Search results for: therapeutic window

Authors: Rizwan H. Khan, Saima Nusrat

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Despite the fact that amyloid associated neurodegenerative diseases and non-neuropathic systemic amyloidosis have allured the research endeavors, as no curative drugs have been proclaimed up till now except for symptomatic cure. Therapeutic compounds which can diminish or disaggregate such toxic oligomers and fibrillar species have been examined and more are on its way. In the present study, we had reported an extensive biophysical, microscopic and computational study, revealing that L-3, 4-dihydroxyphenylalanine (L-Dopa) possess undeniable potency to inhibit heat induced human lysozyme (HL) amyloid fibrillation and also retain the fibril disaggregating potential. L-Dopa interferes in the amyloid fibrillogenesis process by interacting hydrophobically and also by forming hydrogen bonds with the amino acid residues found in amyloid fibril forming prone region of HL as elucidated by molecular docking results. L-Dopa also disaggregates the mature amyloid fibrils into some unorganised species. Thus, L-Dopa and related compounds can work as a promising inhibitor for the therapeutic advancement prospective against systemic amyloidosis.

Keywords: amyloids, disaggregation, human lysozyme, molecular docking

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Authors: Mahsa Fathollahzadeh

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The various nanoparticles employed in drug delivery applications include micelles, liposomes, solid lipid nanoparticles, polymeric nanoparticles, functionalized nanoparticles, nanocrystals, cyclodextrins, dendrimers, and nanotubes. Micelles, composed of amphiphilic block copolymers, can encapsulate hydrophobic molecules, allowing for targeted delivery. Liposomes, vesicular structures made up of phospholipids, can encapsulate both hydrophobic and hydrophilic molecules, providing a flexible platform for delivering therapeutic agents. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are designed to improve the stability and bioavailability of lipophilic drugs. Polymeric nanoparticles, such as poly(lactic-co-glycolic acid) (PLGA), are biodegradable and can be engineered to release drugs in a controlled manner. Functionalized nanoparticles, coated with targeting ligands or antibodies, can specifically target diseased cells or tissues. Nanocrystals, engineered to have specific surface properties, can enhance the solubility and bioavailability of poorly soluble drugs. Cyclodextrins, doughnut-shaped molecules with hydrophobic cavities, can be complex with hydrophobic molecules, allowing for improved solubility and bioavailability. Dendrimers, branched polymers with a central core, can be designed to deliver multiple therapeutic agents simultaneously. Nanotubes and metallic nanoparticles, such as gold nanoparticles, offer real-time tracking capabilities and can be used to detect biomolecular interactions. The use of these nanoparticles has revolutionized the field of drug delivery, enabling targeted and controlled release of therapeutic agents, reduced toxicity, and improved patient outcomes.

Keywords: nanotechnology, nanopharmaceuticals, drug-delivery, proteins, ligands, nanoparticles, chemistry

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Authors: Pamela Del Rosario, Elisabetta Palumbo, Marzia Traverso

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The building sector plays an important role in addressing pressing environmental issues such as climate change and resource scarcity. The energy performance of buildings is considerably affected by the external envelope. In fact, a considerable proportion of the building energy demand is due to energy losses through the windows. Nevertheless, according to literature, to pay attention only to the contribution of windows to the building energy performance, i.e., their influence on energy use during building operation, could result in a partial evaluation. Hence, it is important to consider not only the building energy performance but also the environmental performance of windows, and this not only during the operational stage but along its complete life cycle. Life Cycle Assessment (LCA) according to ISO 14040:2006 and ISO 14044:2006+A1:2018 is one of the most adopted and robust methods to evaluate the environmental performance of products throughout their complete life cycle. This life-cycle based approach avoids the shift of environmental impacts of a life cycle stage to another, allowing to allocate them to the stage in which they originated and to adopt measures that optimize the environmental performance of the product. Moreover, the LCA method is widely implemented in the construction sector to assess whole buildings as well as construction products and materials. LCA is regulated by the European Standards EN 15978:2011, at the building level, and EN 15804:2012+A2:2019, at the level of construction products and materials. In this work, the environmental performance of wooden windows was assessed by implementing the LCA method and adopting primary data. More specifically, the emphasis is given to embedded and operational impacts. Furthermore, correlations are made between these environmental impacts and aspects such as type of wood and window transmittance. In the particular case of the operational impacts, special attention is set on the definition of suitable maintenance scenarios that consider the potential climate influence on the environmental impacts. For this purpose, a literature review was conducted, and expert consultation was carried out. The study underlined the variability of the embedded environmental impacts of wooden windows by considering different wood types and transmittance values. The results also highlighted the need to define appropriate maintenance scenarios for precise assessment results. It was found that both the service life and the window maintenance requirements in terms of treatment and its frequency are highly dependent not only on the wood type and its treatment during the manufacturing process but also on the weather conditions of the place where the window is installed. In particular, it became evident that maintenance-related environmental impacts were the highest for climate regions with the lowest temperatures and the greatest amount of precipitation.

Keywords: embedded impacts, environmental performance, life cycle assessment, LCA, maintenance stage, operational impacts, wooden windows

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Authors: Ghada M. R. Koura, Mohamed N. Mohamed, Ahmed M. F. El Shiwi

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Chronic mechanical Low back dysfunction (CMLBD) is the most common problem of the working-age population in modern industrial sociaty; it causes a substantial economic burden due to the wide use of medical services and absence from work. Aim of work: the aim of this study was to investigate the effect of positional release technique on patients with chronic mechanical low back pain. Materials and Methods: Thirty two patients from both sexes were diagnosed with CMLBP, aged 20 to 45 years and were divided randomly into two equal groups; sixteen patients each; group A (control group) received therapeutic exercises that include (Stretch and Strength exercises for back and abdominal muscles). Group B (experimental group) received therapeutic exercises with positional release technique; treatment was applied 3 days/week for 4 weeks. Pain was measured by Visual Analogue Scale, Lumbar range of motion was measured by Inclinometer and Functional disability was measured by Oswestry disability scale. Measurements were taken at two intervals pre-treatment and post-treatment. Results: Data obtained was analyzed via paired and unpaired t-Test. There were statistical differences between the 2 groups, where the experimental group showed greater improvement than control group. Conclusion: Positional release technique is considered as an effective treatment for reducing pain, functional disability and increasing lumbar range of motion in individuals with chronic mechanical low back pain.

Keywords: chronic mechanical low back pain, traditional physical therapy program, positional release technique, randomized controlled trial

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Authors: Ameni Mahmoudi, Manel Troudi, Paolo Bondavalli, Nabil Sghaier

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In this study, the charge storage on thin-film SWCNT transistors was investigated, and C-V hysteresis tests showed that interface charge trapping effects predominate the memory window. Two electrode materials were utilized to demonstrate that selecting the appropriate metal electrode clearly improves the conductivity and, consequently, the SWCNT thin-film’s memory effect. Because their work function is similar to that of thin-film carbon nanotubes, Ti contacts produce higher charge confinement and show greater charge storage than Pd contacts. For Pd-contact CNTFETs and CNTFETs with Ti electrodes, a sizable clockwise hysteresis window was seen in the dual sweep circle with a threshold voltage shift of V11.52V and V9.7V, respectively. The SWCNT thin-film based transistor is expected to have significant trapping and detrapping charges because of the large C-V hysteresis. We have found that the predicted stored charge density for CNTFETs with Ti contacts is approximately 4.01×10-2C.m-2, which is nearly twice as high as the charge density of the device with Pd contacts. We have shown that the amount of trapped charges can be changed by sweeping the range or Vgs rate. We also looked into the variation in the flat band voltage (V FB) vs. time in order to determine the carrier retention period in CNTFETs with Ti and Pd electrodes. The outcome shows that memorizing trapped charges is about 300 seconds, which is a crucial finding for memory function mimicking.

Keywords: charge storage, thin-film SWCNT based transistors, C-V hysteresis, memory effect, trapping and detrapping charges, stored charge density, the carrier retention time

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Authors: Farhan Saeed

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The core objective of this work is to explicate the biochemical and therapeutic properties of aged garlic. For this purpose, two varieties of garlic were obtained from Ayub Agricultural Research Institute (AARI) Faisalabad-Pakistan. Additionally, fresh garlic was converted into aged garlic via fermentation method in the incubator at 70 to 80 % humidity level and 60C0 temperature for one month. Similarly, biochemical and antioxidant properties of fresh and aged garlic were also elucidated. Mean values showed that moisture content was decreased, whereas crude fat, crude protein, crude fiber, crude ash and total carbohydrates were enhanced after fermentation. Additionally, crude protein of fresh and aged garlic was 7.57±0.16 and 5.52±0.12%, respectively, whilst 9.68±0.41 and 8.78±0.29%, respectively, after the fermentation process. In addition, NFE contents were also enhanced up to 39% after the fermentation method. Moreover, Zn, S, Al, K, Fe, Na, Mg, and Cu contents were also increased. Furthermore, Total phenolic contents (TPC) of fresh and aged garlic were 2498.70 & 2188.50mg GAE/kg whilst 3008.59, & 2591.81mg GAE/kg for aged garlic. In conclusion, aged garlic explicated the better biochemical properties, mineral profile and antioxidant properties as compared to fresh garlic.

Keywords: aged garlic, nutritional values, bioactive properties, fermentation

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Authors: Adrian Reynaldo Sudirman, Siti Farida, Aisyah Aminy Maulidina, Caren Andika Surbakti

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Sedentary lifestyle and imbalance consumption pattern has made metabolic syndrome as the global time bomb phenomenon in the world. The increasing tendency of people in consuming high amount of fructose and cholesterol food has worsened this issue in the society. Pancreas steatosis become one of the most comorbid when early diagnosis and prompt treatment has not been applied on hyperglycemic and hyperlipidemic condition in metabolic syndrome patient. Gemfibrozil become the drug of choice to prevent this issue, yet the efficacy of this regiment was still questionable. Acalypha indica Linn. is the herb that has protective effect on hyperlipidemic and hyperglycemic condition. This study was aimed to compare therapeutic effect of gemfibrozil (G) and Acalypha indica Linn. (AI) on high fructose and cholesterol diet-induced pancreas steatosis in Sprague-Dawley mice. The post induction mice were divided into four groups: control, gemfibrozil, AI extract, and G+AI combination regiment. Each group received four weeks intervention. The result of statistical analysis using the One-Way ANOVA test and Tukey Post Hoc test showed significant decrease in pancreatic steatosis between the control group and administered Acalypha indica group (p = 0.004, 95% CI: 0.170-0.959) and the group administered with a combination of Gemfibrozil-Acalypha indica (p = 0.023, 95% CI: 0.537-0.813). The protective effect of Acalypha indica Linn. shows that this plant has the potential as therapeutic option in overcoming the condition of pancreas steatosis in metabolic syndrome.

Keywords: Acalypha Indica Linn., Cholesterol, Fructose, Gemfibrozil, Pancreas Steatosis

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Authors: Eun-Joong Kim, Sankarprasad Bhuniya, Hyunseung Lee, Hyun Min Kim, Chaejoon Cheong, Su-khendu Maiti, Kwan Soo Hong, Jong Seung Kim

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Metastatic cancers have historically been difficult to treat. However, metastatic tumors have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential anti-metastatic therapy. In this study, prodrug 7 was designed to be activated by H2O2-mediated boronate oxidation, resulting in activation of the fluorophore for detection and release of the therapeutic agent, SN-38. Drug release from prodrug 7 was investigated by monitoring fluorescence after addition of H2O2 to the cancer cells. Prodrug 7 activated by H2O2 selectively inhibited tumor cell growth. Furthermore, intratracheally administered prodrug 7 showed effective anti-tumor activity in a mouse model of metastatic lung disease. Thus, this H2O2-responsive prodrug has therapeutic potential as a novel treatment for metastatic cancer via cellular imaging with fluorescence as well as selective release of the anti-cancer drug, SN-38.

Keywords: hydrogen peroxide, prodrug, metastatic tumors, fluorescence

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Authors: Faizan Rathore, Naveed Sultan, Humphrey O. Connor

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This study was carried out from Jan '12-Dec'12 to assess current practice in Kerry General Hospital against the age-related indicators for colonoscopies. A total of 1474 colonoscopies were performed,1177(79.9%) were diagnostic and 297 (20.1%) were therapeutic, patients were divided into 4 age groups under 75, 75-80, 81-85, 86+. The trend analysis revealed an increase in diagnostic colonoscopies and decrease in therapeutic colonoscopies with age. 664(45.04%) of colonoscopies were reported normal which made up the majority of the total diagnoses, 1330 (90.2%) of colonoscopies occurred without any complications. Main complications were patient discomfort being the highest, present in 112(7.6%) of patients, and lowest being urticaria around the IV site present in 1 (0.1%) of the cases. Patient discomfort was higher in younger patients as evidenced by 98 cases aged <75 , followed by 11 cases aged 75-80, 2 cases aged 81-85 and 1 case aged >86. Highest percentage of poor tolerance was found in 14 (1.1%) of total patients <75, 1 (0.8%) of total patients aged 75-80, 1(1.7%) of total patients in age group 81-85 and none (0%) in age group >86. We have established the safety of colonoscopy, low rate of complications and a better tolerance in the elderly from this study, however, its utility, especially in the presence of other comorbidities in elderly is questionable.

Keywords: colonoscopy, elderly patients, utility, tolerance

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Authors: Chijindu Okpalaoka, Charles Chinedu Onuselogu

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COVID-19, humanity's coronavirus disease caused by SARS-CoV-2, was first detected in late 2019 in Wuhan, China. COVID-19 lacked an established conventional pharmaceutical therapy, and as a result, the outbreak quickly became an epidemic affecting the entire World. Only a qPCR assay is reliable for diagnosing COVID-19. Clustered, regularly interspaced short palindromic repeats (CRISPR) technology is being researched for speedy and specific identification of COVID-19, among other therapeutic techniques. Apart from its therapeutic capabilities, the CRISPR technique is being evaluated to develop antiviral therapies; nevertheless, no CRISPR-based medication has been approved for human use to date. Prophylactic antiviral CRISPR in living being cells, a Cas 13-based approach against coronavirus, has been developed. While this method can be evolved into a treatment approach, it may face substantial obstacles in human clinical trials for licensure. This study discussed the potential applications of CRISPR-based techniques for developing a speedy and accurate feasible treatment alternative for the COVID-19 virus.

Keywords: COVID-19, CRISPR technique, Cas13, SARS-CoV-2, prophylactic antiviral

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Authors: Jorge Martinez, Brandon Roberts, Holly Payton Toca

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Background: Therapeutic hypothermia (TH) is the international standard of care for all comatose patients after cardiac arrest, but criticism focuses on poor outcomes. We sought to develop criteria to identify American urban patients more likely to benefit from TH. Methods: Retrospective chart review of 107 consecutive adults undergoing TH in downtown New Orleans from 2010-2014 yielded records for 99 patients with all 44 survivors or families contacted up to four years. Results: 69 males and 38 females with a mean age of 60.2 showed 63 dead (58%) and 44 survivors (42%). Presenting cardiac rhythm was divided into shockable (Pulseless Ventricular Tachycardia, Ventricular Fibrillation) and non-shockable (Pulseless Electrical Activity, Asystole). Presenting in shockable rhythms with ROSC <20 minutes were 21 patients with 15 (71%) survivors (p=.001). Time >20 minutes until ROSC in shockable rhythms had 5 patients with 3 survivors (78%, p=0.001). Presenting in non-shockable rhythms with ROSC <20 minutes were 54 patients with 18 survivors (33%, p=.001). ROSC >20 minutes in non-shockable rhythms had 19 patients with 2 survivors (8%, p=.001). Survivors of shockable rhythms showed 19 (100%) living post TH. 15 survivors (79%, n=19, p=.001) had CPC score 1 or 2 with 4 survivors (21%, n=19) having a CPC score of 3. A total of 25 survived non-shockable rhythm. Acute survival of patients with non-shockable rhythm showed 18 expired <72 hours (72%, n=25) with long-term survival of 4 patients (5%, n=74) and CPC scores of 1 or 2 (p=.001). Interestingly, patients with time to ROSC <20 minutes exhibiting more than one loss of sustained ROSC showed 100% mortality (p=.001). Patients presenting with shockable >20 minutes ROSC had overall survival of 70% (p=.001), but those undergoing >3 cardiac rhythm changes had 100% mortality (p=.001). Conclusion: Patients presenting with shockable rhythms undergoing TH had overall acute survival of 70% followed by long-term survival of 100% after 4 years. In contrast, patients presenting with non-shockable rhythm had long-term survival of 5%. TH is not recommended for patients presenting with non-shockable rhythm and requiring greater than 20 minutes for restoration of ROSC.

Keywords: cardiac rhythm changes, Pulseless Electrical Activity (PEA), Therapeutic Hypothermia (TH)

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Authors: Nasreen Thebo, W. Shaikh, A. J. Laghari, P. Nangni

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Prunus dulcis (Almond) shell extract is demonstrated for its biomedical applications. Shell extract prepared by soxhlet method and further characterized by UV-Visible spectrophotometer, atomic absorption spectrophotometer (AAS), FTIR, GC-MS techniques. In this study, the antifungal activity of almond shell extract was observed against clinically isolated pathogenic fungi by strip method. The antioxidant potential of crude shell extract of was evaluated by using DPPH (2-2-diphenyl-1-picryhydrazyl) and radical scavenging system. The possibility of short term therapy was only 20 days. The total antioxidant activity varied from 94.38 to 95.49% and total phenolic content was found as 4.455 mg/gm in almond shell extract. Finally the results provide a great therapeutic potential against Tinea capitis infection of scalp. Included in this study of shell extract that show scientific evidence for clinical efficacy, as well as found to be more useful in the treatment of dermatologic disorders and without any doubt it can be recommended to be Patent.

Keywords: Tinea capitis, DPPH, FTIR, GC-MS therapeutic treatment

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Authors: Thomas LaRocca

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This study explores the development of a public-school music teacher’s professional identity within three domains: as an educator in the profession at large, as a music teacher in a school, and as a professional musician. An autoethnographic method is employed by calling upon undergraduate student teaching reflections, graduate writing assignments and presentations, cover letters for employment, professional correspondence, and reflective memos. These artifacts provide a reference for phenomenological insights into the values, hopes, and criticisms within each domain over time –all of which provide a window into the overall ontological perspective of one’s professional life at different moments in their career. While the topic of music teacher identity has been examined using autoethnographical methods before, by accessing materials over the course of ten years, the study is able to investigate the ‘how’ of identity development in a temporal context; from undergraduate student to established professional. Additionally, while the field offers a considerable amount of work surrounding the child and adolescent identity development, there are unmined opportunities to examine identity development in the adult years, especially surrounding adult professional life. Employing a postpositivist approach with social constructionism as a backdrop, this study examines adult identity formation and the contradictions, resonances, and priorities within each domain, between each domain, and perceived expectations of the professional community. What is revealed is a journey of self-improvement motivated by failure and success, marked by negotiation and sacrifice; as each domain competes for mental and temporal resources, identity is viewed as not just who one is, but also as what one leaves behind. These insights offer a window into the ontology of identity of a music educator and may provide considerations for differentiating professional development based on what stage educators are at in their careers.

Keywords: identity, longitudinal autoethnography, music teacher education, music teacher ontology

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Authors: Belhaj Mohamed, M. Saidi, I. Bouazizi, M. Soussi, M. Ben Jrad

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The Late Cenomanian-Early Turonian laminated, black, organic-rich limestones were described in Central Tunisia and attributed to the Bahloul Formation. It covers central and northern Tunisia, and the northern part of the Gulf of Gabes. The Bahloul Formation is considered as one of the main source rocks in Tunisia and is composed of outer-shelf to slop-laminated and dark-gray to black-colored limestones and marls. This formation had been deposited in a relatively deep-marine, calm, and anoxic environment. Rock-Eval analysis and vitrinite reflectance (Ro) measurements were performed on the basis of the organic carbon content. Several samples were chosen for molecular organic geochemistry. Saturate and aromatic hydrocarbons were analyzed by gas chromatography (GC) and GC–mass spectrometry. Geochemical data of the Bahloul Formation in northern and central Tunisia show this level to be a good potential source rock as indicated by the high content of type II organic matter. This formation exhibits high total organic carbon contents (as much as 14%), with an average value of 2% and a good to excellent petroleum potential, ranging between 2 and 50 kg of hydrocarbon/ton of rock. The extracts from the Bahloul Formation are characterized by Pr/Ph ratios ranging between 1.5 and 3, a moderate diasterane content, a C27 sterane approximately equal to C29 sterane, a high C28/C29 ratio, low gammacerane index, a C35/C34 homohopane ratio less than 1 and carbon isotope compositions between -24 and -26‰. The thermal maturity is relatively low, corresponding to the beginning of the oil window in the western area near the Algerian border, in the oil window in the eastern area (Sahel basin) and late mature in northern part.

Keywords: biomarkers, organic geochemistry, source rock, Tunisia

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Authors: Yasser Almazrua

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Terrorism is a multidimensional phenomenon that has increased recently. Many countries started combating terrorism through security forces; however, there has been relatively little attention given to rehabilitation programs for people involved in such terrorism acts. In Saudi Arabia, after facing so many terrorist attacks, they started understanding and countering terrorism differently by establishing Mohammad bin Naif Counselling and Care Center in 2006. The center now is considered one of the top experience centers in the world for terrorist rehabilitation and ideology correction. The center offers different programs such as training, educational, social, art and psychological programs. One of the approaches that have been used by psychological experts at the center is Narrative Therapy. It is a therapeutic approach that focuses on the ability of the client to identify their personal life story. The client during therapy works as a storyteller where he or she gets insight, meaning and better understanding of their own lives. Because each client at the center had a story, it can be better fit method for rehabilitation towards healing and personal development. The case describes a 34-years-old man who was involved in some terrorism activities locally by technically and financially supporting a terrorist group related to Al-Qaida. The beneficiary joined Mohammad bin Naif Counseling and Care Center after serving his sentence. Informed of consent has been given to the beneficiary before starting the therapeutic program. Both qualitative and quantitative data on the beneficiary are collected by self-reporting during the initial session, and by using a psychological measurement. The result found that the beneficiary was not insightful about himself, and he had a high level of repression which relatedly moved him to be targeted for recruitment in the terrorist group. With rehabilitation and by using the therapeutic approach, the beneficiary improved on the level of insight, specifically about himself and also about the experience. This case illustrates the importance of considering the effect of Narrative Therapy in terrorist rehabilitation programs.

Keywords: narrative therapy, rehabilitation, Saudi Arabia, terrorism

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Authors: S. M. Arciniegas, D. Vargas, L. Gutierrez

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The aim of this study was to develop oral drug presentation of doxycycline hyclate that maintains longer therapeutic levels than conventional forms. A polymethacrylate and acrylic acid based matrix were used in different proportions to obtain controlled-release formulations; DOX1 (1:0.25:0.0035), DOX2 (1:2:0.0225) and DOX-C (without excipients). All were tested in vivo in healthy dogs and their serum concentrations vs. time profile was investigated after its oral administration in this species. DOX1 and DOX2 show therapeutic concentrations for 60 hours, while DOX-C only for 24 hours. The pharmacokinetics values tested were K½el, Cmax, Tmax, AUC, AUC∞, AUCt, AUMC, RT, Kel, Vdss, Clb and Frel. DOX1 does not differ significantly from DOX-C, but shows significant differences in all variables with DOX2 (p<0.05). In conclusion, DOX1 presents best pharmacokinetics for time-dependent drug and longer release time of 60 hours, thereby reducing the frequency of administration, the patient's stress, the occurrence of adverse effects and the cost of treatment.

Keywords: tetracyclines, long-acting, sustained-release, carbopol, eudragit, canine

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Authors: Devinder Kaur Sugga, Ekamdeep Kaur, Jaspreet Kaur, C. Rajesh, Preeti Rajesh, Harsimran Kaur

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Withanolides are steroidal lactones and are highly oxygenated phytoconstituents that can be developed as potential anti-carcinogenic agents. The two main withanolides, namely Withaferin A and Withanolides D, have been extensively studied for their pharmacological activities. Both these withanolides are present in the Withania somnifera (WS) leaves belonging to the family Solanaceae, also known as “Indian ginseng .”In this study effects of WS leaf extract on the MCF7 breast cancer cell line were investigated by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects and in vitro wound-healing assay to study the effect on cancer cell migration. Our data suggest WS extracts have cytotoxic effects and are effective anti-migrating agents and thus can be a source of potential candidates for the development of potential agents against metastasis. Thus, it can be a source of potential candidates for the development of potential agents against metastasis. Insight into these results, the in-silico approach to identify the possible protein targets interacting with withanolides was taken. Protein kinase C alpha (PKCα) was among the selected 5 top-ranked target proteins identified by the Swiss Target Prediction tool. PKCα is known to promote the growth and invasion of cancer cells and is being evaluated as a prognostic biomarker and therapeutic target in clinically aggressive tumors. Molecular docking of Withaferin A and Withanolides D was performed using AutoDock Vina. Both the bioactive compounds interacted with PKCα. The targets predicted using this approach will serve as leads for the possible therapeutic potential of withanolides, the bioactive ingredients of WS extracts, as anti-cancer drugs.

Keywords: withania somnifera, withaferin A, withanolides D, PKCα

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Authors: Masaaki Ii, Takashi Saito, Yasuhiko Tabata, Shintaro Nemoto

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Background: Clinical trials of autologous adipose-derived stem cell (AdSC) therapy for ischemic heart diseases (IHD) are now on-going. We have investigated the hypothesis that combination of AdSCs and statin, an agent with pleiotropic effects, could augment the therapeutic effect on myocardial infarction (MI). Methods and Results: Human AdSC functions with different doses of simvastatin-conjugated nanoparticle (STNP) uptake were evaluated by in vitro assays. STNP promoted the migration activity without changing the proliferation activity, and also up-regulated growth factors. Next, MI was induced by LAD ligation in nude mice, and the mice were assigned in the following groups 3 days after MI: 1) PBS (control), 2) NP-AdSCs (50000 cells), 3) STNP, and 4) STNP-AdSCs (50000 cells). Cardiac functional recovery assessed by echocardiography was improved at 4 weeks after surgery in STNP-AdSC group. Masson’s trichrome-stained sections revealed that LV fibrosis length was reduced, and the number of TUNEL-positive cardiomyocytes was less in STNP-AdSC group. Surprisingly, a number of de novo endogenous Nkx-2.5/GATA4 positive immature cardiomyocytes as well as massive vascular formation were observed in outer layer of infarcted myocardium despite of a few recruited/retained transfused STNP-AdSCs 4 weeks after MI in STNP-AdSC group. Finally, massive myocardial regeneration was observed 8 weeks after MI. Conclusions: Intravenously injected small number of statin nanoparticle-loaded hAdSCs exhibited a potent therapeutic effect inducing endogenous cardiac tissue regeneration.

Keywords: statin, drug delivery system, stem cells, cardiac regeneration

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Authors: A. Ghanbari Mardasi, N. Wu, C. Wu

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In this study, a spatial wavelet-based crack localization technique for a thick beam is presented. Wavelet scale in spatial wavelet transformation is optimized to enhance crack detection sensitivity. A windowing function is also employed to erase the edge effect of the wavelet transformation, which enables the method to detect and localize cracks near the beam/measurement boundaries. Theoretical model and vibration analysis considering the crack effect are first proposed and performed in MATLAB based on the Timoshenko beam model. Gabor wavelet family is applied to the beam vibration mode shapes derived from the theoretical beam model to magnify the crack effect so as to locate the crack. Relative wavelet coefficient is obtained for sensitivity analysis by comparing the coefficient values at different positions of the beam with the lowest value in the intact area of the beam. Afterward, the optimal wavelet scale corresponding to the highest relative wavelet coefficient at the crack position is obtained for each vibration mode, through numerical simulations. The same procedure is performed for cracks with different sizes and positions in order to find the optimal scale range for the Gabor wavelet family. Finally, Hanning window is applied to different vibration mode shapes in order to overcome the edge effect problem of wavelet transformation and its effect on the localization of crack close to the measurement boundaries. Comparison of the wavelet coefficients distribution of windowed and initial mode shapes demonstrates that window function eases the identification of the cracks close to the boundaries.

Keywords: edge effect, scale optimization, small crack locating, spatial wavelet

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Authors: Oliveira M., Gonçalves L., Francisco I., Caramelo F., Vale F., Sanz D., Domingues M., Lopes M., Moreia D., Lopes T., Santos T., Cardoso H.

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The ARTHUR project consists of a platform that allows the virtual performance of maxillofacial surgeries, offering, in a photorealistic concept, the possibility for the patient to have an idea of the surgical changes before they are performed on their face. For this, the system brings together several image formats, dicoms and objs that, after loading, will generate the bone volume, soft tissues and hard tissues. The system also incorporates the patient's stereophotogrammetry, in addition to their data and clinical history. After loading and inserting data, the clinician can virtually perform the surgical operation and present the final result to the patient, generating a new facial surface that contemplates the changes made in the bone and tissues of the maxillary area. This tool acts in different situations that require facial reconstruction, however this project focuses specifically on two types of use cases: bone congenital disfigurement and acquired disfiguration such as oral cancer with bone attainment. Being developed a cloud based solution, with mobile support, the tool aims to reduce the decision time window of patient. Because the current simulations are not realistic or, if realistic, need time due to the need of building plaster models, patient rates on decision, rely on a long time window (1,2 months), because they don’t identify themselves with the presented surgical outcome. On the other hand, this planning was performed time based on average estimated values of the position of the maxilla and mandible. The team was based on averages of the facial measurements of the population, without specifying racial variability, so the proposed solution was not adjusted to the real individual physiognomic needs.

Keywords: 3D computing, image processing, image registry, image reconstruction

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Authors: Saleh Alotaibi, Mohammed Quddus, Craig Morton, Jobair Bin Alam

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This paper explores the role of large-scale investment in transport sectors and the impact of increased railway accessibility on the efficiency of the regional economic productivity in the Kingdom of Saudi Arabia (KSA). There are considerable differences among the KSA regions in terms of their levels of investment and productivity due to their geographical scale and location, which in turn greatly affect their relative efficiency. The study used a non-parametric linear programming technique - Data Envelopment Analysis (DEA) - to measure the regional efficiency change over time and determine the drivers of inefficiency and their scope of improvement. In addition, Window DEA analysis is carried out to compare the efficiency performance change for various time periods. Malmquist index (MI) is also analyzed to identify the sources of productivity change between two subsequent years. The analysis involves spatial and temporal panel data collected from 1999 to 2018 for the 13 regions of the country. Outcomes reveal that transport investment and improved railway accessibility, in general, have significantly contributed to regional economic development. Moreover, the endowment of the new railway stations has spill-over effects. The DEA Window analysis confirmed the dynamic improvement in the average regional efficiency over the study periods. MI showed that the technical efficiency change was the main source of regional productivity improvement. However, there is evidence of investment allocation discrepancy among regions which could limit the achievement of development goals in the long term. These relevant findings will assist the Saudi government in developing better strategic decisions for future transport investments and their allocation at the regional level.

Keywords: data envelopment analysis, transport investment, railway accessibility, efficiency

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Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri, S. Kakaei

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Despite the appropriate characteristics of ¹⁷⁷Lu and DOTATOC, to our best knowledge, the therapeutic benefit of ¹⁷⁷Lu-DOTATOC complex in breast cancer has not been reported until now. In this study, biodistribution of ¹⁷⁷Lu-DOTA-TOC in mouse tumor model for evaluation of possible utilization of this complex in breast cancer treatment was investigated.¹⁷⁷Lu was prepared with the specific activity of 2.6-3 GBq.mg^-1 and radionuclidic purity higher than 99%. The radiolabeled complex was prepared in the optimized conditions with the radiochemical purity higher than 99%. The final solution was injected to the BALB/c mice with adenocarcinoma breast cancer. The biodistribution results showed major accumulation in the kidneys as the major excretion route and the somatostatin receptor-positive tissues such as pancreas compared with the other tissues. Also, significant uptake was observed in tumor even in longer time after injection. According to the results obtained in this research study, somatostatin receptors expressed in breast cancers can be targeted with DOTATOC analogues especially with ¹⁷⁷Lu-DOTATOC as an ideal therapeutic agent.

Keywords: ¹⁷⁷Lu, adenocarcinoma breast cancer, DOTATOC, BALB/c mice

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Authors: Edwina Owusu Panin, Kwame Baah Owusu Panin

Abstract:

This abstract intends to demonstrate multiple strategies of autism management in Ghana by exploring the possibilities. The advantages of adopting creative art forms as a therapeutic method. Autism is a developmental disorder that includes social interaction, communication, and repetitive behaviours. In Ghana, as in many other countries, there is a rising demand for effective intervention and support for people with autism and their families. Creative arts such as music, dance, drama and visual arts have shown promise in promoting communication, social interaction and inclusion of people with autism. These art forms provide alternative channels for self-expression and can be powerful tools for autistic people to interact with the world, their friends and families around them. Creative art forms interventions have been found to improve social skills, improve emotion regulation, promote creativity and increase self-confidence in people with autism. This study examines existing programs and interventions in Ghana involving creative art forms for people with autism through a comparative analysis. It explores the different approaches, methods and results of these interventions. By comparing and evaluating these programs, the study aims to identify best practices, challenges and areas for development in managing autism through the creative arts in Ghana. Although many schools and rehabilitation centres employ various forms in therapeutic approaches for autism. There is no comparative analysis of which type of autism and which creative art forms is suitable. The results of this study will contribute to the development of evidence-based practices for the management of autism in Ghana. It provides valuable information about the effectiveness of creative arts interventions and helps inform policy makers, educators, therapists and other stakeholders involved in autism support. Ultimately, the goal is to improve the well-being and quality of life of people with autism in Ghana and their families by promoting inclusive and accessible interventions that harness the power of creative art forms.

Keywords: autism, therapeutic, creative art, art form

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Authors: Pranee Liamputtong, Hala Kurban

Abstract:

Based on the therapeutic landscape theory, this paper examines how young Middle-Eastern refugee individuals perceive their health and well-being and address the barriers they face in their new homeland and the means that helped them to form social connections in their new social environment. Qualitative methods (in-depth interviews and mapping activities) were conducted with ten young people from refugee backgrounds. Thematic analysis method was used to analyse the data. Findings suggested that the young refugees face various structural and cultural inequalities that significantly influenced their health and well-being. Mental health well-being was their greatest health concern. All reported the significant influence the English language had on their ability to adapt and form connections with their social environment. The presence of positive social support in their new social environment had a great impact on the health and well-being of the participants. The findings of this study have implications for social justice among refugees. They also contributed to the role of therapeutic landscapes and social support in helping young refugees to feel that they belonged to the society, and hence assisted them to adapt to their new living situation.

Keywords: young refugees, Middle-Eastern, social support, social justice

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Authors: M. R. Vijayakumar, K. Priyanka, Ramoji Kosuru, Lakshmi, Sanjay Singh

Abstract:

Trans resveratrol (RES) is a non-flavonoid poly-phenolic compound proved for its therapeutic and preventive effect against various types of cancer. However, the practical application of RES in cancer treatment is limited because of its higher dose (up to 7.5 g/day in humans), low biological half life, rapid metabolism and faster elimination in mammals. PEGylated core-shell type lipid polymer hybrid nanoparticles are the novel drug delivery systems for long circulation and improved anti cancer effect of its therapeutic payloads. Therefore, the main objective of this study is to extend the biological half life (long circulation) and improve the therapeutic efficacy of RES through core shell type of nanoparticles. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS), a novel surfactant is applied for the preparation of PEGylated lipid polymer hybrid nanoparticles. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Entrapment efficiency and invitro drug release were determined by ultracentrifugation method and dialysis bag method, respectively. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies after i.v administration were performed in sprague dawley rats. The prepared NPs were found to be spherical in shape with smooth surfaces. Particle size and zeta potential of prepared NPs were found to be in the range of 179.2±7.45 to 266.8±9.61 nm and -0.63 to -48.35 mV, respectively. DSC revealed absence of potential interaction. XRD study revealed presence of amorphous form in nanoparticles. Entrapment efficiency was found to be 83.7 % and drug release was found to be in controlled manner. MTT assay showed low MEC and pharmacokinetic studies showed higher AUC of nanoformulaition than its pristine drug. All these studies revealed that the RES loaded PEG modified core-shell type lipid polymer hybrid nanoparticles can be an alternative tool for chemopreventive and therapeutic application of RES in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating nanoparticles, bioavailability enhancement, core shell nanoparticles, lipid polymer hybrid nanoparticles

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Authors: Seolah Lee, Yoohyk Jang, Soyoung Lee, Kon Chu, Sang Kun Lee

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Objective: The International League Against Epilepsy (ILAE) currently suggests a topiramate serum level range of 5-20 mg/L. However, numerous institutions have observed substantial drug response at lower levels. This study aims to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range. Methods: We retrospectively analyzed topiramate serum samples collected between January 2017 and January 2022 at Seoul National University Hospital. Clinical data, including serum levels, antiseizure regimens, seizure frequency, and adverse events, were collected. Patient responses were categorized as "insufficient" (reduction in seizure frequency <50%) or "sufficient" (reduction ≥ 50%). Within the "sufficient" group, further subdivisions included seizure-free and tolerable seizure subgroups. A population pharmacokinetic model estimated serum levels from spot measurements. ROC curve analysis determined the optimal serum level cut-off. Results: A total of 389 epilepsy patients, with 555 samples, were reviewed, having a mean dose of 178.4±117.9 mg/day and a serum level of 3.9±2.8 mg/L. Out of the samples, only 5.6% (n=31) exhibited insufficient response, with a mean serum level of 3.6±2.5 mg/L. In contrast, 94.4% (n=524) of samples demonstrated sufficient response, with a mean serum level of 4.0±2.8 mg/L. This difference was not statistically significant (p = 0.45). Among the 78 reported adverse events, logistic regression analysis identified a significant association between ataxia and serum concentration (p = 0.04), with an optimal cut-off value of 6.5 mg/L. In the subgroup of patients receiving monotherapy, those in the tolerable seizure group exhibited a significantly higher serum level compared to the seizure-free group (4.8±2.0 mg/L vs 3.4±2.3 mg/L, p < 0.01). Notably, patients in the tolerable seizure group displayed a higher likelihood of progressing into drug-resistant epilepsy during follow-up visits compared to the seizure-free group. Significance: This study proposed an optimal therapeutic concentration for topiramate based on the patient's responsiveness to the drug and the incidence of adverse effects. We employed a population pharmacokinetic model and analyzed topiramate serum levels to recommend a serum level below 6.5 mg/L to mitigate the risk of ataxia-related side effects. Our findings also indicated that topiramate dose elevation is unnecessary for suboptimal responders, as the drug's effectiveness plateaus at minimal doses.

Keywords: topiramate, therapeutic range, low dos, antiseizure effect

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Authors: Xinxiu Li, Chuqian Zheng, Yanyan Qian, Hong Fan

Abstract:

Objectives: In hepatocellular carcinoma (HCC), oncogenes are continuously and robustly transcribed due to aberrant expression of essential components of the trans-acting super-enhancers (SE) complex. Preclinical and clinical trials are now being conducted on small-molecule inhibitors that target core-transcriptional components, including as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7), in a number of malignant tumors. This study aims to explore whether co-overexpression of BRD4 and CDK7 is a potential marker of worse prognosis and a combined therapeutic target in HCC. Methods: The expression pattern of BRD4 and CDK7 and their correlation with prognosis in HCC were analyzed by RNA sequencing data and survival data of HCC patients from TCGA and GEO datasets. The protein levels of BRD4 and CDK7 were determined by immunohistochemistry (IHC), and survival data of patients were analyzed using the Kaplan-Meier method. The mRNA expression levels of genes in HCC cell lines were evaluated by quantitative PCR (q-PCR). CCK-8 and colony formation assays were conducted to assess cell proliferation of HCC upon treatment with BRD4 inhibitor JQ1 or/and CDK7 inhibitor THZ1. Results: It was shown that BRD4 and CDK7 were often overexpressed in HCCs and were associated with poor prognosis of HCC by analyzing the TCGA and GEO datasets. BRD4 or CDK7 overexpression was related to a lower survival rate. It's interesting to note that co-overexpression of CDK7 and BRD4 was a worse prognostic factor in HCC. Treatment with JQ1 or THZ1 alone had an inhibitory effect on cell proliferation; however, when JQ1 and THZ1 were combined, there was a more notable suppression of cell growth. At the same time, the combined use of JQ1 and THZ1 synergistically suppresses the expression of HCC driver genes. Conclusion: Our research revealed that BRD4 and CDK7 coupled can be a useful biomarker in HCC prognosis and the combination of JQ1 and THZ1 can be a promising therapeutic therapy against HCC.

Keywords: BRD4, CDK7, cell proliferation, combined inhibition

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Authors: A. E. Emam, M. Abd Elghany

Abstract:

The change in orbit evolution between collocated satellites (X, Y) inside +/-0.09 ° E/W and +/- 0.07 ° N/S cluster, after one of these satellites is placed in an inclined orbit (satellite X) and the effect of this change in the collocation safety inside the cluster window has been studied and evaluated. Several collocation scenarios had been studied in order to adjust the location of both satellites inside their cluster to maximize the separation between them and safe the mission.

Keywords: satellite, GEO, collocation, risk assessment

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Authors: Pedro Miguel Cardoso Carneiro, Ricardo André Nunes Borges, João Pedro Soares Loureiro, Hermínio Maio Graça Fernandes

Abstract:

Wind energy has been exponentially growing over the last years and will allow countries to progress regarding the decarbonization objective. In parallel, the maintenance activities have also been increasing in consequence of ageing and deterioration of the wind farms. The time available for wind blade maintenance is given by the weather window that is based upon weather conditions. Most of the wind blade repair and maintenance activities require a narrow window of temperature and humidity. Due to this limitation, the current weather windows result only on approximately 35% days/year are used for maintenance, that takes place mostly during summertime. This limitation creates large economic losses in the energy production of the wind towers, since they can be inoperative or with the energy production output reduced for days or weeks due to existing damages. Another important aspect is that the maintenance costs are higher due to the high standby time and seasonality imposed on the technicians. To reduce the relevant maintenance costs of blades and energy loses some technological developments were carried out to significantly improve this reality. The focus of this activity was to develop a series of key developments to have in the near future a suspended access equipment that can operate in harsh conditions, wind rain, cold/hot environment. To this end we have identified key areas that need to be revised and require new solutions to be found; a habitat system, multi-configurable roof and floor, roof and floor interface to blade, secondary attachment solutions to the blade and to the tower. On this paper we will describe the advances produced during a national R&D project made in partnership with an end-user (Onrope) and a test center (ISQ).

Keywords: wind turbine maintenance, cost reduction, technological innovations, wind turbine blade

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Authors: Ammara Khan

Abstract:

Sepsis is characterized by an overwhelming surge of cytokines and oxidative stress to one of many factors, gram-negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damages including hepatotoxicity.The present study was aimed to ascertain the adequacy of three different drugs delivered separately and collectively- low dose steroid-dexamethasone (3mg/kg i.p) ,antioxidant-melatonin(10 mg/kg i.p) ,and phosphodiesterases inhibitor - pentoxifylline (75 mg/kg i.p)in endotoxin-induced hepatotoxicity in mice. Endotoxin/lipopolysaccharides induced hepatotoxicity was reproduced in mice by giving lipopolysaccharide of serotype E.Coli intraperitoneally. The preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas the therapeutic potential of the experimental agent was searched out via post-LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with a histopathological examination of liver tissue. Dexamethasone is given before (Group 3) and after LPS (group 4) significantly attenuated LPS generated liver injury.Pentoxifylline generated similar results and serum ALT; AST histological alteration abated considerably (p≤ 0.05) both in animals subjected to pentoxifylline pre (Group 5) and post-treatment(Group 6). Melatonin was also prosperous in aversion (Group 7) and curation (Group 8) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes in liver sections (p≤0.05). Combination therapies with dexamethasone in conjunction with melatonin (Group 9), dexamethasone together with pentoxifylline (Group 10), and pentoxifylline along with melatonin (Group 11) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably. In conclusion, both melatonin and pentoxifylline set up promising results in endotoxin-induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis-induced liver failure.

Keywords: endotoxin/lipopolysacchride, dexamethasone, hepatotoxicity, melatonin, pentoxifylline

Procedia PDF Downloads 273