Effect of Orally-administration Niclosamide on serum level of VCAM-1 and E-selectin in Collagen induced arthritis: Experimental study

Author(s):  
Ahmed Salim Mahmood ◽  
Ali Ismail Al-Gareeb ◽  
Faiq Isho Gorial

Soluble adhesion molecules (mainly VCAM-1 and E-selectin) have a vital role in the pathogenesis of the rheumatoid arthritis (RA) and consider as angiogenic mediators for this disease. The main goal for this research is to evaluate the efficacy of orally administer niclosamide (NCS) in prevention the angiogenic mediators (VCAM-1 and E-selectin) using collagen induced arthritis model in rats (CIA). Fifty male Spraque-Dawley rats underwent collagen induced arthritis (CIA) model. When arthritis was fully developed, the rats were either treated orally with low-dose (50mg/kg) NCS or high-dose (100mg/kg) NCS or treated intrapertonially (IP) with 30mg/kg NCS or leave without treatment for 4 weeks. Body weight measurement and arthritis index were monitor before and after treatment in all groups. At the end of the treatment period serum level of vascular cell adhesion molecule-1 (VCAM-1), E-selectin and TNFα were measured together with collection of articular synovial tissue to evaluate the pathological changes. The experiment showed that NCS significantly reduce the arthritis index, foot pad thickness and ankle swelling (p value < 0.05) when given orally in a high dose and IP to the experimental animal. Comparing to the CIA model group, significant reduction in the serum level of VCAM1 and E-selectin has been observed in those rats treated with high dose of oral NCS or IP injection of NCS (p value < 0.05). Niclosamide can effectively decrease, in dose dependent manner, the clinical scores, joint swelling, VCAM1, E-selectin and pathological changes in arthritic rats induced by collagen type II.

2019 ◽  
Vol 22 (2) ◽  
pp. 273-279 ◽  
Author(s):  
Helen M Kamens ◽  
Constanza P Silva ◽  
Russell T Nye ◽  
Carley N Miller ◽  
Nayantara Singh ◽  
...  

Abstract Introduction Spectrum research cigarettes have been developed with varying nicotine content for use in studies evaluating the effects of a regulatory policy reducing the permissible nicotine content in cigarettes. This study aimed to characterize the nicotine pharmacokinetic profile of Spectrum cigarettes. Methods Twelve daily smokers attended four sessions and had blood nicotine, exhaled carbon monoxide, and subjective effects measured before and after smoking either a single cigarette of their preferred brand or high (10.9 mg/cigarette), medium (3.2 mg/cigarette), or low (0.2 mg/cigarette) nicotine content Spectrum research cigarettes, in a double-blind design with order counterbalanced. Results The boost in blood nicotine concentration was dose-dependent, with a boost of 0.3, 3.9, and 17.3 ng/mL for low-, medium-, and high-nicotine content Spectrum cigarettes. The high dose Spectrum had a similar nicotine boost to the “preferred brand” cigarettes (19 ng/mL). Subjects took longer puffs on the low nicotine cigarettes, but smoked these cigarettes faster than other cigarette types. High nicotine Spectrum cigarettes reduced the urge to smoke more than other cigarette types. Conclusions This study shows that Spectrum research cigarettes produce blood nicotine absorption in a dose-dependent manner, and therefore, are appropriate for use in studies of nicotine reduction in cigarettes. Implications This is the first study to determine the pharmacokinetic profile of Spectrum reduced nicotine content research cigarettes following an overnight abstinence. These data could provide evidence to regulatory agencies about the effects of reduced nicotine cigarettes when considering regulations on tobacco reduction.


2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Miao Xu ◽  
Qi Zhao ◽  
Donghui Shao ◽  
Hui Liu ◽  
Jianni Qi ◽  
...  

Aim. To investigate the effects of HS-1200 on liver tumorigenesis and liver function in a diethylnitrosamine- (DEN-) induced hepatocellular carcinoma (HCC) rat model.Methods. Rats were randomly assigned into five groups: control, HS-1200, HCC, HCC + low dose HS-1200, and HCC + high dose HS-1200 groups. Rat HCC model was established by intraperitoneal injection of DEN. And rats were given HS-1200 by daily oral gavage. After 20 weeks, we examined animal body weight, liver weight, liver pathological changes, serum levels of AST, ALT, and AFP, andmutT homologue gene 1 (MTH1)in liver tissue.Results. Oral gavage of HS-1200 significantly increased animal body weight and decreased liver weight as well as liver coefficient in HCC rats (P<0.05versus HCC group). Moreover, oral administration of HS-1200 suppressed tumorigenesis, attenuated pathological changes in liver tissues, and decreased serum levels of AST, ALT, and AFP in HCC rats (P<0.05versus HCC group). In addition, the mRNA level of MTH1 was upregulated in the liver tissues of HCC rats (P<0.05versus control group), which was reversed by HS-1200 treatment in a dose-dependent manner (P<0.05versus HCC group).Conclusions. HS-1200 inhibits hepatocarcinogenesis and improves liver function maybe by inducing downregulation of MTH1.


2017 ◽  
Vol 4 (4) ◽  
pp. 1514
Author(s):  
Kiran Suthar ◽  
Pramod Sharma ◽  
Manish Verma ◽  
Vishnu Kr. Goyal

Background: This study was conducted to find out whether high dose hydroxyurea is an effective and safe modality, in inducing haemoglobin synthesis to decrease blood transfusion requirement in transfusion dependent thalassemics.Methods: This quasi experimental un-control before and after comparison study was conducted in Thalassemia Day Care Centre, Department of Pediatrics over a period of six months after obtaining an approval from the Institute’s ethical committee. Fifty transfusions dependent thalassemic children belonging from 2 to 18 yrs were given hydroxyurea in dose of 20mg/kg after getting consent. Pre and post intervention haemoglobin and HbF levels were obtained using Hb electrophoresis by HPLC. Paired t test was applied to find out statistical significance and p value <0.05 was taken as significant.Results: Significant rise in haemoglobin pre and post intervention (p<0.001) but the rise in HbF was not significant (p=0.110). One patient had bone marrow depression which was reversible with drug withdrawal and one patient had rise in s. creatinine.Conclusions: High dose hydroxyurea is an effective and safe drug in inducing Hemoglobin synthesis in transfusion dependent thalassemics.  


2019 ◽  
Vol 1 (1) ◽  
pp. 01-02
Author(s):  
Hamsu Kadriyan ◽  
Muhammad Alfian Sulaksana ◽  
Nurhidayati ◽  
Baiq Endang Suprihartini

Introduction Combination of chemotherapy and radiation are the treatment of choice in advance stage of nasopharyngeal cancer. Cisplatin-based chemotherapy is a regiment of choice in those cases. Several studies show that cisplatin-based chemotherapy affect renal function. Aims of the study to evaluate and compare the renal function before and after chemotherapy through comparing the blood urea nitrogen and creatinine serum level in patients with nasopharyngeal cancer who receive cisplatin and paclitaxel chemotherapy. Methods Design of this study is before and after using medical records data in West Nusa Tenggara General Hospital in Lombok. Result There were 33 patients who fulfill the inclusion and exclusion criteria in this study. Most of the patients are male with male and female ratio 3:1. The youngest patient age is eight years old, on the other hand, the oldest is 70 years old with the average age 46,6 years old. According to histopathology finding, on this study researcher didn't found WHO type I and most the patients were WHO type III (89,9 %). The mean blood urea nitrogen concentration before chemotherapy is 25,00 and after the treatment 33,33 with the p-value 0,01 with the paired t-test. On the other hand, creatinine serum level before and after chemotherapy consecutively 0,99 and 1,10. p-value 0,15, or there is no significant difference. Conclusion Blood urea nitrogen and creatinine serum are increase after cisplatin-based chemotherapy. However, only BUN has a significant difference.


2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P153-P153
Author(s):  
Javier Olarieta ◽  
Teresa Rivera ◽  
Jon Alexander Sistiaga Suarez ◽  
Reyes Eduardo ◽  
Melchor Alvarez de Mon

Objectives 1) To assess the different clinical varieties and the evolution of the patients. 2) To assess the clinical impact of the use of high dose corticotherapy. 3) To analyze the phenotype of the lymphocyte populations in peripheral blood. 4) To study the proliferative answer of mononuclear cells in peripheral blood under polyclonal mitogen stimulus. Methods A prospective study in patients with immunomediated inner ear disease was carried out, dividing them in 4 different clinical presentations: Sudden deafness, fluctuant hearing loss, Meniere's disease, and rapidly progressive hearing loss. We analysed 22 patients, controlling their clinical evolution and response to corticotherapy. We also made an immunophenotypical and functional characterization of the T lymphocytes in patients before and after treatment and comparing them with healthy controls. Mann-Whitney U and Wilcoxon range tests were used as statistical resources. Results 59.09% of the patients treated with corticotherapy improved, with a 95% of treatment fulfillment. The T lymphocyte compartment's proliferative response was significantly lower in these patients (p value less than 0.05) and there was a higher CD56+ (p value less than 0,01) and CD8+ CD45RO+(p value less than 0.01) lymphocyte subpopulations expression in absolute and percentage numbers. Conclusions Immunomediated inner ear disease is related to T, B, and especially NK lymphocytosis associated to a redistribution of the T cell subpopulations.


2012 ◽  
Vol 46 (3) ◽  
pp. 200-206 ◽  
Author(s):  
Mariana Abreu ◽  
Delia Aguado ◽  
Javier Benito ◽  
Ignacio A Gómez de Segura

This study aimed to estimate the reduction in the minimum alveolar concentration (MAC) of sevoflurane induced by low and high doses of methadone (5 and 10 mg/kg), tramadol (25 and 50 mg/kg), butorphanol (5 and 10 mg/kg) or morphine (5 and 10 mg/kg) in the rat. A control group received normal saline. Sixty-three adult male Sprague-Dawley rats were anaesthetized with sevoflurane ( n = 7 per group). Sevoflurane MAC was then determined before and after intraperitoneal administration of the opioids or saline. The duration of the sevoflurane MAC reduction and basic cardiovascular and respiratory measurements were also recorded. The baseline MAC was 2.5 (0.3) vol%. Methadone, tramadol and morphine reduced the sevoflurane MAC (low dose: 31 ± 10, 38 ± 15 and 30 ± 13% respectively; high dose: 100 ± 0, 83 ± 17 and 77 ± 25%, respectively) in a dose-dependent manner. The low and high doses of butorphanol reduced the sevoflurane MAC to a similar extent (33 ± 7 and 31 ± 4%, low and high doses, respectively). Two rats developed apnoea following administration of high-dose butorphanol and methadone. These anaesthetic-sparing effects are clinically relevant and may reduce the adverse effects associated with higher doses of inhalational anaesthetics.


1991 ◽  
Vol 65 (05) ◽  
pp. 504-510 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
Walter Bernini ◽  
Guido Lazzerini ◽  
Giuliana Buti Strata ◽  
...  

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.


1997 ◽  
Vol 78 (04) ◽  
pp. 1202-1208 ◽  
Author(s):  
Marianne Kjalke ◽  
Julie A Oliver ◽  
Dougald M Monroe ◽  
Maureane Hoffman ◽  
Mirella Ezban ◽  
...  

SummaryActive site-inactivated factor VIIa has potential as an antithrombotic agent. The effects of D-Phe-L-Phe-L-Arg-chloromethyl ketone-treated factor VIla (FFR-FVIIa) were evaluated in a cell-based system mimicking in vivo initiation of coagulation. FFR-FVIIa inhibited platelet activation (as measured by expression of P-selectin) and subsequent large-scale thrombin generation in a dose-dependent manner with IC50 values of 1.4 ± 0.8 nM (n = 8) and 0.9 ± 0.7 nM (n = 7), respectively. Kd for factor VIIa binding to monocytes ki for FFR-FVIIa competing with factor VIIa were similar (11.4 ± 0.8 pM and 10.6 ± 1.1 pM, respectively), showing that FFR-FVIIa binds to tissue factor in the tenase complex with the same affinity as factor VIIa. Using platelets from volunteers before and after ingestion of aspirin (1.3 g), there were no significant differences in the IC50 values of FFR-FVIIa [after aspirin ingestion, the IC50 values were 1.7 ± 0.9 nM (n = 8) for P-selectin expression, p = 0.37, and 1.4 ± 1.3 nM (n = 7) for thrombin generation, p = 0.38]. This shows that aspirin treatment of platelets does not influence the inhibition of tissue factor-initiated coagulation by FFR-FVIIa, probably because thrombin activation of platelets is not entirely dependent upon expression of thromboxane A2.


2020 ◽  
Vol 2 (2) ◽  
pp. 66-71
Author(s):  
Parti ◽  
Sumiati Malik ◽  
Nurhayati

Most causes of infant death are problems that occur in newborn/neonatal (0-28 days old), Low Birth Weight Babies (LBW) is one of the factors which has a contribution to infant mortality, especially in the neonatal period. Infant Mortality Rate (IMR) is a benchmark in determining the degree of public health, both at the National and Provincial levels. This study aimed to determine the effect of the Kangaroo Mother Care Method (KMC) on the prevention of hypothermia in low birth weight infants at Morowali District Hospital in 2019. The type of research used was a quasi-experiment. The population is all low birth weight babies born from May to July 2019. The sample in this study was all newborns with low birth weight born from May to July 2019, totaling 30 babies. There is a difference (influence) on the baby's body temperature before and after KMC with a p-value=0,000. The kangaroo mother care can continue to be affiliated considering its benefits for both infants and mothers, as well as increasing the ability of health workers in conducting KMC so that they can provide in-house training for mothers to be carried out at home.


Author(s):  
Juliana Widyastuti Wahyuningsih Juliana Widyastuti Wahyuningsih

ABSTRAK Tidur merupakan kebutuhan yang harus terpenuhi terutama pada fase perkembangan karena selama tidur akan terjadi perkembangan otak maupun tubuh, sehingga gangguan tidur merupakan masalah yang akan menimbulkan dampak buruk terhadap pertumbuhan dan perkembangan bayi. Kualitas tidur bayi yang baik dapat diciptakan dengan memberikan pemijatan bayi secara rutin. Penelitian ini bertujuan untuk membuktikan bahwa pemijatan dapat mempengaruhi kualitas tidur bayi umur 0-3 bulan. Penelitian ini menggunakan desain penelitian Quasy Eksperimental dengan metode One Group Pretest-Postest. Sampel 22 bayi yang dipilih dengan tehnik Total Sampling yang di observasi sebelum dan sesudah diberikan pemijatan. Variabel yang diukur dalam penelitian ini adalah kualitas tidur bayi 0-3 bulan. Hasil penelitian menunjukkan bahwa ada pengaruh pijat bayi terhadap kualitas tidur bayi umur 0-3 bulan (p value  0,008 < α = 0,05).Berdasarkan hasil penelitian ini disarankan agar keluarga dan masyarakat memberikan pemijatan secara rutin dan mandiri untuk meningkatkan kebutuhan tidur bayi yang berkualitas.   ABSTRACT Sleep is a human necessity that must be met, especially in the development phase because during sleep will occur the brain and body developments, so that sleep disturbance is a problem that would cause adverse effects on infants’ growth and development. The good quality of sleep can be created by providing the infants massage routinely. This study aimed to prove that the massage could affect the quality of sleep on the 0-3 months old baby. This study used Quasy-experimental design with One Group Pretest-Posttest. The sample 22 infants selected by total sampling technique observed on before and after the massage. The variables measured in this study are the quality of sleep. The results of study indicate that there is an effect of infant massage to the sleep quality on 0-3 months old babies (p value 0,008 < α = 0,05).Based on the results of this study it recommended for the families and communities to provide infant massage regularly and independently to increase the quality of sleep on the baby.  


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