Comparison between two methods of defining heat waves: a retrospective study in Castile-La Mancha (Spain).

INTRODUCTION: Following the 2003 heat wave, many European countries implemented heat-wave prevention plans. A number of aspects can prove fundamental in determining the effectiveness of such plans, and of these we sought to analyse the criteria used to define threshold temperatures and trigger a higher level of intervention. METHOD: Retrospective study of the days on which heat-wave thresholds were exceeded during the period 1974-2003 was conducted. We compared when and at what level the heat-wave prevention plan would have been activated using a statistical-meteorological criterion (as applied by the Spanish Ministry of Health & Consumer Affairs) versus a temperature-mortality criterion. RESULTS: The number of days on which the threshold was exceeded was far higher when the temperature-mortality criterion was applied. The temperature percentile at which a heat wave occurred was different for each province analysed and was inversely proportional to its respective ageing index. Using both criteria, there was an increase in heat-wave days per decade. CONCLUSION: The establishment of a heat-wave threshold temperature must be based on knowledge of the cause-effect relationship between temperature and the health of a given population. Mortality is an appropriate indicator of population health. The future effects of climate change render it essential for this relationship to be studied on a local scale, so as to enable truly efficient prevention plans to be drawn up.

Fluorescent cisplatin analogues and cytotoxic activity.

Cisplatin is one of the chemotherapeutic agents used the most for testicular, ovarian and several other cancers. In order to overcome cisplatin resistance, other platinum (Pt) compounds have been developed and, in the last ten years, Pt-derivatives with reporting activity have also been synthesized. The first generation of reporting Pt-compounds was based on linking a fluorescent molecule (e.g. cyanine) to cisplatin, but more recent studies have focused on strategies to synthesize intrinsically fluorescent derivatives. Accordingly, bile acid Pt-compounds have shown fluorescence intensity that is stable at room temperature for a long time; this fluorescence is maintained after binding to oligonucleotides or DNA. Because of this, the binding mode of these compounds to DNA can be easily analyzed both by flow injection and fluorescence techniques, showing that although these compounds target the nuclei, they form adducts with the DNA that are different from those due to cisplatin. In line with this, these bile acid derivatives have shown increased cytotoxicity and ability to overcome resistance as compared to cisplatin in several cell lines. Moreover, in contrast to cisplatin, the activity of these compounds does not seem to be restricted to cycling cells but they also seem to kill resting cells. This review summarizes the information available on reporting Pt-compounds and focuses on these novel, intrinsically fluorescent bile acid Pt derivatives, their biochemical characteristics and biological activity.

Diseño y equipamiento actual y de las centrales de esterilización / No disponible

El diseño y equipamiento actual de las centrales de esterilización no es el fruto de un momento puntual y coyuntural. Las centrales de esterilización han ido modificándose con el tiempo, al igual que lo han hecho los hospitales y residencias sanitarias o las formas de gestión y dirección de dichos centros. La situación actual es el producto de la evolución histórica de las primeras iniciativas sanitarias por parte del estado español a principios del siglo XX, hasta la configuración actual de nuestro Sistema Nacional de Salud en pleno siglo XXI (AU)

The current design and equipment of central sterilization is not the result of time and cyclical time. The central sterilization have evolved over time, as we have hospitals and health care residences, or forms of administration and management of these centers. The current situation is the product of the historical development of the first initiatives by the health status of Spanish in the early twentieth century to the present configuration of our National Health System in the XXI century (AU)

New fluorescent antitumour cisplatin analogue complexes. Study of the characteristics of their binding to DNA by flow injection analysis.

The flow injection technique is applied to study the binding to DNA of new platinum complexes-E(1): ethylenediaminechlorocholylglycinateplatinum(II): [PtCl(CG)(en)], C(54)H(92)O(12)Pt and E(2): ethylenediaminebischolylglycinateplatinum(II): [Pt(CG)(2)(en)], C(28)H(50)ClN(3)O(6)Pt-derived from cisplatin in which the exchangeable ligands were replaced by bile acids, such that these anticancer drugs have less toxicity and less resistance is developed towards them. Both compounds are fluorescent and their fluorescence is enhanced when they form adducts with DNA, a property that is extremely useful for monitoring the cytotoxic activity and their mechanisms of action. The binding parameters to DNA of E(1) [apparent intrinsic binding constant K(E1): (11.2 +/- 0.4) x 10(3) M(-1) and maximum number of binding sites per nucleotide, n (E1): 0.121 +/- 2 x 10(-3)) and E(2) (K(E2): 9.2 +/- 0.7) x 10(3) M(-1) and n (E2) 0.098 +/- 2 x 10(-3)] were determined following the Scatchard method and the type of binding was studied experimentally through the modifications introduced by each of the compounds into the ethidium bromide-DNA bond.

Determination of the DNA-binding characteristics of ethidium bromide, proflavine, and cisplatin by flow injection analysis: usefulness in studies on antitumor drugs.

Flow injection analysis was used to study the reactions occurring between DNA and certain compounds that bind to its double helix, deforming this and even breaking it, such that some of them (e.g., cisplatin) are endowed with antitumoral activity. Use of this technique in the merging zones and stopped-flow modes afforded data on the binding parameters and the kinetic characteristics of the process. The first compound studied was ethidium bromide (EtdBr), used as a fluorescent marker because its fluorescence is enhanced when it binds to DNA. The DNA-EtdBr binding parameters, the apparent intrinsic binding constant (0.31+/-0.02 microM(-1)), and the maximum number of binding sites per nucleotide (0.327+/-0.009) were determined. The modification introduced in these parameters by the presence of proflavine (Prf), a classic competitive inhibitor of the binding of EtdBr to the DNA double helix, was also studied, determining the value of the intrinsic binding constant of Prf (K(Prf) = 0.119+/-9x10(-3) microM(-1)). Finally, we determined the binding parameters between DNA and EtdBr in the presence of the antitumor agent cisplatin, a noncompetitive inhibitor of such binding. This provided information about the binding mechanism as well as the duration and activity of the binding of the compound in its pharmacological use.

Logística y trazabilidad en la central de esterilización / Logistics and traceability in the sterilization centre

La Central de Esterilización puede ser considerada un centro productor en el que se diferencian varias áreas funcionales, con su correspondiente dotación de recursos humanos y materiales, integrándose en la estructura física y arquitectónica del hospital o establecimiento sanitario al que pertenezca. La Central de Esterilización debe ofrecer un servicio a sus clientes internos o externos (usuarios) mediante una dinámica de trabajo o ciclo general de actividad. Esta dinámica o ciclo se ajusta a las necesidades de los usuarios mediante los pactos de horarios y circuitos establecidos entre la Central y el hospital o establecimiento sanitario. Una correcta organización y dinámica del trabajo que se desarrolla en la Central permite incrementar y optimizar la efectividad de la misma, la seguridad de los trabajadores y de los pacientes, asegurando un producto de calidad a los clientes de la Central (AU)

Review of the organisation and dynamics of a Sterilization Centre taking into account sorne functional work areas which need to have sorne work protocols and human and material resources determined in arder to ensure the traceability of the products of the sterilization centre (AU)

Structural characterization and cytostatic activity of chlorobischolylglycinatogold(III).

Based on the ability of bile acids for vectorializing the cytostatic activity of other agents, we have designed and synthesized a new bile acid cholylglycinato Au(III) complex, named Bamet-A1. It has been characterized by means of EA (elemental analysis), FT-IR, NMR, FAB-MS (fast atom bombardment-mass spectrometry) and Vis-UV techniques. This characterization allowed us to propose a structure of the type [Au CG(O) CG(N,O) Cl] for the neutral complex, which has the composition C522H84N2O12AuCl and is very soluble in water, methanol, ethanol and DMSO (dimethylsulfoxide). The study in aqueous solution suggested a redox process for its transformation, which is accompanied by the appearance of colloidal gold phase. The behavior in 4 mM NaCl water (in order to mimic the cytoplasmatic fluid) was similar to that observed in water, while in a 150 mM NaCl (similar to extracellular fluid and serum), the apparition of a dark blue precipitate was observed. This complex displays fluorescence, which does not change when incubated with DNA obtained from E. coli. Bamet-A1 was found to inhibit the growth of a variety of cell lines. The cytostatic effect was mild against human hepatoma HepG2, mouse hepatoma Hepa 1-6, rat hepatoma McA RH-7777 and human colon adenocarcinoma LS-174T, and stronger against mouse sarcoma S180-II and mouse leukemia L-1210 cells. The appearance of colloidal Au during the process of hydrolysis under physiological conditions may explains the low cytostatic activity.

Structural characterization, kinetic studies, and in vitro biological activity of new cis-diamminebis-cholylglycinate(O,O') Pt(II) and cis-diamminebis-ursodeoxycholate(O,O') Pt(II) complexes.

The complexes cis-diamminebis-cholylglycinate (O,O') [Pt(II) C(52)H(90)N(4)O(12)Pt, for convenience referred to as Bamet-R1] and cis-diamminebis-ursodeoxycholate (O,O') Pt(II) (C(48)H(84)N(2)O(8)Pt, Bamet-UD2) were prepared. The structural integrity of the compounds was confirmed by elemental analysis, FT-IR, NMR, FAB-MS, and UV spectroscopies. The kinetic study of both compounds was accomplished by combining the conductivity measurement and those of the analysis of the electronic spectra in aqueous solution for NaCl concentrations of 4 mM (similar to cytoplasmatic concentration), 150 mM (similar to plasmatic concentration), and 500 mM. In water, the compound Bamet-R1 showed a half-life, t(1/2), of 3.0 h. This compound forms the chelate species through loss of a ligand, and the other one acts as a bidentate ligand. Ring opening in the presence of chloride ion was produced with a k(Cl)()-of 0.25 M(-)(1) h(-)(1). The half-life of Bamet-UD2 in aqueous solution was 3.2 h. However, since this species is not able to chelate and has a lower degree of solubility in the presence of chloride ion, its kinetic behavior was very different from that of the other compound. We consider this to be of great interest with regards to its cytostatic activity. All kinetic measurements were performed under pseudo-first-order conditions, and a pseudo-first-order behavior was found. The antitumoral effect of Bamet-UD2 on several cell lines derived from rat hepatoma, human hepatoma, mouse leukemia, and human colon carcinoma was found to be, in general, similar to that of cisplatin, but higher than that observed for Bamet-R1.

Synthesis and characterization of sodium cis-dichlorochenodeoxycholylglycinato(O,N) platinum(II)--cytostatic activity.

With a view to using bile acids as shuttles for delivering platinum-related cytostatic drugs to liver tumors, a chenodeoxycholylglycinato(CDCG)-derivative of platinum(II) has been synthesized. The complex--named Bamet-M2--was chemically characterized by elemental analysis, FT-IR, NMR, FAB-MS, and UV spectroscopy. The results indicate the following composition: C26H42N2O5Cl2NaPt(II), the metal Pt(II) being bound to two Cl- and one bidentate CDCG moiety, i.e., Na[Pt CDCG(N,O) Cl2]. The compound is highly soluble (up to 20 mM) in water and (up to 35 mM) in ethanol, methanol and DMSO. Hydrolysis was investigated because this is assumed to be an important step in intracellular activation and interaction with DNA of this type of compounds. The reaction kinetics of this complex in aqueous solution show unusual behaviour; the substitution process with the displacement of two Cl- was almost instantaneous, and the resulting species were found to be very stable. Kinetic studies carried out in the presence of different NaCl concentrations (up to 500 mM) revealed similar fast and nonreversible aquations of Bamet-M2. This contrasts with the slow aquation of cisplatin in extracellular-line solutions (i.e., at high NaCl concentrations) as compared with fast hydrolysis in cells. This difference may partly account for the low cytostatic activity observed here for Bamet-M2 against several tumor cell-lines.

Chloride and ethyl ester morpholine thiourea derivatives and their Ni(II) complexes. Crystal and molecular structures of the thiourea derivative L-leucine methyl ester and its complexes with Cu(II) and Pt(II). Growth of the pathogenic fungus Botrytis cinerea.

We have synthesized a series of ligands (1, 3, 4, 6 and 7) and some of their complexes with Ni(II), Cu(II) and Pt(II) (2, 5, 8 and 9). These compounds were studied and characterized by elemental analysis, IR and UV-Vis spectra, conductivity measurements in solution, FAB+/MS, 1H and 13C NMR, ESR, etc. Compound 7 crystallized in the orthorhombic space group P2(1)2(1)2(1), with Z = 4. Unit cell parameters were as follows: a = 21.307(2) A, alpha = 90 degrees, b = 12.498(1) A, beta = 90 degrees, c = 7.7232(4) A, gamma = 90 degrees. For seven of these compounds, the antifungal activity of a major pathogen responsible for important crop damage was studied. In general, inhibition by the ligands was higher than that of the complexes. When the thiourea was linked to some diethyl groups, the compounds showed higher antifungal activity than the morpholine groups. Compound 3 achieved total inhibition (100%).

DNA interaction and cytostatic activity of the new liver organotropic complex of cisplatin with glycocholic acid: Bamet-R2.

The aim of this study was to investigate the ability of the new liver organotropic complex of cisplatin with glycocholate (GC), Bamet-R2, to interact with DNA, inhibit its replication and hence reduce tumor-cell proliferation. Changes in the electrophoretic mobility of the open and covalently closed circular forms of the pUC18 plasmid DNA from Escherichia coli, a shift in the denaturation temperature of double-stranded DNA, and ethidium-bromide displacement from DNA binding, were induced by Bamet-R2 and cisplatin, but not by GC. Neutral-red retention was used to measure the number of living cells in culture after long-term (72-hr) exposure to these compounds and to evaluate the effect on cell viability after short-term (6-hr) exposure. Bamet-R2 and cisplatin, but not GC, induced significant inhibition of cell growth. This effect ranged from mild to strong, depending upon the sensitivity of the different cell types as follows: cisplatin, rat hepatocytes in primary culture < rat hepatoma McA-RH7777 cells (rH) < human colon carcinoma LS 174T cells (hCC) < mouse hepatoma Hepa 1-6 cells (mH); Bamet-R2, rat hepatocytes < mH approximately equal to hCC < rH. DNA synthesis was measured by radiolabeled-thymidine incorporation into DNA. Bamet-R2 and cisplatin, but not GC, significantly inhibited the rate of DNA synthesis by these cells. After short-term exposure to Bamet-R2 or GC, no acute cell toxicity was observed, except on hCC cells. By contrast, acute toxicity was induced by cisplatin for all cell types studied. The in vivo anti-tumoral effect was investigated in 3 different strains of mice following s.c. implantation of tumor cells (mouse sarcoma S-18011 cells in Swiss and B6 mice and hCC cells in nude mice). In all 3 models, tumor growth was inhibited by Bamet-R2 and cisplatin to a similar degree. However, signs of toxicity (increases in blood urea concentrations and decreases in packed blood cell volume and in liver, kidney and body weight) and a reduction in survival rate were observed only during cisplatin administration. In sum, these results indicate that this bile-acid derivative can be considered as a cytostatic drug whose potential usefulness deserves further investigation.

In vitro cytostatic activity and DNA-interaction of the new liver organotropic complex chloro-bis-cholylglycinate-platinum (II).

BACKGROUND: The liver organotropic properties of the new bioinorganic complex of platinum (II) and glycocholic acid, Bamet-H2 have been reported previously. The aim of this work was to investigate the in vitro cytostatic activity of this compound. MATERIALS AND METHODS: The inhibition of cell growth and DNA synthesis by mouse leukemia L-1210 (mL), mouse hepatoma Hepa 1-6 (mH), rat hepatoma McA-RH7777 (rH) and human colon adenocarcinoma LS-174T (hCC) cells were measured. The effects on the electrophoretic mobility of the pUC18 plasmid, the DNA denaturation temperature and ethidium bromide (EthBr) binding to DNA were studied. RESULTS: A significant antiproliferative effect for Bamet-H2 was found (mH approximately hCC > mL approximately rH). DNA synthesis was also markedly inhibited (mH approximately hCC approximately mL approximately rH). Bamet-H2-induced a change in the electrophoretic mobility of pUC18 and the increase in DNA denaturation temperature suggested the existence of DNA-Bamet-H2 interactions. Scatchard plots obtained from EthBr displacement assays revealed that Bamet-H2 induces a reduction in both the number of DNA sites available and their ability to bind EthBr. CONCLUSION: Bamet H2 is able to interact with DNA, inhibit DNA synthesis, and hence reduce cell proliferation.

Synthesis and characterization of the new cytostatic complex cis-diammineplatinum(II)-chlorocholylglycinate.

Owing to the high efficiency of hepatocytes to take up bile acids, these endogenous compounds or their analogues can be considered as potential shuttles for delivering drugs to the liver. With the aim of using this strategy to target platinum(II)-related cytostatic drugs toward the hepatobiliary system, a cholylglycinate (CG) derivative of cis-diammineplatinum(II) has been synthesized by treatment of cis-diammineplatinum(II) dichloride with sodium cholylglycinate. The complex, named Bamet-R2, was characterized by spectroscopy and elemental analysis. Results obtained in these studies together with conductivity measurements, which pointed to nonelectrolyte behavior, allowed the structure of the complex to be identified as C26H48N3O6ClPt. The compound was found to be soluble (up to 3 mM) in water and was highly soluble (more than 10 mM) in ethanol, methanol, and dimethyl sulfoxide. Its stability in solution was monitored by HPLC analysis. In deionized water, the compound remains > 90% pure in solution for up to 7 days and > 80% for up to 28 days. However, in 150 mM NaCl it remains as > 90% pure compound in solution for only 1 day. By contrast with the parent compound CG, Bamet-R2 was found to significantly inhibit the growth of rat hepatocytes in primary culture and L1210 murine leukemia cells, although in a less marked way than that observed for cisplatin. The cytostatic effect of Bamet-R2 was particularly strong against human colon adenocarcinoma LS174T cells. The results point to the potential usefulness of Bamet-R2 in the antitumoral therapy of enterohepatic-derived neoplasias.

Synthesis and characterization of a new bile acid and platinum(II) complex with cytostatic activity.

With a view to using bile acids as shuttles for delivering platinum-related cytostatic drugs to the liver, a cholylglycine(CG)-derivative of platinum(II) has been synthesized. The complex, named Bamet-H2, was characterized by elemental analysis, FT-IR, NMR, FAB-MS, and UV spectroscopy. The results indicate the following composition: C52H84N2O12ClNa Pt(II). Conductivity data suggest that the complex behaves as a sodium salt (1:1) of a complex of Pt(II) bound to one cl-, one bidentate CG moiety, and another monodentate CG moiety, i.e., Na[Pt(CG-O,N)(CG-O)Cl]. The compound is highly soluble (up to 10 mM) in water, ethanol, methanol, DMF, and DMSO. Bamet-H2 was stable in solution (either water or 150 mM NaCl solution), as measured by HPLC, up to 24 h. At this time, more than 90% of the platinum present in water or saline solutions was found to be Bamet-H2. Cytostatic activity against L1210 murine leukemia cells was found. This characteristic was stronger against rat hepatocytes in primary culture. Isolated in situ rat livers were perfused for 40 min with a recirculating medium containing 1 microM Bamet-H2, CG, or cisplatin. Uptake and excretion into bile were much greater for Bamet-H2 than for cisplatin, but less than for CG. Liver content was higher for Bamet-H2 than for cisplatin or CG. The results point to the potential usefulness of Bamet-H2 in the antitumoral therapy of neoplasias derived from liver parenchymal cells.