Abortive Headache Therapy in the Office With Intravenous Dihydroergotamine Plus Prochlorperazine

Over two years, 92 patients were treated in the office for 146 severe headache episodes. Headaches were aborted using four different intravenous regimens containing 0.5 or 1 mg. of dihydroergotamine and 3.5, 5, or 10 mg. of prochlorperazine. The speed and rate of response were directly proportional to the prochlorperazine dose used. High prochlorperazine doses (10 mg.) aborted the most headaches (95%) in the shortest time, but caused more sedation and akathesia. Low doses (3.5 mg.) aborted less headaches (89%) and responses were delayed; but, on the other hand, sedation was minimal and akathesia mild and uncommon. Dihydroergotamine given alone caused intolerable side effects; but, when it was given with prochlorperazine, efficacy was enhanced and side effects were greatly reduced. Aborting headaches in the office can be reliably achieved with minimal side effects by administering an intravenous mixture containing 1 mg. of dihydroergotamine and 3.5 mg. of prochlorperazine.     

Light and electron microscopic immunocytochemical localization of vasoactive intestinal polypeptide VIP-like activity in the rat small intestine

Vasoactive intestinal polypeptide nerve processes and cell bodies were identified by electron microscopic immunocytochemistry in the rat small intestine. Labeled nerve processes were numerous in the inner circular smooth muscle coat and mainly in the mucosa, but were absent in the longitudinal muscle layer. Submucosal blood vessels were often surrounded by immunoreactive vasoactive intestinal polypeptide positive nerves, in close associations (distance less than 40 mn) to blood vessel basement membranes and to smooth muscle cells. In the ganglia of the myenteric and submucous plexuses, labeled fibers surrounded unstained neural cell bodies. The synaptic vesicles of vasoactive intestinal polypeptide positive terminals were 35-40 nm in diameter and some dense core vesicles (80-120 nm in diameter) were also observed in the same profiles. These observations suggest that vasoactive intestinal polypeptide nerves may participate in regulating smooth muscle activity and local blood flow in the small intestine.     

盐酸二氢埃托啡滥用的流行病学研究

采用《盐酸二氢埃托啡（ＤＨＥ）滥用情况调查表》、《药物依赖性诊断量表》（ＳＣＩＤ－ＤＤ）和《阿片戒断症状评价量表》（ＯＷＳ）对云南等五省（区）２９７例ＤＨＥ成瘾者进行的流行病学研究表明，该群体人均ＤＨＥ滥用剂量为６１．４１　ｓ４５．０５片（１２２８．２　ｇ　ｓ９０１　ｇ），日滥用频率为９．９３　ｓ１３．８１次。ＤＨＥ主要滥用特点是：（１）产生耐受性快，７５．７％的人在使用１０次以内即对ＤＨＥ产生耐受；（２）作用时间短，分别有４２．２％和２８．９％的人在停用ＤＨＥ１ｈ和１－２ｈ之间出现戒断症状；（３）药物依赖性强，据ＳＣＩＤ－ＤＤ诊断标准，综合ＤＨＥ精神依赖性、身体依赖性，以及由此导致的社会功能损害后果，属轻度药物依赖者占１．０％．中度药物依赖者占５．０％，重度药物依赖者占９２．６％。ＤＨＥ滥用时间与剂量分别同ＯＷＳ、ＳＣＩＤ—ＤＤ分值进行相关分析，显示滥用时间同该两量表分值无相关性，而同滥用剂量有显著正相关性。本研究表明ＤＨＥ在人群中具有较强的滥用潜力．滥用造成的后果是严重的和多方面的。     

Lineage-related and particle size-dependent cytotoxicity of chitosan nanoparticles on mouse bone marrow-derived hematopoietic stem and progenitor cells

Chitosan nanoparticles (CSNPs) have potential applications in stem cell research. In this study, ex vivo cytotoxicity of CSNPs on mouse bone marrow-derived (MBMCs) hematopoietic stem and progenitor cells (HSPCs) was determined. MBMCs were exposed to CSNPs of different particle sizes at various concentrations for up to 72 h. Cytotoxicity effect of CSNPs on MBMCs was determined using MTT, Live/Dead Viability/Cytotoxicity assays and flow cytometry analysis of surface antigens on HSCs (Sca-1⁺), myeloid-committed progenitors (CD11b⁺, Gr-1⁺), and lymphoid-committed progenitors (CD45⁺, CD3e⁺). At 24 h incubation, MBMCs' viability was not affected by CSNPs. At 48 and 72 h, significant reduction was detected at higher CSNPs concentrations. Small CSNPs (200 nm) significantly reduced MBMCs' viability while medium-sized particle (∼400 nm) selectively promoted MBMCs growth. Surface antigen assessment demonstrated lineage-dependent effect. Significant decrease in Sca-1⁺ cells percentage was observed for medium-sized particle at the lowest CSNPs concentration. Meanwhile, reduction of CD11b⁺ and Gr-1⁺ cells percentage was detected at high and intermediate concentrations of medium-sized and large CSNPs. Percentage of CD45⁺ and CD3e⁺ cells along with ROS levels were not significantly affected by CSNPs. In conclusion, medium-sized and large CSNPs were relatively non-toxic at lower concentrations. However, further investigations are necessary for therapeutic applications.     

c-Jun NH2-terminal kinase-induced proteasomal degradation of c-FLIPL/S and Bcl2 sensitize prostate cancer cells to Fas- and mitochondria-mediated apoptosis by tetrandrine

Tetrandrine, a constituent of Chinese herb Stephania tetrandra, causes cell death in prostate cancer, but the molecular mechanisms leading to apoptosis is not known. Here we demonstrated that tetrandrine selectively inhibits the growth of prostate cancer PC3 and DU145 cells compared to normal prostate epithelial PWR-1E cells. Tetrandrine-induced cell death in prostate cancer cells is caused by reactive oxygen species (ROS)-mediated activation of c-Jun NH₂-terminal kinase (JNK1/2). JNK1/2-mediated proteasomal degradation of c-FLIP_L/S and Bcl₂ proteins are key events in the sensitization of prostate cancer cells to Fas- and mitochondria-mediated apoptosis by tetrandrine. Tetrandrine-induced JNK1/2 activation caused the translocation of Bax to mitochondria by disrupting its association with Bcl₂ which was accompanied by collapse of mitochondrial membrane potential (MMP), cytosolic release of cytochrome c and Smac, and apoptotic cell death. Additionally, tetrandrine-induced JNK1/2 activation increased the phosphorylation of Bcl₂ at Ser70 and facilitated its degradation via the ubiquitin-mediated proteasomal pathway. In parallel, tetrandrine-mediated ROS generation also caused the induction of ligand-independent Fas-mediated apoptosis by activating procaspase-8 and Bid cleavage. Inhibition of procaspase-8 activation attenuated the cleavage of Bid, loss of MMP and caspase-3 activation suggest that tetrandrine-induced Fas-mediated apoptosis is associated with the mitochondrial pathway. Furthermore, most of the signaling effects of tetrandrine on apoptosis were significantly attenuated in the presence of antioxidant N-acetyl-l-cysteine, thereby confirming the involvement of ROS in these events. In conclusion, the results of the present study indicate that tetrandrine-induced apoptosis in prostate cancer cells is initiated by ROS generation and that both intrinsic and extrinsic pathway contributes to cell death.     

Salvianolic acid B protects human endothelial progenitor cells against oxidative stress-mediated dysfunction by modulating Akt/mTOR/4EBP1, p38 MAPK/ATF2, and ERK1/2 signaling pathways

The vascular endothelium is specifically sensitive to oxidative stress, and this is one of the mechanisms that causes widespread endothelial dysfunction in most cardiovascular diseases and disorders. Protection against reactive oxygen species (ROS)-mediated oxidative damage via antioxidant mechanisms is essential for tissue maintenance and shows therapeutic potential for patients suffering from cardiovascular and metabolic disorders. Salvianolic acid B (SalB), a natural bioactive component known from Traditional Chinese Medicine, has been reported to exert cellular protection in various types of cells. However, the underlying mechanisms involved are not fully understood. Here, we showed that SalB significantly promoted the migratory and tube formation abilities of human bone marrow derived-endothelial progenitor cells (BM-EPCs) in vitro, and substantially abrogated hydrogen peroxide (H₂O₂)-induced cell damage. SalB down-regulated Nox4 and eNOS, as well as nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase expression upon H₂O₂ induction that in turn prevents oxidative-induced endothelial dysfunction. Moreover, SalB suppressed the Bax/Bcl-xL ratio and caspase-3 activation after H₂O₂ induction. Furthermore, our results provide mechanistic evidence that activation of the mTOR/p70S6K/4EBP1 pathways is required for both SalB-mediated angiogenic and protective effects against oxidative stress-induced cell injury in BM-EPCs. Suppression of MKK3/6-p38 MAPK-ATF2 and ERK1/2 signaling pathways by SalB significantly protected BM-EPCs against cell injury caused by oxidative stress via reduction of intracellular ROS levels and apoptosis. Taken together, by providing a mechanistic insight into the modulation of redox states in BM-EPCs by SalB, we suggest that SalB has a strong potential of being a new proangiogenic and cytoprotective therapeutic agent with applications in the field of endothelial injury-mediated vascular diseases.     

Ketorolac Versus DHE and Metoclopramide in the Treatment of Migraine Headaches

Ketorolac IM was compared to DHE and metoclopramide IV in migraine patients whose regular abortive medication had failed and who presented to a headache clinic for acute treatment. Pain scale ratings and ratings of ability to function were recorded before and after injection. Ketorolac provided moderate relief in headache in six of nine patients compared to eight of nine given DHE and metoclopramide. The average improvement in patients receiving DHE and metoclopramide was greater in pain (p = .031) and disability scores (p = .057), than in those patients given ketorolac.     

Esculetin modulates cytotoxicity induced by oxidants in NB4 human leukemia cells

Esculetin is a polyphenolic compound with cytoprotective properties. We previously demonstrated the induction of apoptosis by esculetin in NB4 human leukemia cells, as a model, by a mechanism not well understood. To analyse the antioxidant activity of esculetin on apoptosis, we have studied the influence of co-treatments of esculetin at a concentration of 100 μM with exogenous ROS donors, namely tert-butyl-hydroperoxide and hydrogen peroxide, on NB4 cells. Esculetin (100 μM) exerts a protective effect on cell viability and death necrosis or late apoptosis caused by the oxidant t-BHP whereas it potentiates decrease of cell viability and cell death caused by H₂O₂. In the first case, the O₂^? scavenging activity of esculetin (100 μM) could be implicated. In the last one, cytotoxicity by apoptosis induction seems to be related to the increase in O₂^?, among other possible mechanisms. These results contribute to the study of the antitumor properties of esculetin by regulation of redox balance in leukemia cells.