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Biomedical subjects

A Rico

Publications and source records attributed to A Rico.

At least 19 recordsLinked to original sources

Evaluation of performance of white blood cell reduction filters: an original flow cytometric method for detection and quantification of cell-derived membrane fragments.

BACKGROUND: Contamination of blood products by white blood cells leads to a risk of transmission of infectious agents, particularly abnormal prion protein, the probable causative agent of new-variant Creutzfeldt-Jakob disease. Blood product filtration could reduce this risk, but the filtration systems might generate potentially infectious membrane fragments. We developed an original flow cytometric method that allows the detection and quantification of membrane fragments in filtered products and the evaluation of the quantity of destroyed cells. METHODS: This method has four technical requirements: cytofluorometric acquisition of forward scatter parameters on a log scale, use of a fluorescent aliphatic reporter molecule (PKH26-GL) to identify membrane fragments, quantification with fluorescent beads, and the drawing up of a standard curve on the basis of cells destroyed by freezing/thawing to generate cell debris (i.e., quantity of membrane fragments measured versus quantity of destroyed cells). RESULTS AND CONCLUSIONS: This original method can be used to test new filtration devices and it allows optimization of the filtration process or comparison of different filtration systems. We tested the method with three commercial white cell removal filters. We demonstrated that it is possible to evaluate the filter quality, particularly the likelihood of fragment removal during the filtration process.

Blood Component Removal↗

Chemo-defence system.

By analogy with the immune defence system, the existence is suggested of a chemo-defence system protecting living organisms against toxic substances, whether natural or man-made, that are present in the environment. This paper deals first with the various facets of such a system: mechanisms involving, among others, lipophilic compounds, hydrophilic compounds, oxidants, acidosis, genotoxics and metals; second, with the biological characteristics of the system and a comparison with the immune defence system: partial immaturity of the young, inducibility, non-specificity and specificity, and saturability; we will show that the two systems share many common features; third, with the evolution of the system, which demonstrates that the system is very old and suggesting that it came into existence before the immune defence system; and fourth, with some of its consequences: estimation of the 'toxic effects' of low doses, hormesis, impact of a vegetable diet on health. Finally, it could be emphasised that life is well protected against chemicals by its chemo-defence system, which appeared very early with the first living organisms on the earth.

Biotransformation↗

[Pollution and agricultural practices. 2 concepts: acceptable daily dose and chemo-defense].

Pollution coming from agricultural practices can exist: pesticides, veterinary drugs, heavy metals but also mycotoxins. However, these contaminants are always at low or trace doses in our environment (foods, water, air, soils). In terms of foods, two concepts have been developed to protect the consumers: acceptable daily intake (ADI) and maximum residue limits (MRL). The impact of this pollution on public health is not evident, in contradiction with the level of fear in the population. Moreover, the distinction made between natural and synthetic substances by the public in terms of toxicity is quite nonsense scientifically. Human beings and all living organisms have a good defence system against chemical xenobiotics which ensures their protection.

Adaptation, Physiological↗

PCR-SSCP analysis of human adrenocortical adenomas: absence of K-ras gene mutations.

Little is known about the pathogenesis and etiology of benign tumors of the adrenal cortex. A variety of cellular oncogenes and tumor suppressor genes has been studied so far. The role of K-ras in this process is not yet clearly understood. Recent findings suggest a strong influence of mutated K-ras in the pathogenesis of adrenal adenomas (Lin et al., 1998). Therefore we studied 40 human adrenal tumors for mutations in the coding region of the cellular proto-oncogene K-ras by PCR-SSCP (Single-strand conformation polymorphism) analysis. We did not identify any activating mutation in the coding region of the K-ras gene. We conclude that activating mutations of the K-ras gene are not a major cause for the development of adrenal adenomas, if at all.

Adrenal Cortex Neoplasms↗

Cereal alpha-amylase inhibitors cause occupational sensitization in the wood industry.

BACKGROUND: Cereal flours are used in the wood industry to improve the quality of the glues necessary to produce veneer panels. However, up to now, no cases of sensitization to cereal flour in this kind of industry have been reported. Cereal alpha-amylase inhibitors have been previously described as important occupational allergens responsible for baker's asthma. OBJECTIVE: To determine whether cereal allergens were responsible for occupational sensitization in three wood industry workers. METHODS: The diagnosis was made by clinical questionnaire, physical examination, skin-prick tests to cereals, CAP and immunoblotting. RESULTS: The three patients had positive skin prick tests and CAP to cereal flours. An IgE-immunoblotting revealed that only low molecular weight proteins (under 20 kDa) were detected by the three sera. These main IgE-binding proteins were members of the alpha-amylase inhibitor family which have been described as one of the group of main allergenic proteins in rye, barley and wheat. The three patients changed their workplace and remain asymptomatic in spite of the fact that they are still in contact with different woods and exposed to high concentrations of wood dust and other chemicals such as formaldehyde. CONCLUSION: Proteins from cereal flours are important occupational allergens in some wood industries.

Adhesives↗

Absence of angiotensin II type 1 receptor gene mutations in human adrenal tumors.

Regulatory actions of angiotensin II (AngII), which is involved in the pathophysiology of hypertension and also participates in cell proliferation and cell differentiation, are mainly mediated by AngII type 1 (AT1) receptor. Recently, activating mutations of receptors causing hyperfunctioning endocrine diseases have been described in the case of the TSH and LH receptors, implicating that such mutations might occur in other G-protein-coupled receptors. Furthermore it seems to be possible that genetic variations of AT1 receptor have an influence upon the action of AngII. Therefore, we searched by sequence analysis of the coding region of AT1 receptor gene for activating mutations and genetic polymorphisms in 56 human adrenal tumors (16 aldosterone-producing adenomas, 10 cortisol-producing adenomas, 1 aldosterone-producing carcinoma, and 29 incidentalomas). We were not able to identify any activating mutation in the coding region of AT1 receptor gene. We conclude that activating mutations of the AT1 receptor are not a major cause of the development of adrenal adenomas, if at all. In addition, polymorphic subtypes of AT1 receptor do not seem to play a major role in the pathogenesis of these tumors, even though a tendency towards a higher frequency of the polymorphic base substitution at position 573 (T573-->C) in cortisol-producing tumors needs to be further evaluated.

Adenoma↗

Proguanil resistance in Plasmodium falciparum African isolates: assessment by mutation-specific polymerase chain reaction and in vitro susceptibility testing.

The antifolate proguanil is commonly used in the prophylaxis and treatment of Plasmodium falciparum malaria. A series of point mutations in the dihydrofolate reductase (DHFR) gene has been linked to differential susceptibility of varied P. falciparum clones or isolates to this drug. To survey the efficiency of proguanil prophylaxis in an African endemic region, and to evaluate the level of proguanil resistance in the corresponding parasite population, we performed drug susceptibility assays with P. falciparum isolates from Senegal, Kenya, and Niger. In parallel, we developed a mutation-specific polymerase chain reaction assay that enabled us to characterize mutations in the DHFR gene of the same isolates without in vitro parasite cultivation. We confirm previously available data showing that parasites harboring a point mutation from Ser108 to Asn present a decrease in susceptibility to cycloguanil (the active metabolite of proguanil), and we show that mutations in codons 51 and 59 appear to modulate the level of resistance to cycloguanil. No mutations in codons 16 and 164 were detected in resistant parasites, in contrast with results from some previous studies.

Africa↗

Impact of reduction of lead in gasoline on the blood and hair lead levels in the population of Tarragona Province, Spain, 1990-1995.

The limitation in the use of lead in Spanish gasoline has induced a resulting decrease in atmospheric lead concentrations, a remarkable reduction in the lead levels of edible vegetables, as well as a marked decrease in the dietary lead intake of the population of Tarragona Province (Catalonia, N.E. Spain). The present study evaluates the impact of such decreases on blood lead values and hair lead concentrations in an adult and children population of that region. A total of 250 adult participants between 16-65 years of age and 252 children were included in the study. Blood and hair samples were subjected to lead analyses by graphite furnace atomic absorption spectrophotometry and inductively coupled plasma spectrometry, respectively. A substantial decline in both, blood lead levels in adults (47.5%) and lead concentrations in children's hair (53%) was observed. During the period 1990-1995, blood levels were reduced from 12.0 micrograms dl-1 to 6.3 micrograms dl-1, while the hair lead concentrations decreased from 8.8 micrograms g-1 to 4.1 micrograms g-1. These decreases were noted for all the subgroups (sex, age and place of residence) examined, and were mainly attributable to the reduced leaded gasoline consumption.

Adolescent↗

[Covalently bound residues: theoretical aspects].

Covalently bound residues (CBRs) result from the covalent binding of the parent drug or its metabolites to endogenous macromolecules. They are not extractable from the tissues by exhaustive extraction, denaturation and solubilization techniques, and are not the result of endogenous incorporation. They can be detected in the non-extractable radioactivity which persists in tissues after administration of radiolabeled drugs. The characteristics of CBRs are discussed. Covalent binding is an association of a reactive metabolite (electrophile or free radicals) and endogenous molecules (proteins, lipids). This chemical reaction is non-specific and irreversible. Even if the covalent bond is cleaved, the compound released will not be the highly reactive intermediate metabolite. The covalently bound metabolites can have a potential toxic effect in the target species but they probably represent low toxicity for consumers. Pharmacokinetic analyses of CBRs have demonstrated their specific properties: 1) they make up the largest fraction of late residues, and 2) their bioavailability is low. Several examples are given to support these concepts.

Animals↗

[Covalently bound residues: the case of anthelmintics].

In target species, most anthelmintics produce unextractable residues, which include covalently bound adducts, and a radioactive fraction, possibly incorporated into intermediary metabolism. Both are responsible for the very long half-life of total residues in tissues. Due to the analytical difficulties encountered in distinguishing between these two fractions and to the controversy about the toxicological significance of bound residues, discrepancies exist in the determination of withdrawal periods for a given drug. Withdrawal time varies from one country to another, depending upon the regulations of the different national agencies.

Animals↗

[Effects of sporidesmin on liver zinc, metallothionein and cytochromes in vivo].

In vitro studies have suggested that sporidesmin hepatotoxicity may be related to thiol oxidation and generation of cytotoxic oxygen species. After a single i.p. injection of 2.8 mg/kg bw sporidesmin in guinea-pigs, hepatic and plasma zinc, hepatic metallothionein, cytochromes P-450 and b5, total glutathione and proteins (total, microsomal and cytosolic) were monitored for 21 days. The only variations observed were significant increases in liver concentrations of zinc (cytosolic and total), metallothionein, and cytochromes, which peaked on day 8 after the sporidesmin challenge (+45, 55, 50, 376 and 413%, respectively) and, except for cytochrome b5, went back to control levels before the 21st day. These results suggest that cytochromes P-450 and b5 may be involved in sporidesmin cellular damage.

Animals↗

[Food toxicology: free residues, bound residues: respective toxicity].

Two types of metabolites can be expected in food prepared from animals or plants treated with veterinary drugs or pesticides. The first types are represented by the drug itself and/or its primary metabolites as free or conjugated forms. Except for highly lipophilic compounds, these metabolites generally appear early and are noncumulative, since they are metabolized and eliminated rapidly. These substances may have toxic properties and may be metabolized to highly reactive electrophilic intermediates. We consider that they may be potentially toxic for consumers. The second type include covalently bound metabolites which appear later. Their presence can indicate a potential toxic effect in the target species, although these compounds have lost their chemical reactivity. They therefore probably represent low toxicity for consumers, especially considering their low bioavailability, which has been demonstrated for many veterinary drugs and pesticides.

Animals↗

Protection against mercuric chloride nephrotoxicity by cold exposure in rats.

The influence of cold exposure (+ 1 degree C for 24 h) was studied in rats dosed i.p. with 0, 2.5 or 5.0 mumol HgCl2/kg. Cold exposure of controls caused an increased diuresis and solute elimination, except sodium, with almost no variations in urine alkaline phosphatase (ALP) and gammaglutamyl transferase (GGT). Proximal tubule brush border damage was demonstrated by a marked increase in ALP and GGT in HgCl2-dose animals at room temperature. Cold exposure protected against this kidney damage.

Animals↗

[General schema for safety evaluation of residues of embryotoxic drugs (author's transl)].

Concerned with adapting the withdrawal time to real risks attributed to residues, the authors present a general schema of evaluation based on the metabolism-toxicity relationship. This schema takes into account: a) possible distinction between potentially toxic and atoxic metabolites for extractable residues, b) the more or less large biovailability of residues, c) the methodological evaluation difficulties of toxicity of bound residues. Without neglecting public health, this procedure leads to less constrained restrictions in use of veterinary drugs.

Abnormalities, Drug-Induced↗

Bound residues of veterinary drugs: bioavailability and toxicological implications.

Basic considerations dealing with the biological significance of drug residues and safety evaluation are studied. The specific problem of covalently bound residues is considered from three different points of view. (1) Analytical characteristics clearly distinguish between soluble residues, which deplete relatively fast, and bound material which is slowly eliminated from edible tissues of target animals. (2) These two residual fractions have not the same bioavailability. (3) Finally, toxicity assessment of bound residues is considered.

Animals↗

Methoxyethylmercury nephrotoxicity: effects on enzymuria and kidney function.

The fungicide, methoxyethylmercury chloride, was given in a saline solution to four groups of Sprague-Dawley C D rats (5 male, 5 female) as a single injection (IP) of 0, 0.5, 1.0, and 2.0 mg Hg/kg. In a three-day period, no changes were observed in urine collected every 24 h from rats given 0 or 0.5 mg Hg/kg; 1 mg Hg/kg induced only a transient increase of urine gamma glutamyl transferase (x 4) and alkaline phsophatase (x 2.5) on the day 2; 2.0 mg Hg/kg caused an early increase of enzymuria (day 1 and day 2) and a decrease of Na+, Cl-, K+, urea, and creatinin excretion. Urine enzymes and total mercury excretion were higher in males. These time-related variations of enzymuria, compared to previous results with Hg Cl2, could reflect the existence of metabolites more toxic than the native compound.

Alkaline Phosphatase↗