scholarly journals Quantification of the Relationship between Bacterial Kinetics and Host Response for Monkeys Exposed to AerosolizedFrancisella tularensis

2010 ◽  
Vol 77 (2) ◽  
pp. 485-490 ◽  
Author(s):  
Yin Huang ◽  
Charles N. Haas
Keyword(s):  
Survival Data ◽  
Count Data ◽  
Host Response ◽  
Growth Curves ◽  
Bacterial Count ◽  
Extensive Literature ◽  
Schu S4 ◽  
The Relationship ◽  
Dose Dependent

ABSTRACTFrancisella tularensiscan be disseminated via aerosols, and once inhaled, only a few microorganisms may result in tularemia pneumonia. Effective responses to this threat depend on a thorough understanding of the disease development and pathogenesis. In this study, a class of time-dose-response models was expanded to describe quantitatively the relationship between the temporal probability distribution of the host response and thein vivobacterial kinetics. An extensive literature search was conducted to locate both the dose-dependent survival data and thein vivobacterial count data of monkeys exposed to aerosolizedF. tularensis. One study reporting responses of monkeys to four different sizes of aerosol particles (2.1, 7.5, 12.5, and 24.0 μm) of the SCHU S4 strain and three studies involving fivein vivogrowth curves of various strains (SCHU S4, 425, and live vaccine strains) initially delivered to hosts in aerosol form (1 to 5 μm) were found. The candidate models exhibited statistically acceptable fits to the time- and dose-dependent host response and provided estimates for the bacterial growth distribution. The variation pattern of such estimates with aerosol size was found to be consistent with the reported pathophysiological and clinical observations. The predicted growth curve for 2.1-μm aerosolized bacteria was highly consistent with the available bacterial count data. This is the first instance in which the relationship between thein vivogrowth ofF.tularensisand the host response can be quantified by mechanistic mathematical models.

scholarly journals Dusart syndrome: a new concept of the relationship between fibrin clot architecture and fibrin clot degradability: hypofibrinolysis related to an abnormal clot structure

Blood ◽  
1993 ◽  
Vol 82 (8) ◽  
pp. 2462-2469 ◽  
Author(s):  
JP Collet ◽  
J Soria ◽  
M Mirshahi ◽  
M Hirsch ◽  
FB Dagonnet ◽  
...  
Keyword(s):  
Blood Clot ◽  
Fibrin Clot ◽  
Important Change ◽  
High Incidence ◽  
Gel Porosity ◽  
Clot Structure ◽  
The Relationship ◽  
Dose Dependent ◽  
Thrombotic Disorder

Fibrinogen Dusart is a congenital dysfibrinogenemia (A-alpha 554 Arginine-->Cysteine) associated with severe thrombotic disorder, high incidence of thrombotic embolism, and abnormal fibrin polymerization. This thrombotic disorder was attributed to an abnormal clot thrombolysis with reduced plasminogen binding to fibrin and defective plasminogen activation by tissue plasminogen activator. The purpose of this work was to assess whether clot architecture could be involved in the thromboresistance of the fibrin Dusart and the high incidence of embolism. An important change in Dusart fibrin clot structure was identified with dramatic decrease of gel porosity (Ks), fiber diameters (d), and fiber mass-length ratios (mu) derived from permeation analysis. In addition, rigidity of the Dusart clot was found to be greatly increased compared with normal fibrin. We provide evidence that both thrombolysis resistance and abnormal rigidity of the fibrin Dusart are related to this abnormal architecture, which impairs the access of fibrinolytic enzymes to the fibrin and which is responsible for a brittle clot that breaks easily, resulting in a high incidence of embolism. Indeed, when restoring a normal clot structure by adding dextran 40 (30 mg/mL) before coagulation, clot thrombolysis and clot rigidity recovered normal values. This effect was found to be dose- dependent. We conclude that clot architecture is crucial for the propensity of blood clot to be degraded and that abnormal clot structure can be highly thrombogenic in vivo. The alpha-C domains of fibrinogen are determinant in fibrin clot structure.

scholarly journals Dusart syndrome: a new concept of the relationship between fibrin clot architecture and fibrin clot degradability: hypofibrinolysis related to an abnormal clot structure

Blood ◽  
1993 ◽  
Vol 82 (8) ◽  
pp. 2462-2469 ◽  
Author(s):  
JP Collet ◽  
J Soria ◽  
M Mirshahi ◽  
M Hirsch ◽  
FB Dagonnet ◽  
...  
Keyword(s):  
Blood Clot ◽  
Fibrin Clot ◽  
Important Change ◽  
High Incidence ◽  
Gel Porosity ◽  
Clot Structure ◽  
The Relationship ◽  
Dose Dependent ◽  
Thrombotic Disorder

Abstract Fibrinogen Dusart is a congenital dysfibrinogenemia (A-alpha 554 Arginine-->Cysteine) associated with severe thrombotic disorder, high incidence of thrombotic embolism, and abnormal fibrin polymerization. This thrombotic disorder was attributed to an abnormal clot thrombolysis with reduced plasminogen binding to fibrin and defective plasminogen activation by tissue plasminogen activator. The purpose of this work was to assess whether clot architecture could be involved in the thromboresistance of the fibrin Dusart and the high incidence of embolism. An important change in Dusart fibrin clot structure was identified with dramatic decrease of gel porosity (Ks), fiber diameters (d), and fiber mass-length ratios (mu) derived from permeation analysis. In addition, rigidity of the Dusart clot was found to be greatly increased compared with normal fibrin. We provide evidence that both thrombolysis resistance and abnormal rigidity of the fibrin Dusart are related to this abnormal architecture, which impairs the access of fibrinolytic enzymes to the fibrin and which is responsible for a brittle clot that breaks easily, resulting in a high incidence of embolism. Indeed, when restoring a normal clot structure by adding dextran 40 (30 mg/mL) before coagulation, clot thrombolysis and clot rigidity recovered normal values. This effect was found to be dose- dependent. We conclude that clot architecture is crucial for the propensity of blood clot to be degraded and that abnormal clot structure can be highly thrombogenic in vivo. The alpha-C domains of fibrinogen are determinant in fibrin clot structure.

scholarly journals The correlation between IL-33 and inflammation factors in rheumatoid arthritis patients in vivo and in fibroblast-like synoviocytes in vitro

2020 ◽  
Author(s):  
Jing Wu ◽  
Qiang Li ◽  
Jia-Xin Deng ◽  
Jin-Jun Zhao ◽  
Qing-Hong Yu
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Interleukin 33 ◽  
Cytokines And Chemokines ◽  
Dependent Relationship ◽  
The Relationship ◽  
Dose Dependent ◽  
Fibroblast Like Synoviocytes

Abstract Background: Interleukin-33 (IL-33) is a member of the IL-1 family of cytokines whose role remains controversial in rheumatoid arthritis (RA), because no clear conclusion has been established regarding the relationship between IL-33 and other cytokines and chemokines. The present study was conducted to evaluate the correlation of IL-33 with other cytokines and chemokines in serum and the synovia, and to explore the nature of the relationship.Results: IL-33 was found to exhibit an inverted-U-shaped correlation with multiple cytokines and chemokines in synovial fluid, including IL-6, IL-1β, CXCL8 (IL-8), CXCL9 (MIG) and CXCL10 (IP-10), but not in serum. Moreover, in vitro experiments confirmed that IL-33 also exhibits U-type dose-dependent regulation of FLS function.Conclusions: IL-33 exhibit an inverted-U-shaped correlation with multiple cytokines and chemokines in synovial fluid of RA patients. IL-33 affects the secretion of cytokines and chemokines in the synovium in a U-type dose-dependent relationship.

scholarly journals Physiological and Pathological Role of Circadian Hormones in Osteoarthritis: Dose-Dependent or Time-Dependent?

2019 ◽  
Vol 8 (9) ◽  
pp. 1415 ◽  
Author(s):  
Farhad Md. Hossain ◽  
Yunkyung Hong ◽  
Yunho Jin ◽  
Jeonghyun Choi ◽  
Yonggeun Hong
Keyword(s):  
Circadian Clock ◽  
Thyroid Stimulating Hormone ◽  
Cartilage Erosion ◽  
The Relationship ◽  
Dose Dependent ◽  
Different Levels ◽  
Pro Inflammatory Cytokines

Osteoarthritis (OA), the most common form of arthritis, may be triggered by improper secretion of circadian clock-regulated hormones, such as melatonin, thyroid-stimulating hormone (TSH), or cortisol. The imbalance of these hormones alters the expression of pro-inflammatory cytokines and cartilage degenerative enzymes in articular cartilage, resulting in cartilage erosion, synovial inflammation, and osteophyte formation, the major hallmarks of OA. In this review, we summarize the effects of circadian melatonin, TSH, and cortisol on OA, focusing on how different levels of these hormones affect OA pathogenesis and recovery with respect to the circadian clock. We also highlight the effects of melatonin, TSH, and cortisol at different concentrations both in vivo and in vitro, which may help to elucidate the relationship between circadian hormones and OA.

scholarly journals Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application

2015 ◽  
Vol 2015 ◽  
pp. 1-23 ◽  
Author(s):  
Romilly E. Hodges ◽  
Deanna M. Minich
Keyword(s):  
Genetic Polymorphisms ◽  
Cytochrome P450 Enzymes ◽  
Scientific Review ◽  
Disease States ◽  
Metabolic Detoxification ◽  
The Relationship ◽  
Dose Dependent ◽  
Improve Patient ◽  
Detoxification Pathways

Research into human biotransformation and elimination systems continues to evolve. Various clinical andin vivostudies have been undertaken to evaluate the effects of foods and food-derived components on the activity of detoxification pathways, including phase I cytochrome P450 enzymes, phase II conjugation enzymes, Nrf2 signaling, and metallothionein. This review summarizes the research in this area to date, highlighting the potential for foods and nutrients to support and/or modulate detoxification functions. Clinical applications to alter detoxification pathway activity and improve patient outcomes are considered, drawing on the growing understanding of the relationship between detoxification functions and different disease states, genetic polymorphisms, and drug-nutrient interactions. Some caution is recommended, however, due to the limitations of current research as well as indications that many nutrients exert biphasic, dose-dependent effects and that genetic polymorphisms may alter outcomes. A whole-foods approach may, therefore, be prudent.

scholarly journals ADGRG1 Is a Predictor of Chemoresistance and Poor Survival in Cervical Squamous Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Shuo Zhang ◽  
Kui Guo ◽  
Ying Liang ◽  
Kun Wang ◽  
Shuyan Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Survival Data ◽  
Molecular Mechanisms ◽  
Cell Model ◽  
Squamous Carcinoma ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
The Relationship

BackgroundCisplatin is the first-line chemotherapy for cervical cancer. Cisplatin resistance has always been one of the most significant barriers to acquiring better outcomes. However, the complex molecular mechanisms accounting for the phenomenon are not completely clear.MethodsConstruction of the cisplatin-resistant cell model of cervical cancer, then performing RNA sequencing and bioinformatic analysis of the differential expression genes. Then Adhesion G protein-coupled receptor G1 (ADGRG1) was screened out as our target gene. Gene Expression Profiling Interactive Analysis (GEPIA) was searched to show the expression level of ADGRG1 in cervical cancer and normal tissue. Kaplan-Meier Plotter (Kmplot) was used to explore the relationship of its expression with survival data. Tissue specimens were used to verify the relationship between the clinicopathological characteristics and ADGRG1 expression. Then we explored the roles of ADGRG1 in tumorigenesis through in vitro and in vivo assays.ResultsWe found the ADGRG1 was significantly overexpressed in cervical cancer tissues compared to corresponding normal tissues. Higher ADGRG1 expression was correlated with poor progress-free survival. Knockdown of ADGRG1 markedly suppressed cell proliferation, migration, and invasion and increased cell sensitivity to cisplatin in vitro. Similarly, the role of ADGRG1 knockdown on tumorigenicity and sensitivity to cisplatin treatment was verified in vivo. The underlying mechanism was explored by western blotting that ADGRG1 knockdown inhibited tumorigenesis by PI3K/Akt/mTOR signaling pathway.ConclusionADGRG1 acts as an oncogene to maintain tumorigenicity, migration, and invasion, and its depressed expression prompts sensitivity to cisplatin. Thus, ADGRG1 may represent a potential prognostic marker and possible therapeutic target for cervical cancer.

Skin Organ Culture as an Alternative to In Vivo Dermatotoxicity Testing

1993 ◽  
Vol 21 (4) ◽  
pp. 443-449
Author(s):  
Johannes J.M. van de Sandt ◽  
Jacqueline van Schoonhoven ◽  
Wilfred J.M. Maas ◽  
Alphons A.J.J.L. Rutten
Keyword(s):  
Organ Culture ◽  
Chloroacetic Acid ◽  
Tetrazolium Salt ◽  
Dependent Manner ◽  
Cutaneous Toxicity ◽  
Culture Model ◽  
The Relationship ◽  
Dose Dependent ◽  
Skin Organ Culture

Various aspects of acute cutaneous toxicity were studied in a skin organ culture model. Chemicals were applied topically for four hours, after which cytotoxicity was assessed by measuring the conversion of the tetrazolium salt, MTT. The relationship between pKa and cytotoxicity was investigated for a homologous series of benzoic acids. In this series, salicylic acid had the lowest pKa and proved to be the most toxic compound. Furthermore, the pH of the carrier solution was shown to influence the toxicity of chloroacetic acid and acetic acid in a different way. Using skin discs of both human and rabbit origin, we found that human skin was more resistant to toxicity induced by the irritants benzalkonium chloride and formaldehyde. As an additional aspect of dermal toxicology, the percutaneous absorption of testosterone was studied. After topical application to rabbit skin discs, testosterone was absorbed in a dose-dependent manner and concurrent metabolism was demonstrated.

Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

1982 ◽  
Vol 40 ◽  
pp. 210-211
Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman
Keyword(s):  
Cultured Cells ◽  
Human Tumor ◽  
Cell Type ◽  
Tumor Mass ◽  
Initial Cell ◽  
Cloning Assay ◽  
Human Tumor Cloning ◽  
The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

Do Extra-Platelet Sources Contribute to the Plasma Level of Thrombospondin?

1988 ◽  
Vol 59 (02) ◽  
pp. 273-276 ◽  
Author(s):  
J Dawes ◽  
D A Pratt ◽  
M S Dewar ◽  
F E Preston
Keyword(s):  
Platelet Count ◽  
Background Concentration ◽  
Serum Concentrations ◽  
Bone Marrow Depression ◽  
Serial Sampling ◽  
Control Serum ◽  
Platelet Release ◽  
Highly Correlated ◽  
The Relationship

SummaryThrombospondin, a trimeric glycoprotein contained in the platelet α-granules, has been proposed as a marker of in vivo platelet activation. However, it is also synthesised by a range of other cells. The extraplatelet contribution to plasma levels of thrombospondin was therefore estimated by investigating the relationship between plasma thrombospondin levels and platelet count in samples from profoundly thrombocytopenic patients with marrow hypoplasia, using the platelet-specific α-granule protein β-thromboglobulin as control. Serum concentrations of both proteins were highly correlated with platelet count, but while plasma β-thromboglobulin levels and platelet count also correlated, there was no relationship between the number of platelets and thrombospondin concentrations in plasma. Serial sampling of patients recovering from bone marrow depression indicated that the plasma thrombospondin contributed by platelets is superimposed on a background concentration of at least 50 ng/ml probably derived from a non-platelet source, and plasma thrombospondin levels do not simply reflect platelet release.

Involvement of 5-Hydroxytryptamine in Platelet Aggregation In Vivo in Rats and Guinea Pigs

1989 ◽  
Vol 61 (03) ◽  
pp. 463-467 ◽  
Author(s):  
G M Smith
Keyword(s):  
Platelet Count ◽  
Guinea Pigs ◽  
Platelet Adhesion ◽  
Adenosine Diphosphate ◽  
Rate Of Return ◽  
Low Doses ◽  
Dose Dependent ◽  
Higher Doses ◽  
Rat Platelets

SummaryIn this study, 5-hydroxytryptamine (5-HT) caused a dose- dependent fall in the circulating platelet count suggesting that 5-HT receptors are activated in rat platelets to cause platelet adhesion and aggregation. When low doses of adenosine diphosphate (ADP) were simultaneously injected with 5-HT, there was a significant potentiation of the responses to ADR Ketanserin significantly reduced the potentiated responses. When higher doses of ADP were infused with bolus injections of 5-HT there was no potentiation and ketanserin did not reduce these responses. Ketanserin did not inhibit the collagen-induced fall in circulating platelet count, but did significantly increase the rate of return to the basal platelet count compared with control. 5-HT did not cause a fall in platelet count in guinea-pigs

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