Gustavo Parra - Academia.edu (original) (raw)

Papers by Gustavo Parra

American Journal of Pathology, 2004

A basic conservation of cell migration guidance mechanisms in the nervous and immune systems was ... more A basic conservation of cell migration guidance mechanisms in the nervous and immune systems was proposed when Slit, known for its role in axon guidance, was found to inhibit chemokine-induced leukocyte chemotaxis in vitro. These studies examined the role of Slit2 in modulating inflammation in vivo. In a rat model of glomerulonephritis, endogenous glomerular Slit2 expression fell after disease induction, and its inhibition during the early disease period accelerated inflammation. Ex vivo glomerular leukocytes showed decreased chemokine and chemoattractant-induced chemotaxis in response to Slit2, suggesting an anti-inflammatory role for glomerular Slit2. In contrast to the effect of inhibition, glomerulonephritis was ameliorated by systemic Slit2 administration. Slit2 treatment improved disease histologically and also improved renal function when given early in the disease course. Leukocytes harvested from rats receiving Slit2 showed decreased monocyte chemoattractant protein-1 (MCP)-1-mediated migration, consistent with a peripheral Slit2 effect. In keeping with this functional alteration, Slit2-mediated inhibition of RAW264.7 cell chemotaxis was associated with decreased levels of active cdc42 and Rac1, implicating GTPases in leukocyte Slit2 signaling. These findings suggest a role for endogenous Slit2 in the inhibition of chemoattractant-mediated signals, demonstrate a potentially important anti-inflammatory effect for Slit2 in vivo, and provide further evidence for conserved mechanisms guiding the process of migration in distinct cell types.

Kidney International, 2008

Renal tubulointerstitial inflammation is a constant feature of experimental models of hypertensio... more Renal tubulointerstitial inflammation is a constant feature of experimental models of hypertension and likely plays a role in the pathogenesis of salt-sensitive hypertension. We have previously raised the possibility that the immune cell infiltration is driven by a low grade autoimmune reactivity directed to or facilitated by renal heat shock protein over expression. The present studies were done to gain insight on possible cell-mediated immune mechanisms in experimental hypertension by determining the renal expression of HSP70 and the proliferation index of T lymphocytes cultured with HSP70. We studied male Sprague-Dawley rats with inhibition of nitric oxide (NO) synthase (n ¼ 6), protein overload (PO) proteinuria (n ¼ 7) and short-term angiotensin II (Ang II) infusion (n ¼ 5), and their corresponding control groups. Each model was associated with 2 to 4 fold increase (Po0.05-0.001) in renal HSP70 expression. T cells isolated from the spleens demonstrated a significant two-to nine-fold response compared to controls (Po0.05 or lower for each comparison) when cultured with HSP70. These studies suggest that autoimmunity to stress proteins is involved in the sustained low-grade inflammatory infiltration that occurs in the tubulointerstitial areas of the hypertensive kidney.

Kidney International, 2003

Background. Angiotensin II (Ang II) infusion and nitric oxide synthesis (NOS) inhibition with N -... more Background. Angiotensin II (Ang II) infusion and nitric oxide synthesis (NOS) inhibition with N -nitro-l-arginine-methylester (l-NAME) are experimental models of hypertension associated with renal inflammation and oxidative stress. To gain insight into the nature of the tubulointerstitial injury induced in these models, we studied lectin-binding specificities, vimentin expression, and heat shock protein (HSP) 60 and 70 in these experimental models.

Kidney International, 1999

tration with CD43-and ED1-positive cells in glomeruli and Mycophenolate mofetil prevents the prog... more tration with CD43-and ED1-positive cells in glomeruli and Mycophenolate mofetil prevents the progressive renal failure interstitium was two to five times lower in MMF-treated rats induced by 5/6 renal ablation in rats.

American Journal of Nephrology, 2004

Lymphocytes and macrophages infiltrate the kidney of spontaneously hypertensive rats (SHR) and in... more Lymphocytes and macrophages infiltrate the kidney of spontaneously hypertensive rats (SHR) and interventions leading to their reduction are associated with improvement of the hypertension. The present studies examined the evolution of the interstitial inflammation in the natural course of the SHR to gain insight on the potential role of interstitial immune cell accumulation in the development of hypertension. We studied SHR and control WKY rats at 3 weeks (SHR-3 wk group, n = 11 and WKY-3 wk group, n = 10), 11 weeks (SHR-11 wk group, n = 5 and WKY-11 wk group, n = 5) and 24 weeks (SHR-24 wk group, n = 10 and WKY-24 wk group, n = 10). The SHR-3 wk group was normotensive and older SHR developed hypertension that was severe in the SHR-24 wk group. Tubulointerstitial accumulation of lymphocytes, macrophages, angiotensin II-positive cells, cells expressing the p65 DNA-binding subunit of NF-kappaB and activation of NF-kappaB in the kidney were all significantly increased (p < 0.01) in the prehypertensive SHR-3 wk group and augmented progressively, with the highest values in the SHR-24 wk group. The SHR-24 wk group showed increased (p < 0.001) helper (CD4) T cell infiltration and a high CD4/CD8 ratio. These findings are consistent with the possibility that activation of NF-kappaB and renal interstitial infiltration of immune cells may be part of the pathophysiologic process that drives hypertension in the SHR.

Kidney International, 1998

Background. Cationic streptococcal proteinase (erythrotoxin B) and its precursor, zymogen, are pu... more Background. Cationic streptococcal proteinase (erythrotoxin B) and its precursor, zymogen, are putative nephritogenic antigens. The present study was designed to test whether serum titers to these antigens were good markers of streptococcal infection associated with glomerulonephritis.

Kidney International, 1990

Monocytes have been demonstrated to play an important role in acute serum sickness (AcSS) nephrit... more Monocytes have been demonstrated to play an important role in acute serum sickness (AcSS) nephritis. Because accumulation of monocytes within the glomeruli could be the result of local lymphokine production, we studied migration inhibition factor (MIF) activity in supernatants from glomerular cultures, analyzed its temporal relationship with monocyte and lymphocyte accumulation, and tested the effect of anti-T lymphocyte monoclonal antibody on local MIF production. AcSS was induced in 12 rabbits, and one additional rabbit had antigen elimination without proteinuria. Single nephrectomy was performed at the time of antigen elimination in all animals; the remaining kidney was removed four days (4 rabbits) or 14 days afterwards (5 rabbits). In glomerular cross sections (gcs), lymphocytes were identified using monoclonal antibody M108, and monocytes by nonspecific esterase stain (ES). MIF activity was determined in supernatants of cultures of isolated glomeruli by the agarose microdroplet method. Peak of MIF activity (84.3 +/- 2.6%, SEM) was observed the first day of proteinuria in association with peak of lymphocyte infiltration (1.15 +/- 0.1 lymphocytes/gcs) and monocyte infiltration (2.4 +/- 0.3 mean ES score/gcs). MIF activity diminished by day 4 (66.0 +/- 6.3%) and reached control levels by day 14 (12.8 +/- 3.2%). There was a significant correlation between lymphocyte infiltration and MIF activity (r = 0.776, P less than 0.0001) as well as between MIF activity and monocyte accumulation (r = 0.858, P less than 0.0001). In five additional rabbits with AcSS, glomeruli were isolated, treated successively with M108 and normal rabbit serum, and supernatants harvested from 24-hour cultures were tested for MIF activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Atherosclerosis, 2000

Immunosuppressive therapy has been shown to either improve or, more frequently, enhance the devel... more Immunosuppressive therapy has been shown to either improve or, more frequently, enhance the development of atherosclerosis. We tested the effect of mycophenolate mofetil (MMF), an inhibitor of nucleotide synthesis widely used in transplant therapy, in diet-induced atherosclerosis in the rabbit. Two groups (n=10 each) of New Zealand White (NZW) rabbits were fed a 1% cholesterol diet for 12 weeks. One group received MMF (CHOL+MMF group) by gastric gavage (30 mg/kg daily) and the other group (CHOL) received the same volume of saline by the same route. There were no differences in the serum cholesterol (mean values ≥30 mmol/l in both groups after 2 weeks) or in the triglyceride, blood sugar, total protein, and albumin serum levels and weight gain in both groups of animals. The cholesterol-fed untreated rabbits had atherosclerotic plaques covering 43.9.1±SD 16.40% of their thoracic aorta and 41.9±22.59% of their abdominal aorta, while the MMF treated group had 18.5±7.17% and 17.7±9.71%, respectively (P<0.01). The cholesterol content of the aorta (mg/g) in the cholesterol-fed untreated group was 4.61±SD 1.21 in the thoracic aorta and 4.54±2.07 in the abdominal aorta, whereas the MMF treated group had and 2.83±0.84 and 2.77±1.44, respectively (P<0.01). Infiltrating macrophages (RAM 11 positive cells/100 nuclei) in the intimal layer of the aorta were 58.4±SD26.16 in the CHOL group and 8.5±5.51 in the CHOL+MMF group: (P<0.001). CD18 positive cells/100 nuclei were 27.4±17.6 in the CHOL group and 5.3±3.82 in the CHOL+MMF group (P<0.01), and the intima/media ratio was 0.66±0.11 in the CHOL group and 0.30±0.09 in the MMF treated rabbits (P<0.001). MMF also reduced proliferating smooth muscle cells (HHF35 positive) infiltrating between the macrophages. These results indicate that MMF ameliorates importantly the atherogenic potential of a high cholesterol diet and this effect is associated with a reduction in macrophage and foam cell infiltration and smooth muscle cell proliferation and infiltration. Since chronic treatment with this drug is given routinely in various clinical conditions with relatively minor side effects, consideration may be given to its use as adjuvant therapy in artheriosclerotic cardiovascular disease.

Basic & Clinical Pharmacology & Toxicology, 2009

Abstract: In this work, we aimed to study the effect of uric acid on gentamicin-induced nephroto... more Abstract: In this work, we aimed to study the effect of uric acid on gentamicin-induced nephrotoxicity. Male Sprague-Dawley rats were assigned to one of six groups (six rats each) which received intraperitoneal injections for 9 days: (S) saline; (UA) Uric acid alone; (G) Gentamicin alone; (G + UA) Gentamicin + uric acid; (G rec) Gentamicin recovery and (G + UA rec) Gentamicin + uric acid recovery. In (G rec) and (G + UA rec), rats recovered for 7 days after the last injection. Urine and blood samples were taken on day 0 and at the end of every stage. Kidneys were harvested for histological scoring, determination of renal malondialdehyde (MDA), zymography and western blots for matrix metalloprotease (MMP)-2 and MMP-9. Uric acid alone did not provoke changes in biochemical and histological parameters when compared to controls. Gentamicin alone increased significantly plasma creatinine and blood urea nitrogen and caused a moderate histological damage. When combined with uric acid, these conditions worsened. MMP-9 activity and expression was decreased in rats from group G + UA as compared with rats from group G, while activity of MMP-2 was similarly increased in both groups when compared to controls. The increase in renal MDA induced by gentamicin was not altered when it was combined with uric acid. During the recovery stage, all biochemical parameters returned to normal levels, though a trend for delay of tubular damage recovery was observed in group G + UA rec when compared with group G rec. The results indicate that uric acid worsens gentamicin-induced nephrotoxicity. The mechanism is likely to implicate down-regulation of MMP-9.

Kidney International, 1990

Because the role of systemic hormones in the pathophysiology of edema in acute renal disease rema... more Because the role of systemic hormones in the pathophysiology of edema in acute renal disease remains incompletely understood, we compared the levels of atrial natriuretic factor (ANF) and plasma renin activity (PRA) in patients with acute glomerulonephritis (AGN), nephrotic syndrome (NS), and normal individuals during salt deprivation and salt loading. Sixteen patients with AGN (10 males) and nine patients with NS and hypoalbuminemia (7 males) were studied on admission, and after recovery (12 AGN patients) or remission (4 NS patients). Eighteen normal controls were each studied after five days on a low (20 mEq Na/day), regular (120 mEq Na/day) and high (300 mEq Na/day) dietary salt intake. Patients with AGN and NS had comparable edema (AGN 2.8 +/- 0.53 kg; NS 3.36 +/- 0.47 kg; SE) and urinary Na excretion (mean +/- SEM: AGN 0.97 +/- 0.11 mEq/hr; NS 1.06 +/- 0.16 mEq/hr), but AGN patients had five times higher ANF (AGN 27.2 +/- 4.06 fmol/ml; NS 5.51 +/- 1.02 fmol/ml; P less than 0.001) and six times lower PRA ng/liter.sec levels (AGN 0.187 +/- 0.047; NS 1.144 +/- 0.222; P less than 0.001) than NS patients. The degree of edema was correlated with ANF levels in AGN patients (P less than 0.001) but not in NS patients. There was a strong exponential negative correlation (r = -0.773, P less than 0.0001) between ANF and PRA, in which AGN patients and Na-restricted controls were located in the opposite ends of the volume sensing-response, and NS patients in the middle, alongside controls with regular Na intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Kidney International, 2001

kidney one-clip Goldblatt hypertension [3, 4], aging [5], cyclosporine nephropathy [6], and catec... more kidney one-clip Goldblatt hypertension [3, 4], aging [5], cyclosporine nephropathy [6], and catecholamine infu-

Kidney International, 2001

kidney one-clip Goldblatt hypertension [3, 4], aging [5], cyclosporine nephropathy [6], and catec... more kidney one-clip Goldblatt hypertension [3, 4], aging [5], cyclosporine nephropathy [6], and catecholamine infu-

Clinical Immunology, 1999

Peripheral blood leukocytes infiltrate the kidney in chronic serum sickness (CSS). We therefore s... more Peripheral blood leukocytes infiltrate the kidney in chronic serum sickness (CSS). We therefore studied the expression of CD54 and its ligands CD18 and CD11b/c in CSS in 10 rats with CSS, 6 rats immunized similarly who did not developed proteinuria (no-CSS group), and 10 normal rats (control group). Intense (6 to 35 times more than controls) leukocyte infiltration was observed in CSS. The CSS group over-expressed CD54 in glomeruli and interstitium in association with increments in CD18-and CD11b/c-positive cells ranging 2.5 to 7 times the number found in controls. 75% of infiltrating leukocytes expressed CD18 and 87% expressed CD11b/c. The non-CSS group had leukocyte infiltration and expression of adhesion molecules similar to control group. Adherence of CD43-positive cells to renal tissues was 4 times higher in renal tissue from CSS rats than to normal kidney. Pretreatment with corresponding Mabs reduced adherence by half. We concluded that over-expression of CD54 and its ligands CD18 and CD11b/c in infiltrating leukocytes occur in CSS. Binding experiments suggest the functional relevance of these molecules.

Journal of Structural Engineering-asce, 2006

Results from the tests of six cantilever double-channel built-up members under reversed cyclic be... more Results from the tests of six cantilever double-channel built-up members under reversed cyclic bending are presented. The main parameters investigated were stitch spacing and lateral bracing requirements in order to sustain large inelastic rotations, such as those induced by severe earthquake events. Experimental results indicate that current lateral bracing requirements specified in the AISC-LRFD provisions are not adequate to prevent lateral-torsional buckling of individual elements, as well as of the entire built-up member. Based on the results from this research, a new equation is proposed for stitch spacing for interconnection of individual channels. In addition, lateral bracing for the overall member is required near the plastic hinge region to ensure total plastic hinge rotation capacities on the order of 0.06 rad.

Engineering Structures, 2005

Results from an investigation aimed at developing a moment connection for a new earthquake-resist... more Results from an investigation aimed at developing a moment connection for a new earthquake-resistant framing system that consists of precast hybrid fiber reinforced concrete (FRC)-encased steel truss beams and reinforced concrete (RC) columns are presented. Various connection schemes between the precast hybrid beams and RC columns were experimentally evaluated for adequate moment and shear transfer during large displacement reversals. From

American Journal of Pathology, 2004

A basic conservation of cell migration guidance mechanisms in the nervous and immune systems was ... more A basic conservation of cell migration guidance mechanisms in the nervous and immune systems was proposed when Slit, known for its role in axon guidance, was found to inhibit chemokine-induced leukocyte chemotaxis in vitro. These studies examined the role of Slit2 in modulating inflammation in vivo. In a rat model of glomerulonephritis, endogenous glomerular Slit2 expression fell after disease induction, and its inhibition during the early disease period accelerated inflammation. Ex vivo glomerular leukocytes showed decreased chemokine and chemoattractant-induced chemotaxis in response to Slit2, suggesting an anti-inflammatory role for glomerular Slit2. In contrast to the effect of inhibition, glomerulonephritis was ameliorated by systemic Slit2 administration. Slit2 treatment improved disease histologically and also improved renal function when given early in the disease course. Leukocytes harvested from rats receiving Slit2 showed decreased monocyte chemoattractant protein-1 (MCP)-1-mediated migration, consistent with a peripheral Slit2 effect. In keeping with this functional alteration, Slit2-mediated inhibition of RAW264.7 cell chemotaxis was associated with decreased levels of active cdc42 and Rac1, implicating GTPases in leukocyte Slit2 signaling. These findings suggest a role for endogenous Slit2 in the inhibition of chemoattractant-mediated signals, demonstrate a potentially important anti-inflammatory effect for Slit2 in vivo, and provide further evidence for conserved mechanisms guiding the process of migration in distinct cell types.

Kidney International, 2008

Renal tubulointerstitial inflammation is a constant feature of experimental models of hypertensio... more Renal tubulointerstitial inflammation is a constant feature of experimental models of hypertension and likely plays a role in the pathogenesis of salt-sensitive hypertension. We have previously raised the possibility that the immune cell infiltration is driven by a low grade autoimmune reactivity directed to or facilitated by renal heat shock protein over expression. The present studies were done to gain insight on possible cell-mediated immune mechanisms in experimental hypertension by determining the renal expression of HSP70 and the proliferation index of T lymphocytes cultured with HSP70. We studied male Sprague-Dawley rats with inhibition of nitric oxide (NO) synthase (n ¼ 6), protein overload (PO) proteinuria (n ¼ 7) and short-term angiotensin II (Ang II) infusion (n ¼ 5), and their corresponding control groups. Each model was associated with 2 to 4 fold increase (Po0.05-0.001) in renal HSP70 expression. T cells isolated from the spleens demonstrated a significant two-to nine-fold response compared to controls (Po0.05 or lower for each comparison) when cultured with HSP70. These studies suggest that autoimmunity to stress proteins is involved in the sustained low-grade inflammatory infiltration that occurs in the tubulointerstitial areas of the hypertensive kidney.

Kidney International, 2003

Background. Angiotensin II (Ang II) infusion and nitric oxide synthesis (NOS) inhibition with N -... more Background. Angiotensin II (Ang II) infusion and nitric oxide synthesis (NOS) inhibition with N -nitro-l-arginine-methylester (l-NAME) are experimental models of hypertension associated with renal inflammation and oxidative stress. To gain insight into the nature of the tubulointerstitial injury induced in these models, we studied lectin-binding specificities, vimentin expression, and heat shock protein (HSP) 60 and 70 in these experimental models.

Kidney International, 1999

tration with CD43-and ED1-positive cells in glomeruli and Mycophenolate mofetil prevents the prog... more tration with CD43-and ED1-positive cells in glomeruli and Mycophenolate mofetil prevents the progressive renal failure interstitium was two to five times lower in MMF-treated rats induced by 5/6 renal ablation in rats.

American Journal of Nephrology, 2004

Lymphocytes and macrophages infiltrate the kidney of spontaneously hypertensive rats (SHR) and in... more Lymphocytes and macrophages infiltrate the kidney of spontaneously hypertensive rats (SHR) and interventions leading to their reduction are associated with improvement of the hypertension. The present studies examined the evolution of the interstitial inflammation in the natural course of the SHR to gain insight on the potential role of interstitial immune cell accumulation in the development of hypertension. We studied SHR and control WKY rats at 3 weeks (SHR-3 wk group, n = 11 and WKY-3 wk group, n = 10), 11 weeks (SHR-11 wk group, n = 5 and WKY-11 wk group, n = 5) and 24 weeks (SHR-24 wk group, n = 10 and WKY-24 wk group, n = 10). The SHR-3 wk group was normotensive and older SHR developed hypertension that was severe in the SHR-24 wk group. Tubulointerstitial accumulation of lymphocytes, macrophages, angiotensin II-positive cells, cells expressing the p65 DNA-binding subunit of NF-kappaB and activation of NF-kappaB in the kidney were all significantly increased (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) in the prehypertensive SHR-3 wk group and augmented progressively, with the highest values in the SHR-24 wk group. The SHR-24 wk group showed increased (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) helper (CD4) T cell infiltration and a high CD4/CD8 ratio. These findings are consistent with the possibility that activation of NF-kappaB and renal interstitial infiltration of immune cells may be part of the pathophysiologic process that drives hypertension in the SHR.

Kidney International, 1998

Background. Cationic streptococcal proteinase (erythrotoxin B) and its precursor, zymogen, are pu... more Background. Cationic streptococcal proteinase (erythrotoxin B) and its precursor, zymogen, are putative nephritogenic antigens. The present study was designed to test whether serum titers to these antigens were good markers of streptococcal infection associated with glomerulonephritis.

Kidney International, 1990

Monocytes have been demonstrated to play an important role in acute serum sickness (AcSS) nephrit... more Monocytes have been demonstrated to play an important role in acute serum sickness (AcSS) nephritis. Because accumulation of monocytes within the glomeruli could be the result of local lymphokine production, we studied migration inhibition factor (MIF) activity in supernatants from glomerular cultures, analyzed its temporal relationship with monocyte and lymphocyte accumulation, and tested the effect of anti-T lymphocyte monoclonal antibody on local MIF production. AcSS was induced in 12 rabbits, and one additional rabbit had antigen elimination without proteinuria. Single nephrectomy was performed at the time of antigen elimination in all animals; the remaining kidney was removed four days (4 rabbits) or 14 days afterwards (5 rabbits). In glomerular cross sections (gcs), lymphocytes were identified using monoclonal antibody M108, and monocytes by nonspecific esterase stain (ES). MIF activity was determined in supernatants of cultures of isolated glomeruli by the agarose microdroplet method. Peak of MIF activity (84.3 +/- 2.6%, SEM) was observed the first day of proteinuria in association with peak of lymphocyte infiltration (1.15 +/- 0.1 lymphocytes/gcs) and monocyte infiltration (2.4 +/- 0.3 mean ES score/gcs). MIF activity diminished by day 4 (66.0 +/- 6.3%) and reached control levels by day 14 (12.8 +/- 3.2%). There was a significant correlation between lymphocyte infiltration and MIF activity (r = 0.776, P less than 0.0001) as well as between MIF activity and monocyte accumulation (r = 0.858, P less than 0.0001). In five additional rabbits with AcSS, glomeruli were isolated, treated successively with M108 and normal rabbit serum, and supernatants harvested from 24-hour cultures were tested for MIF activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Atherosclerosis, 2000

Immunosuppressive therapy has been shown to either improve or, more frequently, enhance the devel... more Immunosuppressive therapy has been shown to either improve or, more frequently, enhance the development of atherosclerosis. We tested the effect of mycophenolate mofetil (MMF), an inhibitor of nucleotide synthesis widely used in transplant therapy, in diet-induced atherosclerosis in the rabbit. Two groups (n=10 each) of New Zealand White (NZW) rabbits were fed a 1% cholesterol diet for 12 weeks. One group received MMF (CHOL+MMF group) by gastric gavage (30 mg/kg daily) and the other group (CHOL) received the same volume of saline by the same route. There were no differences in the serum cholesterol (mean values ≥30 mmol/l in both groups after 2 weeks) or in the triglyceride, blood sugar, total protein, and albumin serum levels and weight gain in both groups of animals. The cholesterol-fed untreated rabbits had atherosclerotic plaques covering 43.9.1±SD 16.40% of their thoracic aorta and 41.9±22.59% of their abdominal aorta, while the MMF treated group had 18.5±7.17% and 17.7±9.71%, respectively (P<0.01). The cholesterol content of the aorta (mg/g) in the cholesterol-fed untreated group was 4.61±SD 1.21 in the thoracic aorta and 4.54±2.07 in the abdominal aorta, whereas the MMF treated group had and 2.83±0.84 and 2.77±1.44, respectively (P<0.01). Infiltrating macrophages (RAM 11 positive cells/100 nuclei) in the intimal layer of the aorta were 58.4±SD26.16 in the CHOL group and 8.5±5.51 in the CHOL+MMF group: (P<0.001). CD18 positive cells/100 nuclei were 27.4±17.6 in the CHOL group and 5.3±3.82 in the CHOL+MMF group (P<0.01), and the intima/media ratio was 0.66±0.11 in the CHOL group and 0.30±0.09 in the MMF treated rabbits (P<0.001). MMF also reduced proliferating smooth muscle cells (HHF35 positive) infiltrating between the macrophages. These results indicate that MMF ameliorates importantly the atherogenic potential of a high cholesterol diet and this effect is associated with a reduction in macrophage and foam cell infiltration and smooth muscle cell proliferation and infiltration. Since chronic treatment with this drug is given routinely in various clinical conditions with relatively minor side effects, consideration may be given to its use as adjuvant therapy in artheriosclerotic cardiovascular disease.

Basic & Clinical Pharmacology & Toxicology, 2009

Abstract: In this work, we aimed to study the effect of uric acid on gentamicin-induced nephroto... more Abstract: In this work, we aimed to study the effect of uric acid on gentamicin-induced nephrotoxicity. Male Sprague-Dawley rats were assigned to one of six groups (six rats each) which received intraperitoneal injections for 9 days: (S) saline; (UA) Uric acid alone; (G) Gentamicin alone; (G + UA) Gentamicin + uric acid; (G rec) Gentamicin recovery and (G + UA rec) Gentamicin + uric acid recovery. In (G rec) and (G + UA rec), rats recovered for 7 days after the last injection. Urine and blood samples were taken on day 0 and at the end of every stage. Kidneys were harvested for histological scoring, determination of renal malondialdehyde (MDA), zymography and western blots for matrix metalloprotease (MMP)-2 and MMP-9. Uric acid alone did not provoke changes in biochemical and histological parameters when compared to controls. Gentamicin alone increased significantly plasma creatinine and blood urea nitrogen and caused a moderate histological damage. When combined with uric acid, these conditions worsened. MMP-9 activity and expression was decreased in rats from group G + UA as compared with rats from group G, while activity of MMP-2 was similarly increased in both groups when compared to controls. The increase in renal MDA induced by gentamicin was not altered when it was combined with uric acid. During the recovery stage, all biochemical parameters returned to normal levels, though a trend for delay of tubular damage recovery was observed in group G + UA rec when compared with group G rec. The results indicate that uric acid worsens gentamicin-induced nephrotoxicity. The mechanism is likely to implicate down-regulation of MMP-9.

Kidney International, 1990

Because the role of systemic hormones in the pathophysiology of edema in acute renal disease rema... more Because the role of systemic hormones in the pathophysiology of edema in acute renal disease remains incompletely understood, we compared the levels of atrial natriuretic factor (ANF) and plasma renin activity (PRA) in patients with acute glomerulonephritis (AGN), nephrotic syndrome (NS), and normal individuals during salt deprivation and salt loading. Sixteen patients with AGN (10 males) and nine patients with NS and hypoalbuminemia (7 males) were studied on admission, and after recovery (12 AGN patients) or remission (4 NS patients). Eighteen normal controls were each studied after five days on a low (20 mEq Na/day), regular (120 mEq Na/day) and high (300 mEq Na/day) dietary salt intake. Patients with AGN and NS had comparable edema (AGN 2.8 +/- 0.53 kg; NS 3.36 +/- 0.47 kg; SE) and urinary Na excretion (mean +/- SEM: AGN 0.97 +/- 0.11 mEq/hr; NS 1.06 +/- 0.16 mEq/hr), but AGN patients had five times higher ANF (AGN 27.2 +/- 4.06 fmol/ml; NS 5.51 +/- 1.02 fmol/ml; P less than 0.001) and six times lower PRA ng/liter.sec levels (AGN 0.187 +/- 0.047; NS 1.144 +/- 0.222; P less than 0.001) than NS patients. The degree of edema was correlated with ANF levels in AGN patients (P less than 0.001) but not in NS patients. There was a strong exponential negative correlation (r = -0.773, P less than 0.0001) between ANF and PRA, in which AGN patients and Na-restricted controls were located in the opposite ends of the volume sensing-response, and NS patients in the middle, alongside controls with regular Na intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Kidney International, 2001

kidney one-clip Goldblatt hypertension [3, 4], aging [5], cyclosporine nephropathy [6], and catec... more kidney one-clip Goldblatt hypertension [3, 4], aging [5], cyclosporine nephropathy [6], and catecholamine infu-

Kidney International, 2001

kidney one-clip Goldblatt hypertension [3, 4], aging [5], cyclosporine nephropathy [6], and catec... more kidney one-clip Goldblatt hypertension [3, 4], aging [5], cyclosporine nephropathy [6], and catecholamine infu-

Clinical Immunology, 1999

Peripheral blood leukocytes infiltrate the kidney in chronic serum sickness (CSS). We therefore s... more Peripheral blood leukocytes infiltrate the kidney in chronic serum sickness (CSS). We therefore studied the expression of CD54 and its ligands CD18 and CD11b/c in CSS in 10 rats with CSS, 6 rats immunized similarly who did not developed proteinuria (no-CSS group), and 10 normal rats (control group). Intense (6 to 35 times more than controls) leukocyte infiltration was observed in CSS. The CSS group over-expressed CD54 in glomeruli and interstitium in association with increments in CD18-and CD11b/c-positive cells ranging 2.5 to 7 times the number found in controls. 75% of infiltrating leukocytes expressed CD18 and 87% expressed CD11b/c. The non-CSS group had leukocyte infiltration and expression of adhesion molecules similar to control group. Adherence of CD43-positive cells to renal tissues was 4 times higher in renal tissue from CSS rats than to normal kidney. Pretreatment with corresponding Mabs reduced adherence by half. We concluded that over-expression of CD54 and its ligands CD18 and CD11b/c in infiltrating leukocytes occur in CSS. Binding experiments suggest the functional relevance of these molecules.

Journal of Structural Engineering-asce, 2006

Results from the tests of six cantilever double-channel built-up members under reversed cyclic be... more Results from the tests of six cantilever double-channel built-up members under reversed cyclic bending are presented. The main parameters investigated were stitch spacing and lateral bracing requirements in order to sustain large inelastic rotations, such as those induced by severe earthquake events. Experimental results indicate that current lateral bracing requirements specified in the AISC-LRFD provisions are not adequate to prevent lateral-torsional buckling of individual elements, as well as of the entire built-up member. Based on the results from this research, a new equation is proposed for stitch spacing for interconnection of individual channels. In addition, lateral bracing for the overall member is required near the plastic hinge region to ensure total plastic hinge rotation capacities on the order of 0.06 rad.

Engineering Structures, 2005

Results from an investigation aimed at developing a moment connection for a new earthquake-resist... more Results from an investigation aimed at developing a moment connection for a new earthquake-resistant framing system that consists of precast hybrid fiber reinforced concrete (FRC)-encased steel truss beams and reinforced concrete (RC) columns are presented. Various connection schemes between the precast hybrid beams and RC columns were experimentally evaluated for adequate moment and shear transfer during large displacement reversals. From