Biomedical subjects

M Repetto

Publications and source records attributed to M Repetto.

At least 19 recordsLinked to original sources

PubMed2003

Peripheral parameters of oxidative stress in Graves' disease: the effects of methimazole and 131 iodine treatments.

BACKGROUND: Increased oxidative stress, with elevated levels of free radicals, together with diminished antioxidation have been described previously in models of hyperthyroidism and in patients with Graves' disease. However, controversial results have been found about the antioxidant status and its response to treatment. AIM: To evaluate the antioxidant/oxidant balance in active Graves' disease and the effects of treatment with methimazole (MMI) and 131 iodine (131I). PATIENTS AND METHODS: We studied 69 hyperthyroid (H) patients, 58 female and 11 male, 16-50 years old; total T3: 8 +/- 2 nmol/l, total T4: 264 +/- 65 nmol/l (all mean +/- SD), TSH: 0.1 +/- 0.1 mIU/l, TSH receptor antibody 41 +/- 21%, highest 131Iodine uptake: 67 +/- 16%. As a control group (C), 19 normal adults were studied. DESIGN: Parameters evaluated were: tert-butyl hydroperoxide initiated chemiluminiscence (CL), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and total reactive antioxidant potential (TRAP). RESULTS: In patients vs. controls there was an increase in CL levels (6207 +/- 1434 vs. 3000 +/- 851 cpm/mg of haemoglobin, P < 0.001), decrease in SOD (0.4 +/- 0.1 vs. 0.7 +/- 0.2 U/mg prot, P < 0.05; corresponding to 0.15 micro g/ml), CAT (2.8 +/- 0.6 vs. 3.8 +/- 0.7 pmol/mg prot, P < 0.001) and GSH (1.2 +/- 0.4 vs. 2 +/- 0.7 mmol/l erythrocytes, P < 0.05). The decrease in GPx and TRAP did not show significant differences. The parameters were also recorded in 30 patients who became euthyroid after treatment: 20 of them under MMI therapy (2-12 months) and the rest 3-6 months after 131Iodine administration. All the parameters evaluated were normalized after MMI; however, CL levels stayed high after 131I and only CAT and GSH levels returned to normal values. CONCLUSION: Our results confirm the imbalance of the antioxidant/oxidant status in hyperthyroid patients. MMI treatment was more effective than 131I therapy to improve that balance. We speculate on the benefits of antioxidant therapy administrated together with the habitual treatment of hyperthyroidism, especially in patients after 131I therapy.

Adolescent↗

PubMed2002

Determination of total arsenic, inorganic and organic arsenic species in wine.

Forty-five wine samples from the south of Spain of different alcoholic strength were analysed for total arsenic and its inorganic [As(III), As(V)] and organic (monomethylarsonic acid [MMAA], dimethylarsinic acid [DMAA]) species. The As levels of the wine samples ranged from 2.1 to 14.6 microg l(-1). The possible effect of the alcoholic fermentation process on the levels of the total arsenic and arsenical species was studied. The average total arsenic levels for the different samples were very similar, without significant differences between all types of wines. In table wines and sherry, the percentages of total inorganic arsenic were 18.6 and 15.6%, with DMAA or MMAA being the predominant species, respectively. In most samples, DMAA was the most abundant species, but the total inorganic aresenic fraction was considerable, representing 25.4% of the total concentration of the element. The estimated daily intakes of total arsenic and total inorganic arsenic for average Spanish consumers were 0.78 and 0.15 microg/person day(-1), respectively. The results suggest that the consumption of these types of wines makes no significant contribution to the total and inorganic arsenic intake for normal drinkers. However, wine consumption contributes a higher arsenic intake than through consumption of beers and sherry brandies.

Arsenic↗

PubMed2001

Evaluation of total reactive antioxidant potential (TRAP) of tissue homogenates and their cytosols.

This study evaluates the possibility of obtaining total reactive antioxidant potential (TRAP) indexes in homogenates and their cytosolic fractions by a procedure based on the quenching of luminol luminescence induced by the thermolysis of 2,2'-azo-bis(2-amidinopropane). Measurements were performed in rat brain, liver, kidney, and heart homogenates. TRAP indexes can be easily determined both in homogenates and their cytosolic fractions. The results obtained indicate that heart homogenates are the least and liver homogenates the most protected of the systems considered. Glutathione is the measured antioxidant that contributes the most to TRAP values, while uric acid makes a significant contribution only in liver. A calculation of theoretical TRAP values from the measured concentrations of the main antioxidants (glutathione, uric acid, ascorbic acid, and alpha-tocopherol) for the different homogenates shows that, in most tissues (liver, brain, and kidney), nearly 50% of the experimentally determined TRAP values are not accounted for. This difference is mainly due to the contribution of proteins to the measured TRAP.

Animals↗

PubMed2001

Improved solid-phase extraction method for systematic toxicological analysis in biological fluids.

A method for the simultaneous qualitative and quantitative determination of drugs of abuse (opiates, cocaine, or amphetamines) and prescribed drugs (tricyclic antidepressants, phenotiazines, benzodiazepines, etc.) in biological fluids--blood, urine, bile, and gastric contents--was developed. This procedure involves solid-phase extraction with Bond-Elut Certify columns followed by analysis by gas chromatography-nitrogen-phosphorus detection (GC-NPD) and confirmation by gas chromatography-mass spectrometry (GC-MS), after derivatization, when necessary. Pretreatment was performed on all samples: sonication for 15 min plus enzymatic hydrolysis with beta-glucuronidase in urine. With respect to the internal standards, nalorphine and trihexylamine were used for basic substances, allobarbital for acidic drugs, and prazepam for benzodiazepines. Acidic and basic compounds were extracted from different aliquots of samples at different pH levels: 6-6.5 for the acidic and neutral and 8-8.5 for the basic and the benzodiazepines. Several areas of experimental design were considered in the process of method optimization. These included internal standards, pH, sonication, flow rate and washing solvents. It was found that systematic analysis could be reliably performed using optimized extraction conditions. The recovery rates for the compounds tested were always higher than 61.02%.

Adsorption↗

PubMed2000

Antioxidant activity of Artemisia douglasiana besser extract and dehydroleucodine.

The charge (relative concentration) of antioxidants in aqueous extract and dehydroleucodine (DhL) from Artemisia douglasiana Besser was determined employing a procedure based on the quenching of luminol-enhanced chemiluminescence. Total reactive antioxidant potential (TRAP) and total antioxidant reactivity (TAR) values were determined. The data reported in the present work indicate that the extract of Artemisia douglasiana Besser and DhL showed antioxidant capacity. This activity is more pronounced in the extract, suggesting the presence of several antioxidants in Artemisia douglasiana.

Anti-Ulcer Agents↗

PubMed1999

Presence and distribution of arsenical species in beers.

The total content of arsenic and of its inorganic (As(III) and As(V)) and organic (monomethylarsonic acid, MMAA, and dimethylarsinic acid, DMAA) species were determined in a set of 21 alcoholic and alcohol-free beer samples using the technique of Hydride Generation Atomic Absorption Spectrometry. For total arsenic analysis, beer samples were dried and then microwave digested with nitric acid in polytetrafluoroethylene containers. For the speciation analysis, beers were previously subjected to ion exchange chromatography to elute the mentioned inorganic and organic arsenical species. Both microwave digestion and chromatographic separation methods were validated from certified reference materials and prepared standard solutions, respectively. The results obtained are presented in terms of the distribution and occurrence of arsenical species in the samples. The As levels of the beer samples were in the range of 1.5-12.4 micrograms/l. The influence of the production process for the alcohol-free beers in the speciation of arsenic is discussed. In alcoholic beers MMAA was the most abundant species, and for non-alcoholic beers inorganic As(III) was similar to the organic species. An estimated intake of total As of 0.47 microgram/person/day and 11.4 micrograms/person/day was obtained for average consumers and for heavy drinkers, respectively.

Alcohol Drinking↗

PubMed1999

Concentrations in human fluids: 101 drugs affecting the digestive system and metabolism.

BACKGROUND: The toxicological interpretation of blood and urine concentrations of drugs affecting the digestive system and metabolism, as with other groups of pharmaceutical specialties, is complicated. METHODS: As a continuation of our published studies on the concentrations of drugs of abuse, drugs affecting cardiovascular and hematopoietic systems, and respiratory system, we have reviewed the published data relating to the concentrations of drugs affecting the digestive system and metabolism in clinical and forensic cases. We have selected them on the basis of conservative criteria and our own experience. RESULTS: A table with concentrations of 101 drugs in whole blood, serum/plasma, and urine, corresponding to therapeutic, toxic, or lethal concentrations, is presented. CONCLUSIONS: The data can help interpret analytical results of patient or postmortem samples when there is a suspicion of poisoning with this group of drugs.

Animals↗

PubMed1999

High-dose aprotinin with gentamicin-vancomycin antibiotic prophylaxis increases blood concentrations of creatinine and cystatin C in patients undergoing coronary artery bypass grafting.

Both aprotinin and gentamicin-vancomycin antibiotic prophylaxis have been used widely in cardiac surgery to prevent bleeding and infections, respectively. As the drugs are excreted almost entirely by glomerular filtration, we investigated their action on renal function when administered either separately or together. To increase consistency, we measured serum concentrations of creatinine and cystatin C, a new marker of glomerular filtration rate, that many recent studies have shown to be more sensitive than serum creatinine. One hundred patients undergoing coronary artery bypass surgery were allocated randomly to one of four groups: group A received antibiotic prophylaxis with cefamandole and no aprotinin; group B received cefamandole and high-dose aprotinin; group C received antibiotic prophylaxis with gentamicin and vancomycin, but no aprotinin; and group D received both high-dose aprotinin and gentamicin-vancomycin antibiotic prophylaxis. Data from 84 patients, for whom data collection was complete, were analysed. In the first week after operation, mean serum concentrations of cystatin C and creatinine either remained constant or decreased slowly in all groups, except for group D. In group D, both markers increased gradually from postoperative day 2 onwards. The increase in cystatin C was significant on postoperative day 5 (from mean 1.02 (SD 0.11) mg litre-1 before operation to 1.35 (0.32) mg litre-1; P < 0.05), reaching a peak on postoperative day 7 (1.45 (0.35) mg litre-1; P < 0.05), while the increase in creatinine concentration was significant on postoperative day 6 (from 1.05 (0.16) mg dl-1 before operation to 1.29 (0.34) mg dl-1; P < 0.05). We conclude that simultaneous administration of high-dose aprotinin and prophylactic use of gentamicin with vancomycin increased serum concentrations of cystatin C and creatinine in the first postoperative week in patients undergoing cardiac surgery.

Aged↗

PubMed1999

Biochemical effects of chlorpromazine on mouse neuroblastoma cells.

Chlorpromazine and other phenothiazine derivatives are neuroleptic drugs of widespread use for clinical situations beyond the realm of psychiatry, such as to control nausea, vomiting and intractable hiccups. The present study investigated in vitro different cytotoxic effects of chlorpromazine in cultures of mouse neuroblastoma cell line Neuro-2a exposed to different concentrations of this compound. Indicators assessed were cell proliferation by quantification of total protein content of the cell culture, lysosomal function evaluated by the relative uptake of neutral red cytosolic phosphofructokinase (PFK) and enolase (ENL) activities in glycolysis, mitochondrial succinate dehydrogenase (SDH) activity in the citric acid cycle, lysosomal beta-galactosidase (GAL) activity, and neuronal acetylcholinesterase activity. Marked inhibitory effects were found for cell proliferation and relative neutral red uptake; PFK, ENL and GAL activities had no significant differences from control. Stimulation was specifically detected on SDH and the Krebs cycle at concentrations up to 30 microM. Chlorpromazine did not have high toxicity for cytotoxic effects on lysosomes.

Animals↗

PubMed1998

Intrarenal arteriosclerosis and impairment of kidney function in NIDDM subjects.

It is currently under debate whether the pathogenesis of end-stage renal failure in non-insulin-dependent diabetes mellitus (NIDDM) is a consequence of microangiopathy alone. The aim of this study was to investigate intrarenal arteriosclerosis and its correlation with kidney function in NIDDM. In 36 diabetic subjects, and in 10 age- and sex-matched healthy control subjects we measured kidney volume and resistive index of the interlobar arteries by duplex Doppler ultrasonography. Clinical and metabolic parameters, renal function and vascular sequelae of the disease were also evaluated. In diabetic subjects resistive index (median 0.72, range 0.54-0.79) was higher than in control subjects (median 0.62, range 0.57-0.66) (2p < 0.002). Kidney volume and resistive index correlated with age (p < 0.004), body mass index (p < 0.001), mean blood pressure (p < 0.001), total and LDL cholesterol (p < 0.01) and creatinine clearance (p < 0.001 and < 0.01, respectively). Kidney volume also correlated with HbA1 (p < 0.01) and resistive index with uric acid (p < 0.01). Lower body macroangiopathy was associated with increased resistive index and reduced kidney volume (2p < 0.05), while upper body macroangiopathy and microangiopathy were not. Our data suggest that macroangiopathy rather than microangiopathy is mainly responsible for impairment of kidney function in NIDDM. The resistive index of interlobar arteries seems to be a reliable marker of intrarenal arteriosclerosis and can be used as a non-invasive, easily available parameter of its evolution.

Arteriosclerosis↗

PubMed1998

Diabetic nephropathy: from micro- to macroalbuminuria.

This brief review will focus on the major factors leading to incipient diabetic nephropathy (i.e. microalbuminuria) progressing to overt nephropathy (i.e. macroalbuminuria) and particularly on the role of glycaemic control and hypertension. Both experimental and cohort studies support the role of hyperglycaemia in the development of diabetic nephropathy. Some recent long-term interventional studies in microalbuminuric patients show conflicting results regarding the role played by good metabolic control in reducing the incidence of overt nephropathy. However, strict metabolic control, which is fundamental in normoalbuminuric patients, is of little use even in microalbuminuric patients. In general, levels of glycosylated haemoglobin less than two standard deviations above the upper normal range, commonly <7.5-8%, seem to protect patients from developing nephropathy. The results of many cross-sectional studies have shown that the progression of renal damage regularly is accompanied by arterial hypertension both in insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Many long-term interventional studies have been performed in order to understand the effect of antihypertensive treatment on the incidence of proteinuria in both normotensive and hypertensive patients with IDDM or NIDDM. These data show a marked effect of antihypertensive therapy in preventing the onset of overt nephropathy, and suggest the superiority of angiotensin-converting enzyme (ACE) inhibitors. We believe that optimal blood pressure values are approximately 120/70-75 mmHg in younger patients and 125-130/80-85 mmHg in older patients. In conclusion, antihypertensive treatment, ACE inhibitors per se and possibly strict metabolic control reduce the development of nephropathy, thus playing a striking role in the secondary prevention of renal failure.

Albuminuria↗

PubMed1998

Sequencing analysis of forty-eight human image cDNA clones similar to Drosophila mutant protein.

We have sequenced 48 human IMAGE cDNA clones selected from the public EST database (dbEST) for their significant homology to Drosophila mutant genes. A dynamically updated analysis report was produced by BlastX and BlastN analysis searches in the latest databases available. This analysis led us to estimate the grade of similarity with homologous genes isolated in other species. Bottlenecks were detected in the sequencing process and here we have presented our problem-solving approach. We think the value of this full-length sequencing project is an enrichment of the sequence database information that is currently available to the human genome community.

Animals↗

PubMed1998

Therapeutic, toxic, and lethal concentrations of 73 drugs affecting respiratory system in human fluids.

BACKGROUND: Drugs affecting the respiratory system are an important group of pharmaceutical specialties in poisoning with relatively high frequency. METHODS: As a continuation of our published studies on the concentrations of drugs of abuse and drugs affecting cardiovascular and hematopoietic systems, we have reviewed the published data to select respiratory drugs on the basis of conservative criteria and our own experience. RESULTS: A compilation of the concentrations of 73 drugs affecting the respiratory system--in whole blood, serum/plasma, and urine, and corresponding to therapeutic, toxic, or lethal concentrations--is given. CONCLUSIONS: The table presented can be helpful in interpretation of the concentrations of this group of medicines encountered in clinical, toxicologic, and forensic cases.

Forensic Medicine↗

PubMed1998

Determination of cobalt, manganese, and alcohol content in beers.

The purpose of this study was to investigate the degree of exposure to cobalt and manganese through the consumption of different brands of commercial beers widely consumed in Spain, considered as two groups according to their alcohol content. The Mn and Co concentrations in beer samples ranged from 25.29 to 228.60 micrograms/liter and 0.16 to 0.56 micrograms/liter, respectively. These contents do not differ from those found in other countries, and all comply with the maximum levels permitted by law. Significant differences occurred only in Mn content between beers with and without alcohol. The consumption of alcoholic beers contributes to an increased body burden of Mn among heavy consumers. According to the low levels of Co found in both types of beers, we can suggest that there is no risk of suffering cardiomyopathies and there is no significant contribution to the total intake of the element in heavy beer drinkers.

Alcohols↗

PubMed1998

Deaths from pesticide poisoning in Spain from 1991 to 1996.

Data on 184 deaths from pesticide poisonings that occurred in Spain from 1991 to 1996 have been collated via a survey from the National Institute of Toxicology, Sevilla. Organophosphates and carbamates accounted for the majority of the cases. Other substances involved were organochlorines such as endosulfan and the herbicide paraquat.

Carbamates↗

PubMed1998

Congenital bilateral fibular deficiency with facial dysmorphia, brachydactyly and mental retardation in a girl.

Congenital bilateral fibular deficiency with facial dysmorphia, brachydactyly and mental retardation in which are combined in a syndrome or which do not fit in any of the known syndromes. We report a child with congenital bilateral deficiency of the fibula and an unusual combination of features. The patient, a girl, was born after an uneventful pregnancy at term to young healthy parents. Absent fibulae were noted at birth. At age 4 she was found to have growth retardation with delayed bone age, overlapping, short toes, syndactyly of the toes, clinodactyly of the 5th and 2nd fingers, syndactyly of the three last fingers and facial dysmorphia. Mental retardation was present. Karyotype and laboratory investigations were normal. Differential diagnosis included syndromes with aplasia or hypoplasia of fibula, but none of these syndromes seemed to include the girl's features.

Abnormalities, Multiple↗

PubMed1997

Identification by shotgun sequencing, genomic organization, and functional analysis of a fourth arylsulfatase gene (ARSF) from the Xp22.3 region.

We recently reported the isolation of two new members of the sulfatase gene family, arylsulfatase D (ARSD) and E (ARSE), located approximately 50 kb from each other in the Xp22.3 region. Mutation analysis indicated ARSE as the gene responsible for X-linked recessive chondrodysplasia punctata. Expression of the ARSE gene in COS cells resulted in a heat-labile arylsulfatase activity that was inhibited by warfarin. At the same time, we detected the presence of a 1.2-kb fragment located at approximately 60 kb from ARSD and ARSE with significant homology to these two genes, suggesting the existence of another sulfatase gene, arylsulfatase F (ARSF), in Xp22.3. We have used a combined approach of long-range genomic sequencing and screening of cDNA libraries to isolate the ARSF gene. Expression of the ARSF cDNA in COS cells resulted in a heat-labile arylsulfatase activity that is not inhibited by warfarin, supporting our hypothesis that only ARSE is specifically inhibited by warfarin and is most likely involved in warfarin embryopathy. Genomic analysis revealed that ARSF has an intron/exon organization highly similar to those of ARSD and ARSE, which is also shared by another Xp22.3 sulfatase gene, ARSC (arylsulfatase C, also known as steroid sulfatase), with the splice sites occurring at the same position in all four genes. The data obtained from sequence analysis and presented in this paper indicate that the ARSC, ARSD, ARSE, and ARSF genes are more similar to each other than to other members of the sulfatase gene family, supporting our hypothesis that they represent a subfamily of related proteins created through duplication events that occurred in an ancestral pseudoautosomal region.

Amino Acid Sequence↗

PubMed1997

Time course of cocaine in rabbit hair.

The accurate interpretation of analytical results from hair testing for drugs of abuse continues to be a complex and difficult problem since many questions still remain unanswered. In this paper an animal model was developed to ascertain the time course for the appearance and disappearance of cocaine and its metabolite benzoylecgonine (BE) in hair. Female Fauve Bourgogne red-haired rabbits (n = 6) were intraperitoneally administered a single dose of cocaine at 5 mg/kg. Animal hair was shaved just before drug administration and the newly grown back hair was subsequently shaved and collected daily over a period of two weeks. Samples were analyzed for cocaine and BE by gas chromatography-mass spectrometry (GC-MS). The profiles were quite similar for parent drug and metabolite. Cocaine and BE appeared in the first sampling (day 1), with peak concentration appearing that same day. 1.01 ng/mg and 0.51 ng/mg for cocaine and BE, respectively. Levels declined rapidly on day 2, remaining detectable for ten days after drug administration. This study demonstrates that the initial incorporation of cocaine compounds in rabbit hair is very rapid (24 h). A small fraction of the drug is detected ten days after exposure, at a time when concentrations in other biological specimens (blood or urine) are not detectable.

Animals↗