Dietary supplemented antimicrobial peptide microcin J25 improves the growth performance, apparent total tract digestibility, fecal microbiota, and intestinal barrier function of weaned pigs.

Microcin J25 (MccJ25) is an antimicrobial peptide produced by a fecal strain of Escherichia coli containing 21 AA. This study was performed primarily to evaluate the effects of MccJ25 as a potential substitute for antibiotics (AB) on growth performance, nutrient digestibility, fecal microbiota, and intestinal barrier function in weaned pigs. In the present study, 180 weaned pigs (7.98 ± 0.29 kg initial BW) were randomly assigned to 1 of 5 treatments, including a basal diet (CON) and CON supplemented with AB (20 mg/kg colistin sulfate; ABD) or 0.5, 1.0, and 2.0 mg/kg MccJ25. On d 0 to 14, dietary supplementation with MccJ25 and ABD had positive effects on ADG, ADFI, diarrhea incidence, and G:F ( < 0.05). Pigs fed the 2.0 mg/kg MccJ25 diet had greater ADG ( < 0.05) and marginally greater G:F ( < 0.10) compared with pigs fed the ABD diet. Compared with the CON diet, the 2.0 mg/kg MccJ25 diet sharply improved ( < 0.05) ADG and G:F and decreased ( < 0.05) diarrhea incidence (d 15 to 28 and d 0 to 28). Apparent digestibility of nutrients in pigs fed 1.0 and 2.0 mg/kg MccJ25 was improved ( < 0.05) compared with that of pigs fed CON and ABD. The serum cytokines IL-6 and IL-1ß and tumor necrosis factor-α levels in pigs fed MccJ25 were greater than in pigs fed CON ( < 0.05). Additionally, the IL-10 concentration in pigs fed MccJ25 was sharply increased ( < 0.05) compared with that of pigs fed CON. Pigs fed 1.0 and 2.0 mg/kg MccJ25 diets had remarkably decreased lactate, diamine oxidase, and endotoxin concentrations and fecal numbers ( < 0.05) and improved fecal and numbers ( < 0.05). Compared with the ABD diet, the diet containing 2.0 mg/kg MccJ25 did not increase lactate, diamine oxidase, and endotoxin (d 14) concentrations ( < 0.05) or decrease the and (d 28) numbers ( < 0.05). The diets containing 1.0 and 2.0 mg/kg MccJ25 and ABD (d 28) improved lactate concentration and short-chain fatty acid concentrations, including acetate, propionate, and butyrate, in feces ( < 0.05). Moreover, the pigs fed 2.0 mg/kg MccJ25 had greater lactate, butyrate (d 14), and propionate concentrations than the pigs fed the ABD diet ( < 0.05). In conclusion, dietary supplemented MccJ25 effectively improved performance, attenuated diarrhea and systematic inflammation, enhanced intestinal barrier function, and improved fecal microbiota composition of weaned pigs. Therefore, MccJ25 could be a potential effective alternative to AB for weaned pigs.

Fructus polygoni orentalis extract inhibited liver regeneration and proliferation of bone marrow cells of rat after partial hepatectomy.

To study the effect of fructus polygoni orentalis extract (EFPO) on liver regeneration and proliferation of bone marrow cells on rat model of partial hepatectomy, EFPO was extracted, and 60 adult male Wistar rats were divided randomly into 6 experimental groups. Rats were treated with intergastric administration (ig) with EFPO daily. All rats were euthanized 7 days after administration, and the livers and bone marrow cells were collected. The levels of taxifolin and quercetin in EFPO were 1.238 and 0.381 mg/g, respectively. EFPO decreased the proliferating cell nuclear antigen expression of the regenerating liver. Obvious tissue damage was observed in the EFPO groups, such as a widened hepatic sinusoid cavity, several enlarged nuclei, slightly ballooning degeneration, and spotty and focal necrosis as compared to the control group. Additionally, 1.8 and 3.6 g/kg EFPO significantly inhibited proliferating cell nuclear antigen expression in bone marrows cells (P < 0.05), and induced gathering of these cells during the GO/G1 phases (P < 0.05). The karyocyte and myelosis of bone marrows cells clearly decreased, and mature erythrocytes increased (P < 0.05) in the EFPO groups. Additionally, 3.6 g/kg EFPO induced active proliferation, while the sham operation and control groups showed apparent active myelo-proliferation. The maximum dosage of mice ig EFPO was 148.8 g/kg. Our results indicate that EFPO inhibits rat liver regeneration and bone marrow cell proliferation in regenerating rat liver.

Successful Treatment of Refractory Majocchi's Granuloma with Voriconazole and Review of Published Literature.

Majocchi's granuloma (MG) is a rare deep skin dermatophyte infection that can occur either in immunocompetent or in immunocompromised individuals. Oral itraconazole or terbinafine is considered to be the first choice of treatment. We report an immunocompetent man with deep nodular form of MG, the form which is generally found in immunosuppressed individuals. Previous treatment with either oral itraconazole or terbinafine yielded no apparent improvement. After a series of examination, the man was diagnosed as having Trichophyton rubrum-induced MG mixed with bacterial infection as evidenced by growth of Klebsiella pneumoniae in tissue bacterial culture. The patient was treated with a combination of cefoselis and levofloxacin for bacterial clearance followed by voriconazole treatment. After approximately 4 months of voriconazole treatment, the lesions completely resolved. Alternative medicine (voriconazole) can be considered in case of refractory infections during MG treatment.

Effects of astragalosides on cultured islets after cryopreservation in rats.

OBJECTIVE: To explore the effects of AST (astragalosides) on cultured rat islet yield, purity, and function after cryopreservation in rats. METHODS: Pancreatic islets were isolated from 30 Sprague-Dawley rats using the standard technique of collagenase P digestion and discontinuous Ficoll gradient purification. After thaw, the islets were randomly divided into AST group and control group (n=15). Next, the islet cells were cultured in AST-containing medium or standard medium for 7, 14, and 21 days after cryopreservation and thaw. The quantity, purity, and survival rate were calculated in the two groups before and after culture. Then the in vitro and in vivo function was observed in diabetic rats after islet transplantation. RESULTS: The quantity and purity of islets had no difference between the two groups before culture (P>.05) while the difference after culture was significantly (P<.05). The survival rate of islets was 48% in AST group and 32% in the control group 21 days after thaw (P<.05). After 3 days, there was significantly a higher simulation index in the AST group than in the control group (P<.05). There was a significant difference in blood glucose and insulin concentrations between the groups after 3 days (P<.05). CONCLUSION: AST can be added to the culture medium to reduce the loss of islet cryopreservation and be intravenously injected to improve culture islet function in vitro and prolong islet graft survival in diabetic rats.

Echinosporins as new cell cycle inhibitors and apoptosis inducers from marine-derived Streptomyces albogriseolus.

Bioassay-guided fractionation of the ethyl acetate extract from the fermentation broth of marine-derived Streptomyces albogriseolus A2002 led to the isolation of echinosporin (1) and 7-deoxyechinosporin (2). Compound 1 inhibited the proliferation of tsFT210, K562 and HCT-15 cancer cells (IC(50) 91.5 microM, 25.1 microM and 247 microM respectively) and 2 showed the same effect on K562 cells (IC(50) 143 microM). Flow cytometric analysis suggested that 1 and 2 exert their anti-proliferative effects on those cells through inhibiting cell cycle at the G(2)/M phase and inducing apoptosis.

Sulfoglycolipid from the marine brown alga Sargassum hemiphylum.

One kinds of glycolipid (SBI) have been isolated from the marine brown alga Sargassum hemiphyllum (Turn.) Ag. The structures of SBI have been determined as the sodium salt of 1-0-acyl-3-0-(6'-sulfo-alpha-D-quinovopyrannosyl) glycerol (acyl: tetradecanoyl, pentadecanoyl, 11-hexadecenoyl, hexadecanoyl, 10,13-octadecadienoyl, 9-octade cenoyl, 15-metylheptadecanoyl and 11-eicosenoyl 17: 1.5: 19: 153: 1: 19: 1: 2) on the basis of chemical and spectral evidence and GC-MS analysis, respectively. Four constituents of the SBI were new compounds [the sodium salt of 1-0-(11"-hexadecenoyl)-3-0-(6'-sulfo-alpha-D-quinovopyrannosyl) glycerol, the sodium salt of 1-0-(10",13"-octadecadienoyl)-3-0-(6'-sulfo-alpha-D-quinovopyrannosyl) glycerol, and the sodium salt of 1-0-(15"-metylhexadecenoyl)-3-0-(6'-sulfo-alpha-D-quinovopyrannosyl) glycerol, and the sodium salt of 1-0-(11"-eicosenoyl)-3-0-(6'-sulfo-alpha-D-quinovopyrannosyl) glycerol]. All compounds were isolated from marine brown alga for the first time.

Fission converter and metal-oxide-semiconductor field effect transistor study of thermal neutron flux distribution in an epithermal neutron therapy beam.

The depth distribution of the thermal neutron flux is a major factor in boron neutron capture therapy (BNCT) in determining the efficiency of cell sterilization. In this paper the fission detector method is developed and applied to measure the in-phantom thermal neutron flux depth distribution. Advantages of the fission detector include small size, direct measurement of thermal neutron flux in a mixed radiation field of BNCT beam, self-calibration, and the possibility of on-line measurement. The measurements were performed at epithermal a BNCT facility. The experimental results were compared with the thermal neutron flux calculated by the Monte Carlo method and found to be in good agreement.

Physical and biological doses produced from neutron capture in a 235U foil.

As a follow-on study to the feasibility of neutron capture therapy (NCT) with 235U brachytherapy seeds, physical doses were calculated and measured for the radiation from a 235U foil in a lucite phantom which was irradiated at the epithermal neutron irradiation port of the Brookhaven Medical Research Reactor. In addition, cell survival experiments were performed to obtain the relative biological effectiveness (RBE) for the neutron part of the radiation. The calculated absorbed doses agree with the measured ones. From cell survival experiments, it is deduced that the fission neutrons from the 235U foil have a RBE of 3.0 while the fast neutrons in the beam have a RBE of 3.8. Also observed is that, with the cells 7 mm from the foil, a significant amount of absorbed dose comes from the beta rays of 235U fission events. This absorbed dose from beta rays is a significant addition to the therapeutic dose. Due to the limited ranges of beta rays in tissue, this absorbed dose is restricted to the vicinity of the foil. This is the first demonstration of beta rays as part of NCT.

Design of a high-flux epithermal neutron beam using 235U fission plates at the Brookhaven Medical Research Reactor.

Beams of epithermal neutrons are being used in the development of boron neutron capture therapy for cancer. This report describes a design study in which 235U fission plates and moderators are used to produce an epithermal neutron beam with higher intensity and better quality than the beam currently in use at the Brookhaven Medical Research Reactor (BMRR). Monte Carlo calculations are used to predict the neutron and gamma fluxes and absorbed doses produced by the proposed design. Neutron flux measurements at the present epithermal treatment facility (ETF) were made to verify and compare with the computed results where feasible. The calculations indicate that an epithermal neutron beam produced by a fission-plate converter could have an epithermal neutron intensity of 1.2 x 10(10) n/cm2.s and a fast neutron dose per epithermal neutron of 2.8 x 10(-11) cGy.cm2/nepi plus being forward directed. This beam would be built into the beam shutter of the ETF at the BMRR. The feasibility of remodeling the facility is discussed.

Neutron capture therapy of the 9L rat gliosarcoma using the p-boronophenylalanine-fructose complex.

PURPOSE: Intraperitoneal (IP) injection of the solubilized fructose complex of L-p-boronophenylalanine (BPA-F) produced higher boron concentrations in a rat brain tumor model than was possible using intragastric (IG) administration of L-p-boronophenylalanine (BPA). The effectiveness of IP BPA-F was compared to IG BPA in boron neutron capture therapy irradiations of the 9L rat brain tumor model. METHODS AND MATERIALS: The time course of boron accumulation in tumor and normal tissues was determined in male F344 rats bearing either SC or intracerebral 9L gliosarcomas following a single IP injection of BPA-F. On day 14 after inoculation of intracranial tumors, rats were irradiated with single doses of either: 250 kVp X rays; the thermal neutron beam of the Brookhaven Medical Research Reactor following IG administration of BPA; or thermal neutrons following IP injection of BPA-F. Magnetic resonance imaging was used to visualize the tumor scars and to assess damage to the normal brain in long-term survivors. RESULTS: 4 h after IP injection of 1200 mg/kg of BPA-F the boron concentrations in tumor, blood, and normal brain were 89.6 +/- 7.6, 27.7 +/- 2.8 and 17.5 +/- 1.5 micrograms 10B/g, respectively. Two IG doses of BPA (750 mg/kg each, 3 h apart) produced 39 +/- 5, 12 +/- 1 and 10 +/- 1 micrograms 10B/g in tumor, blood and brain, respectively at 5 h after the second dose. Three groups of rats were treated with thermal neutrons: one following IG BPA and two groups following IP BPA-F. The total physical absorbed doses to the tumor in the three BNCT groups were 15.5 Gy (IG BPA, n = 12), 17.0 Gy (IP BPA-F, n = 8), and 31.5 Gy (IP BPA-F, n = 8), respectively. The median survival of the untreated controls was 22 days. The median survival of the rats treated with 22.5 Gy of 250 kVp X rays (n = 23) was 35 days with 20% long-term survivors. Fifty percent of the rats in the IG BPA + thermal neutrons group survived over 1 year. All rats in both groups that received IP BPA-F + thermal neutrons have survived over 8 months. Magnetic resonance imaging of the brains of the long-term boron neutron capture therapy survivors showed a scar at the site of tumor implantation in all animals. In the IP BPA-F high-dose group one rat showed evidence of edema and one rat showed a fluid-filled cyst replacing the tumor. CONCLUSION: The use of IP BPA-F has significantly improved long-term survival compared to IG BPA. The high percentage of long-term tumor control (100%, n = 16) in the intracerebral rat 9L gliosarcoma brain tumor model, together with little or no damage to the surrounding normal brain in the majority of surviving animals, demonstrate the substantial therapeutic gain produced by boron neutron capture therapy.

Neutron capture therapy with 235U seeds.

A combination of brachytherapy and neutron capture therapy has been evaluated using 235U metal seeds and external neutron beam irradiation. When thermal neutrons are absorbed by 235U, high-energy neutrons and gamma rays are produced and some of these deposit energy in surrounding tissue. A Monte Carlo program, using the code MCNP, has been used to evaluate two sizes of 235U seeds in a water phantom. The results of flux suppression around the seeds and dose distributions are illustrated and discussed. The results show that high doses can be delivered in a relatively short time by using 235U seeds with neutron capture therapy. This therapy with multiple needles or seeds can be envisioned as a substitute for traditional brachytherapy to give an effective killing dose.