PG Group Research Articles

Efficacy and safety of methylcobalamin, alpha lipoic acid and pregabalin combination versus pregabalin monotherapy in improving pain and nerve conduction velocity in type 2 diabetes associated impaired peripheral neuropathic condition. [MAINTAIN]: Results of a pilot study.

Background and Objective: To assess whether methylcobalamin and alpha lipoic acid (ALA) added to pregabalin provide additional benefit compared to pregabalin alone in type 2 diabetes mellitus associated peripheral neuropathy. Setting and Design: An open label, randomized, controlled parallel-group pilot study. Materials and Methods: Thirty adult patients with type 2 diabetes mellitus with symptoms of peripheral neuropathy for ≥6 months were randomized to receive pregabalin 75 mg, methylcobalamin 750 μg, and ALA 100 mg (PMA, n = 15); or pregabalin 75 mg (PG, n = 15) for 12 weeks. Assessment variables were numeric rating scale (NRS), sleep interference scores (SIS), response rate to pain, and global assessment for the usefulness of therapy. The nerve conduction velocity was assessed for sensory and motor nerves. Safety assessment included adverse events reported by the patients, clinical laboratory, and general medical, neurological examinations. Statistical Analysis: Efficacy analyses were done on per-protocol (PP) population, whereas safety analyses were done on intent-to-treat (ITT) population. Results: Significant improvement was seen in pain and sleep interference in both groups. Mean nerve conduction velocity of left common peroneal nerve (CPN) showed significant improvement in PMA group at week 12 compared to baseline (P = 0.018). For right CPN both groups showed significant improvement. (PMA, P = 0.002, PG, P = 0.007). For sensory testing, at week 12, right superficial peroneal nerve showed reduction in nerve conduction velocity in PG group compared to baseline (P = 0.043). Conclusion: Methylcobalamine, ALA and pregabalin combination provides pain relief and improves sleep interference. Addition of methylcobalamin and ALA to pregabalin improves the nerve function. Due to small sample size, most of the efficacy parameters could not reach significant difference between groups; hence benefit of the 3-drug-combimation should be interpreted with reservation.

The use of PGF2α as ovulatory stimulus for timed artificial insemination in cattle

The objective of this study was to evaluate the effect of a PGF2α-analogue (PGF) on ovulation and pregnancy rates after timed artificial insemination (TAI) in cattle. In experiment 1, crossbred dual-purpose heifers, in a crossover design (3 × 3), were given an intravaginal progesterone-releasing insert (controlled internal drug release [CIDR]) plus 1 mg estradiol benzoate (EB) intramuscularly (im) and 250 μg of a PGF-analogue im on Day 0. The CIDR inserts were removed 5 days after follicular wave emergence, and the heifers were randomly divided into three treatment groups to receive the following treatments: (1) 1 mg of EB im (EB group, n = 13); (2) 500 μg of PGF im (PG group, n = 13); or (3) saline (control group, n = 13), 24 hours after CIDR removal. Ovulation occurred earlier in EB (69.81 ± 3.23 hours) and PG groups (73.09 ± 3.23 hours) compared with control (83.07 ± 4.6 hours; P = 0.01) after CIDR removal. In experiment 2, pubertal beef heifers (n = 444), 12 to 14 months of age were used. On Day 0, the heifers were given a CIDR insert plus 2 mg EB im. On Day 9, the CIDR was removed and the heifers were given 500 μg of PGF im. Heifers were randomly assigned into one of three treatment groups: (1) 1 mg of EB (EB group; n = 145); (2) 500 μg of PGF (PG group; n = 149), both 24 hours after CIDR removal; or (3) 600 μg of estradiol cypionate (ECP group; n = 150) at CIDR removal. Timed artificial insemination occurred 48 hours after CIDR removal in the ECP group and 54 hours in the PG and EB groups. The percentage of heifers ovulating was higher in the PG group compared with the other groups (P = 0.08). However, the pregnancy rates did not differ among groups (47.6%, 45%, and 46.6%, for EB, PG, and ECP, respectively; P = 0.9). In experiment 3, 224 lactating beef cows, 40 to 50 days postpartum with 2.5 to 3.5 of body condition score were treated similarly as described in experiment 2, except for the ECP group, which was excluded. The treatments were as follows: 1 mg EB (EB group; n = 117) or 500 μg PGF (PG group; n = 107), 24 hours after CIDR removal. The calves were temporarily separated from their dams from Days 9 to 11. No difference was detected on the pregnancy rate between the EB and PG groups (58.1% vs. 47.6%, respectively; P = 0.11). Taken together, the combined results suggested that PGF2α could be successfully used to induce and synchronize ovulation in cattle undergoing TAI, with similar pregnancy rates when compared with other ovulatory stimuli (ECP and EB).

The effect of prenatal exposure of a non-steroidal anti-inflammatory drug on the optic nerve of female rats: a stereological, histological, and electron microscopic study

Objective: Non-steroidal anti-inflammatory drugs (NSAIDs) can have adverse effects for in both mother and fetus following administration during the prenatal period. If given during pregnancy, diclofenac sodium (DS), an NSAID, is given during the pregnancy, may also affect the development of the central nervous system (CNS) or related structures.Methods: Pregnant rats were separated into pure control (PG), saline (SG) and diclofenac groups (DG). A daily dose of 1 mg/kg of DS and 1 mL/kg saline was injected intraperitoneally to the DG and SG groups, respectively, from the 5th gestation day for a 15 day of period; the PG group received no treatment. After spontaneous delivery, female offspring were obtained from all groups. After the 20th week of postnatal life, the animals (n = 6 for each group) were perfused and the right optic nerves were resected. Sections were subjected to stereological and histological analysis.Results: There were no significant differences (p > 0.05) between PG, SG and DG groups with respect to myelin thickness, axonal cross-sectional area, axon numerical density, total section area of optic nerve and axon number.Conclusions: Histological and stereological results indicated that treatment with DS or saline produced undesirable effects on female rat optic nerve development and myelinization with respect to morphology.

Attenuation of Portal Hypertension by Continuous Portal Infusion of PGE1 and Immunologic Impact in Adult-to-Adult Living-Donor Liver Transplantation

Small-for-size syndrome remains the greatest limiting factor of expanding segmental liver transplantation from living donors. Portal hyperperfusion is considered to substantially contribute to small-for-size syndrome. We investigated the impact of continuous portal infusion of prostaglandin E1 (PGE1) on small-for-size grafts (SFSGs) in adult-to-adult living-donor liver transplantation (LDLT). From July 2003 to December 2009, LDLT was performed in 122 patients. We introduced continuous portal infusion of PGE1 to five SFSG patients (PG group) from November 2007 to December 2009 and retrospectively compared them with a historical control group of eight relevant SFSG patients without PGE1 infusion (non-PG group) from July 2003 to October 2007 to determine the safety and efficacy of continuous PGE1 portal infusion for SFSGs. Splenectomy cases were excluded from analysis. The PG group demonstrated significantly lower postoperative portal pressure than the non-PG group. Moreover, the PG group demonstrated significantly improved liver function in the early posttransplantation period and significantly better recovery from hyperammonemia at 1 week after transplantation and from hyperbilirubinemia in the late posttransplantation period. Overall survival was significantly better in the PG group than in the non-PG group. Three patients in the non-PG group died of rejection-related reasons. Interestingly, immunomonitoring assay revealed that antidonor immune responses were significantly accelerated in the non-PG group compared with the PG group after LDLT. In contrast, the PG group showed well-suppressed antidonor immune responses. Continuous portal infusion of PGE1 for SFSG attenuated portal hypertension, improved graft function, and suppressed antidonor immune responses, resulting in better survival.

Abstract 192: Exposure to high saturated fat acid diet in early life changes the susceptibility to breast cancer in adulthood.

Abstract Nutrition is thought to be involved in 30 to 50% of all breast cancer and intake of animal fat seems to be related to the increase of this type of cancer. It has been suggested that breast cancer can originate in early life, including the in utero and lactation periods. Maternal nutrition can modify the fetal environment and induce epigenetics modifications that change the susceptibility of offspring to breast cancer in adulthood. We hypothesized that exposure to high saturated fatty acid diet (HFS) in early life can change gene expression through the remodeling of epigenetic marks and consequently modify the risk of breast cancer. Sprague-Dawley rats were used in our study, which was composed of three groups: CO (female rats exposed to control diet [AIN-93G] in utero and lactation); PG (female rats exposed to HSF in utero) and PL (female rats exposed to HSF in utero and lactation). The distribution of fatty acid in the HSF was 37%, 38% and 24% of saturated, monounsaturated and polyunsaturated, respectively while in the CO diet, the distribution of those fatty acid was 17%, 27% and 55%, respectively. Female rats were euthanized on post-natal day (PND) 50 and blood and mammary tissue collected. Serum samples were assayed for estradiol, progesterone and leptin levels (radioimmunoassay and immunofluorescence). Mammary glands were evaluated for the number of terminal End Buds (TEBs), global DNA methylation (HPLC-DAD) and global histone modification patterns (western blot). Mammary tumor development induced by oral administration of dimethylbenz[a]anthracene (DMBA) on PND50 was also evaluated. Global DNA methylation were also determined in mammary tumors. There were no differences (P>0.05) in maternal caloric intake, offspring birth weight, serum estradiol levels or number of TEBs among the groups. Serum progesterone levels showed a tendency to increase (P=0.07) in the PG group compared to CO group. Compared to others groups, the PL group showed higher (P≤0.05) serum leptin levels. The PG group showed higher levels (P≤0.05) of global trimethylation of histone 3 lysine 9 (H3K9me3) compared to CO group, but no differences were observed (P>0.05) for global DNA methylation and global H3K9/H4K16 acetylation and H3K27/H3K4 trimethylation. The PG group showed lower incidence (P≤0.05) and average number of tumors compared to CO group and higher latency (P≤0.05) compared to PL group. The tumors from PG group presented lower (P≤0.05) global DNA methylation compared to others groups. In conclusion, exposure to HSF in early life influenced the susceptibility of breast cancer in adulthood. But, differently from what we expected the exposure to this diet in utero decreased breast cancer risk. If this exposure is continued through the period of lactation the protective effect is lost. This modification of breast cancer risk in early life seems to involve epigenetics mechanisms like post-translational histone modification. Citation Format: Fábia O. Andrade, Camile C. Fontelles, Mariana Rosim, Tiago F. Oliveira, Ana PM Loureiro, Marcelo M. Rogero, Fernando S. Moreno, Sonia M. De Assis, Leena Hilakivi-Clarke, Luis F. Barbisan, Thomas P. Ong. Exposure to high saturated fat acid diet in early life changes the susceptibility to breast cancer in adulthood. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 192. doi:10.1158/1538-7445.AM2013-192

Meaning of upper limit of normal range of post-load 1-h plasma glucose level defined by oral glucose tolerance test in Japanese subjects.

To identify upper limit post-load 1-h plasma glucose (1-h PG) after 75-g oral glucose test in a Japanese population. A total of 918 subjects were enrolled. We divided the subjects into two groups: normal 2-h post-load plasma glucose (2-h PG; <140mg/dL) and impaired 2-h PG group (≥140mg/dL). A total of 417 subjects had normal 2-h PG and 501 had impaired 2-h PG. The receiver operating characteristic (ROC) curve showed that the optimal cut-off value of 1-h PG was 179mg/dL (area under ROC curve=0.89), providing that the sensitivity, specificity, and positive and negative predictive value were 85, 79, 82 and 83%, respectively. The subjects with 1-h PG<179mg/dL consisted of 0.5% diabetes and 99.5% non-diabetes, whereas those with 1-h PG≥179mg/dL consisted of 26.9% diabetes and 73.1% non-diabetes (P<0.01). Furthermore, there was a significant correlation between 1-h PG and 2-h PG (r (2)=0.57, P<0.01). These data suggested that 179mg/dL is the upper limit of the normal range of post-load of 1-h PG in a Japanese population. Thus, the subjects with 1-h PG≥179mg/dL might be at risk of developing future diabetes. Therefore, appropriate prospective study should be carried out to test this hypothesis.

Effects of Force Constancy on the Distribution of Interleukin-1 Beta and Tumor Necrosis Factor-Alpha Levels

ABSTRACT Objective: The purpose of this study was to evaluate levels of interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in gingival crevicular fluid (GCF) with hybrid and PG retractors, which have differences in constancy of force. Materials and Method: Forty canine teeth of 10 orthodontic patients were distalized with hybrid or PG retractors. The GCF was sampled from the distal sides of the canines at baseline, hour 1, day 1, month 1, and month 2. In the PG group, samples were re-collected 1 hour and 1 day after reactivation at month 1. Two-way ANOVA, paired t test, and Friedman and Wilcoxon tests were used for statistical analysis. Results: The IL-1β level increased at hour 1 and month 2 in the upper and lower hybrid groups, whereas upper PG group increased at hour 1, month 1 + 1 hour, and month 2. The TNF-α level increased at hour 1 and declined afterward in the upper hybrid group. The only difference between the 2 retractors was found in TNF-α levels, which were higher at day 1 and ...

Association between maternal periodontal disease and preterm delivery and low birth weight

ObjectiveIt has been suggested that periodontal disease is an important risk factor for preterm low birth weight (PLBW). The purpose of this study was to determine the association of maternal periodontitis with low birth weight (LBW) and preterm birth (PB). Materials and MethodsPregnant women (n = 211) aged 22–40 years were enrolled while receiving prenatal care. Dental plaque, probing depth, bleeding on probing, and clinical attachment level were used as criteria to classify three groups: a healthy group (HG; n = 82), a gingivitis group (GG; n = 67), and a periodontitis group (PG; n = 62). At delivery, birth weight was recorded. ResultsMean infant weight at delivery was 3084.9 g. The total incidence of preterm birth and LBW infants was 10.4% and 8.1%, respectively. The incidence of LBW infants was 4.2% for term and 40.9% for preterm gestations. Maternal height was not correlated with infant birth weight (p = 0.245). Significant differences in mean infant birth weight were observed among the HG, GG, and PG groups (p = 0.030). No significant relationship was found between periodontal disease and PB, but the association between periodontal disease and LBW was significant. ConclusionAfter appropriately controlling for confounding variables, our results do not support the hypothesis of an association that was observed in previous studies of maternal periodontal disease and infant PB, but the association between periodontal disease and LBW is significant.

Pediatric Robotic Pyeloplasties: Initial Experience at a Single Center

The purpose of this analysis was to review our initial experience of pediatric robotic-assisted pyeloplasties (RALPs). Our case series spanned a 7-year period (January 2004-February 2011). The initial 20 cases were reviewed retrospectively (RG group), and the later 20 cases were seen prospectively (PG group). We compared outcomes between these two groups. After institutional review board approval, all charts were reviewed, and outcomes were based on postoperative imaging. For continuous variables t tests were performed, and for categorical variables Fisher's exact tests were performed. Statistical analysis was performed with SPSS version 17.0 software (SPSS, Inc., Chicago, IL). There was no significant difference in demographics between the two groups. Median age at time of surgery was 64 months (PG) and 36 months (RG). Narcotic use was statistically similar among the groups when comparing median morphine intravenous equivalent per kilgram. Mean follow-up was 15.6 months (PG) and 41.8 months (RG). Postoperative imaging was stable or improved in 95% (PG) and 100% (RG). RALP in 1 patient in the PG group failed and later required repeat surgery (5%). The only identified significant difference between the two groups was surgical time. Mean operative time was reduced by over an hour between the two time periods (230 minutes for PG, 297 minutes for RG [P<.01]). The experience in pediatric RALP is growing at our institution. As this experience grows, the primary outcome that has changed is faster operative times. This increased efficiency does not correlate with compromised outcomes. We continue enrolling patients in our prospective database to strengthen the power of our outcomes analysis.

The immunoexpression of glomerular NF-κB in proteinuric patients with proliferative and non-proliferative glomerulopathies

Recent studies suggest that NF-κB activation plays an essential role in the activation of mesangial cells and macrophages through the transcriptional induction of inflammatory mediators of glomerular inflammation and injury. The aim of the present study was to determine, using an image analysis system, glomerular immunoexpression of NF-κB (nuclear translocation of p65) in proteinuric patients with proliferative and non-proliferative glomerulopathies. Thirty-six proteinuric patients with idiopathic proliferative glomerulopathies (PG group) and 28 proteinuric participants with non-proliferative glomerulopathies (NPG group) were examined by percutaneous renal biopsy. As a control 12 biopsy specimens of the kidneys removed because of trauma were used. In the PG group the mean values of the glomerular immunoexpression of NF-κB were significantly increased as compared to both NPG patients and controls. In the PG but not in the MPG group glomerular immunoexpression of NF-κB was significantly positively correlated with the degree of proteinuria. Moreover, in the PG group glomerular immunoexpression of NF-κB was positively correlated with the mesangial cells, mesangial area and glomerular monocytes/macrophages. In conclusion, our results strongly suggest a role of NF-κB in glomerular injury in proteinuric patients with proliferative glomerulopathies.

147 AGGREGATION OF IN VIVO FERTILIZED AND PARTHENOGENETICALLY ACTIVATED MOUSE EMBRYOS

Embryonic chimerism – mixing of cells originated from at least two different fertilizations – has been used as a tool for stem cell pluripotency diagnosis, transgenic rodent production, and organogenesis studies. Additionally, parthenotes are used for studies related to gene imprinting and the ability of their cells to compose the placenta and/or an adult animal. The aim of this work was to validate the production and characterize developmental kinetic of parthenogenetic embryos, obtained from C57BL/6 EGFP mice (EGFP), to determine their potential to produce chimeras, and to localize parthenogenetic cells on the produced blastocyst. Embryos were harvested from superovulated females. For the aggregation, pre-compaction IVF (Swiss Webster/SW strain) or parthenogenetic activated (PGA; SW and EGFP) embryos were used. For PGA, strontium chloride hydrate (5 mM for 6 h) was used. Two experiments were outlined in order to: i) evaluate the development and kinetic from IVF (IVF and in vitro developed; 2-cell stage embryos, n = 53) and from PGA (parthenogenetically activated and in vitro developed; n = 409 oocytes) techniques, both from SW; ii) evaluate the aggregation between pairs of control embryos (C; n = 20, 4-cell in vivo produced embryos from SW) or pairs of 4-cell in vivo produced SW embryos and 4- to 8-cell PGA EGFP embryos (parthenogenetic embryo, PG; n = 40). After manipulation (removal of the zona pellucida and approximation of pairs, for C and PG groups), all the groups were kept in vitro culture (37°C, 5% CO2, and saturated humidity) for 48 to 60 h (C and PG), or up to blastocyst stage (IVF and PGA). Chimerism rate and parthenogenetic cells fluorescence (pre- and post-culture) were evaluated under an inverted microscope with epifluorescence source, and digital images were captured (Eclipse Ti and NIS-Elements, Nikon, Japan, respectively), by merging visible and UV light images. The rate of PGA (EGFP oocytes) was 54.5% (66/121), assessed 6 h post-activation by the presence of at least one pronucleus. The assessment was performed with 20× magnification and Hoffman modulation contrast in an inverted microscope. The rate of blastocyst production between IVF and PGA was significantly different (71.4 and 12.9%, respectively; P &lt; 0.001, Fisher’s exact test). When developmental kinetic was evaluated there a difference in the average time to the majority of embryos reach blastocyst stage for IVF (48 h) and PGA (120 h) was observed. The chimerism rate was assessed by the presence of a single and cohesive cell mass (C) or by the incorporation of EGFP cells in the SW embryo (PG). There was difference (P = 0.006; Fisher’s exact test) between C (55.0%; 11/20) and PG (17.5%; 7/40) chimerism rates, assessed from 48 to 60 h of culture. In PG group, the incorporation of EGFP cells in the obtained chimeras was mainly detected in the trophectoderm although one chimeric blastocyst contained EGFP cells only in the inner cell mass. It was concluded that parthenogenetic embryos have a slower developmental kinetic (until 120 h of culture) than embryos derived from IVF. Acknowledgment to FAPESP for fellowship and funding.

Prognosis of Patients With Gastric Cancer Who Underwent Proximal Gastrectomy

Proximal gastrectomy (PG) has been introduced for patients who are preoperatively diagnosed with early gastric cancer located in the upper third of the stomach. In the present study, we compared the prognosis of patients who underwent PG with that of patients who underwent total gastrectomy (TG). Between 1997 and 2006, 51 patients were diagnosed with early gastric cancer located in the upper third of the stomach and underwent PG. In the same period, 35 patients were diagnosed with early gastric cancer and underwent TG. Of these, in 24 patients, the cancer was localized in the middle to upper part of the stomach, and 11 patients had multiple cancers. We compared the clinicopathologic differences and prognoses between the two groups. Significantly fewer lymph nodes were dissected in the PG group (mean, 18.2) than in the TG group (mean, 36.6;P < 0.001). Complications were detected in 17.6% of patients in the PG group and in 14.3% of patients in the TG group, which was not significant (P = 0.678). The overall and disease-specific 5-year survival rates in the 51 patients who underwent PG (88.7% and 97.1%, respectively) were not different from those in the 35 patients who underwent TG (87.6% and 93.4%; P = 0.971 and P = 0.553; respectively). These findings indicate that PG can be performed safely and may have various advantages compared with TG in terms of patients' daily lives.

Eficiência do Estrotect® na identificação de estros em vacas leiteiras mestiças

Among the problems that reduce the reproductive efficiency in dairy cows the failure in estrus detection is a major factor. The objective of this study was to evaluate the efficiency of Estrotect®, a device that aids heat detection in cattle, and to compare it with visual detection in 58 crossbred Holstein/Gyr dairy cows producing 18.5Kg/milk/cow. The animals were divided into two groups: the TAI (n = 21) underwent a fixed-time artificial insemination protocol (TAI), and 10 days after insemination, the device was fixed to the cows. In the PG group (n = 37) prostaglandin (dinoprost tromethamine) 25mg/animal/IM was administered, and then the device was put in place. These cows were then monitored by ultrasound over a period of 28 days to verify the development of the corpus luteum. Logistic regression was used to find out if there were alterations in the efficiency of Estrotect® within the groups, and the McNemar test was used to compare its efficiency to that of visual observation. No group effect was detected (P> 0.05) on the efficiency of visual detection nor on that of the auxiliary device. Neither was there observed any difference between the efficiency of visual detection of estrus and that of the device (P> 0.05). The auxiliary tool for the detection of estrus, (Estrotect ®), proved to be just as effective as visual detection. Thus, it can be used as an auxiliary device in conjunction with visual observation, and also as a unique tool for the detection of estrus in order to simplify the management of large herds.

Expression of cytokines of interleukin-6 family in gingival fibroblasts by Toll-like receptor-2

To investigate whether signaling through Toll-like receptor-2 (TLR-2) can affect the expression of some cytokines in human gingival fibroblasts. The gingival fibroblasts were isolated and cultured in vivo, divided into blank control group, lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg) group and Escherichia coli (Ec) group. mRNA expression levels were measured by real-time polymerase chain reaction (PCR). The protein expression levels were detected by the enzyme linked immunosorbent assay (ELISA). The data was statistically analyzed by SPSS16.0 software package. LPS from Pg could stimulate the expression of interleukin (IL)-6 and leukemia inhibitory factor (LIF) mRNA and protein, which reached the peak (5.87 ± 0.83) at 10 h, and the expression level increased with the increase of the Pg concentration. IL-11 or oncostatin-M (OSM) mRNA expression was not affected by LPS. After treated with Pg for 48 h, the protein expression of IL-6 and LIF was up-regulated, (962 ± 57) ng/L and (47 ± 18) ng/L respectively. Signaling through TLR-2 controls the expression of cytokines of IL-6 family in human gingival fibroblasts.

Prostaglandin F2α promotes ovulation in prepubertal heifers

The objective was to determine the effects of exogenous prostaglandin F2α (PGF), with or without progesterone treatment, on first ovulation in prepubertal heifers. We tested the hypothesis that PGF has a luteolysis-independent ovulatory effect in cattle. Crossbred Angus heifers (12 to 14 mo old, 250 kg body weight, and an average body condition score of 3 out of 5) were examined by transrectal ultrasonography on two occasions, 11 days apart. Heifers in which a CL was not detected at either examination were considered prepubertal. Heifers were assigned randomly to three experimental groups: (1) PG group (N = 14); heifers were treated with a PGF analog (500 μg cloprostenol im) 5 days after the emergence of a spontaneous (i.e., naturally occurring, noninduced) follicular wave; (2) PPG group (N = 12); heifers were given an intravaginal progesterone-releasing insert (CIDR; Pfizer Animal Health, Montreal, QC, Canada), and a follicular wave was induced with 50 mg of progesterone + 2 mg of estradiol benzoate im, and a PGF analog was given at the time of CIDR removal, on Day 5 of the follicular wave (on average, 8.6 ± 0.5 days after CIDR insertion); and (3) control group heifers were given no treatment (N = 14). Heifers were examined daily by transrectal ultrasonography from the start of the experiment to confirmation that ovulation had occurred, or to 5 days after PGF injection (PG and PPG groups) or until dominant follicles of the next follicular wave reached 8 mm (control group). The percentage of heifers that ovulated within 10 days after wave emergence was higher in PPG (10/12; 83.3%) and PG (11/14; 78.5%) groups than in control (1/14; 7.1%; P < 0.0001). Ovulations occurred 69.6 ± 6 h and 93.8 ± 5 h after PGF treatment in PPG and in PG groups, respectively, whereas only one heifer in the control group ovulated 96 h after Day 5 of follicular wave (P = 0.13). In summary, PGF treatment was associated with ovulation in prepubertal heifers whether or not exogenous progesterone was used as a pretreatment. The hypothesis that PGF will induce ovulation by a luteolysis-independent mechanism was supported.

NSABP B-38: Definitive analysis of a randomized adjuvant trial comparing dose-dense (DD) AC→paclitaxel (P) plus gemcitabine (G) with DD AC→P and with docetaxel, doxorubicin, and cyclophosphamide (TAC) in women with operable, node-positive breast cancer.

LBA1000 Background: The primary aims were to determine whether adjuvant DD AC→PG will be superior to DD AC→P as well as to TAC in DFS and to compare the relative DFS of TAC and DD AC→P. Secondary endpoints include survival and toxicity. Methods: From Nov 3, 2004 to May 3, 2007, 4894 women were randomized; 1630 to TAC (docetaxel [T] 75 mg/m2, doxorubicin [A] 50 mg/m2, cyclophosphamide [C] 500 mg/m2 q3 wks x 6), 1634 to DD AC→P (A 60 mg/m2 and C 600 mg/m2 q2 wks x 4 followed by P 175 mg/m2 q2 wks x 4), and 1630 to DD AC→PG (A 60 mg/m2 and C 600 mg/m2 q2 wks x 4 → P 175 mg/m2 + G 2000 mg/m2q2 wks x 4). Primary G-CSF support was required and erythropoiesis-stimulating agents (ESA) were used at investigator discretion. 52% were postmenopausal, 65% had 1 - 3 positive nodes, and 80% had HR+ breast cancer. Log-rank tests were used for pair-wise comparisons of the primary (DFS) and secondary (OS) endpoints among the three treatment arms. Results: With 64 months median follow-up, 5-year DFS in DD AC→PG group was 80.6% compared with 82.2% in DD AC→P group (HR=1.1; p=0.27) and 80.1 % (HR=0.97; p=0.71) in TAC group. 5-year OS was 90.8% in DD AC→PG group as compared with 89.1% (HR=.89; p=0.25) in DD AC→P group and 89.6 % (HR=0.90; p=0.32) in TAC group. HR for DFS and OS of DD AC→P vs. TAC were 0.89 (p=0.14) and 1.01 (p=0.92) respectively. Toxicities for TAC, DD AC→P, DD AC→PG, respectively: febrile neutropenia (Gr 3/4: 9%, 4%, 4% [p&lt;0.001]), sensory neuropathy (Gr 3/4: &lt;1%, 7%, 6% [p&lt;0.001]), diarrhea (Gr 3/4: 8 %, 2%, 2% [p&lt;0.001]). Hgb was &lt;10 in 12%, 26%, 33% with ESA use in 35.2%, 47%, 51.6% and transfusions in 3.7%, 6.3%, 9.4%. Deaths on treatment: N=13, 5, 7 (p=0.2). AML/MDS: N=5, 8, 11. All cycles completed in 91% for TAC and 88% for DD regimens. Conclusions: Addition of G to DD AC→P did not improve outcomes. No significant differences in efficacy endpoints were identified between DD AC→P and TAC, though toxicity profiles differed. Funding: NCI PHS U10-CA-37377, -69974, -12027, -69651 and NCCTG U10-CA25224, with additional funding from Eli Lilly &amp; Company, and Amgen, Inc.

Evaluation of the efficacy of the Allegretto Wave and the Wavefront‐optimized ablation profile in non‐anterior astigmatisms

To assess the efficacy of the Allegretto Wave and the wavefront-optimized ablation profile (WFO) in non-anterior astigmatism correction, in both LASIK and photorefractive keratectomy (PRK) treatments. Seventy-four refractive surgery candidates were recruited prospectively in a non-randomized trial. Only one eye from each candidate was randomly enrolled in the study. Of them, 40 eyes underwent LASIK treatment (LG group), while 34 eyes underwent PRK treatment (PG group). Preoperatively, the ocular residual astigmatism (ORA) was calculated for each eye, according to which each astigmatism fault was characterized as primarily anterior or non-anterior. Twenty LG eyes and 16 PG eyes presented primarily anterior astigmatism (LG-A and PG-A subgroups, respectively), while 20 LG eyes and 18 PG eyes demonstrated primarily non-anterior astigmatism (LG-NA and PG-NA subgroups, respectively). Postoperatively, vector analysis of astigmatism correction was conducted. The following indexes were calculated: (i) correction index (CI), (ii) difference vector (DV) and (iii) index of success (IOS). Preoperatively, mean differences between manifest and topographic astigmatisms for the LG and the PG subgroups were significant (p:0.006 and p<0.001, respectively), while postoperatively, aforementioned differences were non-significant (p:0.18 and p:0.09, respectively). Regarding vector analysis in the LG group, mean CI, IOS and DV were 1.39±1.26, 0.37±1.06 and 0.30±0.51, respectively. Differences in CI, IOS and DV between LG-A and LG-NA subgroups were non-significant. Regarding vector analysis in the PG group, mean CI, IOS and DV were 1.22±0.33, 0.47±0.46 and 0.27±0.25, respectively. Differences in CI, IOS and DV between PG-A and PG-NA subgroups were non-significant. Our results suggest that the Allegretto Wave and WFO profile seem to be equally effective in both anterior and non-anterior astigmatism correction, regardless of treatment type.

EFFECTS OF grape powder SUPPLEMENTATION ON INFLAMMATION IN hemodialysis patients.

Polyphenols and antioxidants anti-inflammatory have been considered pharmacological agents to combat oxidative stress in chronic diseases due the reduction in the formation of free radicals (FR). Hemodialysis (HD) patients have an imbalance between oxidant and antioxidant activity, with increased levels of FR and consequently an increase of lipid peroxidation, thereby raising the risk for cardiovascular disease (CVD). The beneficial health effects of grape juice or red wine for these patients have been attributed to the antioxidant activity of its polyphenols. Then, this study aimed to evaluate the effects of grape powder supplementation on inflammation and glutathione peroxidase levels in hemodialysis (HD) patients. Thirty-two HD patients from CIN , RJ, Brazil were studied and randomly into two groups: placebo group- PG (16 patients, 9 men, 52.7 ± 13.7 yrs) and experimental group EG (16 patients, 9 men, 53.0 ± 9.8 yrs). Each patient received 12g/day of powder grape with grape jelly or only grape jelly (placebo) during 5 weeks. The lipid profile, C-reactive protein (CRP) levels and glutathione peroxidase (GPx) activity were evaluated before and after supplementation (Table). The data suggest that the consumption of grape powder was effective to increase the activity of GPx and decreasing the progression the inflammation. Thus, our results indicate that grape powder plays an important role as an antioxidant agent in HD patients. Placebo Group Experimental Group Before After Before After CRP (mg/mL) 2.6±0.2 2.8±0.2 * 2.6±0.2 2.6±0.2 LDL-C 86.3±38.8 94.4±34.3 80.5±25.0 82.9±22.1 Total cholesterol 154.6±44.9 163.3±44.8 143.9±29.2 145.4±28.3 GPx (U/g prot) 17.5±9.8 29.1±30.7 19.7±20.3 41.0±27.7 * ⁎ p<0.05

New insights in cellular immune response in colostrum-deprived pigs after immunization with subunit and commercial vaccines against Glässer’s disease

Four groups of colostrum-deprived pigs were immunized with Porcilis Glässer® (PG) or with subunit vaccines developed by us (rTbpA, NPAPTM or NPAPTCp) against Glässer’s disease, and they were challenged with 3×108CFU of Haemophilus parasuis. A strong reduction in CD3+γδTCR+ cells was seen in non-immunized control and scarcely protected (rTbpA) groups, suggesting that these cells could represent a target of H. parasuis infection. A significant increase in CD172α+CD163+ cells was detected in all groups but PG, while a reduction in SLAIIDR+ molecules expression was observed after challenge in control animals. Significant increases in CD3ε+CD8α+CD8β+ and B cells were detected respectively in control and NPAPT groups, and in scarcely (rTbpA) and well-protected (NPAPTM and NPAPTCp) groups. Finally, a greater response in CD4+CD8α− cells was observed in NPAPTCp compared to NPAPTM and PG groups. These results state the potential of NPAPT antigen for developing effective vaccines against Glässer’s disease.

Puerarin improve insulin resistance of adipocyte through activating Cb1 binding protein path

To explore the molecular mechanism of puerarin (Pue) in improving insulin resistance through observing its effect on the insulin resistance of 3T3-Li lipocyte induced by free fatty acid (FFA). 3T3-L1 preadipocyte was induced by a culture solution containing insulin, isobutyo-menthyl-xanthine, and dexamethasone to mature lipocyte, and it was divided into six groups: the control group (normal cells), the model group (untreated model cells), and the four drug treatment group exposed to dimethyl biguanide (Met group), highdose puerarin (PueH group), low-dose puerarin (PueL group), and propylene glycol (PG group), respectively. Mature lipocytes in various groups, except those in the normal group, were established into insulin resistance model by FFA induction and treated respectively with corresponding drugs. Peroxisome proliferator-activated receptor-γ (PPAR-γ) mRNA expressions at the fourth, sixth, and eighth day were observed using reverse transcription polymerase chain reaction (RT-PCR); glucose transportation in various groups were observed by 2-deoxy-[(3)H]-D-glucose intake method; mRNA expression of Cb1 binding protein (CAP) was determined by RT-PCR; and glucose transporter-4 (Glut-4) transposition was detected by immune-fluorescence method. PPAR-γmRNA expression increased gradually, and it showed lower levels at the fourth, sixth, and eighth day in all treatment groups than that in the model group. Glucose transportation determination showed that the transportation in the model group was 2.23±0.63, significantly lower than that in the normal group 5.05 ± 0.66 (P<0.01); as compared with the model group, they were significantly higher in the PueH and the PueL groups. In addition, the CAP mRNA expression and membranous distribution of Glut-4 were higher in the two Pue treated groups than those in the model group, respectively. Pue could markedly improve the insulin resistance of 3T3-L1 lipocyte, which is realized possibly by way of inactivating CAP path, promoting Glut-4 transposition to cell membrane to increase the transportation of glucose.