74 research outputs found

    The Immune Cell Composition in Barrett's Metaplastic Tissue Resembles That in Normal Duodenal Tissue

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    BACKGROUND AND OBJECTIVE: Barrett's esophagus (BE) is characterized by the transition of squamous epithelium into columnar epithelium with intestinal metaplasia. The increased number and types of immune cells in BE have been indicated to be due to a Th2-type inflammatory process. We tested the alternative hypothesis that the abundance of T-cells in BE is caused by a homing mechanism that is found in the duodenum. PATIENTS AND METHODS: Biopsies from BE and duodenal tissue from 30 BE patients and duodenal tissue from 18 controls were characterized by immmunohistochemistry for the presence of T-cells and eosinophils(eos). Ex vivo expanded T-cells were further phenotyped by multicolor analysis using flowcytometry. RESULTS: The high percentage of CD4(+)-T cells (69±3% (mean±SEM/n = 17, by flowcytometry)), measured by flowcytometry and immunohistochemistry, and the presence of non-activated eosinophils found in BE by immunohistochemical staining, were not different from that found in duodenal tissue. Expanded lymphocytes from these tissues had a similar phenotype, characterized by a comparable but low percentage of αE(CD103) positive CD4(+)cells (44±5% in BE, 43±4% in duodenum of BE and 34±7% in duodenum of controls) and a similar percentage of granzyme-B(+)CD8(+) cells(44±5% in BE, 33±6% in duodenum of BE and 36±7% in duodenum of controls). In addition, a similar percentage of α4β7(+) T-lymphocytes (63±5% in BE, 58±5% in duodenum of BE and 62±8% in duodenum of controls) was found. Finally, mRNA expression of the ligand for α4β7, MAdCAM-1, was also similar in BE and duodenal tissue. No evidence for a Th2-response was found as almost no IL-4(+)-T-cells were seen. CONCLUSION: The immune cell composition (lymphocytes and eosinophils) and expression of intestinal adhesion molecule MAdCAM-1 is similar in BE and duodenum. This supports the hypothesis that homing of lymphocytes to BE tissue is mainly caused by intestinal homing signals rather than to an active inflammatory response

    CD4+ Regulatory and Effector/Memory T Cell Subsets Profile Motor Dysfunction in Parkinson’s Disease

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    Animal models and clinical studies have linked the innate and adaptive immune system to the pathology of Parkinson’s disease (PD). Despite such progress, the specific immune responses that influence disease progression have eluded investigators. Herein, we assessed relationships between T cell phenotype and function with PD progression. Peripheral blood lymphocytes from two separate cohorts, a discovery cohort and a validation cohort, totaling 113 PD patients and 96 age- and environment-matched caregivers were examined by flow cytometric analysis and T cell proliferation assays. Increased effector/memory T cells (Tem), defined as CD45RO+ and FAS+ CD4+ T cells and decreased CD31+ and α4β7+ CD4+ T cells were associated with progressive Unified Parkinson’s Disease Rating Scale III scores. However, no associations were seen between immune biomarkers and increased age or disease duration. Impaired abilities of regulatory T cells (Treg) from PD patients to suppress effector T cell function was observed. These data support the concept that chronic immune stimulation, notably Tem activation and Treg dysfunction is linked to PD pathobiology and disease severity, but not disease duration. The association of T cell phenotypes with motor symptoms provides fresh avenues for novel biomarkers and therapeutic designs

    HSV-2 Infection of Dendritic Cells Amplifies a Highly Susceptible HIV-1 Cell Target

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    Herpes simplex virus type 2 (HSV-2) increases the risk of HIV-1 infection and, although several reports describe the interaction between these two viruses, the exact mechanism for this increased susceptibility remains unclear. Dendritic cells (DCs) at the site of entry of HSV-2 and HIV-1 contribute to viral spread in the mucosa. Specialized DCs present in the gut-associated lymphoid tissues produce retinoic acid (RA), an important immunomodulator, able to influence HIV-1 replication and a key mediator of integrin α4β7 on lymphocytes. α4β7 can be engaged by HIV-1 on the cell-surface and CD4+ T cells expressing high levels of this integrin (α4β7high) are particularly susceptible to HIV-1 infection. Herein we provide in-vivo data in macaques showing an increased percentage of α4β7high CD4+ T cells in rectal mucosa, iliac lymph nodes and blood within 6 days of rectal exposure to live (n = 11), but not UV-treated (n = 8), HSV-2. We found that CD11c+ DCs are a major target of HSV-2 infection in in-vitro exposed PBMCs. We determined that immature monocyte-derived DCs (moDCs) express aldehyde dehydrogenase ALDH1A1, an enzyme essential for RA production, which increases upon HSV-2 infection. Moreover, HSV-2-infected moDCs significantly increase α4β7 expression on CD4+ T lymphocytes and HIV-1 infection in DC-T cell mixtures in a RA-dependent manner. Thus, we propose that HSV-2 modulates its microenviroment, influencing DC function, increasing RA production capability and amplifying a α4β7highCD4+ T cells. These factors may play a role in increasing the susceptibility to HIV-1

    COMPARATIVE BIOAVAILABILITY OF SINGLE DOSES OF TABLET FORMULATIONS OF CETIRIZINE DIHYDROCHLORIDE IN HEALTHY MALE-VOLUNTEERS

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    The bioavailability of two tablet formulations of cetirizine (Zetir from Abbott and Zyrtek from UCB) were compared in 14 healthy male volunteers who received a single dose of 10 mg of cetirizine dihydrochloride in an open randomized two-period crossover design with a 7-day washout period between doses. Plasma samples were obtained over a 24 h interval and cetirizine concentrations were determined by HPLC with ultraviolet detection. From the plasma cetirizine concentration vs, time curves, AUC((0 - 24)) (area under the concentration vs. time curves from 0 to 24 h), C-max (maximum achieved concentration), T-max (time to achieve C-max), K-e (terminal first order elimination constant), elimination half-life (t(1/2)) and AUC((0-infinity)) (area under the concentration vs. time curves extrapolated to infinity) were obtained. The two cetirizine dihydrochloride tablet brands did not show statistically significant differences in bioavailability as assessed by analysis of AUC((0 - 24)), AUC((0-infinity)), C-max, T-max, K-e and t(1/2) values. Based on these results and on the U.S. Food and Drug Administration requirements [1985, 1993], we conclude that both formulations are bioequivalent.331273

    BIOAVAILABILITY OF 4 PHARMACEUTICAL FORMULATIONS OF METRONIDAZOLE TESTED ON NORMAL HEALTHY-VOLUNTEERS

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    1. Single doses of four metronidazole formulations (the unmarketed Trichomol, 200 mg, 400 mg, 500 mg, and the commercially available Flagyl, 400 mg) were administered to 14 healthy adult male volunteers in order to determine their pharmacokinetic profiles. 2. Plasma metronidazole concentrations were measured by high pressure liquid chromatography. The results were plotted against time and the curves obtained were used to calculate pharmacokinetic parameters (area under the curves, maximum achieved concentration and time at which it occurred, elimination constant, and half-life). 3. Trichomol formulations of 200 mg and 500 mg significantly differed from the 400 mg formulation with respect to area under the curve and maximum concentration. Trichomol 400 mg and Flagyl 400 mg showed no significant differences in maximum concentration or area under the curve. No differences were observed in half-life or time of appearance of maximum concentration among formulations. 4. Good correlations occurred between maximum concentration, area under the curve and amount of metronidazole ingested, indicating a linear pharmacokinetic profile. 5. We conclude that Trichomol 400 mg proved to be bioequivalent to the commercially available reference Flagyl 400 mg according to U.S. Food and Drug Administration requirements.24121251126

    PHARMACOKINETIC PROFILE OF 2 DIFFERENT PHARMACEUTICAL FORMS OF THEOPHYLLINE (A SLOW-RELEASE TABLET AND A SYRUP) AFTER MULTIPLE-DOSE ADMINISTRATION TO HEALTHY-HUMAN VOLUNTEERS

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    Due to the narrow therapeutic range of theophylline, plasma concentrations of this drug are monitored in patients undergoing chronic therapy. Slow-release preparations avoid the fluctuations in plasma levels and improve patient compliance. In this study, we have compared the pharmacokinetic profiles of a theophylline slow-release tablet and a syrup form, when administered in multiple doses to healthy adult volunteers. The classification based upon releasing patterns is confirmed.88115515
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