Autocrine and paracrine purinergic signaling in the most lethal types of cancer.

Cancer comprises a collection of diseases that occur in almost any tissue and it is characterized by an abnormal and uncontrolled cell growth that results in tumor formation and propagation to other tissues, causing tissue and organ malfunction and death. Despite the undeniable improvement in cancer diagnostics and therapy, there is an urgent need for new therapeutic and preventive strategies with improved efficacy and fewer side effects. In this context, purinergic signaling emerges as an interesting candidate as a cancer biomarker or therapeutic target. There is abundant evidence that tumor cells have significant changes in the expression of purinergic receptors, which comprise the G-protein coupled P2Y and AdoR families of receptors and the ligand-gated ion channel P2X receptors. Tumor cells also exhibit changes in the expression of nucleotidases and other enzymes involved in nucleotide metabolism, and the concentrations of extracellular nucleotides are significantly higher than those observed in normal cells. In this review, we will focus on the potential role of purinergic signaling in the ten most lethal cancers (lung, breast, colorectal, liver, stomach, prostate, cervical, esophagus, pancreas, and ovary), which together are responsible for more than 5 million annual deaths.

A chemical status predictor. A methodology based on World-Wide sediment samples.

As a consequence of the limited resources of underdeveloped countries and the limited interest of the developed ones, the assessment of the chemical quality of entire water bodies around the world is a utopia in the near future. The methodology described here may serve as a first approach for the fast identification of water bodies that do not meet the good chemical status demanded by the European Water Framework Directive (WFD). It also allows estimating the natural background (or reference values of concentration) of the areas under study using a simple criterion. The starting point is the calculation the World-Wide Natural Background Levels (WWNBLs) and World-Wide Threshold Values (WWTVs), two indexes that depend on the concentration of seven elements present in sediments. These elements, As, Cd, Cr, Cu, Ni, Pb and Zn, have been selected taking into account the recommendations of the UNEP (United Nations Environment Programme) and USEPA (United States Environmental Protection Agency), that describe them as elements of concern with respect to environmental toxicity. The methodology has been exemplified in a case study that includes 134 sediment samples collected in 11 transitional water bodies from 7 different countries and 4 different continents. Six of the water bodies considered met the good chemical status demanded by the WFD. The rest of them exceeded the reference WWTVs, at least for one of the elements. The estuaries of the Nerbioi-Ibaizabal (Basque Country) and Cavado (Portugal), the sea inlet of Río San Pedro (Spain), the Sepetiba Bay (Brazil) and the Yucateco lagoon (Mexico) belong to that group.

Brazilian coal mining residues and sulphide oxidation by Fenton's reaction: an accelerated weathering procedure to evaluate possible environmental impact.

Fenton's reaction is proposed as an accelerated weathering test for sulphides associated with Brazilian Coal Mining Residues (CMR), that are exposed to oxygen and water during the mining of coal. TEM and SEM/EDX were used to evaluate the nature, occurrence and distribution of minerals in remaining coals and other lithological units, before and after applying the test. Oxidation of CMRs was examined by analyzing soluble sulphur (sulphate) and dissolved metals by ICP-MS or ICP OES. As dissolved sulphate increases, dissolved Zn, Cd, Cu and Co concentrations increase, leading to undetectable amounts in the remaining solid phases; dissolved Ni and Mn also increase with the mobilized sulphur, but the remainder in the solids is the most important fraction; Fe and Pb are not mobilized due to precipitation as jarosite or hematite in the case of Fe or as sulphate in the case of Pb. Agreement between the observed results and the predictions by geochemical modelling is discussed.

[First isolation of Histoplasma capsulatum from the urban bat Eumops bonariensis]. / Primer aislamiento de Histoplasma capsulatum de murciélago urbano Eumops bonariensis.

We report the first isolation of Histoplasma capsulatum var. capsulatum from a male bat Eumops bonariensis captured in Buenos Aires city in 2003. The pathogen was recovered from spleen and liver specimens, and was identified by its phenotypic characteristics. PCR with primers 1283, (GTG)5, (GACA)4 and M13 was used to compare both bat isolates with 17 human isolates, 12 from patients residing in Buenos Aires city, and 5 from other countries of the Americas. The profiles obtained with the four primers showed that both bat isolates were identical to each other and closer to Buenos Aires patients than to the other isolates (similarity percentage: 91-100% and 55-97%, respectively). The high genetic relationship between bat isolates and those from patients living in Buenos Aires suggests a common source of infection. This is the first record of E. bonariensis infected with H. capsulatum in the world, and the first isolation of the fungus in the Argentinean Chiroptera population. In the same way as these wild mammals act as reservoir and spread the fungus in the natural environment, infection in urban bats could well be associated with the increase in histoplasmosis clinical cases among immunosuppressed hosts in Buenos Aires city.

Primer aislamiento de Histoplasma capsulatum de murciélago urbano Eumops bonariensis / First isolation of Histoplasma capsulatum from the urban bat Eumops bonariensis

Se comunica el primer aislamiento de Histoplasma capsulatum var. capsulatum de un murciélago macho de la especie Eumops bonariensis, capturado en la ciudad de Buenos Aires en 2003. Los aislamientos fueron recuperados de bazo e hígado e identificados fenotípicamente. Se los comparó por PCR, con 17 aislamientos clínicos, 12 de pacientes residentes en la ciudad de Buenos Aires y cinco de otros países de América, usando los iniciadores 1283, (GTG)5, (GACA)4 y M13. Con los cuatro iniciadores, los perfiles de los aislamientos de murciélago resultaron idénticos entre sí y más relacionados a los de pacientes de Buenos Aires que a los de otros países (porcentaje de similitud: 91-100% y 55-87%, respectivamente). La alta relación genética entre los aislamientos obtenidos del murciélago y de los humanos residentes en Buenos Aires sugiere una fuente común de infección. Este es el primer registro de E. bonariensis infectado con H. capsulatum en el mundo, y el primer aislamiento del hongo en la población de quirópteros de la Argentina. Así como estos mamíferos actúan como reservorio y dispersan el hongo en la naturaleza, la infección en murciélagos urbanos podría asociarse al elevado número de casos de histoplasmosis entre pacientes inmunodeprimidos en la ciudad de Buenos Aires.

We report the first isolation of Histoplasma capsulatum var. capsulatum from a male bat Eumops bonariensis captured in Buenos Aires city in 2003. The pathogen was recovered from spleen and liver specimens, and was identified by its phenotypic characteristics. PCR with primers 1283, (GTG)5, (GACA)4 and M13 was used to compare both bat isolates with 17 human isolates, 12 from patients residing in Buenos Aires city, and 5 from other countries of the Americas. The profiles obtained with the four primers showed that both bat isolates were identical to each other and closer to Buenos Aires patients than to the other isolates (similarity percentage: 91-100% and 55-97%, respectively). The high genetic relationship between bat isolates and those from patients living in Buenos Aires suggests a common source of infection. This is the first record of E. bonariensis infected with H. capsulatum in the world, and the first isolation of the fungus in the Argentinean Chiroptera population. In the same way as these wild mammals act as reservoir and spread the fungus in the natural environment, infection in urban bats could well be associated with the increase in histoplasmosis clinical cases among immunosuppressed hosts in Buenos Aires city.

Primer aislamiento de Histoplasma capsulatum de murciélago urbano Eumops bonariensis. / [First isolation of Histoplasma capsulatum from the urban bat Eumops bonariensis]

We report the first isolation of Histoplasma capsulatum var. capsulatum from a male bat Eumops bonariensis captured in Buenos Aires city in 2003. The pathogen was recovered from spleen and liver specimens, and was identified by its phenotypic characteristics. PCR with primers 1283, (GTG)5, (GACA)4 and M13 was used to compare both bat isolates with 17 human isolates, 12 from patients residing in Buenos Aires city, and 5 from other countries of the Americas. The profiles obtained with the four primers showed that both bat isolates were identical to each other and closer to Buenos Aires patients than to the other isolates (similarity percentage: 91-100

and 55-97

, respectively). The high genetic relationship between bat isolates and those from patients living in Buenos Aires suggests a common source of infection. This is the first record of E. bonariensis infected with H. capsulatum in the world, and the first isolation of the fungus in the Argentinean Chiroptera population. In the same way as these wild mammals act as reservoir and spread the fungus in the natural environment, infection in urban bats could well be associated with the increase in histoplasmosis clinical cases among immunosuppressed hosts in Buenos Aires city.

[Helicobacter pylori: cagA analysis and vacA genotyping in Chile. Detection of a s2/m1 strain]. / Helicobacter pylori: análisis de cagA y genotipificación de vacA en Chile. Detección de una cepa s2/m1.

BACKGROUND: The genes cagA and vacA encode H pylori virulence factors. AIM: To genotype these genes in H pylori strains isolated from patients with upper gastrointestinal symptoms. MATERIAL AND METHODS: We studied 50 patients who underwent an upper gastrointestinal endoscopy, with positive culture for H pylori. Detection of cagA and vacA genotyping was done using polymerase chain reactions. RESULTS: The gene cagA was detected in 19 samples (38%). Signal sequences s1 and s2 of vacA gene were detected in 16 samples each (32%). There was simultaneous amplification of s1 and s2 in 6 samples and they were not detected in 9 samples. The middle region of vacA was m1 in 9 samples, m2 in 29 samples and there was simultaneous amplification of m1 and m2 in 12 samples. In 16 samples (32%), more than one type of signal sequence or medial region was detected. Of those patients in whom vacA was the only genotype detected, 15 were s2/m2, 7 were s1/m1, 4 were s1/m2 and 1 was s2/m1. CONCLUSIONS: In these patients, the infection with cagA- H pylori strains, predominates, the prevalence of infection with s1 or s2 strains is similar and the predominant medial region is m2.

[Factors that affect DNA content analysis by flow cytometry]. / Aspectos que afectan el análisis de contenido de ADN por citometría de flujo.

DNA ploidy and cell cycle analysis by flow cytometry is used to obtain additional information about the diagnosis and prognosis of different types of cancer. However, there are several disagreements among authors about the tissue source (fresh-frozen or paraffin embedded), cellular dissociation methods (mechanical, enzymatic or other), use of different dyes, lasers, analysis software with different mathematical models and interpretation of results. A discussion about the different aspects that affect the study of DNA ploidy and cell cycle and a consensus in publications is mandatory. A strict control of analysis processes and data interpretation is also necessary.

[Intestinal permeability in the first year of life. The effect of diarrhea]. / Permeabilidad intestinal en el primer año de vida. Efecto de la diarrea.

OBJECTIVE: The permeability of the intestinal mucosa to lactulose and mannitol was explored longitudinally in infants at 1, 3-4 and 11-12 months of age. This was also evaluated during the episodes of diarrhea that they suffered during follow-up. PATIENTS AND METHODS: Sugar excretion was measured by gas chromatography in five-hour urine samples. RESULTS: A decrease in lactulose excretion was observed, which became significant at 11-12 months of age (p = 0.02). No changes were detected in mannitol excretion, although this showed a tendency to decrease. The lactulose/mannitol (L/M) ratio remained unchanged. During the 15 episodes of diarrhea observed in these infants during the 12 month follow-up, a considerable increase in this ratio was seen, due mainly to increased lactulose excretion. CONCLUSIONS: It is hypothesized that the decrease in lactulose excretion between one and 11-12 months of age is part of the maturational process of the intestinal barrier, while diarrhea results in increased permeability due to damage to the absorptive epithelium.

Orthotopic liver transplantation for benign hepatic neoplasms.

OBJECTIVE: To evaluate the frequency and outcome of liver transplantation for symptomatic, unresectable, benign hepatic neoplasms. DESIGN: Retrospective study. SETTING: Presbyterian University Hospital, a tertiary care referral center for liver transplantation affiliated with the University of Pittsburgh (Pa). PATIENTS: All 3239 liver transplant recipients at the University of Pittsburgh from January 1981 until January 1993. RESULTS: Twelve (0.37%) of 3239 patients required liver transplantation for benign, highly symptomatic hepatic neoplasms that were unresectable. Origins included adenoma (n = 6), mesenchymal hamartoma (n = 2), massive hepatic lymphangiomatosis (n = 1), hilar fibrous angiodysplasia (n = 1), focal nodular hyperplasia (n = 1), and hemangioma (n = 1). There were three perioperative deaths and two late deaths at 56 and 84 months. The remaining patients are alive, with follow-up ranging from 36 to 145 months. Median survival for the nine patients who survived the perioperative period is 88 months. The early deaths were attributable to hemorrhagic complications (n = 2) and necrotizing pancreatitis (n = 1). The two late deaths were due to disseminated aspergillosis and hepatitis-associated cirrhosis. CONCLUSION: Patients with severe symptoms from benign hepatic neoplasms that are not resectable can be treated by total hepatectomy and orthotopic liver transplantation, with the expectation of good long-term results.

Experience in hepatic resection for metastatic colorectal cancer: analysis of clinical and pathologic risk factors.

BACKGROUND: The selection of patients for resective therapy of hepatic colorectal metastases remains controversial. A number of clinical and pathologic prognostic risk factors have been variably reported to influence survival. METHODS: Between January 1981 and December 1991, 204 patients underwent curative hepatic resection for metastatic colorectal cancer. Fourteen clinical and pathologic determinants previously reported to influence outcome were examined retrospectively. This led to a proposed TNM staging system for metastatic colorectal cancer (mTNM). RESULTS: No operative deaths occurred (death within 1 month). Overall 1-, 3-, and 5-year survivals were 91%, 43%, and 32%, respectively. Gender, Dukes' classification, site of primary colorectal cancer, histologic differentiation, size of metastatic tumor, and intraoperative blood transfusion requirement were not statistically significant prognostic factors (p > 0.05). Age of 60 years or more, interval of 24 months or less between colorectal and hepatic resection, four or more gross tumors, bilobar involvement, positive resection margin, lymph node involvement, and direct invasion to adjacent organs were significant poor prognostic factors (p < 0.05). In the absence of nodal disease or direct invasion, patients with unilobar solitary tumor of any size, or unilobar multiple tumors of 2 cm or smaller (stages I and II) had the highest survival rates of 93% at 1 year, 68% at 3 years, and 61% at 5 years. Unilobar disease with multiple lesions greater than 2 cm (stage III) resulted in 1-, 3-, and 5-year survivals of 98%, 45%, and 28%, respectively. Patients with bilobar involvement (multiple tumors, any size, or a single large metastasis) (stage IVA) had survival rates of 88% at 1 year, 28% at 3 years, and 20% at 5 years (p < 0.00001). Patients with nodal involvement or extrahepatic disease (stage IVB) experienced the poorest outcome with 1-, 3-, and 5-year survivals of 80%, 12%, and 0%, respectively (p < 0.00001). CONCLUSIONS: The proposed mTNM staging system appears to be useful in predicting the outcomes after hepatic resection of metastatic colorectal tumors.

Corrective treatment and anatomic considerations for laparoscopic cholecystectomy injuries.

BACKGROUND: Complete reports of biliary and vascular injuries after laparoscopic cholecystectomy are rare. STUDY DESIGN: Fifteen patients with complex laparoscopic cholecystectomy injuries underwent corrective operations. The injuries consisted of 14 bile duct injuries and one large laceration of a cirrhotic liver. Five of the bile duct injuries were accompanied by inadvertent occlusion of the right hepatic artery, and one was further complicated by portal vein occlusion. One hepatic artery occlusion and one portal vein occlusion were successfully reconstructed. Two patients with arterial occlusion required right hepatic lobectomy. Corrective biliary operations consisted of common hepaticojejunostomy (seven cases), right and left hepaticojejunostomies (one case), right anterior and left hepaticojejunostomies (two cases), right hepaticojejunostomy (one case), right posterior hepaticojejunostomy (one case), and left hepaticojejunostomy after right lobectomy (two cases). RESULTS: Except for a patient with a severe laceration of a cirrhotic liver who died as a result of hepatic failure, the remaining 14 patients are alive and well with normal hepatic function tests at six and 37 months after corrective operations. CONCLUSIONS: A knowledge of anatomy is critical to the prevention of injuries to the hepatobiliary tree and related structures during laparoscopic cholecystectomy.

Tórax volante: análisis prospectivo de 40 casos / Flail chest: prospective analysis of 40 cases

Con el propósito de analizar el pronóstico del tórax volante se estudiaron 40 casos, separando dos grupos. Grupo A (n=12) pacientes sólo con lesiones intratorácicas, y Grupo B (n=28) pacientes con lesiones extratorácicas asociadas. En el Grupo B, 20 pacientes (71,4%) presentaron un TEC asociado; 7 de éstos además tenían fracturas de extremidades o pelvis y 4 una contusión abdominal complicada. Se operaron 11 pacientes - 7 toracotomizados -; la morbilidad fue de 42,7%y fallecieron 3 pacientes (10,7%). Se concluye que el tórax volante sin lesiones extratorácicas es de buen pronóstico, éste se ensombrece cuando se acompaña de lesiones de órganos extratorácicos

Contusión pulmonar: análisis prospectivo de 57 casos / Lung contusion: prospective analysis of 57 cases

Con el objeto de analizar el pronóstico de la contusión pulmonar estudiamos 57 pacientes diagnosticados por radiología. Se analizaron dos grupos, Grupo A: (n=18) pacientes con lesiones circunscritas al tórax y Grupo B: (n=39) pacientes con lesiones extratorácicas asociadas. Grupo A: la edad fluctuó entre 24 y 80 años, promedio 50,44. Presentaron fracturas costales 17 pacientes (94,4%), tórax volante 4 (22%), hemotórax 16 (88,9%), no hubo mortalidad. Grupo B: la edad fluctuó entre 12 y 66 años promedio 40.10 (25,6%) ingresaron en shock. El 100% tenía fracturas costales, 20 tórax volante (51,3%), 32 (82,1%) presentaron ocupación pleural, 5 bilaterales. Fallecieron 3 pacientes. Conclusión. El pronóstico de la contusión pulmonar es bueno cuando el trauma se circuncribe al toráx; éste se ensombrece cuando se asocia a lesiones extratorácicas