An automated on-line method for simultaneous analysis of phenothiazines in human serum by high-performance liquid chromatography/sonic spray ionization mass spectrometry using backflush column switching

An automated on-line method for simultaneous analysis of five phenothiazine drugs by high-performance liquid chromatography (HPLC)/sonic spray ionization mass spectrometry (SSI-MS) has been established, using backflush column switching. A 400-μl portion of serum sample diluted 81-fold with distilled water was subjected to the on-line system. In the system, an Oasis HLB cartridge was used as the precolumn for extraction; large molecules such as proteins in serum were discarded by use of distilled water containing 0.1% formic acid as a mobile phase. After switching a valve, the analytes trapped in the precolumn were eluted in the backflush mode and separated by a Chromolith Performance RP-18e column, which is composed of C₁₈-bonded monolithic silica. The column effluents were then introduced into the SSI-MS. The present method provided successful separation and determination of six phenothiazines including an internal standard. Satisfactory linearities, reproducibility, and sensitivity were obtained at concentration levels that matched the toxic levels of phenothiazines. All drug peaks appeared within 18 min, and the system could be reequilibrated in only about 8 min for the next run. Because of the simplicity and rapidness of the method, it is likely to be useful in the fields of emergency medicine and forensic toxicology.     

液相色谱质谱联用(LC-MS/MS)在天然化学成分分析中的应用Ⅰ.音喷离子化(SSI)与大气压化学离子化(APCI)对利血平的比较分析

报道应用 L C- MS/ MS,采用音喷离子化 (SSI)与大气压化学离子化 (APCI)对利血平的比较分析 ,应用这两种离子化方法比较所得的利血平的标准质谱 (MS)和二级质谱 (MS2 ) ,实验证明两种离子化方法所得结果完全一致     

Impact of sarcopenia on postoperative surgical site infections in patients undergoing flap reconstruction for oral cancer

Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass and strength. The aim of the study was to investigate the impact of skeletal muscle mass on surgical site infection (SSI) in flap reconstruction for defects after oral cancer resection. The subjects were a non-randomized, retrospective cohort of 106 patients who underwent this procedure after preoperative abdominal-lumbar computed tomography (CT). Cross-sectional areas (cm²) of skeletal muscles in the L3 region were measured by manual outlining on CT images. These areas were then normalized for height (cm²/m²) and defined as the skeletal muscle index (SMI). Recipient site SSI occurred in 28 patients (26.4%). Lower body mass index, haemoglobin and SMI were significantly related to recipient site SSI in univariate analysis (P<0. 05). In a multiple logistic regression model, lower SMI was a significant risk factor for recipient site SSI (odds ratio = 3.95 per 10 cm²/m² decrease, P=0. 005). This result suggests that increasing skeletal muscle mass by exercise or nutrition before surgery may prevent recipient site SSI after resection of oral cancer and subsequent reconstruction.     

Lens cholesterol biosynthesis inhibition: A common mechanism of cataract formation in laboratory animals by pharmaceutical products

CJ‐12,918, a 5‐lipoxygenase (5‐LO) inhibitor, caused cataracts during a 1‐month safety assessment studies in rats whereas the structurally similar ZD‐2138 was without effect. For CJ‐12,918 analogs, blocking different sites of metabolic liability reduced (CJ‐13,454) and eliminated (CJ‐13,610) cataract formation in both rats and dogs. Using this chemical series as a test set, models and mechanisms of toxicity were first explored by testing the utility of ex vivo rat lens explant cultures as a safety screen. This model overpredicted the cataractogenic potential of ZD‐2138 due to appreciably high lens drug levels and was abandoned in favor of a mechanism‐based screen. Perturbations in lens sterol content, from a decline in lathosterol content, preceded cataract formation suggesting CJ‐12,918 inhibited lens cholesterol biosynthesis (LCB). A 2‐day bioassay in rats using ex vivo LCB assessments showed that the level of LCB inhibition was correlated with incidence of cataract formation in animal studies by these 5‐LO inhibitors. Thereafter, this 2‐day bioassay was applied to other pharmaceutical programs (neuronal nitric oxide synthase, sorbitol dehydrogenase inhibitor, squalene synthetase inhibitor and stearoyl‐CoA desaturase‐1 inhibitors/D₄ antagonists) that demonstrated cataract formation in either rats or dogs. LCB inhibition >40% was associated with a high incidence of cataract formation in both rats and dogs that was species specific. Bioassay sensitivity/specificity were further explored with positive (RGH‐6201/ciglitazone/U18666A) and negative (tamoxifen/naphthalene/galactose) mechanistic controls. This body of work over two decades shows that LCB inhibition was a common mechanism of cataract formation by pharmaceutical agents and defined a level of inhibition >40% that was typically associated with causing cataracts in safety assessment studies typically ≥1 month.     

Functional conservation of suppressors of cytokine signaling proteins between teleosts and mammals: Atlantic salmon SOCS1 binds to JAK/STAT family members and suppresses type I and II IFN signaling

Suppressor of cytokine signaling (SOCS) proteins are crucially involved in the control of inflammatory responses through their impact on various signaling pathways including the JAK/STAT pathway. Although all SOCS protein family members are identified in teleost fish, their functional properties in non-mammalian vertebrates have not been extensively studied. To gain further insight into SOCS functions in bony fish, we have identified and characterized the Atlantic salmon (Salmo salar) SOCS1, SOCS2 and CISH genes. These genes exhibited sequence conservation with their mammalian counterparts and they were ubiquitously expressed. SOCS1 in mammalian species has been recognized as a key negative regulator of interferon (IFN) signaling and recent data for the two model fish Tetraodon (Tetraodon nigroviridis) and zebrafish (Danio rerio) suggest that these functions are conserved from teleost to mammals. In agreement with this we here demonstrate a strong negative regulatory activity of salmon SOCS1 on type I and type II IFN signaling, while SOCS2a and b and CISH only moderately affected IFN responses. SOCS1 also inhibited IFNγ-induced nuclear localization of STAT1 and a direct interaction between SOCS1 and STAT1 and between SOCS1 and the Tyk2 kinase was found. Using SOCS1 mutants lacking either the KIR domain or the ESS, SH2 and SOCS box domains showed that all domains affected the ability of SOCS1 to inhibit IFN-mediated signaling. These results are the first to demonstrate that SOCS1 is a potent inhibitor of IFN-mediated JAK-STAT signaling in teleost fish.     

Wide-field conditioning effects on small-field neurons in the posterior sigmoid gyrus of domestic cats

Single neurons were isolated in four different recording sites in sensorimotor cortex of the domestic cat, all sites being topographically related to the contralateral forepaw. Conditioning-testing interactions were made on 409 small-field neurons, the testing input being the contralateral forepaw (also the ipsilateral forepaw in the case of bilateral-field neurons) and the conditioning input being any paw that was ineffective in exciting the neuron. About 29% of the neurons showed inhibitory interactions and 23% showed facilitatory interactions. Of these, about 5.5% showed both effects, according to the conditioning site. Nearly 54% of the neurons failed to show any interaction effects. Most of the latter were isolated in the two posterior recording sites, located in somatosensory area I; the interaction effects were found predominantly in the two anterior recording sites, located in agranular tissue. Neurons that responded only to contralateral forepaw stimulation (sa neurons) and showed facilitatory interactions from the other three paws had response properties characteristic of neurons that respond to all four paws (m neurons). The sa neurons that showed inhibitory interactions from the other three paws did not differ significantly in response properties from those that showed no interaction effects. These findings are relevant to current criteria for the classification of sensorimotor cortex neurons and lead to remarks on the possible thalamic routes that mediate the interaction effects.