Cysteinyl leukotrienes and their receptors: Bridging inflammation and colorectal cancer

Long-standing inflammation has emerged as a hallmark of neoplastic transformation of epithelial cells and may be a limiting factor of successful conventional tumor therapies.A complex milieu composed of distinct stromal and immune cells,soluble factors and inflammatory mediators plays a crucial role in supporting and promoting various types of cancers.An augmented inflammatory response can predispose a patient to colorectal cancer(CRC).Common risk factors associated with CRC development include diet and lifestyle,altered intestinal microbiota and commensals,and chronic inflammatory bowel diseases.Cysteinyl leukotrienes are potent inflammatory metabolites synthesized from arachidonic acid and have a broad range of functions involved in the etiology of various pathologies.This review discusses the important role of cysteinyl leukotriene signaling in linking inflammation and CRC.

Effects of Prostaglandins and Leukotrienes on Hypoxic Pulmonary Vasoconstriction in Rats

To investigate the effects of prostaglandins (PGs) and leukotrienes (LTs) on hypoxic pulmonary vasoconstriction (HPV), in vivo rats experiment and in vitro perfused lung experiment were conducted. The effect of hypoxia on hemodynamics, concentrations of TXB 2 and 6 keto PGF 1α in serum and lung tissue during hypoxia and effects of PGs and LTs on HPV were observed. The results showed that pulmonary arterial pressure (P pa ) and pulmonary vascular resistance were increased during hypoxia, but cardiac output and systemic arterial pressure were decreased. There were increases of the concentrations of TXB 2 and 6 keto PGF 1α and their ratio in serum and lung tissue during hypoxia. After use of cyclooxygenase inhibitor (indomethacin) in vivo and in vitro , HPV was augmented respectively, but after use of lipoxygenase inhibitor (diethylcorbamazine) or leukotriene receptor blocker (LY 171883), HPV was attenuated. It was suggested that LTs mediated pulmonary vasoconstriction, PGs inhibited pulmonary vasoconstriction and they played a modulating role during hypoxia.

Odd couple: The unexpected partnership of glucocorticoid hormones and cysteinyl-leukotrienes in the extrinsic regulation of murine bone-marrow eosinopoiesis

Granulopoiesis in murine bone-marrow is regulated by both intrinsic and extrinsic factors(including hormones, drugs, inflammatory mediators and cytokines). Eosinophils, a minor subpopulation of circulating leukocytes, which remains better understood in its contributions to tissue injury in allergic disease than in its presumably beneficial actions in host defense, provide a striking example of joint regulation of granulopoiesis within murine bone-marrow by all of these classes of extrinsic factors. We first described the upregulation of eosinopoiesis in bone-marrow of allergen-sensitized mice following airway allergen challenge. Over the last decade, we were able to show a critical role for endogenous glucocorticoid hormones and cytokines in mediating this phenomenon through modification of cytokine effects, thereby supporting a positive association between stress hormones and allergic reactions. We have further shown that cysteinylleukotrienes(Cys LT), a major proinflammatory class of lipid mediators, generated through the 5-lipoxygenase pathway, upregulate bone-marrow eosinopoiesis in vivo and in vitro. Cys LT mediate the positive effects of drugs(indomethacin and aspirin) and of proallergic cytokines(eotaxin/CCL11 and interleukin-13) on in vitro eosinopoiesis. While these actions of endogenous GC and Cys LT might seem unrelated and even antagonistic, we demonstrated a critical partnership of these mediators in vivo, shedding light on mechanisms linking stress to allergy: GC are required for Cys LT-mediated upregulation of bone-marrow eosinopoiesis in vivo, but also attenuate subsequent ex vivo responses to Cys LT. GC and Cys LT therefore work together to induce eosinophilia, but through subtle regulatory mechanisms also limit the magnitude of subsequent bone-marrow responses to allergen.

ANISODAMINE INHIBITS ENDOTOXIN-INDUCED PROSTAGLANDINS AND LEUKOTRIENES RELEASE FROM MOUSE MACROPHAGES

It was reported that anisodamine (654-2)reduced thromboxane synthesis by platelets and lowered the plasma prostaglandin level in endotoxic shock animals when administered in the early phase of shock. However, the exact relationship between arachidonic acid (AA) metabolism and the effects of 654-2 has not been completely understood. We found that 654-2 decreased acetylcholine-and norepinephrine-induced PG release from rabbit iris,

Enantioselective synthesis of two key intermediates for leukotrienes A_4 and B_4

Leukotrienes, arachidonic acid derived metabolites of great biological signifi-cance, are present in tissue at extremely low concentrations, so that experimentalquaatities are only accessible by chemical synthesis. In various synthetic routes,[S,S-（E）]-3-（hydroxymethyl） oxiranebutanoic acid methyl ester （1） and （S）-5-（ben-zoyloxy）-6-oxohexanoic acid methyl ester （2） have been frequently used as the C-Cfragment of LTA3 and the C-Cfragment of LTB4, respectively. （Scheme1）

Efficacy and anti-inflammatory analysis of glucocorticoid,antihistamine and leukotriene receptor antagonist in the treatment of allergic rhinitis

BACKGROUND There are many adverse reactions in the treatment of allergic rhinitis(AR)mainly with conventional drugs.Leukotriene receptor antagonists,glucocorticoids and nasal antihistamines can all be used as first-line drugs for AR,but the clinical effects of the three drugs are not clear.AIM To examine the impact of glucocorticoids,antihistamines,and leukotriene receptor antagonists on individuals diagnosed with AR,specifically focusing on their influence on serum inflammatory indexes.METHODS The present retrospective study focused on the clinical data of 80 patients diagnosed and treated for AR at our hospital between May 2019 and May 2021.The participants were categorized into the control group and the observation group.The control group received leukotriene receptor antagonists,while the observation group was administered glucocorticoids and antihistamines.Conducted an observation and comparison of the symptoms,physical sign scores,adverse reactions,and effects on serum inflammatory indexes in two distinct groups of patients,both before and after treatment.RESULTS Subsequent to treatment,the nasal itching score,sneeze score,runny nose score,nasal congestion score,and physical signs score exhibited notable discrepancies(P<0.05),with the observation group demonstrating superior outcomes compared to the control group(P<0.05).The interleukin(IL)-6,IL-10,tumor necrosis factor-alpha,Soluble Intercellular Adhesion Molecule-1,Leukotriene D4 after treatment were significantly different and the observation group It is better than the control group,which is statistically significant(P<0.05).Following the intervention,the incidence of adverse reactions in the observation group,including symptoms such as nasal dryness,discomfort in the throat,bitter taste in the mouth,and minor erosion of the nasal mucosa,was found to be 7.5%.This rate was significantly lower compared to the control group,which reported an incidence of 27.5%.The difference between the two groups was statistically significant(P<0.05).CONCLUSION Glucocorticoids and antihistamines have obvious therapeutic effects,reduce serum inflammatory index levels,relieve symptoms and signs of patients,and promote patients'recovery,which can provide a reference for clinical treatment of AR.

Prophylaxis with ketotifen in rats with portal hypertension:involvement of mast cell and eicosanoids

BACKGROUND:Since we have previously shown an increase of mast cells in the small bowel and in the mesenteric lymph nodes in the rats with prehepatic portal hypertension,it can be hypothesized that this essential inflammatory cell would be involved in the pathogeny of the splanchnic changes related to portal hypertension. METHODS:To verify this hypothesis,we first studied mast cell infiltration in the ileum and in the mesenteric lymph nodes in sham-operated male Wistar rats(n=12) and in short-term prehepatic portal hypertensive rats (n=12),and the serum levels of rat mast cell protease Ⅱ(RMCP-Ⅱ)by ELISA.In a second set of experiments ketotifen,a mast cell stabilizer drug,was administered to sham-operated(n=10)and portal hypertensive(n=12) rats 24 hours before the intervention and prostanoids (PGE2,PGI2,TXB2)and leukotrienes(LTC4,LTB4)were assayed by RIA,mast cell infiltration in the ileum and in the mesenteric lymph nodes and the serum levels of RMCP-Ⅱwere also studied,to show its effectiveness to prevent the mesenteric alterations produced by the inflammatory mediators released by the mast cell. RESULTS:Forty-eight hours after the intervention RMCP-Ⅱ (P<0.05),PGE2(P<0.001)and LTC4 serum levels decreased and mast cell number and RMCP-Ⅱlevels increased in mesenteric lymph nodes in portal hypertensive rats.Prophylactic administration of ketotifen reduced portal pressure(P<0.001),serum levels of PGE2(P<0.001)and RMCP-Ⅱ(P<0.001)in mesenteric lymph nodes. CONCLUSIONS:In acute portal hypertension in the rat,the mast cell translocation from intestinal mucosa to mesenteric lymph nodes,where they are activated and degranulates,would represent a defence mechanism to avoid the activation of an acute and massive inflammatory response in this location.Prophylactic administration of ketotifen is able to reduce the splanchnic inflammatory changes related to acute portal hypertension in the rat.

Association of ALOX5AP with ischemic stroke in eastern Chinese

BACKGROUND：5-1ipoxygenase protein （ALOX5AP） has been recognized as a susceptibility gene for stroke and coronary artery diseases. The present study was to explore the role of this gene in the eastern Chinese patients with ischemic stroke.METHODS： Using a case-control design, we studied 658 patients with ischemic stroke and 704 unrelated population-based controls who were age- and sex-matched. The 658 patients were classified by the Trial of Org 10172 in Acute Stroke Treatment （TOAST）. Two single-nucleotide polymorphisms （SNPs） covering ALOX5AP were genotyped. RESULTS： The genotype frequencies of TG of the SNPs rs17222919 located in the promoter of the ALOX5AP gene were significantly higher in patients with ischemic stroke than in controls （OR＊=1.34, 95%C1＊=1.02-1.75）, especially in patients with ischemic stroke caused by small-artery occlusion （SAO） （OR＊=1.40, 95%C1＊=1.02-1.93）. Meanwhile, the genotype frequencies of TG and TG/ GG were higher in female patients than in the controls. After specification, the genotype frequencies of TG and TG/GG were higher in the patients than in controls with hypertension. The genotype frequencies of AG and AG/GG of the SNPs rs9579646 located in the intron of the ALOX5AP gene were higher in the controls than in the patients. After specification, the genotype frequencies of TG were higher in the controls than patients without hypertension. CONCLUSIONS： The present study suggests that sequence variants in the ALOX5AP gene are significantly associated with ischemic stroke.

Purification and characterization of rat testicular glutathione S-transferases:role in the synthesis of eicosanoids

Aim: Purification of glutathione S-transferases (GSTs) from rat testis; separation and identificationunits and their role in eicosanoid biosynthesis. Methods: Purification of mt testicular GSTs by affit?phy, employing S-hexylglutathione-linked epoxy-activated Sepharose 6B column and separation of indiby reverse phase-high pressure liquid chromatography (RP-HPLC). Characterization of affinity purified,um dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Westem blot analysis. The roGSTs in eicosanoid biosynthesis was determined by incubating GSTs with 5, 6-Leukotriene A_4Me (prostaglandin H_2 (PGH_2) and analyzing the products formed on HPLC/TLC. Results: The present stumajority of rat testicular GSTs are of Y_b size (60%) with molecular weight of 27 kDa. The most preunits, however, are GST Y_(n2) (27% ), followed by GST Y_c (24% ) and GST Y_(nl) (20%). These testiculavery high Leukotriene C_4 (LTC_4) synthase activity with 5, 6-Leukotriene A4Me (LTA_4Me) as theprostaglandin D (PGD) synthase activity with prostaglandin H_2 (PGH_2) as the substrate. Conclusion:testicular GSTs are Y_b sized and are involved in the synthesis of eicosanoids like LTC_4 and PGD_2.(Asian J Androl 2000 Dec; 2: 277-282)

Association ofALOX5,LTA4H and LTC4S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China

BACKGROUND:Genetic variations of the 5-lipoxygenase activating protein and leukotriene A4 hydrolase genes that confer an increased risk of ischemic stroke have implicated the family of leukotrienes as potential mediators of ischemic stroke.This study aimed to explore the association of ALOX5,LTA4 H and LTC4 S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China.METHODS:This case-control study consisted of 690 patients with ischemic stroke and 690 controls.Polymorphisms of ALOX5 rs2029253 A/G,LTA4 H rs6538697 T/C,and LTC4 S rs730012 A/C were genotyped by the polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP) analysis.The multivariate logistic regression model was used to exclude the effects of conventional risk factors on ischemic stroke.RESULTS:Carriers of C allele in rs730012 were more susceptible to ischemic stroke(OR:1.37;95%CI:1.08-1.73;P=0.009).The rs2029253 GG genotype showed a risk-reducing effect on ischemic stroke(OR:0.72;95%CI:0.55-0.93;P=0.013) while the rs6538697 CC genotype had an increased risk of ischemic stroke(OR:1.77;95%CI:1.09-2.89;P=0.022).The rs730012 variant was not associated with ischemic stroke risk after adjusting confounding factors(P>0.05).CONCLUSION:The present study suggested that gene polymorphisms in the leukotrienes pathway may exert influences,with independent genetic effects,on ischemic stroke susceptibility in a cohort of Chinese in east China.

Inhibitory effects of resveratrol on human mast cell degranulation, cytokine, chemokine and leukotriene release

Resveratrol, a polyphenol abundant in peanuts, red wine and the skin of grapes, has been shown to have anti-cancer, anti-oxidant and anti-inflammatory activities, and may also have beneficial effects on allergic inflammation. We investigated the effects of resveratrol on human mast cell activation in comparison to the anti-allergy drug tranilast. In LAD2 mast cells, both resveratrol and tranilast inhibited degranulation induced by the mast cell activators substance P, IgE/anti-IgE, and compound 48/80. Resveratrol inhibition was immediate, preventing degranulation when added simultaneously to physiological stimuli, and the effect was sustained for up to 24 hrs. The inhibitory effect was not cAMP dependent, but may be attributable to calcium modulation, as resveratrol, and to a lesser extent tranilast, prevented substance P-induced increases in intracellular calcium. Resveratrol attenuated substance P-induced TNF and MCP-1 production and inhibited IgE-mediated release of cysteinyl leukotrienes, whereas tranilast was ineffective. Furthermore, both resveratrol and tranilast reduced expression of the high affinity IgE receptor, FcεRI, on LAD2 cells. The effects of resveratrol on mast cell activation were more marked in human primary CD34+-derived mast cells (HuMC), and the polyphenol was significantly more efficacious than tranilast in these cells. In conclusion, resveratrol inhibited key aspects of human mast cell activation to physiological stimuli, and was comparable, if not more efficacious than the anti-allergy drug tranilast. Thus, resveratrol may be an effective therapeutic agent for the treatment of allergic disease.

Exhaled Breath Condensates as a Source for Biomarkers for Characterization of Inflammatory Lung Diseases

Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease are common and difficult to diagnose and characterize. This is due in large part to difficulty in obtaining samples directly from the inflamed lung. The collection of lung secretions by traditional methods including bronchoalveolar lavage and induced sputum collection are limited by their invasive nature. Exhaled breath condensate (EBC) is a simple and non-invasive technique of collecting fluid samples, which are representative of airway lining fluid. Advances in collection methods and evolving molecular techniques have led to development of more sensitive assays for existing biomarkers and identification of new biomarkers, which can be potentially useful in monitoring lung inflammation. In this review, we present the current understanding of various biomarkers including small molecules (H2O2, pH and nitric oxide related biomarkers), lipid mediators (8-isprostane, leukotrienes and prostaglandins), small proteins (cytokines and chemokines) and nucleic acids (DNA and microRNAs). We also discuss the differential profile of biomarkers in recognizing different patterns of lung inflammation. As the sensitivity of methods of EBC improves, this biofluid will play an increasing role in diagnosis and monitoring of lung diseases.

Variants of the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene and risk of ischemic stroke in Han Chinese of eastern China

Variants of the arachidonate 5-1ipoxygenase-activating protein （ALOX5AP） gene have been suggested to play an important role in the pathogenesis of atherosclerosis and ischemic stroke. This study was aimed to explore the association of ALOX5AP variants with ischemic stroke risk in Han Chinese of eastern China. A total of 690 ischemic stroke cases and 767 controls were recruited. The subjects were further subtyped according to the Trial of Org 10172 in Acute Stroke Treatment （TOAST） criteria. On the basis of that, two polymorphisms of the ALOX5AP gene （rs10507391 and rs12429692） were determined by TaqMan genotyping assay. In addition, plasma leukotriene B4 （LTB4） levels were analyzed in these subjects. There was no evidence of association between the two variants of ALOX5AP and the risk of ischemic stroke or its TOAST-subtypes. Haplotype analysis and stratification analysis according to sex, age, body mass index, hypertension, and diabetes also showed negative association. Analysis of LTB4 levels in a subset of cases and controls revealed that LTB4 levels were significantly higher in ischemic stroke cases than in the controls （70.06± 14.75 ng/L vs 57.34±10.93 ng/L; P = 0.000） and carriers of the T allele of the rs10507391 variant were associated with higher plasma LTB4 levels （P = 0.000）. The present study suggests there is no association of the two polymorphisms in the ALOX5AP gene with ischemic stroke risk in Han Chinese of eastern China.

Drug repurposing of histone deacetylase inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene a4 hydrolase and blocking LTB4 biosynthesis

OBJECTIVE Leukotriene B4(LTB4)biosynthesis and subsequently neutrophilic inflammation may provide a potential strategy for the treatment of acute lung injury(ALI)or idiopathic pulmonary fibrosis(IPF).To provide a potential strategy for the treatment of ALI or IPF,we identified potent inhibitors of Leukotriene A4 hydrolase(LTA4H),a key enzyme in the biosynthesis of LTB4.METHODS In this study,we identified two known histone deacetylase(HDAC)inhibitors,suberanilohydroxamic acid(SAHA)and its analogue 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide(M344),as effective inhibitors of LTA4H using enzymatic assay,thermofluor assay,and X-ray crystallographic investigation.We next tested the effect of SAHA and M344 on endogenous LTB4 biosynthesis in neutrophils by ELISA and neutrophil migration by transwell migration assay.A murine experimental model of ALI was induced by lipopolysaccharide(LPS)inhalation.Histopathological analysis of lung tissue using H&E staining revealed the serious pulmonary damage caused by LPS treatment and the effect of the SAHA.We next examined m RNA and protein levels of pro-inflammatory cytokines in lung tissue and bronchoalveolar lavage fluid using q RT-PCR and ELISA to further investigate the underlying mechanisms of anti-inflammatory activities by SAHA.We also investigated the effects of SAHA and M344 on a murine experimental model of bleomycin(BLM)-induced IPF model.RESULTS The results of enzymatic assay and X-ray crystallography showed that both SAHA and M344 bind to LTA4H,significantly decrease LTB4 levels in neutrophil,and markedly diminish early neutrophilic inflammation in mouse models of ALI and IPF under a clinical safety dose.CONCLUSION Collectively,SAHA and M344 would provide promising agents with well-known clinical safety for potential treatment in patients with ALI and IPF via pharmacologically inhibiting LAT4H and blocking LTB4 biosynthesis.

Effect of ONO-4057 and tacrolimus on ischemia-reperfusion injury of the liver

AIM: To investigate the effects of a novel Leukotriene B4 receptor antagonist and/or tacrolimus on ischemia-reperfusion in a rat liver model. METHODS: Male Lewis rats were pretreated with ONO-4057 (100 mg/kg) and/or tacrolimus (1 mg/kg) orally, and divided into four experimental groups; group 1 (control), group 2 (ONO-4057), group 3 (tacrolimus), group 4 (ONO-4057 + tacrolimus). RESULTS: There was a tendency for long survival in the groups treated with tacrolimus alone and ONO-4057 plus tacrolimus. Post-reperfusion serum aspartate aminotransferase levels decreased more signif icantly in ONO-4057 plus tacrolimus group (P < 0.01), than in the tacrolimus alone group (P < 0.05), compared to controls. CONCLUSION: This study demonstrated that pretreat-ment with ONO-4057 in combination with tacrolimus produced additive effects in a rat model of liver isch-emia-reperfusion injury.

Enhanced expressions and activations of leukotriene C4synthesis enzymes in D-galactosamine/lipopolysaccharide-induced rat fulminant hepatic failure model

AIM： To investigate the expression and activity of leukotriene C4 （LTC4） synthesis enzymes and their underlying relationship with cysteinyl leukotriene （cys-LT） generation in a rat fulminant hepatic failure （FHF） model induced by D-galactosamine/lipopolysaccharide （D-GaIN/ LPS）. METHODS： Rats were treated with D-GaIN （300 mg/kg） plus LPS （0.1 mg/kg） for 1, 3, 6, and 12 h. Enzyme immunoassay was used to determine the hepatic cys-LT content. Reverse transcription-polymerase chain reaction （RT-PCR）, Western blot or immunohistochemical assay were employed to assess the expression or location of LTC4 synthesis enzymes, which belong to membrane associated proteins in eicosanoid and glutathione （MAPEG） metabolism superfamily. Activity of LTC4 synthesis enzymes was evaluated by determination of the products of LTA4 after incubation with liver microsomes using high performance liquid chromatography （HPLC）. RESULTS： Livers were injured after treatment with D-GaIN/LPS, accompanied by cys-LT accumulation at the prophase of liver injury. Both LTC4 synthase （LTC4S） and microsomal glutathione-S-transferase （mGST） 2 were expressed in the rat liver, while the latter was specifically located in hepatocytes. Their mRNA and protein expressions were up-regulated at an earlier phase after treatment with D-GaIN/LPS. Meantime, a higher activity of LTC4 synthesis enzymes was detected, although theactivity of LTC4S played the main role in this case. CONCLUSION： The expression and activity of both LTC4S and mGST2 are up regulated in a rat FHF model, which are, at least, partly responsible for cys-LT hepatic accumulation.

Phytochemistry and potential therapeutic actions of Boswellic acids:A mini-review

The pentacyclic triterpenic acids isolated from the oleo gum resin of various Boswellia species are collectively called as Boswellic acids(BA).The oleo gum resin obtained from Indian variety i.e.Boswellia serrata(Family – Burseraceae) is commonly known as Salai guggal.The resin fraction of Salai guggal is rich in Boswellic acids and its essential oil is composed of a mixture of mono,di and sesquiterpenes while gum fraction chiefly contains pentose and hexose sugars.This oleo-gum resin is quite popular among traditional practitioners of traditional Chinese and Indian Systems of medicine owing to their wide range of useful biological properties such as anti-inflammatory,anti-arthritic,antirheumatic,anti-diarrheal,anti-hyperlipidemic,anti-asthmatic,anti-cancer,anti-microbial anti-fungal,anti-complementary and analgesic activity,etc.It has been used as a herbal medicine since the prehistoric time to cure acute and chronic ailments including inflammatory diseases.Phytochemical investigation of this herbal medicine lead to identification of Boswellic acids which are found to be novel,potent,specific antiinflammatory agents due to non-redox inhibition of 5-lipoxygenase(5-LO) enzyme.However,the other important targets of Boswellic acids also include topoisomerases,angiogenesis,and cytochrome p450 enzymes.This review is a sincere attempt to discuss and present the current status of therapeutic potential,phytochemical as well as pharmacological profile of Boswellic acids primarily obtained from B.serrata.

半胱氨酰白三烯受体与支气管哮喘关系研究进展

大量研究已证实CysLTR1在呼吸道炎症和哮喘的发病机理中起着重要的作用,几乎所有参与哮喘作用的炎性细胞表面都有CysLTR1的表达,CysLTR1表达量的增多或者减少与呼吸道炎症密切相关,并且半胱氨酰白三烯受体1拮抗剂（Cysteinyl leukotriene receptor 1 antagonist,CysLTRA）临床应用于拮抗其引起的呼吸道炎症,在哮喘控制中发挥了重要作用。

A New Therapy for Human Endometriosis: The Therapeutic Value of Leukotriene Receptor Antagonist for Endometriosis

Some drugs that regulate estrogen are currently used as therapy for endometriosis. However, these medical treatments have significant side effects and patients who hope to become pregnant cannot overcome infertility. To compare morphological alterations and clinical symptoms, revised American Fertility Society (r-AFS) scores were compared between patients with and without leukotriene receptor antagonist (LTR-A) treatment. LTR-A-treated cases showed significantly decreased r-AFS score. Furthermore, a significant correlation was seen between r-AFS score and LTR-A treatment period. In treated cases, clinical symptoms decreased and some patients achieved pregnancy. Morphologically, lesions in LTR-A-treated cases showed apoptotic fibroblasts and degeneration of collagen fibers. Our findings revealed that LTR-As had significant therapeutic value for the treatment of human endometriosis. Anti-LT therapy appears efficacious not only in the treatment of clinical symptoms and lesions, but also in improving fertility.

Kinetics of Serum and Local Leukotriene B₄Response in Experimental Intravaginal Trichomoniasis by <i>T. vaginalis</i>Isolates from Symptomatic and Asymptomatic Women

Trichomoniasis is most common sexually transmitted disease caused by T. vaginalis. The clinical manifestation varies from severe manifestation to asymptomatic condition. However, the exact virulence markers led to varied symptomatology was not well clarified. The role of leukotriene B4 (LTB4) in the pathogenesis of many parasitic diseases has been reported. The present study reports the leukotriene B4 levels on different days post infection (3rd, 7th, 14th, 21st and 28th d.p.i.) in serum and vaginal washes (VWs) and vaginal tissues of mice infected intravaginally with T. vaginalis isolates from 10 symptomatic and 10 asymptomatic women. A significant increase in LTB4 was observed on the 3rd to 28th d.p.i. in serum and VWs of mice infected with T. vaginalis isolates from asymptomatic as compared to symptomatic women. The present study also reports the histopathological changes of the posterior vaginal fornix’s and upper portion of the vagina of mice infected intravaginally with T. vaginalis isolates from 10 symptomatic and 10 asymptomatic women. The results show that there are no significant differences between symptomatic and asymptomatic isolates regarding histopathological changes.