• The Korean Journal of Physiology and Pharmacology
• /
• 제5권3호
• /
• pp.231-241
• /
• 2001

The mammalian cortical collecting duct (CCD) plays a major role in regulating renal NaCl reabsorption, which is important in $Na^+$ and $Cl^-$ homeostasis. The M-1 cell line, derived from the mouse cortical collecting duct, has been used as a mammalian model of the study on the electrolytes transport in CCD. M-1 cells were grown on collagen-coated permeable support and short circuit current $(I_{sc})$ was measured. M-1 cells developed amiloride-sensitive current $5{\sim}7$ days after seeding. Apical and basolateral addition of ATP induced increase in $I_{sc}$ in M-1 cells, which was partly retained in $Na^+-free$ or $Cl^--free$ solution, indicating that ATP increased $Na^+$ absorption and $Cl^-$ secretion in M-1 cells. $Cl^-$ secretion was mediated by the activation of apical cystic fibrosis transmembrane regulator (CFTR) chloride channels and $Ca^{2+}-activated$ chloride channels, but $Na^+$ absorption was not mediated by activation of epithelal sodium channel (ENaC). ATP increased cAMP content in M-1 cells. The RT-PCR analysis demonstrated that M-1 cells express $P2Y_2,\;P2X_3\;and\;P2Y_4$ receptors. These results showed that ATP regulates $Na^+$ and $Cl^-$ transports via multiple P2 purinoceptors on the apical and basolateral membranes in M-1 cells.

• 대한한방부인과학회지
• /
• 제18권1호
• /
• pp.111-127
• /
• 2005

Objective : This study was conducted to investigate the effect of Mokhyangsaenghwa-tang (MS) and Mokhyangsaenghwa-tang plus Cervi Pantotrichum Cornu (MS-C) on postpartum recovery and lactation. Materials and Methods : We used 18-week pregnant Spraque Dawley rats and administered the decoctions of MS and MS-C to rats once a day for 4 days or 8 days. Then we observed changes in the body weight of pup rats and complete blood cell count, liver function test, renal function test, mammary gland tissue, level of serum prolactin, ${\beta}-casein$ and WAP of postpartum rats. Result : A significant increase in body weight was observed in MS-C treated pup rats compared with in MS treated group. The levels of WBC and platelet from MS group and MS-C group were decreased compared with the control group. The levels of RBC, hemoglobin and hematocrit from MS group and MS-C group showed statistically significant increases compared with the control group. The levels of protein, albumin from MS group and MS-C group were increased compared with the control group. The levels of BUN, creatinine from MS group and MS-C group did not show statistically significant changes compared with the control group. The mammary gland tissues from MS group and MS-C group showed increased angiogenesis. The levels of serum prolactin from MS group and MS-C group were increased compared with the control group. The expression of ${\beta}-casein$ and WAP genes from postpartum rats treated with MS and MS-C was increased. Conclusion : This study shows that MS and MS-C improved postpartum recovery and lactation in rats.

• 대한핵의학회지
• /
• 제11권1호
• /
• pp.59-70
• /
• 1977

Eight patients with polycythemia vera were diagnosed from 1965 through 1977 among the patients of Seoul National University Hospital. In our series there were 4 men and 4 women with average age of 54 years at the time of diagnosis. Symptoms of facial plethora, headache, pruritus and dizziness were the most frequent manifestations of disease in order of frequency. At inital examination 8 of 8 patients had facial plethora, 6 of 8 patients splenomegaly and 4 if 8 patients hepatomegaly. The laboratory data revealed mean Red cell volume of 55+10ml/kg which was elevated in all cases. Leukocytosis was observed in 5 of 8 patients and thrombocytosis 2 of 8 patients. Leukocyte alkaline phosphatase was increased in all cases. Bone marrow aspiration disclosed typical panmyelosis in 5 of 8 patients. In one patient there was diffuse myelofibrosis on bone marrow biopsy. The combined diseases included 2 patient with hypertension and 1 patient with thrombosis of aorta and left renal artery. The patients were treated with phlebotomy alone in 2 patients, chemotherapy with busulfan in 1 patient and $^{32}P$ in 5 patients with favorable results. During the mean 29.9 months follow up period, there were development of iron deficiency in 3 patients, hyperuricemia in 2 patients and thrombosis in 1 patient. The occurrence of acute leukemia of myelofibrosis was not observed in the course of disease.

• 방사선산업학회지
• /
• 제12권4호
• /
• pp.355-363
• /
• 2018

A novel $N_3S_1$ chelate, Pro-Lys-Cys (PKC) to cyclic RGD to radiolabel with $^{99m}Tc$ was conjugated in an effort to decrease the high intestinal accumulation observed for $^{99m}Tc$-labeled PGC-RGD. The target specificity of the resulting PKC-RGD was similar to that of PGC-RGD as determined by a cell binding assay and a competition binding assay. The $^{99m}Tc$ radiolabeling of PKC-RGD resulted in radiochemical yields of 98% under mild conditions at high specific activities. Biodistribution data in normal mice clearly showed a significant decrease in intestinal uptake at 2 h postinjection for the $^{99m}Tc-PKC-c$ (RGDyK) compared to the $^{99m}Tc-GC-c$ (RGDyK) (from $19.65%ID{\cdot}g^{-1}$ to $7.31%ID{\cdot}g^{-1}$ for the GI tract). The $^{99m}Tc-PKC-c$ (RGDyK) biodistribution was also shown by a higher retention of radioactivity in the whole body, but with kidney accumulation over 8-fold higher than observed with $^{99m}Tc-PGC-c$ (RGDyK) at 2 h ($12.62%ID{\cdot}g^{-1}$ for PKC-RGD and $1.54%ID{\cdot}g^{-1}$ for PGC-RGD, respectively). These results show that the biodistribution may be altered especially concerning lipophilicity resulting in renal rather than hepatobiliary excretion. This comparative study made it possible to explore the effects of lipophilicity on the biodistribution of $^{99m}Tc$-labeled c (RGDyK) through the use of different tripeptide $N_3S_1$ chelators. Therefore, $^{99m}Tc-PKC-c$ (RGDyK) may be an attractive alternative for the in vivo imaging of integrin receptors.

• Nutrition Research and Practice
• /
• 제13권5호
• /
• pp.367-376
• /
• 2019

BACKGROUND/OBJECTIVE: The blue honeysuckle berry (Lonicera caerulea var. edulis L.) is a small deciduous shrub belonging to the Caprifoliaceae family that is native to Russia, China, Japan, and Korea. The berry of this shrub is edible, sweet and juicy and is commonly known as the blue honeyberry (BHB). This study examined the anti-diabetic potential of BHB on high-fat-diet-induced mild diabetic mice. The hypoglycemic, and nephroprotective effects of the 12-week oral administration of blue honeyberry extract were analyzed. MATERIALS/METHODS: The hypoglycemic effects were based on the observed changes in insulin, blood glucose, and glycated hemoglobin (HbA1c). Furthermore, the changes in the weight of the pancreas, including its histopathology and immunohistochemical investigation were also performed. Moreover, the nephroprotective effects were analyzed by observing the changes in kidney weight, its histopathology, blood urea nitrogen (BUN), and serum creatinine levels. RESULTS: The results showed that the high-fat diet (HFD)-induced control mice showed a noticeable increase in blood glucose, insulin, HbA1c, BUN, and creatinine levels. Furthermore, growth was observed in lipid droplet deposition related to the degenerative lesions in the vacuolated renal tubules with the evident enlargement and hyperplasia of the pancreatic islets. In addition, in the endocrine pancreas, there was an increase in the insulin-and glucagon-producing cells, as well as in the insulin/glucagon cell ratios. On the other hand, compared to the HFD-treated mice group, all these diabetic and related complications were ameliorated significantly in a dose-dependent manner after 84 days of the continuous oral administration of BHBe at 400, 200 and 100 mg/kg, and a dramatic resettlement in the hepatic glucose-regulating enzyme activities was observed. CONCLUSIONS: By assessing the key parameters for T2DM, the present study showed that the BHBe could act as a potential herbal agent to cure diabetes (type II) and associated ailments in HFD-induced mice.

• Clinical and Experimental Pediatrics
• /
• 제64권7호
• /
• pp.355-363
• /
• 2021

Background: Nephrotic syndrome (NS) is a common renal disorder in children attributed to podocyte injury. However, children with the same diagnosis have markedly variable treatment responses, clinical courses, and outcomes, suggesting molecular heterogeneity. Purpose: This study aimed to explore the molecular responses of podocytes to nephrotic plasma to identify specific genes and signaling pathways differentiating various clinical NS groups as well as biological processes that drive injury in normal podocytes. Methods: Transcriptome profiles from immortalized human podocyte cell line exposed to the plasma of 8 subjects (steroid-sensitive nephrotic syndrome [SSNS], n=4; steroid-resistant nephrotic syndrome [SRNS], n=2; and healthy adult individuals [control], n=2) were generated using microarray analysis. Results: Unsupervised hierarchical clustering of global gene expression data was broadly correlated with the clinical classification of NS. Differential gene expression (DGE) analysis of diseased groups (SSNS or SRNS) versus healthy controls identified 105 genes (58 up-regulated, 47 down-regulated) in SSNS and 139 genes (78 up-regulated, 61 down-regulated) in SRNS with 55 common to SSNS and SRNS, while the rest were unique (50 in SSNS, 84 genes in SRNS). Pathway analysis of the significant (P≤0.05, -1≤ log2 FC ≥1) differentially expressed genes identified the transforming growth factor-β and Janus kinase-signal transducer and activator of transcription pathways to be involved in both SSNS and SRNS. DGE analysis of SSNS versus SRNS identified 2,350 genes with values of P≤0.05, and a heatmap of corresponding expression values of these genes in each subject showed clear differences in SSNS and SRNS. Conclusion: Our study observations indicate that, although podocyte injury follows similar pathways in different clinical subgroups, the pathways are modulated differently as evidenced by the heatmap. Such transcriptome profiling with a larger cohort can stratify patients into intrinsic subtypes and provide insight into the molecular mechanisms of podocyte injury.

• Journal of Medicine and Life Science
• /
• 제19권2호
• /
• pp.46-56
• /
• 2022

The incidence of fever complicating percutaneous coronary intervention (PCI) is rare. However, little is known regarding the cause of fever after PCI. Therefore, this study aimed to determine the clinical characteristics of patients with acute myocardial infarction (AMI), with or without fever, after PCI. We enrolled a total of 926 AMI patients who underwent PCI. Body temperature (BT) was measured every 4 hours or 8 hours for 5 days after PCI. Patients were divided into two groups according to BT as follows: BT<37.7℃ (no-fever group) and BT ≥37.7℃ (fever group). The 2 years clinical outcomes were compared subsequently. Fever after PCI was associated with higher incidence of major adverse cardiac events (MACE) (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.07-2.28; P=0.021), all-cause death (HR, 2.32; 95% CI, 1.18-4.45; P=0.014), cardiac death (CD) (HR, 2.57; 95% CI, 1.02-6.76; P=0.049), and any revascularization (HR, 1.69; 95% CI, 1.02-2.81; P=0.044) than without fever. In women, prior chronic kidney disease, lower left ventricular (LV) ejection fraction, higher LV wall motion score index, white blood cell count, peak creatine kinase-myocardial band level, and longer PCI duration were associated with fever after PCI. Procedures such as an intra-aortic balloon pump, extracorporeal membrane oxygenation, continuous renal replacement therapy, central and arterial line insertion, and cardiopulmonary resuscitation were related to fever after PCI. Fever after PCI in patients with AMI was associated with a higher incidence of MACE, all-cause death, CD, and any revascularization at the 2 years mark than in those without fever.

• Journal of Genetic Medicine
• /
• 제20권1호
• /
• pp.6-14
• /
• 2023

Fabry disease (FD), a rare X-linked lysosomal storage disorder, is caused by mutations in the α-galactosidase A gene gene encoding α-galactosidase A (α-Gal A). The functional deficiency of α-Gal A results in progressive accumulation of neutral glycosphingolipids, causing multi-organ damages including cardiac, renal, cerebrovascular systems. The current treatment is comprised of enzyme replacement therapy (ERT), oral pharmacological chaperone therapy and adjunctive supportive therapy. ERT has been introduced 20 years ago, changing the outcome of FD patients with proven effectiveness. However, FD patients have many unmet needs. ERT needs a life-long intravenous therapy, inefficient bio-distribution, and generation of anti-drug antibodies. Migalastat, a pharmacological chaperone, augmenting α-Gal A enzyme activity only in patients with mutations amenable to the therapy, is now available for clinical practice. Furthermore, these therapies should be initiated before the organ damage becomes irreversible. Development of novel drugs aim at improving the clinical effectiveness and convenience of therapy. Clinical trial of next generation ERT is underway. Polyethylene glycolylated enzyme has a longer half-life and potentially reduced antigenicity, compared with standard preparations with longer dosing interval. Moss-derived enzyme has a higher affinity for mannose receptors, and seems to have more efficient access to podocytes of kidney which is relatively resistant to reach by conventional ERT. Substrate reduction therapy is currently under clinical trial. Gene therapy has now been started in several clinical trials using in vivo and ex vivo technologies. Early results are emerging. Other strategic approaches at preclinical research level are stem cell-based therapy with genome editing and systemic mRNA therapy.

• 대한한방내과학회지
• /
• 제44권5호
• /
• pp.1011-1016
• /
• 2023

We have experienced a case in which herbal medicine was administered to treat drug-induced liver damage and would like to introduce it. A 49-year-old man exhibited a positive result in the interferon-gamma release assay. He had never suffered from tuberculosis in the past, and the route and time of infection could not be confirmed. He had no respiratory or systemic symptoms suggestive of active tuberculosis, and a chest X-ray examination showed no active lung lesions, so he was diagnosed with latent tuberculosis infection. He was confirmed to be within the normal range in the liver function test, renal function test, and complete blood cell count test, and started taking rifampin (600 mg qd). In the screening test performed on the 19th day of taking the drug, other test items were normal, but alanine aminotransferase (ALT) increased to 50 U/L (reference value: 4-40 U/L). In a test performed on the 29th day of taking the drug, ALT was clearly elevated to 102 U/L. Ursodeoxycholic acid and Injinho-tang were taken together with rifampin, and the patient's progress was observed. In a test performed 14 days later, ALT decreased to 26 U/L, within the normal range. It is presumed that Injinho-tang may have partially contributed to alleviating liver damage in this case.

• Genomics & Informatics
• /
• 제21권4호
• /
• pp.44.1-44.10
• /
• 2023

Tumor hypoxia, oxygen deprivation state, occurs in most cancers and promotes angiogenesis, enhancing the potential for metastasis. The vascular endothelial growth factor (VEGF) family genes play crucial roles in tumorigenesis by promoting angiogenesis. To investigate the malignant processes triggered by hypoxia-induced angiogenesis across pan-cancers, we comprehensively analyzed the relationships between the expression of VEGF family genes and hypoxic microenvironment based on integrated bioinformatics methods. Our results suggest that the expression of VEGF family genes differs significantly among various cancers, highlighting their heterogeneity effect on human cancers. Across the 33 cancers, VEGFB and VEGFD showed the highest and lowest expression levels, respectively. The survival analysis showed that VEGFA and placental growth factor (PGF) were correlated with poor prognosis in many cancers, including kidney renal cell and liver hepatocellular carcinoma. VEGFC expression was positively correlated with glioma and stomach cancer. VEGFA and PGF showed distinct positive correlations with hypoxia scores in most cancers, indicating a potential correlation with tumor aggressiveness. The expression of miRNAs targeting VEGF family genes, including hsa-miR-130b-5p and hsa-miR-940, was positively correlated with hypoxia. In immune subtypes analysis, VEGFC was highly expressed in C3 (inflammatory) and C6 (transforming growth factor β dominant) across various cancers, indicating its potential role as a tumor promotor. VEGFC expression exhibited positive correlations with immune infiltration scores, suggesting low tumor purity. High expression of VEGFA and VEGFC showed favorable responses to various drugs, including BLU-667, which abrogates RET signaling, an oncogenic driver in liver and thyroid cancers. Our findings suggest potential roles of VEGF family genes in malignant processes related with hypoxia-induced angiogenesis.