Alexandre Ab’Saber

Intravenous glutamine decreases lung and distal organ injury in an experimental model of abdominal sepsis

IntroductionThe protective effect of glutamine, as a pharmacological agent against lung injury, has been reported in experimental sepsis; however, its efficacy at improving oxygenation and lung mechanics, attenuating diaphragm and distal organ injury has to be better elucidated. In the present study, we tested the hypothesis that a single early intravenous dose of glutamine was associated not only with the improvement of lung morpho-function, but also the reduction of the inflammatory process and epithelial cell apoptosis in kidney, liver, and intestine villi.MethodsSeventy-two Wistar rats were randomly assigned into four groups. Sepsis was induced by cecal ligation and puncture surgery (CLP), while a sham operated group was used as control (C). One hour after surgery, C and CLP groups were further randomized into subgroups receiving intravenous saline (1 ml, SAL) or glutamine (0.75 g/kg, Gln). At 48 hours, animals were anesthetized, and the following parameters were measured: arterial oxygenation, pulmonary mechanics, and diaphragm, lung, kidney, liver, and small intestine villi histology. At 18 and 48 hours, Cytokine-Induced Neutrophil Chemoattractant (CINC)-1, interleukin (IL)-6 and 10 were quantified in bronchoalveolar and peritoneal lavage fluids (BALF and PLF, respectively).ResultsCLP induced: a) deterioration of lung mechanics and gas exchange; b) ultrastructural changes of lung parenchyma and diaphragm; and c) lung and distal organ epithelial cell apoptosis. Glutamine improved survival rate, oxygenation and lung mechanics, minimized pulmonary and diaphragmatic changes, attenuating lung and distal organ epithelial cell apoptosis. Glutamine increased IL-10 in peritoneal lavage fluid at 18 hours and bronchoalveolar lavage fluid at 48 hours, but decreased CINC-1 and IL-6 in BALF and PLF only at 18 hours.ConclusionsIn an experimental model of abdominal sepsis, a single intravenous dose of glutamine administered after sepsis induction may modulate the inflammatory process reducing not only the risk of lung injury, but also distal organ impairment. These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.

Heterogeneous remodeling of lung vessels in idiopathic pulmonary fibrosis

Recently, several reports suggest differences in the vascularization of the various histopathologic patterns of parenchymal remodeling seen in usual interstitial pneumonia (UIP). In this study, we sought to validate the importance of vascular remodeling in patients with idiopathic pulmonary fibrosis (IPF) and to examine the relationship between vascular remodeling and parenchymal remodeling or pulmonary function. Open lung biopsies were performed in 57 patients with IPF, and vascular changes in alternating areas of parenchymal remodeling (UIP histologic patterns) were studied. Quantitative analysis of the internal area, internal perimeter, wall thickness, and surrounding cellularity of medium or large pulmonary arteries, as well as their distribution according to air/parenchymal ratios, was performed. Semiquantitative analysis also was used to determine the grade of vascular occlusion. An inverse association was found between vascularization and UIP parenchymal remodeling (p < 0.05); that is, the decreased internal luminal area and perimeter as well as the increased wall thickness run in parallel with progression from alveolar collapse toward severe mural-organizing fibrosis with honeycombing. Vascular regression (diminished internal area and perimeter of vessels) was also associated with higher FEV1, FVC, and RV values (r = 0.48, p< 0.05), reflecting a tight relationship between vascular remodeling and pulmonary function. A progressive regression of vascularization, reflected by different degrees of luminal occlusion after vascular remodeling, coincided with parenchymal remodeling (alveolar collapse, mural-organizing fibrosis, and honeycombing). This vascular regression may be responsible for the impaired wound healing and progressive fibroproliferation found in patients with IPF. Further studies are needed to determine whether this relationship is causal or consequential.

Different morphology, stage and treatment affect immune cell infiltration and long‐term outcome in patients with non‐small‐cell lung carcinoma

da Costa Souza P, Parra E R, Atanazio M J, da Silva O B, Noleto G S, Ab’Saber A M, de Morais Fernezlian S, Takagaki T & Capelozzi V L 
(2012) Histopathology 61, 587–596

Arterial and interstitial remodelling processes in non‐specific interstitial pneumonia: systemic sclerosis versus idiopathic

Aims:  To compare septal and vascular matrix remodelling, vascular occlusion, pulmonary function tests and survival between two groups: one with idiopathic non‐specific interstitial pneumonia (NSIP) and one with NSIP associated with systemic sclerosis (SSc).

Evaluation of the Combination of Cytology and Hybrid Capture to Safely Predict the High-Grade Lesion Status of Patients Treated with Conization with Large Loop Excision of the Transformation Zone

Objectives: This study aimed to verify whether human papillomavirus (HPV) testing after conization treatment has some potential usefulness for predicting patients’ outcome. Study Design: One hundred and twenty women were treated for HSIL by conization with large loop excision of the transformation zone (LLETZ). Cytology, colposcopy-guided biopsy, and hybrid capture 2 (HC2) HPV DNA tests were performed before the surgical procedure and every 6 months for 2 years at follow-up. Results: More than 90% of the patients tested positive for high-risk HPV prior to the surgical intervention. Six months after the cervical conization, 74.75% of the patients tested negative for high-risk HPV DNA, and 19.41% were positive. Of the women who were HC2 negative, 72 showed normal cytological smears, 3 ASC-US, 2 LSIL, and 1 HSIL. Of those who were HC2 positive, 8 showed normal smears, 2 ASC-US, 2 ASC-H, 5 LSIL, and 1 case had HSIL, AGC, and squamous cells invasive carcinoma. Clinically, the HSIL case with a negative HPV test did not show any sign of high-grade lesions, and the clinical follow-up did not show residual lesions. Conclusions: Negative HPV tests correlated with freedom from high-grade disease after 2 years of postconization follow-up, which strongly suggests that negative HPV tests predict the absence of cervical disease.

Parenchymal and Vascular Interactions in the Pathogenesis of Nonspecific Interstitial Pneumonia in Systemic Sclerosis and Idiopathic Interstitial Pneumonia

Background: Interstitial lung disease is a well-recognized prognostic factor in systemic sclerosis (SSc). As the prognosis in nonspecific interstitial pneumonia (NSIP) has been described to be better in collagen vascular disorders compared to the idiopathic forms, we hypothesize that the mechanisms of repair and remodeling are different between these 2 forms of the disease. Objectives: To compare the mechanisms of repair and remodeling between SSc-associated NSIP and the idiopathic form, its impact on pulmonary function tests and survival rates. Methods: We analyzed 18 biopsies from patients with NSIP associated with SSc and 22 with idiopathic NSIP and compared the epithelial and vascular densities as well as vascular activity. Results: Epithelial cell density was lower in SSc-NSIP when compared with idiopathic NSIP (p < 0.0001). Type II pneumocytes and Clara cells were reduced in idiopathic NSIP (p = 0.02). A decrease in microvessel density was found in SSc-NSIP compared to idiopathic NSIP (p < 0.0001). The vascular activity measured by VCAM expression was higher in NSIP-SSc when compared to the idiopathic group (p < 0.0001). The DLCO/VA in SSc-NSIP was more compromised. A direct association between vascular density and DLCO/VA was found (p = 0.02). There was no difference in the survival rate between the 2 groups after a follow-up of 36 months. Conclusions: Alterations in the epithelium and vasculature seem to differ in the pathogenesis of SSc-NSIP when compared to the idiopathic form of the disease. Further studies may be required to assess the significance of these findings and explore if they can provide prognostic and/or treatment information.

In Situ Evidence of Pulmonary Endothelial Activation in Patients with Granulomatosis with Polyangiitis and Systemic Sclerosis

IntroductionThe aim of this study was to investigate the in situ pulmonary endothelial activation in lung lesions of granulomatosis with polyangiitis (GPA) and systemic sclerosis (SScl).MethodsWe examined the endothelial expression of ICAM-1, VCAM-1, and E-selectin using immunohistochemistry on formalin-fixed, paraffin-embedded sections of lung lesions of GPA, interstitial lung disease associated with SScl and controls.ResultsA significantly enhanced expression of ICAM-1 and E-selectin was observed in GPA and SScl pulmonary endothelium compared to controls. VCAM-1 was more pronouncedly expressed in GPA compared to SScl.ConclusionThese observations are an evidence of in situ pulmonary vascular endothelial activation in lesions of GPA and SScl, adding information to the pathogenic knowledge of both diseases.

Implementing human papillomavirus testing in a public health hospital : challenges and opportunities

Objectives: Robust evidence now supports human papillomavirus (HPV) testing as a more effective option to screening and as more sensitive than cytology in detecting high-grade cervical intraepithelial neoplasia . Our goal was to analyze the performance of the Hybrid Capture II (HC2) assay for high-risk HPV (hrHPV) in women undergoing gynecological examination at a public health hospital as part of the evaluation of HPV screening as an alternative or complement to cytology. Study Design: This analysis is a subset of a cross-sectional study carried out at a large public hospital serving a predominantly low-resource population. A total of 705 women were enrolled; the sensitivity and specificity of each test were estimated and compared. Results: The analysis identified 272 hrHPV-positive women (mean age 36.3 years) and 433 hrHPV-negative women (mean age 41.2 years). HPV testing showed a significantly increased sensitivity of the HC2 assay versus cytology (84.5 vs. 69.7%; p < 0.0001) but a lower specificity (49.90 vs. 88.78%; p < 0.0001). Conclusion: The combination of both methods seems to be useful in improving detection of cervical lesions.

Histomorphometric Evaluation of the Ki-67 Proliferation Rate and CD34 Microvascular and D2-40 Lymphovascular Densities Drives the Pulmonary Typical Carcinoid Outcome

Ki-67 has shown promise as a prognostic factor in pulmonary carcinoids. In this study, we sought to validate the importance of Ki-67 and study the relationships between Ki-67 and other stromal biomarkers of vascular density. We examined Ki-67, CD34, and D2-40 in tumor tissues from 128 patients with surgically excised typical carcinoid of the lung. We used immunohistochemistry and morphometry to evaluate the amount of tumor staining for cellular proliferation (Ki-67), microvascular density (CD34-MVD), and D2-40 lymphovascular density. The main outcome was overall survival, considered as life expectancy until death from metastasis. Specimens from patients with central tumors showed high CD34-MVD (P = .01), which was also significantly associated with a compromised surgical margin, lymph node metastasis, and clinical stage Ib. Equally significant was high D2-40 lymphovascular density in central specimens with a compromised surgical margin and lymph node metastasis. A high Ki-67 proliferation rate was significantly associated with tumors from patients with clinical stage IIb, IIIa, and IV disease. Multivariate Cox model analysis demonstrated that tumor location and stage, surgical margin, tumor size, and N stage were significantly related to survival time (P < .05). Quantitative staining of the tumor for Ki-67 and CD34-MVD served as prognostic factors (P < .05), which were more relevant than the surgical and pathological stage. Ki-67 greater than 5% and CD34-MVD greater than 7% staining comprise a subset of patients with higher death hazard; this outcome may harbor evidence for further prospective studies of target therapy after surgical resection.