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Biomedical subjects

A Leo

Publications and source records attributed to A Leo.

At least 37 records · Page 2Linked 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↗
PubMed1987

Hydrophobicity and central nervous system agents: on the principle of minimal hydrophobicity in drug design.

The problem of getting drugs across the so-called blood-brain barrier (BBB) has long been under extensive investigation; however, the other side of the problem, that of keeping drugs out of the central nervous system (CNS), has not been studied so intently. As we strive to make more and more refined drugs with fewer side effects, the problem of keeping drugs out of the CNS has possibly become more important than getting them in. The role of lipophilicity has long been recognized as being important in CNS penetration by chemicals, but we believe that not enough attention has been devoted to just exactly what is meant when it is said that "a lipophilic drug is needed for CNS penetration." How lipophilic? Can hydrophilic properties keep drugs out of the CNS? How hydrophilic should they be? There are other reasons for making drugs hydrophilic. Hydrophobic drugs, other factors being equal, are more inhibitory of biochemical systems than hydrophilic congeners. Evidence is beginning to show that cytochrome P450 is induced in direct proportion to hydrophobicity by a variety of compounds, and cytochrome P450 may produce modifications in lipophilic molecules in the body. Hydrophobic drugs are more slowly eliminated. This report discusses these problems in terms of the octanol-water (log P) hydrophobic scale. The principle is proposed that, without convincing evidence to the contrary, drugs should be made as hydrophilic as possible without loss of efficacy. Antihistamines are discussed in terms of what kind of hydrophobic-hydrophilic balance is best to avoid CNS-related problems.

Anesthetics↗
PubMed1985

Parameter and structure-activity data bases: management for maximum utility.

Quantitative structure-activity relationships (QSAR) in the fields of medicinal chemistry, pesticide science, biochemistry and toxicology are being published at an ever increasing rate. In addition to these biological correlation equations, thousands of such equations have been published for all kinds of organic reactions. There is a great need to develop a computerized system to enable one to make comparisons and to draw generalizations about the effects of structure on chemical and biological activity. A proposal is made for a systematic approach to this problem based on the physicochemical properties of organic compounds.

Chemical Phenomena↗
PubMed1984

Efficacy of baclofen in trigeminal neuralgia and some other painful conditions. A clinical trial.

Baclofen (beta-4-chlorophenyl-gamma-aminobutyric acid) shows analgesic properties in rats and resembles carbamazepine and phenytoin in its effects on the spinal trigeminal nucleus of cats. We have, therefore, conducted a clinical trial in 25 subjects, 16 suffering from trigeminal neuralgia, and 9 patients were affected by different painful conditions such as postherpetic neuralgia, tabes dorsalis, postarachnoid radiculitis. 5 of the former groups were refractory to or unable to tolerate carbamazepine. Baclofen has significantly exhibited analgesic efficacy: all groups, as a whole, were improved by 68.61%. These results substantiate that baclofen is useful in the treatment of trigeminal neuralgia and other painful conditions.

Adult↗
PubMed1982

Potential antitumor agents. 36. Quantitative relationships between experimental antitumor activity, toxicity, and structure for the general class of 9-anilinoacridine antitumor agents.

Quantitative relationships (QSAR) have been derived between antileukemic (L1210) activity and agent physicochemical properties for 509 tumor-active members of the general class of 9-anilinoacridines. One member of this class is the clinical agent m-AMSA (NSC 249992). Agent hydrophobicity proved a significant but not a dominant influence on in vivo potency. The electronic properties of substituent groups proved important, but the most significant effects on drug potency were shown by the steric influence of groups placed at various positions on the 9-anilinoacridine skeleton. The results are entirely consistent with the physiologically important step in the action of these compounds being their binding to double-stranded DNA by intercalation of the acridine chromophore between the base pairs and positioning of the anilino group in the minor groove, as previously suggested. An equation was also derived for the acute toxicities of 643 derivatives of 9-anilinoacridine. This equation took a somewhat similar form to the one modeling antileukemia potency, emphasizing the usual fairly close relationship between potency and acute toxicity for antitumor agents in general. This study demonstrated the power of QSAR techniques to structure very large amounts of biological data and to allow the extraction of useful information from them bearing on the possible site of action of the compounds concerned.

Aminoacridines↗
PubMed1981

A comparison of mutagenic and carcinogenic activities of aniline mustards.

A set of 15 derivatives of aniline mustard (I) was tested to give a quantitative measure of mutagenicity in Salmonella typhimurium TA-1535 and TA-100 and also carcinogenicity as lung tumors in strain-A mice. The structural variation in the set was chosen to minimize collinearity between hydrophobic, electronic, and molar refractive properties. By these measures, there was not a direct relationship between mutagenicity and carcinogenicity; in fact, since the 4-OPh analogue ranked highest in mutagenicity and among the lowest in carcinogenicity, while the reverse was noted for the 3,5-(NHCONH2)2 analogue, an inverse relationship was marginally significant. S-9 activation was required in the Ames test using TA-100, and the dose-response curve, prior to toxicity, appeared biphasic.

Adenoma↗
PubMed1980

[Lithium therapy in Horton's neuralgia: preliminary results].

Prophylactic use of Lithium salts in patient suffering from cluster headaches has been evaluated looking at the mean number of headache attacks in one critical period and the mean weekly duration of the period itself. These two elements have been compared to those observed on other drugs treatments. Plasma Lithium monitoring has been performed weekly during the trial. Authors discuss the results reported and the hypothetic basis of them.

Cluster Headache↗
PubMed1980

Antitumor structure-activity relations. Nitrosoureas vs. L-1210 leukemia.

A quantitative structure-activity relationship (QSAR) for 90 nitrosoureas acting against L-1210 leukemia in mice has been formulated. This QSAR is compared with one correlating the LD10 of 96 nitrosoureas. The results indicate that neutral nitrosoureas with octanol/water partition coefficients in the range of -1.5 to -2.5 might have better therapeutic indices than those currently in use.

Animals↗
PubMed1980

The quantitative structure-selectivity relationship of anthracycline antitumor activity and cardiac toxicity.

Quantitative structure-activity relationships (QSAR) are developed for both the antitumor activity (B-16 melanoma) and cardiotoxicity of a set of anthracycline derivatives, for the purposes of finding exploitable differences between the two which would lead to improvements in the therapeutic indices of these compounds. It was found that most structural features which lead to improvement in antitumor activity, such as increases in drug hydrophilicity, also lead to increases in cardiotoxicity. However, demethoxylation and demethoxylation at the 4-position of these molecules appears to have much greater effect on cardiotoxicity than on antitumor activity. If these effects are brought about by alterations in the oxidation-reduction potential of the quinone structure, as is suggested, then it may be possible to make analogs with a better therapeutic index by the introduction of small hydrophilic electron-releasing groups in the A-ring of these adriamycin derivatives that are conjugated with the carbonyl functions.

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↗