Search results for: kidney encapsulation

Authors: S. El Ballal, H. El Sabbagh, M. Abd El Gaber, A. Eisa, A. Al Gamal

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Cadmium is one of the most harmful heavy metals able to induce severe injury. In this study, sixty four male Sprague Dawley rats weighing (70-80 gm) were used. Rats were divided into 4 groups each group of 16 rats. Group A: served as control and received commercial ration and distilled water Group B: cadmium chloride was administered orally in water at dose of 300 ppm cadmium (560 mg/L as CdCl2). Group C: Animals received cadmium in drinking water in addition to administration of N-acetylcysteine (NAC) orally at a dose of 150 mg/kg body weight, equivalent to 1500 ppm in food. Group D: Animals received cadmium in drinking water in addition to administration of alpha lipoic acid (ALA) orally at a dose of 150 mg/kg body weight, equivalent to 1500 ppm in food. The experiment was continued for 2 months. Collection of blood and tissue samples was performed at 2, 4, 6, 8 weeks. Blood sample were collected for serum biochemical analysis including malondialdehyde (MDA), total antioxidants, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, albumin, urea and uric acid. Tissue specimens were collected for histopathological examination including liver, kidney, brain and testis. Histopathological examination revealed that cadmium choloride induces pathological alterations which increased in severity with time. The use of NAC and ALA can ameliorate toxic effect of CdCl2. The results showed significant decrease MDA and significant increase total antioxidants in group C and D compared to group B, Liver enzymes include AST and ALT showed significant decrease. Regarding to results of total protein and albumin, they revealed significant increase. Urea and uric acid showed significant decrease. From our study we conclude that NAC and ALA have protective effect against cadmium toxicity.

Keywords: ALA, cadmium, histopathology, NAC

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Authors: M. Grandcolas, N. Rival, H. Bu, S. Jahren, R. Schmid, H. Johnsen

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The concept of an autonomic self-healing material, where initiation of repair is integrated to the material, is now being considered for engineering applications and is a hot topic in the literature. Among several concepts/techniques, two are most interesting: i) Capsules: Integration of microcapsules in or at the surface of coatings or fibre-like structures has recently gained much attention. Upon damage-induced cracking, the microcapsules are broken by the propagating crack fronts resulting in a release of an active chemical (healing agent) by capillary action, subsequently repairing and avoiding further crack growth. ii) Self-healing polymers: Interestingly, the introduction of dynamic covalent bonds into polymer networks has also recently been used as a powerful approach towards the design of various intrinsically self-healing polymer systems. The idea behind this is to reconnect the chemical crosslinks which are broken when a material fractures, restoring the integrity of the material and thereby prolonging its lifetime. We propose here to integrate both self-healing concepts (capsules, self-healing polymers) in electrospun fibres and coatings. Different capsule preparation approaches have been investigated in SINTEF. The most advanced method to produce capsules is based on emulsification to create a water-in-oil emulsion before polymerisation. The healing agent is a polyurethane-based dispersion that was encapsulated in shell materials consisting of urea-benzaldehyde resins. Results showed the successful preparation of microcapsules and release of the agent when capsules break. Since capsules are produced in water-in-oil systems we mainly investigated organic solvent based coatings while a major challenge resides in the incorporation of capsules into water-based coatings. We also focused on developing more robust microcapsules to prevent premature rupture of the capsules. The capsules have been characterized in terms of size, and encapsulation and release might be visualized by incorporating fluorescent dyes and examine the capsules by microscopy techniques. Alternatively, electrospinning is an innovative technique that has attracted enormous attention due to unique properties of the produced nano-to-micro fibers, ease of fabrication and functionalization, and versatility in controlling parameters. Especially roll-to-roll electrospinning is a unique method which has been used in industry to produce nanofibers continuously. Electrospun nanofibers can usually reach a diameter down to 100 nm, depending on the polymer used, which is of interest for the concept with self-healing polymer systems. In this work, we proved the feasibility of fabrication of POSS-based (POSS: polyhedral oligomeric silsesquioxanes, tradename FunzioNano™) nanofibers via electrospinning. Two different formulations based on aqueous or organic solvents have shown nanofibres with a diameter between 200 – 450nm with low defects. The addition of FunzioNano™ in the polymer blend also showed enhanced properties in term of wettability, promising for e.g. membrane technology. The self-healing polymer systems developed are here POSS-based materials synthesized to develop dynamic soft brushes.

Keywords: capsules, coatings, electrospinning, fibers

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Authors: Gabriela Wyszogrodzka, Przemyslaw Dorozynski, Barbara Gil, Maciej Strzempek, Bartosz Marszalek, Piotr Kulinowski, Wladyslaw Piotr Weglarz, Elzbieta Menaszek

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MOFs (Metal-Organic Frameworks) belong to a new group of porous materials with a hybrid organic-inorganic construction. Their structure is a network consisting of metal cations or clusters (acting as metallic centers, nodes) and the organic linkers between nodes. The interest in MOFs is primarily associated with the use of their well-developed surface and large porous. Possibility to build MOFs of biocompatible components let to use them as potential drug carriers. Furthermore, forming MOFs structure from cations possessing paramagnetic properties (e.g. iron cations) allows to use them as MRI (Magnetic Resonance Imaging) contrast agents. The concept of formation of particles that combine the ability to transfer active substance with imaging properties has been called theranostic (from words combination therapy and diagnostics). By building MOF structure from iron cations it is possible to use them as theranostic agents and monitoring the distribution of the active substance after administration in real time. In the study iron-MOF: Fe-MIL-101-NH2 was chosen, consisting of iron cluster in nodes of the structure and amino-terephthalic acid as a linker. The aim of the study was to investigate the possibility of applying Fe-MIL-101-NH2 as inhalable theranostic particulate system for the first-line anti-tuberculosis antibiotic – isoniazid. The drug content incorporated into Fe-MIL-101-NH2 was evaluated by dissolution study using spectrophotometric method. Results showed isoniazid encapsulation efficiency – ca. 12.5% wt. Possibility of Fe-MIL-101-NH2 application as the MRI contrast agent was demonstrated by magnetic resonance tomography. FeMIL-101-NH2 effectively shortening T1 and T2 relaxation times (increasing R1 and R2 relaxation rates) linearly with the concentrations of suspended material. Images obtained using multi-echo magnetic resonance imaging sequence revealed possibility to use FeMIL-101-NH2 as positive and negative contrasts depending on applied repetition time. MOFs micronization via ultrasound was evaluated by XRD, nitrogen adsorption, FTIR, SEM imaging and did not influence their crystal shape and size. Ultrasonication let to break the aggregates and achieve very homogeneously looking SEM images. MOFs cytotoxicity was evaluated in in vitro test with a highly sensitive resazurin based reagent PrestoBlue™ on L929 fibroblast cell line. After 24h no inhibition of cell proliferation was observed. All results proved potential possibility of application of ironMOFs as an isoniazid carrier and as MRI contrast agent in inhalatory treatment of tuberculosis. Acknowledgments: Authors gratefully acknowledge the National Science Center Poland for providing financial support, grant no 2014/15/B/ST5/04498.

Keywords: imaging agents, metal-organic frameworks, theranostics, tuberculosis

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Authors: X. King, E. Nazarzadeh, J. Reboud, J. Cooper

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Pulmonary diseases, such as asthma, are generally treated by the inhalation of aerosols that has the advantage of reducing the off-target (e.g., toxicity) effects associated with systemic delivery in blood. Effective respiratory drug delivery requires a droplet size distribution between 1 and 5 µm. Inhalation of aerosols with wide droplet size distribution, out of this range, results in deposition of drug in not-targeted area of the respiratory tract, introducing undesired side effects on the patient. In order to solely deliver the drug in the lower branches of the lungs and release it in a targeted manner, a control mechanism to produce the aerosolized droplets is required. To regulate the drug release and to facilitate the uptake from cells, drugs are often encapsulated into protective liposomes. However, a multistep process is required for their formation, often performed at the formulation step, therefore limiting the range of available drugs or their shelf life. Using surface acoustic waves (SAWs), a pulmonary drug delivery platform was produced, which enabled the formation of defined size aerosols and the formation of liposomes in situ. SAWs are mechanical waves, propagating along the surface of a piezoelectric substrate. They were generated using an interdigital transducer on lithium niobate with an excitation frequency of 9.6 MHz at a power of 1W. Disposable silicon superstrates were etched using photolithography and dry etch processes to create an array of cylindrical through-holes with different diameters and pitches. Superstrates were coupled with the SAW substrate through water-based gel. As the SAW propagates on the superstrate, it enables nebulisation of a lipid solution deposited onto it. The cylindrical cavities restricted the formation of large drops in the aerosol, while at the same time unilamellar liposomes were created. SAW formed liposomes showed a higher monodispersity compared to the control sample, as well as displayed, a faster production rate. To test the aerosol’s size, dynamic light scattering and laser diffraction methods were used, both showing the size control of the aerosolised particles. The use of silicon superstate with cavity size of 100-200 µm, produced an aerosol with a mean droplet size within the optimum range for pulmonary drug delivery, containing the liposomes in which the medicine could be loaded. Additionally, analysis of liposomes with Cryo-TEM showed formation of vesicles with narrow size distribution between 80-100 nm and optimal morphology in order to be used for drug delivery. Encapsulation of nucleic acids in liposomes through the developed SAW platform was also investigated. In vitro delivery of siRNA and DNA Luciferase were achieved using A549 cell line, lung carcinoma from human. In conclusion, SAW pulmonary drug delivery platform was engineered, in order to combine multiple time consuming steps (formation of liposomes, drug loading, nebulisation) into a unique platform with the aim of specifically delivering the medicament in a targeted area, reducing the drug’s side effects.

Keywords: acoustics, drug delivery, liposomes, surface acoustic waves

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Authors: Mardiana Madjid, Nurpudji Astuti Taslim, Suryani As'ad, Haerani Rasyid, Agussalim Bukhari

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The high level of Urine Urea Nitrogen (UUN) indicates hypercatabolism occurs in hospitalized patients. High levels of Total Lymphocyte Count (TLC) indicates the immune system condition, adequate wound healing, and limit complication. Adequate dietary intake affects to decrease of hypercatabolism status in treated patient’s hospitals. Nitrogen Balance (NB) is simply the difference between nitrogen (N₂) intake and output. If more N₂ intake than output, then positive NB or anabolic will occur. This study aims to evaluate the effect of dietary intake in influencing balance nitrogen and total lymphocyte count. Method: A total of 43 patients admitted to a Wahidin Sudirohusodo Hospital between 2018 and 2019 for 10 days' treats are included. The inclusion criteria were patients who were treated for 10 days and receives food from the hospital orally. Patients did not experience gastrointestinal disorders such as vomiting and diarrhea and experience impair kidney function and liver function and expressed approval to participate in this study. During hospitalization, food intake, UUN, albumin serum, balance nitrogen, and TLC was assessed twice on day 1 and day 10. There is no Physician Clinical Nutritional intervention to correct food intake. UUN is 24 hours of urine collected on the second day after admission and the tenth day. Statistical analysis uses SPSS 24 with observational cohort methods. Result: The Forty-three participants completed the follow-up (27 men and 18 women). The age of fewer than 4 years is 22 people, 45 to 60 years is 16 people, and over 60 years is 4 people. The result of the study on day 1 obtained SGA score A, SGA score B, SGA score C are 8, 32, 3 until day 10 are 8, 31, 4, respectively. According to 24h dietary recalls, the energy intake during observation was from 522.5 ± 400.4 to 1011.9 ± 545.1 kcal/day P < 0.05, protein intake from 20.07 ± 17.2 to 40.3 ± 27.3 g/day P < 0.05, carbohydrates from 92.5 ± 71.6 to 184.8 ± 87.4 g/day, and fat from 5.5 ± 3.86 to 13.9 ± 13.9 g/day. The UUN during the observation was from 6.6 ± 7.3 to 5.5 ± 3.9 g/day, TLC decreased from 1622.9 ± 897.2 to 1319.9 ± 636.3/mm³ value target 1800/mm³, albumin serum from 3.07 ± 0.76 to 2.9 ± 0.57 g/day, and BN from -7.5 ± 7.2 to -3.1 ± 4.86. Conclusion: The high level of UUN needs to correct adequate dietary intake to improve NB and TLC status on hospitalized patients.

Keywords: adequate dietary intake, balance nitrogen, total lymphocyte count, urine urea nitrogen

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Authors: Rima Al Garni, Emad Al Shdaifat, Sahar Elmetwalli, Mohammad Alzaid, Abdulrahman Alghothayyan, Sara Al Abd Al Hai, Seham Al Rashidi

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Aim: To investigate the prevalence of non-adherence of patients on haemodialysis and explore their perception of the importance of adherence to the therapeutic regime and estimate the predictors for adherence to the therapeutic regime. Background: End-stage renal disease is commonly treated by haemodialysis. Haemodialysis treatment alone is not effective in replacing kidney function. Diet and fluid restrictions, along with supplementary medications, are mandatory for the survival and well-being of patients. Hence, adherence to this therapeutic regimen is essential. However, non-adherence to diet and fluid restrictions, medications, and dialysis is common among patients on haemodialysis. Design: Descriptive cross-sectional method was applied to investigate the prevalence of non-adherence to treatment, including adherence to diet and fluid restrictions, medications, and dialysis sessions. Methods: Structured interviews were conducted using the Arabic version of the End-Stage Renal Disease Adherence Questionnaire. The sample included 230 patients undergoing haemodialysis in the Eastern Region of Saudi Arabia. Data were analysed using descriptive statistics and multiple regressions. Results/Findings: Most patients had good adherence (71.3%), and only 3.9% had poor adherence. The divorced or widowed patient had higher adherence compared with single (P=0.011) and married participants (P=0.045) through using the post hoc test. Patients above 60 years had higher adherence compared to patients below 40 years old (P=0.016) using the post hoc test. For the perception of the importance of adherence to the therapeutic regime subscale, two-thirds of the patients had lower scores (<=11). Conclusion: Adherence to therapeutic regime is high for three fourth of patients undergoing haemodialysis in the Eastern Region of Saudi Arabia; this finding is similar to results abstracted from the local literature. This result would help us highlight the needs of patients who are not compliant with their treatment plans and investigate the consequences of non-adherence on their well-being and general health. Hence, plan individualised therapeutic programmes that could raise their awareness and influence their adherence to therapeutic regimes.

Keywords: adherence to treatment, haemodialysis, end stage renal disease, diet and fluid restrictions

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Authors: Arman Kishan, Sanjay Kubsad, Steve Li, Mark Haft, Duc Nguyen, Dawn Laporte

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Objective: Carpal tunnel syndrome can be managed surgically with endoscopic or open carpal tunnel release (CTR). Rheumatoid arthritis (RA) is a known risk factor for Carpal Tunnel Syndrome (CTS) and is believed to be related to compression of the median nerve secondary to inflammation. We aimed to analyze national trends, outcomes, and patient-specific comorbidities associated with ECTR and OCTR in patients with RA. Methods: A retrospective cohort study was conducted using the PearlDiver database, identifying 683 RA patients undergoing ECTR and 4234 undergoing OCTR between 2010 and 2014. Demographic data, comorbidities, and complication rates were analyzed. Univariate and multivariable analyses assessed differences between the treatment methods. Results:  Patients with RA undergoing ECTR in comparison to OCTR had no significant differences in medical comorbidities such as hypertension, obesity, chronic kidney disease, hypothyroidism and diabetes mellitus. Patients in the ECTR group reported a risk ratio of 1.44 (95%CI: 1.10-1.89, p=0.01) of requiring repeat procedures within 90 days of the initial procedure. Five-year trends in ECTR and OCTR procedures reported a combined annual growth rate of 5.6% and 13.15, respectively. Conclusion: Endoscopic and open approaches to CTR are important considerations in surgical planning. RA and ECTR have previously been identified as independent risk factors for revision CTR. Our study has identified the 90-day risk of repeat procedures to be elevated in the ECTR group in comparison to the OCTR group. Additionally, the growth of OCTR procedures has outpaced the growth of ECTR procedures in the same period, likely in response to the trend of ECTR leading to higher rates of repeat procedures. The need for revision following ECTR in patients with RA could be related to chronic inflammation leading to transverse carpal ligament thickening and concomitant tenosynovitis. Future directions could include further characterization of repeat procedures performed in this subset of patients. 

Keywords: endoscopic treatment of carpal tunnel syndrome, open treatment of carpal tunnel syndrome, rheumatoid arthritis, trends analysis, carpal tunnel syndrome

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Authors: Sunghee Nam

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Entomopathogenic fungi is a Cordyceps species that is isolated from dead silkworm and cicada. Fungi on cicadas were described in old Chinese medicinal books and from ancient times, vegetable wasps and plant worms were widely known to have active substance and have been studied for pharmacological use. Among many fungi belonging to the genus Cordyceps, Cordyceps sinensis have been demonstrated to yield natural products possessing various biological activities and many bioactive components. Generally, It is commonly used to replenish the kidney and soothe the lung, and for the treatment of fatigue. Due to their commercial and economic importance, the demand for Cordyceps has been rapidly increased. However, a supply of Cordyceps specimen could not meet the increasing demand because of their sole dependence on field collection and habitat destruction. Because it is difficult to obtain many insect hosts in nature and the edibility of host insect needs to be verified in a pharmacological aspect. Recently, this setback was overcome that P. tenuipes was able to be cultivated in a large scale using silkworm as host. Pharmacological effects of P. tenuipes cultured on silkworm such as strengthening immune function, anti-fatigue, anti-tumor activity and controlling liver etc. have been proved. They are widely commercialized. In this study, we attempted to establish a method for stable growth inhibition of P. tenuipes on silkworm hosts and an optimal condition for synnemata formation. To determine optimum culturing conditions, temperature and light conditions were varied. The length and number of synnemata was highest at 25℃ temperature and 100~300 lux illumination. On an average, the synnemata of wild P. tenuipes measures 70 ㎜ in length and 20 in number; those of the cultured strain were relatively shorter and more in number. The number of synnemata may have increased as a result of inoculating the host with highly concentrated conidia, while the length may have decreased due to limited nutrition per individual. It is not able that changes in light illumination cause morphological variations in the synnemata. However, regulation of only light and temperature could not produce stromata like perithecia, asci, and ascospores.

Keywords: optimization of culture conditions of paecilomyces tenuipes, entomopathogenic fungi optimization of culture conditions of paecilomyces tenuipes, entomopathogenic fungi silkworm larva, bombyx mori

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Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

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Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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Authors: Hansraj Bookun, Angela Tan, Rachel Xuan, Linheng Zhao, Kejia Wang, Animesh Singla, David Kim, Christopher Loupos

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Introduction: Incisional wound complications in vascular surgery patients represent a significant clinical and econometric burden of morbidity and mortality. The objective of this study was to trial the feasibility of applying the Prevena negative pressure incision management system as a routine dressing in patients who had undergone arterial surgery. Conventionally, Prevena has been applied to groin incisions, but this study features applications on multiple wound sites such as the thigh or major amputation stumps. Method: This was a cross-sectional observational, single-centre case series of 12 patients who had undergone major vascular surgery. Their wounds were managed with the Prevena system being applied either intra-operatively or on the first post-operative day. Demographic and operative details were collated as well as the length of stay and complication rates. Results: There were 9 males (75%) with mean age of 66 years and the comorbid burden was as follows: ischaemic heart disease (92%), diabetes (42%), hypertension (100%), stage 4 or greater kidney impairment (17%) and current or ex-smoking (83%). The main indications were acute ischaemia (33%), claudication (25%), and gangrene (17%). There were single instances of an occluded popliteal artery aneurysm, diabetic foot infection, and rest pain. The majority of patients (50%) had hybrid operations with iliofemoral endarterectomies, patch arterioplasties, and further peripheral endovascular treatment. There were 4 complex arterial bypass operations and 2 major amputations. The mean length of stay was 17 ± 10 days, with a range of 4 to 35 days. A single complication, in the form of a lymphocoele, was encountered in the context of an iliofemoral endarterectomy and patch arterioplasty. This was managed conservatively. There were no deaths. Discussion: The Prevena wound management system shows that in conjunction with safe vascular surgery, absolute wound complication rates remain low and that it remains a valuable adjunct in the treatment of vasculopaths.

Keywords: wound care, negative pressure, vascular surgery, closed incision

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Authors: Atitallah Sofien, Bouyahia Olfa, Attar Souleima, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Ciliopathies are a spectrum of diseases that have in common a defect in the synthesis of ciliary proteins. It is a rare cause of neonatal cholestasis. Clinical presentation varies extremely, and the main affected organs are the kidneys, liver, and pancreas. Methodology: This is a descriptive case report of a newborn who was admitted for exploration of neonatal cholestasis in the Paediatric Department C at the Children’s Hospital of Tunis, where the investigations concluded with a rare genetic mutation. Results: This is the case of a newborn male with no family history of hepatic and renal diseases, born to consanguineous parents, and from a well-monitored uneventful pregnancy. He developed jaundice on the second day of life, for which he received conventional phototherapy in the neonatal intensive care unit. He was admitted at 15 days for mild bronchiolitis. On clinical examination, intense jaundice was noted with normal stool and urine colour. Initial blood work showed an elevation in conjugated bilirubin and a high gamma-glutamyl transferase level. Transaminases and prothrombin time were normal. Abdominal sonography revealed hepatomegaly, splenomegaly, and undifferentiated renal cortex with bilateral medullar micro-cysts. Kidney function tests were normal. The infant received ursodeoxycholic acid and vitamin therapy. Genetic testing showed a homozygous mutation in the DCDC2 gene that hadn’t been documented before confirming the diagnosis of renal-hepatic ciliopathy. The patient has regular follow-ups, and his conjugated bilirubin and gamma-glutamyl transferase levels have been decreasing. Conclusion: Genetic testing has revolutionized the approach to etiological diagnosis in pediatric cholestasis. It enables personalised treatment strategies to better enhance the quality of life of patients and prevent potential complications following adequate long-term monitoring.

Keywords: cholestasis, newborn, ciliopathy, DCDC2, genetic

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Authors: Yik Sin Chan, Nam Weng Sit, Fook Yee Chye, van Ofwegen Leen, de Voogd Nicole, Kong Soo Khoo

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Chikungunya fever is an arboviral disease transmitted by the Aedes mosquitoes. It has resulted in epidemics of the disease in tropical countries in the Indian Ocean and South East Asian regions. The recent spread of this disease to the temperate countries such as France and Italy, coupled with the absence of vaccines and effective antiviral drugs make chikungunya fever a worldwide health threat. This study aims to investigate the anti-chikungunya virus activity of selected marine organism samples collected from Malaysian coastal areas, including seaweeds (Caulerpa racemosa, Caulerpa sertularioides and Kappaphycus alvarezii), a soft coral (Lobophytum microlobulatum) and a sponge (Spheciospongia vagabunda). Following lyophilization (oven drying at 40C for K. alvarezii) and grinding to powder form, each sample was subjected to sequential solvent extraction using hexane, chloroform, ethyl acetate, ethanol, methanol and distilled water in order to extract bioactive compounds. The antiviral activity was evaluated using monkey kidney epithelial (Vero) cells infected with the virus (multiplicity of infection=1). The cell viability was determined by Neutral Red uptake assay. 70% of the 30 extracts showed weak inhibitory activity with cell viability ≤30%. Seven of the extracts exhibited moderate inhibitory activity (cell viability: 31%-69%). These were the chloroform, ethyl acetate, ethanol and methanol extracts of C. racemosa; chloroform and ethyl acetate extracts of L. microlobulatum; and the chloroform extract of C. sertularioides. Only the hexane and ethanol extracts of L. microlobulatum showed strong inhibitory activity against the virus, resulting in cell viabilities (mean±SD; n=3) of 73.3±2.6% and 79.2±0.9%, respectively. The corresponding mean 50% effective concentrations (EC50) for the extracts were 14.2±0.2 and 115.3±1.2 µg/mL, respectively. The ethanol extract of the soft coral L. microlobulatum appears to hold the most promise for further characterization of active principles as it possessed greater selectivity index (SI>5.6) compared to the hexane extract (SI=2.1).

Keywords: antiviral, seaweed, sponge, soft coral, vero cell

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Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

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Authors: Itsuo Yokoyama, Rika Kikuti, Naoko Watabe

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Introduction: It has been known that chronic kidney disease (CKD) patients can benefit from physical exercise during dialysis therapy improving aerobic capacity, muscle function, cardiovascular function, and overall health-related quality of life. This study aimed to evaluate the effectiveness of dialysis rehabilitation. Materials and Methods: A total of 55 patients underwent two-hour resistance exercise training during each hemodialysis session for three consecutive months. Various routine clinical data were collected, including the calculation of the planar dimension of the muscle area in both upper legs at the level of the ischial bone. This area calculation was possible in 26 patients who had yearly plain abdominal computed tomography (CT) scans. DICOM files from the CT scans were used with 3D Slicer software for area calculation. An age and sex-matched group of 26 patients without dialysis rehabilitation also had yearly CT scans during the study period for comparison. Clinical data were compared between the two groups: Group A (rehabilitation) and Group B (non-rehabilitation). Results: There were no differences in basic laboratory data between the two groups. The average muscle area before and after rehabilitation in Group A was 212 cm² and 216 cm², respectively. In Group B, the average areas were 230.0 cm² and 225.8 cm². While there was no significant difference in absolute values, the average percentage increase in muscle area was +1.2% (ranging from -7.6% to 6.54%) for Group A and -2.0% (ranging from -12.1% to 4.9%) for Group B, which was statistically significant. In Group A, 9 of 26 were diabetic (DM), and 13 of 26 in Group B were non-DM. The increase in muscle area for DM patients was 4.9% compared to -0.7% for non-DM patients, which was significantly different. There were no significant differences between the two groups in terms of nutritional assessment, Kt/V, or incidence of clinical complications such as cardiovascular events. Considerations: Dialysis rehabilitation has been reported to prevent muscle atrophy by increasing muscle fibers and capillaries. This study demonstrated that muscle volume increased after dialysis exercise, as evidenced by the increased muscle area in the thighs. Notably, diabetic patients seemed to benefit more from dialysis exercise than non-diabetics. Although this study is preliminary due to its relatively small sample size, it suggests that intradialytic physical training may improve insulin utilization in muscle fiber cells, particularly in type II diabetic patients where insulin receptor function and signaling are altered. Further studies are needed to investigate the detailed mechanisms underlying the muscle hypertrophic effects of dialysis exercise.

Keywords: dialysis, excercise, muscle, hypertrophy, diabetes, insulin

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Authors: Brahim Sow

Abstract:

Background: Throughout West Africa, Balanites aegyptiaca (BA), or Zygophyllaceae, is widely used in traditional medicine to treat diabetes, hypertension, inflammation, malaria and liver disorders. In our recent research, we found that BA has nephroprotective potential against diabetes mellitus, hypertension and kidney disorders. However, to our knowledge, no systematic studies have been carried out on its derivative (toxicity) profile. Aim of the study: The study was conducted to assess the potential potency of the hydroalcoholic extract of BA bark in rats by the acute and sub-acute oral route. Materials and methods: Male and female rats in the acute depression study received BA extract orally at single doses of 500 mg/kg, 2000 mg/kg, 3000 mg/kg and 5000 mg/kg (n = 6 per group/sex). To assess acute depression, abnormal behaviour, toxic symptoms, weight and death were observed for 14 consecutive days. For the subacute impairment study, Wistar rats received the extract orally at doses of 125, 250 and 500 mg/kg (n=6 per group/sex) per day for 28 days. Behaviour and body weight were monitored daily. At the end of the treatment period, biochemical, haematological and histopathological examinations were performed, and gross and histopathological examinations of several organs were carried out. To determine the presence or absence of phytochemicals, the BA extract was subjected to gage phage chromatographic examination. Results: The absence of absorption chromatography of BA indicates the absence of cyanide groups. This suggests that the BA extract does not contain toxic substances. No mortality or adverse effects were observed at 5000 mg/kg in the acute depression test. With regard to body weight, general behaviour, relative organ weights, haematological and biochemical parameters, BA extract did not induce any mortality or potentially treatment-related effects in the sub-acute study. The normal architecture of the vital organs was revealed by histopathological examination, indicating the absence of morphological alterations. Conclusion: BA extract administered orally for 28 days at doses up to 500 mg/kg did not cause toxicological damage in rats in the present study. The median lethal dose (LD50) of the extract was estimated to be over 5000 mg/kg in an acute hyperglycaemia study.

Keywords: Balanites aegyptiaca L Delile, haematology, biochemistry, rat

Procedia PDF Downloads 72

Authors: Saima Ali, Liaqat Ali, Nasir Orakzai

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Background: Hydronephrosis is the most common abnormal finding in the urinary tract on prenatal screening with Ultrasonography. The prenatal hydronephrosis is a diagnostic dilemma in differentiating between obstructive variant versus physiologic hydronephrosis. The assessment and prompt diagnosis of prenatal hydronephrosis is important because of the fact that untreated obstructive hydronephrosis usually leads to recurrent UTI, Urosepsis, deterioration of renal functions, non-functioning kidneys, and even end-stage renal disease. Objectives: To determine the etiology and outcome of postnatal treatment of children with prenatal hydronephrosis in two teaching hospitals of Khyber Pakhtunkhwa (KPK) Methods: It is a multicentric descriptive study that was conducted in department of Paediatrics in Kuwait teaching hospital Peshawar and Department of Urology in Institute of Kidney Diseases Hayatabad Medical Complex Peshawar from January 2008 till December 2010. Total numbers of 64 neonates were included in the study with the mean follow-up of 14.5 months. All the diagnostic data in prenatal, postnatal data, and operative and non-operative data were collected on structured Proforma and was analyzed on SPSS version 17. Results: Out of 64 patients, 39 (60.9 %) were male while 25 were female. 52 patients had unilateral while 12 patients had bilateral hydronephrosis. Based upon prenatal USG in term of AP diameter, 37 (57 %) patients had mild hydronephrosis (5-10 mm AP diameter), 14 patients had moderate hydronephrosis (10-15 mm AP diameter) while 13 patients had gross hydronephrosis (More than 15mm). Regarding etiology, 44(76 %) patients were labeled as physiologic hydronephrosis, 11 patients (9.3%) with PUJ obstruction, 5 patients with Vesicoureteric reflux (VUR) and 4 patients with posterior urethral valves. Surgery was performed in total of 15 (23.4%) patients that included open Pyeloplasty in 11 patients, Vesicostomy followed by posterior valve fulguration in 4 patients. All the patients of VUR treated medically. The severity in the grade of prenatal hydronephrosis is significantly associated with the need for definitive urological surgery p < 0.005. Ancillary procedures like percutaneous nephrostomy (PCN) were inserted 7 patients. Conclusions: Prenatal hydronephrosis is a common ailment associated with significant morbidity. Physiological Hydronephrosis and VUR can be successfully treated with medical treatment. However obstructive PUJ obstructions and posterior urethral valves require surgical correction with a good success rate.

Keywords: prenatal hydronephrosis, Pelviureteric Junction (PUJ) Obstruction, vesicoureteric reflux, posterior urethral valve, renography

Procedia PDF Downloads 242

Authors: Khosro Barkhordari, Fateme Sadr, Mina Pashang

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Back ground: Blood transfusion is one of the major issues in cardiac surgery patients. Transfusing patients based on fixed cut-off points of hemoglobin is the current protocol in most institutions. The hemoglobin level of 7- 10 has been suggested for blood transfusion in cardiac surgery patients. We aimed to evaluate if blood transfusion based on change in percentage of hematocrit has different outcomes. Methods: In this retrospective cohort study, we investigated the early postoperative outcome of cardiac surgery patients who received blood transfusions at Tehran Heart Center Hospital, IRAN. We reviewed and analyzed the basic characteristics and clinical data of 700 patients who met our exclusion and inclusion criteria. The two groups of blood transfused patients were compared, those who have 30-50 percent decrease in basal hematocrit versus those with 10 -29 percent decrease. Results: This is ongoing study, and the results would be completed in two weeks after analysis of the date. Conclusion: Early analysis has shown no difference in early post-operative outcomes between the two groups, but final analysis will be completed in two weeks. 1-Department of Anesthesiology and Critical Care, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, IRAN 2- Department of Research, Tehran Heart Center, Tehran, IRAN Quantitative variables were compared using the Student t-test or the Mann‐Whitney U test, as appropriate, while categorical variables were compared using the χ2 or the Fisher exact test, as required. Our intention was to compare the early postoperative outcomes between the two groups, which include 30 days mortality, Length of ICU stay, Length of hospital stay, Intubation time, Infection rate, acute kidney injury, and respiratory complications. The main goal was to find if transfusing blood based on changes in hematocrit from a basal level was better than to fixed cut-off point regarding early post-operative outcomes. This has not been studied enough and may need randomized control trials.

Keywords: post-operative, cardiac surgery, outcomes, blood transfusion

Procedia PDF Downloads 82

Authors: Diea Gamal Abo El-Hassan, Salwa Ahmed Aly, Abdelrahman Mahmoud Abdelgwad

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The major conjugated linoleic acid (CLA) isomers have anticancer effect, especially breast cancer cells, inhibits cell growth and induces cell death. Also, CLA has several health benefits in vivo, including antiatherogenesis, antiobesity, and modulation of immune function. The present study aimed to assess the safety and anticancer effects of milk fat CLA against in vivo Ehrlich ascites carcinoma (EAC) in female Swiss albino mice. This was based on acute toxicity study, detection of the tumor growth, life span of EAC bearing hosts, and simultaneous alterations in the hematological, biochemical, and histopathological profiles. Materials and Methods: One hundred and fifty adult female mice were equally divided into five groups. Groups (1-2) were normal controls, and Groups (3-5) were tumor transplanted mice (TTM) inoculated intraperitoneally with EAC cells (2×106 /0.2 mL). Group (3) was (TTM positive control). Group (4) TTM fed orally on balanced diet supplemented with milk fat CLA (40 mg CLA/kg body weight). Group (5) TTM fed orally on balanced diet supplemented with the same level of CLA 28 days before tumor cells inoculation. Blood samples and specimens from liver and kidney were collected from each group. The effect of milk fat CLA on the growth of tumor, life span of TTM, and simultaneous alterations in the hematological, biochemical, and histopathological profiles were examined. Results: For CLA treated TTM, significant decrease in tumor weight, ascetic volume, viable Ehrlich cells accompanied with increase in life span were observed. Hematological and biochemical profiles reverted to more or less normal levels and histopathology showed minimal effects. Conclusion: The present study proved the safety and anticancer efficiency of milk fat CLA and provides a scientific basis for its medicinal use as anticancer attributable to the additive or synergistic effects of its isomers.

Keywords: anticancer activity, conjugated linoleic acid, Ehrlich ascites carcinoma, % increase in life span, mean survival time, tumor transplanted mice.

Procedia PDF Downloads 83

Authors: Małgorzata Golonka, Jadwiga Laska

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Among self-healing materials, the most unexplored group are thermoplastic polymers. These polymers are used not only to produce packaging with a relatively short life but also to obtain coatings, insulation, casings, or parts of machines and devices. Due to its exceptional resistance to weather conditions, hydrophobicity, sufficient mechanical strength, and ease of extrusion, polyethylene is used in the production of polymer pipelines and as an insulating layer for steel pipelines. Polyethylene or PE coated steel pipelines can be used in difficult conditions such as underground or underwater installations. Both installation and use under such conditions are associated with high stresses and consequently the formation of microdamages in the structure of the material, loss of its integrity and final applicability. The ideal solution would be to include a self-healing system in the polymer material. In the presented study the behavior of resin-coated microcapsules in the extrusion process of low-density polyethylene was examined. Microcapsules are a convenient element of the repair system because they can be filled with appropriate reactive substances to ensure the repair process, but the main problem is their durability under processing conditions. Rapeseed oil, which has a relatively high boiling point of 240⁰C and low volatility, was used as the core material that simulates the reactive agents. The capsule shell, which is a key element responsible for its mechanical strength, was obtained by in situ polymerising urea-formaldehyde, melamine-urea-formaldehyde or melamine-formaldehyde resin on the surface of oil droplets dispersed in water. The strength of the capsules was compared based on the shell material, and in addition, microcapsules with single- and multilayer shells were obtained using different combinations of the chemical composition of the resins. For example, the first layer of appropriate tightness and stiffness was made of melamine-urea-formaldehyde resin, and the second layer was a melamine-formaldehyde reinforcing layer. The size, shape, distribution of capsule diameters and shell thickness were determined using digital optical microscopy and electron microscopy. The efficiency of encapsulation (i.e., the presence of rapeseed oil as the core) and the tightness of the shell were determined by FTIR spectroscopic examination. The mechanical strength and distribution of microcapsules in polyethylene were tested by extruding samples of crushed low-density polyethylene mixed with microcapsules in a ratio of 1 and 2.5% by weight. The extrusion process was carried out in a mini extruder at a temperature of 150⁰C. The capsules obtained had a diameter range of 70-200 µm. FTIR analysis confirmed the presence of rapeseed oil in both single- and multilayer shell microcapsules. Microscopic observations of cross sections of the extrudates confirmed the presence of both intact and cracked microcapsules. However, the melamine-formaldehyde resin shells showed higher processing strength compared to that of the melamine-urea-formaldehyde coating and the urea-formaldehyde coating. Capsules with a urea-formaldehyde shell work very well in resin coating systems and cement composites, i.e., in pressureless processing and moulding conditions. The addition of another layer of melamine-formaldehyde coating to both the melamine-urea-formaldehyde and melamine-formaldehyde resin layers significantly increased the number of microcapsules undamaged during the extrusion process. The properties of multilayer coatings were also determined and compared with each other using computer modelling.

Keywords: self-healing polymers, polyethylene, microcapsules, extrusion

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Authors: Amr Saeb, Khalid Al-Rubeaan, Mohamed Abouelhoda, Manojkumar Selvaraju, Hamsa Tayeb

Abstract:

Background: P. mirabilis is a common uropathogenic bacterium that can cause major complications in patients with long-standing indwelling catheters or patients with urinary tract anomalies. In addition, P. mirabilis is a common cause of chronic osteomyelitis in diabetic foot ulcer (DFU) patients. Methodology: P. mirabilis SCDR1 was isolated from a diabetic ulcer patient. We examined P. mirabilis SCDR1 levels of resistance against nano-silver colloids, the commercial nano-silver and silver containing bandages and commonly used antibiotics. We utilized next generation sequencing techniques (NGS), bioinformatics, phylogenetic analysis and pathogenomics in the identification and characterization of the infectious pathogen. Results: P. mirabilis SCDR1 is a multi-drug resistant isolate that also showed high levels of resistance against nano-silver colloids, nano-silver chitosan composite and the commercially available nano-silver and silver bandages. The P. mirabilis-SCDR1 genome size is 3,815,621 bp with G+C content of 38.44%. P. mirabilis-SCDR1 genome contains a total of 3,533 genes, 3,414 coding DNA sequence genes, 11, 10, 18 rRNAs (5S, 16S, and 23S), and 76 tRNAs. Our isolate contains all the required pathogenicity and virulence factors to establish a successful infection. P. mirabilis SCDR1 isolate is a potential virulent pathogen that despite its original isolation site, wound, it can establish kidney infection and its associated complications. P. mirabilis SCDR1 contains several mechanisms for antibiotics and metals resistance including, biofilm formation, swarming mobility, efflux systems, and enzymatic detoxification. Conclusion: P. mirabilis SCDR1 is the spontaneous nano-silver resistant bacterial strain. P. mirabilis SCDR1 strain contains all reported pathogenic and virulence factors characteristic for the species. In addition, it possesses several mechanisms that may lead to the observed nano-silver resistance.

Keywords: Proteus mirabilis, multi-drug resistance, silver nanoparticles, resistance, next generation sequencing techniques, genome analysis, bioinformatics, phylogeny, pathogenomics, diabetic foot ulcer, xenobiotics, multidrug resistance efflux, biofilm formation, swarming mobility, resistome, glutathione S-transferase, copper/silver efflux system, altruism

Procedia PDF Downloads 326

Authors: Giulia Fredi, Andrea Dorigato, Luca Fambri, Alessandro Pegoretti

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Thermal energy storage (TES) is the storage of heat for later use, thus filling the gap between energy request and supply. The most widely used materials for TES are the organic solid-liquid phase change materials (PCMs), such as paraffin. These materials store/release a high amount of latent heat thanks to their high specific melting enthalpy, operate in a narrow temperature range and have a tunable working temperature. However, they suffer from a low thermal conductivity and need to be confined to prevent leakage. These two issues can be tackled by confining PCMs with carbon nanotubes (CNTs). TES applications include the buildings industry, solar thermal energy collection and thermal management of electronics. In most cases, TES systems are an additional component to be added to the main structure, but if weight and volume savings are key issues, it would be advantageous to embed the TES functionality directly in the structure. Such multifunctional materials could be employed in the automotive industry, where the diffusion of lightweight structures could complicate the thermal management of the cockpit environment or of other temperature sensitive components. This work aims to produce epoxy/carbon structural laminates containing CNT-stabilized paraffin. CNTs were added to molten paraffin in a fraction of 10 wt%, as this was the minimum amount at which no leakage was detected above the melting temperature (45°C). The paraffin/CNT blend was cryogenically milled to obtain particles with an average size of 50 µm. They were added in various percentages (20, 30 and 40 wt%) to an epoxy/hardener formulation, which was used as a matrix to produce laminates through a wet layup technique, by stacking five plies of a plain carbon fiber fabric. The samples were characterized microstructurally, thermally and mechanically. Differential scanning calorimetry (DSC) tests showed that the paraffin kept its ability to melt and crystallize also in the laminates, and the melting enthalpy was almost proportional to the paraffin weight fraction. These thermal properties were retained after fifty heating/cooling cycles. Laser flash analysis showed that the thermal conductivity through the thickness increased with an increase of the PCM, due to the presence of CNTs. The ability of the developed laminates to contribute to the thermal management was also assessed by monitoring their cooling rates through a thermal camera. Three-point bending tests showed that the flexural modulus was only slightly impaired by the presence of the paraffin/CNT particles, while a more sensible decrease of the stress and strain at break and the interlaminar shear strength was detected. Optical and scanning electron microscope images revealed that these could be attributed to the preferential location of the PCM in the interlaminar region. These results demonstrated the feasibility of multifunctional structural TES composites and highlighted that the PCM size and distribution affect the mechanical properties. In this perspective, this group is working on the encapsulation of paraffin in a sol-gel derived organosilica shell. Submicron spheres have been produced, and the current activity focuses on the optimization of the synthesis parameters to increase the emulsion efficiency.

Keywords: carbon fibers, carbon nanotubes, lightweight materials, multifunctional composites, thermal energy storage

Procedia PDF Downloads 157

Authors: Klazina T. Havinga, Hilde R. H. de Geus

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Introduction: Pre-operative coagulation management of Apixaban prescribed patients, a new oral anticoagulant (a factor Xa inhibitor), is difficult, especially when chronic kidney disease (CKD) causes drug overdose. Apixaban is not dialyzable due to its high level of protein binding. An antidote, Andexanet α, is available but expensive and has an unfavorable short half-life. We report the successful extracorporeal removal of Apixaban prior to emergency surgery with the CytoSorb® Hemoadsorption device. Methods: A 89-year-old woman with CKD, with an Apixaban prescription for atrial fibrillation, was presented at the ER with traumatic rib fractures, a flail chest, and an unstable spinal fracture (T12) for which emergency surgery was indicated. However, due to very high Apixaban levels, this surgery had to be postponed. Based on the Apixaban-specific anti-factor Xa activity (AFXaA) measurements at admission and 10 hours later, complete clearance was expected after 48 hours. In order to enhance the Apixaban removal and reduce the time to operation, and therefore reduce pulmonary complications, CRRT with CytoSorb® cartridge was initiated. Apixaban-specific anti-factor Xa activity (AFXaA) was measured frequently as a substitute for Apixaban drug concentrations, pre- and post adsorber, in order to calculate the adsorber-related clearance. Results: The admission AFXaA concentration, as a substitute for Apixaban drug levels, was 218 ng/ml, which decreased to 157 ng/ml after ten hours. Due to sustained anticoagulation effects, surgery was again postponed. However, the AFXaA levels decreased quickly to sub-therapeutic levels after CRRT (Multifiltrate Pro, Fresenius Medical Care, Blood flow 200 ml/min, Dialysate Flow 4000 ml/h, Prescribed renal dose 51 ml-kg-h) with Cytosorb® connected in series into the circuit was initiated (within 5 hours). The adsorber-related (indirect) Apixaban clearance was calculated every half hour (Cl=Qe * (AFXaA pre- AFXaA post/ AFXaA pre) with Qe=plasma flow rate calculated with Ht=0.38 and system blood flow rate 200 ml-min): 100 ml/min, 72 ml/min and 57 ml/min. Although, as expected, the adsorber-related clearance decreased quickly due to saturation of the beads, still the reduction rate achieved resulted in a very rapid decrease in AFXaA levels. Surgery was ordered and possible within 5 hours after Cytosorb initiation. Conclusion: The CytoSorb® Hemoadsorption device enabled rapid correction of Apixaban associated anticoagulation.

Keywords: Apixaban, CytoSorb, emergency surgery, Hemoadsorption

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Authors: Mustafa M. Donma, Orkide Donma

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A growing list of cancers might be influenced by obesity. Obesity is associated with an increased risk for the occurrence and development of some cancers. Inflammation can lead to cancer. It is one of the characteristic features of cancer and plays a critical role in cancer development. C-reactive protein (CRP) is under evaluation related to the new and simple prognostic factors in patients with metastatic renal cell cancer. Obesity can predict and promote systemic inflammation in healthy adults. BMI is correlated with hs-CRP. In this study, SII index and CRP values were evaluated in children with normal BMI and those within the range of different obesity grades to detect the tendency towards cancer in pediatric obesity. A total of one hundred and ninety-four children; thirty-five children with normal BMI, twenty overweight (OW), forty-seven obese (OB) and ninety-two morbid obese (MO) participated in the study. Age- and sex-matched groups were constituted using BMI-for age percentiles. Informed consent was obtained. Ethical Committee approval was taken. Weight, height, waist circumference (C), hip C, head C and neck C of the children were measured. The complete blood count test was performed. C-reactive protein analysis was performed. Statistical analyses were performed using SPSS. The degree for statistical significance was p≤0.05. SII index values were progressively increasing starting from normal weight (NW) to MO children. There is a statistically significant difference between NW and OB as well as MO children. No significant difference was observed between NW and OW children, however, a correlation was observed between NW and OW children. MO constitutes the only group, which exhibited a statistically significant correlation between SII index and CRP. Obesity-related bladder, kidney, cervical, liver, colorectal, endometrial cancers are still being investigated. Obesity, characterized as a chronic low-grade inflammation, is a crucial risk factor for colon cancer. Elevated childhood BMI values may be indicative of processes leading to cancer, initiated early in life. Prevention of childhood adiposity may decrease the cancer incidence in adults. To authors’ best knowledge, this study is the first to introduce SII index values during obesity of varying degrees of severity. It is suggested that this index seems to affect all stages of obesity with an increasing tendency and may point out the concomitant status of obesity and cancer starting from very early periods of life.

Keywords: children, C-reactive protein, systemic immune-inflammation index, obesity

Procedia PDF Downloads 173

Authors: Sergio A. Bernal-Chavez, Sergio Alcalá-Alcalá, Doris A. Cerecedo-Mercado, Adriana Ganem-Rondero

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The prevalence of people with chronic wounds has increased dramatically by many factors including smoking, obesity and chronic diseases, such as diabetes, that can slow the healing process and increase the risk of becoming chronic. Because of this situation, the improvement of chronic wound treatments is a necessity, which has led to the scientific community to focus on improving the effectiveness of current therapies and the development of new treatments. The wound formation is a physiological complex process, which is characterized by an inflammatory stage with the presence of proinflammatory cells that create a proteolytic microenvironment during the healing process, which includes the degradation of important growth factors and cytokines. This decrease of growth factors and cytokines provides an interesting strategy for wound healing if they are administered externally. The use of nanometric drug delivery systems, such as polymer nanoparticles (NP), also offers an interesting alternative around dermal systems. An interesting strategy would be to propose a formulation based on a thermosensitive hydrogel loaded with polymeric nanoparticles that allows the inclusion and application of a platelet lysate (PL) on damaged skin, with the aim of promoting wound healing. In this work, NP were prepared by a double emulsion-solvent evaporation technique, using polylactic-co-glycolic acid (PLGA) as biodegradable polymer. Firstly, an aqueous solution of PL was emulsified into a PLGA organic solution, previously prepared in dichloromethane (DCM). Then, this disperse system (W/O) was poured into a polyvinyl alcohol (PVA) solution to get the double emulsion (W/O/W), finally the DCM was evaporated by magnetic stirring resulting in the NP formation containing PL. Once the NP were obtained, these systems were characterized by morphology, particle size, Z-potential, encapsulation efficiency (%EE), physical stability, infrared spectrum, calorimetric studies (DSC) and in vitro release profile. The optimized nanoparticles were included in a thermosensitive gel formulation of Pluronic® F-127. The gel was prepared by the cold method at 4 °C and 20% of polymer concentration. Viscosity, sol-gel phase transition, time of no flow solid-gel at wound temperature, changes in particle size by temperature-effect using dynamic light scattering (DLS), occlusive effect, gel degradation, infrared spectrum and micellar point by DSC were evaluated in all gel formulations. PLGA NP of 267 ± 10.5 nm and Z-potential of -29.1 ± 1 mV were obtained. TEM micrographs verified the size of NP and evidenced their spherical shape. The %EE for the system was around 99%. Thermograms and in infrared spectra mark the presence of PL in NP. The systems did not show significant changes in the parameters mentioned above, during the stability studies. Regarding the gel formulation, the transition sol-gel occurred at 28 °C with a time of no flow solid-gel of 7 min at 33°C (common wound temperature). Calorimetric, DLS and infrared studies corroborated the physical properties of a thermosensitive gel, such as the micellar point. In conclusion, the thermosensitive gel described in this work, contains therapeutic amounts of PL and fulfills the technological properties to be used in damaged skin, with potential application in wound healing and tissue regeneration.

Keywords: growth factors, polymeric nanoparticles, thermosensitive hydrogels, tissue regeneration

Procedia PDF Downloads 167

Authors: Maria Lucia G. Lourenco, Keylla H. N. P. Pereira, Viviane Y. Hibaru, Fabiana F. Souza, Joao C. P. Ferreira, Simone B. Chiacchio, Luiz H. A. Machado

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Congenital malformations are organ defects due to genetic or teratogenic causes, which can lead to high mortality in dog litters. This study assessed and described the congenital malformations in newborn dogs. The study included litters attend in the São Paulo State University (UNESP) Veterinary Hospital, Botucatu, Sao Paulo, Brazil. One hundred seventy-eight litters and 803 newborns were evaluated. The occurrence of litters with malformations was 24.7%, and of newborns was 6.7%. Twenty-seven different malformations were registered: anasarca, anal atresia, cleft lip, cleft palate, duplicated right ribcage, equinovarus, exencephaly, gastroschisis, hydrocephaly, lissencephaly, macroglossia, microphthalmia, mitral valve dysplasia, omphalocele, eyelid agenesis, persistent urachus, polydactyly, pulmonary hypoplasia, pulmonary valve stenosis, rectovaginal fistula, agenesis of abdominal muscles, rib hypoplasia, scoliosis, segmental aplasia of the intestines, tricuspid valve dysplasia, unilateral kidney agenesis, and vaginal atresia. 68.7% of newborns died as a result of malformations. The pure breeds with the highest chances of manifesting malformations in contrast with mixed breeds were French Bulldog, Pug, English Bulldog, Rottweiler, German Spitz, Pinscher, Pitbull, Yorkshire Terrier, and Shih-Tzu. Significant values (P<0.05) occurred in races French Bulldogs and Pugs. The causes of congenital disabilities are possibly related to hereditary genetic factors considering that the highest incidence of malformations was observed among purebreds. There as one case of exposure to a teratogenic agent, but no other mothers were exposed to such agents during pregnancy. Two cases of consanguineal breeding between siblings were reported. The mortality rate was high. Genetic breeding programs for reproduction, avoiding consanguineous mating, care in choosing parents, and avoiding maternal exposure to teratogenic agents are of utmost importance in reducing dog malformations and consequent mortality.

Keywords: congenital defects, teratogenesis, canine neonatology, newborn puppy

Procedia PDF Downloads 134

Authors: Jelka Pleadin, Nina Kudumija, Ana Vulic, Manuela Zadravec, Tina Lesic, Mario Skrivanko, Irena Perkovic, Nada Vahcic

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Products of animal origin, such as meat and meat products, can contribute to human mycotoxins’ intake coming as a result of either indirect transfer from farm animals exposed to naturally contaminated grains and feed (carry-over effects) or direct contamination with moulds or naturally contaminated spice mixtures used in meat production. Ochratoxin A (OTA) is mycotoxin considered to be of the outermost importance from the public health standpoint in connection with meat products. The aim of this study was to investigate the occurrence of OTA in different traditional meat products circulating on Croatian markets during 2018, produced by a large number of households situated in eastern and north Croatian regions using a variety of technologies. Concentrations of OTA were determined in traditional meat products (n = 70), including dry fermented sausages (Slavonian kulen, Slavonian sausage, Istrian sausage and domestic sausage; n = 28), dry-cured meat products (pancetta, pork rack and ham; n = 22) and cooked sausages (liver sausages, black pudding sausages and pate; n = 20). OTA was analyzed by use of quantitative screening immunoassay method (ELISA) and confirmed for positive samples (higher than the limit of detection) by liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Whereas the bacon samples contaminated with OTA were not found, its level in dry fermented sausages ranged from 0.22 to 2.17 µg/kg and in dry-cured meat products from 0.47 to 5.35 µg/kg, with in total 9% of positive samples. Besides possible primary contamination of these products arising due to improper manufacturing or/and storage conditions, observed OTA contamination could also be the consequence of secondary contamination that comes as a result of contaminated feed the animals were fed on. OTA levels obtained in cooked sausages ranged from 0.32 to 4.12 µg/kg (5% of positives) and could probably be linked to the contaminated raw materials (liver, kidney and spices) used in the sausages production. The results showed an occasional OTA contamination of traditional meat products, pointing that to avoid such contamination on households these products should be produced and processed under standardized and well-controlled conditions. Further investigations should be performed in order to identify mycotoxin-producing moulds on the surface of the products and to define preventative measures that can reduce the contamination of traditional meat products during their production on households and period of storage.

Keywords: Croatian households, ochratoxin-A, traditional cooked sausages, traditional dry-cured meat products

Procedia PDF Downloads 186

Authors: Nabiyeva Jamala

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We divide water into drinking, mineral, industrial, technical and thermal-energetic types according to its use and purpose. Drinking water must comply with sanitary requirements and norms according to organoleptic devices and physical and chemical properties. Mineral water - must comply with the norms due to some components having therapeutic properties. Industrial water must fulfill its normative requirements by being used in the industrial field. Technical water should be suitable for use in the field of agriculture, household, and irrigation, and the normative requirements should be met. Heat-energy water is used in the national economy, and it consists of thermal and energy water. Water is a filter-accumulator of all types of pollutants entering the environment. This is explained by the fact that it has the property of dissolving compounds of mineral and gaseous water and regular water circulation. Environmentally clean, pure, non-toxic water is vital for the normal life activity of humans, animals and other living beings. Chemical pollutants enter water basins mainly with wastewater from non-ferrous and ferrous metallurgy, oil, gas, chemical, stone, coal, pulp and paper and forest materials processing industries and make them unusable. Wastewater from the chemical, electric power, woodworking and machine-building industries plays a huge role in the pollution of water sources. Chlorine compounds, phenols, and chloride-containing substances have a strong lethal-toxic effect on organisms when mixed with water. Heavy metals - lead, cadmium, mercury, nickel, copper, selenium, chromium, tin, etc. water mixed with ingredients cause poisoning in humans, animals and other living beings. Thus, the mixing of selenium with water causes liver diseases in people, the mixing of mercury with the nervous system, and the mixing of cadmium with kidney diseases. Pollution of the World's ocean waters and other water basins with oil and oil products is one of the most dangerous environmental problems facing humanity today. So, mixing even the smallest amount of oil and its products in drinking water gives it a bad, unpleasant smell. Mixing one ton of oil with water creates a special layer that covers the water surface in an area of 2.6 km2. As a result, the flood of light, photosynthesis and oxygen supply of water is getting weak and there is a great danger to the lives of living beings.

Keywords: chemical pollutants, wastewater, SSAM, polyacrylamide

Procedia PDF Downloads 67

Authors: Daniel Thompson, Muhammad Peerbux, Sophie Cerutti, Hansraj Riteesh Bookun

Abstract:

Patients with carotid stenosis, which may be asymptomatic or symptomatic in the form of transient ischaemic attack (TIA), amaurosis fugax, or stroke, often require an endarterectomy to reduce stroke risk. Risks of this procedure include stroke, death, myocardial infarction, and cranial nerve damage. Carotid endarterectomy is most commonly performed under general anaesthetic, however, it can also be undertaken with a regional anaesthetic approach. Our tertiary centre generally performs carotid endarterectomy under regional anaesthetic. Our major tertiary hospital mostly utilises regional anaesthesia for carotid endarterectomy. We completed a cross-sectional analysis of all cases of carotid endarterectomy performed under regional anaesthesia across a 10-year period between January 2010 to March 2020 at our institution. 350 patients were included in this descriptive analysis, and demographic details for patients, indications for surgery, procedural details, length of surgery, and complications were collected. Data was cross tabulated and presented in frequency tables to describe these categorical variables. 263 of the 350 patients in the analysis were male, with a mean age of 71 ± 9. 172 patients had a history of ischaemic heart disease, 104 had diabetes mellitus, 318 had hypertension, and 17 patients had chronic kidney disease greater than Stage 3. 13.1% (46 patients) were current smokers, and the majority (63%) were ex-smokers. Most commonly, carotid endarterectomy was performed conventionally with patch arterioplasty 96% of the time (337 patients). The most common indication was TIA and stroke in 64% of patients, 18.9% were classified as asymptomatic, and 13.7% had amaurosis fugax. There were few general complications, with 9 wound complications/infections, 7 postoperative haematomas requiring return to theatre, 3 myocardial infarctions, 3 arrhythmias, 1 exacerbation of congestive heart failure, 1 chest infection, and 1 urinary tract infection. Specific complications to carotid endarterectomy included 3 strokes, 1 postoperative TIA, and 1 cerebral bleed. There were no deaths in our cohort. This analysis of a large cohort of patients from a major tertiary centre who underwent carotid endarterectomy under regional anaesthesia indicates the safety of such an approach for these patients. Regional anaesthesia holds the promise of less general respiratory and cardiac events compared to general anaesthesia, and in this vulnerable patient group, calls for comparative research between local and general anaesthesia in carotid surgery.

Keywords: anaesthesia, carotid endarterectomy, stroke, carotid stenosis

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Authors: Ashraf Samir Hakim, Randa Mohamed Alarousy

Abstract:

The consumption of food contaminated with molds (microscopic filamentous fungi) and their toxic metabolites results in the development of food-borne mycotoxicosis. The spores of molds are ubiquitously spread in the environment and can be detected everywhere. Ochratoxin A is a potentially carcinogenic fungal toxin found in a variety of food commodities , not only is considered the most abundant and hence the most commonly detected member but also is the most toxic one.Ochratoxin A is the most abundant and hence the most commonly detected member, but is also the most toxic of the three. A very limited research works concerning foods of porcine origin in Egypt were obtained in spite of presence a considerable swine population and consumers. In this study, the quality of various ready-to-eat local and imported pork meat and meat byproducts sold in Egyptian markets as well as edible organs as liver and kidney were assessed for the presence of various molds and their toxins as a raw material. Mycological analysis was conducted on (n=110) samples which included pig livers n=10 and kidneys n=10 from the Basateen slaughter house; local n=70 and 20 imported processed pork meat byproducts.The isolates were identified using traditional mycological and biochemical tests while, Ochratoxin A levels were quantitatively analyzed using the high performance liquid. Results of conventional mycological tests for detecting the presence of fungal growth (yeasts or molds) were negative, while the results of mycotoxins concentrations were be greatly above the permiceable limits or "tolerable weekly intake" (TWI) of ochratoxin A established by EFSA in 2006 in local pork and pork byproducts while the imported samples showed a very slightly increasing.Since ochratoxin A is stable and generally resistant to heat and processing, control of ochratoxin A contamination lies in the control of the growth of the toxin-producing fungi. Effective prevention of ochratoxin A contamination therefore depends on good farming and agricultural practices. Good Agricultural Practices (GAP) including methods to reduce fungal infection and growth during harvest, storage, transport and processing provide the primary line of defense against contamination with ochratoxin A. To the best of our knowledge this is the first report of mycological assessment, especially the mycotoxins in pork byproducts in Egypt.

Keywords: Egyptian markets, mycotoxicosis, ochratoxin A, pork meat, pork by-products

Procedia PDF Downloads 460

Authors: Jessica P. Fiorotti, Maria C. Freitas, Caio J. B. Coutinho-Rodrigues, Mariana G. Camargo, Emily S. Mesquita, Amanda R. C. Corval, Ricardo O. B. Bitencourt, Allan F. Marciano, Diva D. Spadacci-Morena, Patricia S. Golo, Isabele C. Angelo, Vania R. E. P. Bittencourt

Abstract:

The bovine tick, Rhipicephalus microplus, is an arthropod of great importance in veterinary medicine leading to anemia, weight loss, animals' leather depreciation and also acting as a vector of many pathogens. In this way, the parasitism causes a loss of 3.24 billion dollars per year in Brazil. Knowingly, entomopathogenic fungi act as natural controller of some arthropods, acting mainly by active penetration through the cuticle. However, it can also act on the hemolymph and through the production of mycotoxins. Hemocytes are responsible for the cellular immune response and participate in the processes of phagocytosis, nodulation and encapsulation and may undergo changes when challenged by pathogens. The aim of the present study was to evaluate changes in R. microplus hemocytes after inoculation of Metarhizium robertsii using transmission electron microscopy. The isolate ARSEF 2575 and 200 engorged R. microplus females were used. The groups were divided into control, in which the females were inoculated with 5 μL of sterile distilled water solution and 0.1% Tween 80, and a group inoculated with 5 μL of fungal suspension at the concentration of 10⁷ conidia mL⁻¹. The experiment was performed in duplicate and each group contained 50 females. Twenty-four hours after fungal inoculation, hemolymph was collected through the cuticle dorsal surface perforation of the tick females. After collection, the hemolymph samples were centrifuged at 500 x g for 3 minutes at 4 °C, the plasma was discarded and the hemocyte pellet was resuspended in 50 μl PBS. The suspension material was fixed in 2% glutaraldehyde in Millonig buffer for three hours. After fixation, the material was centrifuged at 500 x g for 3 minutes, the supernatant was discarded and the cells were resuspended in a wash solution. Subsequently, the cells were post-fixed with 1% osmium tetroxide in phosphate buffer for one hour at room temperature and dehydrated in increasing concentrations of ethanol, and then embedded in Epon resin. The ultrathin sections were examined under the LEO EM 906E transmission electron microscopy at 80kV. The ultrastructural results revealed that.in control group, the cells were considered intact, in which the granulocytes were observed with granules of different electrodensities, intact mitochondria and cytoplasm without vacuolization. In addition, granulocytes showed plasma membrane projections similar to pseudopodia. Plasmatocytes presented as irregularly shaped cells, with the eccentric nucleus, agranular cytoplasm and some cells presented pseudopodia. Nevertheless, in the group exposed to the fungus, most of the cells presented in degeneration. The granulocytes found had fewer granules in the cytoplasm and more vacuoles. Plasmatocytes, after treatment, presented many vacuoles also in the cytoplasm and the lysosomes presented great amount of electrodense material in their interior. Thus, the results suggest that the fungus has a depressant action in the immune system of the tick, not only by the cell degranulation, but also suggesting that this leads to morphological changes in the hemocytes and may even trigger processes such as phagocytosis.

Keywords: bovine tick, cellular defense, entomopathogenic fungi, immune response

Procedia PDF Downloads 186