Search results for: liver cirrhosis

Authors: Marcela Parra-Vargas, Ana Sandoval-Rodriguez, Roberto Rodriguez-Echevarria, Jose Dominguez-Rosales, Juan Armendariz-Borunda

Abstract:

Non-alcoholic fatty liver disease (NAFLD) is characterized by an excess of hepatic lipids, and it is to author’s best knowledge, the most prevalent chronic liver disorder. Anthocyanin-rich food consumption is linked to health benefits in metabolic disorders associated with obesity and NAFLD, although the precise functional role of anthocyanidin delphinidin (Dp) has yet to be established. The aim of this study was to investigate the effect of the Dp in NAFLD metabolic alterations by evaluating prevention or amelioration of hepatic lipid accumulation, as well as molecular mechanisms in two experimental obesity-related models of NALFD. In vitro: HepG2 cells were incubated with sodium palmitate (PA, 1 mM) to induce lipotoxic damage, and concomitantly treated with Dp (180 uM) for 24 h. Subsequently, total lipid accumulation was measured by colorimetric staining with Oil Red O, and total intrahepatic triglycerides were determined by an enzymatic assay. To assess molecular mechanisms, cells were pre-treated with PA for 24 h and then exposed to Dp for 1 h. In vivo: four-week-old male C57BL/6Nhsd mice were allocated in two main groups. Mice were fed with standard diet (control) or high-fat and high-carbohydrate diet (45% fat, HFD) for 16 wk to induce NAFLD. Then HFD was divided into subgroups: one treated orally with Dp (15 mg/kg bw, HFD-Dp) every day for 4 wk, while HFD group treated with vehicle (DMSO). Weight and fasting glucose were recorded weekly, while dietary ingestion was measured daily. Insulin tolerance test was performed at the end of treatment. Liver histology was evaluated with H&E and Masson’s trichrome stain. RT-PCR was used to evaluate gene expression and Western Blot to determine levels of protein in both experimental models. Parametric data were analyzed with one-way ANOVA and Tukey’s post-hoc test. Kruskal-Wallis and Mann-Whitney U test for non-parametric data, and P < 0.5 were considered significant. Dp prevented hepatic lipid accumulation by PA in HepG2 hepatocytes. Furthermore, Dp down-regulated gene expression of SREBP1c, FAS, and CPT1a without modifying AMPK phosphorylation levels. In vivo, Dp oral administration did not ameliorate lipid metabolic alterations raised by HFD. Adiposity, dietary ingestion, fasting glucose, and insulin sensitivity after Dp treatment remained similar to HFD group. Histological analysis showed hepatic damage in HFD groups and no differences between HFD and HFD-Dp groups were found. Hepatic gene expression of ACC and FAS were not altered by HFD. SREBP1c was similar in both HFD and HFD-Dp groups. No significant changes were observed in SREBP1c, ACC, and FAS adipose tissue gene expression by HFD or Dp treatment. Additionally, immunoblotting analysis revealed no changes in pathway SIRT1-LKB-AMPK and PPAR alpha by both HFD groups compared to control. In conclusion, the antioxidant Dp may provoke beneficial effects in the prevention of hepatic lipid accumulation. Nevertheless, the oral dose administrated in mice that simulated the total intake of anthocyanins consumed daily by humans has no effect as a treatment on hepatic lipid metabolic alterations and histological abnormalities associated with exposure to chronic HFD. A healthy lifestyle with regular intake of antioxidants such as anthocyanins may prevent metabolic alterations in NAFLD.

Keywords: anthocyanins, antioxidants, delphinidin, non-alcoholic fatty liver disease, obesity

Procedia PDF Downloads 198

Authors: Hongping Lu, Kelbinur Tursun, Yaru Li, Yu Zhang, Shunai Liu, Ming Han

Abstract:

Objective: To investigate whether NS5ATP9 is involved in IL-6 mediated autophagy and the relationship between IL-6 and NS5ATP9 in liver cancer cells. Methods: 1. Detect the mRNA and protein levels of Beclin 1 after HepG2 cells were treated with or without recombinant human IL-6 protein. 2. Measure and compare of the changes of autophagy-related genes with their respective control, after IL-6 was silenced or neutralized with monoclonal antibody against human IL-6. 3. HepG2 cells were incubated with 50 ng/ml of IL-6 in the presence or absence of PDTC. The expression of NS5ATP9 was analyzed by Western blot after 48 h. 4. After NS5ATP9-silenced HepG2 cells had been treated with 50 ng/ml recombinant IL-6 protein, we detected the Beclin 1 and LC3B (LC3Ⅱ/Ⅰ) expression. 5. HepG2 cells were transfected with pNS5ATP9, si-NS5ATP9, and their respective control. Total RNA was isolated from cells and analyzed for IL-6. 6. Silence or neutralization of IL-6 in HepG2 cells which has been transfected with NS5ATP9. Beclin 1 and LC3 protein levels were analyzed by Western blot. Result: 1. After HepG2 were treated with recombinant human IL-6 protein, the expression of endogenous Beclin 1 was up-regulated at mRNA and protein level, and the conversion of endogenous LC3-I to LC3-II was also increased. These results indicated that IL-6 could induce autophagy. 2. When HepG2 cells were treated with IL-6 siRNA or monoclonal antibody against human IL-6, the expression of autophagy-related genes were decreased. 3. Exogenous human IL-6 recombinant protein up-regulated NS5ATP9 via NF-κB activation. 4. The expression of Beclin 1 and LC3B was down-regulated after IL-6 treated NS5ATP9-silenced HepG2 cells. 5. NS5ATP9 could reverse regulates IL-6 expression in HepG2 cells. 6. Silence or neutralization of IL-6 attenuates NS5ATP9-induced autophagy slightly. Conclusion: Our results implied that in HCC patients, maybe the higher level of IL-6 in the serum promoted the expression of NS5ATP9 and induced autophagy in cancer cells. And the over-expression of NS5ATP9 which induced by IL-6, in turn, increased IL-6 expression, further, promotes the IL-6/NS5ATP9-mediated autophagy and affects the progression of tumor. Therefore, NS5ATP9 silence might be a potential target for HCC therapy.

Keywords: autophagy, Hepatocellular carcinoma, IL-6, microenvironment, NS5ATP9

Procedia PDF Downloads 246

Authors: Mahesh M. Patil, K. A. Anu-Appaiah

Abstract:

Overweight and obesity is a serious medical problem, increasing in prevalence, and affecting millions worldwide. Investigators have been trying from decades to articulate the burden of obesity and related risk factors. To answer this problem, we suggest a new therapeutic anti-obesity compounds from Garcinia xanthochymus fruit. However, there is little published scientific information on non-hydroxycitric acid Garcinia species. Our findings include biochemical characterization of the fruit; in vivo toxicity and bio-efficacy study of G. xanthochymus in high fat diet wistar rat model. We observed that Garcinia pericarp is a rich source of organic acids, polyphenols, mono- (40.63%) and poly-unsaturated fatty acids (16.45%; omega-3: 10.02%). Toxicological studies have showed that Garcinia is safe and had no observed adverse effect level up to 400 mg/kg/day. Body weight and food intake was significantly (P<0.05) reduced in oral gavage treated rats (sonicated Garcinia powder) in 13 weeks. Subcutaneous fat was significantly (P<0.05) reduced in Garcinia treated rats. Hepatocytes significantly (p<0.05) overexpressed sterol regulatory element binding protein 2, liver X receptor- α, liver X receptor- β, lipoprotein lipase and monoacylglycerol lipase. Fatty acid binding protein 1 and peroxisome proliferator activated receptor- α were down regulated as assessed by real time qPCR. Currently our research is focused on the adipocyte obesity related gene expressions, effect of Garcinia on 3T3-adipocyte cell lines and high fat diet induced mice model. This in vivo pre-clinical data suggests that G. xanthochymus may have clinical utility for the treatment of obesity. However, further studies are required to establish its potency.

Keywords: Garcinia xanthochymus, anti-obesity, high fat diet, real time qPCR

Procedia PDF Downloads 248

Authors: Suang K. Lau, Ismail Goolam, Rafid Al-Asady

Abstract:

Background: The majority of patients with hepatocellular carcinoma (HCC) are not suitable for curative treatment, in the form of surgical resection or transplantation, due to tumour extent and underlying liver dysfunction. In these non-resectable cases, a variety of non-surgical therapies are available, including microwave ablation (MWA), which has shown increasing popularity due to its low morbidity, low reported complication rate, and the ability to perform multiple ablations simultaneously. Objective: The aim of this study was to evaluate the validity of MWA as a viable treatment option in the management of HCC and hepatic metastatic disease, by assessing its efficacy and complication rate at a tertiary hospital situated in Westmead (Australia). Methods: A retrospective observational study was performed evaluating patients that underwent MWA between 1/1/2017–31/12/2018 at Westmead Hospital, NSW, Australia. Outcome measures, including residual disease, recurrence rates, as well as major and minor complication rates, were retrospectively analysed over a 12-months period following MWA treatment. Excluded patients included those whose lesions were treated on the basis of residual or recurrent disease from previous treatment, which occurred prior to the study window (11 patients) and those who were lost to follow up (2 patients). Results: Following treatment of 106 new hepatic lesions, the complete response rate (CR) was 86% (91/106) at 12 months follow up. 10 patients had the residual disease at post-treatment follow up imaging, corresponding to an incomplete response (ICR) rate of 9.4% (10/106). The local recurrence rate (LRR) was 4.6% (5/106) with follow-up period up to 12 months. The minor complication rate was 9.4% (10/106) including asymptomatic pneumothorax (n=2), asymptomatic pleural effusions (n=2), right lower lobe pneumonia (n=3), pain requiring admission (n=1), hypotension (n=1), cellulitis (n=1) and intraparenchymal hematoma (n=1). There was 1 major complication reported, with pleuro-peritoneal fistula causing recurrent large pleural effusion necessitating repeated thoracocentesis (n=1). There was no statistically significant association between tumour size, location or ablation factors, and risk of recurrence or residual disease. A subset analysis identified 6 segment VIII lesions, which were treated via a trans-pleural approach. This cohort demonstrated an overall complication rate of 33% (2/6), including 1 minor complication of asymptomatic pneumothorax and 1 major complication of pleuro-peritoneal fistula. Conclusions: Microwave ablation therapy is an effective and safe treatment option in cases of non-resectable hepatocellular carcinoma and liver metastases, with good local tumour control and low complication rates. A trans-pleural approach for high segment VIII lesions is associated with a higher complication rate and warrants greater caution.

Keywords: hepatocellular carcinoma, liver metastases, microwave ablation, trans-pleural approach

Procedia PDF Downloads 132

Authors: Yu-Tzu Hsu, Alice Wu, Hsiang-Kuang Tseng

Abstract:

Introduction: Hepatitis A virus causes acute hepatitis and is usually transmitted by a fecal-oral route of food contamination, which is more prevalent in areas with poor hygienic practices. However, we described a hepatitis A outbreak associated with a fecal-oral route of sexual behavior in men who has sex with men (MSM) in Northern Taiwan. Methods: We retrospectively collected patients with acute HAV infection in MacKay Memorial Hospital, Taipei, Taiwan between July 2015 and November 2016. Demographic data (age, gender, onset time and infection risk), laboratory data (GOT, GPT, bilirubin, HIV status, HBsAg, HCV antibody and syphilis), clinical symptoms and travel history with a foreign tour were analyzed. We compared variables between HIV and non-HIV group. Unless otherwise stated, continuous variables were expressed as mean ± SD, and categorical variables were expressed as number (percentage) for each item. The t test for continuous variables was applied for the comparison between two groups and chi-square for categorical variables were applied for measures of association. Results: We collected 80 cases during the study period. Among them, 54 (67.5%) cases were MSM and 43 (53.8%) cases were HIV positive. The average age was 32.6±7.59 years-old. The average value of initial liver function was 1324 IU/L for AST (GOT), 2100 IU/L for ALT (GPT), and 5.82 mg/dL for bilirubin. We found seven (8.6%) cases were in the status of HBV carrier, five (6.3%) cases were positive for HCV antibody, and 15 (18.6%) cases were co-infected with syphilis. With regards to associated symptoms, 32 (40%) had fever, 46 (57.5%) had nausea, 34 (42.5%) had abdominal discomfort and 46 (57.5%) had general malaise. To compare the non-HIV patients with HIV patients, HIV patients were more likely to be male (p=0.008), MSM (p=0.000), co-infected syphilis (p=0.000) and slowly improving liver function of transaminases (p=0.033, 0.027). Conclusion: The HAV outbreak in Northern Taiwan was mainly occurred in MSM population. Hereafter, our cohort data support a policy in Taiwan to provide one dose of free HAV vaccine shot in this population. Hopefully, the outbreak could be stop by the free vaccine policy and public education.

Keywords: acute hepatitis A, men who has sex with men, human immunodeficiency virus, vaccine

Procedia PDF Downloads 200

Authors: Sharique Ahmed, Khushtar Anwar Salman

Abstract:

Alpha-1-antitrypsin (AAT) is a major plasma serine protease inhibitor (SERPIN). Hereditary AAT deficiency is one of the common diseases in some part of the world. AAT is mainly produced in the liver and functions to protect the lung against proteolytic damage (e.g., from neutrophil elastase) acting as the major inhibitor for neutrophil elastase. α (1)-Antitrypsin (AAT) deficiency is an under recognized genetic condition that affects approximately 1 in 2,000 to 1 in 5,000 individuals and predisposes to liver disease and early-onset emphysema. Not only does α-1-antitrypsin deficiency lead to disabling syndrome of pulmonary emphysema, there are other disorders too which include ANCA (antineutrophilic cytoplasmic antibody) positive Wegener's granulomatosis, diffuse bronchiectasis, necrotizing panniculitis in α-1-antitrypsin phenotype (S), idiopathic pulmonary fibrosis and steroid dependent asthma. Augmentation therapy with alpha-1 antitrypsin (AAT) from human plasma has been available for specific treatment of emphysema due to AAT deficiency. Apart from this several observations have also suggested a role for endogenous suppressors of HIV-1, alpha-1 antitrypsin (AAT) has been identified to be one of those. In view of its varied important role in humans, serum from a mammalian source was chosen for the isolation and purification. Studies were performed on the homogeneous fraction. This study suggests that the buffalo serum α-1-antritrypsin has characteristics close to ovine, dog, horse and more importantly to human α-1-antritrypsin in terms of its hydrodynamic properties such as molecular weight, carbohydrate content, etc. The similarities in the hydrodynamic properties of buffalo serum α-1-antitrypsin with other sources of mammalian α-1-antitrypsin mean that it can be further studied and be a potential source for "augmentation therapy", as well as a source of AAT replacement therapy to raise serum levels above the protective threshold. Other parameters like the amino acid sequence, the effect of denaturants, and the thermolability or thermostability of the inhibitor will be the interesting basis of future studies on buffalo serum alpha-1 antitrypsin (AAT).

Keywords: α-1-antitrypsin, augmentation therapy , hydrodynamic properties, serine protease inhibitor

Procedia PDF Downloads 484

Authors: W. J. Zhang, Y. Q. Du, M. L. Wang

Abstract:

Noninvasive diagnostics of diseases via breath analysis has attracted considerable scientific and clinical interest for many years and become more and more promising with the rapid advancement in nanotechnology and biotechnology. The volatile organic compounds (VOCs) in exhaled breath, which are mainly blood borne, particularly provide highly valuable information about individuals’ physiological and pathophysiological conditions. Additionally, breath analysis is noninvasive, real-time, painless and agreeable to patients. We have developed a wireless sensor array based on single-stranded DNA (ssDNA)-decorated single-walled carbon nanotubes (SWNT) for the detection of a number of physiological indicators in breath. Eight DNA sequences were used to functionalize SWNT sensors to detect trace amount of methanol, benzene, dimethyl sulfide, hydrogen sulfide, acetone and ethanol, which are indicators of heavy smoking, excessive drinking, and diseases such as lung cancer, breast cancer, cirrhosis and diabetes. Our tests indicated that DNA functionalized SWNT sensors exhibit great selectivity, sensitivity, reproducibility, and repeatability. Furthermore, different molecules can be distinguished through pattern recognition enabled by this sensor array. Thus, the DNA-SWNT sensor array has great potential to be applied in chemical or bimolecular detection for the noninvasive diagnostics of diseases and health monitoring.

Keywords: breath analysis, diagnosis, DNA-SWNT sensor array, noninvasive

Procedia PDF Downloads 345

Authors: Ahlam H. Mahmoud, Samir F. Zohny, Ibrahim H. Boraia, Faten S. Bayoumic, Eman Eissa

Abstract:

Hepatocellular carcinoma is one of the most common cancers worldwide and is known to be resistant to conventional chemotherapy. Therefore, we aimed to assess the Salsola inermis extract as a novel chemopreventive and/or therapeutic agent against N-nitrosodiethylamine (DNE)/phenobarbital (PB)-induced hepatocarcinogenesis in rats. Adult male Wistar albino rats were divided into five groups: group1 rats were served as normal controls; group 2 rats were injected intraperitoneally with S. inermis extract (100 mg/kg body weight/day) for 20 weeks; group 3 rats were subjected to two-phase hepatocarcinogenic regimen (initiation of hepatocarcinogenesis was performed by a single intraperitoneal injection of DEN at a dose of 200 mg/kg body weight, 2 weeks later, the carcinogenic effect was promoted by supplementation of rats with 0.05% PB for 16 weeks); group 4 rats were injected intraperitoneally with S. inermis extract 2 weeks prior to the injection of DEN, the daily injection of S. inermis extract was then continued for 18 weeks along with two-phase hepatocarcinogenic regimen (chemoprevention group); and group 5 rats were subjected to the two-phase hepatocarcinogenic regimen, and then, the animals were injected intraperitoneally with S. inermis extract for 4 weeks (treatment group). The activities of serum liver enzymes and levels of total bilirubin, conjugated bilirubin, α-fetoprotein, vascular endothelial growth factor (VEGF) and soluble intercellular adhesion molecule-1 (sICAM-1) in serum were decreased in chemopreventive and treated rats compared with DEN/PB-administered rats. Interestingly, the serum levels of total protein and albumin were normalized in chemopreventive and treated rats. Moreover, the majority of chemopreventive and treated rats showed an almost normal histological pattern of liver. In conclusion, S. inermis extract possessed chemopreventive and therapeutic activities against hepatocarcinogenesis in rats partially through the inhibition of VEGF and sICAM-1.

Keywords: Salsola inermis extract, hepatocarcinogenesis, α–fetoprotein, VEGF, sICAM-1

Procedia PDF Downloads 366

Authors: Keshari Shrestha, Philip Vatterott

Abstract:

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal drug-related syndrome. DRESS classically presents with a diffuse maculopapular rash, fevers, and eosinophilia more than three weeks after drug exposure. DRESS can present with multi-organ involvement, with liver damage being the most common and severe. Pulmonary involvement is a less common manifestation and is associated with poor clinical outcomes. Chest imaging is often nonspecific, and symptoms can range from mild cough to acute respiratory distress syndrome (ARDS) . This is a case of a 49-year-old female with a history of recent clostridium difficile colitis status post treatment with oral vancomycin who presented with rash, acute liver and kidney failure, as well as diffuse nodular alveolar lung opacities concerning for DRESS syndrome with multi-organ involvement. Clinical Course: This patient initially presented to an outside hospital with clostridium difficile colitis, acute liver injury, and acute kidney injury. She developed a desquamating maculopapular rash in the setting of recent oral vancomycin, meloxicam, and furosemide initiation. She was hospitalized on two additional occasions with worsening altered mental status, liver injury, and acute kidney injury and was initiated on intermittent hemodialysis. Notably, she was found to have systemic eosinophilia (4100 cells/microliter) several weeks prior. She was transferred to this institution for further management where she was found to have encephalopathy, jaundice, lower extremity edema, and diffuse bilateral rhonchorous breath sounds on pulmonary examination. The patient was started on methylprednisolone for suspected DRESS syndrome. She underwent an evaluation for alternative causes of her organ failure. Her workup included a negative infectious, autoimmune, metabolic, toxic, and malignant work-up. Abdominal computed tomography (CT) and ultrasound were remarkable for evidence of hepatic steatosis and possible cirrhotic morphology. Additionally, a chest CT demonstrated diffuse and symmetric nodular alveolar lung opacities with peripheral sparing not consistent with acute respiratory distress syndrome or edema. Ultimately, her condition continued to decline, and she required intubation on several occasions. On hospital day 25 she succumbed to distributive shock in the setting of probable sepsis and multi-organ failure. Discussion: DRESS syndrome occurs in 1 in 1,000 to 10,000 patients with a mortality rate of around 10%. Anti-convulsant, anti-bacterial, anti-viral, and sulfonamide drugs are the most common drugs implicated in the development of DRESS syndrome; however, the list of offending agents is extensive . The diagnosis of DRESS syndrome is made after excluding other causes of disease such as infectious and autoimmune etiologies. The RegiSCAR scoring system is used to diagnose DRESS syndrome with 2-3 points indicating possible disease, 4-5 probable disease, and >5 definite disease. This patient scored a 7 on the RegiSCAR scale for eosinophilia, rash, organ involvement, and exclusion of other causes (infectious and autoimmune). While the pharmacologic trigger in this case is unknown, it is speculated to be caused by vancomycin, meloxicam, or furosemide due to the favorable timeline of initiation. Despite aggressive treatment, DRESS syndrome can often be fatal. Because of this, early diagnosis and treatment of patients with suspected DRESS syndrome is imperative.

Keywords: drug reaction with eosinophilia and systemic symptoms, multi-organ failure, pulmonary involvement, renal failure

Procedia PDF Downloads 167

Authors: Sulaiman Rabiu, Muazu Gusau Abubakar, Jafar Usman Zakari

Abstract:

The consumption of meat is of great importance as it provides a good source of proteins and significant amount of essential trace element to the body. However, contamination of meat and meat products with heavy metals is becoming a serious threat to food safety and public health. Therefore, the present study is aimed to evaluate the concentration of some heavy metals in muscles and entrails of free-ranged cattle, sheep and goats. A total of sixty (60) fresh samples of muscles, liver, kidney, small intestines and stomach of free ranged cattle, sheep and goats were collected from abattoirs of different goldmine communities of Anka, Bukkuyum, Maru andTalata-Mafara Local Government Areas of Zamfara State, Nigeria. The samples were digested using 10 mL of a mixed 70% high grade concentration of HNO₃ and 65% HCl (4:1 v/v); the mixture was heated until dense fumes disappeared forming a clear transparent solution and diluted to 50 mL with deionized water. Actual concentrations of Cd, Cr, Cu, Co, As, Ni, Mn, Pb and Zn were determined using Microwave Plasma Atomic Emission Spectrophotometer (MP-AES). From the results obtained, goat liver had the highest mean concentration of lead, arsenic, cobalt and manganese (12.43± 0.31, 14.25±0.32, 3.47± 0.86 and 12.68± 0.92 mg/kg respectively) while goat kidney had the highest concentration of copper and zinc (10.08±0.61 and 24.16±1.30 mg/kg respectively). The highest concentrations of cadmium and nickel were recorded in sheep kidney (7.75± 0.65 and 2.08±0.10 mg/kg respectively). Cattle muscles had the highest chromium concentration than all the organs analysed. The target hazard quotients (THQs) for all the metals were below 1.0, but TR which is a risk indices for carcinogenicity indicates an alarming result that requires stringent control to protect public health.Therefore, intensive public health awareness on the risk associated with contamination of heavy metals in meat should be advocated.

Keywords: contamination, goldmine, heavy metals, meat

Procedia PDF Downloads 104

Authors: Jose Carlos Tavares Carvalho, Hady Keita, Giovanna Rocha Santana, Igor Victor Ferreira Dos Santos, Jesus Rafael Rodriguez Amado, Ariadna Lafourcade Prada, Adriana Maciel Ferreira, Helison Oliveira

Abstract:

Summary: As animal model, zebrafish can be a good opportunity to establish a profile of tissue alteration caused by Bothrops alternatus venom and to screen new anti-venom drugs. Objective: To establish tissue biomarkers from zebrafish injected by snake venom and elucidate the use of glucocorticoids in ophidic accidents. Materials and Methods: The Danio rerio fish were randomly divided into four groups: control group, venom group, Dexamethasone1h before venom injected group and Dexamethasone 1 h after venom injected group. The concentration of Bothrops alternatus venom was 0.13 mg/ml and the fish received 20µl/Fish. The Body weight measurement and histological characteristics of gills, kidneys, liver, and intestine were determinate. Results: Physical analysis shows necrosis accompanied by inflammation in animals receiving the Bothrops alternatus venom. Significant difference was observed in the variation of weight between the control group, and the groups received the venom (t student test, p < 0.05). The average histological alterations index of gill, liver, kidney or intestine was statistically higher in animals received the venom (t Student test, p < 0.05). The alterations were lower in the groups that received Dexamethasone 1h before and after venom injected compared to the group that received only the venom. Dexamethasone 1h before venom injected group had minor histopathological alterations. Conclusion: The organs of zebrafish may be a tissue biomarker of alterations from Bothrops alternatus venom and dexamethasone reduced the damage caused by this venom in the organs studied, which may suggest the use of zebrafish as animal model for research related to screening new drug against snake venom.

Keywords: zebrafish, snake venom, biomarker, drugs

Procedia PDF Downloads 324

Authors: C. Mayuren, C. K. Paul Wang, K. Purushotham, C. Dinesh Kumar

Abstract:

Diabetes Mellitus (DM) is one of the most common non-communicable diseases globally. Although significant advances have led to better understanding of the condition and the development of effective therapies and preventive strategies, the pathway to cure remains elusive and DM prevails as a serious medical challenge in the 21st century. Oxidative stress has been suggested to contribute to the progression and pathophysiological conditions of diabetes. Madecassoside (MA) a major pentacyclic triterpenoid, has been demonstrated to possess various biological activities. However, no attempt has been made to study the antioxidant activity in diabetic rats. Therefore, the present study is aimed to evaluate the antioxidant effect of MA on streptozotocin-nicotinamide induced type-2 diabetes in Sprague-Dawley rats. The study protocol was approved by the institutional ethical committee prior to the conduct of research. Adult male Sprague-Dawley rats weighing 250-300 g were used in the study. The animals were rendered diabetic with a single intraperitoneal dose of streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg). The diabetic animals after a stabilisation period of 14 days received various treatments (Madecassoside 50 mg/kg; Glimepiride 2.5 mg/kg) suspended in 0.5% carboxymethyl cellulose orally, for a period of 28 days. The animals fasted overnight after the last treatment were sacrificed and the pancreas, liver and kidneys were isolated. The weighted quantity of the samples of various treatments were homogenised in ice-cold condition and were subjected to lipid peroxidation, catalase and superoxide dismutase assay. The data’s obtained were subjected to statistical analysis. Diabetic rats showed significant increase in lipid peroxidation and decrease in enzymatic antioxidant levels. All the treated groups had significantly higher SOD, CAT and reduced LPO activity in the pancreas, liver and kidney. Results suggest madecassoside to have potential antioxidant effect against the diabetic model. However further investigations are necessary to study the mechanism at the cellular level.

Keywords: antioxidant, diabetes, madecassoside, nicotinamide, streptozotocin

Procedia PDF Downloads 376

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

Abstract:

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

Keywords: ALA, cadmium, histopathology, NAC

Procedia PDF Downloads 330

Authors: Getachew Belay Kassahun

Abstract:

Background: Aspartate aminotransferase to Platelet Ratio Index (APRI) currently becomes a biomarker for screening liver fibrosis since liver biopsy procedure is invasive and variation in pathological interpretation. Clinical Laboratory Standard Institute recommends establishing age, sex and environment specific reference interval for biomarkers in a homogenous population. The current study was aimed to derive community based reference interval of APRI aged between 12 and 60 years old in Mekelle city Tigrai, Northern Ethiopia. Method: Six hundred eighty eight study participants were collected from three districts in Mekelle city. The 3 districts were selected through random sampling technique and sample size to kebelles (small administration) were distributed proportional to household number in each district. Lottery method was used at household level if more than 2 study participants to each age partition were found. A community based cross sectional in a total of 534 study participants, 264 male and 270 females, were included in the final laboratory and data analysis but around 154 study participants were excluded through exclusion criteria. Aspartate aminotransferase was analyzed through Biosystem chemistry analyzer and Sysmix machine was used to analyze platelet. Man Whitney U test non parametric stastical tool was used to appreciate stastical difference among gender after excluding the outliers through Box and Whisker. Result: The study appreciated stastical difference among gender for APRI reference interval. The combined, male and female reference interval in the current study was 0.098-0.390, 0.133-0.428 and 0.090-0.319 respectively. The upper and lower reference interval of males was higher than females in all age partition and there was no stastical difference (p-value (<0.05)) between age partition. Conclusion: The current study showed using sex specific reference interval is significant to APRI biomarker in clinical practice for result interpretation.

Keywords: reference interval, aspartate aminotransferase to platelet ratio Index, Ethiopia, tigray

Procedia PDF Downloads 110

Authors: Mustafa Metin Donma, Orkide Donma

Abstract:

Childhood obesity is an important clinical problem because it may lead to chronic diseases during the adulthood period of the individual. Obesity is a metabolic disease associated with low-grade inflammation. The liver occurs at the center of metabolic pathways. Adropin, fibroblast growth factor-21 (FGF-21), and fetuin-A are hepatokines. Due to the immense participation of the liver in glucose metabolism, these liver-derived factors may be associated with insulin resistance (IR), which is a phenomenon discussed within the scope of obesity problems. The aim of this study is to determine the concentrations of adropin, FGF-21, and fetuin-A in childhood obesity, to point out possible differences between the obesity groups, and to investigate possible associations among these three hepatokines in obese and morbidly obese children. A total of one hundred and thirty-two children were included in the study. Two obese groups were constituted. The groups were matched in terms of mean ± SD values of ages. Body mass index values of obese and morbidly obese groups were 25.0 ± 3.5 kg/m² and 29.8 ± 5.7 kg/m², respectively. Anthropometric measurements including waist circumference, hip circumference, head circumference, and neck circumference were recorded. Informed consent forms were taken from the parents of the participants. The ethics committee of the institution approved the study protocol. Blood samples were obtained after overnight fasting. Routine biochemical tests, including glucose- and lipid-related parameters, were performed. Concentrations of the hepatokines (adropin, FGF-21, fetuin A) were determined by enzyme-linked immunosorbent assay. Insulin resistance indices such as homeostasis model assessment for IR (HOMA-IR), alanine transaminase-to aspartate transaminase ratio (ALT/AST), diagnostic obesity notation model assessment laboratory index, diagnostic obesity notation model assessment metabolic syndrome index as well as obesity indices such as diagnostic obesity notation model assessment-II index, and fat mass index were calculated using the previously derived formulas. Statistical evaluation of the study data as well as findings of the study was performed by SPSS for Windows. Statistical difference was accepted significant when p is smaller than 0.05. Statistically significant differences were found for insulin, triglyceride, high-density lipoprotein cholesterol levels of the groups. A significant increase was observed for FGF-21 concentrations in the morbidly obese group. Higher adropin and fetuin-A concentrations were observed in the same group in comparison with the values detected in the obese group (p > 0.05). There was no statistically significant difference between the ALT/AST values of the groups. In all of the remaining IR and obesity indices, significantly increased values were calculated for morbidly obese children. Significant correlations were detected between HOMA-IR and each of the hepatokines. The highest one was the association with fetuin-A (r=0.373, p=0.001). In conclusion, increased levels observed in adropin, FGF-21, and fetuin-A have shown that these hepatokines possess increasing potential going from obese to morbid obese state. Out of the correlations found with the IR index, the most affected hepatokine was fetuin-A, the parameter possibly used as the indicator of the advanced obesity stage.

Keywords: adropin, fetuin A, fibroblast growth factor-21, insulin resistance, pediatric obesity

Procedia PDF Downloads 174

Authors: Bassma A. Abdel Haleem, Ehab K. Emam, George E. Yacoub, Ashraf M. Salem

Abstract:

Background: Obesity is an increasingly common problem in childhood. Childhood obesity is considered the main risk factor for the development of metabolic syndrome (MetS) (diabetes type 2, dyslipidemia, and hypertension). Recent studies estimated that among children with obesity 30-60% will develop MetS. Visceral fat thickness is a valuable predictor of the development of MetS. Computed tomography and dual-energy X-ray absorptiometry are the main techniques to assess visceral fat. However, they carry the risk of radiation exposure and are expensive procedures. Consequently, they are seldom used in the assessment of visceral fat in children. Some studies explored the potential of ultrasound as a substitute to assess visceral fat in the elderly and found promising results. Given the vulnerability of children to radiation exposure, we sought to evaluate ultrasound as a safer and more cost-efficient alternative for measuring visceral fat in obese children. Additionally, we assessed the correlation between visceral fat and obesity indicators such as insulin resistance. Methods: A cross-sectional study was conducted on 46 children with obesity (aged 6–16 years). Their visceral fat was evaluated by ultrasound. Subcutaneous fat thickness (SFT), i.e., the measurement from the skin-fat interface to the linea alba, and visceral fat thickness (VFT), i.e., the thickness from the linea alba to the aorta, were measured and correlated with anthropometric measures, fasting lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR) and liver enzymes (ALT). Results: VFT assessed via ultrasound was found to strongly correlate with the BMI, HOMA-IR with AUC for VFT as a predictor of insulin resistance of 0.858 and cut off point of >2.98. VFT also correlates positively with serum triglycerides and serum ALT. VFT correlates negatively with HDL. Conclusions: Ultrasound, a safe and cost-efficient technique, could be a useful tool for measuring the abdominal fat thickness in children with obesity. Ultrasound-measured VFT could be an appropriate prognostic factor for insulin resistance, hypertriglyceridemia, and elevated liver enzymes in obese children.

Keywords: metabolic syndrome, pediatric obesity, sonography, visceral fat

Procedia PDF Downloads 118

Authors: Uliana N. Tumanova, Viacheslav M. Lyapin, Vladimir G. Bychenko, Alexandr I. Shchegolev, Gennady T. Sukhikh

Abstract:

It is well known that the gas formed as a result of postmortem decomposition of tissues can be detected already 24-48 hours after death. In addition, the conditions of keeping and storage of the corpse (temperature and humidity of the environment) significantly determine the rate of occurrence and development of posthumous changes. The presence of sepsis is accompanied by faster postmortem decomposition and decay of the organs and tissues of the body. The presence of gas in the vessels and cavities can be revealed fully at postmortem CT. Radiologists must certainly report on the detection of intraorganic or intravascular gas, wich was detected at postmortem CT, to forensic experts or pathologists before the autopsy. This gas can not be detected during autopsy, but it can be very important for establishing a diagnosis. To explore the possibility of postmortem CT for the evaluation of gas accumulations in the newborns' vessels, who died from congenital sepsis. Researched of 44 newborns bodies (25 male and 19 female sex, at the age from 6 hours to 27 days) after 6 - 12 hours of death. The bodies were stored in the refrigerator at a temperature of +4°C in the supine position. Grouped 12 bodies of newborns that died from congenital sepsis. The control group consisted of 32 bodies of newborns that died without signs of sepsis. Postmortem CT examination was performed at the GEMINI TF TOF16 device, before the autopsy. The localizations of gas accumulations in the vessels were determined on the CT tomograms. The sepsis diagnosis was on the basis of clinical and laboratory data and autopsy results. Gases in the vessels were detected in 33.3% of cases in the group with sepsis, and in the control group - in 34.4%. A group with sepsis most often the gas localized in the heart and liver vessels - 50% each, of observations number with the detected gas in the vessels. In the heart cavities, aorta and mesenteric vessels - 25% each. In control most often gas was detected in the liver (63.6%) and abdominal cavity (54.5%) vessels. In 45.5% the gas localized in the cavities, and in 36.4% in the vessels of the heart. In the cerebral vessels and in the aorta gas was detected in 27.3% and 9.1%, respectively. Postmortem CT has high diagnostic capabilities to detect free gas in vessels. Postmortem changes in newborns that died from sepsis do not affect intravascular gas production within 6-12 hours. Radiation methods should be used as a supplement to the autopsy, including as a kind of ‘guide’, with the indication to the forensic medical expert of certain changes identified during CT studies, for better definition of pathological processes during the autopsy. Postmortem CT can be recommend as a first stage of autopsy.

Keywords: congenital sepsis, gas, newborn, postmortem CT

Procedia PDF Downloads 141

Authors: Diego R. Boiarski, Camila M. Toigo, Thais M. Sobjak, Andrey F. P. Santos, Silvia Romao, Ana T. B. Guimaraes

Abstract:

Anthropogenic activities promote changes in the community’s structures and decrease the species abundance of amphibians. Biological communities of fluvial systems are assemblies of organisms that have adapted to regional conditions, including the physical environment and food resources, and are further refined through interactions with other species. The aim of this study was to assess neurotoxic alterations and in the antioxidant system on tadpoles of Lithobates catesbeianus exposed to waters from Cascavel River, in the south of Brazil. A total of 420 L of water was collected from the Cascavel River, 140 L from each of the three different locations: Site 1 – headwater; Site 2 – stretch of the stream that runs through an urbanized area; Site 3 – a stretch from the rural area. Twelve tadpoles were acclimated in each aquarium (100 L of water) for seven days. The water from each aquarium was replaced with the ones sampled from the river, except the one from the control aquarium. After seven days, a portion of the liver was removed and conditioned for ChE, SOD, CAT and LPO analysis; other part of the tissue was conditioned for histological analysis. The statistical analysis performed was one-way ANOVA, followed by post-hoc Tukey-HSD test, and the multivariate principal components analysis. It was not observed any neurotoxic effect, but a slight increase in SOD activity and elevation of CAT activity in both urban and rural environment. A decrease in LPO reaction was detected, mainly among the tadpoles exposed to the waters from the rural area. The results of the present study demonstrate the alteration of the antioxidant system, as well as liver histopathologies in tadpoles exposed mainly to waters collected in urban and rural environments. These alterations may cause the reduction in the velocity of the metamorphosis process from the tadpoles. Further, were observed histological alterations, highlighting necrotic areas mainly among the animals exposed to urban waters. Those damages can lead to metabolic dysfunction, interfering with survival capacity, diminishing not only individual fitness but for the whole population. In the interpretation synthesis of all biomarkers, the cellular damage gradient is perceptible, characterized by the variables related to the antioxidant system, due to the flow direction of the stream. This result is indicative that along the course of the creek occurs dumping of organic material, which promoted an acute response upon tadpoles of L. catesbeianus. and it was also observed the difference in tissue damage between the experimental groups and the control group, the latter presenting histological alterations, but to a lesser degree than the animals exposed to the waters of the Cascavel river. These damages, caused by reactive oxygen species possibly resulting from the contamination by organic compounds, can lead the animals to a series of metabolic dysfunctions, interfering with its metamorphosis capacity. Interruption of metamorphosis may affect survival, which may impair its growth, development and reproduction, diminishing not only the fitness of each individual but in a long-term, to the entire population.

Keywords: American bullfrog, histopathology, oxidative stress, urban creeks pollution

Procedia PDF Downloads 184

Authors: Zaw Z Aung

Abstract:

Background: High-risk groups for hepatitis B infection (HBV) are people who injected drugs (PWID), men who have sex with men (MSM), people living with HIV (PLHIV) and persons with hepatitis C (HCV), etc. HBV/HCV coinfected patients are at increased risk of cirrhosis, hepatic decompensation and hepatocellular carcinoma. To the best of author’s knowledge, there is currently no data for hepatitis B vaccine utilization in HCV positive patients and their antibody response. Methodology: From February 2018 to May 2018, consented participants at or above 18 years who came to the clinic in Mandalay were tested with the anti-HCV rapid test. Those who tested HCV positive (n=168) were further tested with hepatitis B profile and asked about their previous hepatitis B vaccination history and risk factors. Results: Out of 168 HCV positive participants, three were excluded for active HBV infections. The remaining 165 were categorized into previously vaccinated 64% (n=106) and unvaccinated 36% (n=59) There were three characteristics groups- PWID monoinfected (n=77), General Population (GP) monoinfected (n=22) and HIV/HCV coinfected participants (n=66). Unvaccinated participants were highest in HIV/HCV, with 68%(n=45) followed by GP (23%, n=5) and PWID (12%, n=9). Among previously vaccinated participants, the highest percentage was PWID (88%, n=68), the second highest was GP (77%, n=17) and lowest in HIV/HCV patients (32%, n=21). 63 participants completed third doses of vaccination (PWID=36, GP=13, HIV/HCV=14). 53% of participants who completed 3 dose of hepatitis B were non-responders (n=34): HIV/HCV (86%, n=12), PWID (44%, n=16), and GP (46%, n=6) Conclusion: Even in the presence of effective and safe hepatitis B vaccine, uptake is low among high risk groups especially PLHIV that needs to be improved. Integration or collaboration of hepatitis B vaccination program, HIV/AIDS and hepatitis C treatment centers is desirable. About half of vaccinated participants were non-responders so that optimal doses, schedule and follow-up testing need to be addressed carefully for those groups.

Keywords: Hepatitis B vaccine, Hepatitis C, HIV, Myanmar

Procedia PDF Downloads 141

Authors: Fei Ye, Åsa Barrefelt, Manuchehr Abedi-Valugerdi, Khalid M. Abu-Salah, Salman A. Alrokayan, Mamoun Muhammed, Moustapha Hassan

Abstract:

With appropriate encapsulation in functional nanoparticles drugs are more stable in physiological environment and the kinetics of the drug can be more carefully controlled and monitored. Furthermore, targeted drug delivery can be developed to improve chemotherapy in cancer treatment, not only by enhancing intracellular uptake by target cells but also by reducing the adverse effects in non-target organs. Inorganic imaging agents, delivered together with anti-cancer drugs, enhance the local imaging contrast and provide precise diagnosis as well as evaluation of therapy efficacy. We have developed biodegradable polymeric vesicles as a nanocarrier system for multimodal bio-imaging and anticancer drug delivery. The poly (lactic-co-glycolic acid) PLGA) vesicles were fabricated by encapsulating inorganic imaging agents of superparamagnetic iron oxide nanoparticles (SPION), manganese-doped zinc sulfide (MN:ZnS) quantum dots (QDs) and the anticancer drug busulfan into PLGA nanoparticles via an emulsion-evaporation method. T2-weighted magnetic resonance imaging (MRI) of PLGA-SPION-Mn:ZnS phantoms exhibited enhanced negative contrast with r2 relaxivity of approximately 523 s-1 mM-1 Fe. Murine macrophage (J774A) cellular uptake of PLGA vesicles started fluorescence imaging at 2 h and reached maximum intensity at 24 h incubation. The drug delivery ability PLGA vesicles was demonstrated in vitro by release of busulfan. PLGA vesicles degradation was studied in vitro, showing that approximately 32% was degraded into lactic and glycolic acid over a period of 5 weeks. The biodistribution of PLGA vesicles was investigated in vivo by MRI in a rat model. Change of contrast in the liver could be visualized by MRI after 7 min and maximal signal loss detected after 4 h post-injection of PLGA vesicles. Histological studies showed that the presence of PLGA vesicles in organs was shifted from the lungs to the liver and spleen over time.

Keywords: biodegradable polymers, multifunctional nanoparticles, quantum dots, anticancer drugs

Procedia PDF Downloads 468

Authors: Jeffey George, Varghese Thomas

Abstract:

Background and Objectives: PHG is an important source of gastrointestinal bleeding in patients with portal hypertension. Aim: To assess the progression to severe portal hypertensive gastropathy(PHG) in patients with cirrhosis who were treated with maximum tolerated dose of propranalol, after variceal eradication to grade II or below. Methods: Cirrhotic patients(child A and B) presenting with upper gastrointestinal bleeding with endoscopic findings of mild or no PHG were followed up over 6 months after variceal eradication to assess the progression to severe PHG. Included patients were randomised to either maximum tolerated doses of propranalol (group A) or to no treatment (group B). Primary end point of the study were the development of gastrointestinal bleed, evidence of hepatic decompensation and death. Progression to severe PHG were compared between the two groups. Results: 56 patients (49 males) were enrolled (group A = 28, group B = 28). 8 patients were excluded from final analysis (gi bleed=5, encephalopathy=2,HCC=1 including 4 deaths).3 patients were lost to follow-up, and 1 developed intolerance to propranalol. Mean dose of propranalol used was 60 mg per day. Progression to severe PHG in the fundus over 6 months was 23.8% in group A versus 15.8 % in group B (p = 0.52). Severe PHG was noted in body in 14.3% in group A versus 21.1% in group B (p = 0.57). 23.8 % in group A had progression to severe PHG compared with 15.8 % in group B (p =0.52). There was no statistically significant difference in the progression of PHG between the two groups(p=0.43). Conclusion: In this short term study propranalol was found not to prevent the progression to severe portal hypertensive gastropathy in cirrhotic patients who had undergone endotherapy for esophageal varices.

Keywords: propranalol, portal hypertensive gastropathy, cirrhotic patients, gastroenterology

Procedia PDF Downloads 342

Authors: Thaer Khaleel Swaid, Maryam Al Ahmad, Ishtiaq Ahmad

Abstract:

47-year-old female, known to have a liver cyst and hemangiomas, presented to the gastroenterology clinic for chronic moderate postprandial epigastric pain, which is aggravated by food, leaning forward and relieved on lying flat. The pain was associated with nausea, vomiting, heartburn and excessive burping. She opened her bowel daily, having well-formed stools without blood or mucus. The patient denied NSAID intake, smoking or alcohol. On physical examination during the episode of pain abdomen revealed a soft, lax abdomen and mild tenderness in the epigastric region without organomegaly. Bowel sounds were audible. Her routine hematological and biochemical parameters were within normal, including CBC, Celiac serology, Lipase, Metabolic profile and H pylori stool antigen. The patient underwent an Ultrasound of the abdomen which showed multiple liver cysts, hemangioma, normal GB and biliary tree. Based on the clinical picture and to narrow our differential diagnosis, an ultrasound Doppler for the abdomen was ordered, and it showed celiac artery peak systolic velocity in expiration is 270cm/s, suggestive of median arcuate ligament syndrome. She Had computerized tomography abdomen done and showed a Narrowing of the celiac artery at the origin, likely secondary to low insertion of the median arcuate ligament. Furthermore, Gastroscopy and, later on colonoscopy were done, which was unremarkable. A laparoscopic decompression of the celiac trunk was indicated, for which the patient was referred to vascular surgery. This case confirms that Median Arcuate Ligament syndrome is an unusual diagnosis and is always challenging. Usually, patients undergo extensive workups before a final diagnosis is achieved. Our case highlights the challenge of diagnosing MALS since this entity is rare. It is a good choice to perform abdominal ultrasound with Doppler imaging on a patient with symptoms such as postprandial angina.

Keywords: Unveiling the Mystery, MALS, rare entity, Rare vascular phenomenon

Procedia PDF Downloads 9

Authors: Cangir Uyarlar, Ismail Bayram, Ibrahim Sadi Cetingul, Mustafa Kabu, Eyup Eren Gultepe

Abstract:

This study was conducted to determine the effects of organic chromium and organic chromium+propylene glycol on milk yield and some blood parameters related with liver fatty acid metabolism in early lactation dairy cows. Thirty multiparous Holstein dairy cows were used as study material. Cows assigned to three groups as control (C), chromium (Cr) and chromium+propylene glycol (CP). Live weight, parity and body condition score were used as covariates for statistical analyses. The study began at calving and finished at 3 weeks after calving. All cows were consumed same diet. Organic chromium and organic chromium+propylene glycol were orally administrated to cows in treatment groups shortly after the morning milking. Blood samples were collected from all cows on 0 (calving), 3rd, 6th, 9th, 12th, 15th, 18th, 21th days after calving. Then, samples were analyzed for BHBA (Betahydroxybutiric acids), NEFA (Non Esterified Fatty Acids), urea, total protein (TP) and glucose concentrations. Weekly milk yields were calculated from daily milk data on farm. Organic chromium treatment had no significant differences on serum biochemical parameters and milk yields. However, administration of organic chromium and propylene glycol combination decreased serum urea and total protein concentration, helped to protection from subclinical metabolic diseases via decreasing serum NEFA and BHBA concentrations. Also, this combination decreased serum glucose levels of cows. Neither only chromium nor chromium and propylene glycol combination did not affect milk yield throughout the study. These findings were suggested that orally administrations of chromium and propylene glycol combination improved liver glucose and fatty acid metabolism, decreased serum parameters which are representing subclinical diseases in early lactation dairy cows.

Keywords: chromium, early lactation dairy cows, propylene glycol, milk yield

Procedia PDF Downloads 488

Authors: Azza A. Ali, Doaa M. Abd El-Latif, Amany M. Gad, Yasser M. A. Elnahas, Karema Abu-Elfotuh

Abstract:

Background: Exposure to Aluminium (Al) has been increased recently. It is found in food products, food additives, drinking water, cosmetics and medicines. Chronic consumption of Al causes oxidative stress and has been implicated in several chronic disorders. Liver is considered as the major site for detoxification while kidney is involved in the elimination of toxic substances and is a target organ of metal toxicity. Social isolation (SI) or protein malnutrition (PM) also causes oxidative stress and has negative impact on Al-induced nephrotoxicity as well as hepatotoxicity. Coenzyme Q10 (CoQ10) is a powerful intracellular antioxidant with mitochondrial membrane stabilizing ability while wheat grass is a natural product with antioxidant, anti-inflammatory and different protective activities, cocoa is also potent antioxidants and can protect against many diseases. They provide different degrees of protection from the impact of oxidative stress. Objective: To study the impact of social isolation together with Protein malnutrition on nephro- and hepato-toxicity induced by chronic Al exposure in rats as well as to investigate the postulated protection using a combination of Co Q10, wheat grass and cocoa. Methods: Eight groups of rats were used; four served as protected groups and four as un-protected. Each of them received daily for five weeks AlCl3 (70 mg/kg, IP) for Al-toxicity model groups except one group served as control. Al-toxicity model groups were divided to Al-toxicity alone, SI- associated PM (10% casein diet) and Al- associated SI&PM groups. Protection was induced by oral co-administration of CoQ10 (200mg/kg), wheat grass (100mg/kg) and cocoa powder (24mg/kg) combination together with Al. Biochemical changes in total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) were measured in serum of all groups. Specimens of kidney and liver were used for assessment of oxidative parameters (MDA, SOD, TAC, NO), inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3) and DNA fragmentation in addition to evaluation of histopathological changes. Results: SI together with PM severely enhanced nephro- and hepato-toxicity induced by chronic Al exposure. Co Q10, wheat grass and cocoa combination showed clear protection against hazards of Al exposure either alone or when associated with SI&PM. Their protection were indicated by the significant decrease in Al-induced elevations in total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels as well as ALT, AST, ALP, LDH. Liver and kidney of the treated groups also showed significant decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation, together with significant increase in total proteins, SOD and TAC. Biochemical results were confirmed by the histopathological examinations. Conclusion: SI together with PM represents a risk factor in enhancing nephro- and hepato-toxicity induced by Al in rats. CoQ10, wheat grass and cocoa combination provide clear protection against nephro- and hepatotoxicity as well as the consequent degenerations induced by chronic Al-exposure even when associated with the risk of SI together with PM.

Keywords: aluminum, nephrotoxicity, hepatotoxicity, isolation and protein malnutrition, coenzyme Q10, wheatgrass, cocoa, nutrients combinations

Procedia PDF Downloads 245

Authors: Majid Afkhami, Maryam Ehsanpour, Reza Khoshnood, Zahra Khoshnood, Rastin Afkhami

Abstract:

Marine pollution is a global environmental problem. Different human activities on land, in the water and in the air contribute to the contamination of seawater, sediments and organisms with potentially toxic substances. Contaminants can be natural substances or artificially produced compounds. After discharge into the sea, contaminants can stay in the water in dissolved form or they can be removed from the water column through sedimentation to the bottom sediments. Histopathological alterations can be used as indicators for the effects of various anthropogenic pollutants on organisms and are a reflection of the overall health of the entire population in the ecosystem. These histo pathological biomarkers are closely related to other biomarkers of stress since many pollutants have to undergo metabolic activation in order to be able to provoke cellular change in the affected organism. In order to make evaluation of the effects of oil pollution, some heavy metals bioaccumulation and explore their histopathological effects on hepatocytes of Oriental sole (Euryglossa orientalis) and Deep flounder (Psettodes erumei), fishes caught from two areas of north coast of the Persian Gulf: Bandar Abbass and Bandar Lengeh. Concentrations of Ni and V in liver of both species in two sampling regions were in following order: Bandar abbass Bandar lengeh; also between two species, these quantities were higher in P. erumei than E. orientalis in both sampling regions. Histopathology of the liver shows some cellular alterations including: degeneration, necrosis and tissue disruption, and histopathological effects were severe in P. erumei than E. orientalis. Results showed that Bandar Abbass region was more polluted than Bandar Lengeh, and because Ni and V were oil pollution indicators, and two flat fishes were benthic, they can receive considerable amount of oil pollution through their biological activities like feeding. Also higher amounts of heavy metal concentrations and major histopathological effects in E. orientalis showed strong relationship between benthic habitat of the fish and amounts of received pollutants from water and sediments, because E. orientalis is more related to the bottom than P. erumei.

Keywords: heavy metals, flatfishes, Persian Gulf, oil pollution

Procedia PDF Downloads 340

Authors: Gulnaz Khan, Meha F. Aftab, Munazza Murtaza, Rizwana S. Waraich

Abstract:

Advanced glycation end products (AGEs) precursor and its abnormal accumulation cause damage to various tissues and organs. AGEs have pathogenic implication in several diseases including diabetes. Existing AGEs inhibitors are not in clinical use, and there is a need for development of novel inhibitors. The present investigation aimed at identifying the novel AGEs inhibitors and assessing their mechanism of action for treating insulin resistance in mice model of diabetes. Novel derivatives of benzylidene of indan-1,3-dione were synthesized. The compounds were selected to study their action mechanism in improving insulin resistance, in vitro, in human hepatocytes and murine adipocytes and then, in vivo, in mice genetic model of diabetes (db/db). Mice were treated with novel derivatives of benzylidene of indane 1,3-dione. AGEs mediated ROS production was measured by dihydroethidium fluorescence assay. AGEs level in the serum of treated mice was observed by ELISA. Gene expression of receptor for AGEs (RAGE), PPAR-gamma, TNF-alpha and GLUT-4 was evaluated by RT-PCR. Glucose uptake was measured by fluorescent method. Microscopy was used to analyze glycogen synthesis in muscle. Among several derivatives of benzylidene of indan-1,3-dione, IDD-24, demonstrated highest inhibition of AGESs. IDD-24 significantly reduced AGEs formation and expression of receptor for advanced glycation end products (RAGE) in fat, liver of db/db mice. Suppression of AGEs mediated ROS production was also observed in hepatocytes and fat cell, after treatment with IDD-24. Glycogen synthesis was increased in muscle tissue of mice treated with IDD-24. In adipocytes, IDD-24 prevented AGEs induced reduced glucose uptake. Mice treated with IDD-24 exhibited increased glucose tolerance, serum adiponectin levels and decreased insulin resistance. The result of present study suggested that IDD-24 can be a possible treatment target to address glycotoxins induced insulin resistance.

Keywords: advance glycation end product, hyperglycemia, indan-1, 3-dione, insulin resistance

Procedia PDF Downloads 155

Authors: Adriana Garcia-Gurrola, Carlos Adrian Peña Natividad, Ana Laura Martinez Martinez, Alberto Abraham Escobar Puentes, Estefania Ochoa Ruiz, Aracely Serrano Medina, Abraham Wall Medrano, Simon Yobanny Reyes Lopez

Abstract:

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by elevated blood glucose levels. Quercetin is a natural flavonoid with a hypoglycemic effect, but reported data are inconsistent due mainly to the structural instability and low solubility of quercetin. Nanoencapsulation is a distinct strategy to overcome the intrinsic limitations of quercetin. Therefore, this work aims to develop a quercetin nano-formulation based on biopolymeric starch nanoparticles to enhance the release and hypoglycemic effect of quercetin in T2DM induced mice model. Starch-quercetin nanoparticles were synthesized using high-intensity ultrasonication, and structural and colloidal properties were determined by FTIR and DLS. For in vivo studies, CD1 male mice (n=25) were divided into five groups (n=5). T2DM was induced using a high-fat and high-sugar diet for 32 weeks and streptozotocin injection. Group 1 consisted of healthy mice fed with a normal diet and water ad libitum; Group 2 were diabetic mice treated with saline solution; Group 3 were diabetic mice treated with glibenclamide; Group 4 were diabetic mice treated with empty nanoparticles; and Group 5 was diabetic mice treated with quercetin nanoparticles. Quercetin nanoparticles had a hydrodynamic size of 232 ± 88.45 nm, a PDI of 0.310 ± 0.04 and a zeta potential of -4 ± 0.85 mV. The encapsulation efficiency of nanoparticles was 58 ± 3.33 %. No significant differences (p = > 0.05) were observed in biochemical parameters (lipids, insulin, and peptide C). Groups 3 and 5 showed a similar hypoglycemic effect, but quercetin nanoparticles showed a longer-lasting effect. Histopathological studies reveal that T2DM mice groups showed degenerated and fatty liver tissue; however, a treated group with quercetin nanoparticles showed liver tissue like that of the healthy mice group. These results demonstrate that quercetin nano-formulations based on starch nanoparticles are effective alternatives with hypoglycemic effects.

Keywords: quercetin, diabetes mellitus tipo 2, in vivo study, nanoparticles

Procedia PDF Downloads 27

Authors: Adnan A. Kadi, Nasser S. Al-Shakliah, Haitham Al-Rabiah

Abstract:

Zorifertinib is a novel, potent, oral, a small molecule used to treat non-small cell lung cancer (NSCLC). zorifertinib is an Epidermal Growth Factor Receptor (EGFR) inhibitor and has good blood–brain barrier permeability for (NSCLC) patients with EGFR mutations. zorifertinibis currently at phase II/III clinical trials. The current research reports the characterization and identification of in vitro, in vivo and reactive intermediates of zorifertinib. Prediction of susceptible sites of metabolism and reactivity pathways (cyanide and GSH) of zorifertinib were performed by the Xenosite web predictor tool. In-vitro metabolites of zorifertinib were performed by incubation with rat liver microsomes (RLMs) and isolated perfused rat liver hepatocytes. Extraction of zorifertinib and it's in vitro metabolites from the incubation mixtures were done by protein precipitation. In vivo metabolism was done by giving a single oral dose of zorifertinib(10 mg/Kg) to Sprague Dawely rats in metabolic cages by using oral gavage. Urine was gathered and filtered at specific time intervals (0, 6, 12, 18, 24, 48, 72,96and 120 hr) from zorifertinib dosing. A similar volume of ACN was added to each collected urine sample. Both layers (organic and aqueous) were injected into liquid chromatography ion trap mass spectrometry(LC-IT-MS) to detect vivozorifertinib metabolites. N-methyl piperizine ring and quinazoline group of zorifertinib undergoe metabolism forming iminium and electro deficient conjugated system respectively, which are very reactive toward nucleophilic macromolecules. Incubation of zorifertinib with RLMs in the presence of 1.0 mM KCN and 1.0 Mm glutathione were made to check reactive metabolites as it is often responsible for toxicities associated with this drug. For in vitro metabolites there were nine in vitro phase I metabolites, four in vitro phase II metabolites, eleven reactive metabolites(three cyano adducts, five GSH conjugates metabolites, and three methoxy metabolites of zorifertinib were detected by LC-IT-MS. For in vivo metabolites, there were eight in vivo phase I, tenin vivo phase II metabolitesofzorifertinib were detected by LC-IT-MS. In vitro and in vivo phase I metabolic pathways wereN- demthylation, O-demethylation, hydroxylation, reduction, defluorination, and dechlorination. In vivo phase II metabolic reaction was direct conjugation of zorifertinib with glucuronic acid and sulphate.

Keywords: in vivo metabolites, in vitro metabolites, cyano adducts, GSH conjugate

Procedia PDF Downloads 193

Authors: Gayatri Swarnakar

Abstract:

Paramphistomiasis and fascioliasis diseases have been prevalent due to presence of trematode parasites in the rumen and liver of domestic buffalo (Bubalus bubalis) in Udaipur, India. The trematode parasites such as Paramphistomum cervi, Gastrothylax crumenifer, Cotylophoron cotylophorum, Orthocoelium scoliocoelium, Fasciola hepatica and Fasciola gigantica were collected from infected rumen and liver of the freshly slaughtered buffaloes (Bubalus bubalis) at local zoo abattoir in Udaipur. Live trematodes were washed in normal saline, fixed in 0.2M cacodylate fixative, post fixed in osmium tetraoxide, dehydrated, dried, coated with gold sputter and observed under scanning electronic microscope (SEM). The surface tegument of Paramphistomum cervi was spineless with transverse folds, discontinuous with ridges and grooves. Two types of sensory papillae such as knob like and button shaped were also observed. The oral opening of Cotylophoron cotylophorum was surrounded by wrinkled and ridged tegument which formed concentric elevated rings. Tegument of Cotylophoron cotylophorum in acetabulum region was observed to be rough and bee-comb like structure. Genital sucker of this worm was surrounded by a tyre- shaped elevation of the tegument. Orthocoelium scoliocoelium showed circular and concentric rings of tegumental folds around the oral sucker. Genital pore had knob like papillae with radial tegumental folds. Surface topography of Fasciola gigantica and Fasciola hepatica were found to be rough due to occurrence of different types of spines, three types of sensory papillae, transverse folds and grooves. Oral and ventral suckers were spineless and covered with thick rims of transverse folds. Genital pore showed small scattered spines. Present research work would provide knowledge for ultrastructural characteristics of trematode parasites for chemotherapeutic measures and help us to evolve suitable strategy for the eradication of trematode parasites from the domestic buffalo (Bubalus bubalis).

Keywords: Domestic buffalo, tegument, trematode parasites, ultrastructure

Procedia PDF Downloads 303

Authors: Medan Isaeva, Anna Degtyareva

Abstract:

Context: Biliary atresia is a common reason for liver transplants in children, and the Kasai procedure can potentially be successful in avoiding the need for transplantation. However, it is important to identify factors that influence surgical outcomes in order to optimize treatment and improve patient outcomes. Research aim: The aim of this study was to develop prognostic models to assess the outcomes of the Kasai procedure in children with biliary atresia. Methodology: This retrospective study analyzed data from 166 children with biliary atresia who underwent the Kasai procedure between 2002 and 2021. The effectiveness of the operation was assessed based on specific criteria, including post-operative stool color, jaundice reduction, and bilirubin levels. The study involved a comparative analysis of various parameters, such as gestational age, birth weight, age at operation, physical development, liver and spleen sizes, and laboratory values including bilirubin, ALT, AST, and others, measured pre- and post-operation. Ultrasonographic evaluations were also conducted pre-operation, assessing the hepatobiliary system and related quantitative parameters. The study was carried out by two experienced specialists in pediatric hepatology. Comparative analysis and multifactorial logistic regression were used as the primary statistical methods. Findings: The study identified several statistically significant predictors of a successful Kasai procedure, including the presence of the gallbladder and levels of cholesterol and direct bilirubin post-operation. A detectable gallbladder was associated with a higher probability of surgical success, while elevated post-operative cholesterol and direct bilirubin levels were indicative of a reduced chance of positive outcomes. Theoretical importance: The findings of this study contribute to the optimization of treatment strategies for children with biliary atresia undergoing the Kasai procedure. By identifying early predictive signs of success, clinicians can modify treatment plans and manage patient care more effectively and proactively. Data collection and analysis procedures: Data for this analysis were obtained from the health records of patients who received the Kasai procedure. Comparative analysis and multifactorial logistic regression were employed to analyze the data and identify significant predictors. Question addressed: The study addressed the question of identifying predictive factors for the success of the Kasai procedure in children with biliary atresia. Conclusion: The developed prognostic models serve as valuable tools for early detection of patients who are less likely to benefit from the Kasai procedure. This enables clinicians to modify treatment plans and manage patient care more effectively and proactively. Potential limitations of the study: The study has several limitations. Its retrospective nature may introduce biases and inconsistencies in data collection. Being single centered, the results might not be generalizable to wider populations due to variations in surgical and postoperative practices. Also, other potential influencing factors beyond the clinical, laboratory, and ultrasonographic parameters considered in this study were not explored, which could affect the outcomes of the Kasai operation. Future studies could benefit from including a broader range of factors.

Keywords: biliary atresia, kasai operation, prognostic model, native liver survival

Procedia PDF Downloads 51