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At least 307 records · Page 17Linked to original sources
PubMed1995

Evaluation of response to methotrexate by a functional index in juvenile chronic arthritis.

In juvenile chronic arthritis (JCA) the indices of disease activity, such as joint swelling, pain, tenderness, and limitation of motion, may poorly correlate with the degree of functional impairment. Since the improvement of functional capacity is one of the main objectives of treatment, we evaluated the effect of methotrexate (MTX) in 29 children with JCA by assessing both the articular indices and a functional status measure. After 6 months of therapy, 15 of the 29 patients had a significant (> or = 50%) reduction in the number of joints with active arthritis and/or the articular severity score and were then judged as responders, while 14 did not respond to MTX. In the responder group, the median functional index score decreased from 17 (range: 13-27) at baseline to 13 (range: 13-15) at 6 months (p < 0.001); the median score of the non-responder group was 20 both at baseline and at 6 months (ranges: 14-27, and 13-36, respectively). These results show an improvement of functional impairment in those patients who respond to MTX according to the conventional indices of articular inflammation.

Adolescent↗
PubMed1993

Acute hemispheric stroke: correlation between three-dimensional transcranial Doppler, MR-angiography, CT and clinical findings.

We examined 50 ischemic stroke patients and 67 controls free of vascular disease, intra- or extracranial. We assessed all subjects clinically by neurological examination (quantified on the Canadian Neurological Scale or CNS), by three-dimensional transcranial Doppler sonography (TCD-3D) and by computed tomography (CT) within 24 h of the acute event, repeating CT 15 days later. 15 patients also underwent magnetic resonance angiography (MRA) and digital subtraction angiography (DSA). We used the following Doppler parameters: interhemispheric asymmetry index (AI), mean flow velocity (mV) and pulsatility index (PI) for the middle cerebral artery (MCA). The difference between patients and controls on analysis of the variance (ANOVA) in respect of AI was significant: F = 50.8, p < 0.0001. The CNS-AI correlation was equally valid: r = -0.56, p < 0.001. The CNS-CT correlation proved to be highly significant: r = -0.72, p < 0.0001. TCD-3D allowed quantitative evaluation of the hemodynamic changes and of the collateral blood supply and proved to be a sound method for the investigation of ischemic stroke, correlating well with the clinical findings, MRA and lesion size on CT.

Acute Disease↗
PubMed1991

Three-dimensional transcranial Doppler in acute ischemic stroke in the territory of the middle cerebral artery: clinical and CT correlation.

We studied 34 patients with acute ischemic stroke in the territory of the middle cerebral artery (MCA) by three-dimensional transcranial Doppler (TCD-3D). The parameters analyzed were: mean blood flow velocity, systolic and diastolic velocities; indices of pulsatility, hemisphere asymmetry and pulsatility transmission. Of the 34 patients 11 presented marked slowing of flow velocity in the MCA on the infarct side with an asymmetry index (AI) of over 40%, 8 patients with slightly reduced flow velocity in the MCA and an AI of 25-40%, 2 patients in whom there was indirect evidence of collateral circulations in the anterior cerebral artery distribution together with slowing of MCA flow; 5 patients had stenosis of the MCA, 9 patients showed no alterations of the Doppler parameters. The correlation between neurological symptom pattern and AI was significant (r = 0.76). Noninvasive, easy to perform, performable at once and reliable, TCD-3D is a great improvement on traditional transcranial Doppler and is especially useful in assessing the hemodynamics of the cerebral circulation in ischemic stroke.

Acute Disease↗
PubMed1986

The squalene-2,3-epoxide cyclase as a model for the development of new drugs.

The 2,3-oxido squalene (SO) cyclases represent a group of enzymes which convert SO into polycyclic triterpenoids such as lanosterol, cycloartenol, cucurbitadienol and beta-amyrin. Taking into account the postulated model of the enzymatic cyclization of SO, we have investigated the possibility of designing compounds that would be selective and potent inhibitors of SO cyclases. Due to the fundamental role of sterols in animal, higher plant and fungal tissues, these inhibitors might behave as very selective (ipocholesterolemic, antifungal or phytotoxic) drugs. Our first approach was the synthesis and biological evaluation of 2-aza-2,3-dihydrosqualene and its derivatives which, being protonated at physiological pH, would present some similarities to the C-2 carbon ion generated by the opening of the oxirane ring of SO. Microsomes from different sources (germinated pea cotyledons, maize seedlings, rat liver and yeasts) were utilized to determine the inhibition values (I50: concentration of inhibitor producing 50% inhibition at a given substrate concentration). From the results obtained so far we conclude that 2-aza-2-dihydrosqualene and its derivatives strongly inhibited the cyclases, the site of the enzyme responsible for binding to the inhibitor is quite sensitive to the steric hindrance, and the degree of the inhibitory activity is greater in higher plants than in rat liver or fungi.

Animals↗
PubMed1993

3-Carboxy-4-nitrophenyl-dithio-1,1',2-trisnorsqualene: a site-directed inactivator of yeast oxidosqualene cyclase.

The role and location of essential thiol groups in 2,3-oxidosqualene cyclase from Saccharomyces cerevisiae was examined (i) by comparing inactivation properties of two known thiol reagents, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and 2-nitro-5-thiocyanobenzoic acid (NTCB), with 3-carboxy-4-nitrophenyl-dithio-1,1',2-trisnorsqualene (CNDT-squalene), a new thiol reagent designed as a site-directed inactivator of oxidosqualene cyclase and (ii) by testing the ability of the substrate to protect the enzyme against inactivation by the reagents. All reagents gave a time-dependent inactivation following pseudo-first order kinetics. DTNB and CNDT-squalene showed comparable inactivation ability (Ki = 0.67 and 1.21 mM), whereas NTCB was less effective (Ki = 15.6 mM). Strong differences between the two most active inhibitors, DTNB and CNDT-squalene, were observed when the enzyme was saturated with substrate prior to incubation with the thiol reagent. While substrate did not protect the enzyme against the inactivation caused by DTNB, a reduction in the inactivation ability of CNDT-squalene was observed under protection conditions. The data suggest that the squalene-like inactivator modifies a thiol group located at the active site of the enzyme.

Binding Sites↗
PubMed1995

2,3-Oxidosqualene cyclase: from azasqualenes to new site-directed inhibitors.

2,3-Oxidosqualene cyclases (OSC) are enzymes which convert 2,3-oxidosqualene (OS) into polycyclic triterpenoids such as lanosterol, cycloartenol, and alpha- and beta-amyrin. Our interest in the study of OSC is the development of new OSC inhibitors for potential use as hypocholesterolemic, antifungal, or phytotoxic drugs. In particular, we describe the biological activity and the mechanism of a series of acyclic azasqualene derivatives mimicking the C-2, C-8, and C-20 carbonium ions formed during OS cyclization. Some of these carbonium ion analogues are very promising as specific hypocholesterolemic agents. The toxicity, the biodistribution, and the pharmacokinetics of different azasqualene derivatives in mice are also presented. In order to obtain new, site-directed irreversible inhibitors of OSC, a series of squalene derivatives containing functional groups that can link covalently to an active-site thiol group was designed. Among these compounds, squalene maleimide was the most active toward mammalian OSC, whereas squalene Ellman behaved as an irreversible inhibitor of OSC from yeast.

Animals↗
PubMed1994

Rat liver chromatin phospholipids.

To shed light on the question whether the phospholipids present in chromatin are native or are due to contamination from nuclear membranes, we labeled the phospholipids of isolated nuclei and determined the amount of phospholipids (PL) and PL fatty acid composition in nuclei and chromatin. The hepatocyte nuclei were isolated and radioiodinated by the lactoperoxidase method under saturating and nonsaturating conditions, and the radioactivity associated with chromatin extracted from these nuclei was monitored. Whereas 97% the label was recovered in the nuclear membranes, only 0.08-0.6% was found in chromatin. The PL present in chromatin were relative to the amounts present in the entire nuclei and calculated as percentage of total, phosphatidylethanolamine (10%), phosphatidylserine (22%), phosphatidylinositol (19%) phosphatidylcholine (14%), and sphingomyelin (35%). In sphingomyelin of chromatin-associated PL an enrichment in polyunsaturated fatty acids was seen. The data indicated that the PL found in isolated chromatin do not seem to be due to contamination from the nuclear membrane.

Animals↗
PubMedDate not supplied

Plasma fibronectin, von Willebrand factor antigen, and blood rheology. Association with diabetic microvascular disease.

Plasma fibronectin might play a role in the pathogenesis and progression of diabetic microvascular disease. To test this hypothesis we measured plasma fibronectin, von Willebrand factor antigen, fibrinogen, erythrocyte filtrability, whole-blood viscosity, proteinuria and albuminuria in 25 control subjects and 29 diabetic patients with and without microvascular complications. Plasma fibronectin was significantly higher in the diabetic patients, especially in those with retinopathy and nephropathy. A significant correlation between fibronectin and von Willebrand factor antigen was found in both patients with and without microangiopathy (p less than 0.001). In diabetic patients with and without microvascular complications, several significant correlations were found between increased fibronectin levels and reduced erythrocyte filtrability (p less than 0.001) and between the increase of fibronectin and whole-blood viscosity (p less than 0.001). Furthermore, a significant correlation was found between plasma fibronectin levels, proteinuria (p less than 0.001) and albuminuria (p less than 0.001). The relationship between plasma fibronectin and changes of blood rheology may be important for the occurrence and progression of diabetic microangiopathy.

Aged↗
PubMedDate not supplied

Pentoxifylline, albumin excretion rate and proteinuria in type I and type II diabetic patients with microproteinuria. Results of a short-term randomized study.

An association between renal microvascular complications and hemorheological alterations has been suggested in diabetes mellitus. Therefore, a hemorheologic approach in the treatment of diabetic microproteinuria has been proposed. Eighty-two type I and type II diabetic patients with microproteinuria were randomized and assigned to two different protocols: protocol A, patients treated with pentoxifylline (Trental 400); protocol B, patients without hemorheologic treatment, in whom hypoglycemic therapy was just more strictly enforced. A significant improvement of the hemorheologic pattern and a significant marked reduction of albumin excretion rate and proteinuria was found in diabetic patients treated with pentoxifylline, independently of the degree of metabolic control. These results were readily achieved and were confirmed throughout the study. Moreover, these results were comparable to those obtained in diabetic patients of protocol B. Pentoxifylline might therefore be considered as the first useful therapeutic agent in the treatment of diabetic microproteinuria.

Adult↗