Development, physicochemical characterization and preclinical efficacy evaluation of a water soluble glucan sulfate derived from Saccharomyces cerevisiae.

This report describes the development, characterization and preclinical efficacy evaluation of water soluble glucan sulfate. Glucan sulfate was derived from insoluble beta-1,3-D-glucan isolated from Saccharomyces cerevisiae. The proposed repeating unit empirical formula of glucan sulfate is [(C6H10O5)5.

A method for the solubilization of a (1----3)-beta-D-glucan isolated from Saccharomyces cerevisiae.

This report describes a method for the solubilization of a micro-particulate beta-D-glucan. Insoluble glucan is dissolved in methyl sulfoxide and urea (8M) and partially phosphorylated at 100 degrees. The resulting water-soluble product is called glucan phosphate.

The role of complement in glucan-induced protection against septic shock.

Previous studies from our laboratory have shown that glucan will significantly enhance survival, decrease bacteremia, maintain reticuloendothelial function, and reduce histopathology in a murine model of gram-negative septic shock [1]. The present study was undertaken to evaluate the role of complement in glucan-enhanced protection against septic shock. AKR/J mice, which are congenitally C5-deficient, and ICR/HSD mice that were complement-depleted by treatment with purified cobra venom factor (CVF), were injected IP with glucan (50 mg/kg) on days 5 and 3 prior to IP challenge with 1 X 10(8) E.

Soluble glucan and lymphokine-activated killer (LAK) cells in the therapy of experimental hepatic metastases.

Previous studies have indicated the efficacy of adoptive immunotherapy utilizing recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells in the treatment of advanced neoplastic disease. However, this therapeutic approach is associated with considerable toxicity, primarily due to the systemic administration of rIL-2. The present study was undertaken to determine the efficacy of a newly developed water-soluble glucan, when administered in combination with LAK cells, in the therapy of experimental hepatic metastases.

Effect of glucan on neutrophil dynamics and immune function in Escherichia coli peritonitis.

Previous studies from our laboratory have demonstrated that glucan, a nonspecific immunomodulator, modifies the course of murine Escherichia coli peritonitis. The protective effect of glucan was mediated, in part, by macrophages. In the present study, leukocyte dynamics in the peritoneal cavity and peripheral blood of glucan-treated mice following E.

Pre-clinical safety evaluation of soluble glucan.

Soluble glucan, a beta-1,3-linked glucopyranose biological response modifier, is effective in the therapy of experimental neoplasia, infectious diseases and immune suppression. Currently, soluble glucan is undergoing phase I clinical trials. The present study describes the pre-clinical safety evaluation of soluble glucan in mice, rats, guinea pigs and rabbits.

Chemoimmunotherapy of experimental hepatic metastases.

Previous studies from our laboratory have demonstrated that particulate glucan is efficacious in the therapy of a syngeneic murine reticulum cell sarcoma (M5706), which specifically metastasizes from its primary site to the liver. The present study was undertaken to examine the therapeutic efficacy of a newly developed soluble glucan, in combination with cyclophosphamide in the treatment of hepatic metastatic disease. Male C57Bl/6J mice were injected subcutaneously on Day 0 with 1 x 10(4) sarcoma cells.

In vitro tumoricidal activity of resting and glucan-activated Kupffer cells.

Kupffer cells compose 80-90% of fixed tissue macrophages and have been suggested to play an important role in hepatic antitumor resistance. In the present study, the ability of resting and activated Kupffer cells to lyse syngeneic mammary adenocarcinoma BW10232 cells was evaluated. Activated Kupffer cells were isolated from C57Bl/6J mice following single of multiple intravenous (IV) injections of glucan (0.

Enhancement of interleukin-1 and interleukin-2 production by soluble glucan.

Soluble glucan, a beta-1,3-linked polyglucose, is a biologic response modifier effective in the therapy of experimental neoplasia, infectious diseases and immunosuppression. Interleukin-1 (IL-1) and interleukin-2 (IL-2) are endogenous immunomodulators which are essential for effective immune responsiveness. In view of its broad spectrum of immunobiological activity, the ability of glucan to enhance the production of IL-1 and IL-2 was evaluated.

Glucan stimulates production of antitumor cytolytic/cytostatic factor(s) by macrophages.

Glucan, a beta 1,3-linked polyglucose, is an effective macrophage activating and tumor-inhibitory agent. Previous studies indicate that glucan enhances macrophage-mediated tumoricidal activity. The present study was designed to examine the ability of glucan to enhance the production of tumor cell cytotoxic/cytostatic factor(s) designated, because of their macrophage origin, as macrophage cytotoxic factor(s) (MCF).

Comparison of the in vitro cytolytic effect of hepatic, splenic and peritoneal macrophages from glucan-treated mice on sarcoma M5076.

Our previous results have demonstrated that glucan will significantly modify the course of syngeneic murine tumors. Additionally, results denote that glucan increases macrophage-mediated lysis of syngeneic tumor cells. The present study was undertaken to more closely examine the effect of parenteral glucan administration on the tumoricidal activity of hepatic, splenic and peritoneal macrophage populations.

Preparation for hapten help by glucan, muramyl dipeptide, and its L-ala-Glycerol-mycolate derivative.

Previously, we reported that one of the factors that determines whether or not an animal will be prepared for hapten help after priming is the type of adjuvant used. The present work was undertaken, therefore, to determine which of a diverse variety of adjuvants or biological response modifiers would be effective. They included Freund's complete (CFA) and incomplete (FICA) adjuvants, particulate glucan, muramyl dipeptide (MDP), and its L-ala-glycerol-mycolate derivative.

Adverse effect of splenectomy in experimental peritonitis.

Patients undergoing splenectomy have increased operative morbidity and mortality, especially when associated with gastrointestinal surgery or injury. This present study was designed to assess the effect of splenectomy on mortality in a polymicrobial fecal peritonitis model and evaluate therapy with antibiotic (cefoxitin) or immunomodulation (glucan). Human stool-barium (0.

Therapeutic efficacy of glucan in a murine model of hepatic metastatic disease.

Glucan, a particulate beta-1,3-polyglucose immunomodulator, was evaluated for its ability to modify hepatic metastases and survival in mice with reticulum cell sarcoma. Sarcoma M5076 cells were injected subcutaneously (1 X 10(5) cells) into syngeneic C57BL/6J male mice. On Day 20, histopathological studies indicated the presence of hepatic micrometastases.

Modification of post-operative C. albicans sepsis by glucan immunostimulation.

Glucan, a beta-1,3 polyglucose, was evaluated for its ability to enhance resistance of post-operative mice to experimentally induced C. albicans sepsis. Male C57BL/6J mice were injected i.

Protective effect of nonspecific immunostimulation in postsplenectomy sepsis.

The enhanced risk of severe sepsis following splenectomy is now well recognized in both adult and pediatric patients. Prophylactic antibiotics and bacterial vaccines have been utilized with limited success to inhibit the high morbidity and mortality. This study reports the use of glucan, a beta-1,3-polyglucose, as a nonspecific immunostimulant for postsplenectomy pneumococcal sepsis.

Immunotherapeutic modification of Escherichia coli--induced experimental peritonitis and bacteremia by glucan.

Previous data from our laboratory have demonstrated that glucan administration significantly alters the course of a variety of experimentally induced infectious diseases. In view of the increasing incidence of gram-negative infections, studies were initiated to evaluate the effect of intraperitoneal glucan therapy on Escherichia coli-induced peritonitis and sepsis. Male ICR/Tex mice were injected intraperitoneally with glucan or dextrose on days 5 and 3 prior to intraperitoneal challenge with 1.

Modification of galactosamine-induced liver injury in rats by reticuloendothelial system stimulation or depression.

The reticuloendothelial system has been implicated in galactosamine-induced liver injury because of a correlation between phagocytic alterations induced by colloidal carbon or endotoxin, and development of liver necrosis. To evaluate this concept, the influence of galactosamine on liver function and histology was determined in rats in which the reticuloendothelial system was normal, stimulated, or depressed. Methyl palmitate was used as a reticuloendothelial system suppressant, and glucan was used as a reticuloendothelial system activating agent.

Glucan-induced enhancement of host resistance to selected infectious diseases.

We conducted studies with mice, rats, and monkeys which demonstrated the ability of glucan to induce either nonspecific or specific enhancement of host resistance to infectious diseases. Intravenous pretreatment of mice with glucan significantly enhanced the survival of mice challenged with either Venezuelan equine encephalomyelitis (VEE) virus or Rift Valley fever virus. Pretreatment was beneficial when initiated 3 days before challenge with VEE virus and 7 days before challenge with Rift Valley fever virus.

Enhancement of host susceptibility to Staphylococcus aureus infection by chronic ethanol ingestion--modification by glucan immunostimulation.

The susceptibility of chronic ethanol-treated mice to S. aureus infection was ascertained, as was the ability of the immunostimulant glucan to modify ethanol-induced susceptibility to infection. Chronic alcohol-treated mice showed enhanced sensitivity to S.