[Various Bypass Surgery:Preoperative Simulation for STA-MCA Bypass].

In STA-MCA bypass surgery, it is important to select the optimal recipient using preoperative simulation to avoid complications. We report a preoperative simulation for STA-MCA bypass using the Brain LAB iPLAN platform®BRAIN LAB)and the 3DCG simulation software GRID®Kompath). Here, we introduce the basics and applications of preoperative simulation for occlusive atherosclerotic lesions and present a target bypass for periventricular anastomosis and peripheral vessels of aneurysms in Moyamoya disease. By creating and visualizing 3D fusion images, the optimal donor and recipient can be selected. Determining the skin incision and extent of craniotomy according to the case is also applicable to the minimally invasive STA-MCA bypass. Preoperative simulations enable accurate pinpoint bypass surgery and prevent complications.

Consideration of the reference value and number of measurements of the urinary sodium-to-potassium ratio based on the prevalence of untreated home hypertension: TMM Cohort Study.

The sodium-to-potassium (Na/K) ratio is known to be associated with blood pressure (BP). However, no reference value has been established since the urinary Na/K (uNa/K) ratio is known to have diurnal and day-to-day variations. Therefore, we investigated the number of days required to yield a better association between the morning uNa/K ratio and home BP (HBP) and determined a morning uNa/K ratio value that can be used as a reference value in participants who are not taking antihypertensive medication. This was a cross-sectional study using data from the Tohoku Medical Megabank Project Cohort Study. A total of 3122 participants borrowed HBP and uNa/K ratio monitors for 10 consecutive days. We assessed the relationship between the morning uNa/K ratio from 1 day to 10 days and home hypertension (HBP ≥ 135/85 mmHg) using multiple logistic regression models. Although a 1-day measurement of the morning uNa/K ratio was positively associated with home hypertension, multiple measurements of the morning uNa/K ratio were strongly related to home hypertension. The average morning uNa/K ratio was relatively stable after 3 days (adjusted odds ratio of home hypertension per unit increase in the uNa/K ratio for more than 3 days: 1.19-1.23). In conclusion, there was no threshold for the uNa/K ratio, and the morning uNa/K ratio was linearly associated with home hypertension. The Na/K ratio 2.0 calculated from the Dietary Reference Intakes for Japanese might be a good indication. Regarding the stability of the association between the morning uNa/K ratio and BP, more than 3 days of measurements is desirable.

Functional Prognosis Following Temporal Bone Chondroblastoma Resection: A Systematic Review and Case Illustration.

BACKGROUND: Chondroblastomas are rare tumors that account for <1% of all bone tumors, and 5.7% of them occur in the skull. The aim of this study was to investigate factors related to their functional prognosis by conducting a systematic review, including our own case. METHODS: A systematic review was conducted of case reports that clearly stated postoperative symptoms in temporal chondroblastomas. Tumor localization was limited to cases of the temporal bone. Cases not described in English were excluded. RESULTS: We obtained 30 articles comprising 44 cases and included our own case for a total of 45 cases. Postoperative asymptomatic cases accounted for 53.3% (24/45), and symptomatic cases accounted for 46.7% (21/45). Complications were observed in 31.1% (14/45) of cases. The main complications were facial palsy (9 cases), occlusal disorders (4 cases), and hearing loss (4 cases). The occurrence of facial palsy as a complication was considered likely. Tumor size was confirmed in 36 cases. Cases with postoperative complications were more likely to involve tumors ≥5 cm in size (77.8%, 7/9) compared with cases without complications (40.7%, 11/27). There was a significant association between rate of postoperative complications and tumor size (P = 0.061). CONCLUSIONS: As temporal chondroblastoma poses a risk of residual postoperative symptoms when the tumor grows, aggressive surgical treatment should be considered even in asymptomatic or small tumors.

The relationship between day-to-day variability in home blood pressure measurement and multiple organ function.

Blood pressure variability (BPV) is associated with the prognosis of cardiovascular diseases. However, it is unclear how BPV is related to various organs. The aim of this study is to investigate the association between BPV and multiple organ functions. A total of three hundred fifteen participants (114 males; mean age: 70 ± 9 years) participated in a community health checkup held in Tarumizu City. Home blood pressure (BP) was measured using a HEM-9700T (OMRON Healthcare, Kyoto, Japan). Day-to-day BPV was evaluated by the coefficient of variation (CV) of home BP measured in the morning for one month. N-terminal pro B-type natriuretic peptide (NT-pro BNP) and high-sensitivity (hs-)troponin T were measured as cardiac biomarkers. Liver stiffness and renal function were evaluated using the Fibrous-4 (Fib4) index and estimated glomerular filtration rate (eGFR), respectively. NT-pro BNP and hs-troponin T were divided by the median value. Fib4 index greater than 2.67 and eGFR less than 60 mL/min/1.73 m2 were defined as high Fib4 index and low eGFR, respectively. In a multivariable logistic regression analysis, the CV of systolic BP was significantly associated with high NT-pro BNP, high Fib 4 index, and low eGFR, but not with high hs-troponin T. In contrast, the CV of diastolic BP was not associated with low eGFR, and the other three biomarkers had the same results as systolic BP. In conclusion, day-to-day BPV of systolic BP is independently associated with NT-pro BNP, eGFR, and Fib4 index, but not with hs-troponin T. In contrast, diastolic BPV was not found to be associated with eGFR.

Impacts of the urinary sodium-to-potassium ratio, sleep efficiency, and conventional risk factors on home hypertension in a general Japanese population.

Recently, a high urinary sodium-to-potassium (Na/K) ratio and reduced sleep efficiency, in addition to conventional risk factors (obesity and excess alcohol intake), have been identified as risk factors for hypertension. We estimated the population attributable fraction (PAF) for home hypertension due to these risk factors in a general Japanese population. We conducted a cross-sectional study including 1384 participants (393 men and 991 women) to estimate the odds ratio (OR) and 95% confidence interval (CI) for the presence of any of the conventional risk factors using multivariable logistic regression analyses. The models were adjusted for sex, age, smoking status, and log-transformed average daily steps. We also estimated the OR and 95% CI for the presence of any of the overall risk factors. Furthermore, we calculated the PAF due to these risk factors. The results showed that the prevalence of home hypertension was 39.0% (540/1384). The presence of any of the conventional risk factors, as well as any of the overall risk factors, was significantly associated with an increased prevalence of hypertension (OR 2.80, 95% CI 2.15-3.65; OR 2.50, 95% CI 1.93-3.22, respectively). The PAF for hypertension due to the presence of any of the conventional risk factors and the PAF due to the presence of any of the overall risk factors were 30.2% and 39.0%, respectively. In conclusion, the impact of the overall risk factors, including the urinary Na/K ratio and sleep efficiency, on home hypertension was higher than that of conventional risk factors alone. The management of the urinary Na/K ratio and sleep efficiency as well as conventional risk factors might be important in the management of blood pressure.

The relationship between home blood pressure measurement and room temperature in a Japanese general population.

Blood pressure (BP) is influenced by various factors, and it is known that temperature and BP have a negative relationship. However, few reports have examined the relationship between BP and temperature throughout the day in the same participant over time. Therefore, this study aimed to investigate the relationship between BP and temperature in the morning and evening in the same participants during a time period of ~1 year. In total, 401 participants, who participated in a community-based health checkup survey in Tarumizu, Japan, were enrolled. Five participants were excluded due to missing data. All participants measured their BP and the room temperature at home using a blood pressure monitor (HEM-9700T, OMRON Healthcare, Kyoto, Japan). The mean systolic BP (SBP) and diastolic BP (DBP) in the morning were significantly higher than the mean of the measurements taken in the evening (SBP: morning vs. evening 128 ± 15 mmHg vs. 122 ± 14 mmHg, P < 0.0001; DBP: morning vs. evening 77 ± 10 mmHg vs. 72 ± 8 mmHg, P < 0.0001). Using a linear mixed model with participants as a random effect, SBP and DBP were significantly associated with temperature in both the morning and evening. In the morning, in almost every month except July, a significant association between SBP and temperature was observed. However, there was a significant relationship between evening BP and temperature in all months. In conclusion, BP was significantly related to temperature in both the morning and evening during the year-long study. Furthermore, BP and temperature were significantly associated in all months except morning measurements in July.

Sodium/potassium ratio change was associated with blood pressure change: possibility of population approach for sodium/potassium ratio reduction in health checkup.

Recently, the sodium (Na)/potassium (K) ratio was reported to be associated with blood pressure (BP). A Na/K ratio self-monitoring device using spot urine was established recently. Here, we assessed whether the urinary Na/K ratio change measured using the Na/K device was associated with BP change in a health checkup setting. We targeted 12,890 participants who attended the health checkup in Tome City, Miyagi between 2017 and 2018. Tome City introduced urinary Na/K ratio measurements during health checkups since 2017. For each year, we compared the baseline characteristics according to the urinary Na/K ratio and BP level. We assessed the relationship between change in urinary Na/K ratio and BP change using multiple regression analyses adjusted for age, sex, and change in body mass index (BMI) and alcohol intake. The average urinary Na/K ratio was significantly lower in 2018 than in 2017 (5.4 ± 3.0 to 4.9 ± 2.2, P < 0.01). The systolic BP of the participants in 2018 (130.9 ± 17.4 mmHg) was lower than that in 2017 (132.1 ± 17.9 mmHg). Moreover, the change in systolic BP and diastolic BP was positively associated with the change in urinary Na/K ratio. In conclusion, the association of the change in urinary Na/K ratio with hypertension and changes in systolic and diastolic BP can be explained by a change in alcohol intake, BMI, and urinary Na/K ratio. Therefore, measuring the urinary Na/K ratio in community settings is a potential population approach for counteracting hypertension.

A Case of Salivary Duct Carcinoma Intracranial Invasion due to Perineural Invasion Through the Facial Nerve.

BACKGROUND: Salivary duct carcinoma (SDC) is a rare parotid tumor that often develops as a rapidly growing mass with a poor prognosis. It has a high rate of distant metastases, sometimes with infiltration along nerves. We describe a case of SDC that originated outside the cranium and extended into the cranium along the path of the facial nerve. CASE DESCRIPTION: A 74-year-old man underwent magnetic resonance imaging at a local hospital, which revealed a tumor in the left internal acoustic canal; the patient was referred to our department. A left facial schwannoma was suspected, and magnetic resonance imaging was performed again 6 months later. Rapid tumor growth was confirmed, and the tumor was resected. The tumor displayed atypical epithelial cells with comedo necrosis and cribriform structure and was diagnosed as SDC. All residual intracranial tumors were removed using the middle fossa approach. The tumor, which was considered to be a primary tumor, was found near the stylomastoid foramen, and it was removed with the parotid gland. Five months after the initial surgery, metastasis to the trigeminal nerve was observed, and this was removed using a retrosigmoid approach, followed by radiation therapy. CONCLUSIONS: All 4 surgical specimens of this case were presented, and the path of tumor progression was examined in detail. Although the primary lesion was small, intracranial invasion along the facial nerve occurred. SDC should be considered as a tumor that can extend into the cranium, even with a small primary lesion.

Reduced sleep efficiency, measured using an objective device, was related to an increased prevalence of home hypertension in Japanese adults.

Few studies have reported the relationship between reduced sleep efficiency and the prevalence of hypertension independent of sleep duration in Japan. This study aimed to evaluate whether reduced sleep efficiency, measured using an objective device for >1 week, was related to an increased prevalence of hypertension independent of sleep duration in the general Japanese population. We conducted a cross-sectional study of 904 participants aged ≥20 years who lived in Miyagi Prefecture, Japan. Sleep efficiency was measured using a contactless biomotion sleep sensor for 10 continuous days. The participants were classified into two groups according to their sleep efficiency: reduced (<90%) or not reduced (≥90%). Hypertension was defined as morning home blood pressure ≥135/85 mmHg or self-reported treatment for hypertension. Multivariable logistic regression models were used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationship between sleep efficiency and hypertension adjusted for potential confounders. The results showed that two hundred and ninety-four individuals (32.5%) had reduced sleep efficiency, and 331 (36.6%) had hypertension. Individuals with reduced sleep efficiency had a higher body mass index and shorter sleep duration. In the multivariable analysis, reduced sleep efficiency was significantly related to an increased prevalence of hypertension (OR, 1.62; 95% CI, 1.15-2.28). In conclusion, reduced sleep efficiency was significantly related to an increased prevalence of hypertension in Japanese adults. Improvements in sleep efficiency may be important to reduce blood pressure in Japanese adults.

Multiple measurements of the urinary sodium-to-potassium ratio strongly related home hypertension: TMM Cohort Study.

Previous studies have reported a positive association between the urinary sodium-to-potassium (Na/K) ratio and hypertension, and multiple measurements of the casual urinary Na/K ratio are more strongly correlated with the 24-h urinary Na/K ratio than a single measurement. Multiple measurements of the urinary Na/K ratio might be more strongly associated with hypertension. We aimed to determine the association between multiple measurements of the casual urinary Na/K ratio and home hypertension compared with a single measurement. A population-based cross-sectional study was performed in Miyagi Prefecture, Japan. Subjects were over 20 years old and participated in the Tohoku Medical Megabank Project Cohort Study. We targeted 3273 subjects who borrowed home blood pressure (HBP) monitors and urinary Na/K ratio monitors for 10 consecutive days. The association between the urinary Na/K ratio and home hypertension (HBP ≥ 135/85 mmHg or under treatment for hypertension) was examined using multiple logistic regression models. To compare the prediction of home hypertension using multiple measurements with that using a single measurement, we calculated the area under the receiver operating characteristic curve (AUROC). Multiple measurements of the urinary Na/K ratio strongly related to home hypertension were better than 1 or 2 days of measurement (adjusted odds ratio of home hypertension per unit increase in urinary Na/K ratio over 6 days: 1.13-1.15). The AUROC of the urinary Na/K ratio measurement for home hypertension was stable after 5 days (AUROC = 0.779). In conclusion, multiple measurements of the urinary Na/K ratio are strongly related to home hypertension. This finding suggests that multiple measurements of the urinary Na/K ratio are useful for evaluating home hypertension.

The factors affecting adherence to a long-term interval walking training program in middle-aged and older people.

No long-term exercise training regimen with high adherence and effectiveness in middle-aged and older people is broadly available in the field. We assessed the adherence to, and effects of, our long-term training program comprising an interval walking training (IWT) and an information technology network system and the factors affecting adherence. Middle-aged and older men and women [n = 696, aged 65 ± 7(SD) yr] underwent IWT. The subjects were instructed to repeat five or more sets of fast and slow walking for 3 min each at ≥70 and 40% peak aerobic capacity for walking (V̇O2peak), respectively, per day ≥4 days/wk for 22 mo. Adherence was assessed as training days accomplished relative to the target of 4 days/wk over 22 mo. The effects on the V̇O2peak and lifestyle-related disease score were evaluated every 6 mo. The independent factors affecting adherence were assessed by multiple-regression analysis after adjustment for baseline physical characteristics and other possible covariates, including vasopressin V1a receptor polymorphisms. The adherence over 22 mo averaged 70% and was highly correlated with a 13% reduction in the lifestyle-related disease score (R(2) = 0.94, P = 0.006) and with a 12% increase in V̇O2peak (R(2) = 0.94, P = 0.006). The major determinant of higher adherence was lower baseline body mass index (BMI) (P < 0.0001) and male sex (P < 0.0001). For men, in addition to BMI, nonsmokers (P = 0.031) and V1a receptor polymorphisms (P = 0.033) were independent determinants of higher adherence. Thus the long-term IWT program is an effective regimen. Moreover, baseline BMI and sex for all subjects, and smoking and V1a receptor polymorphisms for men, were associated with adherence.

Ethanol stress impairs protein folding in the endoplasmic reticulum and activates Ire1 in Saccharomyces cerevisiae.

Impaired protein folding in the endoplasmic reticulum (ER) evokes the unfolded protein response (UPR), which is triggered in budding yeast, Saccharomyces cerevisiae, by the ER-located transmembrane protein Ire1. Here, we report that ethanol stress damages protein folding in the ER, causing activation of Ire1 in yeast cells. The UPR likely contributes to the ethanol tolerance of yeast cells.

Energy expenditure during 2-day trail walking in the mountains (2,857 m) and the effects of amino acid supplementation in older men and women.

We compared relative exercise intensity and active energy expenditure (AEE) on trail walking in the mountains, with those of daily exercise training, and whether branched-chain amino acid (BCAA) and arginine supplementation attenuated the release of markers indicating muscle damage and declines in physical performance. Twenty-one subjects (~63 years) were divided into two groups: amino acid (AA, 51 g of amino acids and 40 g of carbohydrate, male/female = 6/4) or placebo (PL, 91 g of carbohydrate, male/female = 6/5) supplementation during 2 days of trail walking in the mountains. We measured heart rate (HR), AEE, fatigue sensation, water and food intake, and sweat loss during walking. In addition, we measured peak aerobic capacity [Formula: see text] and heart rate (HR(peak)) with graded-intensity walking, vertical jumping height (VJ) before and after walking. We found that average HR and AEE during uphill walking were ~100% HR(peak) and ~60% [Formula: see text], while they were ~80 and ~20% during downhill walking, respectively. Moreover, average total AEE per day was sevenfold that of their daily walking training. VJ after walking remained unchanged compared with the baseline in AA (P > 0.2), while it was reduced by ~10% in PL (P < 0.01), although with no significant difference in the reduction between the groups (P > 0.4). The responses of other variables were not significantly different between groups (all, P > 0.2). Thus, trail walking in the mountains required a high-intensity effort for older people, while the effects of BCAA and arginine supplementation were modest in this condition.

Reduced hyperthermia-induced cutaneous vasodilation and enhanced exercise-induced plasma water loss at simulated high altitude (3,200 m) in humans.

We examined whether less convective heat loss during exercise at high altitude than at sea level was partially caused by reduced cutaneous vasodilation due to enhanced plasma water loss into contracting muscles and whether it was caused by hypoxia rather than by hypobaria. Seven young men performed cycling exercise for 40 min at 50% peak aerobic power in normoxia at (710 mmHg) 610 m, determined before the experiments, in three trials: 1) normobaric normoxia at 610 m (CNT), 2) hypobaric hypoxia [low pressure and low oxygen (LPLO)] at 3,200 m (510 mmHg), 3) normobaric hypoxia [normal pressure and low oxygen (NPLO)] at 610 m, in an artificial climate chamber where atmospheric temperature and relative humidity were maintained at 30°C and 50%, respectively. Subjects in CNT and LPLO breathed room air, whereas those in NPLO breathed a mixed gas of 14% O2 balanced N2, equivalent to the gas composition in LPLO. We measured change in PV (ΔPV), oxygen consumption rate (Vo2), mean arterial blood pressure (MBP), esophageal temperature (T(es)), mean skin temperature (T(sk)), forearm skin blood flow (FBF), and sweat rate (SR) during exercise. Although Vo2, MBP, T(sk), and SR responses during exercise were similar between trials (P > 0.05), the sensitivity of forearm vascular conductance (FBF/MBP) in response to increased T(es) was lower in LPLO and NPLO than in CNT (P < 0.05), whereas that of SR was not, resulting in a greater increase in T(es) from minute 5 to 40 of exercise in LPLO and NPLO than in CNT (P = 0.026 and P = 0.011, respectively). ΔPV during exercise was twofold greater in LPLO and NPLO than in CNT. These variables were not significantly different between LPLO and NPLO. Thus reduced convective heat loss during exercise at 3,200 m was partially caused by reduced cutaneous vasodilation due to enhanced PV loss. Moreover, this may be caused by hypoxia rather than by hypobaria.

Protein and carbohydrate supplementation during 5-day aerobic training enhanced plasma volume expansion and thermoregulatory adaptation in young men.

We examined whether protein and carbohydrate (CHO) supplementation during 5-day training enhanced plasma volume (PV) expansion and thermoregulatory and cardiovascular adaptations in young men. Eighteen men [age 23 ± 4 (SD) yr] were divided into two groups according to supplements: placebo (CNT: 0.93 kcal/kg, 0.00 g protein/kg, n = 9) and protein and CHO (Pro-CHO: 3.6 kcal/kg, 0.36 protein/kg, n = 9). Subjects in both groups performed a cycling exercise at 70% peak oxygen consumption rate (VO2peak), 30 min/day, for 5 consecutive days at 30°C ambient temperature and 50% relative humidity and took either a placebo or Pro-CHO within 10 min after exercise for each day. Before and after training, PV at rest, heart rate (HR), and esophageal temperature (T(es)) during 30-min exercise at 65% of pretraining VO2peak in the same condition as training were determined. Also, the sensitivity of the chest sweat rate (ΔSR/ΔT(es)) and forearm vascular conductance (ΔFVC/ΔT(es)) in response to increased T(es) were determined. After training, PV and cardiac stroke volume (SV) at rest increased in both groups (P < 0.001) but the increases were twofold higher in Pro-CHO than CNT (P = 0.007 and P = 0.078, respectively). The increases in HR from 5 to 30 min and T(es) from 0 to 30 min of exercise were attenuated after training in both groups with greater attenuation in Pro-CHO than CNT (P = 0.002 and P = 0.072, respectively). ΔSR/ΔT(es) increased in CNT (P = 0.052) and Pro-CHO (P < 0.001) and the increases were higher in Pro-CHO than CNT (P = 0.018). ΔFVC/ΔT(es) increased in Pro-CHO (P < 0.001), whereas not in CNT (P = 0.16). Thus protein-CHO supplementation during 5-day training enhanced PV expansion and thermoregulatory adaptation and, thereby, the reduction in heat and cardiovascular strain in young men.

Vasopressin V1a receptor polymorphism and interval walking training effects in middle-aged and older people.

We assessed whether single nucleotide polymorphism rs1042615 of the vasopressin V1a receptor altered the indices of lifestyle-related diseases in middle-aged and older people (mean+/-SD: 64+/-7 years), and, if so, whether it also altered the effects of interval walking training (IWT). CC, CT, and TT carriers of rs1042615 (42, 118, and 64 men, respectively; 113, 263, and 154 women, respectively) performed IWT. We included 5 sets of 3-minute fast walking at > or =70% peak aerobic capacity for walking and 3-minute slow walking at 40% peak aerobic capacity per day for > or =4 days per week for 5 months. Before IWT, the body mass index and diastolic blood pressure (DBP) for men were 25.1+/-0.3 kg/m(2) (mean+/-SE) and 84+/-1 mm Hg in TT, higher than the 23.6+/-0.4 kg/m(2) and 78+/-1 mm Hg in CC, respectively (P<0.01), differences that disappeared after IWT despite similar training achievement between groups (P>0.6). After IWT, body mass index and DBP decreased in TT (-0.9+/-0.1 kg/m(2) and -5+/-1 mm Hg, respectively), more than in CC (-0.5+/-0.1 kg/m(2) and 1+/-1 mm Hg, respectively; P<0.05), with a greater decrease in low-density lipoprotein cholesterol in TT than CC carriers (P<0.01). The decreases in DBP and low-density lipoprotein cholesterol were still greater in TT carriers even after adjustment for their pretraining values. On the other hand, for women, these parameters before IWT and their changes after IWT were similar among CC, CT, and TT carriers. Thus, polymorphism rs1042615 of the V1a receptor altered body mass index and DBP in middle-aged and older men and the training-induced responses of DBP and low-density lipoprotein cholesterol, whereas women did not show any of these responses.

Development of enzyme-linked immunosorbent assay for detection of alkylphenol polyethoxylates and their biodegradation products.

An enzyme-linked immunosorbent assay (ELISA) was developed for the quantitative analysis of alkylphenol polyethoxylates (APnEOs) and their biodegradation products. To generate a specific monoclonal antibody (mAb) for the ELISA, hybridoma cells were produced by the fusion of mouse myeloma cells and spleen cells from mice immunized with nonylphenol polyethoxylate (NPnEO) derivatives coupled to bovine serum albumin. The developed ELISA showed the detection limits of 16 and 30 microg/L NP10EO when 10% and 60% (v/v) methanol solutions were used as assay diluent. The mAb was shown to be specific to APnEOs and their metabolites, such as short-ethoxy-chain APnEOs and alkylphenoxy carboxylic acids, except for nonylphenol. Moreover, no response was observed with non-APnEO surfactants as well as other compounds structurally similar to APnEOs. The percentage river water recoveries of 85-118% were obtained for 10 microg/L NP10EO fortification after preconcentration by C18 solid-phase extraction. The ELISA was also validated by comparing it with high-performance liquid chromatography for the analysis of APnEOs and their metabolites in river samples; the correlation coefficient between the values obtained by these assays was 0.96.

Synthesis and anti-Helicobacter pylori activity of pyloricidin derivatives II. The combination of amino acid residues in the dipeptidic moiety and its effect on the anti-Helicobacter pylori activity.

The novel natural antibiotics pyloricidin A, B and C, consisting of a common (2S,3R,4R,5S)-5-amino-2,3,4,6-tetrahydroxyhexanoyl-beta-D-phenylalanine moiety and a terminal peptidic moiety (pyloricidin A: L-valine-L-valine-L-leucine; pyloricidin B: L-valine-L-leucine; pyloricidin C: L-leucine), exhibit potent and highly selective anti-Helicobacter pylori activity. In order to develop more potent compounds and to investigate structure activity relationships for the peptidic moiety with regard to the combination of amino acids, a series of derivatives with various dipeptidic moieties were prepared and evaluated for their anti-H. pylori activity. The combination of the two amino acids in the moiety was found to have a significant effect on the activity; the compound with Nva-Abu showed excellent anti-H. pylori activity with an MIC value of 0.013 microg/ml against H. pylori TN2. In addition, this compound was found to show 60% clearance of H. pylori from infected Mongolian gerbils upon repetitive oral administration (10 mg/kg, b. i. d. for 7 days).

Total synthesis of novel antibiotics pyloricidin A, B and C and their application in the study of pyloricidin derivatives.

The novel natural antibiotics pyloricidin A, B and C, which possess potent and highly selective anti-Helicobacter pylori activity, were synthesized from D-galactosamine as a chiral template for the common (2S,3R,4R,5S)-5-amino-2,3,4,6-tetrahydroxyhexanoic acid moiety. The synthetic strategy, using 2-amino-2-deoxyuronic acid derivatives as key intermediates, was also useful to prepare a series of derivatives modified at the beta-D-phenylalanine and with altered stereochemistry on the 5-amino-2,3,4,6-tetrahydroxyhexanoic acid moiety. From the drastic decrease of their anti-H. pylori activity, it was clear that the beta-D-phenylalanine part and the stereochemistry of the 5-amino-2,3,4,6-tetrahydroxyhexanoic acid moiety were significant for the activity.