Dose-Response最新文献

{"title":"Dose-dependent Spasmolytic, Bronchodilator, and Hypotensive Activities of Panicum miliaceum L.","authors":"F. Saqib, Arwa A. Al-Huqail, Memona Asma, L. Chicea, M. Hogea, M. Irimie, C. Gavris","doi":"10.1177/15593258221079592","DOIUrl":"https://doi.org/10.1177/15593258221079592","url":null,"abstract":"Panicum miliaceum L. is a medicinally effective plant used in indigenous system of medicine for a variety of ailments. However, there is no comprehensive study explaining its effectiveness in gastrointestinal tract, respiratory, and cardiovascular system ailments. This study was designed to validate the pharmacological basis for the folkloric use of Panicum miliaceum L. in diarrhea, asthma, and hypertension. Panicum miliaceum extract was analyzed to detect the presence of bioactive compounds by HPLC. The isolated rabbit jejunum, trachea, and aorta were used for in vitro experiments using tissue bath assembly coupled with Power Lab data acquisition system to explore their relative effects. In-vivo experiments were performed for anti-diarrheal activity. HPLC analysis revealed the presence of gallic acid, butylated hydroxytoluene, catechin, and quercetin. Concentration dependent activities were observed by relaxing K+ (low) induced contractions having spasmolytic effect with EC50 = .358 ± .052, bronchodilator (EC50 = 2.483 ± .05793), and vasorelaxant (EC50 = .383 ± .063), probably due to the ATP dependent potassium channel activation. It was confirmed through pre-exposure of glibenclamide (specific ATP-dependent K+ channel blocker) having similarities with cromakalim. Pm.Cr revealed its antidiarrheal via in vivo experiments on rats. This study indicates that Panicum miliaceum has antidiarrheal, spasmolytic, bronchodilator, and vasorelaxant activities probably due to the ATP dependent K+ channel activation.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46502463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the Paradox of Smoking: Radioactivity in Tobacco Smoke or Suppressing the SARS-CoV-2 Receptor, Angiotensin-Converting Enzyme 2, via Aryl-Hydrocarbon Receptor Signal?","authors":"S. Mortazavi, J. Bevelacqua, Payman Rafiepour, A. Ghadimi-Moghadam, Pooya Saraie, Najmeh Jooyan, Seyedeh Hanieh Mortazavi, S. M. Javad Mortazavi, J. Welsh","doi":"10.1177/15593258221075111","DOIUrl":"https://doi.org/10.1177/15593258221075111","url":null,"abstract":"Despite current controversies, some reports show a paradoxical mitigating effect associated with smoking in individuals with symptomatic COVID-19 compared to the general population. To explain the potential mechanisms behind the lower number of hospitalized COVID-19 patients, it has been hypothesized that cigarette smoking may reduce the odds of cytokine storm and related severe inflammatory responses through cholinergic-mediated anti-inflammatory mechanisms. Japanese scientists have recently identified a potential mechanism behind the lower numbers of COVID-19 cases amongst smokers compared to non-smokers. However, we believe that this mitigative effect may be due to the relatively high concentration of deposited energy of alpha particles emitted from naturally occurring radionuclides such as Po-210 in cigarette tobacco. Regarding COVID-19, other researchers and our team have previously addressed the anti-inflammatory and immune-modulating effects of low doses of ionizing radiation. MC-simulation using the Geant4 Monte Carlo toolkit shows that the radiation dose absorbed in a spherical cell with a radius of .9 μm for a single 5.5 MeV alpha particle is about 5.1 Gy. This energy deposition may trigger both anti-inflammatory and anti-thrombotic effects which paradoxically lower the risk of hospitalization due to COVID-19 in smokers.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47164837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positive Cofactor 4 as a Potential Radiation Biodosimeter for Early Assessment","authors":"Le Ma, Q. Gong, Gaoyu Liu, Jieping Chen, Yu Wang, P. Luo, C. Shi","doi":"10.1177/15593258221081317","DOIUrl":"https://doi.org/10.1177/15593258221081317","url":null,"abstract":"During a major radiation event, a large number of people need to be rapidly assessed for radiation damage to ensure effective medical treatment and efficient use of medical resources. However, current techniques cannot meet the requirement of rapid detection of large quantities of samples in an emergency. It is essential to develop rapid and accurate radiation biodosimeters in peripheral blood. Here, we identified radiation sensitive genes in mice by RNA sequencing and evaluated their utility as radiation biodosimeters in human cell lines. Mice were subjected to gamma-irradiation with different doses (0–8 Gy, .85 Gy/min), and the tail venous blood was analyzed by RNA sequencing. We have identified 5 genes with significantly differential expression after radiation exposure. We found that positive cofactor 4(PC4) had well correlation with radiation dose in human lymphoblastoid cell line after irradiation. The relative expression of PC4 gene showed a good linear correlation with the radiation dose after 1–5 Gy irradiation (.85 Gy/min). PC4 gene can be rapidly recruited to the DNA damage sites faster than γ-H2AX after radiation in immunofluorescence detection. In conclusion, PC4 may be represented as new radiation biological dosimeter for early assessment.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46032326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dexmedetomidine Protects Against Kidney Fibrosis in Diabetic Mice by Targeting miR-101-3p-Mediated EndMT","authors":"Li Song, Songling Feng, Hao Yu, Sen Shi","doi":"10.1177/15593258221083486","DOIUrl":"https://doi.org/10.1177/15593258221083486","url":null,"abstract":"Objective: Our main purpose is to explore the effect and mechanism of Dexmedetomidine (DEX) in diabetic nephropathy fibrosis. Methods: Diabetic model was established by intraperitoneal injection of streptozotocin (STZ) treated CD-1 mice and high glucose cultured human dermal microvascular endothelial cells (HMVECs). Immunofluorescence was used to detect renal endothelial-mesenchymal transition (EndMT); Hematoxylin and Eosin (HE) staining and Masson’s Trichrome Staining (MTS) was used to analyze renal fibrosis; CCK-8 was used to evaluate cell viability; Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess the expression of miR-101-3p; Western blots were utilized to judge the protein expression levels of EndMT, extracellular matrix and TGF-β1/Smad3 signal pathway. Results: In this study, we first found that the protective effect of DEX on DN was related to EndMT. DEX alleviated kidney fibrosis by inhibiting EndMT in diabetic CD-1 mice. DEX could also inhibit high glucose-induced HMVECs EndMT. Then, we confirmed that miR-101-3p was the regulatory target of DEX. The expression of miR-101-3p was decreased in diabetic CD-1 mice and high glucose-induced HMVECs. After DEX treatment, the miR-101-3p increased, and the inhibition of miR-101-3p could counteract the protective effect of DEX and aggravate the EndMT. Finally, we found that the TGF- β1/Smad3 signal pathway was involved in the protective effect of DEX on DN. DEX inhibited the activation of TGF-β1/Smad3 signal pathway. On the contrary, inhibiting miR-101-3p promoted the expression of TGF-β1/Smad3. Conclusion: DEX protects kidney fibrosis in diabetic mice by targeting miR-101-3p-mediated EndMT.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48487125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Red Blood Cells and their Components in Medical Workers with Occupational Exposure to Low-Dose Ionizing Radiation","authors":"Xue-Lei Tian, X. Lu, Yumin Lyu, Hua Zhao, Qing-Jie Liu, Mei Tian","doi":"10.1177/15593258221081373","DOIUrl":"https://doi.org/10.1177/15593258221081373","url":null,"abstract":"Plenty of reports focus on the effects of low-dose radiation (LDR) on peripheral blood lymphocytes in radiation workers. However, studies on red blood cells (RBCs) in radiation workers are rarely reported. Many studies focused on investigate the hemogram of radiation staffs without detecting other components of RBCs. To explore the potential effect of LDR on RBCs, we detected the level of RBC count, hemoglobin, 2,3-disphosphoglycerate (2,3-DPG), and glutathione (GSH), and then analyzed the factors on these indices in 106 medical radiation workers. As a result, RBC count was affected by sex, age, type of work, length of service (only for females), and annual effective dose (only for males). Hemoglobin status was affected by sex, type of work, and annual effective dose (only for males). Sex, age, and type of work had no effects on the concentration of 2,3-DPG and GSH. Length of service affected 2,3-DPG concentration, and annual effective dose affected GSH level. In conclusion, chronic occupational LDR exposure may have an effect on RBC count, hemoglobin status, and the concentration of 2,3-DPG and GSH in radiation workers to some extent. However, it is still unknown how this kind of influence affects the health of radiation workers.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45391175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Building Blocks Towards a Proportionate Chemicals Policy With a Focus on the Netherlands","authors":"I. Helsloot, J. Hanekamp","doi":"10.1177/15593258221086475","DOIUrl":"https://doi.org/10.1177/15593258221086475","url":null,"abstract":"In this contribution, we propose that ‘sound’ government policy should be characterised by a proportionate, integral vision with due consideration to tradeoffs between social costs and benefits. This principle also applies to government policy regarding the protection of workers from exposure to chemicals. It should be taken into account that having a job is a huge health benefit. Less educated people are statistically likely to enjoy ten additional healthy years, if employed. Although there is no debate about the risks of exposure to high doses of chemicals, there is most certainly debate on the magnitude, nature and possible cumulative effects of low-dose exposure to chemicals. These are established by model-based assumptions. The current advisory structure in which the Health Council of the Netherlands restricts its focus to the immediate health benefits for workers on the basis of risk avoidance models, and the Social and Economic Council of the Netherlands which focuses primarily on policy costs for trade and industry, is hardly a sound basis for well-considered decision making. The challenge for the scientific experts is to provide political administrators with an insightful social cost-benefit analysis, including all the concomitant uncertainties.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41931930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Potential Protective Effect of Curcumin and α-Lipoic Acid on N-(4-Hydroxyphenyl) Acetamide-induced Hepatotoxicity Through Downregulation of α-SMA and Collagen III Expression","authors":"Ahlam Alhusain, Laila Fadda, W. Sarawi, Hatun A. Alomar, H. Ali, Raeesa Mahamad, I. Hasan, A. Badr","doi":"10.1177/15593258221078394","DOIUrl":"https://doi.org/10.1177/15593258221078394","url":null,"abstract":"Background and objectives N-(4-hydroxyphenyl) acetamide (NHPA) is the most commonly used analgesic and antipyretic agent worldwide; however, it remains the leading cause of drug-induced acute liver failure. This study explored the potential impact of curcumin (Curc) and/or α-lipoic acid (Lip acid) on liver damage induced by NHPA overdose. Materials and Methods Male Wistar rats were intoxicated with a single oral dose of NHPA (1000 mg/kg) and treated with Curc (200 mg/kg p. o.) and/or Lip acid (100 mg/kg i. p.). These treatments were given in 2 doses at 2 hours and 10 hours post-NHPA-administration. Animals were sacrificed 24 hours post-NHPA-administration. Results Treatment with Curc and/or Lip acid showed effective reduction of NHPA-induced liver injury, demonstrated by reducing serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, as well as hepatic nitric oxide and malondialdehyde. Curc and/or Lip acid treatments counteracted these changes. They also ameliorated NHPA-induced centrilobular hepatocellular necrosis, evidenced by histopathological examination. Moreover, Curc and Lip acid reduced the expression of alpha-smooth muscle actin and collagen III, upregulated by NHPA intoxication in response to oxidative stress and inflammation. Discussion and Conclusion Curc and Lip acid can be considered as promising natural therapies against liver injury, induced by NHPA, through their antioxidant and antifibrotic actions.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43209151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing Risk Perceptions of Low-Dose Radiation Exposure","authors":"Margot A. Hurlbert, Larissa Shasko, Michaela Neetz","doi":"10.1177/15593258221088428","DOIUrl":"https://doi.org/10.1177/15593258221088428","url":null,"abstract":"Concern over low-dose radiation (LDR) (exposure of less than 100 milligray (mGy)) is resulting in people refusing diagnostic procedures and medical treatment 1 and also inhibiting revision of the linear no-threshold (LNT) assumption that informs much of science policy. This article reviews representative surveys in Ontario and Saskatchewan and focus groups conducted with science and policy stakeholders in addressing how the public and policy stakeholders understand issues of exposure to LDR and how policy issues can be addressed. Research results from focus groups demonstrated that policy stakeholders are knowledgeable about issues surrounding the public and perceptions about LDR and implications for policy consistent with LDR literature. Participants understood that the challenge went beyond providing more education about LDR and issues of emotions and biases must be addressed. This research resulted in rich suggestions for public communication and engagement surrounding LDR and a process for addressing the issue of the LNT.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48030751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Radiological Problems in the Ukrainian War Zone and Challenges for Related Health Risks Assessments","authors":"B. Scott","doi":"10.1177/15593258221090091","DOIUrl":"https://doi.org/10.1177/15593258221090091","url":null,"abstract":"The seriously damaged Chernobyl nuclear power plant is located in the Ukrainian war zone. Intentional or accidental release via detonation of radionuclides from the plant site could pose serious health risks to the nearby population. Cancers in different organs are the main risk of concern for low radiation doses; however, the manner of assessing cancer risks is now controversial in that the linear-nothreshold (LNT) model used by epidemiologists (e.g., ) contradicts current knowledge of the chemico-biological interactions that occur in the body after low radiation doses and also promotes radiation phobia. Which other model to use is unclear. The previous Low Dose Radiation Research Program in the United States that partly focused on radiobiological research that was linked to improving health-risk-assessment approaches was unfortunately canceled about 10 years ago. In establishing an approach to use in addressing health risks for low radiation doses to humans, researchers need to take into consideration that unlike animal-studies data, epidemiologic-studies data for humans are very noisy (wider stochastic error distributions) 5 so that any risk estimates generated using such data likely involve large errors. Animal-studies data with smaller errors (for radiation doses and biological effects) than epidemiologic-studies data could be used in improving modeling methods employed in epidemiologic studies and in testing reliability of cancer risk predictions for low radiation doses. Regarding the risks of specific life-threatening deterministic effects of large radiation doses (unlikely to occur for most individuals in the Ukrainian war zone), the acute lethality and morbidity risks can be approximated using endpoint-specific, nonlinear, hazard-function (HF) models. These models feature dose and dose-rate-related thresholds and allow for external exposure to gamma radiation in combination with internal exposure via alphaparticle-, beta-particle-, and gamma-ray-emitting radionuclides. The HF models also address the complex doserate patterns that are associated with internal radionuclides and can be implemented using existing computer code systems developed in the United States and in Europe for assessing expected health consequences of nuclear power plant accidents for given populations; however, parameters for the endpoint-specific HF models were estimated using deficient data that were available at the time the models were developed (i.e., prior to 1995). Thus, parameters for endpoint-specific HF models need to be updated using now-available data and the updated parameter estimates (and related uncertainties) need to be incorporated into computer codes used in assessing risks (and related uncertainties) of radiation deterministic health effects that include specific morbidity types and lethality modes.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42986670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cefepime Dosing Requirements in Elderly Patients Attended in the Emergency Rooms","authors":"J. Ruiz-Ramos, Sergio Herrera-Mateo, L. López-Vinardell, A. Juanes-Borrego, M. Puig-Campmany, M. A. Mangues-Bafalluy","doi":"10.1177/15593258221078393","DOIUrl":"https://doi.org/10.1177/15593258221078393","url":null,"abstract":"Objective This study aimed to assess the probability of reaching an adequate pharmacokinetic/pharmacodynamic (pK/pD) index for different cefepime dosages in frail patients with bacteremia treated in the emergency room. Methods Simulation study based on Gram-negative bacterial strains that cause bacteremia. The probability of reaching a time above the minimum inhibitory concentration (MIC) at 50% and 100% dosing intervals (fT > 50 and fT > 80% MIC) was assessed for two different renal clearance intervals. Results One hundred twenty nine strains were collected, the predominant species being Escherichia coli (n = 83 [64.3%]). In patients with a ClCr of 30 mL/min, an fT > 50% MIC was reached in more than 90% of the simulations. However, a dose of at least 1 g every 12 h must be administered to reach an fT > 80% MIC. In patients with a ClCr of 30–60 mL/min, the probability of reaching an fT > 50% MIC was higher than 90% with doses of 1 g every 8 h or more, but this value was not reached in > 90% simulations for any of the doses tested in this study. Conclusions Standard cefepime dosing can reach an adequate PK/PD index in frail patients. Nevertheless, a high dose or extended infusion is necessary to reach an fT > 80% MIC in patients with a ClCr > 60 mL/min.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48332658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}