Marlise B. A. Montes

Sepsis-Induced Acute Lung Injury (ALI) Is Milder in Diabetic Rats and Correlates with Impaired NFkB Activation

Acute lung injury (ALI) develops in response to a direct insult to the lung or secondarily to a systemic inflammatory response, such as sepsis. There is clinical evidence that the incidence and severity of ALI induced by direct insult are lower in diabetics. In the present study we investigated whether the same occurs in ALI secondarily to sepsis and the molecular mechanisms involved. Diabetes was induced in male Wistar rats by alloxan and sepsis by caecal ligation and puncture surgery (CLP). Six hours later, the lungs were examined for oedema and cell infiltration in bronchoalveolar lavage. Alveolar macrophages (AMs) were cultured in vitro for analysis of IκB and p65 subunit of NFκB phosphorylation and MyD88 and SOCS-1 mRNA. Diabetic rats were more susceptible to sepsis than non-diabetics. In non-diabetic rats, the lung presented oedema, leukocyte infiltration and increased COX2 expression. In diabetic rats these inflammatory events were significantly less intense. To understand why diabetic rats despite being more susceptible to sepsis develop milder ALI, we examined the NFκB activation in AMs of animals with sepsis. Whereas in non-diabetic rats the phosphorylation of IκB and p65 subunit occurred after 6 h of sepsis induction, this did not occur in diabetics. Moreover, in AMs from diabetic rats the expression of MyD88 mRNA was lower and that of SOCS-1 mRNA was increased compared with AMs from non-diabetic rats. These results show that ALI secondary to sepsis is milder in diabetic rats and this correlates with impaired activation of NFκB, increased SOCS-1 and decreased MyD88 mRNA.

The environmental cofactors in carcinogenesis in high risk HPV/HIV-positive women

The objective of the present study was to assess the presence of human papilloma virus (HPV) in HIV-infected women, with comparison between the Papanicolaou cytologic technique and the molecular PCR technique, as well as to determine the type of HPV, to measure cellular immunocompetence and to identify the presence of risk factors for the acquisition of HPV infection. Thirty HIV-infected women were selected. Vaginal and endocervical samples were collected from 27 of them. The smears were examined by 3 experienced cytologists to diagnose the presence of HPV by the Papanicolaou technique and the results were compared to HPV detection and typing by PCR. HPV-infected patients were interviewed in order to identify the presence of risk factors for the acquisition of the virus. Eight of the 27 patients analyzed (29%) presented HPV in endocervical samples submitted to PCR, 6 of them (75%) presented HPV involving a high risk of development of cervical cancer. For 5 of these patients, the cytologic diagnosis was not confirmed by PCR. When cellular immunocompetence was related to HPV infection, PCR revealed a diagnosis of HPV in 37.50% of the patients at intermediate risk for HPV infection and in 83.33% of the patients at high risk for HPV infection. These immunologically compromised HPV-infected patients are at higher risk of developing cervical neoplasia. We showed here that PCR is adequate for HPV detection and that, if only the Papanicolaou method is used for the follow-up of these patients, we will not provide good prevention of cervical cancer.

Third-generation progestogen type influences hemostatic changes caused by oral contraceptives in Brazilian women ☆

We compared the effects of two third-generation progestogens, desogestrel (DSG) and gestodene (GSD), on coagulation and fibrinolysis in Brazilian users of oral contraceptives (OCs). Forty-six women were evaluated before treatment and after six cycles of treatment. The coagulation, anticoagulant, and fibrinolytic systems were investigated. During the use of the DSG-containing OC, the activity of factors VII, VIII, IX, X, and XII increased significantly whereas the GSD-containing OC caused no changes in coagulation parameters. Concerning the anticoagulant pathways, the DSG-containing OC increased protein C levels and decreased total protein S levels, and the GSD-containing OC only decreased total protein S. Both OCs increased plasminogen activity, although the DSG-containing OC increased fibrin degradation products levels and decreased the tissue plasminogen activator antigen. In conclusion, we have found that in Brazilian women the effects of DSG and GSD on hemostatic parameters are different and, therefore, third-generation progestogens may not contribute equally to the thrombotic risk.

Effect of antiretroviral therapy on hemostasis in Brazilian pregnant women with HIV infection.

Clinical observation shows pregnant women under antiretroviral therapy present bleeding episodes at delivery, although this therapy promotes a decrease in fibrinolysis in nonpregnant patients, suggesting a prothrombotic state in the former. Since these drugs provoke hepatic disorders, they can cause bleeding disturbances. We investigated effects of antiretroviral therapy on hemostasis in pregnant women. Two groups were studied: pregnant women with HIV (n = 11), and (control) pregnant women without HIV (n = 7). Four blood samples were collected from each individual in both groups: one at the beginning of pregnancy before treatment, two during pregnancy and therapy, and one 6 weeks after delivery. Treatment was performed according to recommendations of the Brazilian Health Department for the evaluation of the prothrombin time, activated partial thromboplastin time, factors VII, X, and XII, fibrinogen concentration, protein C, protein S, tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1, and fibrin degradation products (FbDPs). Statistical analysis demonstrated pregnancy caused increased factor VII (P = 0.0313), factor X (P = 0.0156) and factor XII (P = 0.0156) activity, fibrinogen concentration (P = 0.0156), t-PA (P = 0.0313), plasminogen activator inhibitor-1 (P = 0.0156) and FbDP levels (P = 0.0313). HIV infection caused increased factor XII (P = 0.0114), t-PA (P = 0.0346) and FbDPs (P = 0.0003), and decreased protein S levels (P = 0.0441). Antiretroviral therapy reduced the activated partial thromboplastin time (P = 0.0114) and protein S (P = 0.0012), and increased t-PA (P = 0. 0204) and FbDP levels (P = 0.0154). The results suggest a prothrombic state developing during pregnancy, maintenance of hemostatic equilibrium in HIV infection and occurrence of hyperfibrinolysis, not due to hepatotoxicity, during antiretroviral therapy, causing the clinically observed bleeding episodes.

Efeitos do contraceptivo oral contendo 20 µg de etinilestradiol e 150 µg de desogestrel sobre os sistemas de coagulação e fibrinólise

The aim of this work is to evaluate the effects on coagulation and fibrinolysis of the oral contraceptives of third generation in Brazilian women and the impact on these effects by reducing ethinyl estradiol dosage. Eleven Brazilian women taking monophasic oral contraceptive containing 20 µg of ethinyl estradiol combined with 150 µg of desogestrel for six cycles consecutively entered this study. The effects on parameters pro-coagulants, anticoagulants, pro-fibrinolytics and fibrin turnover index were evaluated. The results from oral contraceptive increased significatively the factors VIII, IX, X and XII. With respect to coagulation inhibitors, no antithrombin changes were noted in both groups, increase in the levels of protein C and decrease in the levels of protein S total were noted. Concerning the fibrinolytic parameters, the oral contraceptive increased the plasminogen activity, although no changes on t-PA, and alpha-2-antiplasmin were observed. Similary, no changes on the levels of fibrin degradation products were observed, thus indicating that oral contraceptives did not interfere with generation and degradation of fibrin. The results obtained indicate that the oral contraceptives studied did not promote enough pro-fibrinolytic changes so as to state that a re-establishment occurs on haemostatic balance. Therefore, we suggest the use of this oral contraceptive can result in thromboembolic episode mainly in association with other factors such as congenital deficiency of natural clotting inhibitor antithrombin, protein C or protein S.

Efeito da terapia de reposição hormonal sobre o estado férrico

BACKGROUND: In literature there are many studies about iron status in children, adolescents and fertile women, but investigations of iron stores and erythrocyte parameters variation after hormone replacement therapy (HRT) are rare. Elevated iron stores, oxidative stress, and estrogen deficiency may place premenopausal and menopausal women in a risk of developing heart disease and cancer. OBJECTIVE: To evaluate the effect of HRT in erythrogram and iron status in premenopausal and menopausal women. METHODS: Hematological indices and iron status were assessed by erythrogram, serum ferritin, iron and transferrin iron-binding capacity (TIBC) in 30 pre- and menopausal women before and after HRT with medroxiprogesterone and estradiol. The blood exam, serum iron and iron-binding capacity were determined by laboratory classic methods, while ferritin was measured by quimiluminescent assay. RESULTS: HRT use was followed by a significant reduction in the absolute number of erythrocyte, an increase of hematimetric indexes and a trend towards a reduction of serum iron levels and TIBC. No alterations on serum ferritin and transferrin saturation index were detected after HRT. DISCUSSION AND CONCLUSION: In the present study, alterations in red cell and iron parameters, which could impair the use of HRT in premenopausal and menopausal women, were not observed. Our results suggest that HRT in premenopausal women are beneficial to iron status, maintaining normal iron stores and promoting elevation of red cells indexes.