Bioassay-guided isolation of novel and selective urease inhibitors from Diospyros lotus / 中国天然药物

Two new dimeric naphthoquinones, 5',8'-dihydroxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (1; Di-naphthodiospyrol D) and 5',8'-dihydroxy-5,8-dimethoxy-6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (2; Di-naphthodiospyrol E), along with known naphthoquinones diospyrin (3) and 8-hydroxy diospyrin (4) were isolated from the chloroform fraction of extract of Diospyros lotus roots. Their structures were elucidated by advanced spectroscopic analyses, including HSQC, HMBC, NOESY, and J-resolved NMR experiments. The fractions and compounds 1-4 were evaluated for urease activity and phosphodiesterase-I, carbonic anhydrase-II and α-chymotrypsin enzyme inhibitory activities. Compounds 1 and 2 and their corresponding fractions showed significant and selective inhibitory effects on urease activities. The IC values of 1 and 2 were 260.4 ± 6.37 and 381.4 ± 4.80 µmol·L, respectively, using thiourea (IC = 21 ± 0.11 µmol·L) as the standard inhibitor. This was the first report demonstrating that the naphthoquinones class showed urease inhibition.

Enhanced Expression of Carbonic anhydrase II in Hypokalemic Rat Kidney / 체질인류학회지

A number of acid-base or electrolyte disorders are associated with decreased or increased HCO3- reabsorption in the renal tubules. The present study was to examine the alterations of expression and distribution of Carbonic anhydrase II in the kidneys of normal and potassium-depleted rats using Western blot analysis and immuno-histochemistry. Western blot analysis demonstrated that CA II protein, ~30 kDa at molecular mass, was abundantly expressed in normal group. All potassium-depleted groups showed slightly increased CA II protein compared to normal group. In control group, immunoreactivity of CA II protein was detected in the entire collecting duct. Signal intensity was prominent in the intercalated cells and weak in the principal cells of the cortical collecting ducts. In potassium-depleted groups, the pattern of cellular labeling of CA II protein was identical to that of normal group, but the signal intensity was decreased in cortical collecting duct, markedly increased in the inner stripe of outer medullary and inner medullary collecting ducts, and unchanged in the outer stripe of outer medullary collecting duct. These results suggest that chronic hypokalemia impact the expression pattern of CA II protein depending the portion of the collecting duct.

Carbonic anhydrase II deficiency: A novel mutation.

Carbonic anhydrase II (CA II) deficiency is an extremely rare autosomal recessive disorder, characterised by a triad of osteopetrosis, renal tubular acidosis and cerebral calcifications. A 12-year-old boy with classical features of CA II deficiency is reported who was found to be homozygous for the mutation in CA II gene and parents were heterozygous for the same mutation .To the best of our knowledge this is the first case report of mutation proven CA II deficiency from India.

Carbonic anhydrase II immunostaining in the cerebellum of postnatal mice / 대한해부학회지

The carbonic anhydrase II (CA-II) is specifically expressed in oligodendrocytes, the cells responsible for myelination in the central nervous system. However no direct evidence on relationship between myelin formation and CA-II immunoreactivity has been described. The aims of these studies are to investigate the relationship between CA-II and myelination during cerebellar development of mouse. Myelin staining was found on postnatal (P) 14, and its intensity increased in proportion to developmental age. CA-II positive oligodendrocytes were observed in the white matter of cerebellum on P 14 day. CA-II positive oligoden-drocytes also occured in the granular layer and Purkinje cell layers in the later stage of dvelopment. The parallel development in the CA-II expression and myelination during development suggests that CA-II in oligoendrocyte play a role to myelination.

Chromophobe Renal Cell Carcinoma

We report 13 chromophobe renal cell carcinomas (10.8%) observed among 120 renal cell carcinomas in adults. The average age was 53 (range: 34-72) years old, and 6 were males and 7 females. The mean tumor size was 10 (range: 5-17) cm, mean nuclear grade 2.4, and mean Robson's stage was 1.9. There were two distinct histologic variants; typical variant (n=9) and eosinophilic variant (n=4). Both of them showed typical light microscopic features and positive reaction with Hale's colloidal iron and carbonic anhydrase II, a marker protein of intercalated cells of renal collecting ducts. A strong positive immunoreactivity for epithelial membrane antigen was noted in the cytoplasm in 12 of 13 tumors. Numerous microvesicles, 180~440 nm in diameter, were identified ultrastructurally. DNA aneuploidy was found in 3 out of 10 cases. Neither local recurrence nor metastasis have been identified during the following period of 4~144 (mean 48) months.

Histopathology and Mainz Classification of Renal Cell Tumors: A Histogenetic Study and DNA Content Analysis

The Mainz classification for renal cell tumors was introduced in 1986 and it's utility has been reported in several histogenetic and genetic studies of renal cell tumors. We present a study of 127 cases of renal cell tumors with clinicopathologic correlation, DNA content analysis, and histogenesis studied by histochemical and immunohistochemical staining. The 127 renal cell tumors classified by the Mainz classification were 87 clear cell, 17 chromophilic, 13 chromophobe and 3 sarcomatoid renal cell carcinomas, 5 oncocytomas and 2 adenomas. These subtypes showed significant correlation not with age, sex, Robson's stage, DNA ploidy or tumor recurrence but with nuclear grade (p=0.001) and tumor size (p=0.001). Hall's colloidal iron (p=0.002) and carbonic anhydrase II (p=0.013) stains, representing the origin of distal nephron especially of collecting duct, were significantly correlated with specific subtypes of renal cell tumors, especially chromophobe cell renal carcinoma. This study demonstrates that the Mainz classification suggests several morphologically different subtypes and variants of renal cell tumors and that some of them may have originated from the distal nephron, particularly from the collecting duct.

Immunochemical Study on the Changes of Carbonic anhydrase-II and Iron-binding Proteins in the Demyelinationand and Remyelination model Mouse induced with Cuprizone / 대한해부학회지

O1igodendrocytes are known to be responsible for the synthesis and maintenance of myelin sheath in the central nervous system, and their functional disturbance leads to defect in myelination. But, the fine mechanism of myelination by oligodendrocytes is not yet known, and iron metabolism in central nervous system is suspected to be related with myelination process by oligodendrocytes. Carbonic anhydrase-II[CA-II], transfe-rrin, and ferritin are known to be present at oligodendrocytes and suspected to play a role in iron metabolism of central nervous system. In this study, demyelination and remyelination of ICR mouse brains were induced using cuprizone, the copper-chelating agent, and immunohistochemical changes of CA-II-, transferrin-, and ferritin-immunoreactive oligodendrocytes at corpus callosum were observed. During demyelination by cuprizone feeding, the numbers of CA-II- and transferrin-immunoreactive oligodendrocytes were decreased. Especially, the decrease ratio of CA-II-positive cells was great. In contrast, the number of ferritin-positive oligodendrocytes was increased during demyelination by cuprizone feeding. Cessation of cuprizone feeding leaded remyelination and the numbers of CA-II-, transferrin-, and ferritin-immunoreactive oligodendrocytes were returned to normal level. In conclusion, the derangement of iron metabolism in oligodendrocytes may be related to demyelination mechanism of central nervous system, and the CA-II is suspected to have an important role in iron metabolism of oligodenrocytes in relation to demyelination and remyelination induced with cuprizone.