Unveiling the inflammatory face of antiplatelet drugs.
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Anti-Inflammatory Agents, Non-Steroidal↗
Biomedical subjects
F Santilli
Publications and source records attributed to F Santilli.
Association between circulating adiponectin and interleukin-10 levels in android obesity: effects of weight loss.
OBJECTIVE: Adiponectin inhibits vascular inflammation and increases IL-10 mRNA expression in human macrophages. Thus, we investigated the possible relationship between plasma adiponectin and IL-10 levels and the effects of a diet-induced moderate weight loss on both cytokines. PATIENTS AND STUDY DESIGN: Plasma adiponectin and IL-10 levels were analyzed in 64 android [body mass index (BMI), > 28 kg/m2; waist to hip ratio (WHR), > or = 0.86] and 20 gynoid [BMI, > 28 kg/m2; WHR, < 0.86] obese healthy women. Android obese women (49 +/- 14 yr) had a mean BMI of 37.1 +/- 5.3 kg/m2, similar to that of gynoid obese women (49 +/- 11 yr; BMI, 33.4 +/- 2.6 kg/m2). Twenty nonobese control women (46 +/- 11 yr; BMI, 25.2 +/- 2.2 kg/m2) were also studied. In 15 android obese women, measurements were repeated after a 12-wk diet period (1200 kcal/d). RESULTS: Median adiponectin [5.2 (range, 3.3-7.8) vs. 12.1 (9.7-13.9) vs. 15.0 (12.6-18.2) microg/ml; P < 0.0001] and IL-10 [1.8 (1.2-3.3) vs. 3.5 (2.9-4.3) and vs. 4.1 (3.5-4.8) pg/ml; P < 0.0001] levels were lower in android vs. gynoid vs. nonobese women. Among android obese women, low adiponectin levels were independently related (P < 0.0001) to decreased IL-10 levels, independently of BMI, WHR, or insulin resistance. No significant change in either median adiponectin or IL-10 levels was observed after body weight reduction (8 +/- 4 kg; P < 0.01), although percent changes in adiponectin paralleled those in IL-10 (P < 0.05). CONCLUSIONS: Android obesity is associated with a concomitant reduction of IL-10 and adiponectin levels. However, the antiinflammatory status of obesity might require prolonged periods of energy-restricted diets to revert to normal.
Adiponectin↗
Enhanced soluble CD40 ligand contributes to endothelial cell dysfunction in vitro and monocyte activation in patients with diabetes mellitus: effect of improved metabolic control.
AIMS/HYPOTHESIS: Inflammation plays a pathogenic role in the development of accelerated atherosclerosis in diabetes. Soluble CD40 ligand (sCD40L) is enhanced in diabetes; however, the molecular mechanisms linking sCD40L to accelerated atherosclerosis in diabetes are still unclear. We tested the hypothesis that sCD40L may be involved in the vascular complications in diabetes and exerts its effect by triggering inflammatory reactions on mononuclear and endothelial cells (ECs). METHODS: We studied 70 patients, 40 with type 2 and 30 with type 1 diabetes, with a history or physical examination negative for cardiovascular disease, and 40 non-diabetic and 30 healthy subjects, matched with the type 2 and type 1 diabetic patients, respectively. Plasma and serum sCD40L, and plasma soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin and monocyte chemo-attractant protein-1 (MCP-1) were measured. Adhesion molecules and MCP-1 release, the ability to repair an injury in ECs, and O2- generation in monocytes were analysed in vitro after stimulation with serum from patients or controls. RESULTS: Type 2 and type 1 diabetic patients had significantly higher sCD40L levels than controls. Furthermore, high sCD40L was associated with in vitro adhesion molecules and MCP-1 release, impaired migration in ECs and enhanced O2- generation in monocytes. Improved metabolic control was associated with a reduction of plasma sCD40L by 37.5% in 12 type 1 diabetic patients. Furthermore, elevated sCD40L in diabetic patients was significantly correlated with HbA1c levels. CONCLUSIONS/INTERPRETATION: Upregulation of sCD40L as a consequence of persistent hyperglycaemia in diabetic patients results in EC activation and monocyte recruitment to the arterial wall, possibly contributing to accelerated atherosclerosis development in diabetes.
Adult↗
The role of nitric oxide in the development of diabetic angiopathy.
Diabetic angiopathy is the main cause of morbidity and mortality in patients with diabetes mellitus. Clinical manifestations and pathophysiological mechanisms of diabetic angiopathy can be traced back to the development of endothelial cell dysfunction with alterations in the eNOS/NO system production or availability as the primum movens in its natural history. Hyperglycemia per se or through the accumulation of AGEs, increased oxidative stress, leading to NOS uncoupling and NO-quenching by excess superoxide and peroxynitrite, and individual genetic background are thought to be responsible for this NO metabolism imbalance. The complex interplay of these mechanisms results in a perturbation of the physiological properties of NO in the maintenance of endothelial homeostasis, such as vasodilation, anticoagulation, leukocyte adhesion, smooth muscle cell proliferation, and antioxidant capacity. Hence, abnormality in NO availability results in generalized accelerated atherosclerosis, hyperfiltration, glomerulosclerosis, tubulointerstitial fibrosis and progressive decline in glomerular filtration rate, and apoptosis and neovascularization in the retina. Indeed, the parallel development of nephropathy, retinopathy, and macroangiopathy may be considered as manifestations of endothelial dysfunction at distinct vascular sites. Given this scenario, intervention targeting any of the pathways involved in the NOS/NO system cascade may prove potential therapeutic targets in the prevention of long-term diabetic complications.
Animals↗
[Enucleation of a pleomorphic adenoma of the palate: a conservative choice].
The benign mixed tumor (pleomorphic adenoma) is the most common intraoral salivary gland tumor: more than 50% occurs on the hard and soft palate. The epidemiological data, histopathological and clinical features, preoperative diagnostic methodologies, treatment options, recurrence rates and prediction published in the literature for this neoplasm are discussed. A case of minor salivary gland tumor of the palate in a 26 year old man is reported. The therapy chosen was a surgical conservative enucleation of the lesion. Histological examination showed pleomorphic adenoma; there is no recurrence after 2 years.
Adenoma, Pleomorphic↗
Increased vascular endothelial growth factor serum concentrations may help to identify patients with onset of type 1 diabetes during childhood at risk for developing persistent microalbuminuria.
This study was designed to evaluate whether vascular endothelial growth factor serum concentrations may identify adolescents with onset of type 1 diabetes during childhood at greater risk to develop persistent microalbuminuria and incipient diabetic nephropathy. In January 1989, vascular endothelial growth factor serum levels were measured in 101 normoalbuminuric diabetic children and adolescents (aged 7-14.9 yr; onset of diabetes before age 18 yr; duration of diabetes >7 yr). Participants were clinically examined at baseline and annually thereafter. Vascular endothelial growth factor serum concentrations were measured every year during the 8-yr follow-up period. Over 8 yr, 11 of 101 patients (10.9%) developed persistent microalbuminuria; no patient developed overt nephropathy. The risk of developing microalbuminuria was higher in children with increased vascular endothelial growth factor serum levels (using 160 pg/ml as the arbitrary cut-off point; group 1) compared with those with normal vascular endothelial growth factor serum levels at the beginning of the study (group 2; 19.2 vs. 2.0%; P < 0.01; sensitivity, 90.9%; specificity, 53.3%). The odds ratio for the occurrence of microalbuminuria after adjustment for confounding variables (albumin excretion rate, sex, hemoglobin A(1c), mean blood pressure, cholesterol, and triglycerides) in type 1 diabetic adolescents with elevated vascular endothelial growth factor serum levels was 4.1 (95% confidence interval, 2.0-10.9). These results suggest that vascular endothelial growth factor serum concentrations may be one of the predictors and risk factors for microalbuminuria and incipient diabetic nephropathy in adolescents and young adults with onset of diabetes during childhood. Persistently increased vascular endothelial growth factor serum levels may help to identify normotensive, normoalbuminuric patients with type 1 diabetes who are predisposed to develop persistent microalbuminuria later in life.
Adolescent↗
Role of growth factors in the development of diabetic complications.
The structural changes characterising diabetic microangiopathy, which may be referred to as 'abnormal growth' and 'impaired regeneration', strongly suggest a role for a number of aberrantly expressed growth factors, possibly acting in combination, in the development of these complications. This initial speculation has been supported by the detection of increased concentrations of several growth factors in the target tissues of diabetic long-term complications, and by enhanced expression of these growth factors consequent to the activation of the biochemical pathways linking hyperglycaemia to microvascular changes: the polyol pathway; non-enzymatic glycation of proteins; vasoactive hormones; oxidative stress, and hyperglycaemic pseudohypoxia. As to nephropathy, insulin-like growth factor I (IGF-I) seems to be implicated in the earlier stages of the disease, while transforming growth factor beta (TGF beta) is involved both in the early and later stages, being responsible, at least in part, for extracellular matrix (ECM) accumulation. Vascular endothelial growth factor (VEGF) plays a pivotal role both in non-proliferative and proliferative retinopathy. Finally, deficiency of several neurotrophic factors, namely nerve growth factor (NGF) and IGF-I has been related to the degeneration or impaired regeneration occurring in diabetic neuropathy. Knowledge of the involvement of growth factors in diabetic microangiopathy opens the way to new therapeutic interventions aimed at blocking the deleterious actions of several growth factors.
Diabetes Mellitus, Type 1↗
Diabetes mellitus in the pre-school child.
Diabetes mellitus presents rarely in the pre-school child and presents specific problems because of the peculiarity of the young child physiology. Pathogenesis involves the classic immunological mechanisms, with a higher incidence of other autoimmunity and family history of diabetes. Because of the rarity of the condition in this age group, the delay of the recognition of the signs and symptoms, which are often subtle at onset, determines the increased incidence of ketoacidosis. The reasons for the lower glycaemic control in this age group include the persistence of endogenous insulin, but also a more detailed involvement by the parents in organising diabetes. For the same reason ketoacidosis is an unusual occurrence after diagnosis. As to insulin therapy, three or more injections a day should be recommended, as in the older child, while the modern devices for blood glucose monitoring have proved useful to improve glycaemic control and to decrease the frequency of nocturnal hypoglycaemia, which gives particular concern given the vulnerability of the nervous system in this age group. Management of diabetes in the pre-school child may result very difficult for both parents and health carers because of the erratic daily pattern of activity, sleep and feeding; however, with a cautious strategy which involves insulin therapy, diet and monitoring it is possible to achieve satisfactorily the following aims: physical well-being of the young child, normal growth, lack of hyperglycaemia or hypoglycaemia, acceptable value of glycosilated haemoglobin.
Child, Preschool↗
Antibiotic prophylaxis in elective neurosurgery. Epidemiological study.
The authors present an epidemiological study of patients who have undergone elective neurosurgery and who have been treated with different types of antibiotics throughout a ten year time span. From the statistic analysis of the different parameters taken into consideration (administering modalities of the short-term and long-term antibiotic, type of sepsis encountered, isolated microorganisms) the authors show, as a result, that the long-term antibiotic prophylaxis is a clearly improper method; the short-term prophylaxis is a correct method the effect of which is, however, still controversial as it does not modify a natural low percentage of infections in elective neurosurgery. The role given to the antibiotic seems much less important compared with the adoption of correct antiseptic measures and of proper nursing.
Anti-Bacterial Agents↗
Vascular injury related to lumbar disk surgery.
The authors report a case of left common iliac artery injury, as a complication of diskectomy, in a 57 year-old male patient, with herniated disk at L4-L5. A review shows that L4-L5 disk space is the most common site for this rare complication of lumbar disk surgery.
Hemorrhage↗
Long-term effects of befunolol on the corneal endothelium and the consensual ophthalmotonic reaction.
In a double-blind study, 30 patients with ocular hypertension were randomly assigned to receive one drop of 0.5% befunolol or placebo (the drug vehicle) in each eye twice daily for 120 days. The befunolol used contained no preservatives. Before and after treatment the number and shape of the endothelial cells of the five corneal sectors were evaluated. After 120 days of twice-daily application of befunolol or placebo, no changes in the shape or density of the corneal cells were found in any patient. No differences in the patients receiving befunolol or placebo were noted. The consensual ophthalmotonic reaction was studied in 15 of the patients before and after befunolol administration. A significant decrease in intraocular pressure was noted at 30 minutes and at 1, 2, 3, 4, 5, and 6 hours after befunolol. Intraocular pressure also decreased significantly at 1 to 4 hours after placebo, and then returned to pretreatment levels at 6 hours.
Adrenergic beta-Antagonists↗
Localized bacillary angiomatosis in the oral cavity: observations about a neoplasm with atypical behavior. Description of a case and review of the literature.
Bacillary angiomatosis is a rather frequent infectious pathology appearing mainly in the skin but can also affect the liver, spleen, heart, bones, lungs, muscles, central nervous system and other organs. The localization of the lesion in the oral cavity is rather rare, as it is evident in the literature. Bacillary angiomatosis can be clinically similar to the Kaposi's sarcoma and histologically confused with angiosarcoma, epitheloid hemangioma and pyogenic granuloma. A case of bacillary angiomatosis of the oral cavity in an immuno-competent patient is described. The high tendency to relapse, the capability in migration and to involve several localizations at the same time have induced the authors to deepen the research to exclude the possibility that it could be a Kaposi's sarcoma or a pyogenic granuloma and to get to an accurate diagnosis in order to resolve the disease.
Adolescent↗