Effect of D-glucose feeding on mortality induced by sepsis

Sepsis is the life-threatening response to infection which can lead to tissue damage, organ failure, and death. In the current study, the effect of orally administered D-glucose on the mortality and the blood glucose level induced by D-Galactosamine (GaLN)/lipopolysaccharide (LPS)-induced sepsis was examined in ICR mice. After various amounts of D-glucose (from 1 to 8 g/kg) were orally fed, sepsis was induced by injecting intraperitoneally (i.p.) the mixture of GaLN /LPS. Oral pre-treatment with D-glucose dose-dependently increased the blood glucose level and caused a reduction of sepsis-induced mortality. The oral post-treatment with D-glucose (8 g/kg) up to 3 h caused an elevation of the blood glucose level and protected the mortality observed in sepsis model. However, D-glucose post-treated at 6, 9, or 12 h after sepsis induction did not affect the mortality and the blood glucose level induced by sepsis. Furthermore, the intrathecal (i.t.) pretreatment once with pertussis toxin (PTX; 0.1 microg/5 ml) for 6 days caused a reduction of D-glucose-induced protection of mortality and hyperglycemia. Furthermore, once the hypoglycemic state is continued up to 6 h after sepsis initiated, sepsis-induced mortality could not be reversed by D-glucose fed orally. Based on these findings, it is assumed that the hypoglycemic duration between 3 and 6 h after the sepsis induction may be a critical time of period for the survival. D-glucose-induced protective effect against sepsis-induced mortality appears to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Finally, the production of hyperglycemic state may be critical for the survival against the sepsis-induced mortality.

Effect of pertussis toxin pretreated centrally on blood glucose level induced by stress

In the present study, we examined the effect of pertussis toxin (PTX) administered centrally in a variety of stress-induced blood glucose level. Mice were exposed to stress after the pretreatment of PTX (0.05 or 0.1 µg) i.c.v. or i.t. once for 6 days. Blood glucose level was measured at 0, 30, 60 and 120 min after stress stimulation. The blood glucose level was increased in all stress groups. The blood glucose level reached at maximum level after 30 min of stress stimulation and returned to a normal level after 2 h of stress stimulation in restraint stress, physical, and emotional stress groups. The blood glucose level induced by cold-water swimming stress was gradually increased up to 1 h and returned to the normal level. The intracerebroventricular (i.c.v.) or intrathecal (i.t.) pretreatment with PTX, a Gi inhibitor, alone produced a hypoglycemia and almost abolished the elevation of the blood level induced by stress stimulation. The central pretreatment with PTX caused a reduction of plasma insulin level, whereas plasma corticosterone level was further up-regulated in all stress models. Our results suggest that the hyperglycemia produced by physical stress, emotional stress, restraint stress, and the cold-water swimming stress appear to be mediated by activation of centrally located PTX-sensitive G proteins. The reduction of blood glucose level by PTX appears to due to the reduction of plasma insulin level. The reduction of blood glucose level by PTX was accompanied by the reduction of plasma insulin level. Plasma corticosterone level up-regulation by PTX in stress models may be due to a blood glucose homeostatic mechanism.

Effect of Sulfonylureas Administered Centrally on the Blood Glucose Level in Immobilization Stress Model

Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with 30 microg of glyburide, glipizide, glimepiride or tolazamide attenuated the increased blood glucose level induced by immobilization stress. Immobilization stress causes an elevation of the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v. caused a further elevation of the blood corticosterone level when mice were forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused an elevation of the plasma insulin level. Furthermore, immobilization stress-induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results suggest that lowering effect of sulfonylureas administered supraspinally against immobilization stress-induced increase of the blood glucose level appears to be primarily mediated via elevation of the plasma insulin level.

Inhibition of L-type calcium currents by magnesium sulfate on the rat basilar artery smooth muscle cells

Objective: Vasospasm remains the leading cause of cerebral damage after aneurysmal subarachnoid hemorrhage. Although magnesium regulates the calcium influx in vascular smooth muscle and endothelial cells, it has not been reported whether L-type calcium channels are involved in magnesiuminduced vascular relaxation in rat basilar artery. So, the effect of magnesium sulfate on L-type calcium currents in freshly isolated smooth muscle cells from rat basilar artery was investigated. Methods: The smooth muscle cells were isolated from rabbit basilar artery by enzyme treatment. L-type Ca2+ currents were identified using cesium chloride, a potassium channel blocker and Bay K8644, an activator of L-type Ca2+ channel. Currents were recorded under step pulse whole cell patch clamp technique. Results: In the presence of cesium chloride (in pipette solution), inward currents were observed by depolarizing step pulses. The inward currents were significantly reduced by nimodipine (n=4, p<0.05), an L-type Ca2+ channel blocker and increased by Bay K8644 (n=5, p<0.05), an L-type Ca2+ channel activator. The L-type calcium currents (156±17.0 pA, n=12) were significantly reduced by the application of 5 mM magnesium sulfate (53.8±7.0 pA, n=12, p<0.01). Conclusion: These results suggest that magnesium may relax cerebral vessel of rat basilar artery through decreasing intracellular Ca2+ ion by inhibition of L-type Ca2+ channels.

A Case of Right Upper Abdominal Pain Misdiagnosed on Computerized Tomography

Right upper abdominal pain is a common symptom in patients presenting to surgery emergency. Most of these cases can be diagnosed accurately on clinical evaluation or imaging. We report an unusual case of right upper abdominal pain, which could not be diagnosed correctly pre-operatively despite using various imaging modalities.