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Allopregnanolone (ALLO) is a neurosteroid produced in the brain, but so far, no study has explored its link with itching. Herein, we used a diet-induced atopic dermatitis mouse model to examine whether exogenously administered and endogenously produced ALLO contribute to inducing scratching. Systemic administration of ALLO elicited robust scratching in the atopic dermatitis model, while it did not affect spontaneous and pruritogen-induced scratching in normal mice. ALLO caused scratching when administered intracisternally, but not when administered intrathecally or intradermally, suggesting the involvement of supraspinal mechanisms. Pharmacological analyses suggested that both γ-aminobutyric acid type A receptor activation and serotonin type 3 receptor inhibition were involved in ALLO-induced scratching. We next examined whether endogenously produced ALLO is involved in ethanol-induced scratching in atopic dermatitis mice, because ethanol administration increases ALLO in rodent brain. Acute ethanol administration increased brain ALLO levels, which coincided with increased scratching. Pre-treatment with finasteride, a synthetic ALLO inhibitor, suppressed ethanol-induced scratching and ALLO production in the brain. Collectively, our results demonstrated for the first time that ALLO administration caused marked scratching in atopic dermatitis mice, and ethanol-induced scratching may be mediated through endogenously produced brain ALLO.

In chronic pruritic diseases such as atopic dermatitis, pruritus is exacerbated during nocturnal sleep; however, the underlying mechanism remains unclear. We previously demonstrated that acute administration of the sedative-hypnotics ethanol markedly enhanced itch-associated spontaneous scratching in a diet-induced mouse model of atopic dermatitis. In the present study, to expand our previous finding and provide a general mechanism for the central modulation of chronic itch, we examined whether other hypnotic drugs, such as barbiturates and benzodiazepines, also enhance scratching, and further investigated the underlying mechanism. Barbiturates markedly enhanced spontaneous scratching in the atopic dermatitis model but not controls. However, unexpectedly, benzodiazepines only slightly increased scratching, and the selective γ-aminobutyric acid type A (GABA A ) receptor agonist, muscimol, had no effect. Local injection studies have demonstrated that barbiturates act at the supraspinal level to enhance scratching. Barbiturate-induced scratching was inhibited not only by GABA A receptor antagonists but also by an L-type voltage-dependent calcium channel (L-VDCC) agonist and an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor agonist. An intracisternally injected AMPA receptor antagonist alone or in combination with an L-VDCC antagonist sufficiently enhanced scratching. Barbiturate-induced scratching enhancement was observed in another atopic dermatitis model, NC/Nga, but not in histamine-induced acute itch model in normal healthy mice. Overall, our results suggest that a synergistic effect among AMPA receptor inhibition, GABA A receptor activation, and L-VDCC inhibition in the brain mediates barbiturate-induced scratching in atopic dermatitis mice. This observation may provide a novel clue to understanding a supraspinal itch mechanism in chronic diseases such as atopic dermatitis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A novel transformation reaction of methylene acetals, using a combination of trimethyl(phenylthio)silane (PhSTMS) and N-bromosuccinimide (NBS) under mild reaction conditions, is described. Various methylene acetals were converted to their corresponding bromoformates in good to high yields. Under the given conditions, the reaction proceeded via a radical pathway. Further transformation of bromoformates to their corresponding epoxides was achieved by treatment with NaOMe.

Tea plants (Camellia sinensis) store volatile organic compounds (VOCs; monoterpene, aromatic, and aliphatic alcohols) in the leaves in the form of water-soluble diglycosides, primarily as β-primeverosides (6-O-β-D-xylopyranosyl-β-D-glucopyranosides). These VOCs play a critical role in plant defenses and tea aroma quality, yet little is known about their biosynthesis and physiological roles in planta. Here, we identified two UDP-glycosyltransferases (UGTs) from C. sinensis, UGT85K11 (CsGT1) and UGT94P1 (CsGT2), converting VOCs into β-primeverosides by sequential glucosylation and xylosylation, respectively. CsGT1 exhibits a broad substrate specificity toward monoterpene, aromatic, and aliphatic alcohols to produce the respective glucosides. On the other hand, CsGT2 specifically catalyzes the xylosylation of the 6'-hydroxy group of the sugar moiety of geranyl β-D-glucopyranoside, producing geranyl β-primeveroside. Homology modeling, followed by site-directed mutagenesis of CsGT2, identified a unique isoleucine-141 residue playing a crucial role in sugar donor specificity toward UDP-xylose. The transcripts of both CsGTs were mainly expressed in young leaves, along with β-primeverosidase encoding a diglycoside-specific glycosidase. In conclusion, our findings reveal the mechanism of aroma β-primeveroside biosynthesis in C. sinensis. This information can be used to preserve tea aroma better during the manufacturing process and to investigate the mechanism of plant chemical defenses., (© 2015 American Society of Plant Biologists. All Rights Reserved.)

A/J strain mice have a high spontaneous incidence of cleft lip (ICL) and/or palate. The primary palate-related effects of sevoflurane on developing A/J strain mouse embryos (embryos) were studied using a whole-embryo culture (WEC) system. This system could separate the direct effects of sevoflurane from those that are maternally mediated. A total of 205 10.5-d embryos were cultured for 24 h in either a control group (control gas: 95% O2 and 5% CO2) or sevoflurane-administered groups (1/4, 1/2, and 1 minimum alveolar concentration (MAC) with control gas) for 8 h. After 16 h, 11.5-d culture embryos were examined in terms of crown-rump length, number of somites, and protein content. Crown-rump length in the 1 MAC was significantly shorter than in the control group (p < 0.05). Protein content in the 1/2 MAC (p < 0.05) and 1 MAC (p < 0.001) was significantly lower than in the control group. The ICL showed no significant differences between each group. (The ICL rose with an increase in the sevoflurane concentration, but this was not significant). The positive findings in this study indicate that a WEC system is useful for studying the mechanisms of ICL (teratogenicity) associated with sevoflurane.

Objective and Importance: A type of intrinsic dorsal midbrain glioma known as benign tectal glioma can cause obstructive hydrocephalus. Because of its slow progress and relatively good prognosis, initial treatment should be cerebrospinal fluid diversion and biopsy., Clinical Presentation: We report a 24-year-old man with obstructive hydrocephalus from a tectal glioma, who was admitted to the hospital for malfunction of a shunt placed 16 years previously., Intervention: Magnetic resonance imaging demonstrated enlargement of the dorsal midbrain associated with increased signal intensity on T2-weighted images and fluid attenuation inversion recovery (FLAIR) images. No enhancement occurred with contrast administration. We performed a neuroendoscopic third ventriculostomy and biopsy of the tumor. Histologic examination of the specimen obtained disclosed a low-grade astrocytoma. No postoperative neurologic complications occurred., Conclusion: FLAIR images were superior to T2-weighted images in demonstrating abnormal intensity in the dorsal midbrain. Neuroendoscopy confirmed a yellowish tumor inferior to the posterior commissure occluding the entrance of the aqueduct, an observation useful in planning biopsy of the lesion. As the tumor apparently had existed for a number of years, the case supports the notion that the prognosis associated with these tumors is good.

Two cases of ossified epidural hematomas were reported. Patients were nine and twelve year-old boys. Initially they were both followed up conservatively after injuries. Subsequently they were found on CT scan to have calcifications in the capsules of epidural hematomas which were found four months after injury in one case and twelve days after injury in the other. Both underwent craniotomy and histological ossification was found in the capsules of the hematomas. Epidural hematomas in children are known to ossify, and this condition may prevent natural absorption of epidural hematomas. Therefore, careful follow up of hematomas seems to be mandatory on conservative therapy of epidural hematomas in children.

We reported a case of ruptured aneurysm of the anterior communicating artery with marked dilatation of bilateral cervical carotid arteries. A 38 year old female suffered a subarachnoid hemorrhage. Angiography on admission revealed markedly dilated cervical carotid arteries with smooth lumen and a few segmental areas with mild constrictions in their entire course up to the carotid canals (their maximal sagittal diameters exceeded those of a cervical vertebral body). A saccular aneurysm was also seen at the junction of right A1, A2, and Acom. External carotid arteries were normal in size. Vertebral arteries were not examined because of failures of selective cannulation. The patient was operated upon and trapping of Acom was performed. During the operation, no definite arteriosclerotic changes were identified in the intracranial arteries. Histopathological examination of the surgical specimens revealed marked hyperplasia of the smooth muscle of the tunica media with intact internal elastic lamina both in a superficial temporal artery and a middle meningeal artery. During the operation, pneumothorax developed due to the rupture of bullae in the right lung. Past history of this patient disclosed hypertension noted a few years previously, and frequent severe bruises following minor trauma. Repeated angiography performed three months after the operation disclosed unchanged dilatation of the cervical carotid arteries as well as mild intraluminal irregularities in the proximal one third of the left renal artery. This patient died of pneumonia one year after the operation, but autopsy was not permitted. Possible diagnosis of this patient was discussed, with particular emphasis on fibromuscular dysplasia and Ehlers-Danlos type IV (arterial, ecchymotic, or Sack-Barabas type).(ABSTRACT TRUNCATED AT 250 WORDS)

This 42-year-old man experienced a sudden onset of occipital headache. Neurological examination revealed a moderately disturbed consciousness and a moderate left hemiparesis. CT scan disclosed a hugh hematoma in the right temporo parietal lobe without intraventricular hemorrhage. A cerebral angiography demonstrated typical findings of moyamoya disease and a small saccular aneurysm at the peripheral portion of the right anterior choroidal artery, which was dilated at the collateral circulation to the parietal lobe. The hematoma was removed at once by a craniotomy. He became alert but mild hemiparesis persisted. MRI disclosed a small signal-void lesion lateral to the trigone of the right lateral ventricle. The angiography repeated three weeks after the removal of the hematoma showed the unchanged size of the aneurysm. Direct surgery for the aneurysm was performed via the right parietal transcortical approach. The aneurysm was reached under the guidance of the intraoperative angiography. Trapping of the parent artery and the excision of the aneurysm were performed. On the basis of the presence of an internal elastic lamina at the neck of the aneurysm, the surgical specimen was histologically verified to be a true aneurysm. Since the collateral circulation was well preserved during surgery, no worsening of the neurological manifestation was observed. In view of the unfavorable prognosis for a moyamoya patient with this type of the aneurysm, which often results in a massive ventricular or intracerebral hemorrhage, surgery directed to the aneurysm itself should be considered.

This is a report of a young girl who showed a recurrence of acute worsening and remission of neurological manifestations, with consistent MRI demonstration of transaxial septated syrinxes in the cervical and the lumbar spinal cord in addition to a tight filum terminale. This 8 year-old girl had developed normally since her birth until August 1989 when she developed a gait disturbance. This worsened acutely on January 1, 1990, with the additional manifestation of a urinary bladder disturbance. General examination failed to show any abnormality or scoliosis. Neurologic examination revealed a monoparesis of the right lower extremity with muscle atrophy and pyramidal tract sign. Fecal constipation and urinary retention were noted. The MRI T1 weighted sagittal image demonstrated an incontinuous low intensity signal in the C1-C7 as well as in the T12-L2 without swelling of the cord. The axial image clearly demonstrated the septations in the syrinx which looked like eye glasses. No definite Gd enhancement was demonstrated. Chiari malformation was not associated, but the tethered cord was well identified. With the administration of steroid, she showed a marked improvement of neurological manifestations. She was able to urinate without difficulty and also walk by herself. For one month thereafter she remained well with minor neurological deficits until she developed a worsening of the gait disturbance with a newly manifested weakness of the left upper extremity. Sensory impairment was also demonstrated below L3. In contrast to the worsening of the clinical symptoms, no definite change in the abnormalities found by MRI was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

The patient, a 44-year-old female, was admitted to our department because of right hemiparesis and left oculomotor nerve palsy on February 7, 1986. Neither lymphadenopathy nor hepatosplenomegaly was present. She had been treated with prednisolone for systemic lupus erythematosus (SLE) for one and a half year before admission. The CT scan revealed a homogeneously enhanced mass lesion from the midbrain through the thalamus on the right side. The whole body gallium scintigram showed no abnormal uptake except in the brain. Stereotaxic biopsy was performed. Histopathological diagnosis was malignant lymphoma, diffuse, large cell type (International Working Formulation). The enhanced mass lesion disappeared after radiation therapy. Subsequently, she received chemotherapy. She remained well until May 1988 when she died because of the systemic lymphadenopathy. The association of malignant lymphoma and SLE has appeared occasionally in the literature. Primary intracerebral malignant lymphoma associated with SLE is much rarer but it should be considered in the differential diagnosis of symptoms of the central nervous system in a patient with SLE. Therefore, biopsy of a cerebral mass lesion is mandatory if appropriate therapy such as radiation and chemotherapy is to be administered.

A 55-year-old male was hospitalized with severe headache. On admission, neurological examination revealed no abnormal findings. Plain computed tomography (CT) showed a slightly high-density area in the medial surface of the right parietal lobe. A marked enhancement in the same region was noted in enhanced CT. Cerebral angiography showed an arteriovenous malformation (AVM) in the medial surface of the right parietal lobe and two aneurysms on the right pericallosal artery which fed the AVM. In addition, a saccular aneurysm was noted at the anterior communicating artery. It was not possible to treat the AVM, two aneurysms nearby the AVM, and the unruptured anterior communicating artery aneurysm simultaneously with a single craniotomy. It was therefore decided to perform surgery for the AVM and two aneurysms nearby the AVM prior to clipping of the anterior communicating artery aneurysm. Total excision of the AVM and two aneurysms nearby the AVM was performed. Cerebral angiography performed 18 days after surgery revealed no AVM and also reduction in size was noted of the anterior communicating artery aneurysm. Three months later, repeated cerebral angiography showed disappearance of the aneurysm. This was further confirmed 15 months after surgery by angiography. From the literature, 117 cases of coexistence of AVM and aneurysms of the brain were collected and classified into three types according to their anatomical and hemodynamic correlation. It is suggested that hemodynamic stress, due to increased blood flow caused by the AVM, played a major role in the development of the aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of multiple myeloma forming an intracranial mass which invaded the skull base was reported. A 72-year-old woman was admitted to the hospital because of left oculomotor paresis. Plain craniograms showed multiple punched out lesions. A CT scan demonstrated a mass lesion, which was homogeneously slightly enhanced with contrast medium, in the middle cranial fossa. MRI, both T1 and T2 weighted images, showed an isodensity mass. In the carotid angiograms the tumor was fed by the right branches of the cavernous portion of the internal carotid artery and the maxillary artery. Laboratory data were as follows: ESR: 132mm/30min, serum TP: 9.0g/dl, IgG: 4670mg/dl, IgA: 430mg/dl, and urinary Bence-Jones protein was detected. Bone marrow biopsy of the illiac bone demonstrated myeloma cells. During hospitalization oculomotor paresis disappeared, and the patient was treated with intramuscular interferon-alpha. Multiple myeloma which invades the skull base is rare, and only 10 cases have been reported since 1977. Moreover, the biclonal type is only 0.5% of all multiple myelomas.

The authors investigated the analgesic effects of small morphine doses injected into the paraventricular nucleus (PVN) of normal rats and hypophysectomized (Hx) rats. An injection cannula was stereotactically inserted into the PVN or third ventricle. On the 5-7th postoperative day, morphine (7 micrograms) was injected and the pain threshold (paw lick latency: PLL) was measured using a hot plate analgesia meter (52.0 +/- 0.1 degrees C). PVN morphine injection caused significantly longer PLL than the control (physiological saline) in both normal and Hx rats. Ventricular morphine injection did not increase PLL over the control. PVN is a site of morphine action. The analgesia induced by PVN morphine injection was not affected by hypophysectomy, or induced by leaking of morphine into the third ventricle.

An experiment was performed to determine the projections of the anterior, central, and posterior regions of hippocampus to the spetum in the squirrel monkey. Lesions were placed in each of these regions of hippocampus in 18 animals. Survival times varied from 5 to 7 days. Tissues were stained principally by the Fink-Heimer I method for identification of degenerating axons and their terminals. Following lesions which destroyed one or more fields of the anterior third of hippocampus degenerating axons were traced through the fimbria and fornix to the lateral septal area where dense quantities of terminal degeneration were observed. Smaller quantities of terminal degeneration were noted in the nucleus accumbens as well. After lesions of the middle third of hippocampus terminal degeneration was observed in an intermediolateral position within the septum. Following lesions of the posterior third of hippocampus degenerating terminals were observed in the area of the medial septum. All regions of hippocampus send fibers to the nucleus of the diagonal band and to the olfactory tubercle. These findings indicate that in the primate the projection to the septum from the hippocampus is topographically organized along its longitudinal axis in a manner that links the anterior hippocampus to the lateral septum and the posterior hippocampus to the medial septum.

A rare case of idiopathic brain stone with psychomotor epilepsy is reported. On December 9, 1982, a 29-year-old man with 18 years' history of psychomotor epilepsy was admitted to our neurosurgical service. He had no history of neonatal asphyxia, trauma or other neurological diseases. No neurological deficit was disclosed. Skull x-ray films and plain CT scan demonstrated a calcified mass in the right temporal lobe. No contrast enhancement was noted. Despite an extensive search, the etiology of the calcified mass was not revealed. Conventional EEG showed focal spike discharges in the right anterior temporal lead and telemetered EEG monitoring for 24 hours disclosed sharp wave burst in the right temporal lobe. In spite of appropriate medication, seizures persisted. At surgery, electrocorticogram and stereo-electrocorticogram showed paroxysmal epileptiform events in the right temporal lobe. Anterior temporal lobectomy with excision of calcified mass was done. Histopathological examination demonstrated thick collagen fibers and gliosis around the stone, and diagnosis of idiopathic brain stone was made. We reviewed five previously reported cases. We also emphasized an epileptogenicity of idiopathic brain stone and indication of surgical excision which may result in an excellent control of epilepsy.

Quisqualic acid (QA) is a potent neuroexcitant and a heterocyclic analogue of glutamate as is kainic acid. Twenty micrograms of QA in unilateral lateral amygdaloid nucleus of cats produced a transient limbic status epilepticus lasting 20-30 hours. Over 14 days after recovery from the limbic status, the animals received daily electrical stimulation to the ipsilateral hippocampus at the intensity of afterdischarge threshold which was determined before the injection of QA. These stimulations resulted in secondarily generalized convulsive seizures in all animals within 4 to 12 days. Spontaneous secondarily generalized seizures were confirmed in two cats after completion of the hippocampal kindling. This rapid completion of the kindling process is interesting phenomenon in contrast to the report that the hippocampal kindling took nearly 60 days. This rapid completion of the kindling effect is considered to be due to the transfer effect (Goddard, 1975) established in the ipsilateral hippocampus by severe bombardments from the amygdala stimulated by the injection of QA as the primary focus. In addition, the pathological changes in the amygdala and hippocampus on the injected side might be related to the rapid kindling process of the ipsilateral hippocampus as the irritable foci.

Electrographic and clinical observations were made after the injection of kainic acid into the unilateral hippocampus of freely moving cats. Vehicle solution (phosphate buffer solution) for control study and kainic acid(1, 4 and 12 micrograms) were administered via a chronically implanted cannula. The control group showed no modification during the observation period. After the injection of 1 microgram of kainic acid, focal status epilepticus was observed for 2-3 days and then cats became normal afterwards. In the group of 4 micrograms kainic acid infection, cats demonstrated limbic status for 3 days, and persistent inter-ictal discharges continued during the observation period. Independent amygdaloid seizures and secondary generalized convulsions developed in the cats administered 12 micrograms of kainic acid. The cats died in the status epilepticus. The dose-dependent and substantial effect of KA without the influences of anesthesia and surgery was demonstrated. The results were discussed in relation to the human medial temporal sclerosis and the effects on the emotional mechanism of the limbic system. We suggest this model to be useful in the study of various types of temporal lobe epilepsy and the emotional mechanisms of the limbic system.