Cross-phase modulational instability of circularly polarized helical Bloch modes carrying optical vortices in a chiral three-core photonic crystal fiber.

We report the first, to the best of our knowledge, observation of cross-phase modulational instability (XPMI) of circularly polarized helical Bloch modes carrying optical vortices in a twisted photonic crystal fiber with a three-fold symmetric core, formed by spinning the fiber preform during the draw. When the fiber is pumped by a superposition of left-circular polarization (LCP) and right-circular polarization (RCP) modes, a pair of orthogonal circularly polarized sidebands of opposite topological charge is generated. When, on the other hand, a pure LCP (or RCP) mode is launched, the XPMI gain is zero, and no sidebands are seen. This observation has not been seen before in any system and is unique to chiral structures with N-fold rotational symmetry. The polarization state and topological charge of the generated sidebands are measured. By decomposing the helical Bloch modes into their azimuthal harmonics, we are able to deduce the selection rules for the appearance of modulational instability sidebands. We showed that the four waves in the nonlinear mixing process must exhibit the same set of azimuthal harmonic orders.

Generation of broadband circularly polarized supercontinuum light in twisted photonic crystal fibers.

We compare the properties of the broadband supercontinuum (SC) generated in twisted and untwisted solid-core photonic crystal fibers when pumped by circularly polarized 40 picosecond laser pulses at 1064 nm. In the helically twisted fiber, fabricated by spinning the preform during the draw, the SC is robustly circularly polarized across its entire spectrum whereas, in the straight fiber, axial fluctuations in linear birefringence and polarization-dependent nonlinear effects cause the polarization state to vary randomly with the wavelength. Theoretical modelling confirms the experimental results. Helically twisted photonic crystal fibers permit the generation of pure circularly polarized SC light with excellent polarization stability against fluctuations in input power and environmental perturbations.

Real-time Doppler-assisted tomography of microstructured fibers by side-scattering.

We introduce the concept of Doppler-assisted tomography (DAT) and show that it can be applied successfully to non-invasive imaging of the internal microstructure of a photonic crystal fiber. The fiber is spun at ~10 Hz around its axis and laterally illuminated with a laser beam. Monitoring the time-dependent Doppler shift of the light scattered by the hollow channels permits the azimuthal angle and radial position of individual channels to be measured. An inverse Radon transform is used to construct an image of the microstructure from the frequency-modulated scattered signal. We also show that DAT can image sub-wavelength features and monitor the structure along a tapered fiber, which is not possible using other techniques without cutting up the taper into several short pieces or filling it with index-matching oil. The non-destructive nature of DAT means that it could potentially be applied to image the fiber microstructure as it emerges from the drawing tower, or indeed to carry out tomography on any transparent microstructured cylindrical object.

Measuring mechanical strain and twist using helical photonic crystal fiber.

Solid-core photonic crystal fiber (PCF) with a permanent helical twist exhibits dips in its transmission spectrum at certain wavelengths. These are associated with the formation of orbital angular momentum states in the cladding. Here we investigate the tuning of these states with mechanical torque and axial tension. The dip wavelengths are found to scale linearly with both axial strain and mechanical twist rate. Analysis shows that the tension-induced shift in resonance wavelength is determined both by the photoelastic effect and by the change in twist rate, while the torsion-induced wavelength shift depends only on the change in twist rate. Twisted PCF can act as an effective optically monitored torque-tension transducer, twist sensor, or strain gauge.

Nonreciprocal vortex isolator via topology-selective stimulated Brillouin scattering.

Optical nonreciprocity, which breaks the symmetry between forward and backward propagating optical waves, has become vital in photonic systems and enables many key applications. So far, all the existing nonreciprocal systems are implemented for linearly or randomly polarized fundamental modes. Optical vortex modes, with wavefronts that spiral around the central axis of propagation, have been extensively studied over the past decades and offer an additional degree of freedom useful in many applications. Here, we report a light-driven nonreciprocal isolation system for optical vortex modes based on topology-selective stimulated Brillouin scattering (SBS) in chiral photonic crystal fiber. The device can be reconfigured as an amplifier or an isolator by adjusting the frequency of the control signal. The experimental results show vortex isolation of 22 decibels (dB), which is at the state of the art in fundamental mode isolators using SBS. This device may find applications in optical communications, fiber lasers, quantum information processing, and optical tweezers.

Consequences of the DYT1 mutation on torsinA oligomerization and degradation.

DYT1 is the most common inherited dystonia, a neurological syndrome that causes disabling involuntary muscle contractions. This autosomal dominant disease is caused by a glutamic acid deletion near the carboxy-terminus in the protein torsinA. Cell- and animal-based studies have shown how the DYT1 mutation causes mutant torsinA to redistribute from the endoplasmic reticulum to the nuclear envelope, acting through a dominant negative effect over the wild type protein. As a result, the wild type:mutant torsinA expression ratio would be important for disease pathogenesis, and events that influence it, such as a differential degradation process for each protein, might modulate DYT1 pathobiology. The DYT1 mutation also triggers the formation of abnormal intermolecular disulfide bonds in torsinA, although the significance of this finding is unclear. How the protein quality control machinery handles torsinA, and whether this process is affected by its abnormal oligomerization remain unknown. Here, we first explored how the disease-linked mutation influences the catabolic process of human torsinA, demonstrating that the differences in subcellular localization between both forms of torsinA lead to divergences in their degradation pathways and, whereas torsinA is normally recycled through autophagy, the proteasome is also required for the efficient clearance of the mutated form. Subsequently, we determined that the abnormal disulfide bond-dependent oligomerization of mutant torsinA is not a result of its redistribution to the nuclear envelope, but a direct consequence of the mutation. Finally, we established that the presence of disulfide links in mutant torsinA oligomers interfere with their degradation by the proteasome, thus relying on autophagy as the main pathway for clearance. In conclusion, the abnormal subcellular localization and oligomerization of DYT1-linked torsinA influences its catabolic process, opening the door to the modulation of the wild type:mutant torsinA ratio through pharmacological manipulation of protein degradation pathways.

Long-range optical trapping and binding of microparticles in hollow-core photonic crystal fibre.

Optically levitated micro- and nanoparticles offer an ideal playground for investigating photon-phonon interactions over macroscopic distances. Here we report the observation of long-range optical binding of multiple levitated microparticles, mediated by intermodal scattering and interference inside the evacuated core of a hollow-core photonic crystal fibre (HC-PCF). Three polystyrene particles with a diameter of 1 µm are stably bound together with an inter-particle distance of ~40 µm, or 50 times longer than the wavelength of the trapping laser. The levitated bound-particle array can be translated to-and-fro over centimetre distances along the fibre. When evacuated to a gas pressure of 6 mbar, the collective mechanical modes of the bound-particle array are able to be observed. The measured inter-particle distance at equilibrium and mechanical eigenfrequencies are supported by a novel analytical formalism modelling the dynamics of the binding process. The HC-PCF system offers a unique platform for investigating the rich optomechanical dynamics of arrays of levitated particles in a well-isolated and protected environment.

Twist-induced guidance in coreless photonic crystal fiber: A helical channel for light.

A century ago, Einstein proposed that gravitational forces were the result of the curvature of space-time and predicted that light rays would deflect when passing a massive celestial object. We report that twisting the periodically structured "space" within a coreless photonic crystal fiber creates a helical channel where guided modes can form despite the absence of any discernible core structure. Using a Hamiltonian optics analysis, we show that the light rays follow closed spiral or oscillatory paths within the helical channel, in close analogy with the geodesics of motion in a two-dimensional gravitational field. The mode diameter shrinks, and its refractive index rises, as the twist rate increases. The birefringence, orbital angular momentum, and dispersion of these unusual modes are explored.

Salt-sensitive hypertension develops after short-term exposure to Angiotensin II.

We hypothesized that short-term exposure to angiotensin II (Ang II) could result in structural and functional changes in the kidney that would favor sodium retention and the development of sustained hypertension. To test this hypothesis, rats were exposed to pressor doses (435 ng. kg-1. min-1) of Ang II for 2 weeks. The infusion of Ang II was associated with acute hypertension, renal dysfunction, proteinuria, and focal tubulointerstitial and vascular damage. At sites of the tubulointerstitial damage, there was a reduction in peritubular capillary endothelial cell staining. By use of immunostaining, we found focal loss of endothelial nitric oxide synthase (eNOS) in the peritubular capillaries at sites of injury and a generalized reduction in eNOS in collecting ducts, thin loops of Henle, and vascular bundles in the medulla. When the Ang II infusion ended, the rats became normotensive and renal function returned toward normal. However, exposure of the rats to high salt diet (4% NaCl) resulted in the redevelopment of hypertension after 3 to 4 weeks. Rats maintained on a high salt diet with no prior exposure to Ang II and rats placed on low salt diet (0.1% NaCl) after exposure to Ang II remained normotensive. Thus, we report a new model of salt-sensitive hypertension induced by transient exposure to pressor doses of Ang II. The mechanism may relate to microvascular injury with peritubular capillary loss coupled with functional changes, such as a loss in intrarenal nitric oxide formation, that could alter the ability of the kidney to excrete a salt load.

Renal injury and salt-sensitive hypertension after exposure to catecholamines.

We investigated whether chronic infusion of phenylephrine could induce structural and functional changes in the kidney of rats with the subsequent development of salt-sensitive hypertension. Rats were infused with phenylephrine (0.15 mmol/kg per day) by minipump, resulting in a moderate increase in systolic blood pressure (BP) (17 to 25 mm Hg) and a marked increase in BP variability as measured by an internal telemetry device. After 8 weeks, the phenylephrine infusion was stopped with the return of BP to normal, and a nephrectomy was performed for histological studies. Glomeruli were largely spared, but focal tubulointerstitial fibrosis was present, with the de novo expression of osteopontin by injured tubules, macrophage and "myofibroblast" accumulation, and focal increases in mRNA for transforming growth factor beta by in situ hybridization. Peritubular capillaries at sites of injury had distorted morphology with shrinkage, rounding, and focal rarefaction, and endothelial cell proliferation was also identified. Rats were randomized to a high (8% NaCl or 1.36 mol/kg) or low (0.1% NaCl or 17 mmol/kg) salt diet. After 4 to 8 weeks, phenylephrine-treated rats on a high salt diet developed marked hypertension, which was in contrast with phenylephrine-treated rats placed on a low salt diet or vehicle-treated rats given a high salt diet. Hypertension after phenylephrine exposure correlated with the initial mean systolic BP (r(2)=0.99) and the degree of BP lability (r(2)=0.99) during the phenylephrine infusion, the amount of osteopontin expressed in the initial biopsy/nephrectomy (r(2)=0.74), and the final glomerular filtration rate (r(2)=0.58). These studies provide a mechanism by which a markedly elevated sympathetic nervous system can induce salt-dependent hypertension even when the hyperactive sympathetic state is no longer engaged.

Tubulointerstitial injury and loss of nitric oxide synthases parallel the development of hypertension in the Dahl-SS rat.

OBJECTIVE: Alterations in renal nitric oxide (NO) are involved in the hypertension of the Dahl salt-sensitive (Dahl-SS) rat We sought to identify the kinetics and sites of expression of the major NO synthase (NOS) isoforms. DESIGN: The renal expression of the major NOS were examined in Dahl-SS and salt-resistant rats (Dahl-SR) while on a low salt (0.1% NaCl) diet at 3 and 9 weeks of age. METHODS: Renal biopsies from Dahl-SS and Dahl-SR rats were compared for evidence of renal injury and for alterations in expression of the NOS enzymes by quantitative immunohistochemistry. RESULTS: At 3 weeks of age Dahl-SS and Dahl-SR rats have normal renal histology and similar immunohistochemical expression of NOS1, -2, and -3. At 9 weeks Dahl-SS rats had significantly higher blood pressure than Dahl-SR rats (P< 0.005 ), and lower macula densa NOS1 (P< 0.05) and cortical and medullary NOS3 (P< 0.05). NOS2 was reduced in cortical tubules in biopsies showing severe tubulointerstitial damage, but was not significantly different between Dahl-SS and Dahl-SR groups as a whole. Dahl-SS rats also manifested glomerular and tubulointerstitial injury. Tubular expression of osteopontin (OPN), which is an inhibitor of NOS2, correlated with the systolic BP in individual Dahl-SS rats (r2 = 0.80, P < 0.0001 ). CONCLUSION: Tubulointerstitial injury and the loss of NOS occur after birth and parallel the development of hypertension. We suggest that the structural and functional changes that occur with renal injury in the Dahl-SS rat may contribute to the development of hypertension.

Hyperuricemia exacerbates chronic cyclosporine nephropathy.

BACKGROUND: Hyperuricemia frequently complicates cyclosporine (CSA) therapy. The observation that longstanding hyperuricemia is associated with chronic tubulointerstitial disease and intrarenal vasoconstriction raised the hypothesis that hyperuricemia might contribute to chronic CSA nephropathy. METHODS: CSA nephropathy was induced by the administration of CSA (15 mg/kg/day) for 5 and 7 weeks to rats on a low salt diet (CSA group). The effect of hyperuricemia on CSA nephropathy was determined by blocking the hepatic enzyme uricase with oxonic acid (CSA-OA). Control groups included rats treated with vehicle (VEH) and oxonic acid alone (OA). Histological and functional studies were determined at sacrifice. RESULTS: CSA treated rats developed mild hyperuricemia with arteriolar hyalinosis, tubular injury and striped interstitial fibrosis. CSA-OA treated rats had higher uric acid levels in association with more severe arteriolar hyalinosis and tubulointerstitial damage. Intrarenal urate crystal deposition was absent in all groups. Both CSA and CSA-OA treated rats had increased renin and decreased NOS1 and NOS3 in their kidneys, and these changes are more evident in CSA-OA treated rats. CONCLUSION: An increase in uric acid exacerbates CSA nephropathy in the rat. The mechanism does not involve intrarenal uric acid crystal deposition and appears to involve activation of the renin angiotensin system and inhibition of intrarenal nitric oxide production.

Impaired angiogenesis in the aging kidney: vascular endothelial growth factor and thrombospondin-1 in renal disease.

We investigated the relationship of changes in the microvasculature to age-related structural and functional changes in the kidney to determine whether there was evidence of impaired angiogenesis and whether the loss of microvasculature could be accounted for by changes in the local production of angiogenic or antiangiogenic factors. Glomerular and peritubular capillary number, density, and endothelial cell proliferation were determined in aging (24 months; n = 9) and young (3 months; n = 8) rat kidneys and correlated with renal functional and structural changes and alterations in renal expression of vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1). Aging rats showed a focal decrease in both peritubular capillary (peritubular capillary staining, 5.4% +/- 1.8% versus 11.3% +/- 2.0% per 100 tubules; rarefaction index, 10.6% +/- 4.6% versus 0.6% +/- 0.1%, aging versus young rats; P < 0.05 and P: < 0.001, respectively) and glomerular capillary loops (27.3 +/- 6.9 versus 50.7 +/- 7.4/glomerulus, aging versus young rats; P < 0.001). The number of proliferating endothelial cells was decreased in aging rats compared with young rats (glomerular, 0.04 +/- 0.01 versus 0.15 +/- 0.03 positive cells/glomerular cross-section; peritubular, 0.7 +/- 0.2 versus 4.3 +/- 2.6 positive cells/mm(2); P < 0.05). In the aging kidney, VEGF expression was focally increased in the cortex compared with young rats, whereas a profound decrease was observed in the outer and inner medulla (total area of VEGF expression, 19.2% +/- 11.4% versus 39.3% +/- 7.6%; P < 0.05). Tubular VEGF expression correlated with peritubular capillary density (r(2) = 0.57; P < 0.01) and inversely correlated with tubular osteopontin (r(2) = -0.55; P < 0.05) and macrophage infiltration (r(2) = -0.64; P < 0.01). TSP-1 staining was increased in the glomeruli and tubulointerstitium of the aging rats. Glomerular TSP-1 score correlated inversely with glomerular capillary number (r(2) = -0.89; P < 0.001). Tubulointerstitial TSP-1 also correlated with percentage of positive staining of peritubular capillary (r(2) = -0.59; P < 0.001). Glomerular capillary number showed significant correlation with glomerulosclerosis score, as well as with 24-hour urinary protein excretion. Peritubular capillary density also inversely correlated with interstitial fibrosis score and urinary protein excretion. In conclusion, glomerular and peritubular capillary loss in the aging kidney correlate with alterations in VEGF and TSP-1 expression and also with the development of glomerulosclerosis and tubulointerstitial fibrosis. These findings suggest that impaired angiogenesis associated with progressive loss in renal microvasculature may have a pivotal role in age-related nephropathy.

The ubiquitin ligase F-box/G-domain protein 1 promotes the degradation of the disease-linked protein torsinA through the ubiquitin-proteasome pathway and macroautophagy.

DYT1 dystonia is a dominantly inherited, disabling neurological disorder with low penetrance that is caused by the deletion of a glutamic acid (ΔE) in the protein torsinA. We previously showed that torsinA(wt) is degraded through macroautophagy while torsinA(ΔE) is targeted to the ubiquitin-proteasome pathway (UPP). The different catabolism of torsinA(wt) and (ΔE) potentially modulates torsinA(wt):torsinA(ΔE) stoichiometry. Therefore, gaining a mechanistic understanding on how the protein quality control machinery clears torsinA(ΔE) in neurons may uncover important regulatory steps in disease pathogenesis. Here, we asked whether F-box/G-domain protein 1 (FBG1), a ubiquitin ligase known to degrade neuronal glycoproteins, is implicated in the degradation of torsinA(ΔE) by the UPP. In a first set of studies completed in cultured cells, we show that FBG1 interacts with and influences the steady-state levels of torsinA(wt) and (ΔE). Interestingly, FBG1 achieves this effect promoting the degradation of torsinA not only through the UPP, but also by macroautophagy. To determine the potential clinical significance of these findings, we asked if eliminating expression of Fbg1 triggers a motor phenotype in torsinA(ΔE) knock in (KI) mice, a model of non-manifesting DYT1 mutation carriers. We detected differences in spontaneous locomotion between aged torsinA(ΔE) KI-Fbg1 knock out and control mice. Furthermore, neuronal levels of torsinA were unaltered in Fbg1 null mice, indicating that redundant systems likely compensate in vivo for the absence of this ubiquitin ligase. In summary, our studies support a non-essential role for FBG1 on the degradation of torsinA and uncover a novel link of FBG1 to the autophagy pathway.

Recovery of neuromuscular function after infusion or intermittent bolus doses of atracurium or vecuronium.

Neuromuscular block and postoperative recovery of grip strength and peak expiratory flow (PEF) were compared in patients receiving atracurium or vecuronium administered by continuous infusion or intermittent bolus doses. The same total dose of atracurium (0.92-0.98 mg kg-1) or vecuronium (0.16-0.18 mg kg-1) was given by both methods. A similar degree of neuromuscular block was attained in all groups. A control group receiving no neuromuscular blocking drugs was also studied. Grip strength and PEF were reduced significantly in all groups (less than 80% of preoperative value) 15 min after operation. This was most marked following infusion of vecuronium (less than 50%). Grip strength recovered in all groups in 30-60 min. PEF was still significantly less than control value at 90 min in all groups receiving neuromuscular blocking drugs.

IL-1 beta increases laminin B2 chain mRNA levels and activates NF-kappa B in rat glomerular epithelial cells.

The amount and distribution of laminin in the glomerular basement membrane (GBM) change in the course of many types of glomerular disease. Because interleukin-1 (IL-1) is thought to play a role in the pathogenesis of glomerulonephritis, it raises the possibility that this and other cytokines might regulate laminin gene expression. To determine whether laminin B2 chain mRNA levels change in response to cytokines, total mRNA from rat glomerular epithelial cells (GEC) grown in culture was analyzed by Northern blots. These studies showed an increase in laminin B2 chain mRNA levels in GEC treated with IL-1 beta. Nuclear factor kappa B (NF-kappa B) is a cytokine-responsive factor that regulates transcription of many genes from the cognate kappa B enhancer element. The mouse laminin B2 chain promoter contains several kappa B-like motifs, suggesting that NF-kappa B might be involved in IL-1-induced laminin B2 chain gene expression. Nuclear extracts from IL-1 beta-treated GEC showed increased binding to the immunoglobulin kappa B enhancer element and to a kappa B consensus sequence from the murine laminin B2 chain promoter in an electrophoretic mobility-shift assay (EMSA). The immunoglobulin kappa B and the laminin B2 chain kappa B-like motifs competed for the same DNA binding activity in nuclear extracts from IL-1 beta-treated GEC. Pretreatment of these nuclear extracts with antibodies to either the p50 or p65 subunits of NF-kappa B abrogated the DNA binding activity recognized by either of the two DNA motifs.(ABSTRACT TRUNCATED AT 250 WORDS)

Tubulointerstitial disease in aging: evidence for underlying peritubular capillary damage, a potential role for renal ischemia.

Aging is associated with a progressive decline in renal function and the development of glomerulosclerosis and interstitial fibrosis. Although many studies have addressed the cellular mechanisms of age-related glomerulosclerosis, less is known about the tubulointerstitial fibrosis. In this study, aging (24 mo) rats develop tubulointerstitial fibrosis characterized by tubular injury and focal tubular cell proliferation, myofibroblast activation, macrophage infiltration with increased immunostaining for the adhesive proteins osteopontin and intercellular adhesion molecule-1, and collagen IV deposition. Aging rats demonstrated immunostaining for endothelial nitric oxide synthase (eNOSIII) in renal tubular epithelial cells and infiltrating mononuclear cells in areas of tubulointerstitial injury, with a relative loss of staining of the peritubular capillaries compared with young rats. The aging rats also displayed focal loss of peritubular capillaries (as noted by focally decreased RECA-1 and OX-2 staining) in areas of tubulointerstitial injury. The areas of fibrosis and hypocellularity were associated with increased apoptosis of tubular and interstitial cells compared with young (3 mo) rats (25.4 +/- 5.3 versus 3.5 +/- 2.5 TUNEL-positive cells/0.25 mm2 in old versus young rats, P = 0.0001). It is concluded that tubulointerstitial fibrosis in aging is an active process associated with interstitial inflammation and fibroblast activation. The progressive loss of cells in areas of fibrosis may be due to accelerated apoptosis. Furthermore, the tubulointerstitial injury may be the consequence of ischemia secondary to peritubular capillary injury and altered eNOS expression.

Role of intrinsic renal cells versus infiltrating cells in glomerular crescent formation.

BACKGROUND: Studies were undertaken to characterize the cellular composition that occurs in glomeruli and the tubulointerstitium of a passive model of complement-independent crescentic nephritis in mice. METHODS: Glomerulonephritis was induced by the injection of antibody to whole rabbit glomeruli, and tissue was examined histologically at 7, 14 and 28 days. RESULTS: Mice developed proteinuria, glomerular crescents, and progressive glomerulosclerosis and tubulointerstitial fibrosis. The majority of the cells within the crescents appeared to be intrinsic ezrin-positive epithelial cells of visceral or parietal origin. Many of the ezrin positive cells were proliferating and expressing the PDGF receptor. Despite expression of the macrophage adhesive protein, osteopontin, the early crescents were devoid of infiltrating macrophages, T cells or myofibroblasts, which could be explained by the finding that the Bowman's capsule remained intact. Tubulointerstitial damage also occurred, and included tubular dilation and atrophy, periglomerular and patchy interstitial infiltration and interstitial fibrosis with increased interstitial deposition of type IV collagen and laminin. Interstitial infiltrating cells included macrophages, CD4+ T lymphocytes, CD8+ T lymphocytes, and activated myofibroblasts. Tubular osteopontin expression was increased in the areas of tubulointerstitial damage and was associated with interstitial macrophage infiltration. CONCLUSIONS: We describe an experimental model of complement-independent murine crescentic nephritis associated with tubulointerstitial injury. Proliferating glomerular epithelial cells are the main cellular components of the crescents in this model.

Intravenous immunoglobulin protects against experimental thrombotic microangiopathy.

BACKGROUND: Intravenous immunoglobulin (IVIG) has been utilized in several forms of vasculitis and has many potential mechanisms of action, including the inhibition of C3 activation. We have previously demonstrated that IVIG can reduce glomerular injury in a model of membranous nephropathy mediated by C5b-9 [1]. C5b-9 has also been shown to mediate the thrombotic microangiopathy (TMA) induced by antibody to glomerular endothelial cells leading to a hemolytic uremic syndrome-type lesion [2]. METHODS: To test the hypothesis that IVIG might be effective in treating antibody-induced TMA, male uninephrectomized rats underwent right renal artery perfusion with goat anti-rat glomerular endothelial cell (GEN) antibody (20 mg/kg). Sheep IgG (200 mg/kg) was administered either 30 minutes before the renal artery perfusion (group I, N = 6) or 30 minutes postperfusion (group II, N = 9). A third control group received phosphate-buffered saline (PBS; group III, N = 12). A survival biopsy was performed at 15 minutes, and the animals were sacrificed on day 2. RESULTS: There were no significant differences in proteinuria or hematocrit between the groups. Animals pretreated with IVIG had significantly improved survival and renal function, which was associated with a decrease in glomerular C3 deposition. The protective effect of IVIG was abolished if the administration was delayed 30 minutes after perfusion. CONCLUSIONS: IVIG is effective in reducing injury in experimental TMA only if given prophylactically. The effect is mediated by inhibition of local intraglomerular complement activation.