Biomedical subjects

J M Pérez

Publications and source records attributed to J M Pérez.

At least 19 recordsLinked to original sources

PubMed2006

Sex-difference in the ossification rate of the appendicular skeleton in Capra pyrenaica Schinz, 1838, and its utility in the sex identification of long bones.

The main goal of our work is to quantify differences in the rate of ossification in post-cranial Iberian ibex skeletons, related to sex. Another objective is to improve criteria for assessing the sex of post-cranial bones by combining the degree of ossification of the distal epiphysis and biometrical data. Forty Capra pyrenaica skeletons were examined in order to determine the degree of ossification by means of an Ossification Index. Our results evidence that sexual differences in the rate of ossification become visible at 6 months of age. On average, females complete their bone development 2 years before males do. Finally, by means of lineal classification functions which take into account both biometrical and anatomical criteria, we can achieve, in average, a 95.5% of correct sex discrimination within a sample consisting of ibex metacarpi and metatarsi from individuals aging from <1 to 12 years. Therefore, we conclude that the rhythm of ossification in the post-cranial skeleton of C. pyrenaica may be used as a criterion for assessing the sex of skeletal remains and could be applicable to other dimorphic ungulates. Nevertheless, the results obtained for specimens belonging to a particular population may have limited application to other populations with different medium sizes and living at particular densities within habitats with variable quality.

Animals↗

PubMed2004

Biochemical characterization of a thermostable cysteine synthase from Geobacillus stearothermophilus V.

The cysK gene encoding a cysteine synthase of Geobacillus stearothermophilus V was overexpressed in E. coli and the recombinant protein was purified and characterized. The enzyme is a thermostable homodimer (32 kDa/monomer) belonging to the beta family of pyridoxal phosphate (PLP)-dependent enzymes. UV-visible spectra showed absorption bands at 279 and 410 nm. The band at 279 nm is due to tyrosine residues as the enzyme lacks tryptophan. The 410 nm band represents absorption of the coenzyme bound as a Schiff base to a lysine residue of the protein. Fluorescence characteristics of CysK's Schiff base were influenced by temperature changes suggesting different local structures at the cofactor binding site. The emission of the Schiff base allowed the determination of binding constants for products at both 20 degrees C and 50 degrees C. At 50 degrees C and in the absence of sulphide the enzyme catalyzes the decomposition of O-acetyl-l-serine to pyruvate and ammonia. At 20 degrees C, however, a stable alpha-aminoacrylate intermediate is formed.

Bacillaceae↗

PubMed2004

Pd(II) and Pt(II) complexes with aromatic diamines: study of their interaction with DNA.

Pd(II) and Pt(II) new complexes with simple aromatic diamines were synthesised and characterised with the aim of studying their possible antitumour activity. The aromatic diamines chosen were 2,3-diaminotoluene (2,3 dat), 3,4-diaminotoluene (3,4 dat), 4,5-diaminoxylene (4,5 dax) and 2,3-diaminophenol (2,3 dap). The complexes, of formulae cis-[MCl(2)(diamine)], were characterised by elemental analysis, conductivity measurements, 1H, 13C(1H) and 195Pt NMR spectroscopy. The X-ray crystal structure was also resolved for the palladium complexes with 2,3-diaminotoluene and 4,5-diaminoxylene. The DNA adduct formation of the eight new complexes synthesised was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the complexes on plasmid DNA pBR322 were also obtained. Values of IC50 were also calculated for the four platinum complexes against the cisplatin resistant tumour cell line A2780cisR.

Animals↗

PubMed2004

Ossification of the appendicular skeleton in the Spanish Ibex Capra pyrenaica Schinz, 1838 (Artiodactyla: Bovidae), with regard to determination of age.

We studied ossification macroscopically in 35 Spanish ibex (Capra pyrenaica) appendicular skeletons in order to establish the skeletochronology in both sexes of the species. The age of animals had been determined by means of horn segment counts, teeth replacement and cementum layer counts from first incisors and ranged from <1 to 12 years. Females showed a faster ossification process than males. Moreover, for each age or year class considered, regarding both sexes, different stages of epiphyseal fusion could be found. Therefore, if we try to use data from bone remains in population studies (e.g. differential mortality rates), determination of the ossification stage for ageing bone samples must be carried out with caution.

Age Determination by Skeleton↗

PubMed2004

Chihuahua: a water reuse case in the desert.

Water supply for all kind of uses in Chihuahua is mainly groundwater. During the last decade this city has been damaged with a heavy hydrologic crisis because of a persistent drought. This came up with the overexploitation of groundwater aquifers; therefore a deficit between demand and offer was done. To minimize this problem the government authorities have started an integral plan of optimizing hydrologic resources which considers the treatment of wastewater and the use of reclaimed water. The secondary wastewater treatment facility of the city treats about 30,000 m3/d of a wastewater with high organic contents, and produces an effluent with low concentration of suspended solids, organic matter, fats, detergents, and metals. Reclaimed water is conveyed toward strategic sites for the irrigation of great green areas in sport clubs, educational institutions and industrial zones, besides of its utilization on some manufacturing processes, road service, and also over construction industry. The potential reuse of this water goes farther from those activities; the treatment of the secondary effluent until the required levels of the water-bearing recharge criteria are met for drinking water supply is considered as the next step to achieve through a suitable planning strategy for the best integral resource advantage.

Agriculture↗

PubMed2003

Cisplatin biochemical mechanism of action: from cytotoxicity to induction of cell death through interconnections between apoptotic and necrotic pathways.

Although cisplatin, cis-diamminedichloroplatinum(II), has been successfully used in the chemotherapy of cancer for more than 25 years, its biochemical mechanism of action is still unclear. The current accepted paradigm about cisplatin mechanism of action is that the drug induces its cytotoxic properties through binding to nuclear DNA and subsequent interference with normal transcription, and/or DNA replication mechanisms. If cisplatin-DNA adducts are not efficiently processed by cell machinery, cytotoxic processes eventually end up in cell death. However, before cisplatin enters the cell it may bind to phospholipids and phosphatidylserine in the cell membrane. In addition, in the cytoplasm many potential platinum-binding sites are also available, including RNA and sulfur-containing biomolecules. Moreover, there is much evidence suggesting that the cytotoxic effects induced by binding of cisplatin to non-DNA targets (especially proteins) may contribute to its biochemical mechanism of action. On the other hand, it has been found that several factors such as the dose of drug as well as the metabolic condition of the cell subjected to cisplatin aggression, may determine that cancer cells die through apoptosis or necrosis. In fact, it has recently been reported that both mechanisms of cell demise work in concert so that within a population of tumour cells there is a continuum of possible modes of cell death.

Animals↗

PubMed2002

Novel concepts in the development of platinum antitumor drugs.

The limitations of cisplatin as an anticancer drug have stimulated the search for other antitumor-active platinum complexes with improved pharmacological properties. The two main goals in the search for new platinum anti-cancer agents are the reduction of the dose-limiting toxicities of cisplatin and the circumvention of cisplatin resistance. However, it should be pointed out that this has proven to be a difficult task. In fact, less than 1% of the thousand of platinum complexes tested for pre-clinical antitumor activity have entered clinical trials in the past 30 years. Nonetheless, right now, several new platinum complexes are in clinical trials, a proof of the continued belief that platinum complexes may still fulfil the needs for novel antitumor drugs. This review will focus on the three main innovative approaches found in the platinum anticancer-field, namely, (1) compounds with decreased reactivity against nucleophiles, (2) compounds with carrier ligands, and (3) compounds which bind differently to DNA as compared to cisplatin. In the latter class, special attention is paid to dinuclear and polinuclear platinum complexes.

Animals↗

PubMed2001

Conformations of allylic fluorides and stereoselectivities of their diels-alder cycloadditions.

The preparations of new allylic fluorides from the corresponding alcohols are reported. Conformational analysis is achieved by comparison of experimental NMR measurements with theoretical (B3LYP) calculations of relative energies of conformers and J(H,H) and J(H,F) coupling constants. The Diels-Alder reactions of allylic fluorides are investigated experimentally and theoretically. The stereoselectivities of the reactions were determined by NMR analysis and, in one case, by X-ray crystallography. Theoretical predictions of stereoselectivity based upon transition state modeling provided good agreement with experiment. Theoretical models for allylic fluorides and transition state conformations are reported.

Hydrocarbons, Fluorinated↗

PubMed2001

DNA interstrand cross-linking efficiency and cytotoxic activity of novel cadmium(II)-thiocarbodiazone complexes.

We have prepared mono- and binuclear complexes of Zn(II) and Cd(II) with bis(2-pyridyl aldehyde) thiocarbodiazone (H(2)L(1)) and bis(methyl 3-pyridyl ketone) thiocarbodiazone (H(2)L(2)). Cytotoxicity data against the ovarian tumor cell line A2780cisR (acquired resistance to cisplatin) indicate that the mononuclear complex Cd/H(2)L(2) (1) and the binuclear complex Cd(2)/H(2)L(1) (4) are able to circumvent cisplatin resistance and that their cytotoxic activity does not substantially vary after depletion of intracellular levels of glutathione. Moreover, DNA binding studies show that complexes 1 and 4 have higher efficiency than cisplatin at forming DNA interstrand cross-links in both naked pBR322 plasmid and A2780cisR cellular DNA. Interestingly, the thiocarbodiazone ligands alone do not show the biological properties of complexes 1 and 4. Altogether these results suggest that DNA interstrand cross-link formation by compounds 1 and 4 might be related with their cytotoxic activity in cisplatin-resistant cells. We think that compounds 1 and 4 may represent a novel structural lead for the development of cadmium cytotoxic agents capable of improving antitumor activity in cisplatin-resistant tumors.

Antineoplastic Agents↗

PubMed2001

Thermal unfolding of a llama antibody fragment: a two-state reversible process.

Camelids produce functional "heavy chain" antibodies which are devoid of light chains and CH1 domains [Hamers-Casterman, C., et al. (1993) Nature 363, 446-448]. It has been shown that the variable domains of these heavy chain antibodies (the V(HH) fragments) are functional at or after exposure to high temperatures, in contrast to conventional antibodies [Linden van der, R. H. J., et al. (1999) Biochim. Biophys. Acta 1431, 37-44]. For a detailed understanding of the higher thermostability of these V(HH) fragments, knowledge of their structure and conformational dynamics is required. As a first step toward this goal, we report here the essentially complete (1)H and (15)N NMR backbone resonance assignments of a llama V(HH) antibody fragment, and an extensive analysis of the structure at higher temperatures. The H-D exchange NMR data at 300 K indicate that the framework of the llama V(HH) fragment is highly protected with a DeltaG(ex) of >5.4 kcal/mol, while more flexibility is observed for surface residues, particularly in the loops and the two outer strands (residues 4-7, 10-13, and 58-60) of the beta-sheet. The CD data indicate a reversible, two-state unfolding mechanism with a melting transition at 333 K and a DeltaH(m) of 56 kcal/mol. H-D exchange studies using NMR and ESI-MS show that below 313 K exchange occurs through local unfolding events whereas above 333 K exchange mainly occurs through global unfolding. The lack of a stable core at high temperatures, observed for V(HH) fragments, has also been observed for conventional antibody fragments. The main distinction between the llama V(HH) fragment and conventional antibody fragments is the reversibility of the thermal unfolding process, explaining its retained functionality after exposure to high temperatures.

Amides↗

PubMed2001

Calcium-induced conformational changes in Leishmania infantum kinetoplastid membrane protein-11.

Total-reflection X-ray fluorescence has been used to study whether the Leishmania infantum kinetoplastid membrane protein-11 is a Ca2+-binding protein. The 108 amino acid helix-loop-helix protein has the loop region located between residues 45 and 57, having similarity to the EF-hand motifs. In particular, the sequence alignment of the putative motif revealed the existence of 67% similarity and 33% identity with the EF-hand of the plasmodia-specific 40-kDa protein from Physarum polycephalum. To address the type of conformational changes induced by Ca2+ binding, circular dichroism and fluorescence spectroscopy were used. The data showed that Ca2+ induces changes in both the secondary and tertiary structure of the protein in a temperature- and pH-dependent way. It also induces the precipitation of the protein at pH 7.5, in contrast with what occurs at pH 5.0, and the precipitation process can be reverted by addition of EGTA. At acidic pH values the complex EGTA-Ca2+ causes drastic structural changes, forcing the protein to adopt a structure close to that of a random coil. Because, at acidic pH values, protein:Ca2+:EGTA ternary complexes may be formed, the drastic change may be attributed to the presence of a high density of EGTA negative charges in the neighborhood of the alpha-helices.

Amino Acid Sequence↗

PubMed2001

A kinetic model for the B-Z transition of poly[d(G-C)].poly[d(G-C)] and poly[d(G-m5C)].poly[d(G-m5C)].

The analysis of the kinetic data of the B-Z conformational changes induced by salt in sized double-stranded poly[d(G-C)].poly[d(G-C)] and poly[d(G-m5C)].poly[d(G-m5C)] polymers indicated that there exists a salt threshold which reveals some largely, as yet, unrecognised characteristics of the transition. It was observed that there is a direct correlation between the length of the polymer and the rate of the B-Z transition when the salt concentration in the polymer solution is lower than the salt threshold. The correlation is inverse when the salt concentration is higher than the salt threshold. Thus, the molecular mechanism of the B- to Z-DNA transition varies depending on whether the salt concentration is higher or lower than the threshold. In this context, we have found that the contrasting results reported in the literature describing the rate of the B-Z transition are not contradictory but complementary. The finding of a salt threshold leads to the establishment of a relationship between the cooperativity index of the B-Z transition and the polymer chain length. That relationship is dependent on the chemical structure of the polymer but is temperature independent.

DNA↗

PubMed2001

Treatment of humeral shaft nonunion by external fixation: a valuable option.

We report the treatment of six patients with nonunion of the humerus, using a unilateral fixator and bone grafting. Union was obtained in all patients, with an average time to union of 4.5 months. Superficial pin tract infection was seen in five patients, but resolved uneventfully. One patient had transient radial nerve palsy. The results, according to the Stewart and Hundley criteria, were excellent in one patient, good in three, fair in one, and poor in one. The main cause of the fair and poor results was marked limitation of shoulder and elbow motion. This method, however, seems to be therapeutically effective.

Adult↗

PubMed2001

Sterically hindered cisplatin derivatives with multiple carboxylate auxiliary arms: synthesis and reactions with guanosine-5'-monophosphate and plasmid DNA.

Two novel sterically hindered cisplatin derivatives with the ligand L=NH(2)C(CH(2)CH(2)COOH)(3) were prepared: cis-PtCl(2)L(2) and cis-PtCl(2)L(NH(3)). The starting compound for the syntheses was NH(2)C(CH(2)CH(2)COOtBu)(3), also known as a building block for dendrimers. cis-PtCl(2)L(2) was prepared from K(2)PtCl(4) in an unusual two-phase reaction in water-chloroform, followed by deprotection of the tert-butyl protective groups with formic acid to yield a water-soluble complex. The mixed-ligand compound cis-PtCl(2)L(NH(3)) was prepared from [PPh(4)][PtCl(3)(NH(3))] in methanol, with subsequent deprotection in formic acid. DNA-binding properties of the two compounds were investigated using the model base guanosine-5'-monophosphate (5'-GMP) and pBR322 plasmid DNA. While cisplatin [cis-PtCl(2)(NH(3))(2)] induced an unwinding of 12 degrees in pBR322 plasmid DNA, cis-PtCl(2)L(NH(3)) induced only 3 degrees unwinding, which is indicative of a monofunctional binding mode. Remarkably, cis-PtCl(2)L(2) did not induce any distortion in plasmid DNA, which strongly suggests that the compound does not bind to DNA. Test reactions with 5'-GMP, monitored by 1H and 195Pt NMR, confirmed that cis-PtCl(2)L(2) is unable to bind to DNA, whereas cis-PtCl(2)L(NH(3)) binds only one nucleotide. Apparently, binding of platinum to nucleotides at the coordination site cis with respect to the ligand L is prevented by steric crowding. Thus, cis-PtCl(2)L(NH(3)) must bind DNA monofunctionally at the trans position. Besides, both compounds have a chloride replaced by one of the carboxylate arms, forming a a seven-membered chelate ring. In theory, cis-PtCl(2)L(2) could also form a second chelate ring, but this was not observed.

Antineoplastic Agents↗

PubMed2001

Traumatic disruption of the pancreatic duct: diagnosis with MR pancreatography.

OBJECTIVE. We evaluated the ability of MR pancreatography to reveal traumatic disruptions of the pancreatic duct compared with retrograde pancreatography. CONCLUSION. MR pancreatography is an adequate noninvasive test for the detection of complete traumatic disruptions of the main pancreatic duct. MR pancreatography is especially useful for delineating the segments of the duct that cannot be evaluated with retrograde pancreatography.

Adolescent↗

PubMed2001

[Clinical practice guidelines of the Spanish Society of Cardiology for surgical risk assessment in cardial patients treated with non-cardiac surgery].

All patients undergoing a surgical intervention require a cardiovascular evaluation that establishes the surgical risk. On the other hand, an important proportion of the deaths that happened during the surgery are due to cardiovascular complications, many of them could be avoided with a cardiac risk screening. The surgery and the anesthesia subject the patient to stress situations during the perioperative period that forces the check upon capacity of the patient to respond to those demands, dissuading surgery if it considered that the risk is very high. The rate of major surgery in elderly patients is growing, with the increase in cardiovascular complications, mainly myocardial infarction, unstable angina and perioperative heart failure. Following we establish some recommendations for the cardiovascular assessment of the cardiac patient that will undergo noncardiac surgery.

Anesthesia↗

PubMed2001

Evaluation of neonatal sepsis screening in a tropical area. Part II: Evaluation of intrapartum chemoprophylaxis protocol.

The authors report on an analysis of a chemoprophylaxis protocol at the University Hospital of Guadeloupe in the Caribbean. This study comprised 6,060 consecutive deliveries and was initiated to assess the application of an intrapartum chemoprophylaxis protocol, evaluate its results, and try to identify possible necessary modifications to the existing protocol. Although more than 90% of women had at least one bacterial screening (vaginal or urinary) during the last trimester of pregnancy, approximately 75% of mothers who were heavily colonized group B streptococcus (GBS) at delivery were not detected by this systematic screening. As is also reported in other tropical areas where a great proportion of neonatal sepsis occurs in term babies, low birthweight was not a specific risk factor in this study when controlling for other major risk factors such as fever and premature rupture of membranes. Intrapartum chemoprophylaxis was associated with an approximate threefold decrease in the risk of GBS neonatal bacteraemia among at risk deliveries. The results suggest that, in our tropical context, prolonged rupture of membranes of at least 12 hours' duration should be considered as a cause for intrapartum chemoprophylaxis as it accounted for the majority of cases of neonatal bacteraemia that escaped the existing protocol.

Anti-Bacterial Agents↗

PubMed2001

Evaluation of neonatal sepsis screening in a tropical area Part III: Neonatal sepsis in meconium stained deliveries.

Of the 6,060 consecutive live births delivered at the University Maternity Unit of Guadeloupe (French West Indies) during a 30-month period, 635 newborns (10.4%) presented with meconium stained (MS) amniotic fluid, of which 595 (94%) received bacteriological screening at birth (light MS, n = 543; thick MS, n = 52). Thirty (5%) of MS newborns had a bacteraemia (n = 13, group B streptococcus, GBS), and 128 (21.5%) a bacterial positive gastric aspirate (n = 54, GBS). Sixty-six newborns among MS babies needed tracheal suctioning (11%) in the delivery room for meconium inhalation. Among these 595 screened MS newborns, 286 (48%) presented clinical signs of postmaturity at birth, having therefore an explanation for their MS condition. For the other MS newborns without the postmaturity explanation, we experienced twofold increased risk of neonatal sepsis (OR 1.88 for bacteraemia and 2.61 for external carriage p < 0.02, Chi square) as compared with their MS postmature counterparts. We conclude that when meconium stained deliveries are associated with postmaturity signs, one may not need to initiate prophylactic antibiotic treatment at birth unless they present with other traditional risk factors for neonatal sepsis such as intrapartum fever and prolonged rupture of membranes.

Humans↗