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Biomedical subjects

B Cai

Publications and source records attributed to B Cai.

At least 55 records · Page 3Linked to original sources

Immunogenicity and relative attenuation of different vaccinia-rabies virus recombinants.

Immunogenicity and relative attenuation were examined for the following Tian Tan strain vaccinia-rabies recombinant viruses: 1) NGc-1, which coexpresses the glycoprotein (G) and nucleocapsid protein (N) of the rabies virus Challenge Virus Standard (CVS) strain; 2) Nc-1, which expresses the CVS N; 3) Gc-2, Gc-3, Gc-4, and Gc-5, which express CVS G via promoters from different vaccinia strains or from different vaccinia genome loci; 4) Ga-1, which expresses the G of rabies virus strain aG; and 5) Gas-1; which expresses the carboxyltruncated G ectodomain (Gs) of strain aG. All but Nc-1 and Gas-1 induced rabies virus neutralizing antibodies (VNAs) and protected groups of mice at very high frequencies from intramuscular (IM) or intracranial (IC) challenge with CVS or SW1 Shanghai dog street rabies virus (SRV); Nc-1 and Gas-1 were partly protective, more frequently against IM challenge. NGc-1 and Gc-5 appeared to induce high levels of VNAs sooner after immunization than the other constructs in mice. Relative attenuation assessed by IM infection of neonatal mice, IC infection of adult mice, and intradermal infection of rabbits with varying doses was best for NGc-1. All the recombinants were at least 100-fold more attenuated than the parent, Tian Tan vaccinia virus. Gc-2, Gc-3, Gc-4, Gc-5, and NGc-1 induced VNAs after immunization of dogs, and a subset of VNA-positive animals vaccinated with NGc-1 or Gc-3 were protected against an otherwise lethal IM injection of SRV at 21 days after vaccination.

Animals↗

Familial vulnerability factors to post-traumatic stress disorder in male military veterans.

The question has been frequently raised about whether there are emotional disorders that predispose to post-traumatic stress disorder (PTSD). We do know that those with PTSD do have many comorbid disorders, but due to the difficulty in performing prospective studies it is hard to tell what is cause and what is effect. This study bypassed the problem caused by comorbidity by examining family history of four proband groups: PTSD, mixed anxiety disorders, coexisting anxiety and depressive disorders, and screened normal controls. Two questions were examined. First, whether family history predicted who experienced combat situations and second, whether the proband groups could be distinguished by family history. Logistic regression identified two variables that predicted the experience of combat: major depression (odds ratio 2.17) and the DSM-III dramatic personality disorder cluster (odds ratio 1.36). Although there was considerable overlap, family history variables distinguished PTSD from other proband groups. Overall, the pattern of psychopathology in the families of the PTSD probands most closely resembled that in the families of the coexisting anxiety and depressive disorders probands. We conclude that family history methods may be an addition to possible variables that predict who will be exposed to combat and also that family history variables may be able to distinguish a PTSD population from some other types of emotional disorders.

Adult↗

Processing of nux vomica. VII. Antinociceptive effects of crude alkaloids from the processed and unprocessed seeds of Strychnos nux-vomica in mice.

We examined the antinociceptive effects of the crude alkaloid fractions (CAF) of nux vomica (the dried seeds of Strychnos nux-vomica L.) and the influences of various processing methods upon their antinociception in three analgesic tests in mice. In the tail-pressure test, the CAF (0.01--1 micrograms/kg, i.p.) of nux vomica that was unprocessed or treated with sand-, licorice-, oil- or vinegar and sand-processing showed clear antinociception. The CAF (1 microgram/kg, i.p.) of vinegar-processed nux vomica showed antinociception, without effects at lower doses of 0.01 and 0.1 microgram/kg and those treated with urine- or urine and sand-processing were without effects at doses of 0.01--1 microgram/kg. Morphine (2 mg/kg, s.c.) showed short-lasting antinociception, without effects at a dose of 1 microgram/kg. In the hot-plate test, the CAF (100 microgram/kg, i.p.) of nux vomica having undergone sand-processing produced a significant antinociception, without effects at lower doses of 0.01 and 1 microgram/kg. The CAF (0.01--100 microgram/kg, i.p.) of nux vomica that was unprocessed or treated with oil- or vinegar and sand-processing and morphine (1 and 100 micrograms/kg, s.c.) were without effects. In the acetic acid-induced writhing test, the CAF (1 microgram/kg, i.p.) of nux vomica that was treated with sand-processing significantly inhibited the writhing behavior, while those of nux vomica that was unprocessed or treated with oil- or vinegar and sand-processing and morphine were without effects at a dose of 1 microgram/kg. The present results demonstrate the antinociceptive effects of the CAF of nux vomica and suggest that sand-processing is good for the analgesic potency of nux vomica. It is also suggested that the CAF of nux vomica has distinct antinociceptive potency, even after treatment with licorice-, oil-, vinegar and sand-processing.

Acetic Acid↗

[Effect of ginger-processing on l-ephedrine contents in rhizoma Pinelliae].

The contents of l-ephedrine in Rhizoma Pinelliae have been determined to be approximately 3.44 x 10(-3). The contents vary with the five different processing methods in the following order, Pinellia boiled with ginger juice and alum > raw Pinellia > Pinellia dipped in ginger juice > Pinellia boiled only with ginger juice > Pinellia dipped in alum solution. The alum solution and the Pinellia boiled only with ginger juice bear most strongly on the l-ephedrine contents of Pinellia.

Drugs, Chinese Herbal↗

[Orthogonal experiment design in the optimization of processing technology for Rhizoma Pinelliae by ginger and alum].

Based on the L9(3)1 orthogonal design with the amount of ginger, amount of alum and decocting time as working factors, and using the method of recording comprehensive scores, an experimental study has been made on the optimization of processing technology for Rhizoma Pinelliae by ginger and alum as stipulated in the Pharmacopoeia. The result shows that the best process is to use 15 kg of ginger juice and 8 kg of alum per 100 kg of Pinellia ternata and decoct them together for 2-3 hours till the juice is fully absorbed by Rhizoma Pinelliae.

Alkaloids↗

Production and characterization of monoclonal antibodies against stonustoxin from Synanceja horrida.

Stonustoxin (SNTX), a lethal factor purified from the venom of stonefish Synanceja horrida, is a protein (148,000 mol. wt) existing as a dimer comprising two subunits (alpha and beta) of mol. wts 71,000 and 79,000, respectively. Its LD50 (i.v.) is 17 ng/g in mice and it causes haemolysis of rat and rabbit erythrocytes in vitro. Eight monoclonal antibodies (Mabs) against SNTX have been developed using the Balb/C mouse. These Mabs have been purified by Protein G affinity membrane disc chromatography. They were all classified as IgG1 with half of them having kappa and the rest lambda light chains. They had affinity constants ranging from 3.75 x 10(-9) to 9.74 x 10(-9) M. Six were able to protect mice from a challenge of a lethal dose of SNTX. However, not all protective Mabs were able to neutralize the haemolytic effect in vitro. Only four Mabs (31A, 32B, 38A and 46A) could inhibit rat and rabbit erythrocyte haemolysis, while one Mab (43D) offered partial inhibition and another Mab (8A) did not inhibit haemolysis at all. The non-protective Mabs (43B and 44G) were also incapable of neutralizing haemolysis. Five epitopes were recognized by the eight Mabs. Four Mabs (31A, 32B, 38A and 46A) were found to have similar epitope specificity while the rest were directed at different epitopes on the SNTX molecule. Thus these results suggest that the domain on the SNTX molecule responsible for lethality is probably distinct from the domain important for in vitro haemolytic activity.

Animals↗

Effects of immunosuppressive therapy on expression of inducible nitric oxide synthase (iNOS) during cardiac allograft rejection.

Recent studies have indicated a role for nitric oxide (NO) in alloimmune responses and in allograft rejection. iNOS mRNA, protein and enzyme activity are induced in myocardium during cardiac allograft rejection. NO produced by iNOS is negatively inotropic and has the potential to be cytotoxic to cardiac myocytes. To investigate whether immunosuppressive agents would alter the expression of iNOS during cardiac allograft rejection, hearts from Wistar-Furth rats were transplanted into the abdomen of Lewis recipients. At day 5 allografts from treated and untreated animals were removed for pathological and biochemical examination. At day 5 the untreated allografts exhibited histological evidence of marked rejection (edema, infiltration with macrophages and lymphocytes, necrosis of cardiac muscle fibers). Abundant iNOS mRNA was apparent in Northern blots and iNOS enzyme activity was increased in ventricular homogenates and in cardiac myocytes purified from the untreated rejecting allografts. Incubation of isolated purified cardiac myocytes from normal rats for 24 h with cytokines known to be present during allograft rejection (IL-1 beta, TNF-alpha and IFN-gamma) was also associated with increased iNOS mRNA and enzyme activity. When Wistar-Furth to Lewis allografts were treated from time of transplantation with FK 506, cyclosporine A, dexamethasone or a combination of all three drugs, histological evidence of rejection and the levels of iNOS mRNA and enzyme activity in ventricular homogenates were reduced significantly below those observed in the untreated allografts. The data in a rat model indicate that immunosuppressive drugs reduce myocardial iNOS mRNA and enzyme activity in rejecting cardiac allografts. The results are consistent with the hypothesis that the alloimmune response and cytokine release are involved in the expression of iNOS during cardiac transplantation rejection.

Animals↗

The lethal effects of cytokine-induced nitric oxide on cardiac myocytes are blocked by nitric oxide synthase antagonism or transforming growth factor beta.

Inducible nitric oxide (NO) produced by macrophages is cytotoxic to invading organisms and has an important role in host defense. Recent studies have demonstrated inducible NO production within the heart, and that cytokine-induced NO mediates alterations in cardiac contractility, but the cytotoxic potential of nitric oxide with respect to the heart has not been defined. To evaluate the role of inducible nitric oxide synthase (iNOS) on cardiac myocyte cytotoxicity, we exposed adult rat cardiac myocytes to either cytokines alone or to activated J774 macrophages in coculture. Increased expression of both iNOS message and protein was seen in J774 macrophages treated with IFN gamma and LPS and cardiac myocytes treated with TNF-alpha, IL-1 beta, and IFN gamma. Increased NO synthesis was confirmed in both the coculture and isolated myocyte preparations by increased nitrite production. Increased NO synthesis was associated with a parallel increase in myocyte death as measured by CPK release into the culture medium as well as by loss of membrane integrity, visualized by trypan blue staining. Addition of the competitive NO synthase inhibitor L-NMMA to the culture medium prevented both the increased nitrite production and the cytotoxicity observed after cytokine treatment in both the isolated myocyte and the coculture experiments. Because transforming growth-factor beta modulates iNOS expression in other cell types, we evaluated its effects on cardiac myocyte iNOS expression and NO-mediated myocyte cytotoxicity. TGF-beta reduced expression of cardiac myocyte iNOS message and protein, reduced nitrite production, and reduced NO-mediated cytotoxicity in parallel. Taken together, these experiments show the cytotoxic potential of endogenous NO production within the heart, and suggest a role for TGF-beta or NO synthase antagonists to mute these lethal effects. These findings may help explain the cardiac response to sepsis or allograft rejection, as well as the progression of dilated cardiomyopathies of diverse etiologies.

Amino Acid Oxidoreductases↗

[Experimental comparison of the analgesic action of Aconitum and its processed products].

This paper deals with the effects of crude Aconitum and Aconitum processed by a new method of moistening and steaming, and by method of pharmacopoeial stipulation on the analgesic action with writhing test and hot plate test in mice. The result shows that the Aconitum processed by new method No 1, which applies moistening in water for 48h and then heating with high pressure steam (68.65kPa, 115 degrees C) for 2h has an advantage over that processed according to pharmacopoeial routine (P < 0.05).

Aconitum↗

[Effect of ginger-processing on beta-sitosterol and total alkaloid contents in Rhizoma Pinelliae].

The contents of beta-sitosterol of five processed products of Rhizoma Pinelliae we were determined by TLC. The result showed that the lowest content of beta-sitosterol was found in Rhizoma Pinelliae boiled with ginger juice (0.0180%), and the highest in raw Phizoma Panelliae (0.0572%). The contents of total alkaloid of five processed products of Phizoma Pinelliae were also determined by gravimetry and spectrophotometry with acid dye. The result showed that the highest content of total alkaloid was obtained in Rhizoma Pinelliae boiled with ginger juice and alum, and the lowest in Rhizoma Pinelliae boiled with ginger juice.

Alkaloids↗

Differential effects of pinacidil and cromakalim on vascular relaxation and sympathetic neurotransmission.

We tested the hypothesis that pinacidil and cromakalim acted at different sites to relax vascular smooth muscle, in vitro. We compared the effects of pinacidil and cromakalim on tension development in isolated canine and bovine pulmonary artery and vein and canine mesenteric artery and dorsal metatarsal vein, and on the pre- and post-synaptic responses of the canine blood vessels to transmural nerve stimulation. Both pinacidil and cromakalim relaxed bovine and canine blood vessels precontracted to 50% of maximal tension with U46619, prostaglandin F2 alpha, or norepinephrine. Pinacidil- and cromaklim-mediated relaxations of the blood vessels were not mediated by endothelium-derived factors, prostanoids, muscarinic receptors, beta-adrenoceptors, or Ca(2+)-activated or voltage-dependent K+ channels, since they were unaffected by endothelium-rubbing, indomethacin, L-NG-monomethyl-L-arginine, atropine, propranolol, and charybdotoxin. Glibenchlamide, an inhibitor of ATP-activated K+ channels (K+ATP), and KCl (25-60 mM) sufficient to minimize the role of K+ channels almost abolished cromakalim- but not pinacidil-induced relaxation of the blood vessels. Pinacidil inhibited the contractions of the dorsal metatarsal vein and mesenteric artery to norepinephrine and transmural nerve stimulation and the efflux of 2-[14C]norepinephrine during transmural nerve stimulation. In contrast, 1 and 10 nM cromakalim enhanced while 0.1 and 1 microM cromakalim inhibited the contractions of, and 2-[14C]norepinephrine efflux from, the mesenteric artery and dorsal metatarsal vein during transmural nerve stimulation. Thus, pinacidil and cromakalim relax smooth muscle by stimulation of K+ATP channels. Pinacidil also relaxes the blood vessels by a K+ channel independent mechanism. Pinacidil-induced relaxation may also result from presynaptic inhibition of norepinephrine release from the sympathetic neuron.

Animals↗

Inhibition of inducible nitric oxide synthase in macrophages by oxidized low-density lipoproteins.

Uptake of oxidized low-density lipoprotein (LDL) by monocyte/macrophages to form "foam" cells has been implicated in atherogenesis. Activated monocyte/macrophages synthesize nitric oxide (NO) from L-arginine. NO is cytotoxic, antiproliferative, and a vasodilator that inhibits platelet and monocyte adhesion. NO synthase mRNA, protein, and enzyme activity were induced in J774.A1 macrophages activated with lipopolysaccharide and gamma interferon. When macrophages were incubated with oxidized LDL for 24 hours and activated, there was a dose- and time-dependent inhibition of NO synthesis, assessed as nitrite accumulation in the media. When activated cells were incubated with nontoxic doses of lipoprotein (25 micrograms/mL), neither native LDL nor acetyl LDL inhibited NO production, whereas oxidized LDL produced 50% inhibition. Levels of enzyme protein were unchanged by Western blot. Inhibition was a function of the degree of oxidation of LDL but was independent of cholesteryl esterification by the cells. Incubations of oxidized LDL with cells that had been pretreated with dextran sulfate or cytochalasin B yielded no evidence that inhibition was dependent on the scavenger receptor or directed endocytosis. Kinetic studies of inducible NO synthase from J774.A1 cells that were incubated with increasing doses of oxidized LDL indicated a pattern of noncompetitive inhibition. Inhibition of the enzyme was produced by lipids extracted from oxidized LDL but not by lipids extracted from native LDL. Because phosphatidylcholine (PC) is converted to lysophosphatidylcholine (LPC) during the oxidation of LDL, the effects of LPC were investigated. PC vesicles containing LPC did not inhibit enzyme activity but produced modest reductions in nitrite accumulation from cells. In contrast, PC vesicles had no significant effect. The data indicate that oxidized LDL lipid inhibits the activity of inducible NO synthase in activated macrophages. NO production by this enzyme and its inhibition by oxidized LDL lipid may influence cell-to-cell interactions and vasomotor tone in atherosclerotic blood vessels.

Amino Acid Oxidoreductases↗

Induction of myocardial nitric oxide synthase by cardiac allograft rejection.

Cardiac transplantation, effective therapy for end-stage heart failure, is frequently complicated by allograft rejection, the mechanisms of which remain incompletely understood. Nitric oxide (NO), a vasodilator which is cytotoxic and negatively inotropic, can be produced in large amounts by an inducible NO synthase (iNOS) in response to cytokines. To investigate whether iNOS is induced during cardiac allograft rejection, hearts from Lewis or Wistar-Furth rats were transplanted into Lewis recipients. At day 5, allogeneic grafts manifested reduced contractility and histologic evidence of rejection (inflammatory infiltrate, edema, necrosis of myocytes). The mRNA for iNOS and iNOS protein were detected in ventricular homogenates and in isolated cardiac myocytes from rejecting allogeneic grafts but not in tissue and myocytes from syngeneic control grafts. Immunocytochemistry showed increased iNOS staining in infiltrating macrophages and in microvascular endothelial cells and cardiac muscle fibers and also in isolated purified cardiac myocytes from the rejecting allografts. Using a myocardial cytosolic iNOS preparation, nitrite formation from L-arginine and [3H] citrulline formation from [3H]L-arginine were increased significantly in the rejecting allogeneic grafts (P < 0.01). Myocardial cyclic GMP was also increased significantly (P < 0.05). The data indicate myocardial iNOS mRNA, protein and enzyme activity are induced in infiltrating macrophages and cardiac myocytes of the rejecting allogeneic grafts. Synthesis of NO by iNOS may contribute to myocyte necrosis and ventricular failure during cardiac allograft rejection.

Amino Acid Oxidoreductases↗

Study on preventive and curative effects of liu wei di huang tang on tumors.

Liu Wei Di Huang Tang (LWDHT), a Chinese prescription for strengthening the body resistance, restoring the normal functions of the body to consolidate the constitution, and nourishing and invigorating the kidney yin, has been used to prevent and treat severe hyperplasia of esophageal epithelium for many years. The results of this experiment show that LWDHT can increase markedly the number of lymphocytes, mainly T lymphocytes, in tumor-bearing mice. Free-flow electrophoresis shows that in tumor-bearing mice the electrophoretic characteristics of T lymphocytes are changed, i.e., reduction of the number of T lymphocytes with a higher electrophoretic rate, but LWDHT can alleviate this disorder. Study on the cell membrane fluidity of carcinoma cells in EAC mice demonstrates that LWDHT can decrease the cell membrane fluidity, suggesting that it can inhibit division of carcinoma cells.

Animals↗

[Potentiation of electroacupuncture analgesia on visceral pain by metoclopramide and its mechanism].

The present study was to investigate the effect of metoclopramide (MCP) on electroacupuncture analgesia (EAA) and its mechanism on a rabbit visceral pain model. The results showed that MCP 8mg/kg i.v. could potentiate EAA and prolong the analgesic duration. The potentiation effect could be attenuated by icv apomorphine (APO) (a mixed D1/D2 agonist). The analgesic duration was shortened by icv SKF38393 (a selective D1 agonist) or LY171555 (a selective D2 agonist). Using HPLC-ECD, we also found that the HVA content in CSF significantly increased at 20 min. after electroacupuncture (EA) or MCP 8mg/kg i.v. (P < 0.05), but the change of HVA content was not significant when EA and MCP 8mg/kg i.v. were used together. All these observations indicate that MCP have effects of potentiating EAA and prolonging analgesic duration. These effects are related to the blockade of the central DA receptor. The activations of D1 or D2 receptor is unfavourable to the expression of EA after effect.

Acupuncture Analgesia↗

N-(1-arylpropionyl)-4-aryltetrahydropyridines, a new class of high-affinity selective sigma receptor ligands.

A series of N-(1-arylpropionyl)-4-aryl-1,2,3,6-tetrahydropyridines, prepared by simple Mannich condensations, have been found by radioligand binding assays to have moderate to high affinity (IC50 0.5-500 nM) for bovine cerebellar sigma receptor/binding sites and no measurable affinity (IC50 > 5000 nM) for bovine striatal D2 receptors. The most active of these compounds rival in potency the most active sigma ligands previously reported. Three of these sigma-active compounds were screened for pharmacological activity under the NIMH-NovaScreen program and showed moderate affinity only for D2 and 5-HT2 receptors among the 40 sites assayed. Since these N-(1-arylpropionyl)-4-aryltetrahydropyridines are structurally related to other potent sigma receptor ligands, in particular haloperidol and 4-phenylpiperidines, these data provide insights into the nature of the essential pharmacophore of the sigma receptor. The selective affinity of these materials for sigma receptors indicates they have potential as prototypes of novel psychotherapeutic medicinal agents, particularly as antipsychotic drugs which would be devoid of debilitating side effects associated with blockade of D2 receptors.

Animals↗

Biphasic effects of typical antidepressants and mianserin, an atypical antidepressant, on aggressive behavior in socially isolated mice.

Effects of several typical antidepressants and of an atypical antidepressant, mianserin, on the aggressive behavior (AGB) in long-term isolated mice were examined. IP administration of maprotiline (2.5 and 5 mg/kg), amitriptyline (5 and 10 mg/kg), clomipramine (2.5 and 5 mg/kg), and mianserin (5 mg/kg) significantly increased the duration of AGB. However, at higher doses (maprotiline, 10 mg/kg; amitriptyline, 20 mg/kg; clomipramine, 10 and 20 mg/kg; mianserin, 10 and 20 mg/kg) these antidepressants either did not affect AGB or inhibited it. Amitriptyline (20 mg/kg) and mianserin (10 mg/kg) but not maprotiline (10 mg/kg) or clomipramine (20 mg/kg) decreased spontaneous motor activity in isolated mice. Yohimbine (0.5 mg/kg, IP), an alpha 2-antagonist, changed the antidepressant-induced enhancement of AGB into inhibition without affecting the basal aggressive responses. Prazosin (0.3 mg/kg, IP), an alpha 1-antagonist, did not affect either maprotiline- or clomipramine-induced enhancement of AGB, but it changed the mianserin-induced enhancement of AGB into inhibition. These results indicate that antidepressants that inhibit noradrenaline uptake and/or stimulate noradrenaline output from nerve terminals have biphasic effects on AGB in isolated mice and that the antidepressant-induced enhancement of AGB is mediated by noradrenergic stimulation of alpha 2-adrenoceptors, whereas the antidepressant-induced inhibition of AGB may be mediated by non-alpha 2-adrenoceptors or by nonadrenergic system(s).

Aggression↗