Pulmonary injuries and cytokine levels after the intraperitoneal administration of pancreatic homogenates in rats.

INTRODUCTION: Our objective was to investigate the effects of the administration of pancreatic homogenates, with or without enzymatic activation, to healthy animals regarding cytokine serum levels and the development of pulmonary distress. MATERIAL AND METHODS: 106 male Wistar rats, divided into three groups, were studied: group A, intraperitoneal administration of homogenates activated with enterokinase; group B, homogenates without enterokinase; and group C, control group with administration of physiological saline solution. Each group was divided into 4 subgroups according to the time of sacrifice: 0, 2, 6 and 24 hours. We studied the pulmonary and pancreatic histology, serum parameters of renal and hepatic function, and serum levels of IL-1beta, IL-6 and TNFalpha. RESULTS: There was no mortality in any group. Pancreatic disorders in A and B groups were noted at 24 hours. These two groups had statistically significant higher transaminase serum levels than those of the control group, as well as statistically significant higher creatinine levels in group A. IL-1beta showed a statistically significant higher level at 6 h in both groups, A and B, but was higher in group A, which also exhibited significant pulmonary histologic damage with respect to controls at 6 h. CONCLUSIONS: The higher IL-1beta level in group A may result from production by peritoneal macrophages under the influence of homogenate enzymatic activation. This may be the reason for lung damage.     

Differences in the glutathione system of cultured aortic smooth muscle cells from young and aged rats

We studied the relation between the glutathione (GSH) system and cell proliferation in a model of smooth muscle cells (SMC) derived from the thoracic aorta of 4–6-week-old (young) and 15-month-old (aged) rats. SMC from aged rats showed greater levels of total non-protein thiol compounds (T-SH), increased glutathione transferase (GST) and increased glutathione reductase (GSSG-Red) activities compared with cells from young rats. These changes were associated with an increased proliferation rate of SMC from aged rats. To evaluate the role of GSH on cell proliferation better, a specific inhibitor of gamma-glutamyl-cystein synthetase, -buthionine-SR-sulphoximine (BSO) was used. BSO showed a dose-dependent inhibition of cell growth, with an IC₅₀ of 10⁻⁴ M, after 48–72 h of incubation. Removal of BSO restored cell growth, further suggesting a link between GSH levels and vascular cell proliferation. The inhibitory effect of BSO was about two times greater on SMC from young than on SMC from aged rats. BSO showed 56% inhibition on the proliferation of SMC from young rats and 32% inhibition on SMC from aged rats (10⁻⁴ M, 72 h of incubation). A parallel reduction of GSH levels of 38% and 19% for SMC from young and aged rats, respectively, was observed, suggesting that age-related factors may influence the involvement of GSH system in cell proliferation.     

The value of bone scintigraphy in the follow-up of vertebral osteoporosis

Summary In an open study, we have assessed the bone/soft tissue uptake index in recent osteoporotic vertebral collapse using scintigraphy. The evolution of these cases was followed-up at 6 months in 22 patients treated with 100 IU of salmon calcitonin plus 500 mg of elemental calcium/10 days per month and in 18 patients treated with 500 mg of elemental calcium only on a daily basis. There were no index differences between groups prior to treatment. At six months, the group treated with calcitonin plus calcium showed a significant decrease from 10.2±6.4 to 3.2±1.1 (p<0.001), while the calcium only group did not show any significant changes (12.1±6.6 vs 9.2±4.6), considering that there were significant differences between groups (p<0.001). On a mid-term basis, these results have shown the values of the bone soft tissue index in the follow-up of osteoporotic vertebral collapse.     

Clinical aspects of ACE inhibition in patients with acute myocardial infarction

Summary The purpose of the present article was to review the current evidence on the use of angiotensin-converting enzyme (ACE) inhibitors in acute myocardial infarction (MI). This article is based on published information as well as on our personal experience derived from an extensive analysis of the SMILE study. All the randomized trials have been included irrespective of the primary endpoint, and the results are presented in terms of either hemodynamic or clinical benefit. Short- and long-term treatment with ACE inhibitors in patients with acute MI results in a significant reduction in mortality, which is more evident in high risk patients (i.e., patients with left ventricular dysfunction, congestive heart failure on admission, or anterior myocardial infarction). Development and progression of congestive heart failure after myocardial infarction was significantly reduced by ACE inhibition, which also reduced the rate of reinfarction, the need for revascularization procedures, as well as the occurrence of ventricular arrhythmias, probably through a mechanism involving some drug-dependent effects. In conclusion, the available data strongly support a wide benefit associated with the use of ACE inhibitors in patients with high-risk acute MI.     

Metachromatic leukodystrophy with late adult-onset: diagnostic clues and differences from other genetic leukoencephalopathies with dementia

Journal of Neurology -     

One step arthroscopically assisted Latarjet and posterior bone-block,for recurrent posterior instability and anterior traumatic dislocation

This case presents the challenges of the surgical management for a patient with a history of recurrent posterior shoulder instability and subsequently traumatic anterior dislocation. The patient was already on the waiting list for an arthroscopic posterior stabilization with anchors, when a car accident caused an additional anterior shoulder dislocation. This traumatic anterior dislocation created a bone loss with a glenoid fracture and aggravated the preexisting posterior instability. In order to address both problems, we decided to perform an arthroscopically assisted Latarjet procedure for anterior instability and to stabilize with a bone graft for posterior instability. To our best knowledge, this type of surgical procedure has so far never been reported in the literature. The purpose of this report is to present the surgical technique and to outline the decision making process.     

Chronic treatment with nitric oxide-releasing aspirin reduces plasma low-density lipoprotein oxidation and oxidative stress,arterial oxidation-specific epitopes,and atherogenesis in hypercholesterolemic mice

The effects of chronic treatment with nitric oxide-containing aspirin (NO-aspirin, NCX-4016) in comparison with regular aspirin or placebo on the development of a chronic disease such as atherosclerosis were investigated in hypercholesterolemic low-density lipoprotein (LDL)-receptor-deficient mice. Male mice were assigned randomly to receive in a volume of 10 ml/kg either placebo (n = 10), 30 mg/kg/day NO-aspirin (n = 10), or 18 mg/kg/day of regular aspirin (n = 10). After 12 weeks of treatment, the computer-assisted imaging analysis revealed that NO-aspirin reduced the aortic cumulative lesion area by 39.8 +/- 12.3% compared with that of the placebo (P < 0.001). Regular aspirin did not reduce significantly aortic lesions (-5.1 +/- 2.3%) compared with the placebo [P = 0.867, not significant (NS)]. Furthermore, NO-aspirin reduced significantly plasma LDL oxidation compared with aspirin and placebo, as shown by the significant reduction of malondialdehyde content (P < 0.001) as well as by the prolongation of lag-time (P < 0.01). Similarly, systemic oxidative stress, measured by plasma isoprostanes, was significantly reduced by treatment with NCX-4016 (P < 0.05). More importantly, mice treated with NO-aspirin revealed by immunohistochemical analysis of aortic serial sections a significant decrease in the intimal presence of oxidation-specific epitopes of oxLDL (E06 monoclonal antibody, P < 0.01), and macrophages-derived foam cells (F4/80 monoclonal antibody, P < 0.05), compared with placebo or aspirin. These data indicate that enhanced NO release by chronic treatment with the NO-containing aspirin has antiatherosclerotic and antioxidant effects in the arterial wall of hypercholesterolemic mice.     

Hemorheologic and hemostatic changes in long-standing insulin-dependent (type I) diabetic patients with peripheral and autonomic cardiovascular neuropathy

Summary Diabetic microangiopathy may be associated with the pathogenesis and progression of autonomic and peripheral neuropathy. In 17 long-standing type I diabetic patients with peripheral and autonomic cardiovascular neuropathy, several hemorheological and hemostatic alterations were found compared to 13 matched type I patients without neuropathy. In particular, increased plasma von Willebrand factor antigen (p<0.001), fibronectin (p<0.001) and fibrinogen (p<0.001) levels were demonstrated in neuropathic in comparison with non-neuropathic diabetic patients. Moreover negative correlations between these parameters and both motor and sensitive conduction velocity of median, sural and peroneal nerves were observed in diabetic patients with neuropathy. Higher blood viscosity (p<0.05 at shear-rate of 450 and 225 s⁻¹; p<0.01 at 90 s⁻¹; p<0.001 at 4.5 and 2.25 s⁻¹), plasma viscosity (p<0.001) and lower erythrocyte filtrability (p<0.001) were also found in neuropathic compared to non-neuropathic diabetics. Increased prevalence of retinopathy (p<0.01) and nephropathy (p<0.001) was finally reported in patients with autonomic and peripheral neuropathy. Microvascular disease may be involved in the development of neuropathy in long-term type I diabetes mellitus. This study was presented in part at the 23rd Annual Meeting of the European Association for the Study of Diabetes, Leipzig (GDR), 15–19 September 1987.