The impact of type 2 diabetes and atorvastatin treatment on serum levels of MMP-7 and MMP-8.

AIM: Novel members of matrix metalloproteinases (MMPs), MMP-7 and MMP-8, have emerged as predictors of cardiovascular events. Our study aimed to evaluate serum MMP-7 and MMP-8 concentrations in patients with type 2 diabetes mellitus (T2DM) and the effects of atorvastatin on them. METHODS: We enrolled 85 statin-free subjects with concomitant T2DM and hypercholesterolemia, but without overt micro-/macro-vascular complications (diabetic group - DG). 42 age- and gender-matched healthy subjects without chronic diseases or therapy served as healthy group (HG). All diabetic patients received fix dose of atorvastatin (20 mg/day). Clinical and anthropometrical parameters, lipids, fasting plasma glucose (FPG), serum MMP-7, MMP-8, their inhibitor (TIMP-1), IL-18, hsCRP and insulin resistance (HOMA-IR) were assayed at baseline in all participants and after 3 months in the DG. RESULTS: At baseline, DG showed higher levels of BMI, systolic blood pressure, insulin resistance and FPG compared to HG (p<0.05). Similarly, DG appeared with elevated concentrations of MMP-7 (4.28±1.01 ng/ml vs 2.63±1.11 ng/ml, p<0.001), MMP-8 (73.07±21.96 ng/ml vs. 21.27±10.49 ng/ml, p<0.001) and inflammatory markers (WBC, hsCRP, IL-18, p<0.010). Importantly, atorvastatin treatment improved lipid profile, significantly reduced the concentrations of MMP-7, MMP-8 and inflammatory markers (p<0.01). Moreover, there was considerable suppression of both MMP-7/TIMP-1 and MMP-8/TIMP-1 ratios (p<0.01). In standard multiple regression analysis, the atorvastatin-induced reduction in MMP-7 was independently associated with LDL and IL-18 downregulation (R(2)=0.648, p=0.017). Similarly, IL-18 changes emerged as an independent determinant of MMP-8 alterations (R(2)=0.678, p=0.007). CONCLUSIONS: Hypercholesterolemic patients with T2DM showed elevated MMP-7 and MMP-8 serum concentrations. Atorvastatin reduced the latter concentrations and their ratio with TIMP-1. Those effects seemed mediated by the atorvastatin-induced suppression of inflammatory mediators. ClinicalTrials.gov Identifier: NCT00636766.

The differential anti-inflammatory effects of exercise modalities and their association with early carotid atherosclerosis progression in patients with type 2 diabetes.

OBJECTIVE: Adipokines, visfatin, apelin, vaspin and ghrelin have emerged as novel cardiovascular risk factors. We aimed to evaluate the effects of different exercise modalities on the aforementioned novel adipokines and carotid intima-media thickness in patients with Type 2 diabetes mellitus. METHODS: One hundred patients with Type 2 diabetes were equivalently (n = 25) randomized into four groups: (1) a control group with patients encouraged to perform self-controlled exercise; (2) a supervised aerobic exercise group (exercise four times/week, 60 min/session, 60-75% of maximum heart rate); (3) a resistance training group (60-80% baseline maximum load achieved in one repetition); and (4) a combined aerobic exercise plus resistance training group, as in groups 2 and 3. All participants had HbA(1c) levels ≥ 48 mmol/mol (≥ 6.5%), without overt diabetic vascular complications. Blood samples, clinical characteristics, peak oxygen uptake and carotid intima-media thickness measurements were obtained at baseline and at the end of the study, after 6 months. RESULTS: At baseline, there were non-significant differences between groups. All active groups significantly ameliorated glycaemic profile, insulin sensitivity and triglycerides levels compared with the control group (P < 0.05). Aerobic training further improved lipids, systolic blood pressure and exercise capacity compared with the resistance training and the control groups (P < 0.05). Moreover, high-sensitivity C-reactive protein and visfatin decreased, while vaspin and apelin circulating levels increased within the aerobic exercise group and the aerobic exercise plus resistance training group, and compared with the other groups (P < 0.05). Within- and between-group comparisons showed negligible alterations in ghrelin serum levels and body weight after all exercise modalities. Finally, aerobic training attenuated the carotid intima-media thickness progression (0.017 ± 0.006 mm) compared with the control subjects (0.129 ± 0.042 mm, P < 0.001). That effect was independently associated with visfatin and amelioration of peak oxygen uptake. CONCLUSIONS: In subjects with Type 2 diabetes, all exercise training modalities improved metabolic profile. Importantly, aerobic training predominantly ameliorated adipokines concentrations and carotid intima-media thickness progression.

The behaviour of Ailanthus altissima weed and its effects on natural ecosystems.

Ailanthus altissima is an invasive species for the native flora of Greece and it could pose a serious threat to the biodiversity and the functioning of ecosystems. The purpose of this study was to investigate the spreading of Ailanthus altissima in urban and non urban areas of North and Central Greece and also to evaluate the effects of its spreading on species composition and floristic diversity in natural ecosystems. The spreading of Ailanthus altissima in urban areas is very intense, mainly in abandoned places (35.29%). It is commonly found in non urban areas of Greece, especially in hedgerows of arable lands (36%) and adjacent wetlands (17%). It is less common in forests (4%), shrublands (11%) and grasslands (9%). The spread of Ailanthus altissima in urban and natural ecosystems is relatively recent. Although it has been recorded at altitudes of up to 640 m, it usually appears at low altitudes of up to 200 m. Floristic diversity was found to be higher in the stands that it dominated (H' = 1.574, H' = 1.890) in comparison to stands that were dominated by Quercuspubescens (H' = 1.468) or Q. coccifera (H' = 1.716). This may be contributed to the fact that in those stands synanthropic species, which are usually found in regions of intense human activity, were present together with typical forest vegetation species.

Exercise ameliorates serum MMP-9 and TIMP-2 levels in patients with type 2 diabetes.

AIM: This study assessed the impact of regular exercise on inflammatory markers (high-sensitivity C-reactive protein [hsCRP], fibrinogen), and matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), in patients with type 2 diabetes mellitus (T2DM). PATIENTS: Fifty overweight patients with T2DM were randomly assigned to two groups: (A) an exercise group (EXG, n=25), with self-controlled exercise for at least 150 min/week and one additional supervised exercise session/week; and (B) a control group (COG, n=25), with no exercise instructions. All participants were taking oral antidiabetic drugs, and none had diabetic complications. Clinical parameters, exercise capacity (VO(2 peak)), ventilatory threshold (VT), insulin resistance indices (fasting insulin, HOMA-IR, HOMA%S), hsCRP, fibrinogen, MMP-2, MMP-9, TIMP-1 and TIMP-2 were assessed at baseline and after 16 weeks. RESULTS: No significant changes were found in body mass index, waist/hip ratio, insulin-resistance indices, MMP-2 and TIMP-1 throughout the study in either group (P>0.05). Compared with controls, the EXG showed a significant decrease in systolic and mean blood pressure, total and LDL cholesterol, and HbA(1c) (P<0.05). Also, exercise significantly suppressed levels of fibrinogen (P=0.047), hsCRP (P=0.041) and MMP-9 (P=0.028), and the MMP-9-to-TIMP-1 ratio (P=0.038), whereas VO(2 peak) (P=0.011), VT (P=0.008) and plasma TIMP-2 levels (P=0.022) were considerably upregulated in the EXG vs. COG. Standard multiple-regression analyses revealed that MMP-9 changes were independently associated with fibrinogen and HbA(1c) changes, while fibrinogen changes independently predicted TIMP-2 alterations with exercise. CONCLUSION: Mostly self-controlled exercise of moderate intensity ameliorated serum levels of pro- and anti-atherogenic markers in patients with T2DM, with no effects on body weight. These data offer further insight into the cardioprotective mechanisms of exercise in patients with T2DM.

Intensive lipid-lowering therapy ameliorates novel calcification markers and GSM score in patients with carotid stenosis.

OBJECTIVES/DESIGN: Carotid plaque echogenicity quantified by the Gray-Scale Median (GSM) score has been associated with plaque vulnerability. The aim of this study was to assess whether intensive lipid-lowering treatment with atorvastatin in patients with carotid artery stenosis ameliorates novel vascular calcification inhibitors, such as osteopontin (OPN) and osteoprotegerin (OPG), and improves GSM score. METHODS: Ninety-seven patients with carotid stenosis (>40%), but without indication for intervention, were treated for 6 months with atorvastatin (10mg-80mg) to target LDL<100mg/dl. Fifty-two age-and sex-matched healthy individuals served as the control group. Blood samples and GSM were obtained at the beginning and after 6 months. RESULTS: Systolic blood pressure, hsCRP, fibrinogen, OPN and OPG levels differed significantly between patients with carotid stenosis and healthy controls at baseline (p<0.05). Atorvastatin treatment improved lipid profile and significantly reduced hsCRP (p=0.002), WBC count (p=0.041), OPN (p<0.001) and OPG levels (p<0.001). GSM score increased considerably after atorvastatin therapy (from 58.33+/-24.38 to 79.33+/-22.3; p<0.001) and that effect appeared related to OPN (p=0.001), OPG (p=0.013) and LDL (p=0.01) reduction. CONCLUSIONS: In patients with carotid stenosis, intensive lipid-lowering therapy with statins attenuates serum OPN and OPG levels and enhances carotid plaque echogenicity, outlining their beneficial effects on plaque stability.

Dieulafoy-like lesion of the colon presenting with massive lower gastrointestinal bleeding.

The Dieulafoys lesion is a rare cause of severe gastrointestinal hemorrhage. The lesion is usually located in the stomach, although it may occur anywhere in the gastrointestinal tract. It is characterized by severe bleeding from a minute submucosal arteriole that bleeds through a punctate erosion in an otherwise normal mucosa. We describe an elderly patient who presented with severe lower gastrointestinal bleeding caused by a colonic Dieulafoy-like lesion. This is the third report of colonic Dieulafoys lesion treated successfully with endoscopic hemoclipping. We review the pathophysiology, clinical presentation, diagnosis, and treatment of this rare disease.

Endoscopic snare resection of an intrapapillary pedunculated villous adenoma presenting as acute recurrent pancreatitis.

Tumors of the papillary region are an unusual and heterogeneous group of neoplasms that arise from the major papilla, the ampulla of Vater, and the peripapillary duodenum. Benign adenomas of the papilla of Vater are an increasingly recognized condition in those with familial adenomatous polyposis syndromes as well as sporadic cases. Papillary adenoma is a recognized but rare cause of acute pancreatitis. We describe a patient who presented with acute recurrent pancreatitis that was attributed to an intrapapillary pedunculated villous adenoma. Following diagnosis by endoscopic needle knife sphincterotomy and endoscopic retrograde cholangiopancreatography, endoscopic snare resection of the adenoma resulted in symptomatic improvement.

Pyogenic cholangitis after inadvertent submucosal contrast injection in the papilla of Vater in a patient with cholestatic hepatitis.

Common bile duct stones and tumors constitute the leading cause of acute biliary tract obstruction and cholangitis. Septic complications after diagnostic endoscopic retrograde cholangiopancreatography (ERCP) are very unusual in unobstructed bile ducts. There are only three reported cases of patients without evidence of biliary tract disease who developed cholangitis and liver abscesses due to Pseudomonas aeruginosa. Biliary endoscopists believe that the inadvertent submucosal injection of contrast into the papilla of Vater is an innocent accident that has no serious consequences other than increasing the percentage of unsuccessful catheterizations of the common bile duct. Herein we describe a patient with drug-induced cholestatic hepatitis who developed pyogenic cholangitis after the inadvertent injection of submucosal contrast in the papilla of Vater.