Kim, Kun Pyo;Shin, Kyong-Oh;Park, Kyungho;Yun, Hye Jeong;Mann, Shivtaj;Lee, Yong Moon;Cho, Yunhi
Biomolecules & Therapeutics
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v.23
no.6
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pp.525-530
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2015
Ceramide is the most abundant lipid in the epidermis and plays a critical role in maintaining epidermal barrier function. Overall ceramide content in keratinocyte increases in parallel with differentiation, which is initiated by supplementation of calcium and/or vitamin C. However, the role of metabolic enzymes responsible for ceramide generation in response to vitamin C is still unclear. Here, we investigated whether vitamin C alters epidermal ceramide content by regulating the expression and/or activity of its metabolic enzymes. When human keratinocytes were grown in 1.2 mM calcium with vitamin C ($50{\mu}g/ml$) for 11 days, bulk ceramide content significantly increased in conjunction with terminal differentiation of keratinocytes as compared to vehicle controls (1.2 mM calcium alone). Synthesis of the ceramide fractions was enhanced by increased de novo ceramide synthesis pathway via serine palmitoyltransferase and ceramide synthase activations. Moreover, sphingosine-1-phosphate (S1P) hydrolysis pathway by action of S1P phosphatase was also stimulated by vitamin C supplementation, contributing, in part, to enhanced ceramide production. However, activity of sphingomyelinase, a hydrolase enzyme that converts sphingomyelin to ceramide, remained unaltered. Taken together, we demonstrate that vitamin C stimulates ceramide production in keratinocytes by modulating ceramide metabolicrelated enzymes, and as a result, could improve overall epidermal barrier function.
Medication adherence is an important public health issue. This study is conducted to explore non-adherence of elderly with hypertension and/or diabetes mellitus and to better understand its' influencing factors. To explore non-adherence, 605 elderly patients in community were surveyed with Modified Morisky Scale (MMS), from Aug 18 to Sept 19, 2008. MMS is designed to predict medication-taking behavior and outcomes, and also to explain persistence of the patient's long-term continuation of therapy, which is a significant factor in the long-term management of chronic diseases. Also, MMS is designed to classify patients into a high/low continuum for knowledge and motivation. Patients self reported medication adherence were average 4.66 with MMS (range 0-6), only 78% of patients hold high motivation of medication adherence although 95.5% of patients hold high knowledge of medication adherence. This study explores which factors influence to high motivation of medication adherence and it proved that patients' participation in work, education level, participation in private health insurance, number of medication and medication frequency per day, pharmacists' explanation, experience of non adherence due to cost are important factors to explain high motivation of medication adherence of elderly with hypertension and/or diabetes mellitus.
$Capparis$$zeylanica$ Linn. a 'Rasayana' drug is used for its memory enhancing effects in the traditional Ayurvedic system of medicine. The aim of this study was to evaluate acetylcholinesterase (AChE) inhibitory and memory enhancing activities of $Capparis$$zeylanica$ Linn. The$in-vitro$ and $ex-vivo$ models of AChE inhibitory activity were used along with Morris water maze test to study the effect on memory in rats. The anticholinesterase effect of methanolic and aqueous extracts of $Capparis$$zeylanica$ was measured by spectrophotometric Ellman method at 0.1, 0.3, 1.0, 3.0, 10 and 30 mg/ml and brain monoamine oxidase (MAO-A and MAO-B) activity was assessed by Naoi's method. The results $in-vitro$ and $ex-vivo$ AChE assay revealed that methanolic and aqueous extracts of $Capparis$$zeylanica$ inhibit AChE activity, whereas these extracts did not alter MAO activity at any concentration tested as compared to moclobemide and L-deprenyl. The results indicate that $Capparis$$zeylanica$ improves scopolamine-induced memory deficits through inhibition of AChE activity, and not by direct MAO inhibition.
This study was to undertaken to investigate the impacts of AhR, CYP1A1, GSTM1 genetic polymorphisms on the R273G mutation in exon 8 of the tumor suppressor p53 gene (TP53) among polycyclic aromatic hydrocarbons (PAHs) exposed to coke-oven workers. One hundred thirteen workers exposed to PAH and 82 control workers were recruited. We genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and TP53 R273G mutation in blood by PCR methods, and determined the levels of 1-hydroxypyrene as PAH exposure marker in urine using the high pressure liquid chromatography assay. We found that the distribution of alcohol users and the urinary excretion of 1-OHP in the exposed workers were significantly higher than that of the control workers (p=0.004, p<0.001, respectively). Significant differences were observed in the p53 genotype distributions of smoking subjects (p=0.01, 95%CI: 1.23-6.01) and PAH exposure (p=0.008, 95%CI: 1.24-4.48), respectively. Further, significant differences were observed in the p53 exon 8 mutations for the genetic polymorphisms of Lys/Arg for AhR (p=0.02, 95%CI: 0.70-15.86), Val/Val for CYP1A1 (p=0.04, 95%CI: 0.98-19.09) and null for GSTM1 (p=0.02, 95%CI: 1.19-6.26), respectively. Our findings indicated that polymorphisms of PAH metabolic genes, such as AhR, CYP1A1, GSTM1 polymorphisms may interact with p53 genetic variants and may contribute to PAH related cancers.
In this study, we investigated oxidative stress and tumor marker levels of polycyclic aromatic hydrocarbons (PAHs) in 136 coke oven workers and in 60 control subjects, and evaluated the correlation between oxidative stress and tumor marker levels. Questionnaires on basic demographic information were also administered. Significant differences in employment time and percentages of alcohol drinkers were observed between the control and exposed groups. PAH exposure was assessed using urinary 1-hydroxy-pyrene (1-OHP) levels and was found to be significantly higher in workers than in the controls. Significant differences (P<0.001) of MDA, GST, LDH, NSE, Cyfra21-1, and of SCC and TNF-a (P<0.0001 and P<0.05, P<0.001, respectively) levels were observed among controls and coke-oven workers, except for bottom coke oven workers. Associations between age and risk of increased TNF-a, smoking and increased GST activities, and drinking with increased MDA concentrations, were marginal (P=0.055, P=0.048, P=0.057, respectively). The association between smoking with MDA (P=0.004), NSE (P=0.005), SCC (P=0.004) andTNF-a (P<0.001), and drinking with TNF-a levels was significant (P=0.012). In addition, a significant positive correlation between oxidative stress and tumor markers was found in the present study. These results suggest that a synergistic increase of oxidative stress and tumor markers induced by PAHs may play a role in toxic responses for PAHs in coke oven workers.
Hypertension is an important public health problem because it increases the risk of stroke, angina, myocardial infarction, heart failure, and end-stage renal disease. If it is not actively treated, morbidity and mortality increase with hypertension-induced complications and quality of life decreases. This study was to evaluate the use of antihypertensive drugs and blood pressure changes and to compare algorithms chosen (or the 1st and 2nd line therapy of hypertension based on the JNC VI recommendations. The medical charts of 222 patients with essential hypertension at St. Vincent's Hospital in Suwon from January 1997 to January 2000 were reviewed retrospectively. Data collection and analysis included baseline BP underlying diseases and complications, administered antihypertensives, BP changes, changes of antihypertensive regimen, and adverse effects with treatments. As results, the higher BP the patients had, the more frequent they had target organ damages and clinical cardiovascular diseases. Mean duration to reduce blood pressure less than 140/90 mmHg was 8 weeks in $85.3\%$ of the patients. The rate of control in BP was $82.4\%$ at 6 months. The major antihypertensive drugs prescribed were calcium channel blockers $(61.8\%)$ , ACE inhibitors $(19.1\%),\;\beta-blockers\;(13.7\%)$ and diuretics $(5.3\%)$ as the 1st-line monotherapy. The methods of treatment used as the 1st-line therapy were monotherapy$(59\%)$ and combination therapy $(41\%)$. Blood pressure change was significantly greater for combination therapy than monotherapy$(-26.2\pm21.4\;vs.\;-18.56\pm16.7$ mmHg for systolic blood pressure; P<0.003, $-16.9\pm13.2\;vs.\;-9.2\pm12.8$ mmHg for diastolic blood pressure; p<0.001). When blood pressure was not completely controlled with the first antihypertensive selected, the 2nd line therapy had 4 options: addition of 2nd agent from different class; $66.2\%$, substitution with another drug, $21.9\%$ increase dose $11.9\%$ continue first regimen $27.9\%$ Calcium channel blockers were the most frequently prescribed agents. This was not comparable to the JNC VI guideline which recommended diuretics and $\beta-blockers$ for the 1st-line therapy. Most of patients achieved the goal BP and maintained it until 6 months, but the remaining patients should be controlled more tightly to improve their BP with combination of life style modification, patient education, and pharmacotherapy.
Preservation of fresh algae plays an important role in algae seed subculture and aquaculture. The determination and examination of the changes of cell viability, composition, and bacterial species during storage would help to take suitable preservation methods to prolong the preservation time of fresh algae. Nostoc flagelliforme is a kind of edible cyanobacterium with important herbal and dietary values. This article investigated the changes of bacterial species and biochemical characteristics of fresh N. flagelliforme concentrate during natural storage. It was found that the viability of cells decreased along with the storage time. Fourteen bacteria strains in the algae concentrate were identified by PCR-DGGE and were grouped into four phyla, including Cyanobacteria, Firmicutes, Proteobacteria, and Bacteroidetes. Among them, Enterococcus viikkiensis may be a concern in the preservation. Eleven volatile organic compounds were identified from N. flagelliforme cells, in which geosmin could be treated as an indicator of the freshness of N. flagelliforme. The occurrence of indole compound may be an indicator of the degradation of cells.
Toxoplasma gondii is an important opportunistic pathogen that causes toxoplasmosis, which has very few therapeutic treatment options. The most effective therapy is a combination of pyrimethamine and sulfadiazine; however, their utility is limited because of drug toxicity and serious side effects. For these reasons, new drugs with lower toxicity are urgently needed. In this study, the compound, (Z)-1-[(5-nitrofuran-2-yl)methyleneamino]-imidazolidine-2,4-dione (nitrofurantoin), showed anti-T. gondii effects in vitro and in vivo. In HeLa cells, the selectivity of nitrofurantoin was 2.3, which was greater than that of pyrimethamine (0.9). In T. gondii-infected female ICR mice, the inhibition rate of T. gondii growth in the peritoneal cavity was 44.7% compared to the negative control group after 4-day treatment with 100 mg/kg of nitrofurantoin. In addition, hematology indicators showed that T. gondii infection-induced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, biochemical parameters involved in liver injury, were reduced by nitrofurantoin significantly. Moreover, nitrofurantoin exerted significant effects on the index of antioxidant status, i.e., malondialdehyde (MDA) and glutathione (GSH). The nitrofurantoin-treated group inhibited the T. gondii-induced MDA levels while alleviating the decrease in GSH levels. Thus, nitrofurantoin is a potential anti-T. gondii candidate for clinical application.
Objective: Currently, rivaroxaban is widely used clinically for thromboprophylaxis after surgery. However, there are concerns on effectiveness and safety of rivaroxaban for its proper use. We aimed to evaluate the effectiveness and safety of rivaroxaban in orthopaedic patients after total hip replacement surgery in a large medical centre after the preferred formulary was switched from enoxaparin to rivaroxaban. Methods: The study was conducted on the patients who underwent hip arthroplasty surgery at the department of Orthopaedic Surgery at Seoul St. Mary's Hospital, South Korea. Electronic medical records were retrospectively reviewed to identify patients treated with rivaroxaban following total hip replacement between February 2011 and March 2012. Evaluation criteria included indications for use, dose, initiation and duration of therapy, drug interactions, adverse reactions, and status of health care reimbursement. The patients who were on enoxaparin were also reviewed as a reference. Results: We identified 57 patients who received rivaroxaban and 50 who received enoxaparin. All patients were prescribed the drugs for Korean Food and Drug Administration-approved indications. No thromboembolic or bleeding events were observed in either group. However, only 5.3% of rivaroxaban- treated patients had an appropriate length of prophylaxis and only 3.5% began rivaroxaban treatment at the recommended time. Surprisingly, 47.4% of rivaroxaban-treated patients received rivaroxaban despite being ineligible for reimbursement benefits. Conclusion: Rivaroxaban was generally well tolerated clinically. However, the duration of treatment, the time of initiation and patient eligibility for reimbursement require improvements, emphasising the need for education which indicates the area of pharmacists' involvement.
Khan, Tahir Mehmood;Leong, Jamie Pik Yan;Ming, Long Chiau;Khan, Amer Hayat
Asian Pacific Journal of Cancer Prevention
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v.16
no.13
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pp.5349-5357
/
2015
Background: Breast cancer is the most common cancer and the leading cause of cancer mortality among women of all ethnic and age groups in Malaysia. Delay in seeking help for breast cancer symptoms is preventable and by identifying possible factors for delayed diagnosis, patient prognosis and survival rates could be improved. Objectives: This narrative review aimed to understand and evaluate the level of in-depth breast cancer knowledge in terms of clinical breast examination and breast self-examination, and other important aspects such as side-effects and risk factors in Malaysian females. Since Malaysia is multicultural, this review assessed social perceptions, cultural beliefs and help-seeking behaviour in respect to breast cancer among different ethnic groups, since these may impinge on efforts to 'avoid' the disease. Materials and Methods: A comprehensive literature search of seven databases was performed from December 2015 to January 2015. Screening of relevant published journals was also undertaken to identify available information related to the knowledge, perception and help-seeking behaviour of Malaysian women in relation to breast cancer. Results: A total of 42 articles were appraised and included in this review. Generally, women in Malaysia had good awareness of breast cancer and its screening tools, particularly breast self-examination, but only superficial in-depth knowledge about the disease. Women in rural areas had lower levels of knowledge than those in urban areas. It was also shown that books, magazines, brochures and television were among the most common sources of breast cancer information. Delay in presentation was attributed mainly to a negative social perception of the disease, poverty, cultural and religion practices, and a strong influence of complementary and alternative medicine, rather than a lack of knowledge. Conclusions: This review highlighted the need for an intensive and in-depth breast cancer education campaigns using media and community health programmes, even with the existing good awareness of breast cancer. This is essential in order to avoid misconceptions and to frame the correct mind-set about breast cancer among women in Malaysia. Socio-cultural differences and religious practices should be taken into account by health care professionals when advising on breast cancer. Women need to be aware of the risk factors and symptoms of breast cancer so that early diagnosis can take place and the chances of survival improved.
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