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  1. Fulltext In vitro porcine blood-brain barrier model for permeability studies: pCEL-X software pKa(FLUX) method for aqueous boundary layer correction and detailed data analysis
    Yusof SR, Avdeef A, Abbott NJ
    Eur J Pharm Sci, 2014 Dec 18;65:98-111.
    PMID: 25239510 DOI: 10.1016/j.ejps.2014.09.009
    In vitro blood-brain barrier (BBB) models from primary brain endothelial cells can closely resemble the in vivo BBB, offering valuable models to assay BBB functions and to screen potential central nervous system drugs. We have recently developed an in vitro BBB model using primary porcine brain endothelial cells. The model shows expression of tight junction proteins and high transendothelial electrical resistance, evidence for a restrictive paracellular pathway. Validation studies using small drug-like compounds demonstrated functional uptake and efflux transporters, showing the suitability of the model to assay drug permeability. However, one limitation of in vitro model permeability measurement is the presence of the aqueous boundary layer (ABL) resulting from inefficient stirring during the permeability assay. The ABL can be a rate-limiting step in permeation, particularly for lipophilic compounds, causing underestimation of the permeability. If the ABL effect is ignored, the permeability measured in vitro will not reflect the permeability in vivo. To address the issue, we explored the combination of in vitro permeability measurement using our porcine model with the pKa(FLUX) method in pCEL-X software to correct for the ABL effect and allow a detailed analysis of in vitro (transendothelial) permeability data, Papp. Published Papp using porcine models generated by our group and other groups are also analyzed. From the Papp, intrinsic transcellular permeability (P0) is derived by simultaneous refinement using a weighted nonlinear regression, taking into account permeability through the ABL, paracellular permeability and filter restrictions on permeation. The in vitro P0 derived for 22 compounds (35 measurements) showed good correlation with P0 derived from in situ brain perfusion data (r(2)=0.61). The analysis also gave evidence for carrier-mediated uptake of naloxone, propranolol and vinblastine. The combination of the in vitro porcine model and the software analysis provides a useful tool to better predict BBB permeability in vivo and gain better mechanistic information about BBB permeation.
    Matched MeSH terms: Capillary Permeability/physiology*
  2. Assessment of the Blood-Brain Barrier Permeability of Potential Neuroprotective Aurones in Parallel Artificial Membrane Permeability Assay and Porcine Brain Endothelial Cell Models
    Liew KF, Hanapi NA, Chan KL, Yusof SR, Lee CY
    J Pharm Sci, 2017 02;106(2):502-510.
    PMID: 27855959 DOI: 10.1016/j.xphs.2016.10.006
    Previously, several aurone derivatives were identified with promising neuroprotective activities. In developing these compounds to target the central nervous system (CNS), an assessment of their blood-brain barrier (BBB) permeability was performed using in vitro BBB models: parallel artificial membrane permeability assay-BBB which measures passive permeability and primary porcine brain endothelial cell model which enables determination of the involvement of active transport mechanism. Parallel artificial membrane permeability assay-BBB identified most compounds with high passive permeability, with 3 aurones having exceptional Pevalues highlighting the importance of basic amine moieties and optimal lipophilicity for good passive permeability. Bidirectional permeability assays with porcine brain endothelial cell showed a significant net influx permeation of the aurones indicating a facilitated uptake mechanism in contrast to donepezil, a CNS drug included in the evaluation which only displayed passive permeation. From pH-dependent permeability assay coupled with data analysis using pCEL-X software, intrinsic transcellular permeability (Po) of a representative aurone 4-3 was determined, considering factors such as the aqueous boundary layer that may hinder accurate in vitro to in vivo correlation. The Po value determined supported the in vivo feasibility of the aurone as a CNS-active compound.
    Matched MeSH terms: Capillary Permeability*
  3. Fulltext Classifying dengue: a review of the difficulties in using the WHO case classification for dengue haemorrhagic fever
    Bandyopadhyay S, Lum LC, Kroeger A
    Trop Med Int Health, 2006 Aug;11(8):1238-55.
    PMID: 16903887 DOI: 10.1111/j.1365-3156.2006.01678.x
    BACKGROUND: The current World Health Organisation (WHO) classification of dengue includes two distinct entities: dengue fever (DF) and dengue haemorrhagic fever (DHF)/dengue shock syndrome; it is largely based on pediatric cases in Southeast Asia. Dengue has extended to different tropical areas and older age groups. Variations from the original description of dengue manifestations are being reported.
    OBJECTIVES: To analyse the experience of clinicians in using the dengue case classification and identify challenges in applying the criteria in routine clinical practice.
    METHOD: Systematic literature review of post-1975 English-language publications on dengue classification.
    RESULTS: Thirty-seven papers were reviewed. Several studies had strictly applied all four WHO criteria in DHF cases; however, most clinicians reported difficulties in meeting all four criteria and used a modified classification. The positive tourniquet test representing the minimum requirement of a haemorrhagic manifestation did not distinguish between DHF and DF. In cases of DHF thrombocytopenia was observed in 8.6-96%, plasma leakage in 6-95% and haemorrhagic manifestations in 22-93%. The low sensitivity of classifying DHF could be due to failure to repeat the tests or physical examinations at the appropriate time, early intravenous fluid therapy, and lack of adequate resources in an epidemic situation and perhaps a considerable overlap of clinical manifestations in the different dengue entities.
    CONCLUSION: A prospective multi-centre study across dengue endemic regions, age groups and the health care system is required which describes the clinical presentation of dengue including simple laboratory parameters in order to review and if necessary modify the current dengue classification.
    Matched MeSH terms: Capillary Permeability/physiology
  4. Fulltext Bixa orellana leaf extract suppresses histamine-induced endothelial hyperpermeability via the PLC-NO-cGMP signaling cascade
    Yong YK, Chiong HS, Somchit MN, Ahmad Z
    BMC Complement Altern Med, 2015;15:356.
    PMID: 26468073 DOI: 10.1186/s12906-015-0901-3
    Histamine is established as a potent inflammatory mediator and it is known to increased endothelial permeability by promoting gap formation between endothelial cells. Previous studies have shown that aqueous extract of Bixa orellana leaves (AEBO) exhibits antihistamine activity in vivo, yet the mechanism of its action on endothelial barrier function remains unclear. Therefore, the current study aimed to determine the protective effect of AEBO against histamine-induced hyperpermeability in vitro.
    Matched MeSH terms: Capillary Permeability/drug effects*
  5. Therapeutic prospects of bradykinin receptor antagonists
    Sharma JN
    Gen. Pharmacol., 1993 Mar;24(2):267-74.
    PMID: 8387049
    1. Bradykinin and related kinins may act on four types of receptors designated as B1, B2, B3 and B4. It seems that the B2 receptors are most commonly found in various vascular and non-vascular smooth muscles, whereas B1 receptors are formed in vitro during trauma, and injury, and are found in bone tissues. 2. These BK receptors are involved in the regulations of various physiological and pathological processes. 3. The mode of kinin actions are based upon the interactions between the kinin and their specific receptors, which can lead to activation of several second-messenger systems. 4. Recently, numerous BK receptors antagonists have been synthesized with prime aim to treat diseases caused by excessive kinin production. 5. These diseases are RA, inflammatory diseases of the bowel, asthma, rhinitis and sore throat, allergic reactions, pain, inflammatory skin disorders, endotoxin and anaphylactic shock and coronary heart diseases. 6. On the other hand, BK receptor antagonists could be contraindicated in hypertension, since these drugs may antagonize the antihypertensive therapy and/or may trigger the hypertensive crisis. 7. It is worth suggesting that the BK receptor agonists might be useful antihypertensive drugs.
    Matched MeSH terms: Capillary Permeability/drug effects
  6. Fulltext Malaysian Tualang Honey Inhibits Hydrogen Peroxide-Induced Endothelial Hyperpermeability
    Devasvaran K, Tan JJ, Ng CT, Fong LY, Yong YK
    Oxid Med Cell Longev, 2019;2019:1202676.
    PMID: 31531177 DOI: 10.1155/2019/1202676
    Malaysian Tualang honey (TH) is a known therapeutic honey extracted from the honeycombs of the Tualang tree (Koompassia excelsa) and has been reported for its antioxidant, anti-inflammatory, antiproliferative, and wound healing properties. However, the possible vascular protective effect of TH against oxidative stress remains unclear. In this study, the effects of TH on hydrogen peroxide- (H2O2-) elicited vascular hyperpermeability in human umbilical vein endothelial cells (HUVECs) and Balb/c mice were evaluated. Our data showed that TH concentrations ranging from 0.01% to 1.00% showed no cytotoxic effect to HUVECs. Induction with 0.5 mM H2O2 was found to increase HUVEC permeability, but the effect was significantly reversed attenuated by TH (p < 0.05), of which the permeability with the highest inhibition peaked at 0.1%. In Balb/c mice, TH (0.5 g/kg-1.5 g/kg) significantly (p < 0.05) reduced H2O2 (0.3%)-induced albumin-bound Evans blue leak, in a dose-dependent manner. Immunofluorescence staining confirmed that TH reduced actin stress fiber formation while increasing cortical actin formation and colocalization of caveolin-1 and β-catenin in HUVECs. Signaling studies showed that HUVECs pretreated with TH significantly (p < 0.05) decreased intracellular calcium release, while sustaining the level of cAMP when challenged with H2O2. These results suggested that TH could inhibit H2O2-induced vascular hyperpermeability in vitro and in vivo by suppression of adherence junction protein redistribution via calcium and cAMP, which could have a therapeutic potential for diseases related to the increase of both oxidant and vascular permeability.
    Matched MeSH terms: Capillary Permeability/drug effects*
  7. Preparation and characterization of an amylase-triggered dextrin-linked graphene oxide anticancer drug nanocarrier and its vascular permeability
    Kiew SF, Ho YT, Kiew LV, Kah JCY, Lee HB, Imae T, et al.
    Int J Pharm, 2017 Dec 20;534(1-2):297-307.
    PMID: 29080707 DOI: 10.1016/j.ijpharm.2017.10.045
    We synthesized a dextrin (DEX)-conjugated graphene oxide (GO) nanocarrier (GO100-DEX) as a potential drug delivery system to respond to a tumor-associated stimulus, α-amylase, that has high permeability through the fenestrated endothelial barrier to the tumor site. At acidic pH and in the presence of α-amylase to simulate tumor conditions, GO100-DEX released a 1.5-fold higher amount of doxorubicin (DOX) than of GO100. Under the same conditions, the cytotoxic effects of GO100-DEX/DOX were 2-fold greater than those of free DOX and 2.9-fold greater than those of GO100/DOX. Employing an in vitro biomimetic microfluidic blood vessel model lined with human umbilical vein endothelial cells, we evaluated the tumor vasculature endothelial permeation of GO100-DEX and GO100 using dextrans of 10 and 70kDa for comparison and as standards to validate the microfluidic blood vessel model. The results showed that the permeabilities of GO100-DEX and GO100 were 4.3- and 4.9-fold greater than that of 70kDa dextran and 2.7- and 3.1-fold higher than that of 10kDa dextran, thus demonstrating the good permeability of the GO-based nanocarrier through the fenestrated endothelial barrier.
    Matched MeSH terms: Capillary Permeability/drug effects
  8. Mechanisms of Blood Brain Barrier Disruption by Different Types of Bacteria, and Bacterial-Host Interactions Facilitate the Bacterial Pathogen Invading the Brain
    Al-Obaidi MMJ, Desa MNM
    Cell Mol Neurobiol, 2018 Oct;38(7):1349-1368.
    PMID: 30117097 DOI: 10.1007/s10571-018-0609-2
    This review aims to elucidate the different mechanisms of blood brain barrier (BBB) disruption that may occur due to invasion by different types of bacteria, as well as to show the bacteria-host interactions that assist the bacterial pathogen in invading the brain. For example, platelet-activating factor receptor (PAFR) is responsible for brain invasion during the adhesion of pneumococci to brain endothelial cells, which might lead to brain invasion. Additionally, the major adhesin of the pneumococcal pilus-1, RrgA is able to bind the BBB endothelial receptors: polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell adhesion molecule (PECAM-1), thus leading to invasion of the brain. Moreover, Streptococcus pneumoniae choline binding protein A (CbpA) targets the common carboxy-terminal domain of the laminin receptor (LR) establishing initial contact with brain endothelium that might result in BBB invasion. Furthermore, BBB disruption may occur by S. pneumoniae penetration through increasing in pro-inflammatory markers and endothelial permeability. In contrast, adhesion, invasion, and translocation through or between endothelial cells can be done by S. pneumoniae without any disruption to the vascular endothelium, upon BBB penetration. Internalins (InlA and InlB) of Listeria monocytogenes interact with its cellular receptors E-cadherin and mesenchymal-epithelial transition (MET) to facilitate invading the brain. L. monocytogenes species activate NF-κB in endothelial cells, encouraging the expression of P- and E-selectin, intercellular adhesion molecule 1 (ICAM-1), and Vascular cell adhesion protein 1 (VCAM-1), as well as IL-6 and IL-8 and monocyte chemoattractant protein-1 (MCP-1), all these markers assist in BBB disruption. Bacillus anthracis species interrupt both adherens junctions (AJs) and tight junctions (TJs), leading to BBB disruption. Brain microvascular endothelial cells (BMECs) permeability and BBB disruption are induced via interendothelial junction proteins reduction as well as up-regulation of IL-1α, IL-1β, IL-6, TNF-α, MCP-1, macrophage inflammatory proteins-1 alpha (MIP1α) markers in Staphylococcus aureus species. Streptococcus agalactiae or Group B Streptococcus toxins (GBS) enhance IL-8 and ICAM-1 as well as nitric oxide (NO) production from endothelial cells via the expression of inducible nitric oxide synthase (iNOS) enhancement, resulting in BBB disruption. While Gram-negative bacteria, Haemophilus influenza OmpP2 is able to target the common carboxy-terminal domain of LR to start initial interaction with brain endothelium, then invade the brain. H. influenza type b (HiB), can induce BBB permeability through TJ disruption. LR and PAFR binding sites have been recognized as common routes of CNS entrance by Neisseria meningitidis. N. meningitidis species also initiate binding to BMECs and induces AJs deformation, as well as inducing specific cleavage of the TJ component occludin through the release of host MMP-8. Escherichia coli bind to BMECs through LR, resulting in IL-6 and IL-8 release and iNOS production, as well as resulting in disassembly of TJs between endothelial cells, facilitating BBB disruption. Therefore, obtaining knowledge of BBB disruption by different types of bacterial species will provide a picture of how the bacteria enter the central nervous system (CNS) which might support the discovery of therapeutic strategies for each bacteria to control and manage infection.
    Matched MeSH terms: Capillary Permeability/physiology*
  9. Bixa orellana leaves extract inhibits bradykinin-induced inflammation through suppression of nitric oxide production
    Yoke Keong Y, Arifah AK, Sukardi S, Roslida AH, Somchit MN, Zuraini A
    Med Princ Pract, 2011;20(2):142-6.
    PMID: 21252569 DOI: 10.1159/000319907
    The present study was conducted to assess the anti-inflammatory effect of a crude aqueous extract of Bixa orellana leaves (AEBO) and to examine the possible involvement of nitric oxide (NO) in its anti-inflammatory mechanism.
    Matched MeSH terms: Capillary Permeability/drug effects
  10. Fulltext Common variants of chemokine receptor gene CXCR3 and its ligands CXCL10 and CXCL11 associated with vascular permeability of dengue infection in peninsular Malaysia
    Hoh BP, Umi-Shakina H, Zuraihan Z, Zaiharina MZ, Rafidah-Hanim S, Mahiran M, et al.
    Hum Immunol, 2015 Jun;76(6):421-6.
    PMID: 25858769 DOI: 10.1016/j.humimm.2015.03.019
    Dengue causes significantly more human disease than any other arboviruses. It causes a spectrum of illness, ranging from mild self-limited fever, to severe and fatal dengue hemorrhagic fever, as evidenced by vascular leakage and multifactorial hemostatic abnormalities. There is no specific treatment available till date. Evidence shows that chemokines CXCL10, CXCL11 and their receptor CXCR3 are involved in severity of dengue, but their genetic association with the susceptibility of vascular leakage during dengue infection has not been reported. We genotyped 14 common variants of these candidate genes in 176 patients infected with dengue. rs4859584 and rs8878 (CXCL10) were significantly associated with vascular permeability of dengue infection (P<0.05); while variants of CXCL11 showed moderate significance of association (P=0.0527). Haplotype blocks were constructed for genes CXCL10 and CXCL11 (5 and 7 common variants respectively). Haplotype association tests performed revealed that, "CCCCA" of gene CXCL10 and "AGTTTAC" of CXCL11 were found to be significantly associated with vascular leakage (P=0.0154 and 0.0366 respectively). In summary, our association study further strengthens the evidence of the involvement of CXCL10 and CXCL11 in the pathogenesis of dengue infection.
    Matched MeSH terms: Capillary Permeability*
  11. Nitric oxide participates in IFN-gamma-induced HUVECs hyperpermeability
    Ng CT, Fong LY, Low YY, Ban J, Hakim MN, Ahmad Z
    Physiol Res, 2016 12 13;65(6):1053-1058.
    PMID: 27539106
    The endothelial barrier function is tightly controlled by a broad range of signaling cascades including nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway. It has been proposed that disturbances in NO and cGMP production could interfere with proper endothelial barrier function. In this study, we assessed the effect of interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, on NO and cGMP levels and examined the mechanisms by which NO and cGMP regulate the IFN-gamma-mediated HUVECs hyperpermeability. The flux of fluorescein isothiocyanate-labeled dextran across cell monolayers was used to study the permeability of endothelial cells. Here, we found that IFN-gamma significantly attenuated basal NO concentration and the increased NO levels supplied by a NO donor, sodium nitroprusside (SNP). Besides, application of IFN-gamma also significantly attenuated both the basal cGMP concentration and the increased cGMP production donated by a cell permeable cGMP analogue, 8-bromo-cyclic GMP (8-Br-cGMP). In addition, exposure of the cell monolayer to IFN-gamma significantly increased HUVECs basal permeability. However, L-NAME pretreatment did not suppress IFN-gamma-induced HUVECs hyperpermeability. L-NAME pretreatment followed by SNP or SNP pretreatment partially reduced IFN-gamma-induced HUVECs hyperpermeability. Pretreatment with a guanylate cyclase inhibitor, 6-anilino-5,8-quinolinedione (LY83583), led to a further increase in IFN-gamma-induced HUVECs hyperpermeability. The findings suggest that the mechanism underlying IFN-gamma-induced increased HUVECs permeability is partly related to the inhibition of NO production.
    Matched MeSH terms: Capillary Permeability/drug effects*
  12. Asiatic acid stabilizes cytoskeletal proteins and prevents TNF-α-induced disorganization of cell-cell junctions in human aortic endothelial cells
    Fong LY, Ng CT, Yong YK, Hakim MN, Ahmad Z
    Vascul Pharmacol, 2019 06;117:15-26.
    PMID: 30114509 DOI: 10.1016/j.vph.2018.08.005
    Endothelial hyperpermeability represents an initiating step in early atherosclerosis and it often occurs as a result of endothelial barrier dysfunction. Asiatic acid, a major triterpene isolated from Centella asiatica (L.) Urban, has previously been demonstrated to protect against tumor necrosis factor (TNF)-α-induced endothelial barrier dysfunction. The present study aimed to investigate the mechanisms underlying the barrier protective effect of asiatic acid in human aortic endothelial cells (HAECs). The localization of F-actin, diphosphorylated myosin light chain (diphospho-MLC), adherens junctions (AJs) and tight junctions (TJs) was studied using immunocytochemistry techniques and confocal microscopy. Their total protein expressions were examined using western blot analysis. The endothelial permeability was assessed using In Vitro Vascular Permeability Assay kits. In addition, intracellular redistribution of the junctional proteins was evaluated using subcellular fractionation kits. We show that asiatic acid stabilized F-actin and diphospho-MLC at the cell periphery and prevented their rearrangement stimulated by TNF-α. However, asiatic acid failed to attenuate cytochalasin D-induced increased permeability. Besides, asiatic acid abrogated TNF-α-induced structural reorganization of vascular endothelial (VE)-cadherin and β-catenin by preserving their reticulum structures at cell-cell contact areas. In addition, asiatic acid also inhibited TNF-α-induced redistribution of occludin and zona occludens (ZO)-1 in different subcellular fractions. In conclusion, the barrier-stabilizing effect of asiatic acid might be associated with preservation of AJs and prevention of TJ redistribution caused by TNF-α. This study provides evidence to support the potential use of asiatic acid in the prevention of early atherosclerosis, which is initiated by endothelial barrier dysfunction.
    Matched MeSH terms: Capillary Permeability/drug effects*
  13. Fulltext Comparing the usefulness of the 1997 and 2009 WHO dengue case classification: a systematic literature review
    Horstick O, Jaenisch T, Martinez E, Kroeger A, See LL, Farrar J, et al.
    Am J Trop Med Hyg, 2014 Sep;91(3):621-34.
    PMID: 24957540 DOI: 10.4269/ajtmh.13-0676
    The 1997 and 2009 WHO dengue case classifications were compared in a systematic review with 12 eligible studies (4 prospective). Ten expert opinion articles were used for discussion. For the 2009 WHO classification studies show: when determining severe dengue sensitivity ranges between 59-98% (88%/98%: prospective studies), specificity between 41-99% (99%: prospective study) - comparing the 1997 WHO classification: sensitivity 24.8-89.9% (24.8%/74%: prospective studies), specificity: 25%/100% (100%: prospective study). The application of the 2009 WHO classification is easy, however for (non-severe) dengue there may be a risk of monitoring increased case numbers. Warning signs validation studies are needed. For epidemiological/pathogenesis research use of the 2009 WHO classification, opinion papers show that ease of application, increased sensitivity (severe dengue) and international comparability are advantageous; 3 severe dengue criteria (severe plasma leakage, severe bleeding, severe organ manifestation) are useful research endpoints. The 2009 WHO classification has clear advantages for clinical use, use in epidemiology is promising and research use may at least not be a disadvantage.
    Matched MeSH terms: Capillary Permeability
  14. Dengue-associated adult respiratory distress syndrome
    Lum LC, Thong MK, Cheah YK, Lam SK
    Ann Trop Paediatr, 1995 Dec;15(4):335-9.
    PMID: 8687212 DOI: 10.1080/02724936.1995.11747794
    In dengue shock syndrome, an acute increase in capillary permeability results in leakage of plasma into the interstitial space. Pleural effusion is commonly seen in dengue shock syndrome. We report three cases of dengue-associated adult respiratory distress syndrome (ARDS) in children, in all of whom dengue haemorrhagic fever, presenting with grade 3 or grade 4 dengue shock syndrome with disseminated intravascular coagulopathy, was confirmed. The criteria for the diagnosis of ARDS were based on the expanded definition of ARDS by Murray et al. Treatment consisted of fluid resuscitation, correction of coagulopathy and mechanical ventilation. All three children had multi-organ impairment, but it was more severe in the two who died. The one survivor was well at discharge.
    Matched MeSH terms: Capillary Permeability
  15. Role of cytokines produced by T helper immune-modulators in dengue pathogenesis: a systematic review and meta-analysis
    Tran L, Radwan I, Minh LHN, Low SK, Hashan MR, Gomaa MD, et al.
    Acta Trop, 2021 Jan 06.
    PMID: 33421421 DOI: 10.1016/j.actatropica.2021.105823
    BACKGROUND AND OBJECTIVES: Modulation of the immune reaction is essential in the development of various diseases, including dengue's "Cytokine Tsunami", an increase in vascular permeability with concomitant severe vascular leakage. We aim to identify the role of T-helper (Th) cells, Th2 and Th7, with their related cytokines in dengue pathogenesis.

    MATERIAL AND METHODS: Nine electronic databases and manual search were applied to detect available publications. A meta-analysis using a fixed- or random-effect model was performed to measure standardized mean difference (SMD) with 95% confidence interval (CI). The National Institute of Health (NIH) tools for observational cohort, cross-sectional, and case-control studies were used to examine the risk of bias. The protocol was recorded in PROSPERO with CRD42017060230.

    RESULTS: A total of 38 articles were found including 19 case-control, 11 cross-sectional and 8 prospective cohort studies. We indicated that Th2 cytokines (IL-4, IL-6, IL-8) and Th17 cytokine (IL-17) in dengue patients were notably higher than in a healthy control group in acute phase (SMD = 1.59, 95% CI [0.68, 2.51], p = 0.001; SMD = 1.24, 95% CI [0.41, 2.06], p = 0.003; SMD = 1.13, 95% CI [0.61, 1.66], p<0.0001; SMD = 1.74, 95% CI [0.87, 2.61], p<0.0001), respectively.

    CONCLUSIONS: This study provides evidence of the significant roles of IL-4, IL-6, IL-8, IL-10 and IL-17 in the pathogenesis of developing a severe reaction in dengue fever. However, to fully determine the association of Th cytokines with dengue, it is necessary to perform further studies to assess kinetic levels during the duration of the illness.

    Matched MeSH terms: Capillary Permeability
  16. Montelukast Reduces the Risk of Dengue Shock Syndrome in Dengue Patients
    Ahmad A, Waseem T, Butt NF, Randhawa FA, Malik U, Shakoori TA
    Trop Biomed, 2018 Dec 01;35(4):1115-1122.
    PMID: 33601858
    A significant percentage of dengue patients develop Dengue Shock Syndrome (DSS) which is characterized by increased vascular permeability, circulatory failure and often death. Montelukast, a cysteinyl leukotriene receptor antagonist regulates vascular permeability and we hypothesized that it may be effective in protecting against DSS. An open label, parallel, randomized controlled trial (RCT) was thus carried out at Mayo Hospital, Department of Medicine, Lahore. A total of 200 patients of dengue fever were recruited and randomized into two groups. The group A was treated with Montelukast 10 mg once daily for 5 days along with general supportive treatment. Group B received the standard supportive treatment and served as the control group. The frequency of DSS was compared in the two groups by Chi square test. A binary logistic regression analysis was conducted to assess the effects of montelukast treatment on onset of DSS after adjusting for gender, age, white cell count, platelet count, haematocrit, serum alanine transaminase (ALT) and aspartate transaminase (AST). Relative risk (RR), absolute risk reduction (ARR), relative risk reduction (RRR) and numbers needed to treat (NNT) were calculated. Significance level was set at p0.001, Odds ratio=5.01, 95% CI=2.17-11.60) even after adjusting for confounders. Montelukast reduced the absolute risk (ARR=22%) and the relative risk (RRR=71%) of DSS in dengue fever. Numbers needed to treat were 4.55. We thus conclude that treatment with oral montelukast may protect patients of dengue fever from DSS and greatly reduce mortality.
    Matched MeSH terms: Capillary Permeability
  17. Fulltext Suppressions of serotonin-induced increased vascular permeability and leukocyte infiltration by Bixa orellana leaf extract
    Yong YK, Sulaiman N, Hakim MN, Lian GE, Zakaria ZA, Othman F, et al.
    Biomed Res Int, 2013;2013:463145.
    PMID: 24224164 DOI: 10.1155/2013/463145
    The aim of the present study was to evaluate the anti-inflammatory activities of aqueous extract of Bixa orellana (AEBO) leaves and its possible mechanisms in animal models. The anti-inflammatory activity of the extract was evaluated using serotonin-induced rat paw edema, increased peritoneal vascular permeability, and leukocyte infiltrations in an air-pouch model. Nitric oxide (NO), indicated by the sum of nitrites and nitrates, and vascular growth endothelial growth factor (VEGF) were measured in paw tissues of rats to determine their involvement in the regulation of increased permeability. Pretreatments with AEBO (50 and 150 mg kg⁻¹) prior to serotonin inductions resulted in maximum inhibitions of 56.2% of paw volume, 45.7% of Evans blue dye leakage in the peritoneal vascular permeability model, and 83.9% of leukocyte infiltration in the air-pouch model. 57.2% maximum inhibition of NO and 27% of VEGF formations in rats' paws were observed with AEBO at the dose of 150 mg kg⁻¹. Pharmacological screening of the extract showed significant (P < 0.05) anti-inflammatory activity, indicated by the suppressions of increased vascular permeability and leukocyte infiltration. The inhibitions of these inflammatory events are probably mediated via inhibition of NO and VEGF formation and release.
    Matched MeSH terms: Capillary Permeability/drug effects*
  18. Fulltext Chemical constituents and antihistamine activity of Bixa orellana leaf extract
    Yong YK, Zakaria ZA, Kadir AA, Somchit MN, Ee Cheng Lian G, Ahmad Z
    BMC Complement Altern Med, 2013 Feb 14;13:32.
    PMID: 23410184 DOI: 10.1186/1472-6882-13-32
    BACKGROUND: Bixa orellana L. has been traditionally used in Central and South America to treat a number of ailments, including internal inflammation, and in other tropical countries like Malaysia as treatment for gastric ulcers and stomach discomfort. The current study aimed to determine the major chemical constituents of the aqueous extract of B. orellana (AEBO) and to evaluate the antihistamine activity of AEBO during acute inflammation induced in rats.

    METHODS: Acute inflammation was produced by subplantar injection of 0.1 mL of 0.1% histamine into the right hind paw of each rat in the control and treatment groups. The degree of edema was measured before injection and at the time points of 30, 60, 120, 180, 240 and 300 min after injection. Changes of peritoneal vascular permeability were studied using Evans blue dye as a detector. Vascular permeability was evaluated by the amount of dye leakage into the peritoneal cavity in rats. To evaluate the inhibitory effect of AEBO on biochemical mediators of vascular permeability, the levels of nitric oxide (NO) and vascular endothelial growth factor (VEGF) were determined in histamine-treated paw tissues. The major constituents of AEBO were determined by gas chromatography-mass spectrometry (GC-MS) analysis.

    RESULTS: AEBO produced a significant inhibition of histamine-induced paw edema starting at 60 min time point, with maximal percentage of inhibition (60.25%) achieved with a dose of 150 mg/kg of AEBO at 60 min time point. Up to 99% of increased peritoneal vascular permeability produced by histamine was successfully suppressed by AEBO. The expression of biochemical mediators of vascular permeability, NO and VEGF, was also found to be downregulated in the AEBO treated group. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that the major constituent in AEBO was acetic acid.

    CONCLUSIONS: The experimental findings demonstrated that the anti-inflammatory activity of AEBO was due to its inhibitory effect on vascular permeability, which was suppressed as a result of the reduced expression of biochemical mediators (NO and VEGF) in tissues. Our results contribute towards the validation of the traditional use of Bixa orellana in the treatment of inflammatory disorders.

    Matched MeSH terms: Capillary Permeability/drug effects*
  19. Fulltext Diverse roles of prostaglandins in blastocyst implantation
    Salleh N
    ScientificWorldJournal, 2014;2014:968141.
    PMID: 24616654 DOI: 10.1155/2014/968141
    Prostaglandins (PGs), derivatives of arachidonic acid, play an indispensable role in embryo implantation. PGs have been reported to participate in the increase in vascular permeability, stromal decidualization, blastocyst growth and development, leukocyte recruitment, embryo transport, trophoblast invasion, and extracellular matrix remodeling during implantation. Deranged PGs syntheses and actions will result in implantation failure. This review summarizes up-to-date literatures on the role of PGs in blastocyst implantation which could provide a broad perspective to guide further research in this field.
    Matched MeSH terms: Capillary Permeability
  20. Lung injury related to consuming Sauropus androgynus vegetable
    Wu CL, Hsu WH, Chiang CD, Kao CH, Hung DZ, King SL, et al.
    J. Toxicol. Clin. Toxicol., 1997;35(3):241-8.
    PMID: 9140317 DOI: 10.3109/15563659709001207
    BACKGROUND: Taking Sauropus androgynus, a Malaysian food, to reduce weight began as a fad in Taiwan in 1994. Some advocates of this fad developed pulmonary dysfunction. The aim of this study is to report the lung injury in patients taking Sauropus androgynus.

    METHODS: From July 1995 to November 1995, we investigated 104 nonsmoking patients (one male and 103 females) with chest roentgenography, pulmonary function, test, and Technetium 99m-labeled diethylene triamine penta-acetate (Tc-99m DTPA) radioaerosol inhalation lung scintigraphy.

    RESULTS: Among the 90 patients receiving Tc-99m DTPA inhalation lung scan, 46 (51.1%) patients had increased clearance of Tc-99m DTPA from lung and 20 (22.2%) patients had inhomogeneous deposition of the submicronic radioaerosol. Eighteen (18/100) patients had obstructive ventilatory impairment in pulmonary function test. Analyzing the results, we found that the patients with respiratory symptoms (n = 42) took more vegetables (p = 0.016), had increased clearance of Tc-99m DTPA (p = 0.010) and had lower FEV1 (p = 0.001), FEV1/FVC (p < 0.001), FEF25-75 (p = 0.001), VC (p = 0.002) and DLCO (p = 0.009) than the patients without respiratory symptoms (n = 62). FEV1 and FEV1/FVC were significantly reduced in patients with severe impairment of alveolar permeability. The cumulative dosage and duration of exposure were significantly associated with the reduction of FEV1 and FEV1/FVC.

    CONCLUSION: The lung injury after taking Sauropus androgynus involves alveoli and/or small airways and is manifest as obstructive ventilatory impairment with inhomogeneous aerosol distribution and increased lung epithelial permeability.
    Matched MeSH terms: Capillary Permeability
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