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PubMed1976

Homologous passive cutaneous anaphylaxis (PCA) in mice and heterologous PCA induced in rats with mouse IgE.

A study was made of the effect of anit-histamine, antiserotonin and of different anti-anaphylactic drugs on PCA reactions induced in mice with IgG1 or IgE. Further, using the ability of mouse IgE to sensitize rat mast cells, a comparative study was also made of PCA reactions induced in mice and rats with mouse IgE. Antihistamines produced a partial inhibition of PCA reactions induced in mice with mouse IgG1 or IgE and in rats with mouse IgE whereas antiserotonin inhibited PCA reactions induced in rats with mouse IgE, but had no effect on PCA reactions induced in mice with mouse IgG1 or IgE. The simultaneous use of antihistamine and antiserotonin resulted in a total inhibition of PCA reactions induced in mice with IgG1 and in a marked but not total inhibition of PCA reaction due to IgE; PCA reactions induced in rats with mouse IgE were totally inhibited. Compounds known to change the intracellular level of cyclic AMP were found to have little or no effect on PCA reactions induced in mice with either IgG1 or IgE in spite of producing a complete marked inhibition of PCA reactions induced with mouse IgE in rats. Diethylcarbamazine or disodium cromoglycate were also very effective inhibitors of rat PCA reactions induced with mouse IgE although having no effect on PCA reaction induced in mice with this same antibody or with IgG1. Thus, in spite of sharing common mediators released from the same type of target cell sensitized with the same type of antibody, PCA reactions induced in mice and rats with mouse IgE reacted very differently to the pharmacological effect of most of the drugs tested. This fact seems to indicate that the physiological mechanism operating in mouse mast cells are different from those operating in rat mast cells.

Animals↗

PubMed1992

Interaction of platelets with subendothelium in rats treated with PCA-4230, a new antithrombotic agent. Effect of PCA-4230 on experimental thrombosis.

The effects of a new antithrombotic compound, PCA-4230, versus ticlopidine were investigated using an experimental thrombosis and vascular endothelial injury model in rats. Both PCA-4230 and ticlopidine protected rat arteries from the formation of prominent thrombi and most of microthrombi without modifying the formation of a first platelet monolayer. Neither coagulation parameters nor fibrinolysis were modified by these antithrombotic drugs. Neither PCA-4230 nor ticlopidine affected thromboxane A2 production in rats, whereas unlike PCA-4230, ticlopidine inhibited ex vivo fibrinogen binding to the fibrinogen receptor found on the platelet membrane. In conclusion, PCA-4230 and ticlopidine inhibited thrombus formation in vivo by a platelet-dependent mechanism which may be different for one or the other drug in spite of the fact that the protective effect measured in this thrombosis model is quite similar for either PCA-4230 or ticlopidine. The above-mentioned results clearly show that PCA-4230 is a new potent agent with both antivascular-damaging and antiplatelet activities, and devoid of effects on coagulation and fibrinolytic systems.

Animals↗

PubMed1977

Effect of changing the composition of the bathing solutions upon the isometric tension-pCa relationship in bundles of crustacean myofibrils.

1. The relative isometric tension-pCa relationship has been determined for isolated bundles of barnacle myofibrils under a variety of ionic conditions using [Ca(2+)]-buffered solutions which also contained an ATP regenerating system (creatine phosphate and creatine kinase).2. The results are in better agreement with the ;consecutive' scheme of reaction rather than with the ;independent' alternative (Ashley & Moisescu, 1972) for the co-operative action of two Ca(2+) ions in the process of tension activation in crustacean skeletal muscle.3. Variations in the pH of the activating solutions did have a marked effect on the relative tension-Ca curve, although no effect was observed on the absolute maximum value for isometric tension. A shift in pH by 0.5 u. in the range 6.6-7.6 shifted the Ca(2+)-activation curve by 0.5 log u. towards lower free Ca(2+) concentrations.4. Changes in the free Mg(2+) concentration of the activating solutions in the millimolar range produced a pronounced shift of the relative tension-pCa curve along the pCa axis. Increasing [Mg(2+)] from 1 to 5 mM shifted the curve by about 0.7 log u. to higher free Ca(2+) concentrations, without significantly modifying its steepness.5. Changes in the MgATP concentration of the activating solutions in the range of 1-13 mM had no significant effect on the relative tension-pCa relationship.6. Varying the K(+) concentration in the activating solutions was also observed to have a marked effect upon the tension-pCa relationship in barnacle. An increase in the K(+) concentration from 90 to 170 mM shifted the curve by some 0.6 log u. towards higher free Ca(2+) concentrations.7. Cooling the standard activating solutions from room temperature to +4 degrees C made no apparent difference to the relative tension-pCa relationship, but decreased significantly the absolute tension responses.8. The results presented show that tonicity by itself has a marked effect upon the absolute steady-state tension levels in isolated bundles of myofibrils.9. Maximum isometric tension in this preparation was not simply related to ionic strength, or to the monovalent cation concentration, but it depended, as well, upon the anionic composition of the activating solution. In addition, a change in ionic strength of 25 mM over the range of 245-270 mM did not appear to modify the relative tension-pCa relationship.10. The effect of the physiologically occurring cations H(+), K(+), Mg(2+) upon the relative isometric tension-pCa relationship can be accounted for on the basis of a model of competitive inhibition between these cations and Ca(2+) for the functional unit for tension. This inhibitory effect appears to involve at least one H(+), one Mg(2+) and two K(+) per each Ca(2+) ion participating in the activation process of the functional unit for tension.

Adenosine Triphosphate↗

PubMed1978

Influence of the new 5-HT-uptake inhibitor paroxetine on hypermotility in rats produced by p-chloroamphetamine (PCA) and 4,alpha-dimethyl-7-tyramine (H 77/77).

Two different forms of hypermotility produced by the amphetamine derivatives PCA and H 77/77, 5 mg/kg of each, was studied in rats treated s.c. with the new 5-HT uptake inhibitor paroxetine. The substance inhibited the effect of PCA but did not influence that of H 77/77. The 5-HT-uptake inhibitors paroxetine, imipramine, and chlorimipramine were also administered p.o. at various times before PCA. The three substances inhibited PCA-induced hypermotility. Paroxetine 0.5-2 mg/kg, was active at intervals of 1-4 h and 4 mg/kg was active at 18-h interval. Imipramine and chlorimipramine 25-30 mg/kg showed PCA inhibition at treatment intervals of 1-2h, but 80-100 mg/kg or more was required to inhibit PCA at intervals of 4 and 18 h. Previous results have shown that PCA-induced hypermotility is antagonized by substances inhibiting 5-HT synthesis and uptake, whereas H 77/77-induced hypermotility is inhibited by substances blocking NA synthesis, uptake, and receptors. The previous and present results indicate that paroxetine is a selective 5-HT-uptake inhibitor. After oral administration paroxetine presumably produces a more potent and long-lasting 5-HT-uptake inhibition than imipramine and chlorimipramine.

Amphetamines↗

PubMed1976

p-Chloroamphetamine (PCA): acute and chronic effects on habituation and sensitization of the acoustic startle response in rats.

In a series of 6 experiments the effects of p-chloroamphetamine (PCA) on the acoustic startle response in rats were investigated. 15 min after 5 mg/kg PCA startle amplitude was inhibited, 2-15 hr after PCA startle was facilitated. Rate of habituation however was not altered. Both the inhibitory and excitatory effects of PCA were blocked by pretreatment with p-chlorophenylalanine but not by alpha-methyl-p-tyrosine. 24 hr, 1 week and 4 weeks after PCA, initial startle amplitude was unchanged but PCA increased rate of sensitization over successive tone blocks. Increased sensitization was most pronounced at 10 mg/kg and absent at 2.5 mg/kg. The early inhibitory effect of PCA but not the later facilitatory effect was eliminated by reducing the level of background noise. The results suggest that inhibition of startle sensitization is associated with enhanced release of serotonin (5-HT) whereas enhancement of startle sensitization is associated with 5-HT depletion.

Acoustic Stimulation↗

PubMed1992

Effects of the antithrombitic agent PCA 4230 on agonist-induced Ca2+ entry and Ca2+ release in human platelets.

We have studied the effects of the antithrombitic agent PCA 4230 on the entry of Mn2+, used here as a Ca2+ surrogate for Ca2+ channels, and on the release of Ca2+ from the intracellular stores in stimulated human platelets loaded with fura-2. PCA 4230 prevented receptor-operated calcium entry activated by thrombin, ADP and collagen with no modification of the Ca2+ release from the intracellular stores. PCA 4230 also inhibited cytochrome P-450-mediated O-dealkylase activity with the same concentration-dependence as the thrombin-induced Mn2+ entry. These results suggest that the inhibitory effects of PCA 4230 on Ca2+ influx may be due to its interaction with cytochrome P-450, which has been proposed recently to be involved in the activation of receptor-operated Ca2+ channels. In addition, PCA 4230 inhibited both PAF-induced Ca2+ entry and Ca2+ release, behaving as a PAF-antagonist. All these effects contribute to explain the antithrombitic action of PCA 4230.

Blood Platelets↗

PubMedDate not supplied

The efficacy of intramuscular ketorolac in combination with intravenous PCA morphine for postoperative pain relief.

STUDY OBJECTIVE: To examine the efficacy of intramuscular (IM) ketorolac used in combination with intravenous (IV) patient-controlled analgesia (PCA) morphine for postoperative pain relief following intra-abdominal gynecologic surgery. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Patient care unit at a university medical center. PATIENTS: Thirty-five healthy women undergoing intra-abdominal gynecologic surgery who requested postoperative PCA. INTERVENTIONS: Postoperatively, all patients received IV PCA morphine, with the PCA device programmed to deliver a maximum of 1 mg every 6 minutes (maximum of 30 mg over 4 hours). In addition, patients received one of three regimens: (1) IM saline every 6 hours; (2) IM ketorolac 30 mg while in the postanesthesia care unit (PACU), followed by 15 mg every 6 hours; or (3) IM ketorolac 60 mg while in the PACU, followed by 30 mg every 6 hours. MEASUREMENTS AND MAIN RESULTS: Patients were assessed at regular intervals. Visual analog scale (VAS) scores were used to assess analgesia and patient satisfaction with therapy. Data on morphine usage were obtained from the PCA device, and the frequency and severity of adverse effects were assessed for the presence or absence of side effects. Cumulative morphine dosages were lower (p less than 0.05) in both ketorolac groups at 12, 18, and 24 hours. VAS scores and the frequency of side effects did not differ significantly among groups. CONCLUSIONS: IM ketorolac significantly decreased PCA morphine requirements. The analgesic effects of the two drugs appear to be additive.

Adult↗

PubMed1976

Behavioral evidence for the rapid release of CNS serotonin by PCA and fenfluramine.

Administration of p-chloroamphetamine (PCA) (2.5-10.0 mg/kg) or fenfluramine (FF) (5.0-15.0 mg/kg) to rats induces a behavioral syndrome--consisting of tremor, rigidity, Straub tail, hindlimb abduction, lateral head weaving and reciprocal forepaw treading--which is a reflection of the activity of central serotonin-mediated synapses. The syndrome appears within 3-5 min following i.p. administration of PCA or FF, and the syndrome-inducing effects of PCA and FF are blocked by prior depletion of serotonin with p-chlorophenylalanine. By contrast, the syndrome-inducing effect of 5-methoxy-N,N-dimethyltryptamine (5-M-DMT), which directly stimulates postsynaptic serotonin receptors, is not changed by prior serotonin depletion. Catecholamine depletion with alpha-methyl-p-tyrosine produces essentially no change in the syndrome-inducing effects of PCA, FF or 5-M-DMT. These data indicate that the initial effect of PCA or FF administration is the rapid functional release of stored serotonin.

Amphetamines↗

PubMed1979

Interaction among IgE-mediated hypersensitivity reaction, PCA reaction and delayed hypersensitivity reaction (at local skin sites of monkeys).

The effect of the IgE-mediated reaction on the passive cutaneous anaphylaxis (PCA) reaction was studied at local skin sites of monkeys, and we found that the IgE-mediated reaction appeared to enhance the PCA reaction. Interactions among IgE-mediated reaction, PCA reaction and delayed hypersensitivity reaction were also determined. Contact dermatitis induced with DNCB was utilized as the delayed hypersensitivity reaction. The IgE-mediated reactior or PCA reaction, as well as simple serum irritation, enhanced the delayed hypersensitivity reaction. It is thus assumed that the IgE-mediated reaction enhances the PCA reaction and that this in turn accelerates the delayed hypersensitivity reaction.

Animals↗

PubMed1977

On the nature of the presumed receptor for IgE on mast cells. IV. Inhibition of the PCA-blocking activity of cell-free particulate preparations and intact rat peritoneal mast cells by inhibitors of proteases.

The incubation of IgE-containing solutions from rat serum with particulate preparations from rat peritoneal mast cells results in the disappearance of some of the PCA-reactive IgE in the solution. This PCA blocking assay was used to measure the 'binding' of IgE to intact rat mast cells or to particulate preparations derived from mast cells. The PCA-blocking activity at pH 4.8 was up to 100-fold greater than that seen at a physiologic pH of 6.6. PCA-blodking activity was inhibited at both these pH conditions by high concentrations of several trypsin inhibitors. The inhibitors were generally more active at the more acid pH. Among the active inhibitors were soybean and limabean trypsin inhibitors, chymostatin, and p-nitrophenyl-p'-guanidinobenzoate. Inhibitors of acid proteases, such as pepstatin and diazaacetylnorleucine methyl ester were inactive. The results support the proposition that under certain conditions IgE degradation by a specific proteolytic enzyme which is located uniquely on the plasma membrane of mast cells can account for a major portion of the PCA-blocking activity of these cells.

Animals↗

PubMed1976

Force velocity relations in vascular smooth muscle: the influence of pH, pCa, and noradrenaline.

The kinetics of vascular smooth musclw activity was studied by means of afterloaded isotonic contractions of the tetanized rat portal vein at varied pH (8.0-5.9), pCa (3.4-2.1), and during noradrenaline incubation (0.4 mug/ml). Under control conditions (pH 7.3, pCa 2.6) the following parameters of the force velocity relation were calculated: a of Hill's equation (relating to the isometric peak tension) = 0.36; b (relating to the actual muscle length) = 0.19 ML/s; VM Trelating to the actual muscle length) = 0.56 ML/s. Within the range of pCa between 2.0 and 3.2 the amount of force generation (= delta P) depended on the extracellular calcium level whereas the extrapolated velocity of shortening of the unloaded preparation (= VM) did not. Also pH changes between 8.0 and 6.8 as well as noradrenaline incubation at a pH of 5.9 affected delta P quite considerably, but VM only scarcely. At a pH of 6.3, however, VM was distinctly diminished, and a reduced calcium sensitivity of the ATPase was inferred from the shift of ED50 of extracellular calcium from 0.66 mM Ca at a pH of 7.3 to 1.56 mM Ca at a pH of 6.3 (P less than 0.0005). It is concluded from these results that the experimental conditions-pCa between 2.0 and 3.2, pH between 8.0 and 6.8, and noradrenaline added at a pH of 5.9-obviously change the intracellular calcium concentration which influences the number of activated interaction sites rather than the velocity of crossbridge movement.

Animals↗

PubMed1978

Effects of PCA and DMAE on the namatode Caenorhabditis briggsae.

Concentration of 6.8 mM DMAE did not retard age pigment accumulation in Caenorhabditis briggsae. However, when the nematodes were exposed to 6.8 mM PCA + 6.8 mM DMAE combined, the accumulation of age pigment was significantly retarded. A combination of 3.4 mM DMAE + 3.4 mM PCA had no effect on age pigment. It is concluded from this study that PCA and DMAE act in concert to produce the observed effect on age pigment. In respect to this parameter neither molecule was effective alone. The results indicate that the effect of centrophenoxine on age pigment might be enhanced by retarding the hydrolysis of centrophenoxine. The accumulation of electron dense aggregates, thought to be aggregates of cross-linked molecules, was reduced by 6.8 PCA + 6.8 DMAE. It is suggested that centrophenoxine be tested for its ability to remove random, unwanted cross-linkages in higher animals.

Animals↗

PubMed1978

Quantitation of passive cutaneous anaphylaxis (PCA) by using radiolabelled antigen.

The major problem of detecting reaginic antibody by passive cutaneous anaphylaxis (PCA) is the quantitation of the dye reaction. Radiolabelled antigen was used in an attempt to quantitate the PCA reaction (Radio-PCA). Antisera containing reaginic antibody against human serum albumin (HSA) were produced in rabbits. These antisera were injected into normal rabbit skin in different dilutions. Twenty-four hours later HSA was injected intravenously either with Evans Blue or as 125-I-HSA. Radioactivity found in antibody-containing skin was significantly higher than in control specimens containing saline or normal rabbit serum, as low as antiserum dilutions of 1:1,000. Compared with the Evans Blue technique Radio-PCA was able to distinguish quantitatively between different antiserum dilutions at a higher level of statistical significance.

Animals↗

PubMed2026

PCa Detection in PI-RADS 4 and 5 Lesions: Comparison of [68Ga]Ga-PSMA-11 PET/CT-Guided Robot-Assisted Biopsy Versus mpMRI Cognitive-Fusion TRUS-Guided Prostate Biopsy.

Lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 4 or greater on multiparametric MRI (mpMRI) indicate a high likelihood of prostate cancer (PCa), and guidelines recommend a targeted biopsy. We aimed to compare the diagnostic performance of robotic arm-assisted [68Ga]Ga-PSMA-11 PET/CT-guided prostate biopsy (PGPB) with mpMRI-directed cognitive-fusion transrectal ultrasound-guided biopsy (MCFB) in biopsy-naïve men with clinical findings suggestive of PCa. Methods: This prospective, single-center, randomized clinical trial (NCT05137561) enrolled biopsy-naïve men age 50-90 y with elevated levels of prostate-specific antigen (≥4 ng/mL) and abnormal digital rectal examination findings. All participants underwent mpMRI, and those with a PI-RADS score of 4 or greater were randomized into 2 arms. In arm 1, participants underwent PGPB for a [68Ga]Ga-PSMA-avid lesion, and participants in arm 2 underwent MCFB. Participants in arm 1 with PET-negative findings subsequently underwent MCFB, and participants with negative biopsy results underwent PET and PGPB. The primary outcome was the detection of PCa. Secondary outcomes included complication rates and participant-reported pain. Result: Of the 267 participants enrolled, 81.3% (217) had lesions with a PI-RADS score of 4 or greater and were randomized to either PGPB (n = 112) or MCFB (n = 105). PCa was detected in 97.1% of participants (101/104) in arm 1 and 81.0% (85/105) in arm 2 (P < 0.05). PGPB showed higher diagnostic accuracy for PI-RADS 5 lesions (100% vs. 95.1%, P = 0.09). Major complications were observed in arm 2 only (n = 5). Arm 1 had significantly fewer complications (10.8% vs. 51.4%, P < 0.01), a lower median visual analog scale score for pain (3 vs. 5), and shorter procedure times. The core positivity rate was higher in arm 1 (60% ± 20%), despite obtaining fewer cores. Conclusion: [68Ga]Ga-PSMA-11 PGPB demonstrated higher diagnostic performance, fewer complications, and better tolerability compared with MCFB. This approach enables integrated diagnosis and staging, offering a promising alternative for efficient, safe, and accurate evaluation of prostate cancer.

Humans↗

PubMedDate not supplied

[Postoperative analgesia using the intravenous PCA technique. Results in the first 400 patients treated at a general hospital].

INTRODUCTION: PCA (patient controlled analgesia) has represented a remarkable advance in the treatment of postoperative pain. In this work we describe our experience with this analgesic technique. MATERIAL AND METHODS: One hundred patients undergoing thoracic and abdominal surgery were selected after giving information to the medical and nurse personnel. Pharmacologic agents used in this study were morphine (intravenous PCA) and fentanyl (epidural PCA). Starting of the perfusion pump was done by the anesthesiologist at the Recovery Unit and the treatment was continued by the nurse. Every morning the patients were visited and the degree of analgesia was recorded according to the following score: 1: no pain, and 5: intolerable pain. An anesthesiologist was permanently available. Later on, this study was expanded to 400 patients including other types of surgery. RESULTS: Mean duration of the treatment was 60 hours. The amount of analgesics administered varied among patients and was greater during the first postoperative hours specially in the group of patients treated with fentanyl. The mean degree of pain was 1.5 (grade 1 in 37.5% of cases and grade 5 in 3.5% of patients). Secondary effects were only nausea and vomiting. Inconvenient features of the technique were: patient's difficulties in the management of the technique (3 cases), and spontaneous loss of the program (1 case). Patient's acceptance of the technique was good. CONCLUSIONS: PCA analgesia has been successfully introduced in our hospital since it is effective, safe, easy to manage.

Adolescent↗

PubMed2025

AWGE-ESPCA: An edge sparse PCA model based on adaptive noise elimination regularization and weighted gene network for Hermetia illucens genomic data analysis.

Hermetia illucens is an important insect resource. Studies have shown that exploring the effects of Cu2+-stressed on the growth and development of the Hermetia illucens genome holds significant scientific importance. There are three major challenges in the current studies of Hermetia illucens genomic data analysis: firstly, the lack of available genomic data which limits researchers in Hermetia illucens genomic data analysis. Secondly, to the best of our knowledge, there are no Artificial Intelligence (AI) feature selection models designed specifically for Hermetia illucens genome. Unlike human genomic data, noise in Hermetia illucens data is a more serious problem. Third, how to choose those genes located in the pathway enrichment region. Existing models assume that each gene probe has the same priori weight. However, researchers usually pay more attention to gene probes which are in the pathway enrichment region. Based on the above challenges, we initially construct experiments and establish a new Cu2+-stressed Hermetia illucens growth genome dataset. Subsequently, we propose AWGE-ESPCA: an edge Sparse PCA model based on adaptive noise elimination regularization and weighted gene network. The AWGE-ESPCA model innovatively proposes an adaptive noise elimination regularization method, effectively addressing the noise challenge in Hermetia illucens genomic data. We also integrate the known gene-pathway quantitative information into the Sparse PCA(SPCA) framework as a priori knowledge, which allows the model to filter out the gene probes in pathway-rich regions as much as possible. Ultimately, this study conducts five independent experiments and compared four latest Sparse PCA models as well as representative supervised and unsupervised baseline models to validate the model performance. The experimental results demonstrate the superior pathway and gene selection capabilities of the AWGE-ESPCA model. Ablation experiments validate the role of the adaptive regularizer and network weighting module. To summarize, this paper presents an innovative unsupervised model for Hermetia illucens genome analysis, which can effectively help researchers identify potential biomarkers. In addition, we also provide a working AWGE - ESPCA model code in the address: https://github.com/yhyresearcher/AWGE_ESPCA.

Animals↗

PubMed1976

On the nature of the presumed receptor for IgE on mast cells. III. Kinetics of the blocking of the PCA reaction by cell-free particulate preparations from rat peritoneal mast cells and effect of pH and calcium concentration on the reaction.

The 'binding' of IgE to particulate preparations derived from sonicated purified rat mast cells was measured by the blocking of PCA titrations of the supernatant solutions from incubations with such preparations. It was found that the PCA blocking reaction was inhibited by the addition of calcium ion to the incubations. The blocking reaction was strongly dependent on the pH of the incubations, being maximal at pH values lower than 5-0. The blocking reaction proceeded in a linear manner for at least 3 h provided that no more than 70 percent of the amount of IgE initially supplied had been removed by the particulate fraction. Only mast cell-derived preparations were capable of effecting PCA blocking.

Animals↗

PubMed1979

Interactions between homologous and heterologous IgE in the induction of PCA reactions in rats.

Various inbred strains of rats presented differences in sensitivity to the induction of PCA reactions by mouse reaginic antibody. This was shown to be due to the presence of non-specific IgE in the normal sera of the bad recipients. Both positive and negative interaction, as measured by PCA reactions, could be observed between sera of the two different species. Inhibition of PCA reactions was seen when positive serum was diluted with normal serum from rat and mouse strains which were bad recipients, as opposed to what occured when sera from good recipients, were used to dilute. Synergism, on the other hand, was observed when mixtures of subsensitizing doses of both rat and mouse positive sera were tested. These results give further support to the suggestion that rat mast cells receptors for rat and mouse IgE are either the same, or are present, near enough each other, to produce steric hindrance.

Animals↗