molecules, such as CD63, CD9, and CD81. EVs derived from SMCsPCSK9 tended to be more enriched in calcium and alkaline phosphatase (ALPL), compared to EVs from mocks SMCs. In conclusion, our study reveals a direct role of PCSK9 on vascular calcification induced by higher inorganic phosphate levels associated to CKD condition. This effect appears to be mediated by a positive effect of endogenous PCSK9 on the release of EVs containing Ca2+ and ALP, which facilitate the deposition inorganic calcium phosphate crystals.

Keywords: PCSK9, calcification, extracellular vesicles, chronic kidney disease

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Authors: Mohd. Ashik Shahrier, Hiromi Wada

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Prenatal ethanol exposure has potential to induce difficulties in the social behavior of rats and can alter pup-dam communication suggesting that deficits in pups could result in altered dam behavior, which in turn could result in more aberrant behavior in the pup. Ultrasonic vocalization (USV) is a sensitive tool for investigating social behavior between rat pups and their dam. Rat pups produce USVs on separation from their dam. This signals the dam to locate her pups and retrieve them back to the nest. In this study, it was predicted that prenatal ethanol exposure cause alterations on the acoustic characteristics of USVs in rat pups. Thirteen pregnant rats were purchased and randomly assigned into three groups: high-ethanol (n = 4), low-ethanol (n = 5), and control (n = 4) groups. Laboratory ethanol (purity = 99.5%) was dissolved in tap water and administered to the high- and low-ethanol groups as drinking water from gestational days (GD) 8-20. Ethanol-containing water was administered to the animals in three stages by gradually increasing the concentration between GDs 8–20. From GDs 8–10, 10% and 5%, from GDs 11–13, 20% and 10%, and from GDs 14–20, 30% and 15% ethanol-containing water (v/v) was administered to the high- and low-ethanol groups, respectively. Tap water without ethanol was given to the control group throughout the experiment. The day of birth of the pups was designated as postnatal day (PND) 0. On PND 4, each litter was culled to four male and four female pups. For the present study, two male and two female pups were randomly sampled from each litter as subjects. Thus, eight male and eight female pups from the high-ethanol and control groups and another 10 male and 10 female pups from the low-ethanol group, were sampled. An ultrasonic microphone and the Sonotrack system version 2.4.0 (Metris, Hoofddorp, The Netherlands) were used to record and analyze USVs of the pups. On postnatal days 4, 8, 12 and 16, the resultant pups were individually isolated from their dams and littermates, and USVs were recorded for 5 min in a sound-proof box. Pups in the high-ethanol group produced greater number of USVs compared with that in both low-ethanol and control groups on PND 12. Rat pups in the high-ethanol group also produced higher mean, minimum, and maximum fundamental frequencies of USVs compared with that in both low-ethanol and control groups. Male pups in the high-ethanol group had higher USV amplitudes than in those in low-ethanol and control groups on PND 12. These results suggest that pups in the high-ethanol group relatively experienced more negative emotionality due to the ethanol-induced neuronal activation in the core limbic system and tegmental structures and accordingly, produced altered USVs as distress calls.

Keywords: emotionality, ethanol, maternal separation, ultrasonic vocalization

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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: A. Mirzaei, S. Zolghadri, M. Athari-Allaf, H. Yousefnia, A. R. Jalilian

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Rheumatoid arthritis is the most common autoimmune disease, leading to the destruction of the joints. The aim of this study was the preparation of 90Y-chitosan complex as a novel agent for radiosynovectomy. The complex was prepared in the diluted acetic acid solution. At the optimized condition, the radiochemical purity of higher than 99% was obtained by ITLC method on Whatman No. 1 and by using a mixture of methanol/water/acetic acid (4:4:2) as the mobile phase. The complex was stable in acidic media (pH=3) and its radiochemical purity was above 98% even after 48 hours. The biodistribution data in rats showed that there was no significant leakage of the injected activity even after 48 h. Considering all of the excellent features of the complex, 90Y-chitosan can be used to manipulate synovial inflammation effectively.

Keywords: chitosan, Y-90, radiosynovectomy, biodistribution

Procedia PDF Downloads 465

Authors: Y. Abdulmumin, K. I. Matazu, A. M. Wudil, A. J. Alhassan, A. A. Imam

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Phytochemical analysis of Boswellia papryfera confirms the presence of various phytochemicals such as alkaloids, flavonoids, tannins, saponins and cardiac glycosides in its aqueous stem bark extract at different concentration, with tannins being the highest (0.611 ± 0.002 g %). Acute toxicity test (LD50, oral, rat) of the extract showed no mortality at up to 5000 mg/kg and the animals were found active and healthy. The extract was declared as practically non-toxic, this suggest the safety of the extract in traditional medicine.

Keywords: acute toxicity, aqueous extract, boswellia papryfera, phytochemicals and stem bark

Procedia PDF Downloads 438

Authors: Kuladip Jana

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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased ROS, altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38MAPK, cytosolic translocation of cytochrome-c, up-regulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of PARP and down-regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like StAR, cytochrome P450 IIA1 (CYPIIA1), 3β HSD, 17β HSD showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis.The possible protective role of naturally occurring phytochemicals against B(a)P induced testicular toxicity needs immediate consideration. Curcumin and resveratrol separately were found to protect against B(a)P induced germ cell apoptosis, and their combinatorial effect was more significant. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted their synergistic protective effect against B(a)P induced germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3,8,9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, Apaf1.Curcumin-resveratrol co-treatment thus prevented B(a)P induced germ cell apoptosis. B(a)P induced testicular ROS generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 production. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.

Keywords: benzo(a)pyrene, germ cell, apoptosis, oxidative stress, resveratrol, curcumin

Procedia PDF Downloads 241

Authors: Y. Abdulmumin, K. I. Matazu, A. M. Wudil, A. J. Alhassan, A. A. Imam

Abstract:

Phytochemical analysis of Boswellia papryfera confirms the presence of various phytochemicals such as alkaloids, flavonoids, tannins, saponins and cardiac glycosides in its aqueous stem bark extract at different concentration, with tannins being the highest (0.611 ± 0.002 g %). Acute toxicity test (LD50,oral, rat) of the extract showed no mortality at up to 5000 mg/kg and the animals were found active and healthy. The extract was declared as practically non-toxic, this suggest the safety of the extract in traditional medicine.

Keywords: acute toxicity, aqueous extract, boswellia papryfera, phytochemicals, stem bark extract

Procedia PDF Downloads 409

Authors: Humaira M. Khan, Kanwal Asif

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Ischemic stroke is a neurological disorder with a complex pathophysiology associated with motor, sensory and cognitive deficits. Major approaches developed to treat acute ischemic stroke fall into two categories, thrombolysis and neuroprotection. The objectives of this study were to evaluate the neuroprotective and anti-thrombolytic effects of Olea europaea (olive oil) and Malus domestica (apple cider vinegar) and their combination in rat stroke model. Furthermore, histopathological analysis was also performed to assess the severity of ischemia among treated and reference groups. Male albino rats (12 months age) weighing 300- 350gm were acclimatized and subjected to middle cerebral artery occlusion method for stroke induction. Olea europaea and Malus domestica was administered orally in dose of 0.75ml/kg and 3ml/kg and combination was administered at dose of 0.375ml/kg and 1.5ml/kg prophylactically for consecutive 21 days. Negative control group was dosed with normal saline whereas piracetam (250mg/kg) was administered as reference. Neuroprotective activity of standard piracetam, Olea europaea, Malus domestica and their combination was evaluated by performing functional outcome tests i.e. Cylinder, pasta, ladder run, pole and water maize tests. Rats were subjected to surgery after 21 days of treatment for analysis from stroke recovery. Olea europaea and Malus domestica in individual doses of 0.75ml/kg and 3ml/kg respectively showed neuroprotection by significant improvement in ladder run test (121.6± 0.92;128.2 ± 0.73) as compare to reference (125.4 ± 0.74). Both test doses showed significant neuroprotection as compare to reference (9.60 ± 0.50) in pasta test (8.40 ± 0.24;9.80 ± 0.37) whereas with cylinder test, experimental groups showed significant increase in movements (6.60 ± 0.24; 8.40 ± 0.24) in contrast to reference (7.80 ± 0.37).There was a decrease in percentage time taken f to reach the hidden maize in water maize test (56.80 ± 0.58;61.80 ± 0.66) at doses 0.75ml/kg and 3ml/kg respectively as compare to piracetam (59.40 ± 1.07). Olea europaea and Malus domestica individually showed significant reduction in duration of mobility (127.0 ± 0.44; 123.0 ± 0.44) in pole test as compare to piracetam (124.0 ± 0.70). Histopathological analysis revealed the significant extent of protection from ischemia after prophylactic treatments. Hence it is concluded that Olea europaea and Malus domestica are effective neuroprotective agents alone as compare to their combination.

Keywords: ischemia, Malus domestica, neuroprotection, Olea europaea

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Authors: H. M. El-Rafie, A. H. Abou Zeid, R. S. Mohammed, A. A. Sleem

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Acrocarpus is a genus of flowering plants in the legume family Fabaceae which considered as a large and economically important family. This study aimed to investigate the phytoconstituents of the petroleum ether extract (PEE) of Acrocarpus fraxinofolius bark by Gas chromatography coupled with mass spectrometry (GC/MS) analysis of its fractions (fatty acid and unsaponifiable matter). Concerning this, identification of 52 compounds constituting 97.03 % of the total composition of the unsaponifiable matter fraction. Cycloeucalenol was found to be the major compound representing 32.52% followed by 4a, 14a-dimethyl-A8~24(28)-ergostadien (26.50%) and ß-sitosterol(13.74%), furthermore Gas liquid chromatography (GLC) analysis of the sterol fraction revealed the identification of cholesterol (7.22 %), campesterol (13.30 %), stigmasterol (10.00 %) and β - sitosterol (69.48 %). Meanwhile, the identification of 33 fatty acids representing 90.71% of the total fatty acid constituents. Methyl-9,12-octadecadienoate (40.39%) followed by methyl hexadecanoate (23.64%) were found to be the major compounds. On the other hand, column chromatography and Thin layer chromatography (TLC) fractionation of PEE separate the triterpenoid: 21β-hydroxylup-20(29)-en-3-one and β- amyrin which were structurally identified by spectroscopic analysis (NMR, MS and IR). PEE has been biologically evaluated for 1: management of diabetes in alloxan induced diabetic rats 2: cytotoxic activity against four human tumor cell lines (Cervix carcinoma cell line[HELA], Breast carcinoma cell line [MCF7], Liver carcinoma cell line[HEPG2] and Colon carcinoma cell line[HCT-116] 3: hepatoprotective activity against CCl4-induced hepatotoxicity in rats and the activity was studied by assaying the serum marker enzymes like AST, ALT, and ALP. Concerning this, the anti-diabetic activity exhibited by 100mg of PEE extract was 74.38% relative to metformin (100% potency). It also showed a significant anti-proliferative activity against MCF-7 (IC50= 2.35µg), Hela(IC50=3.85µg) and HEPG-2 (IC50= 9.54µg) compared with Doxorubicin as reference drug. The hepatoprotective activity was evidenced by significant decrease in liver function enzymes, i.e. AST, ALT and ALP by (29.18%, 28.26%, and 34.11%, respectively using silymarin as the reference drug, compared to their concentration levels in an untreated group with liver damage induced by CCl₄. This study was performed for the first time on the bark of this species.

Keywords: Acrocarpus fraxinofolius, antidiabetic, cytotoxic, hepatoprotective

Procedia PDF Downloads 183

Authors: R. L. Shirole, N. L. Shirole, R. B. Patil, M. N. Saraf

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The present investigation aimed to elucidate the probable mechanism of antiasthmatic action of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls (EOPI). EOPI was investigated for its potential antiasthmatic action using in vitro antiallergic assays mast cell degranulation and soyabean lipoxidase enzyme activit, and spasmolytic action using isolated guinea pig ileum preparation. In vivo studies included lipopolysaccharide-induced bronchial inflammation in rats and airway hyperresponsiveness in ovalbumin in sensitized guinea pigs using spirometry. Data was analysed by GraphPad Prism 5.01 and results were expressed as means ± SEM. P < 0.05 was considered to be significant. EOPI inhibits 5-lipoxidase enzyme activity, DPPH scavenging activity and erythropoietin- induced angiogenesis. It showed dose dependent anti-allergic activity by inhibiting compound 48/80 induced mast cell degranulation. The finding that essential oil induced inhibition of transient contraction of acetylcholine in calcium free medium, and relaxation of S-(-)-Bay 8644-precontracted isolated guinea pig ileum jointly suggest that suggesting that the L-subtype Cav channel is involved in spasmolytic action of EOPI. Treatment with EOPI dose dependently (7.5, 15 and 30 mg/kg i.p.) inhibited lipopolysaccharide- induced increased in total cell count, neutrophil count, nitrate-nitrite, total protein, albumin levels in bronchoalveolar fluid and myeloperoxidase levels in lung homogenates. Mild diffused lesions involving focal interalveolar septal, intraluminal infiltration of neutrophils were observed in EOPI (7.5 &15 mg/kg) pretreated while no abnormality was detected in EOPI (30 mg/kg) and roflumilast (1mg/kg) pretreated rats. Roflumilast was used as standard. EOPI reduced the respiratory flow due to gasping in ovalbumin sensitized guinea pigs. The study demonstrates the effectiveness of EOPI in bronchial asthma possibly related to its ability to inhibit L-subtype Cav channel, mast cell stabilization, antioxidant, angiostatic and through inhibition of 5-lipoxygenase enzyme.

Keywords: asthma, lipopolysaccharide, spirometry, Pistacia integerrima J.L. Stewart ex Brandis, essential oil

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Authors: Kun Hua O., Dong Woon Kim, Won Hyung Lee

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Introduction: Neuropathic pain induced by spinal or peripheral nerve injury is highly resistant to common painkillers, nerve blocks, and other pain management approaches. Recently, several new therapeutic drug candidates have been developed to control neuropathic pain. In this study, we used the spinal nerve L5 ligation (SNL) model to investigate the ability of intrathecal or intravenous Evans blue to decrease pain behavior and to study the relationship between Evans blue and the neural structure of pain transmission. Method: Neuropathic pain (allodynia) of the left hind paw was induced by unilateral SNL in Sprague-Dawley rats(n=10) in each group. Evans blue (5, 15, 50μg/10μl) or phosphate buffer saline(PBS,10μl) was injected intrathecally at 3days post-ligation or intravenously(1mg/200 μl) 3days and 5days post-ligation . Mechanical sensitivity was assessed using Von Frey filaments at 3 days post-ligation and at 2 hours, days 1, 2, 3, 5,7 after intrathecal Evans blue injection, and on days 2, 4, 7, and 11 at 14 days after intravenous injection. In the intrathecal group, microglia and glutaminergic neurons in the dorsal horn and VNUT(vesicular nucleotide transporter) in the dorsal root ganglia were tested to evaluate co-staining with Evans blue. The experimental procedures were performed in accordance with the animal care guideline of the Korean Academy of Medical Science(Animal ethic committee of Chungnam National University Hospital: CNUH-014-A0005-1). Results: Tight ligation of the L5 spinal nerve induced allodynia in the left hind paw 3 days post-ligation. Intrathecal Evans blue most significantly(P＜0.001) alleviated allodynia at 2 days after intrathecal, but not an intravenous injection. Glutaminergic neurons in the dorsal horn and VNUT in the dorsal root ganglia were co-stained with Evans blue. On the other hand, microglia in the dorsal horn were partially co-stained with Evans blue. Conclusion: We confirmed that Evans blue might have an analgesic effect through the central nervous system, not another system in neuropathic pain of the SNL animal model. These results suggest Evans blue may be a potential new drug for the treatment of chronic pain. This research was supported by the National Research Foundation of Korea (NRF-2020R1A2C100757512), funded by the Ministry of Education.

Keywords: neuropathic pain, Evas blue, intrathecal, intravenous

Procedia PDF Downloads 81

Authors: C. C .D. Kulathilake, M. Jayatilake, T. Takahashi

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The myocardium is composed of specialized muscle which relies mainly on fatty acid and sugar metabolism and it is widely contribute to the heart functioning. The changes of the cardiac energy-producing system during heart failure have been proved using autoradiography techniques. This study focused on evaluating sugar and fatty acid metabolism in myocardium as cardiac energy getting system using heart-accumulated radiopharmaceuticals. Two sets of autoradiographs of heart cross sections of Lewis male rats were analyzed and the time- accumulation curve obtained with use of the MATLAB image processing software to evaluate fatty acid and sugar metabolic functions.

Keywords: autoradiographs, fatty acid, radiopharmaceuticals, sugar

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Authors: Lin Po-Hsi, Sheu Ming-Thau

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Urea cycle disorders (UCD) are rare genetic metabolic disorders that compromise the body's urea cycle. Sodium phenylbutyrate (SPB) is a medication commonly administered in tablet or powder form to lower ammonia levels. Nonetheless, its high sodium content poses risks to sodium-sensitive UCD patients. This necessitates the creation of an alternative drug formulation to mitigate sodium load and optimize drug delivery for UCD patients. This study focused on crafting a novel oral drug formulation for UCD, leveraging choline bicarbonate and phenylbutyric acid. The active pharmaceutical ingredient-ionic liquids (API-ILs) and therapeutic deep eutectic systems (THEDES) were formed by combining these with choline chloride. These systems display characteristics like maintaining a liquid state at room temperature and exhibiting enhanced solubility. This in turn amplifies drug dissolution rate, permeability, and ultimately oral bioavailability. Incorporating choline-based phenylbutyric acid as a substitute for traditional SPB can effectively curtail the sodium load in UCD patients. Our in vitro dissolution experiments revealed that the ILs and DESs, synthesized using choline bicarbonate and choline chloride with phenylbutyric acid, surpassed commercial tablets in dissolution speed. Pharmacokinetic evaluations in SD rats indicated a notable uptick in the oral bioavailability of phenylbutyric acid, underscoring the efficacy of choline salt ILs in augmenting its bioavailability. Additional in vitro intestinal permeability tests on SD rats authenticated that the ILs, formulated with choline bicarbonate and phenylbutyric acid, demonstrate superior permeability compared to their sodium and acid counterparts. To conclude, choline salt ILs developed from choline bicarbonate and phenylbutyric acid present a promising avenue for UCD treatment, with the added benefit of reduced sodium load. They also hold merit in formulation engineering. The sustained-release capabilities of DESs position them favorably for drug delivery, while the low toxicity and cost-effectiveness of choline chloride signal potential in formulation engineering. Overall, this drug formulation heralds a prospective therapeutic avenue for UCD patients.

Keywords: phenylbutyric acid, sodium phenylbutyrate, choline salt, ionic liquids, deep eutectic systems, oral bioavailability

Procedia PDF Downloads 89

Authors: Amal. N. Al-Kuraieef

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Smoli bread was made by supplementation sunflower flour which was prepared from sunflower (Dahr-EL-Haea) gray after hilling and milling, flour was irradiated by two doses (5 and 10 kGy). After that, the ratios of irradiated sunflower flour were 5 and 10%. All samples of samoli bread were examined for organoleptic and biological evaluation. Biological assay (PER, NPU, FE, DC and BV) was carried out on rats fed 5 and 10% irradiated and non-irradiated sunflower Samoli bread. Results obtained showed that, total lipids, cholesterol and triglycerides were reduced comparable, to that of casein. Also, figures of the biological evaluations were higher than those of the control samoli bread and improved its nutritive values.

Keywords: gamma rays, sunflower, samoli bread, cholesterol, lipids, triglycerides

Procedia PDF Downloads 142

Authors: Esshili Awatef, Manitz Marie-Pierre, Eßlinger Manuela, Gerhardt Alexandra, Plümper Jennifer, Wachholz Simone, Friebe Astrid, Juckel Georg

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Maternal immune activation (MIA) resulting from maternal viral infection during pregnancy is a known risk factor for schizophrenia. The neural mechanisms by which maternal infections increase the risk for schizophrenia remain unknown, although the prevailing hypothesis argues that an activation of the maternal immune system induces changes in the maternal-fetal environment that might interact with fetal brain development. It may lead to an activation of fetal microglia inducing long-lasting functional changes of these cells. Based on post-mortem analysis showing an increased number of activated microglial cells in patients with schizophrenia, it can be hypothesized that these cells contribute to disease pathogenesis and may actively be involved in gray matter loss observed in such patients. In the present study, we hypothesize that prenatal treatment with the inflammatory agent Poly(I:C) during embryogenesis at contributes to microglial activation in the offspring, which may, therefore, represent a contributing factor to the pathogenesis of schizophrenia and underlines the need for new pharmacological treatment options. Pregnant rats were treated with intraperitoneal injections a single dose of Poly(I:C) or saline on gestation day 17. Brains of control and Poly(I:C) offspring, were removed and into 20-μm-thick coronal sections were cut by using a Cryostat. Brain slices were fixed and immunostained with ba1 antibody. Subsequently, Iba1-immunoreactivity was detected using a secondary antibody, goat anti-rabbit. The sections were viewed and photographed under microscope. The immunohistochemical analysis revealed increases in microglia cell number in the prefrontal cortex, in offspring of poly(I:C) treated-rats as compared to the controls injected with NaCl. However, no significant differences were observed in microglia activation in the cerebellum among the groups. Prenatal immune challenge with Poly(I:C) was able to induce long-lasting changes in the offspring brains. This lead to a higher activation of microglia cells in the prefrontal cortex, a brain region critical for many higher brain functions, including working memory and cognitive flexibility. which might be implicated in possible changes in cortical neuropil architecture in schizophrenia. Further studies will be needed to clarify the association between microglial cells activation and schizophrenia-related behavioral alterations.

Keywords: Microglia, neuroinflammation, PolyI:C, schizophrenia

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Authors: M. N. Ofokansi, Onyemelukwe Chisom, Amauche Chukwuemeka, Ezema Onyinye

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The leaves of Clerodendrumcapitatum(Lamiaceae) is mostly used in the treatment of gastric ulcer in Nigerian folk medicine. The aim of this study was to evaluate the antiulcer activity of its crude methanol leaf extract and its ethyl acetate fraction in white albino rats. The effect of crude methanol leaf extract and its ethyl acetate fraction(250mg/kg, 500mg/kg) was evaluated using an absolute ethanol induced ulcer model. Crude methanol leaf extract and the ethyl acetate fraction was treated with distilled water and 6% Tween 80, respectively. crude methanol leaf extract was further investigated using a pylorus ligation induced ulcer model. Omeprazole was used as the standard treatment. Four groups of five albino rats of either sex were used. Parameters such as mean ulcer index and percentage ulcer protection were assessed in the ethanol-induced ulcer model, while the gastric volume, pH, and total acidity were assessed in the pyloric ligation induced ulcer model. Crude methanol leaf extract of Clerodendrumcapitatum(500mg/kg) showed a very highly significant reduction in mean ulcer index(p<0.001) in the absolute ethanol-induced model. ethyl acetate fraction of crude methanol leaf extract of Clerodendrumcapitatum(250mg/kg,500mg/kg) showed a very highly significant dose-dependent reduction in mean ulcer indices (p<0.001) in the absolute ethanol-induced model. The mean ulcer indices (1.6,2.2) with dose concentration (250mg/kg, 500mg/kg) of ethyl acetate fraction increased with ulcer protection (82.85%,76.42%) respectively when compared to the control group in the absolute ethanol-induced ulcer model. Crude methanol leaf extract of Clerodendrumcapitatum(250mg/kg, 500mg/kg) treated animals showed a highly significant dose-dependent reduction in mean ulcer index(p<0.01) with an increase in ulcer protection (56.77%,63.22%) respectively in pyloric ligated induced, ulcer model. Gastric parameters such as volume of gastric juice, pH, and total acidity were of no significance in the different doses of the crude methanol leaf extract when compared to the control group. The phytochemical investigation showed that the crude methanol leaf extracts Possess Saponins and Flavonoids while its ethyl acetate fraction possess only Flavonoids. The results of the study indicate that the crude methanol leaf extract and its ethyl acetate fraction is effective and has gastro protective and ulcer healing capacity. Ethyl acetate fraction is more potent than crude methanol leaf extract against ethanol-induced This result provides scientific evidence as a validation for its folkloric use in the treatment of gastric ulcer.

Keywords: gastroprotective, herbal medicine, anti-ulcer, pharmacology

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Authors: Asma Meddour, Mouloud Yahia, Afaf Benhouda, Souhila Benbia, Hachani Khadhraoui

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Peripheral analgesic activity of defatted methanol extract of root barks of Capparis spinosa was tested orally at the dose of 100 and 200 mg/kg against pain induced by acetic acid in rats. The dose of 200 mg/kg presents significant analgesic effect with a percentage of inhibition of torsions of 88.51% compared to the positive control which is the acetylsalicylic acid which represents a percentage of inhibition of 92.55%. The dose of 100 mg/kg presents a percentage of inhibition of 81.68%.

Keywords: peripheral analgesic activity, Capparis spinosa, percentage of inhibition of torsions, chemical sciences

Procedia PDF Downloads 277

Authors: Fatih Sonmez

Abstract:

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and it is the most common form of dementia that affects aged people. Acetylcholinesterase is a hydrolase involved in the termination of impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter ACh in the central and peripheral nervous system. Carvacrol (5-iso-propyl-2-methyl-phenol) is a main bioactive monoterpene isolated from many medicinal herbs, such as Thymus vulgaris, Monarda punctate and Origanum vulgare spp. It is known that carvacrol has been widely used as an active anti-inflammatory ingredient, which can inhibit the isoproterenol induced inflammation in myocardial infarcted rats. In this paper, a series of 12 carvacrol substituted carbamate derivatives (2a-l) was synthesized and their inhibitory activities on AChE and BuChE were evaluated. Among them, 2d exhibited the strongest inhibition against AChE with an IC50 value of 2.22 µM, which was 130-fold more than that of carvacrol (IC50 = 288.26 µM).

Keywords: Acetylcholinesterase, Butyrylcholinesterase, Carbamate, Carvacrol

Procedia PDF Downloads 337