Anatomía Comparada del Bazo de la Rata Blanca (Rattus norvegicus albinus), Una Revisión de la Literatura / Comparative Anatomy of the Spleen of the White Rat, (Rattus norvegicus albinus) a Literature Review

El bazo es el órgano linfático intraperitoneal más grande del organismo, presentando dos funciones principales: defensiva, mediante respuesta inmunitaria y filtración sanguínea. El objetivo de la presente revisión, fue obtener información actualizada sobre la anatomía del bazo de la rata albina (Rattus norvegicus albinus) y comparativa con la anatomía del bazo humano, perro, gato y cerdo, al representar las principales especies de importancia en la medicina, medicina veterinaria y en las ciencias biomédicas. Se realizó una búsqueda de material bibliográfico actualizado en diferentes sitios web científicos. Es así como, se revisaron 71 fuentes bibliográficas, en su gran mayoría artículos científicos (31), libros de anatomía humana y veterinaria (17), artículos especializados (17) y tesis (6). En general existe consenso, sobre la descripción anatómica del bazo, el cual se sitúa en la región hipocondriaca izquierda del abdomen, entre el fondo del estómago y el diafragma, irrigado por la arteria y vena esplénica. Se evidenció que existen similitudes en aspectos macroscópicos, al comparar el bazo de la rata blanca, con el bazo de otras especies (funcionalidad, peso relativo, ubicación topográfica). En aspectos microscópicos, el bazo en humanos y otros mamíferos se compone de estroma, además de parénquima, constituido a su vez por pulpa blanca y roja. En particular, existen diferencias entre el bazo de rata, humano, gato, perro y cerdo, en formas, tamaños y aspectos microscópicos, relacionados con la microcirculación e inmunidad. Mientras que existen semejanzas en procesos patológicos y respuestas a tratamientos farmacológicos y clínicos. Por lo anteriormente expuesto, se concluye que la rata albina constituye un buen modelo biológico, específicamente en aspectos anatómicos microscópicos del bazo de tipo inmunológico. Mientras que el bazo de cerdo es mejor comparativamente, en estudios anatómicos macroscópicos de tipo quirúrgicos, resultando ambos extrapolables, especialmente a la medicina humana.

SUMMARY: The spleen is the largest intraperitoneal lymphatic organ of the body, presenting two main functions: defensive, through immune response and blood filtration. The objective of the present review was to obtain updated information on the anatomy of the spleen of the albino rat (Rattus norvegicus albinus) and to compare it with the anatomy of the human, dog, cat and pig spleen, representing the main species of importance in medicine, veterinary medicine and biomedical sciences. A search for updated bibliographic material was carried out in different scientific websites. Thus, 71 bibliographic sources were reviewed, mostly scientific articles (31), human and veterinary anatomy books (17), specialized articles (17) and theses (6). In general, there is consensus on the anatomical description of the spleen, which is located in the left hypochondriac region of the abdomen between the fundus of the stomach and the diaphragm, irrigated by the splenic artery and vein. It was evidenced that there are similarities in macroscopic aspects when comparing the spleen of the white rat with the spleen of other species (functionality, relative weight, topographic location). In microscopic aspects, the spleen in humans and other mammals is composed of stroma, in addition to parenchyma, constituted in turn by white and red pulp. In particular, there are differences between rat, human, cat, dog and pig spleens in shapes, sizes and microscopic aspects related to microcirculation and immunity. While there are similarities in pathological processes and responses to pharmacological and clinical treatments. For the above mentioned, it is concluded that the albino rat constitutes a good biological model, specifically in microscopic anatomical aspects of the spleen of immunological type. While the pig spleen is comparatively better in macroscopic anatomical studies of surgical type, both are extrapolable especially to human medicine.

Kappa opioid receptors mediate an initial aversive component of paclitaxel-induced neuropathy.

RATIONALE: Cancer patients receiving the antineoplastic drug paclitaxel report higher incidences and longer duration of treatment-resistant depression than patients receiving other classes of chemotherapeutics. Rodents treated with paclitaxel exhibit a suite of changes in affect-like behaviors. Further, paclitaxel causes chemotherapy-induced peripheral neuropathy (CIPN) in humans and rodents. Kappa opioid receptors (KOR) have a well-established role in depression and neuropathy. The contributions of KOR signaling to paclitaxel-induced aversive-like state and CIPN in rodents remain to be explored. OBJECTIVES: We aimed to investigate whether dysregulation of the KOR/dynorphin system is associated with paclitaxel-mediated pain-like behavior and depression-like behavior. METHODS: Cancer-free male C57BL/6J mice were treated with four injections of vehicle or paclitaxel (32 mg/kg cumulative). The effects of the selective KOR antagonist norbinaltorphimine (norBNI) on paclitaxel-induced sucrose preference deficits and mechanical hypersensitivity were measured. Prodynorphin mRNA and receptor-mediated G protein activation were measured at two time points following the last paclitaxel injection using quantitative real-time polymerase chain reaction and agonist-stimulated [35S]guanosine-5'-O'-(γ-thio)-triphosphate ([35S]GTPγS) binding, respectively, in the nucleus accumbens (NAc), caudate-putamen, amygdala, and spinal cord. RESULTS: Paclitaxel produced a norBNI-reversible sucrose preference deficit, whereas mechanical hypersensitivity was not reversed by norBNI. Paclitaxel treatment increased the levels of mRNA for prodynorphin, a precursor for endogenous KOR agonists, in the NAc. Paclitaxel also had time-dependent effects on KOR-mediated G protein activation in the NAc. CONCLUSIONS: These results suggest that KOR signaling mediates an initial aversive component of paclitaxel, but not necessarily paclitaxel-induced mechanical hypersensitivity.

Highly HLA Sensitized Kidney Transplant Patients in a Transplant Center.

INTRODUCTION: Approximately 10% to 30% of patients on renal transplant waiting lists are sensitized, which gives them more time on the waiting list. Transplantation in this setting has a greater risk of rejection and decreased graft survival. New strategies of donor allocation through virtual crossmatching and optimization of immunosuppressive therapies in induction and maintenance have allowed the allocation of organs for this population, which in other circumstances would not be chosen for a kidney transplant. OBJECTIVE: To describe the experience of renal transplantation in highly sensitized patients with a panel reactive antibody of >80% in a transplant center, through virtual crossmatching, discarding unacceptable antigens, and without desensitization treatment. METHODS: An observational, descriptive, retrospective case series study was conducted on highly sensitized kidney transplant patients with a panel reactive antibody of ≥80% from 2010 to 2016. RESULTS: A total of 10 highly sensitized transplant patients were identified. Six patients were women, all of whom had a history of pregnancy; all patients had undergone blood transfusions, and 40% had undergone a first transplant. Average time spent on dialysis was 148.5 months, and on the waiting list, 45.8 months. Average follow-up was 42 months (range, 10-84 months). The estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration method at year 1 was 75 mL/min/1.73 m2 body surface. Nine patients at 1 year posttransplantation had graft and patient survivals of 100%, as did 5 patients at >3 years posttransplantation. CONCLUSIONS: Renal transplantation based on virtual crossmatching is a good alternative for highly sensitized patients.

Horse chestnut (Aesculus hippocastanum L.) starch: Basic physico-chemical characteristics and use as thermoplastic material.

Starch isolated from non-edible Aesculus hippocastanum seeds was characterized and used for preparing starch-based materials. The apparent amylose content of the isolated starch was 33.1%. The size of starch granules ranged from 0.7 to 35 µm, and correlated with the shape of granules (spherical, oval and irregular). The chain length distribution profile of amylopectin showed two peaks, at polymerization degree (DP) of 12 and 41-43. Around 53% of branch unit chains had DP in the range of 11-20. A. hippocastanum starch displayed a typical C-type pattern and the maximum decomposition temperature was 317 °C. Thermoplastic starch (TPS) prepared from A. hippocastanum with glycerol and processed by melt blending exhibited adequate mechanical and thermal properties. In contrast, plasticized TPS with glycerol:malic acid (1:1) showed lower thermal stability and a pasty and sticky behavior, indicating that malic acid accelerates degradation of starch during processing.

Pharmacophore design of p38α MAP kinase inhibitors with either 2,4,5-trisubstituted or 1,2,4,5-tetrasubstituted imidazole scaffold.

Synthetic compounds with a tri- and tetra-substituted imidazole scaffold are known as selective inhibitors of the p38 mitogen-activated protein (MAP) kinase responsible for proinflammatory cytokine release. The scope is to review the literature describing their design, synthesis and activity studies. To date a great plethora of crystal structures of p38 in complex with small organic ligands have been published. Cocrystallized ligand information is of particular interest to our review study, i.e. ATP itself, the reference inhibitor SB203580 with its aryl-pyridinyl-imidazoles and related imidazole and pyrimidine-based derivatives. The selective inhibitors bind to the pocket of adenosine 5'-triphoshate (ATP) replacing the latter. The hydrophobic region II, however, is not occupied by the natural binder ATP, but accommodates the pyridine substituents preserving the 4-fluorophenyl ring occupation in pocket I as a prerequisite to gain higher binding selectivity and potency than the reference compound SB203580 (4-[5-(4-fluoro-phenyl)-2-(4-methanesulfinyl-phenyl)-3himidazol-4-yl]-pyridine). Experimental and computed work is reviewed which evidence that the 2 position of the pyrimidine ring is amenable to the introduction of a side chain and the replacement of pyridine in SB203580 by a pyrimidine ring improves both inhibitory activity and selectivity for p38 over other kinases. All ligands with a pyridyl C2 side chain occupy the hydrophobic pocket II and in some cases a double hydrogen bond is reported between methionine 109 and glycine 110 of the hinge region, following an observed backbone shift. The substituted pyridine ring binds stronger than the two other side chains on the imidazole scaffold.

Impact of inappropriate antimicrobial therapy on patients with bacteremia in intensive care units and resistance patterns in Latin America.

Patient care in an intensive care unit (ICU) is associated with an increased risk of developing nosocomial infections. Bacteremia is responsible for a great number of cases, 23% of which have attributable mortality in developed countries and can affect up to 52% of ICU patients. The main cause of mortality is inadequate and inappropriate antimicrobial empirical therapy. The incorrect use of antimicrobials is a major risk for identifying multidrug resistant microorganisms, thereby involving increased morbidity, mortality and costs. Implementing several surveillance systems and becoming acquainted with resistance patterns represent a valuable tool for identifying, preventing and treating this infectious complication. There is paucity of data regarding antimicrobial resistance in bacteremic patients in Latin America, and the available data reveals a worrying scenario.

Impact of inappropriate antimicrobial therapy on patients with bacteremia in intensive care units and resistance patterns in Latin America / Impacto de la terapia antimicrobiana inapropiada en pacientes con bacteriemia en unidades de cuidado intensivo y patrones de resistencia en América Latina

Patient care in an intensive care unit (ICU) is associated with an increased risk of developing nosocomial infections. Bacteremia is responsible for a great number of cases, 23% of which have attributable mortality in developed countries and can affect up to 52% of ICU patients. The main cause of mortality is inadequate and inappropriate antimicrobial empirical therapy. The incorrect use of antimicrobials is a major risk for identifying multidrug resistant microorganisms, thereby involving increased morbidity, mortality and costs. Implementing several surveillance systems and becoming acquainted with resistance patterns represent a valuable tool for identifying, preventing and treating this infectious complication. There is paucity of data regarding antimicrobial resistance in bacteremic patients in Latin America, and the available data reveals a worrying scenario.

El manejo médico en la unidad de cuidado intensivo (UCI) se asocia con un mayor riesgo de infecciones intrahospitalarias. Las bacteriemias tienen una alta frecuencia en dichas unidades, se presentan hasta en el 52% de los pacientes allí asistidos y en los países desarrollados se les atribuye una mortalidad del 23%, que se debe fundamentalmente al uso de tratamiento empírico inadecuado o inapropiado. El uso incorrecto de los antimicrobianos es uno de los principales factores de riesgo para el desarrollo de la resistencia bacteriana, que conlleva la selección de microorganismos multirresistentes, el aumento de la morbilidad y la mortalidad y el incremento en los días de estancia hospitalaria y del costo por hospitalización. La implementación de diferentes sistemas de vigilancia y el conocimiento de la variabilidad en la resistencia a los antimicrobianos constituyen valiosas herramientas para identificar y prevenir la resistencia a los antibióticos y para orientar la terapéutica. En América Latina disponemos de pocos datos sobre las tasas de resistencia y aquellos disponibles muestran un panorama preocupante.

The impact of tobacco smoking on perinatal outcome among patients with gestational diabetes.

OBJECTIVE: To determine the effects of tobacco use on perinatal outcomes among patients with gestational diabetes (GDM). STUDY DESIGN: This was a retrospective cohort study of singleton pregnancies with GDM and live births from 2003 to 2006. The primary outcome, large for gestational age (LGA) infants, was compared between smoking and nonsmoking groups. Secondary outcomes included cesarean deliveries, shoulder dystocia, birth trauma, peripartum complications, macrosomia, 5-min Apgar score < or =3, birth defects, and neonatal intensive care unit (NICU) admissions. chi(2) and Student t-tests compared the two groups; a P-value <0.05 was statistically significant and odds ratios (OR) were reported with 95% confidence intervals (CI). A multivariate logistic regression analysis controlled for variables known to affect outcomes in GDM. RESULT: We identified 915 patients with GDM, of which 130 (14.2%) smoked during pregnancy. Women who smoked during pregnancy were less likely to have LGA infants (22.4 vs 31.2%; OR, 0.61; 95% CI, 0.39 to 0.95). In a logistic regression analysis, the inverse relationship between smoking and LGA persisted (OR, 0.59; 95% CI, 0.36 to 0.97) after controlling for maternal age, multiparity, ethnicity, weight status before pregnancy, weight gain during pregnancy, and male gender. Preterm labor, preeclampsia, Cesareans, shoulder dystocia, and birth trauma were similar in both groups. PPROM was more likely to occur in nonsmokers (0 vs 4%, P=0.03), but postpartum hemorrhage was more common among smokers (OR, 2.3; 95% CI, 1.02 to 5.31). Macrosomia, low 5-min Apgar score, birth defects, and NICU admissions were similar between the groups. CONCLUSION: Patients with GDM who smoke during pregnancy were 40% less likely to have LGA infants. However, smoking was not protective of other common morbidities associated with GDM.

Pigment epithelium-derived factor overexpression inhibits orthotopic osteosarcoma growth, angiogenesis and metastasis.

Despite significant improvements, the current management of primary osteosarcoma is still limited by the development of metastatic disease, which occurs in approximately 30% of patients despite aggressive multiagent chemotherapy and tumor-ablative surgery. Therefore, there is a need for the development of novel agents to improve the outcome of these patients. Pigment epithelium-derived factor (PEDF) has been shown to be one of the most potent inhibitors of angiogenesis, and more recently has demonstrated a functional role in tumor growth, invasion and metastasis. In this study we report, for the first time, the multitargeted role of PEDF in the inhibition of growth, angiogenesis and metastasis of two orthotopic models of osteosarcoma (rat UMR 106-01 and human SaOS-2). Through stable plasmid-mediated gene transfer of full-length human PEDF, we show that PEDF overexpression significantly reduced tumor cell proliferation (P<0.05) and Matrigel invasion (UMR(PEDF), P<0.001; SaOS(PEDF), P<0.05) and increased adhesion to collagen type-1 (P<0.01), in vitro. In vivo, PEDF overexpression dramatically suppressed orthotopic osteosarcoma growth (P<0.05) and the development of spontaneous pulmonary metastases (UMR(PEDF), P<0.05; SaOS(PEDF), P<0.001). Furthermore, PEDF-overexpressing tumors exhibited reduced intratumoral angiogenesis, evidenced by a significant decrease in microvessel density (P<0.05). Therefore, together these results suggest that PEDF may be a new and promising approach for the treatment of osteosarcoma.

Cyclospora cayetanensis in three populations at risk in Guatemala.

In 1996 and 1997, outbreaks of Cyclospora cayetanensis in North America were linked to Guatemalan raspberries. From April 1999 to April 2000, we undertook a survey for C. cayetanensis in raspberry farm workers, malnourished children, and human immunodeficiency virus and AIDS patients in Guatemala. Stool samples were analyzed using ethylacetate-formalin concentration, wet preparation, modified acid-fast staining method, and epifluorescence. Oocysts were found in 1.5% of the subjects, none of whom were raspberry farm workers.

Evaluación comparativa de la eficacia y tolerancia del cefadroxilo vs oxacilina en el tratamiento de las infecciones de piel y tejido blandos / Evaluation comparation of the efficacy and tolerance of cefadroxil vs oxacilin in the treatment of the skin infections and soft tissue

Comparar la eficacia y tolerabilidad del cefadroxilo contra la oxacilina en el tratamiento de las infecciones de piel y tejidos blandos. Realizamos un estudio controlado aleatorizado, simple ciego, de grupos de paralelo, donde se incluyeron un total de 64 pacientes adultos divididos al azar en dos grupos para recibir cefadroxilo (31 pacientes) u oxacilina (33 pacientes). Se practicó examen clínico basal que incluyó evaluación local de la lesión con escala de inflamación estandarizada a 15 puntos, temperatura corporal y contaje leucocitario. Esta evaluación se repitió a las 48 horas, al 4to. día y día 10 de ser necesario. En la comparación de efectividad se consideraron parámetros de curación clínica y fracaso terapéutico, además de modificaciones en el score de inflamación, temperatura y contaje blanco. Se comprobó curación definitiva de 89 por ciento de los casos con cefadroxilo, que fue superior al grupo tratado con oxacilina que presentó curación en el 78,8 por ciento. El fracaso terapéutico fue del 12,9 por ciento con cefadroxilo y 21,2 por ciento en el grupo de la oxacilina. La comparación intragrupal del día 0 vs día 2 y día 0 vs día 4, demostraron una reducción significativa en la escala de inflamación de los dos grupos de tratamiento. Ambos tratamientos lograron una mejoría clínica significativa del cuadro inflamatorio en 5 a 6 días, permitiendo el paso del tratamiento de la vía parenteral a la oral en ese lapso. La curación definitiva fue lograda en un promedio de 8 días. No hubo diferencias en el descenso de la temperatura corporal en ambos grupos. El contaje blanco mostró descenso notable y sostenido en los dos grupos, alcanzando significación en los días 2 y 4 del tratamiento. Solo dos pacientes en cada grupo fueron retirados por efectos adversos (cefadroxilo 6,45 por ciento y oxacilina 6,06 por ciento). El cefadroxilo fue mas efectivo que la oxacilina en el tratamiento de infecciones leves a moderadas de piel y partes blandas, bajo los rangos de dosis planteados para los medicamentos en estudios. Oxacilina mostró mayor porcentaje de fracaso en comparación al cefadroxilo. Sin embargo, los pacientes que alcanzaron curación clínica con oxacilina, lo realizaron en un lapso de tiempo mas corto. El cefadroxilo y la oxacilina fueron medicamentos seguros en el tratamiento de infecciones de piel y partes blandas, mostrando una proporción comparable y aceptable de efectos adversos

Identification of 4-(N,N-dipropylamino)benzaldehyde as a potent, reversible inhibitor of mouse and human class I aldehyde dehydrogenase.

As the physiologic roles for the different classes of aldehyde dehydrogenase (ALDH) enzymes are elucidated, the identification of specific, reversible inhibitors becomes of great pharmacologic interest. Previous structure-function studies identified dialkylamino substituted benzaldehyde compounds as a novel class of reversible inhibitors of class I ALDH. To examine further structural requirements for inhibition, we tested a series of 4-(N,N-dialkylamino)benzaldehyde analogs as inhibitors of propanal oxidation by mouse liver and human erythrocyte class I ALDH. 4-(N,N-dipropylamino)benzaldehyde (DPAB) was identified as the most potent, reversible inhibitor of propanal oxidation by class I ALDH in spectrophotometric enzyme assays. In kinetic studies, DPAB showed mixed-type inhibition with respect to the aldehyde substrates propanal, phenylacetaldehyde, benzaldehyde, and aldophosphamide. DPAB exhibited uncompetitive inhibition with respect to the cofactor NAD. Inhibition constants (Ki) for DPAB, estimated from Dixon plots, were 10 nM (propanal) and 77 nM (phenylacetaldehyde) for mouse ALDH and 3 nM (propanal) and 70 nM (phenylacetaldehyde) for human ALDH. These Ki values are 100-fold lower than those reported for class I specific inhibitors. At low (< 1 microM) DPAB concentrations, inhibition of propanal and aldophosphamide oxidation was > 75%, whereas inhibition of benzaldehyde (32%) and phenylacetaldehyde (19%) oxidation was reduced markedly. These results indicate that DPAB exhibits potent, reversible inhibition of mouse and human class I ALDH. The degree of inhibition was highly dependent on the structure of the aldehyde substrate.