Validity and Reliability Studies of the Indonesian Version of Arrhythmia-Specific Questionnaire in Tachycardia and Arrhythmia (ASTA).

BACKGROUND: The Arrhythmia-Specific Questionnaire in Tachycardia and Arrhythmia (ASTA) was developed in Sweden using English which may pose cultural and language barriers for Indonesian patients. As such, we aimed to translate the original ASTA into Indonesian, then assess its validity and reliability. METHODS: Translation of the ASTA from English to Indonesian was done using forward and backward translation. The final version was then validated with the Short Form-36 (SF-36) questionnaire. Test-retest reliability study was done in a 7-14-day interval. RESULTS: The Indonesian version of ASTA was deemed acceptable by a panel of researchers with Cronbach's α of 0.816 and Intraclass Correlation Coefficient (ICC) ranging from 0.856-0.983. In a comparison to the SF-36, the medication utilization domain was poorly correlated with role limitations due to physical health (r:0.384; p<0.01) and pain (r:-0.317; p<0.05). The arrhythmia-specific symptoms domain was poorly correlated with role limitations due to emotional problems (r:0.271; p<0.05). In addition, the health-related quality of life (HRQOL) domain was poorly correlated with role limitations due to physical health (r:0.359; p<0.01) and emotional problems (r:0.348; p<0.01), also total SF-36 score (r:-0.367; p<0.01). The ASTA total score was poorly correlated with role limitations due to physical health (r:0.37; p<0.01), and emotional problems (r:0.376; p<0.01), also total SF-36 score (r:-0.331; p<0.01). CONCLUSION: The Indonesian version of ASTA has good internal and external validity as well as good reliability. Both the physical and mental domains of ASTA are correlated with role limitations due to emotional problems and SF-36 total score.

Phobia and Fear of COVID-19: origins, complications and management, a narrative review.

Introduction: The outbreak of Coronavirus Disease 2019 (COVID-19) have changed into a global crisis. Psychologically, this process of alteration can lead to feelings of fear, insecurity, and anxiety. This fear and anxiety can be caused by a variety of factors. However, due to the lack of extensive studies at this time, there are little data on these conditions related to COVID-19. Therefore, in this narrative review, we have tried to identify the most important possible causes of anxiety and fear due to this disease, based on logical shreds of evidence. Then we tried to discuss the consequences and ways to manage and prevent them. Methods: The current focus was on three major axes of corona-phobia, fear and anxiety. PubMed, Science Direct, Scopus, Google Scholar and authoritative news and information sources were considered as the data sources. Results: Findings from the analysis of the results revealed that, in addition to the real and the logical reasons which belong to the intrinsic properties of SARS-CoV-2, some misleadings and misconceptions induced by media, governmental policies, public awareness level, and non-scientific speculations and contradictory data expressed by experts, researchers and scientific societies, could provide the way for the development of corona-phobia, and fear. Conclusions: Each of these causal components, in its place, leads to some degrees of psychological disorders and subsequent consequences and complications. Finally, here we reviewed, summarized the previous research findings on how to prevent and manage this type of psychological disorder, and made comparisons.

Bothersome menopausal symptoms amongst postmenopausal Iranian women.

OBJECTIVES: This study was undertaken to determine the impact of menopause on middle-eastern women. METHODS: This was a cross-sectional study of 1520 women, aged 40-64 years, living in Sari, Northern Iran, recruited by multistage cluster sampling between October 2016 and April 2017. All women completed the Menopause Quality of Life Questionnaire (MENQOL) and Beck Depression Inventory-II (BDI-II). RESULTS: Of all the women, 54.5% were perimenopausal or postmenopausal. The prevalences of any vasomotor symptom (VMS) and moderate-severely bothersome VMS were greatest for postmenopausal women aged <55 years (66.4%, 95% confidence interval (CI) 59.9-72.3% and 13.5%, 95% CI 9.6-18.6%, respectively). Having moderate-severe VMS was associated with moderate-severe depressive symptoms (adjusted odds ratio (AOR) 2.9; 95% CI 1.6-5.2; p < 0.001). Symptoms of vulvovaginal atrophy (VVA) were reported by 41.1% (95% CI 37.4-45.0%) of perimenopausal and postmenopausal women, with 22.9% (95% CI 19.8-26.3%) reporting their symptoms as moderate-severely bothersome. In women with moderate-severe VMS, the proportion with both moderate-severe depressive symptoms and moderate-severe VVA symptoms (12.1%) was four times that in women with no or mild VMS (3.3%) (p < 0.001). CONCLUSION: One in seven perimenopausal and postmenopausal women has moderate-severely bothersome VMS and few women receive appropriate therapy. The reporting of moderate-severe VMS should alert clinicians to the likelihood of significant concurrent VVA and depressive symptoms.

Depressive symptoms and their risk factors in midlife women in the Middle East: a systematic review.

INTRODUCTION: Women may experience different menopausal symptoms across different cultures around the world. The purpose of this study was to determine the prevalence and contributing factors of depression in midlife women in the Middle East. METHODS: Electronic databases including PubMed, Medline, PsycINFO, CINAHL, Web of Science, SCOPUS, and Google scholar were searched. The quality of articles was assessed by using the risk of bias tool. RESULTS: Sixteen articles were used for this review. The prevalence for depressive symptoms in perimenopausal women is higher than in premenopausal women. The overall data also suggest that depressive symptoms may be more prevalent in postmenopausal women than in premenopausal women. Studies reported sociodemographic, physical, psychological, cultural and sexual risk factors for depressive symptoms in middle-aged women. Risk of bias for a majority of the studies conducted in the Middle Eastern region on depression in midlife was moderate. CONCLUSION: Consistent with other areas in the world, midlife women in the Middle East region are at higher risk for depression due to the presence of different factors. High-quality longitudinal studies of representative samples, using validated questionnaires, are needed to provide more accurate prevalence data and the association between menopause and menopausal symptoms in women in the Middle East.

The p7 viroporin of the hepatitis C virus contributes to liver inflammation by stimulating production of Interleukin-1ß.

Hepatitis C is one of the most widespread infectious diseases worldwide and hepatitis C virus (HCV)-induced chronic inflammation is highly associated with progredient liver damage. It was shown that HCV infection increases levels of pro-inflammatory cytokines via activation of NOD-like receptor (NLRP3) inflammasomes, yet the underlying mechanism is still under question. We propose modulation of intracellular pH by p7, a 63 residue ion channel produced by the hepatitis C virus as a possible pathomechanism for hepatitis C-associated inflammation. Recombinant constructs corresponding to HCV genotypes 1-4 were expressed in HEK 293 and RAW 264.7 cells and changes of intracellular pH were monitored using pH-sensitive fluorescent probes as well as production of inflammatory cytokines. Presence of p7 induced general loss of vesicular acidity as well as producing a significant increase in the levels of interleukin-1ß (IL-1ß). Effects showed a genotype-dependent pattern of IL-1ß production, in agreement with the pH-response profile of p7 channels corresponding to hepatitis C genotypes. Lowering the pH of the extracellular medium increased activity of p7 channels as well as production of IL-1ß for genotypes 1, 3, and 4, but less for genotype 2. Our data are in agreement with the hypothesis that p7 activity can trigger intracellular signaling cascades that are involved in HCV-associated cytopathy.

Protective effects of Smyrnium cordifolium boiss essential oil on pentylenetetrazol-induced seizures in mice: involvement of benzodiazepine and opioid antagonists.

Smyrnium cordifolium as a wild plant is used in traditional medicine in Iran for the treatment of anxiety and insomnia. The anticonvulsant effect of this plant has not been studied to date, therefore this study aimed to evaluate the anticonvulsant effects of its essential oil and curzerene on seizure. Essential oil of the Smyrnium cordifolium plant was prepared by the hydro-distillation method. Gas chromatography and gas chromatography-mass spectroscopy analysis of the essential oil revealed its main components. Anticonvulsant effects of Smyrnium cordifolium essential oil (SCEO) and curzerene were examined on mice using the pentylentetrazole model (PTZ). Flumazenil (2 mg/kg, i.p) and naloxone (5 mg/kg, i.p) were injected into the relevant groups of mice to realize the anticonvulsant mechanism of SCEO and curzerene, respectively. The main identified components of the plant were curzerene (65.26%), δ-Cadinene (14.39%) and γ-elemene (5.15%), which comprised approximately 85.28% of SCEO. The ED50 values of SCEO and curzerene in the PTZ model were 223±15 and 0.25±0.09 mg/kg, respectively. Curzerene at the dosage of 0.4 mg/kg prolonged the onset time of seizure and decreased the duration of seizure among treated group compared to the saline group. At the dosage of 0.4 mg/kg, seizure and mortality protection rates for the treated group were 100%. Flumazenil and naloxone could suppress the anticonvulsant effects of SCEO and curzerene. It seems that SCEO and curzerene are useful for the treatment of absence seizure and this effect may be related to their effects on GABAergic and opioid systems.

Effect of fibrous separators on the performance of lithium-sulfur batteries.

In this paper we systematically investigated effect of separator morphology on the performance of Li-S batteries. We tested two kinds of commercially available non-woven fibrous separators made of polypropylene in conjunction with trilayer PP/PE/PP porous separator. Among the non-woven separators, the fibers of the separator of first kind are rough and more acidic than the fibers of the separator of second art, which are smooth. It was found that batteries with smooth separator demonstrate higher Coulombic efficiency, higher charging/discharging capacity and better cycling stability. We attribute better performance of batteries with smooth fibers of separators to lower acidity than that of rough fibers. We believe that negatively charged polysulfides are unable to adsorb on more acidic rough fibers and diffuse readily to lithium electrode. In contrast, polysulfides are able to adsorb on the surface of less acidic smooth fibers that reduces their polysulfides shuttle and rapid decay of battery capacity. Strategic deployment of non-woven Freudenberg and Celgard separator in combination leads to high active mass utilization, superior wettability, reduced short circuit tendency caused by dendritic growth and slower capacity decay.

Cytosolic expression of functional Fab fragments in Escherichia coli using a novel combination of dual SUMO expression cassette and EnBase® cultivation mode.

AIMS: The Escherichia coli expression system is highly effective in producing recombinant proteins. However, there are some limitations in this system, especially in obtaining correctly folded forms of some complex proteins such as Fab fragments. To improve the solubility and folding quality of Fab fragments, we have examined the effect of simultaneous application of a SUMO fusion tag, EnBase® cultivation mode and a redox mutant strain in the E. coli expression system. METHODS AND RESULTS: A bicistronic gene construct was designed to express an antivascular endothelial growth factor (VEGF) Fab fragment as a model system. The construct contained a dual SUMO fusion gene fragment to encode SUMO-tagged heavy and light chains. While the expression of the construct in batch cultures of BL21 or SHuffle® transformants produced insoluble and unfolded products, the induction of the transformants in EnBase® medium resulted in soluble and correctly folded Fab fragment, reaching as high as 19% of the total protein in shuffle strain. The functional assays indicated that the biological activity of the target Fab is similar to the commercial anti-VEGF, Lucentis® . CONCLUSIONS: This study demonstrated that the combination of SUMO fusion technology, EnBase® cultivation system and recruiting a redox mutant of E. coli can efficiently enhance the solubility and productivity of recombinant Fab fragments. SIGNIFICANCE AND THE IMPACT OF THE STUDY: The presented strategy provides not only a novel method to produce soluble and active form of an anti-VEGF Fab but also may use in the efficient production of other antibody fragments.

Effect of memantine combination therapy on symptoms in patients with moderate-to-severe depressive disorder: randomized, double-blind, placebo-controlled study.

WHAT IS KNOWN AND OBJECTIVE: Current treatments for depressive disorders are far from optimum. This study was planned to evaluate possible antidepressant effects and safety of memantine, a selective N-methyl-d-aspartate receptor antagonist, in humans. METHODS: Sixty-six outpatients with the diagnosis of moderate-to-severe major depressive disorder, based on DSM-V diagnostic criteria, were recruited to participate in a parallel, randomized, controlled trial. Sixty-two participants completed 6 weeks of treatment with either memantine (20 mg/day) plus sertraline (200 mg/day) or placebo plus sertraline (200 mg/day). Patients were evaluated using the Hamilton Depression Rating Scale (HDRS) at baseline and at weeks 2, 4 and 6. Comparison of treatment efficacy in improving depressive symptoms between the two groups was the principal outcome measure. RESULTS AND DISCUSSION: A repeated-measures analysis demonstrated significant time × treatment interaction on HDRS score [F (2·09, 125·67) = 5·09, P = 0·007]. Significantly greater improvement was seen at all three follow-up sessions as well as significantly greater response rates at weeks 4 and 6 (P = 0·018 and P < 0·001, respectively) in the memantine group. Significantly more early improvers and more rapid response to treatment were observed in the memantine group (P = 0·001 and P < 0·001, respectively). A significant reduction was observed in HDRS score from baseline to the study endpoint in both memantine (P < 0·001, Cohen's d = 12·71) and placebo groups (P < 0·001, Cohen's d = 5·13). No serious adverse event occurred. No significantly greater remission rate was seen in the adjunctive memantine therapy. WHAT IS NEW AND CONCLUSION: A 6-week course of treatment with memantine as adjunct to sertraline showed a favourable safety and efficacy profile in patients with major depressive disorder. Nonetheless, larger controlled studies of longer duration are necessary to assess long-term safety, efficacy and optimal dosing.

Effect of brown rice flour fortification on the quality of wheat-based dough and flat bread.

The objective of present study was to investigate the impact of Brown Rice flour (BR) incorporation, at three different levels of 5, 10 and 15 % to the Wheat Flour (WF) preparations on rheological properties of wheat-based dough and quality of wheat-based flat bread. The BR flour incorporation mainly affected the chemical properties of flours, the rheological characteristics of dough and, quality and shelf life of bread. The protein-related properties of flours principally experienced reduction; however, the ash content had an increase, along with BR flour incorporation. The rheological properties of dough were affected considerably by BR flour substitution, wherein the sample containing 5 % BR flour was closest to BR flour-free dough (control). Regarding the yielded bread, BR flour addition affirmatively affected sensorial properties and firmness quality evaluation, wherein the bread made from dough with composite flour fortified with 5 % BR flour was scored the best. The findings from instrumental firmness quality assessment were confirmed as the bread containing 5 % BR flour remained softer and demanded lowest force to be compressed over the storage period. Overall, results showed that adding BR flour up to 5 % can be used in baking of flat bread since it meets the required criteria.

Assessment of the efficacy of polyclonal intravenous immunoglobulin G (IVIG) against the infectivity of clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo.

The response to treatment of severe methicillin-resistant Staphylococcus aureus (MRSA) infections with the traditional antibiotics is sometimes unsatisfactory and multiple antibiotic resistance is common. Adjuvant therapy such as intravenous immunoglobulin G (IVIG) could possibly be helpful in the treatment of such infections. The effect of IVIG on the capacity of human neutrophils to phagocytose and kill MRSA was investigated in vitro using the MTT assay and measuring the production of reactive oxygen species (ROS) and nitric oxide (NO). The efficiency of IVIG in neutralizing α-hemolysin and coagulase of MRSA was also assessed. The capability of IVIG in the treatment and prevention of MRSA infections was also evaluated in a murine peritonitis model. IVIG significantly enhanced (p < 0.01) the killing of MRSA by neutrophils at all concentrations tested (0.1-5 mg/ml) by 30-80 % of control values. It significantly (p < 0.01) increased the level of NO production in a dose-dependent manner, giving up to 60 µM at 5 mg/ml. The ROS level significantly increased (p < 0.01) in the presence of IVIG. In addition, IVIG significantly reduced the hemolytic activity of MRSA 10-fold and its coagulation capabilities by 50 %. When tested in vivo, groups receiving IVIG via tail vein infusion showed no significant improvement in their survival. Only when delivered to the same site of infection did IVIG show an improvement in the survival of mice (n = 80). These results could pave the way for a better understanding of the mechanism of action of IVIG and suggest its clinical potential as an adjuvant preventive and therapeutic agent against life-threatening infections caused by MRSA and other bacteria.

Catheter-based radiofrequency renal-nerve ablation in patients with resistant hypertension.

This review aims to describe the role and the results of catheter-based renal nerve ablation for the treatment of resistant hypertension. Despite the availability of multiple classes of orally active antihypertensive treatments, resistant hypertension remains an important public health issue in 2012 due to its prevalence and association with target-organ damage and poor prognosis. The failure of purely pharmacological approaches to treat resistant hypertension has stimulated interest in invasive device-based treatments based on old concepts. In the absence of orally active antihypertensive agents, patients with severe and complicated hypertension were widely treated by surgical denervation of the kidney until the 1960s, but this approach was associated with a high incidence of severe adverse events and a high mortality rate. A new catheter system using radiofrequency energy has been developed, allowing an endovascular approach to renal denervation and providing patients with resistant hypertension with a new therapeutic option that is less invasive than surgery and can be performed rapidly under local anaesthesia. To date, this technique has been evaluated only in open-label trials including small numbers of highly selected resistant hypertensive patients with suitable renal artery anatomy. The available evidence suggests a favourable blood pressure-lowering effect in the short term (6 months) and a low incidence of immediate local and endovascular complications. This follow-up period is, however, too short for the detection of rare or late-onset adverse events. For the time being, the benefit/risk ratio of this technique remains to be evaluated, precluding its uncontrolled and widespread use in routine practice.

Percutaneous Transhepatic Radiologic Intervention of Biliary Complications following Liver Transplantation: A Single-center Experience.

Background: Biliary complications are the leading cause of morbidity and mortality in patients undergo¬ing Liver Transplantation (LT). Post-biliary transplantation strictures (BSs) are a severe problem with a high risk of graft failure. However, management of these BSs has remained controversial, and consid¬erable variability has been reported in Percutaneous Transhepatic Radiological Interventions (PTRIs) related to broad differences in technical procedures. Objective: This study aimed to evaluate the efficacy of percutaneous treatments in managing post-LT BSs in a center in Shiraz. Methods: PTRIs including balloon dilatation, metallic stent, and internal or internal-external hand-made plastic stent insertion were done for 34 transplanted patients with BSs referring to the Interventional Radiology Unit of Shiraz Namazi Hospital. Technical success rate, patency rates, and complications were evaluated. Results: The. In this study, 31 strictures were successfully treated without any significant difference between the anastomotic and non-anastomotic types of stricture (success rate: 91.2%). Based on the results, 12- , 24-, and 36-month primary patency rates were 90.1%, 84.5%, and 76.8%, respectively. The secondary patency rate was 100% at 12 and 24 months and 93.3% at 36 and 60 months. The rate of minor complica¬tions (mild cholangitis and hemobilia) was 6.4%, and no major complications were detected. Conclusion: According to the findings, PTRI is an effective method for treating anastomotic and non-anas- tomotic strictures with a high success rate and low complications.

Assessment of deep learning algorithms to predict histopathological diagnosis of breast cancer: first Moroccan prospective study on a private dataset.

OBJECTIVE: Breast cancer is a critical public health issue and a leading cause of cancer-related deaths among women worldwide. Its early diagnosis and detection can effectively help in increasing the chances of survival rate. For this reason, the diagnosis and classification of breast cancer using Deep learning algorithms have attracted a lot of attention. Therefore, our study aimed to design a computational approach based on deep convolutional neural networks for an efficient classification of breast cancer histopathological images by using our own created dataset. We collected overall 328 digital slides, from 116 of surgical breast specimens diagnosed with invasive breast carcinoma of non-specific type, and referred to the histopathology department of the National Institute of Oncology in Rabat, Morocco. We used two models of deep neural network architectures in order to accurately classify the images into one of three categories: normal tissue-benign lesions, in situ carcinoma or invasive carcinoma. RESULTS: Both Resnet50 and Xception models achieved comparable results, with a small advantage to Xception extracted features. We reported high degrees of overall correct classification accuracy (88%), and sensitivity (95%) for detection of carcinoma cases, which is important for diagnostic pathology workflow in order to assist pathologists for diagnosing breast cancer with precision. The results of the present study showed that the designed classification model has a good generalization performance in predicting diagnosis of breast cancer, in spite of the limited size of the data. To our knowledge, this approach can be highly compared with other common methods in the automated analysis of breast cancer images reported in literature.

[Advantages and limitations of renin inhibition with aliskiren]. / Intérêts et limites de l'inhibition de la rénine par l'aliskiren.

In the current context of renin-angiotensin-aldosterone system (RAAS) blockade, angiotensin (Ang) converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), or their combination, have proved to be effective in providing cardiovascular and renal protection. However, renin inhibition has long been recognized as the preferred site for blockade of the RAAS because renin represents the first, highly-regulated and rate-limiting step of the system. Up to now, the first orally active renin inhibitors initially tested in humans did not meet the necessary all the criteria (specificity, potency, and pharmacokinetic profile) to become clinically useful drugs. The synthesis of aliskiren, a potent alkane carboxamide renin inhibitor, now provides an orally active compound which, according to its pharmacological profile in normotensive subjects and in patients with hypertension, diabetic nephropathy or heart failure suggests that this drug may be of value for the treatment of patients with cardiovascular and renal disorders. However, long-term studies are needed to demonstrate the efficacy of aliskiren in these clinical settings. The results of the Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Disease Endpoints (ALTITUDE) trial which has already included 8600 patients with type 2 diabetes, proteinuria and a high cardiovascular risk and compared the effects of aliskiren vs. a placebo on a composite endpoint including renal and cardiovascular morbidity and mortality should be provided in 2012.

Flow Cytometric Evaluation of CD4+ and CD8+ T-cell Immune Response in SPF Chickens Induced by Fowlpox Vaccine.

Fowlpox (FP) is a viral disease that is widely distributed throughout the world. The disease has an economic impact on the poultry industry, and its prevalence has even been reported in vaccinated flocks. The present study used flow cytometry to evaluate the CD4+ and CD8+ T-cell immune response of chicks induced by FP vaccine. 120 specific pathogen-free (SPF) 21-day-old chicks were randomly divided into three groups of 40. One group was used as negative control with PBS inoculation, the other two groups were inoculated with the local fowlpox vaccine produced by Razi Institute and commercial FP vaccines, and they were kept for five weeks. Peripheral blood mononuclear cells (PBMC) were isolated using Ficoll-Hypaque density gradients and the percentages of CD3+, CD3+, CD4+, and CD3+CD8+ T lymphocytes were analyzed with flow cytometry. Seven days post-immunization, a maximum (90-100%) swelling formation ("take") on the vaccination site was observed. The ratios of CD4+ to CD8+ T-lymphocytes in both vaccinated groups were significantly higher (p < 0.05) than the control group inoculated with PBS. The percentages of CD3+, CD3+CD4+, and CD3+CD8+ T-lymphocytes were increased in chickens vaccinated with commercial and local FP vaccines. There were no significant differences between the groups receiving commercial and local fowl pox vaccines. The present study showed that protective immunity could be associated with increased cellular immune responses, which has been interpreted as enhancing T-cell proliferation and increasing CD4+ to CD8+ ratios through vaccination with the FP vaccine. This study further suggests that the induction of enhanced immune responses is due mainly to the Th1-type response.

Endothelin receptors blockade blunts hypoxia-induced increase in PAP in humans.

BACKGROUND: Activation of the endothelin-1 (ET-1) pathway may be involved in hypoxia-induced pulmonary vasoconstriction, increase in pulmonary pressure and high altitude pulmonary oedema. Thus, we investigated the effect of the ETA/ETB receptor antagonist, bosentan, on pulmonary artery systolic pressure (PASP) in healthy subjects (n = 10). DESIGN: We used a double-blind, placebo-controlled, randomized, cross-over design to study the effects of a single oral dose of bosentan (250 mg) on PASP after 90-min-exposure to normobaric hypoxia (FiO(2) = 0.12). We measured PASP and cardiac output by echocardiography, systolic arterial blood pressure, arterial O(2) saturation (SaO(2)), and blood gases at rest and during a sub-maximal exercise. RESULTS: PASP in normoxia at rest was 23.5 +/- 2.7 and during exercise 39.8 +/- 11.6 mmHg (P < 0.0001). During the placebo period, hypoxia induced a significant decrease in SaO(2), PaO(2) and PCO(2) and increase in pH. PASP at rest increased significantly: 32.1 +/- 3.5 mmHg (P < 0.001 vs. normoxia). Bosentan significantly blunted the hypoxia-induced increase in PASP: bosentan: 27.0 +/- 3.3 mmHg, P = 0.002 vs. placebo at rest, but not during exercise: bosentan 39.8 +/- 11.6 vs. placebo 43.0 +/- 8.5 mmHg, ns. Bosentan had no effect on the hypoxia-induced changes in blood gases, or on cardiac output and systolic arterial blood pressure, which were not modified by hypoxia. CONCLUSION: A single oral dose of bosentan blunted an acute hypoxia-induced increase in PASP in healthy subjects, without altering cardiac output or systemic blood pressure.

Effects of pentoxifylline on coagulation profile and disseminated intravascular coagulation incidence in Egyptian septic neonates.

BACKGROUND AND OBJECTIVES: Neonatal sepsis is frequently associated with pathological activation of the coagulation system, leading to microcirculatory derangement and multiple organ dysfunction syndrome (MODS). The key role in the pathogenesis of sepsis has been attributed to proinflammatory cytokines. These trigger the development of disseminated intravascular coagulation (DIC) via the tissue factor-dependent pathway of coagulation. Pentoxifylline (PTX), a methylxanthine derivative that is used in peripheral vascular disease, has the potential to modify inflammatory response. The current work was designed to evaluate the potential protective effects of PTX against sepsis-induced microcirculatory derangement in Egyptian neonates. METHODS: A double-blind placebo-controlled quasi-randomized design was used. Thirty-seven neonates with sepsis were randomly allocated into two groups. Seventeen patients were given PTX (5 mg/kg/h for 6 h; for 6 successive days). Twenty patients received equivalent volume of normal saline and represented the placebo group. Prothrombin time (PT), Activated partial thromboplastin time (APTT), fibrinogen, d-dimer, C-reactive protein (CRP), complete blood count (CBC), also hemodynamic parameters comprising arterial blood pressure, heart rate, capillary refill and urinary output were assessed in both groups before and after treatment. RESULTS: Coagulation parameters in the two groups showed no significant differences. However, a higher incidence of DIC was observed in the placebo group neonates. PTX significantly lowered the percentage of bleeding (P = 0.0128) and less frequent use of FFP was observed in the PTX group (35.53% in PTX group vs. 80% in placebo group, P = 0.003). Incidence of MODS was significantly lower (P = 0.037) and hospital stay duration of survivors was significantly shorter (P = 0.044) in the PTX treated-infants. CONCLUSION: Pentoxifylline protects against sepsis-induced microcirculatory derangement in neonates. It significantly lowered the incidence of bleeding and MODS and shortened the length of hospital stay.

Viroporins and inflammasomes: A key to understand virus-induced inflammation.

Viroporins are virus encoded proteins that alter membrane permeability and can trigger subsequent cellular signals. Oligomerization of viroporin subunits results in formation of a hydrophilic pore which facilitates ion transport across host cell membranes. These viral channel proteins may be involved in different stages of the virus infection cycle. Inflammasomes are large multimolecular complexes best recognized for their ability to control activation of caspase-1, which in turn regulates the maturation of interleukin-1 ß (IL-1ß) and interleukin 18 (IL-18). IL-1ß was originally identified as a pro-inflammatory cytokine able to induce both local and systemic inflammation and a febrile reaction in response to infection or injury. Excessive production of IL-1ß is associated with autoimmune and inflammatory diseases. Microbial derivatives, bacterial pore-forming toxins, extracellular ATP and other pathogen-associated molecular patterns trigger activation of NLRP3 inflammasomes. Recent studies have reported that viroporin activity is capable of inducing inflammasome activity and production of IL-1ß, where NLRP3 is shown to be regulated by fluxes of K+, H+ and Ca2+ in addition to reactive oxygen species, autophagy and endoplasmic reticulum stress. The aim of this review is to present an overview of the key findings on viroporin activity with special emphasis on their role in virus immunity and as possible activators of inflammasomes.