Effects of tolcapone, a catechol-O-methyltransferase inhibitor, on motor symptoms and pharmacokinetics of levodopa in patients with Parkinson's disease.

The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the bioavailability and efficacy of levodopa were evaluated in 12 patients with Parkinson's disease (PD), 8 of whom showed signs of daily motor fluctuations (wearing-off phenomenon). Motor disabilities were assessed in 12 patients at 7 time points before and after the chronic administration of tolcapone using the Unified Parkinson's Disease Rating Scale (UPDRS). The UPDRS score was improved at all points of determination.

[Treatment of Parkinson's disease with multiple drugs].

All major symptoms of Parkinson's disease, i.e., rigidity, tremor, hypokinesia and postural instability are induced by an impaired dopaminergic neurotransmission in the nigro-striatal pathway.

Tendinous movement of a human muscle during voluntary contractions determined by real-time ultrasonography.

The degree of shortening or lengthening of muscles during joint actions has not been clarified in humans, although such information is essential in understanding human muscle functions. In this study, the tendinous movement of a muscle was determined by real-time ultrasonography during voluntary contractions. The tibialis anterior muscle (TA) was tested in five healthy men who performed dorsi- and plantar flexion movements (shortening and lengthening of TA) at two frequencies (0.

Does phosphatidylinositol 3-kinase play a role in insulin-induced outgrowth of pseudopodial cables in cultured cells derived from micromeres of sea urchin embryos?

Cultured cells derived from micromeres isolated from sea urchin embryos at the 16-cell stage, which have insulin receptors, undergo pseudopodial cable growth and spicule rod formation in culture with horse serum and only cable growth in culture with insulin. Genistein, an inhibitor of protein tyrosine kinase, and wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3kinase), inhibited pseudopodial cable growth in micromere-derived cells cultured with insulin and also growth accompanied by spicule rod formation in horse serum-treated cells. The PI3kinase activity in the immunoprecipitates obtained by anti-phosphotyrosine antibody from the cells cultured with insulin was higher than that in cells cultured without insulin or with insulin and genistein.

Influence of two different modes of resistance training in female subjects.

In resistance training, it has been empirically accepted that muscle hypertrophy is developed by low intensity and high volume training, while muscle strength and power are developed by high intensity and low volume training. The purpose of the present study was to investigate the influence of two different modes of resistance training on isokinetic strength and muscle cross-sectional area (CSA) in females. Eleven females, who had no experience in resistance training, participated in this study and were randomly divided into two groups.

Relationships between fiber composition and NMR measurements in human skeletal muscle.

The purpose of this study was to examine the relationships between the relative contents of phosphocreatine (PCr), inorganic phosphate (Pi), beta-adenosine triphosphate (ATP), and transverse relaxation time (T2) with fiber composition, which determined histochemically in the human skeletal muscle. The vastus lateralis muscles of 28 volunteers were subjected to phosphorus nuclear magnetic resonance (31P NMR) spectroscopy, magnetic resonance imaging (MRI) and muscle biopsy. Muscle fibers were divided into type I and type II fibers using myosin ATPase stain.

Combined effects of cabergoline and L-dopa on parkinsonism in MPTP-treated cynomolgus monkeys.

The behavioral effects of L-dopa or cabergoline alone were compared with those of the joint administration of the two drugs in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys with attention to the induction of hyperactivity and dyskinesia. Cabergoline alone at 0.2 mg/kg or less improved in a dose-dependent fashion the parkinsonism without inducing hyperactivity and dyskinesia following a single subcutaneous injection.

Eight-year follow-up study of bromocriptine monotherapy for Parkinson's disease.

An 8-year nationwide study of bromocriptine monotherapy and combination therapy with bromocriptine and levodopa in Parkinson's disease is reported. Fifteen patients were on bromocriptine monotherapy, and 44 patients on bromocriptine combined with levodopa for a certain time during an 8-year period. By judging from Hoehn and Yahr's grading, 4 of the 15 patients in the monotherapy group were in a better condition than before treatment, while 7 cases remained in the same grading, and only 4 showed deterioration.

Glycemic control, growth and complications in children with insulin-dependent diabetes mellitus--a study of children enrolled in a Summer camp program for diabetics in Kinki district, Japan.

The influence of glycemic control on growth and on the development of complications in diabetic children was studied. The subjects of the study were 107 children with insulin-dependent diabetes mellitus (IDDM), who were enrolled in a Summer camp program for diabetic children in Kinki District, Japan from 1972 to 1990, and who had at least three determinations of HbA1 during the observation period. Many of the children had high mean levels of HbA1, regardless of age.

Combination treatment of the partial D2 agonist terguride with the D1 agonist SKF 82958 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinsonian cynomolgus monkeys.

The optimal combination of a dopamine D2 agonist and a D1 agonist was evaluated for symptomatic treatment of Parkinson's disease. Behavioral effects of combination treatment of the full D2 agonist quinpirole or the partial D2 agonist terguride with the full D1 agonist SKF 82958 [(I) 6-Chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2, 3, 4, 5-tetra-hydro-1H-3-benzazepine] were investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys with attention to the induction of hyperactivity such as irritability, excitability and aggressiveness and of dyskinesias such as licking of paws, chewing and biting. Both quinpirole and SKF 82958 alone improved the parkinsonism with a slight induction of the hyperactivity and dyskinesias.

Somatic mosaicism of CAG repeat in dentatorubral-pallidoluysian atrophy (DRPLA).

An unstable expansion of CAG repeat in the coding region of the DRPLA gene on chromosome 12p is the mutation specific for hereditary dentatorubral-pallidoluysian atrophy (DRPLA). We studied the CAG expansion in brain and other tissues from six unrelated DRPLA patients. The CAG repeat lengths showed distinct differences between tissues.

Behavioral involvement of central dopamine D1 and D2 receptors in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys.

To clarify the roles of dopamine D1 and D2 receptors in behavioral symptoms of Parkinson's disease, antiparkinsonian effects of various dopamine agonists in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian monkeys were investigated with regard to induction of hyperactivity such as excitability, irritability and aggressiveness. The non-selective dopamine agonist apomorphine ameliorated the parkinsonism, but induced marked hyperactivity dose-dependently. Pretreatment with either the dopamine D1 antagonist SCH 23390 or the dopamine D2 antagonist sulpiride markedly suppressed the apomorphine-induced hyperactivity with slight attenuation of the antiparkinsonian effects.

Training-induced changes in muscle architecture and specific tension.

Five men underwent unilateral resistance training of elbow extensor (triceps brachii) muscles for 16 weeks. Before and after training, muscle layer thickness and fascicle angles of the long head of the triceps muscle were measured in vivo using B-mode ultrasound, and fascicle lengths were estimated. Series anatomical cross-sectional areas (ACSA) of the triceps brachii muscle were measured by magnetic resonance imaging, from which muscle volume (Vm) was determined and physiological cross-sectional area (PCSA) was calculated.

Differential effects of three dopamine receptor agonists in MPTP-treated monkeys.

The behavioral effects of cabergoline, pergolide and bromocriptine were investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys with attention to the induction of hyperactivity, as evidenced by irritability, excitability and aggressiveness. All three drugs improved the parkinsonism in a dose-dependent fashion following a single injection. Among the three dopamine (DA) receptor agonists used, the antiparkinsonian effect of pergolide was the strongest and had an immediate effect, while cabergoline showed the longest duration of the antiparkinsonian effect and was least potent in inducing hyperactivity.

Measurement of muscle fibre displacement during contraction by real-time ultrasonography in humans.

The contact point (P) made by both the echoes of the aponeurosis and from interspaces among fascicles of the tibialis anterior muscle was detected by real-time ultrasound scanning in 12 adults. Movement in the location of P was observed during muscle contraction and its displacement was related to changes in ankle joint angles (r = 0.81, P < 0.

Muscle metabolism during exercise using phosphorus-31 nuclear magnetic resonance spectroscopy in adolescents.

Very little has been reported on muscle energetics during exercise in adolescents. This is attributable to the difficulty of subjecting children to muscle biopsy. The purpose of this study was to investigate the characteristics of muscle metabolism during exercise in vivo in adolescents by comparing firstly, with adults and secondly, the differences resulting from physical activity using phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy.

Several Cell Responses to Insulin of Cultured Cells Derived from Micromeres, Isolated from Sea Urchin Embryos at the 16 Cell Stage: (Sea urchin/development/morphogenesis/insulin/micromere).

In micromere-derived cells of sea urchin embryos, treatment with insulin started for up to 24 h during culture at 20°C resulted in augmentation of P incorporation into protein (protein phosphorylation) followed by activation of P incorporation into RNA (RNA synthesis) and then induced pseudopodial cable growth, accompanied by considerable decreases in the rates of protein phosphorylation and RNA synthesis. This augmentation of RNA synthesis and cable growth induced by insulin were blocked by H-7, which inhibited protein phosphorylation, and were also inhibited by actinomycin D without any inhibition of protein phosphorylation. Similar results were obtained on treatment with horse serum, found to contain insulin-like compounds.

Changes in Insulin-Binding Capacity of the Plasma Membrane Fraction during Culture in vitro of Cells Derived from Micromeres of 16-Cell-Stage Sea Urchin Embryos: (sea urchin/development/micromere/insulin/insulin receptor).

In cultured cells derived from isolated micromeres of 16-cell stage sea urchin embryos, which undergo insulin-induced pseudopodial cable growth, specific and reversible insulin binding by a 52-kDa protein, probably an insulin receptor in the plasma membrane, is augmented during 5 h of culture without any change in the dissociation constant (Kuno et al : 1994). The increase in insulin-binding capacity in micromere-derived cells was only minimally blocked by actinomycin D and cycloheximide, which inhibited [U- H]uridine incorporation into RNA and [ S]methionine incorporation into protein, respectively. Insulin binding capacity was found in the plasma membrane fraction and the microsome fraction of isolated micromeres.

Insulin-Induced Outgrowth of Pseudopodial Cables from Cultured Micromere-Derived Cells Isolated from Sea Urchin Embryos at the 16 Cell Stage, with Special Reference to the Insulin-Receptor.: (sea urchin/micromere/insulin/psedopodial cable/receptor).

Cultured cells derived from micromeres isolated from sea urchin embryos at the 16 cell stage are known to show outgrowth of pseudopodial cables followed by spicule rod formation when cultured in the presence of horse serum. Micromere-derived cells cultured with bovine insulin showed pseudopodial cable growth but did not produce spicule rods. Micromere-derived cells reversibly bound to insulin through out the period between 3 and 20 hr of culture.

Pharmacological characterization of the novel anxiolytic beta-carboline abecarnil in rodents and primates.

beta-Carboline abecarnil was behaviorally and biochemically characterized as a new anxiolytic agent in rodents and primates in comparison with the benzodiazepine (BZ) anxiolytics. Oral treatment with abecarnil (0.5-10 mg/kg) showed a potent anticonflict activity in the water-lick test in rats.

Changes in magnetic resonance images in human skeletal muscle after eccentric exercise.

To investigate the time-course of changes in transverse relaxation time (T2) and cross-sectional area (CSA) of the quadriceps muscle after a single session of eccentric exercise, magnetic resonance imaging was performed on six healthy male volunteers before and at 0, 7, 15, 20, 30 and 60 min and 12, 24, 36, 48, 72 and 168 h after exercise. Although there was almost no muscle soreness immediately after exercise, it started to increase 1 day after, peaking 1-2 days after the exercise (P < 0.01).

Muscle energetics in short-term training during hypoxia in elite combination skiers.

Four well-trained combination skiers were studied through pre- and post-training for the effects of short-term intermittent training during hypoxia on muscle energetics during submaximal exercise as measured by Phosphorus-31 nuclear magnetic resonance and maximal aerobic power (VO2max). The hypoxia and training in the cold was conducted in a hypobaric chamber and comprised 60-min aerobic exercise (at an intensity equivalent to the blood lactate threshold), using a cycle ergometer or a treadmill twice a day for 4, consecutive days at 5 degrees C, in conditions equivalent to an altitude of 2000 m (593 mm Hg). No change in VO2max was observed over the training period, while in the muscle energetics during submaximal exercise, the values of phosphocreatine/(phosphocreatine+inorganic phosphate) and intracellular pH were found to be significantly increased by training during hypoxia.