Search results for: elevated creatinine clearance level
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 13245

Search results for: elevated creatinine clearance level

13215 An Empirical Investigation of Uncertainty and the Lumpy Investment Channel of Monetary Policy

Authors: Min Fang, Jiaxi Yang

Abstract:

Monetary policy could be less effective at stimulating investment during periods of elevated volatility than during normal times. In this paper, we argue that elevated volatility leads to a decrease in extensive margin investment incentive so that nominal stimulus generates less aggregate investment. To do this, we first empirically document that high volatility weakens firms’ investment responses to monetary stimulus. Such effects depend on the lumpiness nature of the firm-level investment. The findings are that the channel exists for all of the physical investment, innovation investment, and organization investment.

Keywords: investment, irreversibility, volatility, uncertainty, firm heterogeneity, monetary policy

Procedia PDF Downloads 81
13214 Journal Bearing with Controllable Radial Clearance, Design and Analysis

Authors: Majid Rashidi, Shahrbanoo Farkhondeh Biabnavi

Abstract:

The hydrodynamic instability phenomenon in a journal bearing may occur by either a reduction in the load carried by journal bearing, by an increase in the journal speed, by change in the lubricant viscosity, or a combination of these factors. The previous research and development work done to overcome the instability issue of journal bearings, operating in hydrodynamic lubricate regime, can be categorized as follows: A) Actively controlling the bearing sleeve by using piezo actuator, b) Inclusion of strategically located and shaped internal grooves within inner surface of the bearing sleeve, c) Actively controlling the bearing sleeve using an electromagnetic actuator, d)Actively and externally pressurizing the lubricant within a journal bearing set, and e)Incorporating tilting pads within the inner surface of the bearing sleeve that assume different equilibrium angular position in response to changes in the bearing design parameter such as speed and load. This work presents an innovative design concept for a 'smart journal bearing' set to operate in a stable hydrodynamic lubrication regime, despite variations in bearing speed, load, and its lubricant viscosity. The proposed bearing design allows adjusting its radial clearance for an attempt to maintain a stable bearing operation under those conditions that may cause instability for a bearing with a fixed radial clearance. The design concept allows adjusting the radial clearance at small increments in the order of 0.00254 mm. This is achieved by axially moving two symmetric conical rigid cavities that are in close contact with the conically shaped outer shell of a sleeve bearing. The proposed work includes a 3D model of the bearing that depicts the structural interactions of the bearing components. The 3D model is employed to conduct finite element Analyses to simulate the mechanical behavior of the bearing from a structural point of view. The concept of controlling of the radial clearance, as presented in this work, is original and has not been proposed and discuss in previous research. A typical journal bearing was analyzed under a set of design parameters, namely r =1.27 cm (journal radius), c = 0.0254 mm (radial clearance), L=1.27 cm (bearing length), w = 445N (bearing load), μ = 0.028 Pascale (lubricant viscosity). A shaft speed as 3600 r.p.m was considered, and the mass supported by the bearing, m, is set to be 4.38kg. The Summerfield Number associated with the above bearing design parameters turn to be, S=0.3. These combinations resulted in stable bearing operation. Subsequently, the speed was postulated to increase from 3600 r.p.mto 7200 r.p.m; the bearing was found to be unstable under the new increased speed. In order to regain stability, the radial clearance was increased from c = 0.0254 mm to0.0358mm. The change in the radial clearance was shown to bring the bearing back to stable an operating condition.

Keywords: adjustable clearance, bearing, hydrodynamic, instability, journal

Procedia PDF Downloads 263
13213 A Study on Behaviour of Normal Strength Concrete and High Strength Concrete Subjected to Elevated Temperatures

Authors: Butchi Kameswara Rao Chittem, Rooban Kumar

Abstract:

Cement concrete is a complex mixture of different materials. Concrete is believed to have a good fire resistance. Behaviour of concrete depends on its mix proportions and its constituent materials when it is subjected to elevated temperatures. Loss in compressive strength, loss in weight or mass, change in colour and spall of concrete are reported in literature as effects of elevated temperature on concrete. In this paper results are reported on the behaviour of normal strength concrete and high strength concrete subjected to temperatures 200°C, 400°C, 600°C, and 800°C and different cooling regimes viz. air cooling, water quenching. Rebound hammer test was also conducted to study the changes in surface hardness of concrete specimens subjected to elevated temperatures.

Keywords: normal strength concrete, high-strength concrete, temperature, NDT

Procedia PDF Downloads 415
13212 Analysis of Radiation-Induced Liver Disease (RILD) and Evaluation of Relationship between Therapeutic Activity and Liver Clearance Rate with Tc-99m-Mebrofenin in Yttrium-90 Microspheres Treatment

Authors: H. Tanyildizi, M. Abuqebitah, I. Cavdar, M. Demir, L. Kabasakal

Abstract:

Aim: Whole liver radiation has the modest benefit in the treatment of unresectable hepatic metastases but the radiation doses must keep in control. Otherwise, RILD complications may arise. In this study, we aimed to calculate amount of maximum permissible activity (MPA) and critical organ absorbed doses with MIRD methodology, to evaluate tumour doses for treatment response and whole liver doses for RILD and to find optimal liver function test additionally. Materials and Methods: This study includes 29 patients who attended our nuclear medicine department suffering from Y-90 microspheres treatment. 10 mCi Tc-99m MAA was applied to the patients for dosimetry via IV. After the injection, whole body SPECT/CT images were taken in one hour. The minimum therapeutic tumour dose is on the point of being 120 Gy1, the amount of activities were calculated with MIRD methodology considering volumetric tumour/liver rate. A sub-working group was created with 11 patients randomly and liver clearance rate with Tc-99m-Mebrofenin was calculated according to Ekman formalism. Results: The volumetric tumour/liver rates were found between 33-66% (Maksimum Tolarable Dose (MTD) 48-52Gy3) for 4 patients, were found less than 33% (MTD 72Gy3) for 25 patients. According to these results the average amount of activity, mean liver dose and mean tumour dose were found 1793.9±1.46 MBq, 32.86±0.19 Gy, and 138.26±0.40 Gy. RILD was not observed in any patient. In sub-working group, the relationship between Bilirubin, Albumin, INR (which show presence of liver disease and its degree), liver clearance with Tc-99m-Mebrofenin and calculated activity amounts were found r=0.49, r=0.27, r=0.43, r=0.57, respectively. Discussions: The minimum tumour dose was found 120 Gy for positive dose-response relation. If volumetric tumour/liver rate was > 66%, dose 30 Gy; if volumetric tumour/liver rate 33-66%, dose escalation 48 Gy; if volumetric tumour/liver rate < 33%, dose 72 Gy. These dose limitations did not create RILD. Clearance measurement with Mebrofenin was concluded that the best method to determine the liver function. Therefore, liver clearance rate with Tc-99m-Mebrofenin should be considered in calculation of yttrium-90 microspheres dosimetry.

Keywords: clearance, dosimetry, liver, RILD

Procedia PDF Downloads 415
13211 Effects of Aggregate Type and Concrete Age on Compressive Strength After Subjected to Elevated Temperature

Authors: Ahmed M. Seyam, Rita Nemes

Abstract:

In this study, the influence of elevated temperature and concrete age on the compressive strength of concrete produced by normal quartz aggregate, expanded clay, expanded glass, crushed andesite and crushed clay bricks aggregates were investigated. For this purpose, six different mixtures were prepared by 100% replacement of the coarse aggregate. The specimens were cured in water for seven days, then kept in the laboratory for 120 days and 240 days. The concrete specimens were heated in an electric furnace up to 200, 400, 600, 800, and 1000 °C and kept at these temperatures for two hours heating, then for 24 hours cooling. The residual compressive strength of the specimens was measured. The results showed that, the elevated temperature induces a significant decrease in a compressive strength in both normal weight and lightweight aggregate concrete, by comparing the behavior of different mixes, in all cases, the strength of the specimens containing crushed andesite aggregates showed a better performance for compressive strength after exposure to elevated temperatures over 800 °C, while the specimens containing expanded glass showing the least residual strength after subjected to elevated temperature; moreover the age of the concrete in all mixes has also been an effective factor, the behavior of the concrete strength loss by increasing heating temperature was not changed but the strength results showing the better performance and higher compressive strength in both ambient and elevated temperature.

Keywords: elevated temperature, concrete age, compressive strength, expanded clay, expanded glass, crushed andesite, crushed clay bricks

Procedia PDF Downloads 87
13210 Role of Oxidative Stress and Nitric Oxide in the Protective Effects of Simvastatine against Isoniazid-Rifampicin-Induced Hepatotoxicity in Rats

Authors: Mabroka Omar Sherehe

Abstract:

Despite the great efficacy of isoniazid (INH) and rifampicine (RIF) combination in the treatment of tuberculosis, hepatotoxicity is the most common serious complication. The potential protective effect of simvastatin (sim) against combination-induced hepatotoxicity was investigated in the present study. The administration of INH-RIF combination (50mg/kg each for 14 days) resulted in a significant increased activities of serum alanine and aspartate aminotransferases, such effects were further supported by histopathological studies. INH-RIF combination produced a significant increase in liver lipid, decreased SOD and CAT, and a significant depletion of GSH level. Additionally, treatment with INH-RIF combination resulted in a significant increase in liver MPO activity. The lipid-lowering drug, Sim demonstrated in the current study an evident antioxidant action, such effect was mediated via decreasing the elevated MDA, MPO, and restoring liver CAT activity. Additionally, Sim restored liver NO level to near basal value Furthermore, one cannot rule out the lipid-lowering effect of Sim that would probably add to its beneficial hepatoprotective antioxidant activity, where Sim decreased the elevated cholesterol, TGs and LDL cholesterol level and increased the serum HDL cholesterol level.

Keywords: isoniazid, rifampicine, oxidative stress, nitric oxide

Procedia PDF Downloads 593
13209 Effective Apixaban Clearance with Cytosorb Extracorporeal Hemoadsorption

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

Abstract:

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

Keywords: Apixaban, CytoSorb, emergency surgery, Hemoadsorption

Procedia PDF Downloads 122
13208 Renoprotective Effect of Alcoholic Extract of Bacopa monnieri via Inhibition of Advanced Glycation End Products and Oxidative Stress in Stz-Nicotinamide Induced Diabetic Nephropathy

Authors: Lalit Kishore, Randhir Singh

Abstract:

Diabetic nephropathy (DN) is the major cause of morbidity among diabetic patients. In this study, the effect of Bacopa monnieri Linn. (Brahmi, BM), was studied in a Streptozotocin (STZ)-induced experimental rat model of DN. Diabetic nephropathy was induced in Male Wistar rats (body weight- 300± 10 gms) by single intra-peritoneal injection of STZ (45mg/kg, i.p.) after 15 min of Nicotinamide (230 mg/kg) administration. Different doses of alcoholic extract i.e. 100, 200 and 400 mg/kg was given for 45 days by oral gavage after induction of DN. Blood glucose level, serum insulin, glycosylated haemoglobin, renal parameters (serum urea, uric acid, creatinine and BUN) and lipid profile (total cholesterol, triglycerides, HDL, LDL and VLDL levels) were measured. Concentration of thiobarbituric acid reactive species (TBARS) and levels of antioxidant enzymes of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were evaluated in the kidney, liver and pancreas. At the end of treatment period the alcoholic extract of BM reduced the elevated level of blood glucose, serum insulin, renal parameters, lipid levels, TBARS, AGE’s in kidney and significantly increased body weight, HDL and antioxidant enzymes in dose dependent manner as compared to diabetic control animals. These results suggested the BM possesses significant renoprotective activity.

Keywords: AGE's, lipid profile, oxidative stress, renal parameters

Procedia PDF Downloads 291
13207 Treatment of Non-Small Cell Lung Cancer (NSCLC) With Activating Mutations Considering ctDNA Fluctuations

Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.

Abstract:

Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.

Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis

Procedia PDF Downloads 33
13206 Preventive Effect of Zinc on Nickel Hepatotoxicity and Nephrotoxicity in Albino (Wistar) Rats

Authors: Zine Kechrid, Samira Bouhalit

Abstract:

Aim: We studied the effect of intraperitonial zinc treatment on nickel sulphate-induced hepatotoxicity and nephrotoxicity in Wistar strain male albino rats. Materials and Methods: Liver and kidney dysfunction parameters represented by aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), blood glucose, serum total protein, serum urea, serum creatinine, and serum belurebin were estimated. Liver glutathione level, catalase and GPx activities were also determined in liver as indicators of oxidative damage. Result: Nickel treatment led to high serum glucose concentration and produced hepatotoxicity and nephrotoxicity characterized by increasing GPT, GOT and alkaline phosphatase activities, serum total protein, serum urea, serum creatinine and serum belurebin concentrations. In addition, liver glutathione level, catalase and GSH-Px activities diminished due to high lipid peroxidation. The simultaneous administration of zinc with nickel sulphate resulted in a remarkable improvement of the previous parameters compared with rats treated with nickel alone. Conclusion: In conclusion, nickel sulphate led to liver and kidney dysfunctions and hepatic lipid peroxidation in animals, but simultaneous treatment with zinc offers a relative protection against nickel induced hepatotoxicity, nephrotoxicity and lipid peroxidation.

Keywords: nickel, zinc, rats, GOT, GPT, nephrotoxicity, hepatotoxicity

Procedia PDF Downloads 431
13205 Relation of Urinary Microalbumin with Glycosylated Hemoglobin (HbA1c) and Duration of Type 2 Diabetes Mellitus (T2DM) in Selected Male and Female Patients

Authors: Junaid Mahmood Alam, Howarh Humaira Ali, Ishrat Sultana

Abstract:

Long term irregularity in the glycemic state, especially in Type 2 diabetes mellitus (T2DM) patients, depicted by higher levels of HbA1c, is noted to be correlated with the development of microalbuminuria. The aim of the current study is to investigate the association of urinary microalbumin with HbA1c and with duration of diabetes mellitus in selected male and female T2DM patients. This cross-sectional study was carried out in a total of 70 patients, thirty-five each male and females with diagnosed T2DM, within the age group of 35-60 years. Biochemical parameters of urea, creatinine, urinary microalbumin, HbA1c, fasting blood glucose and post- parendial blood glucose were determined by standard methods. Data was statistically examined by student’s t-test and Pearson’s correlation. Results showed that comparison of healthy control subjects with both male and female T2DM patients depicted significantly elevated levels of all parameters in (P < 0.05 to P < 0.001). Comparison of duration of T2DM with the existence of urinary microalbumin was moderately significant (P < 0.05) when duration was less than 4 years, significant (P < 0.01) with duration of 4-6 years and markedly significant (P < 0.001) with duration of more than 6 years. It is concluded that in male and female T2DM patients, duration of DM as well as poor glycemic control, depicted by higher levels of HbA1c is significantly correlated with elevated levels of urinary microalbumin.

Keywords: type 2 diabetes mellitus, glycosylated hemoglobin, urinary microalbumin, T2DM, HbA1c

Procedia PDF Downloads 267
13204 Numerical Study on the Ultimate Load of Offshore Two-Planar Tubular KK-Joints at Fire-Induced Elevated Temperatures

Authors: Hamid Ahmadi, Neda Azari-Dodaran

Abstract:

A total of 270 nonlinear steady-state finite element (FE) analyses were performed on 54 FE models of two-planar circular hollow section (CHS) KK-joints subjected to axial loading at five different temperatures (20 ºC, 200 ºC, 400 ºC, 550 ºC, and 700 ºC). The primary goal was to investigate the effects of temperature and geometrical characteristics on the ultimate strength, modes of failure, and initial stiffness of the KK-joints. Results indicated that on an average basis, the ultimate load of a two-planar tubular KK-joint at 200 ºC, 400 ºC, 550 ºC, and 700 ºC is 90%, 75%, 45%, and 16% of the joint’s ultimate load at ambient temperature, respectively. Outcomes of the parametric study showed that replacing the yield stress at ambient temperature with the corresponding value at elevated temperature to apply the EN 1993-1-8 equations for the calculation of the joint’s ultimate load at elevated temperatures may lead to highly unconservative results that might endanger the safety of the structure. Results of the parametric study were then used to develop a set of design formulas, through nonlinear regression analyses, to calculate the ultimate load of two-planar tubular KK-joints subjected to axial loading at elevated temperatures.

Keywords: ultimate load, two-planar tubular KK-joint, axial loading, elevated temperature, parametric equation

Procedia PDF Downloads 129
13203 Simulation of Uniaxial Ratcheting Behaviors of SA508-3 Steel at Elevated Temperature

Authors: Jun Tian, Yu Yang, Liping Zhang, Qianhua Kan

Abstract:

Experimental results show that SA 508-3 steel exhibits temperature dependent cyclic softening characteristic and obvious ratcheting behaviors, and dynamic strain age was observed at temperature range of 200 ºC to 350 ºC. Based on these observations, a temperature dependent cyclic plastic constitutive model was proposed by introducing the nonlinear cyclic softening and kinematic hardening rules, and the dynamic strain age was also considered into the constitutive model. Comparisons between experiments and simulations were carried out to validate the proposed model at elevated temperature.

Keywords: constitutive model, elevated temperature, ratcheting, SA 508-3

Procedia PDF Downloads 281
13202 Effect of Leaf Essential Oil of Citrus sinensis at Different Harvest Time on Some Liver and Kidney Function Indices of Diabetic Rats

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

Abstract:

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

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

Procedia PDF Downloads 336
13201 Execution of Joinery in Large Scale Projects: Middle East Region as a Case Study

Authors: Arsany Philip Fawzy

Abstract:

This study is going to address the hurdles of project management in the joinery field. It is widely divided into two sections; the first one will shed light on how to execute large-scale projects with a specific focus on the middle east region. It will also raise major obstacles that may face the joinery team from the site clearance and the coordination between the joinery team and the construction team. The second section is going to technically analyze the commercial side of the joinery and how to control the main cost of the project to avoid financial problems. It will also suggest empirical solutions to monitor the cost impact (e.g., Variation of contract quantity and claims).

Keywords: clearance, quality, cost, variation, claim

Procedia PDF Downloads 77
13200 Leuprolide Induced Scleroderma Renal Crisis: A Case Report

Authors: Nirali Sanghavi, Julia Ash, Amy Wasserman

Abstract:

Introduction: To the best of our knowledge, there is only one case report that found an association between leuprolide and scleroderma renal crisis (SRC). Leuprolide has been noted to cause acute renal failure in some patients. Given the close timing of the leuprolide injection and the worsening renal function in our patient, leuprolide likely caused exacerbation of lupus nephritis and SRC. Interestingly, our patient on long-term hydroxychloroquine (HCQ) with normal baseline cardiac function was found to have HCQ cardiomyopathy highlighting the need for close monitoring of HCQ toxicity. We know that some of the risk factors that are involved in HCQ induced cardiomyopathy are older age, females, increased dose and >10 years of HCQ use, and pre-existing cardiac and renal insufficiency. Case presentation: A 34-year-old African American woman with a history of overlap of systemic lupus erythematosus (SLE) and scleroderma features and class III lupus nephritis presented with severe headaches, elevated blood pressure (180/120 mmHg) and worsening creatinine levels (2.07 mg/dL). The headaches started 1 month ago after she started leuprolide injections for fibroids. She was being treated with mycophenolate mofetil 1 gm twice a day, belimumab weekly, HCQ 200mg, and prednisone 5 mg daily. She has been on HCQ since her teenage years. The examination was unremarkable except for proximal interphalangeal joint contractures in the right hand and sclerodactyly of bilateral hands, unchanged from baseline. Laboratory findings include urinalysis, which showed 3+ protein, 1+ blood, 6 red blood cells, and 14 white blood cells ruling out thrombotic microangiopathy. C3 was 32 mg/dL, C4 <5 mg/dL, and +dsDNA increased >1000. She was started on captopril and discharged once creatinine and blood pressure was controlled. She was readmitted with hypertension, hyperkalemia, worsening creatinine, nephrotic range proteinuria, complaints of chest pressure, and shortness of breath with pleuritic chest pain. Physical examination and lab findings were unchanged. She was treated with pulse dose methyl prednisone followed by taper and multiple anti-hypertensive agents, including captopril, for presumed lupus nephritis flare versus SRC. Renal biopsy was consistent with SRC and class IV lupus nephritis and was started on cyclophosphamide. While cardiac biopsy showed borderline myocarditis without necrosis and cytoplasmic vacuolization consistent with HCQ cardiomyopathy, hence HCQ was discontinued. Summary: It highlights a rare association of leuprolide causing exacerbation of lupus nephritis or SRC. Although rare, the current case reinforces the importance of close monitoring for HCQ toxicity in patients with renal insufficiency.

Keywords: leuprolide, lupus nephritis, scleroderma, SLE

Procedia PDF Downloads 68
13199 Optimum Design of Combine Threshing Cylinder for Soybean Harvest

Authors: Choi Duckkyu, Choi Yong, Kang Taegyoung, Jun Hyeonjong, Choi Ilsu, Hyun Changsik

Abstract:

This study was carried out to develop a soybean combine thresher that enables to reduce the damage rate of soybean threshing and the rate of unthreshing. The combine threshing cylinder was developed with 6 circular axis at each end and fixed with disc plates. It was attached to the prototype combine thresher. A combine thresher that has a cylinder with circular rod type threshing pegs was used for a comparative test. A series of comparative tests were conducted using dae-won soybean. The test of the soybean thresher was performed at the cylinder speeds of 210, 240, 270 and 300 rpm, and with the concave clearance of 10, 13 and 16 mm. The separating positions of soybean after threshing were researched on a separate box with 4 sections. The soybean positions of front, center, rear and rear outside, of 59.5%, 30.6%, 7.8% and 2.2% respectively, were obtained. At the cylinder speeds from 210 rpm to 300 rpm, the damage rate of soybean was increased from 0.1% to 4.2% correspondingly to speeds. The unthreshed rate of soybean under the same condition was increased from 0.9% to 4.1% correspondingly to speeds. 0.7% of the damage rate and 1.5% of the unthreshed rate was achieved at the cylinder speed of 240 rpm and with the concave clearance of 10 mm. For Daewon soybean, an optimum cylinder speed of 240 rpm and the concave clearance of 10 mm were identified. These results will be useful for the design, construction, and operation of soybean threshing harvesters.

Keywords: soybean harvest, combine threshing, threshing cylinder, optimum design

Procedia PDF Downloads 506
13198 Residual Modulus of Elasticity of Self-Compacting Concrete Incorporated Unprocessed Waste Fly Ash after Expose to the Elevated Temperature

Authors: Mohammed Abed, Rita Nemes, Salem Nehme

Abstract:

The present study experimentally investigated the impact of incorporating unprocessed waste fly ash (UWFA) on the residual mechanical properties of self-compacting concrete (SCC) after exposure to elevated temperature. Three mixtures of SCC have been produced by replacing the cement mass by 0%, 15% and 30% of UWFA. Generally, the fire resistance of SCC has been enhanced by replacing the cement up to 15% of UWFA, especially in case of residual modulus of elasticity which considers more sensitive than other mechanical properties at elevated temperature. However, a strong linear relationship has been observed between the residual flexural strength and modulus of elasticity, where both of them affected significantly by the cracks appearance and propagation as a result of elevated temperature. Sustainable products could be produced by incorporating unprocessed waste powder materials in the production of concrete, where the waste materials, CO2 emissions, and the energy needed for processing are reduced.

Keywords: self-compacting high-performance concrete, unprocessed waste fly ash, fire resistance, residual modulus of elasticity

Procedia PDF Downloads 114
13197 Biochemical Assessments of the Effects of Crude Oil Contaminated Diets Wistar Rats

Authors: Olawuyi Sikiru Owolabi

Abstract:

A research was carried out to assess the biochemical effects of crude oil contaminated cat fish on selected rat kidney function tests. Thirty-six (36) albino rats (rattus novergicus) were grouped into six (6) of (6) in each group. The rats in group one served as control and they were placed on feed formulated with catfish cultured in borehole water while those ones from group 2 to group 6 were placed on feed formulated with catfish exposed to various concentrations of crude oil (0.1%,0.25%,0.5%,0.75% and 1% respectively).The results obtained showed that there was a significant increase in serum concentration of creatinine, Urea, sodium and potassium ions in the kidney of experimental rats when compared with the control. This may be interpreted to mean possible adverse effects on the kidney. Several studies have been done especially on the biological effects of crude oil in fish. These include Direct Lethal Toxicity, Sub-Lethal disruption of physiological and behavioral activities, interference with feeding and reproduction, direct coating or tainting of fish, effect of entry of hydrocarbons into the food web as well as alteration of biological habitat. The present study attempts to assess the effects of crude oil contaminated diet on rat kidney by carrying out some kidney function tests like determination of serum sodium and potassium ions by flame photometry method, determination of serum urea and determination of serum creatinine.

Keywords: crude oil, serum urea, creatinine, wistar rats

Procedia PDF Downloads 218
13196 The Association between C-Reactive Protein and Hypertension with Different US Participants Ethnicity-Findings from National Health and Nutrition Examination Survey 1999-2010

Authors: Ghada Abo-Zaid

Abstract:

The main objective of this study was to examine the association between the elevated level of CRP and incidence of hypertension before and after adjusting by age, BMI, gender, SES, smoking, diabetes, cholesterol LDL and cholesterol HDL and to determine whether the association were differ by race. Method: Cross sectional data for participations from age 17 to age 74 years who included in The National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010 were analysed. CRP level was classified into three categories ( > 3mg/L, between 1mg/LL and 3mg/L, and < 3 mg/L). Blood pressure categorization was done using JNC 7 algorithm Hypertension defined as either systolic blood pressure (SBP) of 140 mmHg or more and disystolic blood pressure (DBP) of 90mmHg or greater, otherwise a self-reported prior diagnosis by a physician. Pre-hypertension was defined as (139 > SBP > 120 or 89 > DPB > 80). Multinominal regression model was undertaken to measure the association between CRP level and hypertension. Results: In univariable models, CRP concentrations > 3 mg/L were associated with a 73% greater risk of incident hypertension compared with CRP concentrations < 1 mg/L (Hypertension: odds ratio [OR] = 1.73; 95% confidence interval [CI], 1.50-1.99). Ethnic comparisons showed that American Mexican had the highest risk of incident hypertension (odds ratio [OR] = 2.39; 95% confidence interval [CI], 2.21-2.58).This risk was statistically insignificant, however, either after controlling by other variables (Hypertension: OR = 0.75; 95% CI, 0.52-1.08,), or categorized by race [American Mexican: odds ratio [OR] = 1.58; 95% confidence interval [CI], 0,58-4.26, Other Hispanic: odds ratio [OR] = 0.87; 95% confidence interval [CI], 0.19-4.42, Non-Hispanic white: odds ratio [OR] = 0.90; 95% confidence interval [CI], 0.50-1.59, Non-Hispanic Black: odds ratio [OR] = 0.44; 95% confidence interval [CI], 0.22-0,87]. The same results were found for pre-hypertension, and the Non-Hispanic black showed the highest significant risk for Pre-Hypertension (odds ratio [OR] = 1.60; 95% confidence interval [CI], 1.26-2.03). When CRP concentrations were between 1.0-3.0 mg/L, in an unadjusted models prehypertension was associated with higher likelihood of elevated CRP (OR = 1.37; 95% CI, 1.15-1.62). The same relationship was maintained in Non-Hispanic white, Non-Hispanic black, and other race (Non-Hispanic white: OR = 1.24; 95% CI, 1.03-1.48, Non-Hispanic black: OR = 1.60; 95% CI, 1.27-2.03, other race: OR = 2.50; 95% CI, 1.32-4.74) while the association was insignificant with American Mexican and other Hispanic. In the adjusted model, the relationship between CRP and prehypertension were no longer available. In contrary, Hypertension was not independently associated with elevated CRP, and the results were the same after grouped by race or adjusted by the confounder variables. The same results were obtained when SBP or DBP were on a continuous measure. Conclusions: This study confirmed the existence of an association between hypertension, prehypertension and elevated level of CRP, however this association was no longer available after adjusting by other variables. Ethic group differences were statistically significant at the univariable models, while it disappeared after controlling by other variables.

Keywords: CRP, hypertension, ethnicity, NHANES, blood pressure

Procedia PDF Downloads 392
13195 Gold Nanoparticle Conjugated with Andrographolide Ameliorates Viper Venom-Induced Inflammatory Response and Organ Toxicity in Animal Model

Authors: Sourav Ghosh, Antony Gomes

Abstract:

Since 1894 anti-snake venom serum (ASVS) is the only available treatment against snake envenomation, although there are many side effects and limitations. The need for a supportive treatment was felt for a long time to overcome the side effects and limitations of ASVS. Andrographolide conjugated with gold nanoparticle (A-GNP) has been found to antagonize viper venom-induced local damages. The present study was aimed to study the protective efficacy of A-GNP against Viper venom-induced inflammatory response and organ toxicity in animal model. Ethical clearance was obtained from animal experiments. Physico-chemical characterization of A-GNP was done by DLS (diameter and zeta potential), FE-SEM and XRD. Swiss albino male mice were divided into 4 groups: Gr.1-Sham control, Gr.2- Russell’s Viper venom (RVV) control, Gr.3- andrographolide treated and Gr.4- A-GNP treated. The 1/5th minimum lethal dose of RVV (500µg/kg, s.c.) was induced in animals of group 2, 3 & 4 animals, followed by treatment with andrographolide (100mg/kg, i.p.) and A-GNP (100mg/kg, i.v.) in group 3 & 4 animals, respectively. Blood was collected after 18 h, serum was prepared, and inflammatory markers (IL 1β, 6, 17a, 10, TNF α) and biochemical markers (AST, ACP, LDH, urea, creatinine) were assessed. Values were expressed as mean±SEM (n=4), one way ANOVA was done, P<0.05 was considered as statistically significant. DLS size showed the hydrodynamic diameter of A-GNP to be 230-260nm with polydispersity index of 0.103 and zeta potential was -18.32mV. XRD data confirmed the presence of crystalline gold in A-GNP, and FESEM indicated the presence of nearly spherical particle with size18-24nm.Treatment with A-GNP significantly decreased viper venom-induced proinflammatory markers (IL 1β, 6, 17, TNF α) increased anti-inflammatory markers (IL 10) and decreased organ toxicity markers (AST, ACP, LDH, urea, creatinine) in animal model. Venom neutralization efficacy of A-GNP was > andrographolide, which confirmed the increased efficacy of andrographolide after gold nanoparticle conjugation. Venom neutralization by A-GNP was due to anti-oxidant/anti-inflammatory activity of andrographolide, which showed increased efficacy after gold nanoparticle tagging. Thus, A-GNP may serve as a supportive therapy in snake-bite (against inflammatory response and organ toxicity) subject to further detail studies.

Keywords: andrographolide, gold nanoparticle, inflammatory response, organ toxicity, snake venom, snake venom neutralization, viper venom

Procedia PDF Downloads 349
13194 Evaluating the Fire Resistance of Offshore Tubular K-Joints Subjected to Balanced Axial Loads

Authors: Neda Azari Dodaran, Hamid Ahmadi

Abstract:

Results of 405 finite element (FE) analyses were used in the present research to study the effect of the joint geometry on the ultimate strength and initial stiffness of tubular K-joints subjected to axial loading at fire-induced elevated temperatures. The FE models were validated against the data available from experimental tests. Structural behavior under different temperatures (200ºC, 400ºC, 500ºC, and 700ºC) was investigated and compared to the behavior at ambient temperature (20ºC). A parametric study was conducted to investigate the effect of dimensionless geometrical parameters (β, γ, θ, and τ) on the ultimate strength and initial stiffness. Afterwards, ultimate strength data extracted from the FE analyses were compared with the values calculated from the equations proposed by available design codes in which the ultimate strength of the joint at elevated temperatures is obtained by replacing the yield stress of the steel at ambient temperature with the corresponding value at elevated temperature. It was indicated that this method may not have acceptable accuracy for K-joints under axial loading. Hence, a design formula was developed, through nonlinear regression analyses, to determine the ultimate strength of K-joints subjected to balanced axial loads at elevated temperatures.

Keywords: axial loading, elevated temperature, parametric equation, static strength, tubular K-joint

Procedia PDF Downloads 132
13193 In vivo Anticandida Activity of Three Traditionally Used Medicinal Plants in East Africa

Authors: Daniel P. Kisangau, Ken M. Hosea, Herbert V. M. Lyaruu, Cosam C. Josep, Zakaria H. Mbwambo, Pax J. Masimba

Abstract:

Crude extracts of Dracaena steudneri bark (DSB), Sapium ellipticum bark (SEB) and Capparis erythrocarpos root (CER) were investigated for their antifungal activity in immunocompromised mice infected with Candida albicans in an in vivo mice infection model. The results revealed a substantial dose dependency in all treatments given, with mice survival to the end of the experiment correlating well to the dose levels. At a dose of 400 mg/kg, C. erythrocarpos was the most effective with mice survival of 60% and organ burden clearance ranging from 64.0%-99.9% (P<0.0001) in all treatments. At the same dose, the least effective plant was S. ellipticum which had a mice survival of 20% and organ burden clearance ranging from 78.0%-96.6 (P>0.05). Mice survival for D. steudneri was 30% with organ burden clearance ranging from 89.0%-99.9% (P<0.05). All mice receiving no active treatment died before ten days post infection. In all treatment groups, there was a steady decline in mean weights of mice immediately after immunosuppression followed by gradual recovery in some cases which appeared to be dose dependent a few days post infection. Thus, extracts of D. steudneri and C. erythrocarpos portrayed the most significant potential as sources of antifungal drugs.

Keywords: antifungal activity, medicinal plants, candida albicans, East Africa

Procedia PDF Downloads 487
13192 Basal Cell Carcinoma Excision Intraoperative Frozen Section for Tumor Clearance and Reconstructive Surgery: A Prospective Open Label Interventional Study

Authors: Moizza Tahir, Uzma Bashir, Aisha Akhtar, Zainab Ansari, Sameen Ansari, Muhammad Ali Tahir

Abstract:

Cancer burden has globally increased. Among cutaneous cancers basal cell carcinoma constitute vast majority of skin cancer. There is need for appropriate diagnostic, therapeutic and prognostic significance evaluation for skin cancers Present study report intraoperative frozen section (FS) histopathological clearance for excision of BCC in a tertiary care center and find the frequency of involvement of surgical margin with reference to anatomical site, with size and surgical technique. It was prospective open label interventional study conducted at Dermatology department of tertiary care hospital Rawalpindi Pakistan in lais on with histopathology department from January 2023 to April 2024. Total of thirty-six (n = 36) patients between age 45-80 years with basal cell carcinoma of 10-20mm on face were included following inclusion exclusion criteria by purposive sampling technique. Informed consent was taken. Surgical excision was performed and intraoperative frozen section histopathology clearance of tumor margin was taken from histopathologist on telephone. Surgical reconstruction was done. Final Histopathology report was reexamined on day 10th for margin and depth clearance. Descriptive statistics were calculated for age, gender, sun exposure, reconstructive technique, anatomical site, and tumor free margin report on frozen section analysis. Chi square test was employed for statistical significance of involvement of surgical margin with reference to anatomical site, size and decision on reconstructive surgical technique, p value of <0.05 was considered significant. Total of 36 patients of BCC were enrolled, males 12 (33.3%) and females were 24 (66.6%). Age ranged from 45 year to 80 year mean of 58.36 ±SD7.8. Size of BCC ranged from 10mm to 35mm mean of 25mm ±SD 0.63. Morphology was nodular 18 (50%), superficial spreading 11(30.6%), morphoeic 1 (2.8%) and ulcerative in 6(16.7%) cases. Intraoperative frozen section for histopathological margin clearance with 2-3 mm safety margin and surgical technique has p-value0.51, for anatomical site p value 0.24 and size p-0.84. Intraoperative frozen section (FS) histopathological clearance for BCC face with 2-3mm safety margin with reference to reconstructive technique, anatomical site and size of BCC were insignificant.

Keywords: basal cell carcinoma, tumor free amrgin, basal cell carcinoma and frozen section, safety margin

Procedia PDF Downloads 26
13191 Effect of Fiber Types and Elevated Temperatures on the Bond Characteristic of Fiber Reinforced Concretes

Authors: Erdoğan Özbay, Hakan T. Türker, Müzeyyen Balçıkanlı, Mohamed Lachemi

Abstract:

In this paper, the effects of fiber types and elevated temperatures on compressive strength, modulus of rapture and the bond characteristics of fiber reinforced concretes (FRC) are presented. By using the three different types of fibers (steel fiber-SF, polypropylene-PPF and polyvinyl alcohol-PVA), FRC specimens were produced and exposed to elevated temperatures up to 800 ºC for 1.5 hours. In addition, a plain concrete (without fiber) was produced and used as a control. Test results obtained showed that the steel fiber reinforced concrete (SFRC) had the highest compressive strength, modulus of rapture and bond stress values at room temperatures, the residual bond, flexural and compressive strengths of both FRC and plain concrete dropped sharply after exposure to high temperatures. The results also indicated that the reduction of bond, flexural and compressive strengths with increasing the exposed temperature was relatively less for SFRC than for plain, and FRC with PPF and PVA.

Keywords: bond stress, compressive strength, elevated temperatures, fiber reinforced concrete, modulus of rapture

Procedia PDF Downloads 397
13190 Protective Effect of Malva sylvestris L. against Sodium Fluoride-Induced Nephrotoxicity in Rat

Authors: Ali Babaei Zarch, S. Kianbakht, H. Fallah Huseini, P. Changaei, A. Mirjalili, J. Salehi

Abstract:

Background: Malva sylvestris L. is widely used in the traditional medicine of Iran and other countries to treat gastrointestinal, respiratory, skin and urological Disorders. Moreover, it has antioxidant property. Objective: In this study the protective effect of Malva sylvestris against sodium fluoride-induced nephrotoxicity in rats were evaluated. Methods: The Malva sylvestris flower extract was injected intraperitoneally at the doses of 100, 200, 400 mg/kg/day to groups of rats ( 10 in each group) for 1 week and subsequently 600 ppm sodium fluoride was added daily to the rats drinking water for 1 additional week. After these steps, the rats’ serum levels of urea, creatinine, reduced glutathione, catalase and malondialdehyde were determined. The histopathology of the rats’ kidney was also studied. Results: Malva sylvesteries extract with doses of 400 mg/kg/day significantly decreased the urea and creatinine levels (P<0.05). Moreover, the levels of catalase and glutathione were increased by this dose, but only the catalase increase was statistically significant (P<0.05). All three extract doses of Malva decreased the malondialdehyde level, but it was significant only for the dose 400 mg/kg/day (P<0.05). Histopathological findings also showed a protective effect of Malva against renal damage induced by sodium fluoride. Conclusion: The results suggest that Malva sylvestris has a protective effect against sodium fluoride-induced nephrotoxicity through its antioxidant property.

Keywords: Malva sylvestris, mephrotoxicity, sodium fluoride, rat  

Procedia PDF Downloads 317
13189 Fluidized-Bed Combustion of Biomass with Elevated Alkali Content: A Comparative Study between Two Alternative Bed Materials

Authors: P. Ninduangdee, V. I. Kuprianov

Abstract:

Palm kernel shell is an important bioenergy resource in Thailand. However, due to elevated alkali content in biomass ash, this oil palm residue shows high tendency to bed agglomeration in a fluidized-bed combustion system using conventional bed material (silica sand). In this study, palm kernel shell was burned in the conical fluidized-bed combustor (FBC) using alumina and dolomite as alternative bed materials to prevent bed agglomeration. For each bed material, the combustion tests were performed at 45kg/h fuel feed rate with excess air within 20–80%. Experimental results revealed rather weak effects of the bed material type but substantial influence of excess air on the behaviour of temperature, O2, CO, CxHy, and NO inside the reactor, as well as on the combustion efficiency and major gaseous emissions of the conical FBC. The optimal level of excess air ensuring high combustion efficiency (about 98.5%) and acceptable level of the emissions was found to be about 40% when using alumina and 60% with dolomite. By using these alternative bed materials, bed agglomeration can be prevented when burning the shell in the proposed conical FBC. However, both bed materials exhibited significant changes in their morphological, physical and chemical properties in the course of the time.

Keywords: palm kernel shell, fluidized-bed combustion, alternative bed materials, combustion and emission performance, bed agglomeration prevention

Procedia PDF Downloads 234
13188 Simulation of Low Cycle Fatigue Behaviour of Nickel-Based Alloy at Elevated Temperatures

Authors: Harish Ramesh Babu, Marco Böcker, Mario Raddatz, Sebastian Henkel, Horst Biermann, Uwe Gampe

Abstract:

Thermal power machines are subjected to cyclic loading conditions under elevated temperatures. At these extreme conditions, the durability of the components has a significant influence. The material mechanical behaviour has to be known in detail for a failsafe construction. For this study a nickel-based alloy is considered, the deformation and fatigue behaviour of the material is analysed under cyclic loading. A viscoplastic model is used for calculating the deformation behaviour as well as to simulate the rate-dependent and cyclic plasticity effects. Finally, the cyclic deformation results of the finite element simulations are compared with low cycle fatigue (LCF) experiments.

Keywords: complex low cycle fatigue, elevated temperature, fe-simulation, viscoplastic

Procedia PDF Downloads 207
13187 Chatter Suppression in Boring Process Using Passive Damper

Authors: V. Prasannavenkadesan, A. Elango, S. Chockalingam

Abstract:

During machining process, chatter is an unavoidable phenomenon. Boring bars possess the cantilever shape and due to this, it is subjected to chatter. The adverse effect of chatter includes the increase in temperature which will leads to excess tool wear. To overcome these problems, in this investigation, Cartridge brass (Cu – 70% and Zn – 30%) is passively fixed on the boring bar and also clearance is provided in order to reduce the displacement, tool wear and cutting temperature. A conventional all geared lathe is attached with vibrometer and pyrometer is used to measure the displacement and temperature. The influence of input parameters such as cutting speed, depth of cut and clearance on temperature, tool wear and displacement are investigated for various cutting conditions. From the result, the optimum conditions to obtain better damping in boring process for chatter reduction is identified.

Keywords: boring, chatter, mass damping, passive damping

Procedia PDF Downloads 339
13186 Studies on Effect of Nano Size and Surface Coating on Enhancement of Bioavailability and Toxicity of Berberine Chloride; A p-gp Substrate

Authors: Sanjay Singh, Parameswara Rao Vuddanda

Abstract:

The aim of the present study is study the factual benefit of nano size and surface coating of p-gp efflux inhibitor on enhancement of bioavailability of Berberine chloride (BBR); a p-gp substrate. In addition, 28 days sub acute oral toxicity study was also conducted to assess the toxicity of the formulation on chronic administration. BBR loaded polymeric nanoparticles (BBR-NP) were prepared by nanoprecipitation method. BBR NP were surface coated (BBR-SCNP) with the 1 % w/v of vitamin E TPGS. For bioavailability study, total five groups (n=6) of rat were treated as follows first; pure BBR, second; physical mixture of BBR, carrier and vitamin E TPGS, third; BBR-NP, fourth; BBR-SCNP and fifth; BBR and verapamil (widely used p-gp inhibitor). Blood was withdrawn at pre-set timing points in 24 hrs study and drug was quantified by HPLC method. In oral chronic toxicity study, total four groups (n=6) were treated as follows first (control); water, second; pure BBR, third; BBR surface coated nanoparticles and fourth; placebo BBR surface coated nanoparticles. Biochemical levels of liver (AST, ALP and ALT) and kidney (serum urea and creatinine) along with their histopathological studies were also examined (0-28 days). The AUC of BBR-SCNP was significantly 3.5 folds higher compared to all other groups. The AUC of BBR-NP was 3.23 and 1.52 folds higher compared to BBR solution and BBR with verapamil group, respectively. The physical mixture treated group showed slightly higher AUC than BBR solution treated group but significantly low compared to other groups. It indicates that encapsulation of BBR in nanosize form can circumvent P-gp efflux effect. BBR-NP showed pharmacokinetic parameters (Cmax and AUC) which are near to BBR-SCNP. However, the difference in values of T1/2 and clearance indicate that surface coating with vitamin E TPGS not only avoids the P-gp efflux at its absorption site (intestine) but also at organs which are responsible for metabolism and excretion (kidney and liver). It may be the reason for observed decrease in clearance of BBR-SCNP. No toxicity signs were observed either in biochemical or histopathological examination of liver and kidney during toxicity studies. The results indicate that administration of BBR in surface coated nanoformulation would be beneficial for enhancement of its bioavailability and longer retention in systemic circulation. Further, sub acute oral dose toxicity studies for 28 days such as evaluation of intestine, liver and kidney histopathology and biochemical estimations indicated that BBR-SCNP developed were safe for long use.

Keywords: bioavailability, berberine nanoparticles, p-gp efflux inhibitor, nanoprecipitation method

Procedia PDF Downloads 365