Breastfeeding duration is inversely associated with asthma in Japanese children aged 3 years.

OBJECTIVE: Recent meta-analyses found an inverse relationship between breastfeeding duration and asthma in children. The present cross-sectional study investigated the associations between breastfeeding duration and the prevalence of wheeze and asthma in Japanese children aged 3 years. METHODS: Subjects were 6412 children who participated in the Kyushu Okinawa Child Health Study. Data were collected using a self-administered questionnaire. Wheeze was defined according to the criteria of the International Study of Asthma and Allergies in Childhood. Asthma was considered present if the child had been diagnosed by a physician as having asthma. Associations of breastfeeding duration with wheeze and asthma were estimated using multivariate generalized estimating equation methods adjusted for maternal, family, and health characteristics. RESULTS: The prevalence values of wheeze and asthma were 19.5% and 7.0%, respectively. Compared with <4 months of exclusive breastfeeding, exclusive breastfeeding for ≥4 months was not significantly associated with wheeze or asthma. Compared with <10 months of breastfeeding duration regardless of exclusivity, 10 to <14 months, 14 to <19 months, and 19 months or more of breastfeeding duration regardless of exclusivity were independently inversely related to asthma: the adjusted odds ratios [ORs; 95% confidence intervals (CIs)] were 0.69 (0.52-0.91, p = 0.01), 0.73 (0.56-0.97, p = 0.03), and 0.67 (0.51-0.88, p = 0.004), respectively. No association was found between breastfeeding duration regardless of exclusivity and wheeze. CONCLUSIONS: We confirmed an inverse association between breastfeeding duration regardless of exclusivity and asthma.

Removal of heavy metal cations by biogenic magnetite nanoparticles produced in Fe(III)-reducing microbial enrichment cultures.

The biogenic magnetite nanoparticles presented here had a high capacity of adsorbing metal cations, which was approximately 30- to 40-fold greater than commercially available magnetite. These results suggest the potential application of microbial magnetite formation in the removal of toxic metal cations from water.

Blockage of spontaneous Ca2+ oscillation causes cell death in intraerythrocitic Plasmodium falciparum.

Malaria remains one of the world's most important infectious diseases and is responsible for enormous mortality and morbidity. Resistance to antimalarial drugs is a challenging problem in malaria control. Clinical malaria is associated with the proliferation and development of Plasmodium parasites in human erythrocytes. Especially, the development into the mature forms (trophozoite and schizont) of Plasmodium falciparum (P. falciparum) causes severe malaria symptoms due to a distinctive property, sequestration which is not shared by any other human malaria. Ca(2+) is well known to be a highly versatile intracellular messenger that regulates many different cellular processes. Cytosolic Ca(2+) increases evoked by extracellular stimuli are often observed in the form of oscillating Ca(2+) spikes (Ca(2+) oscillation) in eukaryotic cells. However, in lower eukaryotic and plant cells the physiological roles and the molecular mechanisms of Ca(2+) oscillation are poorly understood. Here, we showed the observation of the inositol 1,4,5-trisphospate (IP(3))-dependent spontaneous Ca(2+) oscillation in P. falciparum without any exogenous extracellular stimulation by using live cell fluorescence Ca(2+) imaging. Intraerythrocytic P. falciparum exhibited stage-specific Ca(2+) oscillations in ring form and trophozoite stages which were blocked by IP(3) receptor inhibitor, 2-aminoethyl diphenylborinate (2-APB). Analyses of parasitaemia and parasite size and electron micrograph of 2-APB-treated P. falciparum revealed that 2-APB severely obstructed the intraerythrocytic maturation, resulting in cell death of the parasites. Furthermore, we confirmed the similar lethal effect of 2-APB on the chloroquine-resistant strain of P. falciparum. To our best knowledge, we for the first time showed the existence of the spontaneous Ca(2+) oscillation in Plasmodium species and clearly demonstrated that IP(3)-dependent spontaneous Ca(2+) oscillation in P. falciparum is critical for the development of the blood stage of the parasites. Our results provide a novel concept that IP(3)/Ca(2+) signaling pathway in the intraerythrocytic malaria parasites is a promising target for antimalarial drug development.

Suppressive effects of the antiandrogen agent, chlormadinone acetate and the 5alpha-reductase inhibitor, dutasteride on prostate weight and intraprostatic androgen levels in rats.

The objectives of this study were to investigate whether chlormadinone acetate (CMA, Prostal, CAS 302-22-7) more markedly decreased ventral prostate and seminal vesicle weights and exerted more beneficial effects on intraprostatic androgen levels than dutasteride (DUT, CAS 164656-23-9) in rats. Dose-dependent inhibiting effects on prostate and seminal vesicle enlargement were observed after the 14-day administration of CMA (30, 100 mg/kg/day) and DUT (0.3, 1 mg/kg/day). The prostate atrophy rates calculated as the percentages relative to the vehicle-treated group were 50.5 and 67.9% with 30 and 100 mg/kg CMA and 34.9 and 37.0% with 0.3 and 1 mg/kg DUT, respectively, and the atrophying effect of CMA was significantly greater than that of DUT (p < 0.05). The results of 7-day administration were similar to those of 14-day administration. While CMA dose-dependently and significantly (p < 0.05) reduced the testosterone (T) and dihydrotestosterone (DHT) concentrations in prostate, DUT reduced the DHT concentration but markedly increased the T concentration (20-40 times). Even though it was carried out in rats, this study revealed for the first time that the antiandrogen CMA showed a stronger atrophying effect than the 5alpha-reductase inhibitor DUT on direct comparison. The difference between the atrophying effects of CMA and DUT is considered to be attributed to the present results that CMA reduced the concentrations of both androgens (T and DHT) in prostate but DUT did not, and the fact that CMA has a potent androgen receptor-blocking action but DUT does not.

Overproduction of the pro-apoptotic molecule, programmed cell death 5, in Toxoplasma gondii leads to increased apoptosis of host macrophages.

We established a recombinant strain of Toxoplasma gondii that overexpressed programmed cell death 5 (TgPDCD5), in order to evaluate the role of endogenous TgPDCD5 in macrophage apoptosis during T. gondii infection. Immunofluorescence microscopy revealed that overproduced TgPDCD5 with a hemagglutinin tag was localized in the cytosol, which was consistent with the localization of endogenous TgPDCD5. The induced TgPDCD5-HA was recognized as an additional band by Western blot analysis, indicating successful overexpression of TgPDCD5. Secretion and release of TgPDCD5 by the parasite was also up-regulated in a time-dependent manner, which reflected its overproduction. Apoptosis due to parasite infection and interferon-gamma treatment was significantly up-regulated by the overexpression of TgPDCD5. These results suggest that endogenous TgPDCD5 plays a role in macrophage apoptosis during T. gondii infection.

Combination effect of TZT-1027 (Soblidotin) with other anticancer drugs.

BACKGROUND: TZT-1027 (Soblidotin), an antimicrotubule drug, has shown potent antitumor efficacy in various antitumor models, and has entered into phase I clinical trials. To determine those anticancer drugs to be combined with TZT-1027 in clinical trials, the combination effects of TZT-1027 with other anticancer drugs were examined. MATERIALS AND METHODS: Two in vivo antitumor models, the murine P388 leukemia ascites tumor model and the human non-small cell lung cancer A549 solid tumor model, were used and cisplatin (CDDP), gemcitabine (GEM), irinotecan hydrochloride (CPT-11), fluorouracil (5-FU), paclitaxel (PTX) and docetaxel (DTX) were selected to be combined with TZT-1027. Regarding the schedule of combination administration, simultaneous administration and sequential administration (TZT-1027 first and combined drugs administered 24 h later, and vice versa) were employed. RESULTS: A significant increase in lifespan was observed when TZT-1027 was combined with CDDP, GEM and CPT-11 in the P388 cell ascites tumor model, and a significant inhibition of growth was observed when TZT-1027 was combined with CDDP, GEM and DTX in the A549 solid tumor model. Sequential administration, particularly when the combined drug was administered first, showed the most potent antitumor efficacy. CONCLUSION: These findings strongly suggest that a significant combination effect of TZT-1027 and these antitumor drugs can be expected in clinical trials for solid tumors.

An early extrasolar planetary system revealed by planetesimal belts in beta Pictoris.

beta Pictoris (beta Pic) is a main-sequence star with an edge-on dust disk that might represent a state of the early Solar System. The dust does not seem to be a remnant from the original protoplanetary disk, but rather is thought to have been generated from large bodies like planetesimals and/or comets. The history and composition of the parent bodies can therefore be revealed by determining the spatial distribution, grain size, composition and crystallinity of the dust through high-resolution mid-infrared observations. Here we report that the sub-micrometre amorphous silicate grains around beta Pic have peaks in their distribution around 6, 16 and 30 au (1 au is the Sun-Earth distance), whereas the crystalline and micrometre-sized amorphous silicate grains are concentrated in the disk centre. As sub-micrometre grains are blown quickly out from the system by radiation pressure from the central star, the peaks indicate the locations of ongoing dust replenishment, which originates from ring-like distributions of planetesimals or 'planetesimal belts'.

TZT-1027 elucidates antitumor activity through direct cytotoxicity and selective blockade of blood supply.

BACKGROUND: TZT-1027 is a newly developed antitumor agent derived from dolastatin 10. MATERIALS AND METHODS: The in vitro activity of TZT-1027 on MCF-7 and R-27 cells was evaluated by MTT assay. TZT-1027 1 mg/kg/week was administered i.v. for 4 weeks into nude mice bearing MCF-7 and R-27. Subsequently, primary cultured cells from xenografts were also used for CD-DST. Two mg of TZT-1027 or 40 mg docetaxel per kg were injected i.v. into nude mice bearing R-27. 0.2% Evans blue was injected to assess the blood flow. RESULTS: TZT-1027 suppressed the in vitro growth of MCF-7 cells, while R-27 cells were resistant to TZT-1027, although its in vivo antitumor activity was remarkable. TZT-1027 blockaded R-27 tumor blood flow immediately after injection; blood flow was not affected by docetaxel. CONCLUSION: TZT-1027 exerts its antitumor activity through direct cytotoxicity against MCF-7 cells and through selective blockade of tumor blood flow against R-27 cells.

Antitumor activity of TZT-1027 (Soblidotin) against vascular endothelial growth factor-secreting human lung cancer in vivo.

TZT-1027 (Soblidotin), an antimicrotubule agent, has been demonstrated to show potent antitumor effects, though the relationships among antitumor effect, cytotoxicity and anti-vascular effect of TZT-1027 have not been studied. We established in vivo human lung vascular-rich tumor models using a vascular endothelial growth factor-secreting tumor (SBC-3/VEGF). SBC-3/VEGF tumors exhibited a high degree of angiogenesis in comparison with the mock transfectant (SBC-3/Neo) tumors in a dorsal skinfold chamber model and grew much faster and larger than SBC-3/Neo tumors in the tumor growth study. The antitumor activity of antimicrotubule agents, including TZT-1027, was evaluated in both early- and advanced-stage SBC-3/Neo and SBC-3/VEGF tumor models to elucidate the relationship between the antitumor activity and anti-vascular effect of these agents. TZT-1027 exhibited potent antitumor activity against both early- and advanced-stage SBC-3/Neo and SBC-3/VEGF tumors, whereas combretastatin A4 phosphate did not. Vincristine and docetaxel exhibited potent antitumor activity against early-stage SBC-3/Neo and SBC-3/VEGF tumors, and advanced-stage SBC-3/Neo tumors, but did not exhibit activity against advanced-stage SBC-3/VEGF tumors. The difference in antitumor activity between these agents could be ascribed to differences in direct cytotoxicity and anti-vascular effect. Furthermore, a prominent accumulation of erythrocytes in the tumor vasculature, followed by leakage and scattering of these erythrocytes from the tumor vasculature, was observed after TZT-1027 administration to mice bearing advanced-stage SBC-3/VEGF tumors. These findings strongly suggest that TZT-1027 has a potent anti-vascular effect, in addition to direct cytotoxicity.

Restoration of gap junctional intercellular communication by dibutyryl-cAMP in renal epithelial cells treated with renal carcinogen.

Dimethylnitrosamine(DMN) is an alkylating agent and a known renal carcinogen. A short exposure of renal epithelial cells to cytotoxic concentrations of DMN influences the expression of gap junction proteins. In this study, we examined gap junctional intercellular communication and connexin 43 expression in renal epithelial cells treated with 1% DMN and also examined the effects of dibutyryl-cAMP on preventing gap junctional disturbances. Connexin 43 becomes hypophosphorylated after treatment with 1% DMN for 15 minutes, but this hypophosphorylation is inhibited by pretreatment with dibutyryl-cAMP. These results suggest that changes in gap junction protein expression are early events associated with 1% DMN treatment of renal epithelial cells, and such changes are prevented by dibutyryl-cAMP pretreatment.

EPO-producing gastric carcinoma in a hemodialysis patient.

A case of erythrocytosis caused by gastric cancer that produced erythropoietin is described. To the authors' knowledge, no case of erythropoietin-producing gastric cancer has been reported until now. A 73-year-old man with a 4-year history of maintenance hemodialysis for diabetic nephropathy required phlebotomy. Serum erythropoietin level was 181 mU/mL (181 IU/L). Gastroscopy results showed rough mucosa with hemorrhaging caused by gastric cancer. The patient underwent distal gastrectomy, and serum erythropoietin level decreased to 27.1 mU/mL (27.1 IU/L) by postoperative day 8. Existence of erythropoietin in the tumor tissue was confirmed immunohistochemically. The presence of severe acquired cystic disease of the kidney, renal cell carcinoma, and other malignant tumors should be investigated in hemodialysis patients displaying erythrocytosis.

Possible role of immunocompetent cells and the expression of heat shock protein-25 in the process of pulpal regeneration after tooth injury in rat molars.

Recent studies have established that heat shock proteins (HSPs) potentially play a role in immunosurveillance. The purpose of the present study was to clarify the relationship between the chronological changes of immunocompetent cells and the expression of HSP-25 in the process of pulpal regeneration after tooth injury in rat molars by immunocytochemistry for HSP-25 and class II major histocompatibility complex (MHC) antigen. In untreated control teeth, intense HSP-25 immunoreactivity was found in the cell bodies of odontoblasts. Both cavity preparation and tooth replantation caused the degeneration of the odontoblast layer to result in the loss of HSP-25 immunoreactions in the suffered dental pulp at the early stages after tooth injury. Numerous class II MHC-positive cells appeared along the pulp-dentin border and extended their cell processes into the dentinal tubules at 12-24 h after cavity preparation and 3 days after tooth replantation. Newly differentiated odontoblast-like cells with HSP-25 immunoreactivity were arranged at the pulp-dentin border and the class II MHC-positive cells retreated towards the subodontoblastic layer by post-operative days 3-5 after tooth injury. Thus, the common cellular events occur during pulpal regeneration following two different experimental injuries. These findings indicate that the time course of changes in the expression of HSP-25 immunoreactivity reflects the degeneration/regeneration process of odontoblasts and that the temporal appearance of the class II MHC-positive cells at the pulp-dentin border suggests their participation in odontoblast differentiation as well as in initial defence reactions during the pulpal regeneration process.