• Toxicological Research
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• v.28 no.3
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• pp.179-185
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• 2012

Paecilomyces sinclairiis (PS) is known as a functional food or human health supplement. However concerns have been raised about its kidney toxicity. This study was performed to investigate the kidney toxicity of PS by 13 week-oral administration to rats. Blood urea nitrogen (BUN), serum creatinine, and kidney damage biomarkers including beta-2-microglobulin (${\beta}2m$), glutathione S-transferase alpha (GST-${\alpha}$), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were measured during or after the treatment of PS. BUN, creatinine and kidney damage biomarkers in serum were not changed by PS. However, kidney cell karyomegaly and tubular hypertrophy were observed dose-dependently with higher severity in males. KIM-1, TIMP-1 and osteopontin in kidney and urine were increased dose dependently in male or at the highest dose in female rats. Increased urinary osteopontin by PS was not recovered at 2 weeks of post-exposure in both genders. Cystatin C in kidney was decreased at all treatment groups but inversely increased in urine. The changes in kidney damage biomarkers were more remarkable in male than female rats. These data indicate that the PS may provoke renal cell damage and glomerular filtration dysfunction in rats with histopathological lesions and change of kidney damage biomarkers in kidney or urine. Kidney and urinary KIM-1 and cystatin C were the most marked indicators, while kidney weight, BUN and creatinine and kidney damage biomarkers in serum were not influenced.

• Archives of Plastic Surgery
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• v.32 no.6
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• pp.727-732
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• 2005

The treatment of wounds of the lower extremity caused by diabetes or vascular dysfunction remains a difficult problem for the plastic surgeon. The use of negative pressure in wound healing is a relatively new method to facilitate chronic wound healing by secondary healing. The use of vacuum-assisted closure(VAC) system is purposed to reduce local edema, increase regional blood flow, enhance epithelial migration, preserve a moist wound environment, reduce bacterial colonization, promote granulation tissue formation, and mechanically enhance wound closure. The VAC also can be used as a dressing for anchoring an applied split thickness skin graft. We reviewed the data from 20 consecutive patients with non-healing wound in lower extremity at Dong-A University from March 2002 to December 2004. We used the VAC in 20 patients and compared the results with the control group. In the VAC using group, mean application duration was about 3 weeks and dressing change was done every other day. The follow-up period of patients ranged from 3 months to 30 months with a mean of 17 months. The points of comparison with control group are wound size, granulation tissue proliferation rate, operation method, preoperative time, postoperative healing time, complication, and cost. With those points, we propose to approve the efficiency of the VAC in non-healing wound. As a result, the VAC used in non-healing wound decrease wound size, accelerate granulation tissue formation, do a wound closure with less invasive operation method, make less postoperative complication, can make operation time shorter. Therefore it is cost effect. Our results demonstrate the usefulness of VAC as an adjunct in management of chronic wounds with other extrinsic factors.

• Archives of Plastic Surgery
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• v.35 no.1
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• pp.67-72
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• 2008

Purpose: The hand is frequently affected area in high voltage electrical burn injury as an input or output sites. Electrical burn affecting the hand may produce full thickness necrosis of the skin and damage deep structures beneath the eschar, affecting the tendon, nerve, vessel, even bone which result in serious dysfunction of the hand. As promising methods for the reconstruction of the hand defects in electrical burn patients, we have used the peroneal perforator free flaps. Methods: From March 2005 to June 2006, we applied peroneal perforator free flap to five patients with high tension electrical burn in the hand. Vascular pedicle ranged from 4cm to 5cm and flap size was from $4{\times}2.5cm$ to $7{\times}4cm$. Donor site was closed primarily.Results: All flaps survived completely. There was no need to sacrifice any main artery in the lower leg, and there was minimal morbidity at donor site. During the follow-ups, we got satisfactory results both in hand function and in aesthetic aspects.Conclusion: The peroneal perforator flap is a very thin, pliable flap with minimal donor site morbidity and is suitable for the reconstruction of small and medium sized wound defect, especially hand with electrical burn injury.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.3
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• pp.257-262
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• 2015

It is well known that cigarette smoke can cause erectile dysfunction by affecting the penile vascular system. However, the exact effects of nicotine on the corpus cavernosum remains poorly understood. Nicotine has been reported to cause relaxation of the corpus cavernosum; it has also been reported to cause both contraction and relaxation. Therefore, high concentrations of nicotine were studied in strips from the rabbit corpus cavernosum to better understand its effects. The proximal penile corpus cavernosal strips from male rabbits weighing approximately 4 kg were used in organ bath studies. Nicotine in high concentrations ($10^{-5}{\sim}10^{-4}M$) produced dose-dependent contractions of the corpus cavernosal strips. The incubation with $10^{-5}M$ hexamethonium (nicotinic receptor antagonist) significantly inhibited the magnitude of the nicotine associated contractions. The nicotine-induced contractions were not only significantly inhibited by pretreatment with $10^{-5}M$ indomethacin (nonspecific cyclooxygenase inhibitor) and with $10^{-6}M$ NS-398 (selective cyclooxygenase inhibitor), but also with $10^{-6}M$ Y-27632 (Rho kinase inhibitor). Ozagrel (thromboxane $A_2$ synthase inhibitor) and SQ-29548 (highly selective TP receptor antagonist) pretreatments significantly reduced the nicotine-induced contractile amplitude of the strips. High concentrations of nicotine caused contraction of isolated rabbit corpus cavernosal strips. This contraction appeared to be mediated by activation of nicotinic receptors. Rho-kinase and cyclooxygenase pathways, especially cyclooxygenase-2 and thromboxane $A_2$, might play a pivotal role in the mechanism associated with nicotine-induced contraction of the rabbit corpus cavernosum.

• Biomedical Science Letters
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• v.15 no.1
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• pp.31-35
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• 2009

High blood pressure (BP) is the most frequent risk factor among metabolic syndrome components. The control of hypertension is very important to prevent the cardiovascular risk in metabolic syndrome. The dysfunction of calcium channel is responsible in the regulation of the vascular muscle contribution to hypertension. Calcium channel, voltage-dependent, P/Q type, alpha-1A subunit (CACNA1A) gene is located in brain and known to control the intracranial hypertension. In this study, we investigate whether the polymorphisms of CACNA1A gene is associated with hypertension. The 49 CACNA1A genotypes were determined using the Affymetrix Genotyping chip array in 92 hypertension and 279 control individuals from a Korean population. Logistic and multiple regression models were employed to analyze the genetic contributions of polymorphisms. Out of 49 polymorphisms, six SNPs (rs12611029, rs16035, rs7259944, rs10419472, rs17777900, and rs4926294) showed a significant association with hypertension in three alternative models (codominant, dominant, and recessive models; P<0.05 after adjusting for age and sex). Our results suggest that the CACNA1A gene may be associated with hypertension in the Korean population.

• Development and Reproduction
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• v.24 no.3
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• pp.197-205
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• 2020

Diabetes mellitus is a common heterogeneous metabolic disorder, characterized by deposition of extracellular matrix, oxidative stress, and vascular dysfunction, thereby leading to gradual loss of function in multiple organs. However, little attention has been paid to gene expression changes in the lung under hyperglycemic conditions. In this study, we found that diabetes inuced histological changes in the lung of streptozotocin-induced diabetic mice. Global gene expression profiling revealed a set of genes that are up- and down-regulated in the lung of diabetic mice. Among these, expression of Amigo2, Adrb2, and Zbtb16 were confirmed at the transcript level to correlate significantly with hyperglycemia in the lung. We further evaluated the effect of human umbilical cord-derived perivascular stem cells (PVCs) on these gene expression in the lung of diabetic mice. Our results show that administration of PVC-conditioned medium significantly suppressed Amig2, Adrb2, and Zbtb16 upregulation in these mice, suggesting that these genes may be useful indicators of lung injury during hyperglycemia. Furthermore, PVCs offer a promising alternative cell therapy for treating diabetic complications via regulation of gene expression.

• Toxicological Research
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• v.30 no.3
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• pp.149-157
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• 2014

Smoking is one of the most serious but preventable causes of cardiovascular disease (CVD). Key aspects of pathological process associated with smoking include endothelial dysfunction, a prothrombotic state, inflammation, altered lipid metabolism, and hypoxia. Multiple molecular events are involved in smoking-induced CVD. However, the dysregulations of reactive oxygen species (ROS) generation and metabolism mainly contribute to the development of diverse CVDs, and NADPH oxidase (NOX) has been established as a source of ROS responsible for the pathogenesis of CVD. NOX activation and resultant ROS production by cigarette smoke (CS) treatment have been widely observed in isolated blood vessels and cultured vascular cells, including endothelial and smooth muscle cells. NOX-mediated oxidative stress has also been demonstrated in animal studies. Of the various NOX isoforms, NOX2 has been reported to mediate ROS generation by CS, but other isoforms were not tested thoroughly. Of the many CS constituents, nicotine, methyl vinyl ketone, and ${\alpha}$,${\beta}$-unsaturated aldehydes, such as, acrolein and crotonaldehyde, appear to be primarily responsible for NOX-mediated cytotoxicity, but additional validation will be needed. Human epidemiological studies have reported relationships between polymorphisms in the CYBA gene encoding p22phox, a catalytic subunit of NOX and susceptibility to smoking-related CVDs. In particular, G allele carriers of A640G and $-930^{A/G}$ polymorphisms were found to be vulnerable to smoking-induced cardiovascular toxicity, but results for C242T studies are conflicting. On the whole, evidence implicates the etiological role of NOX in smoking-induced CVD, but the clinical relevance of NOX activation by smoking and its contribution to CVD require further validation in human studies. A detailed understanding of the role of NOX would be helpful to assess the risk of smoking to human health, to define high-risk subgroups, and to develop strategies to prevent or treat smoking-induced CVD.

• Journal of Ginseng Research
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• v.37 no.4
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• pp.413-424
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• 2013

Korean Red Ginseng extract (KRGE) is a traditional herbal medicine utilized to prevent endothelium dysfunction in the cardiovascular system; however, its underlying mechanism has not been clearly elucidated. We here examined the pharmacological effect and molecular mechanism of KRGE on apoptosis of human umbilical vein endothelial cells (HUVECs) in a serum-deprived apoptosis model. KRGE protected HUVECs from serum-deprived apoptosis by inhibiting mitochondrial cytochrome c release and caspase-9/-3 activation. This protective effect was significantly higher than that of American ginseng extract. KRGE treatment increased antiapoptotic Bcl-2 and Bcl-$X_L$ protein expression and Akt-dependent Bad phosphorylation. Moreover, KRGE prevented serum deprivation-induced subcellular redistribution of these proteins between the mitochondrion and the cytosol, resulting in suppression of mitochondrial cytochrome c release. In addition, KRGE increased nitric oxide (NO) production via Akt-dependent activation of endothelial NO synthase (eNOS), as well as inhibited caspase-9/-3 activities. These increases were reversed by co-treatment of cells with inhibitors of eNOS and phosphoinositide 3-kinase (PI3K) and pre-incubation of cell lysates in dithiothreitol, indicating KRGE induces NO-mediated caspase modification. Indeed, KRGE inhibited caspase-3 activity via S-nitrosylation. These findings suggest that KRGE prevents serum deprivation-induced HUVEC apoptosis via increased Bcl-2 and Bcl-$X_L$ protein expression, PI3K/Akt-dependent Bad phosphorylation, and eNOS/NO-mediated S-nitrosylation of caspases. The cytoprotective property of KRGE may be valuable for developing new pharmaceutical means that limit endothelial cell death induced during the pathogenesis of vascular diseases.

• Journal of Medicine and Life Science
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• v.20 no.3
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• pp.115-125
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• 2023

Arteriovenous fistula flow dysfunction is the leading cause of vascular access thrombosis and loss in patients undergoing hemodialysis. However, data regarding the influence of access flow rate measurements on the long-term outcomes of access are limited. This study aims to identify accesses at a high risk of thrombosis and loss among patients undergoing hemodialysis by measuring the access flow rate and exploring an optimal threshold value for predicting future access thrombosis. We enrolled 220 patients with arteriovenous fistula undergoing hemodialysis. The primary outcome was the occurrence of access thrombosis. Access flow rates were measured monthly using the ultrasound dilution method and were averaged using all measurements from patients with patent access. In patients experienced access thrombosis, those immediately before the thrombosis were selected. Using these data, we calculated the access flow rate threshold for thrombosis occurrence by analyzing the receiver operating characteristic curve, and the patients were divided into two groups according to whether access flow rates were higher or lower than 400 mL/min. During a median follow-up period of 3.1 years, 4,510 access flows were measured (median measurements per patient, 33 times; interquartile range, 11-54). A total of 65 access thromboses and 19 abandonments were observed. Access thrombosis and loss were higher in the lowflow group than in the high-flow group. This study revealed that low access flow rates are strongly associated with access thrombosis occurrence and subsequent loss of arteriovenous fistulas in patients undergoing hemodialysis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.37 no.6
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• pp.165-171
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• 2023

COVID-19 infection heightens the risk of thromboembolism. To see the similarities between the COVID-19 infection and Taeyang blood retention pattern, we conducted a PubMed search using specific terms related to blood circulation issues in the context of COVID-19, summarizing findings from 13 cases and 4 observational studies involving actual patients. Patients with COVID-19 are at risk of blood coagulation due to factors such as viral-induced cytokine storms, vascular endothelial dysfunction, reduced mobility in bedridden or isolated individuals, and resulting constipation. Additionally, cytokine storms and severe inflammation can lead to delirium in COVID-19 patients. The Taeyang blood retention pattern manifests as symptoms arising from delirium and an increased blood coagulation tendency in patients with a robust immune response. According to the Sanghan theory, certain herbal treatments can alleviate symptoms in patients with a tight lower abdomen who do not experience urinary issues. Studies show that components like Persicae Semen and Rhei Redix et Rhizoma in these prescriptions enhance blood circulation and reduce hypercoagulability. Additionally, these treatments aim to promote blood flow by relieving abdominal pressure through facilitating bowel movements. The excessive inflammation and heightened blood coagulation tendency in COVID-19 resemble the Taeyang blood retention pattern, although they are caused by different pathogens. Reinterpreting classical oriental medicine's principles in a modern context may enhance our understanding of traditional East Asian Medicine and foster future developments.