Postoperative adhesion formation and reproductive outcome using Interceed after ovarian surgery: a randomized trial in the rabbit model

The efficacy of an oxidized regenerated cellulose barrier (Interceed) in reducing postoperative adhesion formation and improving reproductive outcome after ovarian surgery was evaluated in a prospective randomized trial. Twenty-nine New Zealand White female rabbits were submitted to a mid-line laparotomy and a standardized surgical incision was made on both ovaries. At random, one ovary was entirely wrapped in a sheet of Interceed, whereas the contralateral ovary was left uncovered. Four weeks following surgery, the rabbits were mated with a male of proven fertility. Two weeks later, a second-look laparotomy was performed by a blinded observer who evaluated the incidence and score of adhesions, the number of corpora lutea in each ovary, the number of embryos in the ipsilateral uterine horn and also calculated the nidation index for each side. Adhesions were observed in 66% of Interceed-covered and in 97% of control ovaries (P < 0.0001). The adhesion score on the Interceed side was significantly lower than on the control side. The nidation index for the Interceed side was significantly higher than for the control side. The authors conclude that, in the rabbit model, Interceed significantly reduces the incidence and score of postoperative ovarian adhesions and significantly improves reproductive outcome.      

Design, synthesis, structural studies, biological evaluation, and computational simulations of novel potent AT(1) angiotensin II receptor antagonists based on the 4-phenylquinoline structure

Novel AT(1) receptor antagonists bearing substituted 4-phenylquinoline moieties instead of the classical biphenyl fragment were designed and synthesized as the first step of an investigation devoted to the development of new antihypertensive agents and to the understanding of the molecular basis of their pharmacodynamic and pharmacokinetic properties. The newly synthesized compounds were tested for their potential ability to displace [(125)I]Sar(1),Ile(8)-Ang II specifically bound to AT(1) receptor in rat hepatic membranes. These AT(1) receptor binding studies revealed nanomolar affinity in several of the compounds under study. The most potent ligands 4b,t were found to be equipotent with losartan and possessed either a 3-tetrazolylquinoline or a 2-amino-3-quinolinecarboxylic moiety, respectively. Moreover, some selected compounds were evaluated for antagonism of Ang II-induced contraction in rabbit aortic strips, and the most potent compounds in the binding test 4b,t were slightly more potent than losartan in inhibiting Ang II-induced contraction. Finally, the most relevant structure-affinity relationship data were rationalized by means of computational studies performed on the isolated ligands as well as by computational simulations on the ligands complexed with a theoretical AT(1) receptor model.     

Efficient induction of T-cell responses to carcinoembryonic antigen by a heterologous prime-boost regimen using DNA and adenovirus vectors carrying a codon usage optimized cDNA

The immunogenic properties of plasmid DNA and recombinant adenovirus (Ad) encoding the carcinoembryonic antigen (CEA) were examined in mice by measuring both the amplitude and type of immune response, and the immunogenicity of codon usage optimized cDNA encoding CEA (CEAopt) was assessed both in C57Bl/6 and CEA transgenic mice. Vectors were injected into quadriceps muscle either alone or in combination, and plasmid DNA was electroporated to enhance gene expression efficiency and immunogenicity. Injection of plasmid pVIJ/CEA followed by Ad-CEA boost elicited the highest amplitude of both CD4+ and CD8+ T-cell response to the target antigen, measured by both IFNgamma-ELIspot assay and intracellular staining. Vectors carrying cDNA of CEAopt expressed a greater amount of the CEA protein than their wild-type counterparts, and this enhanced expression was associated with greater immunogenicity. Both CD4+ and CD8+ T-cell epitopes were mapped in the C-terminal portion of the protein. In CEA transgenic mice, only immunization based on repeated injections of pVIJ/CEAopt followed by Ad-CEAopt was able to elicit a CEA-specific CD8+ T-cell response, whereas the wild-type vectors did not break tolerance to this target antigen. MC38-CEA tumor cells injected s.c. in CEA transgenic mice vaccinated with CEAopt vectors exhibited delayed growth kinetics. These studies demonstrate that this type of genetic vaccine is highly immunogenic and can break tolerance to CEA tumor antigen in CEA transgenic mice.     

Design, synthesis, and biological evaluation of AT1 angiotensin II receptor antagonists based on the pyrazolo[3,4-b]pyridine and related heteroaromatic bicyclic systems

Novel AT 1 receptor antagonists bearing the pyrazolo[3,4- b]pyridine bicyclic heteroaromatic system (or structurally related moieties) were designed and synthesized as the final step of a large program devoted to the development of new antihypertensive agents and to the understanding of the molecular basis of their pharmacodynamic and pharmacokinetic properties. The preliminary pharmacological characterization revealed nanomolar AT 1 receptor affinity for several compounds of the series and a potent antagonistic activity in isolated rabbit aortic strip functional assay for 7c and 8a. These results stimulated the study of the biopharmaceutical properties of some selected compounds, which were found to be characterized by a permeability from medium to high. Remarkably, the least permeable 7c showed both permeability and oral bioavailability (80%) higher than losartan, but its terminal half-life was shorter. These results suggest that the permeability is not a limiting factor in the pharmacokinetics of these AT 1 receptor antagonists.     

褶合曲线分析法测定复方茶碱片中六种主要成分

应用柱分配色谱,将复方茶碱片分离出各含三个组分的两组混合物,然后分别应用褶合曲线分析法,同时定量测定了两组混合物。六个被测成分的平均百分回收率和相对标准差分别为:咖啡因101.6,1.46%;非那西丁99.7,0.10%;苯巴比妥100.9,1.31%;可可碱99.9,0.81%;茶碱100.2,0.81%;氨基比林100.8,0.48%。     

麝香的药理研究 Ⅱ.麝香及其有效成分的抗炎作用

麝香水提物对小鼠巴豆油耳部炎症,大鼠琼脂性关节肿、酵母性关节肿、佐剂型多发性关节炎均具非常显著的抑制作用。对大鼠烫伤性血管渗透性增加、羧甲基纤维素引起的腹腔白细胞游走亦具非常明显的抑制作用。静脉注射麝香1号对巴豆油小鼠耳炎症的50%抑制剂量为0.63 mg/kg,为氢化可的松作用强度的36倍,如以克分子剂量相比,则为氢化可的松的500倍以上。静脉注射麝香水提物对小鼠的LD_(50)及95%可信限为848±104 mg/kg。     

OLTIPRAZ对小鼠日本血吸虫病的初步治疗

Oltipraz is a new drug against Schistosomiasis mansoni and was used to treat mice Schistosorniasis japonica in our laboratory. The results showed that 48 h after oral administraction of oltipraz at a single dose of 900 mg/kg, 97% Schistosomes in mice infected with Schistosomiasis japonica schifted to the liver of the host. About half of these worms returned to the mesenteric veins in 96 h. Infected mice was given oltipraz orally at the dose of 900 mg/kg.d for 3～5 days, and killed in 28 days after the last dose. Over 95% total worm reduction rate was found.Schistosomes in infected mice treated with oltipraz were collected for histological observation. The results showed that the tegument of schistosomes were damaged and host cells invaded into the worm body; and granuloma formation of dead worm was observed.During the treatment, food uptake and body weight of the infected mice were decreased, but regained soon after the cessation of the treatment.     

脑内注射白细胞介素-1β对淋巴结细胞应激免疫抑制因子生成的影响

our previous work showed that a suppressive factor( a protein with largemolecular weight in serum was induced by restraint stress in mice and rats,which suppressed Con Ainduced lymphocyte proliferation.It was also found that the generation of serum suppressive factorwas under control of the central nervous system.Our further study showed thatintracerebroventricular(icv )injection of interleukin 1 receptor antagonist(IL-1Ra)antagonised thegeneration of serum suppressive factor induced by restraint stress and icv injection of interleukin-1β(IL-1β)increased the generation of the suppressive factor.Our experiment also showed that the serumsuppressive factor induced by restraint stress was first made in lymph tissue and then released intoblood.The present work was designed to investigate the role of IL-1 in the brain in generation of thesuppressive factor in lymph node in mice.Icv injection of IL-1β( 1 pg/mouse) was shown tosignificantly increase the generation of the suppressive factor in lymph node.Icv injection of IL-1Ra,however ,antagonised generation of the suppressive factor.In mice without restraint stress,both thesuppressive factor in serum and in lymph node were found to be induced in dose-dependent manner byicv injection of IL-1β.Taken together,these results suggest that IL-1β in brain played a veryimportant role in generation of the suppressive factor in lymph node.The positive correlation betweenthe suppressive action of lymph node and of serum added to the evidence that lymph tissue is probablythe source of the serum suppressive factor.     

Immunoglobulin and T cell receptor gene configuration in acute lymphoblastic leukemia of infancy

We examined immunoglobulin (Ig) heavy chain, K light chain, and T cell receptor (TCR) gamma and beta gene configuration in the leukemic cells from a series of infants aged less than 1 year with acute lymphoblastic leukemia (ALL). Each of these 11 cases demonstrated leukemic cell surface antigens that have been correlated with a B cell precursor phenotype. Of the 11, lymphoblasts of 4 retained the germline configuration of both Ig and TCR loci, whereas 7 had rearranged the Ig heavy chain gene. Two of these seven showed light chain gene rearrangement. TCB beta chain rearrangement had occurred in only one of the 11 patients' tumors. No TCR gamma chain rearrangements were identified. These results are in contrast to earlier studies of B cell precursor ALL in children in which Ig heavy chain gene rearrangements were evident in every case and approximately 40% showed Ig light chain rearrangement as well. In addition, 45% of cases of B cell precursor ALL of children had rearranged their gamma TCR genes, and 20% had rearranged beta. These data suggest that ALL in infancy represents an earlier stage of B cell development than is found in B cell precursor ALL of children. ALL in the infant age group has been associated with the worst prognosis of all patients with ALL. This study suggests that the disease in infants differs not only clinically, but also at the molecular genetic level, from the disease in children.