Background. Little is known about the effect of pulmonary arterial hypertension (PAH) specific therapy on pulmonary hemodynamics and exercise capacity in patients with portopulmonary hypertension (PoPH) because such patients are usually excluded from randomized clinical trials (RCT) of such therapy. Methods. We searched PUBMED using the terms “(Therapy/Broad (filter)) AND (portopulmonary hypertension).” We included studies that met the following criteria: ≥5 patients, AND PoPH confirmed by right heart catheterization (RHC), AND follow-up RHC data, AND/OR baseline and follow-up 6MWD available. Results. 12 studies met our inclusion criteria. None was a RCT. The baseline mPAP was 48.6 ± 4.4 mmHg, cardiac output (CO) 5.6 ± 0.9 L/min, and pulmonary vascular resistance (PVR) 668.6 ± 219.1 dynes.sec/cm5. The baseline 6MWD was 348.2 ± 35.6 meters. The use of PAH specific therapy improved mPAP by 7.54 mmHg (95% CI 10.2 to 4.9), CO by 1.77 L/min (95% CI 1.1 to 2.4), and PVR by 253 dynes.sec/cm5 (95% CI 291.4 to 214.6) (n = 135) and 6MWD by 61.8 meters (95% CI 47.5 to 76) (n = 122). Conclusions. The use of PAH specific therapy in PoPH results in significant improvement in both pulmonary hemodynamics and 6MWD.
BackgroundStatins are used for treatment of hypercholestremia. Common adverse reports associated with use of statins are generalized bodyache, rhabdomyolysis, muscles weakness and gastrointestinal disorders. The current work is an attempt to explain how smooth muscles of gastrointestinal tissues are affected by the current statins (Simvastatin, atorvastatin, fluvastatin and rosuvastatin).MethodsEffects of the current statins were studied on spontaneous activity of isolated rabbits’ jejunal preparations. Different molar concentrations (10−12–10−2M) of the statins were applied on spontaneously contracting rabbits’ jejunal preparations. As statins relaxed spontaneous activity, so we tested the statins on KCl (80 mM) induced contractions in similar test concentrations. Positive relaxant statins were tested again through construction of Calcium Concentration Response Curves (CCRCs) in the absence and presence of the statins using verapamil, a standard calcium channel blocker. CCRCs of statins were compared with CCRCs of verapamil.ResultsSimvastatin, atorvastatin, fluvastatin and rosuvastatin relaxed the spontaneous and KCl-induced contractions. IC50 for simvastatin on spontaneous rabbit’s jejunal preparations is −5.08 ± 0.1 Log 10 M. Similarly, IC50 for KCl-induced contractions is −4.25 ± 0.01 Log 10 M. Mean IC50 (Log 10 M) for atorvastatin on spontaneous rabbit’s jejunal preparations and KCl-induced contractions are −5.19 ± 0.07 and −4.37 ± 0.09, respectively. Fluvastatin relaxed spontaneous activity of rabbits’ jejunal preparations with an IC50 (Log 10 M) −4.5 ± 0.03. Rosuvastatin relaxed spontaneous as well as KCl (80 mM) induced contractions with respective IC50 (Log 10 M) −3.62 ± 0.04 and −4.57 ± 0.06. In case of CCRCs, tissues pre-treated with 4.6 μg/ml of simvastatin, have IC50 = −1.84 ± 0.03 [log (Ca++) M] vs control IC50 = −2.54 ± 0.04 [log (Ca++) M]. Similarly, atorvastatin, fluvastatin and rosuvastatin produced significant right shift in IC50 for CCRCs (P ≤ 0.05). In case of verapamil, IC50 for control curves is −2.45 ± 0.06 [log (Ca ++) M], while IC50 in presence of verapamil (0.1 μM) is −1.69 ± 0.05 [log (Ca ++) M]. Statins produced right shift in the IC50 of CCRCs. The effects of statins are like that of effects of verapamil, a standard calcium channel blocker.ConclusionsOur findings suggest that current statins have calcium antagonistic effects that act on voltage gated calcium channels that may provide a rationale for cause muscle weakness and gastrointestinal disorders.
pDC are known to produce large amount of IFN-α/β in response to viruses, and act as a major link between the innate and adaptive immune response. This study concentrated on the interaction of human peripheral blood derived pDC with HCV NS3, NS4, and NS5 proteins, and their maturation, cytokine secretion and functional properties. It was shown that HCV NS5 interferes with CD40L induced maturation of pDC as indicated by decreased expression of CD83 and CD86 markers. CpG ODN stimulated HCV NS3 and NS5 treated pDC showed decreased production of IFN-α. In the case of NS3, IFN-α production was reduced to 126 pg/ml as compared to 245 pg/ml in controls (P < 0.01), and with NS5, IFN-α production was reduced to 92 pg/ml as compared to 238 pg/ml in controls (P < 0.05). In the presence of HCV NS5, the T cell stimulatory capacity of pDC was impaired, as indicated by decreased proliferation of T cells, and decreased production by the T cells of IFN-γ, which were down to 86 pg/ml as compared to 260 pg/ml in controls (P < 0.05). These results suggest that HCV NS5 impairs pDC function and is in agreement with several other in vivo studies indicating decreased numbers of, and dysfunctional pDC, in chronic HCV infected patients. Key words dendritic cells, hepatitis C virus, interferon-α, nonstructural proteins.HCV, a member of the Flaviviridiae family of viruses, is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma. HCV infection is characterized by its ability to become chronic in 70% to 80% patients. The clinical course of HCV infection results from the fluctuating balance between the capacity of the virus to replicate, spread, and mutate rapidly and the inability of the host to eliminate it. Following HCV infection, an initial high level List of Abbreviations: APC, antigen presenting cells; CFSE, carboxyfluorescein diacetate succinidyl ester; CpG ODN, cytosine-phosphate-guanisone oligonucleotide; DC, dendritic cells; FACS, fluorescent-activated cell sorting; GADPH, glyceraldehyde-3-phosphate dehydrogenase; HCV, hepatitis C virus; HCVcc, cell culture-produced HCV; IFN, interferon; IL, interleukin; mDC, myeloid dendritic cells; MFI, mean fluorescent intensity; MHC, major histocompatibility complex; NK, natural killer; NS, nonstructural; PBMC, peripheral blood mononuclear cells; pDC, plasmacytoid dendritic cells; PHA, phytohemagglutinin; PI, propidium iodide; Th, helper T cells; TLR, toll like receptor; TNF-α, tumor necrosis factor-α of viremia is generally reduced by the immune system. In those cases where the virus is not completely removed, a controlled infection persists over many years (1). Several ex vivo and in vitro studies have indicated that chronic HCV infected patients show decreased DC function as compared to both healthy individuals and patients who have resolved their infection. A number of groups have confirmed that DC derived from HCV-infected patients
Deep venous thrombosis (DVT) is common in intensive care unit (ICU) patients. It is often silent and may be complicated by pulmonary embolism and death. Thromboprophylaxis with heparin does not always prevent venous thromboembolism (VTE). Aspirin (ASA) reduces the risk of VTE in surgical and high-risk medical patients but it is unknown if ASA may prevent DVT in mechanically ventilated ICU patients. We performed a retrospective chart review of critically ill patients who received mechanical ventilation for >72 h and underwent venous ultrasonography for suspected DVT between Jan 2012 and Dec 2013. We excluded patients who were on therapeutic doses of anticoagulation or had coagulopathy. We used multivariable logistic regression to evaluate association between aspirin use and DVT during hospitalization. There were 193 patients. The mean ± SD age was 58 ± 15.7 years. Half were male. DVT was found in 49 (25.4%). DVT was found in the first 15 days of hospitalization in 67.3% of the patients. The majority (82.8%) received thromboprophylaxis with unfractionated or low molecular weight heparin. Fifty-six (29%) were on ASA. On multivariable regression analysis, ASA use was associated with a significant reduction in the odds of finding DVT (OR 0.39, 95% CI 0.16-0.94; p = 0.036). DVT is common in mechanically ventilated ICU patients despite the use of thromboprophylaxis. Aspirin may prevent DVT in such patients.
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