SB366791, a TRPV1 antagonist, potentiates analgesic effects of systemic morphine in a murine model of bone cancer pain.

BACKGROUND: Bone cancer pain has a major impact on the quality of life of cancer patients but is difficult to treat. Therefore, development of a novel strategy for bone cancer pain is needed for improvement of the patient quality of life. In this study, we examined the analgesic effects of the combination of a transient receptor potential vanilloid subfamily 1 (TRPV1) antagonist and morphine on pain-related behaviours in a murine model of bone cancer pain. METHODS: C3H/HeJ mice underwent injection of osteolytic sarcoma cells into the intramedullary space of the femur. The analgesic effects of intraperitoneal morphine and the analgesic effect of a TRPV1 antagonist, SB366791 [N-(3-methoxyphenyl)-4-chlorocinnamide], on bone cancer pain-related behaviours were examined. The analgesic effects of the combination of SB366791 and morphine on bone cancer pain were also examined. RESULTS: Intraperitoneal morphine significantly reduced the number of spontaneous flinches and improved ambulation only at the highest dose of 10 mg kg(-1) whereas weight-bearing was not improved. Intraperitoneal SB366791 at doses of 0.3 and 1.0 mg kg(-1), but not at a dose of 0.1 mg kg(-1), reduced the number of spontaneous flinches, whereas neither weight-bearing nor ambulation was improved. Addition of a sub-analgesic dose of SB366791 (0.1 mg kg(-1)) to morphine significantly reduced the number of flinches and improved weight-bearing compared with the effects of morphine alone. CONCLUSIONS: Our findings showed that the combination of morphine and SB366791 has potent analgesic effects on bone cancer pain. The findings of this study may lead to novel strategies for the treatment of bone cancer pain.

Contribution of transient receptor potential vanilloid subfamily 1 to endothelin-1-induced thermal hyperalgesia.

Endothelin-1 (ET-1) plays an important role in peripheral pain processing. However, the mechanisms of the nociceptive action of ET-1 have not been fully elucidated. In this study, we investigated the contribution of transient receptor potential vanilloid subfamily 1 (TRPV1) to ET-1-induced thermal hyperalgesia. Intraplantar ET-1-induced thermal hyperalgesia was examined by assessing the paw withdrawal latency to noxious heat stimuli. In electrophysiological study, whole-cell patch-clamp recordings were performed to investigate the interaction of ET-1 and TRPV1 using human embryonic kidney 293 (HEK293) cells expressing endothelin type A receptor (ET(A)) and TRPV1. Intraplantar ET-1 (3, 10 and 30 pmol) produced thermal hyperalgesia in a dose-dependent manner. Thermal hyperalgesia was attenuated by the inhibition of ET(A) and protein kinase C (PKC) but not that of ET(B). ET-1-induced thermal hyperalgesia was significantly attenuated in TRPV1-deficient mice compared with that in wild-type mice. In voltage-clamp experiments, 10 nM capsaicin evoked small inward currents in HEK293 cells expressing TRPV1 and ET(A). In the presence of ET-1, capsaicin produced much larger current responses (P<0.05). Mutation at PKC-specific TRPV1 phosphorylation sites (S800A/S502A) and PKC inhibitors inhibited the potentiating effect of ET-1. In addition, ET-1 decreased the temperature threshold for TRPV1 activation in a PKC-dependent manner (from 41.0+/-0.4 degrees C to 32.6+/-0.6 degrees C). In addition, Western blot analysis was also performed to confirm ET-1-induced phosphorylation of TRPV1. Incubation of ET-1 and intraplantar ET-1 evoked phosphorylation of TRPV1 in HEK293 cells expressing TRPV1 and ET(A) and the skin, respectively. These results suggest that the sensitization of TRPV1 activity through an ET(A)-PKC pathway contributes to ET-1-induced thermal hyperalgesia.

Pemphigus foliaceus developing after metastasis of cutaneous squamous cell carcinoma to regional lymph nodes.

We describe a patient in whom pemphigus foliaceus developed after cutaneous squamous cell carcinoma (SCC) metastasized to regional lymph nodes. Immunologic analysis revealed that production of anti-desmoglein 1 autoantibodies started when SCC metastasized, and the SCC expressed desmoglein 1, suggesting a pathogenic role of metastasized SCC in developing pemphigus foliaceus.

Comparison of the effects in vitro of tea tree oil and plaunotol on methicillin-susceptible and methicillin-resistant strains of Staphylococcus aureus.

The effects in vitro of tea tree oil (TTO) and plaunotol were examined by monitoring the growth of a standard strain of Staphylococcus aureus FDA 209P and of fourteen methicillin-susceptible strains of S. aureus (MSSA), together with twenty methicillin-resistant strains (MRSA). The minimum inhibitory concentrations (MIC) and the doses for 50% inhibition of growth (ID50) were determined by the micro-broth dilution (MD) method, and the broth dilution with shaking (BDS) method, respectively. The MIC of plaunotol for 50 and 90% of the MSSA and MRSA were assessed by the MD method, as 16 microg/ml and > or = 1,024 microg/ml, respectively. No antibacterial effects of TTO on MSSA and MRSA were detected by the MD method. The growth-inhibitory effects of TTO on S. aureus by the BDS method were examined, and it appeared that TTO was effective over a lower range of concentrations than previously reported. It seems that TTO is very effective in vitro against MSSA and MRSA at high concentrations but less effective below 40 microg/ml of TTO.

Purification and characterization of a feruloylesterase from Aspergillus awamori.

A feruloylesterase was purified from the extracellular broth of Aspergillus awamori grown on wheat bran culture. The purified enzyme gave a single band on SDS-polyacrylamide gel electrophoresis and isoelectric focusing, with an apparent M(r) of 35,000 and a pI of 3.8, respectively. The substrate specificity of the purified enzyme differed obviously from that of acetylesterase of A. awamori. The enzyme bound to microcrystalline cellulose.

An Aspergillus awamori acetylesterase: purification of the enzyme, and cloning and sequencing of the gene.

An inducible acetylesterase was purified from the culture medium of Aspergillus awamori strain IFO4033 growing on wheat-bran culture by ion-exchange, gel-filtration and hydrophobic-interaction chromatographies. The purified enzyme had an Mr of 31000 and contained Asn-linked oligosaccharides. The enzyme liberated acetic acid from wheat bran, hydrolysed only alpha-naphthyl acetate and propionate when aromatic esters were used for the substrate, and was tentatively classified as a carboxylic esterase (EC 3.1.1.1). The gene encoding acetylesterase was cloned and sequenced. The deduced amino acid sequence showed that acetylesterase was produced as a 304-amino-acid-residue precursor, which was converted post-translationally into a 275-amino-acid-residue mature protein. Part of the sequence of acetylesterase was similar to the region near the active-site serine of lipases of Geotrichum candidum and Candida cylindracea. A unique site of putative Asn-linked oligosaccharides was presented.

[A combination chemotherapy with CDDP and 5-FU effective for pulmonary metastases in a case of parotid gland carcinoma].

The patient was a 40-year-old female (154 cm, 45 kg). Several months after receiving radiotherapy, surgery and chemotherapy (Epi-ADR, CDDP, PEP) for an undifferentiated carcinoma of the left parotid gland, she had multiple pulmonary metastases without local recurrence. Following 2 cycles of combination chemotherapy with CDDP (30 mg/1 hr, days 1 approximately 5) and 5-FU (1,000 mg/24 hrs, days 2 approximately 6), most pulmonary nodules disappeared. For the remaining pulmonary nodules, one cycle of combination chemotherapy with 5-FU (850 mg/24 hrs, days 1 approximately 5), leucovorin (9 mg x 3/day, days 1 approximately 5) and CDDP (110 mg/2 hrs, day 7) was added, but further improvement was not obtained on chest CT. Side effects were tolerable in both regimens. It was suggested that the combination chemotherapy with CDDP and 5-FU might be useful for the treatment of advanced parotid gland carcinomas.

[A case of congenital subclavian steal].

A case of congenital subclavian steal is reported. A 7-year-old girl was admitted on July 1980 to Shimane Medical University for evaluation of murmur over the region of the chest. Heart murmur was pointed out at the age of three month, however, she had no complaints and was growing normally. On admission, the blood pressure was 108/48 mmHg in the left arm and unobtainable in the right arm. The length of the arm was 53 cm on the right side and 55.4 cm on the left side. On auscultation, a systolic murmur was present over the chest and the right neck. The arch aortography disclosed the left aortic arch, the isolation of the right subclavian artery and the right patent ductus arteriosus (PDA). The left transfemoral vertebral angiography showed the retro-grade filling from the right vertebral artery to the right subclavian and pulmonary artery via the right PDA. The right external carotid angiography showed the filling of the right vertebral artery through muscular branches of the right occipital artery. The right retrograde brachial angiography showed small right subclavian artery and the filling of the pulmonary artery through the right PDA. The recorrective operation was made. Postoperatively, normal blood flow was recognized in angiography. The blood pressure improved in the right side and the murmur was diminished.

[Ocular complications in chronic pansinusitis--report of two cases].

Case 1. A 38-year-old male was admitted with an 8-month history of progressive visual disturbance in his right eye. He had a past history of operations for paranasal sinusitis 24 years and 5 years prior to admission. Neurological examination revealed right anosmia, left hyposmia and vision in his right eye reducing to light perception. Case 2. A 61-year-old male was admitted with complaint of headache and a 2-month history of deteriorating vision in his right eye. On admission, vision in his right eye was found to be reduced to hand motions and associated with a concentric contraction of the visual field. Bilateral hyposmia and the right exophthalmos were also noticed. Plain x-ray films, tomography and especially CT scan were useful to demonstrate the definite inflammatory changes of the paranasal sinuses and the extension of the lesion beyond the confines of the sinuses. In both cases, external ethmoidectomy and sphenoidectomy with removal of the infected granulation tissue from the sinuses were performed, but neither mucocele nor pyocele was found. Vision improved postoperatively. Previous reports about ocular complications of infection in the paranasal sinuses without mucocele or pyocele are few. Early diagnosis of ocular complications of sinusitis is important. Once the diagnosis established, a timely surgical approach is essential to prevent visual loss.

[Moyamoya disease associated with a false aneurysm--case report and review of the literature].

A 67-year-old male was admitted to our clinic on May 1, 1981, because of mild confusion and a left hemiparesis. About 6 years ago, when he had a left-sided homonymous hemianopia, carotid angiography revealed moyamoya disease. CT scan on the admission showed an intracerebral hematoma in the right temporal lobe, which ruptured to the lateral ventricle. An angiogram demonstrated the net work of moyamoya vessels in the base of the brain and a "newly-appeared" aneurysm at the peripheral portion of the right anterior choroidal artery. This artery was shown on the previous angiogram also but did not bear the aneurysm. At the emergent operation the hematoma was evacuated and the aneurysm was excised, which was proved histologically to be a false aneurysm. Thirty-six cases of moyamoya diseases associated with aneurysm including the present case were reviewed. There were 44 aneurysms in this series. They were classified into groups--1) the major artery aneurysms arising from the major cerebral arterial segments; 2) the peripheral artery aneurysms arising from the distal segments of the peripheral cerebral arteries. The major artery aneurysms were found more frequently in the vertebro-basilar system, and the peripheral artery aneurysms in the basal ganglia, near or in the moyamoya vessels. Of 26 major artery aneurysms 12 were proved to be saccular aneurysms, 9 by surgeries and 3 by autopsy studies respectively. Of 18 cases of the peripheral group the aneurysms were excised operatively in two cases, and autopsy studies were performed in other two cases. The peripheral artery aneurysms were examined histologically in three cases; one was proved to be a false aneurysm, the other was thought to be a true aneurysm, and the third one was not verified. In 8 cases, the peripheral artery aneurysms disappeared on the follow-up angiograms and were supposed to be false aneurysms. From these reported cases, it may be suggested that major artery aneurysms are mainly true aneurysms and peripheral artery aneurysms are false aneurysms.

Subependymal hematoma in "Moyamoya" disease.

A 27-year-old woman in the ninth month of her pregnancy suddently developed nausea and motor weakness of her right lower extremity while shopping. Subsequently a disturbance of consciousness and right-sided hemiparesis developed. Spinal puncture yielded clear CSF but CT scan demonstrated a left subependymal hematoma. Angiographical examination led to a diagnosis of "Moyamoya" disease. The source of the intracranial hemorrhage could not be identified. The hematoma could not have been diagnosed accurately without the CT scan.

Treatment of moyamoya disease with STA-MCA anastomosis.

Moyamoya disease is a chronic occlusive cerebrovascular disease of unknown etiology for which no effective treatment has been found. The authors report the result of 23 superficial temporal-middle cerebral artery (STA-MCA) anastomoses and seven encephalomyosynangioses, performed on 13 cases with moyamoya disease and on four additional atypical cases. There were 10 children and seven adults in this study. The follow-up period ranged from 1 year and 4 months to 4 years and 1 month postoperatively; nine patients had excellent results, five good, and one fair; two patients were unchanged. The anastomotic procedure was most effective for transient ischemic attacks, reversible ischemic neurological deficits, and even minor or moderate neurological symptoms. The STA-MCA anastomosis appears to be an effective treatment for moyamoya disease.