Molecular evidence of sporadic Coxiella burnetii excretion in sheep milk, central Portugal.

Coxiella burnetii is the etiologic agent of Q fever, a worldwide zoonosis. Cattle, sheep and goats are considered the main reservoirs of the disease. Transmission to humans occurs mainly through the inhalation of infectious aerosols from milk, faeces, urine, and birth products from infected ruminants. In this study, a 2-year longitudinal approach was performed to ascertain the excretion of C. burnetii in bulk tank milk samples of sheep from a mountain plateau in central Portugal, with sampling conducted during the years 2015 and 2016. From a total of 156 bulk tank milk samples tested by qPCR, only one showed to be positive for C. burnetii (1.28% [95%CI: 0.03-6.94]), from 2015, the first year of collection. Bidirectional sequencing and phylogenetic analysis of IS1111 transposase partial region confirmed the presence of C. burnetii DNA. The presence of C. burnetii in raw milk samples highlights the necessity for additional research to determine if raw milk is a potential source for human infection. Animal health surveillance and prevention measures against this zoonotic disease should be considered.

Parasitic Infection and Immunity-A Special Biomedicines Issue.

Infectious parasitic diseases that affect humans and animals remain a central health concern worldwide [...].

A Questionnaire-Based Survey on the Long-Term Management of Canine Leishmaniosis by Veterinary Practitioners.

Canine Leishmaniosis (CanL) is a chronic and potentially fatal disease. In economically disadvantaged regions, costs associated with long-term patient monitoring may determine that some owners decline veterinary follow-up of their dogs. This online, questionnaire-based survey aimed to assess how Portuguese veterinary practitioners perform long-term patient monitoring and recognize relapses. More than 50% of respondents reported that 50-100% of dog owners declared financial restraints. Hence, in these circumstances, most veterinary practitioners only performed clinical examination and serology. However, when owners did not declare financial restriction, other tests were additionally performed, such as renal and hepatic profiles, hemogram, serum protein electrophoresis and urine protein creatinine ratio. The mean number of exams performed when owners presented financial restraints was significantly lower than the number of exams performed without economic limitations. Most veterinary practitioners prescribed allopurinol ad aeternum or until disease remission and domperidone. CanL relapses were recognized by more than half of respondents "Always", through the reappearance or worsening of clinical signs, whereas about a quarter detected an increase in anti-Leishmania antibody levels and identified abnormalities in the serum protein electrophoresis profile. The relapse rate was higher in the Lisbon Metropolitan Area and north, the most economically favored regions of Portugal. This study confirms that owner financial restraints negatively influence veterinary follow-up and relapse recognition, ultimately compromising clinical decision making and favoring the maintenance of Leishmania infantum infection endemicity.

Occurrence and Distribution of Fasciolosis in a Cohort of Ovine Livestock Restricted to a Mountain Plateau in Central Portugal.

Fasciola hepatica is a parasite that is widespread in Europe, having been reported in ruminants of several European countries and causing an important economic impact. This study ascertained the occurrence and distribution of fasciolosis in Portuguese ovine livestock by assessing F. hepatica IgG antibodies in a cohort of confined sheep from a high-altitude region of central Portugal in a 2-year period. Positive animals were found in most locations and in both years, with 18 of the 92 animals (19.6% [95% confidence interval CI: 12.03-19.15]) and 17 of the same 92 animals (18.5% [95% CI: 11.15-27.93]) showing to be seropositive in the first year and second year, respectively (p = 0.85). Pasture contamination by F. hepatica eggs could be reduced by thorough anthelmintic treatments.

3D-Hepatocyte Culture Applied to Parasitology: Immune Activation of Canine Hepatic Spheroids Exposed to Leishmania infantum.

The application of innovative three-dimensional (3D) spheroids cell culture strategy to Parasitology offers the opportunity to closely explore host-parasite interactions. Here we present a first report on the application of 3D hepatic spheroids to unravel the immune response of canine hepatocytes exposed to Leishmania infantum. The liver, usually considered a major metabolic organ, also performs several important immunological functions and constitutes a target organ for L. infantum infection, the etiological agent of canine leishmaniasis (CanL), and a parasitic disease of major veterinary and public health concern. 3D hepatic spheroids were able to sense and immunologically react to L. infantum parasites, generating an innate immune response by increasing nitric oxide (NO) production and enhancing toll-like receptor (TLR) 2 and interleukin-10 gene expression. The immune response orchestrated by canine hepatocytes also lead to the impairment of several cytochrome P450 (CYP450) with possible implications for liver natural xenobiotic metabolization capacity. The application of meglumine antimoniate (MgA) increased the inflammatory response of 3D hepatic spheroids by inducing the expression of Nucleotide oligomerization domain (NOD) -like receptors 1 and NOD2 and TLR2, TLR4, and TLR9 and enhancing gene expression of tumour necrosis factor α. It is therefore suggested that hepatocytes are key effector cells and can activate and orchestrate the immune response to L. infantum parasites.

Immunophenotyping of Peripheral Blood, Lymph Node, and Bone Marrow T Lymphocytes During Canine Leishmaniosis and the Impact of Antileishmanial Chemotherapy.

Dogs are a major reservoir of Leishmania infantum, etiological agent of canine leishmaniosis (CanL) a zoonotic visceral disease of worldwide concern. Therapeutic protocols based on antileishmanial drugs are commonly used to treat sick dogs and improve their clinical condition. To better understand the impact of Leishmania infection and antileishmanial drugs on the dog's immune response, this study investigates the profile of CD4+ and CD8+ T cell subsets in peripheral blood, lymph node, and bone marrow of sick dogs and after two different CanL treatments. Two CanL groups of six dogs each were treated with either miltefosine or meglumine antimoniate combined with allopurinol. Another group of 10 clinically healthy dogs was used as control. Upon diagnosis and during the following 3 months of treatment, peripheral blood, popliteal lymph node, and bone marrow mononuclear cells were collected, labeled for surface markers CD45, CD3, CD4, CD8, CD25, and intracellular nuclear factor FoxP3, and T lymphocyte subpopulations were immunophenotyped by flow cytometry. CanL dogs presented an overall increased frequency of CD8+ and CD4+CD8+ double-positive T cells in all tissues and a decreased frequency of CD4+ T cells in the blood. Furthermore, there was a higher frequency of CD8+ T cells expressing CD25+FoxP3+ in the blood and bone marrow. During treatment, these subsets recovered to levels similar to those of healthy dogs. Nevertheless, antileishmanial therapy caused an increase of CD4+CD25+FoxP3+ T cells in all tissues, associated with the decrease of CD8+CD25-FoxP3- T cell percentages. These findings may support previous studies that indicate that L. infantum manipulates the dog's immune system to avoid the development of a protective response, ensuring the parasite's survival and the conditions that allow the completion of Leishmania life cycle. Both treatments used appear to have an effect on the dog's immune response, proving to be effective in promoting the normalization of T cell subsets.

Immunohistochemical Studies of Cytokeratins and Differentiation Markers in Bovine Ocular Squamous Cell Carcinoma.

Bovine Ocular Squamous Cell Carcinoma is considered the most common bovine tumour, causing significant economic losses, mainly by abattoir condemnations. To obtain a better insight into the genesis and neoplastic transformation, 19 samples collected at slaughter from Holstein Friesian cattle and diagnosed as Ocular Squamous Cell Carcinoma were studied. Tumours were histologically classified into three categories: poorly (26.3%), moderately (26.3%), and well differentiated (47.4%). Expression of keratins (MNF116 and LP34) and of cornified envelope precursors (involucrin and profilaggrin) was studied. Expression of MNF116 was observed in all carcinomas. LP34 immunostaining was seen in all but three carcinomas, one from each degree. Involucrin immunoreaction was observed in all but one poorly differentiated carcinoma. Profilaggrin was present in only two moderately differentiated carcinomas, in all but one well differentiated, and in all but one poorly differentiated. MNF116 is a useful marker to confirm the epithelial origin of the tumour and stain most neoplastic cells in these tumours. The expression of involucrin and LP34 demonstrates that, in all tumours, cells have reached the final program of differentiation, regardless of the grade. The expression of profilaggrin could indicate molecular changes during malignant transformation but their expression does not seem to be of diagnostic value.

[New-onset trichotillomania during treatment with stimulant drugs. About two pediatric clinical cases]. / Tricotilomanía de nueva aparición durante el tratamiento con fármacos estimulantes. A propósito de dos casos clínicos pediátricos.

Stimulant drugs are commonly used in pediatric population in the treatment of attention deficit hyperactivity disorder, and their side effects are well described, however trichotillomania does not appear as one of them. In the literature we found some published cases of trichotillomania in relation to methylphenidate and dextroamphetamine. We present two cases of new-onset trichotillomania in children followed up in our center by attention deficit hyperactivity disorder and treated with psychostimulant drugs (methylphenidate and lisdexamfetamine), as a probable adverse effect of this treatment.

Los fármacos estimulantes se usan, habitualmente, en la población pediátrica para tratar el trastorno por déficit de atención e hiperactividad, y sus efectos secundarios están bien descritos. Sin embargo, la tricotilomanía no aparece como uno de ellos. En la literatura, hay algunos casos publicados de tricotilomanía en relación con la administración de metilfenidato y dextroanfetamina. Se presentan dos casos de tricotilomanía de nueva aparición en niños en seguimiento en nuestro Centro por déficit de atención e hiperactividad y en tratamiento con fármacos psicoestimulantes (metilfenidato y lisdexanfetamina), como probable efecto adverso de estos.

Meglumine Antimoniate and Miltefosine Combined With Allopurinol Sustain Pro-inflammatory Immune Environments During Canine Leishmaniosis Treatment.

Canine leishmaniosis (CanL) caused by Leishmania infantum is a zoonotic disease of global concern. Antileishmanial drug therapies commonly used to treat sick dogs improve their clinical condition, although when discontinued relapses can occur. Thus, the current study aims to evaluate the effect of CanL treatments in peripheral blood, lymph node, and bone marrow cytokine profile associated with clinical recovery. Two groups of six dogs diagnosed with CanL were treated with miltefosine combined with allopurinol and meglumine antimoniate combined with allopurinol (MT+A and MG+A), respectively. At diagnosis and after treatment, during a 3-month follow-up, clinical signs, hematological and biochemical parameters, urinalysis results and antileishmanial antibody titers were registered. Furthermore, peripheral blood, popliteal lymph node, and bone marrow samples were collected to assess the gene expression of IL-2, IL-4, IL-5, IL-10, IL-12, TNF-α, TGF-ß, and IFN-γ by qPCR. In parallel, were also evaluated samples obtained from five healthy dogs. Both treatment protocols promoted the remission of clinical signs as well as normalization of hematological and biochemical parameters and urinalysis values. Antileishmanial antibodies returned to non-significant titers in all dogs. Sick dogs showed a generalized upregulation of IFN-γ and downregulation of IL-2, IL-4, and TGF-ß, while gene expression of IL-12, TNF-α, IL-5, and IL-10 varied between groups and according to evaluated tissue. A trend to the normalization of cytokine gene expression was induced by both miltefosine and meglumine antimoniate combined therapies. However, IFN-γ gene expression was still up-regulated in the three evaluated tissues. Furthermore, the effect of treatment in the gene expression of cytokines that were not significantly changed by infection, indicates that miltefosine and meglumine antimoniate combined therapy directly affects cytokine generation. Both combined therapies are effective in CanL treatment, leading to sustained pro-inflammatory immune environments that can compromise parasite survival and favor dogs' clinical cure. In the current study, anti-inflammatory and regulatory cytokines do not seem to play a prominent role in CanL or during clinical recovery.

Canine neutrophils cooperate with macrophages in the early stages of Leishmania infantum in vitro infection.

Leishmania infantum is the aetiological agent of human visceral leishmaniasis and canine leishmaniasis, both systemic and potentially fatal diseases. Polymorphonuclear neutrophils (PMN) are the first cells to phagocyte this parasite at the inoculation site, but macrophages (MØ) are the definitive host cells, ensuring parasite replication. The interaction between dog MØ, PMN and L infantum promastigotes was in vitro investigated. It was observed that promastigotes establish contact with blood monocyte-derived MØ mainly by the tip of the flagellum. These cells, that efficiently bind and internalize parasites, underwent major morphological changes, produced nitric oxide (NO) and released histone H1 in order to inactivate the parasite. Transfer of intracellular parasites from PMN to MØ was confirmed by flow cytometry, using L infantum expressing a green fluorescent protein. The interaction of MØ with L infantum-infected PMN lead to NO production and release of extracellular traps, which may contribute to parasite containment and inactivation. This study highlights for the first time the diversity of cellular and molecular events triggered by the interaction between canine PMN and MØ, which can promote a reduction of parasite burden in the early phase of L infantum infection.

Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P < 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P = 0.001). All metastatic tumors were ≥2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off ≥2.8 cm, 44% and 91% for TVDT cut-off of ≤24 months). In 117 of 273 patients, PanNETs >1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8 cm vs ≥2.8 cm (94% vs 85% by 10 years; P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

Parasitismo em aves silvestres residentes e migratórias da Ilha da Marambaia, Estado do Rio de Janeiro / Parasitism in migratory and resident wild birds of Marambaia island, Rio de Janeiro state

O objetivo desta pesquisa foi buscar a presença de microrganismos em esfregaços sanguíneos de aves silvestres residentes ou migratórias da Ilha da Marambaia, município de Mangaratiba, estado do Rio de Janeiro, durante o ano de 2009. Para execução da pesquisa, 86 indivíduos referentes a 22 espécies foram capturados através de rede de neblina e após manuseio liberados ao seu habitat natural. Foi coletado sangue periférico das aves e realizado esfregaços sanguíneos. Como resultados foi diagnosticado a ocorrência de 11 (12,80%) indivíduos positivos para Plasmodium sp., um (1,16%) para microfilária e 16 (18,60%) para Borrelia sp. Foram encontrados carrapatos Amblyomma sp. (Família Ixodidae) parasitando as aves amostradas, o que sugere existir uma interação parasito-vetor-hospedeiro entre esse e o gênero Borrelia. Este estudo deve ser ampliado para outras regiões e o seu conhecimento dará maiores subsídios para outras pesquisas, voltadas principalmente para a preservação de aves em ambiente por elas escolhidos como seu habitat.(AU)

The study intended to analyze the population of migratory and resident wild bird species from Marambaia island, located in the municipality of Mangaratiba, Rio de Janeiro state, regarding the presence of microorganisms in blood smears during the year of 2009. In order to achieve the goal, 86 individuals of 22 bird species were captured using mist nets; peripheral blood was collected and blood smears performed. The birds were released after examined and sampled in situ. The diagnostic results were 11 (12.80%) birds positive for Plasmodium sp., one (1.16%) for microfilaria and 16 (18.60%) for Borrelia sp. Ticks identified as Amblyomma sp. (Ixodidae) were observed parasiting the sampled birds, suggesting that a relationship parasite-vector-host exists between these ticks and the Borrelia genus. This study should be expanded to other regions so that its results may favour other surveys, focused on conservation of wild birds in their habitat.(AU)

Presentation and surgery outcomes in elderly with pheocromocytoma: a comparative analysis with Young patients.

PURPOSE: To evaluate the presentation and early surgical outcomes of elderly patients undergoing adrenalectomy for phaeochromocytoma. PATIENTS AND METHODS: A retrospective search was performed of our adrenal disorders database for patients who underwent surgery for phaeochromocytoma or paraganglioma between 2009 and 2014. Patients >60 years old were classified as elderly. The clinical manifestations, intraoperative course, and early postoperative outcomes of elderly patients were compared to those of younger individuals (<60 years old). RESULTS: The mean (±standard deviation) age in the older (n=10) and younger (n=36) groups was 69.6±5.3 years and 34.0±12.9 years. Germ-line mutations were more common in younger patients (50.0% versus 0%; p=0.004), whereas incidental lesions were more common in the elderly (40.0% versus 5.3%; p=0.003). In both groups, surgery was most commonly performed by videolaparoscopy (90% in the elderly and 82% in the younger group), with similar intraoperative anesthetic and surgical outcomes. Postoperatively, the older group more commonly received vasoactive drugs (60.0% versus 10.5%; p<0.001) and had a longer intensive care unit stay (3.1±2.8 versus 1.4±1.0 days; p=0.014), more clinical complications (60% versus 18.9%; p=0.01), and longer hospital stay (10.2±8.4 versus 5.7±4.9 days; p=0.028). CONCLUSIONS: Although all patients received the same preoperative preparation, the elderly group exhibited a slower and more complicated recovery after adrenalectomy. Meticulous perioperative care should be used in the elderly when treating phaeochromocytoma; nevertheless, adrenalectomy is a relatively safe procedure in this patient population.

Presentation and surgery outcomes in elderly with pheocromocytoma: a comparative analysis with young patients

ABSTRACT Purpose: To evaluate the presentation and early surgical outcomes of elderly patients undergoing adrenalectomy for phaeochromocytoma. Patients and Methods: A retrospective search was performed of our adrenal disorders database for patients who underwent surgery for phaeochromocytoma or paraganglioma between 2009 and 2014. Patients >60 years old were classified as elderly. The clinical manifestations, intraoperative course, and early postoperative outcomes of elderly patients were compared to those of younger individuals (<60 years old). Results: The mean (±standard deviation) age in the older (n=10) and younger (n=36) groups was 69.6±5.3 years and 34.0±12.9 years. Germ-line mutations were more common in younger patients (50.0% versus 0%; p=0.004), whereas incidental lesions were more common in the elderly (40.0% versus 5.3%; p=0.003). In both groups, surgery was most commonly performed by videolaparoscopy (90% in the elderly and 82% in the younger group), with similar intraoperative anesthetic and surgical outcomes. Postoperatively, the older group more commonly received vasoactive drugs (60.0% versus 10.5%; p<0.001) and had a longer intensive care unit stay (3.1±2.8 versus 1.4±1.0 days; p=0.014), more clinical complications (60% versus 18.9%; p=0.01), and longer hospital stay (10.2±8.4 versus 5.7±4.9 days; p=0.028). Conclusions: Although all patients received the same preoperative preparation, the elderly group exhibited a slower and more complicated recovery after adrenalectomy. Meticulous perioperative care should be used in the elderly when treating phaeochromocytoma; nevertheless, adrenalectomy is a relatively safe procedure in this patient population.

Biohythane production from marine macroalgae Sargassum sp. coupling dark fermentation and anaerobic digestion.

Potential biohythane production from Sargassum sp. was evaluated in a two stage process. In the first stage, hydrogen dark fermentation was performed by Caldicellulosiruptor saccharolyticus. Sargassum sp. concentrations (VS) of 2.5, 4.9 and 7.4gL(-1) and initial inoculum concentrations (CDW) of 0.04 and 0.09gL(-1) of C. saccharolyticus were used in substrate/inoculum ratios ranging from 28 to 123. The end products from hydrogen production process were subsequently used for biogas production. The highest hydrogen and methane production yields, 91.3±3.3Lkg(-1) and 541±10Lkg(-1), respectively, were achieved with 2.5gL(-1) of Sargassum sp. (VS) and 0.09gL(-1)of inoculum (CDW). The biogas produced contained 14-20% of hydrogen. Potential energy production from Sargassum sp. in two stage process was estimated in 242GJha(-1)yr(-1). A maximum energy supply of 600EJyr(-1) could be obtained from the ocean potential area for macroalgae production.

Influence of tetracycline on the microbial community composition and activity of nitrifying biofilms.

The present work aims to evaluate the bacterial composition and activity (carbon and nitrogen removal) of nitrifying biofilms exposed to 50 µg L(-1) of tetracycline. The tetracycline removal efficiency and the occurrence of tetracycline resistance (tet) genes were also studied. Two sequencing batch biofilm reactors (SBBRs) fed with synthetic wastewater were operated without (SBBR1) and with (SBBR2) the antibiotic. Both SBBRs showed similar organic matter biodegradation and nitrification activity. Tetracycline removal was about 28% and biodegradation was probably the principal removal mechanism of the antibiotic. Polymerase chain reaction-denaturing gradient gel electrophoresis analysis of the bacterial community showed shifts leading to not only the fading of some ribotypes, but also the emergence of new ones in the biofilm with tetracycline. The study of the tet genes showed that tet(S) was only detected in the biofilm with tetracycline, suggesting a relationship between its occurrence and the presence of the antibiotic.

Eficácia de Chenopodium ambrosioides (erva-de-santa-maria) no controle de endoparasitos de Gallus gallus (galinha caipira) / Effectiveness of Chenopodium ambrosioides (santa maria herb) for controlling Gallus gallus (free range chicken) endoparasites

The present survey was carried out at Zoology Laboratory, Universidade Federal Rural do Rio de Janeiro, and Animal Parasitology Sector, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Rio de Janeiro state, from 2011 to 2012. The aim was to test in vitro and in vivo the effectiveness of the medicinal plant Chenopodium ambrosioides Linnaeus, 1786 (santa maria herb) regarding phytotherapeutic and homeopathic alternative methods to control endoparasites of Gallus gallus Linnaeus, 1758 (free range chicken), a serious problem affecting domestic poultry performance causing losses, retarded development, decreased food conversion rate and increase of susceptibility to infectious diseases. In vitro essay demonstrated high reduction rate on eggs eclosion inhibition (97.18%), and in vivo essay showed high fecal eggs counting reduction rate (91.67%). Presence of the genera Ascaridia (35.00%), Capillaria (30.00%), Heterakis (25.00%) and Strongyloides (10.00%) was displayed by this survey. The plant C. ambrosioides showed upper rates front traditional products (Thiabendalol/Mebendazol) as well as to those ones advocated by the Brazilian Ministry of Agriculture and the World Health Organization as effective.

A pesquisa foi desenvolvida no Laboratório de Zoologia da Universidade Federal Rural do Rio de Janeiro e Setor de Parasitologia Animal da Universidade Estadual do Norte Fluminense Darcy Ribeiro, estado do Rio de Janeiro, no período de 2011 a 2012. O objetivo foi testar in vitro e in vivo a eficácia da planta medicinal Chenopodium ambrosioides Linnaeus, 1786 (erva-de-santa-maria), nas formas fitoterápica e homeopática, como meios alternativos para o controle de endoparasitos de Gallus gallus Linnaeus, 1758 (galinha caipira), um sério problema que afeta a criação e desempenho de aves domésticas, ocasionando morte quando muito intenso, retardo de crescimento, redução do índice de conversão alimentar e aumento na suscetibilidade às doenças infecciosas. As metodologias utilizadas foram preconizadas por Coles et al. (1992), creditada pela World Association for the Advancement of Veterinary Parasitology (WAAVP). O ensaio in vitro demonstrou alta taxa de redução na inibição de eclosão de ovos (97,18%), e o ensaio in vivo, elevada taxa na redução da contagem de ovos nas fezes (91,67%). A pesquisa evidenciou a presença dos gêneros Ascaridia (35,00%), Capillaria (30,00%), Heterakis (25,00%) e Strongyloides (10,00%). C. ambrosioides mostrou em certos momentos superioridade frente ao produto tradicional (Thiabendazole/Mebendazole) e índices superiores aos preconizados pelo Ministério da Agricultura do Brasil e Organização Mundial da Saúde como indicativos de eficácia.

Penetrance of functioning and nonfunctioning pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 in the second decade of life.

CONTEXT: Data are scarce on the penetrance of multiple endocrine neoplasia type 1 (MEN1)-related nonfunctioning pancreatic neuroendocrine tumors (NF-PETs) and insulinomas in young MEN1 patients. A potential positive correlation between tumor size and malignancy (2-3 cm, 18%; >3 cm, 43%) has greatly influenced the management of MEN1 adults with NF-PETs. OBJECTIVE: The aim of the study was to estimate the penetrance of NF-PETs, insulinomas, and gastrinomas in young MEN1 carriers. DESIGN: The data were obtained from a screening program (1996-2012) involving 113 MEN1 patients in a tertiary academic reference center. PATIENTS: Nineteen MEN1 patients (aged 12-20 y; 16 patients aged 15-20 y and 3 patients aged 12-14 y) were screened for NF-PETs, insulinomas, and gastrinomas. METHODS: Magnetic resonance imaging/computed tomography and endoscopic ultrasound (EUS) were performed on 10 MEN1 carriers, magnetic resonance imaging/computed tomography was performed on five patients, and four other patients underwent an EUS. RESULTS: The overall penetrance of PETs during the second decade of life was 42% (8 of 19). All eight PET patients had NF-PETs, and half of those tumors were multicentric. One-fifth of the screened patients (21%; 4 of 19) harbored at least one large tumor (>2.0 cm). Insulinoma was detected in two NF-PET patients (11%) at the initial screening; gastrinoma was not present in any cases. Six of the 11 (54%) screened patients aged 15-20 years who underwent an EUS had NF-PETs. Potential false-positive EUS results were excluded based on EUS-guided biopsy results, the reproducibility of the NF-PET findings, or the observation of increased tumor size during follow-up. Distal pancreatectomy and the nodule enucleation of pancreatic head tumors were conducted on three patients with large tumors (>2.0 cm; T2N0M0) that were classified as grade 1 neuroendocrine tumors (Ki-67<2%). CONCLUSIONS: Our data demonstrated high penetrance of NF-PETs in 15- to 20-year-old MEN1 patients. The high percentage of the patients presenting consensus criteria for surgery for NF-PET alone or NF-PET/insulinoma suggests a potential benefit for the periodic surveillance of these tumors in this age group.

Broadened T-cell repertoire diversity in ivIg-treated SLE patients is also related to the individual status of regulatory T-cells.

PURPOSE: Intravenous IgG (ivIg) is a therapeutic alternative for lupus erythematosus, the mechanism of which remains to be fully understood. Here we investigated whether ivIg affects two established sub-phenotypes of SLE, namely relative oligoclonality of circulating T-cells and reduced activity of CD4 + Foxp3+ regulatory T-cells (Tregs) reflected by lower CD25 surface density. METHODS: We conducted a longitudinal study of 15 lupus patients (14 with SLE and one with discoid LE) treated with ivIg in cycles of 2-6 consecutive monthly infusions. Among these 15 patients, 10 responded to ivIg therapy with clear clinical improvement. We characterized Tregs and determined TCR spectratypes of four Vß families with reported oligoclonality. Cell counts, cytometry and TCR spectratypes were obtained from peripheral blood at various time points before, during and after ivIg treatment. T-cell oligoclonality was assessed as Vß-familywise repertoire perturbation, calculated for each patient in respect to an individual reference profile averaged over all available time points. RESULTS: For 11 out of 15 patients, average Vß1/Vß2/Vß11/Vß14 repertoires were less perturbed under than outside ivIg therapy. The four exceptions with relatively increased average perturbation during ivIg therapy included three patients who failed to respond clinically to an ivIg therapy cycle. Patients' Treg CD25 surface density (cytometric MFI) was clearly reduced when compared to healthy controls, but not obviously influenced by ivIg. However, patients' average Treg CD25 MFI was found negatively correlated with both Vß11 and Vß14 perturbations measured under ivIg therapy. CONCLUSIONS: This indicates a role of active Tregs in the therapeutic effect of ivIg.

Levantamento qualitativo de gêneros de parasitos em amostras fecais de jacarés criados comercialmente em sistema fechado no estado do Rio de Janeiro / Qualitative survey of parasites genera on fecal samples of alligators in a commercial closed farming system in the state of Rio de Janeiro

O objetivo desta pesquisa foi realizar um diagnóstico qualitativo dos gêneros de parasitos encontrados em amostras fecais ambientais de jacarés (Caiman latirostris Daudin, 1802), criados comercialmente em sistema fechado, no período de 2008 a 2009, no estado do Rio de Janeiro. Um total de 300 amostras foi coletado de 150 filhotes, 80 de animais de engorda e 70 de reprodução, e submetido a análises coproparasitológicas, de flutuação (método de Willis-Mollay) e sedimentação simples (método de Lutz), de acordo com Hoffmann (1987). As amostras foram visualizadas à luz da microscopia óptica. Os resultados obtidos evidenciaram a presença de oocistos de Eimeria e Isospora, cistos de Balantidium e ovos de Acanthostomum e Dujardinascaris.

The objective of this paper was to diagnose qualitatively parasite genera found in environmental fecal samples of alligators (Caiman latirostris Daudin, 1802) commercially bred from 2008 to 2009 in a closed farming system in the state of Rio de Janeiro. A total of 300 samples were collected from 150 young, 80 fattening and 70 breeding processed by two different methods, the flotation (method of Willis-Mollay) and simple sedimentation (method of Lutz), according to Hoffmann (1987). The samples were then examined by optical microscopy. The results revealed presence of Eimeria and Isospora oocysts, Balantidium cysts, and Acanthostomum and Dujardinascaris eggs.