One-stage laser-microtextured implants immediately placed in the inter-radicular septum of molar fresh extraction sockets associated with GBR technique. A case series study

The outcome of one-stage trans-mucosal immediate implants with simultaneous guided bone regeneration (GBR) technique has become highly predictable. Furthermore, when this approach is performed to place one-stage implants into the inter-radicular septum of fresh extraction sockets in the molar region, the risk of incorrect emergence profile and off-angle loading is reduced. The aim of the present study was to clinically evaluate the horizontal hard and soft tissue changes, and radiographically the vertical socket walls remodeling, and the early peri-implant marginal bone loss (EMBL) following the placement of immediate one-stage implants in the inter-radicular septum of molar fresh extraction sockets, associated with a collagen membrane. Twenty patients were selected to receive a one-stage implant with laser-microtextured collar surface into the inter-radicular septum of a fresh molar extraction sockets, associated with a simultaneous placement of a collagen membrane. Intraoral radiographs and model casts were used for the evaluation. Correlation between the amount of the keratinized tissue thickness (KTT) with EMBL was also analyzed. After 4 months, the vertical radiographic mesial and distal EMBL around implants was of 0.06 ±0.01 mm and 0.04±0.02 mm, respectively, with no statistically significant difference between T0 and T1 (P >0.05). No statistical differences were found also for each radiographic measure used for the examination of implant sites vertical bone changes (p >0.05). Clinically, horizontal changes of the bucco-lingual central width were found statistically significant (p0.05). In addition, no statistically significant correlation between EMBL and the amount of KTT was found (P >0.05). Results suggest that the immediate placement of one-stage laser-microtextured implants could provide advantages in preserving the extraction socket?s hard and soft tissue remodeling, and the peri-implant marginal bone level before the prosthetic loading

Dynorphin gene expression and release in the myocardial cell.

The expression of the prodynorphin gene was investigated in adult cultured rat ventricular cardiac myocytes by using a sensitive solution hybridization RNase protection assay for the quantitative analysis of prodynorphin mRNA. Myocyte culture in high KCl resulted, after 4 h, in a marked increase in cellular prodynorphin mRNA, while a KCl treatment for 6, 12, or 24 h progressively down-regulated the levels of prodynorphin mRNA below the control value. Immunoreactive dynorphin B, a biologically active end product of the precursor, was found to be present in the culture medium in significantly higher amounts than in the cardiac myocytes. The levels of this biologically active K opioid receptor agonist significantly increased after 4 h of KCl treatment and were markedly reduced following a 24-h exposure of the cardiac myocytes to KCl. These KCl-induced effects were all abolished by cell incubation in the presence of the calcium channel blocker verapamil. In single cardiac myocytes, acute stimulation of K opioid receptors with dynorphin B or with the selective agonist U-50,488H increased the level of cytosolic calcium. This effect was abolished by the specific K opioid receptor antagonist (Mr-1452) and was not affected by the removal of calcium from the bathing medium. These results suggest that an opioid gene may influence the myocardial function in an autocrine or paracrine fashion

Central adiposity markers, plasma lipid profile and cardiometabolic risk prediction in overweight-obese individuals

BACKGROUND: Waist circumference (WC) is the currently recommended marker of central fat for cardiometabolic risk screening. Alternative surrogate markers have been recently proposed to better reflect the metabolic impact of central fat accumulation per se, based on WC normalization by height (Weight-to-Height Ratio - WtoH; Body Roundness Index - BRI) or body mass index (BMI) without (A Body Shape Index - ABSI) or with inclusion of plasma triglyceride and HDL-cholesterol concentrations (Visceral Adiposity Index - VAI). METHODS: We investigated associations between WtoH, BRI, ABSI or VAI and insulin resistance (HOMA-index) or metabolic syndrome (MetS) in a general population cohort from the North-East Italy Mo.Ma. study (n = 1965, age = 49 \ub1 13 years, BMI = 26.7 \ub1 5.2 kg/m2). Baseline values were also evaluated as predictors of future insulin resistance and MetS in overweight-obese individuals undergoing 5-year follow-up (Ow-Ob) (n = 263; age = 54 \ub1 9, BMI = 30,7 \ub1 4,1). RESULTS: Compared to WC or BMI, basal WtoH and BRI were similarly associated with baseline HOMA and MetS prevalence after multiple adjustments (P WtoH-BRI-WC-BMI; p < 0.05] while no predictive value was in contrast observed for ABSI (ROC AUC ABSI < WtoH-BRI-WC-BMI; p < 0.05). Using alternate formulae with plasma lipid inclusion in ABSI and removal from VAI calculations completely reversed their 5-year predictive value and AUC. CONCLUSIONS: The current findings do not support replacement of WC with height-normalized anthropometric central fat surrogate markers to predict cardiometabolic risk in the general and overweight-obese population. BMI-normalization impairs risk assessment unless plasma lipid concentrations are available and included in calculations

Unacylated ghrelin normalizes skeletal muscle oxidative stress and prevents muscle catabolism by enhancing tissue mitophagy in experimental chronic kidney disease

Unacylated ghrelin (UnAG) may lower skeletal muscle oxidative stress, inflammation, and insulin resistance in lean and obese rodents. UnAG-induced autophagy activation may contribute to these effects, likely involving removal of dysfunctional mitochondria (mitophagy) and redox state maintenance. In chronic kidney disease (CKD) oxidative stress, inflammation and insulin resistance may negatively influence patient outcome by worsening nutritional state through muscle mass loss. Here we show in a 5/6 nephrectomy (Nx) CKD rat model that 4 d s.c. UnAG administration (200 \ub5g twice a day) normalizes CKD-induced loss of gastrocnemius muscle mass and a cluster of high tissue mitochondrial reactive oxygen species generation, high proinflammatory cytokines, and low insulin signaling activation. Consistent with these results, human uremic serum enhanced mitochondrial reactive oxygen species generation and lowered insulin signaling activation in C2C12 myotubes while concomitant UnAG incubation completely prevented these effects. Importantly, UnAG enhanced muscle mitophagy in vivo and silencing RNA-mediated autophagy protein 5 silencing blocked UnAG activities in myotubes. UnAG therefore normalizes CKD-induced skeletal muscle oxidative stress, inflammation, and low insulin signaling as well as muscle loss. UnAG effects are mediated by autophagy activation at the mitochondrial level. UnAG administration and mitophagy activation are novel potential therapeutic strategies for skeletal muscle metabolic abnormalities and their negative clinical impact in CKD.-Gortan Cappellari, G., Semolic, A., Ruozi, G., Vinci, P., Guarnieri, G., Bortolotti, F., Barbetta, D., Zanetti, M., Giacca, M., Barazzoni, R. Unacylated ghrelin normalizes skeletal muscle oxidative stress and prevents muscle catabolism by enhancing tissue mitophagy in experimental chronic kidney disease

Unacylated ghrelin reduces skeletal muscle reactive oxygen species generation and inflammation and prevents high-fat diet-induced hyperglycemia and whole-body insulin resistance in rodents

Excess reactive oxygen species (ROS) generation and inflammation may contribute to obesity-associated skeletal muscle insulin resistance. Ghrelin is a gastric hormone whose unacylated form (UnAG) is associated with whole-body insulin sensitivity in humans and may reduce oxidative stress in nonmuscle cells in vitro. We hypothesized that UnAG 1) lowers muscle ROS production and inflammation and enhances tissue insulin action in lean rats and 2) prevents muscle metabolic alterations and normalizes insulin resistance and hyper-glycemia in high-fat diet (HFD)-induced obesity. In 12-week-old lean rats, UnAG (4-day, twice-daily subcutaneous 200-mg injections) reduced gastrocnemius mitochondrial ROS generation and inflammatory cytokines while enhancing AKT-dependent signaling and insulinstimulated glucose uptake. In HFD-treated mice, chronic UnAG overexpression prevented obesity-associated hyperglycemia and whole-body insulin resistance (insulin tolerance test) as well as muscle oxidative stress, inflammation, and altered insulin signaling. In myotubes, UnAG consistently lowered mitochondrial ROS production and enhanced insulin signaling, whereas UnAG effects were prevented by small interfering RNA-mediated silencing of the autophagy mediator ATG5. Thus, UnAG lowers mitochondrial ROS production and inflammation while enhancing insulin action in rodent skeletal muscle. In HFD-induced obesity, these effects prevent hyperglycemia and insulin resistance. Stimulated muscle autophagy could contribute to UnAG activities. These findings support UnAG as a therapeutic strategy for obesity-associated metabolic alterations

Unacylated ghrelin does not alter mitochondrial function, redox state and triglyceride content in rat liver in vivo

Summary Changes in liver mitochondrial function with more oxidized redox state and enhanced inflammation may contribute to the onset of obesity- and insulin resistance-associated hepatic complications, including non-alcoholic fatty liver disease and steato-hepatitis. Unacylated ghrelin (UnAG) is a gastric hormone reported to be associated with lower oxidative stress in different cell types, but its potential effects on liver mitochondrial function, redox state and inflammation in vivo remains undetermined. We investigated the impact of chronic UnAG overexpression (Tg Myh6/Ghrl) leading to systemic upregulation of circulating hormone on mitochondrial ATP production, redox state (oxidized-to-total glutathione) and inflammation markers in lean mice. Compared to wild-type animals (wt), Tg Myh6/Ghrl had superimposable liver weight, triglyceride content and plasma lipid profile. Liver mitochondrial enzyme activities and ATP production as well as oxidized-to-total glutathione were also similar in the two groups. In addition, no differences were observed in tissue inflammation marker TNF-alpha between wild-type and Tg Myh6/Ghrl animals. Thus, chronic systemic UnAG upregulation does not alter liver triglyceride content, mitochondrial function, redox state and inflammation markers in lean mice. These findings do not support a major role of UnAG as a physiological modulator of in vivo liver oxidative-lipid metabolism and inflammation

Gastric bypass-induced weight loss alters obesity-associated patterns of plasma pentraxin-3 and systemic inflammatory markers

Systemic inflammation contributes to obesity-associated complications. The short pentraxin C-reactive protein (CRP) is a validated inflammatory marker, whereas long pentraxin-3 (PTX3) limits inflammation and is adaptively stimulated by proinflammatory cytokines in vitro. Severely obese (SO) patients (body mass index [BMI]>40] have the highest obesity-associated complications and increasingly undergo surgical treatment. SO-associated changes in plasma PTX3 and their interactions with systemic inflammation are, however, unknown

High-Fat Diet with Acyl-Ghrelin Treatment Leads to Weight Gain with Low Inflammation, High Oxidative Capacity and Normal Triglycerides in Rat Muscle

Obesity is associated with muscle lipid accumulation. Experimental models suggest that inflammatory cytokines, low mitochondrial oxidative capacity and paradoxically high insulin signaling activation favor this alteration. The gastric orexigenic hormone acylated ghrelin (A-Ghr) has antiinflammatory effects in vitro and it lowers muscle triglycerides while modulating mitochondrial oxidative capacity in lean rodents. We tested the hypothesis that A-Ghr treatment in high-fat feeding results in a model of weight gain characterized by low muscle inflammation and triglycerides with high muscle mitochondrial oxidative capacity. A-Ghr at a non-orexigenic dose (HFG: twice-daily 200-µg s.c.) or saline (HF) were administered for 4 days to rats fed a high-fat diet for one month. Compared to lean control (C) HF had higher body weight and plasma free fatty acids (FFA), and HFG partially prevented FFA elevation (P<0.05). HFG also had the lowest muscle inflammation (nuclear NFkB, tissue TNF-alpha) with mitochondrial enzyme activities higher than C (P<0.05 vs C, P = NS vs HF). Under these conditions HFG prevented the HF-associated muscle triglyceride accumulation (P<0.05). The above effects were independent of changes in redox state (total-oxidized glutathione, glutathione peroxidase activity) and were not associated with changes in phosphorylation of AKT and selected AKT targets. Ghrelin administration following high-fat feeding results in a novel model of weight gain with low inflammation, high mitochondrial enzyme activities and normalized triglycerides in skeletal muscle. These effects are independent of changes in tissue redox state and insulin signaling, and they suggest a potential positive metabolic impact of ghrelin in fat-induced obesity