Endocannabinoids modulate apoptosis in endometriosis and adenomyosis.

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Endocannabinoids modulate apoptosis in endometriosis and adenomyosis.

Acta Histochem. 2017 May 23;:

Authors: Bilgic E, Meydanli EG, Kose S, Aydin MC, Karaismailoglu E, Akar I, Usubutun A, Korkusuz P

Abstract
Adenomyosis that is a form of endometriosis is the growth of ectopic endometrial tissue within the muscular wall of the uterus (myometrium), which may cause dysmenorrhea and infertility. Endocannabinoid mediated apoptotic mechanisms of endometriosis and adenomyosis are not known. We hypothesized that the down regulation of endocannabinoid receptors and/or alteration in their regulatory enzymes may have a direct role in the pathogenesis of endometriosis and adenomyosis through apoptosis. Endocannabinoid receptors CB1 and CB2, their synthesizing and catabolizing enzymes (FAAH, NAPE-PLD, DAGL, MAGL) and the apoptotic indexes were immunohistochemically assessed in endometriotic and adenomyotic tissues. Findings were compared to normal endometrium and myometrium. Endometrial adenocarcinoma (Ishikawa) and ovarian endometriosis cyst wall stromal (CRL-7566) cell lines were furthermore cultured with or without cannabinoid receptor agonists. The IC50 value for CB1 and CB2 receptor agonists was quantified. Cannabinoid agonists on cell death were investigated by Annexin-V/Propidium iodide labeling with flow cytometry. CB1 and CB2 receptor levels decreased in endometriotic and adenomyotic tissues compared to the control group (p=0,001 and p=0,001). FAAH, NAPE-PLD, MAGL and DAGL enzyme levels decreased in endometriotic and adenomyotic tissues compared to control (p=0,001, p=0,001, p=0,001 and p=0,002 respectively). Apoptotic cell indexes both in endometriotic and adenomyotic tissues also decreased significantly, compared to the control group (p=0,001 and p=0,001). CB1 and CB2 receptor agonist mediated dose dependent fast anti-proliferative and pro-apoptotic effects were detected in Ishikawa and ovarian endometriosis cyst wall stromal cell lines (CRL-7566). Endocannabinoids are suggested to increase apoptosis mechanisms in endometriosis and adenomyosis. CB1 and CB2 antagonists can be considered as potential medical therapeutic agents for endometriosis and adenomyosis.

PMID: 28549792 [PubMed - as supplied by publisher]

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Molecular mechanisms underlying the protective effects of hydrogen-saturated saline on noise-induced hearing loss.

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Molecular mechanisms underlying the protective effects of hydrogen-saturated saline on noise-induced hearing loss.

Acta Otolaryngol. 2017 May 26;:1-6

Authors: Chen L, Han M, Lu Y, Chen D, Sun X, Yang S, Sun W, Yu N, Zhai S

Abstract
OBJECTIVES: This study aimed to explore the molecular mechanism of the protective effects of hydrogen-saturated saline on NIHL.
METHODS: Guinea pigs were divided into three groups: hydrogen-saturated saline; normal saline; and control. For saline administration, the guinea pigs were given daily abdominal injections 3 d before and 1 h before noise exposure. ABR were tested to examine cochlear physiology changes. The changes of 8-hydroxy-desoxyguanosine (8-HOdG), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), intercellular cell adhesion molecule-1 (ICAM-1) and high mobility group box-1 protein (HMGB1) in the cochlea were also examined.
RESULTS: The results showed that pre-treatment with hydrogen-saturated saline could significantly attenuate noise-induced hearing loss. The concentration of 8-HOdG was also significantly decreased in the hydrogen-saturated saline group compared with the normal saline group. After noise exposure, the concentrations of IL-1, IL-6, TNF-α, and ICAM-1 in the cochlea of guinea pigs in the hydrogen-saturated saline group were dramatically reduced compared to those in the normal saline group. The concentrations of HMGB-1 and IL-10 in the hydrogen-saturated saline group were significantly higher than in those in the normal saline group immediately and at 7 d after noise exposure.
CONCLUSIONS: This study revealed for the first time the protective effects of hydrogen-saturated saline on noise-induced hearing loss (NIHL) are related to both the anti-oxidative activity and anti-inflammatory activity.

PMID: 28549396 [PubMed - as supplied by publisher]

http://ift.tt/2s9Dya3

Correction to: Huang H, et al., M2-polarized tumour-associated macrophages in stroma correlate with poor prognosis and Epstein-Barr viral infection in nasopharyngeal carcinoma.

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Correction to: Huang H, et al., M2-polarized tumour-associated macrophages in stroma correlate with poor prognosis and Epstein-Barr viral infection in nasopharyngeal carcinoma.

Acta Otolaryngol. 2017 May 26;:1

Authors:

PMID: 28549389 [PubMed - as supplied by publisher]

http://ift.tt/2s9QEUO

Molecular mechanisms underlying the protective effects of hydrogen-saturated saline on noise-induced hearing loss.

Related Articles

Molecular mechanisms underlying the protective effects of hydrogen-saturated saline on noise-induced hearing loss.

Acta Otolaryngol. 2017 May 26;:1-6

Authors: Chen L, Han M, Lu Y, Chen D, Sun X, Yang S, Sun W, Yu N, Zhai S

Abstract
OBJECTIVES: This study aimed to explore the molecular mechanism of the protective effects of hydrogen-saturated saline on NIHL.
METHODS: Guinea pigs were divided into three groups: hydrogen-saturated saline; normal saline; and control. For saline administration, the guinea pigs were given daily abdominal injections 3 d before and 1 h before noise exposure. ABR were tested to examine cochlear physiology changes. The changes of 8-hydroxy-desoxyguanosine (8-HOdG), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), intercellular cell adhesion molecule-1 (ICAM-1) and high mobility group box-1 protein (HMGB1) in the cochlea were also examined.
RESULTS: The results showed that pre-treatment with hydrogen-saturated saline could significantly attenuate noise-induced hearing loss. The concentration of 8-HOdG was also significantly decreased in the hydrogen-saturated saline group compared with the normal saline group. After noise exposure, the concentrations of IL-1, IL-6, TNF-α, and ICAM-1 in the cochlea of guinea pigs in the hydrogen-saturated saline group were dramatically reduced compared to those in the normal saline group. The concentrations of HMGB-1 and IL-10 in the hydrogen-saturated saline group were significantly higher than in those in the normal saline group immediately and at 7 d after noise exposure.
CONCLUSIONS: This study revealed for the first time the protective effects of hydrogen-saturated saline on noise-induced hearing loss (NIHL) are related to both the anti-oxidative activity and anti-inflammatory activity.

PMID: 28549396 [PubMed - as supplied by publisher]

http://ift.tt/2s9Dya3

Correction to: Huang H, et al., M2-polarized tumour-associated macrophages in stroma correlate with poor prognosis and Epstein-Barr viral infection in nasopharyngeal carcinoma.

Related Articles

Correction to: Huang H, et al., M2-polarized tumour-associated macrophages in stroma correlate with poor prognosis and Epstein-Barr viral infection in nasopharyngeal carcinoma.

Acta Otolaryngol. 2017 May 26;:1

Authors:

PMID: 28549389 [PubMed - as supplied by publisher]

http://ift.tt/2s9QEUO

The Lutonix® drug-coated balloon: A novel drug delivery technology for the treatment of vascular disease

Publication date: Available online 27 May 2017
Source:Advanced Drug Delivery Reviews
Author(s): Ian Schorn, Harrison Malinoff, Steven Anderson, Cyal Lecy, Jeffrey Wang, Joseph Giorgianni, George Papandreou
Local drug delivery of an anti-proliferative drug from balloon catheter systems to the site of arterial injury has been attempted repeatedly over the years with limited success in drug uptake and retention. Accessibility of the drug at the site is critical to combat the body's response to the procedural trauma of angioplasty. Recently, formulations have been designed which achieve delivery of therapeutic doses of the anti-proliferative drug paclitaxel to arteries with higher efficiency and longer tissue retention. These formulations succeed through formation of a drug reservoir in the artery wall enabling release after the initial angioplasty procedure. These formulations have become the cornerstone of several drug coated balloon (DCB) technologies which have found an initial, broad therapeutic application in the treatment of stenosis of the superficial femoral artery (SFA). DCBs achieve drug delivery while leaving no implant behind and represent a new class of combination products developed at the interface of engineering, chemistry and medical science. This review article summarizes the development of the LUTONIX® drug coated balloon catheter. The introduction of DCB technology has provided clinicians and patients with new SFA treatment options while ongoing clinical evidence in additional vascular beds is generated.



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Intra-spinal microstimulation may alleviate chronic pain after spinal cord injury

Publication date: Available online 27 May 2017
Source:Medical Hypotheses
Author(s): Bin Shu, Fei Yang, Yun Guan
Chronic pain after spinal cord injury (SCI) is a form of central neuropathic pain that is debilitating and often refractory to current pharmacological treatments. Neurostimulation pain therapies, such as epidural spinal cord stimulation, have only moderate success in reducing SCI pain. The pathogenesis of SCI pain may involve a state of central neuronal hyperexcitability, especially in the spinal cord dorsal horn, that develops after injury. We hypothesize that the neuronal structures near the spinal cord injury site may be an important pain generator, and intraspinal microstimulation (ISMS) may normalize dorsal horn neuronal hyperexcitability and hence alleviate SCI pain. Specifically, ISMS may induce frequency-dependent conduction block on axons of afferent sensory neurons, in the spinothalamic tract and Lissauer's tract. ISMS may also facilitate primary afferent depolarization that elicits presynaptic inhibition of incoming afferent inputs. Together, these actions will reduce abnormal afferent inputs and ascending pain signals before they can reach the brain. Furthermore, ISMS may directly induce inhibitory postsynaptic potentials in dorsal horn neurons, and trigger the release of endogenous inhibitory neurotransmitters, opioids and serotonin to inhibit postsynaptic neurons and restore the compromised segmental pain inhibition after SCI. Finally, ISMS may alter the frequency and pattern of discharge such that the rostrally conducted impulses no longer code pain or activate brain areas concerned with pain signaling. Based on recent progress in understanding spinal learning and plasticity, we also postulate that repetitive or long-term ISMS may help the dorsal horn "reset" neuronal excitability and regain normal pain processing for a prolonged period. By finely tuning the stimulation parameters (e.g., intensity, pulse width, frequency), position, and geometry of ISMS electrode, multiple spinal structures (e.g., dorsal horn, dorsal column, spinothalamic tract) may be modulated to induce synergistic pain inhibition. Our hypothesis can be readily tested in preclinical models of SCI pain by using a combination of in vivo electrophysiological (neuronal activity) and animal behavioral (pain response) approaches. Since ISMS electrodes stimulate the spinal structures directly, we expect that the effective stimulus intensity and energy consumption can be lower than that for epidural spinal cord stimulation. The proposed hypothesis may provide insights and rationales for developing a novel neurostimulation pain therapy by directly inhibiting the pain generators in the spinal cord, and ISMS may be an alternative strategy to treat SCI pain.



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