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PubMed1979

Changes in pyruvate kinase isozymes of rat small intestine during development and the synergistic effect on them of thyroid and glucocorticoid hormones.

Pyruvate kinase isozymes in rat small intestine changed markedly during the postnatal period. The activities of type M2 subunits rapidly increased before weaning, while those of type L subunits decreased slightly. The administration of hydrocortisone induced normal changes prematurely, whereas the administration of thyroxine increased their extent. On simultaneous administration, the two hormones had synergistic effects.

Aging↗
PubMed1978

Enhancement of cardiac allografts in rats at the major AbG locus. I. Synergistic effect of specific and non-specific immunosuppression.

Investigations of the specific and nonspecific immunosupression of heart transplants in rats are presented. Pretreatment of the Wistar recipient of the August heart with donor strain cellular antigen and anti-donor hyperimmune serum 11 and 10 days before transplantation caused enhancement of the heart graft in this strain combination differing in the major AgB histocompatibility locus. Combination of that protocol with non-specific immunosuppression, i.e. ATS treatment caused synergistic effect. Heart grafts in animal treated with that full protocol of biological immunosuppression survived for 50.8 days.

Animals↗
PubMed1975

Mutation of Bacillus subtilis causing hyperproduction of alpha-amylase and protease, and its synergistic effect.

Mutants that had a genetic lesion increasing the production of alpha-amylase and protease simultaneously were isolated from a transformable strain of Bacillus subtilis Marburg by N-methyl-N'-nitro-N-nitrosoguanidine treatment. These mutants produced two to three times more alpha-amylase and five to 16 times more protease than their parent and were tentatively referred to as AP mutants. As this mutation seems to have occurred at a single gene of the bacterial chromosome and was not located near the alpha-amylase structural gene, the gene was designated as "pap." When pap- and amyR2 (an alpha amylase regulator gene) or pap- and ProH coexisted in the same cell, synergistic effects of the two genetic characters were observed on the alpha-amylase and protease production, respectively. Upon introduction of the pap mutation, the following phenotypic changes were observed in addition to changes in alpha-amylase and protease productivity. (i) Mutants lost the character of competence for the transformation. (ii) When cells were cultured at 30 C for 30 h, mutant cells became filament owing to the formation of chains of cells. (iii) Autolysis of cells was decreased in the mutants. When pap- was transferred to the wild strain by deoxyribonucleic acid-mediated transformation, the transformants showed all these phenotypic alterations simultaneously.

Amylases↗
PubMed1979

Synergistic effect of diethylstilbestrol on the mutagenicity of 2-acetylaminofluorene and N-hydroxy-acetylaminofluorene in the Salmonella assay system.

Salmonella typhimurium, TA-1538, was used to investigate the mutagenic potential of N-2-acetylaminofluorene (2-AAF), N-hydroxy-N-2-acetylaminofluorene (N-OH-2-AAF) and diethylstilbestrol (DES) individual and in combination. In the presence of an induced or uninduced rat liver metabolizing system (S-9), the histidine requiring strain of bacteria was reverted to prototrophy by the aromatic amines but not by the synthetic estrogen. However, when DES was combined with 2-AAF or N-OH-I-AAF in the presence of the induced S-9 fraction, the number of revertant colonies was increased 2- to 4-fold above the levels obtained with the aromatic amines alone. The synergistic effect of DES, a non-mutagen, on the mutagenicity of these aromatic amines was observed only when a 3-methylcholanthrene induced rat liver S-9 fraction was used as the source of mammalian enzymes. When uninduced mouse or rat liver S-9 fractions were used in this test system, an inhibitory effect rather than an enhancing effect was observed.

2-Acetylaminofluorene↗
PubMed1978

Synergistic effects of dietary carbohydrate and cholesterol on serum lipids and lipoproteins in squirrel and spider monkeys.

Serum lipid and lipoprotein responses to diets with a high level of simple carbohydrate (69% w/w sucrose) and a low level of saturated fat (5% w/w butter-coconut oil, polyunsaturated/saturated fatty acid ratio 0.03) containing 0, 0.1, and 1.0 mg/kcal added cholesterol was studied in five squirrel (Saimiri sciurea) monkeys. Variations in response produced by altering the nature of dietary carbohydrate (sucrose versus dextrin) and the fat (polyunsaturated/saturated fatty acid ratio, 0.03 versus 1.5) in the above diets were studied in three groups (five per group) of spider monkeys (Ateles sp.). In the absence of exogenous cholesterol, feeding a sucrose-saturated fat diet for 6 weeks produced a consistent increase in serum cholesterol in both species and an increase in serum triglycerides only in squirrel monkeys. Exogenous cholesterol had a remarkable synergistic effect on the high carbohydrate diet in increasing the serum cholesterol and had a suppressing effect on serum triglycerides in both species. Polyunsaturated fat reduced the hypercholesterolemic effect of sucrose with or without exogenous cholesterol. Dextrin diets resulted in lower serum cholesterol responses than sucrose diets when the diets contained 0 or 0.1 mg/kcal added cholesterol. Serum cholesterol response was reflected in beta- and alpha-lipoproteins. These results emphasize the varied response of serum lipids and lipoproteins to dietary changes in carbohydrate, fat, and cholesterol that might have a bearing on experimental atherosclerosis.

Animals↗
PubMed1979

The synergistic effect of weight loss and changes in dietary lipids on the serum cholesterol of obese men with hypercholesterolaemia: implications for prevention of coronary heart disease.

The hypolipidaemic effect of a low-fat, low-cholesterol diet, alone and in combination with weight reduction, has been evaluated in two groups of obese men with hypercholesterolaemia. In 41 men who lost 10.3 kg over 11 months and maintained their lower weight for 23.5 months serum cholesterol fell by 1.68 mmol/l and remained steady at lower weight. In 20 similar men, the controls, whose weight fell by 0.8 kg over 39.5 months, serum cholesterol fell by 0.80 mmol/l. There was a significant linear correlation between change in weight and change in serum cholesterol. The change in serum cholesterol in the weight losers was greater than could be accounted for by change in dietary lipids. Weight reduction and low-fat, low-cholesterol diets appear to have a synergistic effect in reducing serum cholesterol.

Adult↗
PubMed2025

Integrating network pharmacology and experimental validation to uncover the synergistic effects of Huangqi ()-Ezhu () with 5-fluorouracil in colorectal cancer models.

OBJECTIVE: To evaluate the effects of Huangqi (Radix Astragali Mongolici)-Ezhu (Rhizoma Curcumae Phaeocaulis) (HQEZ) on colorectal cancer therapies and to elucidate the potential mechanisms of HQEZ, especially in combination with 5-Fluorouracil (5-FU). METHODS: The anti-tumor effects of HQEZ were evaluated in colorectal cancer models both in vivo and in vitro. The network pharmacological assay was used to investigate potential mechanisms of HQEZ. Potential target genes were selected by Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, protein-protein interaction network (PPI) and molecular docking. Within key targets, potential targets related to drug sensitivity, especially the sensitivity to 5-FU, were evaluated in HCT116 in vitro by immunofluorescence, quantitative real-time polymerase chain reaction (qPCR) and Western-blot. Then, changes in potential targets were assessed in tumors from tumor-bearing mice and the expression of these targets was also evaluated in colorectal cancer (COAD) patients from the Cancer Genome Atlas Program (TCGA) database. RESULTS: HQEZ significantly enhanced the anti-tumor activity of 5-FU in vivo and inhibit the growth of HCT116 in vitro. By network pharmacological analysis, key targets, such as protein kinase B (AKT1), epidermal growth factor receptor (EGFR), adenosine triphosphate (ATP) binding cassette subfamily B member 1 (ABCB1, also named multidrug resistance protein 1, MDR1), ATP binding cassette subfamily G member 2 (ABCG2), thymidylate synthetase (TYMS, also named TS), prostaglandin-endoperoxide synthase 2 (PTGS2), matrix metallopeptidase 2 (MMP2), MMP9, toll like receptor 4 (TLR4), TLR9 and dihydropyrimidine dehydrogenase (DPYD), were identified. Additionally, 4 potential core active ingredients (Folate, Curcumin, quercetin and kaempferol) were identified to be important for the treatment of colorectal cancer with HQEZ. In key targets, chemoresistance related targets were validated to be affected by HQEZ. Furthermore, 5-FU sensitivity related targets, including MDR1, TS, EGFR, ribonucleotide reductase catalytic subunit M1, Breast and Ovarian Cancer Susceptibility Protein 1 (BRCA1) and mutl homolog 1 were also significantly reduced by HQEZ both in vitro and in vivo. Finally, these validated key targets and 5-FU sensitivity related targets were demonstrated to be up-regulated in COAD patients based on TCGA database. CONCLUSION: HQEZ has synergistic effects on the anti-tumor activity of 5-FU in the treatment of colorectal cancer both in vivo and in vitro. The beneficial effect of HQEZ results from the inhibition of the drug sensitivity targets associated with 5-FU. The combination therapy of HQEZ with 5-FU or other chemotherapeutic drugs will also improve the anti-tumor efficacy of chemotherapy.

Humans↗
PubMed1976

Combination chemotherapy in vitro with adriamycin. Observations of additive, antagonistic, and synergistic effects when used in two-drug combinations on cultured human lymphoma cells.

Adriamycin was paired with 12 other chemotherapeutic drugs in a search for possible synergistic pairs. Cell lethality was investigated by the colony-formation method utilizing a long-term human lymphoma cell line. Addative effects were noted with CCNU, ara-C, prednisolone, DDP, VP-16, and Yoshi, and mild synergistic effects with BLEO and CS. Adriamycin reduced the killing ability of BCNU and MeCCNU when applied simultaneously. This antagonistic effect was canceled by sequential incubation with each drug. It appears that no significant synergism can be expected by simultaneous pairing of adriamycin with some currently available chemotherapeutic agents.

Antineoplastic Agents↗
PubMedDate not supplied

Human exposure to sulfur dioxide and ozone: absence of a synergistic effect.

Studies of the human health effects of exposure to a combination of ozone and sulfur dioxide have produced somewhat conflicting results; the possibility of a synergistic enhancement of toxicity when the two gases are present simultaneously remains equivocal. We evaluated the effects of 0.40 ppm sulfur dioxide, 0.40 ppm ozone, and the combination of these two under one environmental condition (25 degrees C and 45% relative humidity). Subjects alternately walked and rested during a 2-hr exposure. Subjects exposed to filtered air or to 0.40 ppm sulfur dioxide showed no significant changes in pulmonary function. When exposed to either ozone or ozone plus sulfur dioxide, significant decreases in maximum expiratory flow, forced vital capacity, and inspiratory capacity were observed. There were no significant differences in response between ozone alone and ozone plus sulfur dioxide exposures, thus, in our subjects on synergistic effects were discernible.

Adolescent↗
PubMed1979

PS-5, a new beta-lactam antibiotic. III. Synergistic effects and inhibitory activity against a beta-lactamase.

PS-5 was shown to have synergistic activity in combination with other beta-lactam antibiotics and it markedly decreased the minimum inhibitory concentration values of ampicillin or cephaloridine with a beta-lactamase-producing Proteus vulgaris strain on agar plates. The synergistic activities were also shown in bactericidal activity in liquid medium. PS-5 was shown to be inhibitory against an extracted beta-lactamase of P. volgaris.

Anti-Bacterial Agents↗
PubMed1979

Listeria monocytogens: synergistic effects of ampicillin and gentamicin.

Listeria monocytogenes infections are most common in newborn infants and persons with impaired defense mechanisms. There are reports of successful treatment with ampicillin alone: however, there is uncertainty as to what regimen constitutes the most effective therapy. The purpose of this study was to illustrate the in-vitro synergism between ampicillin and gentamicin against L. monocytogenes. Seven strains of L. monocytogenes isolated from bloods or cerebrospinal fluids of infants and three control strains obtained from the Center for Disease Control were tested. Minimal inhibitory concentrations of ampicillin and gentamicin were determined in Todd-Hewitt broth with an inoculum of 10(5) organisms/ml. Killing curves were determined for ampicillin 6 microgram/ml, gentamicin, 0.5 microgram/ml, and the combination of ampicillin, 6 microgram/ml, plus gentamicin, 0.5 microgram/ml. Incubation of approximately 10(7) organisms/ml with these concentrations of ampicillin and gentamicin caused no significant reduction in the viable bacterial population in 24 hours. The combination, on the other hand, was bactericidal in all seven strains isolated from patients and one control strain. The authors believe the ultimate test of the superiority of this combination to ampicillin alone must come from clinical studies. However, the synergistic and bactericidal effects of ampicillin with gentamicin may be very desirable in treatment of newborns and patients with underlying disease.

Ampicillin↗
PubMed1976

The synergistic effect of calcium and prostaglandin F2alpha in second trimester abortion. A pilot study.

A clinical use of the basic science phenomenon that prostaglandin is synergistic with calcium in increasing uterine contractility has been demonstrated. Twenty-five women had midtrimester abortions induced with intraamniotic calcium gluconate followed by prostaglandin F2alpha. All patients aborted within 21 hours with minimal toxicity. The mean injection-to-abortion interval was 13.5 hours in the group of women without a preinjection laminaria and 10.1 hours in patients when a laminaria was included in the protocol.

Abortion, Induced↗
PubMed1978

Two distinct types of helper T cells involved in the secondary antibody response: independent and synergistic effects of Ia- and Ia+ helper T cells.

We have described here two distinct types of carrier-specific helper T cells which act independently and synergistically to augment the B-cell response to a hapten. They are separable by passage through a nylon wool column. The first type of helper T cell, which we designate as Th1, is nylon nonadherent, and can help the response of hapten-primed B cells only if the haptenic and carrier determinants are present on a single molecule (cognate interaction). The second type of helper T cell, Th2, adheres to the nylon wool column, and can help the B-cell response to a hapten coupled to a heterologous carrier upon stimulation with unconjugated relevant carrier (polyclonal interaction). The addition of a small number of Th2 to the mixture of Th1 and B cells significantly augmented the net response to the hapten carrier conjugate. Both Th1 and Th2 cells belong to the Lyt-1+,2-,3- subclass. Th1 has no detectable Ia antigen, whereas Th2 is killed by certain anti-Ia antisera and complement. The Ia antigen detected on Th2 was found to be controlled by a locus in the I-J subregion. The results clearly established the fact that there are two distinct pathways in the T- and B-cell collaboration, which involves two different subsets of carrier-specific helper T cells.

Animals↗
PubMed1977

The synergistic effect of aspirin and dipyridamole upon platelet thrombi in living blood vessels.

In rabbits previously injected i.v. with alloxan, serial observations of platelet thrombus formation in response to topical adenosine diphosphate (ADP) at sites of electrical injuries in pial arteries have been made. Using this model we have studied the effects of oral daily doses of dipyridamole (Persantin) and acetyl salicylic acid (ASA) upon platelet thrombus formation. Oral daily doses of 42 mg of ASA and 6 mg dipyridamole given separately in alloxan-treated rabbits are without effect. When given together orally, 42 mg and 6 mg respectively reduced the level of sensitivity to ADP for producing platelet thrombi to that established for the rabbits before the injection of alloxan. But withdrawal of these combined doses of dipyridamole and ASA caused the sensitivity of ADP for platelet thrombus formation to be raised to the much increased level present in rabbits soon after they are given i.v. alloxan. This apparent synergistic behaviour displayed by dipyridamole and ASA in these rabbits results in antithrombotic effects which are clearly absent when these two agents are given separately. It is of interest that the dose levels used here are equivalent, an a body weight ratio, to those being used in man in the current Persantin-Aspirin Reinfarction Study.

Adenosine Diphosphate↗
PubMed1977

Synergistic effects of the combination of cis-platinum diamminodichloride and 2,2'-anhydro-1-beta-D-arabinofuranosyl-5-fluorocytosine in transplanted mouse leukemias.

cis-Platinum diamminodichloride has been studied in combination with 2,2'-anhydro-1-beta-D-arabinofuranosyl-5-fluorocytosine on an every-4-day schedule in various lines of mouse leukemia. This combination is synergistic in leukemias L1210 and P388 and sublines made resistant to 5-fluorouracil or methotrexate. There is no cross-resistance between cis-platinum diamminodichloride and 2,2'-anhydro-1-beta-D-arabinofuranosyl-5-fluorocytosine, but the combination is no more effective against lines of leukemia made resistant to cis-platinum diamminodichloride or to 2,2'-anhydro-1-beta-D-arabinofuranosyl-5-fluorocytosine than either single active compound alone. Since these compounds have no cross-resistance, act by quite different mechanisms of action, and have different limiting toxicity, the combination is now being evaluated clinically.

Ancitabine↗
PubMed1978

Differential control of synergistic effect with polyene macrolide antibiotics upon Chinese hamster cells in vitro.

An amphotericin B-resistant cell (AMBR-1), which was isolated from aneuploid Chinese hamster cells (V79), was found to show much higher resistance than the parent V79 cells to other polyene antibiotics, such as pentamycin and filipin. To obtain the 50 to 60% inhibition of the control protein synthesis activity by a synergistic combination of fusidic acid and amphotericin B, 50 microgram fusidic acid per ml were combined with 10 microgram amphotericin B in V79 cells, whereas in AMBR cells 50 microgram fusidic acid per ml were combined with 100 microgram polyene antibiotic per ml. Bleomycin (10 microgram/ml), which alone did not affect cellular DNA synthesis, inhibited DNA synthesis of V79 cells by more than 90% of the control activity when combined with only 1 microgram pentamycin per ml, whereas a similar extent of inhibition in AMBR cells was observed by combination with more than 5 microgram pentamycin per ml.

Amphotericin B↗
PubMed1978

Synergistic effect of vitamin C and aspirin on gastric lesions in the rat.

The effects of varying levels of dietary vitamin C on the incidence of aspirin-induced gastric hemorrhagic lesions were studied in young, male rats. Rats fed diets containing either 20, 40, or 60 mg of L-ascorbic acid per gram of diet did not exhibit focal gastric lesions. Administering a single oral dose of aspirin (30 mg aspirin/100 g of body weight) to rats fed control diets produced gastric lesions. When the rats were given aspirin plus a diet containing either 40 or 60 mg ascorbic acid per gram of diet, there was a significant increase in number of gastric lesions. Since vitamin C and aspirin seem to act synergistically in producing hemorrhagic lesions in the stomach, it is recommended that all individuals taking megadoses of vitamin C be cautioned against taking aspirin concurrently.

Animals↗