Effects of Unrestricted Kinematically Aligned Total Knee Arthroplasty with a Modified Soft-Tissue Respecting Technique on the Deformity of Limb Alignment in Japanese Patients.

Background and Objectives: Unrestricted kinematic alignment total knee arthroplasty (KA-TKA) with a soft-tissue respecting technique (STRT) is a soft-tissue-dependent tibial resection entailing the restoration of the original soft-tissue tension using ligamentotaxis after resurfacing the femur, based on the concept of restoring the native or pre-osteoarthritis alignment in each patient. However, there is no consensus on the indications of unrestricted KA-TKA with the STRT. We modified the STRT, followed by an investigation of the effects of surgery on the postoperative hip-knee-ankle angle (HKAA). Materials and Methods: We retrospectively analyzed the clinical background data, including the preoperative and postoperative HKAA, of 87 patients who underwent unrestricted KA-TKA with the modified STRT. Univariate and multivariate analyses were performed to determine the factors affecting the postoperative HKAA. A receiver operating characteristic (ROC) curve was plotted to investigate the change in the cut-off values of preoperative HKAA with respect to the safe zone of the postoperative HKAA. We generated two regression models, the linear regression model and generalized additive model (GAM) using machine learning, to predict the postoperative HKAA. Results: Univariate and multivariate analyses revealed the preoperative HKAA as the factor most relevant to the postoperative HKAA. ROC analysis revealed that the preoperative HKAA exhibited a high predictive utility, with a cut-off value of -10°, when the safe range of postoperative HKAA was set at ±5°. The GAM was the superior machine learning model, indicating a non-linear association between the preoperative and postoperative HKAA. Patients with preoperative HKAAs ranging from -18° to 4° were more likely to fall within the ±5° safe range of the postoperative HKAA. Conclusions: The preoperative HKAA influences the postoperative HKAA in unrestricted KA-TKA with the modified STRT. Machine learning using the GAM may contribute to the selection of patients eligible for the surgical approach.

Fatal case of Capnocytophaga sepsis from a dog bite in a patient with splenic hypoplasia.

Background: Capnocytophaga canimorsus is an oral commensal bacteria in dogs and may cause severe infection following a dog bite. This is a case of fatal C. canimorsus sepsis with acute infectious purpura fulminans (AIPF) in a healthy patient with splenic hypoplasia. Case Presentation: A healthy 49-year-old man was admitted to the intensive care unit (ICU) for septic shock and AIPF 4 days after a dog bite to his mouth. Computed tomography revealed a small spleen measuring 53 cm3 but no other source of infection. Despite intensive care, the patient died of multiple organ failure and progressive shock on the fifth ICU day. Polymerase chain reaction of blood samples identified the C. canimorsus gene on a later day. Conclusion: Capnocytophaga canimorsus from dog bites may cause fatal AIPF. Splenic hypoplasia and bite wounds in well-perfused areas such as the oral cavity are possible risk factors for sepsis. All dog bites should warrant medical attention.

Fluid restriction management in the treatment of COVID-19: a single-center observational study.

The relationship between fluid management and the severity of illness, duration of treatment, and outcome of coronavirus disease 2019 (COVID-19) is not fully understood. This study aimed to evaluate whether weight change during hospitalization was associated with COVID-19 severity, length of hospital stay, and route of admission. In this study, we assessed the effectiveness of fluid restriction management in patients with severe COVID-19. COVID-19 patients admitted to our hospital between July 2020 and October 2021 were analyzed. Patients were treated with standard drug therapy based on the Japanese guidelines and respiratory support according to the severity of the disease. Early enteral nutrition, defecation management, and anticoagulation therapy were also administered. Fluid restriction management was performed using furosemide and continuous renal replacement therapy as needed unless hemodynamic instability or hyperlactatemia was present. Patient background, route of admission (ambulance, A; transfer, T), weight at admission and discharge, the severity of illness (oxygen therapy, G1; mechanical ventilation, G2; extracorporeal membrane oxygenation, G3), in-hospital mortality, and length of hospital stay were analyzed. There were 116 subjects: G1 (n = 48), G2 (n = 43), and G3 (n = 25), with ages (median [IQR]) of 58 (47-70), 65 (53-71.5), 56 (51-62) years, 40 (83.3%), 31 (72.1%), and 19 (76.0%) males, respectively. Hospital stays were 4.5 (2-7), 10 (7-16), and 18 (15-26) days, and the in-hospital mortality rates were 0 (0%), 7 (16.3%), and 8 (32%), respectively. Body mass index on admission was 26 (23.1-30.2), 27.1 (22.7-31.1), and 31.5 (27.1-33.1) kg/m2, and weight loss during admission was 1.1 (0-2.9), 4.6 (2.3-5.7), 9.2 (5.6-10.5) kg (P < 0.001, Jonckheere-Terpstra test. Weight loss in the severe group (G2 + G3) was 3.4 (0.5-5.8) kg [A, n = 12] and 5.6 (4.4-9) kg [T, n = 43] [P = 0.026, Mann-Whitney U test]. The lengths of hospital stay were 5 (2-7), 9 (7-15), and 18 (12-26) days [P < 0.001, Jonckheere-Terpstra test]. In our fluid restriction management, patients with severe COVID-19 had significant longer hospital length of stay, weight loss, especially those who were transferred to the hospital.

Successful application of angioembolization and thoracic endovascular aortic repair (TEVAR) in a retrograde type-A acute aortic dissection with polytrauma.

A 53-year-old man underwent thoracic endovascular aortic repair for persistent false lumen perfusion and limb salvage because of type A aortic dissection, severe lower-limb ischemia, and bleeding (mediastinal hematoma, bilateral lung contusion, liver injury, and splenic injury) caused by blunt trauma. We embolized the left supreme intercostal artery to control active mediastinal hemorrhage. Acute hemorrhage and leg ischemia were well controlled; however, residual blood flow in the false lumen persisted. We performed a Zone 2 thoracic endovascular aortic repair and discharged the patient on day 67. Thoracic endovascular aortic repair is a practical option for treating traumatic type A dissection.

Antifungal Agent Luliconazole Inhibits the Growth of Mouse Glioma-initiating Cells in Brain Explants.

Imidazole antifungal compounds exert their antipathogenic effects through inhibition of sterol biosynthesis. These drugs have also recently been identified as candidate anticancer agents for several solid tumors including glioblastoma. However, their effects on glioma-initiating cells (GICs), i.e., glioma cells with stemlike properties that are able to initiate tumors, remain unclear. Consequently, we examined the effects of the optically active imidazole compound luliconazole on mouse GICs and GIC-based tumors. Luliconazole impaired in a concentration-dependent manner the growth of spheres formed by GICs in vitro. In contrast to the inhibitory effects of ionizing radiation and temozolomide on sphere growth, that of luliconazole was attenuated by the addition of exogenous cholesterol. Exposure to luliconazole of brain slices derived from mice with orthotopic GIC implants for 4 days in culture resulted in a marked increase in the number of tumor cells positive for cleaved caspase-3, but without a similar effect on normal cells. Furthermore, in brain slices, luliconazole inhibited the expansion of GIC-based tumors and the parenchymal infiltration of tumor cells. Our findings therefore indicate that luliconazole effectively targets GICs, thereby providing further support for the antitumorigenic effects of imidazole antifungal compounds.

Correction to: Clinical and histopathological analyses of VEGF receptors peptide vaccine in patients with primary glioblastoma - a case series.

Following publication of the original article [1], the authors reported an error in the author group.

Clinical and histopathological analyses of VEGF receptors peptide vaccine in patients with primary glioblastoma - a case series.

BACKGROUND: The expression of vascular endothelial growth factor (VEGF)-A/ VAGF receptors (VEGFRs) signaling plays a pivotal role in the tumor angiogenesis and the development of the immunosuppressive tumor microenvironment in glioblastomas. We have previously conducted exploratory clinical studies investigating VEGFRs peptide vaccination with and without multiple glioma oncoantigens in patients with recurrent high-grade gliomas. Recently, an exploratory clinical investigation of VEGFRs peptide vaccination was conducted in patients with progressive neurofibromatosis type 2. Those studies suggested that cytotoxic T lymphocytes (CTLs) induced by the vaccination can directly kill a wide variety of cells associated with tumor growth, including tumor vessels, tumor cells, and immunosuppressive cells expressing VEGFR1 and/or 2. In the present study, synergistic activity of the combination of VEGFRs peptide vaccination with chemotherapy was evaluated. METHODS: We performed the first clinical trial to assess VEGFR1 and 2 vaccination along with temozolomide (TMZ) -based chemoradiotherapy for the patients with primary glioblastomas. Furthermore, histopathological changes after the vaccination were evaluated using paired pre- and post- vaccination specimens. RESULTS: The disappearance of radiographically enhanced lesion was observed in 2 patients after the vaccination, including one in which the methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter was not observed. The histopathological findings of pre- and post-vaccination specimens demonstrated that tumor vessels showed negative or slight VEGFRs expressions after the vaccination and most endothelial cells were covered with PDGFR-ß-positive pericytes. Notably, CTLs induced by VEGFRs peptide vaccination attacked not only tumor vessels but also tumor cells and regulatory T cells expressing VEGFRs even in recurrent tumors. CONCLUSIONS: VEGFR1 and 2 vaccination may have a preliminary synergistic effect when administered with TMZ. The limitation of the present study was the paucity of the number of the samples. Further studies involving more patients are warranted to confirm the findings of this study. TRIAL REGISTRATION: This study was registered as UMIN000013381 (University Hospital Medical Information Network-Clinical Trial Registry: UMIN-CTR) on 5 March, 2014 and with the Japan Registry of Clinical Trials (jRCT) as jRCTs031180170 on 1 March, 2019.

A Pilot Study of Vaccine Therapy with Multiple Glioma Oncoantigen/Glioma Angiogenesis-Associated Antigen Peptides for Patients with Recurrent/Progressive High-Grade Glioma.

High-grade gliomas (HGGs) carry a dismal prognosis despite current treatments. We previously confirmed the safety and immunogenicity of a vaccine treatment targeting tumor angiogenesis with synthetic peptides, for vascular endothelial growth factor receptor (VEGFR) epitopes in recurrent HGG patients. In this study, we evaluated a novel vaccine therapy targeting not only tumor vasculature but also tumor cells, using multiple glioma oncoantigen (GOA)/glioma angiogenesis-associated antigen (GAAA) peptides in HLA-A2402+ recurrent/progressive HGG patients. The vaccine included peptide epitopes from four GOAs (LY6K, DEPDC1, KIF20A, and FOXM1) and two GAAAs (VEGFR1 and VEGFR2). Ten patients received subcutaneous vaccinations. The primary endpoint was the safety of the treatment. T-lymphocyte responses against GOA/GAAA epitopes and treatment response were evaluated secondarily. The treatment was well tolerated without any severe systemic adverse events. The vaccinations induced immunoreactivity to at least three vaccine-targeted GOA/GAAA in all six evaluable patients. The median overall survival time in all patients was 9.2 months. Five achieved progression-free status lasting at least six months. Two recurrent glioblastoma patients demonstrated stable disease. One patient with anaplastic oligoastrocytoma achieved complete response nine months after the vaccination. Taken together, this regimen was well tolerated and induced robust GOA/GAAA-specific T-lymphocyte responses in recurrent/progressive HGG patients.

A pilot study of peptide vaccines for VEGF receptor 1 and 2 in patients with recurrent/progressive high grade glioma.

OBJECT: Early-phase clinical studies of glioma vaccines have shown feasibility and encouraging preliminary clinical activity. A vaccine that targets tumor angiogenesis factors in glioma microenvironment has not been reported. Therefore, we performed a pilot study to evaluate the safety and immunogenicity of a novel vaccination targeting tumor angiogenesis with synthetic peptides for vascular endothelial growth factor (VEGF) receptor epitopes in patients with recurrent/progressive high grade gliomas. METHODS: Eight patients received intranodal vaccinations weekly at a dose of 2mg/kg bodyweight 8 times. T-lymphocyte responses against VEGF receptor (VEGFR) epitopes were assessed by enzyme linked immunosorbent spot assays. RESULTS: This treatment was well-tolerated in patients. The first four vaccines induced positive immune responses against at least one of the targeted VEGFR epitopes in the peripheral blood mononuclear cells in 87.5% of patients. The median overall survival time in all patients was 15.9 months. Two achieved progression-free status lasting at least 6 months. Two patients with recurrent GBM demonstrated stable disease. Plasma IL-8 level was negatively correlated with overall survival. CONCLUSION: These data demonstrate the safety and immunogenicity of VEGFR peptide vaccines targeting tumor vasculatures in high grade gliomas.

Gold-nanofève surface-enhanced Raman spectroscopy visualizes hypotaurine as a robust anti-oxidant consumed in cancer survival.

Gold deposition with diagonal angle towards boehmite-based nanostructure creates random arrays of horse-bean-shaped nanostructures named gold-nanofève (GNF). GNF generates many electromagnetic hotspots as surface-enhanced Raman spectroscopy (SERS) excitation sources, and enables large-area visualization of molecular vibration fingerprints of metabolites in human cancer xenografts in livers of immunodeficient mice with sufficient sensitivity and uniformity. Differential screening of GNF-SERS signals in tumours and those in parenchyma demarcated tumour boundaries in liver tissues. Furthermore, GNF-SERS combined with quantum chemical calculation identified cysteine-derived glutathione and hypotaurine (HT) as tumour-dominant and parenchyma-dominant metabolites, respectively. CD44 knockdown in cancer diminished glutathione, but not HT in tumours. Mechanisms whereby tumours sustained HT under CD44-knockdown conditions include upregulation of PHGDH, PSAT1 and PSPH that drove glycolysis-dependent activation of serine/glycine-cleavage systems to provide one-methyl group for HT synthesis. HT was rapidly converted into taurine in cancer cells, suggesting that HT is a robust anti-oxidant for their survival under glutathione-suppressed conditions.

Hyperperfusion after Clipping of Aneurysm: A Rare Entity.

BACKGROUND: Cerebral vasospasm is an uncontrollable and sometimes fatal complication occurring after subarachnoid hemorrhage. However, cerebral hyperperfusion syndrome is a rare complication after subarachnoid hemorrhage. Although plain computed tomography of cerebral hyperperfusion syndrome looks similar to cerebral infarction induced by cerebral vasospasm, they should be distinguished from each other because they require completely different treatments. CASE DESCRIPTION: A 65-year-old man complained of severe headache and vomiting. A computed tomography scan of his head showed subarachnoid hemorrhage with acute hydrocephalus caused by intraventricular hematoma and aneurysm of the left middle cerebral artery. After endoscopic irrigation of the ventricular hematoma to decrease the intracranial pressure, we performed neck clipping for the ruptured aneurysm. We used a temporary clip to the proximal M1 segment twice for a total of 15 minutes. Five days after the clipping, a computed tomography scan of the patient's head showed a large low-density area in the left cerebral hemisphere. Although cerebral infarction caused by cerebral vasospasm was suspected, his perfusion computed tomography demonstrated a state of hyperperfusion corresponding to the low-density area. We started treatment to prevent vasodilation and excessive cerebral blood flow instead of treatment for cerebral vasospasm. After changing the treatment, the patient's symptoms gradually improved, and his perfusion computed tomography (8 days after surgery) showed no excessive increased blood flow. CONCLUSIONS: We present a case of cerebral hyperperfusion syndrome and its successful treatment, distinct from that of cerebral vasospasm, after ruptured aneurysm clipping. In addition, we discuss the mechanism of this rare syndrome based on previous reports.

Postnatal delayed exacerbation of dural sinus malformation associated with brainstem cavernous malformations: A case report.

Dural sinus malformation (DSM) is a rare paediatric vascular malformation characterised by abnormal dilation of the posterior dural sinus. Owing to its rarity, the pathophysiology of DSM has not been fully elucidated. We report a case of prenatally diagnosed DSM with an unusual clinical course. We detected DSM in a male foetus in the 26th week of gestation by using foetal ultrasonography. Although the DSM regressed during the foetal stage and the arteriovenous shunt was insignificant in the neonate, the shunt rapidly developed four months after birth. The neonate also had postnatal de novo brainstem cavernous malformation (CM), which also developed rapidly, supposedly due to the aggravated venous hypertension resulting from the DSM. We successfully treated the aggravated shunts by endovascular transarterial and transvenous embolisation six times over two years and, subsequently, the clinical condition and the size of the brainstem CM became stable. The DSM and CM seemed to have a metameric origin. Such aberrant cases could help to further the understanding of DSM.

A ruptured aneurysm in the vasa corona at the craniocervical junction with dysgenesis of the posterior inferior cerebellar artery.

This paper reports the case of a ruptured aneurysm in the vasa corona at the craniocervical junction with dysgenesis of the posterior inferior cerebellar artery (PICA). Dysgenesis of the proximal PICA in the present case caused the development of a pial anastomosis in the vasa corona, resulting in the formation of an aneurysm because of increased haemodynamic stress at the vasa corona. The aneurysm was successfully treated with transarterial coil embolization. The clinical entity in the present case is extremely rare and it is important to consider an aberrant vascular anomaly as the cause of an isolated spinal aneurysm.

GH-Producing Pituitary Adenoma and Concomitant Rathke's Cleft Cyst: A Case Report and Short Review.

Concomitant pituitary adenoma (PA) and Rathke's cleft cyst (RCC) are rare. In some cases, such PA is known to produce pituitary hormones. A 53-year-old man was admitted to our hospital with a diagnosis of lacunar infarction in the left basal ganglia. Magnetic resonance imaging (MRI) incidentally showed a suprasellar mass with radiographic features of RCC. When he consulted with a neurosurgical outpatient clinic, acromegaly was suspected based on his appearance. A diagnosis of growth hormone- (GH-) producing PA was confirmed from hormonal examinations and additional MRI. Retrospectively, initial MR images also showed intrasellar mass that is compatible with the diagnosis of PA other than suprasellar RCC. The patient underwent endonasal-endoscopic removal of the PA. Since we judged that the RCC of the patient was asymptomatic, only the PA was completely removed. The postoperative course of the patient was uneventful and GH levels gradually normalized. Only 40 cases of PA with concomitant RCC have been reported to date, including 13 cases of GH-producing PA. In those 13 cases, RCC tended to be located in the sella turcica, and suprasellar RCC like this case appears rare. In a few cases, concomitant RCCs were fenestrated, but GH levels normalized postoperatively as in the cases without RCC fenestration. If radiographic imaging shows typical RCC, and PA is not obvious at first glance, the possibility of concomitant PA still needs to be considered. In terms of treatment, removal of the RCC is not needed to achieve hormone normalization.

[Physiognomy-accompanying auditory hallucinations in schizophrenia: psychopathological investigation of 10 patients].

We previously reported two schizophrenic patients with characteristic hallucinations consisting of auditory hallucinations accompanied by visual hallucinations of the speaker's face. The patient sees the face of the hallucinatory speaker in his/her mind and hears the voice talking inwardly. We termed these experiences physiognomy-accompanying auditory hallucinations. In this report, we present 10 patients with schizophrenia showing physiognomy-accompanying auditory hallucinations and evaluate the characteristics of these clinical symptoms. Moreover we consider what the symptoms mean for patients and the metabasis from structural aspects. Lastly, we consider how we can treat these patients living autistic lives with the symptoms. During physiognomy-accompanying auditory hallucinations, the realistic face moves its mouth and talks to the patient expressively. In early onset cases, the faces of various real people appear talking about ordinary things while in late onset cases, the faces can be imaginary but are mainly real people talking about ordinary or delusional things. We suppose that these characteristics of the symptoms unify the schizophrenic world overwhelmed by "a force of non-sense" to "the sense field". "The force of non-sense" is a substantial power but cannot be reduced to the real meaning. And we suppose that not visual reality but the intensity of auditory hallucinations of the face brings about the overwhelming intensity of symptoms and the substantiality of this intensity depends on the states of excessive fullness of "the force of non-sense". With these symptoms patients see the narration of auditory hallucinations through the facial image and the content of auditory hallucinations is compressed into the movement of visual hallucinations of the speaker's face. The form of symptoms is realistic but the speaker's face and voice are beyond ordinary time and space. The symptoms are essentially different from ordinary perception. The visual hallucinations of the speaker's face in "physiognomy-accompanying auditory hallucinations" has the same structural nature as typical auditory hallucinations in schizophrenia. Further the symptoms are different from the organic hallucinations caused by the pathology of consciousness. After onset the patients seem to restructure their living world to coexist with the symptoms. What we can do in treatment is to regard coexistence with the symptoms as a way of life and consider the roles of the symptoms in the patients' world and grope for the possibility that the patients may be able to live without depending on the pathological world.

Chitinase-catalyzed synthesis of an alternatingly N-sulfonated chitin derivative.

An alternatingly N-sulfonated chitin derivative (2) was synthesized via ring-opening polyaddition of an N-sulfonated chitobiose oxazoline derivative (1) catalyzed by chitinases from Bacillus sp. and Serratia marcescens. The polymerization proceeded homogeneously, providing 2 as a water-soluble polysaccharide in good yields with total control of regioselectivity and stereochemistry. M(n) of 2 reached 1900 and 4180 by use of chitinases from Bacillus sp. and Serratia marcescens, which correspond to 8-10 (n = 4-5) and 18-20 (n = 9-10) saccharide units, respectively. These results indicate that M(n) of 2 is controllable by selecting chitinases from different origins. It is considered that the C-2 position of the nonreducing unit in the oxazoline-type monomer is not deeply involved in the catalysis of chitinase.

[Regulation of TH activity by GAD immunoreactivity in rat peri-LC after chronic variable stress].

Locus coeruleus (LC) is the major component of noradrenergic neurons in the brain. The corticotropin-releasing hormone (CRH) and norepinephrine (NE) are suggested to play a role in modulating the central stress response. In a previous study we observed a decrease of the basal level of tyrosine hydroxylase (TH) immunoreactivity (-ir) in the LC of rats treated with chronic variable stress (CVS) for 14 days. Furthermore a novel stressor produced an enhanced response of the TH-ir after CVS. In the present study we examined the effect of CVS on the glutamic acid decarboxylase (GAD)-ir activity of periaqueductal gray (PAG), prepositus hypoglossi (PrH) and peri-LC. The GAD-ir was significantly increased in PrH and peri-LC after CVS. The footshock-induced reactivity in the GAD-ir was decreased in both regions after CVS. Moreover, we investigated the influence of the CRH receptor antagonist, alphah-CRH (i.c.v.) on the CVS-induced activation of the TH-ir in the LC. The alphah-CRH i.c.v. diminished the enhanced-TH reactivity by novel stressor after CVS. Our results suggest that the GABA activity in peri-LC and PrH might regulate the LC-TH response, and also the CRH input from central nucleus of amygdala (CeA) and/or the bed nucleus of stria terminalis (BNST) might regulate the TH reactivity.

[Effect of chronic variable stress on limbic corticotrapin-releasing hormone receptor].

The Corticotropin-releasing hormone (CRH) is a key mediator in the stress response. Two CRH-receptor subtypes have been identified in the brain, CRH-receptor 1 (CRH-R1) and CRH-receptor 2, and stress responses are mediated by the CRH-R1. In this study we have examined the effect of chronic variable stress (CVS) on the CRH-R1 immunoreactivity in the hypothalamic and limbic brain regions of the rat. For CVS we selected the six stressors described in previous reports. Male Wistar rats were randomly exposed to one stressor per a day during 13 days and finally exposed to a novel stressor (footshock). There was a significant increase of the CRH-R1 immunoreactivity 24 hours after CVS in the bed nucleus of the stria terminalis (BNST) and basolateral amygdala (BLA), whereas a single footshock had no influence on the immunoreactivity in any of the regions. A novel stressor after CVS suppressed within 24 hours the CVS-induced increase in the CRH-R1 immuoreactivity in the BNST and BLA. Our results suggest that an up-regulation of the limbic CRH-R1 may contribute to stress sensitization (vulnerability) such as an anxiety, arousal and hypersympathetic autonomic symptoms under stressful situations.

[Effect of concurrent treatment of SSRI on the tyrosine hydroxylase immunoreactivity in the rat locus coeruleus treated with chronic variable stress].

Locus coeruleus (LC) is the major component of noradrenergic neurons in the brain. corticotropine-releasing hormone (CRH) and norepinephrine (NE) are suggested to play significant roles in the pathophysiology of depression, although the involvement of the serotonergic system in the CRH-NE systems is not elucidated. Chronic inescapable and unpredictable stress can result in a sustained dysregulation of both of CRH and NE systems. In the present study we have investigated the TH immunoreactivity in the LC by immunohistochemical staining in rats treated with chronic variable stress (CVS) and concurrent administration with clomipramine or fluvoxamine. There was a significant decrease in TH levels 24 h after the last stressor of CVS, followed by a further decrease in that of 72 h later, whereas a marked increase was observed in TH levels immediately after the last stress of CVS 13 d. Concurrent clomipramine and fluvoxamine treatment prevented the sensitization of TH reactivity and the delayed decrease until 72 h later. These data suggest that an increase in serotonin availability would contribute to the normalization of both hypoactivity and sensitization of LC-NE neurons modified under "chronically stressful" situations.

An Ideal One-Dimensional Antiferromagnetic Spin System Observed in Hydrogen-Bonded Naphth[2,3-d]imidazol-2-yl Nitronyl Nitroxide Crystal: The Role of the Hydrogen Bond.

A novel stable organic radical, 2-(naphth[2,3-d]imidazol-2-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazolyl-1-oxyl-3-oxide (4), has been designed, synthesized, and structurally characterized to examine the effects of ring extension on 2-(benzimidazol-2-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazolyl-1-oxyl-3-oxide (2). 4 forms four-centered intramolecular and intermolecular hydrogen bonds, and the hydrogen bonds are repeated along the c-axis to form a one-dimensional chain structure. This hydrogen-bonding motif contrasts that of 2, which forms three-centered intramolecular and intermolecular hydrogen bonds. The magnetic susceptibility measurement of 4 reveals that an antiferromagnetic interaction is dominant between spins, and the magnetic behavior is reproduced by the Bonner-Fisher model with J = -14 cm-1. Because each hydrogen-bonded chain is well isolated, a magnetic interaction pathway was thought to exist along the chain direction. Two interaction pathways have been assumed: (i) through-space interaction between the O atoms of the nitroxide and (ii) through the NH...ON intermolecular hydrogen bond. We have concluded that pathway (i) is predominant, by considering the identical magnetic data between the NH nondeuterated and deuterated samples. The hydrogen bond mainly has a role in crystal scaffolding.