Alteraciones morfológicas del bazo de ratas (rattus norvergicus), tratadas con trióxido de arsénico / Morphological alterations of the spleen of rats (rattus norvegicus) treated with arsenic trioxide

En América Latina la presencia del arsénico en el ambiente y en las fuentes de agua para consumo humano, se debe a factores naturales de origen geológico como a actividades antropogénicas. El arsénico en las aguas naturales se encuentra principalmente como trivalente (arsenito) o pentavalente (arsenato). El objetivo de este trabajo fue determinar las alteraciones que provoca el trióxido de arsénico a nivel de la morfología del bazo de ratas (Rattus norvegicus - Sprague-Dawley). Se utilizaron 24 ratas de ambos sexos de 55 días de vida. Las ratas fueron pesadas y divididas en 3 grupos (4 hembras y 4 machos). Los grupos tratados fueron inyectados con 5 mg y 10 mg de As2O3 respectivamente, en dosis única diaria vía intraperitoneal por 15 días. Al grupo control se le aplicó agua destilada sin arsénico. Después del tratamiento los animales fueron sacrificados por eutanasia convencional y se obtuvo el bazo, los cuales fueron lavados, pesados y seccionados en cuatro partes, que fueron fijadas en formol tamponado al 10 por ciento. Mediante técnica histológica se obtuvieron 4 muestras seriadas de cada bazo, de 5 micrones de espesor con una separación de 100 micrones entre si. Posteriormente fueron teñidas con H-E. Se analizaron 30 campos (120 campos por órgano). Los datos obtenidos permiten concluir que ratas tratadas con trióxido de arsénico, presentan alteración a nivel de los compartimentos del bazo, con un aumento del compartimento de la pulpa roja, una depleción en el tamaño y número de folículos linfoides y de la zona marginal. A su vez, se observó pérdida de la celularidad de la vaina linfoide periarteriolar (PALS).

In Latin America, the presence of arsenic in the environment and water sources for human consumption is due to natural geological factors and anthropogenic activities. Arsenic in natural waters is mainly found as trivalent (arsenite) or pentavalent (arsenate). The aim of this study was to determine the alterations causing arsenic trioxide-level morphology of the spleen of rats (Rattus norvegicus - Sprague-Dawley). Were used 24 rats of both sexes of 55 days of life. The rats were weighed and divided into 3 groups (4 females and 4 males). The treated groups were injected with 5 mg and 10 mg of As2O3 respectively, intraperitoneally daily dosing for 15 days. The control group was administered arsenic-free distilled water. After treatment the animals were euthanized conventionally, and spleen was removed, which was washed, weighed and sectioned into four parts, which were fixed in 10 percent buffered formalin. Histological technique using four serial samples were obtained from each spleen of 5 microns thick with a spacing of 100 microns between them. Subsequently these were stained with H-E. We analyzed 30 fields (120 fields per organ). The data obtained indicates that rats treated with arsenic trioxide have an altered level of the compartments of the spleen, with an increased red pulp chamber, depletion in the size and number of lymphoid follicles and marginal zone. Furthermore, loss of cellularity of periarteriolar lymphoid sheath (PALS) was observed.

Historia del tratamiento de la Sífilis / The history of Syphilis´ treatment

El nombre sífilis proviene del griego siph: cerdo y philus: amor. Recuerda al personaje de una obra, llamado Syphilo, que fue castigado por los dioses a sufrir una terrible enfermedad. Se analizan los datos sobre la sífilis en la antigüedad (que difieren según su fuente). Su mención en la Edad Media, su controversial origen, la ayuda de los paleopatólogos para encontrarlo. Luego de la Revolución Francesa y el inicio de la Edad Contemporánea, el porcentaje de enfermos fue creciendo y se acentuó la segregación de los mismos por la sociedad. Desde el año 1500 hasta principios del siglo XX el tratamiento de la sífilis dependía del mercurio. Tenía una gran variedad de formas de aplicación. La vía tópica: el ungüento gris, en calomelano o tabletas, en inyecciones, en fricciones y fumigaciones en donde el mercurio se introducía en el cuerpo por lo pulmones. Se adjudicó a la madera del guayaco pretendidas características curativas, que no poseía. Los ioduros se utilizaron para el terciarismo. Ehrlich en 1907, patentó el compuesto 606 o Salvarsan y en 1910, el Neo-Salvarsan o Arsfenamina (compuesto 914). Por estos descubrimientos recibió el Premio Nobel. En 1887, Julios Wagner Jauregg sugirió que la fiebre terapéuticamente inducida era útil en el tratamiento de enfermos psicóticos. En 1912 publicó sus satisfactorios resultados al tratar la paresias con una combinación de mercurio-iodo y tuberculina de Koch. En 1917 ingresó a su servicio un enfermo de malaria, con cuya sangre escarificaron la piel palúdica de tres paréticos, en lugar de darle inmediatamente quinina. Por ello fue galardona con el Premio Nobel. Se utilizó luego el bismuto, a partir de 1922, pero posteriormente fue sustituido por las sulfamidas, de aplicación dificultosa. El avance terapéutico más importante ocurrió en 1943, año en que se comenzó a utilizar la penicilina por Mahoney y colaboradores. Luego se confirmó la eficacia de la tetraciclina para los alérgicos a la penicilina. Últimamente se confirmó la eficacia de la azitromicina en dosis de 500mg cada día, durante los 10 días o el régimen de 500mg en días alternos.

The name Syphilis comes from greek language: Siph: Pig and Philus: Love, meaning, in honor of the Sheppard of a story where the Character, Named Syphilo, is punished by the gods to suffer a terrible disease. Data about Syphilis was analized in ancient times (which differ according to the source). Its mention in the middle age, its controversial origin, the help provided from paleopathologists to find it. When the French revolution and the beginning of the contemporary age began, the percentage of sick people grew. The segregation of these is proved by the society. From the year 1500 to the beginnings of the XX century, the treatment of Syphilis depended on mercury. There were a great variety of application methods: topical: the grey ointment, in «calomelanos or tabs¼, in injections, in frictions and fumigations where the mercury was introduced in the body by the lungs. Guayacos wood was named with curative features which it did not posses. The iodides were used for tertiary syphilis. In 1907, Ehrlich formulates the 606 compound or Salvarsan and in 1910 the Neo-Salvarsan or Arsfenamina or compound 914.Due to these discoveries he received the nobel prize. In 1887, Julius Wagner of Jauregg suggested that: the inducted therapeutic fiber was useful in the treatment of the psychosis. In 1912 he published his satisfactory results in treating the paresis with a combination of mercury and iodides and tuberculin of Koch. In 1917 he treated a patient who had malaria and instead of giving him immediately quinine, he made a scarification with his paludic blood the skin of 3 paretic patients. Because of this he was awarded with the nobel prize. Since 1922 bismuth was used, but then it was substituted by the sulphamidas of difficult application. The most important therapeutical advance happened in 1943, year in which penicillin was put in use by Mahoney and col. Later it was confirmed the efficiency of the tetracycline for the penicillin-allergic patients. Lately it has been confirmed the efficiency of the azithromizine in 500 mg dosis each day during 10 days or the regimen of 500 mg in alternate days.

Absorption and metabolism of paracetamol in rats drinking high concentration of arsenic.

The effect of chronic intake of arsenic on the plasma concentration of paracetamol in rat was investigated. Rats received saline water with or without arsenic trioxide (10 mg/kg body weight/day) by gastric gavage on every alternate day for 29 days. A single dose of paracetamol (range 10 infinity 40 mg/kg body weight) was administered by gastric gavage to both arsenic-untreated and -treated rats on 30(th) day. Rats were sacrificed after 30 min and the amounts of free paracetamol and its metabolites in plasma were estimated using isocratic reverse-phase High Performance Liquid Chromatography (HPLC). Arsenic toxicity reduced the plasma concentration of paracetamol to 53 - 65% when compared with the rats received no added arsenic. There were maximum 67.4 and 76.9% inhibitions of sulfate and cysteine conjugations of paracetamol respectively. But arsenic had no effect on glucuronide and mercapturate conjugations. Both liver and small intestine showed increased accumulation of arsenic and decreased amount of glutathione in arsenic-treated rats. This study suggests that chronic ingestion of arsenic inhibit the absorption and metabolism of paracetamol.

Arsenic trioxide-induced apoptosis is independent of stress-responsive signaling pathways but sensitive to inhibition of inducible nitric oxide synthase in HepG2 cells

Arsenic trioxide (As2O3) has been found to be remarkably effective in the treatment of patients with acute promyelocytic leukemia (APL). Although evidences for the proapoptotic activity of As2O3 have been suggested in leukemic and other solid cancer cells, the nature of intracellular mechanisms is far from clear. In the present study, we investigated As2O3 affect on the stress-responsive signaling pathways and pretreatment with antioxidants using HepG2 cells. When treated with micromolar concentrations of As2O3, HepG2 cells became highly apoptotic paralleled with activation of caspase-3 and members of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK) but not p38 MAP kinase. However, inhibition of each kinase activity failed to inhibit apoptosis by As2O3. Addition of n-acetyl cysteine (NAC) or diphenyleneiodonium (DPI) effectively protected cells from apoptosis and significantly lowered As2O3-induced activation of caspase-3. However, neither NAC nor DPI was able to effect ERK or JNK activation induced by As2O3. Guanidinoethyldisulfide dihydrochloride (GED) and 2-ethyl- 2-thiopseudourea (ETU), known inhibitors of the inducible nitric oxide synthase (iNOS), also suppressed the apoptotic activity of As2O3. These results suggest that As2O3 induces caspase-mediated apoptosis involving a mechanism generating oxidative stress. However, activation of some stress- responsive signaling pathways by As2O3 may not be the major determinant in the course of apoptotic processes.