Protective Actions of Cilnidipine: Dual L/N-Type Calcium Channel Blocker Against Hypertensive Renal Injury in Rats

Background: Cilnidipine belongs to fourth generation dihydropyridine calcium channel blocker (CCB). It is a dual L & N-type CCB. L- type calcium channels are present on the vascular smooth muscle and N-type calcium channels are present on the presynaptic nerve terminals. Cilnidipine has a vasodilating effect, its action is slow and long lasting. Aim and objectives: Aim of present study was to demonstrate the beneficial effects of cilnidipine on the hypertensive renal injury rats. And our objectives is to assess renal injury parameters (Proteinuria, Creatinine clearance, Renal fibrosis/glomerulosclerosis) in response to chronic NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) treatment in the presence or absence of cilnidipine treatment. Material and methods: Male albino Wister rats were procured from institutional animal house, divided into 4 groups (n=6 in each group). Group1 treated with vehicle (control), group2 treated with cilnidipine, group3 treated with L-NAME, group4 treated with L-NAME & cilnidipine. 24 hour urinary protein and creatinine clearance were measured. Serum urea and creatinine levels are also measured. Urinary and serum Angiotensin II levels were measured. Histopathological examination of kidneys was performed. Results: Our results demonstrate that treatment with cilnidipine (group4) there is reduction in 24hr urinary protein, improvement in creatinine clearance. We observed there was renal glomerulosclerosis and tubular degeneration of kidney tubules in group3 rats and reduction of renal injury in group4 rats. We also found reduced urinary and serum Angiotensin II level in cilnidipine treated (group 4) rats. Conclusion: These findings indicated that cilnidipine act as renoprotective agent and reduces glomerular damage in L-NAME induced hypertensive rats.

Real-Life Cause-Effect Relations Between Urinary IL-6 Levels and Specific and Nonspecific Symptoms in a Patient With Mild SLE Disease Activity

BackgroundLittle is known about the real-time cause-effect relations between IL-6 concentrations and SLE symptoms.MethodsA 52-year-old woman with mild SLE activity collected her entire urine for the determination of IL-6/creatinine and protein/creatinine levels (ELISA, HPLC) for a period of 56 days in 12 h intervals (total: 112 measurements). Additionally, she answered questionnaires (VAS) on oral ulceration, facial rash, joint pain, fatigue and tiredness and measured her temperature orally twice a day. Time-series analyses consisted of ARIMA modeling and cross-correlational analyses (one lag = 12 h, significance level = p < 0.05).ResultsStatistical analyses showed that increased urinary IL-6 concentrations preceded increased urinary protein levels by 36–48 h (lag3: r=+.225; p=.017) and that, in the opposite direction of effect, increased urinary protein preceded urinary IL-6 decreases by 12–24 h (lag1: r=–.322; p<.001). Moreover, urinary IL-6 increases co-occurred with increased oral ulceration (lag0: r=+.186; p=.049); after 48–60 h, however, IL-6 increases showed a strong tendency to precede oral ulceration decreases (lag4: r=–.170; p=.072). Increases in facial rash preceded decreases in urinary IL-6 after 84–96 h (lag7: r=–.215; p=.023). As to fatigue, increases in urinary IL-6 co-occurred with decreased fatigue (lag0: r=–.193; p=.042); after 84–96 h, however, IL-6 increases preceded fatigue increases (+lag7: r=+.189; p=.046). Finally, joint pain, tiredness and body temperature did not significantly correlate with urinary IL-6 concentrations in either direction of effect.ConclusionsThe results of this evaluation point to real-life feedback mechanisms between immune activity and SLE symptoms. Comparison with a previous evaluation of this patient suggests a counterregulatory mechanism between Th1 activity and IL-6. These findings are preliminary and require replication to draw firm conclusions about the real-time relation between IL-6 and SLE disease activity.

Diagnostic utility of protein excretion in 24-hour urine and the protein to creatinine ratio for adverse perinatal outcomes and time of delivery

Objective Our study aimed to evaluate the perinatal and neonatal outcomes of hypertensive pregnant women with or without proteinuria. We compared the predictivity of spot urinary protein to creatinine (P/C) ratio and 24-hour protein excretions on outcomes. Methods We retrospectively enrolled 230 pregnant women with a new diagnosis of hypertension between 20 and 37 weeks of gestation. We divided the patients into two groups according to the protein level determined by 24-hour urine collection and P/C ratio. The presence and level of proteinuria, its relationship with the P/C ratio, and the relationship between these findings and perinatal outcomes were evaluated. Results Gestational age at delivery weeks and latency period (duration between diagnosis of hypertension and delivery) were significantly earlier in pregnant women with ≥300 mg/24-h and P/C ratio ≥0.3. Adverse neonatal outcomes were significant in patients with proteinuria ≥300 mg/24-hour and P/C ratio ≥0.3. Urinary protein levels in 24-hour urine were significantly higher in pregnant women with P/C ratio ≥0.3 and a significantly positive correlation was found between 24-h proteinuria and P/C (r=0.382, p<0.001). Conclusion Our study demonstrated that a protein loss of ≥300 mg in 24-h and a P/C ratio in spot urine ≥0.3 in hypertensive pregnant women is associated with adverse perinatal outcomes. Furthermore, we have identified that proteinuria ≥300 mg/day and spot urine P/C ratio ≥0.3 in hypertensive pregnant women make them prone to early delivery risk.

Pheromones that correlate with reproductive success in competitive conditions

The major urinary proteins (MUPs) of house mice (Mus musculus) bind and stabilize the release of pheromones and other volatile organic compounds (VOCs) from urinary scent marks, which mediate chemical communication. Social status influences MUP and VOC excretion, and the urinary scent of dominant males is attractive to females. Urinary pheromones influence the sexual behavior and physiology of conspecifics, and yet it is not known whether they also affect reproductive success. We monitored the excretion of urinary protein and VOCs of wild-derived house mice living in large seminatural enclosures to compare the sexes and to test how these compounds correlate with reproductive success. Among males, urinary protein concentration and VOC expression correlated with reproductive success and social status. Territorial dominance also correlated with reproductive success in both sexes; but among females, no urinary compounds were found to correlate with social status or reproductive success. We found several differences in the urinary protein and volatile pheromones of mice in standard cages versus seminatural enclosures, which raises caveats for conventional laboratory studies. These findings provide novel evidence for chemical signals that correlate with male reproductive success of house mice living in competitive conditions.

Comparison of Allogenic and Autogenic Implantations of Dedifferentiated Fat Cells On Monoclonal Antibody 1-22-3-Induced Glomerulonephritis in Rats

Background We established an adipogenic progenitor cell line derived from mature adipocytes and named these cells dedifferentiated fat (DFAT) cells, which have been shown to have characteristics very similar to those of mesenchymal stem cells (MSCs). The potential application of DFAT cells to support cell-based therapies for regenerative and immunosuppressive therapies has been suggested. The present study was designed to address beneficial ways that DFAT implantation can be used clinically as immunosuppressive therapy to treat immunological glomerulonephritis. Methods We evaluated distribution of DFAT cells after intravenous injection through the tail vein in Wistar rats. We examined effects of allogenic implantation of DFAT cells on BrdU incorporation into kidney from rats with monoclonal antibody (mAb) 1-22-3-induced glomerulonephritis. We compared effects of allogenic and autogenic implantations of DFAT cells on excretion of urinary protein, renal function, and glomerular and nephrotubular injuries in these rats, and serum levels of tumor necrosis factor-stimulated gene-6 (TSG-6), and expression of TSG-6 mRNA in kidney. Results The allogenic implantations of DFAT cells trapped in lung improved excretion of urinary protein and renal function, and significantly suppressed glomerular and nephrotubular injuries in the rats with mAb1-22-3-induced glomerulonephritis compared with the autogenic implantations. The allogenic implantation of DFAT cells increased serum levels of TSG-6 especially in mAb 1-22-3-induced glomerulonephritis and significantly increased the expression of TSG-6 mRNA in kidney compared to the autogenic implantation. Conclusion These findings suggest that allogenic implantation of DFAT cells could be clinically useful immunosuppressive therapy for immunological glomerulonephritis.

The preventive function of low-dose aspirin in mice with preeclampsia induced by PPAR-γ antagonist

BackgroundIn the present study, PPAR-γ antagonist was used to induce preeclampsia model in mice to explore the intervention effect and mechanism of aspirin on preeclampsia model mice.MethodsPregnant mice were injected intraperitoneally with PPAR-γ antagonist (2 mg/kg/d) at 8.5-12.5 days of pregnancy to establish PE mouse models. Two doses of LDA (10 mg/kg/d and 20 mg/kg/d) were given to the PE mouse models for intervention.The blood pressure, 24-hour proteinuria, urine protein/creatinine ratio, interleukin (IL)1-β and endoglin level in peripheral blood, placental PPAR-γ mRNA expression in placenta, the placenta weight and pathology of placenta and kidneys of mice from different groups were detected.ResultsLDA effectively decreased the blood pressure increase caused by PPAR-γ antagonist in mice, and the increase degree of urinary protein and urinary protein creatinine ratio was notably relieved.LDA also inhibited the overexpression of Endoglin and IL-β induced by PPAR-γ antagonist.In addition, LDA evidently increased the placental weight of preeclampsia mice.The placenta and kidney injury were obviously less serious.LDA alleviated the expression inhibition of PPAR-γ mRNA.The remission effect of 20mgLDA was significantly better than that of 10mg.Conclusions(1) LDA has a preventive effect in PE mice induced by PPAR-γ antagonist. (2) The preventive effect of LDA is dose-dependent in PE mouse models induced by PPAR-γ antagonist.