Apicomplexan protozoa responsible for reproductive disorders: Occurrence of dna in blood and milk of donkeys (equus asinus) and minireview of the related literature

Donkeys may be susceptible to many pathological agents and may act as carriers of pathogens for other animal species and humans. This study evaluated the occurrence of potentially abortifacient apicomplexan protozoa DNA in blood and milk samples collected at different time periods during lactation (1, 6, and 10 months) from 33 healthy dairy jennies. A total of 73 blood and 73 milk samples were used for DNA extraction and analysis. Blood specimens from 11/33 (33%) jennies scored positive for Theileria equi, while milk samples scored negative. Blood and milk of 3/33 jennies yielded DNA of Toxoplasma gondii at 6 months (n. 1) and 10 months (n. 2) after parturition. Neospora caninum DNA was found in four milk and in five blood samples only at one month after parturition. This study is the first report about the presence of N. caninum DNA in milk of naturally infected jennies. Moreover, the excretion of N. caninum DNA in some of these jennies at 30 days from the parturition may suggest a possible occurrence of an endogenous cycle, while the presence of T. gondii DNA in the milk collected at 6 and 10 months after parturition may be suggestive of a discontinuous excretion

Detection and genotyping of Toxoplasma gondii DNA in the blood and milk of naturally infected donkeys (Equus asinus)

Background: Toxoplasma gondii is a worldwide zoonotic protozoan. Consumption of raw milk from infected animals is considered a risk factor for acquiring toxoplasmosis in humans. Recently, donkey milk has been indicated for therapeutic and nutritional purposes and T. gondii infection is common in donkeys. The purpose of the present paper was to detect the presence of parasite DNA in milk of T. gondii positive donkeys. Findings. Antibodies to T. gondii were found in 11 out of 44 healthy lactating donkeys by IFAT. T. gondii DNA was detected by PCR in blood of 6 and milk of 3 seropositive jennies. Results of limited RFLP-PCR genotyping indicated the presence of T. gondii genotype II or III, commonly found in Europe. Conclusions: The occurrence of T. gondii DNA in milk suggests that the consumption of raw milk from seropositive donkeys could be a potential source of human infection

Expression and structural features of endoglin (CD105), a transforming growth factor beta1 and beta3 binding protein, in human melanoma.

Human endoglin (CD105) is a member of the transforming growth factor beta (TGF-beta) receptor family that binds TGF-beta1 and -beta3, but not TGF-beta2, on human endothelial cells. Immunohistochemical analyses demonstrated that CD105 is expressed on normal and neoplastic cells of the melanocytic lineage. The anti-CD105 MAb, MAEND3, stained 50, 25 and 34% of intradermal naevi, primary and metastatic melanomas investigated, respectively, and nine out of 12 melanoma cell lines. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed that CD105 expressed by melanoma cells consists of a homodimeric protein with an apparent molecular weight of 180 and 95 kDa under non-reducing and reducing conditions. Cross-linking of 125I-labelled TGF-beta1 to melanoma cells, Mel 97, by disuccinimidyl suberate (DSS) demonstrated that CD105 expressed on pigmented cells binds TGF-beta1; the pattern of binding of TGF-beta1 to melanoma cells was found to be similar to that of human umbilical vein endothelial cells. The addition of exogenous, bioactive TGF-beta1 significantly (P<0.05) inhibited the growth of CD105-positive melanoma cells, Mel 97, but did not affect that of CD105-negative melanoma cells, F0-1. These data, altogether, demonstrate that CD105 is expressed on pigmented cells and might play a functionally relevant role in the biology of human melanoma cells by regulating their sensitivity to TGF-betas

ASPETTI DELLA PRODUZIONE DEI PICCOLI RUMINANTI CON IMPATTO SULLA SALUTE UMANA

Negli ultimi anni l’attenzione del consumatore si è sempre più orientata verso le caratteristiche nutrizionali degli alimenti. Queste proprietà sono di grande importanza anche per quanto riguarda le produzioni dei piccoli ruminanti. Il presente lavoro ha lo scopo di riassumere i principali risultati emersi dal progetto di ricerca “Aspetti della produzione dei piccoli ruminanti con particolare impatto sulla salute umana”. Sono stati analizzati mediante i metodi descritti in letteratura: 1) i polimorfismi genetici dei biopeptidi del latte dei piccoli ruminanti; 2) le attività di alcuni enzimi della membrana del globulo di grasso e la frazione lipidica del latte ovino; 3) la qualità nutrizionale del latte e del formaggio ovino in relazione all’intensità di pascolamento; 4) le componenti bioattive di siero e scotta residui alla produzione dei formaggi ovi-caprini; 5) la resistenza genetica alle encefalopatie spongiformi trasmissibili e l’efficienza economica e biologica in razze ovine. I risultati ottenuti evidenziano, da svariati punti di vista, numerose potenzialità legate alle produzioni dei piccoli ruminanti e alle loro ricadute sulla salute umana

Clinical experience with ipilimumab 10 mg/kg in patients with melanoma treated at Italian centres as part of a European expanded access programme

Background: Patients with advanced melanoma are faced with a poor prognosis and, until recently, limited treatment options. Ipilimumab, a novel immunotherapy that blocks cytotoxic T-lymphocyte-associated antigen-4, was the first agent to improve survival of patients with advanced melanoma in a randomised, controlled phase 3 trial. We used data from an expanded access programme (EAP) at Italian centres to evaluate the clinical activity and safety profile of ipilimumab 10 mg/kg in patients with advanced melanoma in a setting more similar to that of daily practice. Methods. Data were collected from patients enrolled in an ipilimumab EAP across eight participating Italian centres. As per the EAP protocol, patients had life-threatening, unresectable stage III/IV melanoma, had failed or did not tolerate previous treatments and had no other therapeutic option available. Treatment comprised ipilimumab 10 mg/kg every 3 weeks for a total of four doses. If physicians believed patients would continue to derive benefit from ipilimumab treatment, maintenance therapy with ipilimumab 10 mg/kg was provided every 12 weeks. Tumour responses were assessed every 12 weeks using modified World Health Organization criteria and safety continuously monitored. Results: Seventy-four pretreated patients with advanced melanoma were treated with ipilimumab 10 mg/kg. Of these, 9 (13.0%) had an objective response, comprising 3 patients with a complete response and 6 with a partial response. Median overall survival was 7.0 months (95% confidence interval, 5.3-8.7) and 16.6% of patients were alive after 3 years. Forty-five patients (60.8%) reported treatment-related adverse events of any grade, which were most commonly low-grade pruritus, pain, fever and diarrhoea. Grade 3 or 4 treatment-related AEs were reported in 8 patients (10.8%). Conclusions: The clinical activity and safety profile of ipilimumab 10 mg/kg in the EAP was similar to that seen in previous clinical trials of ipilimumab in pretreated patient populations. © 2013 Altomonte et al.; licensee BioMed Central Ltd

Clinical experience with ipilimumab 3&#160;mg/kg: real-world efficacy and safety data from an expanded access programme cohort.

Ipilimumab improves survival in patients with advanced melanoma. The activity and safety of ipilimumab outside of a clinical trial was assessed in an expanded access programme (EAP).Ipilimumab was available upon physician request for patients aged 16 or over with pretreated stage III (unresectable)/IV melanoma, for whom no other therapeutic option was available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Patients with stable disease or an objective response to ipilimumab were eligible for retreatment upon disease progression. Tumour assessments were conducted at baseline and week 12. Patients were monitored for adverse events (AEs) within 3 to 4 days of each scheduled visit.Of 855 patients participating in the EAP in Italy, 833 were evaluable for response. Of these, 13\% had an objective immune response, and the immune-related disease control rate was 34\%. Median progression-free survival and overall survival were 3.7 and 7.2 months, respectively. Efficacy was independent of BRAF and NRAS mutational status. Overall, 33\% of patients reported an immune-related AE (irAE). The frequency of irAEs was not associated with response to ipilimumab.Outside of a clinical trial setting, ipilimumab is a feasible treatment option in patients with pretreated metastatic melanoma, regardless of BRAF and NRAS mutational status. Data from this large cohort of patients support clinical trial evidence that ipilimumab can induce durable disease control and long-term survival in patients who have failed to respond to prior treatment

A survey of clinical features of allergic rhinitis in adults

Background: Allergic rhinitis (AR) has high prevalence and substantial socio-economic burden. Material/Methods: The study included 35 Italian Centers recruiting an overall number of 3383 adult patients with rhinitis (48% males, 52% females, mean age 29.1, range 18–45 years). For each patient, the attending physician had to fill in a standardized questionnaire, covering, in particular, some issues such as the ARIA classification of allergic rhinitis (AR), the results of skin prick test (SPT), the kind of treatment, the response to treatment, and the satisfaction with treatment. Results: Out of the 3383 patients with rhinitis, 2788 (82.4%) had AR: 311 (11.5%) had a mild intermittent, 229 (8.8%) a mild persistent, 636 (23.5%) a moderate-severe intermittent, and 1518 (56.1%) a moderate-severe persistent form. The most frequently used drugs were oral antihistamines (77.1%) and topical corticosteroids (60.8%). The response to treatment was judged as excellent in 12.2%, good in 41.3%, fair in 31.2%, poor in 14.5%, and very bad in 0.8% of subjects. The rate of treatment dissatisfaction was significantly higher in patients with moderate-to-severe AR than in patients with mild AR (p<0.0001). Indication to allergen immunotherapy (AIT) was significantly more frequent (p<0.01) in patients with severe AR than with mild AR. . Conclusions: These fndings confirm the appropriateness of ARIA guidelines in classifying the AR patients and the association of severe symptoms with unsuccessful drug treatment. The optimal targeting of patients to be treated with AIT needs to be reassessed

Autologous graft-versus-host disease induction in advanced breast cancer: role of peripheral blood progenitor cells

The purpose of the present study was to investigate the impact of the use of peripheral blood progenitor cells (PBPCs) on the induction of autologous graft-versus-host disease (GVHD) in patients with advanced breast cancer. 14 women with stage IIIB and 36 women with stage IV breast cancer received cyclosporine (CsA) 2.5 mg kg–1 i.v. daily, d 0–28, and interferon-gamma (IFNg) 0.025 mg/m2 s.c. qod, d7–28, following PBPC-T ± bone marrow transplantation (BMT). Preceding high-dose chemotherapy consisted of cyclophosphamide 6 g/m2 and thiotepa 800 mg/m2. Histologically proven ≥grade II cutaneous GVHD was induced in18/50 (36%) of patients and was independent of the source of haematopoietic support. In vitro studies showed that post-transplant, 76% of patients had developed auto-cytotoxicity against their own pre-transplant PHA-lymphoblasts. A significant correlation between the occurrence of GVHD ≥grade II and cytolysis was observed in the NK cell-line K562 and the T47D breast cancer cell-line. With a median follow-up of 2½ years, the overall survival (OS) is 58%, the disease-free survival (DFS) 26%, both independent of the development of GVHD and similar to what has been observed in other studies on high-dose chemotherapy in advanced breast cancer. It therefore remains unclear whether the induction of autologous GVHD with the occurrence of auto-cytotoxic lymphocytes can result in an anti-tumour effect in this group of patients. © 2000 Cancer Research Campaign http://www.bjcancer.co

Apolipoprotein C3 Polymorphisms, Cognitive Function and Diabetes in Caribbean Origin Hispanics

Apolipoprotein C3 (APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired glucose metabolism are linked to cognitive decline, and all three conditions may decrease lifespan. Associations between apolipoprotein C3 (APOC3) gene polymorphisms and impaired lipid and glucose metabolism are well-established, but potential connections between APOC3 polymorphisms, cognitive decline and diabetes deserve further attention.We examined whether APOC3 single nucleotide polymorphisms (SNPs) m482 (rs2854117) and 3u386 (rs5128) were related to cognitive measures, whether the associations between cognitive differences and genotype were related to metabolic differences, and how diabetes status affected these associations. Study subjects were Hispanics of Caribbean origin (n = 991, aged 45-74) living in the Boston metropolitan area.Cognitive and metabolic measures differed substantially by type II diabetes status. In multivariate regression models, APOC3 m482 AA subjects with diabetes exhibited lower executive function (P = 0.009), Stroop color naming score (P = 0.014) and Stroop color-word score (P = 0.022) compared to AG/GG subjects. APOC3 m482 AA subjects with diabetes exhibited significantly higher glucose (P = 0.032) and total cholesterol (P = 0.028) compared to AG/GG subjects. APOC3 3u386 GC/GG subjects with diabetes exhibited significantly higher triglyceride (P = 0.004), total cholesterol (P = 0.003) and glucose (P = 0.016) compared to CC subjects.In summary, we identified significant associations between APOC3 polymorphisms, impaired cognition and metabolic dysregulation in Caribbean Hispanics with diabetes. Further research investigating these relationships in other populations is warranted