The (1,4)-a-D-glucan (a-D-glucan), derived from medicinal plant, Tinospora cordifolia, activates human lymphocytes with downstream synthesis of the pro-and anti-inflammatory cytokines, in vitro. We investigated physiological and immunological effects of a low and a high dose of a-D-glucan (0.5 and 10 mg/kg), in vivo, testing the hypothesis that intravenous administration of a-D-glucan does not affect haemodynamic, respiratory, haematological, and immune responses in normal rats. Male rats (300-400 g) were anaesthetized, tracheostomized, and catheterized in one femoral artery and vein. The mean arterial blood pressure and heart rate were continuously recorded. The baselines for gas exchange, differential blood cell count, and plasma concentration of TNF-a, IL-1b, IL-4, IL-6, and IFN-c were determined. Rats were then randomly assigned to controls (n ¼ 7), a low dose (0.5 mg/kg; n ¼ 10), and a high dose (10 mg/kg; n ¼ 7) of a-D-glucan for a six 6 hr study period. Gas exchange, differential cell count, plasma concentration of TNF-a, IL-1b, IL-4, IL-6, and IFN-c, and mean arterial blood pressure values remained within physiological range. Intravenous administration of 10 mg/kg a-D-glucan created tachycardia, associated with hyperventilation, and significant reductions in the blood haemoglobin and haematocrit concentrations. We suggest that these in vivo effects of a-D-glucan should be considered for future clinical and/or experimental trials.Extracts from a medicinal plant, Tinospora cordifolia, are shown to have anti-tumour activity [1,2], to reduce the pathological effects of endotoxic shock [3], and to inhibit lethal irradiation injury [4]. Studies suggest that glucans have modulating effects on inflammatory cytokines [5,6]. Extracts from other medicinal plants are known to enhance immune responses [7], and/or participate in scavenging of excessive reactive oxygen and nitrogen species [8,9]. The water-soluble polysaccharide (1,4)-a-d-glucan (a-d-glucan) is isolated from T. cordifolia and is known to activate different subsets of lymphocytes in vitro at 100 lg/ml [10]. This activation is followed by production of both pro-and antiinflammatory cytokines, such as TNF-a, IL-1b, IL-6, IL-12, IL-18, IFN-c, and MCP-1, involving Th1 pathway of T helper cell differentiation [5].The physiological effects of such immune-stimulating agents have been rarely studied. The half-life of glucans, given intravenously, is relatively short [11] and in practice multiple doses of glucans might be required to produce a maintained and significant change in inflammatory cytokine production. No study has examined the immediate effects of a single and relatively low dose of glucans, intravenously, in normal animals. In the present study, therefore, we tried to establish the physiological characteristics of a-d-glucan, to be considered for the design of future experimental and clinical trials. We tested whether intravenous administration of a-d-glucan can affect vital physiological variables, which are ordinarily used during critica...

In critically ill children, drug use density of vancomycin is significantly less when evaluated by the DDD method compared with the prescribed daily dose method, a more appropriate method in children. However, the simplest and most accurate method of assessing drug use density is the number of days of drug use method, which allows comparison of drug use density between different pediatric facilities or clinical units.

A 24-hr exposure to therapeutic hypercapnia in endotoxin-stimulated, spontaneously breathing rats is associated with a proinflammatory immune response in the lung and anti-inflammatory response in the spleen as well as an increase in certain histologic indices of endotoxin-induced lung injury.

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The purpose of this study was to compare the efficacy of CO2 removal during conventional mechanical ventilation (CMV) with and without expiratory phase intratracheal pulmonary ventilation (expiratory ITPV or Exp-ITPV); and to compare CO2 clearance during Exp-ITPV, in pressure-controlled ventilation (PCV) and in volume-controlled ventilation (VCV) modes. Seven anesthetized rabbits were tracheotomized and intubated using a 4 mm endotracheal tube. Venous and arterial lines were established. The rabbits were paralyzed, mechanically ventilated, and ventilation parameters were adjusted to achieve baseline arterial hypercapnia. Animals were then ventilated during 30-minute trials of CMV and Exp-ITPV, in both PCV and VCV modes. A custom-built, microprocessor-controlled solenoid valve was used to limit ITPV gas flow to the expiratory phase. Proximal and carinal airway pressures and hemodynamic variables were continuously recorded, and arterial blood gases were analyzed at the end of each trial. Exp-ITPV, as compared with CMV, reduced arterial PCO2 by 12% and 21% in PCV and VCV modes, respectively (p < 0.02 and p < 0.001; one-sided paired t test), without significant changes in other cardiorespiratory variables. In conclusion, Exp-ITPV is more effective than CMV in clearing CO2 through a small endotracheal tube. Exp-ITPV is also more effective in VCV mode than PCV mode.