scholarly journals Antiviral activity of N-ω-Chloroacetyl-L-Ornithine on in vitro replication of Chikungunya virus

2019 ◽  
Author(s):  
Lucero Luna-Rojas ◽  
Amanda M. Avila-Trejo ◽  
Verónica Alcántara-Farfán ◽  
Lorena I. Rodríguez-Páez ◽  
Marvin Omar Pastor-Alonso ◽  
...  
Keyword(s):  
Viral Replication ◽  
Ornithine Decarboxylase ◽  
Health Problem ◽  
Cytotoxic Effect ◽  
Chikungunya Virus ◽  
Competitive Inhibitor ◽  
Morbidity Rate ◽  
High Morbidity ◽  
High Morbidity Rate

AbstractThe infections causes by Chikungunya virus (CHIKV), family Togaviridae, genus Alfavirus, have become a health problem around the world, due to its widespread occurrence, the high morbidity rate and the absence of vaccines or antiviral treatments. We analyzed a competitive inhibitor of ornithine decarboxylase, enzyme key in the biosynthesis of Polyamines (PAs), N-ω-chloroacetyl-L-ornithine (NCAO), as a possible inhibitor of CHIKV replication because intracellular polyamines participate in the transcription and in vitro translation of CHIKV. NCAO does not have any cytotoxic effect on C6/36 cells even at a concentration of 1000μM at 72h after post-exposure but in Vero cells the cytotoxic effect was presented above 380μM at 48h post-exposure, which was considered when determining the inhibitory effect on viral replication. We demonstrate that NCAO inhibits the replication of CHIKV in Vero and C6/36 cells in a dose-dependent manner causing a decrease in the PFU/mL of at least 4-logarithm (p <0.01) in both cell lines. Viral yields were restored by the addition of exogenous polyamines, mainly putrescine. HPLC analyses it shown that NCAO decrease content of intracellular PAs even though in infected cells mainly decreased spermidine and spermine, so NCAO inhibits CHIKV replication, by depleting the intracellular polyamines in Vero and C6/36 cells, suggesting that this compound is a possible antiviral in CHIKV infections.ImportanceThe infections caused by Chikungunya virus (CHIKV), genus Alfavirus, have become a worldwide health problem, due to its high morbidity rate and the absence of vaccines or antiviral treatments. It is known that CHIKV use intracellular poliamines during transcription and traduction process, so the depletion of intracellular putrescine, spermidine and spermine reduce the viral replication. N-ω-chloroacetyl-L-ornithine (NCAO) is known as a competitive inhibitor of ornithine decarboxylase, key enzyme in Polyamines biosynthesis, but no studies have proven its activity on the inhibition of polyamine-dependent viral replication. Here we demonstrate NCAO inhibits in vitro CHIKV replication, so we propose NCAO as an antiviral candidate.

scholarly journals Antiviral Activity of N-ω-Chloroacetyl-L-Ornithine on In Vitro Replication of the Chikungunya Virus

2020 ◽  
Author(s):  
Lucero Luna-Rojas ◽  
Amanda Marineth Avila-Trejo ◽  
Veronica Alcantara-Farfán ◽  
Lorena I Rodriguez-Paez ◽  
Marvin Omar Pastor-Alonso ◽  
...  
Keyword(s):  
Cytotoxic Effect ◽  
Chikungunya Virus ◽  
Vero Cells ◽  
Competitive Inhibitor ◽  
Morbidity Rate ◽  
High Morbidity ◽  
Dependent Manner ◽  
Post Exposure ◽  
High Morbidity Rate

The infections caused by Chikungunya virus (CHIKV), genus Alphavirus, have become a health problem around the world, due to this virus&rsquo;s widespread occurrence and high morbidity rate and the absence of vaccines or antiviral drugs. In this study, we analyzed a competitive inhibitor of ornithine decarboxylase&mdash;an enzyme that is key in the biosynthesis of polyamines (PAs), N-&omega;-chloroacetyl-L-ornithine (NCAO), which is a possible inhibitor of CHIKV replication because intracellular polyamines participate in the in vitro transcription and translation of CHIKV. NCAO does not have any cytotoxic effect on C6/36 cells even at 1000 &mu;M at 72 h post-exposure. However, in Vero cells, a cytotoxic effect was present above 380 &mu;M at 48 h post-exposure, which was considered when determining the inhibitory effect on viral replication. In this work, we demonstrate that NCAO inhibits the replication of CHIKV in Vero and C6/36 cells in a dose-dependent manner, causing a decrease in the PFU/mL of at least 4 logarithms (p &lt;0.01) in both cell lines. Viral yields were restored by the addition of exogenous polyamines, mainly putrescine. The HPLC analyses showed that NCAO decreases the content of intracellular PAs, even though mainly spermidines and spermines are present in infected cells. NCAO inhibits CHIKV replication by depleting the intracellular polyamines in Vero and C6/36 cells, suggesting that this compound is a possible antiviral for CHIKV infections.

scholarly journals About Minimization of Expenses on Allergy Diagnosis in Children: Analysis of Consistency of in Vitro- and in Vivo-Allergic Examinations Results

2015 ◽  
Vol 70 (6) ◽  
pp. 748-755
Author(s):  
Marina Andreevna Snovskaya ◽  
Anna Sergeevna Batyrova ◽  
Leyla Seymurovna Namazova-Baranova ◽  
Anna Aleksandrovna Alekseeva ◽  
Elena Aleksandrovna Vishneva ◽  
...  
Keyword(s):  
Atopic Disease ◽  
Skin Tests ◽  
Morbidity Rate ◽  
In Vitro Tests ◽  
High Morbidity ◽  
Meadow Fescue ◽  
Ige Antibodies ◽  
High Morbidity Rate

High morbidity rate of atopic diseases among children, including high importance of grass pollen as a sensitizing agent, determine the relevance of studies on diagnostic examination systems for appointment of adequate therapy. The research of the most relevant allergens for patients to exclude of duplicating and uninformative tests became urgent after development of a new type of diagnostic tests that does not require expensive equipment. The objective of this research was to evaluate the results of in vitro- and in vivo-diagnostic examinations of children with various forms of atopic disease caused by pollen of meadow grasses, and to choose the most significant prognostic parameters for the diagnosis. Methods: 277 children aged 4–16 years with various forms of atopic disease were included in the study. There were performed skin prick tests and determination of IgE-antibodies levels to allergen extracts of cocksfoot (g3), meadow fescue (g4), timothy grass (g6). Results: In the studied group of patients 32–50% of children have antibodies to grass allergens. There was a close correlation of antibody response on the investigated allergens, quantitative coincidence of IgE-antibodies to g3 and g4 allergens levels. IgE (g6) concentration was close to the IgE(g3) and IgE(g4) levels (85,0±21,6%). Analysis of the skin tests results showed that 44% of patients have a positive response to grass allergens, and in vivo-tests results coincide with serological tests results, mostly in a qualitative sense. The most significant relationship was noted between in vivo and in vitro-tests in the results of testing the response to meadow fescue pollen.Conclusion: Based on these data IgE concentration index to meadow fescue allergens can be used as a prognostic marker to determine the sensitization of patients with different nosology forms of allergy and can help to improve allergic diagnostics.

In Silico Insights on GD2 : A Potential Target for Pediatric Neuroblastoma

2020 ◽  
Vol 19 (30) ◽  
pp. 2766-2781 ◽  
Author(s):  
Akanksha Limaye ◽  
Jajoriya Sweta ◽  
Maddala Madhavi ◽  
Urvy Mudgal ◽  
Sourav Mukherjee ◽  
...  
Keyword(s):  
In Silico ◽  
Electrostatic Interactions ◽  
3D Structure ◽  
Biological Marker ◽  
Morbidity Rate ◽  
Local Alignment ◽  
Pharmacokinetic Studies ◽  
High Morbidity ◽  
High Morbidity Rate

Background: Originating from the abnormal growth of neuroblasts, pediatric neuroblastoma affects the age group below 15 years. It is an aggressive heterogenous cancer with a high morbidity rate. Biological marker GD2 synthesised by the GD2 gene acts as a powerful predictor of neuroblastoma cells. GD2 gangliosides are sialic acid-containing glycosphingolipids. Differential expression during brain development governs the function of the GD2. The present study explains the interaction of the GD2 with its established inhibitors and discovers the compound having a high binding affinity against the target protein. Technically, during the development of new compounds through docking studies, the best drug among all pre-exist inhibitors was filtered. Hence in reference to the best docked compound, the study proceeded further. Methodology: The In silico approach provides a platform to determine and establish potential inhibitor against GD2 in Pediatric neuroblastoma. The 3D structure of GD2 protein was modelled by homology base fold methods using Smith-Watermans’ Local alignment. A total of 18 established potent compounds were subjected to molecular docking and Etoposide (CID: 36462) manifested the highest affinity. The similarity search presented 336 compounds similar to Etoposide. Results: Through virtual screening, the compound having PubChem ID 10254934 showed a better affinity towards GD2 than the established inhibitor. The comparative profiling of the two compounds based on various interactions such as H-bond interaction, aromatic interactions, electrostatic interactions and ADMET profiling and toxicity studies were performed using various computational tools. Conclusion: The docking separated the virtual screened drug (PubChemID: 10254934) from the established inhibitor with a better re-rank score of -136.33. The toxicity profile of the virtual screened drug was also lesser (less lethal) than the established drug. The virtual screened drug was observed to be bioavailable as it does not cross the blood-brain barrier. Conclusively, the virtual screened compound obtained in the present investigation is better than the established inhibitor and can be further augmented by In vitro analysis, pharmacodynamics and pharmacokinetic studies.

scholarly journals Surveillance of influenza A H1N1 2009 among school children during 2009 and 2010 in São Paulo, Brazil

2012 ◽  
Vol 45 (5) ◽  
pp. 563-566 ◽  
Author(s):  
Sandra Baltazar Guatura ◽  
Aripuana Sakurada Aranha Watanabe ◽  
Clarice Neves Camargo ◽  
Ana Maria Passos ◽  
Sheila Negrini Parmezan ◽  
...  
Keyword(s):  
School Children ◽  
Influenza A ◽  
Respiratory Infections ◽  
Vaccination Campaign ◽  
Sao Paulo ◽  
Morbidity Rate ◽  
High Morbidity ◽  
São Paulo ◽  
High Morbidity Rate ◽  
Influenza A H1n1

INTRODUCTION: Influenza A H1N1 2009 is associated with a high morbidity rate among children around the world, including Brazil. This survey was conducted on samples of symptomatic children (< 12 years) to investigate the influenza virus as the etiological agent of respiratory infections in a day care school in a health facility during the first and second pandemic wave of H1N1 (2009-2010) in São Paulo, Brazil. METHODS: Influenza infections were determined by real-time PCR in 34% (47/137) of children with a median age of 5 years (8 months - 12 years), from June to October 2009 and in 16% (14/85) of those with median age of 6 years (1-12 years), from March to November 2010. RESULTS: In general, most positive cases (64%) occurred in children aged 5-12 years, this age group was significantly the most affected (39.8%, p = 0.001, OR = 8.3, CI 95% 1.9-36.9). Wheezing was reported by 31% (19/61) and dyspnea by 23% (14/61) of the studied patients. An outbreak of influenza H1N1 with an attack rate of 35.7% among children (median age 6 years) was documented in April 2010, before the vaccination campaign against the pandemic virus was extended for children up to 5 years in Brazil. CONCLUSIONS: Therefore, the study reinforces the recommendation to immunize school children to reduce the incidence of the disease.

scholarly journals Unsafe abortion among secondary school girls in a local authority in South-South Nigeria

2020 ◽  
Vol 9 (9) ◽  
pp. 3547
Author(s):  
Matthias G. Abah ◽  
Emem E. Bassey ◽  
Emmanuel B. Edu ◽  
Okupa D. Ovie
Keyword(s):  
Secondary School ◽  
Sex Education ◽  
Unwanted Pregnancy ◽  
Morbidity Rate ◽  
High Morbidity ◽  
School Students ◽  
Cross Sectional ◽  
Level Of Education ◽  
Dilation And Curettage ◽  
High Morbidity Rate

Background: Voluntary abortion for social reasons is illegal in Nigeria; however, the practice remains mostly clandestine and unsafe with varying consequences and determinants yet to be studied in all settings.Methods: A descriptive cross-sectional study design was used to assess the prevalence, practice and determinants of termination of pregnancy amongst 119 female Secondary School students in South-South Nigeria.Results: The prevalence of abortion was 57.1%. Most of the students were above 18years (58.8%), Christian (95.8%) and of rural residence (66.4%). While 58.8% had experienced an unwanted pregnancy, 61.4% had used some form of contraceptive with condom being the commonest (39.5%). Most (89.1%) have heard of abortions while 67.6% and 16.2% have had abortions once and twice respectively with the top reasons for abortion being that they were still in school (33.8%), too young (25.9%) and to avoid shame or stigma associated with the pregnancy (11.7%). Dilation and curettage was the predominant method employed (40.2%) mainly by medical doctors (34.1% and pharmacists (35.6%) while 51 (75%) had post-abortal complaints such as pain (41.2%) and bleeding (21.6%). There was a significant association between having an abortion and place of residence (rural more than urban), (p=0.04), being pregnant more than once (p<0.001), mothers` level of education (p=0.03), fathers` level of education (p=0.02) and mothers occupation (p=0.04).Conclusions: The prevalence of abortion is high and complicated by high morbidity rate despite a higher contraceptive prevalence rate whose major determinants were the socio-demographic characteristics of the parents. There is a need for early sex education from parents as this can influence abortion perception and practice in later years.

scholarly journals Monoclonal Antibodies in Multiple Sclerosis: Present and Future

Biomedicines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 20 ◽  
Author(s):  
Natalia Voge ◽  
Enrique Alvarez
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
Morbidity Rate ◽  
High Morbidity ◽  
Disease Modifying Therapies ◽  
High Morbidity Rate ◽  
New Treatments ◽  
Near Future ◽  
Risk Ratios

The global incidence of multiple sclerosis (MS) appears to be increasing. Although it may not be associated with a high mortality rate, this disease has a high morbidity rate which affects the quality of life of patients and reduces their ability to do their activities of daily living. Thankfully, the development of novel disease modifying therapies continues to increase. Monoclonal antibodies (MABs) have become a mainstay of MS treatment and they are likely to continue to be developed for the treatment of this disease. Specifically, MABs have proven to be some of the most efficacious treatments at reducing relapses and the inflammation in MS patients, including the first treatment for primary progressive MS and are being explored as reparative/remyelinating agents as well. These relatively new treatments will be reviewed here to help evaluate their efficacy, adverse events, immunogenicity, and benefit-risk ratios in the treatment of the diverse spectrum of MS. The focus will be on MABs that are currently approved or may be approved in the near future.

scholarly journals The Population Pharmacokinetics of Rifampicin in Japanese Pulmonary Tuberculosis Patients

Drug Research ◽  
2020 ◽  
Vol 70 (05) ◽  
pp. 199-205
Author(s):  
Takahiro Nishimura ◽  
Haruichi Kohno ◽  
Hideaki Nagai ◽  
Daisuke Maruoka ◽  
Yuichi Koike ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Japanese Patients ◽  
Morbidity Rate ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
High Morbidity ◽  
Power Model ◽  
Time Data ◽  
Nonlinear Mixed Effects Model ◽  
High Morbidity Rate

AbstractIn Japan, tuberculosis has been recognized as one of the major infections requiring urgent measures because of its high morbidity rate even now especially in elderly people suffering from tuberculosis during the past epidemic and its reactivation. Hence, many Japanese clinicians have made efforts to suppress the onset of tuberculosis and treat it effectively. The objectives of this study are to (1) identify covariate(s) that may explain the variation of rifampicin, which is the key antitubercular agent, under the steady-state by evaluating its population pharmacokinetics and (2) to propose an appropriate dosing method of rifampicin to Japanese patients. For this purpose, serum concentration–time data were obtained from 138 patients receiving rifampicin (300–450 mg) and isoniazid (300–400 mg) every day over 14 days, and analyzed using nonlinear mixed effects model. Thereby, population pharmacokinetic parameters were estimated followed by elucidating relations between the parameters and statistical factors. The analysis adopted one-compartment model including Lag-time by assuming that the absorption process is 0+1st order. The analyses demonstrate that meal affected the bioavailability, primary absorption rate constant, and zero order absorption time in the constructed model. A body weight calculated from the power model was selected as the covariate by the Stepwise Covariate Model method and found to highly affect the clearance in the range from −31.6% to 47.4%. We conclude that the dose in Japanese tuberculous patients can be well estimated by the power model formula and should be taken into consideration when rifampicin is administered.

High morbidity rate after converted laparoscopic colorectal surgery

1995 ◽  
Vol 82 (10) ◽  
pp. 1406-1408 ◽  
Author(s):  
K. Slim ◽  
D. Pezet ◽  
Y. Riff ◽  
E. Clark ◽  
J. Chipponi
Keyword(s):  
Colorectal Surgery ◽  
Laparoscopic Colorectal Surgery ◽  
Morbidity Rate ◽  
High Morbidity ◽  
High Morbidity Rate

scholarly journals Analysis Of Heart Decrease In Hypertension Patients With Karotis Artery Massage

2017 ◽  
Vol 1 (2) ◽  
pp. 1-5
Author(s):  
Asnidar ◽  
Tenriwati
Keyword(s):  
Public Health ◽  
Heart Rate ◽  
Carotid Artery ◽  
Health Center ◽  
Sampling Technique ◽  
Morbidity Rate ◽  
High Heart Rate ◽  
High Morbidity ◽  
Public Health Center ◽  
High Morbidity Rate

Hypertension is a disease that causes a high morbidity rate. The purpose of this study was to analyze the decrease in heart rate of hypertensive patients before and after doing massage on the carotid artery at the Bontobangun Public Health Center. design with population and sample that is all hypertension patients in Public Health Center of Bonto Public Health Center as many as 30 people. The sampling technique used was accidentaly sampling. The results of this study were in the pre-test there were 17 people (56.7%) who were in the category of moderate heart rate, 13 people (43.3%) high heart rate, in the post-test there were 25 people (83.3%) who had moderate heart rate , and 5 people (16.7%) had high heart rates. The conclusion of this study is that there is a decrease in heart rate of hypertension patients after carotid artery massage in public polyclinic public clinics at Bonto Wake with a value of p = 0.008 <α = 0.05. suggestions from this study are so that the results of this study can add a reference regarding carotid artery massage to decrease heart rate in patients with hypertension in the general poly bontobangun puskesmas.

scholarly journals SPINK7 Expression Changes Accompanied by HER2, P53 and RB1 may be Potential Biomarkers to Predict Oral Squamous Cell Carcinoma at Molecular Level

2020 ◽  
Author(s):  
Gina Penachiotti ◽  
Fabio Valdez ◽  
Wilfredo A González-Arriagada ◽  
Hector F Montes ◽  
Judith Parra ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Oral Lesion ◽  
Normal Mucosa ◽  
Morbidity Rate ◽  
High Morbidity ◽  
Less Invasive ◽  
High Morbidity Rate

Abstract Background. The oral squamous cell carcinoma (OSCC) affects more than 300,000 patients annually worldwide with a high morbidity rate (37.8%). Several tumor biomarkers have been suggested to anticipate outcome but results were poor. Changes of SPINK7 and associated proteins in precancerous oral lesions could lead to genomic instability and promote oncogenesis. Our aim was to evaluate SPINK7as apotential molecular biomarkerpredictive of OSCC stages, compared with well-known molecules altered in cancer: HER2,TP53, RB1, NFKB and CYP4B1. Methods.Oral biopsies from patientswith dysplasia (n=33), less invasive(n=28) andhighly invasiveOSCC (n=18) were collected. 20 cases with a clinical suspicion but normal mucosa confirmedwere included ascontrol. Gene expression of SPINK7, P53,RB, NFKBand CYP4B1 were quantified by qPCR.SPINK7 levels were correlated with a cohort of 330 patients from the TCGA. Also,SPINK7, HER2, TP53, and RB1, were evaluated by immunohistofluorescence. One-way Kruskal-Wallis test and Dunn's post-hocwith a p<0.05 significance were used to data analyze.Results.In OSCC, SPINK7wasdown regulated andP53, RB, NFKB and CYP4B1were up regulatedrespect tothe others groups (p<0.001). Also,SPINK7 expressionwasdiminished in patients of TCGA(p=2.10e-6). In less invasive OSCC,SPINK7 and HER2 proteinswere decreasedandTP53 and RB1 significantly increasedrespect todysplasia and highly invasivegroups (p<0.05).Conclusion. Our results suggest that SPINK7changes accompanied of HER2, P53 and RB1 can be used to classify the molecular stage of epithelial oral lesion inthe OSCC, allowing a more accuratediagnosis to molecular and histopathological level.

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