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.

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.

Head motion may help mouth opening in children.

Concomitant head and mandibular movement during jaw function is well known in adults; however, its importance in children has not been studied. The brain attains 85-90% of its adult weight at 5 years of age, though the maximum rate of condylar growth is attained at approximately 14 years of age. These findings suggest that the coordination of the head and mandible may differ between children and adults. This study investigated head and mandibular movements of 19 children with complete primary dentition (average age: 5 years 5 months) and compared their functional integration of jaw and head movements to those of 16 female adults (average age: 20 years 3 months) with permanent dentition. Although the mandibular opening distance was significantly greater in the adults, the magnitude of concomitant head motion was greater in children. The results suggest that head extension in children helps increase the magnitude of mouth opening more than in adult women.

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.

Correlations between incisor and condylar movements during lateral excursion in children with primary dentition.

The purpose of this study was to look for associations between lower incisor movement and working and balancing condylar movement during lateral excursion in children with primary dentition and adults with permanent dentition. Mandibular movement was recorded using a TRI-MET (an optoelectronic analysis system with six degrees-of-freedom) at a sampling frequency of 100 Hz. The movement data was transferred to a graphics workstation for analysis. Subjects were categorized by age into two groups. The primary dentition group consisted of 19 children (mean age: 5 years and 5 months, s.d.: 8.7 months), and the permanent dentition group consisted of 22 women (mean age: 20 years and 5 months, s.d.: 26.3 months). The occlusion and TMJ in both groups were normal, with no history of orthodontic treatment. Three orthogonal excursive ranges and the 3D linear distance of the incisal and balancing and working condylar points, along with inter- and intra-individual correlations between the incisor and the balancing and working condyles during lateral excursion, were estimated by using multilevel statistical models. Lateral excursion in children with primary dentition was characterized by smaller incisor excursive ranges and 3D linear distance than in adults, and stronger inter- and intra-individual correlations between incisor and balancing condylar movements than in adults. In both children and adults the lateral excursion of the incisor was a good indicator of the extent of balancing condylar movement, but not working condylar movement.

Characteristics of the gum chewing occlusal phase in children with primary dentition.

Understanding of the growth and development of mandibular function is indispensable to the diagnosis of functional disturbances during childhood. The purpose of this study was to clarify the characteristics of the occlusal phase during gum chewing in children with primary dentition. Chewing motion at the working molar of 14 children with primary dentition and 28 female adults was recorded optoelectrically, and the frontal and sagittal angles of their closing and following opening strokes were measured and compared. In children the closing strokes were entered more vertically and anteriorly than in adults, and the opening strokes shifted to the non-working side in adults but moved to the working side in children. The degree of variance also differed between the two groups; the variance of the frontal angle was larger than that of sagittal angle in adults, but the opposite was true in children. These results suggested that the chewing pattern in children during the occlusal phase is distinctly different from adults and the chewing movement in children is not always less stable than in adults.

Length of the occlusal glide during chewing in children with primary dentition.

Chewing is one of the most important functions of the mandible, but, to date, there are very few studies of this function in children. The purpose of this study was to quantify the length of the occlusal glide at the lower incisal point during gum chewing in children with primary dentition. Eleven girls with primary dentition were selected for this study. Mandibular excursions with occlusal contacts and gum chewing movement were measured using an optoelectronic system that can measure mandibular movement with six degrees-of-freedom at a sampling frequency of 100 Hz. A curved mesh diagram of incisor coordinates during mandibular excursions was established to calculate the length of the occlusal glide for each subject. The occlusal glide lengths of children were compared with previously reported results for adults. The estimated length of the occlusal glide during closing was significantly shorter in children than in adults, contrary to that during opening. This result suggests that children have a characteristic chewing pattern that differs from adults.

Occlusal phase of gum-chewing strokes.

The occlusal phase of chewing is especially interesting because food particles are being pulverized in this phase. For efficient chewing the upper and lower teeth must come together in a congruent fashion with less variation than in other phases. To examine this expectation the chewing motions of 28 women were recorded optoelectrically, and their frontal and sagittal angles of the closing and following opening strokes were measured at 3.0 mm (3-D linear distance) of opening. Closing strokes were more stable than opening strokes. The frontal angle was correlated with the sagittal angle during closing. The opening and closing sagittal angles were moderately correlated, and the opening and closing frontal angles were negatively correlated at the intersubject level. No direct association was found between the closing strokes and following opening strokes at the intra-subject level. These results suggest that closing strokes are more stable than opening strokes, resulting in efficient mastication.

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.

Isolation and identification of two new flavanones and a chalcone from Citrus kinokuni.

Two new flavanones and one chalcone were isolated from the peel of Citrus kinokuni Hort. ex Tanaka and identified as (2S)-5,6,7,8,4'-pentamethoxyflavanone (1), (2S)-5,6,7,3',4'-pentamethoxyflavanone (2) and 2'-hydroxy-3,4,3',4',6'-pentamethoxychalcone (3). The structures of new compounds were elucidated by spectroscopic analysis.

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.

Validity and reproducibility of a self-administered food-frequency questionnaire to assess isoflavone intake in a japanese population in comparison with dietary records and blood and urine isoflavones.

Valid food-frequency questionnaires (FFQ) need to be developed to assess isoflavone intake in investigations of its possible association with the lower incidence of breast and prostate cancer in Asian countries. We investigated the validity and reproducibility of isoflavone (daidzein and genistein) intakes from self-administered semiquantitative FFQ used in the JPHC Study (Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases). We also investigated the number of food items that would be sufficient to ensure validity and reproducibility. We collected FFQ, dietary records (DR), blood and urine samples from 215 subjects among JPHC Study participants, estimated isoflavone intakes from FFQ and DR, and measured serum isoflavone concentration and urine isoflavone excretion. For daidzein, mean intakes estimated from FFQ and DR, serum concentration and urine excretion were 18.3 mg/d, 14.5 mg/d, 119.9 nmol/L and 17.0 micromol/d and for genistein, 31.4 mg/d, 23.4 mg/d, 475.3 nmol/L and 14.2 micromol/d, respectively. Results were similar when analyzed by sex. Spearman correlation coefficients for daidzein of energy-adjusted intakes from FFQ with those from DR, serum concentration and creatinine-adjusted urinary excretion were 0.64, 0.31 and 0.43, respectively. Correlations between two FFQ estimates with a 1-y interval were 0.76. Results were similar for genistein. The shorter version of the FFQ with three items (natto, miso and tofu for miso soup) showed a similar correlation. The original FFQ and the shorter versions have sufficient validity and reproducibility to be used in epidemiologic studies.

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

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.

Baseline data of reproductive system in the JPHC study. Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases.

Hormonal status in the body is closely related to the occurrence of estrogen-related cancers. Baseline survey data about the female reproductive system in JPHC study showed different gynecological and gestational profiles in each study area. Late menarche (15-16 y/o) was characteristic in the rural areas. Earlier gestational age and larger number of children were also more common in the rural areas. Baseline survey data, including gynecological past history, frequency of examination for uterine cancers, and so forth, showed some profile of middle aged women in the different areas in Japan.

Postoperative changes on functional mapping of the motor cortex in patients with brachial plexus injury: comparative study of magnetoencephalography and functional magnetic resonance imaging.

Using magnetoencephalography (MEG) and functional magnetic resonance imaging (f-MRI), we investigated the areas of the cerebral cortex that were activated when patients with brachial plexus injuries performed elbow flexion, a motion re-acquired through nerve transfer surgery. In all patients, elbow flexion on the operated side and on the unaffected side led to the activation of an area in the motor cortex, with these areas being located almost symmetrically on either side of the sagittal midline. These findings suggest that the activity center for the transferred intercostal nerves shifted to the motor cortex for the elbow, from the original intercostal nerve site.

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.

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.

Pregnanes and pregnane glycosides from Hoya carnosa.

Eleven pregnanes were isolated from the hydrolysate of the CHCl3 extract fractionated from the caules of Hoya carnosa. Among these, six pregnanes, including 19-acetoxydigipurpurogenin II, were new, and their structures were elucidated. The structures of twenty new pregnane tetraosides and pentaosides, named hoyacarnosides A-T, besides three known ones from the CHCl3 extract, were determined.

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.