Usnic acid ameliorates bleomycin-induced pulmonary fibrosis in mice via inhibition of inflammatory responses and oxidative stress

Purpose: To Investigate the effect of usnic acid (UA) on bleomycin (BLM)-induced pulmonary fibrosis in mice, and the underlying mechanism. Methods: Male Kunming mice with bleomycin-induced pulmonary fibrosis (PF) were exposed to different concentrations of usnic acid. Lung coefficient and histopathological changes were determined, while MDA, superoxide dismutase (SOD) activity, and expression levels of hydroxyproline, tumor necrosis factor-α, interleukins-1β & 6, and transforming growth factor-β1 were assayed in lung homogenates. Results: UA significantly mitigated lung coefficient and histopathological changes in mice. Compared to the bleomycin group, MDA level was significantly reduced while the content of SOD markedly increased after UA pretreatment (p < 0.05). Moreover, UA significantly reduced the expression levels of all the parameters, relative to bleomycin group (p < 0.05). Conclusion: These results indicate that UA protects mice against bleomycin-induced PF via a mechanism associated with attenuation of pro-oxidant stress and inflammation. Therefore, UA has therapeutic potential for the management of pulmonary fibrosis

Vasopressin and epinephrine versus epinephrine in management of patients with cardiac arrest: a meta-analysis

Objective. A combination of vasopressin and epinephrine may be more effective than epinephrine alone in cardiopulmonary resuscitation (CPR), but evidence is lacking to make clinical recommendations. This meta-analysis compares the efficacy of vasopressin and epinephrine used together versus epinephrine alone in cardiac arrest (CA). Methods. We searched MEDLINE and EMBASE for randomized trials comparing the efficacy of vasopressin and epinephrine versus epinephrine alone in adults with cardiac arrest. The primary outcome was the return of spontaneous circulation (ROSC) and the survival rate on admission and discharge .We also analyzed ROSC in subgroups of patients presenting with different arrest rhythms, such as asystole, pulseless electrical activity (PEA), ventricular fibrillation (VF). Results. We analyzed 6 randomized trials out of 485 articles. We did not find evidence supporting the superiority of vasopressin and epinephrine used in combination, except for the survival rate at 24h 2.99 95% CI(1.43,6.28). No evidence supports the conclusion that vasopressin combined with epinephrine is better than epinephrine alone for ROSC, even amongst subgroups of patients. Conclusion. This systematic review of the efficacy of vasopressin and epinephrine use found that its combined use is better for 24h survival rate but only in one study which included 122 patients. Further investigation will be needed to support the use of this combination for cardiac arrest management

Intracerebroventricular administration of the thyroid hormone analog TRIAC increases its brain content in the absence of MCT8

Patients lacking the thyroid hormone (TH) transporter MCT8 present abnormal serum levels of TH: low thyroxine and high triiodothyronine. They also have severe neurodevelopmental defects resulting from cerebral hypothyroidism, most likely due to impaired TH transport across the brain barriers. The use of TH analogs, such as triiodothyroacetic acid (TRIAC), that can potentially access the brain in the absence of MCT8 and restore at least a subset of cerebral TH actions could improve the neurological defects in these patients. We hypothesized that direct administration of TRIAC into the brain by intracerebroventricular delivery to mice lacking MCT8 could bypass the restriction at the brain barriers and mediate TH action without causing hypermetabolism. We found that intracerebroventricular administration of therapeutic doses of TRIAC does not increase further plasma triiodothyronine or further decrease plasma thyroxine levels and does not alter TH content in the cerebral cortex. Although TRIAC content increased in the brain, it did not induce TH-mediated actions on selected target genes. Our data suggest that intracerebroventricular delivery of TRIAC has the ability to target the brain in the absence of MCT8 and should be further investigated to address its potential therapeutic use in MCT8 deficiency.This work was funded by the Spanish Plan Nacional de I+D+i (grant number SAF2017-86342-R to AG-F), the Sherman Foundation (OTR02211 to AG-F and SB-L), the Center for Biomedical Research on Rare Diseases (Ciberer to AG-F and CG-M), Instituto de Salud Carlos III, Madrid, Spain. X-HL and SR were supported in part by grant DK 15070 from the National Institutes of Health, USA

Ulinastatin attenuates oxidation, inflammation and neural apoptosis in the cerebral cortex of adult rats with ventricular fibrillation after cardiopulmonary resuscitation

OBJECTIVE: The role of Ulinastatin in neuronal injury after cardiopulmonary resuscitation has not been elucidated. We aim to evaluate the effects of Ulinastatin on inflammation, oxidation, and neuronal injury in the cerebral cortex after cardiopulmonary resuscitation. METHODS: Ventricular fibrillation was induced in 76 adult male Wistar rats for 6 min, after which cardiopulmonary resuscitation was initiated. After spontaneous circulation returned, the rats were split into two groups: the Ulinastatin 100,000 unit/kg group or the PBS-treated control group. Blood and cerebral cortex samples were obtained and compared at 2, 4, and 8 h after return of spontaneous circulation. The protein levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were assayed using an enzyme-linked immunosorbent assay, and mRNA levels were quantified via real-time polymerase chain reaction. Myeloperoxidase and Malondialdehyde were measured by spectrophotometry. The translocation of nuclear factor-κB p65 was assayed by Western blot. The viable and apoptotic neurons were detected by Nissl and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). RESULTS: Ulinastatin treatment decreased plasma levels of TNF-α and IL-6, expression of mRNA, and Myeloperoxidase and Malondialdehyde in the cerebral cortex. In addition, Ulinastatin attenuated the translocation of nuclear factor-κB p65 at 2, 4, and 8 hours after the return of spontaneous circulation. Ulinastatin increased the number of living neurons and decreased TUNEL-positive neuron numbers in the cortex at 72 h after the return of spontaneous circulation. CONCLUSIONS: Ulinastatin preserved neuronal survival and inhibited neuron apoptosis after the return of spontaneous circulation in Wistar rats via attenuation of the oxidative stress response and translocation of nuclear factor-κB p65 in the cortex. In addition, Ulinastatin decreased the production of TNF-α, IL-6, Myeloperoxidase, and Malondialdehyde

Pharmacodynamic Evaluation and PK/PD-Based Dose Prediction of Tulathromycin: A Potential New Indication for Streptococcus suis Infection

Tulathromycin is the first member of the triamilide antimicrobial drugs that has been registered in more than 30 countries. The goal of this study is to provide a potential new indication of tulathromycin for Streptococcus suis infections. We investigated the pharmacokinetic and ex vivo pharmacodynamics of tulathromycin against experimental S. suis infection in piglets. Tulathromycin demonstrated a relatively long elimination half-life (74.1 h) and a mean residence time of 97.6 h after a single intramuscular administration. The minimal inhibitory concentration (MIC) and bactericidal concentration in serum were markedly lower than those in broth culture, with Mueller–Hinton broth/serum ratios of 40.3 and 11.4, respectively. The post-antibiotic effects were at 1.27 h (1× MIC) and 2.03 h (4× MIC) and the post-antibiotic sub-MIC effect values ranged from 2.47 to 3.10 h. The ratio of the area under the concentration–time curve divided by the MIC (AUC/MIC) correlated well with the ex vivo antimicrobial effectiveness of tulathromycin (R2 = 0.9711). The calculated AUC12h/MIC ratios in serum required to produce the net bacterial stasis, 1-log10 and 2-log10 killing activities were 9.62, 18.9, and 32.7, respectively. Based on the results of Monte Carlo simulation, a dosage regimen of 3.56 mg/kg tulathromycin was estimated to be effective, achieving for a bacteriostatic activity against S. suis infection over 5 days period. Tulathromycin may become a potential option for the treatment of S. suis infections

Extraction of Prostatic Lumina and Automated Recognition for Prostatic Calculus Image Using PCA-SVM

Identification of prostatic calculi is an important basis for determining the tissue origin. Computation-assistant diagnosis of prostatic calculi may have promising potential but is currently still less studied. We studied the extraction of prostatic lumina and automated recognition for calculus images. Extraction of lumina from prostate histology images was based on local entropy and Otsu threshold recognition using PCA-SVM and based on the texture features of prostatic calculus. The SVM classifier showed an average time 0.1432 second, an average training accuracy of 100%, an average test accuracy of 93.12%, a sensitivity of 87.74%, and a specificity of 94.82%. We concluded that the algorithm, based on texture features and PCA-SVM, can recognize the concentric structure and visualized features easily. Therefore, this method is effective for the automated recognition of prostatic calculi