Impaired NK cell cytotoxicity in multiple myeloma caused by the homozygous A91V polymorphism in the perforin gene: a case report: Citotoxicidade de células NK prejudicada no mieloma múltiplo causada pelo polimorfismo A91V em homozigose no gene da perforina: um relato de caso

We describe a 58-year-old man diagnosed with IgG/Kappa multiple myeloma (International Staging System III) treated for eight years with polychemotherapy (VAD schee) and autologous peripheral hematopoietic stem cell transplantation. The patient studied was homozygous C272T polymorphism (PRF1272T/T) by analysis of perforin gene by direct sequencing. This SNP is considered pathogenic and leads to the substitution of the amino acid alanine for valine in codon 91 of the perforin protein. The cytotoxic lymphocytes (CLs) of the patient and of the healthy wild homozygous individual were evaluated for their cytotoxic capacity. Our results show that PRF1272T/T effector cells had significantly reduced ability to induce specific lysis of K562 cells. The NK cells of the patient had three times less intracellular perforin than observed in the wild-type individual. The gene expression of PRF1 and FAS did not differ between the individuals, however the expression of GZMB was approximately 2.5 times higher in the patient. It was also observed that the T-BET expression was approximately 1.7-fold higher and IFN-γ expression was 4.5-fold higher in the PRF1272T/T patient. In conclusion, functional analysis of the CLs of the patient revealed a significant decrease in their cytolytic capacity as well as the amount of perforin present in NK cell granules

Impaired NK cell cytotoxicity in multiple myeloma caused by the homozygous A91V polymorphism in the perforin gene: a case report: Citotoxicidade de células NK prejudicada no mieloma múltiplo causada pelo polimorfismo A91V em homozigose no gene da perforina: um relato de caso

We describe a 58-year-old man diagnosed with IgG/Kappa multiple myeloma (International Staging System III) treated for eight years with polychemotherapy (VAD schee) and autologous peripheral hematopoietic stem cell transplantation. The patient studied was homozygous C272T polymorphism (PRF1272T/T) by analysis of perforin gene by direct sequencing. This SNP is considered pathogenic and leads to the substitution of the amino acid alanine for valine in codon 91 of the perforin protein. The cytotoxic lymphocytes (CLs) of the patient and of the healthy wild homozygous individual were evaluated for their cytotoxic capacity. Our results show that PRF1272T/T effector cells had significantly reduced ability to induce specific lysis of K562 cells. The NK cells of the patient had three times less intracellular perforin than observed in the wild-type individual. The gene expression of PRF1 and FAS did not differ between the individuals, however the expression of GZMB was approximately 2.5 times higher in the patient. It was also observed that the T-BET expression was approximately 1.7-fold higher and IFN-γ expression was 4.5-fold higher in the PRF1272T/T patient. In conclusion, functional analysis of the CLs of the patient revealed a significant decrease in their cytolytic capacity as well as the amount of perforin present in NK cell granules

Hemolymph of triatomines presents fungistatic activity against Cryptococcus neoformans and improves macrophage function through MCP-I/TNF-α increase

Abstract Background: Triatomines are blood-feeding arthropods belonging to the subfamily Triatominae (Hemiptera; Reduviidae), capable of producing immunomodulatory and water-soluble molecules in their hemolymph, such as antimicrobial peptides (AMPs). In this work, we evaluated the antifungal and immunomodulatory activity of the hemolymph of Meccus pallidipennis (MPH) and Rhodnius prolixus (RPH) against Cryptococcus neoformans. Methods: We assessed the activity of the hemolymph of both insects on fungal growth by a minimum inhibitory concentration (MIC) assay. Further, RAW 264.7 macrophages were cultivated with hemolymph and challenged with C. neoformans. Then, their phagocytic and killing activities were assessed. The cytokines MCP-1, IFN-γ, TNF-α, IL-10, IL-12, and IL-6 were measured in culture supernatants 4- and 48-hours post-infection. Results: Both hemolymph samples directly affected the growth rate of the fungus in a dose-dependent manner. Either MPH or RPH was capable of inhibiting fungal growth by at least 70%, using the lowest dilution (1:20). Treatment of RAW 264.7 macrophages with hemolymph of both insects was capable of increasing the production of MCP-I and TNF-α. In addition, when these cells were stimulated with hemolymph in the presence of C. neoformans, a 2- and a 4-fold increase in phagocytic rate was observed with MPH and RPH, respectively, when compared to untreated cells. For the macrophage killing activity, MPH decreased in approximately 30% the number of viable yeasts inside the cells compared to untreated control; however, treatment with RPH could not reduce the total number of viable yeasts. MPH was also capable of increasing MHC-II expression on macrophages. Regarding the cytokine production, MCP-I and TNF-α, were increased in the supernatant of macrophages treated with both hemolymphs, 4 and 48 hours after stimulation. Conclusion: These results suggested that hemolymph of triatomines may represent a source of molecules capable of presenting antifungal and immunomodulatory activity in macrophages during fungal infection

Innovative technique for the study of pneumoperitoneum in the evaluation of abdominal pain after chemical irritation with zymozan Técnica original para o estudo da influência do pneumoperitônio na avaliação da intensidade da dor abdominal após irritação química com zimozan

PURPOSE: To assess the influence of pneumoperitoneum in mice submitted to peritoneal irritation provoked by the biological agent Saccharomyces cerevisae, by counting the number of abdominal contractions elicited. METHODS: To study the effects of pneumoperitoneum analgesic action, 60 mice were divided into two groups: the experimental group, subjected to pneumoperitoneum; and the control group, without pneumoperitoneum. The both groups received intraperitoneal injection of zymosan at a dose of 1mg/0,2ml/mouse. RESULTS: The sum of the number of abdominal contractions of the experimental group (with pneumoperitoneum) was significantly lower than that of the control group (without pneumoperitoneum). In the experimental group, a lower number of contractions occurred in each min compared to the control. CONCLUSION: The observation of the analgesic effect of pneumoperitoneum using CO2 in mice submitted to peritoneal irritation by zymosan was verified.<br>OBJETIVO: Avaliar a influência do pneumoperitônio em animais submetidos à irritação peritoneal provocada pelo agente biológico Saccharomyces cerevisae mediante a contagem do número de contrações abdominais. MÉTODOS: Para o estudo do efeito da ação analgésica do pneumoperitônio os 60 camundongos foram divididos em dois grupos, grupo experimento (com pneumoperitôneo) e controle (sem pneumoperitôneo). Os dois grupos receberam injeção intraperitoneal de zimosan na dose de 1mg/0,2ml/camundongo. RESULTADOS: O somatório do número de contrações abdominais do grupo experimento (com pneumoperitôneo) foi significativamente menor que no grupo controle (sem pneumoperitôneo). O número médio de contrações no grupo controle foi significativamente maior quando comparado com o grupo experimento. CONCLUSÃO: Observou-se efeito analgésico do pneumoperitônio com CO2 em animais submetidos à irritação peritoneal pelo zimosan

Prevalence of cholelithiasis in patients with chagasic megaesophagus

INTRODUCTION: The prevalence of cholelithiasis in the general population ranges from 9 to 18%. This prevalence is known to be higher in the presence of parasympathetic nerve damage of the biliary tract either due to surgery (vagotomy) or neuronal destruction (Chagas disease). The objective of this study was to evaluate the association of cholelithiasis and chagasic or idiopathic megaesophagus. METHODS: The ultrasound scans of 152 patients with megaesophagus submitted to cardiomyotomy and subtotal esophagectomy surgery were evaluated. The presence of cholelithiasis was compared between chagasic and idiopathic esophagopathy and ultrasound and clinical findings were correlated with age, sex and race. RESULTS: A total of 152 cases of megaesophagus, including 137 with chagasic megaesophagus and 15 with idiopathic megaesophagus, were analyzed. The mean age was 56.7 years (45-67) in the 137 patients with chagasic megaesophagus and 35.6 years (27-44) in the 15 cases of idiopathic megaesophagus, with a significant difference between the two groups (p < 0.0001). The group with chagasic megaesophagus consisted of 59 (43%) women and 78 (56.9%) men, while the group with idiopathic megaesophagus consisted of 8 (53.3%) women and 7 (46.6%) men, showing no significant difference between the groups. Of the 137 patients with confirmed chagasic megaesophagus, 39 (28.4%) presented cholelithiasis versus one case (6.6%) in the 15 patients with idiopathic megaesophagus. CONCLUSIONS: The prevalence of cholelithiasis is high in patients with chagasic megaesophagus and preoperative ultrasound should be performed routinely in these patients in order to treat both conditions during the same surgical procedure

Prevalence of cholelithiasis in patients with chagasic megaesophagus Prevalência de colelitíase em pacientes com megaesôfago chagásico

INTRODUCTION: The prevalence of cholelithiasis in the general population ranges from 9 to 18%. This prevalence is known to be higher in the presence of parasympathetic nerve damage of the biliary tract either due to surgery (vagotomy) or neuronal destruction (Chagas disease). The objective of this study was to evaluate the association of cholelithiasis and chagasic or idiopathic megaesophagus. METHODS: The ultrasound scans of 152 patients with megaesophagus submitted to cardiomyotomy and subtotal esophagectomy surgery were evaluated. The presence of cholelithiasis was compared between chagasic and idiopathic esophagopathy and ultrasound and clinical findings were correlated with age, sex and race. RESULTS: A total of 152 cases of megaesophagus, including 137 with chagasic megaesophagus and 15 with idiopathic megaesophagus, were analyzed. The mean age was 56.7 years (45-67) in the 137 patients with chagasic megaesophagus and 35.6 years (27-44) in the 15 cases of idiopathic megaesophagus, with a significant difference between the two groups (p INTRODUÇÃO: A prevalência de colelitíase observada na população em geral varia de 9 a 18%. Sabe-se que a prevalência de colelitíase é elevada quando existe lesão nervosa parassimpática das vias biliares, causada tanto por procedimentos cirúrgicos (vagotomias),quanto por destruição neuronal, como observado na forma digestiva da doença de Chagas. Propusemo-nos verificar a associação entre megaesôfago de etiologia chagásica e a presença de colelitíase. MÉTODOS: Avaliou-se prospectivamente o exame ultrassonográfico de 152 pacientes portadores de megaesôfago submetidos à cirurgia de cardiomiotomia e esofagectomia subtotal. Analisou-se comparativamente a esofagopatia chagásica e a idiopática com a presença de colelitíase, correlacionando os dados ultrassonográficos com os achados clínicos, idade, sexo e raça. RESULTADOS: Foram analisados 152 casos de megaesôfago, sendo 137 de etiologia chagásica e 15 idiopáticos. Entre os chagásicos, a idade média foi de 56,7 anos (45-67); e nos idiopáticos, a média de idade foi de 35,6 anos (27-44), verificando-se diferença significativa (p < 0,0001) em relação à média de idade. Dos 137 chagásicos, 78 (56,9%) eram do sexo masculino; entre os 15 idiopáticos, 7 (46,6%) eram do sexo masculino. A comparação entre os grupos em relação ao gênero não mostrou diferença significativa. Dentre os 137 chagásicos detectou-se 39 (28,4%) casos de colelitíase e, dentre os 15 casos de megaesôfago idiopático, constatou-se colelitíase em apenas um (6,6%). CONCLUSÕES: Conclui-se que portadores de megaesôfago chagásico possuem alta prevalência de colelitíase, e que a ultrassonografia deve ser realizada rotineiramente no pré-operatório, a fim de tratar ambas as afecções no mesmo ato cirúrgico