Search results for: renal transplantation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 424

Search results for: renal transplantation

94 Adsorptive Membrane for Hemodialysis: Potential, Future Prospection and Limitation of MOF as Nanofillers

Authors: Musawira Iftikhar

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The field of membrane materials is the most dynamic due to the constantly evolving requirements advancement of materials, to address challenges such as biocompatibility, protein-bound uremic toxins, blood coagulation, auto-immune responses, oxidative stress, and poor clearance of uremic toxins. Hemodialysis is a membrane filtration processes that is currently necessary for daily living of the patients with ESRD. Tens of millions of people with ESRD have benefited from hemodialysis over the past 60–70 years, both in terms of safeguarding life and a longer lifespan. Beyond challenges associated with the efficiency and separative properties of the membranes, ensuring hemocompatibility, or the safe circulation of blood outside the body for four hours every two days, remains a persistent challenge. This review explores the ongoing field of metal–Organic Frameworks (MOFs) and their applications in hemodialysis, offering a comprehensive examination of various MOFs employed to address challenges inherent in traditional hemodialysis methodologies. this This review included includes the experimental work done with various MOFs as a filler such as UiO-66, HKUST-1, MIL-101, and ZIF-8, which together lead to improved adsorption capacities for a range of uremic toxins and proteins. Furthermore, this review highlights how effectively MOF-based hemodialysis membranes remove a variety of uremic toxins, including p-cresol, urea, creatinine, and indoxyl sulfate and potential filler choices for the future. Future research efforts should focus on refining synthesis techniques, enhancing toxin selectivity, and investigating the long-term durability of MOF-based membranes. With these considerations, MOFs emerge as transformative materials in the quest to develop advanced and efficient hemodialysis technologies, holding the promise to significantly enhance patient outcomes and redefine the landscape of renal therapy.

Keywords: membrane, hemodailysis, metal organic frameworks, seperation, protein adsorbtion

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93 Stereological Evaluation of Liver of Rabbit Fetuses After Transplantation of Human Wharton’s Jelly-Derived Mesenchymal Stromal/Stem Cells

Authors: Zahra Khodabandeh, Leila Rezaeian, Mohammad Amin Edalatmanesh, Asghar Mogheiseh, Nader Tanideh, Mehdi Dianatpour, Shahrokh Zare, Hossein Bordbar, Neda Baghban, Amin Tamadon

Abstract:

Background: In-utero xenotransplantation of stem cells in abnormal fetuses effectively treats several genetic illnesses. Objective: The current research aimed to evaluate structural and morphological alterations in the liver of rabbit fetuses following xenotransplantation of human Wharton’s jelly-derived mesenchymal stromal cells (hWJ-MSCs) using a stereological technique. Methods: hWJ-MSCs were isolated from the human umbilical cord, and their authenticity was established by flow cytometry and differentiation. At gestational day 14, the rabbits were anesthetized, and hWJ-MSCs were injected into the uteri of 24 fetuses. Twenty-two fetuses were born successfully. Ten rabbit liver specimens were prepared from injected fetuses, including eight rabbits on day three following birth and two rabbits on the 21st post-natal day. The non-injected fetuses were considered positive controls. The livers of the control and hWJ-MSCs-treated rabbits were fixed, processed, stained, and examined through stereological approaches. Results: In the hWJ-MSCs-treated group, the mean liver weight and volume increased by 42% and 78% compared to the control group. The total volume of the hepatocytes increased by 63% and that of sinusoids by threefold in the treated rabbits. The total volume of the central veins increased by 70%. The total number corresponding to hepatocytes in the experimental group increased by 112% compared to the rabbits in the control. The total volume of the hepatocyte nuclei in the experimental group increased by 117% compared to the rabbits in the control. Conclusion: After xenotransplantation of human MSCs, host tissue microenvironments (here, the rabbit liver) were altered, and these included quantitative factors corresponding to the liver tissue and hepatocyte morphometric indices.

Keywords: xenotransplantation, mesenchymal stromal, stem cell, Wharton ‘s jelly, liver

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92 Use of Serum Creatinine as an Incentive to Increase Prep Uptake Among Key Population Groups in South-South Nigeria

Authors: Akhigbe Mark, Abang Roger, Mwoltu Nanaribet, Edet Blessing

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Introduction.: The introduction of pre- exposure prophylaxis (PrEP) as a biomedical prevention method for HIV/AIDS has been around for more than a decade since the first confirmed evidence of its effectiveness when used daily as an oral pill. It is now a very valuable addition for people who are at higher risk of contracting HIV. Although globalacceptanceof PrEP hasincreased, PrEP is still highly concentrated in a small number of countries and within a small sub-population, with Kenya and South Africa accounting for only 19% of people who have received PrEP in Africa region, there is still a significant regionGap in PrEP availability and use, with only 28% of the target of 3 million in low-and middle countries currently using PrEP. Description: The purpose of this study is to find out if serum creatinine could be used as an incentive to improve PrEP uptake among Key population.Numerous approaches to increasing the uptake ofPrEP as a prevention mechanism for HIV in KPs has beenemployed, and one of them is serum creatinine. This approach is a biomarker of renal function, which was used in study as an incentive to increase PrEP uptake among key population groups (female sex workers, men who have sex with men, persons who inject drugs, transgender) in 3 states from South-South Nigeria. Whole blood samples are collected from clients, analysis of the samples is done using the clinical chemistry analyzer before they are initiated onto PrEP. Lessons learned and Recommendations: Secondary data was extracted from 3 states of HALG Implementing facilities in Southern part of Nigeria, PrEP uptake before and afterthe introduction of serum creatinine between March 2020 and August 2020 among key populationsin Nigeria. A total of 5664 patients were initiated on PrEP before, and after the introduction of serum creatinine, the PrEP uptake rate before (March 2020 to May 2020) introduction of serum creatinine accounted for only 5% of the total onset, and after (June 2020 to August 2020) introduction of serum creatinine, the uptake rate accounted for 95% of the total onset. These finding shows that increased uptake of PrEP before/after serum creatineindicates that serum creatine may be an effective stimulus for promoting PrEP in key populations.

Keywords: serum creatinine, incentives, PrEP, key populations, Nigeria

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91 Emblica officinalis Fruit Extract Ameliorates Cisplatin-Induced Nephrotoxicity in Experimental Rats

Authors: Prerna Kalra, Surender Singh

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Cisplatin is the most common chemotherapeutic agent used in different solid tumors, but its main limiting factor is dose-dependent nephrotoxicity by generating reactive oxygen species, by stimulating inflammatory and apoptotic pathways. Additional adjuvant therapies to decrease the toxicity of this chemotherapeutic drug are essential. This study was designed to evaluate the protective role of Emblica officinalis Geartn (Indian gooseberry) against cisplatin induced nephrotoxicity. Emblica officinalis was orally administered to Wistar rats (n=6) for 10 days in 50, 100 and 200mg/kg body weight. On day 7, 8mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. Serum creatinine, blood urea nitrogen and antioxidant levels were measured on day10. The renal damage was evaluated by histopathological and transmission electron microscopy. We found that 200mg/kg dose of Emblica officinalis significantly inhibited the elevation of biochemical parameters i.e. serum creatinine, blood urea nitrogen, oxidant stress marker (malondialdehyde) and increased the reduced levels of antioxidant marker (endogenous glutathione and superoxide dismutase). Cisplatin treated rats have shown acute tubular necrosis and infiltration of inflammatory cells in rat kidney which was reversed after treating the animals with Emblica officinalis in the treatment group. In ultrastructural changes cisplatin treated group showed the damaged mitochondria (M) with dissolved cristae and large number of lysosomes (L) and vacuole (V) formation in tubular epithelial cells. EOE administered group showed visible cristae formation and sign of autophagy vacuoles at a dose of 200mg/kg. Further in-silico studies revealed that ellagic acid is responsible for its nephroprotective effect. The above findings conclude that the Emblica officinalis may be used as an adjuvant therapy in cisplatin induced nephrotoxicity.

Keywords: antioxidant, cisplatin, Emblica officinalis, in silico, nephrotoxicity

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90 Osteoprotegerin and Osteoprotegerin/TRAIL Ratio are Associated with Cardiovascular Dysfunction and Mortality among Patients with Renal Failure

Authors: Marek Kuźniewski, Magdalena B. Kaziuk , Danuta Fedak, Paulina Dumnicka, Ewa Stępień, Beata Kuśnierz-Cabala, Władysław Sułowicz

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Background: The high prevalence of cardiovascular morbidity and mortality among patients with chronic kidney disease (CKD) is observed especially in those undergoing dialysis. Osteoprotegerin (OPG) and its ligands, receptor activator of nuclear factor kappa-B ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been associated with cardiovascular complications. Our aim was to study their role as cardiovascular risk factors in stage 5 CKD patients. Methods: OPG, RANKL and TRAIL concentrations were measured in 69 hemodialyzed CKD patients and 35 healthy volunteers. In CKD patients, cardiovascular dysfunction was assessed with aortic pulse wave velocity (AoPWV), carotid artery intima-media thickness (CCA-IMT), coronary artery calcium score (CaSc) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentration. Cardiovascular and overall mortality data were collected during a 7-years follow-up. Results: OPG plasma concentrations were higher in CKD patients comparing to controls. Total soluble RANKL was lower and OPG/RANKL ratio higher in patients. Soluble TRAIL concentrations did not differ between the groups and OPG/TRAIL ratio was higher in CKD patients. OPG and OPG/TRAIL positively predicted long-term mortality (all-cause and cardiovascular) in CKD patients. OPG positively correlated with AoPWV, CCA-IMT and NT-proBNP whereas OPG/TRAIL with AoPWV and NT-proBNP. Described relationships were independent of classical and non-classical cardiovascular risk factors, with exception of age. Conclusions: Our study confirmed the role of OPG as a biomarker of cardiovascular dysfunction and a predictor of mortality in stage 5 CKD. OPG/TRAIL ratio can be proposed as a predictor of cardiovascular dysfunction and mortality.

Keywords: osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, receptor activator of nuclear factor kappa-B ligand, hemodialysis, chronic kidney disease, cardiovascular disease

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89 Spontaneous Pneumothorax in Mixed Poisoning Presented as Daisley Barton Syndrome

Authors: A. A. Md. Ryhan Uddin, Swarup Das, Rajesh Barua, Joheb Hasan, Rashedul Islam

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Background: The herbicide has toxicological importance because some of them are associated with high mortality rates due to respiratory failure. Organophosphate poisoning (OPC) & Paraquat self-poisoning is a major clinical and public health problems in low and middle-income countries across much of South Asia. Paraquat was not used as a common suicidal agent previously in Bangladesh. We report a case of 15 years old female admitted to the ER with a history of nausea & vomiting after ingestion of an unknown substance in a suicidal attempt, later identified as mixed poisoning- OPC & Paraquat. She was initially asymptomatic but later developed renal shutdown & lung injuries as well as pneumothorax, referred to as Daisley Barton Syndrome. Objective: This case report aims to alert spontaneous pneumothorax in mixed poisoning on uncommon forms of presentation. Pneumothorax in a patient with paraquat poisoning is a less unusual but underdiagnosed finding. It has a high index of early mortality. Case history: The patient's attendant complained about nausea followed by vomiting, which was nonprojectile & contains undigested food materials first, then gastric juice later. After a few hours, she also complains of urinary retention. Her family members treated her with some home remedies for her initial symptoms, but all attempts failed. After admission, the patient was initially asymptomatic. Through repeated history taking, her attendant showed a bottle of OPC in liquid form, which they suspected that she may have ingested some of the liquid from that bottle accidentally or attempted Suicide. So, management started for OPC poisoning. She responded well initially, but on 4th day of admission, the patient's condition became deteriorating. After the workout with the family member, 2nd bottle of Pesticide was discovered, which was Paraquat. Conclusion: Physicians should be aware of the symptoms of mixed poisoning and the timely use of urine dithionate testing for early detection and treatment. Pneumothorax is an early predictor of mortality in patients with paraquat poisoning.

Keywords: pneumothorax, suicide, dithionate, OPC, herbicide

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88 Development of an Experimental Model of Diabetes Co-Existing with Metabolic Syndrome in Rats

Authors: Rajesh Kumar Suman, Ipseeta Ray Mohanty, Manjusha K. Borde, Ujjawala maheswari, Y. A. Deshmukh

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Background: Metabolic syndrome encompasses cluster of risk factors for cardiovascular disease which includes abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. The incidence of metabolic syndrome is on the rise globally. Objective: The present study was designed to develop a unique animal model that will mimic the pathological features seen in a large pool of individuals with diabetes and metabolic syndrome; suitable for pharmacological screening of drugs beneficial in this condition. Material and Methods: A combination of high fat diet (HFD) and low dose of streptozotocin (STZ) at 30, 35 and 40 mg/kg was used to induce metabolic syndrome co-existing with diabetes mellitus in Wistar rats. Results: The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for our study to induce diabetes mellitus. Rat fed HFD (HF-DC) group showed significant (p < 0.001) increase in body weight on 4th and 7th week as compared with NC (Normal Control) group rats. However, the increase in body weight of HF-DC group rats was not sustained at the end of 10th weeks. Various components of metabolic syndrome such as dyslipidemia {(Increased Triglyceride, total Cholesterol, LDL Cholesterol and decreased HDL Cholesterol)}, diabetes mellitus (Blood Glucose, HbA1c, Serum Insulin, C-peptide), hypertension {Systolic Blood pressure (p < 0.001)} were mimicked in the developed model of metabolic syndrome co existing with diabetes mellitus. In addition significant cardiac injury as indicated by CPK-MB levels, artherogenic index, hs-CRP. The decline in hepatic function {(p < 0.01) increase in the level of SGPT (U/L)} and renal function {(increase in creatinine levels (p < 0.01)} when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis and inflammation in Heart, Pancreas, Liver and Kidney of HFD-DC group as compared to NC. Conclusion: The present study has developed a unique rodent model of metabolic syndrome; with diabetes as an essential component.

Keywords: diabetes, metabolic syndrome, high fat diet, streptozotocin, rats

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87 The Characteristics of Withhold Resuscitation in Out-Of-Hospital Cardiac Arrest

Authors: An-Yi Wang, Wei-Fong Kao, Shin-Han Tsai

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Introduction: Information as patient characteristics, resuscitation scene, resuscitation provider perspectives and families wish affects on resuscitation decision-making for out-of-hospital cardiac arrest (OHCA). There is no consistency consensus on how families and emergency physicians approach this decision. The main purpose of our study is to evaluate the characteristics of withholding resuscitation efforts arrival at the hospital. Methods: We retrospectively analyzed patients with OHCA without pre-hospital return-of-spontaneous circulation (ROSC) who was sent to our emergency department (ED) between January 2014 and December 2015. Baseline characteristics, pre-hospital course, and causes of the cardiopulmonary arrest among patients were compared. Results: In 2 years, total 155 arrest patients without pre-hospital ROSC was included. 33(21.3%) patients withhold the resuscitation efforts in ED with mean resuscitation duration 4.45 ± 7.04 minutes after ED arrival. In withholding group, the initial rhythm of arrests was all non-shockable. 9 of them received endotracheal intubation before decision-making. None of the patients in withhold resuscitation group survived to discharge. There was no significant difference among gender, underlying cardiovascular disease, malignancy, chronic renal disease, nor witness collapse between withhold and continue resuscitation groups. Univariate analysis showed there was lower percentage of bystander resuscitation (32.3% vs. 50.4%, p=0.071), and the lower percentage of transport via emergency medical service (EMS) (78.8% vs. 91.8%, p=0.054) in withholding group. Multivariate analysis showed old age (adjusted odds ratio=1.06, 95% C.I.=[1.02-1.11], p<0.05), with underlying respiratory insufficiency (adjusted odds ratio=12.16, 95% C.I.=[3.34-44.29], p<0.05), living at home compared with nursing home (adjusted odds ratio=37.75, 95% C.I.=[1.09-1110.70], p<0.05) were more likely to withhold resuscitation. Transport via EMS was more likely to continue resuscitation (adjusted odds ratio=0.11, 95% C.I.=[0.02-0.71], p<0.05). Conclusion: The decision-making for families and emergency physicians to withhold or continue resuscitation for out-of-hospital cardiac arrest is complex and multi-factorial. Continue resuscitation efforts in nursing home residents is high, and further study among this population is warranted.

Keywords: cardiopulmonary resuscitation, out-of-hospital cardiac arrest, termination resuscitation, withhold resuscitation

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86 Effect of Different Methods to Control the Parasitic Weed Phelipanche ramosa (L. Pomel) in Tomato Crop

Authors: Disciglio G., Lops F., Carlucci A., Gatta G., Tarantino A., Frabboni L, Tarantino E.

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The Phelipanche ramosa is considered the most damaging obligate flowering parasitic weed on a wide species of cultivated plants. The semiarid regions of the world are considered the main center of this parasitic weed, where heavy infestation are due to the ability to produce high numbers of seeds (up to 200,000), that remain viable for extended period (more than 19 years). In this paper 13 treatments of parasitic weed control, as physical, chemical, biological and agronomic methods, including the use of the resistant plants, have been carried out. In 2014 a trial was performed on processing tomato (cv Docet), grown in pots filled with soil taken from a plot heavily infested by Phelipanche ramosa, at the Department of Agriculture, Food and Environment, University of Foggia (southern Italy). Tomato seedlings were transplanted on August 8, 2014 on a clay soil (USDA) 100 kg ha-1 of N; 60 kg ha-1 of P2O5 and 20 kg ha-1 of S. Afterwards, top dressing was performed with 70 kg ha-1 of N. The randomized block design with 3 replicates was adopted. During the growing cycle of the tomato, at 70-75-81 and 88 days after transplantation the number of parasitic shoots emerged in each pot was detected. Also values of leaf chlorophyll Meter SPAD of tomato plants were measured. All data were subjected to analysis of variance (ANOVA) using the JMP software (SAS Institute Inc., Cary, NC, USA), and for comparison of means was used Tukey's test. The results show lower values of the color index SPAD in tomato plants parasitized compared to those healthy. In addition, each treatment studied did not provide complete control against Phelipanche ramosa. However the virulence of the attacks was mitigated by some treatments: radicon product, compost activated with Fusarium, mineral fertilizer nitrogen, sulfur, enzone and resistant tomato genotype. It is assumed that these effects can be improved by combining some of these treatments each other, especially for a gradual and continuing reduction of the “seed bank” of the parasite in the soil.

Keywords: control methods, Phelipanche ramose, tomato crop

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85 Joubert Syndrome and Related Disorders: A Single Center Experience

Authors: Ali Al Orf, Khawaja Bilal Waheed

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Background and objective: Joubert syndrome (JS) is a rare, autosomal-recessive condition. Early recognition is important for management and counseling. Magnetic resonance imaging (MRI) can help in diagnosis. Therefore, we sought to evaluate clinical presentation and MRI findings in Joubert syndrome and related disorders. Method: A retrospective review of genetically proven cases of Joubert syndromes and related disorders was reviewed for their clinical presentation, demographic information, and magnetic resonance imaging findings in a period of the last 10 years. Two radiologists documented magnetic resonance imaging (MRI) findings. The presence of hypoplasia of the cerebellar vermis with hypoplasia of the superior cerebellar peduncle resembling the “Molar Tooth Sign” in the mid-brain was documented. Genetic testing results were collected to label genes linked to the diagnoses. Results: Out of 12 genetically proven JS cases, most were females (9/12), and nearly all presented with hypotonia, ataxia, developmental delay, intellectual impairment, and speech disorders. 5/12 children presented at age of 1 or below. The molar tooth sign was seen in 10/12 cases. Two cases were associated with other brain findings. Most of the cases were found associated with consanguineous marriage Conclusion and discussion: The molar tooth sign is a frequent and reliable sign of JS and related disorders. Genes related to defective cilia result in malfunctioning in the retina, renal tubule, and neural cell migration, thus producing heterogeneous syndrome complexes known as “ciliopathies.” Other ciliopathies like Senior-Loken syndrome, Bardet Biedl syndrome, and isolated nephronophthisis must be considered as the differential diagnosis of JS. The main imaging findings are the partial or complete absence of the cerebellar vermis, hypoplastic cerebellar peduncles (giving MTS), and (bat-wing appearance) fourth ventricular deformity. LimitationsSingle-center, small sample size, and retrospective nature of the study were a few of the study limitations.

Keywords: Joubart syndrome, magnetic resonance imaging, molar tooth sign, hypotonia

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84 Development of Ketorolac Tromethamine Encapsulated Stealth Liposomes: Pharmacokinetics and Bio Distribution

Authors: Yasmin Begum Mohammed

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Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

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83 Blood Flow Estimator of the Left Ventricular Assist Device Based in Look-Up-Table: In vitro Tests

Authors: Tarcisio F. Leao, Bruno Utiyama, Jeison Fonseca, Eduardo Bock, Aron Andrade

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This work presents a blood flow estimator based in Look-Up-Table (LUT) for control of Left Ventricular Assist Device (LVAD). This device has been used as bridge to transplantation or as destination therapy to treat patients with heart failure (HF). Destination Therapy application requires a high performance LVAD; thus, a stable control is important to keep adequate interaction between heart and device. LVAD control provides an adequate cardiac output while sustaining an appropriate flow and pressure blood perfusion, also described as physiologic control. Because thrombus formation and system reliability reduction, sensors are not desirable to measure these variables (flow and pressure blood). To achieve this, control systems have been researched to estimate blood flow. LVAD used in the study is composed by blood centrifugal pump, control, and power supply. This technique used pump and actuator (motor) parameters of LVAD, such as speed and electric current. Estimator relates electromechanical torque (motor or actuator) and hydraulic power (blood pump) via LUT. An in vitro Mock Loop was used to evaluate deviations between blood flow estimated and actual. A solution with glycerin (50%) and water was used to simulate the blood viscosity with hematocrit 45%. Tests were carried out with variation hematocrit: 25%, 45% and 58% of hematocrit, or 40%, 50% and 60% of glycerin in water solution, respectively. Test with bovine blood was carried out (42% hematocrit). Mock Loop is composed: reservoir, tubes, pressure and flow sensors, and fluid (or blood), beyond LVAD. Estimator based in LUT is patented, number BR1020160068363, in Brazil. Mean deviation is 0.23 ± 0.07 L/min for mean flow estimated. Larger mean deviation was 0.5 L/min considering hematocrit variation. This estimator achieved deviation adequate for physiologic control implementation. Future works will evaluate flow estimation performance in control system of LVAD.

Keywords: blood pump, flow estimator, left ventricular assist device, look-up-table

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82 Inhibition of Echis ocellatus Venom Metalloprotease by Flavonoid-Rich Ethyl Acetate Sub-fraction of Moringa oleifera Leaves (Lam.): in vitro and in silico Approaches

Authors: Adeyi Akindele Oluwatosin, Mustapha Kaosarat Keji, Ajisebiola Babafemi Siji, Adeyi Olubisi Esther, Damilohun Samuel Metibemu, Raphael Emuebie Okonji

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Envenoming by Echis ocellatus is potentially life-threatening due to severe hemorrhage, renal failure, and capillary leakage. These effects are attributed to snake venom metalloproteinases (SVMPs). Due to drawbacks in the use of antivenom, natural inhibitors from plants are of interest in studies of new antivenom treatment. Antagonizing effects of bioactive compounds of Moringa oleifera, a known antisnake plant, are yet to be tested against SVMPs of E. ocellatus (SVMP-EO). Ethanol crude extract of M. oleifera was partitioned using n-hexane and ethyl acetate. Each partition was fractionated using column chromatography and tested against SVMP-EO purified through ion-exchange chromatography with EchiTab-PLUS polyvalent anti-venom as control. Phytoconstituents of ethyl acetate fraction were screened against the catalytic site of crystal of BaP1-SVMP, while drug-likeness and ADMET toxicity of compound were equally determined. The molecular weight of isolated SVMP-EO was 43.28 kDa, with a specific activity of 245 U/ml, a percentage yield of 62.83 %, and a purification fold of 0.920. The Vmax and Km values are 2 mg/ml and 38.095 μmol/ml/min, respectively, while the optimal pH and temperature are 6.0 and 40°C, respectively. Polyvalent anti-venom, crude extract, and ethyl acetate fraction of M. oleifera exhibited a complete inhibitory effect against SVMP-EO activity. The inhibitions of the P-1 and P-II metalloprotease’s enzymes by the ethyl acetate fraction are largely due to methanol, 6, 8, 9-trimethyl-4-(2-phenylethyl)-3-oxabicyclo[3.3.1]non-6-en-1-yl)- and paroxypropione, respectively. Both compounds are potential drug candidates with little or no concern of toxicity, as revealed from the in-silico predictions. The inhibitory effects suggest that this compound might be a therapeutic candidate for further exploration for treatment of Ocellatus’ envenoming.

Keywords: Echis ocellatus, Moringa oleifera, anti-venom, metalloproteases, snakebite, molecular docking

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81 Ultrasound as an Aid to Predict the Onset of Leaking in Dengue Haemorrhagic Fever: Experience of a Dengue Treatment Facility in South Asia

Authors: Hasn Perera, Is Almeida, Hnk Perera, Mzf Mohammed, Ade Silva, H. Wijesinghe, Ajal Fernando

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Introduction: Dengue is a major Public Health burden of two clinical entities, Dengue Fever & Dengue Haemorrhagic Fever (DHF). The vast majority of dengue deaths occur in DHF patients, where the diagnosis hinges on the presence of fluid leakage. Limited Ultrasound Scans (USS) of chest and abdomen are used widely at Centre for Clinical Management of Dengue & Dengue Haemorrhagic Fever (CCMDDHF), as the primary method for detecting fluid leaking in DHF. This study analyses the relationship between haematological and USS findings at the onset of leaking and to further determine the usefulness of ultrasound in diagnosing DHF. Methods: A prospective analysis of 80 serologically confirmed dengue patients initially admitted to a General Medical and Paediatric wards who were subsequently transferred to the CCMDDHF from March to September 2017 were analysed. In addition to repeated blood counts and capillary haematocrits’, serial USS were done to detect the onset fluid leaking by three competent and experienced doctors at CCMDDHF. Results: 80 patients (male: female: 38:42) with a mean age of 20 years (SD ±16.8, range 3-74) were evaluated. Dropping of platelet counts below 100,000 and haematocrit rise towards 20% started 4±1.3 day of fever with a mean platelet value of 69x103(range17-98x103). Gallbladder wall thickening was the commonest (98.7%) USS finding followed by fluid in hepato-renal pouch (95%), pelvic fluid (58.7%), right-sided pleural effusion (35%), bilateral effusions (7.5%). USS evidence of plasma leakage was detected in 11.25 %( n=9) of DHF cases from 1 day before significant haematocrit rise was noted. 35 (43.7%) patients with lowering platelets and haematocrit rise showed no objective evidence of plasma leaking on ultrasound scan. Conclusion: This outbreak underscores the importance of USS as a useful, sensitive and cost-effective tool for early diagnosis of suspected DHF cases, facilitating the tracking of progress of leaking and management of epidemics.

Keywords: dengue, ultrasound, plasma leaking, South Asia

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80 Dermatomyositis: It is Not Always an Allergic Reaction

Authors: Irfan Abdulrahman Sheth, Sohil Pothiawala

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Dermatomyositis is an idiopathic inflammatory myopathy, traditionally characterized by a progressive, symmetrical proximal muscle weakness and pathognomonic or characteristic cutaneous manifestations. We report a case of a 60-year old Chinese female who was referred from polyclinic for allergic rash over the body after applying hair dye 3 weeks ago. It was associated with puffiness of face, shortness of breath and hoarse voice since last 2 weeks with decrease effort tolerance. She also complained of dysphagia/ myalgia with progressive weakness of proximal muscles and palpitations. She denied chest pain, loss of appetite, weight loss, orthopnea or fever. She had stable vital signs and appeared cushingoid. She was noted to have rash over the scalp/ face and ecchymosis over the right arm with puffiness of face and periorbital oedema. There was symmetrical muscle weakness and other neurological examination was normal. Initial impression was of allergic reaction and underlying nephrotic syndrome and Cushing’s syndrome from TCM use. Diagnostic tests showed high Creatinine kinase (CK) of 1463 u/l, CK–MB of 18.7 ug/l and Troponin –T of 0.09 ug/l. The Full blood count and renal panel was normal. EMG showed inflammatory myositis. Patient was managed by rheumatologist and discharged on oral prednisolone with methotrexate/ ergocalciferol capsule and calcium carb, vitamin D tablets and outpatient follow up. In some patients, cutaneous disease exists in the absence of objective evidence of muscle inflammation. Management of dermatomyositis begins with careful investigation for the presence of muscle disease or of additional systemic involvement, particularly of the pulmonary, cardiac or gastrointestinal systems, and for the possibility of an accompanying malignancy. Muscle disease and systemic involvement can be refractory and may require multiple sequential therapeutic interventions or, at times, combinations of therapies. Thus, we want to highlight to the physicians that the cutaneous disease of dermatomyositis should not be confused with allergic reaction. It can be particularly challenging to diagnose. Early recognition aids appropriate management of this group of patients.

Keywords: dermatomyositis, myopathy, allergy, cutaneous disease

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79 Ability of Bentonite-lactobacillus Rhamnosus GAF06 Mixture to Mitigate Aflatoxin M1 Damages in Balb/C Mice

Authors: Amina Aloui, Jalila Ben Salah-Abbès, Abdellah Zinedine, Amar Riba, Noel Durand, Catherine Brabet, Didier Montet, Samir Abbès

Abstract:

Mycotoxin contamination of food and feed-isa globaconcern, both economically and for public health. Aflatoxin M1 (AFM1) is the principal hydroxylated metabolite of aflatoxin B1. It is frequently found in milk and other dairy products. It is responsible for the development of hepatocellular carcinoma and immunotoxic in humans and animals. The reduction of its bioavailabilitybecomesa great demand in order to protect human and animal health. The use of probiotic bacteria and clay are demonstrated to be able to bind AFM1 in vitro. This study aimed to investigate, in vivo, the activity of two-component mixture: L. rhamnosusGAF06 (LR) and bentonite for reducing the oxidative stress and the histological alterationsinduced by AFM1 in the liver andkidneys. For the experiment, male mice were divided into 7 groups (6 mice/group) and treated, orally, by AFM1, alone or in combination with LR and/or bentonite, for 10 days as follows: group 1 control, group 2 treated with LR alone (2.108 CFU/ml), group 3 treated with bentonite alone (1g/kg), group 4 treated with AFM1 alone (100μg/kg), group 5 co-treated with LR+AFM1, group 6 co-treated with bentonite+AFM1, group 7 co-treated with bentonite+LR+AFM1. At the end of the treatment, the mice were sacrificed, and the livers and kidneys were collected for histological assays. Intracellular antioxidant activities and lipid peroxidation were also studied. The results showed that AFM1causeddamage in liver and kidney tissues, being evidence of hepatotoxicity and nephrotoxicity marked by necrotic cells. It increased the MDA level and decreased the antioxidant enzyme activities (SOD) in both organs. In contrast, the co-treatment with AFM1 plus LR and/or bentonitesignificantly improved the hepatic and renal tissues, regulated kidney, and liver antioxidant enzyme activities. This improvement was more remarkable with the administration of LR-bentonite mixture with AFM1.LR and bentonite alone showed to be safe during the treatment. This mixture can be a promising candidate for future applications in biotechnological processes that aimed to detoxify AFM1in food and feed.

Keywords: aflatoxin M1, bentonite, L. rhamnosus GAF06, oxidative stress, prevention

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78 Comparison with Two Clinical Cases of Plasma Cell Neoplasm by Using the Method of Capillary Electrophoresis

Authors: Kai Pai Huang

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Background: There are several types of plasma cell neoplasms including multiple myeloma, plasmacytoma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance (MGUS) are found in our lab. Today, we want to compare with two cases using the method of capillary electrophoresis. Method: Serum is prepared and electrophoresis is performed at alkaline PH in a capillary using the Sebia® Capillary 2. Albumin and globulins are detected by the detector which is located in the cathode of the capillary and the signals are transformed to peaks. Serum was treated with beta-mercaptoethanol which reducing the polymerized immunoglobulin to monomer immunoglobulin to clarify two M-protein are secreted from the same plasma cell clone in bone marrow. Result: Case 1: A 78-year-old female presenting dysuria, oliguria and leg edema for several months. Laboratory data showed proteinuria, leukocytosis, results of high serum IgA and lambda light chain. A renal biopsy found amyloid fibrils in the glomerular mesangial area. Serum protein electrophoresis shows a major monoclonal peak in the β region and minor small peak in gamma region, and the immunotyping studies for serum showed two IgA/λ type. Case 2: A 55-year-old male presenting abdominal distension and low back pain for more than one month. Laboratory data showed T12 T8 compression fracture, results of high serum IgM and kappa light chain. Bone marrow aspiration showed the cells from the bone marrow are B cells with monotypic kappa chain expression. Bone marrow biopsy found this is lymphoplasmacytic lymphoma (Waldenstrom macroglobulin). Serum protein electrophoresis shows a monoclonal peak in the β region and the immunotyping studies for serum showed IgM/κ type. Conclusion: Plasma cell neoplasm can be diagnosed by many examinations. Among them, using capillary electrophoresis by a lab can separate several types of gammopathy and the quantification of a monoclonal peak can be used to evaluate the patients’ prognosis or treatment.

Keywords: plasma cell neoplasm, capillary electrophoresis, serum protein electrophoresis, immunotyping

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77 Application of Gamma Frailty Model in Survival of Liver Cirrhosis Patients

Authors: Elnaz Saeedi, Jamileh Abolaghasemi, Mohsen Nasiri Tousi, Saeedeh Khosravi

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Goals and Objectives: A typical analysis of survival data involves the modeling of time-to-event data, such as the time till death. A frailty model is a random effect model for time-to-event data, where the random effect has a multiplicative influence on the baseline hazard function. This article aims to investigate the use of gamma frailty model with concomitant variable in order to individualize the prognostic factors that influence the liver cirrhosis patients’ survival times. Methods: During the one-year study period (May 2008-May 2009), data have been used from the recorded information of patients with liver cirrhosis who were scheduled for liver transplantation and were followed up for at least seven years in Imam Khomeini Hospital in Iran. In order to determine the effective factors for cirrhotic patients’ survival in the presence of latent variables, the gamma frailty distribution has been applied. In this article, it was considering the parametric model, such as Exponential and Weibull distributions for survival time. Data analysis is performed using R software, and the error level of 0.05 was considered for all tests. Results: 305 patients with liver cirrhosis including 180 (59%) men and 125 (41%) women were studied. The age average of patients was 39.8 years. At the end of the study, 82 (26%) patients died, among them 48 (58%) were men and 34 (42%) women. The main cause of liver cirrhosis was found hepatitis 'B' with 23%, followed by cryptogenic with 22.6% were identified as the second factor. Generally, 7-year’s survival was 28.44 months, for dead patients and for censoring was 19.33 and 31.79 months, respectively. Using multi-parametric survival models of progressive and regressive, Exponential and Weibull models with regard to the gamma frailty distribution were fitted to the cirrhosis data. In both models, factors including, age, bilirubin serum, albumin serum, and encephalopathy had a significant effect on survival time of cirrhotic patients. Conclusion: To investigate the effective factors for the time of patients’ death with liver cirrhosis in the presence of latent variables, gamma frailty model with parametric distributions seems desirable.

Keywords: frailty model, latent variables, liver cirrhosis, parametric distribution

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76 Antidiabetic and Antioxidant Potential of Aqueous Extract of Jasminum humile Leaves in Nicotinamide/Streptozotocin induced Type-2 Diabetes Mellitus (T2DM) Rat

Authors: Parminder Nain, Jaspreet kaur, Vipin Saini, Sunil Sharma

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Jasminum humile commonly known as yellow Jasmine or Pili chameli, is a medicinal plant used in Ayurveda for treating various diseases, one of which is diabetes mellitus. The current study aimed to establish the antidiabetic and antioxidant properties of aqueous extract of Jasminum humile leaves (AEJHL) in nicotinamide/streptozotocin induced type 2 diabetic rats. Phytochemical screening, HPLC analysis, and acute toxicity study of AEJHL were carried out. Male albino wistar rats (n=42) were divided into seven equal groups. Rats with moderate diabetes having hyperglycemia (blood glucose 250-400 mg/dl) were taken for the experiment. Various concentrations of aqueous extract of Jasminum humile leaves (50, 100, 200 and 300 mg/kg, p.o.), and glibenclamide (1mg/kg, p.o.) were orally administered to diabetic rats for 45 days. The effect of AEJHL on blood glucose, plasma insulin and biochemical parameters such as hemoglobin, total protein, serum creatinine, serum urea, alkaline phosphate, Glutamic-oxalacetic transaminase (SGOT) and glutamic-pyruvic transaminase (SGPT), as well as total cholesterol, triglycerides, and high-density lipoprotein (HDL) were also studied. The antioxidant effect of AEJHL was determined by analyzing hepatic and renal antioxidant markers, like superoxide dismutase (SOD), catalase (CAT), reduced Glutathione (GSH), Glutathione peroxidase (GPx), and lipid peroxidation (LPO) in diabetic rats. After 45-days oral administration of aqueous extract of Jasminum humile leaves significantly (p<0.05) reduced blood sugar and increase plasma insulin level and also reverse all above biochemical parameters and antioxidant enzyme level at dose dependent manner. These findings provide in vivo evidence that the aqueous extract of Jasminum humile leaves possess significant antidiabetic and antioxidant potential in nicotinamide/streptozotocin-induced type-2 diabetes mellitus in rats.

Keywords: antidiabetic, antioxidant, jasminum humile, nicotinamide/streptozotocin, type-2 diabetic

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75 IL-23, an Inflammatory Cytokine, Decreased by Shark Cartilage and Vitamin A Oral Treatment in Patient with Gastric Cancer

Authors: Razieh Zarei, Hassan zm, Abolghasem Ajami, Darush Moslemi, Narges Afsary, Amrollah Mostafa-zade

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Introduction: IL-23 is responsible for the differentiation and expansion of Th17/ThIL-17 cells from naive CD4+ T cells. Therefore, may be IL-23/IL17 axis involve in a variety of allergic and autoimmune diseases, such as RA, MS, inflammatory bowel disease (IBD), and asthma. TGF-β is also share for the differentiation Th17 producing IL-17 and CD4+CD25+Foxp3hiT regulatory cells from naïve CD4+ T cells which are involved in the regulation of immune response, maintaining immunological self-tolerance and immune homeostasis ,and the control of autoimmunity and cancer surveillance. Therefore, T regulatory cells play a key role in autoimmunity, allergy, cancer, infectious disease, and the induction of transplantation tolerance. Vitamin A and it's derivatives (retinoids) inhibit or reverse the carcinogenic process in some types of cancers in oral cavity,head and neck, breast, skin, liver, and blood cells. Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, in vitro. Our purpose is whether simultaneous oral treatment vitamin A and shark cartilage can modulate IL-23/IL-17 and CD4CD25Foxp3 T regulatory cell/TGF-β pathways and Th1/Th2 immunity in patients with gastric cancer. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23,IL-17,TGF-β,IL-4 and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: An imbalance between IL-17 secretion and TGF-β/Foxp3 t regulatory cell pathway and so, Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) was not seen in patients with gastric cancer treated by vitamin A and shark cartilage. But, the simultaneously presented down-regulation of IL-23 indicated, at least cytokine level. Conclusion: Il-23, as a pro-angiogenesis cytokine, probably, help to tumor growth. Hence, suggested that down-regulation of IL-23, at least cytokine level, is useful for anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4CD25Foxp3 T regulatory pathway, γ-IFN, IL-4, shark cartilage and gastric cancer

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74 Beneficial Effect of Micropropagation Coupled with Mycorrhization on Enhancement of Growth Performance of Medicinal Plants

Authors: D. H. Tejavathi

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Medicinal plants are globally valuable sources of herbal products. Wild populations of many medicinal plants are facing threat of extinction because of their narrow distribution, endemicity, and degradation of specific habitats. Micropropagation is an established in vitro technique by which large number of clones can be obtained from a small bit of explants in a short span of time within a limited space. Mycorrhization can minimize the transient transplantation shock, experienced by the micropropagated plants when they are transferred from lab to land. AM fungal association improves the physiological status of the host plants through better uptake of water and nutrients, particularly phosphorus. Consequently, the growth performance and biosynthesis of active principles are significantly enhanced in AM fungal treated plants. Bacopa monnieri, Andrographis paniculata, Agave vera-curz, Drymaria cordata and Majorana hortensis, important medicinal plants used in various indigenous systems of medicines, are selected for the present study. They form the main constituents of many herbal formulations. Standard in vitro techniques were followed to obtain the micropropagated plants. Shoot tips and nodal segments were used as explants. Explants were cultured on Murashige and Skoog, and Phillips and Collins media supplemented with various combinations of growth regulators. Multiple shoots were obtained on a media containing both auxins and cytokinins at various concentrations and combinations. Multiple shoots were then transferred to rooting media containing auxins for root induction. Thus, obtained in vitro regenerated plants were subjected to brief acclimatization before transferring them to land. One-month-old in vitro plants were treated with AM fungi, and the symbiotic effect on the overall growth parameters was analyzed. It was found that micropropagation coupled with mycorrhization has significant effect on the enhancement of biomass and biosynthesis of active principles in these selected medicinal plants. In vitro techniques coupled with mycorrhization have opened a possibility of obtaining better clones in respect of enhancement of biomass and biosynthesis of active principles. Beneficial effects of AM fungal association with medicinal plants are discussed.

Keywords: cultivation, medicinal plants, micropropagation, mycorrhization

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73 Insulin-Producing Cells from Adult Human Bone Marrow Mesenchymal Stem Cells Control Chemically-Induced Diabetes in Dogs

Authors: Maha Azzam, Mahmoud Gabr, Mahmoud Zakaria, Ayman Refaie, Amani Ismail, Sherry Khater, Sylvia Ashamallah, Mohamed Ghoniem

Abstract:

Evidence was provided that human bone marrow-derived mesenhymal stem cells (HBM-MSCs) could be differentiated to form insulin-producing cells (IPCs). Transplantation of these cells was able to cure chemically-induced diabetes in nude mice. The efficacy of these cells to control diabetes in large animals was carried out to evaluate the sufficient number of cells needed/Kg body weight and to determine the functional longevity in vivo. Materials/Methods: Ten male mongrel dogs weighing 15-20 Kg were used in this study. Diabetes was chemically-induced in 7 dogs by a mixture of alloxan and streptozotocin. Three non-diabetic served as normal controls. Differentiated HBM-MSCs (5 million/Kg) were encapsulated in theracyte capsules and transplanted beneath the rectus sheath. Each dog received 2 capsules. One dog died 4 days postoperative from inhalation pneumonia. The remaining 6 dogs were followed up for 6-18 months. Results: Four dogs became normoglycemic within 6-8 weeks with normal glucose tolerance curves providing evidence that the transplanted cells were glucose-sensitive and insulin-responsive. In the remaining 2 dogs, fasting blood glucose was reduced but did not reach euglycemic levels. The sera of all transplanted dogs contained human insulin and c-peptide but negligible levels of canine insulin. When the HBM-MSCs loaded capsules were removed, rapid return of diabetic state was noted. The harvested capsules were examined by immunofluorescence. IPCs were seen and co-expression of with c-peptide was confirmed. Furthermore, all the pancreatic endocrine genes were expressed by the transplanted cells. Conclusions: This study provided evidence that theracyte capsules could protect the xenogenic HBM-MSCs from the host immune response. This is an important issue when clinical stem cell therapy is considered for definitive treatment for T1DM.

Keywords: diabetes, mesenchymal stem cells, dogs, Insulin-producing cells

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72 Neonatal Subcutaneous Fat Necrosis with Severe Hypercalcemia: Case Report

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

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Introduction: Subcutaneous fat necrosis of the newborn (SCFN) is a rare acute hypodermatitis characterized by skin lesions in the form of infiltrated, hard plaques and subcutaneous nodules, with a purplish-red color, occurring between the first and sixth week of life. SCFN is generally a benign condition that spontaneously regresses without sequelae, but it can be complicated by severe hypercalcemia. Methodology: This is a retrospective case report of neonatal subcutaneous fat necrosis complicated with severe hypercalcemia and nephrocalcinosis. Results: This is a case of a female newborn with a family history of a hypothyroid mother on Levothyrox, born to non-consanguineous parents and from a well-monitored pregnancy. The newborn was delivered by cesarean section at 39 weeks gestation due to severe preeclampsia. She was admitted to the Neonatal Intensive Care Unit at 1 hour of life for the management of grade 1 perinatal asphyxia and immediate neonatal respiratory distress related to transient respiratory distress. Hospitalization was complicated by a healthcare-associated infection, requiring intravenous antibiotics for ten days, with a good clinical and biological response. On the 20th day of life, she developed skin lesions in the form of indurated purplish-red nodules on the back and on both arms. A SCFN was suspected. A calcium level test was conducted, which returned a result of 3 mmol/L. The rest of the phosphocalcic assessment was normal, with early signs of nephrocalcinosis observed on renal ultrasound. The diagnosis of SCFN complicated by nephrocalcinosis associated with severe hypercalcemia was made, and the condition improved with intravenous hydration and corticosteroid therapy. Conclusion: SCFN is a rare and generally benign hypodermatitis in newborns with an etiology that is still poorly understood. Despite its benign nature, SCFN can be complicated by hypercalcemia, which can sometimes be life-threatening. Therefore, it is important to conduct a thorough skin examination of newborns, especially those with risk factors, to detect and correct any potential hypercalcemia.

Keywords: subcutaneous fat necrosis, newborn, hypercalcemia, nephrocalcinosis

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71 Free Fibular Flaps in Management of Sternal Dehiscence

Authors: H. N. Alyaseen, S. E. Alalawi, T. Cordoba, É. Delisle, C. Cordoba, A. Odobescu

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Sternal dehiscence is defined as the persistent separation of sternal bones that are often complicated with mediastinitis. Etiologies that lead to sternal dehiscence vary, with cardiovascular and thoracic surgeries being the most common. Early diagnosis in susceptible patients is crucial to the management of such cases, as they are associated with high mortality rates. A recent meta-analysis of more than four hundred thousand patients concluded that deep sternal wound infections were the leading cause of mortality and morbidity in patients undergoing cardiac procedures. Long-term complications associated with sternal dehiscence include increased hospitalizations, cardiac infarctions, and renal and respiratory failures. Numerous osteosynthesis methods have been described in the literature. Surgical materials offer enough rigidity to support the sternum and can be flexible enough to allow physiological breathing movements of the chest; however, these materials fall short when managing patients with extensive bone loss, osteopenia, or general poor bone quality, for such cases, flaps offer a better closure system. Early utilization of flaps yields better survival rates compared to delayed closure or to patients treated with sternal rewiring and closed drainage. The utilization of pectoralis major flaps, rectus abdominus, and latissimus muscle flaps have all been described in the literature as great alternatives. Flap selection depends on a variety of factors, mainly the size of the sternal defect, infection, and the availability of local tissues. Free fibular flaps are commonly harvested flaps utilized in reconstruction around the body. In cases regarding sternal reconstruction with free fibular flaps, the literature exclusively discussed the flap applied vertically to the chest wall. We present a different technique applying the free fibular triple barrel flap oriented in a transverse manner, in parallel to the ribs. In our experience, this method could have enhanced results and improved prognosis as it contributes to the normal circumferential shape of the chest wall.

Keywords: sternal dehiscence, management, free fibular flaps, novel surgical techniques

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70 Impect of Human on Prey of Birds in North West Rajasthan

Authors: Dau Lal Bohra, Sradha Vyas

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Bird species are already showing climate-related changes in the dates they migrate and breed, and in the timing of other key life-history events. Treats of feeding managements raptors have performed important ecological, traditional and aesthetic functions throughout the Indian subcontinent. The declines in India result from elevated adult and juvenile mortality, and low breeding success. The widespread and rapid pattern of declines, i.e. in all areas irrespective of habitat or protection status suggest that persecution through shooting or poisoning, whilst important at a local scale, are unlikely to have caused the declines. A mass killing of several species of vultures in the Indian subcontinent over the last two decades is largely blamed on the presence of a drug. Veterinary diclofenac caused an unprecedented decline in South Asia’s Gyps vulture populations, with some species declining by more than 97% between 1992 and 2007. Veterinary diclofenac causes renal failure in vultures, and killed tens of millions of such birds in the Indian sub-continent. The drug was finally banned there for veterinary purposes in 2006. This drug is now ‘a global problem’ threatening many vulnerable birds of prey. Recently, stappe eagles are also susceptible to veterinary diclofenac, effectively increasing the potential threat level, and the risks for European biodiversity. Steppe eagles are closely related with golden eagles (Aquila chrysaetus), imperial eagles (Aquila heliaca) and Spanish imperial eagles (Aquila adalberti), and all these species scavenge opportunistically on carcasses throughout their range. The Spanish imperial eagle, considered Vulnerable at global level, is now particularly at risk, due to the availability of diclofenac in Spain. These findings strengthen the case for banning veterinary diclofenac across. From year 2011 to 2014 more than 300 hundred birds dead in jorbeer, Bikaner. Now, with unequivocal evidence that this veterinary drug can cause a much wider impact on Europe´s biodiversity, it is time for action – please ban diclofenac human brand also in multi-dose vial from market.

Keywords: mortility, prey of birds, diclofenac, Rajasthan

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69 A Combination of Mesenchymal Stem Cells and Low-Intensity Ultrasound for Knee Meniscus Regeneration: A Preliminary Study

Authors: Mohammad Nasb, Muhammad Rehan, Chen Hong

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Background Meniscus defects critically alter knee function and lead to degenerative changes. Regenerative medicine applications including stem cell transplantation have showed a promising efficacy in finding alternatives to overcome traditional treatment limitations. However, stem cell therapy remains limited due to the substantially reduced viability and inhibitory microenvironment. Since tissue growth and repair are under the control of biochemical and mechanical signals, several approaches have recently been investigated (e.g., low intensity pulsed ultrasound [LIPUS]) to promote the regeneration process. This study employed LIPUS to improve growth and osteogenic differentiation of mesenchymal stem cells derived from human embryonic stem cells to improve the regeneration of meniscus tissue. Methodology: The Mesenchymal stromal cells (MSCs) were transplanted into the epicenter of the injured meniscus in rabbits, which were randomized into two main groups: a treatment group (n=32 New Zealand rabbits) including 4 subgroups of 8 rabbits in each subgroup (LIPUS treatment, MSC treatment, LIPUS with MSC and control), and a second group (n=9) to track implanted cells and their progeny using green fluorescence protein (GFP). GFP consists of the MSC and LIPUS-MSC combination subgroups. Rabbits were then subjected to histological, immunohistochemistry, and MRI assessment. Results: The quantity of the newly regenerated tissue in the combination treatment group that had Ultrasound irradiation after mesenchymal stem cells were better at all end points. Likewise, Tissue quality scores were also greater in knees treated with both approaches compared with controls and single treatment at all end points, achieving significance at twelve and twenty-four weeks [p < 0.05], and [p = 0.008] at twelve weeks. Differentiation into type-I and II collagen-expressing cells were higher in the combination group at up to twenty-four weeks. Conclusions: the combination of mesenchymal stem cells and LIPUS showed greater adhering to the sites of meniscus injury, differentiate into cells resembling meniscal fibrochondrocytes, and improve both quality and quantity of meniscal regeneration.

Keywords: stem cells, regenerative medicine, osteoarthritis, knee

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68 Ectopic Mediastinal Parathyroid Adenoma: A Case Report with Diagnostic and Management Challenges

Authors: Augustina Konadu Larbi-Ampofo, Ekemini Umoinwek

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Background: Hypercalcaemia is a common electrolyte imbalance that increases mortality if poorly controlled. Primary hyperparathyroidism often presents like this with a prevalence of 0.1-0.3%. Management due to an ectopic parathyroid adenoma in the mediastinum is challenging, especially in a patient with a pacemaker. Case Presentation: A 79-year-old woman with a history of a previous cardiac arrest, permanent pacemaker, ischaemic heart disease, bilateral renal calculi, rectal polyps, liver cirrhosis, and a family history of hyperthyroidism presented to the emergency department with acute back pain. Management and Outcome: The patient was diagnosed with primary hyperparathyroidism due to her elevated corrected calcium and parathyroid hormone levels. Parathyroid investigations consisting of an NM MIBI scan, SPECT-CT, 4D parathyroid scan, and an ultrasound scan of the neck and thorax confirmed an ectopic parathyroid adenoma in the mediastinum at the level of the aortic arch, along with benign thyroid nodules. The location of the adenoma warranted a thoracoscopic surgical approach; however, the presence of her pacemaker and other cardiovascular conditions predisposed her to a potentially poorer post-operative outcome. Discussion: Mediastinal ectopic parathyroid adenomas are rare and difficult to diagnose and treat, often needing a multimodal imaging approach for accurate localisation. Surgery is a definitive treatment; however, in this patient, long-term medical treatment with cinacalcet was the only next suitable treatment option. The difficulty with this is that cinacalcet tackles the biochemical markers of the disease entity and not the disease itself, leaving room for what happens next if there is refractory/uncontrolled hypercalcaemia in this patient with a pacemaker. Moreover, the coexistence of her multiple conditions raises the suspicion of an underlying multisystemic or multiple endocrine disorder, with multiple endocrine neoplasia coming to mind, necessitating further genetic or autoimmune investigations. Conclusion: Mediastinal ectopic parathyroid adenomas are rare, with diagnostic and management challenges.

Keywords: mediastinal ectopic parathyroid adenoma, hyperparathyroidism, SPECT/CT, nuclear medicine, multimodal imaging

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67 Development of a Nursing Care Program Based on Anthroposophic External Therapy for the Pediatric Hospital in Brazil and Germany

Authors: Karina Peron, Ricardo Ghelman, Monica Taminato, Katia R. Oliveira, Debora C. A. Rodrigues, Juliana R. C. Mumme, Olga K. M. Sunakozaua, Georg Seifert, Vicente O. Filho

Abstract:

The nurse is the most available health professional for the interventions of support in the integrative approach in hospital environment, therefore a professional group key to changes in the model of care. The central components in the performance of anthroposophic nursing procedures are direct physical contact, promotion of proper rhythm, thermal regulation and the construction of a calm and empathic atmosphere, safe for patients and their caregivers. The procedures of anthroposophic external therapies (AET), basically composed of the application of compresses and the use of natural products, provide an opportunity to intensify the therapeutic results through an innovative, complementary and integrative model in the university hospital. The objective of this work is to report the implementation of a program of nursing techniques (AET) through a partnership between the Pediatric Oncology Sector of the Department of Pediatrics of the Faculty of Medicine of the University of Sao Paulo and Charite University of Berlin, with lecturers from Berlin's Integrative Hospital Havelhöhe and Witten-Herdecke Integrative Hospital, both in Germany. Intensive training activities of the Hospital's nursing staff and a survey on AET needs were developed based on the most prevalent complaints in pediatric oncology patients in the three environments of the Hospital of Pediatric Oncology: Bone Marrow Transplantation Unit, Intensive Care Unit and Division of Internal Patients. We obtained the approval of the clinical protocol of external anthroposophic therapies for nursing care by the Ethics Committee and the Academic Council of the Hospital. With this project, we highlight the key AET needs that will be part of the standard program of pediatric oncology care with appropriate scientific support. The results of the prevalent symptoms were: vomiting, nausea, pain, difficulty in starting sleep, constipation, cold extremities, mood disorder and psychomotor agitation. This project was the pioneer within the Integrative Pediatrics Program, as an innovative concept of Medicine and Integrative Health presented at scientific meetings.

Keywords: integrative health care, integrative nursing, pediatric nursing, pediatric oncology

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66 Evaluation of Azo Dye Toxicity Using Some Haematological and Histopathological Alterations in Fish Catla Catla

Authors: Jagruti Barot

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The textile industry plays a major role in the economy of India and on the other side of the coin it is the major source for water pollution. As azo dyes is the largest dye class they are extensively used in many fields such as textile industry, leather tanning industry, paper production, food, colour photography, pharmaceuticals and medicine, cosmetic, hair colourings, wood staining, agricultural, biological and chemical research etc. In addition to these, they can have acute and/or chronic effects on organisms depending on their concentration and length of exposure when they discharged as effluent in the environment. The aim of this study was to assess the genotoxic and histotoxic potentials of environmentally relevant concentrations of RR 120 on Catla catla, important edible freshwater fingerlings. For this, healthy Catla catla fingerlings were procured from the Government Fish Farm and acclimatized in 100 L capacity and continuously aerated glass aquarium in laboratory for 15 days. According to APHA some physic-chemical parameters were measured and maintained such as temperature, pH, dissolve oxygen, alkalinity, total hardness. Water along with excreta had been changed every 24 hrs. All fingerlings were fed artificial food palates once a day @ body weight. After 15 days fingerlings were grouped in 5 (10 in each) and exposed to various concentrations of RR 120 (Control, 10, 20, 30 and 40 mg/L) and samples (peripheral blood and gills, kidney) were collected and analyzed at 96 hrs. of interval. All results were compared with the control. Micronuclei (MN), nuclear buds (NB), fragmented-apoptotic (FA) and bi-nucleated (BN) cells in blood cells and in tissues (gills and kidney cells) were observed. Prominent histopathological alterations were noticed in gills such as aneurism, hyperplasia, degenerated central axis, lifting of gill epithelium, curved secondary gill lamellae etc. Similarly kidney showed some detrimental changes like shrunken glomeruli with increased periglomerular space, degenerated renal tubules etc. Both haematological and histopathological changes clearly reveal the toxic potential of RR 120. This work concludes that water pollution assessment can be done by these two biomarkers which provide baseline to the further chromosomal or molecular work.

Keywords: micronuclei, genotoxicity, RR 120, Catla catla

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65 The Psychosocial Issues and Support Needs of Patients with Chronic Kidney Disease Undergoing Hemodialysis: A Qualitative Study from Nepal

Authors: Akriti Kafle Baral, Ruixing Zhang, Dzifa K Lalit, Manthar M Alli

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Introduction: Hemodialysis is the most common type of dialysis globally approximately million are reported to receive this type of dialysis. Psychosocial issues in hemodialysis are the psychological and socioeconomic burdens emanating from the initiation and course of treatment and have the potential for gross deterioration in the quality of life and general well-being of patients. Understanding the psychosocial issues and needs of patients undergoing hemodialysis could pave the way for comprehensive support and therapies designed to reduce stress, improve social support, and foster mental resilience. Objectives: The aim of this study was to explore the psychosocial issues and support needs of patients undergoing hemodialysis at a tertiary care center in Nepal. Methods: A qualitative descriptive study was conducted among 20 purposefully selected patients attending hemodialysis treatment at Pokhara Academy of Health Sciences, Nepal. Data was analyzed via thematic analysis. Results: The study resulted in three major themes which included Emotional, psychological, and spiritual struggles, Social and economic impacts, and Support and information needs. Moreover, 16 sub-themes emerged which are Frustration with daily life, Constant fear of death, Thoughts of self-harm, Perceived Burden on Family, Sense of Divine Punishment, Sense of Unfairness, Fear about future uncertainties, Social avoidance, Social stigmatization, Loss of employment, Financial strain, Transportation challenges, Need for early, clear and comprehensive information, Need for support and reassurance from family, Support through peer connections, and Reassurance from healthcare providers. Conclusion: The findings of this study indicate that patients undergoing hemodialysis in Nepal experience numerous hardships and multifaceted struggles that require support from different dimensions. Establishing robust support systems that include family involvement, peer networks, and effective communication from healthcare professionals can significantly mitigate feelings of anxiety and isolation.

Keywords: hemodialysis, psychosocial issues, support needs, chronic kidney disease, end stage renal disease, Nepal

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