Reduction of podocytes number in late diabetic alloxan nephropathy: prevention by glycemic control

OBJETIVO: Avaliar o número de podócitos e espessamento da membrana basal glomerular (MBG) em ratos diabéticos com e sem controle glicêmico com 6 e 12 meses da indução. MÉTODOS: 100 ratos Wistar com 200-300g compuseram 6 grupos: Normal (N6, N12 - 25 animais) Diabético (D6,D12 - 25 animais) e diabético tratado com insulina 1,8 a 3,0 U/Kg e acarbose misturada a ração (50g para cada 100g de ração) (DT6 e DT12 - 25 animais). Aloxana foi ministrada via endovenosa na dose de 42mg/Kg. Peso, ingestão hídrica e diurese de 24 horas e glicemia e glicosúria foram determinados antes da inoculação, 7 e 14 dias após e mensalmente. No 14ª dia foi iniciado o tratamento. Três grupos de animais (N6, D6 e DT6) foram sacrificados no 6° mês e três grupos (N12, D12 e DT12), no 12ª mês sendo o tecido renal processado para estudo à microscopia eletrônica. RESULTADOS: A glicemia dos animais DT6 e DT12 diferiram significativamente, dos ratos D6 e D12, e não diferiram dos grupos N6 e N12. O número de podócitos do grupo DT6 não diferiu de N6 e D6 (mediana=11); o número de podócitos de DT12 (mediana=11) diferiu de D12 (mediana=8) e não diferiu de N12 (mediana=11). O espessamento da MBG de D6 (0,18 micrômetros) foi menor que D12 (0,29 micrômetros); de DT6 (0,16 micrômetros) foi menor que D6 (0,18 micrômetros) e de DT12 (0,26 micrômetros) foi menor que D12 (0,29 micrômetros). CONCLUSÃO: O controle da hiperglicemia preveniu o espessamento da MBG na nefropatia diabética aloxânica precoce (6 meses) e tardia (12 meses), e a diminuição do número de podócitos.

Effect of mangiferin on the development of periodontal disease: Involvement of lipoxin A(4), anti-chemotaxic action in leukocyte rolling

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Amoxicillin diminishes the thickness of the enamel matrix that is deposited during the secretory stage in rats

The use of amoxicillin during early childhood has been associated with molar incisor hypomineralization. The objective of this study was to determine whether the use of amoxicillin interferes with enamel development, during secretion and early mineralization stages. Fifteen pregnant rats were randomly assigned to three groups that received physiological solution (sham group), 100 mg/kg/day amoxicillin (A100G), and 500 mg/kg/day amoxicillin (A500G). After birth, the pups in each group received the same treatment until post-natal day 7 or 12. The upper first molars were analyzed histomorphometrical and immunostaining with amelogenin on day 7, and MMP-20 on day 12 was performed using a semiquantitative method (H-score). At 7 days, several vacuolar structures were observed in the ameloblasts in the A100G and A500G groups. A significant reduction of the enamel thickness (P < 0.001) was found in amoxicillin-treated rats compared with the sham group. Significant differences were not observed in enamel thickness (P > 0.05) between the groups of 12-day-old rats. Moreover, significant differences were not observed in the number of amelogenin- and MMP-20-immunolabeled ameloblasts (P > 0.05) between groups. The present results suggest that amoxicillin interferes with the initial stages of amelogenesis by causing structural changes in the ameloblasts and a reduction of the enamel matrix.

Laminar Displacement and Prelaminar Tissue Thickness Change after Glaucoma Surgery Imaged with Optical Coherence Tomography

PURPOSE. To study changes in lamina cribrosa position and prelaminar tissue thickness (PTT) after surgical IOP reduction in glaucoma patients. METHODS. Twenty-two patients (mean age, 71.4 years) were imaged with spectral domain optical coherence tomography (SD-OCT; 24 radial B-scans centered on the optic nerve head [ONH]) before trabeculectomy or tube shunt implantation. Follow up images were acquired 1 week, 1 month, 3 months, and 6 months postsurgery. Bruch's membrane opening (BMO), the internal limiting membrane (ILM) and the anterior laminar surface (ALS) were segmented in each radial scan with custom software. Surfaces were fitted to the ILM and ALS with the extracted three-dimesional coordinates. PTT was the distance between the ILM and ALS, perpendicular to a BMO reference plane. Serial postsurgical laminar displacement (LD), relative to the BMO reference plane, and changes in PTT were measured. Positive values indicated anterior LD. RESULTS. Mean (SD) presurgery IOP was 18.1 (6.5) mm Hg, and reduced by 4.7 (5.5), 2.4 (7.7), 7.0 (6.2), and 6.8 (7.5) mm Hg at 1 week, 1 month, 3 months, and 6 months postsurgery, respectively. At the four postsurgery time points, there was significant anterior LD (1.8 [9.5], -1.1 [8.9], 8.8 [20.2], and 17.9 [25.8] mu m) and PTT increase (1.7 [13.3], 2.4 [11.9], 17.4 [13.7], and 13.9 [18.6] mu m). LD was greater in ONHs with larger BMO area (P = 0.01) and deeper ALS (P = 0.04); however, PTT was not associated with any of the tested independent variables. CONCLUSIONS. Both anterior LD and thickening of prelaminar tissue occur after surgical IOP reduction in patients with glaucoma. (Invest Ophthalmol Vis Sci. 2012;53:5819-5826) DOI:10.1167/iovs.12-9924

Carotid plaque and intima-media thickness and the incidence of ischemic events in patients with atherosclerotic vascular disease

We aimed to evaluate whether carotid intima-media thickness (CIMT) or the presence of plaque can confer additional predictive value of future cardiovascular (CV) ischemic events in patients with pre-existing atherosclerotic vascular disease. We identified 2317 patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry who had atherosclerotic vascular disease and baseline CIMT measurements. The entire range of CIMT was divided into quartiles and the fourth quartile (? 1.5 mm) was defined as carotid plaque. Mean ± standard deviation baseline CIMT was 1.31 ± 0.65 mm. Associated CV ischemic events and vascular-related hospitalizations were evaluated over a 2-year follow-up. There was a positive increase in adjusted hazard ratios (HRs) for all-cause mortality (p = 0.04 for trend) and the quadruple endpoint (CV death, myocardial infarction (MI), stroke, hospitalization for CV events) with increasing quartiles of CIMT (p = 0.0008 for trend), which was mainly driven by the fourth quartile (carotid plaque). HRs for all-cause mortality, CV death, CV death/MI/stroke and the quadruple endpoint comparing the highest (carotid plaque) with the lowest CIMT quartile were 2.09 (95% CI, 1.07-4.10; p = 0.03); 2.49 (1.10-5.67; p = 0.03); 1.71 (1.10-2.67; p = 0.02); and 1.73 (1.31-2.27; p = 0.0001). In conclusion, our analyses suggest that the presence of carotid plaque, rather than the thickness of intima-media, appears to be associated with increased risk of CV morbidity and mortality, but confirmation of these findings in other population and prospective studies is required.

Retinal thickness in Parkinson's disease

BACKGROUND: Visual symptoms are common in Parkinson's disease with studies consistently demonstrating reductions in visual acuity, contrast sensitivity, colour and motion perception as well as alterations in electroretinogram latencies and amplitudes. Optical coherence tomography can examine retinal structure non-invasively and retinal thinning has been suggested as a potential biomarker for neurodegeneration in Parkinson's disease. Our aim was to examine the retinal thickness of a cohort of Parkinson's disease subjects (and age-matched controls) to establish the practical utility of optical coherence tomography in a representative older Parkinson's disease group. METHODS: Fifty-one established Parkinson's disease subjects and 25 healthy controls were subjected to ophthalmological assessment and optical coherence tomography (Zeiss Stratus 3000™) of macular thickness and volume and retinal nerve fibre thickness around the optic nerve head. Twenty four percent of control and 20% of Parkinson's disease subjects were excluded from final analysis due to co-morbid ocular pathology. Further data was excluded either due to poor tolerability of optical coherence tomography or poor quality scans. RESULTS: Despite a reduction in both visual acuity and contrast sensitivity in the residual evaluable Parkinson's disease cohort, we did not detect any differences between the two study groups for any measures of retinal thickness, in contrast to previously published work. CONCLUSIONS: In addition to technical problems inherent in the evaluation, the lack of difference between Parkinson's disease and healthy control subjects suggests longitudinal studies, employing newer techniques, will be required to define the role of optical coherence tomography as a potential diagnostic biomarker.

Effects of a latency period between pre-stimulation and teat cup attachment and periodic vacuum reduction on milking characteristics and teat condition in dairy cows

The goal of the present study was to examine the suitability of a short pre-stimulation (P) for 15 s followed by a latency period (L) of 30 s before cluster attachment for machine milking. In addition we tested the effect of a periodic reduction of the vacuum under the teat (VR) during the massage phase from 43 kPa to 12-15 kPa on milking characteristics and teat tissue condition. The study was carried out in 9 cows in a cross-over design. Animals were milked twice daily, and each of the 4 treatment combinations was used for six subsequent milkings (P+L vs. continuous P, and standard pulsation vs. VR, respectively). Milk flow was recorded during all experimental milkings. Longitudinal ultrasound cross sections of the teat were performed by B-mode ultrasound after the last milking of each treatment at 0, 5, and 15 min after the end of milking, respectively. None of the evaluated milking characteristics (total milk yield, main milking time, peak flow rate, average milk flow) differed between treatments. Teat measures as obtained by ultrasound cross sections showed no significant difference if individual treatments were compared at the three time points individually. However, teat wall thickness (TWT) tended to be smaller in VR vs. non-VR treatments at 5 min after milking (P=0·05). In conclusion, teat preparation consisting of a short stimulation followed by a latency period represents a similarly efficient pre-stimulation as a continuous pre-stimulation. VR seems to reduce the load on the teat tissue during milking and thus reduces the development of oedema and hence a less pronounced increase of TWT while milking characteristics are similar with or without VR.

Occurence and thickness of flood layers in varved sediments of Lake Ammersee

Microfacies analyses and X-ray fluorescence scanning (µ-XRF) at sub-mm resolution were conducted on the varved Mid- to Late Holocene interval of two sediment profiles from pre-alpine Lake Ammersee (southern Germany). The coring sites are located in a proximal (AS10prox) and distal (AS10dist) position towards the main tributary River Ammer, in 1.8 km distance from each other. To shed light on sediment distribution within the lake, particular emphasis was (1) the detection of intercalated detrital layers and their micro-sedimentological features, and (2) intra-basin correlation of these event deposits. Detrital layers were dated by microscopic varve counting, verified by accelerator mass spectrometry 14C dating of terrestrial plant macrofossils. Since ~5500 varve years (vyr) BP, in total 1573 detrital layers were detected in either one or both of the investigated sediment profiles. Based on their microfacies, geochemistry, and proximal-distal deposition pattern, detrital layers were interpreted as River Ammer flood deposits. Earlier studies on flood layer seasonality have proven that flood layer deposition occurs predominantly during spring and summer, the flood season at Lake Ammersee. Most prominent features of the record are the onset of regular flood layer deposition at ~5500 vyr BP in AS10prox and ~ 2800 vyr BP in AS10dist as well as three major increases in mean flood layer thickness at ~5500, 2800, and 400 vyr BP. Integrating information from both sediment profiles allowed to interpret these changes in terms of shifts towards higher mean flood intensity. Proposed triggering mechanisms are gradual reduction in Northern Hemisphere orbital summer forcing and superimposed centennial-scale solar activity minima. Likely responses to this forcing are enhanced equator-to-pole temperature gradients and changes in synoptic-scale atmospheric circulation. The consequences for the Ammersee region are more intense cyclones leading to extremer rainfall and flood events in spring and summer.

Seawater carbonate chemistry, thickness and carbonate elemental composition of the test of juvenile sea urchins in a laboratory experiment

Continuous anthropogenic CO2 emissions to the atmosphere and uptake by the oceans will cause a reduction of seawater pH and saturation state (Omega) of CaCO3 minerals from which marine calcifiers build their shells and skeletons. Sea urchins use the most soluble form of calcium carbonate, high-magnesium calcite, to build their skeleton, spines and grazing apparatus. In order to highlight the effects of increased pCO2 on the test thickness and carbonate elemental composition of juvenile sea urchins and potential differences in their responses linked to the diet, we performed a laboratory experiment on juvenile Paracentrotus lividus, grazing on calcifying (Corallina elongata) and non-calcifying (Cystoseira amentacea, Dictyota dichotoma) macroalgae, under different pH (corresponding to pCO2 values of 390, 550, 750 and 1000 µatm). Results highlighted the importance of the diet in determining sea urchin size irrespectively of the pCO2 level, and the relevance of macroalgal diet in modulating urchin Mg/Ca ratio. The present study provides relevant clues both in terms of the mechanism of mineral incorporation and in terms of bottom-up processes (algal diet) affecting top-down ones (fish predation) in rocky subtidal communities

Oxygen Reduction Reaction on Pt Overlayers Deposited onto a Gold Film: Ligand, Strain, and Ensemble Effect

We study the oxygen reduction reaction (ORR), the catalytic process occurring at the cathode in fuel cells, on Pt layers prepared by electrodeposition onto an Au substrate. Using a nominal Pt layer by layer deposition method previously proposed, imperfect layers of Pt on Au are obtained. The ORR on deposited Pt layers decreases with increasing Pt thickness. In the submonolayer region, however, the ORR activity is superior to that of bulk Pt. Using density functional theory (DFT) calculations, we correlate the observed activity trend to strain, ligand, and ensemble effects. At submonolayer coverage certain atom configurations weaken the binding energies of reaction intermediates due to a ligand and ensemble effect, thus effectively increasing the ORR activity. At higher Pt coverage the activity is governed by a strain effect, which lowers the activity by decreasing the oxidation potential of water. This study is a nice example of how the influence of strain, ligand, and ensemble effects on the ORR can be deconvoluted.

Comparison of vibration and rolling noise emission of resilient and solid monobloc railway wheels in underground lines

Flat or worn wheels rolling on rough or corrugated tracks can provoke airborne noise and ground-borne vibration, which can be a serious concern for nearby neighbours of urban rail transit lines. Among the various treatments used to reduce vibration and noise, resilient wheels play an important role. In conventional resilient wheels, a slightly prestressed V­shaped rubber ring is mounted between the steel wheel centre and tyre. The elastic layer enhances rolling noise and vibration suppression, as well as impact reduction on the track. In this paper the effectiveness of resilient wheels in underground lines, in comparison to monobloc ones, is assessed. The analysed resilient wheel is able to carry greater loads than standard resilient wheels used for light vehicles. It also presents a greater radial resiliency and a higher axial stiffness than conventional V­wheels. The finite element method was used in this study. A quarter car model was defined, in which the wheelset was modelled as an elastic body. Several simulations were performed in order to assess the vibrational behaviour of elastic wheels, including modal, harmonic and random vibration analysis, the latter allowing the introduction of realistic vertical track irregularities, as well as the influence of the running speed. Due to numerical problems some simplifications were needed. Parametric variations were also performed, in which the sensitivity of the whole system to variations of rubber prestress and Poisson’s ratio of the elastic material was assessed.Results are presented in the frequency domain, showing a better performance of the resilient wheels for frequencies over 200 Hz. This result reveals the ability of the analyzed design to mitigate rolling noise, but not structural vibrations, which are primarily found in the lower frequency range.

An experimental study on the effect of rolling shutters on the field measurements of airborne sound insulation of façades

The façade is the visible part of a building, and generally consists of various different constructive systems. The sound reduction index of the closing elements for the openings on a room’s façade is a determining factor in the sound insulation from airborne noise inside the space. Windows are the transparent part of the façade, and to improve their thermal behaviour and control solar radiation, they are often fitted with a series of external and internal protections such as shutters, slats and blinds. This work contains a summary of studies carried out using field measurements of airborne sound insulation on façades in rooms, in application of the standard UNE-EN ISO 140-5:1999. In all the rooms the windows were fitted with shutter boxes and rolling shutters, and the acoustic tests were made with the shutter in two positions (extended and fully retracted). The results were analysed considering the window opening system (openable or sliding) and the type of glass pane (monolithic or insulating glass unit, IGU). In the case of sliding windows, the airborne sound insulation of façades is greater when the shutter is extended than when it is retracted, and this should be taken into account when applying the aforementioned standard.

Análisis de la influencia de los diferentes parámetros de diseño en la aparición de fatiga superficial en contactos mecánicos

La fatiga superficial es uno de los principales problemas en las transmisiones mecánicas y es uno de los focos de atención de las investigaciones de los últimos anos en Tribología. La disminución de viscosidad de los lubricantes para la mejora de la eficiencia, el aumento de las potencias a transmitir, el aumento de la vida de los componentes o la mejora de su fiabilidad han supuesto que los fenómenos de fatiga superficial hayan cobrado especial relevancia, especialmente los fenómenos de pitting y micropitting en cajas multiplicadoras/reductoras de grandes potencias de aplicación, por ejemplo, en el sector eólico. Como todo fenómeno de fatiga, el pitting y micropitting son debidos a la aplicación de cargas ciclicas. Su aparición depende de las presiones y tensiones cortantes en el contacto entre dos superficies que al encontrarse en rodadura y deslizamiento varian con el tiempo. La principal consecuencia de la fatiga superficial es la aparición de hoyuelos de diferente magnitud segun la escala del fenómeno (pitting o micropitting) en la superficie del material. La aparición de estos hoyuelos provoca la perdida de material, induce vibraciones y sobrecargas en el elemento que finalmente acaba fallando. Debido a la influencia de la presión y tensión cortante en el contacto, la aparición de fatiga depende fuertemente del lubricante que se encuentre entre las dos superficies y de las condiciones de funcionamiento en las cuales este trabajando. Cuando el contacto trabaja en condiciones de lubricacion mixta-elastohidrodinamica tiende a aparecer micropitting debido a las altas tensiones localizadas en las proximidades de las asperezas, mientras que si el régimen es de lubricación completa el tipo de fatiga superficial suele ser pitting debido a las tensiones mas suavizadas y menos concentradas. En esta Tesis Doctoral se han analizado todos estos factores de influencia que controlan el pitting y el micropitting prestando especial atención al efecto del lubricante. Para ello, se ha dado un enfoque conjunto a ambos fenómenos resolviendo las ecuaciones involucradas en el contacto elastohidrodinamico no-Newtoniano (la ecuación de Reynolds, la deformación elástica de los sólidos y la reologia del lubricante) para conocer la presión y la tensión cortante en el contacto. Conocidas estas, se resuelve el campo de tensiones en el interior del material y, finalmente, se aplican criterios de fatiga multiaxial (Crossland, Dang Van y Liu-Mahadevan) para conocer si el material falla o no falla. Con la metodología desarrollada se ha analizado el efecto sobre las tensiones y la aparición de la fatiga superficial del coeficiente viscosidad-presion, de la compresibilidad, del espesor especifico de película y de la fricción así como de la influencia de las propiedades a fatiga del material y de las condiciones de funcionamiento (radios de contacto, velocidad, deslizamiento, carga y temperatura). Para la validación de los resultados se han utilizado resultados teóricos y experimentales de otros autores junto con normas internacionales de amplia utilización en el mundo industrial, entre otras, para el diseño y calculo de engranajes. A parte del trabajo realizado por simulación y cálculo de los diferentes modelos desarrollados, se ha realizado un importante trabajo experimental que ha servido no solo para validar la herramienta desarrollada sino que además ha permitido incorporar al estudio factores no considerados en los modelos, como los aditivos del lubricante. Se han realizado ensayos de medida del coeficiente de fricción en una maquina de ensayo puntual con la que se ha validado el cálculo del coeficiente de fricción y se ha desarrollado un proceso de mejora del coeficiente de fricción mediante texturizado superficial en contactos puntuales elastohidrodinamicos mediante fotolitografia y ataque quimico. Junto con los ensayos de medida de fricción en contacto puntual se han realizado ensayos de fricción y fatiga superficial en contacto lineal mediante una maquina de discos que ha permitido evaluar la influencia de diferentes aditivos (modificadores de fricción, antidesgaste y extrema-presion) en la aparición de fatiga superficial (pitting y micropitting) y la fricción en el contacto. Abstract Surface fatigue is one of the most important problems of mechanical transmissions and therefore has been one of the main research topics on Tribology during the last years. On the one hand, industrial demand on fuel economy has led to reduce lubricant viscosity in order to improve efficiency. On the other hand, the requirements of power and life of machine elements are continuously increasing, together with the improvements in reliability. As a consequence, surface fatigue phenomena have become critical in machinery, in particular pitting and micropitting in high power gearboxes of every kind of machines, e.g., wind turbines or cranes. In line with every fatigue phenomena, pitting and micropitting are caused by cyclic loads. Their appearance depends on the evolution of pressures and shear stresses with time, throughout the contact between surfaces under rolling and sliding conditions. The main consequence of surface fatigue is the appearance of pits on the surface. The size of the pits is related to the scale of the fatigue: pitting or micropitting. These pits cause material loss, vibrations and overloads until the final failure is reached. Due to the great influence of the pressures and shear stresses in surface fatigue, the appearance of pits depends directly on the lubricant and the operating conditions. When the contact works under mixed regime (or under elastohydrodynamic but close to mixed regime) the main fatigue failure is micropitting because of the high pressures located near the asperities. In contrast, when the contact works under elastohydrodynamic fully flooded conditions the typical fatigue failure is pitting. In this Ph.D. Thesis, the main factors with influence on pitting and micropitting phenomena are analyzed, with special attention to the effect of the lubricant. For this purpose, pitting and micropitting are studied together by solving the equations involved in the non-Newtonian elastohydrodynamic contact. Thus, pressure and shear stress distributions are found by taking into account Reynolds equation, elastic deflection of the solids and lubricant rheology. Subsequently, the stress field inside the material can be calculated and different multiaxial fatigue criteria (Crossland, Dang Van and Liu- Mahadevan) can be applied to predict whether fatigue failure is reached. The influences of the main parameters on pressure and surface fatigue have been studied, taking into account the lubricant compressibility and its viscosity-pressure coefficient, the specific film thickness, the friction coefficient and the fatigue properties of the contacting materials, together with the operating conditions (contact radius, mean velocity, sliding velocity, load and temperature). Several theoretical and experimental studies of different authors have been used to validate all the results obtained, together with international standards used worldwide in gear design industry. Moreover, an experimental stage has been carried out in order to validate the calculation methods and introduce additional influences not included previously, e.g., lubricant additives. The experimentation includes different friction tests in point contacts performed with a tribological equipment in order to validate the results given by the calculations. Furthermore, the reduction and optimization of the friction coefficient is analyzed by means of textured surfaces, obtained combining photolithography and chemical etching techniques. Besides the friction tests with point contact, friction and surface fatigue tests have also been performed with line contact in a tribological test rig. This equipment is also used to study the influence of different types of additives (friction modifiers, anti-wear and extreme-pressure additives) on surface fatigue (pitting and micropitting).

Effect of layer thickness on the high temperature mechanical properties of Al/SiC nanolaminates

Composite laminates on the nanoscale have shown superior hardness and toughness, but little is known about their high temperature behavior. The mechanical properties (elastic modulus and hardness) were measured as a function of temperature by means of nanoindentation in Al/SiC nanolaminates, a model metal–ceramic nanolaminate fabricated by physical vapor deposition. The influence of the Al and SiC volume fraction and layer thicknesses was determined between room temperature and 150 °C and, the deformation modes were analyzed by transmission electron microscopy, using a focused ion beam to prepare cross-sections through selected indents. It was found that ambient temperature deformation was controlled by the plastic flow of the Al layers, constrained by the SiC, and the elastic bending of the SiC layers. The reduction in hardness with temperature showed evidence of the development of interface-mediated deformation mechanisms, which led to a clear influence of layer thickness on the hardness.

Optimal selectin-mediated rolling of leukocytes during inflammation in vivo requires intercellular adhesion molecule-1 expression

Leukocyte interactions with vascular endothelium during inflammation occur through discrete steps involving selectin-mediated leukocyte rolling and subsequent firm adhesion mediated by members of the integrin and Ig families of adhesion molecules. To identify functional synergy between selectin and Ig family members, mice deficient in both L-selectin and intercellular adhesion molecule 1 (ICAM-1) were generated. Leukocyte rolling velocities in cremaster muscle venules were increased significantly in ICAM-1-deficient mice during both trauma- and tumor necrosis factor α-induced inflammation, but rolling leukocyte flux was not reduced. Elimination of ICAM-1 expression in L-selectin-deficient mice resulted in a sharp reduction in the flux of rolling leukocytes during tumor necrosis factor α-induced inflammation. The observed differences in leukocyte rolling behavior demonstrated that ICAM-1 expression was required for optimal P- and L-selectin-mediated rolling. Increased leukocyte rolling velocities presumably translated into decreased tissue emigration because circulating neutrophil, monocyte, and lymphocyte numbers were increased markedly in L-selectin/ICAM-1-deficient mice. Furthermore, neutrophil emigration during acute peritonitis was reduced by 80% in the double-deficient mice compared with either L-selectin or ICAM-1-deficient mice. Thus, members of the selectin and Ig families function synergistically to mediate optimal leukocyte rolling in vivo, which is essential for the generation of effective inflammatory responses.