Psychosis is an extension of mood swings from the perspective of neuronal plasticity impairments.

We previously hypothesized that depressive and manic states may be consecutive presentations of the same underlying neuronal plasticity, and that moderate impairments in neuronal plasticity cause depressive states while further impairment to neuronal plasticity causes manic states. Psychopathological or biological relationships between bipolar disorder and schizophrenia have also been revealed. Therefore, in addition to depressive and manic states, psychosis may also be considered a manifestation resulting from additional impairments to neuronal plasticity. In the present manuscript, we hypothesize that moderate and more severe impairments to neuronal plasticity cause depressive and manic states, respectively, and that more serious impairments to neuronal plasticity cause psychosis. Many studies have suggested that impairments in neuronal plasticity contribute to schizophrenia and other mental disorders with psychotic features, and that the impairment of neuronal plasticity in schizophrenia is more severe than that in bipolar disorder. Therefore, we hypothesize more specifically that impairments in neuronal plasticity may be more severe in the order of the cases featuring psychosis, mania, and depression. This progression notably overlaps with the arrangement of schizophrenia, bipolar disorder, and depressive disorder in the DSM-5. Psychotic symptoms are thought to appear further towards the base of the psychopathological hierarchy than are manic or depressive symptoms. If impairments to neuronal plasticity contribute to this psychopathological hierarchy, as we contest that they do, our hypothesis may serve as a bridge between clinical psychopathology, diagnosis, and biological psychiatry.

Brain imaging for oxidative stress and mitochondrial dysfunction in neurodegenerative diseases.

Oxidative stress, one of the most probable molecular mechanisms for neuronal impairment, is reported to occur in the affected brain regions of various neurodegenerative diseases. Recently, many studies showed evidence of a link between oxidative stress or mitochondrial damage and neuronal degeneration. Basic in vitro experiments and postmortem studies demonstrated that biomarkers for oxidative damage can be observed in the pathogenic regions of the brain and the affected neurons. Model animal studies also showed oxidative damage associated with neuronal degeneration. The molecular imaging method with positron emission tomography (PET) is expected to delineate oxidatively stressed microenvironments to elucidate pathophysiological changes of the in vivo brain; however, only a few studies have successfully demonstrated enhanced stress in patients. Radioisotope copper labeled diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) may be the most promising candidate for this oxidative stress imaging. The tracer is usually known as a hypoxic tissue imaging PET probe, but the accumulation mechanism is based on the electron rich environment induced by mitochondrial impairment and/or microsomal over-reduction, and thus it is considered to represent the oxidative stress state correlated with the degree of disease severity. In this review, Cu-ATSM PET is introduced in detail from the basics to practical methods in clinical studies, as well as recent clinical studies on cerebrovascular diseases and neurodegenerative diseases. Several other PET probes are also introduced from the point of view of neuronal oxidative stress imaging. These molecular imaging methods should be promising tools to reveal oxidative injuries in various brain diseases.

Positron emission tomography radiopharmaceuticals for sex steroid hormone receptor imaging.

Understanding the expression of tumor specific receptors is important not only for tumor diagnosis but also for planning the strategy for patient treatment. Tumor receptor has been one of the most critical targets for treatment in cancer such as breast, prostate and thyroid cancers. Positron emission tomography (PET) is a part of molecular imaging techniques based on detecting the radiopharmaceuticals that can capture functional or phenotypic changes associated with pathology. The advantages of detecting tumor specific receptors by PET are its non-invasiveness, providing comprehensive information about receptor expression, avoiding the sampling errors, selecting strategy for the treatment of patients and monitoring tumor response to therapy. Hormonal therapy plays a major role in cancer treatment. Therefore, we review the PET radiopharmaceuticals for sex steroid hormone receptor imaging in this article.

Oestrogen-related tumour phenotype: positron emission tomography characterisation with ¹8F-FDG and ¹8F-FES.

This article outlines the role of 16α-[(18)F]fluoro-17ß-oestradiol ((18)F-FES) positron emission tomography (PET) combined with 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)F-FDG) in patients with oestrogen-related tumours for evaluating tumour phenotype. (18)F-FES-PET combined with (18)F-FDG is helpful in characterising the distinct phenotypic features of oestrogen-related tumours; that is, inter- and intrapatient tumour heterogeneity, which indicates its great potential as a determinant of individualised treatment and a prognostic predictor for patients with oestrogen-related tumours.

Car-driving abilities of people with tetraplegia.

OBJECTIVES: To examine the relationship between the spinal cord injury (SCI) level, age, and car-driving ability in people with tetraplegia and to explore the association between car-driving ability and social activity. DESIGN: Retrospective clinical survey. SETTING: Rehabilitation center in Japan. PATIENTS: Sixty-two subjects with traumatic complete tetraplegia. INTERVENTIONS: Driving evaluation; comprehensive driver's training (muscle strengthening, transfer training, adjustment of equipment, on-road training); and questionnaire (car-driving status, employment, participation in sports). MAIN OUTCOME MEASURES: The SCI level (Zancolli's classification), age, functional status of activities of daily living (ADLs), and driving ability were obtained from the medical records. Vocational status and engagement in sports activities were investigated by questionnaire. RESULTS: The SCI level and age strongly influenced the patients' ability to drive a car independently. The highest neurologic level in which independent driving was achievable was C6A. Toilet transfer ability almost paralleled the ability to drive a car. Eighty-four percent of the people with tetraplegia who had a defined job could drive independently and 70% of the driving-independent individuals held a job. Half of driving-independent individuals participated in some sports activities. CONCLUSIONS: Toilet transfer ability is a reliable indicator for driver's training. Driving ability is an important factor that allows individuals with tetraplegia to participate in work and sports-related activities.

Regional alterations of myocardial norepinephrine transporter density in streptozotocin-induced diabetic rats: implications for heterogeneous cardiac accumulation of MIBG in diabetes.

Cardiac scintigraphic studies using iodine-123 labeled metaiodobenzylguanidine ([123I]MIBG) have previously demonstrated the heterogeneous myocardial accumulation of radioactivity in diabetes. In this study, we investigated the myocardial regional distribution of [125I]MIBG and the effects of regional myocardial blood flow, myocardial norepinephrine (NE) content, and norepinephrine transporter (NET) function on regional [125I]MIBG accumulation in streptozotocin-induced diabetic (STZ-D) rats. Dual-isotope autoradiographic studies using [125I]MIBG and technetium-99m labeled hexakis (2-methoxy-2-isobutylisonitrile) (99mTc-MIBI), a tracer for the measurement of myocardial blood flow, were carried out to investigate the changes in regional myocardial blood flow in STZ-D rats. Uptake of [125I]MIBG was similar between the anterior wall and the inferior wall in control rats. On the other hand, in STZ-D rats, uptake of [125I]MIBG in the inferior wall was significantly less than that in the anterior wall. Uptake of 99mTc-MIBI was not significantly different between the anterior and inferior walls in control or STZ-D rats, indicating that myocardial blood flow did not change regionally in either control or STZ-D rats, and that the blood flow was not responsible for the heterogeneity of the distribution of [125I]MIBG in STZ-D rats. In STZ-D rats, cardiac NE concentrations determined using an HPLC-electrochemical detection (ECD) system were significantly increased in both the anterior and the inferior wall, although there was no significant difference in NE concentration between the anterior and inferior walls in control or STZ-D rats. Furthermore, the density and affinity of NET were investigated by studying the binding of [3H]desipramine to cardiac membranes. The Bmax values of the NET in the anterior wall were not significantly different between control and STZ-D rats, but the Bmax value of the NET in the inferior wall was significantly lower in STZ-D rats than in controls. In conclusion, myocardial MIBG uptake was reduced in the inferior wall of STZ-D rats compared with control rats; this decrease was correlated with the decrease in NET density, but was not dependent on the regional myocardial blood flow and NE concentration. These results suggest that regional fluctuations in NET levels in the inferior wall contribute to heterogeneous MIBG accumulation in diabetes.

Flap surgery to cover olecranon pressure ulcers in spinal cord injury patients.

In the quadriplegic patient, the periolecranon region is subjected to continuous and permanent mechanical shearing and pressure forces. As the sensation of this region is partially impaired secondary to the level of the spinal cord injury, this anatomical area is prone to develop bursitis and then a chronic open draining wound. This type of wound is refractory to conservative measures. Surgical closure of this functional area can represent a challenge to the plastic and reconstructive surgeon because not all of the surgical options available are suitable for spinal cord injury patients. Therefore, we describe our clinical experience, which consists of seven patients with traumatic complete quadriplegia treated between 1989 and 1998 (all patients were male) who presented with an open olecranon ulcer, septic bursitis, or aseptic bursitis, and who underwent surgical closure by direct closure, local arm fasciocutaneous flap, or cross-chest flap to cover the periolecranon soft-tissue defects. The follow-up period ranged from 3 months to 8 years (mean, 44 months). All types of flaps achieved wound closure without losing range of motion at the elbow; however, at 10 to 12 months after surgery, an olecranon pressure ulcer or septic bursitis recurred in three of seven patients. These three patients required surgical revision. The local fasciocutaneous rotational flap was found to be effective for closing periolecranon soft-tissue defects and can be reused in instances of recurrence. Patient education is essential to prevent re-ulceration in that functional area in the spinal cord injury patient.

Improvement of urological-management abilities in individuals with tetraplegia by reconstructive hand surgery.

OBJECTIVE: To evaluate whether reconstructive hand surgery could improve the ability of tetraplegic patients to perform clean intermittent self-catheterization (CIC). MATERIALS AND METHODS: The subjects were patients with complete traumatic tetraplegia admitted to the Nagano Rehabilitation Center between 1977 and 1996. A total of 63 subjects were included in this study with an age range of 18-73 years (mean 38.2 years). Reconstructive hand surgery was performed on 44 hands (28 cases). Current urological conditions were assessed by interview or mail questionnaire. RESULTS: Fifty-one per cent (22/43) of the patients with C6 level of tetraplegia and 86% (12/14) of those with C7 or C8 neurological level of injury could perform CIC independently and only one subject needed assisted CIC. CONCLUSION: CIC is the preferred option for people with tetraplegia. Reconstructive hand surgery is thus recommended to make urological management more independent for a selected group of people with tetraplegia.

Synthesis and characterization of radioiodinated (S)-5-iodonicotine: a new ligand for potential imaging of brain nicotinic cholinergic receptors by single photon emission computed tomography.

(S)-5-Iodonicotine (4a), an (S)-nicotine analog iodinated at the 5-position of the pyridine ring, was synthesized and evaluated as a potential radiopharmaceutical for investigating brain nicotine receptors by single photon emission computerized tomography (SPECT). [125I]-(S)-Iodonicotine ([125I]-4a) was synthesized by the iododestannylation reaction under no-carrier-added conditions and purified by high-performance liquid chromatography (HPLC). The binding affinity of 4a for brain nicotine receptors was measured in terms of displacement of [3H]cytisine from binding sites in rat cortical membranes. The binding data revealed that the affinity of 4a was the same as that of (S)-nicotine and 80-fold higher than that of the (R)-enantiomer (4b). Biodistribution studies in mice disclosed that the brain uptake of [125I]-4a was rapid and profound. Regional cerebral distribution studies in rats by autoradiography disclosed that the accumulation of [125I]-4a was dense in the thalamus, intermediate in the cortex and striatum, and less marked in the cerebellum. Furthermore, the administration of (S)-nicotine reduced the uptake of [125I]-4a in the thalamus and resulted in a nearly identical level of radioactivity in the cerebellum. [125I]-(R)-5-Iodonicotine ([125I]-4b) showed more rapid washout from the brain and a less extensive regional cerebral distribution than the (S)-enantiomer ([125I]-4a). Thus, 4a bound to brain nicotine receptor in vivo, and therefore iodine-123-labeled 4a may be a potential radioligand for use in vivo cerebral nicotinic receptor studies by SPECT.

Differential regional sympathetic responses to somatic stimulation in anesthetized dogs.

The present study was designed to determine whether regional differences exist in sympathetic responses to somatic nerve stimulation and whether the baroreceptor reflex modulates this somato-sympathetic reflex. The cardiac (CNA), renal (RNA), hepatic (HNA), splenic (SpNA) and adrenal (AdNA) sympathetic postganglionic nerve activities (SNA) were simultaneously recorded in anesthetized dogs with intact (n = 7) or bilaterally sectioned (n = 8) carotid sinus and vagus nerves. In the intact group, electrical stimulation of the left peroneal nerve at low intensity and low frequency (5 V, 5 Hz) produced a fall in mean arterial pressure (MAP) (-9.7 +/- 2.7 mmHg) and a decrease in each SNA with no regional differences RNA (79.2 +/- 8.5%), AdNA (82.7 +/- 5.4%), HNA (89.4 +/- 4.5%), CNA (87.5 +/- 3.5%), SpNA (84.2 +/- 3.2%). In contrast, stimulation at high intensity and high frequency (25 V, 50 Hz) produced a rise in MAP (+21.4 +/- 3.8 mmHg) and increases in SNA with quantitative predominance of RNA (178.6 +/- 13.6%) and AdNA (158.3 +/- 16.1%) over HNA (129.0 +/- 4.2%), CNA (117.7 +/- 7.6%), and SpNA (112.0 +/- 6.2%). Similar responses were observed when the left ulnar nerve was stimulated. The changes in SNA (delta SNA) at 10 s after the start of stimulation were plotted as a function of the changes in MAP (delta MAP) and the regression curves were determined. The best fit regression curve was a logistic sigmoid curve in the intact group and a linear one in the baroreceptor denervated group. Furthermore, delta RNA/delta MAP and delta AdNA/delta MAP during the somato-pressor response were significantly smaller in the intact group than in the denervated group. In conclusion, there are regional differences of sympathetic response during the somato pressor response but not during somato depressor response. The baroreceptor reflex may suppress the somato-sympathetic reflex of RNA and AdNA.

Application of [125I] (S)-5-iodonicotine, a new radioiodinated ligand, in the assay of nicotinic acetylcholine receptor binding in the brain.

[125I](S)-5-Iodonicotine was prepared and its application in the assay of nicotinic acetylcholine receptor binding in the brain was studied. [125I](S)-5-Iodonicotine bound to the rat cortical membrane with high affinity (Kd, 15.0 nm). Various nicotinic cholinergic compounds showed competition with [125I](S)-5-iodonicotine for the binding sites in the rats cortical membrane, and the specificity of its binding was correlated well with that of [H3] cytisine (r = 0.98). These findings suggest that [125I](S)-5-iodonicotine binds to the same sites as [H3] cytisine and indicate that [125I](S)-5-iodonicotine can be applied as a brain nicotine receptor binding assay.

Relationship between canopy depth and other dimensions of coastal Pinus thunbergii Parlat. forests in Japan.

The relationship between canopy depth and other dimensions of coastal Pinus thunbergii Parlat. forests was analyzed from data for 29 stands using a mathematical model describing canopy depth. The model was derived from the relationship between mean diameter at breast height (D) and mean tree height (H). Maximum mean tree height (H(max)), which was calculated as H(max) = AD(B) where A and B are parameters, approximated the upper 95 percentile of H for a given D. Maximum canopy depth (L(cmax)) was calculated as L(cmax) = H(max) - H(B), where H(B) is mean clear length. Relative maximum canopy depth (R(cmax); defined as L(cmax)/H(max)) was approximated as 1/R(cmax) = 1/(aS(R) (b)) + 1, where a and b are parameters. The term S(R) was defined as N(-1/2)/H, where N is stand density (trees m(-2)). From these equations, the canopy depth (L(c))was derived as L(c) = H - H(max)/(aS(R) (b) + 1), because L(c) = H - H(B). From these relationships a diagram showing possible points of regulation of canopy depth was developed.

Properties of NADH-dependent estradiol 2-hydroxylase in rat liver.

The NADH-supported cytochrome P-450-dependent 2-hydroxylation of estradiol in rat liver microsomes has been investigated. Estradiol 2-hydroxylation proceeded well with NADH instead of NADPH as a cofactor. Dimethyltetrahydropterine was incapable of serving as a hydrogen donor for this biotransformation. When both NADH and NADPH were used, the 2-hydroxylation increased additively. Molecular oxygen dissolved in the incubation medium was enough for the occurrence of the NADH-dependent 2-hydroxylation. The presence of carbon monooxide suppressed the formation of catechol estrogen where the CO/O2 ratio needed for 50% inhibition of the bioconversion was 7.7. The inhibitory effect was reversed completely by illumination with white light. p-Chloromercuribenzoate inhibited almost completely the 2-hydroxylase activity, and the enzyme activity was also inhibited by SKF-525A. These results strongly imply the possible involvement of a cytochrome P-450 system in the NADH-dependent 2-hydroxylation of estradiol with rat liver microsomes.