Asymmetric dimethylarginine (ADMA) treatment induces apoptosis in cultured rat mesangial cells via endoplasmic reticulum stress activation.

Asymmetric dimethylarginine (ADMA), a high risk factor for endothelial dysfunction and cardiovascular disease (CVD), has been reported to promote cellular dysfunction via endoplasmic reticulum (ER) stress activation in various cells. Additionally, increased serum ADMA levels have been observed in incipient kidney diseases. Previously, we reported that activated ER stress is associated with mesangial cell apoptosis, observed mainly in overt nephropathy or chronic kidney disease (CKD). However, the effect of ADMA on mesangial cell apoptosis is unknown. Thus, we investigated the effects of ADMA on mesangial cell apoptosis and ER stress signaling. ADMA treatment increased caspase-3 activity and activated three branches of ER stress signaling (PERK, IRE1, and ATF6) that induce mesangial cell apoptosis. Pharmacological inhibitors of ER stress (inhibitors of PERK, IRE1, and S1P) attenuated ADMA-induced cleavage of caspase-3 and induced a decrease in the mitochondrial membrane potential. Furthermore, these inhibitors diminished the number of apoptotic cells induced by ADMA treatment. Taken together, our results indicated that ADMA treatment induces mesangial cell apoptosis via ER stress signaling. These results suggest that ADMA-induced mesangial cell apoptosis could contribute to the progression of overt nephropathy and CKD.

Effects of Disinfectants on Larval Development of Ascaris suum Eggs.

The objective of this study was to evaluate the effects of several different commercial disinfectants on the embryogenic development of Ascaris suum eggs. A 1-ml aliquot of each disinfectant was mixed with approximately 40,000 decorticated or intact A. suum eggs in sterile tubes. After each treatment time (at 0.5, 1, 5, 10, 30, and 60 min), disinfectants were washed away, and egg suspensions were incubated at 25˚C in distilled water for development of larvae inside. At 3 weeks of incubation after exposure, ethanol, methanol, and chlorohexidin treatments did not affect the larval development of A. suum eggs, regardless of their concentration and treatment time. Among disinfectants tested in this study, 3% cresol, 0.2% sodium hypochlorite and 0.02% sodium hypochlorite delayed but not inactivated the embryonation of decorticated eggs at 3 weeks of incubation, because at 6 weeks of incubation, undeveloped eggs completed embryonation regardless of exposure time, except for 10% povidone iodine. When the albumin layer of A. suum eggs remained intact, however, even the 10% povidone iodine solution took at least 5 min to reasonably inactivate most eggs, but never completely kill them with even 60 min of exposure. This study demonstrated that the treatment of A. suum eggs with many commercially available disinfectants does not affect the embryonation. Although some disinfectants may delay or stop the embryonation of A. suum eggs, they can hardly kill them completely.

PRMT1 and PRMT4 Regulate Oxidative Stress-Induced Retinal Pigment Epithelial Cell Damage in SIRT1-Dependent and SIRT1-Independent Manners.

Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is involved in the progression of diabetic retinopathy. Arginine methylation catalyzed by protein arginine methyltransferases (PRMTs) has emerged as an important histone modification involved in diverse diseases. Sirtuin (SIRT1) is a protein deacetylase implicated in the onset of metabolic diseases. Therefore, we examined the roles of type I PRMTs and their relationship with SIRT1 in human RPE cells under H2O2-induced oxidative stress. H2O2 treatment increased PRMT1 and PRMT4 expression but decreased SIRT1 expression. Similar to H2O2 treatment, PRMT1 or PRMT4 overexpression increased RPE cell damage. Moreover, the H2O2-induced RPE cell damage was attenuated by PRMT1 or PRMT4 knockdown and SIRT1 overexpression. In this study, we revealed that SIRT1 expression was regulated by PRMT1 but not by PRMT4. Finally, we found that PRMT1 and PRMT4 expression is increased in the RPE layer of streptozotocin-treated rats. Taken together, we demonstrated that oxidative stress induces apoptosis both via PRMT1 in a SIRT1-dependent manner and via PRMT4 in a SIRT1-independent manner. The inhibition of the expression of type I PRMTs, especially PRMT1 and PRMT4, and increased SIRT1 could be therapeutic approaches for diabetic retinopathy.

Ultrasonographic evaluation of renal dimension and resistive index in clinically healthy Korean domestic short-hair cats.

Renal length, height, width, resistive index (RI), size of cortex, and medulla were determined by renal ultrasonography in 50 healthy Korean domestic short-hair cats. In the sagittal plane, the renal length was 3.83 +/- 0.51 cm (mean +/- SD) in the left kidney and 3.96 +/- 0.48 cm in the right kidney, whereas the renal height was 2.42 plusmn; 0.27 cm in the left kidney and 2.36 plusmn; 0.28 cm in the right kidney. In the transverse plane, the renal height was 2.42 +/- 0.28 cm in the left kidney and 2.38 +/- 0.27 cm in the right kidney, whereas the renal width was: 2.65 +/- 0.35 cm in the left kidney and 2.63 +/- 0.31 cm in the right kidney. In the dorsal plane, the renal length was 3.84 +/- 0.53 cm in the left kidney and 3.97 +/- 0.54 cm in the right kidney, whereas the renal width was 2.65 +/- 0.34 cm in the left kidney and 2.66 +/- 0.33 cm in the right kidney. There were no significant differences (p > 0.05) among the same structure sizes measured in different planes. In the sagittal plane, the size of the renal cortex was 0.47 +/-; 0.08 cm in the left kidney and 0.47 +/- 0.08 cm in the right kidney, whereas of the size of the renal medulla was 0.55 +/- 0.30 cm in the left kidney and 0.50 +/- 0.07 cm in the right kidney. RI evaluated by pulsed wave Doppler sonography was 0.52 +/- 0.05 in the left kidney and 0.55 +/- 0.05 in the right kidney. The actual renal dimensions determined by gross examination were not statistically different from those determined by ultrasonography. Furthermore the renal dimensions and RI were statistically correlated to the body weight of cats.

The micronucleus frequency in cytokinesis-blocked lymphocytes of cattle in the vicinity of a nuclear power plant.

Cytogenetic and hematological analyses were performed on the peripheral blood lymphocytes (PBLs) obtained from Korean native cattle bred in the vicinity of three nuclear power plants (Wolsong, Uljin and Yeonggwang) and in a control area. The micronucleus (MN) rates for the cattle from the Wolsong, Uljin and Yeonggwang nuclear power plants and for the control area were 9.87 +/- 2.64, 8.90 +/- 3.84, 9.20 +/- 3.68 and 9.60 +/- 3.91 per 1,000 cytokinesis-blocked lymphocytes, respectively. The apparent difference is not statistically significant. The MN frequencies of PBLs from cattle bred in the four areas are within the background variation for this study. The MN frequencies and hematological values were similar regardless of whether the cattle were bred near a nuclear power plant or in the control area.

Segmental aplasia of uterine body in an adult mixed breed dog.

Segmental aplasia of the uterine body was diagnosed in a 5-year-old, mixed breed bitch. Abdominal radiography and transabdominal ultrasonography revealed marked dilation of fluid-filled uterine horns with no evidence of a uterine body. Sex hormone assays did not detect the presence of estradiol-17 beta; however, progesterone (2 ng/ml) was found in the serum, indicating anestrus. On gross examination of the reproductive tract, the uterine body was absent, apparently never formed. In its place, a cord-like piece of tissue was identified as an aplastic/dysplastic remnant, connecting the cervix and right uterine horn. The tip of the cord-like piece branched into 5 string-like pieces of tissue, 1 of which was connected to the region dividing the left and right uterine horns. Both the uterine horns were dilated markedly revealing hydrometra. Histologically, uterine body remnant tissues from the endometrium, myometrium, and perimetrium were detected in proximal and distal parts of the uterine body. The string-like piece of tissue connecting the uterine body remnant and the uterine horn consisted of a round cluster of smooth muscle cells surrounding a central core of adipose tissue with blood vessels. It was concluded that the hydrometra observed in both uterine horns was induced by an obstruction resulting from segmental aplasia in the uterine body. This is the first known report of segmental aplasia in the uterine body of a bitch.

Measurement of micronuclei by cytokinesis-block method in human, cattle, goat, pig, rabbit, chicken and fish peripheral blood lymphocytes irradiated in vitro with gamma radiation.

The frequencies of gamma-ray-induced micronuclei (MN) in cytokinesis-blocked (CB) lymphocytes at several doses were measured in three donors of seven species (human, cattle, goat, pig, rabbit, chicken, fish). Measurements performed after irradiation showed a dose-related increases in MN frequency in each of the donors of human, cattle, goat, pig and rabbit. The relative sensitivity of cattle, goat, pig and rabbit in peripheral blood lymphocytes (PBLs) compared with human PBLs was estimated by best fitting linear-quadratic model based on the radiation-induced MN data over the range from 0 cGy to 400 cGy. In the case of MN frequency with 0.2, the relative sensitivities of cattle, goat, pig and rabbit PBLs were 0.86, 0.98, 0.41 and 0.39, respectively. These data indicate that the induction of MN in CB cells following irradiation is similar in human, cattle and goat PBLs, while PBLs from pig and rabbit were much less sensitive to the MN induction effects of gamma-radiation than those from human. The micronucleus counts failed to show any evidence of radiation damage in the cells from chicken and fish. Measurements performed after irradiation showed a dose-related decrease in the formation of binucleated cells. We concluded that the use of CB cell from fish and chicken for detecting the results of radiation exposure was highly questionable. Our in vitro radiobiological study confirmed that the cytogenetic response obtained in blood from selected breeds of mammalian species can be utilized for application in environmental studies.

The effect of herbal medicine on nerve growth factor in estradiol valerate-induced polycystic ovaries in rats.

A type of polycystic ovary resembling some aspects of human polycystic ovarian syndrome (PCOS) can be induced in the rat with a single injection of long-acting estradiol valerate. Among several theories behind the development of polycystic ovaries (PCO), the involvement of the sympathetic nervous system draws much attention, and herbal medicine is known to relieve the abnormal symptoms of PCO. Two herbal formulas, Changbudodam-Tang (cang fu dao tan tang) and Yongdamsagan-Tang (long dan xie gan tang), were used in the present study. The administration of herbal medicine was done every other day for 60 days. The morphological changes of ovaries from herbal medicine treatment were compared to those from an oil-treated control group and an estradiol valerate-injected group. This study also examined the possible hypothesis of neurogenic participation in terms of nerve growth factor (NGF) in the pathology of ovarian dysfunction. The nerve growth factor was analyzed in the central nervous system and ovaries by immunohistochemistry. The main findings of the present study were: (1) PCO were fully developed in rats with a single intramuscular injection of estradiol valerate, (2) PCO resulted in the expression of NGF in the ovaries and the brain tissues, and (3) herbal medicine administration significantly decreased the elevated NGF staining in the ovaries without affecting the brain tissues significantly.