Interaction of Pb2+, PbMe22+ and PbPh22+ with 3-(phenyl)-2-sulfanylpropenoic acid: a coordinative and toxicological approach.

We investigated the reaction of Pb(2+), PbMe(2)(2+) and PbPh(2)(2+) with 3-(phenyl)-2-sulfanylpropenoic acid (H(2)pspa) to give the complexes [Pb(pspa)], [PbMe(2)(pspa)], [PbPh(2)(pspa)], [HQ](2)[Pb(pspa)(2)] and [HQ[(2)[PbPh(2)(pspa)(2)] (HQ=diisopropylammonium), which were characterized by IR and NMR ((1)H, (13)C and (207)Pb) spectroscopy and by fast atom bombardment (FAB) spectrometry. The structures of [PbMe(2)(pspa)], [PbPh(2)(pspa)], [PbPh(2)(pspa)(dmso)].dmso and [HQ[(2)[PbPh(2)(pspa)(2)] are interesting examples of unexplored Pb coordination kernels and supramolecular association. Pig renal proximal tubule LLC-PK1 culture cells were used to determine in vitro the effect of the pretreatment with H(2)pspa (alone or combined with vitamin B(6)) and [HQ](2)[Zn(pspa)(2)] on the cytotoxicity of PbMe(2)(2+) and PbPh(2)(2+) by comparing the results with those of meso-2,3-dimercaptosuccinic acid (dmsa). The results show that the cell viability was scarcely affected by these agents. The ability of these reagents to decorporate lead was investigated in vivo by analysing the lead levels in the liver, kidney, brain and blood. In the case of the dimethyl derivative, and under certain protocols, undesirable effects such as an increase in brain and liver lead levels were detected. These increases were not detected when the diphenyl derivative was assayed but in this case a positive effect was not identified either. The blood lead levels also increased in the case of the dimethyl derivative and the activity of delta-ALAD was significantly recovered upon treatment with vitamin B(6) or H(2)pspa; neither the blood lead levels nor the delta-ALAD activity was modified in the case of the diphenyl derivative.

Úlceras por presión iatrogénicas de localización nasal / Iatrogenic pressure ulcers of nasal location

Introducción: Uno de los riesgos del uso de sondas endonasales (SE) es la apariciónde úlceras por presión (UPP). Objetivo: Averiguar la incidencia de pacientescon UPP nasales, estudiar factores de riesgo de aparición y encontrarvariables predictivas. Metodología: Estudio de doce meses, observacional prospectivo,realizado en pacientes ingresados en la unidad de cuidados intensivosportadores de SE. Conclusiones: Los tiempos de estancia y de permanenciacon la SE, además de la anemia, se asocian estadísticamente con la apariciónde UPP. Tras el estudio multivariante, el tiempo que el paciente permanececon SE es la variable que influye en que aparezcan las UPP nasales (AU)

Introduction: One of the risks of using endonasal tubes (ET) is the developmentof pressure ulcers (PU). Aim: to find out the incidence of patients with nasal PU,study the risks factors for its development and find the predictable variables.Methods: a twelve-month observational and prospective study was carried out incritically ill patients carrying a ET admitted to our intensive care unit. Conclusion:time of stay and time spent carrying the ET, along with the anaemia, is statisticallyassociated with the development of nasal PU. The multivariate studyshowed that the time spent carrying the ET is the most influential variable in thedevelopmente of nasal PU (AU)

Interactions of diorganolead(IV) with 3-(2-thienyl)-2-sulfanylpropenoic acid and/or thiamine: chemical and in vitro and in vivo toxicological results.

The reactions of PbR(2)(OAc)(2) (R = Me, Ph) with 3-(2-thienyl)-2-sulfanylpropenoic acid (H(2)tspa) in methanol or ethanol afforded complexes [PbR(2)(tspa)] that electrospray ionization-mass spectrometry (ESI-MS) and IR data suggest are polymeric. X-ray studies showed that [PbPh(2)(tspa)(dmso)] x dmso, crystallized from a solution of [PbPh(2)(tspa)] in dmso, is dimeric, and that [HQ](2)[PbPh(2)(tspa)(2)] (Q = diisopropylamine), obtained after removal of [PbPh(2)(tspa)] from a reaction including Q, contains the monomeric anion [PbPh(2)(tspa)(2)](2-). In the solid state the lead atoms are O,S-chelated by the tspa(2-) ligands in all these products, and in the latter two have distorted octahedral coordination environments. NMR data suggest that tspa(2-) remains coordinated to PbR(2)(2+) in solution in dmso. Neither thiamine nor thiamine diphosphate reacted with PbMe(2)(NO(3))(2) in D(2)O. Prior addition of H(2)tspa protected LLC-PK1 renal proximal tubule cells against PbMe(2)(NO(3))(2); thiamine had no statistically significant effect by itself, but greatly potentiated the action of H(2)tspa. Administration of either H(2)tspa or thiamine to male albino Sprague-Dawley rats dosed 30 min previously with PbMe(2)(NO(3))(2) was associated with reduced inhibition of delta-ALAD by the organolead compound, and with lower lead levels in kidney and brain, but joint administration of both H(2)tspa and thiamine only lowered lead concentration in the kidney.

La iatrogenia como origen de las úlceras por presión en la Unidad de Cuidados Críticos / Iatrogenis as origin of pressure ulcers in a critical care unit

Introducción: La aparición de úlceras por presión (UPP) es un indicador negativo de la atención sanitaria, debido a que tal evento es evitable y, por ello, no debería aparecer. Las UPP se relacionan inversamente con la atención al enfermo, producen dolor, malestar y aumenta el consumo de recursos y el riesgo de complicaciones. Objetivo: Averiguar el porcentaje de pacientes con úlceras por presión iatrogénicas (UPPI) y el número de estas lesiones existentes en la Unidad de Cuidados Críticos (UCC), así como generar hipótesis sobre los factores relacionados con su aparición. Material y métodos: Estudio descriptivo, analítico, prospectivo y de prevalencia, repetido en varios cortes. Se registraron las siguientes variables: diagnóstico, edad, sexo, tiempo de estancia, puntuación de las escalas Nova 4, NEMS y S.C. Glasgow, tratamiento con drogas vasoactivas, y tratamiento con sedación. Se registraron todos los pacientes con UPP iatrogénicas y el número de UPPI, así como las causas de producción (materiales, utillaje), localización y estadios. El análisis de los datos se realizó utilizando el paquete estadístico SPSS v10.0. Resultados: La muestra constaba de 131 pacientes, 61% hombres y 39% mujeres, con una edad media de 63,4 años; estancia media 7,5 días. Se realizaron un total de 17 cortes de prevalencia. El rango observado de prevalencia de UPP iatrogénicas fue de 0% a 71,4%, con una media global de 28,24% (37 pacientes con UPP iatrogénicas, de un total de 131 pacientes). Se registraron un total de 53 UPPI, 38 (71,7%) de estadio I y 15 (28,3%) en estadio II. En la nariz y orejas se localizaron el 37,7% (20 UPPI). En los dedos se registraron 7 (13,2%), producidas por el dedal del pulsioxímetro. La mascarilla de oxígeno y gafas nasales produjeron 12 UPPI (22,6%); lo mismo sucedió con el tubo orotraqueal y su sistema de fijación 11 (20,7%) UPPI. El manguito de la medición de la presión arterial produjo 10 lesiones por presión (18,8%) en un total de 9 pacientes. No existe asociación entre la edad, días de estancia y el sexo, con la aparición de UPPI. Existe una asociación estadísticamente significativa entre la aparición de UPPI y los pacientes sometidos a sedación o a tratamiento con drogas vasoactivas: en ambos casos la aparición de UPPI es mayor. La S.C. Glasgow y la escala NEMS están relacionadas con la aparición de UPPI. Conclusión: Actuaciones tan banales como la pulsioximetría o control de presión arterial producen un número de lesiones que deben ser tenidas en cuenta. Consideramos que la prevalencia de UPP de origen iatrogénico encontrada indica una magnitud del problema importante. Así mismo, creemos que sería oportuno la realización de protocolos específicos sobre este tipo de lesiones por presión iatrogénicas

Introduction: The appearance of pressure ulcers (PUs) is a negative indicator of health care, for such an event is avoidable and, therefore, it should not appear. PUs are related inversely with the attention to the ill person, they produce pain, uneasiness and increase the consumption of resources and the risk of complications. Objective: To discover the percentage of patients with iatrogenic pressure ulcers (IPU) and the number of these lesions to be found in the Critical Care Unit (UCC), as well as to generate hypothesis about the factors related with their appearance. Material and methods: Descriptive, analytic, prospective prevalence study, repeated in several cross-sections. They registered the following variables: diagnosis, age, gender, stay period, punctuation in the scales Nova 4, NEMS and S.C. Glasgow, treatment with vasoactive drugs, and treatment with sedation. All the patients registered with iatrogenic PUs and the number of IPUs; as well as the producing causes (materials, tools), localization and phases. The analysis of the data was carried out using the statistical package SPSS v10.0. Results: The sample included 131 patients, 61% men and 39% women, with an average age of 63.4 years; and an average stay period of 7.5 days. A total of 17 prevalence cross-sections were carried out. The observed iatrogenic PUs prevalence range expanded from 0% to 71,4%, with a global mean of 28,24% (37 patients with iatrogenic PUs, of a total of 131 patients). They registered a total of 53 IPUs, 38 (71,7%) in stadium-I and 15 (28,3%) in stadium-II. Thirty-seven dot seven per cent were located in the nose and ears, 7 (13.2%) were registered in the fingers (13,2%), due to the thimble of the pulsioximeter. The oxygen mask and nasal glasses produced 12 IPUs (22,6%), the same thing happened with the orotraqueal tube and its fixation system with 11 (20,7%) IPUs. The muff of the mensuration of the arterial pressure produced 10 pressure ulcers (18,8%) in a total of 9 patients. There exists no association between age, stay period and gender, and the appearance of IPU. An statistically significant association exists between the appearance of IPU and the subjected patients to sedation or treatment with vasoactive drugs, in both cases the appearance of IPUs was higher. The S.C.Glasgow and the NEMS scales are related with the appearance of IPUs. Conclusion: So unimportant activities as pulsioximetry or arterial pressure control produce a number of lesions that should be take into account. We find that the prevalence of iatrogenic-originated PUs indicate a far-reaching problem. We consider that it would be advisable to bring forth specific protocols regarding this type of iatrogenic pressure ulcers (AU)

Enantioselective synthesis and pharmacological evaluation of a new type of verapamil analog with hypotensive and calcium antagonist activities.

PURPOSE: The syntheses and evaluation for cardiovascular activity in the rat of both enantiomers of a verapamil analog in which the cyano group has been replaced by hydroxyl. METHODS: (+)- and (-)-alpha-[3-[[2-(3,4-Dimethoxyphenyl)ethyl]methylamino]propyl]- 3,4-dimethoxy-alpha-(1-methyl ethyl)benzyl alcohol were prepared from chiral sulfoxides produced by microbial biotransformations using Mortierella isabellina ATCC 42613 or Helminthsporium species NRRL 4671, and were examined for hypotensive and calcium antagonist activity using anaesthetized normotensive rats and isolated rat aorta and atria. RESULTS: The analogs showed a pharmacological profile similar to that exhibited by verapamil, possessing a remarkable hypotensive activity, accompanied by a significant bradycardia, in anaesthetized normotensive rats. In vitro, these analogs displayed clear inhibitory effects: in isolated rat aorta they inhibited, in a concentration-dependent fashion, the contractions and 45Ca2+ uptake induced by norepinephrine and high KCl, and in isolated rat atria the analogs considerably decreased the rate of contraction (negative chronotropic effects). No significant differences between the quantitative cardiovascular effects produced by the two enantiomers of the verapamil analogs were observed. CONCLUSIONS: The results suggest that, like that of verapamil, the cardiovascular activity exhibited by the new compounds seems to be due, at least in part, to a blockage of transmembrane calcium channels present in vascular smooth muscle cells.

Preliminary study of the potential vasodilator effects on rat aorta of centaurein and centaureidin, two flavonoids from Centaurea corcubionensis.

In this work, the potential vasorelaxant activity of centaurein and centaureidin, two flavonoids from Centaurea corcubionensis, were studied for the first time in rat aorta. Centaureidin (10 microM-0.1 mM) totally relaxed, in a concentration-dependent manner and with almost equal effectiveness, the contractions induced by NA (IC50 = 16.7 +/- 1.9 microM) or by a high K+ concentration (IC50 = 16.1 +/- 3.1 microM) in intact rat aortic rings. Mechanical removal of endothelium did not significantly modify the vasoralexant effects of this flavone (IC50 = 20.8 +/- 2.4 microM for NA; IC50 = 21 +/- 2.9 microM for K+). On the other hand, centaurein (1 microM-0.1 mM) had no effect on NA- and high K(+)-induced contractions in rubbed and intact rat aortic rings. These results indicate that substitution by glucose in the chemical structure of centaureidin leads to the loss of its vasodilator activity.

High serum IgA concentrations in patients with diabetes mellitus: agewise distribution and relation to chronic complications.

In this study we investigated the agewise distributions of serum IgA concentrations in 1251 type 1 and 2224 type 2 diabetic patients, and the association between serum IgA concentration and diabetic complications (retinopathy, neuropathy, nephropathy, macroangiopathy, and hypertension). The IgA concentrations of all groups of diabetic patients were significantly higher than those of the corresponding subgroups of 943 control subjects, except for type 1 patients >60 years of age. High IgA concentrations were found in 23.1% of the whole diabetic group. The prevalence of high IgA was significantly greater in males than in females among type 1 patients (24.4% vs 18%). In conclusion, an increase in circulating IgA concentrations is a generalized phenomenon among diabetic patients; IgA concentrations above the reference range are more common among male than female diabetics; and diabetic complications are associated with a significant increase in serum IgA concentration.

Abnormal serum immunoglobulin concentrations in patients with diabetes mellitus.

Since the recently reported relationship between serum fructosamine and IgA concentrations appears to throw doubt on the clinical utility of fructosamine as a measure of hyperglycemic status if IgA concentration is not taken into account, we studied serum immunoglobulin concentrations in 169 diabetics and their relationship with various clinical and analytical parameters. Over 41% of the patients studied had abnormal serum IgA concentrations. Serum IgA concentration was negatively correlated with serum albumin, and among IDDM patients was positively correlated with age (so that the prevalence of abnormal IgA was 57.7% among IDDM patients aged over 30 years). Among NIDDM patients, abnormal IgA concentrations were especially prevalent among those being treated with oral hypoglycemics. Abnormal IgA was also more frequently found in both IDDM and NIDDM patients, who had been under treatment for 10 years or more. Abnormal IgG concentrations were found in 11.8% of the diabetics, and the mean IgM concentration found in the patients was 41.6% lower than in the normoglycemic group. We conclude that abnormal serum IgA concentrations are very common in diabetic patients and that further research should be carried out to verify whether the determination of serum immunoglobulins, IgA in particular, is of clinical use for monitoring diabetes or evaluating its secondary effects.

Alteration of renal carnitine metabolism by anticonvulsant treatment.

We administered therapeutic doses of valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT), and phenobarbital (PHB) to mice for 7 days, and 8 hours after the final dose we measured the concentrations of carnitine in serum, liver, kidney, skeletal muscle, and heart, and in the 7 days' accumulated urine. The results for serum and urine show that VPA induced a significant increase in renal clearance of acylcarnitine without affecting that of free carnitine, whereas CBZ, PHT, and PHB significant increased clearance of free carnitine but not that of acylcarnitine. Thus, VPA appears to reduce tubular resorption of acylcarnitine, and CBZ, PHT, and PHB appear to reduce tubular resorption of free carnitine.

Short-term effects of administration of anticonvulsant drugs on free carnitine and acylcarnitine in mouse serum and tissues.

1. The short-term evolution of concentrations of free carnitine and acylcarnitine was studied in the serum, liver, kidney, heart and skeletal muscle of mice after administration of single therapeutic doses of the anticonvulsant drugs, valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT) and phenobarbitone (PHB). 2. The effects of the drugs were immediate but transitory, control levels of free carnitine and acylcarnitine having been recovered or almost recovered in serum and in all tissues 8 h post administration (p.a.). 3. VPA was the only drug that significantly reduced free carnitine concentration in serum, which recovered control levels by 4 h p.a. 4. All the drugs studied brought about marked deficits of serum acylcarnitine, which had disappeared 2 h p.a. in the case of VPA and not until 8 h p.a. for CBZ, PHT or PHB. 5. The minimum concentrations of free carnitine and acylcarnitine in serum were invariably associated with the maximum concentration of drug in serum. 6. Free carnitine concentration was not affected by VPA in any tissue, PHT and PHB brought about significant deficits in heart and kidney, and CBZ a significant deficit in muscle. 7. Acylcarnitine concentration was significantly reduced in heart, kidney and muscle by CBZ, PHT and PHB, but in liver the effects of all drugs were very small. 8. These results are compatible with the hypothesis that the primary cause of anticonvulsant-induced alteration of carnitine metabolism is interference with renal reabsorption of carnitine.

Hyperaminoacidemia in epileptic children treated with valproic acid.

Serum amino acids were determined in 22 epileptic children treated with valproic acid. This treatment caused hypocarnitinemia in all, and hyperammonemia in 16. Regardless of the blood ammonia levels, values for glutamic acid, arginine, glycine, serine and alanine were higher than those of normal controls, while aspartic acid and ornithine were lower. These findings suggest that valproate causes intramitochondrial dysfunction of the urea cycle.

Effects of acute valproate administration on carnitine metabolism in mouse serum and tissues.

Carnitine concentrations in serum, liver, kidney, muscle and heart were determined 30 min, 2 hr and 4 hr after administration of single 50 mg/kg doses of valproic acid (VPA) or octanoic acid (OTA) of fasting mice. Half an hour post-administration (p.a.) of VPA, free carnitine concentrations were smaller than in controls in serum, liver, kidney and heart. Four hr p.a., the effects of VPA had disappeared from all the carnitine sources, which now had concentrations that were not significantly different from those of controls. The effects of OTA are different from, and sometimes the opposite of, those of VPA, showing that the effects of VPA are specific to it. Hyperammonemia, on the other hand, was greatest 4 hr p.a. of VPA. These findings show that the effect of VPA on carnitine metabolism is immediate but transient, and accordingly suggest that the carnitine deficiency observed in patients under prolonged treatment with VPA-containing anticonvulsants must be due to a more complex mechanism than direct interaction between carnitine and VPA.

Effects of various serum proteins on quantification of fructosamine.

We determined fructosamine concentrations with the CentrifiChem 600 centrifugal analyzer and the Hitachi 737 discrete analyzer. Reference intervals agreed with the most recently published results, and values in fasting patients were significantly correlated with glycated hemoglobin, plasma glucose, albumin, beta- and gamma-globulins, IgG, IgA, IgM, and total protein. Partial correlation analysis showed that only fructosamine and IgA were dependently related. In a group of nondiabetic patients with pathological values for IgA concentrations, 79.4% had pathological values for fructosamine. These results throw doubt on the clinical value of fructosamine determinations if serum IgA is not taken into account.