scholarly journals Morphological and functional recovery from diaphragm injury: an in vivo rat diaphragm injury model

2001 ◽  
Vol 90 (6) ◽  
pp. 2269-2278 ◽  
Author(s):  
M. Hayot ◽  
E. Barreiro ◽  
A. Perez ◽  
G. Czaika ◽  
A. S. Comtois ◽  
...  
Keyword(s):  
Muscle Force ◽  
Contractile Function ◽  
In Vivo Model ◽  
Force Frequency ◽  
Rat Diaphragm ◽  
Membrane Injury ◽  
Diaphragm Injury ◽  
Injury And Repair

Our objective was to develop an in vivo model to study the timing and mechanisms underlying diaphragm injury and repair. Diaphragm injury was induced in anesthetized rats by the application of a 100 mM caffeine solution for a 10-min period to the right abdominal diaphragm surface. Diaphragms were removed 1, 4, 6, 12, 24, 48, 72, and 96 h and 10 days after the injury, with contractile function being assessed in strips in vitro by force-frequency curves. The extent of caffeine-induced membrane injury was indicated by the percentage of fibers with a fluorescent cytoplasm revealed by inward leakage of the procion orange dye. One hour after caffeine exposure, 32.9 ± 3.1 (SE) % of fibers showed membrane injury that resulted in 70% loss of muscle force. Within 72–96 h, the percentage of fluorescent cells decreased to control values. Muscle force, however, was still reduced by 30%. Complete muscle strength recovery was observed 10 days after the injury. Whereas diaphragmatic fiber repair occurred within 4 days after injury induction, force recovery took up to 10 days. We suggest that the caffeine-damaged rat diaphragm is a useful model to study the timing and mechanisms of muscle injury and repair.

Effects of N-acetylcysteine on in vitro diaphragm function are temperature dependent

1994 ◽  
Vol 77 (5) ◽  
pp. 2434-2439 ◽  
Author(s):  
P. T. Diaz ◽  
E. Brownstein ◽  
T. L. Clanton
Keyword(s):  
Skeletal Muscle ◽  
Salt Solution ◽  
Contractile Function ◽  
Recovery Period ◽  
Physiological Salt Solution ◽  
Force Frequency ◽  
Rat Diaphragm ◽  
Temperature Dependent ◽  
Diaphragm Function

Recent evidence has shown that systemic administration of N-acetylcysteine (NAC), a compound structurally similar to the intracellular antioxidant glutathione, inhibits skeletal muscle fatigue. To further elucidate the actions of NAC, we studied its effects on in vitro rat diaphragm contractile function. Rat diaphragm strips were incubated in tissue baths containing physiological salt solution (n = 29) or physiological salt solution containing 4 mg/ml of NAC (n = 29). Strips were stimulated by either indirect or direct means. After determination of baseline contractile characteristics, strips were fatigued for 4 min at 20 Hz (1 train/s, 0.33 ms train duration). Force-frequency relationships were then studied over a 60-min recovery period. We found that 1) NAC had significant effects on the baseline force-frequency relationship; treated strips had increased peak tension but diminished twitch tension and accelerated twitch kinetics; 2) NAC had significant fatigue-sparing effects that were magnified at 37 degrees C; and 3) NAC treatment did not improve postfatigue recovery. The effects of NAC were generally independent of the stimulation method. We conclude that NAC has direct temperature-dependent effects on diaphragm function. These effects are consistent with the properties of NAC as an antioxidant and suggest important but complex effects of oxidant stress on skeletal muscle.

scholarly journals Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repair

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Nicholas Mikolajewicz ◽  
Elizabeth A Zimmermann ◽  
Bettina M Willie ◽  
Svetlana V Komarova
Keyword(s):  
Mechanical Stimulation ◽  
Cell Injury ◽  
Bone Cells ◽  
Atp Release ◽  
Membrane Repair ◽  
Membrane Injury ◽  
Vesicular Release ◽  
Injury And Repair

Bone cells sense and actively adapt to physical perturbations to prevent critical damage. ATP release is among the earliest cellular responses to mechanical stimulation. Mechanical stimulation of a single murine osteoblast led to the release of 70 ± 24 amole ATP, which stimulated calcium responses in neighboring cells. Osteoblasts contained ATP-rich vesicles that were released upon mechanical stimulation. Surprisingly, interventions that promoted vesicular release reduced ATP release, while inhibitors of vesicular release potentiated ATP release. Searching for an alternative ATP release route, we found that mechanical stresses induced reversible cell membrane injury in vitro and in vivo. Ca2+/PLC/PKC-dependent vesicular exocytosis facilitated membrane repair, thereby minimizing cell injury and reducing ATP release. Priming cellular repair machinery prior to mechanical stimulation reduced subsequent membrane injury and ATP release, linking cellular mechanosensitivity to prior mechanical exposure. Thus, our findings position ATP release as an integrated readout of membrane injury and repair.

scholarly journals Effects of salbutamol on rat diaphragm contractility

1996 ◽  
Vol 81 (3) ◽  
pp. 1103-1110 ◽  
Author(s):  
H. F. Van der Heijden ◽  
R. H. Van Balkom ◽  
H. T. Folgering ◽  
C. L. Van Herwaarden ◽  
P. N. Dekhuijzen
Keyword(s):  
Time Course ◽  
Subcutaneous Administration ◽  
Contractile Properties ◽  
Force Generation ◽  
Force Frequency ◽  
Rat Diaphragm ◽  
Tetanic Force ◽  
Low Concentrations

The aim of this study was to investigate 1) the effects and time course of single doses of salbutamol on isometric contractile properties of isolated rat diaphragm strips and 2) whether these effects were caused by a direct effect on the muscle. Two experiments were performed. In one, salbutamol was administered subcutaneously in doses of 12.5, 25, 50, or 100 micrograms/kg (25 and 50 micrograms/kg sc resulted in serum concentrations of approximately 9 and approximately 15 micrograms/l, respectively, 0.5 h after injection) and in vitro contractile properties were determined 0.5, 1, 2, or 4 h after administration; in the other, salbutamol was added to the tissue bath in a concentration of < or = 2, approximately 10, approximately 20, and approximately 80 micrograms/l. Twice force, maximal tetanic force, and twitch force-to-tetanic force ratio all increased in a dose-dependent way in both experiments. The increases in force generation were slightly higher after subcutaneous administration. Force-frequency curves were shifted upward in both experiments. No significant effects of time of salbutamol administration were found, but the increase in force generation was most pronounced within 2 h after subcutaneous administration. In conclusion, in vitro force generation can be improved by low concentrations of salbutamol. The slightly higher increases in force generation after subcutaneous administration suggest that in vivo salbutamol may have additional positive inotropic actions on diaphragm contractility besides a direct beta 2-adrenergic effect on the muscle itself.

Effects of DAP on diaphragm force and fatigue, including fatigue due to neurotransmission failure

1996 ◽  
Vol 81 (5) ◽  
pp. 2214-2220 ◽  
Author(s):  
Erik Van Lunteren ◽  
Michelle Moyer
Keyword(s):  
Muscle Force ◽  
Channel Blocker ◽  
Force Frequency ◽  
Rat Diaphragm ◽  
Muscle Contractility ◽  
Tetanic Force ◽  
Intermittent Stimulation ◽  
Relative Contribution ◽  
Frequency Relationship

Van Lunteren, Erik, and Michelle Moyer. Effects of DAP on diaphragm force and fatigue, including fatigue due to neurotransmission failure. J. Appl. Physiol. 81(5): 2214–2220, 1996.—Among the aminopyridines, 3,4-diaminopyridine (DAP) is a more effective K+ channel blocker than is 4-aminopyridine (4-AP), and, furthermore, DAP enhances neuromuscular transmission. Because 4-AP improves muscle contractility, we hypothesized that DAP would also increase force and, in addition, ameliorate fatigue and improve the neurotransmission failure component of fatigue. Rat diaphragm strips were studied in vitro (37°C). In field-stimulated muscle, 0.3 mM DAP significantly increased diaphragm twitch force, prolonged contraction time, and shifted the force-frequency relationship to the left without altering peak tetanic force, resulting in increased force at stimulation frequencies ≤50 Hz. During 20-Hz intermittent stimulation, DAP increased diaphragm peak force compared with control during a 150-s fatigue run and, furthermore, significantly improved maintenance of intratrain force. The relative contribution of neurotransmission failure to fatigue was estimated by comparing the force generated by phrenic nerve-stimulated muscles with that generated by curare-treated field-stimulated muscles. DAP significantly increased force in nerve-stimulated muscles and, in addition, reduced the neurotransmission failure contribution to diaphragm fatigue. Thus DAP increases muscle force at low-to-intermediate stimulation frequencies, improves overall force and intratrain fatigue during 20-Hz intermittent stimulation, and reduces neurotransmission failure.

Tamarix articulata (T. articulata) - An Important Halophytic Medicinal Plant with Potential Pharmacological Properties

2019 ◽  
Vol 20 (4) ◽  
pp. 285-292 ◽  
Author(s):  
Abdullah M. Alnuqaydan ◽  
Bilal Rah
Keyword(s):  
Medicinal Plant ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Biological Properties ◽  
In Vivo Model ◽  
Drug Candidate ◽  
Phytochemical Analysis ◽  
Pharmacological Properties

Background:Tamarix Articulata (T. articulata), commonly known as Tamarisk or Athal in Arabic region, belongs to the Tamaricaece species. It is an important halophytic medicinal plant and a good source of polyphenolic phytochemical(s). In traditional medicines, T. articulata extract is commonly used, either singly or in combination with other plant extracts against different ailments since ancient times.Methods:Electronic database survey via Pubmed, Google Scholar, Researchgate, Scopus and Science Direct were used to review the scientific inputs until October 2018, by searching appropriate keywords. Literature related to pharmacological activities of T. articulata, Tamarix species, phytochemical analysis of T. articulata, biological activities of T. articulata extracts. All of these terms were used to search the scientific literature associated with T. articulata; the dosage of extract, route of administration, extract type, and in-vitro and in-vivo model.Results:Numerous reports revealed that T. articulata contains a wide spectrum of phytochemical(s), which enables it to have a wide window of biological properties. Owing to the presence of high content of phytochemical compounds like polyphenolics and flavonoids, T. articulata is a potential source of antioxidant, anti-inflammatory and antiproliferative properties. In view of these pharmacological properties, T. articulata could be a potential drug candidate to treat various clinical conditions including cancer in the near future.Conclusion:In this review, the spectrum of phytochemical(s) has been summarized for their pharmacological properties and the mechanisms of action, and the possible potential therapeutic applications of this plant against various diseases discussed.

scholarly journals Radiofrequency Irradiation Modulates TRPV1-Related Burning Sensation in Rosacea

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1424
Author(s):  
Seyeon Oh ◽  
Myeongjoo Son ◽  
Joonhong Park ◽  
Donghwan Kang ◽  
Kyunghee Byun
Keyword(s):  
Burning Sensation ◽  
In Vivo Model ◽  
Molecular Evidence ◽  
Exposed Skin ◽  
Heat Treated ◽  
Vitro Model ◽  
Effective Use ◽  
Inflammatory Molecules

Rosacea is a skin inflammatory condition that is accompanied by not only redness and flushing but also unseen symptoms, such as burning, stinging, and itching. TRPV1 expression in UVB-exposed skin can lead to a painful burning sensation. Upregulated TRPV1 expression helps release neuropeptides, including calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide, and vasoactive intestinal peptide, which can activate macrophage and inflammatory molecules. In this study, we found that radiofrequency (RF) irradiation reduced TRPV1 activation and neuropeptide expression in a UVB-exposed in vivo model and UVB- or heat-treated in an in vitro model. RF irradiation attenuated neuropeptide-induced macrophage activation and inflammatory molecule expression. Interestingly, the burning sensation in the skin of UVB-exposed mice and patients with rosacea was significantly decreased by RF irradiation. These results can provide experimental and molecular evidence on the effective use of RF irradiation for the burning sensation in patients with rosacea.

scholarly journals Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jennifer K. Dowling ◽  
Remsha Afzal ◽  
Linden J. Gearing ◽  
Mariana P. Cervantes-Silva ◽  
Stephanie Annett ◽  
...  
Keyword(s):  
Metabolic Regulation ◽  
Mitochondrial Dynamics ◽  
Interleukin 10 ◽  
Metabolic Reprogramming ◽  
In Vivo Model ◽  
Macrophage Polarisation ◽  
Inflammatory Status ◽  
Inflammatory Macrophages

AbstractMitochondria are important regulators of macrophage polarisation. Here, we show that arginase-2 (Arg2) is a microRNA-155 (miR-155) and interleukin-10 (IL-10) regulated protein localized at the mitochondria in inflammatory macrophages, and is critical for IL-10-induced modulation of mitochondrial dynamics and oxidative respiration. Mechanistically, the catalytic activity and presence of Arg2 at the mitochondria is crucial for oxidative phosphorylation. We further show that Arg2 mediates this process by increasing the activity of complex II (succinate dehydrogenase). Moreover, Arg2 is essential for IL-10-mediated downregulation of the inflammatory mediators succinate, hypoxia inducible factor 1α (HIF-1α) and IL-1β in vitro. Accordingly, HIF-1α and IL-1β are highly expressed in an LPS-induced in vivo model of acute inflammation using Arg2−/− mice. These findings shed light on a new arm of IL-10-mediated metabolic regulation, working to resolve the inflammatory status of the cell.

scholarly journals Gilteritinib overcomes lorlatinib resistance in ALK-rearranged cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hayato Mizuta ◽  
Koutaroh Okada ◽  
Mitsugu Araki ◽  
Jun Adachi ◽  
Ai Takemoto ◽  
...  
Keyword(s):  
Gene Rearrangement ◽  
Kinase Inhibitors ◽  
Inhibitory Effect ◽  
In Vivo Model ◽  
Resistance Mutations ◽  
Lung Cancer Patients ◽  
Short Period ◽  
Tki Resistance

AbstractALK gene rearrangement was observed in 3%–5% of non-small cell lung cancer patients, and multiple ALK-tyrosine kinase inhibitors (TKIs) have been sequentially used. Multiple ALK-TKI resistance mutations have been identified from the patients, and several compound mutations, such as I1171N + F1174I or I1171N + L1198H are resistant to all the approved ALK-TKIs. In this study, we found that gilteritinib has an inhibitory effect on ALK-TKI–resistant single mutants and I1171N compound mutants in vitro and in vivo. Surprisingly, EML4-ALK I1171N + F1174I compound mutant-expressing tumors were not completely shrunk but regrew within a short period of time after alectinib or lorlatinib treatment. However, the relapsed tumor was markedly shrunk after switching to the gilteritinib in vivo model. In addition, gilteritinib was effective against NTRK-rearranged cancers including entrectinib-resistant NTRK1 G667C-mutant and ROS1 fusion-positive cancer.

scholarly journals mTOR inhibitors potentially reduce TGF-β2-induced fibrogenic changes in trabecular meshwork cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nozomi Igarashi ◽  
Megumi Honjo ◽  
Makoto Aihara
Keyword(s):  
Trabecular Meshwork ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Mtor Inhibitors ◽  
In Vivo Model ◽  
Type I ◽  
Fibrotic Response ◽  
Alpha Smooth Muscle Actin

AbstractWe examined the effects of mTOR inhibitors on the fibrotic response induced by transforming growth factor-beta2 (TGF-β2) in cultured human trabecular meshwork (hTM) cells. TGF-β2-induced expression of fibronectin, collagen type I, alpha 1 chain (COL1A1), and alpha-smooth muscle actin (αSMA) in hTM cells was examined in the presence or absence of mTOR inhibitors using quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry. The migration rates of hTM cells were examined in the presence of TGF-β2 with or without mTOR inhibitors. An in vitro study showed that the expression of fibronectin, COL1A1, and αSMA was upregulated by TGF-β2 treatment of hTM cells; such upregulation was significantly suppressed by mTOR inhibitors. The inhibitors significantly reduced the migration rate of TGF-β2-stimulated hTM cells. mTOR inhibitors may usefully reduce the fibrotic response of hTM cells and we may have to explore if it is also effective in in vivo model.

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