Effects of arginine derivatives on soluble guanylate cyclase from neuroblastoma N1E 115 cells

The effects of L-arginine (Arg) derivatives on soluble guanylate cyclase from neuroblastoma N1E 115 cells were examined. The Arg derivatives were modified at the -NH2, -COOH, C alpha-proton or guanidino group of Arg. Among the synthesized derivatives, eight compounds, i.e. the 5-(dimethylamino)-1-naphthalenesulfonyl (DNS) ones, especially N-cyclohexyl-2-(N-DNSamino)-5-guanidino-2-methylvaleramide and 1-[2-(N-DNSamino)-2-(2-imino-1,2,3,4,5,6-hexahydropyrimidin- 4-yl)acetyl]- piperidine, were found to inhibit the activity of crude guanylate cyclase in the 105,000 g supernatant fraction of the cell homogenate. The enzyme, partially purified by a column of Chelex 100 Na+, was also inhibited by these eight compounds. The mode of the inhibition was competitive. The Ki values were in the range of 2-8 microM for the enzyme in the 105,000 g supernatant fraction and 3-16 microM for the partially purified enzyme, in the presence of Mg2+ as a metal cofactor. In contrast, a new derivative, methyl 2-amino-5-guanidinovalerate (M Arg ME), as well as the Arg methyl ester (Arg ME) and Arg; were found to enhance the activity of the partially purified guanylate cyclase; KA values of M Arg ME, Arg ME and Arg were approximately 9, 4 and 3 microM respectively. From these results, the free guanidino group including 2-imino-1,2,3,4,5,6-hexahydropyrimidin-4-yl or 2-imino-1,2,3,4,5,6-hexahydropyrimidin-5-yl and modification of the --NH2 residue with a hydrophobic group such as DNS seemed to be essential for inhibition of the guanylate cyclase; however, the guanidino and --NH2 residue of Arg should be free for activation by these Arg derivatives.     

Activities of creatine kinase isoenzymes in single skeletal muscle fibres of trained and untrained rats

Biochemical changes in the creatine kinase isoenzyme compositions in single muscle fibres of different types in rats were induced by endurance running training. Single muscle fibres were dissected from the soleus and extensor digitorum longus muscles of Wistarstrain male rats trained on a motor-driven treadmill for 16 weeks. Each fibre was typed histochemically (SO, slow-twitch oxidative; FOG, fast-twitch oxidative glycolytic; FG, fast-twitch glycolytic), and the activities of total creatine kinase and its four isoenzymes (CK-MM, -MB,-BB, and mitochondrial creatine kinase) were measured. The endurance training did not affect the total creatine kinase activity, but resulted in significantly increased activities of CK-MB and CK-BB in SO and FOG fibres, and the mitochondrial enzyme activity in FOG and FG fibres. Endurance training induced biochemical changes in the isoenzyme compositions, specifically in FOG fibres. These results suggest that changes in creatine kinase isoenzymes with endurance training reflect changes in the energy metabolism in the different muscle fibres, supporting the hypothesis that the different isoenzymes play different roles in energy transduction.     

31P magnetic resonance spectroscopy study of cerebral metabolism in developing dog brain and its relationship to neuronal function.

Cerebral metabolism and neuronal function of prefrontal brain cortex were studied in 6 dog litters from birth to 3 months of age. Noninvasive phosphorus magnetic resonance spectroscopy (31P-MRS) was used to observe longitudinal biochemical changes in the phosphorus compounds associated with cerebral metabolism. Neurological tests, examining reflex, motor and sensory nerve function, were performed in conjunction with the 31P-MRS study. During the neonatal period, exponential increases in PCr, Pi, and phophodiesters preceded neurological changes. Phosphomonoesters showed an exponential, nearly linear, decrease and PCr/Pi was maintained during the 3-month period. Developmental increases in high energy phosphates and the maintenance of PCr/Pi indicate that the increased energy demands of the developing animal are met by increased mitochondrial function (ATP turnover).     

Disc and condyle translation in patients with temporomandibular disorder.

OBJECTIVE: The purpose of this study was to elucidate causal relationship between disc and condyle range of movement and clinical signs and symptoms in patients with temporomandibular disorders (TMD), using magnetic resonance imaging (MRI). STUDY DESIGN: The subjects comprised of a study group of 191 patients with TMD and a control group of 43 asymptomatic patients. The clinical assessment consisted of range of maximum mouth opening (MMO) and preauricular pain during mandibular function. After clinical and radiographic findings assessment, disc and condyle condition were examined by MRI and the range of movement was accordingly classified. RESULTS: Disc displacement was observed in 156/191 (81.7%) of the study group and 9/43 (20.9%) of the control group. When disc and condyle mobility was presented around the eminence, wider MMO range was maintained, P < .05. Presence of osteoarthrosis (OA) was not correlated with preauricular pain, because OA variables were mild in the study group. CONCLUSION: Maintenance of disc/condyle translation is an important factor in TMJ function, irrespective of disc displacement or arthritis.     

Globus pallidus calcification in Down syndrome with progressive neurologic deficits.

We report a 10-year-old Down syndrome patient who developed dystonia, choreoathetosis, dysarthria, and dysphagia beginning with hemiparesis. Cranial computed tomography disclosed bilateral calcification in the globus pallidus which resembled a sign of premature aging. Conversely, the clinical course and magnetic resonance imaging findings resembled those of Hallervorden-Spatz syndrome.     

Serotonin reduction in the mouse neostriatum during hyperthermia-induced convulsions studied by immunohistochemistry

Summary Changes occurring in serotonin neurons during hyperthermia-induced convulsions were examined by means of a modified immunohistochemical method. All mice (8–12 weeks of age) exposed to the temperature of 50°C had convulsions, showing a generalized tonic and/or clonic pattern. Immediately after the convulsions, the animals were perfused transcardially with a fixative. A significant reduction in serotonin immunoreactivity was observed in the neostratum (caudate-putamen complex) of the mice which had hyperthermia-induced seizures, while the serotonin immunoreactivity remained unchanged in the neocortex and paleostriatum. These results suggest that serotonin may be an important mediator in the mechanism of hyperthermia-induced convulsions or that the susceptibility of serotonin neurons to a convulsive state is greatest in the neostriatum.Supported in part by Grant No. 86-05 from the National Center for Nervous, Mental and Muscular Disorders (NCNMMD) of the Ministry of Health and Welfare and Grant No. 62770677 from the Ministry of Education, Science and Culture, Japan     

Temperature-responsive cross-linked poly(epsilon-caprolactone) membrane that functions near body temperature.

The objective of this study is to develop a sensitive temperature-responsive material that would function near body temperature. To achieve this purpose, we compounded 2-branched and 4-branched poly(epsilon-caprolactone) macromonomers to modulate the transition temperatures of the resulting cross-linked materials. The temperature-responsive properties were studied using differential scanning calorimetry and X-ray diffraction measurements. As a result, the mixing ratios of each macromonomer or the total macromonomer concentrations were very dominant in modulating the transition temperatures. The materials could successfully control the permeation of the model drug, prednisolone, near body temperature.     

Results of low- and high-dose-rate interstitial brachytherapy for T3 mobile tongue cancer.

PURPOSE: To evaluate the treatment results of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy (ISBT) for T3 mobile tongue cancer. MATERIAL AND METHODS: Between 1974 and 1992, 61 patients with T3 mobile tongue cancer were treated with LDR ISBT using (192)Ir hairpins with or without single pins. In addition, between 1991 and 1999, 14 patients were treated with HDR ISBT. For nine patients treated with ISBT alone, the total dose was 59-94 Gy (median 72 Gy) within one week in LDR ISBT and 60 Gy/10 fractions/5 days in HDR ISBT. For 66 patients treated with a combination therapy of external beam radiotherapy (EBRT) and ISBT, the total dose was 12.5-60 Gy (median 30 Gy) of EBRT and 50-112 Gy (median 68 Gy) within 1 week in LDR ISBT or 32-60 Gy (median 48 Gy)/8-10 fractions/5-7 days in HDR ISBT. RESULTS: The 2- and 3-year local control rates of all patients were both 68%. The 2- and 3-year local control rates of patients treated with LDR ISBT were both 67%, and those with HDR ISBT were both 71%. The local control rate of patients treated with HDR ISBT was similar to those with LDR ISBT. CONCLUSIONS: ISBT for T3 mobile tongue cancer is effective and acceptable. The treatment result of HDR ISBT is almost similar to that of LDR ISBT for T3 mobile tongue cancer.     

Impaired cardiovascular autonomic function in Parkinson's disease with visual hallucinations.

We assessed the relations of visual hallucinations (VH) to cardiovascular autonomic dysfunction in patients with Parkinson's disease (PD). The subjects were 37 patients without VH (VH(-)) and 31 with VH (VH(+)). Autonomic function was evaluated on the basis of cardiac 123-radioiodinated metaiodobenzylguanidine (123I-MIBG) uptake and hemodynamic testing with Valsalva maneuver. Systolic blood pressure (SBP) and plasma norepinephrine concentrations (NE) were measured by tilt-table testing. 123I-MIBG uptake was lower in VH(+) than VH(-). Hemodynamic studies showed that VH(-) had only cardiac sympathetic and parasympathetic dysfunction, while VH(+) additionally had reduced vasomotor sympathetic functions. The fall in SBP during tilt-table testing was greater in VH(+) than VH(-). NE and its difference in the supine and upright positions were decreased in VH(+). We conclude that cardiac and vasomotor sympathetic dysfunction is more severe in VH(+) than in VH(-). Severe dysfunction in PD with VH is probably attributed to Lewy-body lesions or neuronal loss in sympathetic ganglia, the central autonomic system, or both.