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Results for “Synergistic therapy”

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At least 19 recordsLinked to original sources
PubMed1991

Synergistic topical therapy by acyclovir and A1110U for herpes simplex virus induced zosteriform rash in mice.

Combination therapy with A1110U, an inactivator of the herpes simplex virus (HSV) and the varicella zoster virus ribonucleotide reductase, and acyclovir (ACV) was evaluated for treatment of cutaneous herpetic disease in athymic mice infected on the dorsum. In this model, infection with HSV produces a 'zosteriform-like' rash that is first visible on day 3 or 4 post-infection (p.i.) and eventually extends from the anterior mid-line to the dorsal mid-line of the affected flank. In untreated mice, the infection is fatal at about day 7 p.i. presumably due to central nervous system involvement. Topical treatment of infections induced by either wild-type (wt) HSV-1 or wt HSV-2 with 3% A1110U in combination with 5% ACV resulted in synergistic (P less than 0.01) reductions in lesion scores. Therapy was also synergistic in mice infected with an ACV-resistant thymidine kinase-deficient mutant and an ACV-resistant TK-altered mutant HSV-1 isolated. Combination therapy was very effective in reducing lesion scores of mice infected with an ACV-resistant HSV-1 DNA polymerase mutant, but did not result in statistically significant synergy (P = 0.07) because of the enhanced efficacy of A1110U alone against this virus. These results provide encouragement that the combination of A1110U and ACV may offer an effective therapy for topical treatment of cutaneous HSV infections in humans.

Acyclovir↗
PubMed1978

Synergistic combination therapy of 5-fluorouracil, vitamin A and cobalt-60 radiation upon head and neck tumors.

We have applied a triple combination of 5-fluorouracil (5FU), vitamin A and cobalt-60 radiation (FAR therapy) to clinical treatment of head and neck tumors since 1972. The treatment of 33 patients with cancer of larynx and 15 patients with hypopharyngeal or cervical esophageal cancer with FAR therapy during three years from 1972 to 1974 resulted in highly effective synergism in vivo, and the improved points of this therapy were presented.

Cobalt Radioisotopes↗
PubMed1992

Two cases of endocarditis due to Lactobacillus species: antimicrobial susceptibility, review, and discussion of therapy.

Endocarditis caused by lactobacilli may lead to death or to relapse of infection, despite antimicrobial treatment. We report two cases of lactobacillus endocarditis in individuals with native bicuspid aortic valves who survived without relapse and review the 39 other cases reported in the literature. In only 15 previously reported cases have patients been cured with medical therapy alone. One of our patients, who was infected with Lactobacillus acidophilus, was cured by medical therapy alone, and our other patient, who was infected with Lactobacillus casei subspecies rhamnosus, required surgical replacement of his aortic valve. L. acidophilus was tolerant and L. casei subspecies rhamnosus was resistant to many antibiotics tested. Combinations of penicillin or daptomycin and gentamicin were synergistic by time-kill assay. Synergistic therapy with a penicillin and an aminoglycoside was effective clinically and appears to provide optimal medical treatment on the basis of microbiological data.

Adult↗
PubMed1978

Vasodilators in myocardial infarction: rationale and current status.

While digitalis and diuretics constitute conventional therapy of congestive heart failure due to acute myocardial infarction, systemic vasodilator drugs offer an innovative approach of decreasing left ventricular systolic wall tension (afterload) by reducing aortic impedance and/or by reducing cardic venous return. Thus, vasodilators increase lowered cardiac output by diminishing peripheral vascular resistance and/or decreasing increased left ventricular end-diastolic pressure (ventricular preload) by reducing venous tone. Concomitantly, there is a reduction of myocardial oxygen demand thereby potentially limiting infarct size and ischaemia. The vasodilators produce disparate modifications of cardiac function depending on their differing alterations of preload versus impedance: nitrates principally cause venodilatation (decrease left ventricular end-diastolic pressure); sodium nitroprusside, phentolamine and prazosin produced relatively balanced arterial and venous dilatation (decrease left ventricular end-diastolic pressure while increasing cardiac output, provided upper limits of normal left ventricular end-diastolic pressure are maintained); and hydrallazine solely effects arteriolar dilatation (increases cardiac output). Combined sodium nitroprusside and dopamine therapy synergistically enhances cardiac output and decreases left ventricular end diastolic pressure. In addition, sodium nitroprusside is aided by mechanical counterpulsation which sustains myocardial perfusion pressure in acute myocardial infarction.

Animals↗
PubMed1992

Prospects for synergistic immunosuppressive drug therapy in the coming decade.

The major clinical strategy during the past three decades has been to discover a single drug that achieves immunosuppression with minimal toxic side effects. Regimens to optimize CyA immunosuppressive therapy have been limited by marked interindividual variations in drug pharmacokinetics and pharmacodynamics that cause simple drug administration routines to produce variable clinical outcomes. The approach presented herein seeks to employ multiple immunosuppressive agents that act synergistically to inhibit alloactivation. Using the rigorous median effect analysis, synergistic interactions have been discerned both using in vitro systems, as well as in vivo transplant situations. CyA has a profoundly synergistic interaction with RAPA, and a moderately synergistic effect with QCA. The next decade presents important opportunities to determine whether these immunologic effects are beclouded by synergistic drug toxicities. Studies of this type may allow us to achieve a uniformly effective, yet well-tolerated, immunosuppressive regimens in the future.

Cyclosporine↗
PubMed1992

BAL modifications after antiblastic and immunomodulant therapy in lung cancer.

The bronchoalveolar compartment can be easily investigated with BAL (bronchoalveolar lavage) before and after antiblastic therapy. We studied 50 patients affected by primary lung cancer, of whom 31 served as a control group and 19 were submitted to BAL after chemo- and/or radiotherapy. Data from BAL performed in an unaffected lung area show that antiblastic therapy can produce alterations in the terminal airways without clinical evidence. Chemotherapy causes a significant impairment of the alveolo-capillary barrier. Radiotherapy is able to affect lymphocytes, with a CD4/CD8 reduction. The concomitance of both therapies produces synergistic effects. Immunomodulant therapy with thymostimulin in otherwise untreated lung cancer patients seems able to modify alveolar lymphocyte number and subsets, but these are preliminary data which need further substantiation.

Bronchoalveolar Lavage Fluid↗
PubMed2026

Engineered MXene-based nanozyme platform: NIR-II photothermal and dual enzyme-mimetic potentiated chemodynamic synergy for precision tumor eradication.

The antioxidant defense barrier in the tumor microenvironment, particularly glutathione (GSH), considerably restricts the therapeutic efficacy of chemodynamic therapy (CDT). Moreover, CDT generally exhibits relatively mild therapeutic efficacy owing to its intrinsic reaction kinetics, making it difficult to achieve complete tumor eradication within a short time. To address these issues, we construct a functionalized nanotherapeutic platform, Nb2CTx@Ru-PEG2000-FA (NCRPF), for tumor photothermal ablation and enhanced CDT resulting from GSH depletion. NCRPF possesses three key advantages: 1. Efficient near-infrared II photothermal conversion (η = 42.08%), raising the tumor temperature above 45 °C within 90 s for rapid ablation; 2. Dual peroxidase-like and glutathione peroxidase-like activities, simultaneously depleting GSH and generating a burst of ·OH to eliminate residual tumors; 3. Targeted tumor accumulation with 2.9-fold higher efficiency than passive diffusion. Both in vitro and in vivo results confirm that this combined strategy achieves complete tumor eradication with favorable biosafety. Collectively, the NCRPF nanotherapeutic system provides a powerful new paradigm with high translational potential for the complete eradication of breast cancer.

Animals↗
PubMed1992

Inhibition of rat bladder tumor (RBT323) growth by tumor necrosis factor alpha and interferon-gamma in vivo.

The antiproliferative activities of recombinant rat gamma-interferon and recombinant human tumor necrosis factor alpha were evaluated in a new rat bladder tumor model, RBT323. The RBT323 is a spontaneously arisen, serially transplantable, bladder tumor in ACI rats. Histologically and ultrastructurally this tumor is a grade 2-3 transitional tumor without squamous cells. The RBT323 appears to be non-immunogenic in tumor excision and rechallenge experiments. The tumor was transplanted subcutaneously and the drugs were administered peritumorally. Gamma-interferon and tumor necrosis factor monotherapy starting two days after tumor implantation showed dose-dependent growth inhibiting effects in the dose range tested. Combination treatment with gamma-interferon and the highest dose of tumor necrosis factor resulted in synergistic antiproliferative effects. After cessation of the combination treatment all tumors resumed growth, initially with a low doubling time, but finally with their original growth rate. Gamma-interferon treatment initiated at a tumor volume of 0.2 to 0.5 cm.3 had no antitumor effects, whereas treatment with 100 micrograms. tumor necrosis factor per rat inhibited tumor growth significantly. Different combinations of the cytokines had synergistic effects against established tumors. These studies demonstrate antitumor effects of gamma-interferon and tumor necrosis factor in a rat bladder tumor model system. Combination therapy has synergistic effects and prolongs the time to tumor recurrence.

Animals↗
PubMed1977

A multimodality approach to inpatient treatment of obsessive-compulsive disorder.

A case of severely incapacitating obsessive-compulsive neurosis is treated in an inpatient setting for 13 weeks with a combination of insight-oriented, group, family, and behavioral therapies. The synergistic effects of these modalities and the therapeutic community are discussed. Stable changes are evident 2 1/2 years after admission.

Adolescent↗
PubMed1992

New immunosuppressive drugs: needs in and applications to pediatric transplantation.

The evolution of immunosuppressive therapy toward synergistic drug combinations seeks to minimize toxicity while potentiating efficacy. Median effect analysis discerns synergistic drug combinations that may be suitable for in vivo experiments in animals and for subsequent clinical trials. These studies suggest that two drugs rapamycin (RAPA) and brequinar (BQR) display synergistic effects in combination with cyclosporine. This combination must be evaluated for relative toxicity versus efficacy. Clinical trials to assess the individual toxicities of RAPA and BQR are presently underway in order to discern appropriate doses for randomized trials of clinical efficacy.

Child↗
PubMed2026

Metab8D: a metabolic regulome network from multiomics and machine learning.

To explore multiomic regulation of the metabolome, we used machine learning to predict metabolomic variation across ~1000 different cancer cell lines with matched omics data from eight biomolecular classes: genomic copy number variation, mutations, DNA methylation, histone post-translational modifications (PTMs), transcriptomics and RNA splice variants, non-coding transcriptomics (miRNA and lncRNA), proteomics, and phosphoproteomics. Overall, the metabolome is tightly associated with the transcriptome, with coding and non-coding RNAs emerging as top predictors. Peripheral metabolites are predictable via levels of corresponding enzymes, while those in central metabolism require combinatorial predictors in signaling and redox pathways, and may not reflect corresponding pathway expression. We reconstruct multiomic interaction subnetworks for highly predictable metabolites, and YAP1 signaling emerged as a top global predictor across four omic layers. We prioritize predictive multiomic features for single-cell and spatial metabolomics assays. Top predictors were enriched for synthetic-lethal interactions and synergistic combination therapies that target compensatory metabolic modulators.

Machine Learning↗
PubMed1979

Preliminary experience with parenteral mecillinam.

Case reports are reviewed of 26 patients, mainly with severe Gram-negative infections, treatment with parenteral mecillinam. Twenty-three patients received other antibiotics in addition to mecillinam. In 19 patients, potentially synergistic antimicrobial therapy was given. Overall, a beneficial clinical effect was recorded in 17 (68%) of the 25 patients assessed. A better response was observed in those patients who had not received other antibiotics before treatment with mecillinam was instituted. It is concluded that parenteral mecillinam may have an important role in the treatment of severe Gram-negative infections.

Adolescent↗
PubMed1992

Demonstration of synergistic effects of hyperthermia and photodynamic therapy using the chick chorioallantoic membrane model.

The chick chorioallantoic membrane (CAM) model was used to study vascular effects of photodynamic therapy (PDT) and hyperthermia (HPT) and the synergism of these modalities. The CAM is a convenient medium for monitoring the modifications of the vasculature. It is possible to view the CAM and to examine structural changes of individual blood vessels in real time. Moreover, the CAM is a closed system which lends itself to mathematical modeling of the temporal and spatial temperature profile and in which HPT can be performed quantitatively and to a selected depth, using different lasers. A porphyrin-type photosensitizer solution was applied to areas of the CAM, defined by teflon O-rings placed on the surface. Uptake dynamics of the sensitizer into the CAM was determined by analyzing its fluorescence in vivo. The CAM area was irradiated with a dual-wavelength laser system composed of a dye laser at 644 nm (to induce PDT) and a CO2 laser at 10.6 microns (to bring about HPT). Damage to the CAM vasculature, due to combined PDT+HPT, was compared to the outcome of the separate modalities, and a synergistic effect of about 40% was observed.

Allantois↗
PubMed1992

Efficacy of adding nebulized ipratropium bromide to nebulized albuterol therapy in acute bronchiolitis.

Nebulized ipratropium bromide is though to be synergistic with albuterol in therapy for acute childhood asthma. Because the efficacy of ipratropium in bronchiolitis is uncertain and some infants with bronchiolitis do not respond to nebulized albuterol alone, the following study was undertaken. In this double-blind, placebo-controlled trial, 69 infants between 6 weeks and 24 months of age who exhibited the first episode of acute bronchiolitis were randomly assigned to receive either nebulized albuterol (0.15 mg/kg per dose) and ipratropium bromide (250 micrograms per dose) (group A, n = 36) or nebulized albuterol and normal saline (placebo) (group B, n = 33) for two doses, 1 hour apart. The two groups were comparable at baseline. Both therapies resulted in clinically significant improvement. However, the addition of ipratropium resulted in no additional benefit with respect to decrease in the respiratory rate (mean decreases 10.6/min vs decreases 8.6/min, P = .86), accessory muscle score (range 0 through 3) (decreases 0.92 vs decreases 0.82, z = -0.44), wheeze score (range 0 through 3) (decreases 0.94 vs 0.85, z = -0.20), oxygen saturation (increases 0.25% vs increases -0.33%, P = .86), or hospitalization rate (17 vs 10). The number of "nonresponders" and "clear responders" was also very similar in both groups. No toxicity was noted. The increase in heart rate was mild and similar in both groups (increases 6.7 vs increases 11.1). The power of the study to detect a difference between the two treatment groups in the respiratory rate change > or = 8/min is greater than 90%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Effect of stem cell factor with and without granulocyte colony-stimulating factor on neonatal hematopoiesis: in vivo induction of newborn myelopoiesis and reduction of mortality during experimental group B streptococcal sepsis.

Neonatal hematopoiesis and host defense are developmentally immature and under states of increased demand predispose the newborn to peripheral cytopenias and depletion of bone marrow storage pool reserves. We have previously demonstrated that recombinant human granulocyte colony-stimulating factor (rhG-CSF) can significantly modulate neonatal rat granulopoiesis and act synergistically with antibiotic therapy to reduce the mortality rate during experimental group B streptococcal sepsis. Stem cell factor (SCF) has been shown to stimulate early hematopoietic progenitor cells and, in the presence of lineage-specific CSFs, enhance committed progenitor cell proliferation. In the present study we examined the in vivo neonatal hematologic effects of recombinant rat (rr) SCF (14 days), simultaneous rrSCF + rhG-CSF (14 days), and sequential combination of rrSCF (7 days) + rhG-CSF (7 days). Sprague-Dawley newborn rats (less than or equal to 24 hours) were injected intraperitoneal (IP) x 14 days with the above combinations. rrSCF (0 to 200 micrograms/kg/d) had a negligible effect on the peripheral platelet count and absolute neutrophil count (ANC) but the diminution in the hematocrit during the first 10 days of treatment was less pronounced (P = .0001). However, the simultaneous use of rrSCF + rhG-CSF synergistically increased the circulating day 6 to 13 ANC (P = .001). Similarly, sequential rrSCF + rhG-SCF also had a synergistic significant effect during the second week of therapy on the circulating ANC (P = .01). The bone marrow neutrophil storage and proliferative pools were also significantly increased in newborn rats treated with rrSCF + rhG-CSF versus rhG-CSF (P = .02). The bone marrow and liver/spleen CFU-GM pool was unchanged; however, the CFU-GM proliferative rates were significantly increased in the rrSCF + rhG-CSF group (P = .04). rrSCF also induced a significant increase in the bone marrow and liver/spleen mast cell pool (P = .002). Lastly, rrSCF x 14 days +/- rhG-CSF significantly reduced the mortality rate at 48 and 120 hours after experimental group B streptococcus sepsis (P = .03 and .05, respectively). These data suggest that combination SCF + G-CSF therapy compared with G-CSF alone significantly increases the neonatal rat peripheral neutrophil count, bone marrow myeloid pools and proliferative rates, and induces a reduction in the mortality rate during experimental bacterial sepsis. SCF therapy may have future potential applications in the modulation of human neonatal hematopoiesis and host defense.

Animals↗
PubMed1992

Synthetic trehalose dicorynomycolate and antimicrobials increase survival from sepsis in mice immunocompromised by radiation and trauma.

When mammalian antimicrobial defenses are compromised by radiation, death from sepsis may occur. Tissue trauma in irradiated hosts significantly increases mortality from bacterial infections and makes antimicrobial treatments more difficult than when individuals are subjected to trauma or radiation alone. We determined that postirradiation therapy with the immunomodulator synthetic trehalose dicorynomycolate (S-TDCM) and antimicrobials increases survival in mice after lethal irradiation and tissue trauma. Single agent therapy with systemic oxacillin, gentamicin, ofloxacin, and S-TDCM did not increase survival. Topical treatment of the injury with gentamicin cream in addition to systemic therapy with oxacillin or S-TDCM was necessary to enhance survival. Therapy with gentamicin and S-TDCM had a synergistic effect on survival. Therapies combining augmentation of non-specific host defense mechanisms with antimicrobials may be valuable in treating irradiated patients also sustaining tissue trauma.

Animals↗
PubMed1978

Combined therapy in leprosy. Background and findings.

This report is based on data obtained from 64 lepromatous cases. Despite many years of DDS monotherapy, the homogenates from biopsies of these patients revealed 10(4) or more bacteria. From the beginning of combination therapy with synergistic-acting substances (rifampicin + isoprodian (INH + PTH + DDS) the logarithms of the number of bacteria in the homogenates decreased, both during treatment period and during treatment-free observation period (Figs. 3--8). During the whole time biopsies were taken almost monthly. A considerable regression of the bacterial mass or even "negativity" could be observed within a relatively short time. Once started, the process of reduction of bacteria continued also after termination of therapy. To be able to evaluate a medication, therapy-free observation periods (for a minimum of 5 years) are indispensable.

Dapsone↗