Interplay between the Adaptive Immune System and Insulin Resistance in Weight Loss Induced by Bariatric Surgery.

Low-grade chronic inflammation plays a pivotal role among other pathophysiological mechanisms involved in obesity. Innate and adaptive immune cells undergo systemic proinflammatory polarization that gives rise to an increased secretion of proinflammatory cytokines, which in turn leads to insulin resistance. Bariatric surgery is currently the most effective treatment for obesity, as it brings on significant weight loss, glucose metabolism improvement, and a decrease in systemic inflammation biomarkers. After bariatric surgery, several changes have been reported to occur in adaptive immunity, including reduction in CD4+ and CD8+ T cell counts, a decrease in the Th1/Th2 ratio, an increase in B regulatory cells, and reduction in proinflammatory cytokine secretion. Overall, there seems to be a major shift in several lymphocyte populations from a proinflammatory to an anti-inflammatory phenotype. Furthermore, increased antioxidant activity and reduced lipid and DNA oxidation products have been reported after bariatric surgery in circulating mononuclear cells. This paper highlights the shift in the adaptive immune system in response to weight loss and improved insulin sensitivity, as well as the interplay between immunological and metabolic adaptations as a result of bariatric surgery. Finally, based on data from research, we propose several mechanisms such as changes in adaptive immune cell phenotypes and their by-products, recruitment in adipose tissue, reduced oxidative stress, and modification in metabolic substrate availability as drivers to reduce low-grade chronic inflammation after bariatric surgery in severe obesity.

Estado nutricional e tempo de internação de pacientes adultos hospitalizados com diferentes tipos de câncer / Nutritional status and length of stay of adult hospitalized patients with different types of cancer

Introdução: O câncer é uma doença crônica não transmissível e afeta, de modo crescente, a população mundial. A presença da desnutrição é elevada e o estado nutricional tem um papel importante no desfecho clínico e na qualidade de vida de pacientes com câncer. O objetivo desse estudo foi identificar a prevalência dos tipos de câncer, alterações do estado nutricional e tempo de internação de pacientes adultos hospitalizados. Método: Estudo retrospectivo observacional com análise de 354 prontuários de pacientes (idade 60,6±13,8 anos; 34,2% do sexo feminino) com qualquer tipo de câncer, internados no Hospital de Clínicas de Porto Alegre. Resultados: Foi observada maior prevalência de quatro tipos de cânceres: próstata (48,8%), tireoide (26%), digestivo (19%) e ovário e mama (6,2%). Pacientes com câncer digestivo apresentaram maior tempo de internação (aproximadamente 10 dias), menor índice de massa corporal (IMC) (24,8±5,3 kg/ m²), maior prevalência de desnutrição (75%) e associação aos principais sintomas vinculados ao estado nutricional quando comparados aos pacientes com outros tipos de câncer. Indicadores do estado nutricional (IMC, presença da desnutrição, perda de peso e percentual de perda de peso em 6 meses) foram associados a um maior período de internação (p≤0,001). Conclusão: Pacientes com câncer digestivo demonstraram ter pior estado nutricional durante o seu período de internação, apresentando maior risco nutricional associado à presença da desnutrição e maior perda de peso, o que refletiu em maior tempo de permanência hospitalar.(AU)

Introduction: Cancer is a chronic disease and affect, increasingly, the world population. The presence of malnutrition is high and nutritional status plays an important role in clinical outcome and quality of life of cancer patients. The aim of this study was to identify the prevalence of cancers, nutritional status changes and length of stay of hospitalized adult patients. Methods: An observational retrospective study with analysis of 354 records of patients (age 60.6±13.8 years; 34.2% female) with any type of cancer, admitted to the Hospital de Clínicas de Porto Alegre. Results: Was observed a higher prevalence of four types of cancers: prostate (48.8%), thyroid (26%), digestive (19%) and ovarian and breast (6.2%). Patients with digestive cancer had longer hospital stay (about 10 days), lower body mass index (BMI) (24.8±5.3 kg/m²), a higher prevalence of malnutrition (75%) and association with the main symptoms linked nutritional status when compared to patients with other cancers. The indicators of nutritional status (BMI, presence of malnutrition, weight loss and percentage of weight loss at 6 months) were associated with increased hospital stay (p≤0.001). Conclusion: The patients with digestive cancer showed a poor nutritional status during their hospital stay, showing a higher nutritional risk associated with the presence of malnutrition and increased weight loss which resulted in a longer hospital stay time.(AU)

The IL-33/ST2 pathway controls coxsackievirus B5-induced experimental pancreatitis.

Coxsackievirus B (CVB) is a common cause of acute and chronic infectious myocarditis and pancreatitis. Th1 cells producing IFN-γ and TNF-α are important for CVB clearance, but they are also associated with the pathogenesis of inflammatory lesions, suggesting that the modulation of Th1 and Th2 balance is likely important in controlling CVB-induced pancreatitis. We investigated the role of IL-33, which is an important recently discovered cytokine for induction of Th2-associated responses, in experimental CVB5 infection. We found that mice deficient in IL-33R, T1/ST2, significantly developed more severe pancreatitis, had greater weight loss, and contained higher viral load compared with wild-type (WT) mice when infected with CVB5. Conversely, WT mice treated with rIL-33 developed significantly lower viral titers, and pancreatitis was attenuated. Mechanistic studies demonstrated that IL-33 enhances the degranulation and production of IFN-γ and TNF-α by CD8(+) T and NK cells, which is associated with viral clearance. Furthermore, IL-33 triggers the production of IL-4 from mast cells, which results in enhanced differentiation of M2 macrophages and regulatory T cells, leading to the attenuation of inflammatory pancreatitis. Adoptively transferred mast cells or M2 macrophages reversed the heightened pancreatitis in the T1/ST2(-/-) mice. In contrast, inhibition of regulatory T cells exacerbated the disease in WT mice. Together, our findings reveal an unrecognized IL-33/ST2 functional pathway and a key mechanism for CVB5-induced pancreatitis. These data further suggest a novel approach in treating virus-induced pancreatitis, which is a major medical condition with unmet clinical needs.

Relación de la inmunología celular y la viremia plasmática con los cambios en el peso corporal de pacientes infectados con el virus de inmunodeficiencia humana / Relationship of cellular immunology and plasma viremia with changes in body weight of patients infected with human immunodeficiency virus

El manejo nutricional de los pacientes infectados con el virus de inmunodeficiencia humana (VIH) es desafiante; especialmente cuando los recuentos de linfocitos T CD4 son < de 200 células/mm³, debido a los episodios de pérdida de peso que experimentan los pacientes. En este estudio se plantea demostrar la relación entre los niveles de carga del VIH y los valores de linfocitos T CD4+ con los cambios de peso corporal en los pacientes ambulatorios del Centro de Atención a Pacientes con Enfermedades Infectocontagiosas (CAPEI) de la Facultad de Odontología de la Universidad Central de Venezuela. La mayoría de los pacientes que presentaba pérdida de peso tuvo linfocitos TCD4 ‹ de 200 células/mm³. Los que mantuvieron el peso o lo ganaron, presentaron contajes de linfocitos TCD4 entre 200 y 499 células/mm³ (p = 0,012). Con relación con la carga viral se encontró que los pacientes que perdieron peso, cursaban en su mayoría, con valores ‹ 1000 o › 100.000 copias/ml. Al contrario, la mayor parte de los que aumentaron de peso, presentaron valores indetectables de carga viral. Estas diferencias no fueron estadísticamente significativas. Estos resultados tal vez reflejen el pronóstico de la pérdida de peso cuando el contaje de linfocitos TCD4 es ‹ de 200 células/mm³, ya que en este nivel ocurren infecciones oportunistas, favorecidas por la desnutrición, estableciéndose un círculo vicioso que aumentaría la morbi mortalidad. Evaluar el estado inmunológico – nutricional en pacientes ambulatorios con infección por VIH es importante para iniciar estrategias encaso de pérdida de peso corporal

The nutritional management of patients infected with the human immunodeficiency (HIV) virus is challenging; especially when linfocitos T CD4 counts are < of 200 cells/mm³, due to episodes of weight loss experienced patients. This study raises show the relationship between the levels of the HIV load and the values of T CD4 + lymphocytes with changes in body weight in the outpatient care center for patients with diseases transmittable-contagious (CAPEI) of the Faculty of Dentistry of the University Central of Venezuela. Most of the patients who had weight loss had CD4 cell count of ‹ 200 cells/mm³ Those who maintained the weight or won it, presented between 200 and 499 CD4 cell counts cells/mm³ (p = 0.012). In relation with the viral load was found that patients who lost weight, were mostly with values 1000 ‹ or › 100,000 copies/ml. On the contrary, most of those who gained weight, they were undetectable viral load values. These differences were not statistically significant. These results may reflect the prognosis of weight loss when the CD4 cell count is ‹ 200 cells/mm³, since at this level occur opportunistic infections, favored by malnutrition, establishing a vicious circle that would increase the morbidity mortality. Assess the immune status - nutrition in outpatients with HIV infection is important to initiate strategies in the event of loss of body weight

Bariatric surgery reverses natural killer (NK) cell activity and NK-related cytokine synthesis impairment induced by morbid obesity.

BACKGROUND: Obesity is related to a higher rate of infections and some types of cancer. Here we analyzed the impact of obesity and weight loss induced by Roux-en-Y gastric bypass (RYGB) on immunological parameters, i.e., cytokine productions and natural killer cell function. METHODS: We analyzed 28 morbidly obese patients before and 6 months after RYGB. Biochemical parameters were analyzed in plasma. The percent of natural killer (NK) cells, their cytotoxicity, and the production of cytokines by peripheral blood mononuclear cells were analyzed. The percent of NK cells was determined by flow cytometry and cytokine production determined by enzyme-linked immunosorbent assay. NK cytotoxicity was determined by the lactate dehydrogenase release assay. RESULTS: The weight loss 6 months following surgery was 35.3 ± 4.5 kg. RYGB also improves biochemical parameters. No significant difference was found in the percent of NK cells after surgery. We found an increase in the production of interferon-γ, interleukin (IL)-12 and IL-18, but not in IL-2, 6 months after RYGB. Cytotoxic activity of NK cells was significantly enhanced 6 months after RYGB [17.1 ± 14.7% before RYGB vs 51.8 ± 11.3% at 6 months after, at 40:1 effector to target cell ratio; p < 0.001]. We observed significant post-surgical improvement in the cytotoxic activity curve in 22 out of 28 patients (78.6%), irrespective of the target to effector cell ratio. CONCLUSIONS: The weight loss induced by RYGB modifies the production of cytokines related with NK cell function and improves its activity.

Carcinoma bronquíolo-alveolar em leão-africano (Panthera leo) / Bronchioloalveolar carcinoma in an African lion (Panthera leo)

Um caso de carcinoma bronquíolo-alveolar difuso do tipo misto foi diagnosticado em um leão-africano (Panthera leo), hospitalizado com sinais de dispnéia e emagrecimento progressivo. Em todos os lobos pulmonares havia múltiplos nódulos esbranquiçados, macios e homogêneos, de 0,2-0,5cm em diâmetro. Histologicamente, os nódulos eram constituídos por células neoplásicas arranjadas em alvéolos e papilas sustentados por moderado estroma fibrovascular, um padrão que lembrava a estrutura pulmonar pré-existente. Na reação pelo ácido periódico de Schiff (PAS) foi observada marcação positiva no citoplasma de numerosas células neoplásicas. Todas as células neoplásicas demonstraram forte e uniforme imunorreatividade citoplasmática para pancitoceratina. A marcação para o fator 1 de transcrição da tireóide (TTF-1) foi observada em focos nos núcleos das células neoplásicas das margens dos nódulos. Nas secções avaliadas para surfactante A, a marcação foi observada em múltiplas áreas focais, tanto no citoplasma como na membrana citoplasmática das células neoplásicas. O diagnóstico de carcinoma bronquíolo-alveolar difuso do tipo misto foi feito com base nos achados histológicos, histoquímicos e imuno-histoquímicos. Essa parece ser a primeira descrição de um neoplasma pulmonar primário maligno em leão-africano.(AU)

A case of diffuse bronchioloalveolar carcinoma of the mixed type was diagnosed in the lung of an adult female African lion (Panthera leo) with presenting signs of progressive dyspnea and weight loss. In all pulmonary lobes there were multiple 0.2-0.5cm in diameter soft and homogenous white nodules. Histologically, these nodules consisted of neoplastic cells with an alveolar and papillary disposition, a pattern reminiscent of the preexistent pulmonary structure. The cytoplasms of numerous neoplastic cells were positive in the periodic acid-Schiff (PAS) stain. At immunohistochemistry examination, all neoplastic cells reacted strongly and uniformly to pancytokeratin; focal reactivity for thyroid transcription factor 1 (TTF-1) was observed in the nucleus of neoplastic cells mainly in those at the margins of the nodules. Positive reaction for surfactant A was observed in multifocal areas, both in the cytoplasm and plasma membranes of neoplastic cells. The diagnosis of diffuse bronchioloalveolar carcinoma of the mixed type was made based on histological, histochemistry and immunohistochemistry findings. This seems to be the first report of a primary malignant neoplasm in the lung of the African lion.(AU)

Carcinoma bronquíolo-alveolar em leão-africano (Panthera leo) / Bronchioloalveolar carcinoma in an African lion (Panthera leo)

Um caso de carcinoma bronquíolo-alveolar difuso do tipo misto foi diagnosticado em um leão-africano (Panthera leo), hospitalizado com sinais de dispnéia e emagrecimento progressivo. Em todos os lobos pulmonares havia múltiplos nódulos esbranquiçados, macios e homogêneos, de 0,2-0,5cm em diâmetro. Histologicamente, os nódulos eram constituídos por células neoplásicas arranjadas em alvéolos e papilas sustentados por moderado estroma fibrovascular, um padrão que lembrava a estrutura pulmonar pré-existente. Na reação pelo ácido periódico de Schiff (PAS) foi observada marcação positiva no citoplasma de numerosas células neoplásicas. Todas as células neoplásicas demonstraram forte e uniforme imunorreatividade citoplasmática para pancitoceratina. A marcação para o fator 1 de transcrição da tireóide (TTF-1) foi observada em focos nos núcleos das células neoplásicas das margens dos nódulos. Nas secções avaliadas para surfactante A, a marcação foi observada em múltiplas áreas focais, tanto no citoplasma como na membrana citoplasmática das células neoplásicas. O diagnóstico de carcinoma bronquíolo-alveolar difuso do tipo misto foi feito com base nos achados histológicos, histoquímicos e imuno-histoquímicos. Essa parece ser a primeira descrição de um neoplasma pulmonar primário maligno em leão-africano.

A case of diffuse bronchioloalveolar carcinoma of the mixed type was diagnosed in the lung of an adult female African lion (Panthera leo) with presenting signs of progressive dyspnea and weight loss. In all pulmonary lobes there were multiple 0.2-0.5cm in diameter soft and homogenous white nodules. Histologically, these nodules consisted of neoplastic cells with an alveolar and papillary disposition, a pattern reminiscent of the preexistent pulmonary structure. The cytoplasms of numerous neoplastic cells were positive in the periodic acid-Schiff (PAS) stain. At immunohistochemistry examination, all neoplastic cells reacted strongly and uniformly to pancytokeratin; focal reactivity for thyroid transcription factor 1 (TTF-1) was observed in the nucleus of neoplastic cells mainly in those at the margins of the nodules. Positive reaction for surfactant A was observed in multifocal areas, both in the cytoplasm and plasma membranes of neoplastic cells. The diagnosis of diffuse bronchioloalveolar carcinoma of the mixed type was made based on histological, histochemistry and immunohistochemistry findings. This seems to be the first report of a primary malignant neoplasm in the lung of the African lion.

Impaired immune responses in tuberculosis patients are related to weight loss that coexists with an immunoendocrine imbalance.

The study's objective was to examine whether factors related to the host status may bear some relation with the profile of the immune response displayed by tuberculosis (TB) patients. The in vitro immune response (antigen-driven lymphoproliferation and cytokine production) and the presence of alcoholism or disease-related factors, like heart and respiratory rates, and weight loss (body mass index, BMI) were investigated in 31 males with active, untreated TB. Compared to 16 age-matched healthy males, TB patients presented depressed lymphoproliferation and increased IL-10 and TGF-beta production. Multivariate analysis indicated that most differences were no longer significant when controlling for the BMI. Immune and endocrine changes coexisting with weight loss, such as circulating levels of TNF-alpha, IFN-gamma, IL-6, cortisol, dehydroepiandrosterone and thyroid hormones, were also analyzed. While pairwise correlations between serum levels of IFN-gamma, T3 or T4 and BMI were not significant, BMI was negatively correlated with IL-6 levels (p < 0.025). In turn, levels of IL-6 correlated positively with cortisol concentrations (p <0.001). Stepwise regression analysis demonstrated that BMI was only associated with IL-6 (r = -0.423, R(2) = 0.18), with the difference remaining significant following adjustment for the other variables. As regards IL-6, BMI, cortisol and IFN-gamma could explain 74% of variability in IL-6 concentrations (R(2) = 0.74). No evidence for effect modification was shown when performing adjusted calculations. To conclude, the relation between weight loss and abnormal immune response of TB patients is partly associated with the immunoendocrine imbalance observed in parallel.

Enfermedad de Lutz-Splendore-De Almeida sin manifestaciones mucocutáneas: a propósito de un caso / Disease Lutz-Splendore-De Almeida without mucocutaneous manifestations: a purpose of a case

La enfermedad de LUTZ-SPLENDORE-DE ALMEIDA se debe al Paracoccidiodes brasiliensis, presente en Latinoamérica. Al principio la infección pulmonar produce pocos síntomas y la diseminación hasta mucosas, ganglios linfáticos y otros; hace que el paciente acuda al médico. Los signos son: úlceras induradas en mucosas de orofaringe, y nariz, adenomegalias, lesiones cutáneas y genitales, tos productiva, pérdida de peso, disnea y fiebre. Radiológicamente muestra una neumonía con focos dispersos bilaterales, el cultivo de secreciones, las pruebas serológicas confirman el diagnóstico; se trata con Itraconazol o Trimetopín-Sulfametoxazol. Se describe caso de un masculino de 49 años, agricultor, quien consultó por tos y pérdida de peso, confirmado mediante estudios imagenológicos, serológicos, histológicos y fibrobroncospia, durante su evolución no cursó con manifestaciones cutáneo-mucosas, siendo divergentes al común de los casos, ya que dichas lesiones preceden o acompañan la forma pulmonar. Es importante integrar al pensamiento médico la existencia del Paracoccidioides brasiliensis, como agente etiológico de infecciones respiratorias aun sin manifestaciones cutáneas.

Carbohydrate supplementation during intense exercise and the immune response of cyclists.

OBJECTIVE: To evaluate the effect of carbohydrate supplementation upon some aspects of the immune function in athletes during intense indoor cycling. METHODS: Twelve male athletes cycled for 20 min at a velocity corresponding to 90% of that obtained at the anaerobic threshold and rested for 20 min. This protocol was repeated six times. The athletes received, during the trial, water ad libitum, or a solution of carbohydrate (95% glucose polymers and 5% fructose) at 10% (w/v), 1 g kg h every 20 min, starting at the 10th minute of the first exercise period, plus extra water ad libitum. RESULTS: Exercise induced a reduction in peripheral blood mononuclear cell proliferation (37%) as well as in the production of cytokines by cultured cells (interleukin-1 (IL-1), interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), by 37%, 35%, 26% and 16%, respectively). All of these changes were prevented by the ingestion of a carbohydrate drink by the athletes, except that in IFN-gamma production, which was equally decreased (17%) after the second trial. The concentration of plasma glutamine, an important fuel for immune cells, was decreased in the placebo group but maintained in the group that received carbohydrate. CONCLUSION: Carbohydrate supplementation affects positively the immune response of cyclists by avoiding or minimizing changes in plasma glutamine concentration.

Comparación de la evolución de pacientes desnutridos con pacientes sin deficit nutricionales sometidos a procedimientos quirúrgicos / Comparison of the evolution of patients malnutrition with patients without defficit nutritional submission procedure surgical

Se realizó un estudio prospectivó entre marzo de 1998 a diciembre de 1998, comparando un grupo de 30 pacientes con desnutrición severa a quienes se les practicará alguna intervención quirúrgica con un grupo control de 40 pacientes sin deficiencias nutricionales que también fuese necesario realizar alguna intervención quirúrgica. Se comparó la evolución postoperatoria en cuanto a complicaciones de la herida, infecciones respiratorias, fístulas y abscesos intra-abdominales. Se utilizó la escala de Feldtman para catalogar a los pacientes en los dos grupo. El 63 por ciento (n=19) de los pacientes desnutridos presentaron complicaciones, en comparación con el 10 por ciento (n=4) de los pacientes del grupo control, es decir 5,25 veces más frecuente). Cuantro pacientes del primer grupo presentaron 2 complicaciones postoperatorias simultáneas. Dos pacientes fallecieron en el grupo. Se encontró diferencia estadísticamente significativa entre ambos grupos(p<0,005)

Cryptosporidium en pacientes atendidos en el Hospital Provincial "Dr Antonio Luaces Iraola Provincia Ciego de Avila Cuba / Cryptosporidium in patients at the local Dr Antonio Luaces Iraola Hospital Ciego de Avila Cuba

Se realiza estudio mediante la técnica de Ziehl-Nelsen modificada por Henriksen, de las heces fecales de 1221 niños en busca de Crytosporidium. Los resultados fueron: 1121 con diarreas agudas, 50 con diarreas crónicas, 50 con dolor abdominal recurrente. Se obtiene una positividad del 6,8 por ciento en los pacientes con diarreas agudas, 6 por ciento en los portadores de diarreas crónicas y 2 por ciento en niños con dolor abdominal recurrente; la mayor positividad fue en los niños menores de un año. Los vómitos y la fiebre son síntomas que acompañan con frecuencia a las diarreas por Cryptosporidium y sus ooquistes desaparecen de las muestras de heces fecales, en la mayoría de los casos, al desaparecer la diarrea o sólo unos días después.