Linalyl acetate as a major ingredient of lavender essential oil relaxes the rabbit vascular smooth muscle through dephosphorylation of myosin light chain

In a preliminary experiment, we found that lavender essential oil relaxes vascular smooth muscle. Thus, the present experiments were designed to investigate the relaxation mechanism of linalyl acetate as the major ingredient of lavender essential oil in rabbit carotid artery specimens. Linalyl acetate produced sustained and progressive relaxation during the contraction caused by phenylephrine. The relaxation effect of linalyl acetate at a concentration near the EC50 was partially but significantly attenuated by nitroarginine as an inhibitor of nitric oxide synthase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one as an inhibitor of guanylyl cyclase, or by the denudation of endothelial cells. In specimens without endothelium, the phenylephrine-induced contraction and phosphorylation of myosin light chain (MLC) were significantly attenuated after the pretreatment with linalyl acetate. The relaxation caused by linalyl acetate in the endothelium-denuded specimens was clearly inhibited by calyculin A as an inhibitor of MLC phosphatase, although not by ML-9 as an inhibitor of MLC kinase. Furthermore, suppression of the phenylephrine-induced contraction and MLC phosphorylation with linalyl acetate was canceled by the pretreatment with calyculin A. These results suggest that linalyl acetate relaxes the vascular smooth muscle through partially activation of nitric oxide/cyclic guanosine monophosphate pathway, and partially MLC dephosphorylation via activating MLC phosphatase.     

Potential role of chemo-radiation with oral capecitabine in a breast cancer patient with central nervous system relapse

A 54-year-old woman underwent mastectomy and axillary lymph node dissection for infiltrating ductal carcinoma with multiple lymph node involvement. The patient received adriamycin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) (AC) followed by weekly paclitaxel 80 mg/m(2) and external irradiation to the local lymph node regions as adjuvant treatment. After 1 year and 5 months, the patient suffered her first recurrence, developing multiple brain and meningeal metastases. CNS involvement was well controlled by oral capecitabine (2400 mg twice daily, on days 1-21 of a 28-day cycle) and external whole brain irradiation of 50 Gy with minimal toxicity. We suggest that capecitabine contributed to the favorable clinical course in this patient and believe that, as an oral agent, this drug may benefit patients with CNS metastases of breast cancer by allowing home-based therapy.     

Glomerular changes in the KK-Ay/Ta mouse: a possible model for human type 2 diabetic nephropathy

BACKGROUND: In type 2 diabetic nephropathy, there is no animal model which has been completely matched with humans. Advanced glycation end products (AGE) and transforming growth factor-beta (TGF-beta) are closely related to hyperglycaemia and their pathobiochemistry could explain diabetic nephropathy. The objective of the present study was to evaluate the KK-A(y)/Ta mouse as a suitable model for type 2 diabetic nephropathy including pathological changes and immunohistochemical analyses of AGE and TGF-beta, compared with the non-diabetic BALB/cA mouse. METHODS: The urinary albumin/creatinine ratio (ACR), body weight (BW), fasting and casual blood glucose, blood haemoglobin A(1c) (HbA(1c)), creatinine clearance (Ccr) and blood pressure were measured for phenotypic characterisation. The pathological changes of glomeruli were evaluated by light microscopy, immunofluorescence and electron microscopy. AGE and TGF-beta accumulation were evaluated by immunoperoxidase staining. RESULTS: The mean levels of ACR, casual blood glucose, blood HbA(1c) and Ccr in KK-A(y)/Ta mice were higher than those in age-matched non-diabetic BALB/cA mice after 12 weeks of age. There were no significant changes in the levels of systemic blood pressure among all groups. The pathological changes of glomeruli in KK-A(y)/Ta mice were consistent with those in the early stage of human diabetic nephropathy. AGE and TGF-beta protein appeared to be localised in the glomerular mesangial matrices. CONCLUSION: It appears that KK-A(y)/Ta mice, especially in terms of histopathological findings, are a suitable animal model for the early stage of type 2 diabetic nephropathy.     

Effect of storage at 37��C on allergenic potency of dried BCG vaccine

Experiments were carried out to determine the effect of storage at 37°C on the allergenic potency for humans of dried BCG vaccine. From four lots of liquid vaccine, eight kinds of dried vaccine were prepared, four with 1% sodium glutamate and four with 1% sucrose as adjuvant. The eight vaccines were stored at 5°C and at 37°C for periods ranging from 1 month to 9 months, and were then used for the inoculation of primary-school children in Tokyo. These children were tuberculin-tested 1, 3 or 4 and, in a few cases, 12 months after vaccination, and the reactions were read approximately 48 hours after the tuberculin injection had been given.     

Prenatal findings of omphalocele-exstrophy of the bladder-imperforate anus-spinal defects (OEIS) complex

Omphalocele-exstrophy of the bladder (cloaca)-imperforate anus-spinal defects (OEIS) complex describes a rare grouping of more commonly occurring component malformations. We report two cases of OEIS complex diagnosed prenatally by ultrasound and magnetic resonance imaging (MRI). In both cases, OEIS complex was suspected by conventional sonography in the second trimester, and fetal MRI was performed at 27 and 32 weeks of gestation. Conventional sonography revealed low abdominal wall mass, spina bifida, absent bladder and ambiguous genitalia, but those findings were inconclusive. Using fetal MRI, we were able to detect omphalocele, imfraumbilical mass connected to gut tract, absent bladder, ambiguous external genitalia and spinal defect. Our findings suggest that fetal MRI is a useful tool for prenatal diagnosis of OEIS complex. MRI helps prenatal counseling and planning of postnatal early treatment strategy.     

Construction and clinical evaluation of novel methods for detecting autoinomic dysfunction

The autonomic nervous system innervates every organ in the body. Since autonomic disturbances affect patient survival, an understanding of and recognition of these disturbances are important. We adopted several new methods to evaluate autonomic function accurately for detecting the onset of small-fiber neuropathy, such as laser-Doppler flowmetry, ultrasonography, 123I-MIBG scintigraphy, electrogastrography, cystometry, glucose-tolerance test, near-infrared spectrophotoscopy, blood pressure tests, and evaluation of sweating. After these examinations, we applied potential effective treatments to improve the survival and daily activity of these patients. We also evaluated the effect of liver transplantation on autonomic dysfunction of familial amyloidotic polyneuropathy (FAP) patients using our tools. Liver transplantation not only prevents the progression of autonomic dysfunction in these patients but also improves some autonomic symptoms in the early stage after the operation. As all domino-liver transplantation-induced amyloid neuropathies, including our cases, were of the sensory type rather than with autonomic involvement, assessment of the pain threshold by preferential stimulation of A delta fibers is a particularly useful tool for diagnosing the onset of small-fiber neuropathies in these patients in addition to autonomic testing. Analyses and comparison of patients with FAP and domino-liver-transplanted patients with autonomic, sensory and motor dysfunction may give a clue to elucidate the pathogenesis and treatment of neuropathy in FAP. As autonomic disturbances play an important role in the symptomatology of small-fiber neuropathy, liver-transplanted FAP, and domino-liver-transplanted patients, further studies of autonomic dysfunction in these patients may lead to the pathogenesis of the disease.     

Recognition of the importance of reversed CPC in CPC

Clinicopathological conferences (CPC) are one of the most important clinical conferences, and processes of both diagnosis and treatment performed in an autopsy case are retrospectively and finely checked to offer better medical treatment in the future. In CPC, the medical history, physical findings, laboratory data, image findings, diagnosis and treatment are discussed in the order that a physician examines a patient. Differential diagnoses usually decrease and several important diagnoses remain as the CPC discussion progresses. Medical treatment is also reexamined to identify a better approach. In this CPC, several medical doctors in various special fields try to understand the detailed state of the patient from each standpoint, and such a CPC is called an Expert CPC at Shinshu University School of Medicine. This CPC is carried out followed by reversed-CPC (R-CPC) of the same case. The purpose of this CPC is to understand the importance of R-CPC and to understand the correct interpretation of routine laboratory data.     

Neonatal encephalopathy: a prospective comparison of head US and MRI

Background  

Head US, the cornerstone neuroimaging modality in neonates, is believed to be less sensitive than MRI for detecting hypoxic ischemic injury (HII). Most reports comparing these modalities are retrospective and have a long interval between the exams.