Phenotypic characterization of immune cells in fetal tissues of cattle immunized and challenged with Neospora caninum.

The purpose of this work was to characterize the cellular phenotype in inflammatory infiltrates of fetal tissues from pregnant heifers immunized and experimentally challenged with Neospora caninum. Fetuses from 20 heifers separated into 5 groups were obtained. The experiment was designed as follow: Group A, heifers inoculated intravenously with live tachyzoites of Argentine strain NC-6 (n = 4); Group B heifers inoculated subcutaneously with soluble native antigen from the same strain formulated with immune stimulant complexes (ISCOMs) (n = 4); Group C heifers inoculated with recombinant proteins, rNcSAG1, rNcHSP20, rNcGRA7 formulated with ISCOMs (n = 4), Group D heifers inoculated subcutaneously with sterile phosphate buffered solution (n = 4) and Group E heifers inoculated subcutaneously with antigen-free ISCOMs (n = 4). Experimental challenge was performed at 70 days of gestation and all heifers were euthanized 34 days later. Fetal tissues were taken for histological studies. Inflammatory lesions were observed in brain and lung, and immunhistochemistry was used to identify CD3+, CD20+ and MHC II+ cells. The majority of the cells that infiltrate and circumscribe the lesions in the brain and lung tissue expressed MHC II antigen; varying between 70-90% of the total cellular infiltrate. CD3+ cells were also present within the lesions, contributing to up to 30% of the inflammatory cells. CD20+ cells appeared as a marginal group, in some cases, with a range between 10 and 25%. As expected, the immunolabeling of MHC II + and CD3 + cells in fetal tissues was associated with fetal infection with N. caninum. There were statistically significant differences in the distribution and population of the inflammatory infiltrate in relation to the immunogenic treatment and the type of tissue, with inflammatory cells being markedly less extensive fetuses from group A (dams previously exposed to N. caninum) and in brain tissue. This work showed that Neospora-infection induced MHC II+ and CD3+ cells in bovine fetuses from dams receiving experimental vaccines.

Biosecurity assessment of Argentinian pig farms.

The pig industry is growing very fast in Argentina with an increasing need for replacement animals, feedstuff and transportation of animals. One of the main competitive advantages of the Argentinian pig industry is its being free of most major pig diseases. Within this context, applying measures aimed to reduce the risk of introduction and spread of pathogens is critical. The aim of the present study was to assess the biosecurity of Argentinian pig farms. Two types of farms were assessed: firstly, all official suppliers of high-genetic-value (n = 110) and secondly, a sample from commercial farms (n = 192). Data on the external and internal biosecurity practices applied on the farms was collected with a questionnaire. Data was analysed using a correspondence analysis and a hierarchical clustering analysis, which allowed identification of types of farms with regard to the biosecurity measures applied. Key variables characterizing the clusters were identified through an indicator value analysis. In addition, the external biosecurity of the farms was evaluated by using risk assessment tools with respect to the potential introduction of porcine epidemic diarrhoea virus. Results made evident three clusters: the first one which, amongst other measures, applied several barriers to prevent the entry of people, trucks and other vehicles, and could be considered as a group of high biosecurity, and the two other groups which applied a lower number of external and internal biosecurity measures. The results of the risk assessment showed that the routes with the highest risk of disease introduction were: replacement animals, vehicles transporting feed or animals, and visitors. The assessment of the external biosecurity showed that most Argentinian farms were not prepared for the contingency of a pathogen such as porcine epidemic diarrhoea virus. Special efforts should be made in official suppliers of high-genetic-value farms with poor biosecurity scores since they are at the top of the pig production chain and can be key for the spread of diseases.

Does pegvisomant treatment expertise improve control of resistant acromegaly? The Italian ACROSTUDY experience.

OBJECTIVE: GH receptor antagonist pegvisomant is indicated for treatment of patients with resistant acromegaly. We compared safety and treatment outcomes of pegvisomant therapy in patients managed by Italian centers enrolling less or more than 15 cases in ACROSTUDY, a safety surveillance study of long-term pegvisomant treatment of patients with acromegaly. A noninterventional safety surveillance study in which safety and treatment outcomes of pegvisomant were evaluated on the basis of data collected during a 7-year period. METHODS: A total of 204 acromegaly patients treated by seven centers enrolling 16-49 patients each (group A) and 137 subjects by 18 centers following 3-14 cases ( group B). RESULTS: Patients of group A and B were treated for 4.4 ± 2.7 and 4.2 ± 2.2 years, respectively. IGF-1 ULN normalized in 64.4 % (n = 56) and 54.4 % (n = 31) in group A and B, respectively, after 1-year treatment, and in 57.3 % (n = 106) and 72.5 % (n = 87) at last visit. Starting doses were significantly higher in group A. They were progressively increased during treatment in both groups, but were higher in uncontrolled patients than in controlled ones only in group A. Reported adverse events were more frequent, and the prevalence of patients with adverse events was higher in group B. CONCLUSIONS: On the basis of this original study approach, we could speculate that in the centers in which more patients are treated with pegvisomant, less adverse events are reported, but the long-term effectiveness is lower than in centers with less cases, perhaps because of an inadequate patient's selection.

ACROSTUDY: the Italian experience.

ACROSTUDY is a world-wide non-interventional, post marketing surveillance study performed to monitor the safety and outcomes of pegvisomant (PEG) in clinical practice. We report data from acromegaly patients who have been included in the Italian ACROSTUDY registry. The data of 341 acromegaly patients (171 males) were available for analysis using data freeze (12/9/2012). Patients were enrolled in 25 Italian endocrine centres. Before and during PEG treatment IGF-I, liver enzymes, metabolic parameters, and pituitary MRI were assessed. Before PEG, 54.3% patients had been treated with medical therapy and surgery, 22.9% medical therapy only, and 15.8% medical plus radiation and surgical therapy. 199 adverse events were reported in 98 patients (28.7%). Serious adverse events were documented in 29 patients (8.5%). 71.1% of patients had no significant change in tumor volume. Central MRI reading was performed in 34 patients; in 7 patients, an increase in tumor volume was found. Hormonal efficacy progressively increased since the start of PEG. After 6 years, normal IGF-I levels were found in 70.9% of patients (mean daily dose 18.1 mg). 87.1% of patients were treated with daily PEG although in 8.8% of patients, it was administered 2-6 times per week and in 3.8% with weekly injections. 74.8% received a PEG dose 10-15 mg/daily. PEG is a drug with a favorable safety profile which is efficacious also considering that in Italy it is currently available as third-line therapy.

Determination of chlorimuron and metsulfuron residues in two soils of Argentina using a rapid seed-bioassay.

The presence of chlorimuron ethyl and metsulfuron methyl in two soils was determined by a modified petri dish bioassay. Pregerminated seeds of maize and sunflower were placed in petri dishes containing 85 to 100 g of treated soil. Radicle root lengths were measured after 24 h. Chlorimuron had no effect on maize on the Balcarce soil, however 0.007 microg g(-1) decreased sunflower root length. Chlorimuron decreased maize and sunflower root length regardless application dose on the San Cayetano soil. Metsulfuron decreased maize root length at 0.04 microg g(-1) and sunflower at 0.021 microg g(-1) on the Balcarce soil. On the San Cayetano soil metsulfuron at 0.001 microg g(-1) decreased maize and sunflower root length. The phytotoxicity of chlorimuron and metsulfuron changed according to soil type and dose. Maize and sunflower were 1.3-1.5 and 1.3-1.8 times respectively more sensitive to chlorimuron on the San Cayetano soil than on the Balcarce soil. In the case of metsulfuron, maize was similarly sensitive on both soils but sunflower was 1.7-2.0 times more sensitive on the San Cayetano soil than on the Balcarce soil. Phytotoxicity increased as organic matter (OM) content decreased and/or when the soil pH and concentration increased.

Clinical trial of a monophasic estroprogestin oral formulation containing 20 micrograms ethinyl estradiol and 75 micrograms gestodene.

The attempt to decrease the hormonal components of combined estrogen/progestin-containing oral formulations has led to use of low-dose formulations. The monophasic formulation containing ethinyl estradiol 20 micrograms (EE20) plus gestodene 75 micrograms (GSD75) was studied in an open, non-comparative, multicenter, clinical trial investigating its efficacy, safety, effects on body weight, blood pressure and sexual function. To evaluate the impact on sexual function, the Golombok Rust Questionnaire on Sexual Satisfaction (GRISS) was used. The study population comprised 216 women treated for 1 year. The EE20/GSD75 formulation did not show any significant effect on blood pressure, hematological parameters, body weight or sexual function. The treatment was well tolerated with a high compliance rate by the patients, with a low rate of estrogen-dependent symptoms. Moreover, there was no overall effect on sexual function, with no disturbance of sexual behavior or activity. In conclusion, our data show that the EE20/GSD75 has a very good tolerability profile, without any significant side-effects.

Weekly gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase II study.

BACKGROUND: The combination of gemcitabine and cisplatin has proven effective in the treatment of advanced non-small-cell lung cancer (NSCLC). However, the optimal schedule for administration of the two drugs has not yet been determined. In this study we evaluated the activity and toxicity of a weekly gemcitabine and cisplatin schedule. PATIENTS AND METHODS: Thirty-six untreated patients with stage IIIB IV NSCLC entered the study. Treatment consisted of gemcitabine 1000 mg/m2 i.v. and cisplatin 35 mg/m2 i.v., both given weekly on day 1,8, and 15, followed by one week of rest. RESULTS: Ninety-seven courses (273 weekly administrations) were delivered. The median dose-intensity was 612 mg/m2 per week for gemcitabine (82%) and 21 mg/m2 per week for cisplatin (80%). All 36 of the patients were evaluable for toxicity, and 30 for response. Partial remissions were observed in 12 patients, for an overall response rate of 40% (95% confidence interval (95% CI): 22.5%-57.5%). Most of the partial remissions were seen in IIIB patients (54% of the stage IIIB and 22% of the stage IV patients responded). According to the intent-to-treat principle, the response rate was 33.3% (12 of 36 patients). The median response duration was 9.9 months (range 4-23) and the median survival time 11.8 months (range 1-24). World Health Organization (WHO) grade 3-4 myelotoxicity was: thrombocytopenia in nine patients (25%), neutropenia in six (16.6%) and anemia in six (16.6%); there was very little additional major toxicity. CONCLUSIONS: This regimen appears to be active and to have a favourable toxicity profile.

First line chemotherapy in patients with brain metastases from non-small and small cell lung cancer.

In this study we evaluated the role of systemic chemotherapy in 23 previously untreated patients with brain metastases from both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). In NSCLC group, 2 patients out of 14 had a brain response after treatment (1 complete and 1 partial response). In the group of 9 patients with SCLC, we observed 5 brain responses (3 complete and 2 partial responses). Brain responses were in accordance with extracranial responses although this appeared more clearly in SCLC than in NSCLC patients.

Clinical evaluation of an oral contraceptive containing Ethinyl-Oestradiol (30 mcg) and Gestoden (75 mcg).

At the Family Planning Center AIECS in Bari, 383 women have been treated for 6 cycles with an estroprogestinic combination containing Ethinyl-Oestradiol (30 mcg) and Gestoden (75 mcg). We evaluated the following parameters: contraceptive efficacy, cycle control, side effects and acceptability. At the end of the treatment, 346 women (90.4%) decided to continue the treatment while only 22 expressed a negative opinion. The clinical experience has been positively considered by the physician, considering the high contraceptive efficacy, even if 12% of women forgot to take the pill (Pearl Index 0.00) side effects profile and cycle control.

Efficacy, cycle control and side-effects of two monophasic combination oral contraceptives: gestodene/ethinylestradiol and norgestimate/ethinylestradiol.

Two monophasic oral contraceptives containing gestodene (GTD, 75 micrograms) and ethinylestradiol (EE, 30 micrograms) or norgestimate (NGS, 250 micrograms) and EE (35 micrograms) were compared during the first six cycles of use. The subjects were randomly assigned to receive either type: 97 received GTD/EE and 92 NGS/EE. Six women in the GTD/EE group and nine in the NGS/EE group withdrew from the study; three (3%) and two (2%), respectively, withdrew because of adverse reactions. A total of 562 cycles for GTD/EE and 523 for NGS/EE were available. No woman became pregnant during the study. Overall, 94.4% of cycles in the GTD/EE group and 92.8% in the NGS/EE group were normal. A similar incidence of breakthrough bleeding (0.2% of cycles for GTD and 1.6% for NGS) and spotting (5.4% vs. 5.6%) was observed. Amenorrhea was never reported. Duration of withdrawal bleeding tended to be slightly longer in the NGS/EE group, significantly so for cycles 2 (0.5 days, p = 0.016), 4 (0.5 days, p = 0.031) and 5 (0.4 days, p = 0.045). Cycle 2 was significantly longer in the GTD/EE group (0.3 days, p = 0.027). Side-effects were reported by 12 (12%) women in the GTD/EE group and 13 (14%) in the NGS/EE group. The most common side-effects were headache (five cases (5%) in the GTD/EE group and two (2%) in the NGS/EE group) and breast pain (three (3%) and eight (9%) cases respectively). There were no statistically significant differences between the two groups with respect to change in body weight or changes in blood pressure and in laboratory data.(ABSTRACT TRUNCATED AT 250 WORDS)

[Italian multicenter study for the verification of the efficacy and tolerability of short-term substitution hormone therapy using conjugated estrogens and progestagens administered orally in the postmenopausal a period]. / Studio multicentrico italiano di verifica in merito all'efficacia ed alla tollerabilità della terapia ormonale sostitutiva a breve termine con estrogeni coniugati e progestinici per via orale nella postmenopausa.

Three hundred and sixty-three postmenopausal women received 6 months of cyclic hormone replacement therapy with conjugated estrogens in differing doses (0.625 mg and 1.25 mg) associated in a sequential pattern lasting 12 days with progestagens (medroxyprogesterone acetate or medrogestone) in 16 italian health centres. The results of the multicentre study confirm the efficacy of this conjugated estrogen-progestogen regimen in resolving climacteric syndrome, offering cardiovascular protection and vaginal trophic effect and preventing postmenopausal osteoporosis, as well as confirming its tolerability in relation to blood pressure, body weight, breast, endometrium, blood coagulation and hepato-renal function.