Assessment of lytic therapy effect in patients with intermediate-high risk pulmonary embolism for prevention of chronic thromboembolic pulmonary hypertension: A randomized, double-blind trial.

Background and Aims: This study aims to compare the effectiveness of thrombolytic therapy and anticoagulation in preventing chronic thromboembolic pulmonary hypertension (CTEPH). Method: A total of 60 patients with intermediate-high risk pulmonary embolism (PE) were randomly assigned to receive either thrombolytic therapy (n = 30) or anticoagulation (n = 30). Results: Echocardiographic assessments demonstrated no significant differences between the two treatment approaches in terms of right ventricular size (RVS) (on discharge in thrombolytic group: 31.17 ± 3.43 vs. anticoagulant group: 32.73 ± 5.27, p = 0.912), tricuspid annular plane systolic excursion (TAPSE) (on discharge in thrombolytic group: 17.66 ± 2.39 vs. anticoagulant group: 16.73 ± 2.93, p = 0.290), and systolic pulmonary artery pressure (SPAP) (on discharge in thrombolytic group: 32.93 ± 9.73 vs. anticoagulant group: 34.46 ± 9.30, p = 0.840). However, significant changes were observed in all assessed parameters within each treatment group (p < 0.001). The 6-month follow-up showed no significant difference between the two groups in terms of CTEPH incidence (p = 0.781) or functional class of the patients (p = 0.135). Conclusion: Based on the findings of this study, neither thrombolytic therapy nor anticoagulation demonstrated superiority over the other in reducing adverse outcomes associated with intermediate-high risk PE, including right ventricular size, SPAP, TAPSE, or CTEPH.

Long-Term Effects of Opium Consumption Following Percutaneous Coronary Intervention: A 10-year Follow-Up Study.

Background: Opium consumption has been an overlooked health issue in the Iranian population, and the prognostic role of opium consumption in patients undergoing coronary revascularization is unknown. Hypothesis: We aimed to assess the association between opium consumption and long-term cardiovascular outcomes after percutaneous coronary intervention (PCI). Methods: We screened 2203 consecutive patients who underwent elective PCI between April 2009 and April 2010 at Tehran Heart Center. Exclusion criteria were unsuccessful PCI, non-elective PCI, and missing opium use data. Opium consumption was defined as self-reported ever use of any traditional opium substances. Outcomes of interest were all-cause mortality and a composite of major adverse cardiac and cerebrovascular events (MACCE). The association between opium use and study outcomes was evaluated using the inverse probability of treatment weighting (IPTW) method. Cumulative hazard curves were demonstrated to further assess the association visually. Furthermore, the effect of opium consumption on individual components of MACCE was evaluated in a competing risk setting. Results: A total of 2025 elective PCI patients were included (age: 58.7 ± 10.67, 29.1% women), among whom 297 (14.6%) patients were opium users. After a median follow-up of 10.7 years, opium consumption was associated with a higher risk of all-cause mortality (IPTW-hazard ratio [HR] = 1.705, 95% CI: 1.125-2.585; P = 0.012) and MACCE (IPTW-HR = 1.578, 95% CI: 1.156-2.153; P = 0.004). The assessment of MACCE components suggested a non-significant borderline trend for higher non-fatal myocardial infarction (IPTW-sub-distribution HR [SHR] = 1.731, 95% CI: 0.928-3.231; P = 0.084) and mortality (IPTW-SHR = 1.441, 95% CI: 0.884-2.351; P = 0.143) among opium users. Conclusions: Opium consumption is associated with a more than 50% increase in long-term risk of mortality and MACCE in patients undergoing PCI. These findings accentuate the importance of preventive strategies to quit opium addiction in this population.

Antianginal effects of empagliflozin in patients with type 2 diabetes and refractory angina; a randomized, double-blind placebo-controlled trial (EMPT-ANGINA Trial).

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are emerging antidiabetic agents with various potential cardiovascular benefits. The EMPT-ANGINA trial examined the effect of empagliflozin on the angina burden in those with concurrent type 2 diabetes mellitus (T2DM) and refractory angina (RA). METHOD: In this 8-week, double-blind, randomized, placebo-controlled trial, 75 patients with T2DM and RA were randomly assigned to one of two groups: empagliflozin (n = 37) and placebo (n = 38). The primary outcome was an improvement in angina, which was assessed by the Seattle Angina Questionnaire (SAQ). The secondary outcomes of this study included alterations in the SAQ domains and exercise test components. RESULTS: The mean age of individuals in the empagliflozin and placebo groups was 67.46 ± 9.4 and 65.47 ± 7.0 years, respectively (p = .304). Patients who received empagliflozin showed a significant improvement in both the primary endpoint, which was the SAQ Summary Score (192.73 ± 20.70 vs. 224 ± 25.36, p < .001) and the secondary endpoints. Exercise test components, including treadmill exercise duration, time till angina, 1 mm ST-segment depression onset, and heart rate (HR) recovery, were all significantly improved in the empagliflozin group. This positive impact was reached with no clinically significant changes in resting and exertion HR or blood pressure. There were no significant side effects in the empagliflozin group (p = .125). CONCLUSION: Empagliflozin can be safely added as a metabolic modulator agent to existing antianginal medications in individuals with concurrent T2DM and RA to reduce angina symptoms and enhance exercise capacity with minimal side effects.

Telemetric electroencephalography recording in anesthetized mice-A novel system using minimally-invasive needle electrodes with a wireless OpenBCI™ Cyton Biosensing Board.

Telemetric electroencephalography (EEG) recording, using subdermal needle electrodes, is a minimally-invasive method to investigate mammalian neurophysiology during anesthesia. These inexpensive systems may streamline experiments examining global brain phenomena during surgical anesthesia or disease. We utilized the OpenBCI™ Cyton board with subdermal needle electrodes to extract EEG features in six C57BL/6J mice undergoing isoflurane anesthesia. Burst suppression ratio (BSR) and spectral features were compared for a verification of our method. Following an increase from 1.5% to 2.0% isoflurane, the BSR increased (Wilcoxon-signed-rank statistic; p = 0.0313). Furthermore, although the absolute EEG spectral power decreased, the relative spectral power remained comparable (Wilcoxon-Mann-Whitney U-Statistic; 95% CI exclusive AUC=0.5; p < 0.05). Compared to tethered systems, this method confers several improvements for anesthesia specific protocols: 1-Avoiding electrode implant surgical procedures, 2-Anatomical non-specificity for needle electrode placement to monitor global cortical activity representative of anesthetic state, 3-Facility to repeat recordings in the same animal, 4-User-friendly for non-experts, 5-Rapid set-up time, and 6-Lower costs.•Minimally-invasive telemetric EEG recording systems ergonomically improve tethered systems for anesthesia protocols.•Using this method, we verified that higher isoflurane concentrations resulted in an increased EEG burst suppression ratio and decreased EEG absolute spectral power, with no change in frequency distribution.

Plasma biomarkers associated with survival and thrombosis in hospitalized COVID-19 patients.

Severe coronavirus disease-19 (COVID-19) has been associated with fibrin-mediated hypercoagulability and thromboembolic complications. To evaluate potential biomarkers of coagulopathy and disease severity in COVID-19, we measured plasma levels of eight biomarkers potentially associated with coagulation, fibrinolysis, and platelet function in 43 controls and 63 COVID-19 patients, including 47 patients admitted to the intensive care unit (ICU) and 16 non-ICU patients. COVID-19 patients showed significantly elevated levels of fibrinogen, tissue plasminogen activator (t-PA), and its inhibitor plasminogen activation inhibitor 1 (PAI-1), as well as ST2 (the receptor for interleukin-33) and von Willebrand factor (vWF) compared to the control group. We found that higher levels of t-PA, ST2, and vWF at the time of admission were associated with lower survival rates, and that thrombotic events were more frequent in patients with initial higher levels of vWF. These results support a predictive role of specific biomarkers such as t-PA and vWF in the pathophysiology of COVID-19. The data provide support for the case that hypercoagulability in COVID-19 is fibrin-mediated, but also highlights the important role that vWF may play in the genesis of thromboses in the pathophysiology of COVID-19. Interventions designed to enhance fibrinolysis might prove to be useful adjuncts in the treatment of coagulopathy in a subset of COVID-19 patients.

Heterotopic gastrointestinal cyst within the submandibular space in an adult: A case report and review of the literature.

Heterotopic gastrointestinal cysts (HGIC) are rare congenital cysts that arise anywhere along the gastrointestinal tract. HGICs are infrequently reported in the oral cavity; 0.3% of HGICs are reported in the tongue and even more rarely in the submandibular space. Oral HCIGs are more common in children with only 13 reported cases in adults. In the present report, we discuss the differential diagnoses of the submandibular space lesions and describe a rare case of a very large submandibular space HGIC in an adult patient.

Comparison of Pulmonary Emboli Management Between Pulmonary Emboli Response Team and the Conventional Method: The First Study From Iran.

BACKGROUND: We aimed to evaluate the effectiveness of the Pulmonary Embolism Response Team (PERT) for intermediate-high risk and high-risk pulmonary embolism (PE) patients. METHODS: This single-blind clinical trial was performed in 2019-2021, evaluating patients with intermediate-high risk and high risk of PE. Patients in the intervention group were managed by the PERT team, and treatment plans were implemented as soon as possible. Patients in the other group received conventional PE treatments based on the hospital protocols. We compared the primary outcome of short-term mortality between the 2 groups and secondary outcomes, including right ventricle indices, hospital length-of-stay, time to decision, 30-day and in-hospital bleeding. RESULTS: Data of 74 patients were analyzed. We found no significant differences between the 2 groups regarding short-term mortality (P = 0.642), bleeding, and other complications. However, the length-of-stay and time to decision were significantly lower in patients treated by the PERT team (P < 0.001 for both). Further evaluations revealed that patients in the intervention group had a more significant reduction in the right ventricle size and systolic pulmonary pressure compared with the control group (P = 0.015, P = 0.039, respectively). In addition, tricuspid annular plane systolic excursion and fractional area change increased more in the intervention group (P = 0.023, P = 0.016, respectively). CONCLUSIONS: The PERT team led to significantly less time to make decisions, and it was able to select patients for advanced treatments more appropriately. Due to these facts, patients treated by PERT had significantly lower hospitalization duration and better right ventricle indices compared to controls.

Evaluation of correlation between digital vs. mercury sphygmomanometer in a middle-income country: The role of socio-economic situation.

BACKGROUND: Using manometer sphygmomanometers as standard measurement tool, there are controversial data regarding accuracy and validity of digital manometers for measurement of systolic (SBP) and diastolic blood pressure (DBP). Thus, we aimed to compare the accuracy of readings of digital sphygmomanometer in reference to mercury sphygmomanometer in a large population of healthy adults. METHODS AND MATERIALS: This cross-sectional study was performed on 1119 healthy adults. We measured participant's blood pressure once with mercury sphygmomanometer, as gold standard and again with digital mercury sphygmomanometer. Blood pressure was measured in sitting position after 5 min of rest and preferentially from right arm unless deformed. RESULTS: The mean ± standard deviation of age of participants was 37.25 ± 10.45 years. Majority of participants were male 588 (52.5%). The right/left SBP measured by digital sphygmomanometer were significantly higher compared with those measured by mercury sphygmomanometer: 115.37 ± 12.33 vs 110.95 ± 10.06/113.69 ± 11.77 vs 110.23 ± 10.34, respectively (P < .001), while an opposite result was observed about right/left DBP: 68.60 ± 8.55 vs 70.60 ± 8.31/69.39 ± 8.31 vs 70.75 ± 8.41, respectively (P < .001). In subgroup analysis in terms of marital status, education, and income, we observed similar findings. CONCLUSION: According to the results of our data analysis, it was shown that the digital device measurements had significant incompatibility with the mercury sphygmomanometers and it seems that digital devices still cannot be used as the gold standard in blood pressure measurement.

Evaluating value of positive T wave in lead V1 and TV1 > TV6 pattern in predicting significant coronary artery disease in patients undergoing coronary angiography.

BACKGROUND: The aim of this study was to predict significant coronary artery disease (CAD) in patients undergoing coronary angiography. METHODS: In this cross-sectional study, data of 384 patients who underwent angiography during 2015-2017 were reviewed. Electrocardiograms (ECGs) were evaluated in terms of having positive T wave in lead V1 (TV1) described as T wave with amplitude of more than 0.15 mV and angiography records were assessed for presence of significant CAD defined as presence of ≥ 70% internal diameter stenosis in at least one major epicardial coronary artery or more than 50% stenosis in left main artery (LMA). RESULTS: Out of 384 patients who participated in this study with mean age of 63.6 ± 10.2 years (40-89 years), 71.6% showed positive TV1 and significant CAD simultaneously and left anterior descending artery (LAD) and left circumflex artery (LCX) lesions were more frequently reported in coronary angiography. Based on chi-square test, the prevalence of significant CAD was obviously more in those with positive TV1 as compared to those without this finding [odds ratio (OR) = 2.74, 95% confidence interval (CI): 1.80-4.19, P < 0.001]. Mann-Whitney test showed significant difference in number of coronary arteries involved in CAD between presence of positive and negative T wave in lead V1 (P < 0.001). Great number of patients with significant CAD had remarkably higher T wave amplitude in lead V1 in comparison to lead V6 (OR = 6.22, 95% CI: 3.14-12.30, P < 0.001). CONCLUSION: Positive TV1 and TV1 > TV6 pattern can be considered as a predictor for significant CAD in patients with otherwise normal ECG.

Repetitive Anodal Transcranial Direct Current Stimulation Hastens Isoflurane-Induced Emergence and Recovery and Enhances Memory in Healthy Rats.

BACKGROUND: Attaining a rapid and smooth return to consciousness after general anesthesia is a goal for clinical anesthesiologists. This study aimed to investigate the effects of repeated anodal transcranial direct current stimulation (atDCS) on emergence and recovery from isoflurane anesthesia in rats. METHODS: Four days after surgery for atDCS socket implantation, rats received either sham stimulation or repetitive anodal direct electrical current of 0.2 mA intensity applied to the right motor cortex for 20 minutes/d for 10 consecutive days. Isoflurane potency and emergence and recovery from a 2-hour isoflurane challenge were evaluated 24 hours after the last atDCS session. Cognitive performance on novel object recognition and spontaneous alternation Y-maze tests were measured 48 hours after the last atDCS session. Locomotor activity was assessed via automated counting of electric infrared beam crossings. RESULTS: Data are expressed as mean ± standard error of mean (SEM). Isoflurane potency was not affected by atDCS (sham: 1.69% ± 0.06%, transcranial direct current stimulation [tDCS]: 1.73% ± 0.11%, mean difference [MD]: 0.045, 95% confidence interval [CI]: -0.22 to 0.30; P = .72). However, the time to appearance of emergence behavioral marker (eg, return of righting reflex) was hastened in rats receiving atDCS (sham: 486 ± 31 seconds, tDCS: 330 ± 45 seconds, MD: 157, 95% CI: 30-284; P = .008). Similarly, time to acknowledgment of adhesive tape ("sticky dot" applied while anesthetized) was also decreased in atDCS-treated rats as compared to sham (sham: 1374 ± 179 seconds, tDCS: 908 ± 151 seconds, MD: 466, 95% CI: 73-858; P = .015), indicating a faster recovery of isoflurane anesthesia. Rats treated with atDCS spent more time exploring the novel object and environment when compared to sham without affecting activity cycles, indicating visual and working memory can be enhanced by atDCS. CONCLUSIONS: Taken together, our findings suggest that atDCS over cortical areas might hasten recovery from isoflurane anesthesia and could potentially be used as a preventative strategy for disruptions in higher order functions related to sedation/anesthesia.

The relationship of the changes in lateral leads I and aVL in electrocardiogram with echocardiography and coronary angiography findings in patients with acute coronary syndrome.

BACKGROUND: Electrocardiographic (ECG) study is a principle for the symptoms contributed to the acute myocardial infarction (AMI)/acute coronary syndrome (ACS). The diagnosis of involved coronary artery based on ECG changes is still a challenge. This study is aimed to evaluate the association of mere changes in I and aVL leads with the involved region found through echocardiography and involved coronary artery through angiography. METHODS: This cross-sectional study was conducted on 100 patients referred with AMI/ACS symptoms that had mere ECG changes in I and aVL leads (ST elevation + Q wave/ST depression + inverted-T). Transthoracic echocardiography (TTE) and coronary angiography (CAG) were performed for the patients. The correlation of ECG with echocardiography and angiography was assessed. RESULTS: Among the studied population, 39 patients (39%) were women with the mean ± standard deviation (SD) of age of 64.60 ± 9.39 years. There was no significant association between ECG changes in leads I and aVL with neither the stenosis of first diagonal (D1) coronary artery found through angiography (P = 0.580) nor the mid-anterior wall dyskinesia found through echocardiography (P = 0.380). A remarkable association between the echocardiographic findings representing mid-anterior wall ischemic dyskinesia with the stenosis of D1 coronary artery was detected (P < 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100%, 54.54%, 94.68%, and 100% were respectively found as the diagnostic values of mentioned factors. CONCLUSION: Our findings showed significant association between D1 involvement and mid-anterior dyskinesia in echocardiography, while the changes in ECG were associated neither with echocardiographic nor angiographic outcomes.

Montelukast, a cysteinyl leukotriene receptor antagonist, exerts local antinociception in animal model of pain through the L-arginine/nitric oxide/cyclic GMP/KATP channel pathway and PPARγ receptors.

OBJECTIVE: The leukotrienes are inflammatory mediators. In the present study, the analgesic role of local montelukast, a cysteinyl leukotriene receptor antagonist, and the possible involvement of L-arginine/NO/cGMP/KATP channel pathway and PPARγ receptors was assessed in the formalin test in rats. METHODS AND RESULTS: The local administration of montelukast into the hind paw produced dose-related analgesia during both phases of the formalin test. Furthermore, pre-treatment with L-NAME, methylene blue, and glibenclamide prevented montelukast (10 µg/paw)-induced antinociception in both early and late phases of the test. Moreover, the local L-arginine and diazoxide before the sub-effective dose of montelukast (3 µg/paw) produced an analgesic effect. Also, local GW-9662 blocked antinociception induced by montelukast plus pioglitazone (10 µg/paw). CONCLUSION: In conclusion, montelukast produced peripheral analgesia through PPARγ receptors and activation of the L-arginine/NO/cGMP/KATP channel pathway, with potential for a new topical analgesic drug.

Preadministration of high-dose alpha-tocopherol improved memory impairment and mitochondrial dysfunction induced by proteasome inhibition in rat hippocampus.

Objective: The ubiquitin-proteasome system plays a key role in memory consolidation. Proteasome inhibition and free radical-induced neural damage were implicated in neurodegenerative states. In this study, it was tested whether alpha-tocopherol (αT) in low and high doses could improve the long-term memory impairment induced by proteasome inhibition and protects against hippocampal oxidative stress. Methods: Alpha-tocopherol (αT) (60, 200 mg/kg, i.p. for 5 days) was administered to rats with memory deficit and hippocampal oxidative stress induced by bilateral intra-hippocampal injection of lactacystin (32 ng/µl) and mitochondrial evaluations were performed for improvement assessments. Results: The results showed that lactacystin significantly reduced the passive avoidance memory performance and increased the level of malondialdehyde (MDA), reactive oxygen species (ROS) and diminished the mitochondrial membrane potential (MMP) in the rat hippocampus. Furthermore, Intraperitoneal administration of αT significantly increased the passive avoidance memory, glutathione content and reduced ROS, MDA levels and impaired MMP. Conclusions: The results suggested that αT has neuroprotective effects against lactacystin-induced oxidative stress and memory impairment via the enhancement of hippocampal antioxidant capacity and concomitant mitochondrial sustainability. This finding shows a way to prevent and also to treat neurodegenerative diseases associated with mitochondrial impairment.

The Tension-Twist Coupling Mechanism in Flexible Composites: A Systematic Study Based on Tailored Laminate Structures Using a Novel Test Device.

The focus of this research is to quantify the effect of load-coupling mechanisms in anisotropic composites with distinct flexibility. In this context, the study aims to realize a novel testing device to investigate tension-twist coupling effects. This test setup includes a modified gripping system to handle composites with stiff fibers but hyperelastic elastomeric matrices. The verification was done with a special test plan considering a glass textile as reinforcing with different lay-ups to analyze the number of layers and the influence of various fiber orientations onto the load-coupled properties. The results demonstrated that the tension-twist coupling effect strongly depends on both the fiber orientation and the considered reinforcing structure. This enables twisting angles up to 25° with corresponding torque of about 82.3 Nmm, which is even achievable for small lay-ups with 30°/60° oriented composites with distinct asymmetric deformation. For lay-ups with ±45° oriented composites revealing a symmetric deformation lead, as expected, no tension-twist coupling effect was seen. Overall, these findings reveal that the described novel test device provides the basis for an adequate and reliable determination of the load-coupled material properties between stiff fibers and hyperelastic matrices.

Evolving global and national criteria for identifying a suspected case of COVID-19.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) began in December 2019 and continues to spread worldwide. Rapid and accurate identification of suspected cases is critical in slowing spread of the virus that causes the disease. We aimed to highlight discrepancies in the various criteria used by international agencies and highly impacted individual countries around the world. METHODS: We reviewed the criteria for identifying a suspected case of COVID-19 used by two international public health agencies and 10 countries across Asia, Europe, and North America. The criteria included information on the clinical causes of illness and epidemiological risk factors. Non-English language guidelines were translated into English by a co-author who is fluent in that particular language. RESULTS: Although most criteria are modifications of World Health Organization recommendations, the specific clinical features and epidemiological risks for triggering evaluation of patients with suspected COVID-19 differed widely among countries. The rationale for these differences may be related to each country's resources, politics, experience with previous outbreaks or pandemics, health insurance system, COVID-19 outbreak severity, and other undetermined factors. CONCLUSION: We found no consensus regarding the best diagnostic criteria for identifying a suspected case of COVID-19.

Viscoelastic Behavior of Glass-Fiber-Reinforced Silicone Composites Exposed to Cyclic Loading.

The aim of this work was to analyze the influence of fibers on the mechanical behavior of fiber-reinforced elastomers under cyclic loading. Thus, the focus was on the characterization of structure-property interactions, in particular the dynamic mechanical and viscoelastic behavior. Endless twill-woven glass fibers were chosen as the reinforcement, along with silicone as the matrix material. For the characterization of the flexible composites, a novel testing device was developed. Apart from the conventional dynamic mechanical analysis, in which the effect of the fiber orientation was also considered, modified step cycle tests were conducted under tensile loading. The material viscoelastic behavior was studied, evaluating both the stress relaxation response and the capability of the material to dissipate energy under straining. The effects of the displacement rate of the strain level, the amplitude of the strain applied in the loading-unloading step cycle test, and the number of the applied cycles were evaluated. The results revealed that an optimized fiber orientation leads to 30-fold enhanced stiffness, along with 10 times higher bearable stress. The findings demonstrated that tailored reinforced elastomers with endless fibers have a strong influence on the mechanical performance, affecting the structural properties significantly.

Celecoxib inhibits acute edema and inflammatory biomarkers through peroxisome proliferator-activated receptor-γ in rats.

OBJECTIVES: Celecoxib (CLX), a selective cyclooxygenase-II (COX-2) inhibitor, has been used for management of several inflammatory disorders. The present study aimed to explore the role of peroxisome proliferator-activated receptor-gamma (PPARγ) in CLX induced anti-inflammatory response in rats. MATERIALS AND METHODS: Carrageenan-induced paw edema was used as an acute inflammation model. Rats were treated with various intra-peritoneal (IP) doses of CLX (0.3-30 mg/kg) and pioglitazone (PGL; PPARγ agonist, 1-20 mg/kg) alone or in combination. Amounts of PPARγ, COX-2, and prostaglandin E2 (PGE2) in paw tissue, and extents of TNF-α and IL-10 in serum were measured. Moreover, levels of oxidative stress parameters as malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx) activity in the cortex, hippocampus, and paw tissues were also determined. RESULTS: CLX and PGL dose-dependent administration (IP), alone or in combination reduced carrageenan-induced paw edema. Further, both agents, alone or in combination, reduced either the amounts of COX-2, PGE2, and MDA in the inflamed paw, and the levels of TNF-α in serum which were elevated by carrageenan. Both drugs also increased both levels of PPARγ, GSH, GPx activity in paws, and serum levels of IL-10 that were decreased by carrageenan. Intraplantar injection of GW-9662 (IPL), a selective PPARγ antagonist, inhibited all biochemical modifications caused by both single and combined drug treatments. CONCLUSION: CLX produced its anti-inflammatory effects probably through PPARγ receptor activation. Besides, increased anti-inflammatory effects of CLX with PGL suggest that their combination might be applied for the clinical management of inflammation especially in patients suffering from diabetes.

Venlafaxine inhibits naloxone-precipitated morphine withdrawal symptoms: Role of inflammatory cytokines and nitric oxide.

Opioid-induced neuroinflammation plays a role in the development of opioid physical dependence. Moreover, nitric oxide (NO) has been implicated in several oxidative and inflammatory pathologies. Here, we sought to determine whether treatment with venlafaxine during the development of morphine dependence could inhibit naloxone-precipitated withdrawal symptoms. The involvement of neuro-inflammation related cytokines, oxidative stress, and L-arginine (L-arg)-NO pathway in these effects were also investigated. Mice received morphine (50 mg/kg/daily; s.c.), plus venlafaxine (5 and 40 mg/kg, i.p.) once a day for 3 consecutive days. In order to evaluate the possible role of L-arg-NO on the effects caused by venlafaxine, animals received L-arg, L-NAME or aminoguanidine with venlafaxine (40 mg/kg, i.p.) 30 min before each morphine injection for 3 consecutive days. On 4th day of experiment, behavioral signs of morphine-induced physical dependence were evaluated after i.p. naloxone injection. Then, brain levels of tissue necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10), brain-derived neurotrophic factor (BDNF), NO and oxidative stress factors including; total thiol, malondialdehyde (MDA) contents and glutathione peroxidase (GPx) activity were determined. Co-administration of venlafaxine (40 mg/kg) with morphine not only inhibited the naloxone-precipitated withdrawal signs including jumping and weight loss, but also reduced the up-regulation of TNF-α, IL-1ß, IL-6, NO and MDA contents in mice brain tissue. However, repeated administration of venlafaxine inhibited the decrease in the brain levels of BDNF, total thiol and GPx. Pre-administration of L-NAME and aminoguanidine improved, while L-arg antagonized the venlafaxine-induced effects. These results provide evidences that venlafaxine could be used as a candidate drug to inhibit morphine withdrawal through the involvement of inflammatory cytokines and l-arginine-NO in mice.

Tidal peritoneal dialysis versus ultrafiltration in type 1 cardiorenal syndrome: A prospective randomized study.

BACKGROUND: Ultrafiltration is an alternative strategy to diuretic therapy for the treatment of patients with acute decompensated heart failure. Little is known about the efficacy and safety of peritoneal dialysis in patients with acute decompensated heart failure complicated by acute cardiorenal syndrome. METHODS: We randomly assigned a total of 88 patients with type 1 acute cardiorenal syndrome to a strategy of ultrafiltration therapy (44 patients) or tidal peritoneal dialysis (44 patients). The primary endpoint was the change from baseline in the serum creatinine level and left ventricular function represented as ejection fraction, as assessed 72 and 120 h after random assignment. Patients were followed for 90 days after discharge from the hospital. RESULTS: Ultrafiltration therapy was inferior to tidal peritoneal dialysis therapy with respect to the primary endpoint of the change in the serum creatinine levels at 72 and 120 h (p = 0.041) and ejection fraction at 72 and 120 h after enrollment (p = 0.044 and p = 0.032), owing to both an increase in the creatinine level in the ultrafiltration therapy group and a decrease in its level in the tidal peritoneal dialysis group. At 120 h, the mean change in the creatinine level was 1.4 ± 0.5 mg/dL in the ultrafiltration therapy group, as compared with 2.4 ± 1.3 mg/dL in the tidal peritoneal dialysis group (p = 0.023). At 72 and 120 h, there was a significant difference in weight loss between patients in the ultrafiltration therapy group and those in the tidal peritoneal dialysis group (p = 0.025). Net fluid loss was also greater in tidal peritoneal dialysis patients (p = 0.018). Adverse events were more observed in the ultrafiltration therapy group (p = 0.007). At 90 days post-discharge, tidal peritoneal dialysis patients had fewer rehospitalization for heart failure (14.3% vs 32.5%, p = 0.022). CONCLUSION: Tidal peritoneal dialysis is a safe and effective means for removing toxins and large quantities of excess fluid from patients with intractable heart failure. In patients with cardiorenal syndrome type 1, the use of tidal peritoneal dialysis was superior to ultrafiltration therapy for the preservation of renal function, improvement of cardiac function, and net fluid loss. Ultrafiltration therapy was associated with a higher rate of adverse events.