Invited Review Article
Uremic Toxicity of Indoxyl Sulfate
TOSHIMITSU NIWA
pg(s) 1-11
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Indoxyl sulfate, a uremic toxin, is accumulated in the serum of chronic kidney disease (CKD) patients. A part of the dietary protein-derived tryptophan is metabolized into indole by tryptophanase in intestinal bacteria. Indole is absorbed into the blood from the intestine, and is metabolized to indoxyl sulfate in the liver. Indoxyl sulfate is normally excreted into urine. In CKD, however, an inadequate renal clearance of indoxyl sulfate leads to its elevated serum levels. The oral adsorbent AST-120 reduces the serum levels of indoxyl sulfate by adsorbing indole in the intestines and stimulating its excretion into feces. I have proposed a protein metabolite theory by which endogenous protein metabolites such as indoxyl sulfate play a significant role in the progression of CKD. A progressive decline in the glomerular filtration rate leads to increased serum levels of endogenous protein metabolites such as indoxyl sulfate, and to the adverse effects of their overload on the remnant nephrons. Indoxyl sulfate stimulates progressive both tubulointerstitial fibrosis and glomerular sclerosis by increasing the expression of transforming growth factor-b1, a tissue inhibitor of metalloproteinase-1 and proa1 (I) collagen, leading to a further loss of nephrons. AST-120 delays the progression of CKD by removing serum indoxyl sulfate. Moreover, indoxyl sulfate induces oxidative stress in tubular cells, mesangial cells, vascular smooth muscle cells, endothelial cells and osteoblasts as well as stimulating aortic calcification in hypertensive rats, it is also involved in the progression of CKD, cardiovascular disease (CVD) and osteodystrophy. Thus, the removal of indoxyl sulfate by AST-120 ameliorates the progression of not only CKD, but also of CVD and osteodystrophy.
Original Papers
Survival and Ambulatory Function after Endoprosthetic Replacement for Metastatic Bone Tumor of the Proximal Femur
HIROATSU NAKASHIMA, HIROHISA KATAGIRI, MITSURU TAKAHASHI and HIDESHI SUGIURA
pg(s) 13-21
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The purpose of this study was to clarify the ambulatory functional and oncological outcomes of tumor excision and endoprosthetic reconstruction for a metastatic lesion of the proximal femur. Subjects comprised 40 patients (18 women, 22 men; average age 63.4 years). The mean follow-up periods were 15.2 months for patients dying of the disease, and 38.7 months for survivors. Seven patients were lost to follow-up for 1.9 to 13.1 months. Endoprosthesis was performed after intralesional aggressive curettage in 20 patients and following excision of the lesion with a clear margin, in another 20. Postoperative radiation therapy was carried out on 27 limbs (intralesional 13, marginal 6, wide 8). Chemotherapy was administered to 19 patients after discussion with the medical oncologist. The cumulative survival rates at 6 and 12 months were 60% and 35%, respectively, while the rates with ambulant status were 48% at 6 months and 34% at 12 months. An analgesic effect was achieved for all patients. Ambulatory function was restored in 34 patients with a mean ambulant period of 17.8 months; however, the other 6 patients remained non-ambulatory. The ambulant period expressed as a percentage of survival time averaged 75.9%. Though there was local recurrence in 4 of 40 patients, ambulant function was not affected. Postoperative ambulatory function was inferior in patients with a short life expectancy; those with moderate or long life expectancy are good candidates for endoprosthetic replacement after tumor excision and can regain ambulant function for as long as nearly 80% of the survival period.
Factors Affecting the Utilization of Antenatal Care Services among Women in Kham District, Xiengkhouang Province, Lao PDR
YANG YE, YOSHITOKU YOSHIDA, MD. HARUN-OR-RASHID and JUNICHI SAKAMOTO
pg(s) 23-33
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The aim of this study was to identify the socio-demographic characteristics, knowledge, attitude and accessibility factors related to the utilization of antenatal care (ANC) service among pregnant women in the Kham District, Laos. Data for this cross-sectional study were collected in July 2008, using a two-stage cluster sampling strategy from 24 selected villages in the Kham District. A total of 310 married women of reproductive age who had at least one child and had delivered the last child within two years from the date of data collection were interviewed using structured questionnaires. To examine the predictors of ANC utilization, odds ratios (OR) and 95% confidence intervals (CI) were estimated through a logistic regression model. The results showed that about 53.9% of mothers did not receive any ANC service due to the following reasons: no time (93.4%), not necessary (83.8%), feeling embarrassed (74.3%), and living far away from the ANC facility (71.3%). We found that significant predictors of ANC utilization (p-value < 0.05) were: level of education (OR = 6.8, 95% CI = 2.7–16.8), income (OR = 2.6, 95% CI = 1.2–5.7), knowledge (OR = 6.5, 95% CI = 2.4–17.6), attitude (OR = 3.0, 95% CI = 1.3–7.1), distance (OR = 2.9, 95% CI = 1.1–7.6), availability of public transportation (OR = 4.5, 95% CI = 2.0–10.4), cost of transportation (OR = 2.5, 95% CI = 1.1–5.7), and cost of service (OR = 4.6, 95% CI = 2.2–9.6). Our study shows that the utilization of ANC service was very low. Among other factors, limited knowledge, and lack of a good attitude along with misconceptions about ANC services were the major constraints behind this low utilization. Future health care activities should be focusing on improving women’s awareness of ANC. ANC staffs should conduct frequent visits to pregnant women until ANC services become easily accessible to them.
Goshajinkigan (Chinese Herbal Medicine Niu-Che-Sen-Qi-Wan) Improves Insulin Resistance in Diabetic Rats via the Nitric Oxide Pathway
XIAOCHEN HU, JUICHI SATO, GUSTAVO BAJOTTO, OYUN KHOOKHOR, ISAO OHSAWA, YOSHIHARU OSHIDA and YUZO SATO
pg(s) 35-42
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Goshajinkigan (GJG), an aqueous extract of a combination of 10 herbal medicines, is widely used for the treatment of diabetic neuropathy in Japan. In this study, the effect of GJG on insulin-induced glucose disposal in normal and streptozotocin (STZ) diabetic rats was analyzed using the euglycemic clamp technique. Male Wistar rats, aged 9 weeks, were randomly assigned to six groups: group NS, normal rats receiving saline; group NG, normal rats receiving GJG (800 mg·kg–1·day–1, p.o.); group NGL, normal rats receiving GJG + NG-monomethyl-L-arginine (L-NMMA, 1 mg·kg–1·min–1, i.v.); group DS, diabetic rats receiving saline; group DG, diabetic rats receiving GJG; group DGL, diabetic rats receiving GJG + L-NMMA. After daily oral administrations of saline or GJG for one week, euglycemic clamp experiments were performed. The metabolic clearance rates of glucose (MCR) in the DS, DG, and DGL groups (8.7 ± 2.9, 18.2 ± 2.5, and 8.1 ± 1.8 ml·kg–1·min–1, respectively) were significantly lower than those in the NS, NG, and NGL groups (24.1 ± 4.5, 24.5 ± 3.1, and 22.2 ± 2.1 ml·kg–1·min–1, respectively). In addition, the MCR in the DG group was significantly higher than that in the DS and DGL groups, while no significant difference was detected among the NS, NG, and NGL groups. Furthermore, the amelioration of insulin resistance by GJG in diabetic rats was hampered by L-NMMA infusion. These results suggest that daily GJG administrations ameliorate insulin resistance in STZ-diabetic rats, and that the nitric oxide pathway may mediate the effect of GJG.
Dental Caries and Gingivitis among Pregnant and Non-Pregnant Women in Chiang Mai, Thailand
NOOCHPOUNG RAKCHANOK, DEJPITAK AMPORN, YOSHITOKU YOSHIDA, MD. HARUN-OR-RASHID and JUNICHI SAKAMOTO
pg(s) 45-50
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The aims of this study were to identify dental caries and gingivitis among pregnant women, and to compare it with those in non-pregnant women in Chiang Mai, Thailand. Data were collected from 197 women (94 pregnant and 103 non-pregnant) from June to August, 2008. Dental caries and gingivitis was defined clinically according to the World Health Organization (WHO) diagnostic criteria. Over 74.0% of pregnant women had caries, and 86.2% had gingivitis. There were significant differences between pregnant and non-pregnant women with regard to dental caries (p<0.001) and gingivitis (p=0.021). The pregnant women were 2.9 times more likely to suffer from dental caries (95% confidence intervals (CI), 1.6–5.4), and 2.2 times more (95% CI, 1.1–4.7) from gingivitis compared to non-pregnant women. Farmers (Odd ratio (OR), 7.0; 95% CI, 1.8–26.3), high school graduation (OR, 3.0; 95% CI, 1.2–7.3), and universal health insurance coverage (OR, 2.1; 95% CI, 1.0–4.3) were significant predictors for gingivitis. Only high school graduates were found to be significant predictors of dental caries with an OR of 2.8 (95% CI, 1.2–6.3). Poor oral hygiene (OR, 2.2; 95% CI, 0.8–6.5), lack of knowledge (OR, 2.0; 95% CI, 0.6–6.3), and poor oral hygiene habits (OR, 3.0; 95% CI, 1.1–8.6) were important risk factors for dental caries. Similarly, inadequate oral hygiene status (OR, 24.8; 95% CI, 5.5–112.2), and poor oral health habits (OR, 5.2; 95% CI, 1.1–25.2) were found to be significant risk factors for gingivitis among pregnant women indicating, that most women should be trained in proper oral hygiene practices. Community awareness programs should be conducted to increase women’s awareness of such hygienic practices.
Factors Affecting Low Birth Weight at Four Central Hospitals in Vientiane, Lao PDR
LOUANGPRADITH VIENGSAKHONE, YOSHITOKU YOSHIDA, MD. HARUN-OR-RASHID and JUNICHI SAKAMOTO
pg(s) 51-58
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The purpose of this study was to determine the factors affecting low birth weight (LBW) at four central hospitals in Vientiane, the capital city of Lao PDR. We collected data from 235 mothers with LBW babies and 265 with babies of normal birth weight (NBW) who had delivered them at four central hospitals from March to June of 2008. Among the mothers of LBW babies, 84.7% were aged 18–35 years, 7.7% aged <18 years, and another 7.7% aged >35 years, while the corresponding figures among those with NBW babies were 97.7%, 1.1%, and 1.1%, respectively. The mothers in a low income group earning <1 million Kips (1 USD=8,700 Kips) per month numbered 68.9% for the LBW group and 15.1% for the NBW group. We estimated both odds ratios (ORs) and 95% confidence intervals (CIs) to explore associations between LBW outcomes and related factors. Significant associations with LBW were found for delivery at age <18 years (OR=8.6, 95% CI=2.4–30.7), monthly family income <1 million Kips (OR=13.9, 95% CI=8.8–21.9), physical labor during pregnancy (OR=5.0, 95% CI=3.1–8.1), and first child birth (OR=2.2, 95% CI=1.5–3.3). Mothers with an inadequate level of knowledge regarding healthy pregnancy practices were at 10.1 times higher risk of developing LBW babies (95% CI=6.7–15.2). Mothers lacking adequate nutritional practices were more prone to deliver LBW babies with an OR of 8.9 (95% CI=5.6–14.3). The ORs of LBW babies for those factors were high among Lao mothers. Improving a mother’s knowledge of and practice for a healthy pregnancy needs to be emphasized to reverse these LBW trends.
Efficacy of Membranous Cultured Periosteum for the Treatment of Patients with Severe Periodontitis: a Proof-of-Concept Study
HIROKAZU MIZUNO, HIDEAKI KAGAMI, JUNJI MASE, DAIKI MIZUNO and MINORU UEDA
pg(s) 59-70
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Osteogenic cells have been found within periosteal tissue. Periosteal cells will also form a membranous structure under the appropriate culture conditions. We have characterized the osteogenic potential of this membranous cultured periosteum (CP) and have demonstrated that CP can successfully regenerate alveolar bone defects in a canine periodontitis model. The aim of this study is to demonstrate periodontal tissue regeneration by using CP for patients with severe periodontitis. CP was applied in treatments for severe alveolar bone defects for a total of seven teeth among four periodontitis patients. Bone formation was evaluated by dental radiography 4 months after grafting, with a follow-up period of 12 to 15 months. CP was successfully generated and formed a membrane (approximately 4 cm in diameter) about 4 weeks after attachment to the dish. Vertical bone gain (3 to 8 mm) was observed in all grafted areas at 4 months post-surgery. The probing depth was also reduced to its normal depth and remained so beyond one year. Results from the present cases suggest that periodontitis patients with bone defects can benefit from CP treatment. Post-operative evaluation indicates periodontal tissue regeneration after CP treatment, suggesting a broad application for patients with periodontal disease.
Risk Behaviours and Associated Factors among Medical Students and Community Youths in Myanmar
SAN SAN HTAY, MYO OO, YOSHITOKU YOSHIDA, MD. HARUN-OR-RASHID and JUNICHI SAKAMOTO
pg(s) 71-81
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We conducted a cross-sectional study of the risk behaviours inherent in tobacco smoking, alcohol consumption and premarital sex, among 400 medical students (186 males) from a medical university, Yangon, and 410 community youths (244 males) 15 to 24 years of age from selected townships in Myanmar. As a result, we found that 12.8% smoked, 34.5% consumed alcohol and 10.1% engaged in premarital sex, among medical students, whereas among community youths, the corresponding rates were 28.8%, 32.1% and 11.9%. There was a significant difference in the prevalence of all risk behaviours between male and female respondents. Such risk behaviours were more dominant among males, while being very low among females. Among male respondents, the smoking rate was significantly higher among community youths (46.7%) than among medical students (26.9%); however, student alcohol consumption (58.5%) was greater than that of community youths (47.1%). Premarital sexual experience did not differ significantly between the two groups. These risk behaviours were correlated with one another. Having close friends who engaged in similar behaviours was found to be the major contributing factor for those kinds of risk among both groups. Our results highlighted the fact that, despite their relatively sophisticated knowledge of risks, the prevalence of risky behaviour among the medical students was no less frequent than among community youths. To diminish those risks, evaluations of actual conditions, behaviour modifications and specific preventive measures compatible with existing culture and changing lifestyles should be undertaken. Effective adolescent health programs at schools, colleges and universities should be revised and emphasized.
Robustness of the Oxygen Uptake Efficiency Slope to Exercise Intensity in Patients with Coronary Artery Disease
REIZO BABA, KAZUO TSUYUKI, HIROYOSHI YANO, KENJI NINOMIYA and KUNIO EBINE
pg(s) 83-89
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Oxygen uptake efficiency slope (OUES) and ventilatory efficiency (V˙ E/V˙CO2 slope) are widely used as submaximal measurements of cardiopulmonary exercise testing as the evaluator or prognosticator of cardiac diseases. However, very few studies have compared the effects of submaximal exercise on these measurements. A total of 58 patients with coronary artery disease underwent maximal cardiopulmonary exercise testing on a treadmill. We compared the values obtained from the first 75% (V˙ E/V˙CO2 slope75 and OUES75) and 90% (V˙ E/V˙CO2 slope90 and OUES90) of the exercise period with the entire duration (V˙ E/ V˙ CO2 slope100 and OUES100). Although OUES100, OUES90 and OUES75 were virtually identical, submaximal calculations of V˙ E/V˙CO2 slope underestimated the measurements. The Bland-Altman method revealed that submaximal measurements of OUES agreed very well with maximal OUES (limits of agreement –5.0% to +6.0% for OUES90, and –11.5% to +12.9% for OUES75). However, the submaximal calculations of V˙ E/ V˙ CO2 slope showed rather poor agreement with the maximal calculations (limit of agreement –11.8% to +3.1% for V˙ E/V˙CO2 slope90, and –20.8% to +5.3%% for V˙ E/V˙CO2 slope75). These results revealed that both the OUES and the V˙ E/V˙CO2 slopes are not overly influenced by exercise.
Omental Flap Closure of Refractory Wounds: Rat Model
MASASHI HISHIDA, KAZUHIRO TORIYAMA, YORIKO YAMASHITA, SHINYA AKATSUKA, AKEMI HAYAKAWA, SHUHEI TORII and YUZURU KAMEI
pg(s) 91-99
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Omental flaps, with their associated rich and pliable vascular arcades, are frequently used in clinical practice for the reconstruction of complex and irregular defects. There is little experimental evidence, however, to prove that omental flaps can be a useful tool for the defects. Using a gastric-wall defect model, we performed histological and immunocytochemical examinations. We created an omental flap lining a 2.0-mm defect perforating the center of the anterior wall of a rat stomach. We examined the tissue response during gastric wall regeneration by H&E and Masson trichrome stains. We also performed immunocytochemical studies for the detection of proliferating cell nuclear antigen (PCNA), factor VIIIrelated antigen, fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF). One day after the operation, the omental flap was found to firmly adhere to the gastric serosa surrounding the defect. An extensive inflammatory response occurred from Day 1 to 3 with dilated vessels in the omentum. From Days 3 to 7, a significant number of PCNA-positive cells, FGF-2-positive cells and VEGF-positive cells were observed at the edge of the mucosa and within the granulation tissue. On Day 4, in place of extensive inflammation, an exuberant granulation tissue response was observed from the omentum. The defect had been covered by stratified villi by Day 7. This study demonstrated that an omental flap came to rapidly adhere to the defect serving as a source of extensive inflammation and granulation for the rich and pliable vascular arcades.
Note
Introduction of the Standard Prehospital Stroke Life Support (PSLS) Training of EMS Paramedics for the Prehospital Management of Cerebrovascular Disease in Japan
NOBUYUKI SUZUKI
pg(s) 101-106
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Although the introduction of t-PA (tissue plasminogen activator) was considered radical treatment for acute cerebral ischemic disease, the actual number of cases for such administration was limited in Japan for many reasons; one such reason was related to the ability of EMT (emergency medical technician) paramedics to transport patients to the proper hospital for treatment within 2 hours of onset. From this point of view, the Committee of the Prehospital Stroke Life Support (PSLS) of the Japanese Society for Emergency Medicine (JSEM) developed an original standard for prehospital treatment of stroke. In this paper, the author provides an overview of PSLS and the half-day practical course, which has been widely disseminated over a short period of time.
