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Effects of streptokinase and deoxyribonuclease on viscosity of human surgical and empyema pus.

STUDY OBJECTIVE: To investigate the effects of streptokinase and deoxyribonuclease (DNase) on the viscosity of pus to assess whether the DNase in the old preparation of streptokinase-streptodornase used intrapleurally to treat empyema was contributing to easier drainage of pus compared with purified streptokinase. DESIGN: In vitro measurement of pus viscosity. PATIENTS: Pus from three patients with surgically drained soft tissue abscesses and from six patients with empyema thoracis of varying etiology was studied. INTERVENTIONS: Pus samples were incubated with saline solution as control and with streptokinase, streptokinase-streptodornase, human recombinant DNase, and a mixture of streptokinase and DNase in concentrations approximating those achieved in clinical practice. RESULTS: Purified streptokinase had little effect on pus viscosity, with a mean reduction of 11.1% in the surgical specimens and 1.7% in the empyema samples. Streptokinase-streptodornase reduced viscosity by a mean of 52.8% in the surgical samples and 94.8% in the empyema samples. Human recombinant DNase reduced viscosity by a mean of 32. 79% in surgical samples and 93.4% in empyema samples. Adding streptokinase to human recombinant DNase produced no further reduction in viscosity. Final viscosities in samples treated with DNase were very similar whatever the starting viscosity. CONCLUSIONS: DNase significantly reduces pus viscosity, whereas streptokinase has little or no effect, and in empyema may work simply by breaking down loculations. Clinical studies should be undertaken to see if these in vitro changes produce clinical benefits. The simple viscometer devised for these experiments may also prove useful in other contexts.

Deoxyribonucleases↗

Practical aerobic membrane filtration blood culture technique: clinical blood culture trial.

During the course of preliminary clinical trials of an improved membrane filter blood culture system, filter plugging produced by a gelling of the lysing solution was observed when the patients had high leukocyte counts. A solution of streptokinase-streptodornase (Varidase, Lederle Laboratories) dissolved or prevented the gel and permitted rapid filtration without plugging. With streptokinase-streptodornase incorporated in the filtration procedure, a comparison of several culture systems was carried out on 176 blood cultures. Brucella broth with and without sodium polyanethol sulfonate, a prereduced osmotically stabilized broth, pour plates, and an improved aerobic membrane filter system were compared. The membrane filter system yielded 29 of the total of 37 positive cultures, far surpassing all other systems. Eight of these cultures were detected first by the filter technique, and 13 were positive only in this system. Nineteen of the 37 positive cultures were from patients on antimicrobial agents. Fourteen of these were detected by the filter, twice the number detected by any of the other systems.

Aerobiosis↗

Effect of viral and bacterial pneumonias on cell-mediated immunity in humans.

Cell-mediated immunity (CMI) was assessed during infection and after convalescence in 12 patients with influenza pneumonia and 10 patients with bacterial pneumonia. The patients with influenza pneumonia had a marked impairment of skin test reactivity, and their lymphocytes showed a diminished response to phytohemagglutinin and streptokinase-streptodornase stimulation in vitro. Suppression of CMI was related to the severity of the pneumonia. Patients with bacterial pneumonia showed as great a suppression of the response to phytohemagglutinin and streptokinase-streptodornase as the patients with viral pneumonia. All parameters of CMI returned to normal in both groups after convalescence. The depression of CMI could not be related to a decrease in the number of thymus-derived lymphocytes or to serum-suppressive factors in these patients.

Adult↗

Cell-mediated immunity in humans during viral infection: dermal hypersensitivity and in vitro lymphocyte proliferation during mild viral respiratory infections.

In vitro lymphocyte proliferation in response to phytohemagglutinin and streptokinase-streptodornase and delayed dermal hypersensitivity to several antigens were assessed in patients with mild viral upper respiratory infections. The response to phytohemagglutinin in 18 patients was not diminished during the viral infection. Deoxyribonucleic acid synthesis induced by streptokinase-streptodornase remained unaffected by the viral illness in five patients, and skin test reactivity was not depressed during the viral infection. Thus, it appeared that localized viral upper respiratory infections were not associated with suppression of systemic cell-mediated immunity.

DNA↗

Serum immunoglobulin, dermal response, and lymphocyte transformation studies in horses with chronic diarrhea.

Serum specimens from 12 sick and 20 normal horses were examined for levels of different classes of immunoglobulin (Ig) by a single radial immunodiffusion. The level of IgA in the sera of sick horses was about 50% lower than in the sera of normal horses. By contrast, the level of serum IgG was higher in sick than in normal horses. Phytohemagglutinin (PHA) responsiveness of blood lymphocytes showed transient suppression during the stage of severe diarrhea. The regaining of PHA responsiveness of lymphocytes was observed simultaneously with the recovery process. However, the responsiveness of lymphocytes in recovered horses was still markedly lower than in normal horses. Allergic reactions in sick and normal horses were studied by observing dermal response to the injections of saline extracts from some of the horse feeds. A delayed hypersensitivity reaction to streptokinase-streptodornase and PHA was also studied. The allergic reactions to these extracts were not induced in either sick or normal horses; however, inflammatory response to the extracts was about 50% greater in normal than sick horses. Response to the intradermal injection, either streptokinase-streptodornase or PHA, was significantly greater in normal horses than sick horses. These findings are discussed with respect to the pathogenesis of chronic diarrhea and the complexity of immunodeficiency demonstrated in this disease. The possibility that transient defects of cell-mediated immunity may predispose to chronic diarrhea is proposed.

Animal Feed↗

Antigen-dependent heterogeneity of human migration inhibitory factor.

Human migration inhibitory factor (MIF) produced by peripheral blood mononuclear cells stimulated with purified protein derivative, tetanus toxoid, streptokinase-streptodornase, or Candida albicans antigen was analyzed by gel filtration and isoelectrofocusing. In all cases, supernatants harvested after a 24-hr exposure of the mononuclear cells to the antigen yielded only one MIF species with an isoelectric point of 5. In contrast, isoelectrofocusing of supernatants obtained from cells exposed to the antigen for an additional 24 hr demonstrated that different antigens induce the elaboration of different MIF species. Streptokinase-streptodornase and tetanus toxoid induced the production of one MIF species with an isoelectric point of 5 (pH 5-MIF). Stimulation of cells with Candida antigen elaborated a MIF species with an isoelectric point of 3 (pH 3-MIF). In contrast, stimulation of cells with purified protein derivative induced the production of both pH 3-MIF and pH 5-MIF.

Antigens↗

Age-related effects on the number of human lymphocytes in culture initially responding to an antigenic stimulus.

Lymphocyte transformation responses to the antigen streptokinase-streptodornase were evaluated in a group of 14 healthy elderly subjects by enumeration of antigen-responsive cells, first-generation responding lymphocytes and progeny generated per responding cell. Peak lymphocyte transformation responses to the antigen were diminished in the elderly subjects when compared to a group of young adult subjects. Antigen-responsive cells were found by limiting-dilution analysis to be significantly decreased in the elderly subjects (geometric means of antigen-responsive cells per 10(5) mononuclear cells = 4.35 in the elderly versus 14.79 in the younger group, P less than 0.001). The number of cells recruited into the first-generation lymphocyte response per antigen-responsive cell were equivalent in the two groups. Also, the proliferation into progeny of each first-generation lymphocyte was of the same magnitude for the elderly and young subjects within the six to eight cell divisions required for this response. Therefore, in this system the diminished total lymphocyte transformation responses to the antigen streptokinase-streptodornase of cells from elderly humans can be accounted for by a reduction in the number of lymphocytes initially responsive to the antigen.

Adult↗

Cellular immunity in adult marasmus.

Twelve patients with recent weight loss to less than 85% of standard weight-height ratio and a serum albumin level of at least 3 gm/100 ml were considered to have the adult equivalent to marasmus. Cellular immune function was assessed by delayed hypersensitivity skin testing to Monilia and streptokinase-streptodornase, peripheral lymphocyte count, proportion of T and B cells, whole blood and isolated lymphocyte transformation to phytohemagglutinin, pokeweed mitogen, concanavalin A, Monilia, and streptokinase-streptodornase. Significant impairment of skin test reactivity while in vitro responsiveness remained intact was noted in the marasmic patients. No impairment was found in 12 individuals with recent weight loss who remained at a weight greater than the 85% weight-height ratio. In four marasmic individuals in whom weight loss was arrested by nutritional repletion, skin reactivity returned without substantial change in weight. In this type of marasmus, both depleted nutritional status and weight loss must be present for impairement of skin test responsiveness. These findings confirm relative sparing of more vital functions dependent on protein metabolism in adult marasmus compared to the kwashiorkor-like syndromes of hypoalbuminemic malnutrition seen in adults.

Adult↗

Evidence of mitogenic activity in periodontitis-associated bacteria.

This study examines several periodontitis-associated bacterial isolates for the presence of mitogenic activity, as indicated by their capacity to stimulate unsensitized lymphocytes to undergo blastogenesis. Germfree mouse spleen cells responded vigorously to all of the bacterial sonic extracts tested. The kinetics and dose responses to these activators in germfree mouse spleen cell cultures paralleled those seen with the standard murine B-cell mitogen, Escherichia coli lipopolysaccharide. In contrast, Streptokinase-Streptodornase (Varidase; Lederle Laboratories) antigen elicited no response. Human cord blood lymphocytes also responded upon stimulation with these same bacterial isolates but failed to respond to Streptokinase-Streptodornase. The frequency, magnitude, and kinetics of these cord blood lymphocyte responses were remarkably similar to those seen with adult peripheral blood lymphocytes. However, in this and previous studies, individuals with unresponsive peripheral blood lymphocytes have been observed. Studies were initiated to determine whether these unresponsive leukocyte preparations truly lacked the capacity to respond to these bacteria or whether unresponsiveness reflected the presence of a regulatory cell population in these cultures. After the removal of the adherent cells from unresponsive peripheral blood lymphocyte cultures, the nonadherent cells were found to be responsive. Therefore, peripheral blood lymphocyte responsiveness appears to be regulated via an adherent cell population. The removal of adherent cells from unresponsive cord blood lymphocyte preparations resulted in a less consistent alteration to responsiveness. However, cord blood lymphocyte preparations unresponsive at a standard cell density were shown to be responsive at altered cell densities.

Animals↗

Treatment of horses with chronic diarrhea: immunologic status.

All chronically diarrheal horses given (orally) 2 series of treatments with normal horse serum recovered in 2 to 4 weeks. However, mild diarrhea sometimes persisted several months in the group of horses with severe diarrhea. Weight gains were approximately 35% in horses with severe diarrhea and approximately 10% in horses with mild diarrhea. Serum specimens from 12 diarrheal and 20 normal horses were examined for immunoglobulins by single radial immunodiffusion technique. Concentration of immunoglobulin A in serum of diarrheal horses was approximately 50% lower than that in serum of normal horses. By contrast, there was more immunoglobulin G in serum of diarrheal horses than in serum of normal horses. Phytohemagglutinin (PHA-M) responsiveness of blood lymphocytes showed transient suppression during the stage of severe diarrhea. The regaining of PHA-M responsiveness of lymphocytes was observed simultaneously with the recovery process. However, the responsiveness of lymphocytes in recovered horses remained markedly lower than that in normal horses. Allergic reactions in diarrheal and normal horses were studied by observing dermal response to injections of saline extracts from some of the horse feeds. A delayed hypersensitivity reaction to streptokinase-streptodornase and PHA-M was also studied. Allergic reactions to these extracts were not induced in either diarrheal or normal horses; however, inflammatory response to the extracts was approximately 50% greater in normal than in diarrheal horses. Response to intradermal injection of either streptokinase-streptodornase or PHA-M was significantly greater in normal horses than in diarrheal horses.

Animals↗