Search results for: drug discovery
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2459

Search results for: drug discovery

599 Association of Nuclear – Mitochondrial Epistasis with BMI in Type 1 Diabetes Mellitus Patients

Authors: Agnieszka H. Ludwig-Slomczynska, Michal T. Seweryn, Przemyslaw Kapusta, Ewelina Pitera, Katarzyna Cyganek, Urszula Mantaj, Lucja Dobrucka, Ewa Wender-Ozegowska, Maciej T. Malecki, Pawel Wolkow

Abstract:

Obesity results from an imbalance between energy intake and its expenditure. Genome-Wide Association Study (GWAS) analyses have led to discovery of only about 100 variants influencing body mass index (BMI), which explain only a small portion of genetic variability. Analysis of gene epistasis gives a chance to discover another part. Since it was shown that interaction and communication between nuclear and mitochondrial genome are indispensable for normal cell function, we have looked for epistatic interactions between the two genomes to find their correlation with BMI. Methods: The analysis was performed on 366 T1DM patients using Illumina Infinium OmniExpressExome-8 chip and followed by imputation on Michigan Imputation Server. Only genes which influence mitochondrial functioning (listed in Human MitoCarta 2.0) were included in the analysis – variants of nuclear origin (MAF > 5%) in 1140 genes and 42 mitochondrial variants (MAF > 1%). Gene expression analysis was performed on GTex data. Association analysis between genetic variants and BMI was performed with the use of Linear Mixed Models as implemented in the package 'GENESIS' in R. Analysis of association between mRNA expression and BMI was performed with the use of linear models and standard significance tests in R. Results: Among variants involved in epistasis between mitochondria and nucleus we have identified one in mitochondrial transcription factor, TFB2M (rs6701836). It interacted with mitochondrial variants localized to MT-RNR1 (p=0.0004, MAF=15%), MT-ND2 (p=0.07, MAF=5%) and MT-ND4 (p=0.01, MAF=1.1%). Analysis of the interaction between nuclear variant rs6701836 (nuc) and rs3021088 localized to MT-ND2 mitochondrial gene (mito) has shown that the combination of the two led to BMI decrease (p=0.024). Each of the variants on its own does not correlate with higher BMI [p(nuc)=0.856, p(mito)=0.116)]. Although rs6701836 is intronic, it influences gene expression in the thyroid (p=0.000037). rs3021088 is a missense variant that leads to alanine to threonine substitution in the MT-ND2 gene which belongs to complex I of the electron transport chain. The analysis of the influence of genetic variants on gene expression has confirmed the trend explained above – the interaction of the two genes leads to BMI decrease (p=0.0308). Each of the mRNAs on its own is associated with higher BMI (p(mito)=0.0244 and p(nuc)=0.0269). Conclusıons: Our results show that nuclear-mitochondrial epistasis can influence BMI in T1DM patients. The correlation between transcription factor expression and mitochondrial genetic variants will be subject to further analysis.

Keywords: body mass index, epistasis, mitochondria, type 1 diabetes

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598 The Effect of Probiotic and Vitamin B Complex Supplementation on Interferon-γ and Interleukin-10 Levels in Patients with TB Infection during Intensive Phase Therapy

Authors: Yulistiani Yulistiani, Wenny Nilamsari, Laurin Winarso, Rizkiya Rizkiya, Zamrotul Izzah, Budi Suprapti, Arif Bachtiar

Abstract:

Approximately, a million new cases of TB have been found out per year, making Indonesia as the second greatest country with TBC after India. Nevertheless, until now, there are still many patients failure to conventional therapy with oral anti tuberculosis. Thus, the discovery of supplement therapy is urgently needed. Many studies showed that probiotic had the positive impact in lung diseases, diarrhea, pneumonia and it was attributed to its capability to balance the level of cytokine pro-inflammatory and anti-inflammatory. It was demonstrated in active disease the production of IFN-γ is strongly depressed and IL-10 level increases. This study aimed to investigate the effect of probiotic (multi strains) and vitamin B complex supplementation on IFN-γ and IL-10 level in patients with TB infection during intensive phase therapy. A randomized controlled trial, open labeled was conducted in TB patients with the following criteria: 1) age 18-55 years old 2) receiving oral antituberculosis during intensive therapy 3) not using probiotic, vitamin B1, B6, B12 2 weeks before enrollment 4) willing to participate in this study and signed an informed consent. While, patients with HIV, pregnant, had the history of diabetes mellitus, using corticosteroid or other immunosuppressants were excluded. IFN-γ and IL-10 levels were drawn before observation and after a month observation. The assay was performed by ELISA. There were seven patients in treated group and five patients in controlled group obtained in this study. Between groups, there was no statistical difference in comorbid, age, and disease duration. The mean level of IFN-γ after a month observation increased in treated group and controlled group, which were 31.47 ± 105.46 pg/ml and 15.09 ± 24.23 pg/ml, respectively (p> 0.005). Although, there were not statistically different, treated group showed a greater increase of IFN-γ level than that of the controlled group. IFN-γ plays an important role in immune response to Mycobacterium Tuberculosis, by activating macrofag, monosit and furthermore killing Mycobacterium Tuberculosis. Thus the level was expected to increase after supplementation with probiotic and Vitamin B complex. While the mean level of IL-10 also increased after one month observation in the treated group and controlled group (4.28 ± 12.29 pg/ml and 5.77± 6.21 pg/ml, respectively) (p>0.005). To be compared, the increased level of IL-10 in the treated group were lower than the controlled group, although it was not statistically different. IL-10 is a cytokine anti-inflammatory, thus, the level after the observation was expected to decrease. In this study, a month therapy of probiotic and vitamin B complex was not able to demonstrate the decrease of the IL-10 level. It is suggested to prolong observation up to 2 months, because, in intensive phase, the level of cytokine anti-inflammatory is very high, so the longer therapy is needed. It is indicated that supplementation therapy with probiotic and vitamin B complex to Oral Anti-Tuberculosis may have a positive effect on increasing IFN-γ level and slowing the progression of IL-10.

Keywords: TB Infection, IFN-γ, IL-10, probiotic, vitamin B complex

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597 Isolation and Biological Activity of Betulinic and Oleanolic Acids from the Aerial Plant Parts of Maesobotrya Barteri (Baill)

Authors: Christiana Ene Ogwuche, Joseph Amupitan, George Ndukwe, Rachael Ayo

Abstract:

Maesobotrya barteri (Baill), belonging to the family Euphorbiaceae, is a medicinal plant growing widely in tropical Africa. The Aerial plant parts of Maesobotrya barteri (Baill) were collected fresh from Orokam, Ogbadibo local Government of Benue State, Nigeria in July 2013. Taxonomical identification was done by Mallam Musa Abdullahi at the Herbarium unit of Biological Sciences Department, ABU, Zaria, Nigeria. Pulverized aerial parts of Maesobotrya barteri (960g) was exhaustively extracted successively using petroleum ether, chloroform, ethyl acetate and methanol and concentrated in the rotary evaporator at 40°C. The Petroleum ether extract had the second highest activity against test microbes from preliminary crude microbial screenings. The Petroleum ether extract was subjected to phytochemical studies, antimicrobial analysis and column chromatography (CC). The column chromatography yielded fraction PE, which was further purified using preparative thin layer chromatography to give PE1. The structure of the isolated compound was established using 1-D NMR and 2-D NMR spectroscopic analysis and by direct comparison with data reported in literature was confirmed to be a mixture, an isomer of Betulinic acid and Oleanolic acid, both with the molecular weight (C₃₀H₄₈O₃). The bioactivity of this compound was carried out using some clinical pathogens and the activity compared with standard drugs, and this was found to be comparable with the standard drug.

Keywords: Maesobotrya barteri, medicinal plant, bioactivity, petroleum spirit extract, butellinic acid, oleanilic acid

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596 The First Import of Yellow Fever Cases in China and Its Revealing Suggestions for the Control and Prevention of Imported Emerging Diseases

Authors: Chao Li, Lei Zhou, Ruiqi Ren, Dan Li, Yali Wang, Daxin Ni, Zijian Feng, Qun Li

Abstract:

Background: In 2016, yellow fever had been first ever discovered in China, soon after the yellow fever epidemic occurred in Angola. After the discovery, China had promptly made the national protocol of control and prevention and strengthened the surveillance on passenger and vector. In this study, a descriptive analysis was conducted to summarize China’s experiences of response towards this import epidemic, in the hope of providing experiences on prevention and control of yellow fever and other similar imported infectious diseases in the future. Methods: The imported cases were discovered and reported by General Administration of Quality Supervision, Inspection and Quarantine (AQSIQ) and several hospitals. Each clinically diagnosed yellow fever case was confirmed by real-time reverse transcriptase polymerase chain reaction (RT–PCR). The data of the imported yellow fever cases were collected by local Centers for Disease Control and Prevention (CDC) through field investigations soon after they received the reports. Results: A total of 11 imported cases from Angola were reported in China, during Angola’s yellow fever outbreak. Six cases were discovered by the AQSIQ, among which two with mild symptom were initiative declarations at the time of entry. Except for one death, the remaining 10 cases all had recovered after timely and proper treatment. All cases are Chinese, and lived in Luanda, the capital of Angola. 73% were retailers (8/11) from Fuqing city in Fujian province, and the other three were labors send by companies. 10 cases had experiences of medical treatment in Luanda after onset, among which 8 cases visited the same local Chinese medicine hospital (China Railway four Bureau Hospital). Among the 11 cases, only one case had an effective vaccination. The result of emergency surveillance for mosquito density showed that only 14 containers of water were found positive around places of three cases, and the Breteau Index is 15. Conclusions: Effective response was taken to control and prevent the outbreak of yellow fever in China after discovering the imported cases. However, though the similar origin of Chinese in Angola has provided an easy access for disease detection, information sharing, health education and vaccination on yellow fever; these conveniences were overlooked during previous disease prevention methods. Besides, only one case having effective vaccination revealed the inadequate capacity of immunization service in China. These findings will provide suggestions to improve China’s capacity to deal with not only yellow fever but also other similar imported diseases in China.

Keywords: yellow fever, first import, China, suggestion

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595 New Photosensitizers Encapsulated within Arene-Ruthenium Complexes Active in Photodynamic Therapy: Intracellular Signaling and Evaluation in Colorectal Cancer Models

Authors: Suzan Ghaddar, Aline Pinon, Manuel Gallardo-villagran, Mona Diab-assaf, Bruno Therrien, Bertrand Liagre

Abstract:

Colorectal cancer (CRC) is the third most common cancer and exhibits a consistently rising incidence worldwide. Despite notable advancements in CRC treatment, frequent occurrences of side effects and the development of therapy resistance persistently challenge current approaches. Eventually, innovations in focal therapies remain imperative to enhance the patient’s overall quality of life. Photodynamic therapy (PDT) emerges as a promising treatment modality, clinically used for the treatment of various cancer types. It relies on the use of photosensitive molecules called photosensitizers (PS), which are photoactivated after accumulation in cancer cells, to induce the production of reactive oxygen species (ROS) that cause cancer cell death. Among commonly used metal-based drugs in cancer therapy, ruthenium (Ru) possesses favorable attributes that demonstrate its selectivity towards cancer cells and render it suitable for anti-cancer drug design. In vitro studies using distinct arene-Ru complexes, encapsulating porphin PS, are conducted on human HCT116 and HT-29 colorectal cancer cell lines. These studies encompass the evaluation of the antiproliferative effect, ROS production, apoptosis, cell cycle progression, molecular localization, and protein expression. Preliminary results indicated that these complexes exert significant photocytotoxicity on the studied colorectal cancer cell lines, representing them as promising and potential candidates for anti- cancer agents.

Keywords: colorectal cancer, photodynamic therapy, photosensitizers, arene-ruthenium complexes, apoptosis

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594 Numerical and Sensitivity Analysis of Modeling the Newcastle Disease Dynamics

Authors: Nurudeen Oluwasola Lasisi

Abstract:

Newcastle disease is a highly contagious disease of birds caused by a para-myxo virus. In this paper, we presented Novel quarantine-adjusted incident and linear incident of Newcastle disease model equations. We considered the dynamics of transmission and control of Newcastle disease. The existence and uniqueness of the solutions were obtained. The existence of disease-free points was shown, and the model threshold parameter was examined using the next-generation operator method. The sensitivity analysis was carried out in order to identify the most sensitive parameters of the disease transmission. This revealed that as parameters β,ω, and ᴧ increase while keeping other parameters constant, the effective reproduction number R_ev increases. This implies that the parameters increase the endemicity of the infection of individuals. More so, when the parameters μ,ε,γ,δ_1, and α increase, while keeping other parameters constant, the effective reproduction number R_ev decreases. This implies the parameters decrease the endemicity of the infection as they have negative indices. Analytical results were numerically verified by the Differential Transformation Method (DTM) and quantitative views of the model equations were showcased. We established that as contact rate (β) increases, the effective reproduction number R_ev increases, as the effectiveness of drug usage increases, the R_ev decreases and as the quarantined individual decreases, the R_ev decreases. The results of the simulations showed that the infected individual increases when the susceptible person approaches zero, also the vaccination individual increases when the infected individual decreases and simultaneously increases the recovery individual.

Keywords: disease-free equilibrium, effective reproduction number, endemicity, Newcastle disease model, numerical, Sensitivity analysis

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593 Expression of Tissue Plasminogen Activator in Transgenic Tobacco Plants by Signal Peptides Targeting for Delivery to Apoplast, Endoplasmic Reticulum and Cytosol Spaces

Authors: Sadegh Lotfieblisofla, Arash Khodabakhshi

Abstract:

Tissue plasminogen activator (tPA) as a serine protease plays an important role in the fibrinolytic system and the dissolution of fibrin clots in human body. The production of this drug in plants such as tobacco could reduce its production costs. In this study, expression of tPA gene and protein targeting to different plant cell compartments, using various signal peptides has been investigated. For high level of expression, Kozak sequence was used after CaMV35S in the beginning of the gene. In order to design the final construction, Extensin, KDEL (amino acid sequence including Lys-Asp-Glu-Leu) and SP (γ-zein signal peptide coding sequence) were used as leader signals to conduct this protein into apoplast, endoplasmic reticulum and cytosol spaces, respectively. Cloned human tPA gene under the CaMV (Cauliflower mosaic virus) 35S promoter and NOS (Nopaline Synthase) terminator into pBI121 plasmid was transferred into tobacco explants by Agrobacterium tumefaciens strain LBA4404. The presence and copy number of genes in transgenic tobacco was proved by Southern blotting. Enzymatic activity of the rt-PA protein in transgenic plants compared to non-transgenic plants was confirmed by Zymography assay. The presence and amount of rt-PA recombinant protein in plants was estimated by ELISA analysis on crude protein extract of transgenic tobacco using a specific antibody. The yield of recombinant tPA in transgenic tobacco for SP, KDEL, Extensin signals were counted 0.50, 0.68, 0.69 microgram per milligram of total soluble proteins.

Keywords: tPA, recombinant, transgenic, tobacco

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592 Immunoliposomes for Co-Delivery of Doxorubicin and Ribonucleotide Reductase M2 Sirna Inhibit of Gastric Cancer Growth

Authors: Jie Gao

Abstract:

The combination of chemotherapy with gene therapy is highly effective in cancer therapy. To achieve combined therapeutic effects in human gastric cancer over expressing EGFR, we developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab’ for co-delivery of doxorubicin (DOX) and ribonucleotide reductase M2 (RRM2) siRNA (DOX-RRM2-TLPD). The results showed that EGFR was over expressed in several gastric cancer cell lines and gastric cancer tissues. Gene Expression Omnibus (GEO) results showed that RRM2 expression was significantly higher in gastric cancer than in non-gastric cancer tissue, and RRM2 siRNA inhibited the proliferation of several gastric cancer cells, indicating that RRM2 is a candidate target for gastric cancer therapy. Confocal studies and flow cytometry showed that DOX-RRM2-TLPD delivered DOX and RRM2 siRNA to EGFR over expressing gastric cancer cells specifically and efficiently both in vitro and in vivo, resulting in enhanced therapeutic effects (cytotoxicity and apoptosis) compared with single-drug loaded or non-targeted controls, including DOX-NC-TLPD (targeted LPD co-delivering DOX and negative control siRNA), RRM2-TLPD (targeted LPD delivering RRM2 siRNA) and DOX-RRM2-NTLPD (non-targeted LPD co-delivering DOX and RRM2 siRNA). The in vivo antitumor assay showed that the average weight of the gastric cancer in mice treated with DOX-RRM2-TLPD was significantly lighter than that of mice treated with other controls. DOX-RRM2-TLPD represents an effective approach for combined therapy of gastric cancer over expressing EGFR.

Keywords: gene therapy, chemotherapy, immunoliposomes, gastric cancer

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591 The Contribution of the Lomé Charter to Combating Drugs Trafficking at Sea: Nigerian and South African Legal Perspectives

Authors: Obinna Emmanuel Nkomadu

Abstract:

The sea attracts many criminal activities including drug trafficking. The illicit traffic in narcotic drugs and psychotropic substances by sea poses a serious threat to maritime security globally. The seizure of drugs, particularly, on the African continent is on the raise. In terms of Southern Africa, South Africa is a major transit point for Latin American drugs and South Africa is the largest market for illicit drugs entering the Southern African region. Nigeria and South Africa have taken a number of steps to address this scourge, but, despite those steps, drugs trafficking at sea continues. For that reason and to combat a number of other threats to maritime security around the continent, a substantial number of AU members in 2016 adopted the African Charter on Maritime Security and Safety and Development in Africa (“the Charter”). However, the Charter is yet to come into force due to the number of States required to accede or ratify the Charter. This paper set out the pre-existing international instruments on drugs, to ascertain the domestic laws of Nigeria and South Africa relating to drugs with the relevant provisions of the Lomé Charter in order to establish whether any legal steps are required to ensure that Nigeria and South Africa comply with its obligations under the Charter. Indeed, should Nigeria and South Africa decide to ratify it and should it come into force, both States must cooperate with other relevant States in establishing policies, as well as a regional and continental institutions, and ensure the implementation of such policies. The paper urged the States to urgently ratify the Charter as it is a step in the right direction in the prevention and repression of drugs trafficking on the African maritime domain.

Keywords: cooperation against drugs trafficking at sea, Lomé Charter, maritime security, Nigerian and South Africa legislation on drugs

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590 Elucidation of Mechanism of Action of Antidepressant-Like Effect of Valeriana wallichii Maaliol Chemotype in Mice

Authors: Sangeeta Pilkhwal Sah, C. S. Mathela, Kanwaljit Chopra

Abstract:

Valeriana wallichii DC, an ayurvedic traditional medicine, popularly named as Indian valerian exist as three chemotypes. GC-MS analysis of V. wallichii essential oil in present study showed maaliol as the major constituent followed by the presence of β-gurjunene, acoradiene, guaiol and α-santalene. The results thus confirmed it to be a maaliol chemotype. Further, the antidepressant-like effect of root essential oil (10, 20 and 40 mg/kg p.o.) was investigated in both acute and chronic treatment study using forced swim test in mice. Single administration of different doses produced an inverted U shaped curve and significantly inhibited the immobility period (39.7% and 58%) at doses 10 and 40 mg/kg respectively. Standard drug imipramine significantly decreased immobility period (59.8%). None of the doses altered locomotor activity except a significant decrease of 44.9% was observed with 40 mg/kg (p < 0.05). Similarly, daily administration of essential oil for 14 days produced a dose dependent effect with significantly reduced immobility period (70.9%) at 40 mg/kg dose only whereas imipramine produced 86% decrease (p < 0.05). The neurotransmitter levels in mouse brain were estimated on day 14 after the behavioral study. Significant increase in the level of norepinephrine (10%) and dopamine (23%) (p < 0.05) was found at 40 mg/kg dose, while no change was observed at 10 and 20 mg/kg doses. The antidepressant-like effect of essential oil (40 mg/kg) was prevented by pretreatment of mice with L-arginine (750 mg/kg i.p.) and sildenafil (5 mg/kg i.p). On the contrary, pretreatment of mice with L-NAME (10 mg/kg i.p.) or methylene blue (10 mg/kg i.p.) potentiated the antidepressant action of essential oil (20 mg/kg). The findings thus demonstrated that nitric oxide pathway is involved in mediating antidepressant like effect of essential oil from this chemotype.

Keywords: Valeriana wallichii DC chemotype, essential oil, forced swim test, nitric oxide modulators, neurotransmitters

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589 Modulation of Tamoxifen-Induced Cytotoxicity in Breast Cancer Cell Lines by 3-Bromopyruvate

Authors: Yasmin M. Attia, Hanan S. El-Abhar, Mahmoud M. Al Marzabani, Samia A. Shouman

Abstract:

Background: Tamoxifen (TAM) is the most commonly used hormone therapy for the treatment of early and metastatic breast cancer. Although it significantly decreases the tumor recurrence rate and provides an overall benefit, as much as 20–30% of women still relapse during or after long-term therapy. 3-Bromopyruvate (3-BP) is a promising agent with impressive antitumor effects in several models of animal tumors and cell lines. Aim: This study was designed to investigate the combined effect of (TAM) and (3-BP) in breast cancer cells and to explore their molecular interaction via assessment of apoptotic, angiogenic, and metastatic markers. Methods: In vitro cytotoxicity study was carried out for both compounds to determine the combination regimen producing a synergistic effect and mechanistic pathways were studied using RT-PCR and western techniques. Moreover, the anti-oncolytic and anti-angiogenic potentials were assessed in mice bearing solid Ehrlich carcinoma (SEC). Results: The combined treatment significantly increased the expressions and protein levels of caspase 7, 9, and 3 and decreased of angiogenic markers VEGF, HIF-1α, and HK2 compared to cells treated with either drug individually. However, there were no significant changes in MMP-2 and MMP-9 protein levels. Interestingly, the in vivo results supported the in vitro findings; there was a decrease in the tumor volume and VEFG using immunohistochemistry in the combination-treated groups compared to either TAM or 3-BP treated one. Conclusion: 3-BP synergizes the cytotoxic effect of TAM by increasing apoptosis and decreasing angiogenesis which makes this combination a promising regimen to be applied clinically.

Keywords: tamoxifen, 3-bromopyruvate, breast cancer, cytotoxicity, angiogenesis

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588 Plasmonic Nanoshells Based Metabolite Detection for in-vitro Metabolic Diagnostics and Therapeutic Evaluation

Authors: Deepanjali Gurav, Kun Qian

Abstract:

In-vitro metabolic diagnosis relies on designed materials-based analytical platforms for detection of selected metabolites in biological samples, which has a key role in disease detection and therapeutic evaluation in clinics. However, the basic challenge deals with developing a simple approach for metabolic analysis in bio-samples with high sample complexity and low molecular abundance. In this work, we report a designer plasmonic nanoshells based platform for direct detection of small metabolites in clinical samples for in-vitro metabolic diagnostics. We first synthesized a series of plasmonic core-shell particles with tunable nanoshell structures. The optimized plasmonic nanoshells as new matrices allowed fast, multiplex, sensitive, and selective LDI MS (Laser desorption/ionization mass spectrometry) detection of small metabolites in 0.5 μL of bio-fluids without enrichment or purification. Furthermore, coupling with isotopic quantification of selected metabolites, we demonstrated the use of these plasmonic nanoshells for disease detection and therapeutic evaluation in clinics. For disease detection, we identified patients with postoperative brain infection through glucose quantitation and daily monitoring by cerebrospinal fluid (CSF) analysis. For therapeutic evaluation, we investigated drug distribution in blood and CSF systems and validated the function and permeability of blood-brain/CSF-barriers, during therapeutic treatment of patients with cerebral edema for pharmacokinetic study. Our work sheds light on the design of materials for high-performance metabolic analysis and precision diagnostics in real cases.

Keywords: plasmonic nanoparticles, metabolites, fingerprinting, mass spectrometry, in-vitro diagnostics

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587 Emergency Management of Poisoning Tracery Care Hospital in India

Authors: Rajiv Ratan Singh, Sachin Kumar Tripathi, Pradeep Kumar Yadav

Abstract:

The timely evaluation, diagnosis, and treatment of people who have been exposed to toxic chemicals is a crucial component of emergency poison management in the medical field. The various substances that can poison include chemicals, medications, and naturally occurring poisons. The toxicology of the particular drug involved, as well as the symptoms and indicators of poisoning, must be thoroughly understood to handle poisoning emergencies effectively. One of the most important aspects of emergency poison management in medicine is the prompt examination, diagnosis, and treatment of persons who have been exposed to dangerous substances. To properly manage poisoning crises, one must have a good understanding of the toxicology of the particular medication concerned, as well as the signs and indicators of poisoning. Emergency management of poisoning includes not only prompt medical attention but also patient education, follow-up care, and monitoring for any long-term consequences. To achieve the greatest results for patients, the management of poisoning is a complicated and dynamic process that calls for collaboration between medical professionals, first responders, and toxicologists. All poisoned patients who present to the emergency room are assessed and diagnosed based on a collection of symptoms and a biochemical diagnosis, and they are then provided targeted, specialized treatment for the toxin identified. This article focuses on the loxodromic strategy as the primary method of treatment for poisoned patients. The authors of this article conclude that mortality and morbidity can be reduced if patients visit the emergency room promptly and receive targeted treatment.

Keywords: antidotes, blood poisoning, emergency medicine, gastric lavage, medico-legal aspects, patient care

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586 Molecular Diagnosis of Influenza Strains Was Carried Out on Patients of the Social Security Clinic in Karaj Using the RT-PCR Technique

Authors: A. Ferasat, S. Rostampour Yasouri

Abstract:

Seasonal flu is a highly contagious infection caused by influenza viruses. These viruses undergo genetic changes that result in new epidemics across the globe. Medical attention is crucial in severe cases, particularly for the elderly, frail, and those with chronic illnesses, as their immune systems are often weaker. The purpose of this study was to detect new subtypes of the influenza A virus rapidly using a specific RT-PCR method based on the HA gene (hemagglutinin). In the winter and spring of 2022_2023, 120 embryonated egg samples were cultured, suspected of seasonal influenza. RNA synthesis, followed by cDNA synthesis, was performed. Finally, the PCR technique was applied using a pair of specific primers designed based on the HA gene. The PCR product was identified after purification, and the nucleotide sequence of purified PCR products was compared with the sequences in the gene bank. The results showed a high similarity between the sequence of the positive samples isolated from the patients and the sequence of the new strains isolated in recent years. This RT-PCR technique is entirely specific in this study, enabling the detection and multiplication of influenza and its subspecies from clinical samples. The RT-PCR technique based on the HA gene, along with sequencing, is a fast, specific, and sensitive diagnostic method for those infected with influenza viruses and its new subtypes. Rapid molecular diagnosis of influenza is essential for suspected people to control and prevent the spread of the disease to others. It also prevents the occurrence of secondary (sometimes fatal) pneumonia that results from influenza and pathogenic bacteria. The critical role of rapid diagnosis of new strains of influenza is to prepare a drug vaccine against the latest viruses that did not exist in the community last year and are entirely new viruses.

Keywords: influenza, molecular diagnosis, patients, RT-PCR technique

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585 Efficacy of Ethanolic Extract of Aerva javanica Aerial Parts in the Amelioration of CCl4-Induced Hepatotoxicity and Oxidative Damage in Rats

Authors: Mohammad K. Parvez, Ahmed H. Arbab, Mohammed S. Al-Dosari, Adnan J. Al-Rehaily

Abstract:

We investigated ex vivo and in vivo antioxidative and hepatoprotective effect of Aerva javanica. Total ethanol extract of A. javanica aerial parts was prepared, and tested on DCFH-toxicated HepG2 cell in CCl4-injured Wistar rats. MTT-assay was used to determine cell viability, and serum biochemical markers of liver injury as well as histopathology were performed. In vitro DPPH and β-carotene free-radical scavenging assay and phytochemical screening of the extract was done. Furthermore, A. javanica total extract was standardized and validated by HPTLC method. While DCFH-injured cells were recovered to about 56.7% by 100 microg/ml of the extract, a 200 microg/ml dose resulted in hepatocytes recovery by about 90.2%. Oral administration of the extract (100 and 200 mg/kg.bw/day) significantly normalized the serum SGOT, SGPT, GGT, ALP, bilirubin, cholesterol, HDL, LDL, VLDL, TG and MDA levels, including tissue NP-SH and TP in CCl4-injured rats. In addition, the histopathology of dissected liver also revealed that A. javanica cured the tissue lesion compared to reference drug, Silymarin. In vitro assays revealed strong free-radical scavenging ability of the extract and presence of alkaloids, flavonoids, tannins, sterols and saponins where Rutin, a well-known antioxidant flavonoid was identified. Our finding therefore, suggests the therapeutic potential of A. javanica in various liver diseases. However, isolation of the active principles, their mechanism of action and other therapeutic contribution remain to be addressed.

Keywords: Aerva javanica, antioxidant, hepatoprotection, rutin

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584 Evaluation of Antarctic Bacteria as Potential Producers of Cellulolytic Enzymes of Industrial Interest

Authors: Claudio Lamilla, Andrés Santos, Vicente Llanquinao, Jocelyn Hermosilla, Leticia Barrientos

Abstract:

The industry in general is very interested in improving and optimizing industrial processes in order to reduce the costs involved in obtaining raw materials and production. Thus, an interesting and cost-effective alternative is the incorporation of bioactive metabolites in such processes, being an example of this enzymes which catalyze efficiently a large number of enzymatic reactions of industrial and biotechnological interest. In the search for new sources of these active metabolites, Antarctica is one of the least explored places on our planet where the most drastic cold conditions, salinity, UVA-UVB and liquid water available are present, features that have shaped all life in this very harsh environment, especially bacteria that live in different Antarctic ecosystems, which have had to develop different strategies to adapt to these conditions, producing unique biochemical strategies. In this work the production of cellulolytic enzymes of seven bacterial strains isolated from marine sediments at different sites in the Antarctic was evaluated. Isolation of the strains was performed using serial dilutions in the culture medium at M115°C. The identification of the strains was performed using universal primers (27F and 1492R). The enzyme activity assays were performed on R2A medium, carboxy methyl cellulose (CMC)was added as substrate. Degradation of the substrate was revealed by adding Lugol. The results show that four of the tested strains produce enzymes which degrade CMC substrate. The molecular identifications, showed that these bacteria belong to the genus Streptomyces and Pseudoalteromonas, being Streptomyces strain who showed the highest activity. Only some bacteria in marine sediments have the ability to produce these enzymes, perhaps due to their greater adaptability to degrade at temperatures bordering zero degrees Celsius, some algae that are abundant in this environment and have cellulose as the main structure. The discovery of new enzymes adapted to cold is of great industrial interest, especially for paper, textiles, detergents, biofuels, food and agriculture. These enzymes represent 8% of industrial demand worldwide and is expected to increase their demand in the coming years. Mainly in the paper and food industry are required in extraction processes starch, protein and juices, as well as the animal feed industry where treating vegetables and grains helps improve the nutritional value of the food, all this clearly puts Antarctic microorganisms and their enzymes specifically as a potential contribution to industry and the novel biotechnological applications.

Keywords: antarctic, bacteria, biotechnological, cellulolytic enzymes

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583 Problem Solving Courts for Domestic Violence Offenders: Duluth Model Application in Spanish-Speaking Offenders

Authors: I. Salas-Menotti

Abstract:

Problem-solving courts were created to assist offenders with specific needs that were not addressed properly in traditional courts. Problem-solving courts' main objective is to pursue solutions that will benefit the offender, the victim, and society as well. These courts were developed as an innovative response to deal with issues such as drug abuse, mental illness, and domestic violence. In Brooklyn, men who are charged with domestic violence related offenses for the first time are offered plea bargains that include the attendance to a domestic abuse intervention program as a condition to dismiss the most serious charges and avoid incarceration. The desired outcome is that the offender will engage in a program that will modify his behavior avoiding new incidents of domestic abuse, it requires accountability towards the victim and finally, it will hopefully bring down statistic related to domestic abuse incidents. This paper will discuss the effectiveness of the Duluth model as applied to Spanish-speaking men mandated to participate in the program by the specialized domestic violence courts in Brooklyn. A longitudinal study was conducted with 243 Spanish- speaking men who were mandated to participated in the men's program offered by EAC in Brooklyn in the years 2016 through 2018 to determine the recidivism rate of domestic violence crimes. Results show that the recidivism rate was less than 5% per year after completing the program which indicates that the intervention is effective in preventing new abuse allegations and subsequent arrests. It's recommended that comparative study with English-speaking participants is conducted to determine cultural and language variables affecting the program's efficacy.

Keywords: domestic violence, domestic abuse intervention programs, Problem solving courts, Spanish-speaking offenders

Procedia PDF Downloads 107
582 Electrochemical Coordination Polymers of Copper(II) Synthesis by Using Rigid and Felexible Ligands

Authors: P. Mirahmadpour, M. H. Banitaba, D. Nematollahi

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The chemistry of coordination polymers in recent years has grown exponentially not only because of their interesting architectures but also due to their various technical applications in many fields including ion exchange, chemical catalysis, small molecule separations, and drug release. The use of bridging ligands for the controlled self-assembly of one, two or three dimensional metallo-supramolecular species is the subject of serious study in last decade. Numerous different synthetic methods have been offered for the preparation of coordination polymers such as (a) diffusion from the gas phase, (b) slow diffusion of the reactants into a polymeric matrix, (c) evaporation of the solvent at ambient or reduced temperatures, (d) temperature controlled cooling, (e) precipitation or recrystallisation from a mixture of solvents and (f) hydrothermal synthesis. The electrosynthetic process suggested several advantages over conventional approaches. A general advantage of electrochemical synthesis is that it allows synthesis under milder conditions than typical solvothermal or microwave synthesis. In this work we have introduced a simple electrochemical method for growing metal coordination polymers based on copper with a flexible 2,2’-thiodiacetic acid (TDA) and rigid 1,2,4,5-benzenetetracarboxylate (BTC) ligands. The structure of coordination polymers were characterized by scanning electron microscopy (SEM), X-ray powder diffraction (XRD), elemental analysis, thermal gravimetric (TG) and differential thermal analyses (DTA). The single-crystal X-ray diffraction analysis revealed that different conformations of the ligands and different coordination modes of the carboxylate group as well as different coordination geometries of the copper atoms. Electrochemical synthesis of coordination polymers has different advantages such as faster synthesis at lower temperature in compare with conventional chemical methods and crystallization of desired materials in a single synthetic step.

Keywords: 1, 2, 4, 5-benzenetetracarboxylate, coordination polymer, copper, 2, 2’-thiodiacetic acid

Procedia PDF Downloads 180
581 Anthelminthic Effect of Clitoria Ternatea on Paramphistomum Cervi in Buffalo (Bubalus Bubalis) of Udaipur, Rajasthan, India

Authors: Bhanupriya Sanger, Kiran Roat, Gayatri Swarnakar

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Helminths including Paramphistomum Cervi (P. cervi) are a major cause of reduced production in livestock or domestic ruminant. Rajasthan is the largest state of India having a maximum number of livestock. The economy of rural people largely depends on livestock such as cow, buffalo, goat and sheep. The prevalence of P. cervi helminth parasite is extremely high in buffalo (Bubalus bubalis) of Udaipur, which causes the disease paramphistomiasis. This disease mainly affects milk, meat, wool production and loss of life of buffalo. Chemotherapy is the only efficient and effective tool to cure and control the helminth P. cervi infection, as efficacious vaccines against helminth have not been developed so far. Various veterinary drugs like Albendazole have been used as the standard drug for eliminating P. cervi from buffalo, but these drugs are unaffordable and inaccessible for poor livestock farmers. The fruits, leaves and seeds of Clitoria ternatea Linn. are known for their ethno-medicinal value and commonly known as “Aprajita” in India. Seed extract of Clitoria ternatea found to have a significant anthelmintic action against Paramphistomum cervi at the dose of 35 mg/ml. The tegument of treated P. cervi was compared with controlled parasites by light microscopy. Treated P. cervi showed extensive distortion and destruction of the tegument including ruptured parenchymal cells, disruption of musculature cells, swelling and vacuolization in tegumental and sub tegumental cells. As a result, it can be concluded that the seeds of Clitoria ternatea can be used as the anthelmintic agent. Key words: Paramphistomiasis, Buffalo, Alcoholic extract, Paramphistomum cervi, Clitoria ternatea.

Keywords: buffalo, Clitoria ternatea, Paramphistomiasis, Paramphistomum cervi

Procedia PDF Downloads 204
580 Comparative Study Between Oral and Intralesional Injection of Beta Blocker in the Treatment of Infantile Capillary Hemangioma

Authors: Nadeen Eltoukhy, Sahar S. Sheta, Walaa Elnaggar, Karim Bakr

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Purpose: The aim of this study is to compare the clinical efficacy and side effects of oral versus intralesional propranolol treatment of infantile capillary hemangiomas in infants. Methods: The study enrolled 40 infants diagnosed with infantile capillary hemangiomas. Patients were divided into 2 groups: Group A (Non-invasive group) included 20 infants who received oral propranolol hydrochloride starting at a dose of 1 mg/kg/day BID, then increased to a max of 2 mg/kg/day BID gradually over 2 weeks for 3 months. Group B (Invasive group) included 20 infants who received intralesional propranolol injection at a dose of 1 mg/mL; the volume of the injected drug depended on the size of the lesion (0.2 mL injected per cm of lesion diameter), with a maximum volume of 1 mL for a lesion of 5 cm diameter under complete aseptic conditions in the operating theater. Results: At three months after initiating treatment, the circumferential size of the hemangioma showed a statistically significant decrease in both groups; in Group A from 3.66±2.89 cm to 1.56±1.26 cm with p-value <0.05 and in Group B from 2.99±2.73 cm to 1.32±1.18 cm with p-value <0.05. There is no statistically significant comparative difference between the two groups (p-value = 0.538 = insignificant). Regarding the complications of oral propranolol, one patient (5%) had bradycardia, and one patient (5%) had diarrhea. In the injection group, 20 patients (100%) had local edema, and one patient (5%) had a local infection. Conclusions: Both oral non-invasive and intralesional invasive propranolol are safely used to successfully treat and decrease the size of infantile hemangioma while showing no statistically comparative difference between both treatment techniques.

Keywords: hemangioma, oral beta blocker, intralesional beta blocker, infants

Procedia PDF Downloads 27
579 The 10,000 Fold Effect Retrograde Neurotransmission: A Newer Concept for Paraplegia’s Physiological Revival by the Use of Intrathecal Sodium Nitroprusside

Authors: V. K. Tewari, M. Hussain, H. K. D. Gupta

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B-Methylprednisolone-level-1-benefit (20%) usually given in paraplegia (but within 8hrs). Patients wait-long-duration for physiological-recovery. Intrathecal-Sodium-Nitroprusside(ITSNP) has been used-in vasospasm-due-to-subarachnoid-hemorrhage. ITSNP-has been studied-here for wide-window-period-range for-treatment, fast-recovery/affordability. 2- for acute-cases-and 1-mechanism-for chronic-cases, which-are-interrelated, are being-proposed-for-physiological-recovery. retrograde-neurotransmission, vasospasm and long-term-potentiation-(ltp) mechanisms are proposed here for recovery. It’s a case-control-prospective-study. 82paraplegia-patients(10patients taken as control-no superfusion or dextrose5% superfusion and 72patients as ITSNP-group). The mean time for superfusion was 14.11 days. ITSNP administered at a dosage of 0.2 mg/kg bo wt. Pre/post ITSNP monitored by SSEP/MEP. After-2-Hours in ITSNP-group Mean-Change-From-Baseline-Asia Motor/Sensory-Score 13.84%/13.10%, after-24-hours MOTOR-1.27-points decrease(3.77%) and SENSORY 10.5points-increase(6.22%)as compared to Control-group no-change noted upto 24-hours, At-7days ITSNP motor/sensory;11.56%/6.22% as compared to Control-group 7.60/4.48%, At-2-months in ITSNP 27.69%/6.22% as compared to Control-group 16.02/4.5%. SSEP/MEP-documented-improvements-noted. ITSNP, a-swift-acting-drug in treatment-of-paraplegia, is effective within-two-hours(mean-change-MOTOR-13.84% and SENSORY-13.10%) on-mean14.11th postparaplegia-day with a small-detrimental-response after-24-hours which-recovers-fast.

Keywords: paraplegias, intrathecal sodium nitroprusside, retrograde transmission, the 10, 000 fold effect, perforators, vasodilatations, long term potenciations

Procedia PDF Downloads 385
578 Strengthening the Security of the Thai-Myanmar Border Trade of the People in the Mae Sot Customs Checkpoint Area, Tak Province

Authors: Sakapas Saengchai

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A Study on Strengthening the Security of the Thai-Myanmar Border Trade Area of the people in the Mae Sot customs checkpoint area, Tak province, was designed as a qualitative research study. Its objectives were to study the principles of strengthening border trade security and enhancing people's participation. To develop a border trade model that enhances the spatial economy and improves people's quality of life by collecting data using a participant observation method. In-depth interview group chats border checkpoint administrators, Mae Sot customs checkpoint, Tak province, private entrepreneurs, community leaders, and the opening of a community forum to exchange opinions with people in the area. The results of the study found that 1. Security development is to promote crime reduction. Reduce drug trafficking problems Smuggling and human trafficking have been reduced. Including planning and preparation to protect people from terrorism, epidemics, and communicable diseases, including cooperation with Burma on border rules for people and workers, 2. Wealth development is to promote investment. Transport links value chain logistics Cross-border goods and services on the Thai-Myanmar border Both amending regulations and laws to promote fair trade. Emphasis on convenient and fast service as well as promoting the Thai border area to be a tourist attraction that can create prosperity and income for the community in the area By using balanced natural resources, with production and consumption that are environmentally friendly, and emphasizes the participation of the public sector, the private sector, and people from all sectors in the sustainable development of the Thai border.

Keywords: security, border trade, customs, participation, people

Procedia PDF Downloads 152
577 Investigation the Photocatalytic Properties of Fe3O4-TiO2 Nanocomposites Prepared by Sonochemical Method

Authors: Zh. Saffari, A. Naeimi, M. S. Ekrami-Kakhki, F. Hamidi

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Fe3O4 is one of the important magnetic oxides with spinel structure; it has exhibited unique electric and magnetic properties based on the electron transfer between Fe2+ and Fe3+ in the octahedral sites. Fe3O4 has received considerable attention in various areas such as cancer therapy, drug targeting, enzyme immobilization catalysis, magnetic cell separation, magnetic refrigeration systems and super-paramagnetic materials Fe3O4–TiO2 nanostructures were synthesized by simple, effective and new co-precipitation method assisted by ultrasonic reaction at room temperatures with organic surfactant. The effect of various parameters such as temperature, time, and power on the size and morphology of the product was investigated. Alternating gradient force magnetometer shows that Fe3O4 nanoparticles exhibit super-paramagnetic behaviour at room temperature. For preparation of nanocomposite, 1 g of TiO2 nanostructures were dispersed in 100 mL of ethanol. 0.25 g of Fe(NO3)2 and 2 mL of octanoic acid was added to the solution as a surfactant. Then, NaOH solution (1.5 M) was slowly added into the solution until the pH of the mixture was 7–8. After complete precipitation, the solution placed under the ultrasonic irradiation for 30 min. The product was centrifuged, washed with distilled water and dried in an oven at 100 °C for 3 h. The resulting red powder was calcinated at 800 °C for 3 h to remove any organic residue. The photocatalytic behaviour of Fe3O4–TiO2 nanoparticles was evaluated using the degradation of a Methyl Violet (MV) aqueous solution under ultraviolet light irradiation. As time increased, more and more MV was adsorbed on the nanoparticles catalyst, until the absorption peak vanish. The MV concentration decreased rapidly with increasing UV-irradiation time

Keywords: magnetic, methyl violet, nanocomposite, photocatalytic

Procedia PDF Downloads 234
576 Animated Poetry-Film: Poetry in Action

Authors: Linette van der Merwe

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It is known that visual artists, performing artists, and literary artists have inspired each other since time immemorial. The enduring, symbiotic relationship between the various art genres is evident where words, colours, lines, and sounds act as metaphors, a physical separation of the transcendental reality of art. Simonides of Keos (c. 556-468 BC) confirmed this, stating that a poem is a talking picture, or, in a more modern expression, a picture is worth a thousand words. It can be seen as an ancient relationship, originating from the epigram (tombstone or artefact inscriptions), the carmen figuratum (figure poem), and the ekphrasis (a description in the form of a poem of a work of art). Visual artists, including Michelangelo, Leonardo da Vinci, and Goethe, wrote poems and songs. Goya, Degas, and Picasso are famous for their works of art and for trying their hands at poetry. Afrikaans writers whose fine art is often published together with their writing, as in the case of Andries Bezuidenhout, Breyten Breytenbach, Sheila Cussons, Hennie Meyer, Carina Stander, and Johan van Wyk, among others, are not a strange phenomenon either. Imitating one art form into another art form is a form of translation, transposition, contemplation, and discovery of artistic impressions, showing parallel interpretations rather than physical comparison. It is especially about the harmony that exists between the different art genres, i.e., a poem that describes a painting or a visual text that portrays a poem that becomes a translation, interpretation, and rediscovery of the verbal text, or rather, from the word text to the image text. Poetry-film, as a form of such a translation of the word text into an image text, can be considered a hybrid, transdisciplinary art form that connects poetry and film. Poetry-film is regarded as an intertwined entity of word, sound, and visual image. It is an attempt to transpose and transform a poem into a new artwork that makes the poem more accessible to people who are not necessarily open to the written word and will, in effect, attract a larger audience to a genre that usually has a limited market. Poetry-film is considered a creative expression of an inverted ekphrastic inspiration, a visual description, interpretation, and expression of a poem. Research also emphasises that animated poetry-film is not widely regarded as a genre of anything and is thus severely under-theorized. This paper will focus on Afrikaans animated poetry-films as a multimodal transposition of a poem text to an animated poetry film, with specific reference to animated poetry-films in Filmverse I (2014) and Filmverse II (2016).

Keywords: poetry film, animated poetry film, poetic metaphor, conceptual metaphor, monomodal metaphor, multimodal metaphor, semiotic metaphor, multimodality, metaphor analysis, target domain, source domain

Procedia PDF Downloads 38
575 Polymerization of Epsilon-Caprolactone Using Lipase Enzyme for Medical Applications

Authors: Sukanya Devi Ramachandran, Vaishnavi Muralidharan, Kavya Chandrasekaran

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Polycaprolactone is polymer belonging to the polyester family that has noticeable characteristics of biodegradability and biocompatibility which is essential for medical applications. Polycaprolactone is produced by the ring opening polymerization of the monomer epsilon-Caprolactone (ε-CL) which is a closed ester, comprising of seven-membered ring. This process is normally catalysed by metallic components such as stannous octoate. It is difficult to remove the catalysts after the reaction, and they are also toxic to the human body. An alternate route of using enzymes as catalysts is being employed to reduce the toxicity. Lipase enzyme is a subclass of esterase that can easily attack the ester bonds of ε-CL. This research paper throws light on the extraction of lipase from germinating sunflower seeds and the activity of the biocatalyst in the polymerization of ε-CL. Germinating Sunflower seeds were crushed with fine sand in phosphate buffer of pH 6.5 into a fine paste which was centrifuged at 5000rpm for 10 minutes. The clear solution of the enzyme was tested for activity at various pH ranging from 5 to 7 and temperature ranging from 40oC to 70oC. The enzyme was active at pH6.0 and at 600C temperature. Polymerization of ε-CL was done using toluene as solvent with the catalysis of lipase enzyme, after which chloroform was added to terminate the reaction and was washed in cold methanol to obtain the polymer. The polymerization was done by varying the time from 72 hours to 6 days and tested for the molecular weight and the conversion of the monomer. The molecular weight obtained at 6 days is comparably higher. This method will be very effective, economical and eco-friendly to produce as the enzyme used can be regenerated as such at the end of the reaction and can be reused. The obtained polymers can be used for drug delivery and other medical applications.

Keywords: lipase, monomer, polycaprolactone, polymerization

Procedia PDF Downloads 273
574 Pharmacodynamic Interaction between Tamsulosin and Finasteride Treatment on Induced Benign Prostate Hyperplasia in Mice by Using Chou-Talalay Method

Authors: Firas Rashad Al-Samarai

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Introduction: Benign prostatic hyperplasia (BPH) is a common condition as men get older. An enlarged prostate gland can cause uncomfortable urinary symptoms, such as blocking the flow of urine out of the bladder. It can also cause bladder, urinary tract, or kidney problems. Objective: to evaluate the efficacy and interaction of tamsulosin with finasteride treatment on induced benign prostate hyperplasia (BPH) in mice. Methods: BPH was induced by subcutaneous injection of testosterone propionate (20 mg/kg) for 30 days. Eighty-five mice were divided into five groups. The first group (G1): twenty-five mice induced BPH treated with tamsulosin orally and divided into five equal subgroups with doses (0.017, 0.052, 0.087, 0. 123, and 0.158) mg/kg, the second group (G2): twenty-five mice induced BPH treated with finasteride orally and divided into five equal subgroups with doses (0.175, 0.527, 0.878, 1.23, and 1.580) mg/kg. the third group (G3): twenty-five mice induced BPH treated with a combination of tamsulosin with finasteride orally, and divided into five equal subgroups with doses (0.0085, 0.0875), (0.026, 0.2635), (0.0435, 0.439) , (0.0615, 0.615) and ( 0.079 , 0.790 ) mg/kg respectively. Fourth group (G4): five mice induced BPH and treated distilled water. Fifth group (G5): five mice were not inducing BPH and without any treatment. Results: The results showed a gradual significant increase in prostate weight % and prostate index % Inhibitions until reached saturation in the last two doses of tamsulosin, finasteride, and combination groups, the maximum effective dose of tamsulosin and finasteride were (0.156) and (1.495) mg/kg respectively. Moreover, the effective dose of the combination (tamsulosin and finasteride) was estimated (0.06876, 0.6876) mg/kg, respectively, as well as the type of interaction was synergism and the value of the combination index was 0.046. Conclusions: We concluded that the combination of tamsulosin with finasteride showed a synergistic effect in BPH treatment by minimizing the side effect of each drug as s result of decreasing the dose of each one.

Keywords: Tamsulosin, Finasteride, combination, BPH

Procedia PDF Downloads 51
573 Biodistribution of Fluorescence-Labelled Epidermal Growth Factor Protein from Slow Release Nanozolid Depots in Mouse

Authors: Stefan Gruden, Charlott Brunmark, Bo Holmqvist, Erwin D. Brenndorfer, Martin Johansson, Jian Liu, Ying Zhao, Niklas Axen, Moustapha Hassan

Abstract:

Aim: The study was designed to evaluate the ability of the calcium sulfate-based NanoZolid® drug delivery technology to locally release the epidermal growth factor (EGF) protein while maintaining its biological activity. Methods: NanoZolid-formulated EGF protein labelled with a near-infrared dye (EGF-NIR) depots or EGF-NIR dissolved in PBS were injected subcutaneously into mice bearing EGF receptor (EGFR) positive human A549 lung cancer tumors inoculated subcutaneously. The release and biodistribution of the EGF-NIR were investigated in vivo longitudinally up to 96 hours post-administration, utilizing whole-body fluorescence imaging. In order to confirm the in vivo findings, histological analysis of tumor cryosections was performed to investigate EGF-NIR fluorescent signal and EGFR expression level by immunofluorescence labelling. Results: The in vivo fluorescence imaging showed a controlled release profile of the EGF-NIR loaded in the NanoZolid depots compared to free EGF-NIR. Histological analysis of the tumors further demonstrated a prevailing distribution of EGF-NIR in regions with high levels of EGFR expression. Conclusion: Calcium sulfate based depots can be used to formulate EGF while maintaining its biological activity, e.g., receptor binding capability. This may have good clinical potential for local delivery of biomolecules to enhance treatment efficacy and minimize systemic adverse effects.

Keywords: bioresorbable, calcium sulfate, controlled release, NanoZolid

Procedia PDF Downloads 140
572 Quartz Crystal Microbalance Based Hydrophobic Nanosensor for Lysozyme Detection

Authors: F. Yılmaz, Y. Saylan, A. Derazshamshir, S. Atay, A. Denizli

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Quartz crystal microbalance (QCM), high-resolution mass-sensing technique, measures changes in mass on oscillating quartz crystal surface by measuring changes in oscillation frequency of crystal in real time. Protein adsorption techniques via hydrophobic interaction between protein and solid support, called hydrophobic interaction chromatography (HIC), can be favorable in many cases. Some nanoparticles can be effectively applied for HIC. HIC takes advantage of the hydrophobicity of proteins by promoting its separation on the basis of hydrophobic interactions between immobilized hydrophobic ligands and nonpolar regions on the surface of the proteins. Lysozyme is found in a variety of vertebrate cells and secretions, such as spleen, milk, tears, and egg white. Its common applications are as a cell-disrupting agent for extraction of bacterial intracellular products, as an antibacterial agent in ophthalmologic preparations, as a food additive in milk products and as a drug for treatment of ulcers and infections. Lysozyme has also been used in cancer chemotherapy. The aim of this study is the synthesis of hydrophobic nanoparticles for Lysozyme detection. For this purpose, methacryoyl-L-phenylalanine was chosen as a hydrophobic matrix. The hydrophobic nanoparticles were synthesized by micro-emulsion polymerization method. Then, hydrophobic QCM nanosensor was characterized by Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, atomic force microscopy (AFM) and zeta size analysis. Hydrophobic QCM nanosensor was tested for real-time detection of Lysozyme from aqueous solution. The kinetic and affinity studies were determined by using Lysozyme solutions with different concentrations. The responses related to a mass (Δm) and frequency (Δf) shifts were used to evaluate adsorption properties.

Keywords: nanosensor, HIC, lysozyme, QCM

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571 Post Operative Analgesia after Orthotopic Liver Transplantation; A Clinical Randomized Trial

Authors: Soudeh Tabashi, Mohammadreza Moshari, Parisa Sezari

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Introduction: Postoperative analgesia in Orthotopic Liver Transplantation (OLT) surgery is challenging for anesthesiologists. Although OLT is one of the most extensive abdominal operations, it seems that patients don’t suffer from severe post operative pain. On the other hands drug metabolism is unpredictable due to unknown graft function. The aim of this study was to compare intraoperative infusion of remifentanil versus fentanyl in postoperative opioid demand in patients with OLT and evaluating the complications in two groups. Method: In this double-blind clinical trial 34 patients who had OLT were included. They divided randomly in two groups of Remifentanil (R) and Fentanyl (F). Patients in group R and F received infusion of Remifentanil 0.3-1 µg/Kg/min and Fentanyl 0.3-1 µg/Kg/min during maintenance of anesthesia. Post operative pain were measured in 6, 12, 18, 24 hours and second and third days after surgery with Numeric Rate Scale (NRS). Patients had received intravenous acetaminophen as rescue therapy with NRS of 3 or more. In addition to demographic information, post operative opioid consumption were recorded as the primary outcome. Intraoperative blood transfusion, intraoperative inotropic drugs consumption, weaning time and intensive care unit stay were also evaluated. Results: Total dose of acetaminophen consumption in first 3 days after surgery did not have significant difference between two groups (Pvalue=0.716). intraoperative inotrope consumption, blood transfusion and post operative weaning time and ICU stay were also similar in both groups. Conclusion: This study demonstrates that intraoperative infusion of remifentanil in OLT have the same effect on post operative pain management as fentanyl. Despite the complications of operation were not increased by remifentanil.

Keywords: liver transplantation, postoperative pain, remifentanil, fentanyl

Procedia PDF Downloads 46
570 Hepatic Regenerative Capacity after Acetaminophen-Induced Liver Injury in Mouse Model

Authors: N. F. Hamid, A. Kipar, J. Stewart, D. J. Antoine, B. K. Park, D. P. Williams

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Acetaminophen (APAP) is a widely used analgesic that is safe at therapeutic doses. The mouse model of APAP has been extensively used for studies on pathogenesis and intervention of drug induced liver injury based on the CytP450 mediated formation of N-acetyl-p-benzo-quinoneimine and, more recently, as model for mechanism based biomarkers. Delay of the fasted CD1 mice to rebound to the basal level of hepatic GSH compare to fed mice is reported in this study. Histologically, 15 hours fasted mice prior to APAP treatment leading to overall more intense cell loss with no evidence of apoptosis as compared to non-fasted mice, where the apoptotic cells were clearly seen on cleaved caspase-3 immunostaining. After 15 hours post APAP administration, hepatocytes underwent stage of recovery with evidence of mitotic figures in fed mice and return to completely no histological difference to control at 24 hours. On the contrary, the evidence of ongoing cells damage and inflammatory cells infiltration are still present on fasted mice until the end of the study. To further measure the regenerative capacity of the hepatocytes, the inflammatory mediators of cytokines that involved in the progression or regression of the toxicity like TNF-α and IL-6 in liver and spleen using RT-qPCR were also included. Yet, quantification of proliferating cell nuclear antigen (PCNA) has demonstrated the time for hepatic regenerative in fasted is longer than that to fed mice. Together, these data would probably confirm that fasting prior to APAP treatment does not only modulate liver injury, but could have further effects to delay subsequent regeneration of the hepatocytes.

Keywords: acetaminophen, liver, proliferating cell nuclear antigen, regeneration, apoptosis

Procedia PDF Downloads 404