Effects of Synthetic Tetronamides and Methylated Denigrins on Bacterial Quorum Sensing and Biofilm Formation.

Detrimental biofilms of bacterial pathogens cause chronic infections with a high-level tolerance to antibiotics. To identify new control agents, we synthesized and tested a total of 14 tetronamides (including 5 new compounds) and 6 denigrin intermediates on the model species Escherichia coli. At a concentration of 50 µg/mL, two tetronamides and two methylated denigrins exhibited significant inhibitory effects against biofilm formation of E. coli RP437, e.g., by 60 and 94%, respectively. Structural analysis of the tested compounds revealed that p-methoxybenzylidene and p-methoxyphenethyl moieties of denigrins are important for biofilm inhibition, while the former group is also essential to the activity against quorum sensing (QS) via AI-2. Specifically, tetramethyldenigrin B has strong inhibitory effects against both E. coli biofilm formation and AI-2-mediated QS and thus provides a promising lead structure for designing better control agents. Consistently, tetramethyldenigrin B also showed inhibitory activity against biofilm formation of uropathogenic E. coli. Together, these findings provide new insights for the rational design of novel biofilm and QS inhibitors.

Designing a Zn-Ag Catalyst Matrix and Electrolyzer System for CO2 Conversion to CO and Beyond.

CO2 emissions can be transformed into high-added-value commodities through CO2 electrocatalysis; however, efficient low-cost electrocatalysts are needed for global scale-up. Inspired by other emerging technologies, the authors report the development of a gas diffusion electrode containing highly dispersed Ag sites in a low-cost Zn matrix. This catalyst shows unprecedented Ag mass activity for CO production: -614 mA cm-2 at 0.17 mg of Ag. Subsequent electrolyte engineering demonstrates that halide anions can further improve stability and activity of the Zn-Ag catalyst, outperforming pure Ag and Au. Membrane electrode assemblies are constructed and coupled to a microbial process that converts the CO to acetate and ethanol. Combined, these concepts present pathways to design catalysts and systems for CO2 conversion toward sought-after products.

Oxidation State and Surface Reconstruction of Cu under CO2 Reduction Conditions from In Situ X-ray Characterization.

The electrochemical CO2 reduction reaction (CO2RR) using Cu-based catalysts holds great potential for producing valuable multi-carbon products from renewable energy. However, the chemical and structural state of Cu catalyst surfaces during the CO2RR remains a matter of debate. Here, we show the structural evolution of the near-surface region of polycrystalline Cu electrodes under in situ conditions through a combination of grazing incidence X-ray absorption spectroscopy (GIXAS) and X-ray diffraction (GIXRD). The in situ GIXAS reveals that the surface oxide layer is fully reduced to metallic Cu before the onset potential for CO2RR, and the catalyst maintains the metallic state across the potentials relevant to the CO2RR. We also find a preferential surface reconstruction of the polycrystalline Cu surface toward (100) facets in the presence of CO2. Quantitative analysis of the reconstruction profiles reveals that the degree of reconstruction increases with increasingly negative applied potentials, and it persists when the applied potential returns to more positive values. These findings show that the surface of Cu electrocatalysts is dynamic during the CO2RR, and emphasize the importance of in situ characterization to understand the surface structure and its role in electrocatalysis.

Soluciones tecnológicas de las farmacias comunitarias al desabastecimiento de medicamentos: aplicación del modelo colaborativo en red y 'big data' / Technological solutions of community pharmacies to medicines shortage: Application of the collaborative network model and big data

INTRODUCCIÓN: la falta de suministro de medicamentos provoca resultados económicos, clínicos y humanísticos negativos en los pacientes, generando también carga de trabajo adicional a los agentes sanitarios. Para ayudar a los farmacéuticos comunitarios se ha diseñado Luda Farma® (LF), una plataforma electrónica de gestión y colaboración entre farmacias destinada a la mejora de la eficiencia en el control del stock, que proporciona un entorno colaborativo compartiendo información puntual sobre stock de medicamentos concretos entre ellas. OBJETIVOS: analizar el número de medicamentos en desabastecimiento, según la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) y el Centro de Información sobre el Suministro de Medicamentos (CISMED) que se localizan para los pacientes a través de la plataforma LF. Identificar qué medicamentos, que se encuentran en desabastecimiento, se localizan a través de la plataforma. MATERIAL Y MÉTODOS: estudio retrospectivo, observacional, utilizando los datos generados a través de LF durante el año 2019 (del 1 de enero al 31 de diciembre). Se utilizó LF para buscar aquellos medicamentos en desabastecimiento según CISMED y AEMPS. Se cruzaron los datos de la red con los listados de CISMED y AEMPS. El análisis estadístico se realizó con el lenguaje de programación R. RESULTADOS: participaron 389 farmacias comunitarias adheridas libre y gratuitamente a la red LF. Realizaron 7.628 encargos de medicamentos: 1.993 con problemas de suministro en AEMPS y 1.794 en CISMED. El resto de los encargos son medicamentos no declarados en falta, en ninguna base de datos y productos que no son medicamentos. Son encargos que realizan las farmacias, ya sea porque no tienen el producto demandado, no pueden ponerlo a disposición del paciente tan rápido como necesita el paciente, aunque lo encarguen, porque se les ha acabado y recurrieron a LF para buscar el producto concreto en otra farmacia para que el paciente pueda recogerlo cuando lo desee el paciente. Los medicamentos que mayor número de veces se reservaron fueron: Apocard® 100 mg 60 comp, Trankimazin Retard® 0,5 mg 30 comp y Elontril® 150 mg 30 comp. CONCLUSIONES: LF ayuda a los farmacéuticos comunitarios al dar una solución in situ a los pacientes que no encuentran los medicamentos que buscan, disminuyendo el impacto del desabastecimiento de los medicamentos

BACKGROUND: Medicine shortages cause negative economic, clinical and humanistic results for patients, also generating additional workload for healthcare stakeholders.Luda Farma (LF) is a pharmacy electronic management and collaborative platform aimed at improving efficiency in stock control, and to help pharmacists by providing them a collaborative tool that allows sharing specific information on the stock of partic­ular medications among pharmacies. OBJECTIVES: To analyze the number of medicines in short supply (according to the AEMPS and CISMED listings) that patients locate through the LF platform. To identify which medicines in short supply are located through the platform. METHOD: This retrospective, observational study, used the data generated through LF during the year 2019 (from January 1st to December 31st).LF was used to search for those medicines in short supply according to CISMED and AEMPS. Data from the network was searched at the CISMED and the AEMPS listings. Data were processed with programming language R. RESULTS: 389 pharmacies that freely and voluntarily affiliated to the LF network par­ticipated. They carried out 7,628 orders between pharmacies: 1993 of those medicines had supply problems according to the AEMPS, and 1,794 medicines had supply problems according to the CISMED listings. The drugs with the most significant number of reservations were: Apocard® 100mg 60 tablets, Trankimazin Retard® 0.5mg 30 tablets, and Elontril® 150 mg 30 tablets. CONCLUSIONS: LF helps pharmacists by providing an on­site solution to patients who cannot find the drugs they are looking for, lessening the impact of drug shortages

Synthesis of new tetronamides displaying inhibitory activity against bloom-forming cyanobacteria.

BACKGROUND: The increasing frequency and intensity of cyanobacterial blooms pose a serious threat to aquatic ecosystems. These blooms produce potent toxins that can contaminate drinking water and endanger the life of wild and domestic animals as well as humans. Consequently, the development of effective methods for their control is a matter of high priority. We have previously shown that some γ-benzylidenebutenolides, related to the rubrolide family of natural products, are capable of inhibiting the photosynthetic electron transport chain (Hill reaction), a target of commercial herbicides. Here we report the synthesis and biological properties of a new class of rubrolide-inspired molecules featuring a tetronamide motif. RESULTS: A total of 47 N-aryl tetronamides, including 38 aldol adducts, were prepared bearing phenyl, biphenyl, naphthyl, aliphatic and heteroaromatic groups. Some of the aldol adducts were dehydrated to the corresponding γ-benzylidenetetronamides, although satisfactory yields were obtained in only three cases (52-97%). None of the synthesized compounds were capable of blocking the Hill reaction. This notwithstanding, several aldol adducts equipped with a biphenyl substituent displayed excellent inhibitory activity against Synechococcus elongatus and other cyanobacterial strains (IC50  = 1-5 µM). Further, these tetronamides were found to be essentially inactive against eukaryotic microorganisms. CONCLUSION: Several newly synthesized biphenyl-containing tetronamides were shown to display potent and selective inhibitory activity against cyanobacteria. These compounds appear to exert their biological effects without interfering with the Hill reaction. As such, they represent novel leads in the search of environmentally benign agents for controlling cyanobacterial blooms. © 2019 Society of Chemical Industry.

Synthesis of the Marine Myxobacterial Antibiotic Enhygrolide A.

The first synthesis of enhygrolide A, a scarce γ-alkylidenebutenolide antibiotic of the obligate marine myxobacterium Enhygromyxa salina, was achieved in five steps and 54% overall yield from tetronic acid. Key steps include (i) organocatalytic reductive alkylation, (ii) iron-catalyzed sp2-sp3 cross-coupling, and (iii) vinylogous aldol condensation. Aside from its brevity and reliance on environmentally sustainable processes, the synthesis demonstrates the serviceability of butenolide pivalates in cross-coupling reactions.

Síndrome de Herlyn Werner Wünderlich. Reporte de caso / Herlyn Werner Wünderlich syndrome. Case report

El síndrome de Herlyn Werner Wünderlich (SHWW) se caracteriza por la triada útero didelfo, hemivagina obstruida y agenesia renal homolateral; fue descrito en 1976. Es una entidad poco conocida en ginecología; se debe a una alteración de la fusión de los conductos de Müller y la estrecha relación del origen embrionario de los aparatos genital y urinario. Su diagnóstico es tardío ya que los síntomas inician generalmente después de la menarquia y su intensidad puede variar. Su tratamiento se sustenta en el correcto diagnóstico y la correspondiente resolución quirúrgica. La resección del tabique uterino mejora, generalmente, las condiciones de la paciente y el pronóstico, pudiendo lograrse la gestación. (AU)

Herlyn-Werner-Wünderlich is a syndrome characterized by the triad of uterus didelphys, obstructed hemivagina and ipsilateral renal agenesis. It is an uncommon müllerian ducts congenital anomaly, affecting the urogenital tract because of the close embryonic origin of the urogenital system. Its diagnosis is of late onset because symptoms appear after the menarche and the intensity of the symptoms varies among patients. Treatment is based on a proper and timely diagnosis, as well as a surgical correction of the defects. A resection of the uterine septum generally improves the symptoms and creates a favorable future prognosis, making an intrauterine pregnancy possible. We present a case of a 22-year old female patient with delayed diagnosis of Herlyn-Werner-Wünderlich syndrome, with no hemivaginal septum, whose chief complaints were dysmenorrhea and recurring purulent vaginal discharge despite unsuccessful surgical interventions. A mini laparotomy Strassman metroplasty was performed, resolving her symptomatology. (AU)

Total Synthesis of the Antitumor Antibiotic Basidalin.

The first synthesis of the tetronamide antibiotic basidalin was accomplished in five steps and 39% overall yield from readily available 4-bromo-2-triisopropylsilyloxyfuran and 2-formyl-1,3-dithiane. Highlights include: (i) regio- and stereocontrolled assemblage of a pivotal (Z)-γ-ylidene-ß-bromobutenolide intermediate by stereodirected vinylogous aldol condensation (SVAC), (ii) installation of the amino group via aza-Michael addition/elimination, and crucially (iii) facile access to basidalin by late-stage dithiane removal.

Thermodynamically driven, syn-selective vinylogous aldol reaction of tetronamides.

A stereoselective vinylogous aldol reaction of N-monosubstituted tetronamides with aldehydes is described. The procedure is simple and scalable, works well with both aromatic and aliphatic aldehydes, and affords mainly the corresponding syn-aldol adducts. In many cases, the latter are obtained essentially free of their anti-isomers (dr > 99 : 1) in high yields (70-90%). Experimental and computational studies suggest that the observed diastereoselectivity arises through anti-syn isomer interconversion, enabled by an iterative retro-aldol/aldol reaction.

Complete Genome Sequence of Hepatitis B Virus Genotype E, the First Molecular Characterization from an Imported Case in Mexico.

Hepatitis B virus infection is currently a global public health problem. Here, we present the first characterization and complete genome sequence of a strain belonging to genotype E in Mexico, obtained from a foreign carrier with chronic infection.

Pathway Analysis using Gene-expression Profiles of HPV-positive and HPV-negative Oropharyngeal Cancer Patients in a Hispanic Population: Methodological Procedures.

OBJECTIVE: The incidence of oral cavity and pharyngeal cancer in Puerto Rican men is higher than it is in the men of any other ethnic/racial group in the United States of America (US). The information regarding the effect of the human papilloma virus (HPV) in the gene-expression profile among patients with this cancer is limited in Hispanic community. We aim to describe the methodology for future studies to identify the molecular networks for determining overrepresented signaling and metabolic canonical pathways, based on the differential gene-expression profiles of HPV+ and HPV- samples from patients with oropharyngeal squamous cell carcinoma in Puerto Rico. METHODS: We analyzed the RNA expression of 5 tissue samples from subjects diagnosed with oropharyngeal squamous cell carcinoma, 2 HPV+ and 3 HPV-, using Affymetrix GeneChips. The relative difference between the average gene expressions of the HPV+ and HPV- samples was assessed, based on the fold change (log2-scale). RESULTS: Our analysis revealed 10 up regulated molecules (Mup1, LRP1, P14KA, ALYREF, and BHMT) and 5 down regulated ones (PSME4, KEAP1, ELK3, FAM186B, and PRELID1), at a cutoff of 1.5-fold change. Ingenuity Pathway Analysis showed the following biological functions to be affected in the HPV+ samples: cancer, hematological disease, and RNA post-transcriptional modification. QRT-PCR analysis confirmed only the differential regulation of ALYREF, KEAP1, and FAM186B genes. CONCLUSION: The relevant methodological procedures described are sufficient to detect the most significant biological functions and pathways according to the HPV status in patients with oropharyngeal cancer in Puerto Rico.

Robotic-assisted salvage supraglottic laryngectomy.

Traditional open surgery has historically been the standard approach to treating many head and neck conditions. The introduction of the first robot into the surgical world in 1985 has been a keystone in the development of minimally invasive surgical (MIS) techniques. Transoral robotic surgery (TORS) is a minimally invasive technique used for the treatment of head and neck pathologies, including benign and malignant lesions. When performed in select patients, TORS offers low post-operative morbidity, along with very few functional and cosmetic compromises. Herein, we present the first TORS supraglottic partial laryngectomy performed in Puerto Rico or in any region in Latin America. A 68-year-old male who had previously undergone radiation therapy presented with hoarseness and weight loss. A suspension microlaryngoscopy showed a lesion of the left false vocal cord; a biopsy was performed. The patient was diagnosed with a supraglottic squamous cell carcinoma (T2N0M0); the tumor was completely excised using TORS. No post-operative complications occurred.

Pie equino varo congénito en el síndrome de Moebius / Clubfoot in Moebius disease

El síndrome de Moebius es una rara enfermedad en la que hay compromiso de los pares craneales, principalmente del sexto y séptimo. Se puede acompañar de malformaciones congénitas en las extremidades como el pie equino varo congénito (PEVC) que con frecuencia es rígido y de difícil tratamiento con el método descrito por Ponseti. Se ha encontrado asociación entre el síndrome de Moebius y el uso de misoprostol, una medicación abortiva de uso extendido. En este artículo se presentan 5 casos de PEVC asociado al síndrome de Moebius.

Laparoscopic nephrectomy with laparoscopically assisted transvaginal extraction of intact kidney.

PURPOSE: Describe the first laparoscopic transperitoneal nephroureterectomy followed by laparoscopically assisted transvaginal extraction of the intact kidney performed in Puerto Rico. CASE HISTORY/RESULTS: A 39 year-old female patient consulted her urologist regarding chronic urinary tract infection. A diagnosis of a non-functioning left kidney was made, secondary to long standing obstruction due to a distal ureteral stone. Laparoscopic nephroureterectomy procedure was performed and the intact specimen was removed through a transverse posterior colpotomy. Patient was discharged home the next day without intraoperative or post-operative complications. CONCLUSIONS: Laparoscopic nephrec-tomy with transvaginal extraction of the intact specimen provides a surgical option as a minimally invasive technique with very few functional and cosmetic compromises and with low post-operative morbidity when performed in appropriate female patients.

Fructose-induced metabolic syndrome is associated with glomerular hypertension and renal microvascular damage in rats.

Fructose intake has been recently linked to the epidemic of metabolic syndrome and, in turn, the metabolic syndrome has been epidemiologically linked with renal progression. The renal hemodynamic effects of fructose intake are unknown, as well as the effects of different routes of administration. Metabolic syndrome was induced in rats over 8 wk by either a high-fructose diet (60%, F60, n = 7) or by adding fructose to drinking water (10%, F10, n = 7). Body weight and food and fluid intake of each rat were measured weekly during the follow-up. At baseline and at the end of wk 8, systolic blood pressure, plasma uric acid, and triglycerides were measured. At the end of week 8 glomerular hemodynamics was evaluated by micropuncture techniques. Wall thickening in outer cortical and juxtamedullary afferent arterioles was assessed by immunohistochemistry and computer image analysis. Fructose administration either in diet or drinking water induced hypertension, hyperuricemia, and hypertriglyceridemia; however, there was a progressive increment in these parameters with higher fructose intake (C

Effects of acute and chronic L-arginine treatment in experimental hyperuricemia.

Experimental hyperuricemia (HU) results in preglomerular arteriolopathy, cortical vasoconstriction, and glomerular hypertension. Recently, uric acid has been shown to induce endothelial dysfunction. We therefore studied the effect of acute and chronic administration of l-arginine (a substrate for endothelial nitric oxide synthase) on the renal hemodynamic and vascular structural alterations induced by HU. To induce HU, oxonic acid (OA; 750 mg.kg(-1).day(-1)) was administered in male Sprague-Dawley rats. To study the acute effect of arginine, nine rats received l-arginine (l-Arg; 15 mg.kg(-1).min(-1)) during micropuncture. To elucidate the chronic effect of l-Arg, OA + 1% l-Arg (n = 8) and OA + 2.5% l-Arg (n = 6; drinking water) were evaluated throughout the 5-wk period. Eight normal control (N), and eight OA, rats were also studied. Kidneys were fixed by perfusion and afferent arteriole morphology was evaluated. HU rats developed the renal functional and structural alterations described and had suppressed urinary excretion of NO(2)(-)/NO(3)(-). Acute stimulation of nitric oxide (NO) synthesis markedly increased urinary NO(2)(-)/NO(3)(-), lowered systemic blood pressure, and relieved cortical vasoconstriction despite a significant increment of glomerular hypertension and afferent arteriole damage. Increasing doses of chronic l-Arg were associated with increasing excretion of urinary NO(2)(-)/NO(3)(-), reduction of systemic hypertension, and prevention of cortical vasoconstriction (2.5% l-Arg). In addition, both doses prevented glomerular hypertension and preglomerular arteriolopathy. Thus an acute relief of renal vasoconstriction in the setting of afferent arteriole damage cannot reverse glomerular hypertension, likely due to impairment in preglomerular autoregulation. On the other hand, chronic l-Arg preserved arteriolar structures probably mediated by the antiproliferative effect of NO on vascular smooth muscle cells.

Chronic inhibition of NOS-2 ameliorates renal injury, as well as COX-2 and TGF-beta 1 overexpression in 5/6 nephrectomized rats.

BACKGROUND: Chronic renal damage is associated with inflammatory infiltration, fibrosis and vascular lesion, coupled with increased expression of cyclo-oxygenase 2 (COX-2) and transforming growth factor-beta1 (TGF-beta1). However, the role of inducible nitric oxide synthase (NOS-2) is still controversial. Thus, we studied the contribution of NOS-2 to the expression levels of COX-2 and TGF-beta1, as well as the structural renal injury in rats with subtotal renal ablation (5/6 Nx). METHODS: Four groups of rats were studied: sham, 5/6 Nx, 5/6 Nx+aminoguanidine (AG) and 5/6 NX+L-NIL (L-N6-iminoethyl-lysine). Systolic blood pressure (SBP), proteinuria and creatinine (Cr) clearance were measured. NOS-2, COX-2 and TGF-beta1 gene expression was determined by real-time reverse transcription-polymerase-chain reaction. Protein expression was evaluated by western blot and ELISA (TGF-beta1). Immunohistochemistry and morphometry were performed for NOS-2, microvascular thickening and fibrosis. RESULTS: Systemic hypertension and marked proteinuria, increased expression of NOS-2, COX-2 and TGF-beta1, thickening of arteriolar wall and tubulointerstitial fibrosis were produced in 5/6 Nx rats. Chronic inhibition of NOS-2 did not prevent arterial hypertension or the fall in Cr clearance, but partially reduced proteinuria. Nevertheless, AG and L-NIL preserved arteriolar morphology and the administration of both selective inhibitors of inducible NOS (AG and L-NIL) prevented NOS-2 overexpression. CONCLUSION: This study shows that NOS-2 was markedly enhanced in renal tissue of 5/6 Nx rats. Moreover, treatment with AG and L-NIL prevented the morpho-functional changes induced by subtotal renal ablation, despite persistence of systemic hypertension, suggesting that high concentrations of nitric oxide produced by NOS-2 could act as a positive modulator of the proinflammatory and profibrotic pathways involved in the progression of renal disease.

Angiotensin II, interstitial inflammation, and the pathogenesis of salt-sensitive hypertension.

Transient administration of ANG II causes persistent salt-sensitive hypertension associated with arteriolopathy, interstitial inflammation, and cortical vasoconstriction; blocking the vascular and inflammatory changes with mycophenolate mofetil (MMF) prevents vasoconstriction. While infiltrating leukocytes during the salt-sensitive hypertension phase express ANG II, the functional role of ANG II during this phase is not known. We examined the acute effect of candesartan on renal hemodynamics during the established salt-sensitive hypertensive phase and related these findings to direct measurement of intrarenal ANG II and inflammatory cells in rats previously exposed to ANG II with or without MMF treatment. Sham controls were also examined. The administration of ANG II, followed by exposure to high-salt diet, resulted in hypertension, cortical vasoconstriction, an increase in interstitial inflammatory cells (44.8 +/- 1.3 lymphocytes/mm2, and 30.8 +/- 1.2 macrophages/mm2 ANG II vs. 19.6 +/- 2 lymphocytes/mm2, and 22 +/- 0.7 macrophages/mm2 Sham), and increase in renal ANG II levels (1,358 +/- 74.6 pg/ml ANG II vs. 194 +/- 9.28 pg/ml Sham). Treatment with MMF during the administration of exogenous ANG II resulted in reduction in renal interstitial inflammation (19.7 +/- 0.9 lymphocytes/mm2 and 15.9 +/- 0.8 machophages/mm2), ANG II levels (436.9 +/- 52.29 pg/ml), cortical vasoconstriction, and stable blood pressure levels during the subsequent challenge with a high-salt diet. Acute administration of candesartan similarly reduced renal vasoconstriction and blood pressure. We conclude that the cortical vasoconstriction occurring with salt-sensitive hypertension following exposure to ANG II is mediated by intrarenal ANG II, related, at least in part, to the interstitial inflammation.

Uric acid--a uremic toxin?

Uric acid might often be regarded as a simple marker of renal disease. Although it is well known that hyperuricemia causes gout which is associated with renal insufficiency and cardiovascular disease, one might think that it could attribute to the intrarenal urate crystal, but not to uric acid per se. In order to clarify the role of uric acid in the kidney, we hypothesized that uric acid causes renal disease. To generate mild hyperuricemia without intrarenal crystal in rats, we used low doses of an uricase inhibitor (2% oxonic acid). Hyperuricemia induced systemic hypertension, glomerular hypertrophy/hypertension, afferent arteriolar sclerosis, and macrophage infiltration in normal rat kidney. In progressive renal disease, such as cyclosporine nephropathy and remnant kidney in rat, uric acid accelerated the progression of renal disease. Thus, we concluded that uric acid is not a simple marker, but a cause of renal disease.

Hormonal and cytokine effects of uric acid.

PURPOSE OF REVIEW: Current evidence supports the role of soluble uric acid as a true mediator of injury, exerting its effects through the induction of growth factors, cytokines, hormones and autacoids. In the present review, we summarize recent studies on the mechanisms involved in the uric acid deleterious effects. RECENT FINDINGS: Although uric acid is considered an antioxidant in plasma, recent clinical and epidemiological studies have found that hyperuricemia is associated with mortality and development of hypertension, cardiovascular and chronic renal diseases. Experimental studies suggest that uric acid induce its detrimental effects at the cellular level entering to vascular smooth muscle cells (VSMC) via an organic anion transport system, and followed by the activation of specific MAP kinases, nuclear transcription factors, with stimulation of COX-2, PDGF A and C chain, PDGF alpha receptor, and various inflammatory mediators, including C-reactive protein and monocyte chemoattractant protein-1. Physiologically, these effects translate into a rise of arterial pressure, VSMC hypertrophy, tubulointerstitial infiltration and glomerular hypertension in the setting of renal vasoconstriction. Uric acid also promotes endothelial dysfunction through inactivation of NO and arresting the proliferation of endothelial cells. Thus, arteriosclerosis induced by hyperuricemia may be a novel mechanism for the development of essential hypertension. SUMMARY: Soluble uric acid has important biologic roles. While it acts as an antioxidant, there is also evidence that uric acid has pro-inflammatory and proliferative effects on VSMC, and causes dysfunction of endothelial cells. These cellular mechanisms may translate into why uric acid is associated with renal and cardiovascular disease.