Effect of astaxanthin on kidney function impairment and oxidative stress induced by mercuric chloride in rats.

Reactive oxygen species are implicated as mediators of tissue damage in the acute renal failure induced by inorganic mercury. Astaxanthin (ASX), a carotenoid with potent antioxidant properties, exists naturally in various plants, algae, and seafoods. This paper evaluated the ability of ASX to prevent HgCl(2) nephrotoxicity. Rats were injected with HgCl(2) (0 or 5 mg/kg b.w., sc) 6h after ASX had been administered (0, 10, 25, or 50mg/kg, by gavage) and were killed 12h after HgCl(2) exposure. Although ASX prevented the increase of lipid and protein oxidation and attenuated histopathological changes caused by HgCl(2) in kidney, it did not prevent creatinine increase in plasma and delta-aminolevulinic acid dehydratase inhibition induced by HgCl(2). Glutathione peroxidase and catalase activities were enhanced, while superoxide dismutase activity was depressed in HgCl(2)-treated rats when compared to control and these effects were prevented by ASX. Our results indicate that ASX could have a beneficial role against HgCl(2) toxicity by preventing lipid and protein oxidation, changes in the activity of antioxidant enzymes and histopathological changes.

Adenomas túbulo-vellosos duodenales. Análsis de 3 casos / Duodenal tubular villous adenomas. Analisys of three cases

Se presentan 3 casos de adenomas túbulo-vellosos duodenales en 3 varones, coincidiendo en uno de ellos con la presencia de adenomas en colon derecho, uno de ellos degenerado que obligó a una hemicolectomía amplia. La clínica fue de dispepsia gástrica acompañada en ocasiones de dolor tipo ulceroso, por lo cual se indicó una gastroscopia (origen de su descubrimiento) y en el tercer caso con la sospecha clínica tras la intervención de la neoplasia de colon con adenomas túbulo-vellosos. En todos ellos pudo realizarse extirpación local incluyendo submucosa y con buena evolución clínica, siendo las revisiones endoscópicas normales (AU)

We present 3 cases of tubular-villous adenomas in males. One of them presented this adenoma at the same time than others adenomas in the right bowel, which degenerated to a carcinoma that obligated us to do a hemicolectomy. The patient presented dyspepsia with an ulcerous pain. Because of these symptoms it was indicated a gastroscopy. In the third case, after the clinical suspicion of neoplasia, it was found after surgery of a bowel with tubular-villous adenomas. In all the cases a local surgery could be done, including the subumucosa, and all of them presented a good clinical evolution. All of the next endoscopies were normal (AU)

[One year prevalence of mental disorders comorbidity and associated socio-demographic risk factors in the general population of Spain. Results of the ESEMeD-Spain study]. / Prevalencia-año de la comorbilidad de los trastornos mentales y factores de riesgo sociodemográficos asociados en la población general de España. Resultados del estudio ESEMeD-España.

INTRODUCTION: Comorbidity among mental disorders in the general population is common, affecting more than the 50 % of individuals with a lifetime mental disorder. In Spain, there are no data describing it or its associated risk factors. METHOD: The ESEMeD-Spain study is an epidemiological study assessing mental disorders in a sample of 5,473 individuals from the general population of Spain aged 18 years or older. The aims of the present study were to evaluate the frequency of mental disorders comorbidity in Spain (assessed with the Composite International Diagnostic Interview: CIDI 3.0) and associated sociodemographic risk factors. Response rate was 78.6%. RESULTS: Mood disorders showed the highest comorbidity frequency. Analysing specific disorders, generalized anxiety disorder, dysthymic and panic disorders showed the highest comorbidity percentages. Female gender, ages above 24 years old and being previously married were found to be risk factors associated to the presence of comorbid mood and anxiety disorders. CONCLUSIONS: As it has been suggested for other European countries and for the United States, in the general population of Spain mental disorders, specially mood disorders, are frequently comorbid. When treating mental disorders, comorbidity should be taken into account.

[The impact of mood and anxiety disorders, and physical chronic conditions in the quality of life of general population of Spain. Results of the ESEMeD-Spain study]. / Impacto de los trastornos del ánimo, de ansiedad y de las enfermedades físicas crónicas en la calidad de vida de la poblacíon general de España. Resultados del estudio ESEMeD-España.

INTRODUCTION: Mental disorders and chronic physical conditions significantly impair health related quality of life (HRQOL). To date, there are no studies in the general population of Spain about their impact. The aim of the present study is to evaluate the impact of mood and anxiety disorders and chronic physical conditions in HRQOL and functional disability (estimated considering work loss days). METHODS: The ESEMeD-Spain is an epidemiological study carried out in the general population of Spain aged 18 years or older. Mental disorders were assessed with the Composite International Diagnostic Interview (CIDI 3.0); the HRQOL with the SF-12; and functional disability with the WHO Disability Assessment Schedule. Additionally, chronic physical conditions were assessed. RESULTS: A total of 5,473 individuals were assessed. Response rate was 78.6 %. Mental disorders, specially mood disorders, showed the highest impairment in HRQOL and functional disability (more work loss days). This impairment was even higher than the impairment associated to chronic physical conditions. Comorbidity between mood and anxiety disorders was associated to the worst HRQOL. In general, mental HRQOL was more impaired than physical HRQOL. CONCLUSIONS: Mood disorders substantially impair HRQOL and augment functional disability in Spain. Their comorbidity with anxiety disorders in especially impairing.

Risk factors for suicidality in Europe: results from the ESEMED study.

BACKGROUND: Precise knowledge of the epidemiology of suicidality provides necessary information for designing prevention programs. The aims of the present study were to investigate the prevalence and correlates of suicidal ideas and attempts in the general population of Europe. METHODS: The European Study on the Epidemiology of Mental Disorders (ESEMED) is a cross-sectional household survey carried out in a probability representative sample of non-institutionalised adults (aged 18 years or older) of six European countries (Belgium, France, Germany, Italy, the Netherlands and Spain). The Composite International Diagnostic Interview (CIDI 3.0) was administered to 21,425 individuals. RESULTS: Lifetime prevalence of suicidal ideation was 7.8% and of suicidal attempts 1.3%. Being women, younger and divorced or widowed were associated with a higher prevalence of suicide ideation and attempts. Psychiatric diagnoses were strongly related to suicidality. Among them, major depressive episode (Rate ratio 2.9 for lifetime ideas and 4.8 for lifetime attempts), dysthymia (RR 2.0 and 1.6), GAD (RR 1.8 and 2.3 for lifetime), PTSD (RR 1.9 and 2.0) and alcohol dependence (RR 1.7 and 2.5) were the most important. Population attributable risks for lifetime suicidal attempt was 28% for major depression. LIMITATIONS: Information about suicidal ideas and attempts was self reported, psychiatric diagnoses were made using fully structured lay interviews rather than clinician-administered interviews. CONCLUSIONS: In spite of meaningful country variation in prevalence, risk factors for suicidality are consistent in the European countries. Population prevention programmes should focus on early diagnosis and treatment of major depression and alcohol abuse and in those individuals with recent appearance of suicidal ideas.

Medical examiner samples: a source for dengue surveillance

Post-mortem medical examiner samples may be useful for sentinel surveillance of disorders usually detected by antibody determinations on specimens from ill patients or from surveys. We found anti-dengue IgM positivity in 3(23/780) and anti-dengue IgG positivity in 77(597/777) of sera obtained at the Puerto Rico medical examiner (Institute of Forensic Sciences) in December 2000, April 2001, and October 2001. This approach may be a useful alternative for estimating the population prevalence of serologic markers for dengue and other infectious diseases.

Metabolismo oxidativo en las neoplasias ováricas / Oxidative metabolism in ovarian neoplasms

Objetivo: Valorar el estatus oxidativo de las neoplasias ováricas mediante la determinación de las enzimas antioxidantes más importantes, los valores de glutatión reducido y oxidado, la formación de malondialdehído, como índice de peroxidación molecular, y el grado de oxidación del material genético mediante la cuantificación de la base mutagénica 8-oxo-deoxiguanosina. Material y métodos: Estudio prospectivo de 52 casos de neoplasia ovárica: 43 casos de cáncer de ovario epitelial, de los que nueve habían recibido quimioterapia previa a la cirugía, y otros nueve con tumoraciones benignas. Resultados: En el tejido tumoral, al compararlo con tejido sano de las mismas pacientes, se evidenció disminución de las enzimas antioxidantes catalasa y superóxido-dismutasa, así como un aumento del resto de los parámetros estudiados. La quimioterapia anuló las diferencias entre el ovario sano y el tumoral. Conclusiones: El metabolismo oxidativo se encuentra alterado en el tejido tumoral ovárico si se compara con el tejido sano de las mismas pacientes. La quimioterapia ejerce efecto sobre dicho metabolismo (AU)

Hidrosadenitis supurativavulvar / Vulvar suppurative hidrosadenitis

Presentamos un caso de una mujer con hidrosadenitis perianal y vulvar, de 20 años de evolución intervenida en múltiples ocasiones que tuvo que someterse a vulvectomía. La hidrosadenitis supurativa es una enfermedad inflamatoria supurativa crónica que afecta a las glándulas sudoríparas apocrinas de la axila, área genital, mamas y otras localizaciones; es rara antes de la pubertad y tiende a declinar tras la menopausia (AU)

Enfermedad de Paget de la vulva: estudio inmunohistoquímico / Paget's disease of the vulva: an immunohistochemical study

La enfermedad de Paget de la vulva es una lesión intraepitelial no escamosa que comprende entre el 0,2 y el 5% de los cánceres de vulva. En la mayoría de los casos no existe asociación con otra neoplasia subyacente y no se ha establecido el origen de la célula de Paget en esta enfermedad. Para acercarnos al mismo, analizamos ciertas características inmunohistoquímicas celulares: CK 6, 7, 8, 18, 19 y 20; proteínas Ki 67, BCL 2, p 53 y C-erb B2. Los resultados obtenidos son los siguientes: todas las CK son positivas excepto la 20, Ki 67 positiva, BCL 2 negativa, p53 negativa y C-erb B2 positiva. Estos resultados apoyan la teoría, predominante en la actualidad, del origen de la célula de Paget de la vulva en el estrato germinativo de células pluripotenciales del epitelio y no en los apéndices cutáneos (AU)

Papel de la trombocitosis en el adenocarcinoma de endometrio / The role of thrombocytosis in endome-trial adenocarcinoma

Es conocida la asociación entre neoplasia maligna y trombocitosis. En el presente trabajo se analiza la prevalencia de esta condición en el adenocarcinoma de endometrio, su relación con otros factores y su impacto pronóstico. Se estudiaron 499 casos, comparando el número de plaquetas con la edad, la paridad, el intervalo fértil, la duración de la sintomatología, el retraso terapéutico, los marcadores tumorales CA125, CA153, CA199 y CEA, la estadificación de la FIGO, la histología y el grado tumorales, y la invasión miometrial. Asimismo, se analizó el impacto pronóstico de la trombocitosis. Tomando como punto de corte un número de plaquetas de 300.000/µl (hiperplaquetosis), se observaron cifras significativamente más elevadas de CA125, CA153 y CEA. Tomando como punto de (..) (AU)

Impairment of Gag-specific CD8(+) T-cell function in mucosal and systemic compartments of simian immunodeficiency virus mac251- and simian-human immunodeficiency virus KU2-infected macaques.

The identification of several simian immunodeficiency virus mac251 (SIV(mac251)) cytotoxic T-lymphocyte epitopes recognized by CD8(+) T cells of infected rhesus macaques carrying the Mamu-A*01 molecule and the use of peptide-major histocompatibility complex tetrameric complexes enable the study of the frequency, breadth, functionality, and distribution of virus-specific CD8(+) T cells in the body. To begin to address these issues, we have performed a pilot study to measure the virus-specific CD8(+) and CD4(+) T-cell response in the blood, lymph nodes, spleen, and gastrointestinal lymphoid tissues of eight Mamu-A*01-positive macaques, six of those infected with SIV(mac251) and two infected with the pathogenic simian-human immunodeficiency virus KU2. We focused on the analysis of the response to peptide p11C, C-M (Gag 181), since it was predominant in most tissues of all macaques. Five macaques restricted viral replication effectively, whereas the remaining three failed to control viremia and experienced a progressive loss of CD4(+) T cells. The frequency of the Gag 181 (p11C, C-->M) immunodominant response varied among different tissues of the same animal and in the same tissues from different animals. We found that the functionality of this virus-specific CD8(+) T-cell population could not be assumed based on the ability to specifically bind to the Gag 181 tetramer, particularly in the mucosal tissues of some of the macaques infected by SIV(mac251) that were progressing to disease. Overall, the functionality of CD8(+) tetramer-binding T cells in tissues assessed by either measurement of cytolytic activity or the ability of these cells to produce gamma interferon or tumor necrosis factor alpha was low and was even lower in the mucosal tissue than in blood or spleen of some SIV(mac251)-infected animals that failed to control viremia. The data obtained in this pilot study lead to the hypothesis that disease progression may be associated with loss of virus-specific CD8(+) T-cell function.

RNAIII inhibiting peptide (RIP), a global inhibitor of Staphylococcus aureus pathogenesis: structure and function analysis.

Staphylococcus aureus are gram-positive bacteria that can cause serious diseases in humans and animals. S. aureus infections can be prevented by the heptapeptide RNAIII inhibiting peptide (RIP). RIP was originally isolated from culture supernatants of coagulase negative staphylococci presumed to be S. xylosus. The sequence of RIP was identified as YSPXTNF. Native RIP and its synthetic analogue YSPWTNF have been shown to be effective inhibitors of diseases caused by various strains of S. aureus, including, cellulitis, keratitis, septic arthritis, osteomylitis and mastitis. RIP is therefore considered to be a global inhibitor of S. aureus. We show here that: 1) the amide form of RIP (YSPWTNF-NH2) is highly stable and is therefore the one recommended for use. 2) RIP inhibits S. aureus pathogenesis by inhibiting the synthesis of both agr transcripts RNAII and RNAIII. 3) Although RIP inhibits agr, it also reduces bacterial adherence to mammalian cells and to plastic (tested on HEp2 cells and on polystyrene by fluorescence and atomic force microscopy), suggesting that RIP can be used safely as a therapeutic molecule. 4) RIP derivatives were designed and tested for their ability to inhibit RNAIII in vitro and cellulitis in vivo. Not all peptides that inhibited RNAIII also inhibited an infection in vivo, indicating that studies must be carried out in vivo before considering a peptide to be of therapeutic potential. 5) The RIP derivative containing Lysine and Isoleucine at positions 2 and 4, respectively, inhibited S. aureus infections in vivo (tested on cellulitis), suggesting that both RIP YSPWTNF and its derivative YKPITNF are effective inhibitors of infections caused by S. aureus.

Overcoming original (antigenic) sin.

Original antigenic sin describes a phenomenon in which the antibody response elicited in an individual after a secondary viral infection reacts more strongly to the viral variant that originally infected the individual. As T helper cells play critical roles in promoting antibody responses, a similar phenomenon may hold true for T helper cell responses. This concept is particularly relevant to the development of vaccines against viruses such as human immunodeficiency virus and hepatitis C virus, in which myriad viral variants are present throughout the human population. We have compared the effects of priming the immune system with a single peptide epitope or with a cocktail of related peptides based on the epitope. Our data demonstrate that immunization with multiple peptide variants expands a more broadly reactive and durable T helper cell response than does immunization with a single peptide. This vaccine strategy may circumvent original antigenic sin.

Up-regulation of urokinase-type plasminogen activator by insulin-like growth factor-I depends upon phosphatidylinositol-3 kinase and mitogen-activated protein kinase kinase.

Elevated levels of urokinase plasminogen activator-1 (uPA) and the insulin-like growth factor-I receptor (IGF-IR) are associated with breast cancer recurrence and decreased survival. It is possible that activation of IGF-IR and elevations in uPA are mechanistically linked. Our laboratory recently showed that insulin-like growth factor-I (IGF-I) induces uPA protein and mRNA in the breast cancer cell line MDA-MB-231. We also found that IGF-IR and uPA were commonly overexpressed in primary breast cancers. In this study, we investigated the signal transduction pathway through which IGF-I regulates uPA. Phosphatidylinositol 3-kinase, mitogen-activated protein kinase kinase, and p70 kinase were inhibited with LY294002, PD98059, and rapamycin, respectively. Induction of uPA protein by IGF-I was partially inhibited by LY294002 (60% inhibition) or PD98059 (30% inhibition) but not by rapamycin. The production of uPA protein induced by IGF-I was blocked up to 90% by the tyrosine kinase inhibitor herbimycin A. Furthermore, herbimycin A suppressed the phosphorylation of AKT and Erk1/2. Next, we tested the impact of the signal transduction inhibitors on uPA gene expression. Both LY294002 and PD98059 were required to completely inhibit uPA mRNA expression, whereas each drug alone resulted in approximately 50% reduction in uPA expression. Next, using a minimal uPA-luciferase promoter construct containing the binding sites for the AP-1 and Ets transcription factors, we observed that IGF-I stimulated the uPA promoter via these sites. Furthermore, both Ly294002 and PD98059 were necessary to block IGF-I-stimulated uPA-Luc activity. In summary, we conclude that IGF-I requires both phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase-dependent pathways to optimally induce uPA expression. These findings suggest that the development of drugs targeting these pathways may benefit breast cancer patients at a high risk of recurrence, such as those who have primary tumors overexpressing IGF-IR and uPA.

A retroviral DNA vaccine vector.

A versatile DNA vaccine (pdIV3) was constructed by replacing the integrase, vif, vpx, and vpr genes of a pathogenic simian immunodeficiency virus (SIV) molecular clone with a linker containing unique cloning sites. The 5' long terminal repeat (LTR) is truncated and transcription is controlled by a cytomegalovirus (CMV) promoter. The construct expresses Gag and Env in vitro and noninfectious virus particles are produced from transfected cells. The ability of pdIV3 to promote cellular and humoral immune responses, along with the flexibility of the linker design to allow insertion of immunostimulatory genes in future constructs, makes this a useful base vector for immunization against primate lentiviruses. We present the construction of a retroviral plasmid designed to serve as a template for the development of safe and effective vaccines against primate immunodeficiency retroviruses. This vaccine component should facilitate the simultaneous induction of cellular and humoral immune responses that protect primates against infection with SIV and human immunodeficiency virus (HIV) and the development of acquired immune deficiency syndrome (AIDS). This plasmid could induce the appropriate immune response required to attack both cell-free and cell-associated viruses. The lack of infectivity, the inability to integrate, and the SIV origin make this construct a safe alternative to attenuated vaccines based on HIV. In addition, we intend to develop this construct as an immunotherapeutic approach to lower the viremia in AIDS patients.

Prevention of diseases caused by Staphylococcus aureus using the peptide RIP.

Staphylococcus aureus causes many diseases including cellulitis, keratitis, osteomyelitis, septic arthritis and mastitis. The heptapeptide RIP has been shown to prevent cellulitis in mice, which was induced by S. aureus strain Smith diffuse. Here we show that RIP can also significantly reduce the overall pathology and delay the onset of disease symptoms in several other models of S. aureus infections, including: keratitis (tested in rabbits against S. aureus 8325-4), osteomyelitis (tested in rabbits against S. aureus MS), mastitis (tested in cows against S. aureus Newbould 305, AE-1, and environmental infections) and septic arthritis (tested in mice against S. aureus LS-1). These findings substantiate that RIP is not strain specific in its inhibitory activity and that RIP is an effective inhibitor of bacterial pathology at multiple body sites following diverse routes and doses of administration. These findings strongly evidence the potential value of RIP as a chemotherapeutic agent.

Preparation and induction of immune responses by a DNA AIDS vaccine.

In an effort to evaluate the feasibility of developing a safe DNA vaccine for acquired immunodeficiency syndrome (AIDS), we have prepared a plasmid-based immunogen modeled after a naturally occurring noninfectious mutant of the simian immunodeficiency virus (SIV). The mutant SIV genome produces defective virus particles that are noninfectious in vitro and nonpathogenic in vivo in rhesus macaques. Analysis of the mutant genome revealed a 1.6 kb deletion that is in frame and spans integrase, vif, vpx, and most of vpr and results in a pol/vpr gene fusion. This deletion was introduced into the parental pathogenic molecular clone and the U3 region of the 5' LTR was replaced with a cytomegalovirus promoter to produce a candidate DNA vaccine, pIV. After transfection with this plasmid, SIV gag and envelope proteins are expressed and properly processed in vitro. When injected into rabbits, pIV elicited an antibody response to SIV gp130 envelope glycoprotein with titers reaching 1:2048, and a strong lymphoproliferative response to SIV gp130 and whole SIV. The potential to produce defective virus particles in vivo without integrating into the host genome should result in both a strong humoral and cellular immune response in rhesus macaques. In addition, this approach offers a safe alternative to live attenuated vaccines and DNA vaccines that are capable of integration.

Morphine induces gene expression of CCR5 in human CEMx174 lymphocytes.

All HIV-1 strains studied to date use CCR5, CXCR4, or both receptors to enter cells. Simian immunodeficiency virus (SIV) infection of non-human primates has served as a useful model for understanding AIDS pathogenesis in humans. Research on several genetically divergent SIV isolates has revealed that SIV uses CCR5, and not CXCR4, for entry. CEM x174, a human lymphoid cell line, has been routinely used to cultivate and maintain various SIV strains. However, questions have arisen about how CEM x174, which reportedly was unable to express detectable amounts of CCR5 transcripts, efficiently supports the growth of SIV. In searching for an answer, we resorted to a sensitive competitive reverse transcriptase-polymerase chain reaction procedure in an attempt to detect as well as quantify the amount of CCR5 expression. Here we present our findings, which indicate that CEM x174 indeed expresses CCR5 and that the amount of CCR5 is increased in cells pretreated with morphine. These results correlate well with our previous observations that morphine treatment causes CEM x174 cells to be more susceptible to SIV infection. Similar morphine effect was not observed on CEM x174 cells infected with simian retroviruses, which do not depend on CCR5 for entry. These findings suggest a plausible mechanism whereby opiate drug users render themselves more susceptible to HIV infection, thereby explaining the vast prevalence of HIV infection among endemic drug use populations.

Unappreciated agenesis of cerebellum in an adult: case report of a 38-year-old man.

An unexpected finding at autopsy of almost complete agenesis of the cerebellum in an apparently functional, mentally subnormal 38-year-old man who died as the result of an accidental electrocution is reported. The posterior fossa was normal in appearance despite nearly complete absence of the cerebellum. A number of syndromes of cerebellar atrophy or dysgenesis have been reported, but congenital agenesis is considered a very rare condition. It does not resemble most common cerebellar malformations or acquired conditions, especially in an adult, who apparently had reasonable motor and coordinative function. The relevant literature is reviewed.

The kinetics of specific immune responses in rhesus monkeys inoculated with live recombinant BCG expressing SIV Gag, Pol, Env, and Nef proteins.

Development of an effective preventive or therapeutic vaccine against HIV-1 is an important goal in the fight against AIDS. Effective virus clearance and inhibition of spread to target organs depends principally on the cellular immune response. Therefore, a vaccine against HIV-1 should elicit virus-specific cytotoxic lymphocyte (CTL) responses to eliminate the virus during the cell-associated stages of its life cycle. The vaccine should also be capable of inducing immunity at the mucosal surfaces, the primary route of transmission. Recombinant Bacille Calmette-Guérin (BCG) expressing viral proteins offers an excellent candidate vaccine in view of its safety and ability to persist intracellularly, resulting in the induction of long-lasting immunity and stimulation of the cellular immune response. BCG can be administered orally to induce HIV-specific immunity at the mucosal surfaces. The immunogenicity of four recombinant BCG constructs expressing simian immunodeficiency virus (SIV) Gag, Pol, Env, and Nef proteins was tested in rhesus macaques. A single simultaneous inoculation of all four recombinants elicited SIV-specific IgA and IgG antibody, and cellular immune responses, including CTL and helper T cell proliferation. Our results demonstrate that BCG recombinant vectors can induce concomitant humoral and cellular immune responses to the major proteins of SIV.