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[Interleukin-8].

Interleukin 8 (IL-8) is one of the most widely studied chemoattractants for leukocytes. It belongs to the newly classified CXC family of chemokine which possesses biological activities mainly on neutrophils. The potential role of IL-8 in inflammation is substantiated by the growing evidences of clinical relevance of IL-8 in various diseases such as infection, ischemia and autoimmune disorders. The common characteristic pathological feature of these events is neutrophil infiltration. Although little is known about the mechanism of neutrophil recruitment into the urine, urinary tract infections (UTI) are accompanied by pyuria. Elevated urinary IL-8 levels were found in patients with UTI. Bioactive, multiple forms of IL-8 were produced locally within the urinary tract, and implied that IL-8 participated in the induction of neutrophil migration into the inflammatory site. Similar findings were observed in the peritoneal dialysate of patients on continuous ambulatory peritoneal dialysis with peritonitis. The notion of involvement of IL-8 in local infection was reinforced by the findings obtained on the rabbit UTI model. Finally, the clinical usefulness, as well as the problems of IL-8 level determination in various body fluids are discussed.

Humans↗

[Complications and errors in use of the gamma nail. Causes and prevention].

The analysis of 310 cases of fractures of the femur, treated with a Gamma-nail osteosynthesis, done in two clinics for trauma surgery in Vienna, revealed to a high number of complications. For this reason we decided to start an evaluation aming at complications in connection to this type of treatment, with 440 patients treated over a five year period. We observed 148 complications, which will be described. The intraoperative failures were as follows: False drilling during the interlocking procedure 64, wrong length of lag screw 13, breakage of the drill bit during interlocking procedure 7, additional shattering of shaft 5, external malrotation of diaphysis (> or = 20 degrees) 6, internal malrotation of the diaphysis (> or = 20 degrees) 1, elongation of diaphysis (2 cm) 1, mistakes in using the proximal nail-plaque 4, breakage of bone elevator, used for reduction procedure 1 and 1 failure at the target-device during nailing. The complications during the postoperative treatment were: Infection 11, perforation of lag screw towards cranial 10, towards central 2, migration of the lack screw within the femoral head 7, diaphysial fracture at the distal end of nail 6, movement of interlocking bolts 4, osteolytic process at fracture site 2 and 3 haematomas, needing a revision. Most of these reported complications were due to technical failures, lack of experience or inadequate treatment modality. The specifications and descriptions should give information about the reasons of these complications, but it is the purpose of this publication too, to figure out the technical errors which were responsible for most of the complications described.

Aged↗

Calcium-independent regulation of pigment granule aggregation and dispersion in teleost retinal pigment epithelial cells.

In the eyes of teleosts and amphibians, melanin pigment granules of the retinal pigment epithelium (RPE) migrate in response to changes in light conditions. In the light, pigment granules disperse into the cells' long apical projections, thereby shielding the rod photoreceptor outer segments and reducing their extent of bleach. In darkness, pigment granules aggregate towards the base of the RPE cells. In vitro, RPE pigment granule aggregation can be induced by application of nonderivatized cAMP, and pigment granule dispersion can be induced by cAMP washout. In previous studies based on RPE-retina co-cultures, extracellular calcium was found to influence pigment granule migration. To examine the role of calcium in regulation of RPE pigment granule migration in the absence of retinal influences, we have used isolated RPE sheets and dissociated, cultured RPE cells. Under these conditions depletion of extracellular or intracellular calcium ([Ca2+]o, [Ca2+]i) had no effect on RPE pigment granule aggregation or dispersion. Using the intracellular calcium dye fura-2 and a new dye, fura-pe3, to monitor calcium dynamics in isolated RPE cells, we found that [Ca2+]i did not change from basal levels when pigment granule aggregation was triggered by cAMP, or dispersion was triggered by cAMP washout. Also, no change in [Ca2+]i was detected when dispersion was triggered by cAMP washout in the presence of 10 microM dopamine, a treatment previously shown to enhance dispersion. In addition, elevation of [Ca2+]i by addition of ionomycin neither triggered pigment movements, nor interfered with pigment granule motility elicited by cAMP addition or washout. Since other studies have indicated that actin plays a role in both pigment granule dispersion and aggregation in RPE, our findings suggest that RPE pigment granule migration depends on an actin-based motility system that is not directly regulated by calcium.

Animals↗

Expression and distribution of adhesion molecule CD44 in healing corneal epithelia.

PURPOSE: To study isoform expression and cellular distribution of CD44, a cell surface glycoprotein thought to be an adhesion molecule in cell-cell and cell-substratum interactions, during corneal epithelial wound healing. METHODS: Reverse transcription-polymerase chain reaction was performed to determine alternatively spliced rat CD44 isoforms. In situ hybridization was carried out on frozen sections of the rat corneas obtained at different time points after epithelial debridement. 35S-Labeled sense and antisense cRNA that recognizes rat CD44 standard form was used as a probe. Immunofluorescence was used to assess expression and localization of CD44 in the rat corneas during reepithelialization. RESULTS: Corneal epithelia contained several alternatively spliced CD44 variants. Four large CD44 variants with inserts V1 through V10, V2 through V10, V3 through V10, and V4 through V10 were differentially expressed in migratory epithelia. The silver grains, indicating CD44 transcripts, started to increase in the epithelial cells surrounding the wound margin 3 hours after wounding and peaked at 18 hours in the basal epithelial cell layers, at which time the epithelia were actively migrating. As the cells began proliferation after wounding, the density of CD44 mRNA label declined but was still significantly higher than that in control specimens. The label returned to basal level as epithelial cells reverted to their normal phenotype. The location of CD44 on cell surfaces during corneal reepithelialization was consistent with the pattern of mRNA production. In the corneas at 18 hours after wounding, CD44 immunoreactivity was elevated in the entire epithelium, from the leading edge to the limbal-corneal border. As happened for the mRNA, the cell surface CD44 declined as cells differentiated to reestablish the multilayered epithelium. CONCLUSIONS: The expression of CD44 correlates with corneal reepithelialization, suggesting that CD44 may be involved in cell-cell interactions that provide adhesive strength for the much-stressed epithelial sheet and in the cell-substratum interactions that mediate cell migration during reepithelialization.

Alternative Splicing↗

Critical evaluation of the current indications for transition zone biopsies.

OBJECTIVES: Two primary indications for the performance of anteriorly directed transition zone (TZ) biopsies are (a) an elevated prostate-specific antigen (PSA) level and an enlarged, non-nodular prostate and (b) prior negative sextant biopsies of the prostate. These indications are, however, based on a study population evaluated early in the PSA era (1989 to 1992). The current analysis targeted a more contemporary series of patients (1995 to 2000) presenting with these two indications for TZ biopsies, who underwent ultrasound scanning and biopsies by the same examiner and with the same equipment as in the earlier series. METHODS: We evaluated 390 men, 274 (70.3%) of whom underwent sextant plus TZ biopsies for elevated PSA levels and an enlarged, non-nodular prostate; 116 (28.7%) underwent this biopsy strategy because of an elevated or rising PSA in whom prior sextant biopsies had not revealed cancer. RESULTS: Of the 274 patients who underwent initial sextant biopsies plus anterior biopsies for an enlarged, non-nodular prostate, 49 (17.9%) were found to have adenocarcinoma and in only 4 (1.5%) did only the TZ biopsies reveal cancer. Of the 116 patients who underwent TZ biopsies after prior negative sextant biopsies, 36 (31.0%) were found to have prostate cancer and in 11 (9.5%) only the TZ biopsies demonstrated cancer. CONCLUSIONS: The cancer detection rate for sextant plus TZ biopsies in this contemporary series of patients presenting with enlarged, non-nodular prostates was substantially lower than the rate in earlier reports (1.5% compared with 36.9%), despite the consistency in the equipment and examining physician. This may have been due to the stage migration of prostate cancer, which has been observed as a result of the widespread use of PSA measurement for early detection. Sextant plus TZ biopsies are more productive in patients with prior negative biopsies who have a persistent clinical suspicion for prostate cancer on the basis of an elevated and/or rising PSA level.

Aged↗

Suppressed smooth muscle proliferation and inflammatory cell invasion after arterial injury in elafin-overexpressing mice.

Elastases degrade the extracellular matrix, releasing growth factors and chemotactic peptides, inducing glycoproteins such as tenascin, and thereby promoting vascular cell proliferation and migration. Administration of serine elastase inhibitors reduces experimentally induced vascular disease. The ability to mount an intrinsic anti-elastase response may, therefore, protect against intimal/medial thickening after vascular injury. To investigate this, we showed that wire-induced endothelial denudation of the carotid artery is associated with transient elevation in elastase activity and confirmed that this is abolished in transgenic mice overexpressing the serine elastase inhibitor, elafin, targeted to the cardiovascular system. Ten days after injury, nontransgenic littermates show vessel enlargement, intimal thickening, increased medial area and cellularity, and 2-fold increase in tenascin. Injured vessels in transgenic mice become enlarged but are otherwise similar to sham-operated controls. Injury-induced vessel wall thickening, which is observed only in nontransgenic mice, is related to foci of neutrophils and macrophages, in addition to smooth muscle cells that fail to stain for alpha-actin and are likely dedifferentiated. Our study therefore suggests that a major determinant of the vascular response to injury is the early transient induction of serine elastase activity, which leads to cellular proliferation and inflammatory cell migration.

Animals↗

Acetaldehyde adducts with hemoglobin.

Clinical studies on the minor hemoglobins (hemoglobin A1a-c) have suggested that a novel adduct may form in people abusing alcohol. Such patients were found to have an elevated concentration of minor hemoglobins, but normal or subnormal amounts of glycosylated hemoglobin (hemoglobin A1c) as determined by radioimmunoassay, Acetaldehyde, a reactive metabolite of ethanol, was postulated to form adducts with hemoglobin A that change its chromatographic properties. At physiological concentrations, acetaldehyde was found to form adducts with hemoglobin that were stable to extensive dialysis for several days. The amount of hemoglobin adducts formed were a function of the concentration and number of exposures to acetaldehyde. The reaction of acetaldehyde with hemoglobin A produced chromatographic variants, some of which migrated in the hemoglobin A1a-c region. Analysis of stable acetaldehyde-hemoglobin adducts demonstrated that valine, lysine, and tyrosine residues of globin were sites of reaction. The acetaldehyde-modified amino acid residues appear to exist in interconvertible conformations, only one of which is reducible by sodium borohydride. The amount of these adducts was found to be significantly elevated in hemoglobin from alcoholics as compared with normal volunteers.

Acetaldehyde↗

Immune responsiveness to retinal S-antigen and opsin in serpiginous choroiditis and other retinal diseases.

The immune responsiveness to bovine retinal S-antigen and opsin has been investigated in some retinal disorders by means of in vitro lymphocyte proliferation, leukocyte migration inhibition and enzyme linked immune sorbent assays (ELISA). Sensitisation to S-antigen was observed in serpiginous choroiditis, but not in acute posterior multifocal placoid pigment epitheliopathy (APMPPE) or retinitis pigmentosa. No significant immune responsiveness was detected to opsin in any of the three diseases. Elevated antibody titers to S-antigen were observed in some individual patients and healthy subjects. However, none of the patient groups exhibited an elevated antibody titer as compared to the control group. Although serpiginous choroiditis and APMPPE share some prominent clinical characteristics, the sensitisation in the former disease may perhaps be attributed to more severe and prolonged damage of the photoreceptor cells and blood-retina barrier. A combination of previous and present results suggests that in immunological investigations of retinitis pigmentosa patients it is more effective to use human than bovine S-antigen as test antigen because a species specific epitope seems to be involved.

Antibody Formation↗

Multiple sclerosis and optic neuritis: CCR5 and CXCR3 expressing T cells are augmented in blood and cerebrospinal fluid.

A role for chemokines as mediators of Th1 cell recruitment to the central nervous system (CNS) is probable in MS. Therefore we studied expression of Th1-related CCR5 and CXCR3 chemokine receptors in patients with MS and controls. Patients with untreated MS had elevated percentages of CCR5 and CXCR3 expressing T cells vs. healthy controls (HC) in blood, and vs. other non-inflammatory neurological diseases (OND) patients in CSF. Such elevation was not found in MS patients examined during ongoing treatment with IFN-beta. Patients with optic neuritis (ON), a common first manifestation of MS, had elevated percentages of CXCR3 expressing T cells in blood compared with HC, and of CCR5 expressing T cells in CSF compared with OND patients. High chemokine receptor expression may be one prerequisite for Th1 cells to migrate to the CNS. Inhibition of chemokine receptor expression may constitute a potentially important therapeutic effect of IFN-beta.

Adult↗

Modulation of the synthesis and glycosylation of the glucose transporter protein by transforming growth factor-beta 1 in Swiss 3T3 fibroblasts.

Transforming growth factor-beta 1 (TGF-beta 1) stimulated growth and glucose uptake in Swiss mouse fibroblasts. DNA synthesis was increased 2-3-fold after 48 h incubation of growing 3T3 cells with TGF-beta 1 in calf serum-containing medium. Glucose transport activity in the cells was increased within 3 h after addition of TGF-beta 1 and this stimulation continued during incubation for 48 h. TGF-beta 1 also increased the levels of a brain type-glucose transporter (GLUT1) mRNA and the GLUT1 protein (55 kDa) in the membranes, consistent with the increase in glucose uptake. Furthermore, a longer exposure of TGF-beta 1 for 24-48 h induced a marked increase in the 65 kDa GLUT1 in 3T3 cell membranes. Other growth factors such as epidermal growth factor, fibroblast growth factor, transforming growth factor-alpha, and insulin did not elevate glucose uptake and the levels of 55 and 65 kDa GLUT1 proteins. Adding tunicamycin or deoxymannojirimycin to the TGF-beta 1-treated and untreated cells caused these 55 and 65 kDa glucose transporters to migrate as one band at 40-43 kDa. In addition, treating membrane proteins with glycopeptidase F, which removes N-linked oligosaccharides, also generated a glucose transporter of 40 kDa, suggesting that the 55 and 65 kDa GLUT1 proteins have a similar or identical core polypeptide but with different N-linked oligosaccharides. These results indicate that TGF-beta 1 modulates the synthesis of GLUT1 protein as well as its glycosylation in Swiss 3T3 cells, and that these changes may contribute to the control of cell proliferation by TGF-beta 1.

3T3 Cells↗

The ecophysiology of air-breathing in crabs with special reference to Gecarcoidea natalis.

To succeed on land rather than in water, crabs require a suite of physiological and morphological changes, and ultimately the ability to reproduce without access open water. Some species have modified gills to assist in gas exchange but accessory gas exchange organs, usually lungs, occur in many species. In accomplished air-breathers the lung becomes larger and more vascularised with pulmonary vessels directing oxygenated haemolymph to the heart. The relative abundance of O(2) in air promotes relative hypoventilation and thus an internal hypercapnia to drive CO(2) excretion. Land crabs have a dual circulation via either lungs or gills and shunting between the two may depend on respiratory media or exercise state. During their breeding migration on Christmas Island Gecarcoidea natalis maintained arterial Po(2) by branchial O(2) uptake, while pulmonary O(2) pressure was reduced; partly because exercise doubled relative haemolymph flow through the gills. Related species rely on elevated haemocyanin concentration and affinity for O(2) to assist uptake but this compromises unloading at the tissues and thus the aerobic scope of tissues. Aquatic crabs exchange salt and ammonia with water via the gills but in land crabs this is not possible. Birgus latro has adopted uricotelism but other species excrete ammonia in either the urine or as gas. Land crabs minimise urinary salt loss using a filtration-reabsorption system analogous to the kidney. Urine is redirected across the gills where salt reabsorption occurs in systems under hormonal control, although in G. natalis this is stimulatory and in B. latro inhibitory. While crabs occupy a range of habitats from aquatic to terrestrial, these species do not comprise a physiological continuum but across the crab taxa individual species possess appropriate and specific physiological features to survive in their individual habitat.

Air↗

Clinical interest of PPARs ligands.

Cardiovascular disease is significantly increased in patients with metabolic syndrome and type 2 diabetes. Several factors such as chronic hyperglycemia, lipId abnormalities, endothelium dysfunction, inflammation, oxIdative stress, increased thrombosis and decreased fibrinolysis are likely to promote cardiovascular events in these patients. Because of positive effects on glucose homeostasis, lipId metabolism, proteins involved in all stages of atherogenesis, endothelium function, inflammation, thrombosis and fibrinolysis, PPARS alpha (fibrates) and PPARs gamma (glitazones) agonists are good candIdates to reduce cardiovascular disease, more precisely in subjects with metabolic syndrome or type 2 diabetes. PPARS alpha agonists (fibrates) are potent hypolipIdemic agents increasing plasma HDL-cholesterol and reducing free fatty acIds, triglycerIdes, LDL-cholesterol and the number of small dense LDL pArticles. Moreover, they reduce vascular inflammation and thrombosis, promote fibrinolysis and inhibit the production of the vasoconstrictor factor, endothelin-1, by the endothelium. They have been shown, in clinical trials, to reduce cardiovascular disease, more particularly in patients displaying lipId abnormalities typical of metabolic syndrome and type 2 diabetes (high triglycerIdes, low HDL-cholesterol). PPARS gamma agonists (glitazones) have not only beneficial effects on glucose homeostasis, by increasing insulin sensitivity and reducing blood glucose level but also on lipId metabolism by elevating plasma HDL-cholesterol, decreasing free fatty acIds and the number of small dense LDL pArticles, and for pioglitazone by reducing plasma triglycerIdes. Furthermore, they diminish vascular inflammation and vasoconstriction, inhibit monocyte chemotaxis, proliferation and migration of smooth muscle cells, in the vascular wall and decrease the production of adhesion molecules and metalloproteinases. PPARs gamma agonists (glitazones) have been shown to reduce the development of atherosclerotic lesions in rats. The potential clinical benefit of PPARs gamma agonists on the reduction of cardiovascular disease, in type 2 diabetic patients, will be specified by the ongoing intervention studies.

Animals↗

Monitoring oxidation of chlorinated ethenes by permanganate in groundwater using stable isotopes: laboratory and field studies.

Permanganate injection is increasingly applied for in situ destruction of chlorinated ethenes in groundwater. This laboratory and field study demonstrates the roles that carbon isotope analysis can play in the assessment of oxidation of trichloroethene (TCE) by permanganate. In laboratory experiments a strong carbon isotope fractionation was observed during oxidation of TCE with similar isotopic enrichment factors (-25.1 to -26.8 per thousand) for initial KMnO4 concentrations between 67 and 1,250 mg/L. At the field site, a single permanganate injection episode was conducted in a sandy aquifer contaminated with TCE as dense nonaqueous liquid (DNAPL). After injection, enriched delta13C values of up to +204% and elevated Cl- concentrations were observed at distances of up to 4 m from the injection point. Farther away, the Cl- increased without any change in delta13C of TCE suggesting that Cl- was not produced locally but migrated to the sampling point Except for the closest sampling location to the injection point, the delta13C rebounded to the initial 613C again, likely due to dissolution of DNAPL Isotope mass balance calculations made it possible to identify zones where TCE oxidation continued to occur during the rebound phase. The study indicates that delta13C values can be used to assess the dynamics between TCE oxidation and dissolution and to locate zones of oxidation of chlorinated ethenes that cannot be identified from the Cl- distribution alone.

Chlorine Compounds↗

Ion chemistry of OV(OCH3)3 in the gas phase: molecular cations and anions and their primary fragmentations.

Trimethyl vanadate(V), OV(OCH(3))(3) (1), is examined by various mass spectrometric means. Photoionization experiments yield an ionization energy of IE(OV(OCH(3))(3)) = 9.54 +/- 0.05 eV for the neutral molecule. The primary fragmentation of the molecular cation 1(+), i.e., loss of neutral formaldehyde, can occur via two independent routes of hydrogen migrations to afford the formal V(IV) compounds HOV(OCH(3))(2)(+) and OV(OCH(3))(CH(3)OH)(+), respectively. These two pathways are associated with low-lying activation barriers of almost identical height. At elevated energies, direct V-O bond cleavage of 1(+) allows for expulsion of a methoxy radical concomitant with the generation of the cationic fragment OV(OCH(3))(2)(+), a formal V(V) compound. Trimethyl vanadate can also form a molecular anion, 1(-), whose most abundant dissociation channel involves loss of a methyl radical, thereby leading to the formal V(V) compound OV(OCH(3))(2)O(-). Various mass spectrometric experiments and extensive theoretical studies provide detailed insight into the ion structures and the relative energetics of the primary dissociation reactions of the molecular cations and anions of 1.

Journal Article↗

H-ras(val12) induces cytoplasmic but not nuclear events of the cell cycle in small Xenopus oocytes.

Microinjection of H-ras(val12) protein into fully grown Xenopus oocytes has been shown to induce meiotic maturation. In the present study, mRNA encoding the mutant ras protein was injected into both fully grown (stage 6) and growing (stage 4) oocytes. The mRNA induced nuclear breakdown in stage 6 oocytes, as expected. However, the mRNA induced neither nuclear breakdown nor maturation promoting factor when injected into stage 4 oocytes. Instead, the response in stage 4 oocytes included an activation pulse of calcium, cortical granule breakdown, elevation of the vitelline envelope, and abortive cleavage furrows, all of which are characteristics of the activation response in mature eggs. In addition, the injected mRNA led to increased rates of endogenous protein synthesis and the migration of subcortical organelles into the oocyte interior. These observations are discussed relative to the suggestion that oncogenic ras protein leads to an increase in both diacylglycerol and inositol trisphosphate, which then regulate the various cytoplasmic events described.

Animals↗

Mechanisms of lymphocytic choriomeningitis virus-induced hemopoietic dysfunction.

Results of this study showed that lymphocytic choriomeningitis virus infection causes a marked activation of natural killer (NK) cells not only in the spleen but also in the bone marrow. This activity reached its peak at about day 3 of infection and declined after days 6 to 7. Enhanced NK cell activity was found to correlate with decreased receptivity for syngeneic stem cells in bone marrow and spleen, with the notable exception that decreased receptivity persisted longer in bone marrow. Treatment of infected recipients with anti-asialo GM1 (ganglio-N-tetraosylceramide) significantly increased the receptivity for syngeneic hemopoietic cells. These findings are consistent with the hypothesis that NK cell activation causes rejection of syngeneic stem cells, thus resulting in hemopoietic depression. To understand the mechanisms behind the prolonged decrease in bone marrow receptivity (and bone marrow function in the intact mouse) mentioned above, we followed the changes in the number of pluripotential stem cells (CFU-S) circulating in the peripheral blood and in endogenous spleen colonies in irradiated mice, the limbs of which were partially shielded. It was found that following a marked early decline, both parameters increased to normal or supranormal levels at about day 9 after infection. Because the bone marrow pool of CFU-S is only about 20% of normal at this time after infection, a marked tendency for CFU-S at this stage in the infection to migrate from the bone marrow to the spleen is suggested. It seems, therefore, that as NK cell activity declines, the spleen regains the ability to support growth of hemopoietic cells and the bone marrow resumes an elevated export of stem cells to the spleen. This diversion of hemopoiesis could explain both the long-standing deficiencies of the bone marrow compartment and the prolonged decrease in the receptivity of this organ.

Animals↗

Role of osteopontin in cellular signaling and toxicant injury.

Osteopontin (OPN) is a glycosylated phosphoprotein found in all body fluids and in the proteinaceous matrix of mineralized tissues. It can function both as a cell attachment protein and as a cytokine, delivering signals to cells via a number of receptors including several integrins and CD44. Expression of OPN is enhanced by a variety of toxicants, especially those that activate protein kinase C. In its capacity as a signaling molecule, OPN can modify gene expression and promote the migration of monocytes/macrophages up an OPN gradient. It has both inflammatory and anti-inflammatory actions. Some experiments suggest that it may inhibit apoptosis, possibly contributing to the survival of cells in response to toxicant injury. Elevated OPN expression often correlates with malignancy and has been shown to enhance the tumorigenic and/or metastatic phenotype of the cancer cell. Recent studies have revealed that OPN plays critical roles in bone remodeling and cell-mediated immunity.

Animals↗

Renal ischemic-reperfusion injury in L-selectin-deficient mice.

L-selectin on leukocyte surfaces mediates cell rolling on endothelium. L-selectin blockade with antibodies attenuated ischemic-reperfusion injury (IRI) in heart and skeletal muscle, but its role in renal IRI is unknown. We evaluated the role of L-selectin in renal IRI using L-selectin-deficient mice. Neutrophil migration to chemically inflamed peritoneum was reduced by 47% (P < 0.01) in L-selectin-deficient mice. Ischemia was induced by bilateral renal pedicle clamping for 30 min. Control and L-selectin groups had similar elevations of serum creatinine (1.8 +/- 0.3 vs. 1.7 +/- 0.2 mg/dl) and blood urea nitrogen (111 +/- 17 vs. 128 +/- 12 mg/dl) 24 h postischemia. Pathological assessment showed comparable degrees of tubular necrosis at 24 h. The postischemic increase in peritubular neutrophils per 10 high-power field was similar in control and L-selectin-deficient groups at 4 (28 +/- 10 vs. 22 +/- 5), 12 (245 +/- 80 vs. 236 +/- 78), and 24 h (130 +/- 12 vs. 156 +/- 18). These data argue against a significant role for L-selectin in renal IRI. Patho-physiological roles of L-selectin in vivo appear to be more complex than in vitro data would suggest.

Animals↗