Search results for: in vitro and in vivo cancer therapy
Commenced in January 2007
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Edition: International
Paper Count: 4950

Search results for: in vitro and in vivo cancer therapy

1230 Spectrum of Acute Kidney Injury in Obstetrics

Authors: Seema Chopra, Amandeep Kaur, Vanita Suri, Shalini Gainder, Minakshi Rohilla

Abstract:

Background: Acute kidney injury (AKI) associated with pregnancy is a serious medical complication which can lead to significant maternal as well as perinatal morbidity and mortality. Material and methods: This prospective observational study was carried out in the Obstetrics and Gynaecology department and dialysis unit of Nephrology department of PGIMER, Chandigarh from July 2013 to June 2014. Forty antenatal/postnatal/postabortal patients who fulfilled the AKIN criteria were enrolled in the study. All patients were followed up till 3 months postpartum. Results: Majority of the patients 23/40 (57.5%) with AKI presented in postpartum period, 14/40 (35%) developed AKI in antenatal period, and 3/40 (7.5%) were postabortal. AKI was attributable mostly to sepsis in 11/40 (27.5%) and PPH in 5/40 (12.5%). Hypertension and its complications causing AKI included eclampsia in 5/40 (12.5%) followed by 3/40 (7.5%) as HELLP syndrome and abruption placentae in 2/40(5%) patients. Three patients each (7.5%) had AFLP, TMA, and HEV as the cause of AKI. Renal replacement therapy in the form of hemodialysis was the treatment in majority of them (28 (70%)). After the acute event, 25 (62.5%) had complete recovery of their renal functions at 3 months follow up. Maternal mortality was seen in 25% (n=10) of the study patients. Conclusion: Timely initiation of RRT in patients with AKI associated with pregnancy has a good maternal outcome in the form of complete recovery of renal functions in 62.5% (25/40) of patients.

Keywords: AKI, dialysis, hypertension, sepsis, renal parameters

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1229 NeuroBactrus, a Novel, Highly Effective, and Environmentally Friendly Recombinant Baculovirus Insecticide

Authors: Yeon Ho Je

Abstract:

A novel recombinant baculovirus, NeuroBactrus, was constructed to develop an improved baculovirus insecticide with additional beneficial properties, such as a higher insecticidal activity and improved recovery, compared to wild-type baculovirus. For the construction of NeuroBactrus, the Bacillus thuringiensis crystal protein gene (here termed cry1-5) was introduced into the Autographa californica nucleopolyhedrovirus (AcMNPV) genome by fusion of the polyhedrin–cry1-5–polyhedrin genes under the control of the polyhedrin promoter. In the opposite direction, an insect-specific neurotoxin gene, AaIT, from Androctonus australis was introduced under the control of an early promoter from Cotesia plutellae bracovirus by fusion of a partial fragment of orf603. The polyhedrin–Cry1-5–polyhedrin fusion protein expressed by the NeuroBactrus was not only occluded into the polyhedra, but it was also activated by treatment with trypsin, resulting in an_65-kDa active toxin. In addition, quantitative PCR revealed that the neurotoxin was expressed from the early phase of infection. NeuroBactrus showed a high level of insecticidal activity against Plutella xylostella larvae and a significant reduction in the median lethal time against Spodoptera exigua larvae compared to those of wild-type AcMNPV. Rerecombinant mutants derived from NeuroBactrus in which AaIT and/or cry1-5 were deleted were generated by serial passages in vitro. Expression of the foreign proteins (B. thuringiensis toxin and AaIT) was continuously reduced during the serial passage of the NeuroBactrus. Moreover, polyhedra collected from S. exigua larvae infected with the serially passaged NeuroBactrus showed insecticidal activity similar to that of wild-type AcMNPV. These results suggested that NeuroBactrus could be recovered to wild-type AcMNPV through serial passaging.

Keywords: baculovirus, insecticide, neurotoxin, neurobactrus

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1228 Exploring the Role of Phosphorylation on the β-lactamase Activity of OXA24/40

Authors: Dharshika Rajalingam, Jeffery W. Peng

Abstract:

Acinetobacter baumannii is a challenging threat to global health, recognized as a multidrug-resistant pathogen. -lactamase is one of the principal resistant mechanisms developed by A. baumannii to survive against -lactam antibiotics. OXA24/40 is one of the types of -lactamases, a well-documented carbapenem hydrolyzing class D -lactamases (CHDL). It was revealed that OXA24/40 showed resistivity against doripenem, one of the carbapenems, by two different mechanisms as hydrolysis and -lactonization. Furthermore, it undergoes genetic mutations to broaden the -lactamase activity to survive against antibiotic environments. One of the crucial characterizations of prokaryotes to develop adaptation is post-translational modification (PTM), mainly phosphorylation. However, the PTM of OXA24/40 is an unknown feature, and the impact of PTM on antibiotic resistivity is yet to be explored. We approached these hypotheses using NMR and MS techniques and found that the OXA24/40 could be phosphorylated in vitro. The Ser81 at the active STFK motif of OXA24/40 of catalytic pocket was identified as the site of phosphorylation using 1D 31P NMR experiment, whereas S81 is required to form an acyl-enzyme complex between enzyme and -lactam antibiotics. The activity of completely phosphorylated OXA24/40 wild type against doripenem revealed that the phosphorylation of active Ser inactivates the -lactamases activity of OXA24/40. The 1D 1H CPMG NMR-based activity assay of phosphorylated OXA24/40 against doripenem confirmed that both deactivating mechanisms are inhibited by phosphorylation. Carbamylated Lysine at the active STFK motif is one of the critical features of CHDL required for the acylation and deacylation reactions of the enzyme. The 1D 13C NMR experiment confirmed that the K84 of phosphorylated OXA24/40 is de-carbamylated. Phosphorylation of OXA24/40 affects both active S81 and carbamylated K84 of OXA24 that are required for the resistivity of -lactamase. So, phosphorylation could be one of the reasons for the genetic mutation of OXA24/40 for the development of antibiotic resistivity. Further research can lead to an understanding of the effect of phosphorylation on the clinical mutants of the OXA24-like -lactamase family on the broadening of -lactamase activity.

Keywords: OXA24/40, phosphorylation, clinical mutants, resistivity

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1227 Case Report: Clinical Improvement of Forbrain Neurologic Signs in 3- Month- Old Persian Mastiff Dog with Calvarial Hyperostosis Syndrome after Corticosteroid, Antiepileptic and Antibiotic Therapy

Authors: Hamidreza Jahani, Zahra Salehzadeh, Ehsan Amini, Mohsen Tohidifar

Abstract:

Calvarial Hyperostosis Syndrome (CHS) is a benign bone disease of the skull. It is a non-neoplastic and proliferative bone disease, and the main feature of the disease is progressive and asymmetrical bone involvement. CHS is mostly reported in young male and female bullmastiff dogs and less frequently in other breeds. The etiology of CHS is unknown. This is the first case report of CHS in Iran. A 3-month-old male Persian Mastiff was presented with chief complaints of multiple episodes of seizure, pacing, bizarre behavior, delayed growth, head pressing, and difficulty in opening the mouth. Central blindness and open fontanelles were observed in clinical examination. No abnormality was found in the complete blood count and routine blood biochemical tests. CT scan findings include cortical thickening of frontal and parietal bones and enlargement of the left retropharyngeal lymph node. For treatment, oral clindamycin for two weeks, prednisolone and phenobarbital for one month, respectively, were administrated, and the case showed improvement after a week and recovered after one month.

Keywords: calvarial hyperostosis, Persian Mastiff, frontal bone, seizure

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1226 The Effects of Orally Administered Bacillus Coagulans and Inulin on Prevention and Progression of Rheumatoid Arthritis in Rats

Authors: Khadijeh Abhari, Seyed Shahram Shekarforoush, Saeid Hosseinzadeh

Abstract:

Probiotics have been considered as an approach to treat and prevent a wide range of inflammatory diseases. The spore forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic, inulin, also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota. An in vivo trial was conducted to evaluate the effects of probiotic B. coagulans, and inulin, either separately or in combination, on down regulate immune responses and progression of rheumatoid arthritis using induced arthritis rat model. Forty-eight male Wistar rats were randomly divided into 6 groups and fed as follow: 1) control: Normal healthy rats fed by standard diet, 2) Disease control (RA): Arthritic induced (RA) rats fed by standard diet, 3) Prebiotic (PRE): RA+ 5% w/w long chain inulin, 4) Probiotic (PRO): RA+ 109 spores/day B. coagulans by orogastric gavage, 5) Synbiotic (SYN): RA+ 5% w/w long chain inulin and 109 spores/day B. coagulans and 6) Treatment control: (INDO): RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with mentioned diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund’s adjuvant (CFA) to induce arthritis. Arthritis activity was evaluated by biochemical parameters and paw thickness. Biochemical assay for Fibrinogen (Fn), Serum Amyloid A (SAA), TNF-α and Alpha-1-acid glycoprotein (α1AGp) was performed on day 21, 28 and 35 (1, 2 and 3 weeks post RA induction). Pretreatment with PRE, PRO and SYN diets significantly inhibit SAA and Fn production in arthritic rats (P < 0.001). A significant decrease in production of pro-inflammatory cytokines, TNF-α, was seen in PRE, PRO and SYN groups (P < 0.001) which was similar to the effect of the anti-inflammatory drug Indomethacin. Further, there were no significant anti-inflammatory effects observed following different treatments using α1AGp as a RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001). Conclusion: Results of this study support that oral intake of probiotic B. coagulans and inulin are able to improve biochemical and clinical parameters of induced RA in rat.

Keywords: rheumatoid arthritis, bacillus coagulans, inulin, animal model

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1225 Application of Latent Class Analysis and Self-Organizing Maps for the Prediction of Treatment Outcomes for Chronic Fatigue Syndrome

Authors: Ben Clapperton, Daniel Stahl, Kimberley Goldsmith, Trudie Chalder

Abstract:

Chronic fatigue syndrome (CFS) is a condition characterised by chronic disabling fatigue and other symptoms that currently can't be explained by any underlying medical condition. Although clinical trials support the effectiveness of cognitive behaviour therapy (CBT), the success rate for individual patients is modest. Patients vary in their response and little is known which factors predict or moderate treatment outcomes. The aim of the project is to develop a prediction model from baseline characteristics of patients, such as demographics, clinical and psychological variables, which may predict likely treatment outcome and provide guidance for clinical decision making and help clinicians to recommend the best treatment. The project is aimed at identifying subgroups of patients with similar baseline characteristics that are predictive of treatment effects using modern cluster analyses and data mining machine learning algorithms. The characteristics of these groups will then be used to inform the types of individuals who benefit from a specific treatment. In addition, results will provide a better understanding of for whom the treatment works. The suitability of different clustering methods to identify subgroups and their response to different treatments of CFS patients is compared.

Keywords: chronic fatigue syndrome, latent class analysis, prediction modelling, self-organizing maps

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1224 Gender Stereotypes in Reproductive Medicine with Regard to Parental Age

Authors: Monika Michałowska, Anna Alichniewicz

Abstract:

Detrimental outcomes of advanced maternal age on the chances of fertilization, pregnancy as well as mother and fetus health have been recognized for several decades. It seemed interesting to investigate whether there is a comparable awareness of the detrimental influence on the reproductive outcomes of late fatherhood, given that it has been already ten years since an intense and growing interest concerning later-age fatherhood commenced in medical research. To address that issue a two-step research was done. First, we performed a review of the subject literature to answer the following questions: 1) What age is defined as advanced?; 2) Is the same age defined as advanced in both genders?; 3) What terminology concerning age issues is used?; 4) Is the same age terminology used regarding both genders? The second part of our studies was devoted to the views of medical students. This part of our research comprised both quantitative and qualitative studies. Opinions of medical students in one of the Polish medical universities on several issues connected with assisted reproduction technology (ART) were gathered: 1) students’ attitude to in vitro fertilization (IVF) for women over 40 and for postmenopausal women; 2) students’ attitude to late fatherhood; 3) students’ reasoning given against acceptability of IVF procedure for all of these group of patients involved in an IVF procedure. Our analyses revealed that: First, there is no universal definition of the term ‘advanced age’; secondly, there is a general tendency to adopt different age limits depending on whether they refer to maternal or paternal age, but no justification is provided by the researchers explaining why they set different age limits for women and men; thirdly, the image of postponed fatherhood stands in stark contrast to postponed motherhood - while postponed fatherhood is frequently portrayed as a reasonable and conscious decision enabling a stable family environment for a child, the reasonableness of postponed motherhood is often questioned; finally, the bias regarding maternal versus paternal age is deeply embedded in medical students’ attitude to IVF for women over 40 and for postmenopausal women.

Keywords: gender stereotypes, reproductive medicine, maternal age, paternal age

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1223 Sensing Endocrine Disrupting Chemicals by Virus-Based Structural Colour Nanostructure

Authors: Lee Yujin, Han Jiye, Oh Jin-Woo

Abstract:

The adverse effects of endocrine disrupting chemicals (EDCs) has attracted considerable public interests. The benzene-like EDCs structure mimics the mechanisms of hormones naturally occurring in vivo, and alters physiological function of the endocrine system. Although, some of the most representative EDCs such as polychlorinated biphenyls (PCBs) and phthalates compounds already have been prohibited to produce and use in many countries, however, PCBs and phthalates in plastic products as flame retardant and plasticizer are still circulated nowadays. EDCs can be released from products while using and discarding, and it causes serious environmental and health issues. Here, we developed virus-based structurally coloured nanostructure that can detect minute EDCs concentration sensitively and selectively. These structurally coloured nanostructure exhibits characteristic angel-independent colors due to the regular virus bundle structure formation through simple pulling technique. The designed number of different colour bands can be formed through controlling concentration of virus solution and pulling speed. The virus, M-13 bacteriophage, was genetically engineered to react with specific ECDs, typically PCBs and phthalates. M-13 bacteriophage surface (pVIII major coat protein) was decorated with benzene derivative binding peptides (WHW) through phage library method. In the initial assessment, virus-based color sensor was exposed to several organic chemicals including benzene, toluene, phenol, chlorobenzene, and phthalic anhydride. Along with the selectivity evaluation of virus-based colour sensor, it also been tested for sensitivity. 10 to 300 ppm of phthalic anhydride and chlorobenzene were detected by colour sensor, and showed the significant sensitivity with about 90 of dissociation constant. Noteworthy, all measurements were analyzed through principal component analysis (PCA) and linear discrimination analysis (LDA), and exhibited clear discrimination ability upon exposure to 2 categories of EDCs (PCBs and phthalates). Because of its easy fabrication, high sensitivity, and the superior selectivity, M-13 bacteriophage-based color sensor could be a simple and reliable portable sensing system for environmental monitoring, healthcare, social security, and so on.

Keywords: M-13 bacteriophage, colour sensor, genetic engineering, EDCs

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1222 Screening of Antioxidant Activity of Exopolysaccharides Produced by Lactic Acid Bacteria From Human Origin

Authors: Piña-Ronces Laura Gabriela, Reyes-Escogido María de Lourdes

Abstract:

Exist a large variability in Exopolysaccharides (EPS) produced by LAB depending on carbon source, they have multiple applications in food industry mainly, but they have become important for the health. In this study, we identified EPS-producing strains belonging to the BAL group; they were previously isolated from humans. After that, we extracted and evaluated the antioxidant activity of EPS produced by all strains. Antioxidant activity was determined by DPPH method using ascorbic acid as standard for both comparison and quantification. 31 strains (51.66 %) produced EPS at concentrations between 451 and 1.561 mg/l, 16 of EPS extracted showed antioxidant effect superior to ascorbic acid at the same concentrations. EPS-producing strains were L. plantarum, L. sp and L. fermentum corresponding to Lactobacillus genus and, E. faecium, E. durans, and E. hirae of Enterococcus genus. Antioxidant activity showed by EPS from 3 strains of L. plantarum and 3 strains of E. faecium was different into specie, while the antioxidant activity determined for EPS obtained from the other strains did not show difference at specie level, but was superior to ascorbic acid. EPS produced by L. plantarum and E. hirae had the best activity, it could be considerate for selection them as a possible new alternative for therapy or treatment of diseases related whit oxidative stress. Further studies about biological functions of EPS have to be conducted for new applications in health.

Keywords: oxidative stress, lactic acid bacteria, exopolysaccharides, antioxidant activity

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1221 Trends of Cutaneous Melanoma in New Zealand: 2010 to 2020

Authors: Jack S. Pullman, Daniel Wen, Avinash Sharma, Bert Van Der Werf, Richard Martin

Abstract:

Background: New Zealand (NZ) melanoma incidence rates are amongst the highest in the world. Previous studies investigating the incidence of melanoma in NZ were performed for the periods 1995 – 1999 and 2000 – 2004 and suggested increasing melanoma incidence rates. Aim: The aim of the study is to provide an up-to-date review of trends in cutaneous melanoma in NZ from the New Zealand Cancer Registry (NZCR) 2010 – 2020. Methods: De-identified data were obtained from the NZCR, and relevant demographic and histopathologic information was extracted. Statistical analyses were conducted to calculate age-standardized incidence rates for invasive melanoma (IM) and melanoma in situ (MIS). Secondary results included Breslow thickness and melanoma subtype analysis. Results: There was a decline in the IM age-standardized incidence rate from 30.4 to 23.9 per 100,000 person-years between 2010 to 2020, alongside an increase in MIS incidence rate from 37.1 to 50.3 per 100,000 person-years. Men had a statistically significant higher IM incidence rate (p <0.001) and Breslow thickness (p <0.001) compared with women. Increased age was associated with a higher incidence of IM, presentation with melanoma of greater Breslow thickness and more advanced T stage. Conclusion: The incidence of IM in NZ has decreased in the last decade and was associated with an increase in MIS incidence over the same period. This can be explained due to earlier detection, dermoscopy, the maturity of prevention campaigns and/or a change in skin protection behavior.

Keywords: melanoma, incidence, epidemiology, New Zealand

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1220 Effective Sexual Assault Treatment as Viewed by Survivors and Expert Therapists

Authors: Avigail Moor

Abstract:

Rape and sexual assault have been widely linked to severe psychological sequelae, the recovery from which often requires professional help. Thanks to the current shift in societal attitudes towards sexual violence, the victim's perspective is increasingly being heard. The present study is yet another step in that direction. Through the investigation of what recovered survivors of sexual assault identify as the therapeutic interventions that most assisted them in overcoming their trauma, guidelines for optimal sexual assault treatment are established. These receive further support from a comparison with expert therapists as to what they view as being most conducive to recovery from rape. In-depth semi-structured interviews were conducted with 15 survivors who have experienced a successful course of therapy and 15 therapists with extensive expertise in the field. The results document considerable agreement between the two perspectives, which share much in common. First, irrespective of the specific techniques involved, both survivors and therapists placed the greatest importance on a respectful and validating therapeutic relationship, that operates to counter the dehumanization and degradation entailed in the assault. In addition, specific interventions were identified, which include the reprocessing of all rape-specific peri-traumatic reactions coupled with the intentional countering of their consequences within the therapeutic relationship. Together, these reports provide a detailed account of post-rape treatment needs and the interventions required for their effective resolution.

Keywords: sexual assault, rape, treatment efficacy, survivors

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1219 The Impact of Lipids on Lung Fibrosis

Authors: G. Wojcik, J. Gindlhuber, A. Syarif, K. Hoetzenecker, P. Bohm, P. Vesely, V. Biasin, G. Kwapiszewska

Abstract:

Pulmonary fibrosis is a rare disease where uncontrolled wound healing processes damage the lung structure. Intensive changes within the extracellular matrix (ECM) and its interaction with fibroblasts have a major role in pulmonary fibrosis development. Among others, collagen is one of the main components of the ECM, and it is important for lung structure. In IPF, constant production of collagen by fibroblast, through TGFβ1-SMAD2/3 pathways, leads to an uncontrolled deposition of matrix and hence lung remodeling. Abnormal changes in lipid production, alterations in fatty acids (FAs) metabolism, enhanced oxidative stress, and lipid peroxidation in fibrotic lung and fibrotic fibroblasts have been reported; however, the interplay between the collagen and lipids is not yet established. One of the FAs influx regulators is Angiopoietin-like 4 (ANGPTL4), which inhibits lipoprotein lipase work, decreasing the availability of FAs. We hypothesized that altered lipid composition or availability could have the capability to influence the phenotype of different fibroblast populations in the lung and hence influence lung fibrosis. To prove our hypothesis, we aim to investigate lipids and their influence on human, animal, and in vitro levels. In the bleomycin model, treatment with the well-known metabolic drugs Rosiglitazone or Metformin significantly lower collagen production. Similar results were noticed in ANGPTL4 KO animals, where the KO of ANGPTL4 leads to an increase of FAs availability and lower collagen deposition after the bleomycin challenge. Currently, we study the treatment of different FAs on human lung para fibroblasts (hPF) isolated from donors. To understand the lipid composition, we are collecting human lung tissue from donors and pulmonary fibrosis patients for Liquid chromatography-mass spectrometry. In conclusion, our results suggest the lipid influence on collagen deposition during lung fibrosis, but further research needs to be conducted to understand the matter of this relationship.

Keywords: collagen, fibroblasts, lipidomics, lung, pulmonary fibrosis

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1218 The Morphological Changes of POV in Diabetic Patients and Its Correlation with Changes in Corneal Epithelium, Corneal Nerve, and the Fundus in Using Vivo Confocal Microscopy

Authors: Ji Jiazheng, Wang Jingrao, Jin Xin, Zhang Hong

Abstract:

Diabetes mellitus is a metabolic disease characterized by high blood sugar. A long-standing hyperglycemic state can lead to various tissue damage. Diabetic retinopathy is the most common and widely studied ocular complication and has become the leading cause of blindness in my country. At the same time, diabetes has profound clinically relevant effects on the cornea, leading to keratopathy and vision-threatening. The cornea is an avascular tissue and is sensitive to hyperglycemia, Keratopathy caused by diabetes is usually chronic, they are called diabetic keratopathy or diabetic neurotrophic keratopathy, leading to several diabetic corneal complications including delayed epithelial wound healing, recurrent erosions, neuropathy, loss of sensitivity. Corneal stem cell dysfunction in diabetic patients as an important influencing factor of diabetic keratopathy. The consequences of this condition are often underestimated. The limbus is located between the cornea and the sclera tissue. The limbal stroma consists of a series of radial elevations with fibrovascular centers known as palisades of Vogt (POV). Previous studies have shown that palisades of Vogt (POV), as the main site of limbal stem cells, plays an important role in the homeostasis of the corneal epithelium. Therefore, POV plays a vital role in the healing of corneal epithelial surgery and postoperative evaluation. IVCM can observe the condition of the corneal epithelium at the cellular level. It has profound significance and guidance for the evaluation of limbal and limbal stem cells. We have previously observed structural changes in POV in HSK and HZO patients on IVCM. At present, there have been reports involving limbal stem cell dysfunction in diabetic patients, but the specific pathogenesis is still unclear. However, there are no studies on POV morphological changes in patients with DM. Therefore, we performed statistics and compared the correlation between POV morphological changes and corneal epithelial basal cell density, corneal nerves, and length of disease in DM patients and normal humans using IVCM studies. At the same time, fundoscopy was used to observe the correlation between the thickness of RNFL and the thickness of GCC and POV in diabetic patients. And to observe the correlation between SVD, DVD and POV for research.

Keywords: confocal microscopy, fundus, limbal stem cells, diabetes

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1217 Sequence Analysis of the Effect of HPV-16 E1 Variation on Cervical Carcinogenesis

Authors: Fern Baedyananda, Arkom Chaiwongkot, Somchai Niruthisard, Nakarin Kitkumthorn, Parvapan Bhattarakosol

Abstract:

High-risk human papillomavirus (HPV) infections cause transformation of the host cells by down-regulating and inhibiting host regulatory proteins such as p53 and pRb by overexpressing the viral oncoproteins E6 and E7. However, the E1 protein which is the only enzyme encoded by HPV has also been shown to cause DNA instability leading to the integration of the virus into the host genome and triggering carcinogenic events. A 63bp duplication in the E1 helicase region has been detected in European patients. However, the clinical prognosis of these patients is still controversial. This study was performed to determine the presence of the HPV-16 E1 63bp duplication in patient cervical samples in Thai women and determine the sequence of the variant in the Thai population. Detection of the HPV-16 E1 duplication in the helicase region was performed in 90 patient cell samples across normal, cervical intraepithelial neoplasia I-III, and squamous cervical carcinoma stages by PCR. The PCR products were purified and sequenced to determine the presence of duplication variants.The variant form was found in 10% of all CIN 1 patients. In this study, the presence of the 63 bp duplication variant in the Thai population was found to be present and was further characterized. Interestingly, all samples that exhibited the variant form of HPV-16 E1 were classified as CIN I. Presence of the variant, constricted to mild dysplasia signifies the importance of HPV-16 E1 in carcinogenesis.

Keywords: carcinogenesis, cervical cancer, human papillomavirus, HPV-16 E1

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1216 A Review on Future of Plant Based Medicine in Treatment of Urolithiatic Disorder

Authors: Gopal Lamichhane, Biswash Sapkota, Grinsun Sharma, Mahendra Adhikari

Abstract:

Urolithiasis is a condition in which insoluble or less soluble salts like oxalate, phosphate etc. precipitate in urinary tract and causes obstruction in ureter resulting renal colic or sometimes haematuria. It is the third most common disorder of urinary tract affecting nearly 2% of world’s population. Poor urinary drainage, microbial infection, oxalate and calcium containing diet, calciferol, hyperparathyroidism, cysteine in urine, gout, dysfunction of intestine, drought environment, lifestyle, exercise, stress etc. are risk factors for urolithiasis. Wide ranges of treatments are available in allopathic system of medicine but reoccurrence is unpreventable even with the surgical removal of stone or lithotripsy. So, people prefer alternative medicinal systems such as Unani, homeopathic, ayurvedic etc. systems of medicine due to their fewer side effects over allopathic counterpart. Different plants based ethnomedicines are being well established by their continuous effective use in human since long time in treatment of urinary problem. Many studies have scientifically proved those ethnomedicines for antiurolithiatic effect in animal and in vitro model. Plant-based remedies were found to be therapeutically effective for both prevention as well as cure of calcium oxalate urolithiasis. Plants were known to show these effects through a combination of many effects such as antioxidant, diuretic, hypocalciuric, urine alkalinizing effect in them. Berberine, triterpenoids, lupeol are the phytochemicals established for antiurolithiatic effect. Hence, plant-based medicine can be the effective herbal alternative as well as means of discovery of novel drug molecule for curing urolithiatic disorder and should be focused on further research to discover their value in coming future.

Keywords: urolithiasis, herbal medicine, ethnomedicine, kidney stone, calcium oxalate

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1215 Controlling Olive Anthracnose with Antifungal Metabolites from Bacillus Species: A Biological Approach

Authors: Hafiz Husnain Nawaz

Abstract:

Anthracnose disease in olive, caused by the fungal pathogen Colletotrichum acutatum, is considered one of the most critical issues in olive orchards in Pakistan. This disease poses a significant threat as it results in infections that can lead to the complete damage of olive plants, affecting leaves, stems, and fruits in the field. Controlling this disease is particularly challenging due to the absence of an effective fungicide that does not pose risks to farmer health and the environment. To address this challenge, our study aimed to evaluate the antagonistic activity of a biosurfactant produced by the Bacillus subtilis PE-07 strain against the anthracnose-causing agent in olive plants. This strain was selected after screening sixty rhizobacteria strains. Additionally, we assessed the heat stability, pH range, and toxicity of the biosurfactant produced by strain PE-07. Our results revealed that the biosurfactant exhibited maximum antifungal activity against C. acutatum. In vitro studies indicated that the biosurfactant could reduce fungal activity by inhibiting the spore germination of C. acutatum. Furthermore, the biosurfactant demonstrated a wide pH and temperature range, displaying antifungal activity at pH levels ranging from 5 to 10 and a temperature range from room temperature to 110°C. To evaluate the biosurfactant's safety, we conducted toxicity tests on zebra fish (Danio rerio). The results showed that the biosurfactant had minimal harmful effects, even at maximum concentrations. In conclusion, our study confirmed that the biosurfactant produced by B. subtilis exhibited high pH and heat stability with minimal harmful effects. Therefore, it presents a promising alternative to chemical pesticides for effectively controlling olive anthracnose in Pakistan.

Keywords: biological control, heat stability and PH range, toxicity, Danio rerio

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1214 The Differences of Vascular Endothelial Growth Factor Levels in Serum to Determine Follicular Adenoma and Follicular Carcinoma of Thyroid

Authors: Tery Nehemia Nugraha Joseph, J. D. P. Wisnubroto

Abstract:

Thyroid cancer is a healthcare problem with high morbidity and mortality. Follicular adenoma and follicular carcinoma are thyroid tumors from the thyroid follicular cells differentiation with a microfollicular pattern that consists of follicular cuboidal cells. vascular endothelial growth factor (VEGF) is a potent and powerful mitogen for endothelial cells and increases vascular permeability. Therefore, due to an increase in thyroid-stimulating hormone (TSH), VEGF production is activated in the thyroid that leads to the end of mitogenic TSH stimulation and initiation of angiogenesis. The differences in VEGF levels in the follicular carcinoma of thyroid tissue with follicular adenoma thyroid can be used as a basis in differentiating the two types of neoplasms. This study aims to analyze VEGF in the serum so that it can be used to differentiate the types of thyroid carcinoma before surgery. This study uses a cross-sectional research design. Samples were carried out by taking serum samples, and the VEGF levels were calculated. Data were analyzed using the Mann-Whitney test. The results found a significant difference between VEGF levels in the follicular carcinoma thyroid group and VEGF levels in the follicular adenoma thyroid group with a value of p = 0.007 (p < 0.05). The results obtained are 560,427 ± 160,506 ng/mL in the type of follicular carcinoma thyroid and 320.943 ± 134.573 ng/mL in the type of follicular adenoma thyroid. VEGF levels between follicular adenoma and follicular carcinoma are different. VEGF levels are higher in follicular carcinoma thyroid than follicular adenoma thyroid.

Keywords: follicular adenoma thyroid, follicular carcinoma thyroid, thyroid, VEGF

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1213 Determination of Poisson’s Ratio and Elastic Modulus of Compression Textile Materials

Authors: Chongyang Ye, Rong Liu

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Compression textiles such as compression stockings (CSs) have been extensively applied for the prevention and treatment of chronic venous insufficiency of lower extremities. The involvement of multiple mechanical factors such as interface pressure, frictional force, and elastic materials make the interactions between lower limb and CSs to be complex. Determination of Poisson’s ratio and elastic moduli of CS materials are critical for constructing finite element (FE) modeling to numerically simulate a complex interactive system of CS and lower limb. In this study, a mixed approach, including an analytic model based on the orthotropic Hooke’s Law and experimental study (uniaxial tension testing and pure shear testing), has been proposed to determine Young’s modulus, Poisson’s ratio, and shear modulus of CS fabrics. The results indicated a linear relationship existing between the stress and strain properties of the studied CS samples under controlled stretch ratios (< 100%). The newly proposed method and the determined key mechanical properties of elastic orthotropic CS fabrics facilitate FE modeling for analyzing in-depth the effects of compression material design on their resultant biomechanical function in compression therapy.

Keywords: elastic compression stockings, Young’s modulus, Poisson’s ratio, shear modulus, mechanical analysis

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1212 Patients' Perceptions of Receiving a Diagnosis of a Haematological Malignancy, following the SPIKES Protocol

Authors: Lauren Dixon, David Galvani

Abstract:

Objective: Sharing devastating news with patients is often considered the most difficult task of doctors. This study aimed to explore patients’ perceptions of receiving bad news including which features improve the experience and which areas need refining. Methods: A questionnaire was written based on the steps of the SPIKES model for breaking bad news. 20 patients receiving treatment for a haematological malignancy completed the questionnaire. Results: Overall, the results are promising as most patients praised their consultation. ‘Poor’ was more commonly rated by women and participants aged 45-64. The main differences between the ‘excellent’ and ‘poor’ consultations include the doctor’s sensitivity and checking the patients’ understanding. Only 35% of patients were asked their existing knowledge and 85% of consultations failed to discuss the impact of the diagnosis on daily life. Conclusion: This study agreed with the consensus of existing literature. The commended aspects include consultation set-up and information given. Areas patients felt needed improvement include doctors determining the patient’s existing knowledge and exploring how the diagnosis will affect the patient’s life. With a poorer prognosis, doctors should work on conveying appropriate hope. The study was limited by a small sample size and potential recall bias.

Keywords: cancer, diagnosis, haematology, patients

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1211 Development of Functional Cosmetic Materials from Demilitarized Zone Habiting Plants

Authors: Younmin Shin, Jin Kyu Kim, Mirim Jin, Jeong June Choi

Abstract:

Demilitarized Zone (DMZ) is a peace region located between South and North Korea border to avoid accidental armed conflict. Because human accessing to the area was forced to be prohibited for more than 60 years, DMZ is one of the cleanest land keeping wild lives as nature itself in South Korea. In this study, we evaluated the biological efficacies of plants (SS, PC, and AR) inhabiting in DMZ for the development of functional cosmetics. First, we tested the cytotoxicity of plant extracts in keratinocyte and melanocyte, which are the major cell components of skin. By 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with the cell lines, we determined the safety concentrations of the extracts for the efficacy tests. Next, we assessed the anti-wrinkle cosmetic function of SS by demonstrating that SS treatment decreased the expression of Matrix metalloproteinase-1 (MMP-1) in UV-irradiated keratinocytes via real-time PCR. The suppressive effect of SS was greatly potentiated by combination with other DMZ-inhabiting plants, PC and AR. The expression of tyrosinase, which is one the main enzyme that producing melanin in melanocyte, was also down-regulated by the DMZ-inhabiting SS extract. Wound healing activity was also investigated by in vitro test with HaCat cell line, a human fibroblast cell line. All the natural materials extracted form DMZ habiting plants accelerated the recovery of the cells. These results suggested that DMZ is a treasure island of functional plants and DMZ-inhabiting natural products are warranted to develop functional cosmetic materials. This study was carried out with the support of R&D Program for Forest Science Technology (Project No. 2017027A00-1819-BA01) provided by Korea Forest Service (Korea Forestry Promotion Institute).

Keywords: anti-wrinkle, Demilitarized Zone, functional cosmetics, whitening

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1210 In vitro Antioxidant and Antisickling Effects of Aerva javanica, and Ficus palmata Extracts on Sickle Cell Anemia

Authors: E. A. Alaswad, H. M. Choudhry, F. Z. Filimban

Abstract:

Sickle Cell Anemia (SCA) is one type of blood diseases related to autosomal disorder. The sickle shaped red blood cells are the main cause of many problems in the blood vessels and capillaries. Aerva Javanica (J) and Ficus Palmata (P) are medicinal plants that have many popular uses and have been proved their efficacy. The aim of this study was to assess the antioxidants activity and the antisickling effect of J and P extractions. The period of this study, air-dried leaves of J, and P plants were ground and the active components were extracted by maceration in water (W) and methanol (M) as solvents. The antioxidants activity of JW, PW, JM, and PM were assessed by way of the radical scavenging method using 2,2-diphenyl-1-picrylhydrazyl (DPPH). To determine the antisickling effect of J and P extracts. 20 samples were collected from sickle cell anemia patients. Different concentrations of J and P extracts (200 and 110 μg/mL) were added on the sample and incubated. A drop of each sample was examined with light microscope. Normal and sickled RBCs were calculated and expressed as the percent of sickling. The stabilization effect of the extracts was measured by the osmotic fragility test for erythrocytes. The finding suggests as estimated by DPPH method, all the extracts showed an antioxidant activity with a significant inhibition of the DPPH radicals. PM has the least IC50% with 71.49 μg/ml while JM was the most with 408.49 μg/ml. Sickle cells treated with extracts at different concentrations significantly reduced the percentage of sickling compering to control samples. However, JM 200 μg/mL give the highest anti-sickling affect with 17.4% of sickling compared to control 67.5 of sickling while PM at 200 μg/mL showed the highest membrane cell stability. In a conclusion, the results showed that J and P extracts have antisickling effects. Therefore, the Aerva javanica and Ficus palmata may have a role in SCA management and a good impact on the patient's lives.

Keywords: Aerva javanica, antioxidant, antisickling, Ficus palmata, sickle cell anemia

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1209 Effect of Low-Intensity Laser on Severe Tinnitus in Idiopathic Sudden Hearing Loss Patients

Authors: Z. Mowafy Emam Mowafy, Ahmed R. Sayed, M. El Sayed Mohmmed Hassan

Abstract:

Purpose: to evaluate the effect of low intensity laser on severe tinnitus in idiopathic sudden hearing loss patients. Methods of evaluation (Visual analogue scale and tinnitus handicap inventory scale):- Thirty patients who had unilateral tinnitus with sensorineural hearing loss were participated in the study. Subjects aged from 40 to 50 were randomly divided into two equal groups: group (A): composed of 15 patients who received the routine medical care (Systemic steroids) in addition to the low-intensity laser therapy (LILT) while group (B): composed of 15 patients who received only the routine medical care. Continuous 632.8nm He-Ne laser was used with 5mW power for 15 min\day, 3 days per week for 3 months. Results and conclusion: Results showed that application of the LILT had a valuable effect on severe tinnitus in idiopathic sudden hearing loss patients as evidenced by the highly decreased visual analogue scale and tinnitus handicap inventory scale.

Keywords: idiopathic sudden hearing loss, low intensity laser, tinnitus, tinnitus handicap inventory scale and visual analogue scale

Procedia PDF Downloads 375
1208 Endemic Medicinal Plants in Eritrea: Scientific Name, Botanical Description and Geographical Location

Authors: Liya Abraham

Abstract:

Medicinal plants are globally valuable sources of herbal products, either as lifesaving or life maintaining medicines. Studies reveal that more than 25% of modern drugs in the world are derived from plants. The Horn of Africa as a world hotspot; it has more than 1500 endemic plants. Eritrea, a country located in the Horn of Africa, is blessed with medicinal flora and fauna and marine and terrestrial biodiversity. Previous studies of flora of Ethiopia and Eritrea, incomplete species lists, indicate figures ranging between 6000 and 7000 species, with levels of endemism between 12–20%. In the past two decades, there has been growing interest in natural remedy herbal medicines owing to, but not limited to; resistance to antimicrobials, intolerance of side effects of modern drugs, and rise in chronic diseases like diabetes, hypertension, cancer, etc. Hence, owing to the rising demand for nature based health solutions, deforestation, construction purposes, grazing, and agricultural expansion; several medicinal plants in general and the endemic ones, in particular, are in the verge of extinction. Therefore, conservation strategies of endangered and endemic medicinal plants, especially those located in hot spot regions, must be promoted at global level. Thus, the author aims to share certain information regarding the endemic medicinal plants in Eritrea with the international scientific world.

Keywords: endemic, eritrea, horn of Africa, medicinal plants, species

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1207 Medicinal and Aromatic Plants of Ardanuç (Artvi̇n, Türki̇ye)

Authors: Özgür Emi̇nağaoğlu, Hayal Akyildirim Beğen, Şevval Sali̇oğlu, Emrah Yüksel

Abstract:

This study was carried out in order to determine the scientific name, common name, local names, location, botanical characteristics, used parts, intended use, local usage patterns, usage in the literature of plant species used for medicinal and aromatic purposes in Ardanuç (Artvin, Türkiye) between 2020-2023 years. The research area is located in the A9 square according to Davis’s grid system and is phytogeographically located in the colchic subsection of the Euxine part of the Euro-Siberian flora area of the Holarctic region. As a result of the studies, it has been determined that 167 plant species belonging to 79 families are used for medicinal and aromatic purposes. The families that contain the most taxa in the research area are, respectively, Rosaceae (19 taxa), Asterecaeae (15 taxa), and Lamiaceae (14 taxa). It has been determined that the medicinal, aromatic plants of the Ardanuç region are mostly used in the treatment of diseases (59%), and the plants are mostly used in the treatment of diabetes (37%). It was determined that the most applied method in the internal use of plants was decoction (48%). As a result of the research, the most commonly used plants in different diseases are Sambucus nigra, Plantago lanceolata, Satureja hortensis, Hypericum perforatum, Juniperus communis. These plants are used in the treatment of many diseases, such as colds, cancer, anemia and diabetes.

Keywords: Ardanuç, Artvin, Medicinal and Aromatic plant, Türkiye

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1206 Successful Management of a Boy with Mild Persistent Asthma: A Longitudinal Case

Authors: A. Lubis, L. Setiawati, A. R. Setyoningrum, A. Suryawan, Irwanto

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Asthma is a condition that causing chronic health problems in children. In addition to basic therapy against disease, we must try to reduce the impact of chronic health problems and also optimize their medical aspect of growth and development. A boy with mild asthma attack frequent episode did not showed any improvement with medical treatment and his asthma control test was 11. From radiologic examination he got hyperaerated lung and billateral sinusitis maxillaris; skin test results were house dust, food and pet allergy; an overweight body; bad school grades; psychological and environmental problem. We followed and evaluated this boy in 6 months, treated holistically. Even we could not do much on environmental but no more psychological and school problems, his on a good bodyweight and his asthma control test was 22. A case of a child with mild asthma attack frequent episode was reported. Asthma clinical course show no significant improvement when other predisposing factor is not well-controlled and a child’s growth and development may be affected. Improving condition of the patient can be created with the help of loving and caring way of nurturing from the parents and supportive peer group. Therefore, continuous and consistent monitoring is required because prognosis of asthma is generally good when regularly and properly controlled.

Keywords: asthma, chronic health problems, growth, development

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1205 Development of Nanostructrued Hydrogel for Spatial and Temporal Controlled Release of Active Compounds

Authors: Shaker Alsharif, Xavier Banquy

Abstract:

Controlled drug delivery technology represents one of the most rapidly advancing areas of science in which chemists and chemical engineers are contributing to human health care. Such delivery systems provide numerous advantages compared to conventional dosage forms including improved efficacy, and improved patient compliance and convenience. Such systems often use synthetic polymers as carriers for the drugs. As a result, treatments that would not otherwise be possible are now in conventional use. The role of bilayered vesicles as efficient carriers for drugs, vaccines, diagnostic agents and other bioactive agents have led to a rapid advancement in the liposomal drug delivery system. Moreover, the site avoidance and site-specific drug targeting therapy could be achieved by formulating a liposomal product, so as to reduce the cytotoxicity of many potent therapeutic agents. Our project focuses on developing and building hydrogel with nanoinclusion of liposomes loaded with active compounds such as proteins and growth factors able to release them in a controlled fashion. In order to achieve that, we synthesize several liposomes of two different phospholipids concentrations encapsulating model drug. Then, formulating hydrogel with specific mechanical properties embedding the liposomes to manage the release of active compound.

Keywords: controlled release, hydrogel, liposomes, active compounds

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1204 Comparative Study of Dose Calculation Accuracy in Bone Marrow Using Monte Carlo Method

Authors: Marzieh Jafarzadeh, Fatemeh Rezaee

Abstract:

Introduction: The effect of ionizing radiation on human health can be effective for genomic integrity and cell viability. It also increases the risk of cancer and malignancy. Therefore, X-ray behavior and absorption dose calculation are considered. One of the applicable tools for calculating and evaluating the absorption dose in human tissues is Monte Carlo simulation. Monte Carlo offers a straightforward way to simulate and integrate, and because it is simple and straightforward, Monte Carlo is easy to use. The Monte Carlo BEAMnrc code is one of the most common diagnostic X-ray simulation codes used in this study. Method: In one of the understudy hospitals, a certain number of CT scan images of patients who had previously been imaged were extracted from the hospital database. BEAMnrc software was used for simulation. The simulation of the head of the device with the energy of 0.09 MeV with 500 million particles was performed, and the output data obtained from the simulation was applied for phantom construction using CT CREATE software. The percentage of depth dose (PDD) was calculated using STATE DOSE was then compared with international standard values. Results and Discussion: The ratio of surface dose to depth dose (D/Ds) in the measured energy was estimated to be about 4% to 8% for bone and 3% to 7% for bone marrow. Conclusion: MC simulation is an efficient and accurate method for simulating bone marrow and calculating the absorbed dose.

Keywords: Monte Carlo, absorption dose, BEAMnrc, bone marrow

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1203 Regulation of RON-Receptor Tyrosine Kinase Functions by Epstein-Barr-Virus (EBV) Nuclear Antigen 3C

Authors: Roshika Tyagi, Shuvomoy Banerjee

Abstract:

Among various diseases, cancer has become a huge threat to human beings globally. In the context of viral infection, Epstein–Barr virus (EBV) infection is ubiquitous in nature world-wide as well as in India. Recepteur d’Origine Nantais (RON) receptor tyrosine kinase is overexpressed in Lymphoblastoid cell lines (LCLs) but undetectable in primary B-cells. Biologically, RON expression was found to be essential for EBV transformed LCLs proliferation. In our study, we investigated whether EBV latent antigen EBNA3C is playing a crucial role in regulating RON receptor tyrosine kinase function in EBV-induced malignancies. Interestingly, we observed that expression pattern of RON was modulated by EBNA3C in EBV transformed LCLs compared with EBV negative BJAB cell line by PCR and western blot analysis. Moreover, in the absence of EBNA3C, RON expression was found low in western blot and immunofluorescence analysis and cell proliferation rate was significantly reduced in LCLs by cell viability assays. Therefore, our study clearly indicating the potential role of EBNA3C expressed in EBV-infected B-cells for modulating the functions of oncogenic kinases that leads to EBV induced B-cell transformation.

Keywords: apoptosis, cell proliferation, Epstein–barr virus, receptor tyrosine kinase

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1202 Potential Use of Thymus mastichina L. Extract as a Natural Agent against Cheese Spoilage Microorganisms

Authors: Susana P. Dias, Andrea Gomes, Fernanda M. Ferreira, Marta F. Henriques

Abstract:

Thymus mastichina L. is an endogenous medicinal and aromatic plant of the Mediterranean flora. It has been used empirically over the years as a natural preservative in food. Nowadays, the antimicrobial activity of its bioactive compounds, such as essential oils and extracts, has been well recognized. The main purpose of this study was to evaluate the antimicrobial effect of Thymus mastichina ethanolic and aqueous extracts on pathogens and spoilage microorganisms present in cheese during ripening. The effect that the extract type and its concentration has on the development of Staphylococcus aureus, Escherichia coli, and Yarrowia lipolytica populations during 24 hours, was studied 'in vitro' using appropriate culture media. The results achieved evidenced the antimicrobial activity of T. mastichina extracts against the studied strains, and the concentration of 2 mg/mL (w/v) was selected and used directly on the cheese surface during ripening. In addition to the microbiological evaluation in terms of total aerobic bacteria, Enterobacteriaceae, yeasts (particularly Y. lipolytica) and molds, the treated cheeses physicochemical evaluation (humidity, aw, pH, colour, and texture) was also performed. The results were compared with cheeses with natamicyn (positive control) and without any treatment (negative control). The physicochemical evaluation showed that the cheeses treated with ethanolic extract of Thymus mastichina, except the fact that they lead to a faster water loss during ripening, did not present considerable differences when compared to controls. The study revealed an evident antimicrobial power of the extracts, although less effective than the one shown by the use of natamycin. For this reason, the improvement of the extraction methods and the adjustment of the extract concentrations will contribute to the use of T. mastichina as a healthier and eco-friendly alternative to natamycin, that is also more attractive from an economic point of view.

Keywords: antimicrobial activity, cheese, ethanolic extract, Thymus mastichina

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1201 The Effects of Maternal Exposure Riboflavin to Prevent Uterus Arsenic Damage in Offspring Rats

Authors: Ali Olfati, Parichehr Nouri

Abstract:

Objective: In this study, we have investigated for the first time in the literature the efficacy of riboflavin [VB2] in preventing uterus As₂O₃ damage. Methods: Rats received 40 μg LHRHa for estrus synchronization. 48 pregnant Wistar rats were included. Four groups were formed with 7 rats in each group: Sham, 1.5 mg arsenic trioxide (As₂O₃/L) alone or in combination with VB2 [20 and 40 mg/L] in drinking water [for 21 days continuously]. Similar to maternal generation treatment, the F1-female generation was also arranged [for 35 days continuously until puberty]. Results: Data indicated that As₂O₃ reduced body weight and feed intake (p<0.05). Furthermore, the serum malondialdehyde levels in the As₂O₃ group were significantly higher than that of the control group (p<0.05). At the same time, total antioxidative status and the activities of glutathione peroxidase, superoxide dismutase, and catalase were reduced (p<0.05). Meanwhile, As₂O₃ remarkably increased the production of inflammatory markers [interleukin 6 and C-reactive protein](p<0.05). As₂O₃ administration induced uterus apoptosis-related genes by upregulating caspase-3, iNOS, and Bax genes and downregulating Bcl-2 gene of pubertal F1-female rats (p<0.05). Conclusion: Our observation indicated that VB2 therapy is potentially an effective strategy to modifying the detrimental effects of As₂O₃ in pubertal F1-female rats via suppresses oxidative damages.

Keywords: As₂O₃, inflammation, puberty, vitamin B2

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