mTORC2 critically regulates renal potassium handling

The mTOR pathway orchestrates cellular homeostasis. The rapamycin-sensitive mTOR complex (mTORC1) in the kidney has been widely studied; however, mTORC2 function in renal tubules is poorly characterized. Here, we generated mice lacking mTORC2 in the distal tubule (Rictorfl/fl Ksp-Cre mice), which were viable and had no obvious phenotype, except for a 2.5-fold increase in plasma aldosterone. Challenged with a low-Na+ diet, these mice adequately reduced Na+ excretion; however, Rictorfl/fl Ksp-Cre mice rapidly developed hyperkalemia on a high-K+ diet, despite a 10-fold increase in serum aldosterone levels, implying that mTORC2 regulates kaliuresis. Phosphorylation of serum- and glucocorticoid-inducible kinase 1 (SGK1) and PKC-α was absent in Rictorfl/fl Ksp-Cre mice, indicating a functional block in K+ secretion activation via ROMK channels. Indeed, patch-clamp experiments on split-open tubular segments from the transition zone of the late connecting tubule and early cortical collecting duct demonstrated that Ba2+-sensitive apical K+ currents were barely detectable in the majority of Rictorfl/fl Ksp-Cre mice. Conversely, epithelial sodium channel (ENaC) activity was largely preserved, suggesting that the reduced ability to maintain K+ homeostasis is the result of impaired apical K+ conductance and not a reduced electrical driving force for K+ secretion. Thus, these data unravel a vital and nonredundant role of mTORC2 for distal tubular K+ handling

MTOR regulates endocytosis and nutrient transport in proximal tubular cells

Renal proximal tubular cells constantly recycle nutrients to ensure minimal loss of vital substrates into the urine. Although most of the transport mechanisms have been discovered at the molecular level, little is known about the factors regulating these processes. Here, we show that mTORC1 and mTORC2 specifically and synergistically regulate PTC endocytosis and transport processes. Using a conditional mouse genetic approach to disable nonredundant subunits of mTORC1, mTORC2, or both, we showed that mice lacking mTORC1 or mTORC1/mTORC2 but not mTORC2 alone develop a Fanconi-like syndrome of glucosuria, phosphaturia, aminoaciduria, low molecular weight proteinuria, and albuminuria. Interestingly, proteomics and phosphoproteomics of freshly isolated kidney cortex identified either reduced expression or loss of phosphorylation at critical residues of different classes of specific transport proteins. Functionally, this resulted in reduced nutrient transport and a profound perturbation of the endocytic machinery, despite preserved absolute expression of the main scavenger receptors, MEGALIN and CUBILIN. Our findings highlight a novel mTOR–dependent regulatory network for nutrient transport in renal proximal tubular cells

Abnormal Elevated CA 19-9 in the Dermoid Cyst: A Sign of the Ovarian Torsion?

Dermoid cyst is the most common germ cell tumor of the ovary containing various tissue elements. Ovarian torsion is a common complication of which ultrasonographic diagnosis is confusing. We report here a 14-year-old adolescent with painless torsion of the ovary including dermoid cyst and with abnormal elevated CA 19-9 serum levels. Elevated CA 19-9 level may be related to ovarian torsion and may predict the extent of tissue necrosis

A Rare Complication: Blue Urine Developed After Laparoscopic Chromopertubation

Methylene blue is a dye that is widely used in medicine. The underlyin reason this widespread use is that it is easily accessible, inexpensive and safe. Although rarely seen, some complications may develop during use of methylene blue. It is important that clinicians should be aware of these unwanted conditions, recognize these complications at an earlier stage, and take suitable measures

Wpływ rodności na kształt fali przepływu Dopplera w pierwszym trymestrze pojedynczej ciąży niskiego ryzyka

Objectives: The aim of the study was to evaluate the effect of parity on uteroplacental blood flow during the first trimester in low-risk singleton pregnancies. Materials and methods: Uterine artery Doppler examinations were performed in 190 singleton pregnancies between 11-14 gestational weeks. Twenty-five pregnancies were excluded from the study due to history of preeclampsia, diabetes mellitus or inherited thrombophilia. A total of 165 low-risk singleton pregnancies were included in the study. Mean uterine artery pulsatility index (PI) was recorded and compared between nulliparous and multiparous women. The relation between maternal age, gestational week, maternal weight, parity, biochemical markers and abnormal uterine artery Doppler flows was evaluated. T-test and logistic regression analyses were used for the statistical analysis. Results: A total of 165 singleton pregnancies without any risk factors for uteroplacental insufficiency were included in the study. Of them, 58 (36.7%) were nulliparous and 107 (63.3%) were parous. Correlation analysis revealed that the uterine artery pulsatility indices during the first trimester were not affected by maternal age and parity. Conclusions: Mean uterine artery pulsatility indices are not different in nulliparous and multiparous low risk pregnancies at 11-14 weeks of gestation.Cel: Celem badania była ocena wpływu rodności na przepływ maciczno-łożyskowy w pierwszym trymestrze pojedynczej ciąży niskiego ryzyka. Materiał i metoda: Przepływ w tętnicy macicznej zbadano w 190 pojedynczych ciążach w 11-14 tygodniu. Z analizy wyłączono 25 ciąż z powodu dodatniego wywiadu w kierunku stanu przedrzucawkowego, cukrzycy lub wrodzonej trombofilii. Ostatecznie do badania włączono 165 pojedynczych ciąż niskiego ryzyka. Zmierzono średni indeks pulsacji w tętnicy macicznej (PI), który porównano pomiędzy nieródkami i wieloródkami. Oceniono również związek pomiędzy wiekiem matki, wiekiem ciążowym, masą matki, liczbą porodów, markerami biochemicznymi a nieprawidłowym przepływem w tętnicach macicznych. T-test i regresji logistycznej zostały wykorzystane do analizy statystycznej. Wyniki: Do badania włączono 165 pojedynczych ciąż bez czynników ryzyka niewydolności maciczno-łożyskowej. Z tej grupy, 58 (36,7%) kobiet było nieródkami a 107 (63,3%) wieloródkami. Analiza statystyczna wykazała brak związku pomiędzy indeksem pulsacji w pierwszym trymestrze ciąży a wiekiem matki i rodnością. Wnioski: Średni indeks pulsacji w tętnicy macicznej nie różni się pomiędzy nieródkami a wieloródkami w ciąży niskiego ryzyka w 11-14 tygodniu

Instability tests for air-jet textured yarns

The air-jet texturing process is briefly introduced and its advantages over other texturing processes are summarized. Characteristics of air-jet textured yarns are stated with special reference to the stability of the yarns. Test methods used in industry and research to determine the "stability" or "instability" of air-jet textured yarns are critically reviewed. These methods involve different basic principles and therefore inevitably give different results. There is no consensus on a standard method. Effects of various test parameters, such as specimen length, test duration, and the alternatives of using a single yarn, a hank, or a skein as a test specimen are investigated. An improved test method is suggested as a standard instability test, and various existing methods are compared with it. Results of all the methods show similar trends for varying values of air pressure. Other yarn characteristics such as linear density, breaking elongation, and tenacity are also determined, and their indications of yarn quality are compared with the indications of instability tests. Stability test results alone provide misleading information regarding air-jet textured yarn quality

Impact of Phosphorus Restriction and Vitamin D-Substitution on Secondary Hyperparathyroidism in a Proteinuric Mouse Model

Background/Aims: Since the discovery of FGF23, secondary hyperparathyroidism (SHPT) in renal disease has been considered to result primarily from phosphorus retention rather than vitamin D deficiency. However, the impact of phosphorus restriction and vitamin D supplementation on SHPT is still ill defined. Methods: We investigated the development of SHPT in a doxorubicin-induced proteinuric mouse model and tested different treatment strategies including a low phosphorus diet and substitution with native or active vitamin D in 129 S1/SvImJ wild-type mice. Results: Development of SHPT at day 30 was strongly related to the magnitude of induced proteinuria. In mice with a proteinuria 100 mg/mg creatinine) developed marked SHPT (PTH increase 10.1-fold) accompanied by massive increase in FGF23 (27.0-fold increase), hyperphosphatemia (1.8-fold increase), renal failure (7.3-fold urea increase) and depletion of both 25-OH vitamin D and 1,25-OH vitamin D. Substitution with native or active vitamin D was unable to suppress SHPT, whereas a low-phosphorus diet (Pi content 0.013%) completely suppressed SHPT in mice with both mild and heavy proteinuria. Conclusions: The development of SHPT resulted from phosphate retention in this proteinuric model and could completely be suppressed with a low-phosphorus diet

Güçlendirilmiş dental seramiklerin vickers sertlikleri ve yük altında kırılma davranışları

Objective: The objectives of this study were to determine the Vicker`s hardness of reinforced dental ceramics and determine the modes of fractures under load. Methods: Four ceramic core groups (n=7/group) from leucite (Evopress,Wegold&De), low leucite (Finesse, Ceramco), glass-infiltrated (Inceram Alumina,Vita) and lithium disilicate materials (E.max press, Ivoclar) were fabricated according to each manufacturers’ instructions (thickness: 3 mm, diameter: 5 mm). Their individual veneering ceramics were vibrated, condensed in a stainless steel mold (diameter: 5 mm, height: 5 mm) and fired on the core materials. The specimens were stored in distilled water at 37°C for 24 hours prior to indentation tests and embedded in polyesther moulds. Vickers hardness values (DUH±SD) were measured (cross-head speed:7,2 gf/s, load:200 gf) and statistically analysed (ANOVA). A load of 400 N was applied on the surfaces of specimens with a diamond indentor (diameter:1 mm) at the macro hardness test machine for crack formation. The crack modes for each group were observed under the scanning electrone microscope. Results: The Vickers hardness values for low leucite veneering ceramic were significantly (P<0.05) higher (236±17), followed by the leucite (129±51), glass-infiltrated (117±38), and lithium disilicate (85±34) veneering ceramic materials in decreasing order. Mainly radial or cone cracks were observed after the application of load. Conclusion: The increase in the hardness of the material led to more crack formation and resulted in longer cracks. No crack formation extending to the core materials were observed in neither of the ceramic groups under these experimental conditions. ÖZET Amaç: Bu çalışmanın amacı güçlendirilmiş dental seramiklerin Vickers sertlik değerlerinin ve yük altındaki kırılma şekillerinin belirlenmesidir. Gereç ve Yöntem: Lösit (Evopress,Wegold&De), düşük lösit (Finesse, Ceramco), cam infiltrasyonlu aluminöz seramik (Inceram Alumina,Vita) ve lityum disilikat (E.max press, Ivoclar) bazlı dört farklı seramik alt yap_ materyali (n=7/grup) her bir üretici firmanın önerileri doğrultusunda hazırlandı (3 mm kalınlıkta; 5 mm çapta). Her bir alt yapı seramiğine özgü kaplama seramikleri; paslanmaz çelik bir metal kalıpta (5mm çap 5mm yükseklikte) vibrasyonla kondanse edildi ve alt yapı seramiklerinin üzerine pişirildi. Örnekler batırma testlerinden önce 37°C’ de 24 saat distile suda bekletildikten sonra polyester kalıplara gömüldü. Vickers sertlik değerleri (DUH±SD) ölçüldü (çene hızı:7,2 gf/s, yük:200 gf) ve veriler istatistiksel olarak analiz edildi (ANOVA). Çatlak oluşumu için örneklerin üst yüzeylerine makro sertlik test cihazında batıcı elmas uç ile (1 mm çaplı) 400 N yük uygulandı. Alınan taramalı elektron mikroskop görüntüleri ile her bir gruba ilişkin çatlak şekilleri gözlemlendi. Bulgular: Gruplar arasında ortalama Vickers sertlik değerleri düşük lösit grubu için anlamlı olarak (P<0.05) en yüksek bulunur iken (236±17), bunu lösit (129±51), cam infiltrasyonlu aluminöz seramik (117±38), ve lityum disilikat (85±34) kaplama seramik materyalleri azalan sırayla izledi. Yük uygulaması sonrasında genellikle ışınsal ya da koni şekilli çatlakların oluştuğu gözlendi. Sonuç: Seramik materyalin sertliğinin artması daha fazla ve daha uzun çatlak oluşumuna yol açtı. Bu çalışmadaki deneysel koşullar altında kaplama seramik gruplarının hiçbirinde alt yapı seramiklerine ulaşan çatlak oluşumu gözlenmedi

Lack of the serum and glucocorticoid-inducible kinase SGK1 attenuates the volume retention after treatment with the PPARγ agonist pioglitazone

PPARgamma-agonists enhance insulin sensitivity and improve glucose utilization in diabetic patients. Adverse effects of PPARgamma-agonists include volume retention and edema formation. Recent observations pointed to the ability of PPARgamma agonists to enhance transcription of the serum and glucocorticoid-inducible kinase SGK1, a kinase that is genomically upregulated by mineralocorticoids and stimulates various renal channels and transporters including the renal epithelial Na+ channel ENaC. SGK1 has been proposed to mediate the volume retention after treatment with PPARgamma agonists. To test this hypothesis, food containing the PPARgamma agonist pioglitazone (0.02%, i.e., approximately 25 mg/kg bw/day) was administered to gene-targeted mice lacking SGK1 (sgk1-/-, n=12) and their wild-type littermates (sgk1+/+), n=12). According to in situ hybridization, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence, treatment with pioglitazone significantly increased renal SGK1 mRNA and protein expression in sgk1+/+ mice. The treatment increased body weight significantly in both, sgk1+/+ mice (+2.2+/-0.3 g) and sgk-/- mice (+1.3+/-0.2 g), and decreased hematocrit significantly in sgk1+/+ mice (-6.5+/-1.0%) and sgk1-/- mice (-3.1+/-0.6%). Both effects were significantly (p<0.05) more pronounced in sgk1+/+ mice. According to Evans Blue distribution, pioglitazone increased plasma volume only in sgk1+/+ mice (from 50.9+/-3.9 to 63.7+/-2.5 microl/g bw) but not in sgk-/- mice (from 46.8+/-3.8 to 48.3+/-5.2 microl/g bw). Pioglitazone decreased aldosterone plasma levels and blood pressure and increased leptin plasma levels in both genotypes. We conclude that SGK1 contributes to but does not fully account for the volume retention during treatment with the PPARgamma agonist pioglitazone