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Interactive effects of volatile anesthetics, verapamil, and ryanodine on contractility and calcium homeostasis of isolated pregnant rat myometrium.

OBJECTIVE: Both volatile anesthetics and Ca2+ antagonists decrease uterine contractility. The interactive effects of anesthetics, verapamil, and ryanodine on myometrial muscular activity and on intracellular Ca2+ availability were examined. STUDY DESIGN: The effects of minimum alveolar concentrations of 0.5, 1.0, and 2.0 of halothane, enflurane, and isoflurane on electrically stimulated isometric mechanical activity of isolated longitudinal myometrium strips from 45 pregnant rats (15 to 21 days), superfused with Krebs' solution with or without 5.0 mmol/L Ca2+, 10(-7) and 10(-6) mol/L verapamil, and 10(-6) mol/L ryanodine, were compared. Analysis was performed by analysis of variance and Duncan test. RESULTS: All three anesthetics and verapamil produced dose-dependent depression of contractility. Increasing the Ca2+ concentration from 2.5 to 5.0 mmol/L in the superfusate partly reversed the depression. An additive effect of verapamil and anesthetics, especially enflurane, on contractile force was observed. Ryanodine had no effect on contractility, but it could partly counteract the depressant effect of anesthetics. CONCLUSION: Clinically used concentrations of volatile anesthetics modify Ca2+ availability and depress uterine contractility. General anesthesia, especially by enflurane, in patients being treated with calcium antagonists may represent a higher risk.

Anesthetics

Interactive effects of dietary chromium tripicolinate and crude protein level in growing-finishing pigs provided inadequate and adequate pen space.

An experiment was conduct to determine the interactive effects of dietary chromium tripicolinate (CrPic), CP, and pen space (PS) as a stress on growth performance, carcass traits, and plasma hormones and metabolites of crossbred growing-finishing pigs (128 pigs; initial BW 27.2 kg). A factorial arrangement of treatments included two levels of Cr (0 and 400 ppb as CrPic), two levels of CP (80 [80P] and 120% [120P] of the lysine requirement; NRC, 1988), and two levels of PS (adequate [APS] or inadequate [IPS]). In the grower phase, ADG was decreased more by IPS when pigs were fed 80P (CP x PS, P < .08). Gain/feed (G/F) was decreased by IPS in pigs fed 80P; however, in pigs fed 120P, IPS increased G/F (CP x PS, P < .01). Supplemental Cr did not affect (P > .10) ADG, ADFI, or G/F in the grower phase. In the finisher phase, pigs, fed 120P had less (P < .10) ADFI but similar (P > .10) ADG compared with pigs fed 80P. Gain/feed was higher (P < .10) in pigs fed 120P than in pigs fed 80P. Daily gain ADFI were lower (P < .03) in pigs provided IPS than in pigs provided APS. In pigs fed 80P, CrPic tended to result in higher ADG and G/F; however, in pigs fed 120P, Cr tended to result in lower ADG and G/F (CP x Cr, P < .09). Pigs fed 120P had greater (P < .03) longissimus muscle area (LMA) and percentage of muscling (PM) and less (P < .03) 10th rib fat thickness (TRF) than pigs fed 80P. Pigs provided IPS had greater LMA and PM and less TRF than pigs provided APS (P < .03). Pigs fed CrPic had higher TRF when provided IPS but lower TRF when provided APS (Cr x PS, P < .07). Feeding CrPic had minimal effect on plasma urea N, cholesterol, glucose, NEFA, insulin, or growth hormone.

Analysis of Variance

Interactive effects among porcine somatotropin, the beta-adrenergic agonist salbutamol, and dietary lysine on growth performance and nitrogen balance of finishing swine.

An experiment was conducted to evaluate the interactive effects among porcine somatotropin (pST), salbutamol, and dietary lysine on growth performance, nitrogen balance, and carcass characteristics of finishing barrows (n = 32; 62.8 kg initially). Two replicate 32-d studies were set up in a split-plot design to evaluate singular and combined use of pST (0 or 4 mg/d) and salbutamol (0 or 2.75 ppm of the diet) as whole-plot treatments and diets containing .8, 1.2, 1.6, or 2.0% lysine as subplot treatments. Dietary lysine levels were administered within subplots in a 4 x 4 Latin square with pigs allowed 4 d of adjustment to diets followed by 4 d of urine and feces collection for determination of N retention and apparent digestibility of DM and N. Interactions between lysine and salbutamol were not found (P > .16). A pST x lysine interaction (P < .05) resulted in ADG being maximized at 1.2% lysine for pST-treated pigs (lysine quadratic, P < .02) but decreased linearly (P < .02) with increasing lysine for pigs receiving buffer. Pigs injected with 4 mg/d of pST had improved gain:feed (G:F) up to 1.2% lysine (lysine quadratic, P < .05), but no further increase to 2% lysine, whereas pigs injected with buffer showed no benefit from increased lysine (pST x lysine, P < .06). Pigs receiving buffer had greater increases in plasma urea N (PUN) as lysine increased than those receiving pST (pST x lysine, P < .002), but PUN was reduced by pST (P < .001) regardless of lysine level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue

Interactive effects of monensin, roxarsone, and copper in young chickens infected with Eimeria tenella or a combination of E: tenella and E. acervulina.

Experiments were conducted with crossbred male chicks to evaluate the interactions among roxarsone (50 mg/kg), monensin (121 mg/kg), and copper sulfate (100 mg/kg) as treatments for experimental Eimeria tenella and E. acervulina infections. When diets containing monensin, roxarsone, or a combination of both were offered to chicks for 15 min or 1, 3, 5, or 8 days prior to E. tenella challenge (5 X 10(4) sporulated oocysts), monensin fed for 15 min or roxarsone fed for 1 day prior to challenge prevented morbidity. A mixed infection of E. tenella and E. acervulina (5 X 10(4) and 4 X 10(5) sporulated oocysts, respectively) reduced gain and gain:feed conversion ratios and caused severe duodenal and cecal lesions at Day 6 of the experiment. Infected chicks gained faster when diets were supplemented with either monensin or roxarsone, but monensin produced a larger response than roxarsone. The mixed infection decreased shank pigmentation, with amelioration activity evident from monensin but not from roxarsone. Lesion scores at Day 6 indicated markedly reduced lesions in the duodenum due to monensin but not due to roxarsone; likewise, reductions in cecal lesions occurred in birds fed roxarsone but less so in birds fed monensin. Lesion scores showed little evidence of additivity due to monensin and roxarsone. In general, copper sulfate exerted no independent or interactive effect on any of the parameters evaluated. In a subsequent experiment, the effect of feeding roxarsone in combination with the biological reducing agent, cysteine, was evaluated in E. tenella-infected chicks. Rate and efficiency of gain were improved and lesion scores were reduced by supplementary roxarsone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The effect of high altitude and other risk factors on birthweight: independent or interactive effects?

OBJECTIVES: This study examined whether the decline in birth-weight with increasing altitude is due to an independent effect of altitude or an exacerbation of other risk factors. METHODS: Maternal, paternal, and infant characteristics were obtained from 3836 Colorado birth certificates from 1989 through 1991. Average altitude of residence for each county was determined. RESULTS: None of the characteristics related to birthweight (gestational age, maternal weight gain, parity, smoking, prenatal care visits, hypertension, previous small-for-gestational-age infant, female newborn) interacted with the effect of altitude. Birthweight declined an average of 102 g per 3300 ft (1000 m) elevation when the other characteristics were taken into account, increasing the percentage of low birthweight by 54% from the lowest to the highest elevations in Colorado. CONCLUSIONS: High altitude acts independently from other factors to reduce birthweight and accounts for Colorado's high rate of low birthweight.

Adult

Interacting effects of temperature and extracellular calcium on the spontaneous release of transmitter at the frog neuromuscular junction.

1. Temperature has a characteristic effect on the frequency of m.e.p.p.s at the frog neuromuscular junction; the spontaneous release of transmitter is not affected by temperature changes below 10 degrees C whereas the system is highly temperature-sensitive above 20 degrees C.2. A very similar result is obtained when the experiment is repeated in saline containing Ca(2+) buffered at 5 x 10(-7)M, suggesting that it is unlikely that the major action of temperature is to cause an increase in Ca(2+) influx.3. It is suggested that the main effect of temperature at the presynaptic terminals is a modification of [Ca(2+)](i) by an action on intracellular Ca(2+) stores.4. The interacting effects of theophylline and the divalent cation ionophore A23187 on m.e.p.p. frequency suggest that intracellular Ca(2+) stores, in addition to the mitochondria, may well be of importance in controlling [Ca(2+)](i).5. Changes in [Ca(2+)](o) produce a modification of m.e.p.p. frequency, but the details of the response are dependent on temperature. The spontaneous release of transmitter is most sensitive to an increase in [Ca(2+)](o) at 23 degrees C, whereas the greater effect is found at 13 degrees C when [Ca(2+)](o) is lowered.6. It is suggested (i) that m.e.p.p. frequency is primarily determined by [Ca(2+)](i) at the presynaptic terminals, (ii) that the presynaptic terminals are normally able to maintain [Ca(2+)](i) almost constant in spite of increases in Ca influx associated with ionophore treatment or with a rise in [Ca(2+)](o). However, if the steady-state position of [Ca(2+)](i) is previously raised by an increased efflux from intracellular stores (produced by elevated temperature or theophylline pre-treatment), increased influx causes a rise in both [Ca(2+)](i) and in m.e.p.p. frequency.

Animals

Interactive effects of K+, acidosis, and catecholamines on isolated rabbit heart: implications for exercise.

Intense exercise can double arterial K+ concentration, decrease pH by 0.4 units, and increase catecholamines 15-fold. Any one of these changes may be cardiotoxic in a subject at rest, yet these changes are well tolerated in exercise. We tested the interactive effects of extracellular K+ concentration ([K+]o), metabolic acidosis (pH 7.0), and raised catecholamines in the isolated working rabbit heart when they were changed with similar kinetics and concentrations to those seen in exercise. Raised [K+]o (8 and 12 mM) significantly decreased aortic flow (AF) by 23 and 76%, respectively (P < 0.01). Acidosis decreased AF by 19% (P < 0.05) and by 38% in combination with 8 mM [K+]o (P < 0.05), making their combined effect additive. Either epinephrine (80 nM), norepinephrine (80 nM) or extracellular Ca2+ concentration (5 mM) offset the negative effects of 8 and 12 mM [K+]o on AF. Norepinephrine also improved AF in 8 mM [K+]o with acidosis. Thus, there may be a beneficial interaction among changes in K+, catecholamines, and acidosis during exercise such that each could offset the others' potentially harmful effects.

Acidosis

Social influence on group moral decisions: the interactive effects of moral reasoning and sex role orientation.

In this study, we examined the effects of moral reasoning level and sex role orientation on social influence in group decision making. We predicted that these two individual difference constructs would have an interactive effect such that people who are compatible or nonconflicted on the two dimensions would have more influence on a group task with moral implications than would people who are conflicted. All subjects individually completed a distributive decision task that required ranking terminally ill patients for access to a life-saving kidney machine. They then met in small groups and reached a group decision on the same task. The subjects' moral reasoning level and sex role orientation--assessed via the Rest Defining Issues Test (Rest, 1979) and the Bem Sex Role Inventory (Bem, 1974), respectively--were used to predict influence on the group decision. Influence was measured in three ways: similarity between individual and group ranks, self-rated influence, and selection of the most influential group member. The results of all three influence measures provided support for the interactive hypothesis. In the discussion we consider the implications of the data for individual difference models of moral reasoning, the need for further understanding of goal competition and personality conflict, and the importance of considering the impact of moral factors on group decision-making proceses.

Adult

Interaction effects of ethanol and pyrazole in laboratory rodents.

1. Interactions of pyrazole and ethanol were studied in three laboratory test procedures. They included sleeping time in mice, rotor rod balance in rats and lever pressing behaviour of rats.2. Equimolar concentrations of pyrazole and 3-methylpyrazole were compared for effects on enhancement of ethanol's activity on rotor rod holding time of rats.3. Minimally effective doses of pyrazole, the LADH inhibitor, and 3-methylpyrazole, a non-inhibitor of LADH, when administered before ethanol, resulted in an increased behavioural depression. These interaction effects are probably not caused by inhibition of LADH but rather by an increase in the direct depressant action of either one or both of the compounds.

Alcohol Oxidoreductases

1H-n.m.r. evaluation of the ferricytochrome c-cardiolipin interaction. Effect of superoxide radicals.

The interaction between ferricytochrome c and cardiolipin was investigated by 1H n.m.r. at 270 MHz. From the phospholipid-induced changes of the protein spectral features it is concluded that the first 2 equivalents of cardiolipin cause a conformational change at the lower part of the solvent-exposed haem edge, involving a rearrangement of the hydrogen-bond interactions of propionate 6, thus partly accounting for the lowered redox potential of cytochrome c in the presence of cardiolipin. The increased value for the pK of the alkaline isomerization of ferricytochrome c shows that cardiolipin stabilizes the native structure of the protein, indicating that the oxidized form assumes ferrocytochrome c-like properties. Peroxidation of cardiolipin by superoxide radical ions drastically decreases the protein binding to this phospholipid. The implications of this finding, and the likelihood of the ternary cytochrome c-cardiolipin-cytochrome c oxidase complex, for the binding of cytochrome c to cytochrome c oxidase in vivo, are discussed in relation to peroxidative damage following ischaemia and reperfusion.

Animals

Familial risk, abortion and their interactive effect on the risk of breast cancer--a combined analysis of six case-control studies.

In a previous study in France, we reported that the relative risk of breast cancer associated with a family history of breast cancer was higher in those subjects with a history of abortions. The present study was undertaken to check the existence of this interaction in other studies and to investigate whether the interaction is modified by the time at which abortions occur. Data were obtained from six case-control studies in France, Australia and Russia, with information on family history of breast cancer and abortion for 2693 breast cancer cases and 3493 controls. The interaction effect was estimated in each study separately, then combined using a multivariate weighted average. The relative risk conferred by a family history of breast cancer increased with the number of abortions (1.8 for no abortion, 1.9 for one abortion, 2.8 for two or more). There was a significant interaction between total number of abortions and family history (P = 0.04), but this was no longer significant when adjusted for other risk factors. The familial risk was highest for those who had had an abortion before first childbirth (1.9 for abortion after first childbirth, 2.7 for abortion before first childbirth). The adjusted risk associated with family history was significantly higher in those with an abortion before first childbirth (P = 0.04). Our findings suggest a synergism between familial factors and abortion. The interaction was not substantially modified by the type of abortion (spontaneous or induced) but was modified by the time at which it occurred in relation to first childbirth. This suggests an effect of abortion itself rather than predisposition to abortion. Further studies of breast cancer cases, particularly among BRCA1 gene carriers and their families, could improve our understanding of this effect.

Abortion, Induced

IL-4, IL-10 and IFN-gamma have distinct, but interacting, effects on differentiation-induced changes in TNF-alpha and TNF receptor release by cultured human monocytes.

Monocytes cultured in vitro differentiate to a macrophage-like phenotype and undergo functional changes, including reduced capacity for release of TNF-alpha and the soluble p55 receptor for TNF (sTNF-R55) but enhanced capacity for release of the soluble p75 receptor (sTNF-R75). The cytokines IL-4 and IL-10 act on monocytes to suppress the release of pro-inflammatory cytokines, including TNF-alpha, and to influence the release of sTNF-R. We therefore investigated the influence of differentiation over 15 days in vitro on the spontaneous and LPS- and IFN-gamma-induced release of TNF-alpha and sTNF-R from human monocytes and examined the actions of IL-4 and IL-10 on these. Unstimulated monocytes did not release TNF-alpha at any stage but released progressively larger amounts of sTNF-R75 with time. LPS-stimulated release of TNF-alpha declined substantially after the first day and was consistently suppressed by IL-10 and IL-4 but increased by IFN-gamma. Monocytes cultured with IL-10 released more sTNF-R75 at all times and expressed more mRNA for TNF-R75 at day 8. LPS stimulation consistently enhanced both spontaneous and IL-10-augmented release of sTNF-R75, whilst IFN-gamma co-stimulation consistently suppressed them. The influence of IL-4 on sTNF-R75 release, however, depended qualitatively on both the length of time in culture and on conditions of stimulation. The effects of LPS and IFN-gamma on TNF-alpha and sTNF-R75 release were progressively lost with increasing time in culture in the presence of IL-4. sTNF-R55 was not detectable after the first day of culture under any of these conditions. IL-4, IL-10 and IFN-gamma therefore have distinct, but interacting, effects on the balance between TNF-alpha and sTNF-R75 release by maturing monocytes. These interactions may be relevant to the pathogenesis or treatment of TNF-alpha-mediated diseases, where sTNF-R may act to neutralize or stabilise TNF, thereby modifying biological activity.

Analysis of Variance

Stimulation of group II phospholipase A2 mRNA expression and release in an immortalized astrocyte cell line (DITNC) by LPS, TNF alpha, and IL-1 beta. Interactive effects.

Astrocytes are immunoactive cells in brain and have been implicated in the defense mechanism in response to external injury. Previous studies using cultured glial cells indicated the ability of astrocytes to respond to bacteria endotoxin and cytokines, resulting in the release of phospholipase A2. In this study, we examined the interactive effects of lipopolysaccharides (LPS), interleukin 1 beta (IL-1 beta) and tumor necrosis factor (TNF alpha) to stimulate phospholipase A2 (PLA2) in an immortalized astrocyte cell line (DITNC) with many properties of type I astrocytes. Northern blot analysis using oligonucleotide probes derived from the cDNA encoding the rat spleen group II PLA2 indicated the ability of DITNC cells to respond to all three factors in the induction of gene expression and the release of PLA2. After an initial lag time of 2 h, PLA2 release was proportional to time, reaching a plateau by 12 h. This event occurred at a time period preceding any signs of cell death. Cycloheximide at 1.25 microM completely inhibited cytokine-induced PLA2 release. When suboptimal amounts of TNF alpha were added to the DITNC culture together with IL-1 beta or LPS, a synergistic increase in the induction of PLA2 release could be observed. On the other hand, combination of IL-1 beta and LPS resulted only in an additive increase in PLA2 release. Antibodies to IL-1 beta and TNF alpha completely neutralized the effects of these two agents on PLA2 release. However, neither antibody was able to inhibit the PLA2 release induced by LPS, suggesting that the effect of LPS was not complicated by the release of IL-1 beta or TNF alpha. Taken together, results show that the immortalized astrocyte cell line (DITNC) can be used for studies to elucidate the molecular mechanism underlying the cytokine signaling cascade and subsequent induction of PLA2 synthesis.

Animals

Interactive effects of antifungal and antineoplastic agents on yeasts commonly prevalent in cancer patients.

The effects of combinations of antifungal and antineoplastic drugs on inhibition of the growth of yeasts which commonly infect cancer patients have been analyzed. It was shown that (i) inhibitory drug combinations could be selected in which all drugs were at levels far below their individual MICs; (ii) interactive effects among antineoplastic and antifungal drugs may be very large; (iii) optimum combinations of drugs for inhibition of yeast growth depended upon both the relative and absolute concentrations of the drugs in the mixture; (iv) drug combinations which were effective at low levels in inhibiting one test yeast were also generally effective against other species, but the levels of susceptibilities and, to a lesser extent, the best ratios of drugs in the test combinations varied with species; and (v) to quantitatively evaluate drug interactions, it is necessary to carefully define and control all experimental conditions, absolute and relative concentrations of drugs used, and the organisms tested.

Antifungal Agents

Examining the interaction effects of coping style and brief interventions in the treatment of postsurgical pain.

The present study sought to ameliorate two major deficiencies in the literature on treating response to surgery, viz., the failure to compare clearly delineated treatments, alone and in combination; and the failure to examine treatment X coping style interactions. Information imparting and brief relaxation were examined in this study as they interacted with an avoidance-sensitization coping style. No differences were found between treatments or coping styles. Sensitizers, on the other hand, were found to profit most from the relaxation training. Avoiders appeared to do well when they were left alone. The interaction effect was demonstrated for both self-report measures of pain and a behavioral measure of potency of medications ingested. The effects on self-report of pain were more evident on the second postsurgical day than on the fourth postsurgical day. The results indicate that brief relaxation training, often the only kind available to the medical psychologist dealing with surgical patients, is best confined to patients with a sensitizing coping style. Further, the results of this study, in conjunction with a reanalysis of previous studies, cast considerable doubt on information imparting when presented alone as a viable technique for reducing the distress consequent on surgery.

Adaptation, Psychological

Interactive effects of unleaded gasoline and estrogen on liver tumor promotion in female B6C3F1 mice.

We tested whether a concentration of unleaded gasoline (UG) vapor that was selectively hepatocarcinogenic in female mice in a chronic bioassay is antiestrogenic and whether liver tumor promotion by UG is secondary to antiestrogenicity. Twelve-day-old female C57BL/6 x C3H F1 mice (hereafter called B6C3F1) received i.p. injections of N-nitrosodiethylamine (5 mg/kg) or vehicle. Beginning at 5-7 weeks of age, mice were exposed to 0, 292, or 2056 ppm of PS-6 blend UG vapor for 6 h/day, 5 days/week for 16 weeks, 1 ppm ethinyl estradiol (EE2) in the diet, or 2056 ppm UG vapor and 1 ppm EE2 in the diet. Treatment with 2026 ppm UG but not 292 ppm UG increased relative liver weight, the number of macroscopic hepatic neoplasms, and the size and volume fraction of altered hepatic foci in N-nitrosodiethylamine-initiated mice. Treatment with 2056 ppm UG reduced relative uterus, ovary, and pituitary weights but did not change serum 17 beta-estradiol levels, uterine peroxidase activity, or uterine cytosolic estrogen receptor levels. EE2 treatment reduced the number and size of altered hepatic foci in N-nitrosodiethylamine-initiated mice, caused weight loss, anestrus, vaginal keratinization, decreased uterine peroxidase activity, and decreased uterine cytosolic estrogen receptor levels. UG/EE2 co-treatment attenuated the weight loss, anestrus, and vaginal keratinization caused by EE2 treatment alone but dramatically increased the number of macroscopic hepatic neoplasms and the size and volume fraction of altered hepatic foci as compared to UG treatment alone. Thus, in this two-stage model of carcinogenesis (a) 2056 ppm UG had antiestrogenic effects, particularly with respect to pharmacological actions of EE2; (b) 2056 ppm UG but not 292 ppm UG acted as a liver tumor promoter; (c) EE2 inhibited liver tumor promotion; and (d) EE2 strongly potentiated liver tumor promotion by UG. These data demonstrate significant individual and interactive effects of UG vapor and estrogens in liver tumor promotion in female mice.

Animals

Interactive effect of Gm and Km allotypes on cellular immune responses to streptococcal cell wall antigen.

Serum samples from 121 unrelated, healthy Japanese individuals were typed for several Gm and Km(1) allotypes. Peripheral blood lymphocytes from these subjects were cultured with streptococcal cell wall (SCW) antigen and the incorporation of 3H-thymidine into T lymphoblasts was measured. Log-linear analysis showed a significant interactive effect of Gm1,17;13,16,21 and Km(1) on the cellular immune response to group A SCW antigen.

Adult

Interactive effects of age and brain disease on reaction time.

Simple visual and auditory reaction time (RT) was studied in younger (16 to 44 years old) and older (46 to 63 years old) control and brain-diseased patients. Differences in RT related to age were larger for brain-diseased than control patients. Differences in RT related to diagnostic category were larger for older than younger patients. Analysis indicated an interactive effect of age and brain disease on RT supporting the suggestion that acquired brain disease leads to a more pronounced retardation in RT in older patients.

Acoustic Stimulation