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Minocycline attenuates white matter damage in a rat model of chronic cerebral hypoperfusion

White matter lesions are thought to result from chronic cerebral ischemia and constitute a core pathology of subcortical vascular dementia. This rarefaction has been known to be associated with microglial activation. We investigated whether minocycline, a microglial inhibitor, attenuates the white matter damage induced by chronic cerebral hypoperfusion that is used as a model of vascular dementia. Male Wistar rats were subjected to bilateral, permanent occlusion of the common carotid arteries (BCCAO) to induce chronic cerebral hypoperfusion. Minocycline or saline was injected daily for 2 weeks after BCCAO. In the corpus callosum and the optic tract, white matter damage observed with Klüver‐Barrera staining was significantly attenuated in the minocycline‐treated group compared to saline‐treated controls. In control rats, immunoreactivities of major basic protein (MBP), Ox‐42 as a microglial marker, and matrix metalloproteinase (MMP)‐2 were increased in the corpus callosum. Minocycline significantly reduced these changes. Co‐expression of Ox‐42 and MMP‐2 was confirmed by double immunofluorescence histochemistry. Our results suggest that chronic treatment with minocycline could be protective against at least some ischemic white matter damage, and its mechanism may be related to suppressing microglial activation.

Comparison of budesonide and dexamethasone for local treatment of oral chronic graft-versus-host disease

PURPOSE The results of a prospective study of topical budesonide versus topical dexamethasone therapy for oral manifestations of chronic graft-versus-host disease (cGVHD) are presented. METHODS In a prospective single-center investigation, a cohort of patients who developed oral symptoms of cGVHD after allogeneic stem cell transplantation were assigned to topical treatment with 0.03% budesonide rinse (group A, n = 26) or 0.01% dexamethasone rinse (group B, n = 24). Diagnosis of oral cGVHD symptoms, clinical staging, and treatment response scoring were performed at baseline and one month later according to current National Institutes of Health consensus criteria. RESULTS At one-month follow-up, there was a significant decrease in the median oral cGVHD examination score in both groups (p < 0.001); the decrease in the median examination score was greater with budesonide versus dexamethasone therapy (2.5 points versus 1.0 point, p = 0.045). The rates of overall treatment response, including complete and partial responses, were 53.8% and 29.2% in groups A and B, respectively (p = 0.093). In addition, there was a significant decrease from baseline in the median self-rated oral pain severity score in group A (p < 0.001). CONCLUSION Patients who received topical budesonide or dexamethasone rinse to treat oral manifestations of cGVHD had decreased cGVHD severity and pain scores after 30 days compared with baseline scores, though no statistical differences were seen between groups.

Electrically Stimulated Relaxation is not Mediated by GABA in Cat Lower Esophageal Sphincter Muscle

This study examined the effect of Gamma-Amino butyric acid (GABA) and selective GABA receptor related drugs on the electrically stimulated relaxation in the lower esophageal sphincter muscle (LES) of a cat. Tetrodotoxin (10−6 M) suppressed the electrically stimulated (0.5–5 Hz) relaxation of the LES. However, guanethidine (10−6 M) and atropine (10−6 M) had no effect indicating that the relaxations were neurally mediatedvia the nonadrenergic and noncholinergic (NANC) pathways. NG-nitro-L-arginine methyl ester (10−4 M, L-NAME) also inhibited the relaxant response but did not completely abolish the electrically stimulated relaxation with 60% inhibition, which suggests the involvement of nitric oxide as an inhibitory transmitter. This study examined the role of GABA, an inhibitory neurotransmitter, on neurally mediated LES relaxation. GABA (10−3–10−5 M, non selective receptor agonist), muscimol (10−3–10−5 M, GABA-A agonist), and baclofen (10−3–10−5 M, GABA-B agonist) had no significant effect on the electrically stimulated relaxation. Moreover, bicuculline (10−5 M, GABA-A antagonist) and phaclofen (10−5 M, GABA-B antagonist) had no inhibitory effect on the electrically stimulated relaxation. This suggests that GABA and the GABA receptor are not involved in the electrically stimulated NANC relaxation in the cat LES.

Effect of hydrogen peroxide on VIP-induced relaxation of the cat lower esophageal sphincter

We investigated the effects of hydrogen peroxide (H2O2) on relaxation of the cat lower esophageal sphincter (LES). Vasoactive intestinal peptide (VIP) caused dose-dependent relaxation of LES, and H2O2 reduced VIP-induced relaxation. Relaxation was also attenuated by pertussis toxin (PTX), indicating a Gi/o component. VIP treatment increased [35S]GTPγS binding to Gs and Gi3 protein, but not to Go, Gq, Gi1 or Gi2. This increase in Gs or Gi3 binding was reduced by H2O2. However, the relaxation induced by sodium nitroprusside (SNP), 3-morpholino sydnomine (SIN-1), 8-br cGMP (cGMP analog), forskolin (adenylate cyclase activator), and dibutyryl-cAMP (a stable cAMP analog) was not reduced by H2O2. These data suggest that H2O2 inhibits VIP-induced relaxation via a Gi-dependent pathway, perhaps by inhibiting the activation of Gi3 or Gs downstream of the VIP receptor and independent of cAMP or NO-cGMP signaling.

Comparisons of doxycycline solution with talc slurry for chemical pleurodesis and risk factors for recurrence in South Korean patients with spontaneous pneumothorax

Purpose Talc slurry (TS) has been commonly used with high success rates in managing spontaneous pneumothroax (SP), but there were concerns of post-procedural complications. Alternatively, doxycycline solution (DS) was used successfully. This retrospective study aims to compare the effectiveness and safety between talc and doxycycline as a sclerosing agent and to investigate risk factors for recurrence in patients with SP. Methods The review of medical records between January 2011 and December 2014 was conducted on 83 patients with SP who underwent pleurodesis with either TS (n=16) or DS (n=67). Recurrence and complications were compared between the DS and TS groups. Associations between recurrence after DS treatment and various factors were analysed. Results Recurrence was significantly higher in the DS group than in the TS group (P=0.033), whereas complications were higher in the TS group than the DS group: fever was significantly higher in the TS group (P=0.001). Recurrences associated with doxycycline use were found significantly more often in patients with recurrent diagnosis of SP, height/weight ≥3.25 cm/kg and weight <55 kg. Conclusion Talc was more effective without recurrence compared with doxycycline. Clinically insignificant fever associated with pleurodesis was more common with talc. Low weight, high height to weight ratio and recurrent diagnosis of SP were associated with higher recurrence after doxycycline treatment.

Endothelium-Independent Effect of Fisetin on the Agonist-Induced Regulation of Vascular Contractility.

Fisetin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of fisetin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Fisetin significantly relaxed fluoride-, thromboxane A2- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, fisetin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1 and MEK activity and the subsequent phosphorylation of ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of fisetin on agonist-induced vascular contraction regardless of endothelial function.