The role of prostaglandin E2 (PGE 2) in toll-like receptor 4 (TLR4)-mediated colitis-associated neoplasia

<p>Abstract</p> <p>Background</p> <p>We have previously found that TLR4-deficient (TLR4-/-) mice demonstrate decreased expression of mucosal PGE ₂and are protected against colitis-associated neoplasia. However, it is still unclear whether PGE ₂is the central factor downstream of TLR4 signaling that promotes intestinal tumorigenesis. To further elucidate critical downstream pathways involving TLR4-mediated intestinal tumorigenesis, we examined the effects of exogenously administered PGE ₂in TLR4-/- mice to see if PGE ₂bypasses the protection from colitis-associated tumorigenesis.</p> <p>Method</p> <p>Mouse colitis-associated neoplasia was induced by azoxymethane (AOM) injection followed by two cycles of dextran sodium sulfate (DSS) treatment. Two different doses of PGE ₂(high dose group, 200 μg, n = 8; and low dose group, 100 μg, n = 6) were administered daily during recovery period of colitis by gavage feeding. Another group was given PGE ₂during DSS treatment (200 μg, n = 5). Inflammation and dysplasia were assessed histologically. Mucosal Cox-2 and amphiregulin (AR) expression, prostanoid synthesis, and EGFR activation were analyzed.</p> <p>Results</p> <p>In control mice treated with PBS, the average number of tumors was greater in WT mice (n = 13) than in TLR4-/- mice (n = 7). High dose but not low dose PGE ₂treatment caused an increase in epithelial proliferation. 28.6% of PBS-treated TLR4-/- mice developed dysplasia (tumors/animal: 0.4 ± 0.2). By contrast, 75.0% (tumors/animal: 1.5 ± 1.2, P < 0.05) of the high dose group and 33.3% (tumors/animal: 0.3 ± 0.5) of the low dose group developed dysplasia in TLR4-/- mice. Tumor size was also increased by high dose PGE ₂treatment. Endogenous prostanoid synthesis was differentially affected by PGE ₂treatment during acute and recovery phases of colitis. Exogenous administration of PGE ₂increased colitis-associated tumorigenesis but this only occurred during the recovery phase. Lastly, PGE ₂treatment increased mucosal expression of AR and Cox-2, thus inducing EGFR activation and forming a positive feedback mechanism to amplify mucosal Cox-2.</p> <p>Conclusions</p> <p>These results highlight the importance of PGE ₂as a central downstream molecule involving TLR4-mediated intestinal tumorigenesis.</p

Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB:HIV study

Objectives Mortality among HIV patients with tuberculosis (TB) remains high in Eastern Europe (EE), but details of TB and HIV management remain scarce. Methods In this prospective study, we describe the TB treatment regimens of patients with multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). Results A total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug resistance) and 130 pan-susceptible TB. Adequate initial TB treatment was provided for 8% of patients with MDR-TB compared with 80% of those with pan-susceptible TB. By twelve months, an estimated 57.3% (95%CI 41.5\u201374.1) of MDR-TB patients had started adequate treatment. While 67% received ART, HIV-RNA suppression was demonstrated in only 23%. Conclusions Our results show that internationally recommended MDR-TB treatment regimens were infrequently used and that ART use and viral suppression was well below the target of 90%, reflecting the challenging patient population and the environment in which health care is provided. Urgent improvement of management of patients with TB/HIV in EE, in particular for those with MDR-TB, is needed and includes widespread access to rapid TB diagnostics, better access to and use of second-line TB drugs, timely ART initiation with viral load monitoring, and integration of TB/HIV care

Rezonans magnetyczny i spektroskopowa ocena metabolitow tkanki mozgowej w przebiegu kryptokokozy OUN

Cryptococcus neoformans is the causative agent of cryptococcosis and cryptococcal meningitis, which are serious pathological conditions affecting up to 10% of patients with AIDS. In this paper we present results magnetic resonance imaging and spectroscopic metabolites (1H MR) in brain cryptococcosis. In 1HMR spectroscopy we tind decreased metabolic ratios to nonsaturated water (H2O) signal N-acetylaspartate (NA/H20, creatine (Cr/H20), choline (Cho/H20). We show increased mioinositol to H2O ratio. Spectroscopy results suggest about massive neuronal injury and accompanying gliosis in brain cryptococcosis

Beta 2-microglobulin and neopterin in patients with giardiasis

The aim of the study was to evaluate serum beta 2-microglobulin (beta-2m) and neopterin (NPT) in in patients with giardiasis. Twenty-two patients with giardiasis were examined and compared with twelve healthy subjects as a control group. Serum beta-2m and NPT concentration were determined twice: at the moment of diagnosis of giardiasis and six months after antiparasitic treatment with metronidazole. It was shown that serum beta-2m concentration in patients with giardiasis was remarkably elevated. It decreased significantly, but six months after treatment it was still higher as compared to the control group. However, serum NPT before antiparasitic treatment was slightly lower than in the control group, but after elimination of Giardia an increase of NPT concentration above control values was observed. It is concluded that Giardia infection leads to long-lasting disturbances in the immunological status of the host and may influence macrophage function and downregulate their parasiticidal effects.Celem pracy była ocena stężenia beta 2-mikroglobuliny (beta 2-m) i neopteryny (NPT) u pacjentów z giardiozą przed i po leczeniu przeciwpasożytniczym metronidazolem. Wykazano, że stężenie beta 2-m u chorych było podwyższone, a 6 miesięcy po leczeniu obniżało się, lecz nadal było wyższe niż w grupie kontrolnej. Natomiast stężenie NPT przed leczeniem przeciwpasożytniczym było niższe niż w grupie kontrolnej, a po eliminacji zarażenia obserwowano wzrost stężenia NPT powyżej wartości kontrolnych. Przeprowadzone badania wykazały, zarażenie Giardia intestinalis prowadzi do długotrwałych zaburzeń immunologicznych w organizmie gospodarza i może również mieć wpływ na przeciwpasożytnicze funkcje makrofagów

in men who have sex with men, Warsaw, Poland,

Hepatitis A and hepatitis A virus/HIV coinfectio

Toksoplazmoza mozgu jako przyklad inwazji oporutynistycznej u kobiety zyjacej z HIV

Most toxoplasmosis infections occur in the brain. Cerebral toxoplasmosis is a specially serious complication in patients with AIDS. Similarly to other opportunistic pathogens, Toxoplasma gondii causes rapidly progressive, and often fatal disease in immunosuppressed patients. The diagnosis is difficult, since no sensitive and specific non-invasive diagnostic tests exist. The subject of our study is a 27-old fornale initially diagnosed with metastasis in central nervous system