M Sato

Probiotics are live microorganisms ingested for the purpose of conferring a health benefit on the host. Development of new probiotics includes the need for safety evaluations that should consider factors such as pathogenicity, infectivity, virulence factors, toxicity, and metabolic activity. Clostridium butyricum MIYAIRI 588(®) (CBM 588(®)), an anaerobic spore-forming bacterium, has been developed as a probiotic for use by humans and food animals. Safety studies of this probiotic strain have been conducted and include assessment of antimicrobial sensitivity, documentation of the lack of Clostridium toxin genes, and evaluation of CBM 588(®) on reproductive and developmental toxicity in a rodent model. With the exception of aminoglycosides, to which anaerobes are intrinsically resistant, CBM 588(®) showed sensitivity to all antibiotic classes important in human and animal therapeutics. In addition, analysis of the CBM 588(®) genome established the absence of genes for encoding for α, β, or ε toxins and botulin neurotoxins types A, B, E, or F. There were no deleterious reproductive and developmental effects observed in mice associated with the administration of CBM 588(®) These data provide further support for the safety of CBM 588(®) for use as a probiotic in animals and humans.

Effects of reduction of the number of primordial follicles on follicular development and concentrations of circulating hormones were examined in immature female rat offspring of dams given busulfan intraperitoneally on day 14 of gestation. The offspring of dams treated with 5 mg busulfan kg(-1) showed vaginal opening at an age comparable with the offspring of dams treated with 2.5 mg busulfan kg(-1) or with corn oil as a control, although they exhibited an irregular oestrous cycle until week 14 after birth. The serum concentrations of immunoreactive inhibin and FSH on day 26 after birth of the offspring treated with 5 mg busulfan kg(-1) were similar to those of age-matched controls. On day 15 after birth, however, the concentration of their immunoreactive inhibin was markedly lower than that of controls, whereas the concentration of their FSH was increased inversely. Comparison of the numbers of ovarian follicles in the controls and groups treated with 2.5 mg busulfan kg(-1) and 5 mg busulfan kg(-1) revealed that prenatal treatment with busulfan reduced the number of follicles in the primordial or primary phase and in the preantral phase on day 7 after birth. Although the increase of the ratio of the number of preantral follicles during days 7-13 after birth tended to vary with the prenatal dose of busulfan, the number of preantral follicles in the group treated with 5 mg busulfan kg(-1) was still smaller than in the controls. The concentration of serum immunoreactive inhibin of the offspring treated with busulfan was reduced on day 7 after birth without alteration of the concentration of gonadotrophin. On day 13 after birth, the concentration of serum immunoreactive inhibin was reduced only in the offspring treated with 5 mg busulfan kg(-1), and the concentration of serum FSH of the offspring was increased inversely as found on day 15 after birth. These results indicate that a reduction in the number of primordial follicles decreases the number of follicles that enter the growing phase, a major source of circulating inhibin in the neonatal and infantile ovary, and that consequently increased circulating FSH may accelerate follicular development to achieve puberty.

Neutrophil activation initiates myocardial ischemia/reperfusion (I/R) injuries. The aim of this study is to evaluate the in vitro functions of an anti-neutrophil monoclonal antibody, Urge-8, and its therapeutic efficacy against myocardial ischemia (MI) in rats. We measured in vitro functions of rat neutrophils including chemotactic activity, superoxide production, phagocytic function, and neutrophil degranulation. MI was induced in Wistar rats by clamping the left coronary artery for 1 h. Rats received either isotype-negative control IgG(1) (control group, n = 20), 250 microg/kg of Urge-8 before (pre-treatment group, n = 20) or after (post-treatment group, n = 20) MI. The three groups were compared during the first 24 h after reperfusion with respect to changes in mean arterial pressure, heart rate, body temperature, biochemistry, serum cytokines, myocardial neutrophil infiltration, survival rate, and size of MI. Urge-8 effectively suppressed in vitro functions of rat neutrophils including chemotactic activity, superoxide production, phagocytic function, and neutrophil degranulation. The Urge-8 treated groups showed higher levels of arterial pressure and survival rate, lower values of interleukin-6 and interleukin-8, lower grade of myocardial neutrophil infiltration, and smaller MI size as compared to the control group. In conclusion, Urge-8 is effective against myocardial I/R injury by suppressing certain functions and myocardial infiltration of neutrophils in rats.

We describe a patient with Graves' disease in whom marked proteinuria, microhematuria and hypoalbuminemia were associated. Renal biopsy demonstrated electrondense deposits in the capillary basement membrane, a finding consistent with immune complex glomerulonephritis. Indirect immunofluorescent examination with rabbit antihuman thyroglobulin indicated that these electron-dense deposits were thyroid antigen-mediated immune complexes.