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Biomedical subjects

M Saari

Publications and source records attributed to M Saari.

At least 19 recordsLinked to original sources

Pulmonary distribution and clearance of two beclomethasone liposome formulations in healthy volunteers.

The pulmonary distribution and clearance of 99mTc-labelled beclomethasone dipropionate (Bec) dilauroylphosphatidylcholine (DLPC) and dipalmitoylphosphatidylcholine (DPPC) liposomes were compared in 11 healthy volunteers using gamma scintigraphy. As delivered by using the Aerotech jet nebulizer both liposome aerosols had a suitable droplet size (mass median aerodynamic diameter 1.3 microm) allowing deep pulmonary deposition. However, in the total drug output during the inhalation there was a relatively large difference between DLPC and DPPC of 11.4 and 3.1 microg, respectively. In a gamma camera study no significant differences existed in the central/peripheral lung deposition between the DLPC and DPPC formulations. Progressive clearance of both Tc-labelled Bec liposomes was seen: 24 h after inhalation, 79% of the originally deposited radioactivity of DLPC liposomes and 83% of that of DPPC liposomes remained in the lungs. Thus there was slightly slower clearance of inhaled liposomes using DPPC instead of DLPC. We conclude that both liposome formulations are suitable for nebulization, although aerosol clouds were more efficiently made from the DLPC liposome suspension. Our results support the view that liposome encapsulation of a drug can offer sustained release and drug action in the lower airways.

1,2-Dipalmitoylphosphatidylcholine↗

Haemolytic-uraemic syndrome caused by vero toxin-producing Escherichia coli serotype Rough: K-: H49.

The first case of haemolytic-uraemic syndrome (HUS) caused by Vero toxin-producing Escherichia coli (VTEC) which belonged to a novel serotype, Rough: K-: H49, is reported. The case was initially diagnosed as nephropathia epidemica caused by Puumala virus, but the subsequent diagnosis of HUS caused by VTEC was made after bacteriological investigation. The strain isolated fermented sorbitol produced VT2 toxin but not enterohaemolysin, nor did it carry the eaeA gene. In VTEC strains, the O antigen, the eaeA gene and enterohaemolysin production have been characterized as virulence-associated factors and believed to have an effect on pathogenesis of these strains to cause haemorrhagic colitis or HUS. The findings of this study demonstrate that there is a need for further studies to evaluate the pathogenetic mechanism of VTEC and need for easy diagnostic methods exploiting other properties than O157 antigen and non-fermentation of sorbitol to find all VTEC in human infections.

Adult↗

Shiga toxin-producing Escherichia coli in finland from 1990 through 1997: prevalence and characteristics of isolates.

During the past 10 years Shiga toxin-producing Escherichia coli (STEC) has emerged as one of the most important causes of food-borne infections in industrialized countries. In Finland, with a population of 5.1 million, however, only four STEC O157:H7 infections were identified from 1990 through 1995; the occurrence of non-O157 STEC infections was unknown. In 1996, we established a national prospective study to determine the prevalence of STEC serotypes in feces of Finns with bloody diarrhea. During this enhanced 1-year study period eight sporadic cases of STEC infection were found; of them, only two were indigenously acquired O157:H7 infections. In 1997, O157 infections increased dramatically, with O157 strains causing 51 of all 61 STEC infections. Altogether 14 non-O157:H7 STEC strains were found in Finland in the 1990s: O26:H11 (four strains), O26:HNM (HNM indicates nonmotile), O2:H29, O91:H21, O91:H40, O101:HNM, O107:H27, O157:HNM, O165:H25, OX3:H21, and Rough:H49. All O157:H7 and O26:H11 isolates produced enterohemolysin, but seven of the other STEC strains did not. Most (n = 63) of the 71 STEC strains isolated carried the stx2 gene only, five carried the stx1 gene only, and three carried both genes. The eaeA gene was detected in all other isolates except five non-O157 strains. There were seven distinct pulsed-field gel electrophoresis (PFGE) genotypes among 57 O157 strains and three distinct PFGE types among four O26:H11 strains. The main PFGE type was found among 65% of all O157 isolates.

Adolescent↗

Plasma ANP and cyclic GMP after physical exercise in patients with mitral valve disease and in healthy subjects.

Plasma levels of both atrial natriuretic peptide (ANP) and cyclic GMP are elevated in patients with various heart diseases as compared to healthy subjects. In this study patients with advanced mitral valve disease (Group A) and healthy subjects (Group B) were exposed to symptom-limited upright stepwise physical exercise on a cycle ergometer. Concentrations of ANP and cyclic GMP were measured in plasma at rest (20 min in supine position) or 5 min after physical exercise by specific radioimmunoassays. Here we show that short dynamic exercise caused a significant increase in plasma levels of ANP and cyclic GMP, in both groups. In Group A strong correlation between plasma ANP and cyclic GMP was found at rest (r = 0.91, P < 0.001, n = 11) and after physical exercise (r = 0.85, P < 0.001, n = 11). In contrast, there was no correlation between plasma concentrations of ANP and cyclic GMP in Group B at rest (r = -0.16, P > 0.05, n = 10) or after exercise loading (r = 0.14, P > 0.05, n = 10). Absolute increases in circulating levels of both substances were not found to correlate in either group. These data suggest that exercise-induced elevations in plasma cyclic GMP may be due not only to ANP release but also to an as yet undetermined factor, possibly EDRF/NO.

Adult↗

Systemic absorption of ocular cyclopentolate in children.

Cyclopentolate plasma levels were quantitated and heart rate and pupil size were monitored after ocular application of the drug to juveniles. In all, 12 children were given one 35-microliters eyedrop of either 1% cyclopentolate (n = 6) or placebo (n = 6) in randomized order in the lower cul-de-sac of one eye. A sensitive radioreceptor assay was used to determine the systemic drug absorption. With the exception of one child, detectable cyclopentolate concentrations were seen in plasma at as early as 3 min after the ocular drug application. There was a marked interindividual variation in peak plasma cyclopentolate concentrations ranging from undetectably low to 5.8 ng/ml (median, 2.9 ng/ml). In some children a second drug concentration peak was detected. Cyclopentolate increased the pupillary diameter from 4.8 +/- 1 mm before drug application to 8 +/- 0.9 mm at 30 min after administration, but the children's heart rate did not alter.

Absorption↗

Forebrain norepinephrine and neurobehavioral plasticity: neonatal 6-hydroxydopamine eliminates enriched-impoverished experience effects on maze performance.

Newborn male rats were depleted of forebrain norepinephrine (NE) by systemic 6-hydroxydopamine injection and then reared from 25 to 60 days under either isolated or enriched conditions. They were subsequently tested for acquisition of either the Lashley III maze or the Hebb-Williams maze problems. Isolated rearing impaired Lashley maze performance of the controls but not the 6-OHDA injected rats. Similarly, for the Hebb-Williams maze, the isolation-reared controls made more errors than their enriched-reared counterparts while no differences were observed between the isolated and enriched reared, 6-OHDA injected rats. These results are consistent with the hypothesis that forebrain NE is permissive to the deleterious behavioral consequences of restricted experience during maturation.

Animals↗

Neonatal 6-hydroxydopamine attenuates the neural and behavioral effects of enriched rearing in the rat.

Newborn male rats were administered subcutaneous 6-hydroxydopamine (6-OHDA) to deplete forebrain norepinephrine and after weaning were reared in normal or enriched environments. Subsequently the 6-OHDA treated rats and their vehicle controls were trained in a Lashley type III maze and then sacrificed for assay of regional brain weights and brain catecholamines. Whereas for the control rats, enriched rearing was found to: (1) increase hypothalamic and posterior cortical dopamine; (2) increase forebrain and decrease hypothalamic weight; and (3) to enhance maze acquisition, none of these consequences of enriched rearing was found in the 6-OHDA treated rats. We conclude that forebrain norepinephrine plays a permissive role in the neuroanatomical, neurochemical and behavioral alterations induced by the enriched rearing of weanling rats and that it is essential to at least some aspects of the shaping of the brain by experiential factors.

Animals↗

Intraventricular 6-hydroxydopamine in the newborn rat and locomotor responses to drugs in infancy: no support for the dopamine depletion model of minimal brain dysfunction.

Bilateral intraventricular injections of 6-hydroxydopamine (6-OHDA) after desmethylimipramine (DMI) in rats 1 and 2 days of age, severely depleted brain dopamine (DA) particularly in the neostriatum, where levels in adulthood were about 7% of control. Compared to vehicle-injected controls these rats were hyperactive only at 15 and 20 days of age, and in adulthood were impaired in a two-way avoidance. Rats with similar 6-OHDA treatment but without DMI pretreatment showed severe depletion of brain norepinephrine (NE) as well as DA, and were behaviorally similar to the DA-depleted only rats. This behavioral syndrome is similar to that reported after intracisternal injection of 6-OHDA in 5-day-old rats, which has been argued as a model for minimal brain dysfunction (MBD). Contrary to expectation from this model, however, challenge doses of either d-amphetamine or methylphenidate did not reduce, but instead increased activity of these rats. The 6-OHDA treatments also did not alter the enhancement of locomotor activity by scopolamine, which was present at 30 days but not at 15 days.

Aging↗

Fuchs' heterochromic cyclitis associated with retinitis pigmentosa: a family study.

To determine the hereditary, clinical histopathological aspects of the association between Fuchs' heterochromic cyclitis (FHC) and retinitis pigmentosa (RP), the family of a patient with FHC and bilateral RP was studied genealogically, ophthalmologically and immunogenetically. The oldest brother and the youngest sister of the proband had bilateral RP and glaucoma which in the brother lead to enucleation of an eye which was studied histologically. The proband, his brother with RP, and 2 of their healthy siblings were homozygous for the haplotype A3, B7, w6. The parents of the siblings were healthy, and the pedigree showed much parental consanguinity and indicated autosomal recessive inheritance of RP.

Adult↗