The response of NG2-expressing oligodendrocyte progenitors to demyelination in MOG-EAE and MS

Remyelination of primary demyelinated lesions is a common feature of experimental models of multiple sclerosis (MS) and is also suggested to be the normal response to demyelination during the early stages of MS itself. Many lines of evidence have shown that remyelination is preceded by the division of endogenous oligodendrocyte precursor cells (OPCs) in the lesion and its borders. It is suggested that this rapid response of OPCs to repopulate the lesion site and their subsequent differentiation into new oligodendrocytes is the key to the rapid remyelination. Antibodies to the NG2 chondroitin sulphate proteoglycan have proved exceedingly useful in following and quantitating the response of endogenous OPCs to demyelination. Here we review the literature on the response of NG2-expressing OPCs to demyelination and provide some new evidence on their response to the chronic inflammatory demyelinating environment seen in recombinant myelin oligodendrocyte glycoprotein (MOG) induced experimental allergic encephalomyelitis (EAE) in the DA rat. NG2-expressing OPCs responded to the inflammatory demyelination in this model by becoming reactive and increasing in number in a very focal manner. Evidence of NG2⁺OPCs in lesioned areas beginning to express the oligodendrocyte marker CNP was also seen. The response of OPCs appeared to occur following successive relapses but did not always lead to remyelination, with areas of chronic demyelination observed in the spinal cord. The presence of OPCs in the adult human CNS is clearly of vital importance for repair in multiple sclerosis (MS). As in rat tissue, the antibody labels an evenly distributed cell population present in both white and grey matter, distinct from HLA-DR⁺microglia. NG2⁺cells are sparsely distributed in the centre of chronic MS lesions. These cells apparently survive demyelination and exhibit a multi-processed or bipolar morphology in the very hypocellular environment of the lesion.     

DNA index of colorectal carcinoma and follow-up]

In relation to DNA index we have studied 18 cases of differently evoluted carcinoma of the colon, some incoherently (8) other in agreement (10) with staging. Static and flow cytometric techniques have been employed, the first by means of densitometric study on paraffin sections with the Feulgen method, the second based on application of Hedley method on paraffin included material. DNA content, pressed by the DNA index, is inversely proportional to survival with similar results in both techniques, from which the possible prognostic significance is argued.     

Noninvasive evaluation of systolic and diastolic function in severe congestive heart failure secondary to coronary artery disease or idiopathic dilated cardiomyopathy

The usefulness of systolic time intervals, diastolic time intervals and echocardiography in evaluating left ventricular (LV) function was determined in 69 patients with severe congestive heart failure. All systolic time intervals were markedly abnormal (preejection period/LV ejection time 0.59 +/- 0.18 vs 0.30 +/- 0.04, preejection period index 170 +/- 37 vs 117 +/- 11, LV ejection time index 372 +/- 26 vs 410 +/- 17; patients vs control subjects, p less than 0.05). Diastolic time intervals in patients were not different from those in control subjects. Echocardiographic measurements were all markedly abnormal (LV end-diastolic dimension 6.9 +/- 1.0 vs 4.8 +/- 0.4 cm, patients vs control subjects, p less than 0.05). No pattern of abnormalities distinguished ischemic cardiomyopathies from idiopathic dilated cardiomyopathies. The presence of LV conduction delay did not substantially alter results, except that exclusion of patients with LV conduction delay normalized the total time of systole (QA2) index (from 542 +/- 40 to 531 +/- 31 ms) and reduced but did not normalize prolongation in the preejection period index (from 170 +/- 37 to 162 +/- 29 ms). No systolic or diastolic interval strongly correlated with any hemodynamic or other independent measure of LV performance. Twenty-four patients were given inotropic or unloading agents, which significantly improved hemodynamic values. Systolic and diastolic intervals were measured at baseline and at maximal hemodynamic effect. The correlation of changes in hemodynamics with changes in systolic and diastolic intervals was only modest. Thus, although systolic time intervals and associated echocardiographic measurements can detect abnormal LV function, they cannot reliably detect a change in LV function or distinguish gradations of abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fibrinogen as a predictor of mortality after acute myocardial infarction: a forty-two-month follow-up study.

BACKGROUND: Several studies suggest that fibrinogen may be considered an independent risk factor for coronary artery disease, but it is still on debate if we need its evaluation during an acute myocardial infarction (AMI) to prevent future fatal or non-fatal cardiovascular events. Therefore, we decided to investigate this field. METHODS: We studied 92 male patients with AMI, evaluating at admission age, body mass index, systolic blood pressure, cigarette smoking, ejection fraction, plasma levels of total cholesterol, triglycerides, fibrinogen, glycemia, and white blood cell count. All patients were followed up for 42 months to evaluate total mortality and cardiovascular morbidity. RESULTS: During the follow-up 5 patients died and 64 had one or more non-fatal cardiovascular events: angina (n = 78), heart failure (n = 17), re-AMI (n = 3), stroke (n = 3), or revascularization procedure (n = 16). A multivariate analysis revealed that fibrinogen plasma levels at admission (r = +0.213, p < 0.05) were independently associated with mortality, while systemic thrombolysis was negatively associated (r = -0.447, p < 0.0001). CONCLUSIONS: Plasma fibrinogen levels were the only independent predictor of mortality in a 42-month follow-up post-AMI. This finding, together with other observations from recent studies, suggest that fibrinogen evaluation during AMI may be useful in identifying patients at higher risk of acute event recurrence.     

Digestive endoscopy and portal hypertension. North Italian Endoscopic Club

Improved knowledge of pathophysiology of portal hypertension and technological progress have contributed to development of new endoscopic techniques and pharmacological approaches to treatment of this condition. To put the role of endoscopy in the right perspective, it is important to consider that liver transplantation has greatly modified prognosis of cirrhosis. Because of the increase of indications for transplantation, these complications are no longer regarded as the last, but rather as an intermediate stage before a possible transplantation. We have reviewed some pathophysiologic, diagnostic and therapeutic aspects on portal hypertension, especially the role of endoscopy in diagnosis, natural history and therapeutic options for complications of cirrhosis. In addition to sclerotherapy, new endoscopic methods have been developed, with a low complication rate and possibility of being applied for treatment of gastric varices, i.e. injection of tissue adhesives and rubber band ligation. Besides oesophageal varices, gastric varices and portal hypertensive gastropathy (and portal colopathy) are important findings in cirrhosis. Further information is needed on natural history and treatment of these conditions. Digestive haemorrhage is the most important consequence of portal hypertension, so treatment should be aimed at controlling acute bleeding, rebleeding and, more important, at preventing first haemorrhagic episode. Good results will probably be obtained using a combination of drugs, a combination of endoscopic methods or a combination of both. All will need evaluation in randomised, controlled trials. These considerations renew interest in strategies for diagnosis and treatment of portal hypertension and a multidisciplinary approach may be necessary, involving gastroenterologists, endoscopists, interventionist radiologists and surgeons, ideally in a departmental environment.     

Morphologies and prognostic significance of left ventricular volume/time curves with cardiac magnetic resonance in patients with non-ischaemic heart failure and left bundle branch block

The International Journal of Cardiovascular Imaging - Patients with non-ischaemic systolic heart failure (HF) and left bundle branch block (LBBB) can display a wide or narrow pattern (WP/NP) of the...     

Combined blockade of AT1-receptors and ACE synergistically potentiates antihypertensive effects in SHR

OBJECTIVES AND DESIGN: To check whether antihypertensive effects are additive or synergistic upon blockade of both angiotensin (AT1)-receptors and angiotensin-converting enzyme (ACE), spontaneously hypertensive rats (SHR) were treated with candesartan-cilexetil (0.1-30 mg/kg per day), ramipril (0.03-10 mg/kg per day), the calcium-antagonist mibefradil (1-150 mg/kg per day) or combinations thereof. Systolic blood pressure (SBP), left ventricular weight (LVW) and the cardiac activity/mRNA levels of ACE were determined. RESULTS: SBP was decreased by candesartan-cilexetil [inhibitory concentration (IC50) (mg/kg): 2.47], ramipril (1.97), mibefradil (4.41), candesartan-cilexetil/ramipril (0.68), and candesartan-cilexetil/mibefradil (5.68). Combining candesartan-cilexetil with ramipril increased SBP reduction synergistically rather than additively, since the dose-response curve was shifted 6.6-fold leftwards compared to a hypothetically generated additive curve, calculated by summing up the doses and corresponding effects of the ramipril and candesartan-cilexetil monotreatment regimes. A total threshold dose < 5.14 mg/kg (derived from dose-response curves) was found to exert synergistic effects when candesartan-cilexetil was combined with ramipril. Antihypertensive effects of mibefradil can not be increased when combined with candesartan-cilexetil. When LVW was correlated with SBP reduction, regression lines of candesartan-cilexetil, ramipril and their combination were congruent, while that for mibefradil was significantly flatter and became steeper under candesartan-cilexetil co-administration. Cardiac ACE activity was greatly reduced by ramipril independently of SBP reduction and dosage. With SBP-ineffective doses of ramipril, cardiac ACE mRNA levels were doubled, indicating a positive feedback mechanism. The increase in ACE mRNA was renormalized when SPB-effective ramipril doses were applied, suggesting a blood pressure-dependent regulation of cardiac ACE expression. CONCLUSIONS: Since synergy was observed only after combining low doses of ramipril and candesartan-cilexetil, prospective clinical trials should be performed on a low-dose combination, revealing the antihypertensive/antiproliferative benefits.