Persistent induction of nitric oxide synthase in tumours from mice treated with the anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid.

An anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid (5,6-MeXAA) induced nitric oxide synthase (NOS) in the tumour, spleen, thymus and small intestine, but not in the lung, liver, kidney, heart or skeletal muscle in B6D2F1 mice bearing subcutaneous colon 38 tumours. This pattern of induction is distinct from that caused by agents such as endotoxin, muramyl dipeptide or Corynebacterium parvum. The induction of NOS (iNOS) in the tumour was more persistent (maximal at 3 days) than in other tissues (maximal at 12 h). Immunohistochemical staining suggested that iNOS was located in macrophages and endothelial cells within and around the tumour. Treatment with 5,6-MeXAA also caused substantial increases in plasma nitrite and nitrate (NOx) concentrations that peaked at 8-12 h after 5,6-MeXAA. The increase in plasma NOx was prevented by a NOS inhibitor N-iminoethyl-L-ornithine (L-NIO), indicating that it was due to enhanced production of NO. Tumour-bearing mice were more responsive than controls to 5,6-MeXAA both in their plasma NOx increase and in their lower maximally tolerated dose. L-NIO was unable to prevent the complete tumour necrosis and regression caused by 5,6-MeXAA at a dose that substantially inhibited the increase of plasma NOx. In conclusion, the experimental anti-tumour agent 5,6-MeXAA induced NO synthesis in tumour-associated macrophages and in immunologically active tissues in parallel with its effects on tumour growth. The experiments with a non-selective NOS inhibitor L-NIO, however, suggest that NO is not a significant component in the mechanism of the anti-tumour action of 5,6-MeXAA in this particular model.     

Blood-brain barrier and blood volume imaging of cerebral glioma using functional CT: A pictorial review

Five cases of cerebral glioma are presented here that illustrate the benefit of functional CT imaging of blood-brain barrier permeability and cerebral blood volume. Functional CT uses Patlak analysis of a single location dynamic sequence to extract physiological information that is useful clinically in the assessment of cerebral gliomas. Functional CT offers distinct advantages over other functional modalities including clearer delineation of tumour, tumour grading, measurement of tumour activity and monitoring response to therapy.     

Calcium binding proteins in motoneurons at low and high risk for degeneration in ALS

Recent reports challenge the hypothesis that expression of calcium binding proteins contributes to the greater resistance of some motoneurons to degeneration in amyotrophic lateral sclerosis (ALS). We therefore re-examined, using immunohistochemistry, the expression of calbindin, calretinin and parvalbumin in vulnerable (hypoglossal, XII; and cervical spinal) and resistant (oculomotor, III) motoneurons of adult rats. Calbindin immunoreactivity was lacking in motor nuclei but strong in the dorsal horn. Calretinin was expressed in spinal, but not III or XII, motoneurons. Parvalbumin immunoreactivity, tested with a polyclonal antibody, was intense in spinal and III, but not XII, motoneurons; however, no staining in the ventral horn was observed with a monoclonal antibody. Differential expression of calretinin and parvalbumin within vulnerable motoneurons suggests that immunoreactivity for these proteins is not a reliable marker for resistance to degeneration in ALS.     

An investigation of human and rat liver microsomal mycophenolic acid glucuronidation: evidence for a principal role of UGT1A enzymes and species differences in UGT1A specificity.

Mycophenolic acid (MPA; 1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzylfuranyl)-4-methyl-4-hexenoate), the active metabolite of the immunosuppressant prodrug, mycophenolate mofetil, undergoes glucuronidation to its 7-O-glucuronide as a primary route of metabolism. Because differences in glucuronidation may influence the efficacy and/or toxicity of MPA, we investigated the MPA UDP-glucuronosyltransferase (UGT) activities of human liver microsomes (HLMs) and rat liver microsomes with the goal of identifying UGTs responsible for MPA catalysis. HLMs (n = 23) exhibited higher average MPA glucuronidation rates (14.7 versus 6.0 nmol/mg/min, respectively, p < 0.001) and higher apparent affinity for MPA (K(m) = 0.082 mM versus 0.20 mM, p < 0.001) compared with rat liver microsomes. MPA UGT activities were reduced >80% in liver microsomes from Gunn rats. To identify the active enzymes, human and rat UGT1A enzymes were screened for MPA-glucuronidating activity. UGT1A9 was the only human liver-expressed UGT1A enzyme with significant activity and exhibited both high affinity (K(m) = 0.077 mM) and high activity (V(max) = 28 nmol x min(-1) x mg(-1)). Spearman correlation analyses revealed a stronger relationship between HLM MPA UGT activities and 1A9-like content (r(2) = 0.79) relative to 1A1 (r(2) = 0.20), 1A4-like (r(2) = 0.22), and 1A6 (r(2) = 0.41) protein. A different profile was observed for rat with three active liver-expressed UGT1A enzymes: 1A1 (medium affinity/capacity), 1A6 (low affinity/medium capacity), and 1A7 (high affinity/capacity). Our data suggest that UGT1A enzymes are the major contributors to hepatic MPA metabolism in both species, but 1A9 is dominant in human, whereas 1A1 and 1A7 are likely the principal mediators in control rat liver. This information should be useful for interpretation of MPA pharmacokinetic and toxicity data in clinical and animal studies.     

Microvascular decompression for trigeminal neuralgia in Charcot-Marie-Tooth disease

The authors report on three patients suffering from coexistent trigeminal neuralgia (TGN) and Charcot-Marie-Tooth disease who, based on preoperative magnetic resonance tomographic angiography findings, underwent microvascular decompression. All patients had demonstrable neural compression and all experienced immediate postoperative pain relief. Symptoms recurred in one patient and required a second procedure in the form of a neurotomy. Two patients suffered from bilateral TGN. When a patient with TGN suffers coexistent neurological disease and experiences bilateral symptoms, preoperative imaging and subsequent decompressive surgery may avoid the unacceptable risk of morbidity associated with bilateral ablative procedures.     

Condylomas of the uterine cervix initially interpreted as squamous carcinoma: a report of four cases including a lesion resembling the Buschke-Loewenstein giant condyloma

The recognition of human papilloma virus (HPV)-induced cervicovaginal condylomatous lesions is in a period of dynamic development. It is estimated that condylomatous involvement of the uterine cervix is epidemic and that is particularly true in the younger, more sexually active woman. While cervical condylomas are often associated with cervical dysplasia, carcinoma in situ, or even invasive carcinoma, they are sometimes misdiagnosed as these entities. Four cases of cervical condylomas are presented that were clinically suspicious for malignancy and initially interpreted as squamous carcinomas on the basis of the histopathological findings.     

白首乌化学成分的研究

自白首乌主要品种耳叶牛皮消(Cynanchum auriculatum Royle ex Wight)根中首次分得三个已知甾体酯型甙元:告达亭(caudatin),开德甙元(kidjolanin),萝藦甙元(Metaplexigenin)和一种新的二苯酮衍生物(Ⅳ),经光谱分析推定其结构为2,6,2′,5′-四羟基,3-乙酰基,6′-甲基二苯酮,命名白首乌二苯酮。     

白首乌化学成分的研究

自白首乌主要品种耳叶牛皮消(Cynanchum auriculatum Royle ex Wight)根中首次分得三个已知甾体酯型甙元:告达亭(caudatin),开德甙元(kidjolanin),萝藦甙元(Metaplexigenin)和一种新的二苯酮衍生物(Ⅳ),经光谱分析推定其结构为2,6,2′,5′-四羟基,3-乙酰基,6′-甲基二苯酮,命名白首乌二苯酮。     

Digital Image Correlation Characterization and Formability Analysis of Aluminum Alloy TWB during Forming

The formability of aluminum alloy 5754-O tailor-welded blanks prepared by friction stir welding was studied experimentally. The strain evolution and deformation during limiting dome height experiments were studied using digital image correlation and the ARAMIS software. The influence of the sheet thickness of the base materials on the punch loading, fracture strain and formability were investigated experimentally. It was found that the punch loading, fracture strain and limiting dome height values increase with the increasing sheet thickness of the base materials. A linear relationship between the limiting dome height value and the sheet thickness was demonstrated. An increase of 16.8% in the fracture strain of aluminum tailor-welded blanks was observed for an increase of 36% in sheet thickness. This paper provides a methodology for experimentally determining the forming limits of aluminum alloy tailor-welded blanks accurately.