Mechanical load and chemical factors as stimuli for the different pattern of the extracellular matrix (ECM) could be responsible for cardiac dysfunction. Since fibroblasts can both synthesize and degrade ECM, ventricular fibroblasts from adult rat hearts underwent cyclical mechanical stretch (CMS; 0.33 Hz) by three different elongations (3%, 6%, 9%) and four different serum concentrations (0%, 0.5%, 5%, 10%) within 24 h. Expression of collagen I and III, as well as matrix metalloproteinase-2 (MMP-2), tissue inhibitor of MMP-2 (TIMP-2), and colligin were analyzed by RNase protection assay. In the absence of serum, 9% CMS increased the mRNA of collagen I by 1.70-fold and collagen III by 1.64-fold. This increase was prevented by the inhibition either of PKC or of tyrosine kinase but not of PKA. Inhibition of PKC or tyrosine kinase itself reduced the expression of collagen I and collagen III mRNA. The mRNA of MMP-2, TIMP-2, and colligin showed the same tendency by stretch. Combined with 10% serum, 6% CMS reduced the mRNA of collagen I (0.62-fold) and collagen III (0.79-fold). Inhibition of PKC or tyrosine kinase, but not of PKA, prevented the reduction of collagen I and collagen III mRNA in 10% serum. The results show that the response of fibroblasts to CMS depends on the serum concentration. At least two signaling pathways are involved in the stretch-induced ECM regulation. Myocardial fibrosis due to ECM remodeling contributes to the dysfunction of the failing heart, which might be attributed to changes in hemodynamic loading.
The main localization of spondylodiscitis was the lumbar spine (55%) followed by the thoracic spine (34%). The classification of patients into 3 grades of severity depends on clinical and laboratory parameters, the morphological vertebral destruction seen in radiological examinations and the current neurological status. Therapies are adapted according to severity and they include a specific surgical management, systemic antibiotic therapy according to culture and sensitivity tests, physiotherapy and initiation of post-hospital follow-up. 40.6% of patients are associated with neurological deficits, classified as severity grade 3 and treated surgically with spinal stabilization and decompression. 46.9% of patients corresponded to severity grade 2, with concomitant vertebral destruction were dorsoventrally stabilized. The 31 patients of severity Grade 1 were treated surgically with dorsal stabilization. From 1998 to 2013, the time from the onset of symptoms to the first surgical treatment was about 69.4 days and has not changed significantly. However, the time from admission to surgical treatment had been reduced to less than 2 days. Also the time of hospitalization was reduced and we see positive effects regarding the sensation of pain. 270 patients underwent surgery. We treated 89% dorsally and 21% dorsoventrally. With the spondylodiscitis severity code, a classification of the severity of spondylodiscitis could be established and used for a severity-based treatment. In addition, specific parameters for the treatment of individual grades of severity can be determined in a clinical pathway.
Abstract-Transforming growth factor- (TGF-) is a ubiquitous growth-regulating protein with an essential role in tissue repair and formation of extracellular matrix (ECM). To better understand the role of different isoforms of TGF- in the cardiac remodeling process induced by norepinephrine (NE), the expression of TGF-1, TGF-2, and TGF-3 was studied and compared with the expression of collagen. NE (0.1 mg/kg ⅐ h) was intravenously infused in female and male Sprague-Dawley rats for several time periods, and freshly obtained ventricular myocardium after 1 day was dissociated into myocyte and nonmyocyte fractions. Prazosin (0.1 mg/kg ⅐ h) and metoprolol (1 mg/kg ⅐ h) were used to block ␣-and -adrenoceptors, respectively. After NE infusion, the three isoforms of TGF- were differentially induced as far as the magnitude and the time course is concerned. The increased expression of TGF-2 started earlier with a maximum after 12 hours and was more pronounced (10-fold elevation) than that of the other two isoforms, with a clear specificity for the left ventricle in female hearts. This specificity was also seen in male rats with 16-fold elevation of TGF-2 after 1 day of NE-stimulation. The increase of TGF-2 was significant only in the myocyte fraction obtained from female as well as from male hearts. The expression of the mRNA of all TGF- isoforms of collagen type I and type III, and of the matrix metalloproteinase (MMP)-2 and its inhibitor TIMP-2 was reduced predominantly by ␣-adrenoceptor blockade with prazosin. The increase in TGF- isoforms correlated with that of the mRNA expression of collagens, MMP-2 and TIMP-2.
The literature on sternal injuries and their treatment is low. Combinations of sternum and spine injuries have not yet been processed systematically in literature. Thus, there is no concerted standard of therapeutic options. The very rare occurrence of this injury combination often leads to this injury type being forgotten in the primary evaluation of casualties.
Background Spondylodiscitis is a chameleon among infectious diseases due to the lack of specific symptoms with which it is associated. It is nevertheless a serious infection, with 7% mortality of hospitalized patients, in large part because of delayed diagnosis. The aim of this study was to develop a diagnosis and course-of-disease index to optimize its treatment. Material and methods Through analysis of 296 patients between January 1998 and December 2013, we developed a scoring system for spondylodiscitis, which we term SponDT (Spondylodiscitis Diagnosis and Treatment) based on three traits: (1) the inflammatory marker C-reactive protein (CRP) (mg/dl), (2) pain according to a numeric rating scale (NRS) and (3) magnetic resonance imaging (MRI), to monitor its progression following treatment. Results The number of patients receiving treatment increased over the past 15 years of our study. We also found an increasing age of patients at the point of diagnosis across the study, with an average age of 67.7 years. In 34% of patients, spondylodiscitis developed spontaneously. Almost 70% of them did not receive treatment until the first diagnosis using SponDT. Following treatment against spondylodiscitis, pain intensity decreased from 6.0 to 3.1 NRS. The inflammatory markers also decreased (CRP from 119.2 to 46.7 mg/dl). Similarly, MRI revealed a regression in inflammation following treatment. By employing SponDT, patients were diagnosed and entered into treatment with a score of 5.6 (severe spondylodiscitis) and discharged with a score of 2.4 (light/healed spondylodiscitis). Conclusion SponDT can be used to support the diagnosis of spondylodiscitis, particularly in patients suffering from back pain and elevated levels of inflammation, and can be used during the course of treatment to optimize control of therapy. Level of evidence IIa—evidence from at least one well-designed controlled trial which is not randomized
IT-based clinical pathways are applicable for routine use in trauma departments. For certain surgical procedures they are a suitable management device, even in a tertiary care facility. Clinical pathways lead to an improved operational structure of medical treatment and moreover to a complete and continuous documentation through the electronic file.
Background: Transgenic (tg) mice with chronic overexpression of the human erythropoietin gene are characterized by an increased hematocrit of about 0.80 in adulthood. This is accompanied by cardiac dysfunction and premature death. The aim of this study was to examine whether this cardiac dysfunction was accompanied by hypertrophy of the heart with remodeling of the extracellular matrix (ECM). Methods: 3-months-old wild type (wt) and tg mice without cardiac hypertrophy were compared with the respective 7-months-old mice. The mRNA of brain natriuretic peptide (BNP), of the matrix metalloproteinases (MMP)-2, -8, -9, -13, of the tissue inhibitor of metalloproteinase (TIMP)-1, -2, -3, -4 and of collagen I and III was detected by ribonuclease protection assay. The activity of MMPs was measured by zymography. Results: There was hypertrophy of both ventricles in 7-months-old tg mice, which was accompanied by elevated mRNA expression of BNP. MMP-2 activity was increased and MMP-9 activity was decreased in the left ventricle (LV) of 3-months-old tg mice. This was accompanied by elevated TIMP-4 expression, followed by a shift of collagen mRNA expression from type III to type I in this ventricle. Conclusion: The shift to collagen I in the heart of tg mice might be associated with a stiffer ventricle resulting in diastolic dysfunction. This may be responsible for a relative and intermittent LV- and right ventricle (RV)-insufficiency which was likely to have occurred as evidenced by the elevation of lung and liver weight with hemorrhage and interstitial fibrosis after 7 months..
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