Objective: To study the effect of a new fermented milk product containing GABA (FMG) on the blood pressure (BP) of patients with mild hypertension. Design: A randomized, placebo-controlled, single-blind trial. Setting: The study was carried out at the outpatient clinic of the Cardiovascular Disease Center, Tokyo Metropolitan Police Hospital, Japan. Subjects: The study population comprised 39 mildly hypertensive patients (16 women and 23 men) aged 28 -81 y (mean, 54.2 y). Interventions: The study consisted of a 12-week period of daily intake of FMG or placebo (weeks 1 -12) followed by 2 weeks of no intake (weeks 13 and 14). We measured the peripheral BP and heart rate of seated patients at weeks 0, 2, 4, 8, 12 and 14. Routine blood study and urinalysis were performed before and after the intake. Results: There was a significant decrease of BP within 2 or 4 weeks, and it remained decreased throughout the 12-week intake period. For the FMG recipients, the mean decrease after 12 weeks was 17.4 AE 4.3 mmHg in the systolic BP (SBP) and 7.2 AE 5.7 mmHg in the diastolic BP (DBP). Both of these values differed statistically from baseline levels (P < 0.01), and the SBP of the FMG group differed from the placebo group (P < 0.05). Heart rate, body weight, hematological and blood chemistry variables, and urinalysis results (glucosuria and proteinuria) did not vary both groups throughout the study. Conclusion: FMG may contribute to lowering BP in mildly hypertensive people.
Repeated administration of antigen often leads to consequences different from those expected with fewer encounters with the antigen, but little attention has been paid to the effects of repeated epicutaneous application of antigens. To investigate whether repeated epicutaneous application of a contact-sensitizing agent that is generally thought to evoke a typical delayed-type hypersensitivity response could result in adverse or different consequences, BALB/c mice were sensitized with 2,4,6-trinitro-1-chlorobenzine and then were repeatedly elicited on the original sensitized site with the same antigen for 24-48 d. Detailed analyses showed that the time-course of antigen-specific hypersensitivity responses shifted from a delayed-type hypersensitivity to an immediate-type response followed by a late reaction as epicutaneous applications were repeated, a finding different from that previously reported. Development of these hypersensitivity responses was antigen specific, and this shift was associated with epidermal hyperplasia, accumulation of large numbers of mast cells and CD4+ T cells beneath the epidermis, and elevated serum levels of antigen-specific IgE. The immediate-type response to 2,4,6-trinitro-1-chlorobenzine was also induced in 2,4,6-trinitro-1-chlorobenzine-treated, genetically mast cell-deficient W/Wv mice that contained significant numbers of mast cells, but not in similarly treated S1/S1d mice devoid of mast cells. Our experimental system would provide a simple, reproducible animal model for chronic skin inflammation induced by various antigens.
We investigated the blood-pressure-lowering effects of g-aminobutyric acid (GABA) and a GABA-enriched fermented milk product (FMG) by low-dose oral administration to spontaneously hypertensive (SHR/Izm) and normotensive Wistar -Kyoto (WKY/Izm) rats. FMG was a non-fat fermented milk product produced by lactic acid bacteria, and the GABA contained in FMG was made from the protein of the milk during fermentation. A single oral dose of GABA or FMG (5 ml/kg; 0·5 mg GABA/kg) significantly (P,0·05) decreased the blood pressure of SHR/Izm from 4 to 8 h after administration, but did not increase that of WKY/Izm rats. The hypotensive activity of GABA was dose-dependent from 0·05 to 5·00 mg/kg in SHR/Izm. During the chronic administration of experimental diets to SHR/Izm, a significantly slower increase in blood pressure with respect to the control group was observed at 1 or 2 weeks after the start of feeding with the GABA or FMG diet respectively (P, 0·05) and this difference was maintained throughout the period of feeding. The time profile of blood-pressure change due to administration of FMG was similar to that of GABA. FMG did not inhibit angiotensin 1-converting enzyme. Furthermore, an FMG peptide-containing fraction from reverse-phase chromatography lacked a hypotensive effect in SHR/ Izm rats. The present results suggest that low-dose oral GABA has a hypotensive effect in SHR/Izm and that the hypotensive effect of FMG is due to GABA.
Effector-memory T cells are strategically placed to epithelial tissues to provide frontline immune protection against pathogens. Their detrimental effects, however, have been rarely examined because of difficulty in sampling these T cells in pathological settings. Our previous studies suggested persistence of a similar subset of intraepidermal CD8(+) T cells at high frequencies in the lesions of fixed drug eruption, a localized variant of drug-induced dermatoses. In situ activation of this subset resulting in localized epidermal injury can be traced in the lesions after antigen challenge by paired immunohistochemical staining, reverse transcriptase-polymerase chain reaction in situ, and flow cytometry of dispersed cells. Here we show that effector-memory T cells were greatly enriched in these intraepidermal CD8(+) T cells, but not dermal and circulating counterparts, and that they constitutively express an early activation marker CD69 even before challenge. Surprisingly, a large proportion of these T cells expressed immediate effector function as evidenced by the rapid production of high levels of interferon-gamma in situ with much faster kinetics than their counterparts at the mRNA and protein levels after challenge. This was followed by localized epidermal injury. The intracellular cytokine assay ex vivo shows that the great majority of these dispersed T cells produce interferon-gamma. This study provides the first in situ description of the detrimental effects specifically mediated by effector-memory T cells residing at the effector site of immunopathology.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.