Exertional chest pain is sometimes more than just coronary atherosclerosis.

CLINICAL CASE: A 64-year-old male, with cardiovascular risk factors and previous history of bilateral carpal tunnel syndrome, presented with exertional retrosternal pain. The resting echocardiogram was unremarkable. A stress echocardiogram with dobutamine revealed hypokinesis of the inferior wall, associated with angina, followed by ventricular tachycardia. The coronary angiography revealed slow flow, a dominant right coronary artery with non-obstructive atherosclerosis and a left anterior descending artery with intermediate lesions in mid and distal segments. The invasive functional evaluation, including fractional flow reserve, thermodilution coronary flow reserve and index of microvascular resistance, led to the diagnosis of microvascular angina, treated with calcium channel blockers and transdermal nitrate, giving symptom relief. EVOLUTION: Three years later he developed complete atrioventricular block and a dual chamber pacemaker was implanted. Shortly after, the patient developed progressive symmetrical tetraparesis, associated with marked muscle atrophy, hand numbness, orthostatic hypotension and dysphagia. The neurology workup led to the diagnosis of familial amyloidotic polyneuropathy, with the Val30Met mutation in the transthyretin gene. The following year he developed congestive heart failure. The echocardiogram showed moderate concentric left ventricular hypertrophy with preserved ejection fraction. A 99mTc-DPD Scintigraphy showed significant myocardial tracer uptake, leading to a diagnosis of TTR amyloid infiltration. DISCUSSION: Patients with exertional angina and microvascular disease should be kept under close surveillance, as they may have systemic disease with cardiac involvement. Carpal tunnel syndrome, in the context of undiagnosed cardiac disease, should trigger suspicion of cardiac amyloidosis.

Use of high-throughput targeted exome-sequencing to screen for copy number variation in hypertrophic cardiomyopathy.

INTRODUCTION: The role of copy-number variants (CNV) as a cause of hypertrophic cardiomyopathy (HCM) is poorly studied. The aim of this study was to use high-throughput sequence (HTS) data combined with a read-depth strategy, to screen for CNV in cardiomyopathy-associated genes in a large consecutive cohort of HCM patients. METHODS: Five-hundred-and-five unrelated HCM patients were genotyped using a HTS approach for 41 cardiovascular genes. We used a previously validated read-depth strategy (ExomeDepth) to call CNVs from the short-read sequence data. Detected CNVs in 19 cardiomyopathy-associated genes were then validated by comparative genomic hybridization array. RESULTS: Twelve CNVs were identified. Four CNVs in 4 patients (0.8% of the cohort) were validated: one large deletion in MYBPC3, one large deletion in PDLIM3, one duplication of the entire TNNT2 gene and one large duplication in LMNA. CONCLUSIONS: Our data suggest that the proportion of HCM cases with pathogenic CNVs is small (<1%). For the small subset of patients with clearly interpretable CNVs, our findings have direct clinical implications. Short read sequence data can be used for CNV calling, but the high false positive rate requires a validation step. The two-step strategy described here is effective at identifying novel genetic causes of HCM and similar techniques should be applied whenever possible.

Reactive oxygen species and the structural remodeling of the visual system after ocular enucleation.

Redox processes associated with controlled generation of reactive oxygen species (ROS) by NADPH oxidase (Nox) add an essential level of regulation to signaling pathways underlying physiological processes. We evaluated the ROS generation in the main visual relays of the mammalian brain, namely the superior colliculus (SC) and the dorsal lateral geniculate nucleus (DLG), after ocular enucleation in adult rats. Dihydroethidium (DHE) oxidation revealed increased ROS generation in SC and DLG between 1 and 30 days postlesion. ROS generation was decreased by the Nox inhibitors diphenyleneiodonium chloride (DPI) and apocynin. Real-time PCR results revealed that Nox 2 was upregulated in both retinorecipient structures after deafferentation, whereas Nox 1 and Nox 4 were upregulated only in the SC. To evaluate the role of ROS in structural remodeling after the lesions, apocynin was given to enucleated rats and immunohistochemistry was conducted for markers of neuronal remodeling into SC and DLG. Immunohistochemical data showed that ocular enucleation produces an increase of neurofilament and microtubule-associated protein-2 immunostaining in both SC and DLG, which was markedly attenuated by apocynin treatment. Taken together, the findings of the present study suggest a novel role for Nox-induced ROS signaling in mediating neuronal remodeling in visual areas after ocular enucleation.

Role of nitrites in the genesis of adenocarcinoma associated with Barrett's esophagus.

BACKGROUND: Barrett's esophagus (BE) is one of the complications of gastroesophageal reflux disease (GERD) and a premalignant condition. It consists of a process of replacement of the squamous epithelium of the esophagus by intestinal columnar epithelium containing goblet cells, known as specialized intestinal metaplasia with goblet cells, and several factors have been related to its pathogenesis. The objective of this study was to evaluate an experimental model of duodenogastroesophageal reflux and the effect of ingestion of sodium nitrite solution on the genesis of adenocarcinoma associated with Barrett's esophagus. MATERIALS AND METHODS: Sixty male Wistar rats were divided into four groups. Twenty were not submitted to surgery and served as controls (10 animals ingesting only water and 10 ingesting water plus a solution of sodium nitrite), while the remaining 40 animals were submitted to side-to-side duodenogastroesophageal anastomosis (20 animals ingesting only water and 20 ingesting water plus the sodium nitrite solution). The Vienna classification for dysplasia and adenocarcinoma was used in the analysis of results. RESULTS: After 42 weeks of observation, Barrett's esophagus was found in 26.3% (5/19) of the animals submitted to surgery that had not ingested nitrites compared to 72.3% (13/18) of the animals in the group submitted to surgery and given nitrites. Six cases of adenocarcinoma (33.3%) were also found in this latter group. Barrett's esophagus was not found in any of the animals that were not submitted to surgery. Categories 2, 3 and 5 of the Vienna classification were only found in the animals submitted to surgery that also received sodium nitrite (66.7%). CONCLUSION: The ingestion of sodium nitrite associated with duodenogastroesophageal reflux plays an important role in the genesis of adenocarcinoma associated with Barrett's esophagus.

Treatment of achalasia: lessons learned with Chagas' disease.

Chagas' disease (CD) is highly prevalent in South America. Brazilian surgeons and gastroenterologists gained valuable experience in the treatment of CD esophagopathy (chagasic achalasia) due to the high number of cases treated. The authors reviewed the lessons learned with the treatment of achalasia by different centers experienced in the treatment of Chagas' disease. Preoperative evaluation, endoscopic treatment (forceful dilatation and botulinum toxin injection), Heller's myotomy, esophagectomy, conservative techniques other than myotomy, and reoperations are discussed in the light of personal experiences and review of International and Brazilian literature. Aspects not frequently adopted by North American and European surgeons are emphasized. The review shows that nonadvanced achalasia is frequently treated by Heller's myotomy. Endoscopic treatment is reserved to limited cases. Treatment for end-stage achalasia is not unanimous. Esophagectomy was a popular treatment in advanced disease; however, the morbidity/mortality associated to the procedure made some authors seek different alternatives, such as Heller's myotomy and cardioplasties. Minimally invasive approach to esophageal resection may change this concept, although few centers perform the procedure routinely.

Evidence that arachidonic acid derived from neutrophils and prostaglandin E2 are associated with the induction of acute lung inflammation by lipopolysaccharide of Escherichia coli.

OBJECTIVE: The involvement of arachidonic acid (AA) and PGE2 during the E. coli lipopolysaccharide (LPS)-induced acute lung injury was investigated. MATERIAL: Adult male Wistar rats were used. For in vitro studies, rat neutrophils, bronchoalveolar lavage (BAL) fluid, and lug vascular endothelium were used, as described below. TREATMENT: Rats were given an intratracheal injection of LPS (750 microg). METHODS: Total and differential cell counts in BAL fluid; enzyme-linked immunoassay (ELISA) analyses of TNF-alpha, IL-1beta, LTB4 and PGE2 in BAL, and immunohistochemical detection of ICAM-1 on lung vascular endothelium were performed six h after LPS challenge. Fatty acid composition of blood neutrophils and plasma was analyzed by HPLC. RESULTS: Rats instilled with LPS presented a sixty three-fold increase in the number of neutrophils in BAL (from 0.5 x 10(6) to 31.5 x 10(6) cells), accompanied by increased levels of TNF-alpha and IL-1beta (p < 0.001), and a three-fold increase in ICAM-1 expression on vascular endothelium. The content of AA in blood neutrophils was reduced by 50%, whereas the level of PGE2 in BAL was increased by 3.5 fold, without changes in the levels of LTB4. CONCLUSIONS: These findings suggest that AA and PGE2 are associated with LPS challenge.

Effect of surgical treatment on the cellular immune response of gastric cancer patients.

Patients with gastric cancer have a variety of immunological abnormalities. In the present study the lymphocytes and their subsets were determined in the peripheral blood of patients with gastric cancer (N = 41) both before and after surgical treatment. The percent of helper/inducer CD4 T cells (43.6 +/- 8.9) was not different after tumor resection (43.6 +/- 8.2). The percent of the cytotoxic CD8+ T cell population decreased significantly, whether patients were treated surgically (27.2 +/- 5.8%, N = 20) or not (27.3 +/- 7.3%, N = 20) compared to individuals with inflammatory disease (30.9 +/- 7.5%) or to healthy individuals (33.2 +/- 7.6%). The CD4/CD8 ratio consequently increased in the group of cancer patients. The peripheral blood lymphocytes of gastric cancer patients showed reduced responsiveness to mitogens. The defective blastogenic response of the lymphocytes was not associated with the production of transforming growth factor beta (TGF- ) since the patients with cancer had reduced production of TGF- Beta1 (269 +/- 239 pg/ml, N = 20) in comparison to the normal individuals (884 +/- 175 pg/ml, N = 20). These results indicate that the immune response of gastric cancer patients was not significantly modified by surgical treatment when evaluated four weeks after surgery and that the immunosuppression observed was not due to an increase in TGF- 1 production by peripheral leukocytes.

Effect of surgical treatment on the cellular immune response of gastric cancer patients

Patients with gastric cancer have a variety of immunological abnormalities. In the present study the lymphocytes and their subsets were determined in the peripheral blood of patients with gastric cancer (N = 41) both before and after surgical treatment. The percent of helper/inducer CD4 T cells (43.6 ± 8.9) was not different after tumor resection (43.6 ± 8.2). The percent of the cytotoxic CD8+ T cell population decreased significantly, whether patients were treated surgically (27.2 ± 5.8 percent, N = 20) or not (27.3 ± 7.3 percent, N = 20) compared to individuals with inflammatory disease (30.9 ± 7.5 percent) or to healthy individuals (33.2 ± 7.6 percent). The CD4/CD8 ratio consequently increased in the group of cancer patients. The peripheral blood lymphocytes of gastric cancer patients showed reduced responsiveness to mitogens. The defective blastogenic response of the lymphocytes was not associated with the production of transforming growth factor beta (TGF-á) since the patients with cancer had reduced production of TGF-á1 (269 ± 239 pg/ml, N = 20) in comparison to the normal individuals (884 ± 175 pg/ml, N = 20). These results indicate that the immune response of gastric cancer patients was not significantly modified by surgical treatment when evaluated four weeks after surgery and that the immunosuppression observed was not due to an increase in TGF-á1 production by peripheral leukocytes

Effect of pilocarpine mouthwash on salivary flow

Pilocarpine is a cholinergic agonist that increases salivary flow and has been used to treat xerostomia. Oral intake is the most frequent route of administration. Adverse effects are dose-dependent and include sudoresis, facial blushing and increased urinary frequency. The objective of the present study was to evaluate the effects of topical pilocarpine solutions as mouthwashes on salivary flow and their adverse effects on healthy subjects. Forty volunteers received 10 ml 0.5, 1 and 2 percent pilocarpine solutions or 0.9 percent saline in a randomized, double-blind, placebo-controlled manner. Salivation was measured before and 45, 60 and 75 min after mouth rinsing for 1 min with 10 ml of saline or pilocarpine solutions. Vital signs were measured and ocular, gastrointestinal and cardiovascular symptoms, anxiety and flushing were estimated using visual analog scales. There was a dose-dependent increase in salivation. Salivation measured after 1 and 2 percent pilocarpine (1.4 +/- 0.36 and 2.22 +/- 0.42 g, respectively) was significantly (P<0.001) higher than before (0.70 +/- 0.15 and 0.64 +/- 0.1 g), with a plateau between 45 and 75 min. Cardiovascular, visual, gastrointestinal and behavioral symptoms and signs were not changed by topical pilocarpine. Mouth rinsing with pilocarpine solutions at concentrations of 1 to 2 percent induced a significant objective and subjective dose-dependent increase in salivary flow, similar to the results reported by others studying the effect of oral 5 mg pilocarpine. The present study revealed the efficacy of pilocarpine mouthwash solutions in increasing salivary flow in healthy volunteers, with no adverse effects. Additional studies on patients with xerostomia are needed

Effect of pilocarpine mouthwash on salivary flow.

Pilocarpine is a cholinergic agonist that increases salivary flow and has been used to treat xerostomia. Oral intake is the most frequent route of administration. Adverse effects are dose-dependent and include sudoresis, facial blushing and increased urinary frequency. The objective of the present study was to evaluate the effects of topical pilocarpine solutions as mouthwashes on salivary flow and their adverse effects on healthy subjects. Forty volunteers received 10 ml 0.5, 1 and 2% pilocarpine solutions or 0.9% saline in a randomized, double-blind, placebo-controlled manner. Salivation was measured before and 45, 60 and 75 min after mouth rinsing for 1 min with 10 ml of saline or pilocarpine solutions. Vital signs were measured and ocular, gastrointestinal and cardiovascular symptoms, anxiety and flushing were estimated using visual analog scales. There was a dose-dependent increase in salivation. Salivation measured after 1 and 2% pilocarpine (1.4 +/- 0.36 and 2.22 +/- 0.42 g, respectively) was significantly (P<0.001) higher than before (0.70 +/- 0.15 and 0.64 +/- 0.1 g), with a plateau between 45 and 75 min. Cardiovascular, visual, gastrointestinal and behavioral symptoms and signs were not changed by topical pilocarpine. Mouth rinsing with pilocarpine solutions at concentrations of 1 to 2% induced a significant objective and subjective dose-dependent increase in salivary flow, similar to the results reported by others studying the effect of oral 5 mg pilocarpine. The present study revealed the efficacy of pilocarpine mouthwash solutions in increasing salivary flow in healthy volunteers, with no adverse effects. Additional studies on patients with xerostomia are needed.

[Conservative treatment of benign esophageal strictures using dilation. Analysis of 500 cases]. / Tratamento conservador das estenoses benignas do esôfago através de dilatações. Análise de 500 casos.

UNLABELLED: The benign esophageal stenoses (BES) are common complications owing to many etiologies: gastroesophageal reflux, ingestion of corrosive agents, esophageal surgery, radiotherapy, postendoscopic variceal sclerotherapy, drug ingestion, prolonged nasogastric intubation, extrinsic compression and esophageal webs. Esophageal dilatations are worldwide recommended to treat this complication, employing dilators of many types and diameters and facilitating the food ingestion. PURPOSE: Evaluation of the results and advantages of the conservative treatment of the BES using esophageal dilatations, in outpatient service of upper digestive endoscopy. METHODS: During the period from 1981 to 1999, 500 patients with BES were treated and followed up at the Gastrocenter - UNICAMP, in an individually Program of Esophageal Dilatation for each case. The highest number of cases was under ages from 31 to 60 years old (52,8%), and males (59,2%). The most predominant etiologies were: peptic stenosis (30,4%), caustic ingestion (23,6%), anastomosis (23,2%), megaesophagus (8,0%) and prolonged nasogastric ingestion entubation (6,4%), totalizing 91,6% of the BES. Most of patients (94,2%) were submitted to the maximum of 25 dilations. Dilators from 10,5 to 16 mm were employed in 95,6% of the cases. The duration of the treatment was 24 months in 76,2% of the BES. Esophageal perforations occurred in 6 patients (1,2%), without mortality. RESULTS: Were considered excellent, good and bad results, respectively in 76,2%, 18,2% and 5,6% of the cases. On the other hand, excellent results were recorded in 81,0% of the peptic stenosis, 66,1% of the caustic stenosis and 82,7% of the anastomotic stenosis. The conservative treatment failed in 9,3% of the caustic stenosis, 4,3% of the anastomotic stenosis and 3,9% of the peptic stenosis. Thus, the caustic stenosis were unsuccessfull in the highest percentage of unsuccessful. CONCLUSION: The conservative treatment using guidewire dilators (Savary-Gilliard and Eder-Puestow) is the first choice in the BES, is effective for long time, with short complications and the surgical treatment is indicated only when the dilatations failed.

Tratamento conservador das estenoses benignas do esôfago através de dilataçöes. Análise de 500 casos / Conservative treatment of benign esophageal strictures by dilatations. Analysis of 500 cases

As estenoses benignas do esôfago (EBE) säo complicaçöes muito freqüentes, resultado de várias etiologias, a saber: refluxo gastro-esofágico, ingestäo de agentes corrosivos, pós-cirurgias do esôfago, pós-radioterapia no tórax, pós-escleroterapia endoscópica de varizes do esôfago, ingestäo de medicamentos, uso prolongado de cateter nasogástrico, compressäo extrínseca e membranas esofágicas congênitas. As dilataçöes esofágicas säo recomendadas no tratamento dessa complicaçäo, empregando dilatadores de vários tipos e diâmetros, facilitando ao doente a ingestäo alimentar. OBJETIVOS: Avaliaçäo dos resultados e vantagens do tratamento conservador das EBE através de dilataçöes esofágicas realizadas ambulatorialmente com auxílio da endoscopia digestiva flexível. MÉTODOS: No período de 1981 a 1999 foram tratados, conservadoramente e seguidos no Gastrocentro -- UNICAMP, 500 doentes com EBE, através de um Programa de Dilataçöes Esofágicas instituído para cada caso. A maioria era do sexo masculino (59,2 por cento) e a faixa etária mais acometida encontra-se entre 31 anos e 60 anos, compreendendo 52,8 por cento dos pacientes em estudo. As estenoses mais prevalentes foram as estenoses pépticas (30,4 por cento), cáusticas (23,6 por cento), de anastomoses (23,2 por cento), por megaesôfago (8,0 por cento) e por uso prolongado de cateter nasogástrico (6,4 por cento), perfazendo um total de 91,6 por cento das EBE. Quanto ao número de procedimentos, 94,2 por cento dos casos foram submetidos a no máximo 25 dilataçöes do esôfago. Em 95,6 por cento deles foram utilizados dilatadores com diâmetro entre 10,5 mm e 16,0 mm. A duraçäo do tratamento foi até 24 meses em 76,2 por cento dos casos. Perfuraçöes esofágicas ocorreram em seis doentes (1,2 por cento), sem mortalidade. RESULTADOS: Foram considerados bons em 76,2 por cento, regulares em 18,2 por cento e maus em 5,6 por cento dos doentes. O sucesso do tratamento variou conforme a etiologia da estenose, ocorrendo bons resultados em 81,0 por cento das estenoses pépticas, em 66,1 por cento das estenoses cáusticas e em 82,7 por cento das estenoses de anastomoses. A falha do tratamento conservador ocorreu em 9,3 por cento das estenoses cáusticas, 4,3 por cento das estenoses de anastomose e 3,9 por cento das estenoses pépticas. A estenose cáustica propiciou a falha maior da terapêutica conservadora em relaçäo aos demais. CONCLUSÄO: O tratamento conservador, através de dilataçöes orientadas por fio-guia...

[Videolaparoscopic surgical treatment of gastroesophageal reflux disease: modified Nissen technique - clinical and functional results]. / Tratamento cirúrgico videolaparoscópico da doença do refluxo gastroesofagiano: técnica de Nissen modificada - resultados clínicos e funcionais.

BACKGROUND: Gastroesophageal reflux disease is highly common worldwide and surgical treatment is being indicated more frequently. Currently, laparoscopic is the access of choice and several antireflux techniques may be used. We prefer a modified Nissen technique. PURPOSE: To analyze preoperative clinical and functional parameters and compare with postoperative outcome of a modified valve technique performed by laparoscopy. METHODS: A group of 59 patients underwent laparoscopic modified Nissen valve. Preoperative diagnosis was made by radiological contrast exams and endoscopy in all patients. Esophagus manometry was performed in 35 patients and scintigraphy scan in 15 patients. Complicated esophagitis occurred in 54.2%, with 21 (35.6%) patients presenting a Barrett's epithelium. Laparoscopic surgery was performed in all patients with no conversion to open surgery, with an average time of 123.9 minutes. RESULTS: There were no intraoperative complications. Hospital discharge occurred in an average of 47.6 hours. Symptoms as dysphagia, pain, regurgitation and flatus occurred in 48.1% of the patients in the first thirty days. Average follow-up was 20.8 months. Postoperative radiological, endoscopic, manometric and scintigrafic scan exams showed a significant improvement, as well as clinical assessment using Visick's classification, which showed excellent and good results in 93.1% of the patients. CONCLUSION: Comparative analysis of clinical assessment and exam results lad us to conclude that modified Nissen surgery by laparoscopic access corrects gastroesophageal reflux in most patients followed-up.

Tratamento cirúrgico videolaparoscópico da doença do refluxo gastroesofagiano: técnica de Nissen modificada - resultados clínicos e funcionais / Videolaparoscopic surgical treatment of gastroesophageal reflux disease: modified Nissen technique - clinical and functional results

A doença do refluxo gastroesofagiano é muito freqüente na populaçäo e o tratamento cirúrgico é indicado em um número respeitável de pacientes. A escolha da via de acesso é a laparoscopia. Várias técnicas anti-refluxo podem ser empregadas e preferimos a técnica de Nissen modificada. OBJETIVO: Analisar os parâmetros clínicos e funcionais pré-operatórios comparados com os mesmos parâmetros pós-operatórios com a técnica empregada. MÉTODOS: Um grupo de 59 pacientes foi submetido a tratamento cirúrgico pela técnica de Nissen modificada videolaparoscópica. O diagnóstico pré-operatório foi feito por exame radiográfico contrastado e endoscopia digestiva alta em todos os pacientes. A manometria do esôfago realizada em 35 e a cintilografia em 15. Esofagite complicada ocorreu em 54,2 por cento sendo 21 pacientes (35,6 por cento) com epitélio de Barrett. A técnica cirúrgica laparoscópica foi concluída em todos os pacientes. O tempo médio de cirurgia foi de 123,9 minutos. RESULTADOS: Näo ocorreram complicaçöes intra-operatórias. A alta se deu em média com 47,6 horas. Sintomas de disfagia, dor, epigastralgia, regurgitaçäo e flatulência até o 30° dia ocorreram em 48,1 por cento dos pacientes. Ocorreu uma reoperaçäo por recurrência da doença e um óbito por necrose do fundo gástrico. O seguimento médio foi de 20,8 meses. Os exames pós-operatórios radiográficos, endoscópicos, manométricos e de cintilografia mostraram melhora significativa, bem como a avaliaçäo clínica, que mostrou excelentes e bom resultados em 93,1 por cento dos pacientes. CONCLUSÄO: A cirurgia de Nissen modificada videolaparoscópica corrigiu a doença do refluxo gastroesofagiano na maioria dos doentes acompanhados, associada à baixa morbimortalidade

Effect of fatty acids on leukocyte function

Fatty acids have various effects on immune and inflammatory responses, acting as intracellular and intercellular mediators. Polyunsaturated fatty acids (PUFAs) of the omega-3 family have overall suppressive effects, inhibiting lymphocyte proliferation, antibody and cytokine production, adhesion molecule expression, natural killer cell activity and triggering cell death. The omega-6 PUFAs have both inhibitory and stimulatory effects. The most studied of these is arachidonic acid that can be oxidized to eicosanoids, such as prostaglandins, leukotrienes and thromboxanes, all of which are potent mediators of inflammation. Nevertheless, it has been found that many of the effects of PUFA on immune and inflammatory responses are not dependent on eicosanoid generation. Fatty acids have also been found to modulate phagocytosis, reactive oxygen species production, cytokine production and leukocyte migration, also interfering with antigen presentation by macrophages. The importance of fatty acids in immune function has been corroborated by many clinical trials in which patients show improvement when submitted to fatty acid supplementation. Several mechanisms have been proposed to explain fatty acid modulation of immune response, such as changes in membrane fluidity and signal transduction pathways, regulation of gene transcription, protein acylation, and calcium release. In this review, evidence is presented to support the proposition that changes in cell metabolism also play an important role in the effect of fatty acids on leukocyte functioning, as fatty acids regulate glucose and glutamine metabolism and mitochondrial depolarization

Effect of fatty acids on leukocyte function.

Fatty acids have various effects on immune and inflammatory responses, acting as intracellular and intercellular mediators. Polyunsaturated fatty acids (PUFAs) of the omega-3 family have overall suppressive effects, inhibiting lymphocyte proliferation, antibody and cytokine production, adhesion molecule expression, natural killer cell activity and triggering cell death. The omega-6 PUFAs have both inhibitory and stimulatory effects. The most studied of these is arachidonic acid that can be oxidized to eicosanoids, such as prostaglandins, leukotrienes and thromboxanes, all of which are potent mediators of inflammation. Nevertheless, it has been found that many of the effects of PUFA on immune and inflammatory responses are not dependent on eicosanoid generation. Fatty acids have also been found to modulate phagocytosis, reactive oxygen species production, cytokine production and leukocyte migration, also interfering with antigen presentation by macrophages. The importance of fatty acids in immune function has been corroborated by many clinical trials in which patients show improvement when submitted to fatty acid supplementation. Several mechanisms have been proposed to explain fatty acid modulation of immune response, such as changes in membrane fluidity and signal transduction pathways, regulation of gene transcription, protein acylation, and calcium release. In this review, evidence is presented to support the proposition that changes in cell metabolism also play an important role in the effect of fatty acids on leukocyte functioning, as fatty acids regulate glucose and glutamine metabolism and mitochondrial depolarization.

Reduced inflammatory response in rats fed fat-rich diets: role of leukotrienes.

The effect of fat-rich diets on the acute inflammatory response was examined. Male Wistar rats aged 21 days were fed, for 6 weeks, with a control diet (4% fat content), or a control diet supplemented with coconut or soybean oils (15% fat content). Carrageenan-induced paw oedema and pleurisy were evaluated. Prostaglandin (PG) E2 and leukotriene (LT) C4/D4 concentrations were determined in the pleural exudate (ELISA). Pleural samples were tested for their effect on cutaneous vascular permeability of control rats and the effect of a LTD4 receptor antagonist (L660-711; 10 mg/kg; i.v.) examined. Relative to controls, rats fed both fat-rich diets presented a significant reduction in protein leakage and oedema formation without affecting the number of migrating leukocytes. Production of LTC4/D4 in pleural exudate was significantly increased from 1.8 +/- 0.2 ng/ml in controls to 2.8 +/- 0.2 and 3.0 +/- 0.3 ng/ml in animals fed coconut and soybean oil enriched diets, respectively, without changes in PGE2 production. The activity of these samples on cutaneous vascular permeability was 50% reduced, returning to control values after treatment of testing animals with a LTD4 receptor antagonist. Rats fed fat-rich diets presented a reduced inflammatory response due, at least in part, to the LTC4/D4 mediated vasoconstrictor effect.

[Importance of upper digestive endoscopy using lugol dye solution for the diagnosis of superficial esophageal cancer and dysplasia in patients with head and neck neoplasms]. / A importância da endoscopia digestiva alta com solução de lugol no diagnóstico de câncer superficial e displasia em esôfago de doentes com neoplasias de cabeça e pescoço.

Head and neck cancer has a high incidence in Brazil, with cancer of the oral cavity being one of the five most common cancers among Brazilians. Alcohol and tobacco consumption may contribute to synchronous or metachronous head and neck cancer and esophageal cancer. A prospective study involving 60 patients with head and neck cancer was carried out at the State University of Campinas--UNICAMP, Campinas, SP, Brazil to screen for superficial esophageal cancer and dysplasia using endoscopy and a 2% lugol dye solution followed by biopsy of the suspicious areas. Five patients (8.3%) had superficial esophageal cancer, which was diagnosed as intraepithelial carcinoma in three of them (5.0%). In four patients, the superficial esophageal cancer was synchronous and in one it was metachronous to head and neck cancer. Five patients (8.3%) had dysplasias in the esophageal epithelium (three were classified as mild and two as moderate). These results demonstrate the value of endoscopic screening of the esophagus using lugol dye in patients with head and neck cancer, particularly since superficial esophageal cancer is extremely difficult to detect by conventional methods in asymptomatic patients.

[Laparoscopy in the diagnosis of intra-abdominal diseases. Analysis of 168 cases]. / A laparoscopia no diagnóstico das doenças intra-abdominais. Análise de 168 casos.

UNLABELLED: The laparoscopy has been more and more frequently indicated in the last years, for the complementary diagnosis of intraabdominal diseases and abdominal repercussion of systemic diseases. Modern equipaments including videolaparoscopy and the use of either forceps or biopsy needle permit higher safety and significant diagnostic capacity. PURPOSE: To perform laparoscopy for the diagnosis of intraabdominal and sistemic diseases. METHODS: During the last 9 years 168 patients were submitted to laparoscopy and the main indications were: ascites--43 cases (25.5%); liver diseases--42 cases (25%); gastric cancer--37 cases (22%); lymphoma--17 cases (10.1%); abdominal tumour--9 cases (5.4%); peritoneal tuberculosis--8 cases (4.8%); liver tumour--6 cases (3.6%); mesenteric cyst--1 case (0.6%) and other diseases--5 cases (3.0%). Ninety nine patients were male (58.9%) aging from 9 to 78 years old (median 47.6 years). Liver biopsies were performed in 92 cases (54.7%) and other tumour biopsies in 26 cases (15.4%). RESULTS: The diagnosis of the diseases were established or confirmed by laparoscopy in 145 patients (86.3%). In 25 cases of gastric cancer (67.5%) laparoscopy contraindicated the laparotomy, owing to advanced disease. Two patients presented bleeding (1.2%) after liver biopsies and laparotomy was immediately indicated. One of them, whose diagnosis was systemic lupus, presented abdominal abscess, bronchopneumony and died (0.6%). CONCLUSION: Laparoscopy has small number of complications, and when employed as a diagnostic complementary method therapeutic procedures, avoids laparotomies and accelerate therapeutic procedures.

Activation of the leukocyte NADPH oxidase by protein kinase C in a partially recombinant cell-free system.

The leukocyte NADPH oxidase is an enzyme present in phagocytes and B lymphocytes that when activated catalyzes the production of O-2 from oxygen at the expense of NADPH. A correlation between the activation of the oxidase and the phosphorylation of p47(PHOX), a cytosolic oxidase component, is well recognized in whole cells, and direct evidence for a relationship between the phosphorylation of this oxidase component and the activation of the oxidase has been obtained in a number of cell-free systems containing neutrophil membrane and cytosol. Using superoxide dismutase-inhibitable cytochrome c reduction to quantify O-2 production, we now show that p47(PHOX) phosphorylated by protein kinase C activates the NADPH oxidase not only in a cell-free system containing neutrophil membrane and cytosol, but also in a system in which the cytosol is replaced by the recombinant proteins p67(PHOX), Rac2, and phosphorylated p47(PHOX), suggesting that neutrophil plasma membrane plus those three cytosolic proteins are both necessary and sufficient for oxidase activation. In both the cytosol-containing and recombinant cell-free systems, however, activation by SDS yielded greater rates of O-2 production than activation by protein kinase C-phosphorylated p47(PHOX), indicating that a system that employs protein kinase C-phosphorylated p47(PHOX) as the sole activating agent, although more physiological than the SDS-activated system, is nevertheless incomplete.