Conocimientos de los estudiantes de la carrera Medicina sobre educación ambiental / The students' of the medicine career knowledge have more than enough environmental education

Se realizó una investigación, con el objetivo de determinar los conocimientos de los estudiantes de la carrera medicina sobre educación ambiental. Se emplearon como métodos del nivel teórico, el análisis documental, la sistematización e histórico-lógico, como método del nivel empírico se aplicó la encuesta en su modalidad de cuestionario a los estudiantes de la carrera medicina. Se estructuró de forma que se reflejaron las dimensiones objeto de estudio a través de los indicadores propuestos en el instrumento. En los resultados de la aplicación de estos instrumentos se puede observar, de manera general que solamente los estudiantes del 5to. año de la carrera medicina, poseen un conocimiento satisfactorio sobre educación ambiental, aunque persisten debilidades en cuanto a los conocimientos, procedimientos, actitudes y desarrollo. Sin embargo, existen potencialidades y oportunidades que permiten transformar esta situación a partir de la organización didáctica de los contenidos.

The investigation, with the objective of determining the knowledge of the students of the career medicine has more than enough environmental education. They were used as methods of the theoretical level the documental analysis, the systematizing and historical-logical, as method of the empiric level the survey was applied in its questionnaire modality to the students of the career medicine. It was structured so that they were reflected the dimensions study object through the indicators proposed in the instrument. In the results of the application of these instruments one can observe, in a general way that only the students of the fifth year of the career medicine, possess a satisfactory knowledge on environmental education, although weaknesses persist as for the knowledge, procedures, attitudes and development. However, potentialities and opportunities that allow transforming this situation starting from the didactic organization of the contents exist.

Conocimientos de los estudiantes de la carrera Medicina sobre educación ambiental / The students' of the medicine career knowledge have more than enough environmental education

Se realizó una investigación, con el objetivo de determinar los conocimientos de los estudiantes de la carrera medicina sobre educación ambiental. Se emplearon como métodos del nivel teórico, el análisis documental, la sistematización e histórico-lógico, como método del nivel empírico se aplicó la encuesta en su modalidad de cuestionario a los estudiantes de la carrera medicina. Se estructuró de forma que se reflejaron las dimensiones objeto de estudio a través de los indicadores propuestos en el instrumento. En los resultados de la aplicación de estos instrumentos se puede observar, de manera general que solamente los estudiantes del 5to. año de la carrera medicina, poseen un conocimiento satisfactorio sobre educación ambiental, aunque persisten debilidades en cuanto a los conocimientos, procedimientos, actitudes y desarrollo. Sin embargo, existen potencialidades y oportunidades que permiten transformar esta situación a partir de la organización didáctica de los contenidos(AU)

The investigation, with the objective of determining the knowledge of the students of the career medicine has more than enough environmental education. They were used as methods of the theoretical level the documental analysis, the systematizing and historical-logical, as method of the empiric level the survey was applied in its questionnaire modality to the students of the career medicine. It was structured so that they were reflected the dimensions study object through the indicators proposed in the instrument. In the results of the application of these instruments one can observe, in a general way that only the students of the fifth year of the career medicine, possess a satisfactory knowledge on environmental education, although weaknesses persist as for the knowledge, procedures, attitudes and development. However, potentialities and opportunities that allow transforming this situation starting from the didactic organization of the contents exist(AU)

Resultados de las pruebas de desempeño en la superación posgraduada para Enfermería en servicios clínico-quirúrgicos por competencias profesionales especializadas / Results of the performance tests of specialized professional competences in postgraduate education for nursing at the clinical-surgical services

Se realizó un estudio, donde se aplicó un pre-experimento desde las Ciencias Pedagógicas, que nos permitió comparar los resultados de dos pruebas de desempeño realizadas a una muestra de profesionales de la Enfermería, de los hospitales clínicos quirúrgicos y especializados del segundo y tercer nivel de atención de salud de La Habana. Este estudio tuvo como objetivo identificar la necesidad de una formación posgraduada para Enfermería en servicios clínico-quirúrgicos, para satisfacer las necesidades de aprendizaje de estos profesionales y elevar la calidad de la atención a los pacientes en hospitales. Se aplicó una prueba de desempeño antes de la intervención y otra después, en una muestra pareada no paramétrica. Estas pruebas se realizaron previa identificación de competencias profesionales especializadas para la Enfermería Clínico-Quirúrgica, las que dieron como resultados la necesidad de una formación posgraduada para estos profesionales y que con la intervención propuesta, se logró un mejoramiento en el desempeño profesional y la satisfacción de los pacientes con la atención de enfermería recibida.

A study was conducted where a pre-experiment was applied in pedagogic sciences which allowed us to compare the results of two performance tests carried out in a sample of nursing professionals and of clinical surgical hospital professionals and 2nd and 3rd degree specialists in La Habana province. This study was aimed to identify the need for postgraduate formation for clinical and surgical nursing in order to meet the learning requirements of these professionals and to increase the quality of care in hospitals. A performance test was made before and after the intervention using non-parametric paired sample. These tests were carried out after determining the specialized professional competencies for the clinical and surgical nursing and yielded as results the need for postgraduate formation. The suggested intervention managed to improve the professional performance and to make patients feel satisfied with the nursing care rendered.

Resultados de las pruebas de desempeño en la superación posgraduada para Enfermería en servicios clínico-quirúrgicos por competencias profesionales especializadas / Results of the performance tests of specialized professional competences in postgraduate education for nursing at the clinical-surgical services

Se realizó un estudio, donde se aplicó un pre-experimento desde las Ciencias Pedagógicas, que nos permitió comparar los resultados de dos pruebas de desempeño realizadas a una muestra de profesionales de la Enfermería, de los hospitales clínicos quirúrgicos y especializados del segundo y tercer nivel de atención de salud de La Habana. Este estudio tuvo como objetivo identificar la necesidad de una formación posgraduada para Enfermería en servicios clínico-quirúrgicos, para satisfacer las necesidades de aprendizaje de estos profesionales y elevar la calidad de la atención a los pacientes en hospitales. Se aplicó una prueba de desempeño antes de la intervención y otra después, en una muestra pareada no paramétrica. Estas pruebas se realizaron previa identificación de competencias profesionales especializadas para la Enfermería Clínico-Quirúrgica, las que dieron como resultados la necesidad de una formación posgraduada para estos profesionales y que con la intervención propuesta, se logró un mejoramiento en el desempeño profesional y la satisfacción de los pacientes con la atención de enfermería recibida(AU)

A study was conducted where a pre-experiment was applied in pedagogic sciences which allowed us to compare the results of two performance tests carried out in a sample of nursing professionals and of clinical surgical hospital professionals and 2nd and 3rd degree specialists in La Habana province. This study was aimed to identify the need for postgraduate formation for clinical and surgical nursing in order to meet the learning requirements of these professionals and to increase the quality of care in hospitals. A performance test was made before and after the intervention using non-parametric paired sample. These tests were carried out after determining the specialized professional competencies for the clinical and surgical nursing and yielded as results the need for postgraduate formation. The suggested intervention managed to improve the professional performance and to make patients feel satisfied with the nursing care rendered(AU)

Genetic analysis of the endemic fungal pathogens Coccidioides posadasii and Coccidioides immitis in Mexico.

Coccidioidomycosis (CM) is a mycotic disease that affects mammals, including humans. Official data relative to CM in Mexico has not been collected since 1995, thus its prevalence remains unknown. The objectives of this study were to identify the predominant Coccidioides species in Mexico, infer their current geographical distribution and explore the correlation between species and clinical presentation. We collected 154 strains, which were cultured, inactivated, and processed for DNA extraction. Nine microsatellite loci, the Ag2/PRA gene and Umeyama Region were amplified from each isolate. To infer the current geographical distribution of Coccidioides spp. and to establish a correlation between genotype and clinical presentation, we evaluated genetic population structure under the following grouping criteria: putative origin and clinical presentation records. Microsatellite analysis showed that 82% of the isolates corresponded to C. posadasii and 18% were C. immitis. The species identification results obtained using Umeyama region, Ag2/PRA, and microsatellites of five of the isolates were inconsistent with the data collected for the remaining isolates. C. posadasii strains were found primarily in the northeastern region and C. immitis in the northwestern region. However, there was no relationship between clinical presentation and Coccidioides species. The molecular markers used in this study proved to have a high power of resolution to identify the Coccidioides species recovered in culture. While we found C. posadasii to be the most abundant species in Mexico, more detailed clinical records are needed in order to obtain more accurate information about the infections in specific geographical locations.

Caracterización del rendimiento académico de los estudiantes del plan de estudios D de Enfermería / Characterization of the academic performance in students of nursing plan D

A partir de las indicaciones del Ministerio de Educación Superior de transitar hacia una nueva generación de planes de estudios, surge el Plan D para la carrera de Enfermería en la búsqueda de un perfeccionamiento curricular. El trabajo expone algunos resultados finales de una investigación aprobada como Proyecto Ramal por la Dirección de Ciencia y Tecnología del Ministerio de Salud Pública con el objetivo general de caracterizar el rendimiento académico de los estudiantes en la Facultad 10 de Octubre de la Universidad de Ciencias Médicas de La Habana a partir de la realización de un estudio cuantitativo, analítico, de cohortes, longitudinal y retroprospectivo con utilización de técnicas cualitativas en el período comprendido entre los cursos académicos 2006-2007 y 2012-2013. De forma global, el rendimiento académico de los estudiantes varió significativamente según su formación como técnicos: tecnológica o emergente. Las causas que incidieron en este comportamiento son de origen multifactorial, destacándose fundamentalmente los aspectos personológicos y de vocación a la profesión(AU)

Plan D for the Nursing career arises from the search of a curricular improvement from the instructions of the Ministry of Higher Education of moving toward a new generation of syllabi. This paper shows some final results from an investigation which was approved as a Branch Project by the Office of Science and Technology of the Public Health Ministry. The general objective of this paper was to characterize the students' academic performance at 10 de Octubre Medical School (Havana Medical University). It is a cohort study, which was also quantitative, analytical, longitudinal and retroprospective with the use of qualitative techniques from the academic year 2006-2007 to 2012-2013. As a whole the academic performance of the students changed significantly according to their vocational training as technicians either technological or emergent. The causes of these results depend on many factors and the main ones are personal and vocation to the profession(AU)

Diseño curricular del diplomado en Enfermería clínico-quirúrgica para el sistema de salud cubano / Curricular design of the clinical-surgical nursing diploma's course for the Cuban health system

Se realizó una investigación con el objetivo de proponer un diseño curricular de posgrado en Enfermería clínico-quirúrgica, como respuesta a las necesidades de aprendizaje de enfermería en estos servicios y a las exigencias de salud de los pacientes. Para la propuesta se parte de la necesidad de superación posgraduada en estos servicios y garantizar la calidad de la atención. Los principales métodos utilizados fueron: revisión documental, talleres nacionales, modelación y enfoque de sistema, los que permitieron realizar el diseño curricular para garantizar el mejoramiento profesional y humano de los recursos laborales de Enfermería. La propuesta pretende preparar y actualizar a estos profesionales para la atención especializada a los pacientes, en una de las áreas más complejas y abarcadoras. No existes antecedentes en Cuba hasta donde hemos indagado, de propuestas posgraduadas específicas para estos servicios, el que se realizó a partir de un sistema de competencias profesionales especializadas

A research study was made to submit a curricular design of a postgraduate course in clinical-surgical nursing, in response to the learning requirements of nursing in these services and to the health demands of patients. This proposal stems from the need of postgraduate upgrading in these services and of guaranteeing the quality of care. The main methods were documentary review, national workshops, modeling and system approach, all of which allowed making the curricular design for professional and human improvement of the nursing resources. The proposal intends to prepare these professionals and update their knowledge on specialized care to patients in one of the most comprehensive and complex areas of health care. As far as we have researched, there are no previous specific proposals in terms of postgraduate studies for these services. The current proposal of curricular design took as a basis a system of specialized professional competencies

Diseño curricular del diplomado en Enfermería clínico-quirúrgica para el sistema de salud cubano / Curricular design of the clinical-surgical nursing diploma's course for the Cuban health system

Se realizó una investigación con el objetivo de proponer un diseño curricular de posgrado en Enfermería clínico-quirúrgica, como respuesta a las necesidades de aprendizaje de enfermería en estos servicios y a las exigencias de salud de los pacientes. Para la propuesta se parte de la necesidad de superación posgraduada en estos servicios y garantizar la calidad de la atención. Los principales métodos utilizados fueron: revisión documental, talleres nacionales, modelación y enfoque de sistema, los que permitieron realizar el diseño curricular para garantizar el mejoramiento profesional y humano de los recursos laborales de Enfermería. La propuesta pretende preparar y actualizar a estos profesionales para la atención especializada a los pacientes, en una de las áreas más complejas y abarcadoras. No existes antecedentes en Cuba hasta donde hemos indagado, de propuestas posgraduadas específicas para estos servicios, el que se realizó a partir de un sistema de competencias profesionales especializadas(AU)

A research study was made to submit a curricular design of a postgraduate course in clinical-surgical nursing, in response to the learning requirements of nursing in these services and to the health demands of patients. This proposal stems from the need of postgraduate upgrading in these services and of guaranteeing the quality of care. The main methods were documentary review, national workshops, modeling and system approach, all of which allowed making the curricular design for professional and human improvement of the nursing resources. The proposal intends to prepare these professionals and update their knowledge on specialized care to patients in one of the most comprehensive and complex areas of health care. As far as we have researched, there are no previous specific proposals in terms of postgraduate studies for these services. The current proposal of curricular design took as a basis a system of specialized professional competencies(AU)

Administration of poly-D-glutamic acid induces proliferation of erythropoietin-producing peritubular cells in rat kidney.

Erythropoietin (EPO), a 34-kDa glycoprotein, is produced predominantly by peritubular interstitial cells (PIC) in the renal cortex and is physiologically released when ambient oxygen pressure falls. However, the exact nature of EPO-producing cells in the kidney is not well understood. We discovered that brief administration of a low-molecular-weight synthetic peptide, poly-D-glutamic acid (PDG), induced prompt and robust expansion of EPO-producing PIC in rat kidney, without evidence of tubular cell necrosis/apoptosis or fibrotic reaction. Proliferating PIC in PDG-treated rats were noninflammatory, alpha-smooth muscle actin negative, and specifically expressed CD73 (ecto-5'-nucleotidase), EPO mRNA, and protein. Increased numbers of EPO-positive PIC persisted even after the cessation of PDG treatment. No erythropoietic effects of EPO were detected, potentially suggesting maintained physiological control of EPO secretion in this normoxic model. We showed previously that PDG is readily filtered and is rapidly taken up and stored in lysosomes of proximal tubular cells (PTC), resulting in an apparently nonnoxious lysosomal storage condition by virtue of its nonhydrolyzable nature (Kishore BK, Maldague P, Tulkens PM, Courtoy PJ. Lab Invest 74: 1013-1023, 1996). Based on these findings, we suggest that unknown signaling molecules, produced by PTC in response to lysosomal PDG storage, appear to specifically stimulate the proliferation of EPO-producing PIC. We conclude that this model is uniquely suited to investigate the biology of EPO production by PIC and may thus facilitate the development of novel and more economical therapies of anemias and other EPO-responsive conditions.

Extent of glomerular tubularization is an indicator of the severity of experimental acute kidney injury in mice.

BACKGROUND: Acute kidney injury (AKI) secondary to ischemia continues to be a major clinical problem due to its high morbidity and mortality, and limited treatment options. Animal models are critical to both the study of the pathophysiology of AKI and the development of new interventions. Although histological changes at the glomerulotubular junction have been described in AKI, we examined here whether the extent of glomerular tubularization correlates with the degree of renal insufficiency in this condition. METHODS: Groups of mice with ischemia/reperfusion AKI were utilized in which the severity of renal insufficiency was defined. The resulting level of glomerular tubularization was analyzed, and the involved cell type was identified by immunohistochemistry and electron microscopy. RESULTS: The extent of glomerular tubularization increased significantly with the degree of renal insufficiency. Low level glomerular tubularization was present in normal mouse kidneys, while it was more common and increasingly circumferential in mice with more severe loss of kidney function. The parietal monolayer of cuboidal cells in glomeruli was contiguous with proximal tubular cells, showing a well-developed luminal brush border and positive staining for proliferating cell nuclear antigen and Lotus tetragonolobus, a proximal tubular cell-specific lectin. CONCLUSION: Increased levels of glomerular tubularization represent a poorly understood response to ischemic AKI in mice. As such, this glomerular 'tubularization score' may be useful to complement standard injury scores in experimental and, if detected, in clinical AKI.

Fibroepithelial polyp of the prostatic urethra in an adolescent.

Benign fibroepithelial polyp of the prostatic urethra is a rare congenital lesion most commonly diagnosed in the pediatric population because of diverse urinary symptoms. We report a case of a 16-year-old adolescent boy who presented with urinary retention. Imaging and endoscopic studies confirmed the presence of a polypoid lesion at the bladder base/posterior prostatic urethra. Following transurethral resection of this polypoid mass, the diagnosis of a congenital fibroepithelial polyp of the prostatic urethra was rendered by pathologic evaluation. Although this is considered a benign lesion with no previous reports of recurrence or malignant behavior, it produces dramatic urinary symptoms in the pediatric population with a wide differential diagnosis. Imaging and endoscopic findings may suggest a malignancy and are not sufficient to render a precise diagnosis, which can only be made by pathologic examination.

A c-kit-negative gastrointestinal stromal tumor with a platelet-derived growth factor receptor alpha mutation.

Gastrointestinal stromal tumors (GISTs) are well-recognized mesenchymal neoplasms of the intestinal tract. A diagnosis of GIST is not always possible using IHC techniques for detection of c-kit. The authors describe a 64-year-old man who presented with an upper abdominal quadrant mass. Histology showed a predominantly epithelioid neoplasm with focal "spindle cell" areas. IHC studies were positive for muscle markers and negative for c-kit. The morphologic and immunophenotypic appearance could be compatible with either a smooth muscle tumor or a GIST. Because of the differences in treatment protocols and prognosis between these two entities, molecular studies to detect c-kit or platelet-derived growth factor receptor (PDGFR) activating mutations were performed. No mutations were found in the c-kit gene, but a mutation was detected in the PDGFR gene. This additional molecular study allowed the authors to formulate the precise diagnosis of a c-kit-negative GIST with strong smooth muscle marker expression.

Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury.

BACKGROUND: Stem cell and leukocyte migration during homeostasis and inflammation is regulated by a number of chemokines. Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 are important mediators of leukocyte homeostasis. The postischemic kidney has been shown to recruit different leukocyte populations, including bone marrow-derived stem cells. Therefore, we investigated the SDF-1/CXCR4 system in the kidney after ischemic acute renal failure (ARF). METHODS: We used immunohistochemistry, in situ hybridization, enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription-polymerase chain reaction (RT-PCR) to detect SDF-1 and CXCR4 in the normal kidney and the kidney after ischemia/reperfusion (I/R) ARF. Mobilization was assessed by flow cytometry for CD34 and colony assays. RESULTS: We show that SDF-1 is expressed in the normal mouse kidney and tubular cells express CXCR4. SDF-1 expression in the kidney increases after I/R induced ARF and decreases in the bone marrow, thereby reversing the normal gradient between bone marrow and the periphery. This causes mobilization of CD34-positive cells into the circulation and their subsequent homing to the kidney with ARF. In vitro and in vivo chemotaxis of bone marrow cells toward damaged kidney epithelium is reversibly inhibited by anti-CXCR4 antibodies. CONCLUSION: Our data show that renal SDF-1 is a currently unrecognized mediator of homing to and migration of CXCR4 expressing cells in the injured kidney. Because certain cells that express CXCR4 may have renoprotective effects, our results suggest that SDF-1 may be a major signal involved in kidney repair.

Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms.

Severe acute renal failure (ARF) remains a common, largely treatment-resistant clinical problem with disturbingly high mortality rates. Therefore, we tested whether administration of multipotent mesenchymal stem cells (MSC) to anesthetized rats with ischemia-reperfusion-induced ARF (40-min bilateral renal pedicle clamping) could improve the outcome through amelioration of inflammatory, vascular, and apoptotic/necrotic manifestations of ischemic kidney injury. Accordingly, intracarotid administration of MSC (approximately 10(6)/animal) either immediately or 24 h after renal ischemia resulted in significantly improved renal function, higher proliferative and lower apoptotic indexes, as well as lower renal injury and unchanged leukocyte infiltration scores. Such renoprotection was not obtained with syngeneic fibroblasts. Using in vivo two-photon laser confocal microscopy, fluorescence-labeled MSC were detected early after injection in glomeruli, and low numbers attached at microvasculature sites. However, within 3 days of administration, none of the administered MSC had differentiated into a tubular or endothelial cell phenotype. At 24 h after injury, expression of proinflammatory cytokines IL-1beta, TNF-alpha, IFN-gamma, and inducible nitric oxide synthase was significantly reduced and that of anti-inflammatory IL-10 and bFGF, TGF-alpha, and Bcl-2 was highly upregulated in treated kidneys. We conclude that the early, highly significant renoprotection obtained with MSC is of considerable therapeutic promise for the cell-based management of clinical ARF. The beneficial effects of MSC are primarily mediated via complex paracrine actions and not by their differentiation into target cells, which, as such, appears to be a more protracted response that may become important in late-stage organ repair.

Expression of NTPDase1 and NTPDase2 in murine kidney: relevance to regulation of P2 receptor signaling.

The regulation of renal function by extracellular nucleotides encompasses alterations in glomerular hemodynamics, microvascular function, tubuloglomerular feedback, tubular transport, cell growth or apoptosis, and transport of water and solutes in the medullary collecting duct. Nearly all cells can release ATP or other nucleotides that are then rapidly hydrolyzed in the extracellular milieu. However, little information is available on the cellular expression of ectoenzymes that hydrolyze extracellular nucleotides within the kidney. Nucleoside triphosphate diphosphohydrolases (NTPDases) are plasma membrane-bound ectonucleotidases. NTPDase1 has identity with CD39, a B lymphocyte activation marker, and hydrolyzes extracellular ATP and ADP to AMP within the vasculature, whereas NTPDase2/CD39L(ike)1 preferentially converts ATP to ADP outside of blood vessels. Using immunohistochemical and in situ hybridization approaches, we localized the protein and mRNA of NTPDase1 and 2 in murine renal tissues. In the renal cortex, NTPDase1 is expressed by vascular smooth muscle cells and endothelium in interlobular arteries, afferent glomerular arterioles, and peritubular capillaries. In the inner medulla, NTPDase1 is expressed in ascending thin limbs of Henle's loop, ducts of Bellini, and in the pelvic wall. In contrast, NTPDase2 is expressed in Bowman's capsule, glomerular arterioles, adventitia of blood vessels, and pelvic wall. Thus the distribution patterns of NTPDases have parallels to the known distribution of P2 receptors within the kidney. NTPDases may modulate regulatory effects of ATP and degradation products within the vasculature and other sites and thereby potentially influence physiological as well as multiple pathological events in the kidney.

Global hypomethylation is common in prostate cancer cells: a quantitative predictor for clinical outcome?

This study was designed to determine if cytological detection of 5-methylcytosine (5MC) was feasible on prostate tumor sections and to determine if levels of 5MC differed in malignant compared to normal prostate tissue. We further sought to see if 5MC levels correlated with any clinical outcome data. Thirty prostate tumor sections were obtained from patients who underwent radical prostatectomies from 1988 to 1995; these represented a mix of low to high grade tumors. Clinical data were maintained for each of these patients with a minimum of 7 years of follow up. Sections were stained with a commercially available antibody to 5MC and immunocytochemistry levels were subsequently quantified using a computer-assisted true-color imaging system. Tumor and benign regions of the same archived sections were compared, in addition to a series of 12 normal prostate samples. Prostate cancer cells exhibited a pronounced global decrease in methylation compared with benign and normal tissue. This was observed in 29 of 30 patients (96.7%) studied and densitometric scanning of methylation staining indicated that this value was quantifiable. Overall, higher methylation values were detected in men who had positive surgical margins and recurrent disease. These data suggest that loss of methylation is a feature of prostate cancer, and partial gain of methylation (presumably at promoters of specific genes) is associated with clinical outcome and is measurable using whole-cell assays.

Hematopoietic stem cell mobilization-associated granulocytosis severely worsens acute renal failure.

Acute renal failure (ARF), resulting from ischemic or toxic insults, remains a major health care problem because of its grave prognosis and the limited effectiveness of available treatment modalities. On the basis of the recent demonstration that hematopoietic stem cells can differentiate into renal cells and the authors' observation here that ARF results in a rise in peripheral CD34+ cells, the authors tested whether a further increase in circulating stem cell numbers, induced by their mobilization from the bone marrow, would improve renal function and outcome in mice with ischemic ARF. Unexpected, it was found that the boosting of peripheral stem cell numbers failed to exert any renoprotective effects but rather was associated both with greatly increased severity of renal failure and mortality. Because identical ischemic injury in neutropenic mice resulted in milder renal insufficiency and significantly reduced mortality, it was deduced that the adverse effects of pharmacologic stem cell mobilization are primarily mediated by the concomitant induction of marked granulocytosis. In this manner, high numbers of activated granulocytes seem to obscure the potential renoprotective and positive survival effects of pluripotent hematopoietic stem cells, mediated by both their injurious renal and systemic actions. The data strongly argue against the clinical use of granulocytosis-inducing hematopoietic stem cell mobilization protocols for the prevention or treatment of ischemic ARF. Additional caution with this regimen may be warranted in patients with underlying renal insufficiency and those who develop renal insufficiency while undergoing stem cell mobilization in preparation for an autologous bone marrow transplant.

Cellular and molecular studies on cisplatin-induced apoptotic cell death in rat kidney.

Using morphological and molecular approaches, we characterized cisplatin-induced cell necrosis and apoptosis in rat kidney. Male Sprague-Dawley rats ( n=5 per group) received a single intraperitoneal injection of either cisplatin (5 mg/kg) or saline, and were killed on day 5. Functionally, cisplatin-treated rats developed polyuric acute renal failure. Morphologically, kidneys of cisplatin-treated rats showed overt tubular necrosis associated with apoptosis in the corticomedullary junction. Cell necrosis was segment-specific and was distributed in radial fashion at the corticomedullary junction. The apoptosis was limited to discrete cells in apparently intact tubules in the vicinity of the necrosed tubules. The apoptotic changes were confirmed by TUNEL (TdT-mediated deoxyuridine triphosphate nick-end labeling) and staining for cleaved caspase-3. Analysis of outer medullary tissue for apoptosis-related molecules by RNase protection assay revealed a significant increase in the expression of pro-apoptotic mRNAs (caspases 1, 2, and 8, and Bax) in cisplatin-treated rats. On the other hand, the expression of mRNA for the anti-apoptotic Bcl-2 did not change, resulting in a decrease in relative ratio of Bcl-2/Bax, and thus favoring apoptosis. The above changes were paralleled by a marked increase in caspase-3 precursor, the executioner protease. Furthermore, these pro-apoptotic molecular changes were associated with a 3-fold increase in the activity of JNK1 in the outer medulla, but not in the cortex, of cisplatin-treated rat kidneys, localizing to the site of maximal apoptosis. Upregulation of JNK1 activity in the outer medulla was not accompanied by changes in the activities of ERK or p38 kinase. In conclusion, these data suggest that cisplatin-induced apoptotic cell death in native kidney may be mediated by cooperative activation of the JNK1 pathway and Bax in the outer medulla.