Search results for: kidney inflammation

Authors: Dins Sumerags, Mara Pilmane, Vita Konopecka, Gunta Sumeraga

Abstract:

Reinke’s oedema is a specific type of chronic laryngitis evolving only in smokers. Our study aimed to identify the presence and interaction of the immunohistochemical markers for inflammation [IL-1α] and [IL-10], proliferation [Ki-67] and immunoreactive innervation [PGP 9.5] in the laryngeal mucosa using biotin-streptavidin immunochemical staining method. The laryngeal tissue samples were taken from the vocal cord during the surgery of the Reinke’s oedema and compared to the control group from the tissue samples of the cadavers without any visual laryngeal disease. The study results confirm increased cellular proliferation and elevation of the inflammation markers in the laryngeal mucosa in the case of Reinke’s oedema by comparing with the control.

Keywords: reinke`s oedema, immunohistochemical markers, laryngeal mucosa, biotin-streptavidin

Procedia PDF Downloads 137

Authors: Hitoshi Minakuchi, Izumi Takei, Shu Wakino, Koichi Hayashi, Hiroshi Itoh

Abstract:

Objectives: Among type 2 diabetics, patients with CKD(chronic kidney disease), insulin resistance, impaired glyconeogenesis in kidney and reduced degradation of insulin are recognized, and we observed different fluctuational patterns of blood sugar between CKD patients and non-CKD patients. On the other hand, non-dipper type blood pressure change is the risk of organ damage and mortality. We performed cross-sectional study to elucidate the characteristic of the fluctuation of blood glucose and blood pressure at insulin-treated diabetic patients with chronic kidney disease. Methods: From March 2011 to April 2013, at the Ichikawa General Hospital of Tokyo Dental College, we recruited 20 outpatients. All participants are insulin-treated type 2 diabetes with CKD. We collected serum samples, urine samples for several hormone measurements, and performed CGMS(Continuous glucose measurement system), ABPM (ambulatory blood pressure monitoring), brain computed tomography, carotid artery thickness, ankle brachial index, PWV, CVR-R, and analyzed these data statistically. Results: Among all 20 participants, hypoglycemia was decided blood glucose 70mg/dl by CGMS of 9 participants (45.0%). The event of hypoglycemia was recognized lower eGFR (29.8±6.2ml/min：41.3±8.5ml/min, P<0.05), lower HbA1c (6.44±0.57%：7.53±0.49%), higher PWV (1858±97.3cm/s：1665±109.2cm/s), higher serum glucagon (194.2±34.8pg/ml：117.0±37.1pg/ml), higher free cortisol of urine (53.8±12.8μg/day：34.8±7.1μg/day), and higher metanephrin of urine (0.162±0.031mg/day：0.076±0.029mg/day). Non-dipper type blood pressure change in ABPM was detected 8 among 9 participants with hypoglycemia (88.9%), 4 among 11 participants (36.4%) without hypoglycemia. Multiplex logistic-regression analysis revealed that the event of hypoglycemia is the independent factor of non-dipper type blood pressure change. Conclusions: Among insulin-treated type 2 diabetic patients with CKD, the events of hypoglycemia were frequently detected, and can associate with the organ derangements through the medium of non-dipper type blood pressure change.

Keywords: chronic kidney disease, hypoglycemia, non-dipper type blood pressure change, diabetic patients

Procedia PDF Downloads 415

Authors: Amadou Wurry Jallow, Adama N. S. Bah, Karamo Bah, Shih-Ye Wang, Kuo-Chung Chu, Chien-Yeh Hsu

Abstract:

Chronic kidney disease (CKD) is a major public health challenge with high prevalence, rising incidence, and serious adverse consequences. Developing effective risk prediction models is a cost-effective approach to predicting and preventing complications of chronic kidney disease (CKD). This study aimed to develop an accurate machine learning model that can dynamically identify individuals at risk of CKD using various kinds of diagnostic data, with or without laboratory data, at different follow-up points. Creatinine is a key component used to predict CKD. These models will enable affordable and effective screening for CKD even with incomplete patient data, such as the absence of creatinine testing. This retrospective cohort study included data on 19,429 adults provided by a private research institute and screening laboratory in Taiwan, gathered between 2001 and 2015. Univariate Cox proportional hazard regression analyses were performed to determine the variables with high prognostic values for predicting CKD. We then identified interacting variables and grouped them according to diagnostic data categories. Our models used three types of data gathered at three points in time: non-laboratory, laboratory, and metabolic indices data. Next, we used subgroups of variables within each category to train two machine learning models (Random Forest and XGBoost). Our machine learning models can dynamically discriminate individuals at risk for developing CKD. All the models performed well using all three kinds of data, with or without laboratory data. Using only non-laboratory-based data (such as age, sex, body mass index (BMI), and waist circumference), both models predict chronic kidney disease as accurately as models using laboratory and metabolic indices data. Our machine learning models have demonstrated the use of different categories of diagnostic data for CKD prediction, with or without laboratory data. The machine learning models are simple to use and flexible because they work even with incomplete data and can be applied in any clinical setting, including settings where laboratory data is difficult to obtain.

Keywords: chronic kidney disease, glomerular filtration rate, creatinine, novel metabolic indices, machine learning, risk prediction

Procedia PDF Downloads 106

Authors: Hakan Duger, Alparslan Ersoy, Canan Ersoy

Abstract:

Diabetes mellitus is the most common etiology of end-stage renal disease (ESRD). Also, diabetic nephropathy is the etiology of ESRD in approximately 23% of kidney transplant recipients. A successful kidney transplant improves the quality of life and reduces the mortality risk for most patients. However, patients require close follow-up after transplantation due to medical complications. Diabetes mellitus can affect patient morbidity and mortality due to possible effects of immunosuppressive therapy on glucose metabolism. We compared the frequency of medical complications and the outcomes in diabetic and non-diabetic kidney transplant recipients. Materials and Methods: This retrospective study conducted in 498 patients who underwent kidney transplant surgery at our center in 10-year periods. The patients were divided into two groups: diabetics (46 ± 10 year, 26 males, 16 females) and non-diabetics (39 ± 12 year, 259 males, 197 females). The medical complications, graft functions, causes of graft loss and death were obtained from medical records. Results: There was no significant difference between recipient age, duration of dialysis, body mass index, gender, donor type, donor age, dialysis type, histories of HBV, HCV and coronary artery disease between two groups. The history of hypertension in diabetics was higher (69% vs. 36%, p < 0.001). The ratios of hypertension (50.1% vs. 57.1%), pneumonia (21.9% vs. 20%), urinary infection (16.9% vs. 20%), transaminase elevation (11.5% vs. 20%), hyperpotasemia (14.7% vs. 17.1%), hyponatremia (9.7% vs. 20%), hypotension (7.1% vs. 7.9%), hypocalcemia (1.4% vs. 0%), thrombocytopenia (8.6% vs. 8.6%), hypoglycemia (0.7% vs. 0%) and neutropenia (1.8% vs. 0%) were comparable in non-diabetic and diabetic groups, respectively. The frequency of hyperglycaemia in diabetics was higher (8.6% vs. 54.3%, p < 0.001). After transplantation, primary non-function (3.4% vs. 2.6%), delayed graft function (25.1% vs. 34.2%) and acute rejection (7.3% vs. 10.5%) ratios of in non-diabetic and diabetic groups were similar, respectively. Hospitalization durations in non-diabetics and diabetics were 22.5 ± 17.5 and 18.7 ± 13 day (p=0.094). Mean serum creatinine levels in non-diabetics and diabetics were 1.54 ± 0.74 and 1.52 ± 0.62 mg/dL at 6th month. Forty patients had graft loss. The ratios of graft loss and death in non-diabetic and diabetic groups were 8.2% vs. 7.1% and 7.1% vs. 2.6% (p > 0.05). There was no significant relationship between graft and patient survivals with the development of medical complication. Conclusion: As a result, medical complications are common in the early period. Hyperglycaemia was frequently seen following transplantation due to the effects of immunosuppressant regimens. However, the frequency of other medical complications in diabetic patients did not differ from non-diabetic one. The most important cause of death is still infections. The development of medical complications during the first 6 months did not significantly affect transplant outcomes.

Keywords: kidney transplantation, diabetes mellitus, complication, graft function

Procedia PDF Downloads 331

Authors: Nisrine Chlif, Mohammed Diouri, Amar Bentayeb

Abstract:

Background: The Leaves of Brocchia cinerea (Vis.) (Asteraceae) is used traditionally and ethnomedicinally to alleviate pain, fever, and inflammation conditions. Objective: The current study investigates the anti-inflammatory, analgesic, and antipyretic activities of aqueous extract of the leaves of Brocchia cinerea (LBC). Material and methods: The extract was screened for anti-inflammatory (carrageenan-induced paw edema) and analgesic (acetic acid-induced writhing) activities in Wistar rats. Before acetic acid or carrageenan injection, rats were orally fed LBC (200 and 400 mg/ kg), Indomethacin (10 mg/kg), or Aspirin (100 mg/kg). The antipyretic effect was studied in brewer’s yeast-induced pyrexia model in rats using Paracetamol (100 mg/kg) as a standard drug. Results: The crude extract tested significantly prevented the increase in paw volume as compared to the control at 200 mg/kg and 400 mg/kg. The LBC treatment significantly inhibited pain at 400 mg/kg with a percent inhibition of 55.82%, as well as showing a significant reduction in hyperpyrexia in rats at 400 mg/kg. LBC extract produced a comparable activity to paracetamol at 100 mg/kg (p <0.01). Conclusion: The results of the present study that the leaves of B. cinerea extract exhibited strongly anti-inflammatory, analgesic, and antipyretic properties and justify the traditional use of this plant in inflammation, pain, and fever.

Keywords: analgesic, anti-inflammation, antipyretic, brocchia cinerea

Procedia PDF Downloads 160

Authors: Yan Lu, Song Hong, Janakiraman Udaiyappan, Aarti Nagayach, Quoc-Viet A. Duong, Masao Morita, Shun Saito, Yuichi Kobayashi, Yuhai, Zhao, Hongying Peng, Nicholas B. Pham, Walter J Lukiw, Christopher A. Vuong, Nicolas G. Bazan

Abstract:

Aims: Neurodegeneration and behavior dysfunction occurs in patients with Alzheimer's Disease (AD), and as the disease progresses many patients develop cognitive impairment. 5XFAD mouse model of AD is widely used to study AD pathogenesis and treatment. This study aimed to investigate the effect of maresin like 1 (MaR-L1) treatment in AD pathology using 5XFAD mice. Methods: We tested 12-month-old male 5XFAD mice and wild type control mice treated with MaR-L1 in a battery of behavioral tasks. We performed open field test, beam walking test, clasping test, inverted grid test, acetone test, marble burring test, elevated plus maze test, cross maze test and novel object recognition test. We also studied neuronal loss, amyloid β burden, and inflammation in the brains of 5XFAD mice using immunohistology and Western blotting. Results: MaR-L1 treatment to the 5XFAD mice showed improved cognitive function of 5XFAD mice. MaR-L1 showed decreased anxiety behavior in open field test and marble burring test, increased muscular strength in the beam walking test, clasping test and inverted grid test. Cognitive function was improved in MaR-L1 treated 5XFAD mice in the novel object recognition test. MaR-L1 prevented neuronal loss and aberrant inflammation. Conclusion: Our finding suggests that behavioral abnormalities were normalized by the administration of MaR-L1 and the neuroprotective role of MaR-L1 in the AD. It also indicates that MaR-L1 treatment is able to prevent and or ameliorate neuronal loss and aberrant inflammation. Further experiments to validate the results are warranted using other AD models in the future.

Keywords: Alzheimer's disease, motor and cognitive behavior, 5XFAD mice, Maresin Like 1, microglial cell, astrocyte, neurodegeneration, inflammation, resolution of inflammation

Procedia PDF Downloads 179

Authors: Amal Yamani, Jaber Elgtou, Aziz Mohammed, Lazaar Jamila, Elachouri Mostafa

Abstract:

Peganum harmala used traditionally as an emenagogue and abortifacient agent in Morocco phytotherapy. Even thought its benefits effects, Peganum harmala remained severely toxic for the organism especially in strong doses. The present study was initiated to evaluate the nephrotoxic effects of aqueous extract of Peganum harmala seeds (PHS). The solution containing aqueous extract of PHS was administered orally by gavage at the dose of 2g/kg body weight during twenty days. Rats were used in this study, two groups were considered, a treated group received an extract of PHS at dose 2g/kg bodyweight and control group received an amount of tap water equivalent to the volume of the vehicle used for the dose of PHS extract. The data we collected showed that aqueous extracts of PHS administered during twenty days induced a significant changes in renal function expressed in decreases of diuresis (from 10 ± 0,58 to 5,33 ± 0,33 ml/24 hours) and the same profile for mean arterial blood pressure (from 125 ± 2,89 to 96,67 ± 6,01 mmHg). The histopathological study showed an alteration of kidney cells in treated group with regard the control group which is not affected. In conclusion: our results indicate that the aqueous extract of PHS induces toxicity may affect severely kidney function and causes renal histopathology.

Keywords: peganum harmala seeds, nephrotoxic, diuresi, histpathology, kidney

Procedia PDF Downloads 299

Authors: Uzma Saqib, Mirza S. Baig

Abstract:

Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

Procedia PDF Downloads 306

Authors: Magdalena Barbara Kaziuk, Waldemar Kosiba, Marek Jan Kuzniewski

Abstract:

Introduction: Vitamin D3 has a proven pleiotropic effect, not only responsible for calcium and phosphate management, but also influencing normal functioning of the whole body. Aim: Evaluation of vitamin D3 resources and its effect on a nutritional status, obesity type and glomerular filtration in kidney transplant recipients. Methods: Group of 152 (81 women and 71 men, average age 47.8 ± 11.6 years) patients with a functioning renal transplant their body composition was assessed using the bioimpendance method (BIA) and anthropometric measurements more than 3 months after the transplant. The nutritional status and the obesity type were determined with the Waist to Height Ratio (WHtR) and the Waist to Hip Ratio (WHR). 25- Hydroxyvitamin D3 (25 (OH)D3) was determined, together with its correlation with the obesity type and the glomerular filtration rate (eGFR) calculated with the MDRD formula. Results: The mean 25 (OH)D3 level was 20.4 ng/ml. 30ng/ml was considered as a minimum correct level 22,7% of patients from the study group were classified to be a correct body weight, 56,7% of participants had an android type and 20,6% had a gynoid type. Significant correlation was observed between 25 (OH)D3 deficiency and abdominal obesity (p < 0.005) in patients. Furthermore, a statistically significant relationship was demonstrated between the 25 (OH)D3 levels and eGFR in patients after a kidney transplant. Patients with an android body type had lower eGFR versus those with the gynoid body type (p=0.004). Conclusions: Correct diet in patients after a kidney transplant determines minimum recommended serum levels of vitamin D3. Excessive fatty tissue, low levels of 25 (OH)D3), may be a predictor for android obesity and renal injury; therefore, correct diet and pharmacological management together with physical activities adapted to the physical fitness level of a patient are necessary.

Keywords: kidney transplantation, glomerular filtration rate, obesity, vitamin D3

Procedia PDF Downloads 279

Authors: Mustafa Metin Donma, Orkide Donma

Abstract:

Obesity in children particularly draws attention because it may threaten the individual’s future life due to many chronic diseases it may lead to. Most of these diseases, including obesity itself altogether are related to inflammation. For this reason, inflammation-related parameters gain importance. Within this context, complete blood cell counts, ratios or indices derived from these counts have recently found some platform to be used as inflammatory markers. So far, mostly adipokines were investigated within the field of obesity. The liver is at the center of the metabolic pathways network. Metabolic inflammation is closely associated with cellular dysfunction. In this study, hematologic inflammatory markers and two major hepatokines, cytokines produced predominantly by the liver, fibroblast growth factor-21 (FGF-21) and fetuin A were investigated in pediatric obesity. Two groups were constituted from seventy-six obese children based on World Health Organization criteria. Group 1 was composed of children whose age- and sex-adjusted body mass index (BMI) percentiles were between 95 and 99. Group 2 consists of children who are above the 99ᵗʰ percentile. The first and the latter groups were defined as obese (OB) and morbid obese (MO). Anthropometric measurements of the children were performed. Informed consent forms and the approval of the institutional ethics committee were obtained. Blood cell counts and ratios were determined by an automated hematology analyzer. The related ratios and indexes were calculated. Statistical evaluation of the data was performed by the SPSS program. There was no statistically significant difference in terms of neutrophil-to lymphocyte ratio, monocyte-to-high density lipoprotein cholesterol ratio and the platelet-to-lymphocyte ratio between the groups. Mean platelet volume and platelet distribution width values were decreased (p<0.05), total platelet count, red cell distribution width (RDW) and systemic immune inflammation index values were increased (p<0.01) in MO group. Both hepatokines were increased in the same group; however, increases were not statistically significant. In this group, also a strong correlation was calculated between FGF-21 and RDW when controlled by age, hematocrit, iron and ferritin (r=0.425; p<0.01). In conclusion, the association between RDW, a hematologic inflammatory marker, and FGF-21, an inflammation-related hepatokine, found in MO group is an important finding discriminating between OB and MO children. This association is even more powerful when controlled by age and iron-related parameters.

Keywords: childhood obesity, fetuin A , fibroblast growth factor-21, hematologic markers, red cell distribution width

Procedia PDF Downloads 198

Authors: Hakan Duger, Alparslan Ersoy, Canan Ersoy

Abstract:

The improvement of surgical techniques in recent years has reduced the frequency of postoperative complications in kidney transplant recipients. Novel immunosuppressive agents have reduced rates of graft loss due to acute rejection to less than 1%. However, surgical complications may still lead graft loss and morbidity in recipients. Because of potent immunosuppression, impaired wound healing and complications are frequent after transplantation. We compared the frequency of post-operative surgical complications in diabetic and non-diabetic patients after kidney transplantation. Materials and Methods: This retrospective study conducted in consecutive patients (213 females, 285 males, median age 39 years) who underwent kidney transplant surgery at our center between December 2005 and October 2015. The patients were divided into two groups: diabetics (46 ± 10 year, 26 males, 16 females) and non-diabetics (39 ± 12 year, 259 males, 197 females). Characteristics of both groups were obtained from medical records. Results: We performed 225 living and 273 deceased donor transplantations. Renal replacement type was hemodialysis in 60.8%, peritoneal dialysis in 17.3% and preemptive in 12%. The mean body mass indexes of the recipients were 24 ± 4.6 kg/m², donor age was 48.6 ± 14.3 years, cold ischemic time was 11.3 ± 6.1 hours, surgery time was 4.9 ± 1.2 hours, and recovery time was 54±31 min. The mean hospitalization duration was 19.1 ± 13.5 days. The frequency of postoperative surgical complications was 43.8%. There was no significant difference between the ratios of post-operative surgical complications in non-diabetic (43.5%) and diabetic (47.4%) groups (p=0.648). Post-operative surgical complications were lymphocele (24.6% vs. 23.7%), delayed wound healing (13.2% vs. 7.6%), hematoma (7.8% vs.15.8 %), urinary leak (4.6% vs. 5.3%), hemorrhage (5.1% vs. 0%), hydronephrosis (2.2% vs. 0%), renal artery thrombosis (1.5% vs. 0%), renal vein thrombosis (1% vs. 2.6%), urinoma (0.7% vs. 0%), urinary obstruction (0.5% vs. 0%), ureteral stenosis (0.5% vs. 0%) and ureteral reflux (0.2% vs. 0%) in non-diabetic and diabetic groups, respectively (p > 0.05). Mean serum creatinine levels in non-diabetics and diabetics were 1.43 ± 0.81 and 1.61 ± 0.96 mg/dL at 1st month (p=0.198). At the 6th month, the mean graft and patient survival times in patients with post-operative surgical complications were significantly lower than in those who did not (162.9 ± 3.4 vs. 175.6 ± 1.5 days, p=0.008, and 171 ± 2.9 vs. 176.1 ± 1.6 days, p=0.047, respectively). However, patient survival durations of non-diabetic (173 ± 27) and diabetic (177 ± 13 day) groups were comparable (p=0.396). Conclusion: As a result, we concluded that surgical complications such as lymphocele and delayed wound healing were common and that frequency of these complications in diabetic recipients did not differ from non-diabetic one. All persons involved in the postoperative care of kidney transplant recipients be aware of the potential surgical complications for rapid diagnosis and treatment.

Keywords: kidney transplantation, diabetes mellitus, surgery, complication

Procedia PDF Downloads 179

Authors: Jade Edey, Andrew Bennett, Gareth Hathway

Abstract:

Nuclear receptor-related 1 protein (also known as Nurr1 or NR4A2) is an orphan nuclear receptor which plays a vital role in the development, survival and maintenance of dopaminergic (DA) neurons particularly in the substantia nigra (SN). Increasing research has investigated Nurr1’s additional role within microglia and astrocytes where it has been suggested to act as a negative regulator of inflammation; potentially offering neuroprotection. Considering both DA neurodegeneration and neuroinflammation are commonly accepted constituents of Parkinson’s Disease (PD), understanding the mechanisms by which Nurr1 regulates inflammatory processes could provide an attractive therapeutic target. Nurr1 regulates inflammation via a transrepressive mechanism possibly dependent upon SUMOylation. In addition, Nurr1 can transactivate numerous genes involved in DA synthesis, such as Tyrosine Hydroxylase (TH). A C-terminal splice variant of Nurr1, Nurr-1a, has been reported in both neuronal and glial cells. However, research into its transcriptional activity is minimal. We employed in vitro methods such as SUMO-Pulldown experiments alongside Luciferase reporter assays to investigate the SUMOylation status and transactivation capabilities of Nurr1 and Nurr-1a respectively. The SUMO-Pulldown assay demonstrated Nurr-1a undergoes significantly more SUMO modification than its full-length variant. Consequently, despite having less transcriptional activation than Nurr1, Nurr1a may play a more prominent role in repression of microglial inflammation. Contrary to published literature we also identified that SUMOylation enhances transcriptional activation by Nurr1 and Nurr1a. SUMOylation-dependent increases in Nurr1 and Nurr1a transcriptional activation were only evident in neuronal SHSY5Y cells but not in HEK293 cells. This research provides novel insight into the regulation of Nurr-1a and indicates differential effects of SUMOylation dependent regulation in neuronal and inflammatory cells.

Keywords: nuclear receptors, Parkinson’s disease, inflammation, transcriptional regulation

Procedia PDF Downloads 154

Authors: Lamees A. Ben Saad, Kah Hwi Kim, Chin Chew Quah, Mustafa Shahimi

Abstract:

Background: Punica granatum (pomegranate) was used as a traditional medicine in different parts of the world. It has been used in the treatment of pain and inflammatory conditions such as peptic ulcer. The numerous risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of pain and inflammation give rise to using medicinal herbs as alternative therapies. This study aimed to evaluate the anti-inflammatory effect of the ethyl acetate pomegranate fraction (EtOAc) by determination of its inhibitory effects on lipopolysaccharide (LPS), stimulated nitric oxide (NO), prostaglandin E2 (PGE-2), interleukin-6 (IL-6) and cyclooxxgenase-2 (COX2) release from RAW264.7cells. Methods: The inhibitory effect of EtOAc was evaluated on (LPS) induced NO production, PGE2, and IL-6 quantified by immunoassay kit and prostaglandin E2 competitive ELISA kit. COX2 production is an in vitro indication of possible anti-inflammatory activity and was estimated by Western blotting. Results: EtOAc potentially inhibited LPS-induced nitric oxide, prostaglandin, and IL-6 production. With these findings, it was evident that the EtOAc could reduce the LPS-induced cyclooxygenase-2 (COX-2) at the protein level in a dose-dependent manner as determined by Western blotting. Conclusion: The results emphasize potential therapeutic applications of Punica granatum in the treatment of inflammation.

Keywords: inflammation, Punica granatum, cytotoxicity, cytokines

Procedia PDF Downloads 660

Authors: Aniekan Peter, ECS Naidu, Edidiong Akang, U. Offor, R. Kalhapure, A. A. Chuturgoon, T. Govender, O. O. Azu

Abstract:

Introduction: Nano-drugs are novel innovations in the management of human immunodeficiency virus (HIV) pandemic, especially resistant strains of the virus in their sanctuary sites: testis and the brain. There are safety concerns to be addressed to achieve the full potential of this new drug delivery system. Aim of study: Our study was designed to investigate toxicity profile of Tenofovir Nanoparticle (TDF-N) synthesized by University of Kwazulu-Natal (UKZN) Nano-team for prevention and treatment of HIV infection. Methodology: Ten adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit UKZN were used for the study. The animals were weighed and divided into two groups of 5 animal each. Control animals (A) were administered with normal saline. Therapeutic dose (4.3 mg/kg) of TDF-N was administered to group B. At the end of four weeks, animals were weighed and sacrificed. Liver and kidney were removed fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT), liver function test (LFT) and full blood count (FBC) using appropriate analysers. Cellular measurements were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, values < 0.05 were significant. Results: We reported no histological alterations in the liver, kidney, FBC, LFT and RFT between the TDF-N animals and saline control. There were no significant differences in weight, organo-somatic index and histological measurements in the treatment group when compared with saline control. Conclusion/recommendations: TDF-N is not toxic to the liver, kidney and blood cells in our study. More studies using human subjects is recommended.

Keywords: tenofovir nanoparticles, liver, kidney, blood cells

Procedia PDF Downloads 185

Authors: Arezou Ghadi, Nasrollah Vahedi, Azam Sinkakarimi

Abstract:

For determination of antibiotic residues in slaughtered cow carcasses of Amol city in Iran, sampling has done from 100 heads of cow. For this purpose, the microbiological F.P.T (Four-Plate Test) method was used. Basis of this method, a clear zone is creating around the leachate on the plate that already has cultured a uniform layer of under test bacteria on agar plate. In this study from 100 heads of cow carcasses, at least 75 cases (75%) in one of the tested organs (muscle-liver-kidney) have been antibiotic residues. Also, it has been found that kidney have the most positive cases (60%) than other organs (liver and muscle), then the liver (58%) and finally are muscles (51%).

Keywords: antibiotic residues, agar plate test, cow carcass

Procedia PDF Downloads 457

Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

Abstract:

Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

Procedia PDF Downloads 119

Authors: Abul B. M. M. K. Islam, Mandar Dave, Roderick V. Jensen, Ashok R. Amin

Abstract:

A systems approach was applied to characterize differentially expressed transcripts, bioinformatics pathways, and proteins and prostaglandins (PGs) from lung fibroblasts procured from wild-type (WT), COX-1-/- and COX-2-/- mice to understand system level control mechanism. Bioinformatics analysis of COX-2 and COX-1 ablated cells induced COX-1 and COX-2 specific signature respectively, which significantly overlapped with an 'IL-1β induced inflammatory signature'. This defined novel cross-talk signals that orchestrated coordinated activation of pathways of sterile inflammation sensed by cellular stress. The overlapping signals showed significant over-representation of shared pathways for interferon y and immune responses, T cell functions, NOD, and toll-like receptor signaling. Gene Ontology Biological Process (GOBP) and pathway enrichment analysis specifically showed an increase in mRNA expression associated with: (a) organ development and homeostasis in COX-1-/- cells and (b) oxidative stress and response, spliceosomes and proteasomes activity, mTOR and p53 signaling in COX-2-/- cells. COX-1 and COX-2 showed signs of functional pathways committed to cell cycle and DNA replication at the genomics level. As compared to WT, metabolomics analysis revealed a significant increase in COX-1 mRNA and synthesis of basal levels of eicosanoids (PGE2, PGD2, TXB2, LTB4, PGF1α, and PGF2α) in COX-2 ablated cells and increase in synthesis of PGE2, and PGF1α in COX-1 null cells. There was a compensation of PGE2 and PGF1α in COX-1-/- and COX-2-/- cells. Collectively, these results support a broader, differential and collaborative regulation of both COX-1 and COX-2 pathways at the metabolic, signaling, and genomics levels in cellular homeostasis and sterile inflammation induced by cellular stress.

Keywords: cyclooxygenases, inflammation, lung fibroblasts, systemic

Procedia PDF Downloads 293

Authors: Alia Ali, Azeem Taj, Muhammed Joher Amin, Farrukh Iqbal, Zafar Iqbal

Abstract:

Background: Hypertension is commonly found in patients with Diabetic Kidney Disease (DKD). Microalbuminuria is the first clinical sign of involvement of kidneys in patients with type 2 diabetes. Uncontrolled hypertension induces a higher risk of cardiovascular events, including death, increasing proteinuria and progression to kidney disease. Objectives: To determine the correlation between microalbuminuria and hypertension and their association with other risk factors in type 2 diabetic patients. Methods: One hundred and thirteen type 2 diabetic patients were screened for microalbuminuria and raised blood pressure, attending the diabetic clinic of Shaikh Zayed Hospital, Lahore, Pakistan. The study was conducted from November 2012 to June 2013. Results: Patients were divided into two groups. Group 1, those with normoalbuminuria (n=63) and Group 2, those having microalbuminuria (n=50). Group 2 patients showed higher blood pressure values as compared to Group 1. The results were statistically significant and showed poor glycemic control as a contributing risk factor. Conclusion: The study concluded that there is high frequency of hypertension among type 2 diabetics but still much higher among those having microalbuminuria. So, early recognition of renal dysfunction through detection of microalbuminuria and to start treatment without any delay will confer future protection from end-stage renal disease as well as hypertension and its complications in type 2 diabetic patients.

Keywords: hypertension, microalbuminuria, diabetic kidney disease, type 2 Diabetes mellitus

Procedia PDF Downloads 399

Authors: Ludmila A. Gavriliuc, Jerry McLarty, Heather E. Kleiner, J. Michael Mathis

Abstract:

Abstract -- Background: The citrus coumarine Auraptene (Aur) is an effective chemopreventive agent, as manifested in many models of diseases and cancer. Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1, and peroxiredoxin 1, by activating the antioxidant response element (ARE). Genetic and biochemical evidence has demonstrated that glutathione (GSH) and glutathione-dependent enzymes, glutathione reductase (GR), glutathione peroxidases (GPs), glutathione S-transferases (GSTs) are responsible for the control of intracellular reduction-oxidation status and participate in cellular adaptation to oxidative stress. The effect of Aur on the activity of GR, GPs (Se-GP and Se-iGP), and content of GSH in the liver, kidney, and spleen is insufficiently explored. Aim: Our goal was the examination of the Aur influence on the redox-system of GSH in Nrf2 wild type and Nrf2 knockout mice via activation of Nrf2 and ARE. Methods: Twenty female mice, 10 Nrf2 wild-type (WT) and 10 Nrf2 (-/-) knockout (KO), were bred and genotyped for our study. The activity of GR, Se-GP, Se-iGP, GST, G6PD, CytP450 reductase, catalase (Cat), and content of GSH were analyzed in the liver, kidney, and spleen using Spectrophotometry methods. The results of the specific activity of enzymes and the amount of GSH were analyzed with ANOVA and Spearman statistical methods. Results: Aur (200 mg/kg) treatment induced hepatic GST, GR, Se-GP activity and inhibited their activity in the spleen of mice, most likely via activation of the ARE through Nrf2. Activation in kidney Se-GP and G6PD by Aur is also controlled, apparently through Nrf2. Results of the non-parametric Spearman correlation analysis indicated the strong positive correlation between GR and G6PD only in the liver in WT control mice (r=+0.972; p < 0.005) and in the kidney KO control mice (r=+0.958; p < 0.005). The observed low content of GSH in the liver of KO mice indicated an increase in its participation in the neutralization of toxic substances with the absence of induction of GSH-dependent enzymes, such as GST, GR, Se-GP, and Se-iGP. Activation of CytP450 in kidney and spleen and Cat in the liver in KO mice probably revealed another regulatory mechanism for these enzymes. Conclusion: Thereby, obtained results testify that Aur can modulate the activity of genes and antioxidant enzymatic redox-system of GSH, responsible for the control of intracellular reduction-oxidation status.

Keywords: auraptene, glutathione, GST, Nrf2

Procedia PDF Downloads 149

Authors: Blanche Aguida, Marootpong Pooam, Nathalie Jourdan, Margaret Ahmad

Abstract:

COVID-19-related morbidity is associated with exaggerated inflammation and cytokine production in the lungs, leading to acute respiratory failure. The cellular mechanisms underlying these so-called ‘cytokine storms’ are regulated through the Toll-like receptor 4 (TLR4) signaling pathway and by reactive oxygen species (ROS). Both light (photobiomodulation) and magnetic fields (e.g., pulsed electromagnetic field) stimulation are non-invasive therapies known to confer anti-inflammatory effects and regulate ROS signaling pathways. Here we show that daily exposure to two 10-minute intervals of moderate-intensity infra-red light significantly lowered the inflammatory response induced via the TLR4 receptor signaling pathway in human cell cultures. Anti-inflammatory effects were likewise achieved by electromagnetic field exposure of cells to daily 10-minute intervals of either pulsed electromagnetic fields (PEMF) or to low-level static magnetic fields. Because current illumination and electromagnetic field therapies have no known side effects and are already approved for some medical uses, we have here developed protocols for verification in clinical trials of COVID 19 infection. These treatments are affordable, simple to implement, and may help to resolve the acute respiratory distress of COVID 19 patients both in the home and in the hospital.

Keywords: COVID 19, electromagnetic fields therapy, inflammation, photobiomodulation therapy

Procedia PDF Downloads 144

Authors: Ayesha Waqar Khan, Mariam Altaf, Jamil Ahmad, Shaheen Shahzad

Abstract:

Kidney fibrosis is an anticipated outcome of possibly all types of progressive chronic kidney disease (CKD). Epithelial-mesenchymal transition (EMT) signaling pathway is responsible for production of matrix-producing fibroblasts and myofibroblasts in diseased kidney. In this study, a discrete model of TGF-beta (transforming growth factor) and CTGF (connective tissue growth factor) was constructed using Rene Thomas formalism to investigate renal fibrosis turn over. The kinetic logic proposed by Rene Thomas is a renowned approach for modeling of Biological Regulatory Networks (BRNs). This modeling approach uses a set of constraints which represents the dynamics of the BRN thus analyzing the pathway and predicting critical trajectories that lead to a normal or diseased state. The molecular connection between TGF-beta, Smad 2/3 (transcription factor) phosphorylation and CTGF is modeled using GenoTech. The order of BRN is CTGF, TGF-B, and SMAD3 respectively. The predicted cycle depicts activation of TGF-B (TGF-β) via cleavage of its own pro-domain (0,1,0) and presentation to TGFR-II receptor phosphorylating SMAD3 (Smad2/3) in the state (0,1,1). Later TGF-B is turned off (0,0,1) thereby activating SMAD3 that further stimulates the expression of CTGF in the state (1,0,1) and itself turns off in (1,0,0). Elevated CTGF expression reactivates TGF-B (1,1,0) and the cycle continues. The predicted model has generated one cycle and two steady states. Cyclic behavior in this study represents the diseased state in which all three proteins contribute to renal fibrosis. The proposed model is in accordance with the experimental findings of the existing diseased state. Extended cycle results in enhanced CTGF expression through Smad2/3 and Smad4 translocation in the nucleus. The results suggest that the system converges towards organ fibrogenesis if CTGF remains constructively active along with Smad2/3 and Smad 4 that plays an important role in kidney fibrosis. Therefore, modeling regulatory pathways of kidney fibrosis will escort to the progress of therapeutic tools and real-world useful applications such as predictive and preventive medicine.

Keywords: CTGF, renal fibrosis signaling pathway, system biology, qualitative modeling

Procedia PDF Downloads 180

Authors: Imdad Ullah Khan, Yongseok Yoon, Kyeung Uk Choi, Kwang Rae Jo, Namyul Kim, Eunbee Lee, Wan Hee Kim, Oh-Kyeong Kweon

Abstract:

The primary spinal cord injury (SCI) causes mechanical damage to the neurons and blood vessels. It leads to secondary SCI, which activates multiple pathological pathways, which expand neuronal damage at the injury site. It is characterized by vascular disruption, ischemia, excitotoxicity, oxidation, inflammation, and apoptotic cell death. It causes nerve demyelination and disruption of axons, which perpetuate a loss of impulse conduction through the injured spinal cord. It also leads to the production of myelin inhibitory molecules, which with a concomitant formation of an astroglial scar, impede axonal regeneration. The pivotal role regarding the neuronal necrosis is played by oxidation and inflammation. During an early stage of spinal cord injury, there occurs an abundant expression of reactive oxygen species (ROS) due to defective mitochondrial metabolism and abundant migration of phagocytes (macrophages, neutrophils). ROS cause lipid peroxidation of the cell membrane, and cell death. Abundant migration of neutrophils, macrophages, and lymphocytes collectively produce pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1β), matrix metalloproteinase, superoxide dismutase, and myeloperoxidases which synergize neuronal apoptosis. Therefore, it is crucial to control inflammation and oxidation injury to minimize the nerve cell death during secondary spinal cord injury. Therefore, in response to oxidation and inflammation, heme oxygenase-1 (HO-1) is induced by the resident cells to ameliorate the milieu. In the meanwhile, neurotrophic factors are induced to promote neuroregeneration. However, it seems that anti-stress enzyme (HO-1) and neurotrophic factor (BDNF) do not significantly combat the pathological events during secondary spinal cord injury. Therefore, optimum healing can be induced if anti-inflammatory and neurotrophic factors are administered in a higher amount through an exogenous source. During the first experiment, the inflammation and neuroregeneration were selectively targeted. HO-1 expressing MSCs (HO-1 MSCs) and BDNF expressing MSCs (BDNF MSC) were co-transplanted in one group (combination group) of dogs with subacute spinal cord injury to selectively control the expression of inflammatory cytokines by HO-1 and induce neuroregeneration by BDNF. We compared the combination group with the HO-1 MSCs group, BDNF MSCs group, and GFP MSCs group. We found that the combination group showed significant improvement in functional recovery. It showed increased expression of neural markers and growth-associated proteins (GAP-43) than in other groups, which depicts enhanced neuroregeneration/neural sparing due to reduced expression of pro-inflammatory cytokines such as TNF-alpha, IL-6 and COX-2; and increased expression of anti-inflammatory markers such as IL-10 and HO-1. Histopathological study revealed reduced intra-parenchymal fibrosis in the injured spinal cord segment in the combination group than in other groups. Thus it was concluded that selectively targeting the inflammation and neuronal growth with the combined use of HO-1 MSCs and BDNF MSCs more favorably promote healing of the SCI. HO-1 MSCs play a role in controlling the inflammation, which favors the BDNF induced neuroregeneration at the injured spinal cord segment of dogs.

Keywords: HO-1 MSCs, BDNF MSCs, neuroregeneration, inflammation, anti-inflammation, spinal cord injury, dogs

Procedia PDF Downloads 119

Authors: Chargui Abderrahman, Nehdi Afef , BelaïD Amine , Djerbi Nadir, Tauc Michel, Hofman Paul, Mograbi Baharia, El May MichèLe

Abstract:

K63-linked ubiquitination — i.e. conjugation of a chain of ubiquitins (Ub) linked through lys63 — has emerged as a key mechanism regulating signalling transduction pathways. Although critical, very little information is currently available about how subversion of K63 ubiquitination might contribute to cancers and inflammatory diseases. The present study provides the first evidence that Cadmium (Cd), a widespread environmental carcinogen and toxicant, is a powerful activator of K63 ubiquitination. Indeed, Cd induces accumulation of K63 polyUb proteins. Importantly, Cd-induced ubiquitination does not stem on oxidative damage or proteasome impairment. Rather, we demonstrate that Cd not only activates K63 ubiquitination but also amplifies their accumulation by overloading the capacity of autophagy pathway. At molecular level, Cd-induced ubiquitination is correlated with stabilization of HIF-1 and the activation of NF-B, two transcription factors. Strikingly, prolonged cell exposure to high Cd concentrations induces an exaggerated K63 ubiquitination that fosters aggresome formation, thus precluding these proteins from interacting with their downstream nuclear targets. We therefore propose that the aberrant activation of K63 ubiquitination by the carcinogen Cadmium could promote cell proliferation and inflammation at low levels while high levels committed cell to death.

Keywords: cadmium, environmental exposure, Lysine-63-ubiquitination, kidney, apoptosis, proliferation, autophagy

Procedia PDF Downloads 210

Authors: Wessam H. Abd-Elsalam, Mona M. Saber, Samar M. Abouelatta

Abstract:

Non-steroidal anti-inflammatory drugs (NSAIDs) are considered a double edged sword in inflammatory bowel diseases (IBDs). Some studies reported their advantageous effect in decreasing inflammation, and other studies reported that their use is associated with colitis aggravation. This study aimed to use specifically formulated trehalose-based nano-carriers that targets the colon in an attempt to alleviate inflammation caused by NSAIDs. L-α-phosphatidylcholine (PL), trehalose, and transcutol were used to prepare the trehalosomes (THs), which were also loaded with Tenoxicam(TXM) as a model NSAID. To optimize the formulation variables, a full 23 factorial design, using Design-Expert® software, was performed. The optimized formulation composed of trehalose: PL at a weight ratio of 1:1, 377.72 mg transcutol, and sonicated for 4 min, possessed a spherical shape with a size of 268.61 nm and EE% of 97.83% and released 70.22% of its drug content over 24 h. The superior protective action of TXM loaded THs compared to TXM suspension and drug-free THs was shown by the inhibition of the inflammatory biomarkers, namely; IL-1ß, IL-6, and TNF-alpha levels, as well as oxidative stress markers, measured as GSH and MDA. Improved histopathology of the colonic tissue in male New Zealand rabbits also confirmed the superiority of the TXM loaded THs compared to the unformulated drug or the drug free nano-carriers. Our findings highlight the prosperous role of THs in colon targeting and its anti-inflammatory characteristics in guarding against possible NSAIDs-driven exacerbation of colitis.

Keywords: inflammatory bowel disease, trehalose, trehalosomes, colon targeting

Procedia PDF Downloads 138

Authors: Bindu Kumari, Bindu Kumari Singh

Abstract:

Endosulfan is known to be one of the highly toxic agricultural pesticides commonly used in our societies. With the widespread use of Endosulfan in agriculture, human beings are most likely to be exposed to it, either orally by eating Endosulfan-contaminated foods or by nose and whole body inhalation in the farms during its application. The present study was conducted to observe the changes in the serum uric acid level of the Swiss albino rats due to the administration of Endosulfan. 3.0 mg Endosulfan/kg body weight was daily administered orally to albino rats for 28 days period. Alterations in their K.F.T. parameters were recorded at a regular interval of 7 days within this 28 days period and were compared with those of control rats. All rats were monitored for any observable toxic symptoms throughout the experimental period and they also were weighted weekly to monitor body weight gain. Alteration recorded in K.F.T. parameters within the groups were due to Endosulfan exposure and serum uric acid level was significantly elevated in the 3mg/kg dose group. Pathological changes of rats treated with Endosulfan were observed with typical signs of toxicity. Uric acid is a heterocyclic compound formed as an end product of metabolism of purine nucleotides. It forms ions and salts known as urate and acid urate which are harmful to our health. Uric acid clearance is one of the numerous important functions of the kidney. Defects in this process resulted in Gout, kidney stone or Kidney failure.

Keywords: KFT parameters, blood uric acid level, endosulfan, eat

Procedia PDF Downloads 293

Authors: Styliani Kotrotsiou, Evagelia Kotrotsiou, Fani Mokia, Theodosis Paralikas, Konstantinos Tsaras

Abstract:

Objective: The objective of this study was the investigation of the mental health of patients undergoing chronic or transient hemodialysis at Artificial Kidney Unit, as well as its relationship to the demographic characteristic of patients. Material and Method: The study took place in Larisa during the month of December in 2016 and the sample was composed of 60 patients undergoing in chronic or transient hemodialysis at Artificial Kidney Unit of the University General Hospital of Larisa. For the investigation of the physical and mental health of patients who participated in the study, the tool measurement << General Health Questionnaire- 28 >> (GHQ-28) was used. The questionnaires were administered with the interview method during the hemodialysis. This survey is designed for the existence or not of a mental disorder. It examines four factors (physical symptoms, anxiety, social dysfunction and depression). Results: The hemodialysis patients gave the following scores: -to the physical symptoms, women showed a higher average value than men (1,16 ± 1,26 against 0,49 ± 0,93), -at the anxiety scale, it seems that women are superior to men (1,68 ± 1,20 against 0,90 ± 1,22), -at the social dysfunction scale, the elderly patients ( > 65 years old) were presented a with higher average (2,59), and -at the depression scale, patients with a higher average value were those who lived in non-urban areas. The appearance of mental disorder, in relation to patient characteristics, did not show significant statistical correlation. The sex, the age and the place of residence affect more the assessment of mental health, while education did not seem to have any significant effect on the other. Conclusions: The hemodialysis process can significantly affect the patient’s Quality of Life and it can bring adverse changes in lifestyle, affecting the physical, social and psychological state of the individual. For that reason, hemodialysis should be aimed not only at extending life but in upgrading the Quality of Life.

Keywords: hemodialysis, chronic kidney disease, depression, social dysfunction, physical condition

Procedia PDF Downloads 164

Authors: D. M. El-Tanbouly, R. M. Abdelsalam, A. S. Attia, M. T. Abdel-Aziz

Abstract:

Lipopolysaccharide (LPS) endotoxin, a component of the outer membrane of Gram-negative bacteria, is involved in the pathogenesis of sepsis. LPS administration induces systemic inflammation that mimics many of the initial clinical features of sepsis and has deleterious effects on several organs including the liver and eventually leading to septic shock and death. The present study aimed to investigate the protective effect of magnesium, a well-known cofactor in many enzymatic reactions and a critical component of the antioxidant system, on hepatic damage associated with LPS induced- endotoxima in mice. Mg (20 and 40 mg/kg, po) was administered for 7 consecutive days. Systemic inflammation was induced one hour after the last dose of Mg by a single dose of LPS (2 mg/kg, ip) and three hours thereafter plasma was separated, animals were sacrificed and their livers were isolated. LPS-treated mice suffered from hepatic dysfunction revealed by histological observation, elevation in plasma transaminases activities, C-reactive protein content and caspase-3, a critical marker of apoptosis. Liver inflammation was evident by elevation in liver cytokines contents (TNF-α and IL-10) and myeloperoxidase (MPO) activity. Additionally, oxidative stress was manifested by increased liver lipoperoxidation, glutathione depletion, elevated total nitrate/nitrite (NOx) content and glutathione peroxidase (GPx) activity. Pretreatment with Mg largely mitigated these alternations through its anti-inflammatory and antioxidant potentials. Mg, therefore, could be regarded as an effective strategy for prevention of liver damage associated with septicemia.

Keywords: LPS, liver damage, magnesium, septicemia

Procedia PDF Downloads 397

Authors: Jitpisute Chunthorng-Orn, Thana Juckmeta, Onmanee Prajuabjinda, Arunporn Itharat

Abstract:

Inflammation and oxidative stress work together to produce symptoms in cancer patients. The whole part of it is used as a preparation to treat cancer patients in Khampramong temple which has been a place of treatment and palliative care for cancer patients since 2005. Thus, the objective of this study was to investigate anti-inflammatory and antioxidant activities of Heliotropium indicum extracts. Dried plant materials were extracted in a similar manner to those practiced by the Khampramong Temple i.e. maceration in 95% ethanol and boiling in water. For anti-inflammation activity, both extracts were tested for suppression of nitric oxide (NO) production in LPS-induced RAW 264.7 cells. They were also tested for antioxidant activity by DPPH radical scavenging assay. This study found that the ethanolic extract of Heliotropium indicum exhibited higher inhibitory activity of NO release than Indomethacin as a positive control (IC50 value of 24.17±2.12 and 34.67±6.23 μg/mL, respectively). For DPPH radical scavenging assay, the ethanolic extract also exhibited antioxidant activity but less than BHT as a antioxidant compound (EC50 values = 28.91±4.26 and 13.08±0.29 μg/mL, respectively). In contrast, its water extract had no inhibitory activity on NO release (IC50 > 100 μg/mL) and no inhibitory activity on DPPH radicals (EC50 values > 100 μg/mL). The results showed correlation between anti-inflammation and antioxidant activity and these results also support using this plant to treat cancer patients.

Keywords: Heliotropium indicum, RAW 264.7, DPPH, Khampramong Temple

Procedia PDF Downloads 541

Authors: Kathleen Cooney, Jennifer Coates, Lesley Leach, Kristin Hrenchir

Abstract:

The objective of this retrospective study was to determine whether intrarenal injection of pentobarbital sodium is a practicable method of euthanasia in client-owned cats. 131 Cats were anesthetized using a combination of tiletamine, zolazepam, and acepromazine given by of subcutaneous or intramuscular injection. Once an appropriate plane of anesthesia was reached, 6 ml of pentobarbital sodium was injected into either the left or right kidney. The patient’s age, sex, estimated weight, presenting condition, estimated dehydration level, palpable characteristics of the kidney pre and post injection, physical response of the cat, and time to cardiopulmonary arrest were recorded. Analysis of 131 records revealed that cats receiving an intrarenal injection of pentobarbital sodium had an average time to cardiopulmonary arrest of 1 minute. The great majority (79%) experienced cardiopulmonary arrest in less than one minute with the remainder experiencing cardiopulmonary arrest between 1 and 8 minutes of the injection. 95% of cats had no observable reaction to intrarenal injection other than cardiopulmonary arrest. In the 19% of cases where kidney swelling was not palpable upon injection, average time to cardiopulmonary arrest increased from 0.9 to 1.6 min. Conclusions and Clinical Relevance: Intrarenal injections of pentobarbital sodium are similar in effect to intravenous methods of euthanasia. Veterinarians who elect to use intrarenal injections can expect cardiopulmonary arrest to occur quickly in the majority of patients with few agonal reactions. Intrarenal injection of pentobarbital sodium in anesthetized cats has ideally suited for cases of owner observed euthanasia when obtaining intravenous access would difficult or disruptive.

Keywords: euthanasia, injection, intrarenal, pentobarbital sodium

Procedia PDF Downloads 343

Authors: Shao-Ju Chien, Yi-Chien Wu, Ting-Ying Huang, Li-Tsen Li, You-Jin Chen, Cheng-Nan Chen

Abstract:

Homocysteine and pro-inflammatory mediators such as cyclooxygenase-2 (COX-2) have been linked to vascular dysfunction and risks of cardiovascular diseases. Fulvic acid (FA) is class of compounds of humic substances and possesses various pharmacological properties. However, the effect of FA on inflammatory responses of the monocytes remains unclear. We investigated the regulatory effect of FA on homocysteine-induced COX-2 expression in human monocytes. Peripheral blood monocytes and U937 cells were kept as controls or pre-treated with FA, and then stimulated with homocysteine. The results show that pretreating monocytes with FA inhibited the homocysteine-induced COX-2 expression in a dose-dependent manner. The inhibitor for nuclear factor-kB (NF-kB) attenuated homocysteine-induced COX-2 expression. Our findings provide a molecular mechanism by which FA inhibit homocysteine-induced COX-2 expression in monocytes, and a basis for using FA in pharmaceutical therapy against inflammation.

Keywords: homocysteine, monocytes, cyclooxygenase-2, fulvic acid, anti-inflammation

Procedia PDF Downloads 597