Increased aquaporin 1 expression in the tunica albuginea of Peyronie's disease patients: an in vivo pilot study.

Peyronie's disease (PD) is a localized disorder of the connective tissue of the tunica albuginea (TA) whose etiology has not been elucidated. Although several studies have implicated genetic susceptibility and/or mechanical trauma as triggering events for PD, the underlying molecular mechanisms remain largely unknown. Aquaporin 1 (AQP1) is a water channel protein potentially implicated in connective tissue resistance to mechanical stress, acting primarily by increasing tension within the collagen network. Although it represents a potentially attractive molecular target in PD, to date no studies had ever addressed whether AQP1 is detectable and/or differentially expressed in the TA of these patients. Herein the present study, through immunohistochemical and biochemical approaches, we were able to detect AQP1 expression in the TA of control and PD affected patients. We demonstrated that AQP1-like immunoreactivity and expression are significantly increased in plaques of PD patients Vs controls, implying that AQP1 overexpression might be the consequence of a localized maladaptive response of the connective tissue to repeated mechanical trauma. In summary, these data support the idea that AQP1 might represent a potentially useful biomarker of mechanical injury in the TA and a promising target for the treatment of PD.

Genetic blockade of the dopamine D3 receptor enhances hippocampal expression of PACAP and receptors and alters their cortical distribution.

Dopamine D3 receptors (D3Rs) are implicated in several aspects of cognition, but their role in aversive conditioning has only been marginally uncovered. Investigations have reported that blockade of D3Rs enhances the acquisition of fear memories, a phenomenon tightly linked to the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP). However, the impact of D3R ablation on the PACAPergic system in regions critical for the formation of new memories remains unexplored. To address this issue, levels of PACAP and its receptors were compared in the hippocampus and cerebral cortex (CX) of mice devoid of functional D3Rs (D3R(-/-)) and wild-types (WTs) using a series of comparative immunohistochemical and biochemical analyses. Morphometric and stereological data revealed increased hippocampal area and volume in D3R(-/-) mice, and augmented neuronal density in CA1 and CA2/3 subfields. PACAP levels were increased in the hippocampus of D3R(-/-) mice. Expression of PACAP receptors was also heightened in mutant mice. In the CX, PACAP immunoreactivity (IR), was restricted to cortical layer V in WTs, but was distributed throughout layers IV-VI in D3R(-/-) mice, along with increased mRNAs, protein concentration and staining scores. Consistently, PAC1, VPAC1 and VPAC2 IRs were variably redistributed in CX, with a general upregulation in cortical layers II-IV in knockout animals. Our interpretation of these findings is that disturbed dopamine neurotransmission due to genetic D3R blockade may enhance the PACAP/PAC1-VPAC axis, a key endogenous system for the processing of fear memories. This could explain, at least in part, the facilitated acquisition and consolidation of aversive memories in D3R(-/-) mice.

Assessing environmental impacts of constructed wetland effluents for vegetable crop irrigation.

The objective of this study was to monitor and assess environmental impacts of reclaimed wastewater (RW), used for irrigation of vegetable crops, on soil, crop quality and irrigation equipment. During 2013, effluents of a horizontal sub-surface flow constructed treatment wetland (TW) system, used for tertiary treatment of sanitary wastewater from a small rural municipality located in Eastern Sicily (Italy), were reused by micro-irrigation techniques to irrigate vegetable crops. Monitoring programs, based on in situ and laboratory analyses were performed for assessing possible adverse effects on water-soil-plant systems caused by reclaimed wastewater reuse. In particular, experimental results evidenced that Escherichia coli content found in RW would not present a risk for rotavirus infection following WHO (2006) standards. Irrigated soil was characterized by a certain persistence of microbial contamination and among the studied vegetable crops, lettuce responds better, than zucchini and eggplants, to the irrigation with low quality water, evidencing a bettering of nutraceutical properties and production parameters.

Dopamine D3 receptor deletion increases tissue plasminogen activator (tPA) activity in prefrontal cortex and hippocampus.

Considerable evidence indicates that dopamine (DA) influences tissue plasminogen activator (tPA)-mediated proteolytic processing of the precursor of brain-derived neurotrophic factor (proBDNF) into mature BDNF (mBDNF). However, specific roles in this process for the dopamine D3 receptor (D3R) and the underlying molecular mechanisms are yet to be fully characterized. In the present study, we hypothesized that D3R deletion could influence tPA activity in the prefrontal cortex and hippocampus. Using D3R knockout (D3(-/-)) mice, we show that receptor inactivation is associated with increased tPA expression/activity both in the prefrontal cortex and, to a greater extent, in the hippocampus. Augmented tPA expression in D3(-/-) mice correlated with increased BDNF mRNA levels, plasmin/plasminogen protein ratio and the conversion of proBDNF into mBDNF, as well as enhanced tPA and mBDNF immunoreactivity, as determined by quantitative real time polymerase chain reaction (qRT-PCR), immunoblot and immunohistochemistry. In addition, when compared to wild-type controls, D3(-/-) mice exhibited increased basal activation of the canonical cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)-driven Akt/cAMP-response element-binding protein (CREB) signaling cascade, as determined by the increased Akt phosphorylation both at Thr304 and Ser473 residues, of DA and cAMP-regulated protein of 32kDa (DARPP-32) at Thr34 and a phosphorylation state-dependent inhibition of glycogen synthetase kinase-3ß (GSK-3ß) at Ser9, a substrate of Akt whose constitutive function impairs normal CREB transcriptional activity through phosphorylation at its Ser129 residue. Accordingly, CREB phosphorylation at Ser133 was significantly increased in D3(-/-) mice, whereas the GSK-3ß-dependent phosphorylation at Ser129 was diminished. Altogether, our finding reveals that mice lacking D3Rs show enhanced tPA proteolytic activity on BDNF which may involve, at least in part, a potentiated Akt/CREB signaling, possibly due to hindered GSK-3ß activity.

Epidermal growth factor receptor (EGFR) and neuregulin (Neu) activation in human airway epithelial cells exposed to nickel acetate.

Nickel compounds are potential carcinogenic agents that produce a range of biological effects, including inhibition of cell death. Because suppression of apoptosis is thought to contribute to the initiation of carcinogenesis, we investigated the effects of nickel acetate (Ni(2+)) treatment on apoptosis in two different airway epithelial cell lines (A549 and Beas-2B, respectively). Furthermore, since both the epidermal growth factor receptor (EGFR) and neuregulin (Neu) are involved in neoplastic development, mRNAs and expression levels of total and phosphorylated proteins (p-EGFR(Tyr1173) and p-Neu(Tyr1248), respectively) were also measured. We found that exposure of A549 cells to Ni(2+) resulted in significantly reduced cell viability, as well as increased apoptosis and DNA fragmentation at relatively low concentrations (0.1 and 0.5mM) after 24 and 48h. These changes were accompanied by reduced EGFR and Neu mRNAs and proteins, phosphorylated proteins as well as decreased Bcl-2 and increased BAX protein expression. Conversely, Beas-2B cells exposed to equivalent concentrations of Ni(2+) did not show evident signs of apoptosis and DNA damage, hence showing increased expression and phosphorylation of both EGFR and Neu, increased Bcl-2 and reduced BAX expression. Altogether, our finding indicate that Ni(2+) exposure differently affects apoptosis initiation either in non-tumorigenic (Beas-2B) and tumorigenic airway epithelial cells (A549), suggesting a potential involvement of EGFR/Neu receptors.

Protective effect of the dopamine D(3) receptor agonist (7-OH-PIPAT) against apoptosis in malignant peripheral nerve sheath tumor (MPNST) cells.

Emerging evidence indicates that the dopamine D(3) receptor (D(3)R) mediates protective roles both in neuronal and non-neuronal cell lines. In a previous study we proposed that neurofibromin, a large tumor suppressor protein encoded by the neurofibromatosis type 1 gene (NF1), may increase susceptibility to apoptosis after serum deprivation in malignant peripheral nerve sheath tumor (MPNST) cells, thus acting as a proapoptotic gene. In addition, it has been observed that D(3)Rs are functionally correlated to neurofibromin. In this study, we examined whether 7-OH-PIPAT, a potent dopamine D(3)R agonist, exerts an antiapoptotic role under the same culture conditions and then correlated this effect to changes in NF1 expression. Results showed that serum deprivation caused a significant reduction of cell viability (MTT assay) both after 24 and 48 h (p<0.001). Treatment with increasing concentrations of 7-OH-PIPAT (10(-9)-10(-5) M) induced a progressive increase in cell viability both after 24 and 48 h as compared to vehicle-treated cells, with significant changes at the highest concentrations tested (10(-6) and 10(-5) M). Consistently, at the latter two concentrations, a significant reduction in oligonucleosomes formation was observed, thus suggesting an antiapoptotic role of 7-OH-PIPAT. These results were confirmed by Hoechst 33254 nuclear staining. To investigate whether these effects were correlated to changes in NF1 transcript and protein expression, quantitative real-time PCR, Western blot and immunofluorescence analyses were performed. Results demonstrated that the upregulation of NF1 transcripts and protein levels induced by serum withdrawal were remarkably attenuated by 10(-6) and 10(-5) M agonist treatment within 24 h (p<0.01 and p<0.001, respectively), whereas similar effects were observed already at a lower concentration (10(-7) M) after 48 h treatment (p<0.001). In conclusion, these results suggest that D(3)R might mediate the protective response to serum deprivation in MPNST cells through the inhibition of NF1 gene expression, further underlying a subtle role of these receptors in MPNST development.

Expression profile of ErbB receptor's family in human alveolar type 2-like cell line A549 exposed to hexavalent chromium.

Occupational exposure to hexavalent chromium (Cr (VI)) compounds is associated with increased risk of pulmonary disease. In the present study we have investigated temporal expression of ErbB's receptors family in A549 cells after exposure to Cr (VI). Treatment with 10 microM or 300 microM of Na2CrO4 induced apoptotic cell death within 24h. Based on data obtained by ELISA cell death detection method and fluorescence microscopy, the concentration of 10 microM was chosen to study the expression of ErbB receptors family. Such concentration reflects a condition of acute toxicity in which cells survived up to 24h. Real time quantitative PCR has been performed to analyze the expression profiles of ErbB family genes following chromium toxicity. The expression of EGFR and ErbB2 receptors was significantly reduced after 1h and 4h of treatment while ErbB2 receptor was significantly increased and EGFR receptor returned to basal value after 24h. Instead, ErbB3 receptor was overexpressed after 1h, returned to basal level after 4h and increased its level after 24h. Exposure to chromium did not change expression level of ErbB4 receptor in A549 cell line. The present data suggests that expression changes in ErbB receptors might have a role in the carcinogenic effects induced by this pneumotoxic agent.

¿Es el antyecedente de tumores previos un factor de mal pronóstico en el cváncer superficial de vejiga? / Is the antecedent of former tumors, a bad pronostic factor in superficial bladder cancer?

Objetivo: Establecer si la presencia de recurrencias tumorales es un factor de pronóstico en el carcinoma transicional de vejiga en estadio t1. Material y métodos: Análisis retrospectivo de los carcinomas transicionales en estadio T1 operados por miembros del C.U.S.P.B.A. Se consignaron: la edad, sexo, características del tumor (número, grado, tamaño, etc.), la aparición y tipo de recidiva, así como la presencia de progresión tumoral en éstas. Se registro en cada ficha si el paciente había sido operado previamente de tumores vesicales transicionales. De este modo se conformaron dos grupos a estudiar: Aquéllos sin antecedentes de tumores previos (grupo 1), y aquéllos con antecedentes de los mismos (grupo 2). Resultados: Se analizaron 371 pacientes con diagnóstico de carcinoma transicional de vejiga en estadio T1, operados por miembros del C.U.S.P.B.A. durante el período 1993-1998. Se halló que 331 pacientes no habían presentado nunca cirugías por carcinomas transicionales anteriores (grupo 1), mientras que 40 casos sí habían sido operados previamente por este tipo de tumores (grupo 2). De esta manera se constituyeron los dos grupos a estudiar. Dentro del grupo 1 el 35,6 por ciento presentó recidiva, mientras que este porcentaje fue del 60 por ciento en el grupo 2 (p=0,002). Akl evaluar la aparición de progresión en lasd recidivas se observó que ésta estuvo presente en el 12,6 por ciento de los pacientes en el grupo 1 y el 30 por ciento de los pacientes en el grupo 2 (p=0,003). Comparando aquellos pacientyes que sólo progresaron en el estadio (T) se encontró progresión en el 5,1 por ciento dentro del grupo 1...

Tumores incidentales de rñón y tumores menores de cinco centímetros / Incidental renal tumours and tumours less than five cm. in diameter

Objetivo: Establecer la experiencia de un grupo cooperativo sobre tumores renales incidentales y los menores de 5 centímetros. Material y métodos: Se realizó un análisis retrospectivo de los adenocarcinomas renales operados con nefrectomía radical en el período 1986-1996. Se seleccionaron los tumores incidentales, los menores de 5 centímetros, y se realizó un análisis de la función renal posoperatoria de los pacientes. Resultados: Se analizaron 231 tumores renales; 32 por ciento fueron dianóstico incidental (74 pacientes); 35,5 poor cientoi fueron tumores menores de 5 cm (82 pacientes). Se halló que los tumores incidentales se poresentaron en estadios más bajos (62 por ciento Edios 1 y 2), y con mayor porcentaje de tumores menores de 5 cm (51,3 por cientoi) (p=<0,01). La sobrevida de los tumores menores de 5 cm fue estadísticamente superior a los mayores a esa cifra (p=<0,001). Se halló un 7,8 por ciento de detioro de la función renal posoperatoria (3,9 transitoriay 3,9 definitiva), con cifras de creatinina superiores a 1,5 mg/dl. Ningún paciente con tumor incidental o menor de 5 cm requirió hemodiálisis. Conclusiones: Los tumores renalrs incidentales de 5 cm son una entidad cada vez m,ás frecuente, y suelen coincidir con estadios bajos. La nefrectomía radical parece ser una técnica adecuada para su tratamiento, con escaso deterioro de la función renal posoperatoria, y 0 por ciento de necesidad de hemodiálisis

Adenocarcinoma renal: factores pronósticos: Experiencia de 10 años del club urológico del sur de la Provincia de Buenos Aires (C.U.S.P.B.A) / Renal adenocarcinoma: prognostic factors: 10 years experience of the Provincia Buenos Aires urologic Club

Objetivo: Establecer factors pronósticos en el adenocarcinoma renal.Material y método: Se realizó un estudio retrospectivo de todos los casos de adenocarcinoma renal operados por los miembros del Club urológico del sur de la provincia de Buenos Aires que participaron en este estudio, entre los años 1986 y 1996. Resultados: Se revisaron 231 casos de carcinoma renal operados en ese período. La edad fue de 62+= 11,63 por ciento fueron hombres. La sobrevida a 5 años fue : 100 por ciento estadio I, 77 por ciento estadio II, 51 por ciento estadio III y, 0 por ciento estadio IV; 32 por ciento fueron incidentales. Los pacientes < de 60 años y los tumores > de 5 cm presentaronmenor sobrevida. Conclusiones: Los tumores de bajo estadio (I y II), < de 5 cm, y en pascientes mayores de 60 años tienen mejor pronóstico en cuanto a la sobrevida global

Insuficiencia renal en pacientes nefrectomizados por cancer. Experiencia de diez años del Club Urológico del Sur de la Provincia de Buenos Aires / Renal failure in patients who undergone nephrectomy because of cancer. Experience of CUSPBA

Objetivo: Establecer la incidencia de insuficiencia renal posoperatoria en pacientes nefrectomizados por adenocarcinoma renal. Material y método: Se analizaron retrospectivamente todas las nefrectomías por cancer renal realizadas por los participantes en el estudio entre los años 1986 y 1996. Se evaluó la presencia de insuficiencia renal pre y posoperatoria tomando valores de creatinina de 1,5 mg/dl como límite superior. Se evaluó si hubiera sido posible realizar cirugía conservadora en cada caso. Resultados: se revisaron 231 casos de nefrectomía por cáncer. El 7,8 por ciento presentó insuficiencia reanl posoperatoria (3,9 por ciento transitoria y 3,9 por ciento definitiva) con creatininas>1,5 mg/dl. Sólo el 0,43 por ciento requirió hemodiálisis crónica. La falla renal se presentó a los 18,7 meses posoperatorios. Dentro del grupo donde se hubiera podido efectuar cirugía conservadora, el 2,1 por ciento presentó insuficiencia renal definitiva. Conclusiones: La incidencia de falla renal posnefrectomía es del 7,8 por ciento(3,9 definitiva y 3,9 por ciento transitoria). Sólo el 0,43 por ciento requiere hemodiálisis crónica

Carcinoma transcional de vejiga en estadios Ta-T1: experiencia del Club urológico del sur de la provincia de Buenos Aires (CUSPBA) / Transitional cell carcinoma of the bladder in stages Ta-T1: experience of CUSPBA

Objetivo: Analizar la experiencia de un grupo cooperativo sobre tumores superficiales de vejiga. Material y métodos: Se examinaron todos los tumores operados en el período 1992-1998 por los integrantes delClub Urológico del sur de la Provincia de Buenos Aires, y se consignaron las características iniciales, la aparición de recidevas o progresión tumoral, y los esquemas terapéuticos utilizados. Resultados: Se analizaron 451 casos (375 TI y 76 Ta); los tumores Ta tuvieron predominancia en ser únicos, de menor tamaño y de grado tumoral menor que los TI (valores de p de 0,05 o menor). Los tumores TI presentaron un mayor número de recidivas y la aparición de éstas guardó relación estadísticamentesignificativa con el grado y el número tumoral (p<0,001). A los 48 meses se hallaban libres de recidivas el 72 por ciento de los tumores Ta y el 55,7 por ciento de los tumores T1 (p=0,009). Los tumores T1 progresaron a estadios invasores en el 13,3 por ciento de las recidivas, proporción estadísticamente significativa en relación con los tumores Ta (p=0,02). Los esquemas de quimio/inmunoprofilaxis utilizados fueron de utilidad en la prevención de recurrencias en ambos grupos (p=0,04 en TI y p=0,02 en Ta). Conclusiones: Los tumores en estadio inicial pTI, y dentro de este grupo los de alto grado y/o multicéntricos, tienen una mayor tendencia a la aparición de recidivas y progresión tumoral, independientemente del esquema profiláctico utilizado

Complicaciones de la inmunoterapia endovesical con BCG / Complications of endovesical immunotheraphy with BCG

Veinte años han pasado desde que Morales comunicara los primeros resultados del uso de BCG como tratamiento del cáncer superficial de vejiga. Desde entonces varias cepas del bacilo han demostrados ser de utilidad en la profilaxis de recidivas y son aceptadas como la terapia más eficaz para el carcinoma in situ. A diferencia de los agentes quimioterápicos comúnmente utilizados, el bacilo de Calmette Guérin es un organismo vivi, y, aunque su virulencia está altamente atenuada, puede producir efectos regionales o sistémicos muy diferentes a los causados por aquéllos. El objetivo del presente estudio es el de establecer una revisión actualizada de las complicaciones relacionadas con el uso de BCG intravesical y su tratamiento

Tratamiento del adenoma de próstata clínicamente localizado (T1-T2) / Treatment of prostate adenocarcinoma clinically localized (T1-T2)

El adenocarcinoma de próstata es la neoplasia no cutánea de más frecuente diagnóstico en Estados Unidos,supera actualmente al de cáncer de pulmón por un estrecho márgen. Este hecho, atribuible en gran medida a las campañas de difusión, al screening y fundamentalmente a la incorporación del PSA y de la ultrasonografía transrectal como complemento del exámen clínico, ha traído como consecuencia no sólo un aumento en la detección del cáncer de próstata, sino un incremento sustancial en la proporción de neoplasias en estadios precoces de la enfermedad. Sin embargo, el hecho de que la detección precoz haya variado los índices de mortalidad por tumores prostáticos es un punto aún por demostrarse. El objetivo del presente trabajo es el de establecer una revisión actualizada de las pautas terapéuticas frente a un tumor de próstata clínicamente localizado

[Antibiotic therapy of bacterial infections of the oral cavity]. / Antibioticoterapia nelle infezioni batteriche del cavo orale.

More than 300 commencial bacterial species may be found in the oral cavity. Other microorganisms, such as mycoplasms, mycetes, protozoa and viruses are present as well. The virulency of the saprofites and additional contamination by outside microorganisms are factors determining the development of infectious process in the oral tissues. Moreover, streptococci and anaerobes are the most frequent aetiology agents. The antibiotic therapy should comply with the general treatment criteria, on the one hand, and should be specific for these microorganism, on the other. The penicillines (ampicillin, bacampicillin and especially amoxycillin) process pharmacokinetic properties which make them a favorable choice for treatment. These drugs are effective in case of streptococcal infections, with cariogenic processes involvement and dissemination (endocarditis, glomerulonephritis). Other, frequently used drugs are spiramycin, erythromycin, josamycin and myocamycin that are selectively taken up by the oral tissues and present in large quantities in the saliva. The macrolides have a large spectrum of action on microorganisms normally found in the oral cavity. Lincosamides (lincomycin and clindamycin) are active on anaerobes and are drugs of choice for treatment of staphylococcal osteomyelitis. Tetracycline therapy is restricted usually to parodontite cases caused by Actinobacillus actinomycetemcomitans and Capnocytophaga. In conclusion, the choice of antibacterial therapy should be based on the bacterial aetiology, as well as on the intrinsic drug characteristics (pharmacokinetic, side effects, toxicity etc.).