Smoothelin-B deficiency results in reduced arterial contractility, hypertension, and cardiac hypertrophy in mice

BACKGROUND: Smoothelins are actin-binding proteins that are abundantly expressed in healthy visceral (smoothelin-A) and vascular (smoothelin-B) smooth muscle. Their expression is strongly associated with the contractile phenotype of smooth muscle cells. Analysis of mice lacking both smoothelins (Smtn-A/B(-/-) mice) previously revealed a critical role for smoothelin-A in intestinal smooth muscle contraction. Here, we report on the generation and cardiovascular phenotype of mice lacking only smoothelin-B (Smtn-B(-/-)). METHODS AND RESULTS: Myograph studies revealed that the contractile capacity of the saphenous and femoral arteries was strongly reduced in Smtn-B(-/-) mice, regardless of the contractile agonist used to trigger contraction. Arteries from Smtn-A/B(-/-) compound mutant mice exhibited a similar contractile deficit. Smtn-B(-/-) arteries had a normal architecture and expressed normal levels of other smooth muscle cell-specific genes, including smooth muscle myosin heavy chain, alpha-smooth muscle actin, and smooth muscle-calponin. Decreased contractility of Smtn-B(-/-) arteries was paradoxically accompanied by increased mean arterial pressure (20 mm Hg) and concomitant cardiac hypertrophy despite normal parasympathetic and sympathetic tone in Smtn-B(-/-) mice. Magnetic resonance imaging experiments revealed that cardiac function was not changed, whereas distension of the proximal aorta during the cardiac cycle was increased in Smtn-B(-/-) mice. However, isobaric pulse wave velocity and pulse pressure measurements indicated normal aortic distensibility. CONCLUSIONS: Collectively, our results identify smoothelins as key determinants of arterial smooth muscle contractility and cardiovascular performance. Studies on mutations in the Smtn gene or alterations in smoothelin levels in connection to hypertension in humans are warranted

Особенности дуговой сварки вертикальных швов резервуара

Цель работы – расчет режимов сварки и выбор сварочных материалов для получения равнопрочного коррозионностойкого соединения. Сложность изготовления стенок резервуара состоит в том, что резервуар РВС предназначен работать в агрессивной среде и должен выдерживать большое давление и нагрузку на свои основные части. При выборе стали необходимо руководствоваться основными её характеристиками - минимальным пределом текучести, толщиной проката и ударной вязкости.The aim of this work is the calculation of the modes of welding and selection of welding materials to obtain a durable corrosion-resistant connection

Global sensitivity analysis of stochastic computer models with joint metamodels

The global sensitivity analysis method used to quantify the influence of uncertain input variables on the variability in numerical model responses has already been applied to deterministic computer codes; deterministic means here that the same set of input variables gives always the same output value. This paper proposes a global sensitivity analysis methodology for stochastic computer codes, for which the result of each code run is itself random. The framework of the joint modeling of the mean and dispersion of heteroscedastic data is used. To deal with the complexity of computer experiment outputs, nonparametric joint models are discussed and a new Gaussian process-based joint model is proposed. The relevance of these models is analyzed based upon two case studies. Results show that the joint modeling approach yields accurate sensitivity index estimatiors even when heteroscedasticity is strong

Plant sterol or stanol esters retard lesion formation in LDL receptor-deficient mice independent of changes in serum plant sterols

Statins do not always decrease coronary heart disease mortality, which was speculated based on increased serum plant sterols observed during statin treatment. To evaluate plant sterol atherogenicity, we fed low density lipoprotein-receptor deficient (LDLr(+/-)) mice for 35 weeks with Western diets (control) alone or enriched with atorvastatin or atorvastatin plus plant sterols or stanols. Atorvastatin decreased serum cholesterol by 22% and lesion area by 57%. Adding plant sterols or stanols to atorvastatin decreased serum cholesterol by 39% and 41%. Cholesterol-standardized serum plant sterol concentrations increased by 4- to 11-fold during sterol plus atorvastatin treatment versus stanol plus atorvastatin treatment. However, lesion size decreased similarly in the sterol plus atorvastatin (-99% vs. control) and the stanol plus atorvastatin (-98%) groups, with comparable serum cholesterol levels, suggesting that increased plant sterol concentrations are not atherogenic. Our second study confirms this conclusion. Compared with lesions after a 33 week atherogenic period, lesion size further increased in controls (+97%) during 12 more weeks on the diet, whereas 12 weeks with the addition of plant sterols or stanols decreased lesion size (66% and 64%). These findings indicate that in LDLr(+/-) mice 1) increased cholesterol-standardized serum plant sterol concentrations are not atherogenic, 2) adding plant sterols/stanols to atorvastatin further inhibits lesion formation, and 3) plant sterols/stanols inhibit the progression or even induce the regression of existing lesions

Plant sterol or stanol esters retard lesion formation in LDL receptor-deficient mice independent of changes in serum plant sterols

Statins do not always decrease coronary heart disease mortality, which was speculated based on increased serum plant sterols observed during statin treatment. To evaluate plant sterol atherogenicity, we fed low density lipoprotein-receptor deficient (LDLr(+/-)) mice for 35 weeks with Western diets (control) alone or enriched with atorvastatin or atorvastatin plus plant sterols or stanols. Atorvastatin decreased serum cholesterol by 22% and lesion area by 57%. Adding plant sterols or stanols to atorvastatin decreased serum cholesterol by 39% and 41%. Cholesterol-standardized serum plant sterol concentrations increased by 4- to 11-fold during sterol plus atorvastatin treatment versus stanol plus atorvastatin treatment. However, lesion size decreased similarly in the sterol plus atorvastatin (-99% vs. control) and the stanol plus atorvastatin (-98%) groups, with comparable serum cholesterol levels, suggesting that increased plant sterol concentrations are not atherogenic. Our second study confirms this conclusion. Compared with lesions after a 33 week atherogenic period, lesion size further increased in controls (+97%) during 12 more weeks on the diet, whereas 12 weeks with the addition of plant sterols or stanols decreased lesion size (66% and 64%). These findings indicate that in LDLr(+/-) mice 1) increased cholesterol-standardized serum plant sterol concentrations are not atherogenic, 2) adding plant sterols/stanols to atorvastatin further inhibits lesion formation, and 3) plant sterols/stanols inhibit the progression or even induce the regression of existing lesion

Degradation of mesh coatings and intraperitoneal adhesion formation in an experimental model

In laparoscopic ventral hernia repair a mesh is placed in direct contact with the viscera, often leading to substantial adhesions. In this experimental study the ability of different coated and uncoated meshes to attenuate adhesion formation was examined. Six commercially available meshes were placed intraperitoneally against a closed peritoneum in rats: Prolene (polypropylene), Timesh and Ultrapro (polypropylene composites with titanium and polyglecaprone respectively), Proceed and Parietex Composite (polypropylene and polyester meshes coated with a layer of cellulose and collagen respectively) and C-Qur (polypropylene mesh coated with a layer of omega-3 fatty acids). Adhesions and incorporation were evaluated macroscopically and microscopically after 7 and 30 days. Parietex Composite and C-Qur significantly reduced adhesion formation at 7 days' follow-up compared with all other meshes. By 30 days, this effect had diminished as a significant increase in adhesions together with phagocytosis of the coating was seen for all meshes with layered coatings (Proceed, Parietex Composite and C-Qur. Incorporation was insufficient for all meshes. The absorbable layers of Parietex Composite and C-Qur reduce adhesion formation to intraperitoneal mesh in the short term, but the effect diminishes and phagocytosis of absorbable coatings may contribute to adhesion formatio

Coated meshes for hernia repair provide comparable intraperitoneal adhesion prevention

BACKGROUND: Laparoscopic incisional hernia repair with intraperitoneal mesh is associated with a certain degree of adhesion formation to the mesh. This experimental study examined the efficacy of several coated meshes for adhesion reduction. METHODS: Five commercially available meshes with a layered coating were placed intraperitoneally in rats and followed up for 90 days: polypropylene and polyester meshes, both coated with absorbable collagen (Parietene Composite and Parietex Composite, respectively), and three polypropylene meshes respectively coated with absorbable omega-3 fatty acids (C-Qur Edge), absorbable cellulose (Sepramesh IP), and nonabsorbable expanded polytetrafluoroethylene (Intramesh T1). Uncoated polypropylene and collagen meshs (Parietene and Permacol, respectively) served as the control condition. Adhesions, incorporation, and tissue reaction were evaluated macro- and microscopically. Additionally, the development of the neoperitoneum was examined. RESULTS: All the coated meshes performed equally well in terms of adhesion reduction. The collagen mesh performed comparably, but the uncoated polypropylene mesh performed significantly worse. The different coatings led to very differing degrees of inflammation. Ingrowth was observed only at the place of suture but was comparable for all the meshes except C-Qur Edge, which showed the weakest incorporation. Development of a neoperitoneum on the mesh surface occurred independently of whether an absorbable or nonabsorbable coating or no coating at all was present. CONCLUSIONS: Commercially available meshes with a layered coating deliver comparable adhesion reduction. The physical presence of a layered coating between the intraperitoneal content and the abdominal wall seems to be more important than the chemical properties of the coating in adhesion formation

Polypropylene meshes to prevent abdominal herniation. Can stable coatings prevent adhesions in the long term?

Abdominal surgery is associated with a significant risk for incisional herniation. Hernia repair is routinely performed by implantation of synthetic meshes. Such meshes may cause serious adhesions between the implanted material and organs leading to intestinal obstruction or enterocutaneous fistulas. This study compares three knitted meshes for their capacity to prevent adhesion formation in an in vivo study. The meshes evaluated are polypropylene (Prolene), polypropylene coated with oxygenated regenerated cellulose-in principle-a biodegradable biomaterial (Proceed, and Prolene coated with a nondegradable copolymer of the hydrophilic building block N-vinyl pyrrolidone (NVP) and the hydrophobic building block n-butylmethacrylate (BMA). The meshes were implanted in the abdomen of rats (follow-up 7 or 30 days). After 7 days, the formation of adhesions decreased in the order: Prolene > NVP/BMA-coated Prolene > Proceed; after 30 days, this order changed into: Proceed > Prolene > NVP/BMA-coated Prolene. Both at 7 and at 30 days, Proceed was the only mesh surrounded by macrophage cells that contained foreign materials, presumably degradation products of the (biodegradable) surface coating. The data indicate that long-term protection of implanted meshes against excessive adhesions may be achieved through stable biocompatible hydrogel surface coating

Long-term evaluation of adhesion formation and foreign body response to three new meshes

INTRODUCTION: Mesh-related adhesions are a significant clinical problem following intraperitoneal mesh placement. In this study, we evaluated adhesion formation to three relatively new meshes for intraperitoneal use. METHODS: Three new meshes for intraperitoneal use (Omyra(R) mesh, Physiomesh(R), and Hi-Tex Endo-IP(R)) were implanted intraperitoneally in rats and compared with a polypropylene control mesh (Parietene(R)) after 7 or 90 days. Adhesion formation, incorporation (tensile strength), shrinkage, and foreign body reaction were scored. RESULTS: Hi-Tex Endo-IP and Physiomesh(R) showed significantly less adhesion formation when compared to Parietene at both time points (p < 0.05). Shrinkage was highest in Omyra mesh after 90 days, which was significantly more compared to Parietene(R) (p < 0.001). Physiomesh(R) only showed a significant reduction in craniocaudal mesh length, compared to Parietene and Hi-Tex Endo-IP (p < 0.05). After 90 days, Hi-Tex Endo-IP(R) showed significantly higher and Physiomesh(R) significantly lower incorporation strengths compared to all other groups (p < 0.05). Microscopic evaluation revealed massive foreign body reaction to Hi-Tex Endo-IP(R), leading to an extensive and thick collagenous scar adherent to the abdominal wall. Fractioning of the Physiomesh(R) coating over time led to an increase in interfilamentary granuloma formation, leading to scar plate formation, but with only minimal to no abdominal wall adherence. Both Parietene(R) and Omyra(R) showed a mild foreign body response. CONCLUSION: Although clear distinctions can be made between meshes and some meshes excel, none of the meshes are superior in all aspects required for effective and safe incisional hernia repair