Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity

Cisplatin is a chemotherapeutic agent, which is used in the treatment of various solid organ cancers, and its main dose limiting side effect of cisplatin is nephrotoxicity. The aim of this study is to investigate the role of pioglitazone and creatine on cisplatin nephrotoxicity in vitro. Real-time cell analyzer system (RTCA) was used for real-time and time-dependent analysis of the cellular response of HK-2 cells following incubation with cisplatin and combination with creatine or pioglitazone hydrochloride. First, half-maximal inhibitory concentrations (IC50) of cisplatin, creatine and pioglitazone were calculated by RTCA system. Afterwards creatine and pioglitazone was administered with serial dilutions under RTCA system. IC50 dose for cisplatin was 7.69?M?×?10^?5 at 24th hour and 3.93?M?×?10^?6 at 48th hour. IC50 dose for pioglitazone was 1.61?M?×?10^?3 at 24th hour and 2.85?M?×?10^?4 at 48th hour. Although cells were treated the dose of 40,225?mM creatine, IC50 dose could not been reached. Neither pioglitazone nor creatine had additional protective effect in any dose. Consequently, beneficial effect of creatine and pioglitazone on cisplatin-induced cell death could not be found. Further studies and clinical trials are needed to evaluate the effect of different doses of these drugs in cisplatin-induced nephrotoxicity.     

The impact of pretreatment with bolus dose of enteral glutamine on acute lung injury induced by oleic acid in rats

Purpose

Both parenteral and enteral glutamine have shown beneficial effects in sepsis and ischemia/reperfusion-induced acute lung injury (ALI). Oleic acid (OA) has been used to induce ALI in experimental studies. In this study, we investigated the effects of pretreatment of a bolus dose of enteral glutamine on ALI induced by OA in rats.

Methods

Twenty-eight adult female Sprague–Dawley rats weighing 240–300 g were divided into four groups, 7 in each. Group I and group II received normal saline for 30 days, group III and group IV received glutamine at a dose of 1 g/kg for 10 days by gavage, and in group II and group IV 100 mg/kg OA was administered i.v. Histopathological examination of the lung was performed with light and electron microscopy. Levels of protein carbonyl, malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase levels were measured in tissue samples. Levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and total tissue oxidant status and total tissue antioxidant status were measured in serum samples.

Results

Light microscopy showed that the total lung injury score of group IV was significantly lower than group II. Change in thickness of the fused basal lamina was not significantly different in groups II and IV under electron microscopy. TNF-α, IL-6, and IL-10 serum levels were higher in group II when compared to group I and significantly attenuated in group IV.

Conclusion

Pretreatment with a bolus dose of enteral glutamine minimized the extent of ALI induced by OA in rats.     

Eculizumab therapy in a patient with dense-deposit disease associated with partial lipodystropy

Background

Dense deposit disease (DDD) (also known as membranoproliferative glomerulonephritis type II) in childhood is a rare glomerulonephritis with frequent progression to end-stage renal disease (ESRD) and a high recurrence after kidney transplantation. The pathophysiologic basis of DDD is associated with the uncontrolled systemic activation of the alternative pathway (AP) of the complement cascade.

Case-diagnosis/treatment

A 14-year-old girl presented with edema and nephrotic range proteinuria. Blood tests showed hypoalbuminemia, nephrotic range proteinuria, normal renal function, and a low C3 level. Renal biopsy confirmed the diagnosis of crescentic DDD. Complement analysis revealed strong AP activation (low C3), positive C3 nephritic factor (C3NeF), and a decreased complement factor H (CFH) levels with CFH polymorphisms. Therapy with eculizumab was considered after the failure of corticosteroid and plasmapheresis to modulate the ongoing massive proteinuria and persistence of low serum C3 levels. There was a marked clinical and biochemical response following the administration of eculizumab.

Conclusions

Our case emphasizes the efficacy of eculizumab in the management of crescentic DDD in a patient with a normal renal function, in a short follow-up period. Considering previously reported cases, it appears that eculizumab represents a promising new approach which may prevent progression to ESRD in a subset of patients with DDD.     

Effect of different surface treatments on the shear and microtensile bond strength of resin-modified glass ionomer cement to dentin

Objective. The aim of this study was to evaluate the effect of different surface treatments on the microtensile bond strength (μTBS) and shear bond strength (SBS) of resin-modified glass ionomer cement (RMGIC) to dentin. Materials and methods. Fifty-two extracted human molars were flattened to obtain dentin surfaces. For SBS assessment 40 teeth were divided into four groups according to their surface treatments (acid etching, Er:YAG laser QSP mode, Er:YAG laser MSP mode and control-SiC) (n = 10). A plastic cylinder was placed over the differently treated dentin surfaces and RMGIC was placed into the rings and polymerized. Twelve teeth were used for the μTBS test. The treated dentin surfaces described above were restored with 4 mm high RMGIC and light cured; then, the specimens were sectioned into serial sticks (n = 15) and μTBS and SBS were tested for failure in a testing machine with a 1 mm/min crosshead speed. The data were analyzed by one-way ANOVA and Tukey HSD tests (α = 0.05). Results. Acid etching showed significantly higher SBS than the other groups (p < 0.05). Er:YAG QSP and MSP-treated groups showed higher SBS values than the control group, but the difference was not statistically significant (p > 0.05). Er:YAG MSP showed the highest μTBS value followed by acid etching, whereas the control group exhibited the lowest value (p < 0.05) and the differences between the control group and Er:YAG QSP were not significant (p > 0.05). Conclusions. The application of Er:YAG MSP mode and acid etching to dentin can be used for improving the bond strength of RMGIC.     

Hormone Replacement Therapy Shortens QT Dispersion in Healthy Postmenopausal Women

Background: The aim of the study was to investigate the effects of hormone replacement therapy (HRT) on myocardial repolarization characteristics in postmenopausal women without coronary artery disease. Methods: Fifty‐one consecutive healthy postmenopausal women (age 48 ±; 5) with negative exercise stress testing were prospectively enrolled into the study. Standard 12‐lead electrocardiograms were obtained to evaluate the effects of 6 months of HRT on QT intervals, corrected QT intervals (QTcmax and QTcmin), QT dispersion (QTd), and corrected QTd (QTcd). Hormone regimens were continuous 0.625 mg/day conjugated equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate (MPA) or 0.625 mg/day CEE alone depending on the hysterectomy status. Results: Although not statistically significant, CEE alone or in combination with MPA increased QTmax and QTmin values. However, the increase in QTmin was greater than the increase in QTmax, which resulted in statistically significant shortening of QTd (P = 0.007 in CEE and P < 0.001 in CEE + MPA groups). There was a significant prolongation of QTcmin values after 6 months in patients assigned to the CEE group (P = 0.001). The QTcd values were significantly shortened by HRT with both regimens (for CEE group 49 ±; 13 ms vs 38 ±; 13 ms, P = 0.01; for CEE + MPA group 49 ±; 14 ms vs 36 ±; 13, P < 0.001). Conclusion: HRT significantly decreased the QTd and QTcd in postmenopausal women without coronary artery disease, independent of the addition of MPA to the regimen. This improvement in myocardial repolarization may be one of the mechanisms of the favorable effects of HRT on cardiovascular system. However, the clinical implications of the shortening of QTd in postmenopausal women with HRT must be clarified. A.N.E. 2001; 6(3):193–197     

Cumulative exposure to high estradiol levels during the follicular phase of IVF cycles negatively affects implantation

Purpose: To investigate the effect of the cumulative exposure to estradiol (E₂) during the follicular phase on IVF outcome. Methods: Patients were stimulated with recombinant FSH after GnRH agonist suppression and had a day 3-embryo transfer. Estrogen exposure was determined as the area under the curve (AUC) for serum E₂ levels measured from the first day of stimulation through the day after hCG administration. Results: E₂ AUC thresholds for 10th and 90th percentiles were 4704 pg/ml and 16338 pg/ml, respectively. The pregnancy and implantation rates were highest in the 10th–90th percentile group, and were statistically higher in this group than in the >90th percentile group (54.6% vs. 33.3% and 24.8% and 12.9%, respectively, for pregnancy and implantation rates, P < 0.05). Recovered mature oocytes, fertilization, and number and mean score of transferred embryos were similar. Conclusions: High cumulative E₂ exposure during the follicular phase of IVF cycles has detrimental effects on implantation.