Perspectives on Adipose Tissue, Chagas Disease and Implications for the Metabolic Syndrome

The contribution of adipose tissue an autocrine and endocrine organ in the pathogenesis of infectious disease and metabolic syndrome is gaining attention. Adipose tissue and adipocytes are one of the major targets of T. cruzi infection. Parasites are detected 300 days postinfection in adipose tissue. Infection of adipose tissue and cultured adipocytes triggered local expression of inflammatory mediators resulting in the upregulation of cytokine and chemokine levels. Adipose tissue obtained from infected mice display an increased infiltration of inflammatory cells. Adiponectin, an adipocyte specific protein, which exerts antiinflammatory effects, is reduced during the acute phase of infection. The antiinflammatory regulator peroxisome proliferator activated receptor-γ (PPAR-γ) is downregulated in infected cultured adipocytes and adipose tissue. T. cruzi infection is associated with an upregulation of signaling pathways such as MAPKs, Notch and cyclin D, and reduced caveolin-1 expression. Adiponectin null mice have a cardiomyopathy and thus we speculate that the T. cruzi-induced reduction in adiponectin contributes to the T. cruzi-induced cardiomyopathy. While T. cruzi infection causes hypoglycemia which correlates with mortality, hyperglycemia is associated with increased parasitemia and mortality. The T. cruzi-induced increase in macrophages in adipose tissue taken together with the reduction in adiponectin and the associated cardiomyopathy is reminiscent of the metabolic syndrome

Relationship of arterial and exhaled CO2 during elevated artificial pneumoperitoneum pressure for introduction of the first trocar.

The present study evaluated the correlation between arterial CO2 and exhaled CO2 during brief high-pressure pneumoperitoneum. Patients were randomly distributed into two groups: P12 group (n=30) received a maximum intraperitoneal pressure of 12mmHg, and P20 group (n=37) received a maximum intraperitoneal pressure of 20mmHg. Arterial CO2 was evaluated by radial arterial catheter and exhaled CO2 was measured by capnometry at the following time points: before insufflation, once intraperitoneal pressure reached 12mmHg , 5 minutes after intraperitoneal pressure reached 12mmHg for the P12 group or 20mmHg for the P20 group, and 10 minutes after intraperitoneal pressure reached 12mmHg for the P12 group or when intraperitoneal pressure had decreased from 20mmHg to 12mmHg, for the P20 group. During brief durations of very high intraperitoneal pressure (20mmHg), there was a strong correlation between arterial CO2 and exhaled CO2. Capnometry can be effectively used to monitor patients during transient increases in artificial pneumoperitoneum pressure

Native and aspirin-triggered lipoxins control innate immunity by inducing proteasomal degradation of TRAF6

Innate immune signaling is critical for the development of protective immunity. Such signaling is, perforce, tightly controlled. Lipoxins (LXs) are eicosanoid mediators that play key counterregulatory roles during infection. The molecular mechanisms underlying LX-mediated control of innate immune signaling are of interest. In this study, we show that LX and aspirin (ASA)-triggered LX (ATL) inhibit innate immune signaling by inducing suppressor of cytokine signaling (SOCS) 2–dependent ubiquitinylation and proteasome-mediated degradation of TNF receptor–associated factor (TRAF) 2 and TRAF6, which are adaptor molecules that couple TNF and interleukin-1 receptor/Toll-like receptor family members to intracellular signaling events. LX-mediated degradation of TRAF6 inhibits proinflammatory cytokine production by dendritic cells. This restraint of innate immune signaling can be ablated by inhibition of proteasome function. In vivo, this leads to dysregulated immune responses, accompanied by increased mortality during infection. Proteasomal degradation of TRAF6 is a central mechanism underlying LX-driven immune counterregulation, and a hitherto unappreciated mechanism of action of ASA. These findings suggest a new molecular target for drug development for diseases marked by dysregulated inflammatory responses

Diacylglycerol kinase ζ regulates microbial recognition and host resistance to Toxoplasma gondii

Mammalian Toll-like receptors (TLRs) recognize microbial pathogen-associated molecular patterns and are critical for innate immunity against microbial infection. Diacylglycerol (DAG) kinases (DGKs) regulate the intracellular levels of two important second messengers involved in signaling from many surface receptors by converting DAG to phosphatidic acid (PA). We demonstrate that the ζ isoform of the DGK family (DGKζ) is expressed in macrophages (Mφ) and dendritic cells. DGKζ deficiency results in impaired interleukin (IL) 12 and tumor necrosis factor α production following TLR stimulation in vitro and in vivo, increased resistance to endotoxin shock, and enhanced susceptibility to Toxoplasma gondii infection. We further show that DGKζ negatively controls the phosphatidylinositol 3–kinase (PI3K)–Akt pathway and that inhibition of PI3K activity or treatment with PA can restore lipopolysaccharide-induced IL-12 production by DGKζ-deficient Mφ. Collectively, our data provide the first genetic evidence that an enzyme involved in DAG/PA metabolism plays an important role in innate immunity and indicate that DGKζ promotes TLR responses via a pathway involving inhibition of PI3K

Sows’ parity and coconut oil postnatal supplement on piglets performance

ABSTRACTObjectives. The study aimed to evaluate the effect of sows’ of different parities and the supplement of coconut oil for piglets, on the development of litter. Materials and methods. A total of 51 sows of different parities and their 642 piglets were used in the trial. Each piglet was weighed and identified at birth in a sequential order. They were randomly distributed in two treatments (CG=control group and TG=test group). TG piglets had the first access to a dosage of 3.0 ml of coconut oil 12 hours after birth, and the second at 36 h after the first. Piglets were weighed at 21 days. In order to analyze the effect of the coconut oil supplement as a function of the weight at birth, piglets were grouped according to their weight (0.600 to 0.900 kg; 1.000 to 1.499kg; 1.500 to 1.999 kg; and 2.000 to 2.499 kg). Results. Sows parity affected the number and weight of born piglets. Sows in 4th, 5th and 7th parity had a larger litter than those from the 2nd parity. Sows from 2nd and 3rd parity had a lower number of piglets but heavier litter. No effect of the coconut oil supplement on neonatal piglets’ performance was found. Conclusions. The coconut meal was neither beneficial to neonatal piglets nor to those with low weight at birth, which usually present low body energy.RESUMENObjetivo. El objetivo del estudio fue evaluar el efecto del número de partos y el suplemento de aceite de coco en lechones recien nacidos. Materiales y métodos. Se utilizaron 51 cerdas de diferentes partos y sus 642 lechones. Cada lechón se pesó y se identificó al nacer en orden secuencial. Fueron distribuidos aleatoriamente en dos grupos (CG = control y TG=tratamiento). Lechones TG tenían el primer acceso a una dosis de 3.0 ml de aceite de coco 12 horas después del nacimiento, y el segunda a las 36 h después de la primera. Los lechones fueron pesados a los 21 días. Con el fin de analizar el efecto de los suplementos de aceite de coco con relación al peso al nacer. Los lechones fueron agrupados de acuerdo con su peso (0.600 a 0.900 kg; 1.000 a 1.499 kg; 1.500 a 1.999 kg y 2.000 a 2.499 kg). Resultados. El número de partos afectó el peso y el número de lechones nacidos. Cerdas en cuarto, quinto y séptimo parto, tuvieron una camada mayor que las de segundo parto. Las cerdasde segundo y tercer parto tuvieron menor número de lechones y con peso mayor. No se encontró efectodel suplemento de aceite de coco en el desarrollo de los lechones recién nacidos. Conclusiones. Loaceite de coco no es favorable para los lechones recién nacidos, tampoco para aquellos con el bajopeso al nacer, que normalmente presentan la energía corporal baja

The prevalence of hepatitis A antibodies in HIV exposed and/or infected children and adolescents

OBJECTIVE: To evaluate the prevalence of hepatitis A virus antibodies in HIV-exposed and/or HIV-infected children and adolescents. METHODS: Between September 1996 and August 2002, 352 patients (200 exposed, but not HIV-infected and 152 HIV exposed and infected) were included in this study. These children and adolescents (age ranged between 1 and 14 years) were all followed up at the Pediatric AIDS Clinic of the Federal University of São Paulo (UNIFESP) and had anti-HAV antibodies determined by a commercially available ELISA method (tests for total anti-HAV antibodies and specific IgM antibodies) (Dia Sorin and Radim). Statistical analyses were done with chi-squared and t test. RESULTS: The prevalence of hepatitis A virus antibodies in HIV-infected and HIV-exposed, but uninfected patients was 34% and 19.7%, respectively. We noticed that in the age range between 2 years and 10 years, the group of HIV-infected children presented a higher prevalence of hepatitis A virus antibodies (35.5%) than the group of uninfected children (16.7%) (p = 0.005). In the HIV infected group, children from B and C categories had a prevalence of hepatitis A virus antibodies (40.5%) higher than N and A categories (24.1%) (p = 0.042). Mean age did not differ when children from B and C categories were compared with N and A categories (5.18 and 5.66 years, respectively) (p = 0.617). CONCLUSIONS: The prevalence of hepatitis A virus antibodies in HIV exposed and/or infected children and adolescents between 1 and 14 years old was 26%. Considering the possibility of HIV infection aggravation when associated with hepatitis A virus infection, we suggest that hepatitis A virus inactivated vaccine should be administered to these patients.OBJETIVO: Avaliar a prevalência de anticorpos contra o vírus da hepatite A em crianças e adolescentes expostos e/ou infectados pelo HIV. MÉTODOS: Entre setembro de 1996 e agosto de 2002, foram incluídos neste estudo 352 crianças e adolescentes, filhos de mães soropositivas para o HIV (200 expostos e não-infectados pelo HIV, e 152 expostos e infectados pelo HIV). Essas crianças e adolescentes, com idade entre 1 e 14 anos, acompanhados no Ambulatório de AIDS Pediátrica da Universidade Federal de São Paulo (UNIFESP), fizeram teste sorológico contra hepatite A como parte da avaliação de rotina. A dosagem de anticorpos anti-HAV (anticorpos totais e IgM) foi realizada através do método ELISA (Dia Sorin e Radim). A comparação das faixas etárias entre os grupos foi feita utilizando o teste do qui-quadrado e, para comparar as médias de idade das categorias clínicas entre as crianças infectadas, utilizou-se o teste t. RESULTADOS: A prevalência de anticorpos contra o vírus da hepatite A foi de 34% nos pacientes infectados e expostos ao HIV e 19,7% no grupo de soro-revertidos (expostos ao HIV e não-infectados). Estratificando a amostra por faixa etária, observamos que, para as crianças de 2 a 10 anos, o grupo de infectados pelo HIV apresentou prevalência de anticorpos para o vírus hepatite A (35,5%) maior do que o grupo de soro-revertidos (16,7%) (p = 0,005). Dentro do grupo de infectados pelo HIV, estratificando a amostra em relação à categoria clínica da infecção pelo HIV, observamos que as crianças pertencentes às categorias B e C apresentaram prevalência de anticorpos para o vírus da hepatite A maior (40,5%) do que aquelas pertencentes às categorias N e A (24,1%) (p = 0,042), apesar de apresentarem média de idade sem diferença estatística: 5,66 anos para as categorias N e A e 5,18 anos para as categorias B e C (p = 0,617). CONCLUSÕES: A prevalência de anticorpos contra o vírus da hepatite A na população de crianças e adolescentes infectados e/ou expostos ao HIV na faixa etária de 1 a 14 anos foi de 26%. Considerando-se a possibilidade de agravamento da infecção pelo HIV quando associada à infecção pelo vírus da hepatite A, sugerimos a profilaxia vacinal nesse grupo de indivíduos.Universidade Federal de São Paulo (UNIFESP) Ambulatório de Infectologia PediátricaUniversidade Federal de São Paulo (UNIFESP) Laboratório de Infectologia PediátricaUniversidade Federal de São Paulo (UNIFESP) Departamento de PediatriaUniversidade Federal de São Paulo (UNIFESP) Centro de Referência para Imunobiológicos EspeciaisUNIFESP Ambulatório da Disciplina de Infectologia PediátricaUNIFESP, Ambulatório de Infectologia PediátricaUNIFESP, Laboratório de Infectologia PediátricaUNIFESP, Depto. de PediatriaUNIFESP, Centro de Referência para Imunobiológicos EspeciaisUNIFESP, Ambulatório da Disciplina de Infectologia PediátricaSciEL

Performance and plasma urea nitrogen of immunocastrated males pigs of medium genetic potential

ABSTRACT Objective. A study was carried out to evaluate the performance and the plasma urea nitrogen (PUN) of male pigs of medium genetic potential for lean meat deposition in carcass, which underwent immunocastration. Materials and methods. Forty-five seventy-days old Large White x Landrace crossbred were used. The pigs were distributed in a randomized design in three treatments: castrated males, females and immunocastrated males. Each treatment group was replicated three times with five pigs per replicate. The trial period was of 70 days, divided into phases of growing (70 to 110 days old) and finishing (111 to 140 days old). The pigs were weighed four times: at the beginning of the trial, at the first immunocastration vaccine dose (80 days old), at the second immunocastration vaccine dose (110 days old) and just before slaughter (140 days old). Blood samples were taken on the same day that the animals were weighed. Results. Between 80 and 110 days old, there was an increase in PUN value, only for castrated males and females. No differences were found in weight gain between the studied groups within the periods. Immunocastrated males had lower feed intake than females and these had a lower feed intake than castrated males. To 110 days old, immunocastrated animals showed feed conversion ratio similar to females and better than castrated males. However, after the second dose of the vaccine, feed conversion was similar between groups. Conclusions. The benefits of immunocastration are prominent in animals with low to medium genetic potential. RESUMEN Objetivo. Se realizó un estudio para evaluar el rendimiento y la concentración de urea en plasma (PUN) de los cerdos machos de medio potencial genético de carne magra en la canal sometidos a la inmunocastración. Materiales y métodos. Se utilizaron 45 cerdos de 70 días de edad Landrace x Large White. Los animales se distribuyeron en un diseño completamente al azar con tres tratamientos: machos castrados, hembras y machos inmunocastrados. Cada tratamiento consistió en tres repeticiones, con cinco animales por réplica. El período experimental fue de 70 días, divididos en las etapas de crecimiento (70 a 110 días de edad) y terminación (111 a 140 días de edad). Los cerdos fueron pesados cuatro veces: al inicio del experimento, en la primera dosis de vacuna de inmunocastración (80 días de edad), en la segunda dosis de la vacuna de inmunocastración (110 días de edad) y antes de el sacrificio (140 días de edad). Las muestras de sangre se recogieron en el mismo día en que se pesaron los animales. Resultados. Entre 80 y 110 días de edad, hubo un aumento en la cantidad de PUN, sólo para machos castrados y hembras. No hubo diferencias en la ganancia de peso entre los grupos en ninguno de los períodos estudiados. Machos inmunocastrados tuvieron menor consumo de alimento que las hembras y éstas mostraron un menor consumo que los machos castrados. En 110 días de edad, los animales inmunocastrados mostraron la conversión de alimento similar a las hembras y mejor que los machos castrados. Sin embargo, después de la segunda dosis de la vacuna, la conversión alimenticia fue similar entre los grupos. Conclusiones. Los beneficios de inmunocastración son prominentes en animales con bajo a médio potencial genético.

Profile of interstitial cells of Cajal in a murine model of chagasic megacolon

Abstract Disorders of gastrointestinal motility are the major physiologic problem in chagasic megacolon. The contraction mechanism is complex and controlled by different cell types such as enteric neurons, smooth muscle, telocytes, and an important pacemaker of the intestine, the interstitial cells of Cajal (ICCs). The role of ICCs in the progression of acute and chronic Chagas disease remains unclear. In the present work, we investigate the aspects of ICCs in a long-term model of Chagas disease that mimics the pathological aspects of human megacolon. Different subsets of ICCs isolated from Auerbach’s myenteric plexuses and muscle layers of control and Trypanosoma cruzi infected animals were determined by analysis of CD117, CD44, and CD34 expression by flow cytometer. Compared with the respective controls, the results showed a reduced frequency of mature ICCs in the acute phase and three months after infection. These results demonstrate for the first time the phenotypic distribution of ICCs associated with functional dysfunction in a murine model of chagasic megacolon. This murine model proved valuable for studying the profile of ICCs as an integrative system in the gut and as a platform for understanding the mechanism of chagasic megacolon development

Chagas Disease in the New York City Metropolitan Area

Background Chagas disease, caused by the parasite Trypanosoma cruzi, once considered a disease confined to Mexico, Central America, and South America, is now an emerging global public health problem. An estimated 300 000 immigrants in the United States are chronically infected with T. cruzi. However, awareness of Chagas disease among the medical community in the United States is poor. Methods We review our experience managing 60 patients with Chagas disease in hospitals throughout the New York City metropolitan area and describe screening, clinical manifestations, EKG findings, imaging, and treatment. Results The most common country of origin of our patients was El Salvador (n = 24, 40%), and the most common detection method was by routine blood donor screening (n = 21, 35%). Nearly half of the patients were asymptomatic (n = 29, 48%). Twenty-seven patients were treated with either benznidazole or nifurtimox, of whom 7 did not complete therapy due to side effects or were lost to follow-up. Ten patients had advanced heart failure requiring device implantation or organ transplantation. Conclusions Based on our experience, we recommend that targeted screening be used to identify at-risk, asymptomatic patients before progression to clinical disease. Evaluation should include an electrocardiogram, echocardiogram, and chest x-ray, as well as gastrointestinal imaging if relevant symptoms are present. Patients should be treated if appropriate, but providers should be aware of adverse effects that may prevent patients from completing treatment

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets