Amplification of steroid-mediated SP-B expression by physiological levels of caffeine

Factors positively influencing surfactant homeostasis in general and surfactant protein B (SP-B) expression in particular are considered of clinical importance regarding an improvement of lung function in preterm infants. The objective of this study was to identify effects of physiological levels of caffeine on glucocorticoid-mediated SP-B expression in vitro and in vivo. Levels of SP-B and pepsinogen C were quantified by quantitative real-time RT-PCR or immunoblotting in NCI-H441 cells daily exposed to caffeine and/or dexamethasone (DEX). In vivo, SP-B expression was analyzed in bronchoalveolar lavage (BAL) of preterm sheep exposed to antenatal DEX and/or postnatal caffeine. If DEX and caffeine were continuously present, SP-B mRNA and protein levels were increased for up to 6 days after induction ( P < 0.05). Additionally, caffeine enhanced SP-B mRNA expression in DEX-pretreated cells ( P < 0.05). Moreover, caffeine amplified DEX-induced pepsinogen C mRNA expression ( P < 0.05). After short-term treatment with caffeine in vivo, only slightly higher SP-B levels could be detected in BAL of preterm sheep following antenatal DEX, combined with an increase of arterial oxygen partial pressure ( P < 0.01). Our data demonstrated that the continuous presence of caffeine in vitro is able to amplify DEX-mediated SP-B expression. In contrast, short-term improvement of lung function in vivo is likely to be independent of altered SP-B transcription and translation. An impact of caffeine on release of surfactant reservoirs from lamellar bodies could, however, quickly affect SP-B content in BAL, which has to be further investigated. Our findings indicate that caffeine is able to amplify main effects of glucocorticoids that result from changes in surfactant production, maturation, and release.

Download Full-text

Evaluation of cytotoxicity and mutagenicity of the benzodiazepine flunitrazepam in vitro and in vivo

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502014000200003 ◽

2014 ◽

Vol 50 (2) ◽

pp. 251-256

Author(s):

Igor Vivian de Almeida ◽

Giovana Domingues ◽

Lilian Capelari Soares ◽

Elisângela Düsman ◽

Veronica Elisa Pimenta Vicentini

Keyword(s):

Rattus Norvegicus ◽

Bone Marrow Cells ◽

Micronucleus Test ◽

Term Treatment ◽

Genotoxic Effects ◽

Short Term ◽

Short Term Treatment ◽

Chromosomal Aberration Test

Flunitrazepam (FNZ) is a sedative benzodiazepine prescribed for the short-term treatment of insomnia. However, there are concerns regarding possible carcinogenic or genotoxic effects of this medicine. Thus, the aim of this study was to evaluate the cytotoxic, clastogenic and aneugenic effects of FNZ in hepatoma cells from Rattus norvegicus (HTC) in vitro and in bone marrow cells of Wistar rats in vivo. These effects were examined in vitro following treatment with 0.2, 1.0, 5.0 or 10 μg/mL FNZ using a micronucleus test with a cytokinesis block or in vivo using a chromosomal aberration test following treatment with 7, 15 or 30 μg/mL/kg body weight. The results showed that the benzodiazepine concentrations tested were not cytotoxic, aneugenic or clastogenic. However, considering the adverse effects of using this benzodiazepine, more studies are required.

Download Full-text

Activity of ketoconazole against Mycobacterium tuberculosis in vitro and in the mouse model

Journal of Medical Microbiology ◽

10.1099/jmm.0.47058-0 ◽

2007 ◽

Vol 56 (8) ◽

pp. 1047-1051 ◽

Cited By ~ 24

Author(s):

Sean T. Byrne ◽

Steven M. Denkin ◽

Peihua Gu ◽

Eric Nuermberger ◽

Ying Zhang

Keyword(s):

Mycobacterium Tuberculosis ◽

Term Treatment ◽

New Drugs ◽

Bacteriostatic Effect ◽

Short Term ◽

Short Term Treatment ◽

Neutral Conditions

There is an urgent need for the development of new drugs that are active against drug-resistant Mycobacterium tuberculosis strains and can shorten tuberculosis (TB) therapy. It has previously been reported that the azole class of antifungals has anti-TB activity in vitro. This study evaluated ketoconazole (KTC) for activity against M. tuberculosis. The MIC of KTC for different M. tuberculosis strains ranged from 8 to 16 μg ml−1 under both acidic and neutral conditions, with the minimum bactericidal concentration being about twofold higher than the MIC. KTC had enhanced activity against old, non-growing bacilli in vitro when combined with pyrazinamide (PZA) and rifampicin (RIF). A single oral dose of KTC at 75 mg kg−1 led to an inhibitory serum concentration 2 h after administration. The in vivo activity of KTC was evaluated in established pulmonary TB in the murine model, compared alone and in combination with isoniazid (INH), PZA and RIF. KTC alone exhibited little effect after short-term treatment, with a borderline bacteriostatic effect on spleen colony counts but not on lung counts. KTC, when added in combination with INH, PZA and RIF, significantly improved the treatment outcome in the lungs (compared with treatment with INH, PZA and RIF). The lowest numbers of bacilli in lungs were found in mice treated with KTC, PZA and RIF. Further investigation is necessary to determine the role of KTC in the treatment of TB.

Download Full-text

Pepsinogen C: a type 2 cell-specific protease

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00310.2003 ◽

2004 ◽

Vol 286 (2) ◽

pp. L382-L387 ◽

Cited By ~ 37

Author(s):

Cherie Foster ◽

Amana Aktar ◽

Denel Kopf ◽

Peggy Zhang ◽

Susan Guttentag

Keyword(s):

Cell Differentiation ◽

Developmental Regulation ◽

Fetal Lung ◽

Surfactant Protein ◽

Specific Marker ◽

Pepsinogen C ◽

Adult Lung

Pepsinogen C, also known as progastricsin or pepsinogen II, is an aspartic protease expressed primarily in gastric chief cells. Prior microarray studies of an in vitro model of type 2 cell differentiation indicated that pepsinogen C RNA was highly induced, comparable to surfactant protein RNA induction. Using second-trimester human fetal lung, third-trimester postnatal and adult lung, and a model of type 2 cell differentiation, we examined the specificity of pepsinogen C expression in lung. Pepsinogen C RNA and protein were only detected in >22 wk gestation samples of neonatal lung or in adult lung tissue. By immunohistochemistry and in situ hybridization, pepsinogen C expression was restricted to type 2 cells. Pepsinogen C expression was rapidly induced during type 2 cell differentiation and rapidly quenched with dedifferentiation of type 2 cells after withdrawal of hormones. In all samples, pepsinogen C expression occurred concomitantly with or in advance of processing of surfactant protein-B to its mature 8-kDa form. Our results indicate that pepsinogen C is a type 2 cell-specific marker that exhibits tight developmental regulation in vivo during human lung development, as well as during in vitro differentiation and dedifferentiation of type 2 cells.

Download Full-text

Short-term treatment with mycophenolic acid and tacrolimus is tolerogenic for INS-1 cell clone transplantation and the deleterious effects of the drugs are limited: in vivo and in vitro studies

Journal of Endocrinology ◽

10.1677/joe.1.06122 ◽

2005 ◽

Vol 186 (1) ◽

pp. 213-220

Author(s):

M Asfari ◽

S Berta ◽

S Coffy ◽

M Kergoat ◽

C Charon ◽

...

Keyword(s):

Mycophenolic Acid ◽

Cell Clone ◽

Day Treatment ◽

Immunosuppressive Drugs ◽

Term Treatment ◽

Β Cell ◽

Short Term ◽

Short Term Treatment

One of the major requirements for a successful and life-lasting organ transplant is the access to safe, least toxic and permanent tolerance-inducing drugs. In this study we wished to evaluate the effects of tolerogenic doses of the immunosuppressive drugs mycophenolic acid (MPA) and tacrolimus (Tac) on clonal β-cell lines, both in vivo and in vitro. Here we demonstrate that combined administration of low-dose MPA and Tac for 23 days induced permanent tolerance in an allogeneic β-cell line transplant in Wistar rat liver through the portal vein. This short-term treatment of tolerogenic doses of the two drugs was deleterious to the survival of the transplanted cells but a small percentage of the cells could resist the effect and become fully active when the drugs were removed. The surviving cells, retrieved from growth in vivo, did not exhibit increased resistance in comparison to the original cells when tested in vitro at two glucose concentrations, 10 and 20 mM. The presence of a small percentage of resistant cells at the two glucose concentrations was also detected in the in vitro study after a continuous 8-day treatment demonstrating that the in vivo resistance was not related to micro-environmental protection but possibly to a phenotypic cell state that is yet to be determined.

Download Full-text

Lymphocyte Immunoglobulin Secretion during Short-term Treatment with Cephalosporins in Vivo and in Vitro: Effects on Plaque-forming Cell Response of Human Peripheral Blood Lymphocytes

Scandinavian Journal of Infectious Diseases ◽

10.3109/00365548609032311 ◽

1986 ◽

Vol 18 (1) ◽

pp. 83-84

Author(s):

Palle Tauris ◽

Finn T. Black

Keyword(s):

Cell Response ◽

Human Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Term Treatment ◽

Short Term ◽

Short Term Treatment ◽

Human Peripheral Blood Lymphocytes ◽

In Vitro Effects

Download Full-text

DER TSH-RESERVE-TEST AN DER RATTE

Acta Endocrinologica ◽

10.1530/acta.0.0440570 ◽

1963 ◽

Vol 44 (4) ◽

pp. 570-580 ◽

Cited By ~ 2

Author(s):

H. W. Iff ◽

H. Studer ◽

F. Wyss

Keyword(s):

Time Course ◽

Term Treatment ◽

Short Term ◽

Iodide Uptake ◽

Short Term Treatment ◽

Similar Time ◽

Clinical Method ◽

Tsh Secretion

ABSTRACT A rebound of 131I-uptake by the thyroid gland after a thyrostatic treatment may be taken as evidence of an unimpaired pituitary TSH-secretion. The iodide uptake in vivo and the iodide accumulation in vitro were studied in rat thyroids following a short-term treatment of the animals with carbimazole. The experiments served as models for the clinical method of assaying the pituitary TSH-reserve. The total iodide uptake reaches a peak 36 hours after the end of a carbimazole treatment and returns to normal after 96 hours. The rebound of the iodide accumulation has a similar time course. Extending the carbimazole treatment from 6 to 12 days leads to a definite increase in the peak iodide accumulation while the peak of the total iodide uptake was not significantly increased. The duration of the rebound-phase is not changed by prolonged carbimazole treatment.

Download Full-text

Unsuccessful intravenous D-mannose treatment in PMM2-CDG

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-019-1213-3 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 5

Author(s):

Sarah C. Grünert ◽

Thorsten Marquardt ◽

Ekkehart Lausch ◽

Hans Fuchs ◽

Christian Thiel ◽

...

Keyword(s):

Term Treatment ◽

First Year ◽

Short Term ◽

Multisystem Disorder ◽

Short Term Treatment ◽

Congenital Disorder Of Glycosylation ◽

First Year Of Life ◽

Glycosylation Defect

Abstract Background PMM2-CDG (Phosphomannomutase 2 - Congenital disorder of glycosylation-Ia; CDG-Ia) is the most common glycosylation defect, often presenting as a severe multisystem disorder that can be fatal within the first years of life. While mannose treatment has been shown to correct glycosylation in vitro and in vivo in mice, no convincing effects have been observed in short-term treatment trials in single patients so far. Results We report on a boy with a severe PMM2-CDG who received a continuous intravenous mannose infusion over a period of 5 months during the first year of life in a dose of 0.8 g/kg/day. N-glycosylation of serum glycoproteins and mannose concentrations in serum were studied regularly. Unfortunately, no biochemical or clinical improvement was observed, and the therapy was terminated at age 9 months. Conclusion Postnatal intravenous D-mannose treatment seems to be ineffective in PMM2-CDG.

Download Full-text

PM2.5 Induced Airway Remodeling via Wnt5a/β-catenin Pathway in Chronic Obstructive Pulmonary Diseases

10.21203/rs.3.rs-775888/v1 ◽

2021 ◽

Author(s):

Weifeng Zou ◽

Xiaoqian Wang ◽

Ruiting Sun ◽

Jinxing Hu ◽

Dong Ye ◽

...

Keyword(s):

Smooth Muscle ◽

Lung Function ◽

Protein Expression ◽

Mrna Expression ◽

Airway Remodeling ◽

C Protein ◽

Tenascin C ◽

Tgf Β1

Abstract Background: PM2.5-associated airway remodeling has recently been recognized as a central feature of COPD. The activation of Wnt/β-catenin pathway is closely related to the occurrence of airway remodeling. Accordingly, the goal of this study was to determine whether Wnt5a/β-Catenin is involved in PM2.5-induced smooth muscle proliferation in vivo and vitro, which promoted the development of airway remodeling in COPD.Methods: The effect of Wnt5a on β-Catenin-mediated airway remodeling was assessed by using an in vivo model of PM2.5-induced COPD and PM2.5-exposed human bronchial smooth muscle cell (HBSMC) in vitro. Small animal spirometry to measure lung function in mice. H&E staining and immunohistological inspection of emphysema and airway remodeling indexes. qPCR to detect Wnt5a, β-Catenin, TGF-β1, CyclinD1 and c-myc mRNA expression. CCK8 assay for cellular activity. Western blotting for PCNA, α-SMA, Wnt5a, β-Catenin, PDGFRβ and TenascinC protein expression. Detection of β-Catenin expression by cellular immunofluorescence.Results: The exposure to PM2.5 led to emphysema, airway wall thickening, increased smooth muscle layer thickness, decreased lung function and induced the expression of Wnt5a, β-Catenin, PDGFRβ and Tenascin C protein expression in lung tissue of mice. BOX5 alleviated PM2.5-induced these outcomes in mice. Moreover, PM2.5 induced the mRNA expression of Wnt5a, β-Catenin, TGF-β1, CyclinD1 and c-myc in HBSMC. BOX5 also inhibited PM2.5-induced the increase of PCNA, α-SMA, Wnt5a, β-Catenin, PDGFRβ and Tenascin C protein expression in HBSMC. Conclusions: Our findings suggest that PM2.5 exposure induce HBSMC proliferation, contributing to airway remodeling via Wnt5a/β-Catenin signaling pathway in vivo and in vitro, which could be a target of treatment of COPD.

Download Full-text

Healing effects of curcumin nanoparticles in deep tissue injury mouse model.

Current Drug Delivery ◽

10.2174/1567201818666201214125237 ◽

2020 ◽

Vol 18 ◽

Author(s):

Zirui Zhang ◽

Shangcong Han ◽

Panpan Liu ◽

Xu Yang ◽

Jing Han ◽

...

Keyword(s):

Wound Healing ◽

Mrna Expression ◽

Tissue Injury ◽

Inflammatory Cells ◽

Pcr Analysis ◽

Protective Effects ◽

Deep Tissue ◽

Deep Tissue Injury

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

Download Full-text