Platelet Cyclic GMP Levels Are Reduced in Patients with Primary Aldosteronism.

BACKGROUND AND AIM: Nitric oxide inhibits platelet aggregation by increasing the second messenger cyclic guanosine-3',5'-monophosphate (cGMP) through the activation of soluble guanylyl cyclase in target cells. Within this context, the oxidative stress associated with the aldosterone excess impairs the nitric oxide availability. Thus, the aim of the present study was to assess the impact of chronic aldosterone excess on the platelet nitric oxide/cGMP pathway in humans. METHODS: The levels of cGMP were evaluated in platelets of male patients, 12 with primary aldosteronism (PA) and 32 with uncomplicated essential hypertension (EH), matched for age and blood pressure (BP) values. RESULTS: PA and EH patients were 52.8 ± 3 years old and 51.6 ± 1.6 years old, respectively. Systolic and diastolic BP were 158 ± 5.0 mmHg and 105.9 ± 2.3 mmHg in PA and did not differ compared to EH patients (156.6 ± 2.4 mmHg and 104.7 ± 1.2 mmHg). Mean aldosterone levels were significantly higher in PA (25.5 ± 8.8 ng/dL) compared toEH (8.11 ± 0.73 ng/dL), whereas potassium was significantly lower in PA (3.52 ± 0.18 mEq/L) compared to EH (4.08 ± 0.04 mEq/L). Aldosterone and potassium were inversely related (r = -0.49, p = 0.0006) in the whole study population (n = 44). Platelet cGMP was significantly lower in PA (5.1 ± 0.36 pM/109 cells) than in EH (7.1 ± 0.53 pM/109 cells), and in the entire study cohort, it was directly related to plasma potassium (r = 0.43, p = 0.0321). CONCLUSIONS: These results show an impairment of nitric oxide/cGMP signaling in platelets of PA patients. This effect is likely related to the potassium-depleting effect of chronic aldosterone excess. Future studies are needed to understand whether the platelet nitric oxide/cGMP system is involved in the atherothrombotic events in these patients.

Industrial Pollutants and Nasopharyngeal Cancer: An Open Question.

INTRODUCTION AND OBJECTIVES: Nasopharyngeal Carcinoma represents 0.7% of the total cancer cases in the world with an ASR index of 1.7 and is widely associated with Epstein-Barr virus. It is not common in Italy (ASR index of 0.5) while in China (ASR 1.9), one third of the clinical cases are observed in Guangdong (ASR index 11.3). It is also quite common in Malaysia and Indonesia. The activation of the cancerogenesis process happens after the exposure to some environmental parameters that epidemiological studies have indicated with various dietary habits, mainly for salted fish consumption. The purpose of this work is to highlight such as exposure to compounds, such as formaldehyde, which is present in the different working conditions of these countries and may lead to the real cause to establish the carcinogenic process. MATERIALS AND METHODS: The most recent publications regarding the impact of various external factors on Pub Med, Google, TOXLINE, Chem Abstract, were analyzed with the radiological data that were found in Milan hospitals database. RESULTS: The relationship between food consumption and nasopharyngeal cancer are not clear and statistically insignificant in Indonesia. In Malaysia, the preparation of natural rubber for the use of formaldehyde is a dangerous environmental factor. The same exposure is a risk factor in Guangdong, where many workers are employed in the wood panel industry. Incidence of cancer in these Chinese ethnic groups decreases when they migrate to other countries. In the last 5 years, few cases were recorded in Italy, without any apparent change in ethnic environmental factors or HBV infection Discussion: In the production of natural rubber, a lot of people are exposed to formaldehyde during the various steps of preparation and production such as stripping, drying and coagulation without observing proper environmental hygiene precautions. The same working conditions are present in industrial production of wood panels in Guangdong, China. The relationship between exposure to formaldehyde and nasopharyngeal cancer is demonstrated by the fact that epidemiological studies on the population of this Chinese district whose immigrant populations were not exposed to these pollutants, the appearance of these tumors decreases. Also an examination of our radiological data in Italy shows that in about one hundred sixty cases of nasopharyngeal cancer none of the patients were Indonesian or Chinese Conclusion: The preliminary results of our study suggest that EPST-BARR virus could be a risk factor if associated with exposure to compounds such as formaldehyde which is present in industrial productions of countries like Indonesia, Malaysia, and China.

The Possible Role of Diabetes in the Etiology of Laryngeal Cancer.

BACKGROUND: Laryngeal cancer and oral cancer are not always correlated with genetic mutations, HPV infection, smoking, and alcohol abuse. In the absence of these risk factors, there is an increase on these cancers with a parallel increase of diabetes. The aim of this study is to verify if diabetes could be a risk factor for the laryngeal cancer. METHODS: A questionnaire was given to a group of ninety laryngectomees to verify if these patients have presented diabetes and xerostomia before surgery. In two groups, diabetics and healthy persons, the values of the salivary mucins and the pH were evaluated. The results were statistically analysed using Fisher Exact Test and Chisquare Test Results: Diabetes is a risk factor: p= 0.0445 for laryngectomees male vs control group. Xerostomia inlaryngectomees male is a risk factor: p= 0.050. The values of mucins and pH in diabetic group show significant difference: p=0.05 vs control group Discussion: In all autoimmune diseases, a decrease in the value of pH and salivary flow consequently decreases the value of spinnbarkeit which measures the capacity of the mucous layer to adhere to the epithelium and alter the protective oral mucin layer. We find that diabetes is epidemiologically correlated with laryngeal cancer. In fact, only diabetes increases the concentration of salivary mucins with a formation of mucin layer even more reduced, and so completely ineffective in protecting the mucosa. CONCLUSIONS: The increase of mucin secretion in diabetes alters much the protective layer allowing the risk factors to promote cancer growth.

Mesenchymal stem cells: potential for therapy and treatment of chronic non-healing skin wounds.

Wound healing is a complex physiological process including overlapping phases (hemostatic/inflammatory, proliferating and remodeling phases). Every alteration in this mechanism might lead to pathological conditions of different medical relevance. Treatments for chronic non-healing wounds are expensive because reiterative treatments are needed. Regenerative medicine and in particular mesenchymal stem cells approach is emerging as new potential clinical application in wound healing. In the past decades, advance in the understanding of molecular mechanisms underlying wound healing process has led to extensive topical administration of growth factors as part of wound care. Currently, no definitive treatment is available and the research on optimal wound care depends upon the efficacy and cost-benefit of emerging therapies. Here we provide an overview on the novel approaches through stem cell therapy to improve cutaneous wound healing, with a focus on diabetic wounds and Systemic Sclerosis-associated ulcers, which are particularly challenging. Current and future treatment approaches are discussed with an emphasis on recent advances.

Clinical and functional correlates of platelet cyclic GMP in essential hypertensives.

BACKGROUND: Platelets play a central role in atherothrombosis, which is responsible of major cardiovascular complications in human hypertension. Nitric oxide (NO) inhibits platelet aggregation via the second messenger cyclic guanosine monophosphate (cGMP). In essential hypertensives (EHs), we examined the relationship between platelet cGMP and clinical, hemodynamic, humoral variables as well as the responses to aggregating agents. METHODS: In untreated EHs (male/female 106/43, age 44.4 +/- 1.1 years, smokers yes/no 38/111), blood pressure (BP), heart rate (HR), and stroke volume (SV) (impedance cardiography) were assessed after supine rest and venous blood was sampled for platelet cGMP (radioimmunoassay on acid extracts of washed platelets), plasma cGMP, atrial natriuretic peptide (ANP), renin activity, aldosterone and platelet aggregation to epinephrine (EPI, 5 micromol/l), and adenosine diphosphate (ADP) (4 micromol/l) (optical aggregometry on platelet-rich plasma (PRP)). RESULTS: Platelet cGMP (7.0 +/- 0.3 pmol/10(9) cells, mean +/- s.e.m.) was lower in males and smokers than in their counterparts (P < 0.01 for both). Among the variables tested, platelet cGMP was related to number of cigarettes (-0.21), high-density lipoprotein cholesterol (HDLc) (r = 0.32), aldosterone (r = -0.21), and hemoglobin (-0.16); in a multivariate analysis that also included sex, HDLc was the best predictor of platelet cGMP. The aggregating response to EPI (r = -0.28), but not to ADP (r = -0.07, ns), was inversely related to platelet cGMP levels. CONCLUSIONS: cGMP in resting platelets of EHs is positively predicted by HDLc and is inversely related to the aggregating response to EPI. It is suggested that a defect of the platelet NO/cGMP system could identify uncomplicated EHs at higher risk of thrombotic events during surges of sympathetic activity.

Elevated serum procollagen type III peptide in splanchnic and peripheral circulation of patients with inflammatory bowel disease submitted to surgery.

BACKGROUND: In the hypothesis that the increased collagen metabolism in the intestinal wall of patients affected by inflammatory bowel disease (IBD) is reflected in the systemic circulation, we aimed the study to evaluate serum level of procollagen III peptide (PIIIP) in peripheral and splanchnic circulation by a commercial radioimmunoassay of patients with different histories of disease. METHODS: Twenty-seven patients, 17 with Crohn and 10 with ulcerative colitis submitted to surgery were studied. Blood samples were obtained before surgery from a peripheral vein and during surgery from the mesenteric vein draining the affected intestinal segment. Fifteen healthy age and sex matched subjects were studied to determine normal range for peripheral PIIIP. RESULTS: In IBD patients peripheral PIIIP level was significantly higher if compared with controls (5.0 +/- 1.9 vs 2.7 +/- 0.7 microg/l; p = 0.0001); splanchnic PIIIP level was 5.5 +/- 2.6 microg/l showing a positive gradient between splanchnic and peripheral concentrations of PIIIP. No significant differences between groups nor correlations with patients' age and duration of disease were found. CONCLUSIONS: We provide evidence that the increased local collagen metabolism in active IBD is reflected also in the systemic circulation irrespective of the history of the disease, suggesting that PIIIP should be considered more appropiately as a marker of the activity phases of IBD.