Effects of antioxidant supplementation on postprandial oxidative stress and endothelial dysfunction: a single-blind, 15-day clinical trial in patients with untreated type 2 diabetes, subjects with impaired glucose tolerance, and healthy controls

BACKGROUND: Increased generation of reactive oxygen species (ROS) and oxidative stress may be of crucial importance in the pathogenesis of endothelial damage. Furthermore, there is understood to be a relationship between endothelial damage, glycemic control, disorders of lipid metabolism, and coagulative hemostatic disorders. OBJECTIVE: This study investigated within- and between-group changes in various circulating markers of oxidation-reduction balance and endothelial function after a balanced moderate-fat meal with and without antioxidant supplementation in patients with early-stage, untreated type 2 diabetes mellitus; subjects with impaired glucose tolerance (IGT); and healthy controls. METHODS: In this single-blind, controlled clinical study, groups of patients with type 2 diabetes and subjects with IGT were identified and compared with a group of healthy controls. All groups followed a controlled, well-balanced diet for 10 days before and throughout the study. Before and after consumption of a standardized moderate-fat meal, plasma levels of oxidants (malondialdehyde, 4-hydroxynonenal, oxidized low-density lipoprotein), the antioxidant glutathione peroxidase, and markers of endothelial function (NO, endothelin-1, von Willebrand factor [vWF], vascular cell adhesion molecule-1 [VCAM-1]) were determined. These measures were then reassessed after 15 days of standard antioxidant treatment consisting of a thiol-containing antioxidant (N-acetylcysteine 600 g/d), a bound antioxidant (vitamin E 300 g/d), and an aqueous phase antioxidant (vitamin C 250 mg/d). The efficacy of antioxidant treatment in reversing abnormalities in oxidation-reduction balance after a moderate-fat meal was assessed by evaluating changes in plasma levels of ROS on the morning of the 16th day following an overnight fast. Safety was monitored in terms of adverse events, vital signs, physical findings, and laboratory values. RESULTS: The study included 46 patients with type 2 diabetes (23 men, 23 women; mean [SD] age, 41 [3] years; mean body mass index [BMI], 24 [2] kg/m(2)), 46 with IGT (23 men, 23 women; mean age, 39 [3] years; mean BMI, 23 [3] kg/m(2)), and 46 control subjects (23 men, 23 women; mean age, 40 [1] years; mean BMI, 22 [1] kg/m(2)). Before supplementation, all 3 groups had significantly increased levels of oxidants, vWF, and VCAM-1 (all, P < 0.001) and significantly decreased levels of antioxidants and NO (both, P < 0.001) after consumption of a moderate-fat meal. After 15 days of antioxidant treatment, significant improvements in these measures were seen in all groups (P < 0.05). CONCLUSIONS: This study showed changes in oxidation-reduction balance, NO bioavailability, and nonthrombogenic endothelial factors after a moderate-fat meal in patients with type 2 diabetes and those with IGT, but these postprandial changes were reverse in all subjects after 15 days of standard antioxidant supplementation. These findings suggest that the use of anti-oxidants may have decreased oxidative stress in these subjects.     

Type III a glycogenosis

Summary A combined biochemical and ultrastructural study, including cytochemical and negative staining techniques, has been made of three tissues, liver, muscle and leucocytes, in a case of type III A glycogenosis.The electron microscopic studies revealed an increased accumulation of glycogen in the liver, in the skeletal muscle and in the leucocytes.The hepatic glycogen, either isolated or within the hepatocytes, is mostly represented in the form of monoparticulate granules and of rosettes with fewer component units, whereas the typical rosettes are rare. The isolated and intracellular glycogen of muscle cells appears composed of monoparticulate granules, as in normal muscle cells.The biochemical studies confirm the diagnosis of type III A glycogenosis and seem to exclude the simultaneous occurrence of the enzymatic defect responsible for type II glycogenosis.

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Typ III A GlykogenoseEine biochemische und ultrastrukturelle Untersuchung

Zusammenfassung Die Beobachtung einer Glykogenose (Typus III A) bei einem 11 Jahre alten Jungen wurde biochemisch, elektronenmikroskopisch, cytotopochemisch und durch eine Reihe sog. Negativfärbungen durchgearbeitet. In Leber, Muskulatur und Leukocyten wurden starke Glykogenanhäufungen nachgewiesen. Das Leberglykogen war, sowohl in Schnittpräparaten als auch bei isolierter Untersuchung, von dem normalen Glykogen des gesunden Menschen deutlich verschieden. Sogenannte typische Rosetten wurden nur ganz ausnahmsweise gefunden. Dagegen fanden sich sog. kleine Rosetten, jeweils zusammengesetzt aus einigen wenigen Partikeln, vor allem aber monopartikuläre Granula. In der Muskulatur jedoch trat das Glykogen, wie auch beim gesunden Menschen, monopartikulär und granuliert auf.Biochemisch konnte die Diagnose einer Glykogenose des Typus III A eindeutig gestellt werden. Es haben sich keine Anzeichen dafür nachweisen lassen, daß ein sog. Fermentdefekt, etwa wie bei einer Glykogenose des Typus II, zugrunde lag.

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This work was supported by Grant N. 115/815/1270 from the Consiglio Nazionale delle Ricerche, Comitato Biologia e Medicina. Italy.

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Dr.Minio Paluello and Dr.Bruni are fellows of Consiglio Nazionale delle Ricerche.     

Systemic hemostasis with recombinant-activated factor VII followed by local thrombolysis with recombinant tissue plasminogen activator in intraventricular hemorrhage

Introduction: A 51-year-old woman on warfarin thromboprophylaxis for transient ischemic attacks developed sudden onset nausea, vomiting, and decreased mental status, rapidly becoming comatose. Head computed tomography (CT) showed intracerebral hemorrhage, extending into all ventricular chambers, and acute obstructive hematocephalus requiring urgent ventricular drainage. CT angiogram showed no evidence of an aneurysm or vascular malformation. Methods: The pretreatment international normalized ratio (INR) of 4.9 was rapidly corrected with recombinant activated factor VII and an external ventricular drain was placed. Despite accurate positioning, the ventriculostomy thrombosed and became nonfunctional. Recombinant tissue plasminogen activator was given intraventricularly and resulted in partial ventricular decompression within 24 hours, with dramatic improvement in the patient’s level of consciousness. Results: Repeated intraventricular fibrinolysis resulted in further reduction of the intraventricular hematoma within a few days and a good patient outcome. The patient did not require permanent ventricular shunt. Conclusion: To our knowledge, this is the first reported case of combined systemic enhancement of hemostasis and local fibrinolysis as a life-saving measure in intracranial hemorrhage.     

Outpatient treatment with corticosteroids and antibiotics for acalculous cholecystitis in chronic granulomatous disease

We report the outpatient management of acalculous colecistitis in an 18-y-old male with X-linked chronic granulomatous disease. The patient complained of abdominal pain and the initial ultrasound showed a gallbladder with a thickened wall.CONCLUSION: In chronic granulomatous disease, pain from a thickened gallbladder disappears after oral treatment with glucocorticoids and antibiotics.     

Adolescents and sexually transmitted infections: knowledge and behaviour in Italy

OBJECTIVE: Sexually transmitted infections (STI) among adolescents continue to be an important public health problem for many industrialized and developing countries. This study evaluated knowledge and behaviour in adolescents regarding prevention of STI. METHODS: Information was obtained by using self-reported questionnaire from a random sample of 644 undergraduate students at university and at public high schools aged 14-20 years in Catanzaro (Italy). RESULTS: Only 14.2% of respondents knew about the main STI and that they can be transmitted through sexual intercourse with HIV seropositive partners; this knowledge was significantly higher among adolescents who had had a higher number of sexual partners in their lifetime and who had received information from physicians about STI. A total of 33.8% reported having had sexual intercourse at least once and the mean age at first intercourse was 16 years. Older males and adolescents with employed mothers were more likely to have reported having had a sexual experience. The prevalence of using condoms every time during sexual intercourse was 51.8% and such behaviour was more likely in younger adolescents and males. The prevalence of condom use on the last occasion of sex was 71.9%. Younger adolescents, those with a higher perception of the risk of contracting STI and those with lesser knowledge about STI were independent predictors for using condoms. The mean total score of the respondents' perception of a risk of contracting STI was 5.8. CONCLUSIONS: Evidence to develop and implement strategies with the hope of improving adolescents' level of knowledge and reducing unsafe sexual practices.     

Preliminary report on the interaction of apolipoprotein E polymorphism with aortic atherosclerosis and acute nephropathy after CABG

Background

Renal dysfunction is a serious complication of cardiac surgery that is highly associated with short- and long-term adverse outcome. While the apolipoprotein E (APOE) ?4 allele has been linked to the occurrence of both postcardiac surgery acute renal injury (?4 favorable) and ascending aortic arteriosclerosis (?4 unfavorable), the role of ?4 in the relationship between these two conditions is unknown. We hypothesized that patients with and without the ?4 allele (E4/non-E4) would have different associations between atheroma burden and postoperative renal dysfunction.

Methods

Ascending, arch, and descending aorta atheromatous burden and APOE status were evaluated for 130 coronary bypass patients. Multivariable analyses were performed for aortic regions to assess the relationship of atheroma burden and APOE ?4 status with peak in-hospital postoperative serum creatinine. All p < 0.05 were considered significant.

Results

We found an interaction between E4 status (E4/non-E4; 24/106) and atheroma burden, with a much greater predicted peak in-hospital postoperative serum creatinine for increases in ascending aorta atheroma load for non-E4 patients versus E4 patients (beta coefficient −0.13; p = 0.002). We also confirmed the association between ascending aorta atheroma and peak creatinine (beta coefficient 0.11; p = 0.0008), after controlling for E4 status, preoperative creatinine, and the E4-atheroma interaction.

Conclusions

Equivalent ascending aortic atheroma burden is associated with a greater susceptibility to postoperative renal injury among patients undergoing cardiac operation who lack the APOE ?4 allele. Findings may be attributable to APOE-related differences in inflammation, susceptibility to atheroma detachment (eg, during operative aortic manipulation), or renal vulnerability to embolic injury.     

Palliative endoscopic treatment of pancreatic cancer

Pancreatic cancer has a very poor chance of being radically resected (20-25%) at the time of diagnosis. Palliation has thus proved to be the mode of treatment adopted in the majority of cases. When a radical surgical resection is not feasible, the endoscopic approach is one of the most common options among the therapeutic methods available. Endoscopic palliation for the treatment of jaundice is regarded as the best choice. It is associated with very low morbidity and no mortality. Hospitalization is short and the treatment is also inexpensive compared to other procedures. The authors report on their experience with endoscopic palliation for the treatment of inoperable pancreatic cancer.     

Intraparenchymal renal artery aneurysms. Case report with review and update of the literature

Increased interest in aneurysms involving therenal artery and its branches has occurredduring the past 3 decades. The prevalence ofrenal artery aneurysms is approximately 0.01%–1% in the general population as well as2.5% in hypertensive patients undergoingangiography. Intraparenchymal renal arteryaneurysms (IPRAAs) are rare since beingdetected in less than 10% of patients withrenal artery aneurysms. The Authorsreport an unusual case of multiple smallintrarenal artery aneurysms associatedwith a large IPRAA located in the mid portionof the right kidney. Usually, IPRAAs aresecondary to diseases or injuries of the kidneyvascular network. They are classified as true,false, saccular, fusiform, dissecting, andmicroaneurysms. Potential complications ofIPRAAs include peripheral dissection,thrombosis, hypertension, renal infarction andrupture. IRAAs may be detected incidentally aswell as present with urologic symptoms andsigns related to complications. Actually, IRAAsare investigated by non invasive modalitiesincluding duplex ultrasound, magnetic resonanceangiography, spiral three-dimensional computedtomography angiography, and three-dimensionalreconstructed rotational digital substractionangiography of the segmental and distantbranches of the renal artery. Angiography withintrarterial injection of contrast material isthe gold standard in diagnosing IPRAAs.Treatment options for IPRAAs includeobservation, aneurysmectomy with surgicalrepair, endovascular procedures, nephrectomy orpartial nephrectomy. Observation is indicatedfor asymptomatic intraparenchymal renal arteryaneurysms measuring less than 2 cm in diameter.Surgical repair of IPRAAs includesaneurysmectomy and reconstruction of the renalartery by in vivo or ex vivo technique. Theprocedure is indicated for IPRAAs causingrenovascular hypertension, dissection, urologicsymptoms, embolization, local expansion andwomen of childbearing age with a potential forpregnancy. In recent years, transcatheterarterial embolization has emerged as a simple,useful and effective technique in managingIRAAs. The procedure is performed bytransfemoral catheterization as well as bysuperselective catheterization and embolizationof interlobar arteries with 3F microcatheters.Endovascular occlusion is obtained by usinggelatin sponge, steel coils, detachablebaloons, and conventional non-detachablemicrocoils delivered through a microcatheter.Nephrectomy or partial nephrectomy are reservedfor conditions precluding renalrevascularization which include overt RAArupture, covert RAA rupture, artery-to-veinfistula, renal cell carcinoma, end stagenephropaty, renal infarction, severe ischemicrenal atrophy or complex intrarenal aneurysms.Recently, partial nephrectomy by thelaparoscopic approach has been proposed formanaging IPRAAs and the procedure is consideredfeasible and safe.     

Predictors of inotrope use during separation from cardiopulmonary bypass

OBJECTIVE: To identify the demographic, clinical, and echocardiographic features that predict the use of inotropic support at separation from cardiopulmonary bypass (CPB). Design: Retrospective study of consecutive patients undergoing coronary artery bypass graft (CABG) surgery. SETTING: Referral center for cardiothoracic surgery at a university hospital. PARTICIPANTS: One thousand nine patients undergoing either CABG or combined CABG and valve surgery with CPB in whom an intraoperative transesophageal echocardiography (TEE) examination was performed. INTERVENTIONS: Inotropic support was defined as the use of dopamine >/=5 microg/kg/min; any dose of epinephrine, norepinephrine, dobutamine, and milrinone; or the insertion of an IABP during separation from CPB. Support was implemented by the anesthesia care team as clinically indicated. Comprehensive TEE examinations were conducted before CPB in all patients according to published guidelines and subsequently reviewed by a single, independent operator. MEASUREMENTS and MAIN RESULTS: Inotropic support was used in a total of 394 patients (39%) at separation from CPB. The study identified 6 significant, independent predictors of inotrope use: (1) Wall Motion Score Index, (2) combined CABG and mitral valve repair or replacement surgery, (3) left ventricular ejection fraction <35%, (4) reoperation, (5) moderate-to-severe mitral regurgitation, and (6) aortic cross-clamp time. CONCLUSIONS: Incorporating data from a comprehensive intraoperative TEE examination, the authors identified 6 reproducible factors that independently predict the use of inotropic support at separation from CPB.