Anthocyanins Activate Membrane Estrogen Receptors With Nanomolar Potencies to Elicit a Nongenomic Vascular Response Via NO Production.

Background The vascular pharmacodynamics of anthocyanins is only partially understood. To examine whether the anthocyanin-induced vasorelaxation is related to membrane estrogen receptor activity, the role of ERα or GPER antagonism was ascertained on anthocyanins or 17-ß estradiol-(E2) induced vasodilatations and NO production. Methods and Results The rat arterial mesenteric bed was perfused with either anthocyanins or corresponding 3-O-glycosides, or E2, to examine rapid concentration-dependent vasorelaxations. The luminally accessible fraction of NO in mesenteric perfusates before and after anthocyanins or E2 administration was quantified. Likewise, NO-DAF signal detected NO production in primary endothelial cells cultures incubated with anthocyanins or E2 in the absence and presence of ERα (ICI 182,780) or GPER (G-36) selective antagonists. Anthocyanins or corresponding glycosides elicited, within minutes, vasodilation with nanomolar potencies; half maximal anthocyanin response reached 50% to 60% efficacy, in contrast to acetylcholine. The vasorelaxation is of rapid onset and exclusively endothelium-dependent; NOS inhibition annulled the vasorelaxation. The delphinidin vascular response was not modified by 100 nmol/L atropine but significantly attenuated by joint application of ICI plus G-36 (52±4.6 versus 8.5±1.5%), revealing the role of membrane estrogen receptors. Moreover, the anthocyanin or E2-induced NO production was antagonized up to 70% by these antagonists. NO-DAF signal elicited by anthocyanins was annulled by NOS inhibition or by ICI plus G-36 addition. Conclusions The biomedical effect of anthocyanins or 3-O-glycosylates derivatives contained in naturally purple-colored foods or berries is due to increased NO production, and not to the phytochemical's antioxidant potential, highlighting the nutraceutical role of natural products in cardiovascular diseases.

Valoración con termografía infrarrojo, de la capacidad vasodilatadora de las diferentes corrientes analgésicas y factores implicados / Assessment of the vasodilatory capacity of different analgesic currents using infrared thermography

Objetivos. Primero, hacer una valoración cuantitativa, mediante termografía infrarrojo (TIR) del proceso de vasodilatación provocado por las corrientes analgésicas; segundo, valorar las diferencias entre ellas, y tercero, comprobar si la vasodilatación es debida al efecto Joule o existen otros mecanismos. Material y método. Incluidos 12 individuos (6 mujeres y 6 varones); edades comprendidas entre los 23 y 47 años (media 34 años y 4 meses) y estudio de TIR, previo al tratamiento, normal. En todos se hizo una valoración con TIR de su columna vertebral, al inicio, después del tratamiento y a los 30 y 60 minutos de finalizado. Corrientes valoradas: bifásica compensada, interferencial, ultraexcitante y diadinámica. Resultados. Tras finalizar el tratamiento aparecía una zona de hiperemia debajo de los electrodos con gradiente de temperatura de +3,7°C±0,82°C (p<0,001), respecto de la inicial. En las zonas interpolares, hiperemia inapreciable, pero con gradiente térmico de +0,9°C±0,2°C (p<0,05). A los 30 y 60 minutos desaparición de la hiperemia local, extendiéndose por la espalda y con gradiente de temperatura a la hora de +1,3°C±0,03°C (p<0,05). Conclusiones. Las corrientes analgésicas provocan una vasodilatación en las zonas polares (mayor en el cátodo en las corrientes monofásicas), que decrece progresivamente y se extiende por toda la región interpolar. No existen diferencias manifiestas a la hora entre las diferentes corrientes. Pueden existir otros mecanismos vasodilatadores además del efecto Joule (AU)

Objectives. To make a quantitative assessment, using infrared thermography (IRT) of the vasodilation process induced by different analgesic currents, and to assess the differences between them. It will also be determined whether the vasodilation is due to the Joule effect or whether there are other mechanisms. Materials and methods. The study included 12 subjects (6 men and 6 women), with an age range of 23-47 years (mean 34 years and 4 months) and who were assessed by infrared thermography prior to the normal treatment. An assessment with infrared thermography of the spinal column was performed on all of them, at the beginning, after treatment and at 30 and 60minutes after the treatment was finished. The currents assessed were, biphasic, interferential, ultra-excitatory and diadynamic. Results. After finishing the treatment an area of hyperaemia appeared beneath the electrodes using a temperature gradient of 3.7°C±0.82°C (P<0.001) from the baseline. Negligible hyperaemia was observed in the interpolar zones with temperature gradient of 0.9°C±0.2°C (P<0.05). At 30 and 60minutes, the local hyperaemia disappeared, being extended across the back and with a temperature gradient at one hour of 1.3°C±0.03°C (P<0.05). Conclusions. Analgesic currents produce vasodilation in the polar areas (higher in the cathode in single-phase currents) that gradually decreases and extends throughout the interpolar area. There are no significant differences between the currents at one hour. There may be other vasodilatory mechanisms as well as the Joule effect (AU)

Successful multiple pregnancy (triplets) in a kidney transplant recipient: a case report.

Renal failure generally accompanies an alteration in reproduction function. Even though a renal transplantation does in fact improve this function, there are few cases described in medical literature of multiple pregnancies in transplant patients that ended in a successful manner. In addition, there is a greater incidence of complications such as hypertension, preeclampsia, and premature delivery. This article describes a 31-year-old patient who became pregnant with triplets at 3 years and 6 months after receiving a renal transplant from a cadaver. The patient received treatment with cyclosporine, azathioprine, and prednisolone. During the pregnancy, there was a increase in hypertension, proteinuria, cholestasia gravidic symptoms, and premature delivery. Pregnancy control included evaluation of the fetoplacental unit together with hypertensive management and adjustment of immunosuppressant treatment, especially the cyclosporine dose, seeking to facilitate greater fetal maturity. Three newborns of 840, 860, and 1020 were delivered by cesarean section. The newborns spent 6 to 8 weeks in the neonatal unit and were released without complications. The newborns have presented adequate psychomotor and physical development to date. The triplets are now 4 years old. The transplant recipient has a creatinine clearance of 81 mL/min at 7 years after transplantation.

Histidine 140 plays a key role in the inhibitory modulation of the P2X4 nucleotide receptor by copper but not zinc.

To elucidate the role of extracellular histidines in the modulation of the rat P2X4 receptor by trace metals, we generated single, double, and triple histidine mutants for residues 140, 241, and 286, replacing them with alanines. cDNAs for the wild-type and receptor mutants were expressed in Xenopus laevis oocytes and in human embryonic kidney 293 cells and examined by the two electrode and patch clamp techniques, respectively. Whereas copper inhibited concentration-dependently the ATP-gated currents in the wild-type and in the single or double H241A and H286A receptor mutants, all receptors containing H140A were insensitive to copper in both cell systems. The characteristic bell-shaped concentration-response curve of zinc observed in the wild-type receptor became sigmoid in both oocytes and human embryonic kidney cells expressing the H140A mutant; in these mutants, the zinc potentiation was 2.5-4-fold larger than in the wild-type. Results with the H140T and H140R mutants further support the importance of a histidine residue at this position. We conclude that His-140 is critical for the action of copper, indicating that this histidine residue, but not His-241 or His-286, forms part of the inhibitory allosteric metal-binding site of the P2X4 receptor, which is distinct from the putative zinc facilitator binding site.

[Opioid receptors in the era of molecular biology: they account for more than 6,000 years of empirical pharmacology]. / Receptores opioides a la luz de la biología molecular: explican mas de 6.000 años de farmacología empírica.

The medicinal use of opium and of morphine in different cultures and ancient civilizations is described. Research within the past 40 years have demonstrated the existence of brain opiate receptors. Morphine and related opioid analgetic interact at these sites in the nervous system to produce the characteristic pharmacological effects of these drugs. The opiate receptors have structural homologies with a variety of other cell membrane receptors; they activate second messenger-based chemical transduction systems in the cell membrane and are endowed with several regulation mechanisms. These opiate receptors are presumably activated under specific physiological conditions by endogenous ligands (opiopeptins). It is currently thought that morphine mimicks the opiopeptins by interacting with these receptors either at different molecular subsites or with a different mode of action.

Receptores opioides a la luz de la biología molecular: explican mas de 6.000 años de farmacología empírica / Opioid receptors in the era of molecular biology: explain more than 6.000 years of empiric pharmacology

The medicinal use of opium and of morphine in different cultures and ancient civilizations is described. Research within the past 40 years have demonstrated the existence of brain opiate receptors. Morphine and related opioid analgetic interact at these sites in the nervous system to produce the characteristic pharmacological effects of these drugs. The opiate receptors have structural homologies with a variety of other cell membrane recpetors; they activate second messenger-based chemical transduction systems in the cell embrane and are endowed with several regulation mechanisms. These opiate receptors are presumably activated under specific physiological conditions by endogenous ligands (opiopeptins). It is currently thought thar morphine mimicks the opiopeptins by interacting with these receptors either at different molecular subsites or with a different mode of action

[The usefulness of biofeedback in children with encopresis. A preliminary report]. / Utilidad del biofeedback en niños con encopresis. Comunicación preliminar.

Children with encopresis (costiveness) have a social problem, and (BFB) offers them a valid therapeutic alternative. The present prospective study compares the advantages of this technique with conventional treatment in 21 patients, with average ages of 10.13 and 8.54 years in each group. The patients were studied by clinical, manometric and electromyographic parameters. Those treated with BFB showed clinical improvement, with manometric significant enhancement (p < 0.001) of the percentage of internal anal sphincter (IAE) relaxation, relaxation interval of the IAE and rectal sensation threshold (RST), on the other hand, patients treated by conventional therapy only improved the RST (p < 0.01). Biofeedback seems useful in the treatment of the child with encopresis.

cis-element combinations determine phenylalanine ammonia-lyase gene tissue-specific expression patterns.

The bean phenylalanine ammonia-lyase gene 2 (PAL2) is expressed in the early stages of vascular development at the inception of xylem differentiation, associated with the synthesis of lignin precursors. This is part of a complex program of developmental expression regulating the synthesis of functionally diverse phenylpropanoid natural products. Analysis of the expression of PAL2 promoter-beta-glucuronidase gene fusions in transgenic tobacco plants showed that functionally redundant cis elements located between nucleotides -289 and -74 relative to the transcription start site were essential for xylem expression, but were not involved in expression in leaf primordia and stem nodes or in establishing tissue specificity in petals. The -135 to -119 region implicated in xylem expression contains a negative element that suppresses the activity of a cryptic cis element for phloem expression located between -480 and -289. The functional properties of each vascular element are conserved in stem, petiole, and root, even though the xylem and phloem are organized in different patterns in these organs. We conclude that the PAL2 promoter has a modular organization and that tissue-specific expression in the vascular system involves a negative combinatorial interaction, modulation of which may provide a flexible mechanism for modification of tissue specificity.

Behavioral treatment of a case of psychogenic urinary retention.

The case involved a thirteen-year-old girl with a history of different urological disorders who since the age of four showed several rituals associated with micturition as well as progressively intense urinary retention. Micturition occupied 2 to 12 hours a day. Treatment consists of systematic desensitization through imagery and in vivo together with progressive response prevention of ritualized behaviours. Cognitive therapy and parent counselling is also used. Normality is attained after 7 weeks treatment and maintained at 18 months follow-up. Psychiatric diagnosis is simple phobia to micturition.

New beta-lactamase-resistant cephem treatment of guinea pigs infected with Legionella pneumophila.

The in vivo antimicrobial effect of seven new beta-lactamase-resistant cephems (cefotaxime, latamoxef, ceftazidime, ceftriaxone, cefotiam, cefbuperazone, and MT-141) on Legionella pneumophila (strain 81-066, serogroup IV) in guinea pigs was compared with that of erythromycin. As the minimal LD100 within one week was about 4.0 X 10(9) CFU/ml by intraperitoneal injection of the strain, the animals were inoculated with 2.0 ml of twofold dilutions of a suspension of this bacterium. The animals developed purulent peritonitis and systemic involvement demonstrated by the development of periangitis, pneumonia and pleuritis in the lungs. Three different doses of antibiotics were administered intraperitoneally immediately after the rectal temperature reached more than 40 C. Erythromycin had a significant therapeutic effect but none of the new cephems tested death of the infected guinea pigs.

Hydrolysis of substance P and bradykinin by black widow spider venom gland extract.

Black widow spider venom gland extract was found to contain significant peptidase activity. Aliquots of the venom gland extract incubated at 37 degrees inactivated substance P (SP) and bradykinin but not angiotensin II or the enkephalins. The peptide inactivation was proportional to the duration of the incubation and the amount of extract used. Analysis of the peptides on high pressure liquid chromatography demonstrated that the loss in biological activity of SP and bradykinin in the longitudinal muscle of the guinea pig ileum was correlated with cleavage of the peptides into several fragments. Kinetic studies revealed that SP was initially split into two fragments but that these products underwent further degradation into smaller peptides. The optimal pH for the peptidase activity was 6.5. At 0 degree the enzymatic activity was undetectable, and it was irreversibly destroyed by incubation at 100 degrees for 5 min or by pretreatment of the extract with 100 microM diisopropyl fluorophosphate. In addition, the gland extract preparation hydrolyzed artificial substrates designed to detect trypsin or chymotrypsin-like activity.