Nitric oxide modulates Na+, K+-ATPase activity through cyclic GMP pathway in proximal rat trachea

The present work demonstrated that nitric oxide (NO) modulates Na+, K+-ATPase activity in the proximal rat trachea. Sodium nitroprusside induced concentration-dependent (10-100 microM) stimulation in proximal trachea Na+, K+-ATPase activity. The effect was specific for Na+, K+-ATPase since Mg-ATPase activity was unaffected. This NO-donor changed neither Na+, K+-ATPase nor Mg-ATPase activity in the distal segment. The modulatory action on Na+, K+-ATPase induced by sodium nitroprusside was linked to an increase in nitrates/nitrites and cyclic GMP levels in proximal segments. Modulation of proximal Na+, K+-ATPase activity by sodium nitroprusside was mimicked by S-nitroso-N-acetylpenicillamine (100 microM) and 8-bromo-cyclic GMP (100 microM). Both sodium nitroprusside and 8-bromo-cyclic GMP effects on Na+, K+-ATPase activity of proximal segments of trachea were blocked by 2 microM of KT 5823 (a cyclic GMP-dependent protein kinase inhibitor), but not by 0.5 microM of KT 5720 (a cyclic AMP-dependent protein kinase inhibitor). Both kinase inhibitors decreased proximal Na+, K+-ATPase activity, but did not change Mg-ATPase activity. Okadaic acid (1 microM), a phosphatase-1 inhibitor, increased proximal Na+, K+-ATPase but not Mg-ATPase activity. The effect of okadaic acid was non-additive with that of 8-bromo-cGMP on Na+, K+-ATPase activity. Our results suggest that NO modulates proximal rat trachea Na+, K+-ATPase activity through cyclic GMP and cyclic GMP-dependent protein kinase.     

Effects of eggplant (Solanum melongena) on the atherogenesis and oxidative stress in LDL receptor knock out mice (LDLR(-/-)).

Eggplant (Solanum melongena) has been used as hypocholesterolemic agent in many countries. However, few controlled studies were addressed to this subject and atherogenesis. We have evaluated the effect of eggplant on cholesterol metabolism and atherogenesis in LDLR(-/-) mice. Animals were fed on chow (n=17) or atherogenic (n=21) diet during 12 weeks receiving water (control) or eggplant extract. Liver, serum and fecal lipids, together with serum lipoproteins were measured. Oxidative stress was evaluated through conjugate diene formation and ox-LDL antibodies by enzyme immunoassay. Atherosclerotic lesions were measured in different sites of aorta. Total cholesterol and atherogenic lipoproteins did not decrease after eggplant intake. Animals receiving eggplant and chow diet showed increased anti-ox-LDL antibodies and a decreased lag phase of conjugated diene formation, indicating a higher oxidative stress than controls. No differences were seen in lesion area of aortic valve. Eggplant extract had high histamine and other amine levels that could enhance LDL oxidation and its endocytosis. Eggplant did not decrease plasma cholesterol nor prevent the development of atherosclerosis in LDLR(-/-) mice. Surprisingly, eggplant increased oxidative stress, representing a risk factor for atherosclerosis. These results did not support the use of eggplant extract as hypocholesterolemic agent.     

Role of Intracystic Cytokines and Nitric Oxide in Ovarian Neoplasms

The development of new biomarkers for the diagnosis and prognosis of ovarian cancer may provide an opportunity for new therapies. In this study, we aimed to compare cytokines (interleukin [IL]‐2, IL‐5, IL‐6, IL‐8, IL‐10 and tumour necrosis factor [TNF]‐α) and nitric oxide (NO) metabolite levels in non‐neoplastic tumours, benign primary ovarian tumours and malignant primary ovarian neoplasms. The secondary aim was to relate cytokine and intracystic NO metabolite levels to clinical, laboratory and pathologic characteristics for patients with primary ovarian malignancies. We evaluated 110 patients with adnexal masses. Cytokine concentrations were quantified by enzyme‐linked immunosorbent assay and nitrate concentrations by enzymatic reduction of nitrite by nitrate reductase. Patients with malignant neoplasms had higher IL‐6, IL‐8 and NO levels compared to patients with benign neoplasms. Histologic grade 1 tumours were associated with elevated IL‐2 levels, whereas anaemia was associated with elevated IL‐6 levels. On average, those patients with elevated IL‐8 levels also had a neutrophil/lymphocyte ratio (NLR) greater than 2.6 and less than 36 months of disease‐free survival (DFS). Patients with normal CA 19‐9 levels had elevated IL‐10 levels. TNF‐α was elevated in patients with two carcinogenesis and those with a platelet/lymphocyte ratio (PLR) less than 300. NO levels were higher in patients with an NLR less than 2.6 and CA 19‐9 greater than 35 U/ml. Elevated intracystic cytokine levels, especially IL‐6 and IL‐8, are associated with worse prognosis in ovarian cancer.     

Streptococcal tonsillitis as a cause of urticaria: Tonsillitis and urticaria

BackgroundThe primary role of infections in chronic urticaria (CU) is controversial. We hypothesised that streptococcal tonsillitis (ST) could be a primary cause of CU or acute recurrent urticaria (ARU).MethodsRetrospective study of 14 outpatients observed between January 2000 and December 2009, with CU/ARU and clinical and/or laboratorial suspicion of an aetiopathogenic link with ST. Clinical history, objective examination and laboratorial study were looked for. Three groups were defined: spontaneous resolution of urticaria, resolution after tonsillectomy, and still symptomatic.ResultsIn these patients, a causal relationship between ST and urticaria is supported by: markers of streptococcal infection, the perception of a clinical relationship between tonsillitis and urticaria, the decrease of urticaria severity with early antibiotherapy to tonsillitis and urticaria resolution after tonsillectomy.ConclusionsOur study encourages the investigation of tonsillitis in these otherwise idiopathic patients, especially until young adulthood and even in the absence of any symptoms.     

Activity of Bisnaphthalimidopropyl Derivatives against Trypanosoma brucei

Current treatments for African trypanosomiasis are either toxic, costly, difficult to administer, or prone to elicit resistance. This study evaluated the activity of bisnaphthalimidopropyl (BNIP) derivatives against Trypanosoma brucei. BNIPDiaminobutane (BNIPDabut), the most active of these compounds, showed in vitro inhibition in the single-unit nanomolar range, similar to the activity in the reference drug pentamidine, and presented low toxicity and adequate metabolic stability. Additionally, using a murine model of acute infection and live imaging, a significant decrease in parasite load in BNIPDabut-treated mice was observed. However, cure was not achieved. BNIPDabut constitutes a new scaffold for antitrypanosomal drugs that deserves further consideration.     

Longer Times of Receipt of Adjuvant Endocrine Therapy Correspond to Improved Functional Capacity and Lower Adiposity in Women Receiving Adjuvant Therapy

Purpose

To study the use of functional capacity (FC) level and duration of aromatase inhibitor (AI) therapy with adiposity parameters in women with breast cancer.