Renal Vascular Permeability Research Articles

The combined effect of zinc oxide nanoparticles and milrinone on acute renal ischemia/reperfusion injury in rats: Potential underlying mechanisms

AimTo investigate the efficacy of zinc oxide nanoparticles (ZnO-NPs) and/or milrinone (MIL) on renal ischemia/reperfusion injury (I/RI) in rats and their possible underlying mechanisms. Materials and methodsForty-eight adult male Sprague-Dawley albino rats were randomly assigned into six equal-sized groups (n = 8): normal control, sham-operated, I/R group (45 min/24 h), ZnO-NPs group (10 mg/kg i.p.), MIL group (0.5 mg/kg i.p.), and ZnO-NPs + MIL group in the same previous doses. Key findingsIn comparison to the I/R-operated group, administration of either ZnO-NPs or MIL significantly decreased serum creatinine and urea concentrations, and renal vascular permeability (p < 0.05). The oxidative stress was significantly declined, as evidenced by increased GPx, CAT, and SOD activities and decreased MDA and NO concentrations. Renal expressions of TNF-α, NF-κB, KIM-1, NGAL, and caspase-3 decreased significantly, while Nrf2 increased significantly. Histopathology investigation revealed improvement with minimal renal lesions and fibrosis after ZnO-NPs or MIL treatments. The combined treatments synergistically improved the studied parameters more than either treatment alone. These findings were validated by molecular modeling, which revealed that MIL inhibited TNF-α, NF-kB, caspase-3, KIM-1 and NGAL. SignificanceBoth ZnO-NPs and MIL exerted cytoprotective effects against acute renal I/RI, and a combination of both was found to be even more effective. This renoprotective effect is suggested to be mediated through activation of Nrf2 and the prevention of the NF-κB activation-induced oxidative stress and inflammation, which may strengthen the potential role of ZnO-NPs or MIL in renal I/RI protection during surgical procedures.

RENAL INVOLVEMENT IN PATIENTS WITH RHEUMATOID ARTHRITIS- A HOSPITAL-BASED OBSERVATIONAL STUDY.

Background: Rheumatoid arthritis is a chronic multisystem, immuno-inammatory disease characterized by articular and extra-articular manifestations. The disease's hallmark is synovial inammation and potential to cause cartilage damage, bone erosion, and subsequent damage to joint integrity. Rheumatoid arthritis is a systemic disease with a variety of extra-articular manifestations. The predominant well-recognized systemic manifestations include Sjogren's syndrome, pulmonary, cardiac, neurological, renal, gastrointestinal, dermal involvement, vasculitis, and Felty's syndrome. Regarding renal involvement in connective tissue disease, the focus is on systemic lupus erythematosus (SLE). The affection of kidneys in RA is more or less overlooked and mainly attributed to drugs (NSAIDs, DMARDs like gold and d-penicillamine, which are less commonly used in today's scenario. The other primary etiology of kidney involvement in RA is secondary amyloidosis, commonly associated with the long-term disease process. Vasculitis with RA is a relatively less common etiology of renal involvement in RA. Renal involvement in Rheumatoid arthritis has been well documented with a prevalence of 1-5%. Although impairment of renal function is often mild to moderate, renalrelated mortality signicantly contributes to the increased mortality of RA. The kidney is involved in RA with both glomerular and tubular damage. Renal damage in RA, however, is usually asymptomatic and is detected on laboratory investigation. It is often difcult to differentiate between damage due to disease activity and drugs used to treat RA. It is a hospita Methods: l based observational study conducted at Gauhati Medical college, Assam, for one year. All Adult (&gt; 18 years) patients fullled the 2010 American College of Rheumatology Criteria for Rheumatoid arthritis were included. Patients with diabetes mellitus congestive heart failure, urinary tract infection, long standing and uncontrolled hypertension, preexisting renal disease , overlap syndrome and pregnant patients were excluded. Detailed clinical history was taken from all included patients regarding onset and duration of disease. Disease activity was measured using disease activity score -28 -(DAS-28). Routine investigation, ESR, CRP, renal function test, ultrasonography and urine for microalbuminuria were measured in all included patients. The maximum age was Results: 68 years, the minimum was 20 years, and the mean age was 40.22 ± 11.58. The study group included 38 females and 12 males accounting for 76% and 24%, respectively. The mean disease duration was 18.6 months with a range of 3-60 months. All patients presented with polyarthritis(100%). History of morning stiffness was present in 54% of patients, while 46% had generalized weakness and constitutional symptoms. In our study, microalbuminuria was found in 15 patients (30%). Mmicroalbuminuria was seen more commonly in the age group between 41-50 years. Microalbuminuria was signicantly associated with higher ESR values. Out of 15 patients positive for microalbuminuria, 13 patients had ESR &gt;50, and 7 had ESR &gt;100 with a p-value &lt;0.001. Mean CRP was 42.45 mg/l in microalbuminuria-positive patients as compared to 16.19mg/l in microalbuminuria-negative patient. Out of 15 patients with microalbuminuria positive had evidence of erosion on x-ray, with a p-value of 0.017. Conclusion: From the present study, it can be concluded that the peak age of the disease is 31-50 years, with female preponderance. Polyarthritis is the most common presenting symptom, and most patients have an insidious onset. Constitutional symptoms like fever, malaise, and anorexia are more common among the extra-articular features. Asymptomatic renal involvement is common, and microalbuminuria is frequently seen in patients with Rheumatoid Arthritis. The presence of microalbuminuria is a sensitive indicator of increased renal vascular permeability in rheumatoid arthritis patients. Immunological methods for detecting microalbuminuria should be routinely used in all Rheumatoid Arthritis patients to detect renal involvement in its initial phase to devise the most appropriate treatment.

The Effect of Venom of Egyptian Spitting Cobra Naja nubiae on Vascular Permeability of Hepatic and Renal Tissues

Background: Among venomous elapid snakes, cobras have the highest public awareness, as their venom represents a combination of proteins, peptides, and enzymes that have a range of biochemical and pharmacological roles and are also the main constitutes of biological activity and lethal toxicity. Objectives: The study aimed to evaluate the effect of the venom of Egyptian Spitting Cobra, Naja nubiae, on the vascular permeability based on the extravasation of the azo dye Evans blue (EB) into the tissues of the liver and kidneys of animals envenomed with low (¼ LD50; 0.32 mg/kg) and high (½ LD50; 0.65 mg/ kg) doses at three sampling times (30, 120, 360 min) post-injection of the venom. Methods: Fifty-four adult male Albino rats (8 weeks old and 180±2 0 g body weight) were divided into three main groups (n=6). In the control group, rats were subcutaneously (SC) injected with saline solution. Envenomed groups were SC injected, one group with 0.32 mg/kg and the other group with 0.65 mg/kg body weight of crude venom, respectively. Rats were I.V injected with EB dye 20 minutes before SC injection with saline solution as control animals and with Naja nubiae venom as treatment groups. Results: The results illustrated a high significant rate of EB extravasation to hepatic and renal tissues by the colorimetric determination of EB dye concentration. Conclusion: The venom of Naja nubiae can cause increased hepatic and renal vascular permeability which may explain the inflammatory effect induced by this venom.

Ranolazine alleviates contrast-associated acute kidney injury through modulation of calcium independent oxidative stress and apoptosis

This study investigates the role of ranolazine in contrast-associated acute kidney injury (CA-AKI) and potential mechanisms. For in vivo studies, mouse models of CA-AKI and control mice were treated with ranolazine or vehicle. Blood urea nitrogen (BUN) and serum creatinine were detected by spectrophotometry. Anti-T-cell immunoglobulin and mucin domain 1 (TIM 1) and anti-lipocalin 2 antibody (LCN2) were detected by immunofluorescence. Hemodynamic parameters were detected via invasive blood pressure measurement and renal artery color doppler ultrasound, capillary density was measured by CD31 immunofluorescence, vascular permeability assay was performed by Evans blue dye. The expressions of oxidative stress and apoptotic markers were measured and analyzed by immunofluorescence and western blotting. For in vitro studies, intracellular calcium concentration of HUVECs was measured with Fluo 3-AM under confocal microscopy. Results show that compared with control mice, serum BUN, creatinine, TIM 1 and LCN2 levels were elevated in CA-AKI mice, but this effect was alleviated by ranolazine-pretreatment. Safe doses of ranolazine (less than 64 mg/kg) had no significant effect on overall blood pressure, but substantially improved renal perfusion, reduced contrast-induced microcirculation disturbance, improved renal capillary density and attenuated renal vascular permeability in ranolazine-pretreated CA-AKI mice. Mechanistically, ranolazine markedly down-regulated oxidative stress and apoptosis markers compared to CA-AKI mice. Intracellularly, ranolazine attenuated calcium overload in HUVECs. These results indicate that ranolazine alleviates CA-AKI through modulation of calcium independent oxidative stress and apoptosis.

The hemodynamic and metabolic effects of spironolactone treatment in acute kidney injury assessed by hyperpolarized MRI.

Renal ischemia-reperfusion injury (IRI) is one of the most common types of acute kidney injury. Spironolactone has shown promising kidney protective effects in renal IRI in rats. We investigated the hemodynamic and metabolic effects of spironolactone (100 mg/kg) administered immediately after 40 min unilateral kidney ischemia in rats. Hyperpolarized MRI using co-polarized [1-13 C]pyruvate and [13 C,15 N2 ]urea as well as 1 H dynamic contrast-enhanced (DCE) MRI was performed 24 h after induction of ischemia. We found a significant decrease in renal blood flow (RBF) in the ischemic kidney compared with the contralateral one measured using DCE and [13 C,15 N2 ]urea. The RBF measured using [1-13 C]pyruvate and [13 C,15 N2 ]urea was significantly altered by spironolactone. The RBFs in the ischemic kidney compared with the contralateral kidney were decreased similarly as measured using both [13 C,15 N2 ]urea and [1-13 C]pyruvate in the spironolactone-treated group. Spironolactone treatment increased the perfusion-corrected pyruvate metabolism by 54% in both the ischemic and contralateral kidney. Furthermore, we showed a correlation between vascular permeability using a histological Evans blue analysis and the ratio of the volumes of distribution (VoDs), ie VoD-[13 C,15 N2 ]urea/VoD-[1-13 C]pyruvate. This suggests that [13 C,15 N2 ]urea/[1-13 C]pyruvate VoD ratio may be a novel indicator of renal vascular permeability associated with renal damage in rodents.

Renal interstitial permeability changes induced by microbubble-enhanced diagnostic ultrasound

Ultrasound-targeted microbubble (MB) destruction (UTMD) has been shown to increase the glomerular permeability, providing a potential novel therapeutic approach in targeted drug release for kidney diseases. Therefore, we investigated the impact of UTMD on renal interstitial permeability using MB-mediated diagnostic ultrasound (DUS). The left kidney of Sprague–Dawley (SD) rat was insonated by UTMD with either continuous or intermittent mode for 5 min. Evans blue (EB) revealed that both modes induced renal vascular permeability increase after DUS but recovered after 24 h. Intermittent insonation caused more severe injury than continuous mode. Red blood cells leaked out of the capillaries into interstitium without glomerular capillary hemorrhage (GCH) by hematoxylin and eosin (HE) staining. Electronic microscopy revealed the disruption of focal capillary wall in interstitial tissues. Morphological results confirmed capillary wall recovered in 24 h post-treatment. Results from fluorescence-labeled MBs showed that MBs were mainly localized in the interstitial portion of the tubular region and retained at 24 h. Intriguingly, urinalysis showed no clinical proteinuria after treatment. Our results indicated that MB plus DUS specifically and reversibly enhanced the interstitial permeability without affecting glomerulus, which may be developed into a therapeutic approach for targeting drug release to individual renal compartments.

Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA.

Sphingosine‐1‐phosphate receptor 1 agonist SEW2871 decreases sepsis‐induced renal microvascular permeability but not peritubular capillary hypoperfusion

Renal microcirculatory failure and vascular leakage are hallmarks of sepsis‐induced acute kidney injury (AKI). To investigate the mechanism of renal capillary hypoperfusion, the cecal ligation and puncture (CLP) model of sepsis was used in male 40 wk C57BL/6 mice. Since activation of sphingosine‐1‐phosphate receptor 1 (S1P1) has been reported to enhance endothelial barrier function and decrease vascular permeability, mice were administered the S1P1 agonist SEW2871 (1, 3, 10 or 30mg/kg ip) at the time of CLP. Evans blue dye leakage assay was used to measure renal microvascular permeability and intravital video microscopy was used to quantitate changes in renal peritubular capillary perfusion. CLP caused a rapid increase in capillary permeability at 2h, prior to decreased renal capillary perfusion at 4h. SEW2871 dose‐dependently decreased renal vascular permeability at 6h post CLP. However, peritubular capillary perfusion was not improved compared to CLP mice at 6h. Results suggest that renal microvascular leakage is an early event during the development of sepsis and that activation of S1P1 may decrease vascular permeability but cannot prevent the deterioration of renal capillary perfusion. Overall, our study suggested that the early renal capillary hypoperfusion is independent of the increased vascular permeability in CLP septic mice. Supported by AHA 10PRE4140065 (ZW) and NIH DK075991 (PRM).

Effect of T cells on vascular permeability in early ischemic acute kidney injury in mice

Although previous studies have demonstrated that microvascular dysfunction and inflammation occur in ischemia–reperfusion injury (IRI), the underlying mechanisms are poorly understood. We hypothesized that T cells could mediate renal vascular permeability (RVP) during IRI. We evaluated renal vascular permeability by extravasation of Evans blue dye from the kidney in CD3, CD4 or CD8 T cell deficient mice as well as in TNF receptor knock out mice in our mouse model of kidney ischemia–reperfusion injury. In wild type mice, RVP was significantly increased at 3 h, peaked at 6 h and declined by 24 h after ischemia. Immunohistochemistry revealed that CD3 + T cells trafficked into ischemic kidney at 1 h and peaked at 6 h. Gene microarray analysis demonstrated that endothelial-related genes including TNF-α were up-regulated in ischemic kidney. The production of TNF-α and IFN-γ protein was increased in CD3 and CD4 T cells from the blood and kidney after ischemia. The rise in RVP after ischemia in wild type mice was attenuated in CD3, CD4 or CD8 T cell deficient mice as well as in TNF receptor knock out mice. The attenuation of RVP in CD3 T-cell deficient mice after ischemia was restored by adoptive transfer of T cells from WT mice. Our data demonstrate that T cells directly contribute to the increased RVP after kidney ischemia–reperfusion, potentially through T cell cytokine production.

Activation of Sensory Neurons Reduces Ischemia/Reperfusion-induced Acute Renal Injury in Rats

Prostaglandin I2 (PGI2) produced by endothelial cells improves ischemia/reperfusion-induced acute renal injury by inhibiting leukocyte activation in rats. However, the underlying mechanism(s) of increased PGI2 production is not fully understood. Activation of sensory neurons increases endothelial PGI2 production by releasing calcitonin gene-related peptide (CGRP) in rats with hepatic ischemia or reperfusion. We examined here whether activation of sensory neurons increases PGI2 endothelial production, thereby reducing ischemia/reperfusion-induced acute renal injury. Anesthetized rats were subjected to 45 min of renal ischemia/reperfusion. Rats were pretreated with CGRP, capsazepine (a vanilloid receptor-1 antagonist), CGRP(8-37) (a CGRP receptor antagonist), or indomethacin (a cyclooxygenase inhibitor), or subjected to denervation of primary sensory nerves before ischemia/reperfusion. Renal tissue levels of CGRP and 6-keto-prostaglandin F1alpha, a stable metabolite of PGI2, increased after renal ischemia/reperfusion, peaking at 1 h after reperfusion. Overexpression of CGRP was also noted at 1 h after reperfusion. Increases in renal tissue levels of 6-keto-prostaglandin F1alpha at 1 h after reperfusion were significantly inhibited by pretreatment with capsazepine, CGRP(8-37), and indomethacin. Pretreatment with capsazepine, CGRP(8-37), indomethacin, and denervation of primary sensory nerves significantly increased blood urea nitrogen and serum creatinine levels, renal vascular permeability, renal tissue levels of myeloperoxidase activity, cytokine-induced neutrophil chemoattractant, and tumor necrosis factor-alpha, and decreased renal tissue blood flow. However, pretreatment with CGRP significantly improved these changes. Our results suggest activation of sensory neurons in the pathologic process of ischemia/reperfusion-induced acute renal injury. Such activation reduces acute renal injury by attenuating inflammatory responses through enhanced endothelial PGI2 production.

Acute kidney injury after hepatic ischemia and reperfusion injury in mice

Hepatic ischemia reperfusion (IR) is the leading cause of acute liver failure (ALF) during the perioperative period and patients with ALF frequently develop acute kidney injury (AKI). There is no effective therapy for AKI associated with ALF because pathomechanisms are incompletely characterized, in part due to the lack of an animal model. In this study, we characterize a novel murine model of AKI following hepatic IR. Mice subjected to ∼70% liver IR not only developed acute liver dysfunction, but also developed severe AKI 24 h after liver injury. Mice subjected to liver IR developed histological changes of acute tubular injury including focal proximal tubular cell necrosis involving the S3 segment, cortical tubular ectasia, focal tubular simplification and granular bile/heme cast formation. In addition, there was focal interstitial edema and hyperplasia of the juxtaglomerular apparatus. Inflammatory changes in the kidney after hepatic IR included neutrophil infiltration of the interstitium and upregulation of several proinflammatory mRNAs (tumor necrosis factor-α, keratinocyte-derived cytokine, monocyte chemotactic protein-1, macrophage inflammatory protein-2, intercellular adhesion molecule-1). In addition, marked renal endothelial cell apoptosis was detected involving peritubular interstitial capillaries, accompanied by increased renal vascular permeability. Finally, there was severe disruption of renal proximal tubule epithelial filamentous-actin. Our results show that AKI rapidly and reproducibly develops in mice after hepatic IR and is characterized by renal tubular necrosis, inflammatory changes and interstitial capillary endothelial apoptosis. Our murine model of AKI after liver injury closely mimics human AKI associated with ALF and may be useful in delineating the mechanisms and potential therapies for this common clinical condition.

OLPRINONE REDUCES ISCHEMIA/REPERFUSION-INDUCED ACUTE RENAL INJURY IN RATS THROUGH ENHANCEMENT OF cAMP

Activated leukocytes are implicated in development of ischemia/reperfusion (I/R)-induced organ injuries. Phosphodiesterase 3 inhibitors have anti-inflammatory effects by preventing cyclic adenosine monophosphate (cAMP) degradation. We examined the effects of olprinone, a specific phosphodiesterase 3 inhibitor, on I/R-induced acute renal injury model in rats. Forty-five minute renal I/R was induced in uni-nephrectomized rats. Rats were divided into a vehicle group, an olprinone group, and a dibutyril (DB) cAMP group. Olprinone (0.2 microg/kg/minute) infusion began 30 min after reperfusion and continued for 3 h. DBcAMP (5 mg/kg), a stable analog of cAMP, was intraperitoneally administered 5 min after reperfusion to clarify the effect of cAMP in our model. Olprinone reduced the I/R-induced increases in serum levels of blood urea nitrogen and creatinine, and improved histological changes, including acute tubular necrosis in the outer medulla. Hemodynamic status was not affected by olprinone. I/R-induced a decrease in renal tissue blood flow, an increase in renal vascular permeability, and an enhancement of leukocyte activation, reflected by renal tissue levels of myeloperoxidase activity, and the tissue levels of cytokine-induced neutrophil chemoattractant (an equivalent of human interleukin 8) and tumor necrosis factor-alpha were all significantly decreased by olprinone. Olprinone also increased the renal tissue and plasma levels of cAMP in rats subjected to renal I/R. DBcAMP showed similar effects. Our results indicated that olprinone reduced the I/R-induced acute renal injury, probably by inhibiting leukocyte activation. The effects of olprinone could be explained through its action on cAMP levels.

Effect of glucocorticoid receptor blockade on pulmonary and renal vascular permeability in scalded rats.

Effect of glucocorticoid receptor blockade on pulmonary and renal vascular permeability in scalded rats.

Uptake of Indium-111-Labeled Platelets and Indium-111 Oxine by Murine Kidneys after Total-Body Irradiation

Radiation nephropathy is a well-known late manifestation of renal irradiation in human beings and experimental animals. Its pathogenesis is unclear, but vascular injury may play a role. Endothelial cells have been demonstrated to manifest a variety of abnormalities within hours of exposure to radiation. In the present experiments mice were exposed to lethal doses of whole-body radiation, and the distribution of 111In-labeled platelets was evaluated during the first week after irradiation. The purpose was to determine if early abnormalities of endothelial cells would be manifested by altered sequestration of platelets in kidneys and other organs. It was found that the indium accumulated in the kidneys of irradiated mice to a greater extent than in nonirradiated mice, supporting the possibility of early vascular injury. In control experiments, administration of 111In-oxine was also followed by excessive accumulation of radioactivity in kidneys of irradiated mice, but the pattern of accumulation differed from that seen after injection of radiolabeled platelets. Renal hyperemia was not demonstrable with 51Cr-labeled red cells, renal vascular permeability was not detected with 125I-labeled albumin, and the pattern of renal uptake of plasma proteins labeled with 59Fe or 111In did not coincide with that seen from 111In administered as labeled platelets or oxine. Renal uptake of 111In-oxine was not associated with alterations in urinary or fecal excretion or an increase in total-body retention of the radioisotope. The findings are consistent with the notion that renal vascular injury at the time of irradiation results in accumulation of platelets or platelet constituents during the first week after total-body irradiation of mice.

Renal permeability alteration precedes hypertension and involves bradykinin in the spontaneously hypertensive rat.

Vascular permeability disorders have been described in experimental models, as well as in human hypertension. We recently described the fact that vascular permeability to albumin is heterogeneous in the normal rat. In the present study, we examine the contents of Evans blue dye (EB) bound to albumin in selected organs of unanesthetized Wistar Kyoto (WKY) and in spontaneously hypertensive rats (SHR) at various stages of development of hypertension. EB was injected in the caudal vein of paired 4, 8, 12, and 16-wk-old WKY and SHR. Rats were killed 10 min after EB injection and extraction of the marker was measured in selected tissues. In additional 4 and 16-wk-old animals, bradykinin B1 and B2 receptor antagonists (BKA) were also injected with EB. Renal contents of EB bound to albumin were higher in the SHR than in the WKY: 196 +/- 9, 202 +/- 10, 182 +/- 7, and 196 +/- 9, compared with 158 +/- 8, 155 +/- 7, 138 +/- 7, and 118 +/- 6 micrograms/g dry tissue, in the 4, 8, 12, and 16-wk-old rats, respectively. In the 4-wk-old SHR and WKY, blood pressure values were normal and comparable, yet the alteration in EB permeability was already present in the SHR. Both BKA failed to alter the renal EB extravasation in the WKY, but the B2-BKA restored the renal permeability to control levels in the SHR. We conclude that a selective defect in the renal vascular permeability to EB developed in the SHR. Since this finding precedes hypertension and is corrected by a selective B2-BKA, it is suggested that bradykinin is involved at an early stage of the disease in the SHR.

Myocardial atrio-venous junctions and extensions (sleeves) over the pulmonary and caval veins. Anatomical observations in various mammals.

Aim: To determine whether treatment with the stem cell stimulator Olimpiq® Stem×Cell prevents increase of retinal and renal vascular permeability in alloxan-induced diabetic rats. Materials and Methods: Two groups of Wistar rats were made diabetic by single intraperitoneal injection of Alloxan. The third, the control group, received vehicle alone. One diabetic group received Olimpiq® Stem×Cell treatment for 4 weeks. The permeability of the blood–retinal barrier (BRB) and renal vessels were measured by the extravasation of fluorescein–labeled bovine serum albumin. Results: Six weeks subsequently to Alloxan injection, significantly elevated the tissue fluorescence, the renal vascular leakage and BRB breakdown was demonstrated in the diabetic group, compared to the nondiabetic group. Olimpiq® Stem×Cell treatment significantly reduced the BRB breakdown, tissue fluorescence, and vascular leakage. Conclusion: Olimpiq® Stem×Cell would be a useful choice of treatment for complications associated with increased vascular permeability of diabetes, such as retinopathy or nephropathy.

On vascular permeability factor from the kidney cortex.

(1) The vascular permeability factor is present in the renal cortex.This factor has no pressor activity and is quite different from renin. (2) The vascular permeability factor has the characteristics of a protein. Immunoelectrophoretic study reveals a single precipitation line. (3) Administration of the vascular permeability factor to mice causes cerebral hemorrhage. (4) Rabbits subjected to renal ischemia develop cerebral hemorrhages but are provided protection against it through lanolin feeding. (5) Some evidence is presented indicating that the renal vascular permeability factor plays an important role in the development of vascular lesions.