Furoxan derivatives demonstrated in vivo efficacy by reducing Mycobacterium tuberculosis to undetectable levels in a mouse model of infection.

OBJECTIVES: The most recent survey conducted by the World Health Organization described Tuberculosis (TB) as one of the top 10 causes of death and the leading cause of death from a single infectious agent. The increasing number of TB-resistant cases has contributed to this scenario. In light of this, new strategies to control and treat the disease are necessary. Our research group has previously described furoxan derivatives as promising scaffolds to be explored as new antitubercular drugs. RESULTS: Two of these furoxan derivatives, (14b) and (14c), demonstrated a high selectivity against Mycobacterium tuberculosis. The compounds (14b) and (14c) were also active against a latent M. tuberculosis strain, with MIC90 values of 6.67 µM and 9.84 µM, respectively; they were also active against monoresistant strains (MIC90 values ranging from 0.61 to 20.42 µM) and clinical MDR strains (MIC90 values ranging from 3.09 to 42.95 µM). Time-kill experiments with compound (14c) showed early bactericidal effects that were superior to those of the first- and second-line anti-tuberculosis drugs currently used in therapy. The safety of compounds (14b) and (14c) was demonstrated by the Ames test because these molecules were not mutagenic under the tested conditions. Finally, we confirmed the safety, and high efficacy of compounds (14b) and (14c), which reduced M. tuberculosis to undetectable levels in a mouse aerosol model of infection. CONCLUSION: Altogether, we have identified two advanced lead compounds, (14b) and (14c), as novel promising candidates for the treatment of TB infection.

Effects of -mannanase on Egg Production Performance, Egg Quality, Intestinal Microbiota, Viscosity, and Ammonia Concentration in Laying Hens

Two experiments were conducted to evaluate the effects of -mannanase on egg production performance, egg quality, intestinal microbiota, viscosity, and ammonia concentration in laying hens. In Exp. 1, two hundred and seventy 30-wk-old Hy-Line Brown laying hens were assigned to 6 diets arranged in a 3 × 2 factorial of three levels of MEn and CP [(a corn-soybean meal based diet (HEHP), a diet containing 50 kcal of MEn/kg and 1.0% less energy and CP than the HEHP (MEMP), and a diet containing 80 kcal of MEn/kg and 1.5% less energy and CP than HEHP (LELP)], and -mannanase supplementation (0 or 0.04%). In Exp. 2, A total of two hundred and sixteen62-wk-old Hy-Line Brown laying hens were assigned to 6 dietary treatments in a 3 × 2 factorial arrangement. In Exp. 1, -mannanase supplementation increased egg production rate in hens fed LELP diet, but not in those fed HEHP or MEMP diet (interaction, p 0.01), and the interaction was significant (p 0.01) for egg mass. -mannanase supplementation decreased (p 0.05) ammonia concentration. In Exp. 2, the supplementation of -mannanase increased egg production rate and egg mass in hens fed LELP diet, whereas no differences were found in those fed HEHP or MELP diet (interaction, p 0.01). The supplementation of -mannanase in a lower energy and protein diet resulted in similar production performance when compared to high-energy and high-protein diet during early and late stages of egg production.

Effects of -mannanase on Egg Production Performance, Egg Quality, Intestinal Microbiota, Viscosity, and Ammonia Concentration in Laying Hens

Two experiments were conducted to evaluate the effects of -mannanase on egg production performance, egg quality, intestinal microbiota, viscosity, and ammonia concentration in laying hens. In Exp. 1, two hundred and seventy 30-wk-old Hy-Line Brown laying hens were assigned to 6 diets arranged in a 3 × 2 factorial of three levels of MEn and CP [(a corn-soybean meal based diet (HEHP), a diet containing 50 kcal of MEn/kg and 1.0% less energy and CP than the HEHP (MEMP), and a diet containing 80 kcal of MEn/kg and 1.5% less energy and CP than HEHP (LELP)], and -mannanase supplementation (0 or 0.04%). In Exp. 2, A total of two hundred and sixteen62-wk-old Hy-Line Brown laying hens were assigned to 6 dietary treatments in a 3 × 2 factorial arrangement. In Exp. 1, -mannanase supplementation increased egg production rate in hens fed LELP diet, but not in those fed HEHP or MEMP diet (interaction, p 0.01), and the interaction was significant (p 0.01) for egg mass. -mannanase supplementation decreased (p 0.05) ammonia concentration. In Exp. 2, the supplementation of -mannanase increased egg production rate and egg mass in hens fed LELP diet, whereas no differences were found in those fed HEHP or MELP diet (interaction, p 0.01). The supplementation of -mannanase in a lower energy and protein diet resulted in similar production performance when compared to high-energy and high-protein diet during early and late stages of egg production.(AU)

Effects of dietary fermented garlic on the growth performance, relative organ weights, intestinal morphology, cecal microflora and serum characteristics of broiler chickens

The present study was conducted to evaluate the effects of feeding broilers with garlic fermented by Leuconostoc citreum SK2556. A total of 250 male broiler chicks was randomly housed into 25 floor pens. Five dietary treatments with five replicates of 10 chicks each (n=50 chicks/treatment). A corn and soybean meal based diet was used as the control diet (NC). The experimental diets were formulated by mixing the basal diet either with antibiotics (10 ppm; PC) or fermented garlic (FG) at the concentrations of 0.1% (FG1), 0.3% (FG3) or 0.5% (FG5) in diets. Daily weight gain, feed intake, and feed:gain ratio were not affected by any of the dietary treatments. Average daily gain on day 21 linearly increased (p= 0.024) with increasing FG levels. The relative weight of the bursa of Fabricius showed a progressive decline with increasing the FG levels. Jejunal villus height was not influenced by dietary treatments. Villus width linearly decreased as FG levels increased (p= 0.17). Jejunal crypt depth was significantly lower (p < 0.05) in the FG1 and FG3 groups compared with the NC group. Villus height: crypt depth ratio linearly increased (p= 0.018) with increasing FG levels. The population of cecal microflora was not altered by dietary treatments. Broiler chickens fed the FG5 diet exhibited (p < 0.05) higher blood levels of total protein and cholesterol compared with those fed the NC diet. Collectively, the results show that dietary FG marginally affected growth performance, especially during the first days rearing, improved intestinal morphology, and altered blood characteristics of broiler chickens.

Effects of dietary fermented garlic on the growth performance, relative organ weights, intestinal morphology, cecal microflora and serum characteristics of broiler chickens

The present study was conducted to evaluate the effects of feeding broilers with garlic fermented by Leuconostoc citreum SK2556. A total of 250 male broiler chicks was randomly housed into 25 floor pens. Five dietary treatments with five replicates of 10 chicks each (n=50 chicks/treatment). A corn and soybean meal based diet was used as the control diet (NC). The experimental diets were formulated by mixing the basal diet either with antibiotics (10 ppm; PC) or fermented garlic (FG) at the concentrations of 0.1% (FG1), 0.3% (FG3) or 0.5% (FG5) in diets. Daily weight gain, feed intake, and feed:gain ratio were not affected by any of the dietary treatments. Average daily gain on day 21 linearly increased (p= 0.024) with increasing FG levels. The relative weight of the bursa of Fabricius showed a progressive decline with increasing the FG levels. Jejunal villus height was not influenced by dietary treatments. Villus width linearly decreased as FG levels increased (p= 0.17). Jejunal crypt depth was significantly lower (p < 0.05) in the FG1 and FG3 groups compared with the NC group. Villus height: crypt depth ratio linearly increased (p= 0.018) with increasing FG levels. The population of cecal microflora was not altered by dietary treatments. Broiler chickens fed the FG5 diet exhibited (p < 0.05) higher blood levels of total protein and cholesterol compared with those fed the NC diet. Collectively, the results show that dietary FG marginally affected growth performance, especially during the first days rearing, improved intestinal morphology, and altered blood characteristics of broiler chickens.(AU)

Additional chromosomal abnormalities in core-binding factor acute myeloid leukemia.

Despite sharing a similar genetic abnormality, patients with core binding factor acute myeloid leukemia (CBF-AML), which is characterized by the presence of t(8;21) or inv(16)/t(16;16), show heterogeneous survival. Other molecular or cytogenetic factors are supposed to have an impact on the prognosis. We enrolled 24 CBF-AML patients to determine the impact of cytogenetic abnormality, and c-KIT, FLT3, NPM1, and CEBPA mutations on the prognosis. Only three patients had the c-KIT mutation (3/24, 12.5%) and one had the FLT3 mutation. However, over half of the patients (14/24) harbored additional cytogenetic changes, including ten with loss of sexual chromosomes (LOS) [all in the t(8;21) group], and six had additional abnormalities (two cases had both LOS and additional abnormalities). From this small-number study, no association was found between c-KIT mutation and survival and relapse rate. However, additional chromosome abnormalities had a significant association with relapse of the disease (P = 0.027). Stem cell transplant had a trend of benefitting patients after relapse (P = 0.065). This implies that chromosome abnormalities occur in CBF-AML and might take part in the heterogeneous nature of CBF-AML.

First Report of Powdery Mildew Caused by Podosphaera xanthii on Verbena brasiliensis in Korea.

Verbena brasiliensis Vell., commonly known as Brazilian verbena, is native to South America and has been introduced into North America, coastal Europe, southern Africa, and Australasia. Though partly cultivated for garden use, it is invasive in riverine areas and also on roadsides, forest margins, pastures, and waste areas (4). In Korea, this plant was first reported in 1998 in Jeju Island and has become widely naturalized by replacing indigenous plants and disrupting native ecosystems in most of southern part of Korea (3). Since 2009, powdery mildew on Brazilian verbena has been consistently found in several locations of Busan City, Korea. Symptoms appeared as circular to irregular white patches, which subsequently showed abundant hyphal growth on both sides of the leaves and on stems. High disease severity caused poor growth of the plants, resulting in premature senescence and reduced flowering. Specimens (n = 5) were deposited in the Korea University Herbarium (KUS). Appressoria on the mycelium were nipple-shaped or nearly absent. Conidiophores were 140 to 190 × 11 to 12.5 µm and produced 2 to 7 immature conidia in chains with a crenate outline. Foot-cells in conidiophores were straight, cylindric, relatively short, 50 to 65 µm long, and constricted at the very base of branching point from the hypha. Conidia were hyaline, ellipsoid to ovate, measured 28 to 38 × 18.5 to 22 µm (length/width ratio of 1.2 to 1.8), and contained distinct fibrosin bodies. Germ tubes were produced from the lateral position of conidia. No chasmothecia were observed. These structures are typical of the powdery mildew Euoidium anamorph of the genus Podosphaera. The morphological characteristics and measurements were consistent with those of P. xanthii (Castagne) U. Braun & Shishkoff (1). To confirm the identity, the complete internal transcribed spacer (ITS) region of rDNA of the isolate KUS-F27220 was amplified with primers ITS1/ITS4, and sequenced. The resulting 477-bp sequence was deposited in GenBank (Accession No. KJ472787). A GenBank BLAST search of this sequence revealed 100% identity with Podosphaera sp. on V. bonariensis and V.× hybrida from Japan (AB462804 and AB040347). The Podosphaera sp. isolates listed above are now placed in P. xanthii (1). Pathogenicity was confirmed through inoculation by gently pressing a diseased leaf onto leaves of three healthy, potted 2-month-old Brazilian verbena plants. Three non-inoculated plants served as controls. Inoculated plants developed signs and symptoms after 6 days, whereas the control plants remained symptomless. The fungus present on the inoculated leaves was identical morphologically to that originally observed on diseased plants. Powdery mildew of Verbena spp. associated with Podosphaera sp. (including Sphaerotheca sp.) has been globally reported, but not on V. brasiliensis (1,2). To our knowledge, this is the first report of powdery mildew disease caused by P. xanthii on V. brasiliensis globally. Our field observations suggest that the powdery mildew could limit expansion of V. brasiliensis in Korea. References: (1) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No.11. CBS, Utrecht, 2012. (2) D. F. Farr and A. Y. Rossman. Fungal Databases. Syst. Mycol. Microbiol. Lab., Online publication, ARS, USDA, Retrieved February 18, 2014. (3) C. G. Song and Y. H. Yang. The Naturalized Plants in Jeju Island. Nam-Jeju County, Jeju, Korea, 2005. (4) P. F. Yao. Kew Bull. 45:101, 1990.

Change of telomerase activity in peripheral whole blood of head and neck squamous cell carcinoma patients before and after surgery: a pilot study.

BACKGROUND The purpose of this study was to evaluate telomerase activity in peripheral whole blood from head and neck squamous cell carcinoma (HNSCC) patients as a biomarker for diagnosis of HNSCC or detection of recurrence during follow-up. MATERIALS AND METHODS Telomerase activity was measured from peripheral whole blood extracts by telomerase repeat amplification protocol (TRAP) in HNSCC patients before and after surgery and in a control group. Sixty-two HNSCC patients and 42 control subjects were included. RESULTS Telomerase activity was found in 41 out of 62 (66.1%) HNSCC patients before surgery and in 8 out of 42 (19.0%) controls (p<0.001). Among 41 HNSCC patients who showed positive telomerase activity before surgery, 32 (78.1%) showed a conversion of telomerase activity to negative after surgery. In follow-up, 6 out of 8 (75%) showed conversion of telomerase activity from negative to positive after recurrence. Telomerase activity was changed to negative in 4 out of 6 (66%) recurred patients with positive telomerase activity after second surgery. CONCLUSION The telomerase activity in peripheral whole blood extracts of HNSCC patients might be a useful biomarker for detecting recurrence after treatment. Further study with larger sample size using a more sensitive detection method of telomerase activity is necessary to verify these results.

[Wheat bran and breast cancer: revisiting the estrogen hypothesis]. / Salvado de trigo y cáncer de mama: revisitando la hipótesis del estrógeno.

Breast cancer is the most relevant form of cancer among women in Latin America. Many studies have evaluated the hormonal mechanisms involved in mammary carcinogenesis, although new focus is aimed towards factors that can potentially be used individually to reduce risk. Wheat bran seems to show a consistent protective effect in mammary carcinogenesis. Wheat bran, besides high level of insoluble fiber, also contains phytic acid and lignins, phytochemicals that have shown to inhibit in vitro and in vivo growth of mammary cancer. The protective effect of wheat bran in breast carcinogenesis is greatest at the promotional phase and when supplemented to a high fat diet. Doses of wheat bran in the 9-12% range have been consistently protective and the inconsistencies observed at higher doses may be dependent on the animal model used. This review examines the protective role of wheat bran in the development of breast cancer and the possible mechanisms involved.

Detection of IgA anti-PGL-I specific antigen to Mycobacterium leprae in mangabey monkeys inoculated with M. leprae.

Using sera from 4 pairs of mangabey monkeys inoculated with titrated doses of Mycobacterium leprae we demonstrated that IgA antibodies against M. leprae specific PGL-I antigen were present in 75% of inoculated monkey's sera. High IgA antibody was detected in 50% (3/6) of infected animals and all three developed lepromatous leprosy (LL). Antibody titers correlated with PGL-I antigen in serum. The highest IgA peak appeared late and corresponded to the beginning of treatment, and in two of them appeared shortly after or corresponded with neurological damage. Low IgA response was found in the other 3 monkeys (50%-3/6), two of which developed indeterminate leprosy (I) and the other one LL. Low IgA levels appeared late after IgG and IgM, and shortly after neurologic signs. Both I monkeys were negative for PGL-I in serum. The remaining 2 monkeys (25%-2/8) did not show an IgA response; one of them developed LL but the disease regressed to I. IgM seemed to correspond to the appearance of PGL-I in serum. The other animal did not develop clinical symptoms of leprosy, and PGL-I in serum was negative. Although there was no clear relation between the development of anti-PGL-I IgA and experimental leprosy, the finding of a high IgA response in some animals suggests that further studies are needed to evaluate the role of antigen-specific IgA in the disease process.

Status of intestinal parasite infections in inhabitants of Palmar, Guayas Province, Ecuador.

Status of intestinal protozoan and helminthic infections was surveyed in mestizo population living in rural parish of Palmar and its nearby recintos(villages). Three of the surveyed villages were at the Pacific coast and 5 villages were in inner pasture land, located about 100 km west of Guayaquil, the second largest city in Ecuador. One stool sample was examined by one cellophane thick smear for helminth ova and one direct smear stained with Lugol's iodine solution for protozoan cysts. Of 325 persons examined, 66.1% were positive for any ova or cyst. The positive rates were: 18.1% for Ascaris lumbricoides, 19.4% for Trichuris trichiura, 0.6% for hookworm, 3.7% for Hymenolepsis nana, 1.8% for Taenia sp., 19.4% for Entamoeba histolytica, 28.6% for Entamoeba coli, 5.5% for Endolimax nana, 1.5% for Iodamoeba buetschlii, 11.1% for Giardia lamblia and 0.6% for Chilomastix mesnili. Poor supply of potable water was considered the main cause of high prevalence of intestinal protozoan infections.

The pediatric nephrologist's dilemma: growth after renal transplantation and its interaction with age as a possible immunologic variable.

Two important criteria for successful end-stage renal disease therapy in children are achievement of optimal growth and possession of a well-functioning renal transplant. We describe eight children with accelerated post-transplant growth. Accelerated and even catch-up growth was achievable if the transplant occurred at an early age (less than 9 years), the daily dose of prednisone was low (less than or equal to 0.24 mg/kg/d), and renal function was excellent (creatinine clearance greater than or equal to 89 mL/min/1.73 m2). However, the benefit to growth of transplanting a kidney in young children may be offset by reduced cadaver graft survival in children younger than 6 years. To study whether the less favorable graft survival was attributable to an increased immunologic responsiveness in the younger child, we examined three tests of nonspecific immune responsiveness, each of which, when increased, may indicate a propensity toward rejection: total T cell absolute number, T helper/suppressor ratio, and spontaneous blastogenesis. Each measurement was significantly increased in 20 uremic children 5 years old or younger, compared with 81 children 6 to 23 years of age. These data suggest that improved growth may be attained by transplanting a kidney in the young child with end-stage renal disease, but the young child may be at increased risk for rejection. This hypothesis suggests that for optimal rehabilitation, strategies should take into account the unique needs of the young child.