Ultrastructural evidence for the uptake of a neurotoxic snake venom phospholipase A2 into mammalian motor nerve terminals

A mutant form of ammodytoxin A, a neurotoxic phospholipase A₂ from the venom of the long nosed viper Vipera ammodytes ammodytes, was prepared by site-directed mutagenesis, conjugated to a nanogold particle and inoculated into the antero-lateral aspect of one hind limb of female mice. Eight hours later the mice were killed, the soleus muscles of both ipsi- and contra-lateral hind limbs were removed, exposed to a silver enhancing medium and then prepared for transmission electron microscopy. Silver-enhanced particles were subsequently found concentrated in the peri-synaptic area, particularly within the synaptic gutter and the deep synaptic folds, and in many cases had been taken up into the cytoplasm of the terminal boutons of the motor axon. The results suggest that the presynaptic neurotoxicity of snake venom phospholipases A₂ involves several components of the neuromuscular apparatus, including intracellular organelles of the motor nerve terminal.     

Spigelian hernias: a prospective analysis of baseline parameters and surgical outcome of 34 consecutive patients

Most of the papers published on spigelian hernia are either case reports or small retrospective series. In this prospective multicenter study, we aimed to outline the specific features of spigelian hernias and patients’ characteristics more clearly. Surgeons enrolled patients to be entered into the database as they diagnosed and treated the hernias at will. The baseline and surgical outcome parameters were noted in each patient. A painful mass was the main presenting complaint in half of 34 patients. Accurate preoperative diagnosis was possible in 31 patients. Open intraperitoneal mesh repair was the preferred technique. The mean hospital stay and time until return to normal daily activities were 4.1 and 15.6 days. Although a rare condition, diagnosis of a spigelian hernia is not difficult once remembered. Its surgical repair seems to cause few complications and is very well tolerated by the patient.     

重症胆管炎23例临床治疗分析

目的：探讨急性重症胆管炎患者的手术时机和死亡原因。方法：回顾性分析23例急性重症胆管炎患者的治疗及预后情况。结果：死亡2例（手术死亡及传统治疗死亡各1例）。早期大剂量短期应用糖皮质激素患者休克得到纠正率85％，明显高于未用糖皮质激素患者休克纠正率50％。结论：急性重症胆管炎患者应在出现休克和（或）精神症状之前手术，对已出现休克的患者，应先给予充分的保守治疗，待病情稳定后再手术。贻误手术时机，严重合并症如多器官功能衰竭及高龄是死亡的主要原因。     

Elimination of malignant clonogenic cells from human bone marrow using multiple myeloid cell-specific monoclonal antibodies and complement.

Single or combined monoclonal antibodies (McAbs) Zh53, Zh820, and Zh2-1 have been used to eliminate malignant clonogenic cells from human bone marrow. The test of cytotoxicity showed that all of these McAbs could express high specific cytotoxic action against HL-60 cells and were selectively complement-dependent cytotoxic to various types of fresh leukemic cells. Clonogenic assay detected that single treatment with antibody and rabbit complement (RC) could reduce clonogenic units of HL-60 cells by more than 2 logs and two treatments reduced clonogenic units by more than 4 logs. However, combination of 2 McAbs could reduce clonogenic units by 4-5 logs. The data suggest that multiple treatments with McAbs and RC or a combination of 2 McAbs are more effective than a single treatment in eliminating clonogenic tumor cells. Treatment of normal human bone marrow with Zh53, Zh2-1 and RC did not produce a loss of normal CFU-GM, but treatment with Zh820 reduced the clonic units of normal CFU-GM by 24%.

     

Central metabotropic glutamate receptors differentially participate in interleukin-1beta-induced mechanical allodynia in the orofacial area of conscious rats.

The present study investigated the role of central metabotropic glutamate receptors (mGluRs) in interleukin-1beta (IL-1beta)-induced mechanical allodynia and mirror-image mechanical allodynia in the orofacial area. Experiments were carried out on male Sprague-Dawley rats weighing 230 to 280 g. After administration of 0.01, 0.1, 1, or 10 pg of IL-1beta into a subcutaneous area of the vibrissa pad, we examined the withdrawal behavioral responses produced by 10 successive trials of an air-puff ramp pressure applied ipsilaterally or contralaterally to the IL-1beta injection site. Subcutaneous injection of IL-1beta produced mechanical allodynia and mirror-image mechanical allodynia in the orofacial area. Intracisternal administration of CPCCOEt, a mGluR1 antagonist, or MPEP, a mGluR5 antagonist, reduced IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia. Intracisternal administration of APDC, a group II mGluR agonist, or L-AP4, a group III mGluR agonist, reduced both IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia. The antiallodynic effect, induced by APDC or L-AP4, was blocked by intracisternal pretreatment with LY341495, a group II mGluR antagonist, or CPPG, a group III mGluR antagonist. These results suggest that groups I, II, and III mGluRs differentially modulated IL-1beta-induced mechanical allodynia, as well as mirror-image mechanical allodynia, in the orofacial area. PERSPECTIVE: Central group I mGluR antagonists and groups II and III mGluR agonists modulate IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia in the orofacial area. Therefore, the central application of group I mGluR antagonists or groups II and III mGluR agonists might be of therapeutic value in treating pain disorder.