Acute and chronic toxicity studies on partially purified hypoglycemic preparation from water extract of bark ofFicus bengalensis.

Acute and chronic toxicity studies were conducted to assess toxicity of a partially purified preparation from the water extract of the bark ofFicus bengalensis, which was demonstrated in our earlier studies to have significant hypoglycemic and hypocholesteroiemic effect on alloxan induced, mild and severe diabetes in rabbits. LD(50) of this preparation was found to be ∼1 gm/kg in rats when given orally. For chronic toxicity studies 3 doses of aqueous preparation were given to 3 groups of rats. First group received 5 times ED(50) (50 mg/kg), second group 10 times ED(50) (100 mg/kg) and the third group 15 times ED(50) (150 mg/kg) for 3 months. Fourth group which served as control was given water. After three months, blood was collected for studying biochemical and hematological parameters. Blood glucose, serum cholesterol, liver and kidney function tests, haemoglobin, total and differential leukocyte count were determined. Animals were sacrificed and histopathological examination of liver, heart and kidneys was carried out. Results of the study showed that partially purified preparation fromFicus bengalensis is not toxic by all the above mentioned parameters.

Effect of endotoxin on opossum gallbladder motility: a model of acalculous cholecystitis.

OBJECTIVE: To determine whether endotoxin causes histologic changes in the gallbladder consistent with acalculous cholecystitis, and to determine the effects of endotoxin on gallbladder motility. SUMMARY BACKGROUND DATA: Acute acalculous cholecystitis is frequently seen in critically ill, septic patients, after prolonged fasting and gallbladder stasis. The pathogenesis of acalculous cholecystitis is unknown; however, previous studies have suggested that ischemia may play a role. METHODS: Adult opossums received Escherichia coli lipopolysaccharide. The gallbladder was removed for histologic examination or for physiologic studies 4 hours to 2 weeks later. For histologic examination, gallbladder strips underwent standard hematoxylin-and-eosin processing. For physiologic studies, they were mounted in a tissue bath to determine responses to cholecystokinin octapeptide or electrical field stimulation. RESULTS: Intravenous endotoxin at a dose of 0.005 mg/kg resulted in disrupted mucosal surfaces and areas of hemorrhage; higher doses of endotoxin resulted in coagulation necrosis, hemorrhage, areas of fibrin deposition, and extensive mucosal loss, consistent with an acute ischemic insult. Endotoxin abolished the contractile response to cholecystokinin octapeptide in gallbladder strips 4 hours after endotoxin administration. The 0.005-mg/kg dose of endotoxin decreased the contractile response to cholecystokinin octapeptide for up to 96 hours after endotoxin administration and decreased the contractile response to electrical field stimulation for 48 hours after administration. Inhibition of nitric oxide synthase reversed the decreased contractile response to cholecystokinin octapeptide. CONCLUSIONS: Endotoxin causes an ischemic insult to the gallbladder similar to that seen in acalculous cholecystitis. Also, endotoxin may lead to gallbladder stasis by decreasing gallbladder contractile responses to hormonal and neural stimuli.

Lung surfactant proteins A and D can inhibit specific IgE binding to the allergens of Aspergillus fumigatus and block allergen-induced histamine release from human basophils.

Aspergillus fumigatus is an opportunistic fungal pathogen which, in the immunocompetent host, causes allergic disorders such as allergic rhinitis, allergic sinusitis, hypersensitivity pneumonitis, and allergic bronchopulmonary Aspergillosis (ABPA). In the present study, the interaction of 3-week culture filtrate (3wcf) allergens and various purified glycosylated and non-glycosylated allergens of A. fumigatus with lung surfactant proteins, SP-A and SP-D, was investigated. Purified SP-A and SP-D, isolated from human bronchoalveolar lavage fluid, bound to the 3wcf allergens and purified allergens, gp55 and gp45, in a carbohydrate-specific and calcium-dependent manner. Both SP-A and SP-D did not bind to deglycosylated allergens, suggesting that the ability of SP-A and SP-D to bind certain allergens is mediated through their carbohydrate recognition domains, interacting with the carbohydrate residues on the allergen. Both SP-A and SP-D could inhibit the ability of allergen-specific IgE from Aspergillosis patients to bind these allergens, suggesting that SP-A and SP-D may be involved in the modulation of allergic sensitization and/or development of allergic reactions. The view that SP-A and SP-D play a protective role against airborne allergens is further supported by the demonstration of their ability to inhibit A. fumigatus allergen-induced histamine release from allergic patients' basophils.

Binding of pulmonary surfactant proteins A and D to Aspergillus fumigatus conidia enhances phagocytosis and killing by human neutrophils and alveolar macrophages.

To determine whether the lung surfactant proteins A (SP-A) and D (SP-D) are involved in the initial protective immunity against opportunistic pulmonary fungal infections caused by Aspergillus fumigatus, we performed a series of in vitro functional studies to see if SP-A and SP-D enhanced binding, phagocytosis, activation, and killing of A. fumigatus conidia by human alveolar macrophages and circulating neutrophils. Both SP-A and SP-D bound to carbohydrate structures on A. fumigatus conidia in a calcium-dependent manner. SP-A and SP-D were also chemoattractant and significantly enhanced agglutination and binding of conidia to alveolar macrophages and neutrophils. Furthermore, in the presence of SP-A and SP-D, the phagocytosis, oxidative burst, and killing of A. fumigatus conidia by neutrophils were significantly increased. These findings indicate that SP-A and SP-D may have an important immunological role in the early antifungal defense responses in the lung, through inhibiting infectivity of conidia by agglutination and by enhancing uptake and killing of A. fumigatus by phagocytic cells.