Recovery of motor function and dopaminergic parameters in a mouse model of Parkinson's disease induced by co-administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and diethyldithiocarbamate.

Diethyldithiocarbamate (DDC) enhances the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We studied the time course of dopaminergic parameters and motor function of MPTP+DDC-lesioned C57BL/6 mice, a model of Parkinson's disease. MPTP+DDC-lesioned mice showed a decrease in dopamine (DA) and its metabolites contents in their striata 1, 3 and 6 weeks after MPTP+DDC-treatment, compared with those of each control group. The partial and significant recoveries in DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid contents were also observed after 6 weeks, compared with those at 1 week after treatment. In addition, bradykinesia due to DA depletion was observed in mice 1 week after MPTP+DDC-treatment, but it was not significant 3 weeks after the treatment. l-DOPA alone and a co-administration of l-DOPA and a monoamine oxidase-B inhibitor selegiline improved bradykinesia of this model, also suggesting that bradykinesia observed in the model was mediated to dopaminergic deficiency. On the other hand, the serotonin content increased slightly but significantly after 3 or 6 weeks, suggesting compensatory activation of the serotonergic system against DA depletion. Thus, the partial recovery of dopaminergic parameters, the recovery of motor function and the compensatory activation of the serotonergic system were observed in this model 3-6 weeks after MPTP+DDC treatment.

Downregulation of vascular soluble guanylate cyclase induced by high salt intake in spontaneously hypertensive rats.

1. Cyclic guanosine monophosphate (cyclic GMP)-mediated mechanism plays an important role in vasodilatation and blood pressure regulation. We investigated the effects of high salt intake on the nitric oxide (NO) - cyclic GMP signal transduction pathway regulating relaxation in aortas of spontaneously hypertensive rats (SHR). 2. Four-week-old SHR and normotensive Wistar-Kyoto rats (WKY) received a normal salt diet (0.3% NaCl) or a high salt diet (8% NaCl) for 4 weeks. 3. In aortic rings from SHR, endothelium-dependent relaxations in response to acetylcholine (ACh), adenosine diphosphate (ADP) and calcium ionophore A23187 were significantly impaired by the high salt intake. The endothelium-independent relaxations in response to sodium nitroprusside (SNP) and nitroglycerin were also impaired, but that to 8-bromo-cyclic GMP remained unchanged. On the other hand, high salt diet had no significant effects on the relaxations of aortic rings from WKY. 4. In aortas from SHR, the release of NO stimulated by ACh was significantly enhanced, whereas the production of cyclic GMP induced by either ACh or SNP was decreased by the high salt intake. 5. Western blot analysis showed that the protein level of endothelial NO synthase (eNOS) was slightly increased, whereas that of soluble guanylate cyclase (sGC) was dramatically reduced by the high salt intake. 6. These results indicate that in SHR, excessive dietary salt can result in downregulation of sGC followed by decreased cyclic GMP production, which leads to impairment of vascular relaxation in responses to NO. It is notable that chronic high salt intake impairs the sGC/cyclic GMP pathway but not the eNOS/NO pathway.

Ascites due to hypothyroidism in a patient with alcoholic cirrhosis.

Myxedema is the cause of ascites in less than 1% of new-onset ascites cases, where as only 4% of patients with hypothyroidism present ascites. When ascites is the first manifestation of thyroid insufficiency, there is usually a delay in diagnosis. We report here a case of myxedema ascites occurring in a patient with alcoholic cirrhosis, that was first thought to be the cause of the ascites, and review the features of 48 cases previously reported. Some clinic and analytical findings that have been commonly reported, are the long duration of the ascites before diagnosis, the prompt response (with resolution of ascites) to thyroid replacement treatment, a high total protein concentration in ascites fluid, white moderate white blood cell counts and a lymphocyte predominance. Serum-ascites albumin gradient has been postulated to be high in myxedema ascites, but we believe this has been studied in too few cases thus far, to be conclusive.

Ascites due to hypothyroidism in a patient with alcoholic cirrhosis

Myxedema is the cause of ascites in less than 1 per cent of new-onset ascites cases, where as only 4 per cent of patients with hypothyroidism present ascites. When ascites is the first manifestation of thyroid insufficiency, there is usually a delay in diagnosis. We report here a case of myxedema ascites occuring in a patient with alcoholic cirrhosis, that was first thought to be the cause of the ascites, and review the features of 48 cases previously reported. Some clinic and analytical findings that have been commonly reported, are the prompt response (with resolution of ascites) to thyroid replacement treatment, a high total protein concentration in ascitec fluid, white moderate white blood cell counts and a lymphocyte predominance. Serum-ascites albumin gradient has been postulated to be high in myxedema ascites, but we believe this has been studied in too few cases thus far, to be conclusive. (Au)

Ascites due to hypothyroidism in a patient with alcoholic cirrhosis.

Myxedema is the cause of ascites in less than 1

of new-onset ascites cases, where as only 4

of patients with hypothyroidism present ascites. When ascites is the first manifestation of thyroid insufficiency, there is usually a delay in diagnosis. We report here a case of myxedema ascites occurring in a patient with alcoholic cirrhosis, that was first thought to be the cause of the ascites, and review the features of 48 cases previously reported. Some clinic and analytical findings that have been commonly reported, are the long duration of the ascites before diagnosis, the prompt response (with resolution of ascites) to thyroid replacement treatment, a high total protein concentration in ascites fluid, white moderate white blood cell counts and a lymphocyte predominance. Serum-ascites albumin gradient has been postulated to be high in myxedema ascites, but we believe this has been studied in too few cases thus far, to be conclusive.

Ascites due to hypothyroidism in a patient with alcoholic cirrhosis

Myxedema is the cause of ascites in less than 1 per cent of new-onset ascites cases, where as only 4 per cent of patients with hypothyroidism present ascites. When ascites is the first manifestation of thyroid insufficiency, there is usually a delay in diagnosis. We report here a case of myxedema ascites occuring in a patient with alcoholic cirrhosis, that was first thought to be the cause of the ascites, and review the features of 48 cases previously reported. Some clinic and analytical findings that have been commonly reported, are the prompt response (with resolution of ascites) to thyroid replacement treatment, a high total protein concentration in ascitec fluid, white moderate white blood cell counts and a lymphocyte predominance. Serum-ascites albumin gradient has been postulated to be high in myxedema ascites, but we believe this has been studied in too few cases thus far, to be conclusive.

Excessive salt or cholesterol intake alters the balance among endothelium-derived factors released from renal arteries in spontaneously hypertensive rats.

We investigated the vasorelaxation in renal arteries isolated from spontaneously hypertensive rats (SHRs) fed a basal, a high-salt, or a high-cholesterol diet for 8 weeks. In renal arterial rings from the control group, acetylcholine (ACh)-induced endothelium-dependent relaxations were markedly increased by indomethacin (IND) and ONO-3708, a prostaglandin H2/thromboxane A2-receptor antagonist, but not affected by OKY-046, a thromboxane A2 synthetase inhibitor. These increased relaxations were partially inhibited by either NG-nitro-L-arginine methyl ester (L-NAME) or charybdotoxin (CTX), and almost completely abolished by the combination of L-NAME plus CTX. The ACh-induced endothelium-dependent relaxations in the absence of IND were significantly attenuated by the high-salt intake but not affected by the high-cholesterol intake. The degrees of relaxations in the presence of IND were approximately equal among the three diet groups. On the other hand, the relaxations in the presence of IND plus L-NAME were significantly augmented by a high-cholesterol intake and abolished by a high-salt intake, and the relaxations in the presence of IND plus CTX were slightly reduced by a high-cholesterol intake and significantly augmented by a high-salt intake. The production of cyclic guanosine monophosphate (cGMP) in response to ACh was significantly decreased by a high-cholesterol intake and tended to be increased by a high-salt intake. These findings indicate that in the renal artery of SHRs, ACh causes production of a sufficient amount of nitric oxide (NO), together with a relaxing factor resembling endothelium-derived hyperpolarizing factors (EDHFs) and also endothelium-derived contracting factors (EDCFs), probably prostaglandin H2. Our results also suggest that excessive salt intake increases the release of EDCF and NO and decreases that of an EDHF-like factor, whereas excessive cholesterol intake increases release of an EDHF-like factor and decreases that of NO.

Left ventricular aneurysm with 1- to 2-mm-thick myocardium: a variant of the classic true aneurysm?

From January 1983 to July 1985, 64 patients underwent left ventricular aneurysmectomy in our surgical unit. In 11 (17%) of these cases, the lesion was a variant of the true aneurysm that included an extremely thin (1- to 2-mm), well-defined area of myocardium. In 9 of the cases, the aneurysm was confirmed preoperatively by means of high-quality ventriculography (high resolution and many hues of gray). Surgical and pathologic criteria established the lesion's clinical significance. To the best of our knowledge, these aneurysms constitute a heretofore undescribed variant of the classic true left ventricular aneurysm, exhibiting certain gross characteristics of the false left ventricular aneurysm and sharing with false aneurysms their greater risk of rupture. While it is impossible to tell whether these aneurysms are progressing toward rupture, we believe that all such lesions should undergo urgent repair in the presence of cardiac symptoms. Following aneurysmectomy, ventriculoplasty or septoplasty using an elliptical woven Dacron patch helps to preserve the internal contour and surface anatomy of the ventricle. In our series, this procedure resulted in early and late postoperative mortality figures comparable to those associated with the surgical treatment of classic true left ventricular aneurysms.

The low profile bioprosthesis: results with 491 valves implanted in 453 patients for up to 5 years.

This report summarizes results of the first 453 consecutive patients who had 491 low profile bioprostheses implanted at the Italian Hospital in Buenos Aires over a 5-year period. During this time, with the goal of long-term durability, the valve mounting technique was slightly modified, whereas the materials and design of the annulus underwent more extensive changes.