Levofloxacin and rhabdomyolysis in a renal transplant patient.
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Aged↗
Biomedical subjects
Uzi Gafter
Publications and source records attributed to Uzi Gafter.
A worrying thought--could there be a connection between encapsulating peritoneal sclerosis, tamoxifen and calciphylaxis?
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Calciphylaxis↗
Effect of hemodialysis on the thickness of vocal folds: a possible explanation for postdialysis hoarseness.
BACKGROUND: Determining the dry weight of chronically hemodialysed patients is a common problem. Patients on intermittent hemodialysis often experience transient hoarseness at the end of dialysis. The vocal folds may be affected by the hydration state. AIM: To test the hypothesis that postdialysis hoarseness may be related to changes in the thickness of the vocal folds. METHODS: Twenty-five stable chronic hemodialysis patients underwent endoscopic nasopharyngeal laryngoscopy before and after dialysis. Pictures of the vocal folds were taken and the folds were measured using computer software. Eighteen vocal folds from 16 patients were technically adequate for analysis. The change in the width/length ratio of the vocal folds (W/L) was used as a measurement of the folds' thickness. RESULTS: W/L decreased from 0.175 +/- 0.011 before dialysis to 0.152 +/- 0.009 after dialysis (p < 0.01, mean reduction 10.9 +/- 3.8%). Patients' weight decreased by 4.7 +/- 0.3% (p < 0.0001), systolic blood pressure decreased by 15.0 +/- 3.1% (p < 0.001), diastolic blood pressure decreased by 13.0 +/- 3.6% (p < 0.01), and mean blood pressure decreased by 14.1 +/- 3.1% (p < 0.001). Sixty percent of the patients had postdialysis hoarseness, and in 72% of the patients a decrease in the vocal folds' thickness was observed. CONCLUSIONS: Chronic hemodialysis patients may experience transient postdialysis hoarseness, and a decrease in the vocal folds' thickness. The latter may result from dehydration.
Adult↗
Pregnancy in renal transplant recipients: long-term effect on patient and graft survival. A single-center experience.
BACKGROUND: There are limited data on the effect of pregnancy on long-term renal allograft function. The aim of the study was to compare long-term graft and patient outcome between pregnant and nonpregnant women after renal transplantation. METHODS: The study group consisted of 39 women attending the Perinatal Division of the Rabin Medical Center who conceived after undergoing renal transplantation (total number of live births: 55). All had a functioning allograft at the time of conception. Each patient was matched with 3 controls for 12 factors known to affect graft survival. The controls were derived from a cohort of 250,000 transplant patients registered in the Collaborative Transplantation Study (CTS) database. The groups were compared for graft survival, long-term patient survival, and kidney function (CTS clinical grading scale). RESULTS: Graft (61.6%) and patient (84.8 %) survival from transplantation to the end of follow-up (15 years) in the women who conceived after transplantation did not differ from the rates observed in the 177 women in the matched control group (68.7% and 78.8 %, respectively). There were no between-group differences in long-term graft function. CONCLUSION: Pregnancy does not appear to have adverse effects on long-term graft or patient survival or kidney function in women after renal transplantation.
Adolescent↗
How to improve anti-hepatitis B vaccination.
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Hepatitis B↗
Spontaneous DNA repair in human mononuclear cells is calcium-dependent.
Spontaneous DNA repair in peripheral blood mononuclear cells (PBMC) has been recently described. The aim of this study was to evaluate whether spontaneous DNA repair is Ca(2+)-dependent, as in vitro-stimulated DNA repair. Spontaneous DNA repair in PBMC was measured in a 1mM Ca2+ medium. The effect of extracellular Ca2+ chelation by EGTA, intracellular Ca2+ chelation by bapta-AM, and Ca2+ loading by the ionophore A23187 was examined. The signal transduction pathway was evaluated by inhibiting protein tyrosine kinase with genistein, calmodulin with W7, and calcineurin with cyclosporin A and tacrolimus. Extracellular Ca2+ chelation had no effect on spontaneous DNA repair, while both intracellular chelation and calcium overloading inhibited the DNA repair. Inhibition of protein tyrosine kinase, calmodulin or calcineurin reduced DNA repair. In conclusion, spontaneous DNA repair is mainly Ca(2+)-dependent at a narrow range of intracellular Ca2+ concentrations. The signal transduction cascade includes protein tyrosine kinase, calmodulin, and calcineurin.
Calcimycin↗
Non-occlusive mesenteric ischemia in chronically dialyzed patients: a disease with multiple risk factors.
BACKGROUND: Non-occlusive mesenteric ischemia (NOMI) can be a fatal complication in dialysis patients. Intradialytic hypotension is usually the precipitating factor. The occurrence of 16 cases in 5 years (1998-2002), compared with only 4 in previous years, led us to investigate other risk factors contributing to NOMI. A control group of stable hemodialysis patients was used for comparison. RESULTS: 20 patients were studied: 17 diagnosed surgically, and 3 clinically. The mean age was 70.8 +/- 1.8 years, and the male:female ratio 7:13. Nineteen patients were on hemodialysis. Clinically overt atherosclerosis was present in 17 patients. Preceding dialysis-associated hypotension was identified in all patients studied and access thrombosis in 6 patients. In all patients, abdominal pain was the presenting symptom. Initial abdominal examination was unimpressive in 16 patients. The hemoconcentration, leukocytosis and metabolic acidosis were the most prominent laboratory findings. 5/11 abdominal sonograms showed intestinal pathology. 2/3 angiographies were diagnostic. Three patients responded to early fluid challenge and did not require surgery. Pathology was related to the area of the superior mesenteric artery in all 15 patients operated. Twelve (60%) patients died from the event. The 1-year mortality rate was 17/20 patients (85%). Possible contributing factors, other than dialysis-associated hypotension, included: high-dose recombinant human erythropoietin (rhEPO) therapy (179 +/- 35 vs. 116 +/- 10 U/kg/week in the control group, p < 0.05); metastatic calcifications (abdominal aorta 14/14, aortic valve 11/18; medial calcification of mesenteric arteries in 2/11 pathology specimens); digoxin, and hypoalbuminemia. CONCLUSIONS: The increased incidence of NOMI in dialysis patients may be related to overly aggressive rhEPO therapy and the unsuspected presence of mesenteric arterial medial calcifications. Identification of patients at risk, prevention of intradialytic hypotension and a controlled increase in dry weight may help to reduce the incidence of NOMI in chronically dialyzed patients.
Aged↗
Baseline oxysterols and other markers of oxidative stress, inflammation and malnutrition in the vitamin e and intima media thickness progression in end-stage renal disease (VIPER) cohort.
BACKGROUND AND OBJECTIVES: Oxysterols are markers of oxidative stress, levels of which have not yet been reported in hemodialysis (HD) patients. This study was designed to compare levels of the oxysterols 7-ketocholesterol (7KC) and 7beta-hydroxycholesterol (7betaOH) between a cohort of HD patients and healthy controls. METHODS: This nested cross-sectional study reflects baseline (pre-intervention) values for markers of oxidative stress, inflammation and nutrition status in the 160-member vitamin E and carotid intima media thickness progression in end-stage renal disease (VIPER) cohort (age 64.1 +/- 8.8, 33.5% female). Age- and sex-matched healthy volunteers served as controls. Plasma oxysterols 7KC and 7betaOH were determined by isotope dilution gas chromatography/mass spectrometry. RESULTS: Despite higher plasma alpha-tocopherol levels in HD patients than controls (36.0 +/- 9.3 vs. 31.8 +/- 8.4 micromol/l, p = 0.007), 7KC levels (9.8 +/- 6.9 vs. 5.9 +/- 2.8 nmol/mmol cholesterol, p < 0.0001) and 7betaOH levels (8.7 +/- 4.3 vs. 2.7 +/- 1.6 nmol/mmol cholesterol, p < 0.0001) were higher in HD patients. The oxysterol 7betaOH was significantly, inversely associated with prealbumin (r = -0.18, p = 0.03), though neither oxysterol was significantly associated with any other marker of oxidative stress, inflammation or nutrition status and did not discriminate for CVD in HD patients. CONCLUSIONS: Elevated levels of the oxysterols 7KC and 7betaOH indicate that HD patients are in a state of oxidative stress compared to healthy controls. However, oxysterols 7KC and 7betaOH did not appear to contribute additional information about oxidative stress among HD patients.
Adult↗
Spontaneous DNA repair in human peripheral blood mononuclear cells.
DNA molecules are constantly damaged during mitosis and by oxygen-free radicals produced by either cellular metabolism or by external factors. Populations at risk include patients with cancer-prone disease, patients under enhanced oxidative stress, and those treated with immunosuppressive/cytotoxic therapy. The DNA repair process is crucial in maintaining the genomal DNA integrity. The aim of this study was to evaluate spontaneous DNA repair capacity of peripheral blood mononuclear cells (PBMC) from normal blood donors. PBMC DNA repair ability represents DNA repair by other tissues as well. It is shown in the present study that in vitro incorporation of [3H]thymidine in non-stimulated PBMC expresses the ability of the cells to repair DNA damage. This method was validated by double-stranded DNA measurements. Both catalase and Fe2+ increased DNA repair, the former by preventing re-breakage of newly repaired DNA and the latter by introducing additional DNA damage, which enhanced DNA repair. Better understanding of DNA repair processes will enable to minimize DNA damage induced by oxidative stress.
Cytarabine↗
Inhibition of interleukin-10 by the immunomodulator AS101 reduces mesangial cell proliferation in experimental mesangioproliferative glomerulonephritis: association with dephosphorylation of STAT3.
Mesangial cell (MC) proliferation is essential for the pathogenesis and progression of glomerular disease. Using an acute model of mesangial proliferative glomerulonephritis (Thy1 GN), we show that neutralization of interleukin (IL)-10 greatly ameliorated the disease as expressed by both decreased MC expansion and proteinuria. Treatment with the tellurium compound AS101 (ammonium trichloro(dioxoethylene-o,o')tellurate) resulted in favorable effects provided that the compound was administered 24 h before insult, whereas partial effects were obtained when administered after insult. We identified STAT3 as playing a pivotal role in IL-10-induced MC proliferation in vitro and in vivo. IL-10 activates MC STAT3 in vitro as expressed by its phosphorylation and nuclear translocation. The role of STAT3 in MC proliferation induced by IL-10 was deduced from results showing that IL-10-induced proliferation was abrogated if MC transfected with STAT3 antisense oligonucleotides were used or if cells were incubated with inhibitors of STAT3. AS101 deactivates STAT3 in control but not in MC transfected with IL-10 antisense oligonucleotides. Inactivation of STAT3 prevents reduction of MC proliferation by AS101. We further demonstrate the role of STAT3 in the regulation of cell cycle and survival regulatory proteins by AS101 in MC via inhibition of IL-10. IL-10 increased MC expression of Bcl-2 and Bcl-X1 and simultaneously decreased the levels of p27kip1. These survival factors were decreased by AS101 in a STAT3- and IL-10-dependent manner, whereas p27kip1 was similarly increased. In Thy1 GN, phosphorylated STAT3 in glomerular MC peaked at day 6 and correlated with MC expansion. Neutralization of IL-10 or its inhibition by AS101 abolished phosphorylation of STAT3. This effect positively correlated with amelioration of the disease. These in vitro and in vivo studies indicate that the autocrine MC growth factor IL-10 induces MC proliferation via STAT3. We suggest that IL-10 or its downstream target STAT3 might be therapeutic targets for kidney diseases induced by mesangial proliferation.
Active Transport, Cell Nucleus↗
Cyclosporin A-induced hair growth in mice is associated with inhibition of hair follicle regression.
BACKGROUND: Cyclosporin A (CsA) often causes hair growth in transplant recipients. Our objectives were to evaluate the effect of CsA on follicular hair keratinocyte growth in nude mice by assessing their proliferation in vivo, and to assess the ability of CsA to prevent follicular keratinocyte apoptosis in vivo and chemotherapy-induced keratinocyte apoptosis in vitro. METHODS: Nude mice were fed various daily doses of CsA (10-100 mg/kg). Dorsal skin sections stained with hematoxylin and eosin, followed by immunostaining with 4-deoxybromouridine, were examined for determination of hair follicle number and hair follicle keratinocyte proliferation. Follicular keratinocytes were isolated and examined for apoptotic status. Apoptosis was induced in vitro in a keratinocyte cell line by 4-hydroperoxycyclophosphamide. The antiapoptotic effects of various CsA concentrations (0.1-5 microg/ml) were measured by annexin-V/propidium iodide binding. RESULTS: CsA caused a dose-dependent increase in the number of hair follicles but had no effect on follicular keratinocyte proliferation. Treatment with CsA decreased the number of apoptotic follicular keratinocytes. In vitro, there was a dose-dependent inhibition of the extent of early and late apoptosis of treated keratinocytes. CONCLUSION: CsA may induce hair growth by increasing the number of hair follicles and inhibiting apoptosis of follicular keratinocytes, thereby delaying hair follicle regression.
Animals↗
Improved immunogenicity of a novel third-generation recombinant hepatitis B vaccine in patients with end-stage renal disease.
Hepatitis B (HBV) infection remains a significant epidemiological problem in the end-stage renal disease (ESRD) population. Vaccination programs using second-generation vaccines lead to effective seroprotection in only 50-60% of these patients. The purpose of this case series was to describe our experience with a novel third-generation vaccine, Bio-Hep-B, in ESRD patients who had not developed protective anti-HBs titers following a second-generation HBV vaccination protocol. Twenty-nine ESRD patients who had not responded in the past to a standard second-generation HBV vaccination protocol were included in this series. Each patient received 10 microg of Bio-Hep-B) intramuscularly at 0, 1 and 6 months. A month after completion of the vaccination protocol, anti-HBs antibody levels were measured. Following immunization, 25 of 29 patients (86%) developed seroprotective anti-HBs levels > or =10 mIU/ml. There was a significant difference in the titers of anti-HBs antibodies prior to and following vaccination (p < 0.0001). Statistical analysis of the variables age, gender, diagnosis, dialysis mode, weight, hemoglobin, albumin, and KT/V failed to detect predictors of antibody response. A retrospective analysis of the results of a second-generation vaccination program for the years 1999-2001 in our department showed that 19 of 36 (56.4%) ESRD patients developed seroprotection. In conclusion, the results of this study show that the third-generation HBV vaccine Bio-Hep-B is highly immunogenic in the population of ESRD patients who did not respond in the past to a second-generation vaccine. This enhanced seroprotection offers hope that the new vaccine will reduce the rate of non-responders and help to eliminate HBV infection from dialysis centers.
Adult↗
Renin-angiotensin system blockade prevents the increase in plasma transforming growth factor beta 1, and reduces proteinuria and kidney hypertrophy in the streptozotocin-diabetic rat.
INTRODUCTION: Combination therapy with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) is used to improve renal outcome achieved by monotherapy in diabetic patients. In addition, interference with the renin-angiotensin system (RAS) reduced expression and excretion of transforming growth factor beta 1 (TGF-beta 1) in diabetic nephropathy. The aim of this study was to investigate the effects of interrupting the RAS by ACE inhibitor (ACE-I) or ARB monotherapy or by combination therapy on proteinuria, kidney hypertrophy and plasma TGF-beta 1 in diabetic rats. MATERIALS AND METHODS: Forty-one male Wistar rats were allocated to five groups: 1 = control rats, 2 = diabetic rats (streptozotocin [STZ] 55 mg/kg), 3 = diabetic rats as above receiving enalapril (20 mg/kg/day), 4 = diabetic rats receiving losartan (80 mg/kg/day), 5 = diabetic rats receiving both losartan and enalapril. The study lasted 60 days. RESULTS: Urinary protein excretion, kidney weight, serum ACE activity and plasma TGF-beta1 increased significantly in untreated diabetic rats compared with controls. Administration of losartan, enalapril, or both for 60 days prevented these changes. Furthermore, combined therapy for 30 days normalised urinary protein excretion, while monotherapy did not. Losartan inhibited serum ACE activity both in vivo and in vitro. Plasma TGF-beta 1 levels were positively correlated with blood glucose levels (r=0.4059) and with urinary protein excretion (r=0.3558). CONCLUSIONS: Combination therapy with losartan and enalapril was more effective than monotherapy with either drug in achieving an early antiproteinuric response. Long-term treatment with losartan was as effective as the combined treatment, possibly due to a dual inhibitory effect on the RAS. The antiproteinuric effect may be related, in part, to reduced TGF-beta 1.
Angiotensin II Type 1 Receptor Blockers↗
Hair growth induction by the Tellurium immunomodulator AS101: association with delayed terminal differentiation of follicular keratinocytes and ras-dependent up-regulation of KGF expression.
The synthetic immunomodulator AS101[ammonium trichloro(dioxoethylene-o,o')tellurate] was previously found to protect cancer patients from chemotherapy-induced bone marrow toxicity and alopecia. Here we show that AS101 induces hair growth in nude and normal mice. AS101 possesses the dual ability to both induce anagen and retard spontaneous catagen in the C57BL/6 mouse model. Anagen induced by AS101 is mediated by keratinocyte growth factor (KGF), as it is abrogated both in nude mice co-treated with AS101 plus neutralizing anti KGF antibodies and in AS101-treated transgenic mice expressing a dominant-negative KGF receptor transgene in basal keratinocytes. AS101 up-regulates KGF expression by activating the ras signaling pathway in cultured fibroblasts. AS101-induced delayed catagen is associated with inhibition of terminal differentiation marker expression both in nude and C57BL/6 mice epidermal follicular keratinocytes and in cultures of primary mouse follicular keratinocytes induced to differentiate. This activity is associated with relatively sustained elevation of p21waf. Delayed expression of terminal differentiation markers was not induced by AS101 in follicular keratinocytes from p21waf knockout mice. Because similar results were obtained with cultures of primary human keratinocytes and fibroblasts, preliminary case report studies revealed substantial hair growth when AS101 was topically applied on three adolescents who had remained alopeciac 1-2 years after chemotherapy. The results emphasize the unique mode of action of AS101 and highlight its potential clinical use for treating certain types of alopecia.
Adjuvants, Immunologic↗
Electrolyte disorders following oral sodium phosphate administration for bowel cleansing in elderly patients.
BACKGROUND: Oral sodium phosphate is currently used for colon preparation prior to colonoscopy or barium enema. Sodium phosphate induces hyperphosphatemia, hypocalcemia, and hypokalemia. Elderly patients are at an increased risk for phosphate intoxication due to decreased glomerular filtration rate, medication use, and systemic and gastrointestinal diseases. We investigated these electrolyte disorders and their correlation with creatinine clearance, coexistent diseases, medications, and functional status. METHODS: Thirty-six hospitalized patients were included in the study. On day 1, patients were administered 2 doses of oral sodium phosphate. Venous blood samples for electrolyte determination were obtained at 7 AM on days 1, 2 (the procedure day), and 3. Urine samples were obtained from 10 patients. RESULTS: An increase in serum phosphorus level was correlated with a decreased creatinine clearance (R = -0.52; P =.001). Hypocalcemia and hypokalemia were present in 21 (58%) and 20 (56%) patients, respectively. Patients with a serum potassium concentration of 3.5 mEq/L or less on day 2 had a lower serum potassium concentration on day 1 vs those with a serum potassium concentration greater than 3.5 mEq/L on day 2 (P =.03). Five (dependent patients) had a serum potassium concentration of 3 mEq/L or less and 2 had severe diarrhea, necessitating treatment. There were more demented patients with hypokalemia compared with normokalemic patients (P<.05). Urinary fractional excretion of phosphorus tripled on day 2 (P =.01). Potassium and sodium fractional excretion remained unchanged. CONCLUSIONS: Sodium phosphate induces serious electrolyte abnormalities in the elderly. The frequency and severity of hypokalemia is due to intestinal potassium loss associated with inadequate renal potassium conservation and is apparently more prevalent in frail patients. Assessment of serum electrolytes, phosphorus, and calcium prior to sodium phosphate preparation is advised, and in selected patients, postprocedural assessment and correction may be required.
Administration, Oral↗
Insulin and losartan reduce proteinuria and renal hypertrophy in the pregnant diabetic rat.
This study was designed to investigate the effect of hyperglycemia and angiotensin II (AngII) on renal hypertrophy and proteinuria in the pregnant diabetic rat. Secondary objectives were to evaluate changes in components of the renin-angiotensin axis and the effects of administration of losartan on pregnancy outcome. Fifty-three pregnant rats were allocated to 6 groups (1) nondiabetic controls (n = 12), (2) nondiabetic controls administered losartan (70-80 mg/kg/day; n = 10), (3) rats in which intravenous streptozotocin (STZ) was used to induce diabetes (55 mg/kg on day 10 of pregnancy; n = 10), (4) diabetic rats treated with losartan (n = 7), (5) diabetic rats treated with insulin (4 U/day; n = 7), and (6) diabetic rats treated with insulin and losartan (n = 7). Urinary protein excretion measured 4 days after STZ was 4 times greater in the rats with STZ-induced diabetes and significantly less in diabetic rats given losartan, insulin, or both. Postpartum kidney weight was greater in the rats with STZ-induced diabetes (2.04 +/- 0.21 g) than in the controls (1.37 +/- 0.14 g; P <.05) and reduced in the diabetic rats given losartan, insulin, or both (1.57 +/- 0.22, 1.73 +/- 0.13, and 1.51 +/- 0.14 g, respectively; P <.05). Plasma levels of angiotensin II in rats given losartan were more than 3.5 times greater than those in controls (749 +/- 436, 596 +/- 323, 567 +/- 349, and 159 +/- 28 pg/mL; P <.001). Postpartum activity of angiotensin-converting enzyme was increased in the untreated diabetic rats compared with that in control rats (162 +/- 12 vs 117 +/- 16 nmol/mL/min; P <.05). This increase was abolished by treatment with losartan or insulin. The number of newborns and mean weight of each newborn was similar in all groups. In summary, administration of losartan or insulin prevented, in part, kidney hypertrophy and protein excretion in the diabetic pregnant rat. Losartan did not affect the number or weight of newborns. Because angiotensin II receptor-blockers are contraindicated in pregnancy, good control of diabetes through the use of insulin should be advantageous.
Angiotensin II↗
Prevalence and characterization of uremic pruritus in patients undergoing hemodialysis: uremic pruritus is still a major problem for patients with end-stage renal disease.
BACKGROUND: Pruritus is a common disabling problem in patients with advanced end-stage renal disease. Few studies have evaluated the clinical characteristics of uremic itch. OBJECTIVES: The aim of this multicenter study was to provide a comprehensive description of the prevalence and clinical characteristics of pruritus affecting patients with end-stage renal disease who are undergoing hemodialysis. METHODS: A detailed questionnaire recently developed was used to evaluate pruritus in 219 patients undergoing hemodialysis treatment in 3 dialysis units. We examined the relationship of the quality of dialysis and various factors and medical parameters to itch. RESULTS: Pruritus was a common symptom in the study population. Approximately 66% of the patients had pruritus at some point, and 48% were affected by it at the time of the study. There was no correlation between the occurrence of pruritus and demographic or medical parameters (type of kidney disease, medical management, dialysis efficacy as expressed by Kt/V) of the patient. The data suggest that uremic pruritus tends to be prolonged, frequent, and intense, and it can impair the patient's quality of life including a negative effect on sleep and mood. Major factors found to exacerbate pruritus include rest, heat, dry skin, and sweat. Major factors found to reduce pruritus include activity, sleep, hot and cold shower, and cold. Treatment with angiotensin inhibitors seemed to be more common among those with uremia who had itch (P =.02) whereas furosemide was more commonly used among those who never itched (P =.002). CONCLUSION: This study provides a detailed description of uremic pruritus with new data on its characteristics including affective and sensory dimensions and associated symptoms.
Adult↗
Production of the novel mesangial autocrine growth factors GDNF and IL-10 is regulated by the immunomodulator AS101.
Mesangial cell (MC) proliferation is essential for the pathogenesis and progression of various glomerular diseases. This study shows that glial cell line-derived neurotrophic factor (GDNF) and IL-10 are mesangial autocrine growth factors that play a pivotal role in rat MC proliferation in vitro. Downstream targets of GDNF signaling and their role in MC hyperplasia are identified. The phosphatidylinositol 3-kinase (PI3K) pathway and its downstream target NF-kappaB were found to mediate GDNF-induced MC mitogenesis. This pathway also mediates GDNF-induced decrease in the cyclin-dependent kinase inhibitor p27(kip1) expression, resulting in the increased formation of cyclin D1/cdk4 and cyclin E/cdk2 complexes, followed by hyperphosphorylation of retinoblastoma, a key event for G1 to S phase progression. IL-10 appears to be a more potent MC growth factor that negatively regulates GDNF expression. Indeed, its inhibition by the nontoxic tellurium anti-IL-10 compound, ammonium trichloro(dioxoethylene-o,o') tellurate (AS101), extensively decreased MC clonogenicity despite GDNF upregulation. Identification of the mesangial GDNF and IL-10 pathways as critical mediators of mesangial cell proliferation may provide another target for therapeutic intervention in certain glomerular diseases. In vivo animal studies using AS101, currently undergoing phase II clinical trials on cancer patients, are warranted to determine its potential in the management of glomerular diseases associated with mesangial cell proliferation.
Adjuvants, Immunologic↗