The factors associated with pain severity in patients with knee osteoarthritis vary according to the radiographic disease severity: a cross-sectional study.

OBJECTIVES: Knee osteoarthritis (OA) pain is suggested to be associated with inflammation and detrimental mechanical loading across the joint. In this cross-sectional study, we simultaneously examined the inflammation and alignment of the lower limb and examined how the pain components varied depending on the disease progression. DESIGN: One-hundred sixty female medial type of early- [n = 74 in Kellgren-Lawrence (K/L) 2] to advanced-stage (n = 96 in K/L >2) knee OA subjects (70.5 years on average) were enrolled. Knee pain was evaluated using a pain visual analog scale (VAS) and the pain-related subcategory of the Japanese Knee Osteoarthritis Measure (JKOM-pain). The serum interleukin (sIL)-6 level reflecting synovitis, and the high sensitivity C-reactive protein (hs-CRP) level were measured to evaluate the severity of inflammation. The anatomical axis angle (AAA) was measured as an alignment index. The ß-coefficient was estimated after adjusting for age and the body mass index (BMI) using a multiple linear regression analysis. RESULTS: Multiple linear regression analyses showed that the sIL-6 levels, but not AAA, associated with the pain VAS [ß = 10.77 (95% confidence interval (CI): 4.14-17.40), P < 0.01] and JKOM-pain scores [ß = 3.19 (95% CI: 1.93-4.44), P < 0.001] in the early stage. Conversely, AAA, but not the sIL-6 levels, was found to be associated with the pain VAS [ß = -1.29 (95% CI: -2.51 to -0.08), P < 0.05] and JKOM-pain scores [ß = -0.49 (95% CI: -0.82 to -0.16), P < 0.01] in the advanced stage. CONCLUSIONS: The presence of a higher level of sIL-6 and the varus alignment of the joint is associated with pain in early- and advanced-stage knee OA patients, respectively.

Is the reverse cycle during chewing abnormal in children with primary dentition?

The purpose of this study was to clarify whether the reverse cycle during chewing is abnormal in children with primary dentition. Children with normal primary dentition (N = 23; 5.5 +/- 0.8 years) and female adults (N = 25; 20.7 +/- 1.9 years) participated in this study. Chewing movement was recorded using an opto-electronic analysis system with six degrees-of-freedom (TRI-MET, Tokyo-shizaisha; Tokyo, Japan). Each subject was given a stick of chewing gum (new TRIDENT, WARNER-LAMBERT CO., Morris Plains, NJ, USA) and instructed to chew it normally. Starting from the maximum intercuspal position, each chewing sequence was recorded over a period of 20 s. A custom computer program identified individual chewing cycles. Frontal views were used to distinguish seven types of cycle shapes according to Ahlgren (Acta Odontol Scand, 24, 1966, 1-109; Acta Odontol Scand, 25, 1967, 3-13). Multilevel statistical models evaluated differences between children and adults. In the adults, type II cycles that initially opened towards the balancing side and then moved towards the working side were the most common, and the closing pathway was lateral to the opening pathway. In the children, type V (reverse) cycles that opened towards the working side were most common, the closing pathway was medial to the opening pathway, and there was a smaller lateral component during opening and closing than in adults (P < 0.05). We conclude that the reverse cycle is not abnormal because normal children with primary dentition have a smaller lateral component and difficulty in controlling asymmetric muscle activity.

Differential activation of dopaminergic systems in rat brain basal ganglia by morphine and methamphetamine.

Typical abused drug-induced behavioral changes are ordinarily mediated by the mesolimbic dopaminergic system and even the phenotypes of behavior are different from each other. However, the mechanisms that underlie the behavioral changes induced by these abused drugs have not yet been elucidated. The present study was designed to investigate the mechanisms that underlie how abused drugs induce distinct behavioral changes using neurochemical as well as behavioral techniques in rats. Methamphetamine (2mg/kg) more potently increased dopamine release from the striatum more than that from the nucleus accumbens. In contrast, the administration of morphine (10mg/kg) produced a significant increase in the release of dopamine from the nucleus accumbens, but not the striatum, which is accompanied by a decrease in the release of GABA in the ventral tegmental area. These findings indicate that morphine and methamphetamine differentially regulate dopaminergic systems to produce behavioral changes, even though both drugs have abuse potential through activation of the mesolimbic dopaminergic system.

Inhibitory effect of flavonoids from citrus plants on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.

To search for possible anti-tumor promoters, thirteen flavones (1-13) obtained from the peel of Citrus plants were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these flavones, 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT) (13) exhibited significant inhibitory effects on the EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, compound 13 exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

Inhibitory effect of Epstein-Barr virus activation by Citrus fruits, a cancer chemopreventor.

To search useful compounds in Citrus fruit for cancer chemoprevention, we carried out a primary screening of extracts of fruit peels and seeds from 78 species of the genus Citrus and those from two Fortunella and one Poncirus species, which were closely related to the genus Citrus. These Citrus extracts inhibited the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) as a useful screening method for anti-tumor promoters. Our results indicated that Citrus containing substances may be inhibit susceptibility factors involved in the events leading to the development of cancer.

Cancer chemopreventive activity of 3,5,6,7,8,3',4'-heptamethoxyflavone from the peel of citrus plants.

Nobiletin and 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT), isolated from the peel of Citrus plants, were examined for the anti-tumor-initiating activity on two-stage carcinogenesis of mouse skin tumors induced by a nitric oxide donor, (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexenamide, as an initiator and 12-O-tetradecanoylphorbol-13-acetate as a promoter. HPT exhibited the remarkable anti-tumor-initiating effect on mouse skin and it suggested the possibility of HPT being a chemopreventive agent against nitric oxide (NO) carcinogenesis.

Inhibitory effect of flavonoid derivatives on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.

To search for possible anti-tumor promoters, ten flavonoid derivatives (1-10) synthesized from morin and quercetin were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these compounds, pentaallyl ethers (9, 10) showed significant inhibitory effects on EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate. Further, quercetin pentaallyl ether (10) exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

Smoking-induced body sway and its suppression by periodic saccades.

The effect of cigarette smoking on body sway, the everlasting displacement of the center of gravity while standing upright, was studied and smoking was found to induce an unusual, oscillatory body sway that was higher in frequency and greater in amplitude than that in controls and lasted in general for several minutes after smoking. This characteristic body oscillation was strongly suppressed by periodic, saccadic eye movements. These results suggest that nicotine absorbed into blood during smoking affects the structures in the brain stem related to the regulation of standing posture and the saccadic eye movement.

Effects of periodic saccades on the body sway in human subjects.

The body sway in upright standing was decreased by periodic saccades. The decrease was also observed during voluntary rapid eye movements in complete darkness, indicating that the visual information was not concerned with the decrease of the sway. Continuous eye rotations did not affect the body sway, showing that the repetitive activation of eye muscle proprioceptors was not the cause of the sway reduction. These results suggest that some information related to the execution of saccades may affect the spinal motor system and cause the stabilization of the standing posture.

A silent period in sural muscle occurring prior to the voluntary forward inclination of the body.

A silent period lasting for 300-500 msec was observed in triceps surae muscle when the subject inclined forward from the normal standing. This silent period preceded 100 msec or more the beginning of the body inclination and was terminated by an abrupt refiring in the midst of the body swing. The silence was not preceded by the increase in activity of the sural muscle itself or any other leg muscles studied. H-reflex in soleus was strongly inhibited or disappeared during the silent period, indicating that the excitability of the spinal motoneurons was greatly decreased during this period. These findings suggest that the silent period was not induced by some reflex activity in the spinal cord, but was caused by the inhibitory activity based on a central program on the spinal motoneurons.

Visualization of signal propagation from sciatic nerve to spinal cord in canine.

The neuroelectric activity that ascends the sciatic nerve and moves to the spinal cord was visualized by measuring the magnetic compound action fields (CAFs) with a superconducting quantum interference device gradiometer. The sciatic nerve of a dog was stimulated electrically, and propagating evoked CAFs were measured non-invasively. Isomagnetic field maps were made on the basis of this data, and the signal propagation was visualized. The evoked magnetic fields presented a quadrupole consisting of two elements: depolarization and repolarization. Measuring the magnetic CAFs of the sciatic nerve on the body surface enabled us to visualize the non-invasively the signal movement continuously from the sciatic nerve to the spinal cord.

Occlusal contacts during lateral excursions in children with primary dentition.

The presence of non-working occlusal contacts in adults is considered abnormal and may initiate parafunctional activity. Few studies have looked for non-working occlusal contacts in children with primary dentition. The purposes of this study were (1) to prove the existence of non-working-side occlusal contacts, and (2) to quantify their area during lateral excursion in children with primary dentition. To achieve this purpose, we developed a measurement system that combined a tracking system for mandibular movements with a three-dimensional digitizer for tooth shape. Ten children were selected for this study. Estimated occlusal contact area of the primary second molar on the non-working side was 0.8 mm2, in contrast to 2.0 mm2 on the working side, at 3.0 mm of movement of the lower incisor. All children examined had some occlusal contacts on the non-working side during the first part of lateral excursion.

Flavonol sinapoyl glycosides from leaves of Thevetia peruviana.

From the leaves of Thevetia peruviana four new flavonol glycosides, kaempferol 3-glucosyl(1 --> 4) [6"'-sinapoylglucosyl] (1 --> 2) galactoside and 3-[2""-sinapoylglucosyl](1 --> 4)[6"'-sinapoylglucosyl](1 --> 2)galactoside and kaempferol and quercetin 3-[6"'-sinapoylglucosyl](1 --> 2)galactoside were isolated, together with the known compounds, kaempferol and quercetin 3-glucosyl(1 --> 2)galactoside. The glycosides were characterized from FAB mass, 1H and 13C NMR and UV spectral data.

Minor daphnane-type diterpenoids from Wikstroemia retusa.

In addition to huratoxin, pimelea factor P2, and wikstroelides A-G from the fresh bark, eight daphnane-type diterpenoids, wikstroelides H-O, were isolated from the bark and stem, and their structures established. Cytotoxicity was assayed on some wikstroelides.

Interpopulation and intrapopulation variability of nutrient intake in five regions of Japan.

OBJECTIVES: To determine the extent to which interpopulation (between-population) variance, relative to intrapopulation (within-population) variance, contribute to the total variability in nutrient intakes. DESIGN: Cross-sectional study. SETTING: Five Public Health Center districts in Japan. SUBJECTS: Two hundred and seven men and 183 spouses. INTERVENTIONS: A three-day weighed food record. MAIN OUTCOME MEASURES: The total variance in the consumption of 17 nutrient variables was partitioned by analysis of variance into its inter- and intrapopulation components separately for men and women. RESULTS: The percentage contribution of the interpopulation to total variance differed according to the nutrient; it was notable (8-17%) for total energy, carbohydrates, phosphorus, and sodium in both men and women, but was negligible (less than 4%) for micronutrients such as retinol, carotene, thiamin, riboflavin, niacin and ascorbic acid. The ratio of intra- to interpopulation variance was estimated for 31 nutrients (17 in men and 14 in women). The point estimates of the ratio were larger than unity in all nutrients, and the lower limit of the 95% confidence intervals exceeded unity for all but 5 nutrients. Of the two sources of intrapopulation variation, intraindividual variance was larger than interindividual variance in most of the nutrient. CONCLUSIONS: The relative magnitude of interpopulation variation in dietary data can be used to quantify the range of exposure in ecological studies and to examine the heterogeneity of populations pooled for individual-based analysis.

Multimodal inclusion complexes between barbiturates and 2-hydroxypropyl-beta-cyclodextrin in aqueous solution: isothermal titration microcalorimetry, (13)C NMR spectrometry, and molecular dynamics simulation.

Multiple types (structures) of inclusion complexes between barbiturates and 2-hydroxypropyl-beta-cyclodextrin (HPCD) were evaluated by isothermal titration microcalorimetry and (13)C NMR spectroscopy. The geometries of the inclusion complexes were suggested by molecular dynamics simulation. Barbituric acid (BA), barbital (B), amobarbital (AB), pentobarbital (PB), secobarbital (SB), cyclobarbital (CB), and phenobarbital (PHB) were used as barbiturates with different substituents on the barbituric acid ring and compared for inclusion types in aqueous solution. The association constants (K), stoichiometries, and thermodynamic parameters change in free energy (DeltaG) change in enthalpy (DeltaH), and change in entropy [DeltaS] for each type of complex were determined from the calorimetric data. The inclusion complexation was largely entropy driven because of hydrophobic interactions. The values of K increased in the order BA

Dysmorphogenic effects of di-n-butyltin dichloride in cultured rat embryos.

Dysmorphogenic effects of di-n-butyltin dichloride (DBTC) were evaluated in vitro using the rat whole embryo culture system. Wistar rat embryos were explanted on day 8 of gestation and cultured for 68 hr. DBTC was added to the culture medium at the start of culture to achieve final concentrations of 3, 10 and 30 ng/ml. At the end of culture, the embryos were examined for vascularization development in the body and yolk sac, yolk sac diameter, crown-rump length, number of somite pairs, morphological score and external anomalies. Significantly and markedly decreased incidences of embryos with well developed vascularization in the body and yolk sac, yolk sac diameter, crown-rump length and number of somite pairs were found at 30 ng/ml. A concentration-dependent decrease in the morphological score and increase in the incidence of embryos with anomalies were noted, and the differences were significant for embryos exposed to 10 and 30 ng/ml DBTC. Open anterior neuropore and craniofacial abnormality were predominantly observed. It is concluded that DBTC possesses dysmorphogenic effects on postimplantation embryos in vitro.

In vitro study of teratogenic effects of caffeine on cultured rat embryos and embryonic cells.

The teratogenic potential of caffeine was examined in vitro by a whole embryo culture system (WECS) and an embryonic cell culture system (micromas teratogen assay: MTA) in the rat. In the WECS, hyperemia of the tail, and a reduction of the placental size was induced by caffeine at concentrations higher than 50 micrograms/ml; hypoplasia of the forelimb bud was induced at concentrations higher than 100 micrograms/ml; hematoma in the yolk sac and dysmorphogenesis of the fore- and hind-limb buds, prosencephalon and tail were induced by 200 micrograms/ml caffeine. In the MTA, even with 200 micrograms/ml caffeine, the toxicological parameters obtained by proliferation and differentiation assays of the midbrain and limb bud cells were almost the same as in the control. In conclusion, caffeine induced various morphological anomalies, but did not affect proliferation or differentiation of cells in these experimental systems.

An Interlaboratory Validation Study of the Improved Transformation Assay Employing Balb/c 3T3 Cells: Results of a Collaborative Study on the Two-stage Cell Transformation Assay by the Non-genotoxic Carcinogen Study Group.

The Non-genotoxic Carcinogen Study Group of the Environmental Mutagen Society of Japan organised the first step of an interlaboratory validation study on an improved cell transformation assay employing Balb/c 3T3 A31-1-1 cells. Nineteen laboratories participated in this study. The modified transformation assay was evaluated for its responsiveness, its interlaboratory reproducibility and its transferability. In this study, a mixture of Dulbecco's modified Eagle's medium and nutrient mixture F12, supplemented with insulin-transferrin-ethanolamine-sodium selenite and 2% fetal bovine serum (FBS) was used during the period of expression of transformed foci, intead of the usual minimum essential medium with 10% FBS. 20-Methylcholanthrene (MCA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) were selected as a prototype initiator and a tumour promoter, respectively. Two series of experiments were conducted. In the first series, the transformation activity of MCA was examined at various concentrations. In the absence of the promoting treatment with TPA, exposure to MCA only weakly induced transformed foci. In the presence of 0.1µg/ml TPA, all laboratories observed significant dose-dependent increases in the number of transformed foci with increasing MCA concentrations. In the second series of experiments, various concentrations of TPA were tested. In the absence of initiating treatment with MCA, exposure to TPA weakly induced transformed foci in about half of the laboratories. In the presence of 0.2µg/ml MCA, all the laboratories observed significant dose-dependent increases in the number of transformed foci with increasing TPA concentrations. The results from this study support the usefulness of this modified two-stage transformation assay with Balb/c 3T3 cells.

[Pharmacokinetic study of cefmenoxime concerning its transfer into tissues].

Cefmenoxime (1 g) was intravenously administered by one shot to investigate its pharmacokinetic profile with respect to transfer into the kidney, vesical wall and prostatic adenoma. The concentration of cefmenoxime in the kidney reached a peak of 403 micrograms/g at 0.17 hour after administration. The biological half-life was 0.74 hour. In the vesical wall, the level of cefmenoxime reached a peak of 28 micrograms/g at 0.67 hour after administration. The half-life was 2.30 hours. The peak level of cefmenoxime in the prostatic adenoma was 22 micrograms/g at 0.39 hour after administration. The half-life was 2.90 hours. The concentrations of cefmenoxime in these urogenital tissues were higher than its MIC80 and MBC80 against various Gram-negative organisms.