Effects of irbesartan on intracellular antioxidant enzyme expression and activity in adolescents and young adults with early diabetic angiopathy

OBJECTIVE: Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. The objective of this study was to evaluate the effects of irbesartan, an angiotensin II receptor antagonist, on IAP in adolescents and young adults with type 1 diabetes and early signs of retinopathy and nephropathy. RESEARCH DESIGN AND METHODS: This prospective, matched case-control study was conducted between November 2001 and December 2002 among 14 type 1 diabetic patients with early signs of angiopathy (ages 14-21 years), 11 type 1 diabetic patients without angiopathy (ages 12-22 years), and 10 healthy volunteers (ages 16-22 years). Skin fibroblasts were obtained by skin biopsies from the anterior part of the forearm and cultured in Dulbecco's modified Eagle's medium. The activity and mRNA expression of CuZn superoxide dismutase (CuZnSOD), Mn superoxide dismutase (MnSOD), catalase (CAT), and glutathione peroxidase (GPX) were measured before and after 6 months of treatment with irbesartan (150 mg/day); on both occasions, antioxidant enzyme activity was evaluated at different glucose concentrations (5 and 22 mmol/l). RESULTS: At a normal glucose concentration (5 mmol/l), the activity and mRNA expression of CuZnSOD (0.50 +/- 0.21 units/mg protein, 4.4 +/- 1.5 mRNA/glyceraldehyde-3-phosphate dehydrogenase), MnSOD (0.26 +/- 0.04 units/mg protein, 0.08 +/- 0.07 mRNA), CAT (0.32 +/- 0.08 units/mg protein, 4.8 +/- 1.3 mRNA), and GPX (0.53 +/- 0.09 units/mg protein, 2.2 +/- 0.9 mRNA) were not different among the three groups (only values of diabetic subjects with angiopathy are shown). At high glucose concentrations, the activity and mRNA expression of CuZnSOD increased similarly in all groups (diabetic subjects with angiopathy: 0.93 +/- 0.26 units/mg protein, 9.4 +/- 2.1 mRNA); that of CAT and GPX increased in only control subjects and diabetic subjects without angiopathy (diabetic subjects with angiopathy: 0.33 +/- 0.09 units/mg protein and 5.0 +/- 1.4 mRNA; 0.54 +/- 0.10 units/mg protein and 2.3 +/- 1.0 mRNA, respectively). MnSOD did not change in any group. Treatment with irbesartan in adolescents with diabetic angiopathy was able to restore CAT and GPX activity and mRNA expression after exposure to high glucose concentrations. Markers of oxidative stress (serum malondialdehyde, fluorescent products of lipid peroxidation, monocyte chemoattractant protein-1, and 8-isoprostanes prostaglandin F(2alpha)) were significantly reduced after treatment with irbesartan. CONCLUSIONS: Adolescents and young adults with early signs of diabetic angiopathy have defective intracellular antioxidant enzyme production and activity. Treatment with irbesartan can substantially improve the activity and production of these enzymes in skin fibroblasts.     

Bone-to-implant apposition with machined and MTX microtextured implant surfaces in human sinus grafts

The goal of this study was to histologically document the effect of two different implant surfaces on the percentage of bone-to-implant apposition achieved with implants placed in human sinus grafts. The influences of implant site and post-grafting delay time were also examined. Nine healthy volunteers were scheduled to undergo posterior maxillary sinus floor augmentation in preparation for delayed implant placement. In addition to the conventional dental implants selected for each case, titanium alloy experimental implants, 2.5 mm in diameter and 8 mm in length, were custom manufactured. Each microimplant was prepared longitudinally with two different surface topographies: machined on one side and MTX microtextured on the other side. A notch prepared across the superior aspect of the implants facilitated placement and provided a reference line between the two surfaces. Patients were divided into two groups that received the experimental microimplants at the time of conventional implant placement: Group A (six patients) received the experimental microimplants in the regenerated lateral wall of the sinus graft 11 months after graft placement, and group B (three patients) received them in the alveolar crest 6 months after graft placement. After 6 months of submerged healing, all experimental and conventional implants appeared to be clinically osseointegrated. Histologic analysis revealed that the mean bone-to-implant apposition was significantly greater with MTX (72.31% +/- 17.76%) compared to machined surfaces (38.01% +/- 19.32%), regardless of bone quality. The healing time between graft and implant placement and implant location did not statistically impact the percentage of bone-to-implant apposition.     

Improved hepatic perfusion after iloprost infusion in patients with HCV chronic infection: a pilot study with possible therapeutic implications.

We performed a pilot study to evaluate whether portal flow volume (PFV) changed in subjects with chronic hepatitis C virus (HCV) infection with respect to control patients after infusion of iloprost, a prostacyclin analog. Six subjects with chronic HCV infection and arteriopathy of the lower limbs (CHCVIA) and 4 control patients affected only by HCV infection (CHCV) were studied with color Doppler sonography. CHCVIA patients were examined before and after 3 days of iloprost infusion, and CHCV patients were examined before and after 3 days with no treatment. In each patient, PFV was obtained after calculating portal flow velocity (PV), portal diameter, and portal vein cross-sectional area. The mean difference between basal and final values of the PFV of CHCVIA patients was significant (p = 0.03), as was the difference in the PFV (final values expressed as percent of basal values) in CHCVIA patients compared with those obtained in the CHCV patients (p = 0.01). We have observed significant improvement in hepatic perfusion in CHCVIA patients compared with CHCV patients after iloprost infusion. In light of these results, we suggest some possible therapeutic implications in patients with HCV infection. Further studies are necessary to confirm this hypothesis.     

Transurethral polydimethylsiloxane implantation: a valid option for the treatment of stress urinary incontinence due to intrinsic sphincter deficiency without urethral hypermobility

PURPOSE: In this study we evaluated the 5-year followup results of periurethral polydimethylsiloxane (PDMS) injection for female stress urinary incontinence (SUI) secondary to intrinsic sphincter deficiency (ISD) without hypermobility of the vesicourethral junction. MATERIALS AND METHODS: A total of 61 female patients with ISD were enrolled in this prospective, observational study. Preoperative and postoperative assessment included a standardized urogynecologic history with questions regarding urinary function, urogynecologic and neurological physical examination, and urodynamic assessment. All patients underwent periurethral PDMS injection. Patient followup was performed 1, 6, 12, 24, 36, 48 and 60 months after surgery. RESULTS: At 60 months after injection the SUI cure rate was 18%, the improvement rate was 39% and the failure rate was 43%. The success rate was 57%. Of the patients 45 (74%) subjectively improved with respect to the severity of urinary incontinence. No postoperative early complications were found. At 60 months of followup only minor complications were reported (11%). CONCLUSIONS: Careful patient selection by optimal diagnostic tools are essential for maximizing the results of urethral bulking agent therapy. PDMS injection in women with SUI due to ISD with limited urethral mobility is a valid, minimally invasive procedure.     

Complications after radial artery harvesting for coronary artery bypass grafting: our experience

BACKGROUND: The aim of this study was to evaluate the incidence of complications in the upper limbs as a new event after radial artery (RA) harvesting for coronary artery bypass grafting (CABG). METHODS: From June 1997 to August 2001, the RA graft was used in 271 patients who underwent cardiac surgery at our department. These patients were prospectively reviewed. All patients were preoperatively examined to determine the presence of normal sensation and circulation in the upper limbs; then we evaluated the incidence of complications at discharge, 8 weeks, and 6 months. RESULTS:No donor arms developed symptoms of ischemia or motor dysfunction. At 8 weeks 2 patients (0.7%) reported donor arm weakness, and cutaneous paresthesia was noted postoperatively in 10 upper limbs (3.7%). The univariate statistical analysis showed that significant risk factors for persistent cutaneous paresthesia were diabetes and smoking. CONCLUSIONS: This study demonstrates that complications after harvesting the RA for CABG are a rare consequence. The main symptom is a persistent cutaneous paresthesia present in 10 patients at 6-month follow-up.