Search results for: kidney encapsulation

Authors: Mario Isaza-Ruget, Claudia C. Colmenares-Mejia, Nancy Yomayusa, Camilo A. González, Andres Cely, Jossie Murcia

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Quantification of risks associated with complications development from chronic kidney disease (CKD) through accurate survival models can help with patient management. A retrospective cohort that included patients diagnosed with CKD from a primary care program and followed up between 2013 and 2018 was carried out. Time-dependent and static covariates associated with demographic, clinical, and laboratory factors were included. Deep Learning (DL) survival analyzes were developed for three CKD outcomes: CKD stage progression, >25% decrease in Estimated Glomerular Filtration Rate (eGFR), and Renal Replacement Therapy (RRT). Models were evaluated and compared with Random Survival Forest (RSF) based on concordance index (C-index) metric. 2.143 patients were included. Two models were developed for each outcome, Deep Neural Network (DNN) model reported C-index=0.9867 for CKD stage progression; C-index=0.9905 for reduction in eGFR; C-index=0.9867 for RRT. Regarding the RSF model, C-index=0.6650 was reached for CKD stage progression; decreased eGFR C-index=0.6759; RRT C-index=0.8926. DNN models applied in survival analysis context with considerations of longitudinal covariates at the start of follow-up can predict renal stage progression, a significant decrease in eGFR and RRT. The success of these survival models lies in the appropriate definition of survival times and the analysis of covariates, especially those that vary over time.

Keywords: artificial intelligence, chronic kidney disease, deep neural networks, survival analysis

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Authors: Fergal Fouhy, Alan O’Keeffe, Sean Costelloe, Michael Clarkson

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Background: Sarcoidosis is a systemic, non-infectious disease of unknown aetiology, characterized by non-caseating granulomatous inflammation. The lung is most often affected (90%); however, the condition can affect all organs, including the kidneys. There is limited evidence describing the incidence and characteristics of renal involvement in sarcoidosis. Serum angiotensin-converting enzyme (ACE) is a recognised biomarker used in the diagnosis and monitoring of sarcoidosis. Methods: A single-centre, retrospective cohort study of patients presenting to Cork University Hospital (CUH) in 2015 with first-time elevations of serum ACE was performed. This included an initial database review of ACE and other biochemistry results, followed by a medical chart review to confirm the presence or absence of sarcoidosis and management thereof. Acute kidney injury (AKI) was staged using the AKIN criteria, and chronic kidney disease (CKD) was staged using the KDIGO criteria. Follow-up was assessed over five years tracking serum creatinine, serum calcium, and estimated glomerular filtration rates (eGFR). Results: 119 patients were identified as having a first raised serum ACE in 2015. Seventy-nine male patients and forty female patients were identified. The mean age of patients identified was 47 years old. 11% had CKD at baseline. 18% developed an AKI at least once within the next five years. A further 6% developed CKD during this time period. 13% developed hypercalcemia. The patients within the lowest quartile of serums ACE had an incidence of sarcoidosis of 5%. None of this group developed hypercalcemia, 23% developed AKI, and 7% developed CKD. Of the patients with a serum ACE in the highest quartile, almost all had documented diagnoses of sarcoidosis with an incidence of 96%. 3% of this group developed hypercalcemia, 13% AKI and 3% developed CKD. Conclusions: There was an unexpectedly high incidence of AKI in patients who had a raised serum ACE. Not all patients with a raised serum ACE had a confirmed diagnosis of sarcoidosis. There does not appear to be a relationship between increased serum ACE levels and increased incidence of hypercalcaemia, AKI, and CKD. Ideally, all patients should have biopsy-proven sarcoidosis. This is an initial study that should be replicated with larger numbers and including multiple centres.

Keywords: sarcoidosis, acute kidney injury, chronic kidney disease, hypercalcemia

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Authors: Raja Ezman Raja Shariff

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Acute kidney injury (AKI) is commonly seen in inpatients, and places a great cost on the NHS and patients. Timely and appropriate management is both nephron sparing and potentially life-saving. Ultrasound scanning (USS) is a well-recognised method for stratifying patients. Subsequently, the NICE AKI guidance has defined groups in whom scanning is recommended within 6 hours of request (pyonephrosis), within 24 hours (obstruction/cause unknown), and in whom routine scanning isn't recommended (cause for AKI identified). The audit looks into whether Stockport NHS Trust USS practice was in line with such recommendations. The audit evaluated 92 patients with AKI who had USS, between 01/01/14 to 30/04/14. Data collection was divided into 2 parts. Firstly, radiology request cards and the online imaging software (PACS) were evaluated. Then, the electronic case notes (ADVANTIS) was evaluated further. Based on request cards, 10% of requests were for pyonephrosis. Only 33% were scanned within 6hours and a further 33% within 24hours. 75% were requested for possible obstructions and unknown cause collectively. Of those due to possible obstruction, 71% of patients were scanned within 24 hours. Of those with unknown cause, 50% were scanned within 24 hours. 15% of requests had a cause declared and so potentially did not require scanning. Evaluation of the patients’ notes suggested further interesting findings. Firstly, potentially 39% of patients had a known cause for AKI, therefore, did not need USS. Subsequently, the cohort of unknown cause and possible obstruction was collectively reduced to 45%. Alarmingly the patient cohort with possible pyonephrosis went up to 16%, suggesting an under-recognition of this life-threatening condition. We plan to highlight these findings within our institution and make changes to encourage more appropriate requesting and timely scanning. Time will tell if we manage to save or increase our costs in this cost-conscious NHS. Patient benefits, though, seem to be guaranteed.

Keywords: AKI, ARF, kidney, renal

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Authors: Senthil Rajan Dharmalingam, Shamala Nadaraju, Srinivasan Ramamurthy

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Doxorubicin is the most widely used anticancer drugs in chemotherapy treatment. However, problems related to the development of multidrug resistance (MDR) and acute cardiotoxicity have led researchers to investigate alternative forms of administering doxorubicin for cancer therapy. Several methods have been attempted to overcome MDR, including the co-administration of a chemosensitizer inhibiting the efflux caused by ATP binding cassette transporters with anticancer drugs, and the bypass of the efflux mechanism. Co encapsulation of doxorubicin (Dox) and cyclosporine A (CSA) into poly (DL-lactide-co-glycolide) nanoparticles was emulsification-solvent evaporation method using polyvinyl alcohol as emulsion stabilizers. The Dox-CSA loaded nanoparticles were evaluated for particle size, zeta potential and PDI by light scattering analysis and thermal characterizations by differential scanning calorimetry (DSC). Loading efficiency (LE %) and in-vitro dissolution samples were evaluated by developed and validated HPLC method. The optimum particle size obtained is 298.6.8±39.4 nm and polydispersity index (PDI) is 0.098±0.092. Zeta potential is found to be -29.9±4.23. Optimum pH to increase Dox LE% was found 7.1 which gave 42.5% and 58.9% increase of LE% for pH 6.6 and pH 8.6 compared respectively. LE% achieved for Dox is 0.07±0.01 % and CSA is 0.09±0.03%. Increased volume of PVA and weight of PLGA shows increase in size of nanoparticles. DSC thermograms showed shift in the melting peak for the nanoparticles compared to Dox and CSA indicating encapsulation of drugs. In conclusion, these preliminary studies showed the feasibility of PLGA nanoparticles to entrap Dox and CSA and require future in-vivo studies to be performed to establish its potential.

Keywords: doxorubicin, cyclosporine, PLGA, nanoparticles

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Authors: Jimmy Jiun-Ming Su, Yuan-Min Lin

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Bioprinting has been applied to produce 3D cellular constructs for tissue engineering. Microextrusion printing is the most common used method. However, printing low viscosity bioink is a challenge for this method. Herein, we developed a new 3D printing system to fabricate cell-laden hydrogels via a DLP-based projector. The bioprinter is assembled from affordable equipment including a stepper motor, screw, LED-based DLP projector, open source computer hardware and software. The system can use low viscosity and photo-polymerized bioink to fabricate 3D tissue mimics in a layer-by-layer manner. In this study, we used gelatin methylacrylate (GelMA) as bioink for stem cell encapsulation. In order to reinforce the printed construct, surface modified hydroxyapatite has been added in the bioink. We demonstrated the silanization of hydroxyapatite could improve the crosslinking between the interface of hydroxyapatite and GelMA. The results showed that the incorporation of silanized hydroxyapatite into the bioink had an enhancing effect on the mechanical properties of printed hydrogel, in addition, the hydrogel had low cytotoxicity and promoted the differentiation of embedded human bone marrow stem cells (hBMSCs) and retinal pigment epithelium (RPE) cells. Moreover, this bioprinting system has the ability to generate microchannels inside the engineered tissues to facilitate diffusion of nutrients. We believe this 3D bioprinting system has potential to fabricate various tissues for clinical applications and regenerative medicine in the future.

Keywords: bioprinting, cell encapsulation, digital light processing, GelMA hydrogel

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Authors: Yi Xiong, Tao Kong

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Traditional safety, risk and reliability analysis approaches are problem-oriented, which make it great workload when analyzing complicated and huge system, besides, too much repetitive work would to do if the analyzed system composed by many similar components. It is pressing need an object and function oriented approach to maintain high consistency with problem domain. A new approach is proposed to overcome these shortcomings of traditional approaches, the concepts: class, abstract, inheritance, polymorphism and encapsulation are introduced into FTA and establish the professional class library that the abstractions of physical objects in real word, four areas relevant information also be proposed as the establish help guide. The interaction between classes is completed by the inside or external methods that mapping the attributes to base events through fully search the knowledge base, which forms good encapsulation. The object oriented fault tree analysis system that analyze and evaluate the system safety and reliability according to the original appearance of the problem is set up, where could mapped directly from the class and object to the problem domain of the fault tree analysis. All the system failure situations can be analyzed through this bottom-up fault tree construction approach. Under this approach architecture, FTA approach is developed, which avoids the human influence of the analyst on analysis results. It reveals the inherent safety problems of analyzed system itself and provides a new way of thinking and development for safety analysis. So that object oriented technology in the field of safety applications and development, safety theory is conducive to innovation.

Keywords: FTA, knowledge base, object-oriented technology, reliability analysis

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Authors: Wassim Guermazi, Saoussan Boukhris, Neila Annabi Trabelsi, Tarek Rebai, Alya Sellami-Kamoun, Habib Ayadi

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This work investigates the protective effects of the microalga Halamphora sp. extract (H. Ext) as a natural product on lead-intoxicated liver and kidney human cells in vitro and in vivo on rats wistar. HepG2 cells line derived from human hepatocellular carcinoma and HEK293 cells line derived from human embryonic kidney were used for the in vitro study. The analysis of the fatty acids methyl esters of the extract was performed by a GC/MS. Four groups of rats, each of which was composed of six animals, were used for the in vivo experiment. The pretreatment of HepG2 and HEK293 cells line with the extract (100 µg mL-1) significantly (p < 0.05) protected against cytotoxicity induced by lead exposure. In vivo, the biochemical parameters in serum, namely malondialdehyde level (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities, were measured in supernatants of organ homogenates. H. Ext was found to be rich in fatty acids, essentially palmitic and palmitoleic accounting respectively 29.46% and 42.07% of total fatty acids. Both in vitro and in vivo, the co-treatment with H. Ext allowed the protection of the liver and kidney cells structure, as well as the significant preservation of normal antioxidant and biochemical parameters in rats. Halamphora extract rich in fatty acids has been proven to be effective in protection against Pb-induced toxicity.

Keywords: microalga extract, human cells line, fatty acid, lead exposure, oxidative stress, rats

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Authors: O. Soji-Omoniwa, N. O. Muhammad, L. A. Usman, B. P. Omoniwa

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This study was conducted to investigate the effect of the leaf essential oil of C. sinensis harvested at 7.00a.m and 4.00p.m on some Liver and Kidney function indices of diabetic rats as well as investigate the effect of time of harvest on the observed effect. Experimental animals were divided into 4 groups (A, B, C and D). Diabetes mellitus was induced in all animals, except the normal control group (Group A), by injecting 150mg/kg body weight of alloxan monohydrate intraperitoneally. Group A received distilled water while group B (diabetic control group) was not treated. Group C and D were treated with leaf essential oil of C. sinensis harvested at 7.00 a.m and 4.00 p.m respectively at a dose of 110 mg/kg body weight every other day for 15 days. Alkaline phosphatase (ALP), Alanine Transaminase (ALT) and Aspartate Transaminase (AST) activity was evaluated in the serum, Liver and Kidney of studied animals. Total and Direct Bilirubin level, Total Protein and Globulin, Creatinine and Urea level were also evaluated. Result showed that creatinine and urea, serum ALP, AST and ALT levels was significantly reduced (p < 0.05), while the levels of total Protein and Globulin increased significantly (p < 0.05) for the treated animals compared to the diabetic control group. In conclusion, the leaf essential oil of Citrus sinensis ameliorated the impaired renal and liver function; however, the time of harvest of the leaf does not significantly affect its ameliorative effect.

Keywords: C. sinensis, function indices, harvest time, leaf essential oil.

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Authors: Namfon Samsalee, Rungsinee Sothornvit

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Turmeric is a natural plant herb and generally extracted as essential oil and widely used in food, cosmetic, pharmaceutical products including insect repellent. However, turmeric oil is a volatile essential oil which is easy to be lost during storage or exposure to light. Therefore, biopolymers such as protein and polysaccharide can be used as wall materials to encapsulate the essential oil which will solve this drawback. Approximately 60% plasma from porcine blood contains 6-7% of protein content mainly albumin and globulin which can be a good source of animal protein at the low-cost biopolymer from by-product. Microencapsulation is a useful technique to entrap volatile compounds in the biopolymer matrix and protect them to degrade. The objective of this research was to investigate the different ratios of two biopolymers (PPP and maltodextrin; MD) as wall materials at 100:0, 75:25, 50:50, 25:75 and 0:100 at a fixed ratio of wall material: core material (turmeric oil) at 3:1 (oil in water) on the qualities of microencapsulated powder using freeze drying. It was found that the combination of PPP and MD showed higher solubility of microencapsules compared to the use of PPP alone (P < 0.05). Moreover, the different ratios of wall materials also affected on color (L*, a* and b*) of microencapsulated powder. Morphology of microencapsulated powder using a scanning electron microscope showed holes on the surface reflecting on free oil content and encapsulation efficiency of microencapsules. At least 50% of MD was needed to increase encapsulation efficiency of microencapsulates rather than using only PPP as the wall material (P < 0.05). Microencapsulated turmeric oil powder can be useful as food additives to improve food texture, as a biopolymer material for edible film and coating to maintain quality of food products.

Keywords: microencapsulation, turmeric oil, porcine plasma protein, maltodextrin

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Authors: S. Sreeja, Radhakrishnan R. Nair, Noble Gracious, Sreeja S. Nair, M. Radhakrishna Pillai

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Background: Tacrolimus is a potent immunosuppressant clinically used for the long term treatment of antirejection of transplanted organs in liver and kidney transplant recipients though dose optimization is poorly managed. However, So far no study has been carried out on the South Indian kidney transplant patients. The objective of this study is to evaluate the potential influence of a functional polymorphism in CYP3A5*3 gene on tacrolimus physiological availability/dose ratio in South Indian renal transplant patients. Materials and Methods: Twenty five renal transplant recipients receiving tacrolimus were enrolled in this study. Their body weight, drug dosage, and therapeutic concentration of Tacrolimus were observed. All patients were on standard immunosuppressive regime of Tacrolimus-Mycophenolate mofetil along with steroids on a starting dose of Tac 0.1 mg/kg/day. CYP3A5 genotyping was performed by PCR followed with RFLP. Conformation of RFLP analysis and variation in the nucleotide sequence of CYP3A5*3 gene were determined by direct sequencing using a validated automated generic analyzer. Results: A significant association was found between tacrolimus per dose/kg/d and CYP3A5 gene (A6986G) polymorphism in the study population. The CYP3A5 *1/*1, *1/*3 and *3/*3 genotypes were detected in 5 (20 %), 5 (20 %) and 15 (60 %) of the 25 graft recipients, respectively. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus Concentration/Dose ratio in kidney transplant recipients. Significantly higher L/D was observed among non-expressors 9.483 ng/mL(4.5- 14.1) as compared with the expressors 5.154 ng/mL (4.42-6.5 ) of CYP3A5. Acute rejection episodes were significantly higher for CYP3A5*1 homozygotes compared to patients with CYP3A5*1/*3 and CYP3A5*3/*3 genotypes (40 % versus 20 % and 13 %, respectively ). The dose normalized TAC concentration (ng/ml/mg/kg) was significantly lower in patients having CYP3A5*1/*3 polymorphism. Conclusion: This is the first study to extensively determine the effect of CYP3A5*3 genetic polymorphism on tacrolimus pharmacokinetics in South Indian renal transplant recipients and also shows that majority of our patients carry mutant allele A6986G in CYP3A5*3 gene. Identification of CYP3A5 polymorphism prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus for each patient.

Keywords: kidney transplant patients, CYP3A5 genotype, tacrolimus, RFLP

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Authors: Fouad Chebib, Marie Hogan, Ziad El-Zoghby, Maria Irazabal, Sarah Senum, Christina Heyer, Charles Madsen, Emilie Cornec-Le Gall, Atta Behfar, Barbara Ehrlich, Peter Harris, Vicente Torres

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Background: Mutations in PKD1 and PKD2, the genes encoding the proteins polycystin-1 (PC1) and polycystin-2 (PC2) cause autosomal dominant polycystic kidney disease (ADPKD). ADPKD is a systemic disease associated with several extrarenal manifestations. Animal models have suggested an important role for the polycystins in cardiovascular function. The aim of the current study is to evaluate the association of various cardiomyopathies in a large cohort of patients with ADPKD. Methods: Clinical data was retrieved from medical records for all patients with ADPKD and cardiomyopathies (n=159). Genetic analysis was performed on available DNA by direct sequencing. Results: Among the 58 patients included in this case series, 39 patients had idiopathic dilated cardiomyopathy (IDCM), 17 had hypertrophic obstructive cardiomyopathy (HOCM), and 2 had left ventricular noncompaction (LVNC). The mean age at cardiomyopathy diagnosis was 53.3, 59.9 and 53.5 years in IDCM, HOCM and LVNC patients respectively. The median left ventricular ejection fraction at initial diagnosis of IDCM was 25%. Average basal septal thickness was 19.9 mm in patients with HOCM. Genetic data was available in 19, 8 and 2 cases of IDCM, HOCM, and LVNC respectively. PKD1 mutations were detected in 47.4%, 62.5% and 100% of IDCM, HOCM and LVNC cases. PKD2 mutations were detected only in IDCM cases and were overrepresented (36.8%) relative to the expected frequency in ADPKD (~15%). The prevalence of IDCM, HOCM, and LVNC in our ADPKD clinical cohort was 1:17, 1:39 and 1:333 respectively. When compared to the general population, IDCM and HOCM was approximately 10-fold more prevalent in patients with ADPKD. Conclusions: In summary, we suggest that PKD1 or PKD2 mutations may predispose to idiopathic dilated or hypertrophic cardiomyopathy. There is a trend for patients with PKD2 mutations to develop the former and for patients with PKD1 mutations to develop the latter. Predisposition to various cardiomyopathies may be another extrarenal manifestation of ADPKD.

Keywords: autosomal dominant polycystic kidney (ADPKD), polycystic kidney disease, cardiovascular, cardiomyopathy, idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy, left ventricular noncompaction

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Authors: Maria Giovanna Lupo, Marina Camera, Marcello Rattazzi, Nicola Ferri

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A complex interplay among chronic kidney disease, lipid metabolism and aortic calcification has been recognized starting from results of many clinical and experimental studies. Here we investigated the influence of kidney function on PCSK9 levels, both in uremic rats and in clinical observation study, and its potential direct action on cultured smooth muscle cells (SMCs) calcification. In a cohort of 594 subjects enrolled in a single centre, observational, cross-sectional and longitudinal study, a negative association between GFR and plasma PCSK9 was found. Atherosclerotic cardiovascular disease (ASCVD), as co-morbidity, further increased PCSK9 plasma levels. Diet-induced uremic condition in rats, induced aortic calcification and increased total cholesterol and PCSK9 levels in plasma, livers and kidneys. Immunohistochemical analysis confirmed PCSK9 expression in aortic SMCs. SMCs overexpressing PCSK9 (SMCsPCSK9), cultured for 7-days in a pro-calcification environment (2.0mM or 2.4mM inorganic phosphate, Pi) showed a significantly higher extracellular calcium (Ca2+) deposition compared to mocked SMCs. Under the same experimental conditions, the addition of exogenous recombinant PCSK9 did not increase the extracellular calcification of SMCs. By flow cytometry analysis we showed that SMCsPCSK9, in response to 2.4mM Pi, released higher number of extracellular vesicles (EVs) positive for three tetraspanin molecules, such as CD63, CD9, and CD81. EVs derived from SMCsPCSK9 tended to be more enriched in calcium and alkaline phosphatase (ALPL), compared to EVs from mocks SMCs. In conclusion, our study reveals a direct role of PCSK9 on vascular calcification induced by higher inorganic phosphate levels associated to CKD condition. This effect appears to be mediated by a positive effect of endogenous PCSK9 on the release of EVs containing Ca2+ and ALP, which facilitate the deposition inorganic calcium phosphate crystals.

Keywords: PCSK9, calcification, extracellular vesicles, chronic kidney disease

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Authors: Zhazira Shemsheyeva, Zhanara Suleimenova, Olga Shemshura, Gulnaz Mombekova, Zhanar Rakhmetova

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Bacteria that colonize plant roots and promote plant growth are referred to as plant growth-promoting rhizobacteria (PGPR). They not only provide nutrients to the plants (direct plant growth promotion) and protect plants against the phytopathogens (indirect plant growth promotion) but also increase the soil fertility. Indirectly PGPRs improve the plant growth by becoming a biocontrol agent for a fungal pathogen. The antifungal activities of the PGPrhizobacteria were assayed against different species of phytopathogenic fungi such as Fusarium tricinctum, Fusarium oxysporum, Sclerotiniasclerotiorum, and Botrytis cinerea. Pseudomonas putidaSM-1, Azotobacter sp., and Bacillus thuringiensis AKS/16 strains have been used in experimental tests on growth inhibition of phytopathogenic fungi infecting Kidney beans. Agar well diffusion method was used in this study. Diameters of the zones of inhibition were measured in millimeters. It was found that Bacillus thuringiensis AKS/16 strain showed the lowest antifungal activity against all fungal pathogens tested. Zones of inhibition were 15-18 mm. In contrast, Pseudomonas putida SM-1 exhibited good antifungal activity against Fusarium oxysporum and Fusarium tricinctum by producing 29-30 mm clear zones of inhibition. The moderate inhibitory effect was shown by Azotobacter sp. against all fungal pathogens tested with zones of inhibition from24 to 26 mm. In summary, Pseudomonas putida SM-1 strain demonstrated the potential of controlling root rot diseases in kidney beans.

Keywords: PGPR, pseudomonas putida, kindey beans, antifungal activity

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Authors: L. A. Bosnea, T. Moschakis, C. Biliaderis

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Two probiotic strains of Lactobacillus paracasei subsp. paracasei (E6) and Lactobacillus paraplantarum (B1), isolated from traditional Greek dairy products, were microencapsulated by complex coacervation using whey protein isolate (WPI, 3% w/v) and gum arabic (GA, 3% w/v) solutions mixed at different polymer ratio (1:1, 2:1 and 4:1). The effect of total biopolymer concentration on cell viability was assessed using WPI and GA solutions of 1, 3 and 6% w/v at a constant ratio of 2:1. Also, several parameters were examined for optimization of the microcapsule formation, such as inoculum concentration and the effect of ionic strength. The viability of the bacterial cells during heat treatment and under simulated gut conditions was also evaluated. Among the different WPI/GA weight ratios tested (1:1, 2:1, and 4:1), the highest survival rate was observed for the coacervate structures made with the ratio of 2:1. The protection efficiency at low pH values is influenced by both concentration and the ratio of the added biopolymers. Moreover, the inoculum concentration seems to affect the efficiency of microcapsules to entrap the bacterial cells since an optimum level was noted at less than 8 log cfu/ml. Generally, entrapment of lactobacilli in the complex coacervate structure enhanced the viability of the microorganisms when exposed to a low pH environment (pH 2.0). Both encapsulated strains retained high viability in simulated gastric juice (>73%), especially in comparison with non-encapsulated (free) cells (<19%). The encapsulated lactobacilli also exhibited enhanced viability after 10–30 min of heat treatment (65oC) as well as at different NaCl concentrations (pH 4.0). Overall, the results of this study suggest that complex coacervation with WPI/GA has a potential to deliver live probiotics in low pH food systems and fermented dairy products; the complexes can dissolve at pH 7.0 (gut environment), releasing the microbial cells.

Keywords: probiotic, complex coacervation, whey, encapsulation

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Authors: Tara Gurung, Suprina Prajapati

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Health and well being of people is a crucial for accomplishing sustainable development goals of any country. The present study focuses on quality of life of patients undergoing hemodialysis. Hemodialysis is a life sustaining treatment for patients with end stage renal disease (ESRD). Hemodialysis can bring about significant impairment in health related quality of life (HRQOL). The purpose of this study was to assess the quality of life of hemodialysis patients undergoing hemodialysis. A descriptive cross-sectional research design was utilized in total 100 samples using random sampling technique. The findings revealed that the total quality of life of the patients was 30.41±3.99 out of 100. The total physical component score was statistically significant with education status of the patients where p value for t test was 0.03 (p=0.03) and occupation of the patients where p value for the ANOVA test was 0.007 (p=0.007). The study recommended that it would be better if awareness programs regarding chronic kidney disease and life style modification in hemodialysis patients is given to the patients so that it would help patients to maintain the HRQOL.

Keywords: health and well bing, hemodialysis, patients quality of life

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Authors: Valentina Colonnello, Paolo Maria Russo

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Living kidney donation requires psychological evaluation and ongoing follow-up. A crucial aspect of this evaluation is assessing the social functioning of donors after donation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a review of quantitative and qualitative studies on the psychological assessment of living kidney donors' social functioning. The majority of quantitative studies examining the long-term social health post-donation have primarily utilized the Short Form Health Survey (SF) and the World Health Organization Quality of Life-BREF (WHOQoL-BREF) questionnaires. These studies have indicated that donors' social functioning and relationships either remained stable post-donation or returned to pre-donation levels. In some instances, donors' social functioning even surpassed that of the general population. Qualitative studies, conducted through interviews and focus groups, have revealed donors' experiences and emotional concerns that are often overlooked in quantitative analyses. Specifically, qualitative analysis has identified two main themes: "connecting to others" and "acknowledgment and social support." Our review highlights that the majority of published quantitative studies on donors have employed measures of social functioning that may not fully capture donors' experiences and needs. It underscores the importance of further investigation in quantitative studies to assess donors' actual social health and psychological needs accurately. Overall, this review provides valuable insights into specific constructs that warrant deeper exploration in quantitative studies concerning the assessment of donors' social health and psychological well-being.

Keywords: reported outcomes, personalized medicine, individual differences, emotions, psychological assessment

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Authors: Turan Yaman, Zabit Yener, Ismail Celik

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The aim of this study was to investigate the antioxidant properties and protective role of honey, considered a part of traditional medicine, against carcinogen chemical aflatoxin (AF) exposure in rats, which were evaluated by histopathological changes in liver and kidney, measuring level of serum marker enzymes [aspartate aminotransferase (AST), alanin aminotransferase (ALT), gamma glutamil transpeptidase (GGT)], antioxidant defense systems [Reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT)], and lipid peroxidation content in liver, erythrocyte, brain, kidney, heart and lungs. For this purpose, a total of eighteen healthy Sprague-Dawley rats were randomly allocated into three experimental groups: A (Control), B (AF-treated) and C (AF+honey-treated). While rats in group A were fed with a diet without AF, B, and C groups received 25 µg of AF/rat/day, where C group additionally received 1 mL/kg of honey by gavage for 90 days. At the end of the 90-day experimental period, we found that the honey supplementation decreased the lipid peroxidation and the levels of enzyme associated with liver damage, increased enzymatic and non-enzymatic antioxidants in the AF+honey-treated rats. Hepatoprotective and nephroprotective effects of honey is further substantiated by showing almost normal histological architecture in AF+honey-treated group, compared to degenerative changes in the liver and kidney of AF-treated rats. Additionally, honey supplementation ameliorated antioxidant defense systems and lipid peroxidation content in other tissues of AF+honey-treated rats. In conclusion, the present study indicates that honey has a hepatoprotective and nephroprotective effect in rats with experimental aflatoxicosis due to its antioxidant activity.

Keywords: aflatoxicosis, honey, histopathology, malondialdehyde, antioxidant, rat

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Authors: Bárbara Durão, Pedro Almeida, David Ramilo, André Meneses, Rute Canejo-Teixeira

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The importance of quality of life (QoL) assessment in veterinary medicine is an integral part of patient care. This is especially true in cases of chronic diseases, such as chronic kidney disease (CKD), where the ever more advanced treatment options prolong the patient’s life. Whether this prolongment of life comes with an acceptable quality of life remains has been called into question. The aim of this study was to evaluate the relationship between CKD disease biomarkers and QoL in cats. Thirty-seven cats diagnosed with CKD and with no known concurrent illness were enrolled in an observational study. Through the course of several evaluations, renal biomarkers were assessed in blood and urine samples, and owners retrospectively described their cat’s quality of life using a validated instrument for this disease. Correlations between QoL scores (AWIS) and the biomarkers were assessed using Spearman’s rank test. Statistical significance was set at p-value < 0.05, and every serial sample was considered independent. Thirty-seven cats met the inclusion criteria, and all owners completed the questionnaire every time their pet was evaluated, giving a total of eighty-four questionnaires, and the average-weighted-impact-score was –0.5. Results showed there was a statistically significant correlation between the quality of life and most of 17 the studied biomarkers and confirmed that CKD has a negative impact on QoL in cats especially due to the management of the disease and secondary appetite disorders. To our knowledge, this is the attempt to assess the correlation between renal biomarkers and QoL in cats. Our results reveal a strong potential of this type of approach in clinical management, mainly in situations where it is not possible to measure biomarkers. Whilst health-related QoL is a reliable predictor of mortality and morbidity in humans; our findings can help improve the clinical practice in cats with CKD.

Keywords: chronic kidney disease, biomarkers, quality of life, feline

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Authors: Aneena Suresh, C. S. Sidharth

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Drug related problems (DRPs) are common in chronic kidney disease (CKD) patients and end stage patients undergoing hemodialysis. To treat the co-morbid conditions of the patients, more complex therapeutic regimen is required, and it leads to development of DRPs. So, this calls for frequent monitoring of the patients. Due to the busy work schedules, physicians are unable to deliver optimal care to these patients. Addition of a clinical pharmacist in the team will improve the standard of care offered to CKD patients by minimizing DRPs. In India, the role of clinical pharmacists in the improving the health outcomes in CKD patients is poorly recognized. Therefore, this study is conducted to put an insight on the role of clinical pharmacist in improving Drug Related Problems in patients with chronic kidney disease, thereby helping them to achieve desired therapeutic outcomes in the patients. A prospective interventional study was conducted for a year in a 620 bedded tertiary care hospital in India. Data was collected using an unstructured questionnaire, medication charts, etc. DRPs were categorized using Hepler and Strand classification. Relationships between the age, weight, GFR, average no of medication taken, average no of comorbidities, and average length of hospital days with the DRPs were identified using Mann Whitney U test. The study population primarily constituted of patients above the age of 50 years with a mean age of 59.91±13.59. Our study showed that 25% of the population presented with DRPs. On an average, CKD patients are prescribed at least 8 medications for the treatment in our study. This explains the high incidence of drug interactions in patients suffering from CKD (45.65%). The least common DRPs in our study were found to be sub therapeutic dose (2%) and adverse drug reactions (2%). Out of this, 60 % of the DRPs were addressed successfully. In our study, there is an association between the DRPs with the average number of medications prescribed, the average number of comorbidities, and the length of the hospital days with p value of 0.022, 0.004, and 0.000, respectively. In the current study, 86% of the proposed interventions were accepted, and 41 % were implemented by the physician, and only 14% were rejected. Hence, it is evident that clinical pharmacist interventions will contribute significantly to diminish the DRPs in CKD patients, thereby decreasing the economic burden of healthcare costs and improving patient’s quality of life.

Keywords: chronic kidney disease, clinical pharmacist, drug related problem, intervention

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Authors: Filipa Vasconcelos

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The administration of endoplasmic reticulum amino peptidases (ERAP1 or ERAP2) inhibitors can be used for therapeutic approaches against cancer and auto-immune diseases. However, one of the main shortcomings of drug delivery systems (DDS) is associated with the drug off-target distribution, which can lead to an increase in its side effects on the patient’s body. To overcome such limitations, the encapsulation of four representative compounds of ERAP inhibitors into Polycaprolactone (PCL), Polyvinyl-alcohol (PVA), crosslinked PVA, and PVA with nanoparticles (liposomes) electrospun fibrous meshes is proposed as a safe and controlled drug release system. The use of electrospun fibrous meshes as a DDS allows efficient solvent evaporation giving limited time to the encapsulated drug to recrystallize, continuous delivery of the drug while the fibers degrade, prevention of initial burst release (sustained release), tunable dosages, and the encapsulation of other agents. This is possible due to the fibers' small diameters and resemblance to the extracellular matrix (confirmed by scanning electron microscopy results), high specific surface area, and good mechanical strength/stability. Furthermore, release studies conducted on PCL, PVA, crosslinked PVA, and PVA with nanoparticles (liposomes) electrospun fibrous meshes with each of the ERAP compounds encapsulated demonstrated that they were capable of releasing >60%, 50%, 40%, and 45% of the total ERAP concentration, respectively. Fibrous meshes with ERAP_E compound encapsulated achieved higher released concentrations (75.65%, 62.41%, 56.05%, and 65.39%, respectively). Toxicity studies of fibrous meshes with encapsulated compounds are currently being accessed in vitro, as well as pharmacokinetics and dynamics studies. The last step includes the implantation of the drug-loaded fibrous meshes in vivo.

Keywords: drug delivery, electrospinning, ERAP inhibitors, liposomes

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Authors: Rajni Kant Panik

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The aim of the present study was to develop and evaluate mupirocin loaded nanoparticle incorporated into hydrogel as an infected wound healer. Incorporated Nanoparticle in hydrogel provides a barrier that effectively prevents the contamination of the wound and further progression of infection to deeper tissues. Hydrogel creates moist healing environment on wound space with good fluid absorbance. Nanoparticles were prepared by double emulsion solvent evaporation method using different ratios of PLGA polymer and the hydrogels was developed using sodium alginate and gelatin. Further prepared nanoparticles were then incorporated into the hydrogels. The formulations were characterized by FT-IR and DSC for drug and polymer compatibility and surface morphology was studied by TEM. Nanoparticle hydrogel were evaluated for their size, shape, encapsulation efficiency and for in vitro studies. The FT-IR and DSC confirmed the absence of any drug polymer interaction. The average size of Nanoparticle was found to be in range of 208.21-412.33 nm and shape was found to be spherical. The maximum encapsulation efficiency was found to be 69.03%. The in vitro release profile of Nanoparticle incorporated hydrogel formulation was found to give sustained release of drug. Antimicrobial activity testing confirmed that encapsulated drug preserve its effectiveness. The stability study confirmed that the formulation prepared were stable. Present study complements our finding that mupirocin loaded Nanoparticle incorporated into hydrogel has the potential to be an effective and safe novel addition for the release of mupirocin in sustained manner, which may be a better option for the management of wound. These finding also supports the progression of antibiotic via hydrogel delivery system is a novel topical dosage form for the management of wound.

Keywords: hydrogel, nanoparticle, PLGA, wound healing

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Authors: Sonal Gupta, Rakhi Bansal, Javed Ali, Reema Gabrani, Shweta Dang

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Nanoemulsions (NEs) and microemulsions (MEs) have been an attractive tool for encapsulation of both hydrophilic and lipophillic actives. Both these systems are composed of oil phase, surfactant, co-surfactant and aqueous phase. Depending upon the application and intended use, both oil-in-water and water-in-oil emulsions can be designed. NEs are fabricated using high energy methods employing less percentage of surfactant as compared to MEs which are self assembled drug delivery systems. Owing to the nanometric size of the droplets these systems have been widely used to enhance solubility and bioavailability of natural as well as synthetic molecules. The aim of the present study is to assess the effect of % age of surfactants on cell viability of Vero cells (African Green Monkeys’ Kidney epithelial cells) via MTT assay. Green tea catechin (Polyphenon 60) loaded ME employing low energy vortexing and NE employing high energy ultrasonication were prepared using same excipients (labrasol as oil, cremophor EL as surfactant and glycerol as co-surfactant) however, the % age of oil and surfactant needed to prepare the ME was higher as compared to NE. These formulations along with their excipients (oilME=13.3%, SmixME=26.67%; oilNE=10%, SmixNE=13.52%) were added to Vero cells for 24 hrs. The tetrazolium dye, 3-(4,5-dimethylthia/ol-2-yl)-2,5-diphi-iiyltclrazolium bromide (MTT), is reduced by live cells and this reaction is used as the end point to evaluate the cytoxicity level of a test formulation. Results of MTT assay indicated that oil at different percentages exhibited almost equal cell viability (oilME ≅ oilNE) while surfactant mixture had a significant difference in the cell viability values (SmixME < SmixNE). Polyphenon 60 loaded ME and its PlaceboME showed higher toxicity as compared to Polyphenon 60 loaded NE and its PlaceboNE that can be attributed to the higher concentration of surfactants present in MEs. Another probable reason for high % cell viability of Polyphenon 60 loaded NE might be due to the effective release of Polyphenon 60 from NE formulation that helps in the sustenance of Vero cells.

Keywords: cell viability, microemulsion, MTT, nanoemulsion, surfactants, ultrasonication

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Authors: Moetazza M. Alshafei, Ahmed M. Mabrouk, Emtenan M. Hanafi, Manal M. Ramadan, Reda M. S. Korany, Seham S. Kassem, Dina Mostafa Mohammed

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Metabolic syndrome (MeS) is a major health problem with a high incidence of obese individuals worldwide. Increased related morbidity of diabetes, hypertension and fatty liver disease, and complicated cardiovascular disease are inevitable. Boswellia serrata gum (Bos) is a promising traditional medicinal plant; it has several pharmacological properties, including anti-inflammatory, antioxidant, and antilipase activities. Probiotics (Bac) supplements have good benefits on health and MeS, whether it is supplemented in combination with prebiotics or alone. Microencapsulation helps to mask unpalatable taste and odor and deliver active ingredients to targeted organs. Methodology MeS rat model was produced by feeding rats with a high fat, high CHO diet (HFD). Bos was extracted, and both Bos and the probiotic were microencapsulated with a spray drier. Female rats were divided into 5 groups (N8). HFD control, control normal receiving basic diet, HFD treated, from the start of the experiment, either with encapsulated Bos, Bac and Bos or Bac only, all treatments were received for eight weeks (after approval from NRC animal ethical committee). Serum was collected to analyze lipid profile, blood sugar, liver and kidney functions, antioxidants, leptin, and progesterone. Rat's organs and body fat were weighed and collected for histopathology. Statistical analysis was done by use of one way Anova test in the SPSS program. Results showed control of elevated body weight, lipid profile, and glucose levels as well as decrease of body fat index and improvement of histopathology of liver and heart, especially in combination. Conclusion: We concluded that both microencapsulated Bos and probiotics have a controlling effect on MeS parameters.

Keywords: metabolic syndrome, Boswellia serata, probiotic, micro-encapsulation, histopathology, liver steatosis

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Authors: Sara Ataei, Maryam Taghizadeh-Ghehi, Amir Sarayani, Asieh Ashouri, Amirhossein Moslehi, Molouk Hadjibabaie, Kheirollah Gholami

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Background: Acute kidney injury (AKI) is common in hematopoietic stem cell transplantation (HSCT) patients with an incidence of 21–73%. Prevention and early diagnosis reduces the frequency and severity of this complication. Predictive biomarkers are of major importance to timely diagnosis. Neutrophil gelatinase associated lipocalin (NGAL) is a widely investigated novel biomarker for early diagnosis of AKI. However, no study assessed NGAL for AKI diagnosis in HSCT patients. Methods: We performed further analyses on gathered data from our recent trial to evaluate the performance of urine NGAL (uNGAL) as an indicator of AKI in 72 allogeneic HSCT patients. AKI diagnosis and severity were assessed using Risk–Injury–Failure–Loss–End-stage renal disease and AKI Network criteria. We assessed uNGAL on days -6, -3, +3, +9 and +15. Results: Time-dependent Cox regression analysis revealed a statistically significant relationship between uNGAL and AKI occurrence. (HR=1.04 (1.008-1.07), P=0.01). There was a relation between uNGAL day +9 to baseline ratio and incidence of AKI (unadjusted HR=.1.047(1.012-1.083), P<0.01). The area under the receiver-operating characteristic curve for day +9 to baseline ratio was 0.86 (0.74-0.99, P<0.01) and a cut-off value of 2.62 was 85% sensitive and 83% specific in predicting AKI. Conclusions: Our results indicated that increase in uNGAL augmented the risk of AKI and the changes of day +9 uNGAL concentrations from baseline could be of value for predicting AKI in HSCT patients. Additionally uNGAL changes preceded serum creatinine rises by nearly 2 days.

Keywords: acute kidney injury, hemtopoietic stem cell transplantation, neutrophil gelatinase-associated lipocalin, Receiver-operating characteristic curve

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Authors: Suhair Saleh, Ahmad Aljaberi

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Cationic lipid-mediated delivery of nucleic acids represents an exciting approach for developing therapeutically realistic gene medicines. Elucidation of the molecular and formulation requirements for efficient lipofection is a prerequisite to enhance the biological activity of such delivery systems. To this end, the in vitro lipofection activity of the ionizable asymmetric 1,2-dialkoylamidopropane-based derivatives bearing single primary amine group as the cationic head group was evaluated. The electrostatic interactions of these cationic lipids with plasmid DNA in physiologically relevant medium were investigated by means of gel electrophoresis retardation and Eth-Br quenching assays. The effect of the presence of the helper lipid on these interactions was evaluated. The physicochemical properties of these lipids in terms of bilayer fluidity and extent of ionization were investigated using fluorescence anisotropy and surface potential techniques, respectively. The results showed that only the active lipid, 1,2lmp[5], existed in a liquid crystalline state at physiological temperature. Moreover, the extent of ionization of this lipid in assemblies was significantly higher that it's saturated analogues. Inclusion of the helper lipid DOPE improved the encapsulation and association between 1,2lmp[5] and plasmid DNA, which was reflected by the significant boost of lipofection activity of the 1,2lmp[5]/DOPE formulation as compared to the lipid alone. In conclusion, membrane fluidity and sufficient protonation of ionizable cationic lipid are required for efficient association and encapsulation of plasmid DNA and promoting improved in vitro lipofection activity.

Keywords: cationic lipids, gene delivery, lipofection, membrane fluidity, helper lipids, surface potential

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Authors: Gomes C. C. Izabel, Lanzotti B. Rafaela, Orlandi S. Fabiana

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Chronic Kidney Disease is considered a serious public health problem. The exploitation of resilience has been guided by studies conducted in various contexts, especially in hemodialysis, since the impact of diagnosis and restrictions produced during the treatment process because, despite advances in treatment, remains the stigma of the disease and the feeling of pain, hopelessness, low self-esteem and disability. The objective was to evaluate the level of resilience of patients in chronic renal dialysis. This is a descriptive, correlational, cross and quantitative research. The sample consisted of 100 patients from a Renal Replacement Therapy Unit in the countryside of São Paulo. For data collection were used the characterization instrument of Participants and the Resilience Scale. There was a predominance of males (70.0%) were Caucasian (45.0%) and had completed elementary education (34.0%). The average score obtained through the Resilience Scale was 131.3 (± 20.06) points. The resiliency level submitted may be considered satisfactory. It is expected that this study will assist in the preparation of programs and actions in order to avoid possible situations of crises faced by chronic renal patients.

Keywords: hemodialysis units, renal dialysis, renal insufficiency chronic, resilience psychological

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Authors: Bouzidi Abdelouahab, Ghadjati Nadhra, Bettihi Sara, Mahdeb Nadia, Daamouche Z. El Youm

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The effects of acute administration of TOTAL alkaloids, the main active principle of Datura stramonium, with toxic properties, were studied in female Albino-Wistar rats. After acute intraperitoneal administration of dose 120 mg kg-1 (≈1/3 DL50) of total alkaloids to the seeds of D. stramonium, there were no remarkable changes in general appearance and no deaths occurred in any experimental group. After 5 days a significant reduction was observed in total alkaloids of seeds. The Red Blood Cells (RBC), Hematocrit (HCT) and Hemoglobin (HGB) show significant changes in the treated groups. There were no statistical differences in Glutamic-pyruvic Transaminase (GPT), Alkaline Phosphatase (ALP), urea, glucose and total protein observed between groups. After 24 h Glutamic-Oxaloacetic Transaminase (GOT) and creatinine were significantly higher in the treated male rats than the control group histological examination of liver showed no histopathological changes.

Keywords: datura stramonium, rat, liver, kidney, alkaloids, toxicity

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Authors: Adegbegi Ademuyiwa Joshua, Onoagbe Iyare

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Medicinal plants have been recognized to have therapeutic effects and they may also have toxic side effects. The present study was undertaken to investigate the effect of extracts of Cymbopogon citratus on normal rats. Blood glucose levels of all animals were determined. Biochemical studies carried out to determine the oxidative status by measuring activities of superoxide dismutase (SOD) and catalase (CAT), and in the liver, kidney and pancrease. Oral administration of ethanolic and aqueous extract of C. citratus at a doses of 200 mg/kg body weight, for a period of 30 days, caused a significant (p<0.05) reduction in blood glucose levels. Effect on hormonal profile (TSH, T3, and T4) was also determined, and was found to be significantly higher in all the administered groups when compared with control. Lipid profiles levels; Total cholesterols, triglycerides, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol were significantly (p>0.05) higher for all treated rats as compared against control. SOD, catalase, GSH and Vitamin C activities in the tissues (liver, kidney and pancrease) of the rats treated with the medicinal plants were generally higher or statistical slightly similar to control. Histopathology result showed that both ethanolic and aqueous extracts (200 mg/kg body weight) of C. citratus was safer as no adverse effects were observed in the organs examined. Findings in this study showed that this plant has hypoglycemic properties and did not exert oxidative damage; in some instances, particularly in the liver, kidney and pancreas as well as its relative safety and possible use for weight gain.

Keywords: medicinal plants, blood glucose, cymbopogon citratus, hypoglycaemic, oxidative status

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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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Authors: Farhan Sohail, Gul Shahnaz Irshad Hussain, Shoaib Sarwar, Ibrahim Javed, Zajif Hussain, Akhtar Nadhman

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The present study was aimed to develop a hybrid nanocarrier (NC) system with enhanced membrane permeability, bioavailability and targeted delivery of Docetaxel (DTX) in breast cancer. Hybrid NC’s based on folic acid (FA) grafted thiolated chitosan (TCS) enveloped liposomes were prepared with DTX and evaluated in-vitro and in-vivo for their enhanced permeability and bioavailability. Physicochemical characterization of NC’s including particle size, morphology, zeta potential, FTIR, DSC, PXRD, encapsulation efficiency and drug release from NC’s was determined in vitro. Permeation enhancement and p-gp inhibition were performed through everted sac method on freshly excised rat intestine which indicated that permeation was enhanced 5 times as compared to pure DTX and the hybrid NC’s were strongly able to inhibit the p-gp activity as well. In-vitro cytotoxicity and tumor targeting was done using MDA-MB-231 cell line. The stability study of the formulations performed for 3 months showed the improved stability of FA-TCS enveloped liposomes in terms of its particles size, zeta potential and encapsulation efficiency as compared to TCS NP’s and liposomes. The pharmacokinetic study was performed in vivo using rabbits. The oral bioavailability and AUC0-96 was increased 10.07 folds with hybrid NC’s as compared to positive control. Half-life (t1/2) was increased 4 times (58.76 hrs) as compared to positive control (17.72 hrs). Conclusively, it is suggested that FA-TCS enveloped liposomes have strong potential to enhance permeability and bioavailability of hydrophobic drugs after oral administration and tumor targeting.

Keywords: docetaxel, coated liposome, permeation enhancement, oral bioavailability

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