The Calcium-sensing Receptor (CaR) is involved in strontium ranelate-induced osteoblast differentiation and mineralization.

Strontium ranelate is known to reduce fracture risk in osteoporotic patients by stimulating bone formation and suppressing bone resorption. However, the mechanism by which strontium exerts this beneficial effect on bone is unclear. We examined whether or not the calcium-sensing receptor (CaR), which is activated by divalent cations including Sr (2+), is involved in this mechanism. Both strontium ranelate and strontium chloride dose-dependently stimulated phosphorylation of extracellular signal-regulated kinase (ERK) in Human Embryonic Kidney 293 cells transiently transfected with the human CaR. Strontium ranelate also dose- and time-dependently stimulated phosphorylation of ERK in mouse osteoblastic MC3T3-E1 cells expressing the CaR endogenously. Strontium ranelate increased mRNA expression of osteocalcin and bone morphogenetic protein-2 in MC3T3-E1 cells as well as mineralization and proliferation of the cells. Pretreatments of NPS2390, a CaR inhibitor, almost totally antagonized strontium ranelate-induced mineralization and proliferation of MC3T3-E1 cells. These findings indicate that strontium ranelate induces not only osteoblast proliferation but also its differentiation and mineralization by activating the CaR, and confirm that the therapeutic efficacy of strontium ranelate for osteoporosis may be partly mediated by the CaR.

Postoperative delirium after reconstructive surgery for oral tumor: a retrospective clinical study.

The aim of this study was to perform a statistical evaluation of the risk factors for postoperative delirium after oral tumor resection and reconstructive surgery. The records of 69 consecutive patients who underwent major head and neck tumor resection and reconstructive surgery, and who received postoperative management in the high care unit (HCU) or intensive care unit (ICU) of Tsukuba University Hospital between January 2013 and December 2017, were analysed retrospectively. Delirium was diagnosed in 23 patients (33.3%) after surgery. There were significant differences in age, sex, history of diabetes mellitus and chronic obstructive pulmonary disease, recent hospitalization history, sedation period, duration of ventilator use, length of ICU/HCU stay, postoperative blood tests (haemoglobin and potassium), and postoperative medication with a major tranquilizer between those with and without delirium. Logistic regression analysis of selected independent variables revealed a hazard ratio (95% confidence interval) of 1.42 (1.09-1.86) for the sedation period. Delirium was hyperactive type in 15 cases, hypoactive type in five, and mixed type in three. There was no obvious difference in postoperative day of onset or delirium period according to subtype. In conclusion, a history of diabetes and the sedation period were found to be related to postoperative delirium. However, this study was small and retrospective, so further investigation is necessary.

Neuroprotective effect of NMDA receptor glycine recognition site antagonism persists when brain temperature is controlled.

Several lines of inquiry have indicated that glycine plays an important role in both glutamatergic neurotransmission and pathophysiology of cerebral ischemia. However, subacute outcome trials demonstrating the efficacy of glycine antagonists as neuroprotectants have not been performed with rigorous control of brain temperature. In this study, we investigated the effect of N-methyl-D-aspartate (NMDA) receptor glycine recognition site antagonism in a temperature-controlled rodent model of transient focal ischemia. Male Wistar rats underwent 75 min of intraluminal middle cerebral artery occlusion (MCAO). During MCAO and the first 24 h of reperfusion, rats (n = 10) were administered e55-nitro-6,7-dichloro-2,3-quinoxalinedione (ACEA 1021) i.v. as a bolus infusion of 5 mg/kg followed by 3.5 mg/kg/h (Low-Dose) or 10 mg/kg followed by 7 mg/kg/ h (High-Dose) for 24 h. Cortical temperature was controlled at 38.0 +/- 0.1 degrees C during MCAO and the first 6 h of reperfusion. A 7-day recovery interval was allowed. Mean total infarct volume was reduced by approximately 40% in both high- and low-dose groups (p < 0.01). The preponderance of infarct reduction occurred in the cortex (p < 0.01). Neurologic function correlated with the size of cerebral infarct (p = 0.001). Neurologic grade was similarly improved by treatment with either dose (p = 0.01). These results demonstrate that neuroprotection achieved by antagonism of the glycine recognition site persists when brain temperature is controlled, indicating a potent mechanism of action other than attenuating a hyperthermic response to ischemia.

A new solid support for sandwich enzyme immunoassays of human immunoglobulin G.

Two antibodies were prepared for use in a sandwich enzyme immunoassay of human IgG. Completely purified guinea pig anti-human IgG was labelled with beta-D-galactosidase (EC 3.2.1.23), using a heterobifunctional cross-linker named GMBS. Partially purified anti-human IgG was immobilized on a new solid support: Amino-Dylark balls. Optimal conditions for immobilizing the antibody, using glutaraldehyde as the coupling reagent, were studied in detail. With the enzyme-labelled antibody and the solid-phase anti-human IgG, a sandwich enzyme immunoassay of human IgG with a lower limit of detection at 10.5 pM (0.3 ng/tube) was developed. A comparative study of the EIA method and a laser nephelometric method showed a good correlation. The specificity of the assay was excellent: all 4 types of IgG tested showed the maximum 0.0001%; human IgA, IgM and albumin possessed the maximum 0.54% in their cross-reactivity values with human IgG.

Macrophyllols A and B, two unusual novel sesquiterpene and monoterpene dimers from the bark of Inula macrophylla.

[structure: see text] Two novel sesquiterpene and monoterpene dimers, macrophyllols A (1) and B (2), were isolated from the bark of Inula macrophylla. Their structures were determined on the basis of spectral evidence (especially HREIMS and 2D NMR) as well as chemical transformation. The structure of macrophyllol A (1) was confirmed by X-ray analysis. The possible biosynthetic pathways of macrophyllols A (1) and B (2) are discussed.

Glycine antagonism does not block ischemic spontaneous depolarization in the rat.

This study examined the effect of glycine recognition site antagonism (ACEA 1021) on the incidence of spontaneous depolarizations in the penumbra of a focal ischemic lesion. Rats were administered either vehicle (n = 7), ACEA 1021 (n = 7) or dizocilpine (n = 5) and then underwent 90 min middle cerebral artery occlusion. The cortical direct current (DC) potential was recorded. During ischemia, 7 +/- 3 DC shifts occurred in the vehicle group. ACEA 1021 did not reduce this frequency (7 +/- 2 DC shifts) although dizocilpine did (1 +/- 1 DC shifts; p = 0.02). The previously demonstrated neuroprotective property of ACEA 1021 during focal cerebral ischemia cannot be attributed to reduction of spontaneous depolarization in the ischemic penumbra.

Hypothermia reduces the propensity of cortical tissue to propagate direct current depolarizations in the rat.

Both spreading depression (SD) and spontaneous cortical ischemic depolarizations are known to be sensitive to brain temperature. What is unknown is whether this temperature effect is caused by altered sensitivity of cortical tissue to the initiating stimulus or is attributable to an altered ability of cortex to propagate the depolarization wave. To address this, halothane anesthetized rats underwent surface heating/cooling to produce pericranial temperatures of 33 degrees C, 38 degrees C, or 40 degrees C. Spreading depression was first initiated by electrocortical stimulation and then by topical application of KCl. The electrical threshold for SD and the time to direct current shift onset after KCl administration were unaffected by temperature. In contrast, the ability of cortical tissue to propagate the SD wave was temperature dependent. Decreasing temperature from 40 degrees C to 33 degrees C was associated with a slowing of the rate of propagation by 25-30% while the duration of the propagated direct current (DC) shifts was increased by 80% regardless of the initiating stimulus. After elicitation of persistent local DC shift with KCl, the interval between initial waves of SD was progressively increased as temperature was decreased. For either method of stimulation, once SD was initiated, the amplitude of the waveform was temperature independent. These results confirm the importance of temperature regulation in procedures examining SD in vivo. Further, temperature effects on SD reflect propensity of the tissue to propagate depolarization waves although ability of cortex to depolarize in direct response to the stimulus does not undergo substantive change.

Pinguisane and dimeric pinguisane-type sesquiterpenoids from the Japanese liverwort Porella acutifolia subsp. tosana.

Two new pinguisane-type, three new Diels-Alder reaction-type dimeric pinguisane sesquiterpenoids and known sesqui and diterpenoids were isolated from the ether extract of the Japanese liverwort Porella acutifolia subsp. tosano. Their absolute stereostructures were established by a combination of extensive 2D-NMR, CD spectra, X-ray crystallographic analysis, modified Mosher's method and chemical correlation.

Four alkaloids, lucidine B, oxolucidine A, lucidine A, and lucidulinone from Lycopodium lucidulum.

The structures of four alkaloids extracted from Lycopodium lucidulum (Lycopodiaceae) were established by X-ray and 2D NMR spectroscopic analyses. The dihydro-derivative of oxolucidine A, which was obtained by NaBH4 reduction of oxolucidine A, was treated with p-bromobenzoyl chloride to afford crystals, whose X-ray crystallographic analysis established the stereostructure, including the absolute configuration. The 2D NMR spectra of tetrahydrodeoxylucidine B were fully analyzed to establish the full structure of lucidine B, and the hitherto unknown stereochemistry at the C-14 position was established as beta-H. The structure of a new alkaloid, lucidulinone, was determined by spectroscopic analysis to be luciduline lactam.

[A 77-year-old woman with myoclonus and epilepsy].

We present a 77-year-old woman with myoclonus and epilepsy. She was well until 35 years of age, when she noted an onset of trembling of the legs upon standing. Her symptom slowly progressed, and she felt a difficulty in standing when she was 39-year-old. She had a major motor seizure without an apparent focal onset when she was 46-year-old. She also developed tremor in her hands, and she felt difficulty in holding a glass filled with water. She was admitted to our service for the first time in 1965 when she was 51-year-old. She showed wide-based ataxic gait with truncal titubation. In finger to nose test, myoclonic jerks were induced in the upper extremities. Otherwise neurological examination was unremarkable. She was treated with primidone and phenobarbital, and was discharged for out patient follow up. Her symptoms slowly progressed, and gait and station became more difficult. Mentally she was sound. Three months prior to the present admission, she developed more difficulty in gait, and decrease in food intake. On the 14th of September in 1991, she was seen by a local physician who found an abnormal shadow in her chest X-ray, and she was admitted to our service for further work-up on September 18, 1991. On admission, the patient was a chronically ill and emaciated woman. Her blood pressure was 140/84 mmHg, heart rate 115/minutes and regular, and the body temperature 36.9 degrees C. The palpebral conjunctivae were anemic. No cervical adenopathy was noted. The lung fields were clear, and no heart murmur was audible. The abdomen was soft, and no organomegaly was present. On neurologic examination, she looked somnolent with disorientation to time and place. Her memory was poor, and she could not do well serial 7s. The disc was flat and the ocular movements appeared intact. Other cranial nerves were also unremarkable. She showed diffuse muscle wasting. She was unable to stand or walk. Maintaining the sitting position was also difficult. She was able to raise her arms, but almost unable to move her lower extremities. The precise muscle testing was impossible. No abnormal involuntary movement was seen. Finger to nose test could not be performed.(ABSTRACT TRUNCATED AT 400 WORDS)

[A 64-year-old man with recurrent blurred vision and an abdominal mass].

We report a 64-year-old man with recurrent bouts of blurred vision who died after developing an abdominal mass. He was well until June of 1985 when he was 59-years-old when he had an acute onset of loss of vision in his right eye. He was treated by prednisolone with a complete remission. In August of 1986, he had another bout of blurring of vision in his left eye. Once he lost his left vision completely, from which he showed slow recovery. In January of 1987, he developed blurring of his right eye and loss of pain and touch sensation in his right leg. Since then he repeated loss of vision in his right or left eye five times, and he was admitted to our hospital in May of 1990. On admission, he was alert and oriented. General physical examination was unremarkable. Neurologic examination revealed bilateral optic nerve atrophy. He could not discriminate light or dark by either eye. Other cranial nerves were unremarkable. He could walk in a wide-base only with support; spasticity was noted in his left leg. Muscle strength was preserved. Deep reflexes were exaggerated in both legs with extensor plantar reflex bilaterally. Pain and touch sensation was decreased in the left leg by 30%, and vibration was diminished in both feet. Position sense was preserved. Routine blood counts and chemistries were unremarkable. Cranial MRI scans revealed multiple high-signal intensity lesions in both pontine bases, basal ganglia, thalami, and in the deep cerebral white matters. He was treated with oral prednisolone, plasmapheresis, lymphocytapheresis, and then immuran. His vision showed only slight recovery to discriminate light and dark. In October of 1990, slight weakness appeared in his both legs. In December of that year, he developed nausea, and a fiber colonoscopic study revealed a stenosis in the transverse colon. In March of 1991, he developed anemia and liver dysfunction. In July of that year, jaundice appeared, and his serum bilirubin was increased. In October, his leg weakness became more prominent, and his cranial CT scans at that time revealed a low density change in the right cerebellum in the right superior cerebellar artery territory; in addition, multiple low density spots were scattered to be seen in both cerebral hemispheres including the basal ganglia and thalamic areas with ventricular dilatation and cortical atrophy.(ABSTRACT TRUNCATED AT 400 WORDS)

[A 47-year-old woman with meningeal signs and consciousness disturbance].

We report a 47-year-old woman with SLE, who developed meningeal signs and consciousness disturbance. She noted an onset of fever, and swelling and pain in her face, hands and feet in 1990. She was seen in another hospital and the diagnosis of SLE was made. She was treated with prednisolone with marked improvement in her symptoms. She was well with 5 mg of oral prednisolone daily until January of 1991, when she developed fever, myalgia and weakness in her legs. She was admitted to the medical service of our hospital on August 5. She was receiving 15 mg of prednisolone daily. Gram positive rods were cultured from her blood on August 5. She became incoherent 2 days later, and had a convulsive episode on August 8. After the convulsion, she lost consciousness from which she did not recover. Her CSF contained 304/3 microliters cells, 29 of which were neutrophils, 6 lymphocytes, 90 others, and 179 destructed cells. The CSF protein content was 345 mg/dl, and glucose 23 mg/dl. A neurological consultation was asked on August 9. Physical examination at that time revealed a semicomatous woman. Respiration was 30/min and regular. BP 132/82 mmHg, heart rate 122/min and regular, and BT 39.6 degrees C. General physical examination was unremarkable. Pertinent neurologic findings were positive Kernig sign and spasticity in all four limbs. Brain stem reflexes were retained. Upon painful stimulation, withdrawal response was elicited both lower extremities. She was treated with pipiracillin, latamoxef and phenobarbital, however, she had frequent seizures. She was deeply comatose on December 10. She became flaccid and no more meningeal signs were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Anesthetic management of a multiallergic patient scheduled for cholecystectomy].

A 64-year-old woman was scheduled for cholecystectomy. Her past history revealed that serious anaphylactic reactions including generalized flushing and urticaria, severe hypotension and unconsciousness which occurred after eating crab four years ago. Puncture and/or intradermal skin test and subsequent lymphocyte stimulation test to several drugs commonly used in perioperative period were performed prior to anesthesia. Positive reactions to intravenous anesthetics and muscle relaxants, and negative reactions to inhalational and local anesthetics were found. Famotidine and ketotifen fumarate were given to prevent histamine release for four days before operation. After premedication with scopolamine, a catheter was inserted into epidural space at Th9-T10 level and 2% lidocaine 2 ml was administered initially into the epidural space. Anesthesia was induced with inhalation of nitrous oxide and oxygen, and deepened gradually by the increments of sevoflurane. Tracheal intubation was performed smoothly without adjunct muscle relaxant. Anesthesia was maintained with sevoflurane and epidural anesthesia with intermittent lidocaine administration. No adverse responses were noted at the time of iopamidol injection for intraoperative cholangiography. The anesthesia and postoperative course of this patient were uneventful.

[Bone mineral density (BMD) distribution in edentulous mandible--a measuring system for bone mineral content with computed radiography (CR)].

The purpose of this study was to develop a measuring system for bone mineral density(BMD) using computed radiography and to measure BMD distribution in the edentulous mandible. Nine 2-3 mm thick sequential cross-sectional bone slices were obtained from five cadaveric mandibles. Each slice in cross-sectional view on X-ray image was divided into 64 elements and BMD distribution was investigated. The results were as followed: 1. BMD measuring system: The accuracy was 1.4%(relative error) and the reproducibility was 1.1%(CV). 2. BMD distribution in edentulous mandible: 1) BMD varied from slice to slice, decreasing from anterior to posterior in both cortical and cancellous bone on the inferior and lingual side. The BMD of buccal cancellous bone was relatively higher than that of the lingual side and remained fairly constant throughout. The BMD of buccal cortical bone showed a slight posterior increase. 2) Greater individual variation of BMD was observed near mental foramen and in incisor lingual and inferior cancellous bone. Our system demonstrated excellent precision and reproducibility BMD distribution varied near regions of muscle attachment and the mandibular canal. Further, it was suggested that strong implant stability in the molar region may be obtained by installation of the fixtures in the buccal cancellous area.

[Severe left ventricular dysfunction in a patient with primary Sjögren's syndrome].

A 43-year-old woman was admitted to our hospital for evaluation of shortness of breath and palpitation on exertion. She had a 20-year history of dry mouth and a 10-year history of recurrent pneumonia. She had been diagnosed as having primary Sjögren's syndrome with interstitial pneumonia at 42 years of age. On admission, cardiac ultrasonography revealed reduced left ventricular systolic function. Complications that would elicit cardiac manifestations such as viral myocarditis, amyloidosis, sarcoidosis, and ischemic heart disease, were excluded. Oral corticosteroid therapy was effective for alleviating symptoms. In this patient, it appears that primary Sjögren's syndrome is involved in the reduced left ventricular systolic function.