Rationale:The extracellular matrix (ECM) is a major determinant of the structural integrity and functional properties of the myocardium in common pathological conditions, and changes in vasculature contribute to cardiac dysfunction. Collagen (Col) XV is preferentially expressed in the ECM of cardiac muscle and microvessels.Objective: We aimed to characterize the ECM, cardiovascular function and responses to elevated cardiovascular load in mice lacking Col XV (Col15a1 ؊/؊ ) to define its functional role in the vasculature and in age-and hypertension-associated myocardial remodeling. Methods and Results:Cardiac structure and vasculature were analyzed by light and electron microscopy.Cardiac function, intraarterial blood pressure, microhemodynamics, and gene expression profiles were studied using echocardiography, telemetry, intravital microscopy, and PCR, respectively. Experimental hypertension was induced with angiotensin II or with a nitric oxide synthesis inhibitor. Under basal conditions, lack of Col XV resulted in increased permeability and impaired microvascular hemodynamics, distinct early-onset and age-dependent defects in heart structure and function, a poorly organized fibrillar collagen matrix with marked interstitial deposition of nonfibrillar protein aggregates, increased tissue stiffness, and irregularly organized cardiomyocytes. In response to experimental hypertension, Col15a1 gene expression was increased in the left ventricle of wild-type mice, and mRNA expression of natriuretic peptides (ANP and BNP) and ECM modeling were abnormal in Col15a1 ؊/؊ mice. Key Words: cardiomyopathy Ⅲ collagen Ⅲ extracellular matrix Ⅲ hypertension Ⅲ microcirculation T he extracellular matrix (ECM) has an important role in cardiac remodeling, defined by the adaptive changes in left ventricular structure, geometry, and function that follow cardiovascular stress in hypertensive heart disease, cardiomyopathies, or myocardial infarction and also as a function of age. 1 Degradation of myocardial collagens results in decreased ventricular stiffness and dilatation, whereas an increase in the total interstitial collagen content and crosslinking results in a stiffer myocardium and ventricular diastolic dysfunction. 2 Cardiomyopathy may result from a variety of acquired or genetic factors. In the absence of coronary artery disease, a significant proportion of cardiomyopathies are attributable to a genetic cause, eg, hereditary forms are present in approximately 30% to 50% of patients experiencing dilative cardiomyopathy (DCM), and mutations in more than 30 genes have been linked to this disease. 3 Many defects in cytoskeletal and sarcomeric proteins involved in cardiomyocyte contraction and force production have been associated with familial DCM, but most of the genetic defects and pathophysiological mechanisms have still not been identified. 4 Recent studies using genetically modified mice suggest that altered cell-ECM interactions and cell-cell adhesion via the intercalated discs may be involved in DCM pathogenesis. [5][6]...
To clarify whether avascular purified endocrine cell aggregates derived from islets of Langerhans (pseudoislets) revascularize similarly to what is known for intact pancreatic islet grafts, we studied the process of angiogenesis and revascularization of syngeneically transplanted pseudoislets using intravital fluorescence microscopy. Pseudoislets were composed of pure beta-cells (B) or non-beta-cells (NB), as well as of mixed beta- and non-beta-cells (B/NB; 70/30%) or nonsorted-cells (NC), and were transplanted into the dorsal skinfold of Syrian golden hamsters. Intact islet grafts served as controls. At day 6 after transplantation, microvascularization of all types of pseudoislets was found to be less than in controls, as indicated by a reduced number of transplants that contained newly formed microvessels (take-rate: B, 38.8; NB, 38.7; B/NB, 43.8; and NC, 40.3% vs. intact islet grafts, 71.9%; P < 0.01). Moreover, those pseudoislets that had developed a microvascular network revealed a significantly lower functional capillary density (145.8+/-49.5 to 241.0+/-47.5 cm(-1) vs. intact islet grafts: 459.8+/-65.6 cm(-1); P < 0.05). After 20 days, the take-rate of pseudoislets was still lower (B, 67.4; NB, 45.3; B/NB, 48.4; and NC, 64.2%) when compared with intact islet grafts (88%; P < 0.05); however, islet-like aggregates with vascularization now showed an islet-specific glomerulus-like network of capillaries with a functional capillary density (498.5+/-49.1 to 601.4+/-124.0 cm[-1]) similar to that of intact islet grafts (644.3+/-26.8 cm[-1]). We conclude that the dissociation of pancreatic islets, followed by reaggregation of the purified endocrine cells to islet-like clusters (pseudoislets), delays the process of angiogenesis and revascularization after free transplantation; however, this does not influence the capacity to form an intact islet-specific microvasculature (angio-architecture), which appears to be independent from the cellular composition of pseudoislets.
Assumedly our patient suffered from a partial anterior spinal artery syndrome, possibly caused by a disc herniation-related compression that was reversible following surgery. This was accompanied by a complete resolution of spinal cord signal abnormalities in T2WI and DWI.
NLM is a tool which could be adapted for neurosurgical intraoperative applications with the potential to diagnose tumours and recognise the tumour centre and infiltration zone in vivo. Further applications of NLM to characterise subcellular structures and vascular architecture are possible.
PurposeOpen surgical muscle biopsy (OB) and percutaneous Bergstroem needle muscle biopsy (NB) are equally accepted procedures. However, there are no data comparing intraprocedural pain for both techniques. We designed this prospective trial to test the hypothesis that the less invasive NB causes less intraprocedural pain than OB.MethodsIn a two-center prospective trial, 33 patients underwent both procedures in one session. All patients quantified intraprocedural pain using the numeric rating scale (NRS). Mean NRS values were calculated along with the difference in NRS values (ΔNRS) between both types of biopsies.ResultsMean NRS values were 4.5 (±2.7 standard deviation [SD]) for NB and 3.2 (±2.1) for OB (P=0.02). Of the patients, 57.6% described the ΔNRS as ≤2 NRS points. Regarding the pain categories “mild” (NRS 0–3), “moderate” (NRS 4–7), and “severe” (NRS 8–10), no significant difference was observed between NB and OB. Patients who found NB to be more uncomfortable were more likely to quantify the ΔNRS as >2 NRS points than patients finding OB more uncomfortable.ConclusionOur results do not support the hypothesis that intraprocedural pain in NB is less than in OB. When informing the patient about both types of muscle biopsies, the amount of intraprocedural pain should not serve as a differentiating characteristic.
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