Search results for: in vivo wound healing

Authors: Rekaya A. Shabbir, Marco Mingarelli, Glenn Flux, Ananya Choudhury, Tim A. D. Smith

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Introduction: Heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. Gold nanoparticles (AuNPs) enhance dose-distributions of targeted radionuclides. The aim of this study is to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (¹⁷⁷Lu and ⁹⁰Y) in breast cancer cells produced homogeneous dose distributions. Moreover, in vitro and in vivo studies were conducted to study the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs in breast and colorectal cancer cells. Methods: AuNPs were functionalised with DOTA and OPPS-PEG-SVA to optimise labelling with radionuclide tracers and targeting with Erbitux. Radionuclides were chelated with DOTA, and the uptake of the radiolabelled AuNPs and targeted activity in vitro in both cell lines measured using liquid scintillation counting. Cells with medium (HCT8) and high (MDA-MB-468) EGFR expression were incubated with targeted ¹⁷⁷Lu-AuNPs for 4h, then washed and allowed to form colonies. Nude mice bearing tumours were used to study the biodistribution by injecting ¹⁷⁷Lu-AuNPs or ⁹⁰Y-AuNPs via the tail vein. Heterogeneity of dose-distribution in tumours was determined using autoradiography. Results: Colony formation (% control) was 81 ± 4.7% (HCT8) and 32 ± 9% (MDA-MB-468). High uptake was observed in the liver and spleen, indicating hepatobiliary excretion. Imaging showed heterogeneity in dose-distributions for both radionuclides across the tumours. Conclusion: The cytotoxic effect of EGFR-targeted AuNPs is greater in cells with higher EGFR expression. Dose-distributions for individual radiolabelled nanoparticles were heterogeneous across tumours. Further strategies are required to improve the uniformity of dose distribution prior to clinical trials.

Keywords: cancer cells, dose distributions, radionuclide therapy, targeted gold nanoparticles

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Authors: C. Panebianco, K. Adamberg, S. Adamberg, C. Saracino, M. Jaagura, K. Kolk, A. Di Chio, P. Graziano, R. Vilu, V. Pazienza

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Background/Aims: Despite recent advances in treatment options, a modest impact on the outcome of the pancreatic cancer (PC) is observed so far. Short-term fasting cycles have the potential to improve the efficacy of chemotherapy against PC. However, diseased people may refuse to follow the fasting regimen and fasting may worsen the weight loss often occurring in cancer patients. Therefore, alternative approaches are needed. The aim of this study was to assess the effect of Engineered Low glycemic food ELGIF mimicking diet on growth of cancer cell lines in vitro and in an in vivo pancreatic cancer mouse xenograft model. Materials and Methods: BxPC-3, MiaPaca-2 and Panc-1 cells were cultured in control and ELGIF mimicking diet culturing condition to evaluate the tumor growth and proliferation pathways. Pancreatic cancer xenograft mice were subjected to ELGIF to assess the tumor volume and weight as compared to mice fed with control diet. Results: Pancreatic cancer cells cultured in ELGIF mimicking medium showed decreased levels of proliferation as compared to those cultured in the standard medium. Consistently, xenograft pancreatic cancer mice subjected to ELGIF diet displayed a significant decrease in tumor growth. Conclusion: A positive effect of ELGIF diet on proliferation in vitro is associated with the decrease of tumor progression in the in vivo PC xenograft mouse model. These results suggest that engineered dietary interventions could be supportive as synergistic approach to enhance the efficacy of existing cancer treatments in pancreatic cancer patients.

Keywords: functional food, microbiota, mouse model, pancreatic cancer

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Authors: Paula Buldres, Jorge Toledo

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Objectives: This study aimed to characterize potential probiotic strains isolated from canine breast milk for use in dogs with enteropathies. Methodology: Six canine breast milk strains, one canine colostrum strain, and one control porcine breast milk strain were characterized. According to its functional properties of resistance to acids, different concentrations of bile salts, and pancreatin, its presumptive properties of safety and inhibitory effect on pathogens, non-cytotoxic characteristics, and adhesion to the intestine. The immunomodulatory effect of formulations with better probiotic characterization in vitro and in vivo was also analyzed. Results: Two strains characterized as potential probiotics were obtained, which corresponded to the canine strains (TUCO-16 and TUCO-17), presenting resistance to acidic pH, bile salts, and pancreatin, as well as an inhibitory effect on pathogenic Escherichia coli, Salmonella sp., and Clostridium perfringens. Strains TUCO-16 and TUCO-17 induced a significant increase in the expression of TNF-α and IL-8 in canine macrophages, respectively. Expression analyses of pattern recognition receptors in DH82 cells suggest that TUCO-16 and TUCO-17 might increase the TLR2 expression marker, and porcine strain (TUCO-4) increases the NOD2 expression marker. Based on the count obtained and the encapsulation yield, the best formulations correspond to FOS-Inulin for the TUCO-17 and TUCO-4 strains; Maltodextrin-Inulin for TUCO-16. All the strains are non-cytotoxic. The strain that showed the highest adhesion to intestinal epithelial cells was TUCO-17 with the FOS-Inulin formulation. On the other hand, the probiotics decreased the expression of pro-inflammatory markers in vivo, both in the intestine and in the spleen of mice. Conclusion: The combination of these three strains under study (TUCO-16, TUCO-17, and TUCO-4) would cover the probiotic properties in formulation and immunomodulation of all the markers under study.

Keywords: probiotics, gastrointestinal infec, dog, probiotic formulation, immunomodulatory probiotics

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Authors: Lina Fernanda González

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Through this essay, an attempt will be made to make visible the work of the international network of the Women in Black (henceforth WB), on the one hand. On the other hand, the work of Women International Courts as a political practice will be showed as well, focusing their work into generating a collective identity - becoming thusly a peace building space, rescuing in this way the symbolic value of their practices consisting in peaceful resistance as political scenarios, that serve, too, a pedagogical and healing purposes.

Keywords: collective actions, women, peace, human rights and humanitarian international law

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Authors: Calvin A. Omolo, Rahul S. Kalhapure, Mahantesh Jadhav, Sanjeev Rambharose, Chunderika Mocktar, Thirumala Govender

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Treatment of infections is compromised by limitations of conventional dosage forms and drug resistance. Nanocarrier system is a strategy to overcome these challenges and improve therapy. Thus, the development of novel materials for drug delivery via nanocarriers is essential. The aim of the study was to synthesize a multi-arm polymer (6-mPEPEA) for enhanced activity of vancomycin (VM) against susceptible and resistant Staphylococcus aureus (MRSA). The synthesis steps of the star polymer followed reported procedures. The synthesized 6-mPEPEA was characterized by FTIR, ¹H and ¹³CNMR and MTT assays. VM loaded micelles were prepared from 6-mPEPEA and characterized for size, polydispersity index (PI) and surface charge (ZP) (Dynamic Light Scattering), morphology by TEM, drug loading (UV Spectrophotometry), drug release (dialysis bag), in vitro and in vivo efficacy against sensitive and resistant S. aureus. 6-mPEPEA was synthesized, and its structure was confirmed. MTT assays confirmed its nontoxic nature with a high cell viability (77%-85%). Unimolecular spherical micelles were prepared. Size, PI, and ZP was 52.48 ± 2.6 nm, 0.103 ± 0.047, -7.3 ± 1.3 mV, respectively and drug loading was 62.24 ± 3.8%. There was a 91% drug release from VCM-6-mPEPEA after 72 hours. In vitro antibacterial test revealed that VM-6-mPEPEA had 8 and 16-fold greater activity against S. aureus and MRSA when compared to bare VM. Further investigations using flow cytometry showed that VM-6-mPEPEA had 99.5% killing rate of MRSA at the MIC concentration. In vivo antibacterial activity revealed that treatment with VM-6-mPEPEA had a 190 and a 15-fold reduction in the MRSA load in untreated and VM treated respectively. These findings confirmed the potential of 6-mPEPEA as a promising bio-degradable nanocarrier for antibiotic delivery to improve treatment of bacterial infections.

Keywords: biosafe, MRSA, nanocarrier, resistance, unimolecular-micelles

Procedia PDF Downloads 188

Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

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Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

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Authors: Manisha Massey, Mariette Berndsen, Helen McLaren

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The existing body of literature concerning the incidence, prevalence, and experiences of childhood sexual abuse (CSA) lacked cultural inclusivity, primarily reflecting Euro-centric perspectives. This study investigated and reviewed the existing literature to understand the experiences of women of color from South Asia, addressing the gap in understanding how culture and diversity impact CSA. While individualist cultures emphasize autonomy, collectivist societies prioritize interdependence. South Asia's diverse intersections, including gender, caste, religion, and class, have intensified child sexual exploitation, challenging assumed homogeneity and safety. Additionally, the power exploitation in the space of abuse and grooming supplementing with the prevalence of honor violence makes disclosures of sexual abuse for children daunting and unsafe in these cultures. This scoping review examined the connection between CSA, psychological trauma, re-traumatization, and shame among adult South Asian women from India, Pakistan, and Bangladesh. Despite distinct borders, these countries share historical, linguistic, and traditional ties. Following PRISMA guidelines, the review employed thematic analysis. Findings underscored cultural factors' influence on CSA incidence, help-seeking barriers, and treatment challenges. The pivotal role of shame (sharam) and honor (izzat) in disclosure and healing processes was highlighted. The study emphasized the need for culturally sensitive interventions while noting limited literature on re-traumatisation. Incorporating a culturally informed perspective, this research aims to decolonize trauma therapy by contributing to the CSA discourse, shedding light on its intricate interaction with trauma, shame, and healing among South Asian women.

Keywords: Childhood sexual abuse, decolonizing psychology, trauma, re-trauma, shame

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Authors: John Yahng, Hansraj Riteesh Bookun

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Objective: This was a retrospective cross-sectional study evaluating the safety of discharge on the first postoperative day following carotid surgery - principally carotid endarterectomy. Methods: Between January 2010 to October 2017, 252 patients with mean age of 72 years, underwent carotid surgery by seven surgeons. Their medical records were consulted and their operative as well as complication timelines were databased. Descriptive statistics were used to analyse pooled responses and our indicator variables. The statistical package used was STATA 13. Results: There were 183 males (73%) and the comorbid burden was as follows: ischaemic heart disease (54%), diabetes (38%), hypertension (92%), stage 4 kidney impairment (5%) and current or ex-smoking (77%). The main indications were transient ischaemic attacks (42%), stroke (31%), asymptomatic carotid disease (16%) and amaurosis fugax (8%). 247 carotid endarterectomies (109 with patch arterioplasty, 88 with eversion and transection technique, 50 with endarterectomy only) were performed. 2 carotid bypasses, 1 embolectomy, 1 thrombectomy with patch arterioplasty and 1 excision of a carotid body tumour were also performed. 92% of the cases were performed under general anaesthesia. A shunt was used in 29% of cases. The mean length of stay was 5.1 ± 3.7days with the range of 2 to 22 days. No patient was discharged on day 1. The mean time from admission to surgery was 1.4 ± 2.8 days, ranging from 0 to 19 days. The mean time from surgery to discharge was 2.7 ± 2.0 days with the of range 0 to 14 days. 36 complications were encountered over this period, with 12 failed repairs (5 major strokes, 2 minor strokes, 3 transient ischaemic attacks, 1 cerebral bleed, 1 occluded graft), 11 bleeding episodes requiring a return to the operating theatre, 5 adverse cardiac events, 3 cranial nerve injuries, 2 respiratory complications, 2 wound complications and 1 acute kidney injury. There were no deaths. 17 complications occurred on postoperative day 0, 11 on postoperative day 1, 6 on postoperative day 2 and 2 on postoperative day 3. 78% of all complications happened before the second postoperative day. Out of the complications which occurred on the second or third postoperative day, 4 (1.6%) were bleeding episodes, 1 (0.4%) failed repair , 1 respiratory complication (0.4%) and 1 wound complication (0.4%). Conclusion: Although it has been common practice to discharge patients on the second postoperative day following carotid endarterectomy, we find here that discharge on the first operative day is safe. The overall complication rate is low and most complications are captured before the second postoperative day. We suggest that patients having an uneventful first 24 hours post surgery be discharged on the first day. This should reduce hospital length of stay and the health economic burden.

Keywords: carotid, complication, discharge, surgery

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Authors: B.L. España-Sánchez, E. Luna-Hernández, R.A. Mauricio-Sánchez, M.E. Cruz-Soto, F. Padilla-Vaca, R. Muñoz, L. Granados-López, L.R. Ovalle-Flores, J.L. Menchaca-Arredondo, G. Luna-Bárcenas

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Treatment of burn injured has been considered an important clinical problem due to the fluid control and the presence of microorganisms during the healing process. Conventional treatment includes antiseptic techniques, topical medication and surgical removal of damaged skin, to avoid bacterial growth. In order to accelerate this process, different alternatives for tissue regeneration have been explored, including artificial skin, polymers, hydrogels and hybrid materials. Some requirements consider a nonreactive organic polymer with high biocompatibility and skin adherence, avoiding bacterial infections. Chitin-derivative biopolymer such as chitosan (CS) has been used in skin regeneration following third-degree burns. The biological interest of CS is associated with the improvement of tissue cell stimulation, biocompatibility and antibacterial properties. In particular, antimicrobial properties of CS can be significantly increased when is blended with nanostructured materials. Silver-based nanocomposites have gained attention in medicine due to their high antibacterial properties against pathogens, related to their high surface area/volume ratio at nanomolar concentrations. Silver nanocomposites can be blended or synthesized with chitin-derivative biopolymers in order to obtain a biodegradable/antimicrobial hybrid with improved physic-mechanical properties. In this study, nanocomposites based on chitosan/silver nanoparticles (CS/nAg) were synthesized by the in situ chemical reduction method, improving their antibacterial properties against pathogenic bacteria and enhancing the healing process in thermal burn injuries produced in an animal model. CS/nAg was prepared in solution by the chemical reduction method, using AgNO₃ as precursor. CS was dissolved in acetic acid and mixed with different molar concentrations of AgNO₃: 0.01, 0.025, 0.05 and 0.1 M. Solutions were stirred at 95°C during 20 hours, in order to promote the nAg formation. CS/nAg solutions were placed in Petri dishes and dried, to obtain films. Structural analyses confirm the synthesis of silver nanoparticles (nAg) by means of UV-Vis and TEM, with an average size of 7.5 nm and spherical morphology. FTIR analyses showed the complex formation by the interaction of hydroxyl and amine groups with metallic nanoparticles, and surface chemical analysis (XPS) shows low concentration of Ag⁰/Ag⁺ species. Topography surface analyses by means of AFM shown that hydrated CS form a mesh with an average diameter of 10 µm. Antibacterial activity against S. aureus and P. aeruginosa was improved in all evaluated conditions, such as nAg loading and interaction time. CS/nAg nanocomposites films did not show Ag⁰/Ag⁺ release in saline buffer and rat serum after exposition during 7 days. Healing process was significantly enhanced by the presence of CS/nAg nanocomposites, inducing the production of myofibloblasts, collagen remodelation, blood vessels neoformation and epidermis regeneration after 7 days of injury treatment, by means of histological and immunohistochemistry assays. The present work suggests that hydrated CS/nAg nanocomposites can be formed a mesh, improving the bacterial penetration and the contact with embedded nAg, producing complete growth inhibition after 1.5 hours. Furthermore, CS/nAg nanocomposites improve the cell tissue regeneration in thermal burn injuries induced in rats. Synthesis of antibacterial, non-toxic, and biocompatible nanocomposites can be an important issue in tissue engineering and health care applications.

Keywords: antibacterial, chitosan, healing process, nanocomposites, silver

Procedia PDF Downloads 287

Authors: Malay K. Das, Bhanu P. Sahu

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Furosemide is a weakly acidic diuretic indicated for treatment of edema and hypertension. It has very poor solubility but high permeability through stomach and upper gastrointestinal tract (GIT). Due to its limited solubility it has poor and variable oral bioavailability of 10-90%. The aim of this study was to enhance the oral bioavailability of furosemide by preparation of nanosuspensions. The nanosuspensions were prepared by nanoprecipitation with sonication using DMSO (dimethyl sulfoxide) as a solvent and water as an antisolvent (NA). The prepared nanosuspensions were sterically stabilized with polyvinyl acetate (PVA).These were characterized for particle size, ζ potential, polydispersity index, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) pattern and release behavior. The effect of nanoprecipitation on oral bioavailability of furosemide nanosuspension was studied by in vitro dissolution and in vivo absorption study in rats and compared to pure drug. The stable nanosuspension was obtained with average size range of the precipitated nanoparticles between 150-300 nm and was found to be homogenous showing a narrow polydispersity index of 0.3±0.1. DSC and XRD studies indicated that the crystalline furosemide drug was converted to amorphous form upon precipitation into nanoparticles. The release profiles of nanosuspension formulation showed up to 81.2% release in 4 h. The in vivo studies on rats revealed a significant increase in the oral absorption of furosemide in the nanosuspension compared to pure drug. The AUC0→24 and Cmax values of nanosuspension were approximately 1.38 and 1.68-fold greater than that of pure drug, respectively. Furosemide nanosuspension showed 20.06±0.02 % decrease in systolic blood pressure compared to 13.37±0.02 % in plain furosemide suspension, respectively. The improved oral bioavailability and pharmacodynamics effect of furosemide may be due to the improved dissolution of furosemide in simulated gastric fluid which results in enhanced oral systemic absorption of furosemide from stomach region where it has better permeability.

Keywords: furosemide, nanosuspension, bioavailability enhancement, nanoprecipitation, oral drug delivery

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Authors: Eda Arat Maden, Ceyhan Altun, Bilal Ozmen, Feridun Basak

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Purpose: The purpose of this study was to compare the antimicrobial effect of toothpastes containing fluoride, xylitol or xylitol-probiotic in vivo, Streptococcus mutans and Lactobacillus in 13-15 years old children. Method: The study consisted of 60 pediatric patients were randomly divided into 3 groups of 20 each. Group 1 received fluoride toothpaste (Colgate Max Fresh), group 2 used xylitol toothpaste (Xyliwhite) and group 3 used xylitol-probiotic toothpaste (PerioBiotic). Subjects were asked to use the allocated dentifrice two times a day, for 6 weeks. We performed tests on the samples of saliva in the beginning of the study and after 6 weeks’ duration following the use of toothpaste. Result and Conclusion: All of the participants of the study stated that they brushed their teeth well twice a day by using the toothpastes given to them for 6 weeks. Majority of the subjects had high counts of salivary mutans streptococci and Lactobacillus at baseline. When the number of cariogenic bacteria (S. mutans and Lactobacillus) at the start of the PerioBiotic Probiotic toothpaste usage are compared with the results measured after 6 weeks, an important decrease is observed in the S. mutans and Lactobacillus bacteria according to the CRT Tests. After the 6-week use of Probiotic toothpaste, the S. mutans (≥105) decreased to 20% from 75% in the group with S. mutans and Lactobacillus (≥105) decreased to 30% from 60% in the group with Lactobacillus. In addition, an important decrease was recorded in the participants with the S. mutans percentage (80% - 45%) and Lactobacillus (70% - 55%) after using the Colgate Max Fresh toothpaste for six weeks. On the other hand, it was determined with the Chi-square that there were not important changes between the Xyliwhite toothpaste group and the other groups with S. mutans (80% - 75%) and Lactobacillus (75% -65%). It was also determined after the comparison of the groups that the decrease in the S. mutans was higher than the group using PerioBiotic Probiotic toothpaste at a significant level, when compared with the Colgate Max Fresh toothpaste and Xyliwhite toothpaste. S. mutans were more sensitive to the antimicrobial activity of the PerioBiotic Probiotic toothpaste and to the Colgate Max Fresh toothpaste when compared with the Lactobacillus. In the light of the data obtained in this in vivo study, the use of probiotics ensure the balance between the bacterial flora in the oral cavity.

Keywords: lactobacillus, probiotic, Streptococcus mutans, toothpaste

Procedia PDF Downloads 260

Authors: Miao Zhang, Limin Liu, Feng Zhi, Panpan Niu, Mengya Yang, Xuemei Zhu, Ying Diao, Jun Wang, Ying Zhao

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Background and Aims: Clinical studies have demonstrated that serum semicarbazide-sensitive amine oxidase (SSAO) activities positively correlate with the progression of atherosclerosis. The aim of the present study is to investigate the effect of SSAO inactivation on the development of atherosclerosis. Methods: Female LDLr knockout (KO) mice were given the Western-type diet for 6 and 9 weeks to induce the formation of early and advanced lesions, and semicarbazide (SCZ, 0.125%) was added into the drinking water to inactivate SSAO in vivo. Results: Despite no impact on plasma total cholesterol levels, abrogation of SSAO by SCZ not only resulted in the enlargement of both early (1.5-fold, p=0.0043) and advanced (1.8-fold, p=0.0013) atherosclerotic lesions, but also led to reduced/increased lesion contents of macrophages/smooth muscle cells (SMCs) (macrophage: ~0.74-fold, p=0.0002(early)/0.0016(advanced); SMC: ~1.55-fold, p=0.0003(early) /0.0001(advanced)), respectively. Moreover, SSAO inactivation inhibited the migration of circulating monocytes into peripheral tissues and reduced the amount of circulating Ly6Chigh monocytes (0.7-fold, p=0.0001), which may account for the reduced macrophage content in lesions. In contrast, the increased number of SMCs in lesions of SCZ-treated mice is attributed to an augmented synthetic vascular SMC phenotype switch as evidenced by the increased proliferation of SMCs and accumulation of collagens in vivo. Conclusion: SSAO inactivation by SCZ promotes the phenotypic switch of SMCs and the development of atherosclerosis. The enzymatic activity of SSAO may thus represent a potential target in the prevention and/or treatment of atherosclerosis.

Keywords: atherosclerosis, phenotype switch of smooth muscle cells, SSAO/VAP-1, semicarbazide

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Authors: Anca Maria Cimpean, Serban Comsa

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Chick embryo chorioallantoic membrane (CAM) is a well vascularised in vivo experimental model used as a platform for testing the behavior of different implants inserted on it from tumor fragments to therapeutic agents or various biomaterials. Five types of collagen-based biomaterials with 2D and 3D structure (MotifMesh, Optimaix2D, Optimaix3D, Dual Layer Collagen and Xenoderm) were implanted on CAM and continuously evaluated by stereomicroscope for up to 5 days post-implant with an emphasis of their ability to requisite and develop new blood vessels (BVs) followed by microscopic analysis. MotifMEsh did not induce any angiogenic response lacking to be invaded by BVs from the CAM, but it induced intense inflammatory response necrosis and fibroblastic reaction around the implant. Optimaix2D has good adherence. CAM with minimal or no inflammatory reaction, a good integration of the CAM between the collagen mesh’s fibers, consistent adhesion of the cells to the collagen fibers,and a good ability to form pseudo-vascular channels filled with cells. Optimaix3D induced the highest angiogenic effects on CAM. The material shows good integration on CAM. The collagen fibers of the material show the ability to organize themselves into linear and tubular structures. It is possible to see blood elements, especially at the periphery of the implant. Dual-layer collagen behaves similar to Optimaix 3D, while Xenoderm induced a moderate angiogenic effect on CAM. Based on these data, we may conclude that collagen-based materials have variable ability to requisite and develop new blood vessels. A proper selection of collagen-based biomaterial scaffolds may crucially influence the acquisition and development of blood vessels during angiogenesis assays.

Keywords: chick embryo chorioallantoic membrane, collagen scaffolds, blood vessels, vascular microenvironment

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Authors: Shahira M. Ezzat, Marwa I. Ezzat, Mona M. Okba, Esther T. Menze, Ashraf B. Abdel-Naim, Shahnas O. Mohamed

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Background: In order to decrease the burden of the high cost of synthetic drugs, it is important to focus on phytopharmaceuticals. The aim of our study was to search for the mechanism of ginger (Zingiber officinale Roscoe) anti-inflammatory potential and to correlate it to its biophytochemicals. Methods: Various extracts viz. water, 50%, 70%, 80%, and 90% ethanol were prepared from ginger rhizomes. Fractionation of the aqueous extract (AE) was accomplished using Diaion HP-20. In vitro anti-inflammatory activity of the different extracts and isolated compounds was evaluated by protein denaturation inhibition, membrane stabilization, protease inhibition, and anti-lipoxygenase assays. In vivo anti-inflammatory activity of AE was estimated by assessment of rat paw oedema after carrageenan injection. Prostaglandin E2 (PGE2), certain inflammation markers (TNF-α, IL-6, IL-1α, IL-1β, INFr, MCP-1MIP, RANTES, and Nox) levels and MPO activity in the paw edema exudates were measured. Total antioxidant capacity (TAC) was also determined. Histopathological alterations of paw tissues were scored. Results: All the tested extracts showed significant (p < 0.1) anti-inflammatory activities. The highest percentage of heat induced albumin denaturation (66%) was exhibited by the 50% ethanol (250 μg/ml). The 70 and 90% ethanol extracts (500 μg/ml) were more potent as membrane stabilizers (34.5 and 37%, respectively) than diclofenac (33%). The 80 and 90% ethanol extracts (500 μg/ml) showed maximum protease inhibition (56%). The strongest anti-lipoxygenase activity was observed for the AE. It showed more significant lipoxygenase inhibition activity than that of diclofenac (58% and 52%, respectively) at the same concentration (125 μg/ml). Fractionation of AE yielded four main fractions (Fr I-IV) which showed significant in vitro anti-inflammatory. Purification of Fr-III and IV led to the isolation of 6-poradol (G1), 6-shogaol (G2); methyl 6- gingerol (G3), 5-gingerol (G4), 6-gingerol (G5), 8-gingerol (G6), 10-gingerol (G7), and 1-dehydro-6-gingerol (G8). G2 (62.5 ug/ml), G1 (250 ug/ml), and G8 (250 ug/ml) exhibited potent anti-inflammatory activity in all studied assays, while G4 and G5 exhibited moderate activity. In vivo administration of AE ameliorated rat paw oedema in a dose-dependent manner. AE (at 200 mg/kg) showed significant reduction (60%) of PGE2 production. The AE at different doses (at 25-200 mg/kg) showed significant reduction in inflammatory markers except for IL-1α. AE (at 25 mg/kg) is superior to indomethacin in reduction of IL-1β. Treatment of animals with the AE (100, 200 mg/kg) or indomethacin (10 mg/kg) showed significant reduction in TNF-α, IL-6, MCP-1, and RANTES levels, and MPO activity by about (31, 57 and 32% ) (65, 60 and 57%) (27, 41 and 28%) (23, 32 and 23%) (66, 67 and 67%) respectively. AE at 100 and 200 mg/kg was equipotent to indomethacin in reduction of NOₓ level and in increasing the TAC. Histopathological examination revealed very few inflammatory cells infiltration and oedema after administration of AE (200 mg/kg) prior to carrageenan. Conclusion: Ginger anti-inflammatory activity is mediated by inhibiting macrophage and neutrophils activation as well as negatively affecting monocyte and leukocyte migration. Moreover, it produced dose-dependent decrease in pro-inflammatory cytokines and chemokines and replenished the total antioxidant capacity. We strongly recommend future investigations of ginger in the potential signal transduction pathways.

Keywords: anti-lipoxygenase activity, inflammatory markers, 1-dehydro-6-gingerol, 6-shogaol

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Authors: Ahmad Saad, Shuja Abbas, Breanna Marine

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Introduction: This study explores the potential applications of autologous pedal fat pad grafting as a minimally invasive therapeutic strategy for addressing pedal fat pad loss. Without adequate shock absorbing tissue, a patient can experience functional deficits, ulcerations, loss of quality of life, and significant limitations with ambulation. This study details a novel technique involving autologous adipose grafting from the abdomen to enhance plantar fat pad thickness in a patient involved in a severe motor vehicle accident which resulted in total fat pad loss of the heel. Autologous adipose grafting (AAG) was used following adipose allografting in an effort to recreate a normal shock absorbing surface to allow return to activities of daily living and painless ambulation. Methods: A 46-year-old male sustained multiple open pedal fractures and necrosis to the heel fat pad after a motorcycle accident, which resulted in complete loss of the calcaneal fat pad. The patient underwent serial debridement’s, utilization of wound vac therapy and split thickness skin grafting to accomplish complete closure, despite complete loss of adipose to area. Patient presented with complaints of pain on ambulation, inability to bear weight on the heel, recurrent ulcerations, admitted had not been ambulating for two years. Clinical exam demonstrated complete loss of the plantar fat pad with a thin layer of epithelial tissue overlying the calcaneal bone, allowing visibility of the osseous contour of the calcaneus. Scar tissue had formed in place of the fat pad, with thickened epithelial tissue extending from the midfoot to the calcaneus. After conservative measures were exhausted, the patient opted for initial management by adipose allograft matrix (AAM) injections. Post operative X-ray imaging revealed noticeable improvement in calcaneal fat pad thickness. At 1 year follow up, the patient was able to ambulate without assistive devices. The fat pad at this point was significantly thicker than it was pre-operatively, but the thickness did not restore to pre-accident thickness. In order to compare the take of allograft versus autografting of adipose tissue, the decision to use adipose autograft through abdominal liposuction harvesting was deemed suitable. A general surgeon completed harvesting of adipose cells from the patient’s abdomen via liposuction, and a podiatric surgeon performed the AAG injection into the heel. Total of 15 cc’s of autologous adipose tissue injected to the calcaneus. Results: There was a visual increase in the calcaneal fat pad thickness both clinically and radiographically. At the 6-week follow up, imaging revealed retention of the calcaneal fat pad thickness. Three months postop, patient returned to activities of daily living and increased quality of life due to their increased ability to ambulate. Discussion: AAG is a novel treatment for pedal fat pad loss. These treatments may be viable and reproducible therapeutic choices for patients suffering from fat pad atrophy, fat pad loss, and/or plantar ulcerations. Both treatments of AAM and AAG exhibited similar therapeutic results by providing pain relief for ambulation and allowing for patients to return to their quality of life.

Keywords: podiatry, wound, adipose, allograft, autograft, wound care, limb reconstruction, injection, limb salvage

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Authors: Monika Patel, Kazuaki Matsumura

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Synthetic hydrogels, with their unique properties such as porosity, strength, and swelling in aqueous environment, are being used in many fields from food additives to regenerative medicines, from diagnostic and pharmaceuticals to drug delivery systems (DDS). But, hydrogels also have some limitations in terms of homogeneity of drug distribution and quantity of loaded drugs. As an alternate, polymeric micelles are extensively used as DDS. With the ease of self-assembly, and distinct stability they remarkably improve the solubility of hydrophobic drugs. However, presently, combinational therapy is the need of time and so are systems which are capable of releasing more than one drug. And it is one of the major challenges towards DDS to control the release of each drug independently, which simple DDS cannot meet. In this work, we present an amphiphilic polypeptide based micelle hydrogel composite to study the dual drug release for wound healing purposes using Amphotericin B (AmpB) and Curcumin as model drugs. Firstly, two differently charged amphiphilic polypeptide chains were prepared namely, poly L-Lysine-b-poly phenyl alanine (PLL-PPA) and poly Glutamic acid-b-poly phenyl alanine (PGA-PPA) through ring opening polymerization of amino acid N-carboxyanhydride. These polymers readily self-assemble to form micelles with hydrophobic PPA block as core and hydrophilic PLL/PGA as shell with an average diameter of about 280nm. The thus formed micelles were loaded with the model drugs. The PLL-PPA micelle was loaded with curcumin and PGA-PPA was loaded with AmpB by dialysis method. Drug loaded micelles showed a slight increase in the mean diameter and were fairly stable in solution and lyophilized forms. For forming the micelles hydrogel composite, the drug loaded micelles were dissolved and were cross linked using genipin. Genipin uses the free –NH2 groups in the PLL-PPA micelles to form a hydrogel network with free PGA-PPA micelles trapped in between the 3D scaffold formed. Different composites were tested by changing the weight ratios of the both micelles and were seen to alter its resulting surface charge from positive to negative with increase in PGA-PPA ratio. The composites with high surface charge showed a burst release of drug in initial phase, were as the composites with relatively low net charge showed a sustained release. Thus the resultant surface charge of the composite can be tuned to tune its drug release profile. Also, while studying the degree of cross linking among the PLL-PPA particles for effect on dual drug release, it was seen that as the degree of crosslinking increases, an increase in the tendency to burst release the drug (AmpB) is seen in PGA-PPA particle, were as on the contrary the PLL-PPA particles showed a slower release of Curcumin with increasing the cross linking density. Thus, two different pharmacokinetic profile of drugs were seen by changing the cross linking degree. In conclusion, a unique charged amphiphilic polypeptide based micelle hydrogel composite for dual drug delivery. This composite can be finely tuned on the basis of need of drug release profiles by changing simple parameters such as composition, cross linking and pH.

Keywords: amphiphilic polypeptide, dual drug release, micelle hydrogel composite, tunable DDS

Procedia PDF Downloads 207

Authors: Soad Ali Yehia, Mohamed Shafik El-Ridi, Mina Ibrahim Tadros, Nolwa Gamal El-Sherif

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Fexofenadine hydrochloride (FXD) is a slightly soluble, bitter-tasting, drug having an oral bioavailability of 35%. The maximum plasma concentration is reached 2.6 hours (Tmax) post-dose. The current work aimed to develop taste-masked FXD orodispersible tablets (ODTs) to increase extent of drug absorption and reduce Tmax. Taste masking was achieved via solid dispersion (SD) with chitosan (CS) or sodium alginate (ALG). FT-IR, DSC and XRD were performed to identify physicochemical interactions and FXD crystallinity. Taste-masked FXD-ODTs were developed via addition of superdisintegrants (crosscarmelose sodium or sodium starch glycolate, 5% and 10%, w/w) or sublimable agents (camphor, menthol or thymol; 10% and 20%, w/w) to FXD-SDs. ODTs were evaluated for weight variation, drug-content, friability, wetting time, disintegration time and drug release. Camphor-based (20%, w/w) FXD-ODT (F12) was optimized (F23) by incorporation of a more hydrophilic lubricant, sodium stearyl fumarate (Pruv®). The topography of the latter formula was examined via scanning electron microscopy (SEM). The in vivo estimation of FXD pharmacokinetics, relative to Allegra® tablets, was evaluated in healthy human volunteers. Based on the gustatory sensation test in healthy volunteers, FXD:CS (1:1) and FXD:ALG (1:0.5) SDs were selected. Taste-masked FXD-ODTs had appropriate physicochemical properties and showed short wetting and disintegration times. Drug release profiles of F23 and phenylalanine-containing Allegra® ODT were similar (f2 = 96) showing a complete release in two minutes. SEM micrographs revealed pores following camphor sublimation. Compared to Allegra® tablets, pharmacokinetic studies in healthy volunteers proved F23 ability to increase extent of FXD absorption (14%) and reduce Tmax to 1.83 h.

Keywords: fexofenadine hydrochloride, taste masking, chitosan, orodispersible

Procedia PDF Downloads 343

Authors: Recep Keşli, Gülşah Aşık, Cengiz Demir, Onur Türkyılmaz

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Objective: Serratia species are identified as aerobic, motile Gram negative rods. The species Serratia marcescens (S. marcescens) causes both opportunistic and nosocomial infections. The genus Providencia is Gram-negative bacilli and includes urease-producing that is responsible for a wide range of human infections. Although most Providencia infections involve the urinary tract, they are also associated with gastroenteritis, wound infections, and bacteremia. The aim of this study was evaluate the antimicrobial resistance rates of S. marcescens and Providencia spp. strains which had been isolated from various clinical materials obtained from different patients who belongs to intensive care units (ICU) and inpatient clinics. Methods: A total of 35 S. marcescens and Providencia spp. strains isolated from various clinical samples admitted to Medical Microbiology Laboratory, ANS Research and Practice Hospital, Afyon Kocatepe University between October 2013 and September 2015 were included in the study. Identification of the bacteria was determined by conventional methods and VITEK 2 system (bio-Merieux, Marcy l’etoile, France) was used additionally. Antibacterial resistance tests were performed by using Kirby Bauer disc (Oxoid, Hampshire, England) diffusion method following the recommendations of CLSI. Results: The distribution of clinical samples were as follows: upper and lower respiratory tract samples 26, 74.2 % wound specimen 6, 17.1 % blood cultures 3, 8.5%. Of the 35 S. marcescens and Providencia spp. strains; 28, 80% were isolated from clinical samples sent from ICU. The resistance rates of S. marcescens strains against trimethoprim-sulfamethoxazole, piperacillin-tazobactam, imipenem, gentamicin, ciprofloxacin, ceftazidime, cefepime and amikacin were found to be 8.5 %, 22.8 %, 11.4 %, 2.8 %, 17.1 %, 40 %, 28.5 % and 5.7 % respectively. Resistance rates of Providencia spp. strains against trimethoprim-sulfamethoxazole, piperacillin-tazobactam, imipenem, gentamicin, ciprofloxacin, ceftazidime, cefepime and amikacin were found to be 10.2 %, 33,3 %, 18.7 %, 8.7 %, 13.2 %, 38.6 %, 26.7%, and 11.8 % respectively. Conclusion: S. marcescens is usually resistant to ampicillin, amoxicillin, amoxicillin/clavulanate, ampicillin/sulbactam, cefuroxime, cephamycins, nitrofurantoin, and colistin. The most effective antibiotic on the total of S. marcescens strains was found to be gentamicin 2.8 %, of the totally tested strains the highest resistance rate found against to ceftazidime 40 %. The lowest and highest resistance rates were found against gentamiycin and ceftazidime with the rates of 8.7 % and 38.6 % for Providencia spp.

Keywords: Serratia marcescens, Providencia spp., antibiotic resistance, intensive care unit

Procedia PDF Downloads 244

Authors: Manuel A. Alonso-Tarajano, Roberto Mosca, Patrick Aloy

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Protein kinases participate in a myriad of cellular processes of major biomedical interest. The in vivo substrate specificity of these enzymes is a process determined by several factors, and despite several years of research on the topic, is still far from being totally understood. In the present work, we have quantified the contributions to the kinase substrate specificity of i) the phosphorylation sites and their surrounding residues in the sequence and of ii) the association of kinases to adaptor or scaffold proteins. We have used position-specific scoring matrices (PSSMs), to represent the stretches of sequences phosphorylated by 93 families of kinases. We have found negative correlations between the number of sequences from which a PSSM is generated and the statistical significance and the performance of that PSSM. Using a subset of 22 statistically significant PSSMs, we have identified specificity determinant residues (SDRs) for 86% of the corresponding kinase families. Our results suggest that different SDRs can function as positive or negative elements of substrate recognition by the different families of kinases. Additionally, we have found that human proteins with known function as adaptors or scaffolds (kAS) tend to interact with a significantly large fraction of the substrates of the kinases to which they associate. Based on this characteristic we have identified a set of 279 potential adaptors/scaffolds (pAS) for human kinases, which is enriched in Pfam domains and functional terms tightly related to the proposed function. Moreover, our results show that for 74.6% of the kinase– pAS association found, the pAS colocalize with the substrates of the kinases they are associated to. Finally, we have found evidence suggesting that the association of kinases to adaptors and scaffolds, may contribute significantly to diminish the in vivo substrate crossed- specificity of protein kinases. In general, our results indicate the relevance of several SDRs for both the positive and negative selection of phosphorylation sites by kinase families and also suggest that the association of kinases to pAS proteins may be an important factor for the localization of the enzymes with their set of substrates.

Keywords: kinase, phosphorylation, substrate specificity, adaptors, scaffolds, cellular colocalization

Procedia PDF Downloads 343

Authors: Maksim Barsakov

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Introduction. In modern plastic surgery, there are a large number of breast lift techniques.Due to the spreading information about the "side effects" of silicone implants, interest in implant-free mastopexy is increasing year after year. However, despite the variety of techniques, patients sometimes do not get full satisfaction from the results of mastopexy because of the unexpressed filling of the upper pole, extended anchoring postoperative scars and sometimes because of obtaining an aesthetically unattractive breast shape. The stability of the result after mastopexy depends on many factors, including postoperative rehabilitation. Stability of weight and hormonal background, stretchability of tissues. The high recurrence rate of ptosis and short-term aesthetic effect of mastopexy indicate the urgency of improving surgical techniques and increasing the stabilization of breast tissue. Purpose of the study. To develop and introduce into practice a technique of mastopexy based on the use of a modified Ribeiro flap, as well as elements of tissue movement and fixation designed to increase the stability of postoperative mastopexy. In addition, to give indications for the application of this surgical technique. Materials and Methods. it operated on 103 patients aged 18 to 53 years from 2019 to 2023 according to the reported method. These were patients with primary mastopexy, secondary mastopexy, and also patient with implant removal and one-stage mastopexy. The patients were followed up for 12 months to assess the stability of the result. Results and their discussion. Observing the patients, we noted greater stability of the breast shape and upper pole filling compared to the conventional classical methods. We did not have to resort to anchoring scars. In 90 percent of cases, a inverted T-shape scar was used. In 10 percent, the J-scar was used. The quantitative distribution of complications identified among the operated patients is as follows: worsened healing of the junction of vertical and horizontal sutures at the period of 1-1.5 months after surgery - 15 patients; at treatment with ointment method healing was observed in 7-30 days; permanent loss of NAC sensitivity - 0 patients; vascular disorders in the area of NAC/areola necrosis - 0 patients; marginal necrosis of the areola-2 patients. independent healing within 3-4 weeks without aesthetic defects. Aesthetically unacceptable mature scars-3 patients; partial liponecrosis of the autoflap unilaterally - 1 patient. recurrence of ptosis - 1 patient (after weight loss of 12 kg). In the late postoperative period, 2 patients became pregnant, gave birth, and no lactation problems were observed. Conclusion. Thus, in the world of plastic surgery methods of breast lift continue to improve, which is especially relevant in modern times, due to the increased attention to this operation. The author's proposed method of mastopexy with glandular autoflap allows obtaining in most cases a stable result, a fuller breast shape, avoiding the presence of extended anchoring scars, and also preserves the possibility of lactation. The author of this article has obtained a patent for invention for this method of mastopexy.

Keywords: mastopexy, mammoplasty, autoflap, personal technique

Procedia PDF Downloads 36

Authors: Yuli Hou, Jianping Sun, Mengdan Gao, Hui Liu, Ling Qin, Ang Li, Dongfu Li, Yonghong Zhang, Yan Zhao

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Background and Aims: Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. IFITM3 has been recognized as a key signal molecule regulating cell growth in some tumors. However, the function of IFITM3 rs12252-CC genotype in the hepatocellular carcinoma (HCC) remains unknown to author’s best knowledge. A cohort study was employed to clarify the relationship between IFITM3 rs12252-CC genotype and HCC progression, and cellular experiments were used to investigate the correlation of function of IFITM3 and the progress of HCC. Methods: 336 candidates were enrolled in study, including 156 with HBV related HCC and 180 with chronic Hepatitis B infections or liver cirrhosis. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3. The functions of IFITM3 were detected in PLC/PRF/5 cell with different treated:LV-IFITM3 transfected with lentivirus to knockdown the expression of IFITM3 and LV-NC transfected with empty lentivirus as negative control. The IFITM3 expression, proliferation and migration were detected by Quantitative reverse transcription polymerase chain reaction (qRT-PCR), QuantiGene Plex 2.0 assay, western blotting, immunohistochemistry, Cell Counting Kit(CCK)-8 and wound healing respectively. Six samples (three infected with empty lentiviral as control; three infected with LV-IFITM3 vector lentiviral as experimental group ) of PLC/PRF/5 were sequenced at BGI (Beijing Genomics Institute, Shenzhen,China) using RNA-seq technology to identify the IFITM3-related signaling pathways and chose PI3K/AKT pathway as related signaling to verify. Results: The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC compared with the patients with chronic HBV infection or liver cirrhosis. The distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Patients with CC genotype found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes. The expression of IFITM3 was higher in HCC tissues than adjacent normal tissues, and the level of IFITM3 was higher in HCC tissues with low differentiation and metastatic than high/medium differentiation and without metastatic. Higher RNA level of IFITM3 was found in CC genotype than TT genotype. In PLC/PRF/5 cell with knockdown, the ability of cell proliferation and migration was inhibited. Analysis RNA sequencing and verification of RT-PCR found out the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) pathway was associated with knockdown IFITM3.With the inhibition of IFITM3, the expression of PI3K/AKT/mTOR signaling pathway was blocked and the expression of vimentin was decreased. Conclusions: IFITM3 rs12252-CC with the higher expression plays a vital role in the progress of HCC by regulating HCC cell proliferation and migration. These effects are associated with PI3K/AKT/mTOR signaling pathway.

Keywords: IFITM3, interferon-induced transmembrane protein 3, HCC, hepatocellular carcinoma, PI3K/ AKT/mTOR, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin

Procedia PDF Downloads 124

Authors: Glenn Auld Knierim

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Automated robotic winding of high-temperature superconductors (HTS) addresses precision, efficiency, and reliability critical to the commercialization of products. Today’s HTS materials are mature and commercially promising but require manufacturing attention. In particular to the exaggerated rectangular cross-section (very thin by very wide), winding precision is critical to address the stress that can crack the fragile ceramic superconductor (SC) layer and destroy the SC properties. Damage potential is highest during peak operations, where winding stress magnifies operational stress. Another challenge is operational parameters such as magnetic field alignment affecting design performance. Winding process performance, including precision, capability for geometric complexity, and efficient repeatability, are required for commercial production of current HTS. Due to winding limitations, current HTS magnets focus on simple pancake configurations. HTS motors, generators, MRI/NMR, fusion, and other projects are awaiting robotic wound solenoid, planar, and spherical magnet configurations. As with conventional power cables, full transposition winding is required for long length alternating current (AC) and pulsed power cables. Robotic production is required for transposition, periodic swapping of cable conductors, and placing into precise positions, which allows power utility required minimized reactance. A full transposition SC cable, in theory, has no transmission length limits for AC and variable transient operation due to no resistance (a problem with conventional cables), negligible reactance (a problem for helical wound HTS cables), and no long length manufacturing issues (a problem with both stamped and twisted stacked HTS cables). The Infinity Physics team is solving manufacturing problems by developing automated manufacturing to produce the first-ever reliable and utility-grade commercial SC cables and magnets. Robotic winding machines combine mechanical and process design, specialized sense and observer, and state-of-the-art optimization and control sequencing to carefully manipulate individual fragile SCs, especially HTS, to shape previously unattainable, complex geometries with electrical geometry equivalent to commercially available conventional conductor devices.

Keywords: automated winding manufacturing, high temperature superconductor, magnet, power cable

Procedia PDF Downloads 140

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

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

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

Procedia PDF Downloads 397

Authors: Aditya Arya, Hairin Taha, Ataul Karim Khan, Nayiar Shahid, Hapipah Mohd Ali, Mustafa Ali Mohd

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This study has investigated the antidiabetic and antioxidant potential of Pseudovaria macrophylla bark extract on streptozotocin–nicotinamide induced type 2 diabetic rats. LCMS-QTOF and NMR experiments were done to determine the chemical composition in the methanolic bark extract. For in vivo experiments, the STZ (60 mg/kg/b.w, 15 min after 120 mg/kg/1 nicotinamide, i.p.) induced diabetic rats were treated with methanolic extract of Pseuduvaria macrophylla (200 and 400 mg/kg∙bw) and glibenclamide (2.5 mg/kg) as positive control respectively. Biochemical parameters were assayed in the blood samples of all groups of rats. The pro-inflammatory cytokines, antioxidant status and plasma transforming growth factor βeta-1 (TGF-β1) were evaluated. The histological study of the pancreas was examined and its expression level of insulin was observed by immunohistochemistry. In addition, the expression of glucose transporters (GLUT 1, 2 and 4) were assessed in pancreas tissue by western blot analysis. The outcomes of the study displayed that the bark methanol extract of Pseuduvaria macrophylla has potentially normalized the elevated blood glucose levels and improved serum insulin and C-peptide levels with significant increase in the antioxidant enzyme, reduced glutathione (GSH) and decrease in the level of lipid peroxidation (LPO). Additionally, the extract has markedly decreased the levels of serum pro-inflammatory cytokines and transforming growth factor beta-1 (TGF-β1). Histopathology analysis demonstrated that Pseuduvaria macrophylla has the potential to protect the pancreas of diabetic rats against peroxidation damage by downregulating oxidative stress and elevated hyperglycaemia. Furthermore, the expression of insulin protein, GLUT-1, GLUT-2 and GLUT-4 in pancreatic cells was enhanced. The findings of this study support the anti-diabetic claims of Pseudovaria macrophylla bark.

Keywords: diabetes mellitus, Pseuduvaria macrophylla, alkaloids, caffeic acid

Procedia PDF Downloads 357

Authors: Chee Wee Gan, Anthony Herr Cheun Ng, Yee Shan Wong, Subbu Venkatraman, Lynne Hsueh Yee Lim

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Otitis media with effusion (OME) is the leading cause of hearing loss in children worldwide. Surgery to insert grommet tube into the eardrum is usually indicated for OME unresponsive to antimicrobial therapy. It is the most common surgery for children. However, current commercially available grommet tubes are non-bioresorbable, not drug-treated, with unpredictable duration of retention on the eardrum to ventilate middle ear. Their functionality is impaired when clogged or chronically infected, requiring additional surgery to remove/reinsert grommet tubes. We envisaged that a novel fully bioresorbable grommet tube with sustained antibiotic release technology could address these drawbacks. In this study, drug-loaded bioresorbable poly(L-lactide-co-ε-caprolactone)(PLC) copolymer grommet tubes were fabricated by microinjection moulding technique. In vitro drug release and degradation model of PLC tubes were studied. Antibacterial property was evaluated by incubating PLC tubes with P. aeruginosa broth. Surface morphology was analyzed using scanning electron microscopy. A preliminary animal study was conducted using guinea pigs as an in vivo model to evaluate PLC tubes with and without drug, with commercial Mini Shah grommet tube as comparison. Our in vitro data showed sustained drug release over 3 months. All PLC tubes revealed exponential degradation profiles over time. Modeling predicted loss of tube functionality in water to be approximately 14 weeks and 17 weeks for PLC with and without drug, respectively. Generally, PLC tubes had less bacteria adherence, which were attributed to the much smoother tube surfaces compared to Mini Shah. Antibiotic from PLC tube further made bacteria adherence on surface negligible. They showed neither inflammation nor otorrhea after 18 weeks post-insertion in the eardrums of guinea pigs, but had demonstrated severe degree of bioresorption. Histology confirmed the new PLC tubes were biocompatible. Analyses on the PLC tubes in the eardrums showed bioresorption profiles close to our in vitro degradation models. The bioresorbable antibiotic-loaded grommet tubes showed good predictability in functionality. The smooth surface and sustained release technology reduced the risk of tube infection. Tube functional duration of 18 weeks allowed sufficient ventilation period to treat OME. Our ongoing studies include modifying the surface properties with protein coating, optimizing the drug dosage in the tubes to enhance their performances, evaluating their functional outcome on hearing after full resoption of grommet tube and healing of eardrums, and developing animal model with OME to further validate our in vitro models.

Keywords: bioresorbable polymer, drug release, grommet tube, guinea pigs, otitis media with effusion

Procedia PDF Downloads 450

Authors: Kayla Belanger, Pascale Vigneron, Guy Schlatter, Bernard Devauchelle, Christophe Egles

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A severe injury to a peripheral nerve leads to its degeneration and the loss of sensory and motor function. To this day, there still lacks a more effective alternative to the autograft which has long been considered the gold standard for nerve repair. In order to overcome the numerous drawbacks of the autograft, tissue engineered biomaterials may be effective alternatives. Silk fibroin is a favorable biomaterial due to its many advantageous properties such as its biocompatibility, its biodegradability, and its robust mechanical properties. In this study, bio-mimicking multi-channeled nerve guidance conduits made of aligned nanofibers achieved by electrospinning were functionalized with signaling biomolecules and were tested in vitro and in vivo for nerve regeneration support. Silk fibroin (SF) extracted directly from silkworm cocoons was put in solution at a concentration of 10wt%. Poly(ethylene oxide) (PEO) was added to the resulting SF solution to increase solution viscosity and the following three electrospinning solutions were made: (1) SF/PEO solution, (2) SF/PEO solution with nerve growth factor and ciliary neurotrophic factor, and (3) SF/PEO solution with nerve growth factor and neurotrophin-3. Each of these solutions was electrospun into a multi-layer architecture to obtain mechanically optimized aligned nanofibrous mats. For in vitro studies, aligned fibers were treated to induce β-sheet formation and thoroughly rinsed to eliminate presence of PEO. Each material was tested using rat embryo neuron cultures to evaluate neurite extension and the interaction with bio-functionalized or non-functionalized aligned fibers. For in vivo studies, the mats were rolled into 5mm long multi-, micro-channeled conduits then treated and thoroughly rinsed. The conduits were each subsequently implanted between a severed rat sciatic nerve. The effectiveness of nerve repair over a period of 8 months was extensively evaluated by cross-referencing electrophysiological, histological, and movement analysis results to comprehensively evaluate the progression of nerve repair. In vitro results show a more favorable interaction between growing neurons and bio-functionalized silk fibers compared to pure silk fibers. Neurites can also be seen having extended unidirectionally along the alignment of the nanofibers which confirms a guidance factor for the electrospun material. The in vivo study has produced positive results for the regeneration of the sciatic nerve over the length of the study, showing contrasts between the bio-functionalized material and the non-functionalized material along with comparisons to the experimental control. Nerve regeneration has been evaluated not only by histological analysis, but also by electrophysiological assessment and motion analysis of two separate natural movements. By studying these three components in parallel, the most comprehensive evaluation of nerve repair for the conduit designs can be made which can, therefore, more accurately depict their overall effectiveness. This work was supported by La Région Picardie and FEDER.

Keywords: electrospinning, nerve guidance conduit, peripheral nerve regeneration, silk fibroin

Procedia PDF Downloads 246

Authors: Lori Lioce, Gary Maddux, Norven Goddard, Ishella Fogle, Bernard Schroer

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This paper presents the integration of technologies into nursing education. The collaborative effort includes the College of Nursing (CoN) at the University of Alabama in Huntsville (UAH) and the UAH Systems Management and Production Center (SMAP). The faculty at the CoN conducts needs assessments to identify education and training requirements. A team of CoN faculty and SMAP engineers then prioritize these requirements and establish improvement/development teams. The development teams consist of nurses to evaluate the models and to provide feedback and of undergraduate engineering students and their senior staff mentors from SMAP. The SMAP engineering staff develops and creates the physical models using 3D printing, silicone molds and specialized molding mixtures and techniques. The collaboration has focused on developing teaching and training, or clinical, simulators. In addition, the onset of the Covid-19 pandemic has intensified this relationship, as 3D modeling shifted to supplied personal protection equipment (PPE) to local health care providers. A secondary collaboration has been introducing students to clinical benchmarking through the UAH Center for Management and Economic Research. As a result of these successful collaborations the Model Exchange & Development of Nursing & Engineering Technology (MEDNET) has been established. MEDNET seeks to extend and expand the linkage between engineering and nursing to K-12 schools, technical schools and medical facilities in the region to the resources available from the CoN and SMAP. As an example, stereolithography (STL) files of the 3D printed models, along with the specifications to fabricate models, are available on the MEDNET website. Ten 3D printed models have been developed and are currently in use by the CoN. The following additional training simulators are currently under development:1) suture pads, 2) gelatin wound models and 3) printed wound tattoos. Specification sheets have been written for these simulations that describe the use, fabrication procedures and parts list. These specifications are available for viewing and download on MEDNET. Included in this paper are 1) descriptions of CoN, SMAP and MEDNET, 2) collaborative process used in product improvement/development, 3) 3D printed models of training and teaching simulators, 4) training simulators under development with specification sheets, 5) family care practice benchmarking, 6) integrating the simulators into the nursing curriculum, 7) utilizing MEDNET as a pandemic response, and 8) conclusions and lessons learned.

Keywords: 3D printing, nursing education, simulation, trainers

Procedia PDF Downloads 122

Authors: Martin Tazky, Rudolf Hela, Lucia Osuska, Petr Novosad

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Concrete’s volumetric changes are natural process caused by silicate minerals’ hydration. These changes can lead to cracking and subsequent destruction of cementitious material’s matrix. In most cases, cracks can be assessed as a negative effect of hydration, and in all cases, they lead to an acceleration of degradation processes. Preventing the formation of these cracks is, therefore, the main effort. Once of the possibility how to eliminate this natural concrete shrinkage process is by using different types of dispersed reinforcement. For this application of concrete shrinking, steel and polymer reinforcement are preferably used. Despite ordinarily used reinforcement in concrete to eliminate shrinkage it is possible to look at this specific problematic from the beginning by itself concrete mix composition. There are many secondary raw materials, which are helpful in reduction of hydration heat and also with shrinkage of concrete during curing. The new science shows the possibilities of shrinkage reduction also by the controlled formation of hydration products, which could act by itself morphology as a traditionally used dispersed reinforcement. This contribution deals with the possibility of controlled formation of mono- and tri-sulfate which are considered like degradation minerals. Mono- and tri- sulfate's controlled formation in a cementitious composite can be classified as a self-healing ability. Its crystal’s growth acts directly against the shrinking tension – this reduces the risk of cracks development. Controlled formation means that these crystals start to grow in the fresh state of the material (e.g. concrete) but stop right before it could cause any damage to the hardened material. Waste materials with the suitable chemical composition are very attractive precursors because of their added value in the form of landscape pollution’s reduction and, of course, low cost. In this experiment, the possibilities of using the fly ash from fluidized bed combustion as a mono- and tri-sulphate formation additive were investigated. The experiment itself was conducted on cement paste and concrete and specimens were subjected to a thorough analysis of physicomechanical properties as well as microstructure from the moment of mixing up to 180 days. In cement composites, were monitored the process of hydration and shrinkage. In a mixture with the used admixture of fluidized bed combustion fly ash, possible failures were specified by electronic microscopy and dynamic modulus of elasticity. The results of experiments show the possibility of shrinkage concrete reduction without using traditionally dispersed reinforcement.

Keywords: shrinkage, monosulphates, trisulphates, self-healing, fluidized fly ash

Procedia PDF Downloads 186

Authors: Pengzhou Lu, Liming Xin, Payam Tavakoli, Zhonghua Lin, Roberto V. P. Ribeiro, Mitesh V. Badiwala

Abstract:

Ex vivo Heart Perfusion (EVHP) has been developed as an alternative strategy to expand cardiac donation by enabling resuscitation and functional assessment of hearts donated from marginal donors, which were previously not accepted. EVHP parameters, such as perfusion flow (PF) and perfusion pressure (PP) are crucial for optimal organ preservation. However, with the heart’s constant physiological changes during EVHP, such as coronary vascular resistance, manual control of these parameters is rendered imprecise and cumbersome for the operator. Additionally, low control precision and the long adjusting time may lead to irreversible damage to the myocardial tissue. To solve this problem, an automatic heart perfusion system was developed by applying a Human-Machine Interface (HMI) and a Programmable-Logic-Controller (PLC)-based circuit to control PF and PP. The PLC-based control system collects the data of PF and PP through flow probes and pressure transducers. It has two control modes: the RPM-flow mode and the pressure mode. The RPM-flow control mode is an open-loop system. It influences PF through providing and maintaining the desired speed inputted through the HMI to the centrifugal pump with a maximum error of 20 rpm. The pressure control mode is a closed-loop system where the operator selects a target Mean Arterial Pressure (MAP) to control PP. The inputs of the pressure control mode are the target MAP, received through the HMI, and the real MAP, received from the pressure transducer. A PID algorithm is applied to maintain the real MAP at the target value with a maximum error of 1mmHg. The precision and control speed of the RPM-flow control mode were examined by comparing the PLC-based system to an experienced operator (EO) across seven RPM adjustment ranges (500, 1000, 2000 and random RPM changes; 8 trials per range) tested in a random order. System’s PID algorithm performance in pressure control was assessed during 10 EVHP experiments using porcine hearts. Precision was examined through monitoring the steady-state pressure error throughout perfusion period, and stabilizing speed was tested by performing two MAP adjustment changes (4 trials per change) of 15 and 20mmHg. A total of 56 trials were performed to validate the RPM-flow control mode. Overall, the PLC-based system demonstrated the significantly faster speed than the EO in all trials (PLC 1.21±0.03, EO 3.69±0.23 seconds; p < 0.001) and greater precision to reach the desired RPM (PLC 10±0.7, EO 33±2.7 mean RPM error; p < 0.001). Regarding pressure control, the PLC-based system has the median precision of ±1mmHg error and the median stabilizing times in changing 15 and 20mmHg of MAP are 15 and 19.5 seconds respectively. The novel PLC-based control system was 3 times faster with 60% less error than the EO for RPM-flow control. In pressure control mode, it demonstrates a high precision and fast stabilizing speed. In summary, this novel system successfully controlled perfusion flow and pressure with high precision, stability and a fast response time through a user-friendly interface. This design may provide a viable technique for future development of novel heart preservation and assessment strategies during EVHP.

Keywords: automatic control system, biomedical engineering, ex-vivo heart perfusion, human-machine interface, programmable logic controller

Procedia PDF Downloads 175

Authors: Kruttika Bhuse

Abstract:

Aim: Synergism between periodontists and orthodontists (periodontal accelerated osteogenic orthodontics- PAOO) creates crucial opportunities to enhance clinical outcomes of combined therapies regarding both disciplines and has made adult orthodontics a reality. Thus, understanding the biomechanics of bone remodelling may increase the clinical applications of corticotomy facilitated orthodontics with or without alveolar augmentation. Wilckodontics can be an attractive treatment option and be a “win-win” situation for both the dental surgeon and patient by reducing the orthodontic treatment time in adults. Materials and methods: In this review, data related to the clinical aspects, steps of procedure, biomechanics of bone, indications and contraindications and final outcome of wilckodontic shall be discussed. 50 supporting articles from various international journals and 70 clinical cases were reviewed to get a better understanding to design this wilckodontic - meta analysis. Various journals like the Journal Of Clinical And Diagnostic Research, Journal Of Indian Society Of Periodontology, Journal Of Periodontology, Pubmed, Boston Orthodontic University Journal, Good Practice Orthodontics Volume 2, have been referred to attain valuable information on wilckodontics which was then compiled in this single review study. Result: As a promising adjuvant technique based on the transient nature of demineralization-remineralisation process in healthy tissues, wilckodontics consists of regional acceleratory phenomenon by alveolar corticotomy and bone grafting of labial and palatal/lingual surfaces, followed by orthodontic force. The surgical wounding of alveolar bone potentiates tissue reorganization and healing by a way of transient burst of localized hard and soft tissue remodelling.This phenomenon causes bone healing to occur 10-50 times faster than normal bone turnover. Conclusion: This meta analysis helps understanding that the biomechanics of bone remodelling may increase the clinical applications of corticotomy facilitated orthodontics with or without alveolar augmentation. The main benefits being reduced orthodontic treatment time, increased bone volume and post-orthodontic stability.

Keywords: periodontal osteogenic accelerated orthodontics, alveolar corticotomy, bone augmentation, win-win situation

Procedia PDF Downloads 391