Objectives The aim of this study was to test the hypothesis that angiotensin (Ang)-converting enzyme-2 (ACE2) overexpression may inhibit myocardial collagen accumulation and improve left ventricular ...(LV) remodeling and function in diabetic cardiomyopathy. Background Hyperglycemia activates the renin-Ang system, which promotes the accumulation of extracellular matrix and progression of cardiac remodeling and dysfunction. Methods Ninety male Wistar rats were divided randomly into treatment (n = 80) and control (n = 10) groups. Diabetes was induced in the treatment group by a single intraperitoneal injection of streptozotocin. Twelve weeks after streptozotocin injection, rats in the treatment group were further divided into adenovirus-ACE2, adenovirus–enhanced green fluorescent protein, losartan, and mock groups (n = 20 each). LV volume; LV systolic and diastolic function; extent of myocardial fibrosis; protein expression levels of ACE2, Ang-converting enzyme, and Ang-(1-7); and matrix metalloproteinase–2 activity were evaluated. Cardiac myocyte and fibroblast culture was performed to assess Ang-II and collagen protein expression before and after ACE2 gene transfection. Results Four weeks after ACE2 gene transfer, the adenovirus-ACE2 group showed increased ACE2 expression, matrix metalloproteinase–2 activity, and LV ejection fractions and decreased LV volumes, myocardial fibrosis, and ACE, Ang-II, and collagen expression in comparison with the adenovirus–enhanced green fluorescent protein and control groups. ACE2 was superior to losartan in improving LV remodeling and function and reducing collagen expression. The putative mechanisms may involve a shift in balance toward an inhibited fibroblast-myocyte cross-talk for collagen and transforming growth factor–beta production and enhanced collagen degradation by matrix metalloproteinase–2. Conclusions ACE2 inhibits myocardial collagen accumulation and improves LV remodeling and function in a rat model of diabetic cardiomyopathy. Thus, ACE2 provides a promising approach to the treatment of patients with diabetic cardiomyopathy.
Background Confocal laser endomicroscopy (CLE) is a novel endoscopic modality that allows subsurface analysis of the gastric mucosa during ongoing endoscopy. Several studies have reported that this ...technique is of value in the diagnosis of premalignant lesions in the GI tract, but as yet no investigations have reported its application in the analysis of gastric intraepithelial neoplasia (GIN). Objective To assess the feasibility of CLE for the identification and grading of GIN. Design Prospective double-blind feasibility study. Setting Qilu Hospital, Shandong University, Jinan, China. Patients CLE images of 33 patients were first evaluated to establish the diagnostic criteria for gastric lesions. Eligible patients were then prospectively investigated by CLE using the newly established criteria. Interventions All endoscopically suspicious lesions were examined by CLE, and CLE diagnoses were compared with corresponding histopathologic results. Main Outcome Measurements Sensitivity, specificity, and positive and negative likelihood ratios of CLE diagnosis of biopsy-proven intraepithelial neoplasia by per-lesion analysis. Results The sensitivity, specificity, and positive and negative likelihood ratios of CLE diagnosis of GIN were 77.8%, 81.8%, 4.28, and 0.27, respectively. The mean κ value for interobserver agreement for the diagnosis of GIN was 0.70 among endoscopists and 0.71 between endoscopist and GI pathologist. Intraepithelial neoplasia score ≥5 differentiated high-grade from low-grade intraepithelial neoplasia with a sensitivity of 66.7% and a specificity of 88.0%. Limitations Nonrandomized single-center study, limited number of patients. Conclusions CLE is an acceptable and potentially useful technology for the identification and grading of GIN in vivo. The diagnostic accuracy needs to be improved.
Background Detection and differentiation of esophageal squamous neoplasia (ESN) are of value in improving patient outcomes. Probe-based confocal laser endomicroscopy (pCLE) can serve in targeted ...biopsies in the diagnosis of GI neoplasia. However, its performance in ESN has not yet been reported. Objective To investigate the diagnostic value of pCLE for early ESN screened by high-definition virtual chromoendoscopy (I-Scan) and verified by Lugol chromoendoscopy and histopathology. Design Prospective and noninferiority trial. Setting Single center in China. Patients Patients were enrolled who (1) previously had histologically verified early ESN or (2) were about to undergo screening endoscopy and were 50 to 80 years of age between February 2013 and February 2014. Interventions The esophagus was investigated sequentially by white-light endoscopy, I-Scan, then pCLE and iodine chromoendoscopy. The results were interpreted and compared with histopathologic results. Main Outcome Measurements Diagnostic characteristics of pCLE and I-Scan. Results In total, 356 patients were enrolled. In all, 42 patients were histologically proven to have 47 neoplasias. The diagnostic value of pCLE for ESN during ongoing endoscopy has a sensitivity, specificity, and accuracy of 94.6%, 90.7%, and 92.3%, respectively. The interobserver and intraobserver agreement was good and excellent, with κ values of 0.699 and 0.895, respectively. The detection rate by using I-Scan and Lugol chromoendoscopy was 10.4% and 12.9%, respectively ( P < .01 for noninferiority). Limitations Single center. Conclusions pCLE shows promise in diagnosing and differentiating ESN in vivo. The screening performance of I-Scan in the detection of ESN is noninferior to that of iodine chromoendoscopy.
Background Confocal endomicroscopy is a newly developed endoscopic imaging technology that produces 1000-fold magnification cross-sectional images of the GI surface and subsurface tissue during ...routine endoscopy. The gastric pit patterns identified by confocal endomicroscopy and correlation with histopathologic examination have not yet been established. Objective Our purpose was to explore the appearance of various kinds of gastric pits and clarify the relationship between gastric pit patterns and the histopathologic findings. Design Descriptive study. Setting Qilu Hospital, Shandong University, Jinan, China. Patients A total of 132 consecutive patients underwent confocal endomicroscopy after 7 healthy volunteers had been examined in vivo and 10 samples resected from 10 patients with gastric cancer had been examined ex vivo by use of confocal endomicroscopy. The confocal images obtained from the 132 patients were compared with the histopathologic findings of the biopsy specimens from the corresponding confocal imaging sites in a prospective and blinded fashion. Main Outcome Measurements The relationship between the pit patterns and the histopathologic findings. Results Gastric pit patterns were classified into 7 types. Normal mucosa with fundic glands mainly showed type A (round pits), and corporal mucosa with histologic gastritis showed type B (noncontinuous short rod-like); normal mucosa with pyloric glands mainly showed type C (continuous short rod-like), and antral mucosa with histologic gastritis showed type D (elongated and tortuous branch-like). Goblet cells were easily distinguished by confocal endomicroscopy in intestinal metaplasia mucosa, which showed type F. The sensitivity and specificity of the type E pattern for predicting gastric atrophy were 83.6% and 99.6%, respectively. Corresponding values of the type G pattern for predicting gastric cancer were 90.0% and 99.4%. Limitations No data on interobserver and intraobserver variability. Conclusions The patterns of gastric pits identified by confocal endomicroscopy correlate well with the histopathologic findings. Confocal endomicroscopy may prove useful in predicting histopathologic diagnoses during routine endoscopic procedures.
Summary Our aim was to investigate the expression of micro-RNA-200b (miR-200b) and cAMP-responsive element-binding protein 1 (CREB-1) in astrocytoma and its efficacy for predicting outcome. Both ...miR-200b and CREB-1 messenger RNA expression was measured in 122 astrocytomas and 30 nonneoplastic brain specimens by quantitative real-time polymerase chain reaction. Expression of miR-200b was significantly lower in astrocytoma than in nonneoplastic brain ( P < .001), whereas CREB-1 messenger RNA expression was significantly elevated in the tumors ( P < .001). Both miR-200b down-regulation and CREB-1 up-regulation were significantly associated with advanced pathologic grade ( P = .002 and P = .006, respectively). Low miR-200b expression correlated negatively with Karnofsky performance score ( P = .03), and high CREB-1 expression correlated positively with mean tumor diameter ( P = .03). By Kaplan-Meier analysis, low miR-200b, high CREB-1, and coexistence of abnormal miR-200b and CREB-1 expression (low miR-200b/high CREB-1) were predictive of shorter progression-free survival and overall survival in both grade III and grade IV astrocytoma. By multivariate analysis, only low miR-200b/high CREB-1 expression was an independent prognostic factor for poor prognosis in astrocytoma of advanced grade. Both miR-200b and CREB-1 may play important cooperative roles in the progression of human astrocytoma. The efficacy of miR-200b and CREB-1 together as a predictor of prognosis in astrocytoma patients is shown for the first time.
Background Helicobacter pylori infection and intestinal metaplasia (IM) are associated with gastric cancer. An impaired gastric mucosal barrier could be involved in this carcinogenesis. Objective To ...evaluate laser confocal laser endomicroscopy (CLE) for in vivo functional imaging of mucosal barrier defects in patients with IM. Design Prospective, controlled study. Setting A tertiary-care academic center. Patients This study involved patients with IM of the gastric mucosa who underwent CLE for surveillance. Interventions Specific IM mucosa and non-IM mucosa in patients were identified by CLE, and targeted biopsy samples were taken for histopathology and electron microscopy. Main Outcome Measurements Post-CLE assessment of paracellular fluorescein leakage was devised and validated by electron microscopy. We also evaluated the effect of H pylori eradication on the mucosal barrier. Results Forty-two patients were included. Of non-IM samples, the paracellular permeability was significantly increased in H pylori –positive samples compared with H pylori –negative controls (54 ± 31% vs 3 ± 6%, P < .05). Of IM samples, the permeability was significantly increased in both H pylori –negative and H pylori –positive samples (67 ± 34% and 72 ± 28% vs 3 ± 6%, both P < .05). The results of post-CLE assessment correlated well with the electron microscopy findings ( R 2 0.834, P < .0001). After the eradication of H pylori , the paracellular barrier dysfunction of non-IM mucosa was significantly improved as shown by electron microscopy and CLE (both P < .001). However, there was no significant change in IM mucosa. Limitations Single-center study. Conclusions CLE allows functional imaging of mucosal barrier defects. Gastric IM is associated with an impaired paracellular barrier irrespective of H pylori eradication.
Abstract Background To clarify whether propofol (PROP) and dexmedetomidine (DEX) differentially affect preload dependency in an endotoxemic model based on evaluations of the systemic vascular system ...and cardiac function. Methods Animals were prepared under PiCCO monitoring (BL), and endotoxemic shock was induced using an intravenous bolus of lipopolysaccharide (055:B5) in 16 New Zealand ketamine-anesthetized rabbits. After fluid resuscitation and norepinephrine infusion (SD0), the animals were randomized to PROP ( n = 8) or DEX ( n = 8) sedation at two incremental doses (SD1 and SD2). The mean arterial pressure and the central venous pressure were monitored. Pulse pressure variation (PPV) was assessed to evaluate preload dependency. Global end-diastolic volume, vascular resistance, mean systemic filling pressure, and cardiac function index were assessed at each time point. Results PPV progressively and significantly increased with increasing infusion rates of PROP (SD1 versus SD0, P < 0.01; SD2 versus SD0, P < 0.001; and SD2 versus SD1, P = 0.024) but not DEX. PPV was higher at SD1 and SD2 in the PROP group than in the DEX group ( P < 0.001). PROP increased the heart rate without affecting cardiac contractility or vascular resistance. In contrast, DEX decreased heart contractility and increased vascular resistance at the highest dose. However, neither drug affected mean arterial pressure, central venous pressure, mean systemic filling pressure, global end-diastolic volume, or venous return. Conclusions PROP more effectively increased PPV than DEX in an endotoxemic shock model after fluid resuscitation during norepinephrine infusion. DEX, but not PROP, at the highest dose influenced vascular resistance and heart contractility.
Abstract Background Predicting fluid responsiveness is crucial for fluid administration in septic shock patients. Midazolam and propofol decrease vascular tone and venous return, which may influence ...preload dependency. However, little is known about the effects of these two sedatives on preload dependency in septic shock patients. We evaluated the effects of sedation with propofol or midazolam on preload dependency in septic shock patients who have been fluid resuscitated. Methods Forty-three septic shock patients who were undergoing early goal-directed therapy resuscitated within 24 h were enrolled. The patients were randomly divided into the midazolam group and the propofol group. An initial passive leg-raising test (PLR1) was performed to evaluate passive leg raising test (PLR) responsiveness. Then, the patients were infused with midazolam or propofol. After increasing the doses of the sedatives to titrate to a Ramsay 4 score, a second passive leg raising test (PLR2) was conducted to evaluate PLR responsiveness. The primary end-point was the preload dependency before and after sedation with midazolam or propofol. Results In the midazolam-PLR1-negative patients, there was no difference between the changes in the cardiac index induced by PLR1 (PLR1-Δ cardiac function index CI) and the changes in the cardiac index induced by PLR2 (PLR2-Δ CI) (+1.4% ± 7.4% versus +1.7% ± 6.4%, P > 0.05). However, in the propofol-PLR1-negative patients, there was a significant increase in the PLR-Δ CI after sedation to a Ramsay 4 score compared with a Ramsay 3 score (+7.3% ± 4.8% versus +3.2% ± 4.7%, P = 0.008). There were no differences between PLR1-Δ CI and PLR2-Δ CI within the midazolam-PLR1-positive patients or within the propofol-PLR1-positive patients. Conclusions In titrating the sedation level from a Ramsay 3 score to a Ramsay 4 score, propofol but not midazolam increased preload dependency in septic shock patients with fluid nonresponsiveness.
Purpose To evaluate the quality of regenerating myelinated axons and motor-sensory specificity in an end-to-side nerve repair model. Methods We divided 20 rats into 3 groups: (1) end-to-side ...neurorrhaphy using the ulnar nerve as donor nerve and the musculocutaneous nerve as recipient nerve; (2) normal control; and (3) transected nerve with the stumps buried. At 5 months, we monitored the grooming test, the electrophysiological response, and the histologic changes in nerve and muscle. Results Grooming recovered successfully, and electrophysiological investigations revealed that the target muscles had been reinnervated in the end-to-side group. The mean wet weight of the reinnervated biceps brachii muscle was 72% of the normal muscle, and the mean muscle fiber cross-sectional area of the reinnervated muscle was similar to the normal muscle. The implanted musculocutaneous nerve contained varying but satisfactory numbers of axons (end-to-side group: 596 ± 348 vs normal group: 1,340 ± 241). Acetylcholinesterase staining revealed a similar percentage of myelinated fibers in the musculocutaneous nerve (39%) and the biceps brachii branch of the musculocutaneous nerve (38%) in the end-to-side group. This was similar to the number of myelinated fibers in the donor ulnar nerve (37%). Conclusions The present study confirms that limited but functional reinnervation can occur on the basis of collateral sprouting of intact axons from the ulnar nerve. The motor-sensory specificity is not important.
A simpler cardiac arrest model in rats Chen, Meng-Hua, MD; Liu, Tang-Wei, MD; Xie, Lu, DPharm ...
The American journal of emergency medicine,
07/2007, Letnik:
25, Številka:
6
Journal Article
Recenzirano
Abstract Two disadvantages of electrical induction of cardiac arrest used currently are that it is a technically complicated procedure and the consequent thermal injury, which prompts us to search ...for a simpler method with less adverse effect to induce ventricular fibrillation (VF) in rats. Different potential (18, 24, 30, and 36 V) of alternating current (AC) were administered to elicit VF in 15 rats via pacing electrode placed in esophagus. Four minutes after onset of VF, conventional cardiopulmonary resuscitation (CPR) was initiated. Restoration of spontaneous circulation was defined as the return of supraventricular rhythm with a mean aortic pressure of 20 mm Hg or greater for a minimum of 5 minute. Ventricular fibrillation was achieved by short interval of AC stimulation in all of the rats. After the termination of prolonged AC stimulation, electrocardiogram indicated VF occurred in 6 of 15 rats, asystole in 3 of 15 rats and pulseless electrical activity in 6 of 15 rats. Before CPR, however, electrocardiogram indicated that only 2 of 15 and 4 of 15 animals remained in VF and pulseless electrical activity, respectively, whereas 9 of 15 animals presented as asystole. After CPR, 11 of 15 animals were resuscitated. Necropsy showed that there was no gross evidence of thermal injury on the surface layer of the heart. Therefore, development of a rat cardiac arrest model by transesophageal AC stimulation is simpler and less adverse effect, which may have practical significance for facilitating experimental investigation on cardiac arrest and CPR.
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