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L Espinosa

Publications and source records attributed to L Espinosa.

At least 19 recordsLinked to original sources
PubMed2006

Nuclear IKK activity leads to dysregulated notch-dependent gene expression in colorectal cancer.

Nuclear functions for IkappaB kinase (IKK), including phosphorylation of histone H3 and nuclear corepressors, have been recently described. Here, we show that IKK is activated in colorectal tumors concomitant with the presence of phosphorylated SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) corepressor that is aberrantly localized in the cytoplasm. In these tumors, IKKalpha associates to the chromatin of specific Notch targets, leading to the release of SMRT. Abrogation of IKK activity by BAY11-7082 or by expressing dominant negative IKKalpha restores the association of SMRT with Notch target genes, resulting in specific gene repression. Finally, BAY11-7082 significantly reduces tumor size in colorectal cancer xenografts (CRC-Xs) implanted in nude mice.

Animals↗
PubMed2003

Posterior urethral valves: prognostic factors.

OBJECTIVE: To determine which variables besides bladder dysfunction can help to predict the outcome of renal function in boys with posterior urethral valves (PUV). PATIENTS AND METHODS: All 40 patients with PUV in this retrospective study were diagnosed and began treatment in our hospital within the first 3 months of life, and have had >or= 5 years of follow-up. At the time of diagnosis, 33 were in renal insufficiency (RI) and seven had normal renal function (RF). At the time of the study 16 were in chronic renal failure (CRF) and 24 had normal RF. We compared their RF (initial and during follow-up), vesico-ureteric reflux (VUR), urinary tract infection (UTI), proteinuria, hypertension, renal echogenicity, final patient age and initial management. RESULTS: The mean serum creatinine values before and after initial treatment were worse in boys who developed CRF than in those who did not (P = 0.08); the mean glomerular filtrate rate (GFR) at 1 year old was 52 mL/min/1.73 m2 in the former and 102 in the latter (P < 0.001). Proteinuria was present during the follow-up in 79% of patients in CRF and in only 17% of those with normal RF. All patients who developed CRF had echogenic renal changes while only 53% of the others had (P < 0.01). Other variables showed no statistically significant differences (VUR, UTI, hypertension and final patient age). Of 33 patients in RI at diagnosis, nine were treated by valve ablation and 24 by temporary pyelo-ureterostomy. The initial mean serum creatinine value was worse in the latter than in the former (20.8 vs 13.0 mg/L). However, at 1 year old the mean GFR was better in the latter than in the former (P < 0.05). These GFR differences persisted during the first years of life but had disappeared by the fifth. CONCLUSIONS: The most significant prognostic factor for the future development of CRF is the GFR at 1 year old. The onset of proteinuria during the follow-up is associated with a worse prognosis. Echogenic renal changes may help to identify those dysplastic kidneys that will develop RI. Neonatal boys in RI who underwent pyelo-ureterostomy had better RF during the first years of life than those who underwent valve ablation.

Adolescent↗
PubMed2002

Domestic scorpion control with pyrethroid insecticides in Mexico.

Scorpion stings cause more morbidity in Mexico than any other country, leading to about 100 deaths annually. In 1999, the State of Morelos reported nine deaths among 30663 cases of scorpion sting. To replace lindane used for scorpion control, field trials of pyrethroid pesticides were undertaken in Morelos during 1998-2000 at the village of Chalcatzingo (population initially with 2760 inhabitants and 530 houses). Pre-intervention surveys detected scorpions (Scorpiones: Buthidae) of two species in the majority of houses: Centruroides limpidus limpidus Karsch outnumbering Vaejovis mexicanus smithi Koch. Scorpion prevalence was assessed, pre- and post-spray, directly by searching (40 min/house) and by householder reports of sightings inside houses. Pre-intervention perceptions of scorpion abundance were similar for all areas, with sightings in 12-18% of houses, whereas daytime searches detected more infestations in eastern parts of the village (prevalence 17% indoors, 22% outdoors) than in other sectors (9% indoors, 14% outdoors). Pyrethroids were evaluated as residual treatments in separate sectors of Chalcatzingo, with almost complete coverage indoors and peridomestically, using the following four formulations: bifenthrin 10% wettable powder (WP) applied at 50mg a.i./m2, cyfluthrin 10% WP (Solfac 10 WP) at 44-55 mg a.i./m2, deltamethrin 2.5% suspension concentrate (Biothrin 25 SC) at 11 mg a.i./m2 and 5% WP (K-Othrine 50 WP) at 35 mg a.i./m2. Phase 1 compared bifenthrin 10 WP, Solfac 10 WP and Biothrin 25 SC sprayed in December 1998; phase 2 compared Solfac 10 WP and K-Othrine 50 WP sprayed in June and again in December 2000, with follow-up surveys of scorpions one month post-spray and subsequently. Scorpion prevalence was reduced by 64-77% peridomestically one month post-spray and by 83, 46 and 15% in houses sprayed with cyfluthrin WP, bifenthrin WP or deltamethrin SC, respectively. Householder reports of sighting scorpions indoors were 33-85% below pre-intervention levels. Cumulative effects of the three spray-rounds over 3 years reduced scorpion prevalence by approximately 60% in the deltamethrin WP re-sprayed area and by approximately 90% in the cyfluthrin WP re-sprayed area. Householder sightings also fell by 67 and 28% in the cyfluthrin and delta-methrin re-sprayed areas, respectively. Operational efficacy of these products against scorpions at the dosages applied was ranked as cyfluthrin WP > bifenthrin WP > deltamethrin SC > WP. Reported cases of scorpion sting intoxication fell by 17% during this study after having risen by approximately 40% over four previous years.

Animals↗
PubMed2002

Bladder dysfunction as a prognostic factor in patients with posterior urethral valves.

OBJECTIVE: To investigate the extent to which different types of bladder dysfunction can affect long-term renal function in boys with posterior urethral valves (PUV). PATIENTS AND METHODS: Renal and bladder function were retrospectively assessed in 59 boys with PUV (mean age 10 years, range 5-17). All patients included in the study had at least 4 years of follow-up and their bladder behaviour had been evaluated in at least two urodynamic studies. At the time of the study, of the 59 PUV boys, 37 had normal renal function and 22 had end-stage renal disease (ESRD). RESULTS: Of the 59 boys with PUV evaluated by urodynamic studies, 25 had normally behaving bladders (42%) and 34 had some type of bladder dysfunction (58%). Of the 22 in ESRD, 15 had abnormally behaving bladders (68%) and only seven had bladders with normal behaviour (32%). Of the 37 boys with normal renal function, 19 had dysfunctional bladders (51%) and 18 had normal bladders (49%). Instability was found in 17 of 19 boys with bladder dysfunction and normal renal function. On the contrary among 22 boys with ESRD, poor compliance was the most frequent urodynamic pattern (eight, 53%) while instability was only found in five. Overall, eight of nine boys with poorly compliant bladders, two of three with myogenic failure and a five of 22 with instability were in ESRD, and this situation occurred at an earlier age in patients with poorly compliant bladders. CONCLUSION: Bladder dysfunction should be considered as a prognostic factor in renal failure. Those with poor bladder compliance and myogenic failure have the worst outcome, while bladder instability was associated with the lowest incidence of renal failure.

Adolescent↗
PubMed2002

Reversibility of electrophysiological changes induced by chronic high-altitude hypoxia in adult rat heart.

Recent studies indicate that regression of left ventricular hypertrophy normalizes membrane ionic current abnormalities. This work was designed to determine whether regression of right ventricular hypertrophy induced by permanent high-altitude exposure (4,500 m, 20 days) in adult rats also normalizes changes of ventricular myocyte electrophysiology. According to the current data, prolonged action potential, decreased transient outward current density, and increased inward sodium/calcium exchange current density normalized 20 days after the end of altitude exposure, whereas right ventricular hypertrophy evidenced by both the right ventricular weight-to-heart weight ratio and the right ventricular free wall thickness measurement normalized 40 days after the end of altitude exposure. This morphological normalization occurred at both the level of muscular tissue, as shown by the decrease toward control values of some myocyte parameters (perimeter, capacitance, and width), and the level of the interstitial collagenous connective tissue. In the chronic high-altitude hypoxia model, the regression of right ventricular hypertrophy would not be a prerequisite for normalization of ventricular electrophysiological abnormalities.

Aging↗
PubMed2001

Phosphorylation of Ser2078 modulates the Notch2 function in 32D cell differentiation.

Notch signaling is involved in the regulation of many cell fate determination events in both embryonic development and adult tissue homeostasis. We previously demonstrated that Notch1 and Notch2 molecules inhibit myeloid differentiation in a cytokine-specific manner and that the Notch cytokine response domain is necessary for this functional specificity. We have now investigated the putative role of phosphorylation in the activity of Notch in response to cytokine signals. Our results show that the granulocyte colony-stimulating factor (G-CSF) stimulation of 32D cells expressing the intracellular Notch2 protein induces phosphorylation at specific sites of this molecule, rendering the molecule inactive and permitting differentiation of these cells. In contrast, when cells are stimulated with granulocyte macrophage colony-stimulating factor (GM-CSF), intracellular notch2 is not phosphorylated at these residues and differentiation is inhibited. We also show that deletion of the Ser/Thr-rich region between amino acids 2067 and 2099 abrogates G-CSF-induced phosphorylation and results in a molecule that inhibits differentiation in response to either G-CSF or GM-CSF. Our results further indicate that Ser(2078) is a critical residue for phosphorylation and modulation of Notch2 activity in the context of G-CSF-induced differentiation of 32D cells.

Amino Acid Sequence↗
PubMed2000

Opposite effects of halothane on guinea-pig ventricular action potential duration.

Halothane protects the heart against the reperfusion injury observed after an ischemia. In ischemic or anoxic conditions, a large ATP-sensitive K(+) (K(ATP)) conductance is supposed to provide an endogenous protection to the myocardium. In this study, we tested the possibility that halothane acted by modulating this conductance. Isolated guinea-pig cardiomyocytes were successively studied in current clamp and in voltage-clamp conditions. Action potentials regulation by halothane was tested in control conditions and in situations where the K(ATP) channels were activated. In control conditions, halothane decreased action potential duration of myocytes but did not significantly alter the inward rectifying K(+) current. Conversely, halothane lengthened action potential of cells in which the K(ATP) conductance was activated, by inhibiting the K(ATP) current. In ischemic conditions, simultaneous shortening of long action potentials and lengthening of shortened ones would be expected to homogenize the absolute refractory period at the border between normoxic and anoxic zones. This effect, together with a decrease in calcium load, could protect the myocardium against re-entrant arrhythmias.

Action Potentials↗
PubMed2000

Specific antagonists of NMDA receptors prevent osteoclast sealing zone formation required for bone resorption.

N-Methyl-d-aspartate (NMDA) glutamate receptors, widely distributed in the nervous system, have recently been identified in bone. They are expressed and are functional in osteoclasts. In the present work, we have studied the effects of specific antagonists of NMDA receptors on osteoclast activation and bone resorption. Using an in vitro assay of bone resorption, we showed that several antagonists of NMDA receptors binding to different sites of the receptor inhibit bone resorption. Osteoclast activation requires adhesion to the bone surface, cytoskeletal reorganization and survival. We demonstrated by autoradiography that the specific NMDA receptor channel blocker, MK 801, binds to osteoclasts. This antagonist had no effect on osteoclast attachment to bone and did not induce osteoclast apoptosis. In contrast, MK 801 rapidly decreased the percentage of osteoclasts with actin ring structures that are associated with actively resorbing osteoclasts. These results suggest that NMDA receptors expressed by osteoclasts may be involved in adhesion-induced formation of the sealing zone required for bone resorption.

Actins↗
PubMed2000

Increased sodium-calcium exchange current in right ventricular cell hypertrophy induced by simulated high altitude in adult rats.

Ventricular hypertrophy is associated with an increase in action potential (AP) duration which is potentially arrhythmogenic. The implication of the Na-Ca exchange current (I(Na-Ca)) in the lengthening of the AP is controversial. The role of this current in the increased duration of the low plateau of the AP in hypertrophied adult rat ventricular myocytes by simulated chronic high-altitude exposure ( approximately 4500 m) was evaluated. Electrophysiological experiments were carried out on isolated right ventricular myocytes from exposed and control rats with the perforated patch or the conventional whole-cell technique in current or in voltage clamp condition. With the two techniques, a significant increase of the low plateau duration was observed in hypertrophied myocytes as compared to controls. The low plateau in hypertrophied myocytes was depressed when Na was replaced by Li and was no longer recorded when intracellular Ca was buffered with EGTA. Inward tail currents, evoked either on repolarization to -80 mV following a depolarizing pulse to +10 mV or by interrupted AP technique, were greater in hypertrophied than in control myocytes and were abolished when Na was replaced by Li or when intracellular Ca was buffered with EGTA, indicating an increased Na-Ca exchange activity. The Li-sensitive current-voltage curves, obtained by a voltage clamp ramp protocol with an intracellular calcium buffered solution, were not significantly different in both hypertrophied and control myocytes, suggesting no modification in the density of the Na-Ca exchange protein. This was corroborated by the lack of difference in NCX1 mRNA levels between right ventricles from control and exposed rats. We conclude that increased duration of the low plateau of rat ventricular AP in altitude cardiac hypertrophy may be attributed to an increase of the inward I(Na-Ca). This augmented I(Na-Ca)may result from a modification in the intracellular Ca homeostasis.

Action Potentials↗
PubMed2000

Analysis of chromosome 6p in Spanish families with recessive polycystic kidney disease.

Several previous reports have suggested that autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in a single gene (the PKDH1 gene). Linkage analysis showed a positive linkage for polymorphic markers at the short arm of chromosome 6 (6p) in all families. PKHD1 has not been cloned. Recombinants in the critical region would permit the narrowing of the 6p interval containing the PKHD1 gene, thus facilitating the final identification (cloning) of this gene. Our study included 30 Spanish families. Each family consisted of both parents and at least two children, with at least one diagnosed with ARPKD by clinical and pathological parameters. DNA was obtained and 6p microsatellite markers were used to establish haplotypes for each family. A positive linkage to chromosome 6p was found for all families. In 2 cases, recombinants in the region containing the PKHD1 gene were found. These families will help narrow the size of the 6p region, facilitating the efforts to position and clone the PKHD1 gene. In conclusion, our analysis of Spanish ARPKD families confirms the lack of linkage heterogeneity. This suggests that mutations at a single locus on chromosome 6p21.1-p12 are responsible for the broad clinical spectrum of variable phenotypes.

Adolescent↗
PubMed2000

Improving quality of expressed sequence tag (EST) databases: recovery of reversed, antisense cDNA sequences.

Expressed sequence tag (EST) databases contain a significant number (5-20%) of reversed, antisense, cDNA sequences that can be recognized by the label "reversed clone: similarity on wrong strand" in the annotations to the sequence. Despite this high number of altered sequences, no attempt has been made to explain the alteration in molecular terms, or to evaluate their effect on the quality of the information curated in EST databases. In this paper we try to explain the way these altered sequences are originated, and propose a plausible mechanism: a "double priming" of the first strand oligo-dT primer at both ends of nascent cDNAs. In this way, a symmetrical cDNA intermediate is generated, an intermediate that can be cloned after partial digestion with the restriction enzyme used for the directional cloning. Furthermore, when "secondary" priming takes place inside the cDNA, the chain synthesized is prone to be truncated prematurely, with the subsequent loss of upstream information. One of the most subtle effects of this cloning alteration is the generation of virtual open reading frames (ORFs) in sequences with no homologues available for comparison. Nevertheless, and according to our model and our data, the "double priming mechanism" does not shift the ORF effected, so antisense sequences should be considered as normal ones after a simple transformation in their inverse-complementary forms.

Artifacts↗
PubMed2000

Does neonatal pyeloureterostomy worsen bladder function in children with posterior urethral valves?

PURPOSE: We determine whether long-term bladder dysfunction is more frequent in children with posterior urethral valves who undergo early supravesical urinary diversion (pyeloureterostomy) than in those who undergo valve ablation. MATERIALS AND METHODS: Urodynamic studies were performed in 59 boys with severe posterior urethral valves who were divided into 2 groups based on initial treatment of valve ablation (30) and bilateral pyeloureterostomy (29). RESULTS: Of the 59 boys 25 (42%) had a normal bladder, including 11 with an over distended bladder and 34 (58%) had bladder dysfunction, including instability in 22, poor compliance in 9 and myogenic failure in 3. Of the 30 boys initially treated with valve ablation 14 (46.6%) had a normal bladder, including 7 with an over distended bladder and 16 (53.4%) had bladder dysfunction, including instability in 10, poor compliance in 4 and myogenic failure in 2. Of the 29 boys initially treated with temporary bilateral pyeloureterostomy 11 (38%) had normal bladders, 4 with an over distended bladder and 18 (62%) had bladder dysfunction, including instability in 12, poor compliance in 5 and myogenic failure in 1. There were no statistically significant differences in the number or type of bladder dysfunction between the diversion and valve ablation groups. CONCLUSIONS: Therefore, temporary pyeloureterostomy did not affect bladder function adversely in the long term.

Humans↗
PubMed2000

Influence of nephron mass in development of chronic renal failure after prolonged warm renal ischemia.

The present study examined the long-term consequences of warm renal ischemia (WRI) with or without renal ablation. Male Sprague-Dawley rats (250-300 g) were subjected to 60 min of complete WRI by pedicle clamping and then followed for 52 wk. Animals were organized into four groups: rats in which both kidneys were subjected to warm ischemia (2WIK); rats with left WRI and right nephrectomy (1WIK); uninephrectomized rats with a left nonischemic kidney (1NK); and sham-operated rats (2NK). Additional animals were studied at 24 h, 7 days, and 16 and 32 wk. In the first week after WRI, rats from the 2WIK and 1WIK groups displayed a similar degree of acute renal damage. After recovering from acute renal failure, 1WIK rats developed progressive and severe proteinuria, whereas it was mild in the 2WIK group, as well as in the 1NK and 2NK groups. Only animals from the 1WIK group developed severe chronic renal failure, glomerulosclerosis, interstitial fibrosis, and upregulation of transforming growth factor-beta(1) (TGF-beta(1)) gene, which was associated with increased TGF-beta(1) protein expression in tubular epithelial cells, arterioles, and in areas of mononuclear interstitial cell infiltrate. On the contrary, long-term renal TGF-beta(1) expression, function, and histology were similar in 2WIK and 2NK rats. The present study shows that prolonged bilateral WRI, when both kidneys are retained in place, induces very mild long-term renal lesions as opposed to the severe renal scarring observed when WRI is combined with contralateral nephrectomy.

Acute Kidney Injury↗
PubMed1999

Expressed sequence tag (EST) phenotyping of HT-29 cells: cloning of ser/thr protein kinase EMK1, kinesin KIF3B, and of transcripts that include Alu repeated elements.

To study the mechanisms that control epithelial commitment and differentiation we have used undifferentiated HT-29 colon cancer cells and a subpopulation of mucus secreting cells obtained by selection of HT-29 cells in 10-6 M methotrexate (M6 cells) as experimental models. We isolated cDNAs encoding transcripts overexpressed in early confluent M6 cells regarding steady-state levels in HT-29 cells by subtractive hybridisation. Fifty-one cDNA clones, corresponding to 34 independent transcripts, were isolated, partially sequenced by their 5' end, and classified into four groups according to their identity: transcripts that included a repeated sequence of the Alu family (10 clones, among them those encoding ribonucleoprotein RNP-L and E-cadherin), transcripts encoded by the mitochondrial genome (nine clones), transcripts encoding components of the protein synthesis machinery (23 clones, including the human ribosomal protein L38 not previously cloned in humans) and nine additional cDNAs that could not be classified in the previous groups. These last included ferritin, cytokeratin 18, translationally controlled human tumour protein (TCHTP), mt-aldehyde dehydrogenase, as well as unknown transcripts (three clones), and the human homologues of the molecular motor kinesin KIF3B and of the ser/thr protein kinase EMK1. Spot dot and Northern blot analyses showed that ser/thr protein kinase EMK1 was differentially expressed in M6 cells when compared with parental HT-29 cells. Steady-state levels of EMK1 were higher in proliferating, preconfluent, M6 and HT-29 cells than in 2 days post confluence (dpc) and 8dpc M6 and HT-29 cells. Transcripts that included an Alu repeat were also shown to be differentially expressed and accumulated in differentiating M6 cells when analysed by Northern blot. The significance of the transcripts cloned is discussed in the context of the commitment and differentiation of the M6 cells to the mucus secreting lineage of epithelial cells.

Alu Elements↗
PubMed1999

Active NMDA glutamate receptors are expressed by mammalian osteoclasts.

1. The N-methyl-D-aspartate (NMDA) glutamate receptor, widely distributed in the mammalian nervous system, has recently been identified in bone. In this study, we have investigated whether NMDA receptors expressed by osteoclasts have an electrophysiological activity. 2. Using the patch clamp technique two agonists of the NMDA receptor, L-glutamate (Glu) and NMDA, were shown to activate whole-cell currents recorded in isolated rabbit osteoclasts. 3. The current-voltage (I-V ) relationships of the currents induced by Glu (IGlu) and NMDA (INMDA) were studied using Mg2+-free solutions. The agonist-induced currents had a linear I-V relationship with a reversal potential near 0 mV, as expected for a voltage independent and non-selective cationic current. 4. IGlu and INMDA were sensitive to specific blockers of NMDA subtype glutamate receptors, such as magnesium ions, (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten -5,10-imine (MK-801) and 1-(1,2-diphenylethyl) piperidine (DEP). The block of IGlu and INMDA by these specific antagonists was voltage dependent, strong for negative potentials (inward current) and absent for positive potentials (outward current). 5. These results demonstrate that NMDA receptors are functional in rabbit osteoclasts, and that their electrophysiological and pharmacological properties in these cells are similar to those documented for neuronal cells. Active NMDA receptors expressed by osteoclasts may represent a new target for regulating bone resorption.

Animals↗
PubMed1999

Long-term protective effect of UR-12670 after warm renal ischemia in uninephrectomized rats.

BACKGROUND: The phospholipid platelet-activating factor (PAF) participates in the pathogenesis of renal ischemia/reperfusion injury, and in vitro, it induces synthesis of extracellular matrix proteins by mesangial and tubular epithelial cells. This study investigated the long-term effects of the potent orally active PAF antagonist UR-12670 in warm ischemic uninephrectomized rats, which was given according to different therapeutic schedules. METHODS: Uninephrectomized male Sprague-Dawley rats were divided into five groups and were followed for 52 weeks: rats without ischemia (SK); ischemic kidney for 60 minutes (SIK); ischemic kidney and UR-12670 from 0 to the 7th day (UR 0-7); ischemic kidney and UR-12670 from day 0 to 52 weeks (UR 0-E); and ischemic kidney and UR-12670 from day 8 to week 52 (UR 8-E). Two more groups (ischemic and UR treated) served to evaluate the UR-12670-protective effect on ischemic acute renal failure at one week. RESULTS: UR-12670 administration exerted functional and morphological protection against post-ischemic acute renal failure. The ischemic untreated (SIK) group developed progressive proteinuria from week 12. The onset of proteinuria in ischemic UR-12670-treated groups was delayed to the 24th week, and it was significantly lower than in SIK group throughout the study. Only SIK and ischemic-treated UR 0-7 rats presented with chronic renal failure, as shown by creatinine, creatinine clearance, glomerular filtration rate (GFR), and renal plasma flow (GFR 52 weeks: SK, 2525 +/- 267; SIK, 992 +/- 149; UR 0-7, 1551 +/- 385 microliter/min). Kidneys from the short-term treated group (UR 0-7) showed a reduction of glomerulosclerosis (SK, 14.4 +/- 3.7; SIK, 75.7 +/- 7.7; UR 0-7, 41. 5 +/- 8.5%) and vascular myointimal hyperplasia, but the tubulointerstitial damage (tubulointerstitial score: SK, 0.2 +/- 0. 2; SIK, 4.4 +/- 0.5; UR 0-7, 3.7 +/- 0.7) was similar to that in the ischemic untreated group. Long-term ischemic treated rats (UR 0-E, UR 8-E) did not develop chronic renal failure (GFR: UR 0-E, 2059 +/- 314; UR 8-E, 2410 +/- 208 microliter/min). In these groups, glomerulosclerosis (UR 0-E, 32.8 +/- 5.8; UR 8-E, 24.3 +/- 3.0%), tubulointerstitial damage (tubulointerstitial score: UR 0-E, 2.1 +/- 0.5; UR 8-E, 1.9 +/- 0.3) and vascular myointimal hyperplasia were significantly lower than in the ischemic untreated group. By in situ hybridization, an increase of transforming growth factor-beta1 mRNA expression in glomerular and tubular cells was observed in ischemic untreated and ischemic treated UR 0-7 rats. UR-12670 long-term treated rats showed a clear reduction of transforming growth factor-beta1 mRNA-positive glomerular cells. CONCLUSION: The chronic administration of the PAF antagonist UR-12670 attenuates the long-term effects of ischemia-reperfusion injury in uninephrectomized rats. The beneficial effect of this agent, even when given beyond the initial ischemia/reperfusion injury, suggests that PAF plays a role in the mechanisms of progression to late renal damage in this model.

Acute Kidney Injury↗