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Biomedical subjects

A Leo

Publications and source records attributed to A Leo.

12 recordsLinked to original sources
PubMed1992

Mechanical fragility of erythrocyte membrane in neonates and adults.

The shortened life span of neonatal red blood cells (RBC) is associated with accelerated membrane loss. The present study was designed to measure the critical shear force that causes membrane failure and the rate of membrane failure for neonatal and adult RBC. A micropipette technique was used to determine the membrane extensional (shear) elastic modulus (i.e. resistance of the membrane to extensional elastic deformation), the rate of extensional membrane deformation (i.e. surface viscosity), and the tension for local membrane fragmentation. A flow channel system was used to determine the critical shear force of plastic membrane deformation (i.e. beginning of membrane tether formation), the rate of plastic deformation, and the plastic shear viscosity coefficient. The extensional elastic modulus of neonatal RBC was 18% smaller and the rate of elastic deformation was 25% longer compared with adult cells (p less than 0.05). Membrane surface viscosity was similar for both cell types. The tension for local membrane fragmentation in the micropipette was 23% lower in neonates than in adults. However, the strain (i.e. extent of membrane deformation calculated as ratio of the stress resultant and the elastic modulus) at which membrane rupture in the micropipette occurred was similar for neonatal and adult RBC. This indicates that the smaller critical tension for neonatal RBC membrane failure was due to increased membrane elastic deformability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Increased aggregation with normal surface charge and deformability of red blood cells in children with nephrotic syndrome.

Hemorheological risk factors for thromboembolic disease were evaluated in 25 pediatric patients with idiopathic nephrotic syndrome (NS). In patients with increased proteinuria (greater than 100 mg/m2/24 h) red blood cell (RBC) aggregation and plasma viscosity were significantly increased when compared with patients in remission (less than 100 mg/m2/24 h) and with healthy controls. RBC surface charge was normal during increased proteinuria and remission. RBC aggregation correlated positively with plasma viscosity, fibrinogen, alpha 2-macroglobulin, immunoglobulin M, and the degree of proteinuria, and negatively with plasma albumin levels. RBC aggregation showed no correlation to RBC surface charge. Hematocrit and RBC deformability (rheoscope) were similar in both patient groups and in controls. Increased RBC aggregation and plasma viscosity may contribute to the increased risk of venous thromboembolism in NS.

Blood Viscosity↗
PubMed1991

Partitioning of solutes in different solvent systems: the contribution of hydrogen-bonding capacity and polarity.

Published partition coefficient values of 121 solutes in five solvent systems (1-octanol-water, n-heptane-water, chloroform-water, diethyl ether-water, and n-butyl acetate-water) were correlated with solute properties, namely intrinsic molecular volume (indicator of cavity formation) and the solvatochromic parameters pi* (dipolarity/polarizability), beta (H-bond acceptor basicity), and alpha (H-bond donor acidity). While the cavity term and the H-bond accepting capacity played a comparable role in all solvent systems, the H-bond donor acidity was significant only in the alkane-water and chloroform-water systems. Comparison of the regression coefficients of pi*, beta, and alpha demonstrated the important role that water content at saturation in the organic solvents plays in the partitioning of solutes. Analysis of the differences between 1-octanol-water and n-heptane-water partition coefficients (delta log Poct-hep) and between 1-octanol-water and chloroform-water partition coefficients (delta log Poct-chf) showed that these values mainly quantitate the capacity of solute to donate hydrogen bonds. In contrast, the differences between 1-octanol-water and diethyl ether-water or n-butylacetate-water partition coefficients, (delta log Poct-dee and delta log Poct-ba, respectively) contain no structural information.

Chemical Phenomena↗
PubMed1991

Percutaneous penetration of drugs: a quantitative structure-permeability relationship study.

Human skin permeation data taken from the literature were analyzed for quantitative relationships with physicochemical properties and structural descriptors. No correlations exist with molecular weights and solvent-accessible surface areas. In most cases, skin permeation was inversely correlated with the parameter delta log Poct-hep (i.e., log Poctanol minus log Pheptane), which is mainly a measure of the H-bond donor acidity of the solutes. Lipophilicity itself, as expressed by log Poctanol, also contributes positively to skin permeation in some cases. The results of this quantitative structure-permeability relationship study are interpreted in terms of a unified mechanistic model whereby drugs can permeate via an intercellular route (correlation with both delta log Poct-hep and log Poct) and/or a transcellular route (correlation with log Poct only).

Administration, Topical↗
PubMed1991

Acute respiratory fatality associated with exposure to sheet metal and cadmium fumes.

The authors report on a case of an acute fatality characterized by abdominal pain and respiratory failure occurring soon after beginning to weld and solder galvanized sheet metal. Heating of galvanized sheet metal is a recognized cause of metal fume fever, data from this patient suggests an additional and unrecognized risk for cadmium poisoning.

Aged↗
PubMed1988

Evidence for a differential interaction of buprenorphine with opiate receptor subtypes controlling prolactin secretion.

We studied the effects of various doses of the opiate derivative buprenorphine on serum prolactin levels and whether these effects could be counteracted by pretreatment with the opiate receptor blocker naloxone. The administration of increasing doses of buprenorphine exerted a dual effect on serum prolactin levels. At low doses (3, 10 and 30 micrograms/kg) this agent increased serum prolactin levels. This effect disappeared with increasing doses (100 and 300 micrograms/kg), and at the highest doses (1000 and 3000 micrograms/kg) the levels of serum prolactin decreased. Naloxone (30 mg/kg) decreased serum prolactin levels and reversed both the stimulatory and the inhibitory action of buprenorphine. These data are compatible with the hypothesis that buprenorphine could interfere with two different, but inter-dependent receptors: at low doses the oripavine derivative could act at one receptor site to cause an increase of serum prolactin, whereas at higher doses it could interact with a second site of lower affinity that is responsible for the inhibition of prolactin secretion. When buprenorphine (at high doses) activates the lower affinity site, the interaction with this receptor counteracts and reverses the effects of the high affinity site. On the basis of this hypothesis, naloxone should block both receptors.

Animals↗
PubMed1979

Structure-activity relationship of aniline mustards acting against B-16 melanoma in mice.

A set of 23 aniline mustards [X-C6H4N(CH2CH2Cl)2] have been tested for their activity against B-16 melanoma in mice. The following quantitative structure-activity relationship (QSAR) correlates the data well: log 1/C = -2.06 sigma - 0.15 pi - 0.13 pi2 + 4.13 (r = 0.936). When this equation is compared with those formulated for aniline mustards acting against leukemia, it is found that log P0 (ideal lipophilicity) is higher for solid tumors. The QSAR brings out the unique activity of phenylalanine aniline mustard.

Aniline Mustard↗
PubMed1978

Structure-activity relationships in antitumor aniline mustards.

Quantitative structure-activity relationships (QSAR) have been formulated for the hydrolysis of aniline mustards and their antitumor activity against Walker 256 tumor and L1210 and P388 leukemia. In general, the antitumor activity parallels hydrolysis under the conditions defined by Ross; toxicity (LD50) parallels antitumor efficacy. Chlorambucil is an exception. A most important finding is that ideal lipophilicity for effectiveness against Walker tumor appears to be much higher than for the leukemias which suggests that solid tumors may, in general, require more lipophilic drugs than leukemias.

Aniline Mustard↗
PubMed1977

Substituent constants for correlation analysis.

Constants for pi and omega ahve been measured for a miscellaneous group of aromatic substituents of interest to medicinal chemists. Swain and Lupton's gamma and kappa values have been calculated from the omego constants. Values for molar refractivity are also given for each of the substituents.

Chemical Phenomena↗
PubMed1976

Dependence of hydrophobicity of apolar molecules on their molecular volume.

Cavity size is the primary determinant of the partition coefficient (P) of apolar solutes between octanol and water. Although the energy of cavity formation would be expected to be related to cavity area, older methods of area calculation give a poorer correlation with log P than does volume. Apolar solutes clearly fall into two classes based on their log P/volume relationship, the distinction possibly being whether the solute exposes mostly hydrogen atoms or unbonded electrons.

Chemical Phenomena↗
PubMed1975

Calculation of hydrophobic constant (log P) from pi and f constants.

The highest level of confidence can be placed in calculated log P values when (1) the log P of a parent solute is known, (2) pi constants for the required substituent(s) are available, and (3) the substituents either do not have an effect on groups already present in the parent or else this effect has been previously determined. In some instances there are no values available for any related structures which could serve as a parent; then, rather than substitute groups for hydrogen, it is easier to begin "from scratch", as suggested by Nys and Rekker, and assemble the structure from fragments, each of which has been assigned a hydrophobic value. In the present paper some new log P values for the lower alkanes and the inert gases are analyzed with the view of separating hydrophobic effects according to volume (including branching and flexibility) and polarity. Modified fragment values appear to enable reliable calculations to be made for a wider range of structures than was possible with the originally proposed constants.

Alkenes↗