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.     

Rehabilitation after anterior cruciate ligament reconstruction: a prospective, randomized, double-blind comparison of programs administered over 2 different time intervals

BACKGROUND: There are adverse effects associated with immobilization of the knee after anterior cruciate ligament reconstruction, yet very little is known about how much activity will promote adequate rehabilitation without permanently elongating the graft, producing graft failure, or creating damage to articular cartilage. HYPOTHESIS: Rehabilitation with either an accelerated or nonaccelerated program produces no difference in anterior-posterior knee laxity, clinical assessment, patient satisfaction, functional performance, and the synovial fluid biomarkers of articular cartilage metabolism. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1. METHODS: Twenty-five patients who tore their anterior cruciate ligament were enrolled and underwent anterior cruciate ligament reconstruction. Patients were randomized to accelerated rehabilitation or nonaccelerated rehabilitation. At the time of surgery and 3, 6, 12, and 24 months later, measurements of anterior-posterior knee laxity, clinical assessment, patient satisfaction, functional performance, and cartilage metabolism were completed. RESULTS: At the 2-year follow-up, there was no difference in the increase of anterior knee laxity relative to the baseline values that were obtained immediately after surgery between the 2 groups (2.2-mm vs 1.8-mm increase relative to the normal knee). The groups were similar in terms of clinical assessment, patient satisfaction, activity level, function, and response of the bio-markers. After 1 year of healing, synthesis of collagen and turnover of aggrecan remained elevated in both groups. CONCLUSION: Anterior cruciate ligament reconstruction with a bone-patellar tendon-bone graft followed by either accelerated or nonaccelerated rehabilitation produces the same increase of anterior knee laxity. Both programs had the same effect in terms of clinical assessment, patient satisfaction, functional performance, and the biomarkers of articular cartilage metabolism. There is concern that the cartilage biomarkers remained elevated for an extended period.     

Predominance of serotype V and frequency of erythromycin resistance in Streptococcus agalactiae in Ohio

OBJECTIVE: The purpose of this study was to test the serotype distribution and antibiotic sensitivity patterns of group B Streptococcus from three Ohio regions in comparison to other areas of the United States. STUDY DESIGN: Three hundred forty-nine group B Streptococcus isolates from three Ohio hospitals were serotyped specifically, and disk diffusion was used to determine antibiotic susceptibility. RESULTS: Serotype V was isolated most frequently (27%); major types Ia, Ib, II, and III had frequencies of 18%, 9%, 11%, and 17%, respectively. Erythromycin and clindamycin resistance was 12% (n = 200 isolates) and 8% (n = 49 isolates), respectively. CONCLUSION: The prevalence shift of resistant serotype V group B streptococci in Ohio reflects regional increases and suggests that alternative therapies for patients who are allergic to penicillin may be inadequate.     

Treatment of intestinal worms is associated with decreased HIV plasma viral load

BACKGROUND: We have previously suggested that helminthic infections make the host more susceptible to HIV infection and enhance its progression due to the chronic immune activation they cause. OBJECTIVE: To study the effect of antihelminthic treatment on HIV plasma viral load (VL) in HIV- and helminth-infected individuals living in Ethiopia. METHODS: Fifty-six clinically asymptomatic HIV-1-infected individuals, 31 (55%) of whom were also infected with helminths, were studied. All participants received antihelminthic treatment at baseline and at 3 and 6 months. Worm egg excretion, HIV plasma VL, and T-cell subsets were determined at baseline and 6 months after treatment. RESULTS: The mean age, number of CD4 T cells, and gender distribution were similar in the helminth-infected and -noninfected groups. At baseline, HIV plasma VL was strongly correlated to the number of eggs excreted (p <.001) and was higher in individuals infected with more than one helminth (5.28 +/- 0.35 versus 4.30 +/- 1.13 log RNA copies/mL, respectively; p =.16). After treatment of helminths, the 6-month change in HIV plasma VL was significantly different between the successfully treated group and the persistently helminth-positive group (p =.04) CONCLUSIONS: Helminth "load" is correlated to HIV plasma VL, and successful deworming is associated with a significant decrease in HIV plasma VL. The results of the current study, if confirmed in a larger study, may have important implications for slowing disease progression and reducing risks of transmission.     

Italian Cooperative Study for the treatment of children and young adults with localized Ewing sarcoma of bone: a preliminary report of 6 years of experience.

BACKGROUND: In 1991, the Italian Association for Pediatric Hematology-Oncology and the National Council of Research (CNR) initiated an Italian Cooperative Study (SE 91-CNR Protocol) with the main objective of improving the overall survival (SUR) and the event free survival (EFS) of children and young adults with localized Ewing sarcoma and primitive neuroectodermal tumors of bone compared with a previous study (IOR/Ew2 Protocol). METHODS: Between November 1991 and November 1997, 165 patients were enrolled in this study, 160 of whom were evaluable. The patients were treated with a multimodal approach characterized by intensified chemotherapy, hyperfractionated and accelerated radiation therapy, and the addition of ifosfamide and etoposide to standard chemotherapy with vincristine, actinomycin-D, doxorubicin, and cyclophosphamide. RESULTS: After a median follow-up of 37 months, 126 of the 160 evaluable patients remained free of disease recurrence. Thirty-one patients developed a disease recurrence (20 with disseminated disease). CONCLUSIONS: The 3-year SUR and EFS rates found in the current study (83.6% and 77.8%, respectively) may be considered satisfactory. Only age at diagnosis < or =14 years and a good histologic response appeared to affect the outcome of patients with localized Ewing sarcoma positively. These results appear to demonstrate the efficacy of the addition of ifosfamide in induction chemotherapy to four-drug standard combination chemotherapy, as confirmed by the improved outcome in terms of 3-year EFS reported in the SE 91-CNR Protocol compared with the IOR/Ew2 Protocol (77.8% vs. 60.7%). In addition, the better outcome also could be explained by the change in treatment strategy with a trend toward the use of more surgery than radiation therapy compared with the authors' previous protocol.     

High-dose cyclophosphamide followed by autografting can improve the outcome of relapsed or resistant non-Hodgkin's lymphomas with involved or hypoplastic bone marrow

We report our experience of high-dose cyclophosphamide (HDCY) followed by high-dose therapy (HDT) and peripheral blood progenitor cell (PBPC) autografting in patients with diffuse, intermediate and high-grade non-Hodgkin's lymphomas who have failed conventional treatment. From 1991 to 1996, 54 consecutive patients pre-treated with a median of two chemotherapy lines entered the study. Eighteen patients (33%) were still responders to conventional chemotherapy (sensitive relapse), and 20 patients (37%) were in partial response (PR) after chemotherapy (CT). Sixteen patients (30%) were resistant to conventional CT either at presentation (non responder) or in relapse (resistant relapse). Thirty-nine patients had bone marrow involved by disease and fifteen had an hypoplastic marrow following conventional treatment. Patients received HDCY (7gr/m2) and G-CSF or GM-CSF in order to collect PBPC. Median collected CD34+ cells was 12.3 x 10(6)/Kg (range 0.7-197). After HDT (BEAM or Melphalan + TBI) 50 patients underwent PBPC autografting. According to intention to treat, 44 (81%) of 54 patients achieved complete remission (CR) (50% after HDCY and 31% after HDT). Procedure related death occurred in 6 patients (11%), one after HDCY and 5 after autografting. Twenty-nine (66%) of 44 patients are still in CR, 7 to 63 months (median 27 months) after the procedure. Three-year probability of survival, disease-free survival and progression-free survival are 63%, 64% and 52% respectively. In conclusion, HDCY is an effective procedure not only in mobilizing PBPC, but also in reducing tumour burden. HDT with PBPC support may further improve the outcome in this category of high-risk non-Hodgkin's lymphomas.     

Sildenafil citrate use in Addis Ababa: characteristics of users and pharmacists’ dispensing practices

International Journal of Clinical Pharmacy - Background Studies have reported misuse of sildenafil citrate for recreational purpose, not least by healthy young men. This is becoming a major...     

Autonomic responses in chest pain syndromes as compared to normal subjects

The heart rate response to standing, cough, hand grip, and deep breathing were examined in normal subjects and coronary artery disease patients (greater than 70% diameter narrowing). The heart rate responses to these maneuvers were reduced in coronary patients and in anginal patients with normal coronary angiograms, as compared to normals. Detection (with the heart rate response to standing) was determined by using an RR interval cutoff of 140 ms for males and 120 ms for females discriminated between normals and CAD patients. In men sensitivity was 0.58, specificity 0.87 and CCR 0.75, and in women sensitivity was 0.67, specificity 0.79 and CCR 0.75. These values are similar to those reported for ST segment depression in similar populations. When separating normals from those with 2 and 3 vessel disease--sensitivity is 0.67, specificity 0.87, predictive value 0.71 and CCR 0.80. The response to cough, hand grip, and deep breathing showed similar trends but had less specificity than the response to standing. Thus, the heart rate response to most autonomic maneuvers is blunted in subjects with coronary disease and in those with pain syndromes sent for coronary angiography. These findings need testing in larger populations but autonomic maneuvers fail to discriminate patients with coronary disease from those with normal angiograms presenting with chest pain syndromes.     

Different charge forms of aromatic-l-amino-acid decar☐ylase

The isoelectric points (pI) of aromatic-l-amino-acid decar☐ylase (AADC) from two species, rat and cow, were determined by chromatofocusing. The enzyme from both rat brain and adrenal has a pI of 5.5, while the bovine adrenal enzyme has a different pI of 5.0. Thus, the variation of isoelectric point for AADC is limited to species differences but not tissue differences.     

Le fratture di polso e la lesione di Galeazzi

LO SCALPELLO-OTODI Educational - Fractures of the distal radius are the most common fractures in children and adolescents, accounting for 40% of all fractures. Distal radius fractures occur most...