Endothelial dysfunction and increased responses to renal nerve stimulation in rat kidneys during rhabdomyolysis-induced acute renal failure: role of hydroxyl radical

Rhabdomyolysis is an important cause of acute renal failure (ARF) and renal vasoconstriction is the main mechanism in the pathogenesis of ARF. Lipid peroxidation due to hydroxyl radical (.OH) formation and redox cycling of myoglobin also have a role. We investigated the disturbance in renal vascular reactivity to reveal the mechanisms leading to ARF. Female Wistar rats (n = 7) were injected with glycerol (10 mL/kg, 50% in saline) intramuscularly to induce rhabdomyolysis, and then the kidneys were isolated and perfused. We investigated acetylcholine (ACh)-induced endothelium-dependent and papaverine (PAP)-induced endothelium-independent vasodilation responses and renal nerve stimulation (RNS)-induced vasoconstrictions. These were also investigated both in rats which received either .OH scavenger, dimethylthiourea (DMTU: 500 mg/kg before glycerol injection and 125 mg/kg 8 h after glycerol injection, n = 7), or myoglobin redox cycling inhibitor, acetaminophen (ApAP: 100 mg/kg 2 h before glycerol injection and 100 mg/kg each 4 h, and 22 h after glycerol injection, n = 7). ACh-induced responses in glycerol group were decreased (p < 0.001), but PAP-induced vasodilation did not change. RNS-induced vasoconstriction in all kidneys was greater (p < 0.001) in glycerol group. DMTU restored both endothelium-dependent vasodilation and RNS-induced vasoconstriction. ApAP had no effect on vascular responses. Both DMTU and ApAP exerted a partial protective effect in renal histology without restoring serum creatinine and blood urea nitrogen (BUN) levels or creatinine clearance. This study showed that endothelial dysfunction and increased vasoconstriction developed during rhabdomyolysis. .OH plays an important role in the development of these vascular responses. These findings suggest that decreased endothelium-dependent vasodilation and augmented renal sympathetic tonus contribute to the development of renal vasoconstriction during rhabdomyolysis-induced ARF.     

胰岛素受体底物-1 G972R变异体与妊娠期糖尿病患者基线特性的关系

目的：妊娠期胰岛素受体底物-1（IRS-1）的表达和酪氨酸磷酸化减低。妊娠可能是一个检测与IRS-1多态性有关的任何异常的合适状态。本研究旨在探讨IRS-1G972R多态性在妊娠期糖尿病（GDM）患者中的发生率和对代谢的影响。研究设计：2例根据100g口服葡萄糖耐量试验诊断为GDM妇女的人体测量和代谢变量根据IRS-1多态性进行单变量协方差分析。结果：IRS-1G972R的患者在妊娠开始就出现肥胖及高空腹血胰岛素和血糖水平。两组间在妊娠期间体重增加、胰岛素和葡萄糖水平相似。     

Evaluation of pelvic contractility in ureteropelvic junction obstruction: an experimental study.

BACKGROUND/PURPOSE: Ureteropelvic junction (UPJ) obstruction causes adaptive and/or compensatory alterations in renal pelvic contractility. As these alterations directly affect the outcome after renal damage, definition of these alterations is of the utmost importance from a clinical point of view. Thus, an experimental study was designed to determine the alterations of renal pelvic contractility in response to partial and complete UPJ obstruction. METHODS: Fifteen adult female New Zealand white rabbits were randomly assigned into three groups (each containing 5 rabbits) according to the degree of unilateral UPJ obstruction. Group I: sham operation was performed and served as the control group; group II: partial UPJ obstruction was made; group III: complete UPJ obstruction was made. The animals in groups I and II were sacrificed after three weeks and the rabbits in group III were sacrificed after two weeks. Muscle strips from the renal pelvis were prepared. Spontaneous mechanical activity and contractile responses to phenylephrine (PE), serotonin (5-HT), and KCl were recorded isometrically and compared in all groups. RESULTS: Both the frequency and amplitude of spontaneous mechanical contractions were significantly (p < 0.05) increased in partial (group II) and complete UPJ obstruction (group III) groups. PE and 5-HT-induced tonic contractions, which were more prominent in the complete and partial obstruction groups when compared with the control group (p < 0.05). PE and 5-HT also increased the frequency of spontaneous contractions in both partial and complete obstruction groups. KCl induced long lasting tonic contractions in the control muscles. The duration of contraction to reach the maximum amplitude was shortened in the obstruction groups and the amplitudes of the contractions were significantly augmented when compared to control preparations. CONCLUSION: UPJ obstruction alters the contractile properties of renal pelvis smooth muscle. Increased frequency of spontaneous mechanical activity suggests that pacemaker cells of the renal pelvis change their activities in response to UPJ obstruction. Increase in tonic contraction amplitudes in response to PE and 5-HT suggests an increased sensitivity of smooth muscle cells to these agents. Potentiation of the contractile response to KCl suggests that adaptive changes take place at the level of excitation-contraction coupling in the smooth muscle of the renal pelvis following UPJ obstruction.     

Cryopreserved/thawed semen for in vitro fertilization: results from fertile donors and infertile patients

We evaluated the in vitro fertilization (IVF) outcome in 54 cycles using cryopreserved/thawed semen from fertile donors. Controls were other IVF patients matched by time frame, female age, stimulation protocol, number of pre-embryos transferred, and absence of a male factor using freshly ejaculated normal semen samples. In the study group and controls, respectively, post-thaw swim-up motility was 83.1% and 89.5%; fertilization rate of preovulatory oocytes (91.8%, 95.7%) and ongoing pregnancy rate (PR) per transfer (21.1%, 25.0%) were similar. The excellent fertilization rate with frozen/thawed semen was achieved through high-concentration insemination (0.5 x 10(6) motile sperm/mL). With use of frozen/thawed samples from infertile men (normal and subfertile samples), PR was similar but fertilization rate was lower. Cryopreserved semen is a valuable option for infertile couples in IVF therapy.     

Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor γ and the retinoid X receptor

Induction of terminal differentiation represents a promising therapeutic approach to certain human malignancies. The peroxisome proliferator-activated receptor γ (PPARγ) and the retinoid X receptor α (RXRα) form a heterodimeric complex that functions as a central regulator of adipocyte differentiation. Natural and synthetic ligands for both receptors have been identified. We demonstrate here that PPARγ is expressed at high levels in each of the major histologic types of human liposarcoma. Moreover, primary human liposarcoma cells can be induced to undergo terminal differentiation by treatment with the PPARγ ligand pioglitazone, suggesting that the differentiation block in these cells can be overcome by maximal activation of the PPAR pathway. We further demonstrate that RXR-specific ligands are also potent adipogenic agents in cells expressing the PPARγ/RXRα heterodimer, and that simultaneous treatment of liposarcoma cells with both PPARγ- and RXR-specific ligands results in an additive stimulation of differentiation. Liposarcoma cell differentiation is characterized by accumulation of intracellular lipid, induction of adipocyte-specific genes, and withdrawal from the cell cycle. These results suggest that PPARγ ligands such as thiazolidinediones and RXR-specific retinoids may be useful therapeutic agents for the treatment of liposarcoma.     

Panoramic radiographs: a tool for investigating skeletal pattern.

The objective of this study was to investigate the possibility of enhancing the clinical versatility of the panoramic radiograph, which is an indispensable tool for dental diagnosis. The material of this study consisted of lateral cephalograms and panoramic radiographs obtained from 30 patients. A correlation test was performed between the parametric measurements, and the predictability level of the cephalometric measurements from panoramic radiograms was determined by using regression equations. The equations showed that the Go-Gn/S-N, ANS-PNS/Go-Me (palatal plane/mandibular plane), and Co-Go/Go-Me parameters could be predicted from panoramic radiographs within statistically significant levels, and their predictability levels were 20.6%, 15.6%, and 11.2%, respectively. Statistically significant correlations and predictability levels were also determined for the cephalometric and corresponding panoramic parameters in which Frankfort horizontal plane was used. It can be concluded that even though panoramic radiographs provide information on the vertical dimensions of craniofacial structures, clinicians should be vigilant when predicting skeletal cephalometric parameters from panoramic radiographs, because of their lower predictability percentages.