Changes in serum S100A12 and sRAGE associated with improvement of the PaO(2)/FiO(2) ratio following PMX-DHP therapy for postoperative septic shock.

BACKGROUND: Endotoxin (Et) adsorption therapy with a column of polymyxin B-immobilized fibers (PMX) is effective in improving the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (PaO(2)/FiO(2) ratio) and increasing mean arterial blood pressure (MAP) in sepsis. S100A12 and soluble receptor for advanced glycation end product (sRAGE) are useful as early markers of acute lung injury. PURPOSE: To investigate the effect of improving the PaO(2)/FiO(2) ratio by PMX-direct hemoperfusion (PMX-DHP) on production of S100A12 and sRAGE. SUBJECTS AND METHODS: Sepsis patients after surgery for perforation of the lower gastrointestinal tract were adopted as the subjects. We retrospectively reviewed the cases of 20 patients on mechanical ventilation and continuous administration of norepinephrine. We recorded PaO(2)/FiO(2) ratio, MAP, and norepinephrine doses. S100A12, sRAGE, and Et levels were measured before and after PMX-DHP. RESULTS: The PaO(2)/FiO(2) ratio and MAP improved significantly after PMX-DHP (p < 0.05). S100A12 and Et decreased significantly after PMX-DHP (p < 0.05). No differences were observed in sRAGE. CONCLUSION: S100A12 is useful as a marker that reflected improvement in the PaO(2)/FiO(2) ratio after PMX-DHP. We consider PMX-DHP to be useful as adjunctive therapy for sepsis that reduces the Et and corrects the pathology in the early stage.

Preliminary study on glucose control with an artificial pancreas in postoperative sepsis patients.

BACKGROUND: Glucose control is essential to avoid hypoglycemia in postoperative patients. AIM: To conduct a preliminary examination to evaluate the feasibility of the use of an artificial pancreas for glucose control as well as the accuracy of assessment by the artificial pancreas of the insulin dose required. SUBJECTS AND METHODS: Glucose control using an artificial pancreas was undertaken in 8 postoperative sepsis patients. The blood glucose level was set at 80-150 mg/dl. Blood glucose levels over time, insulin dose requirements, and occurrence of hypoglycemia (≤40 mg/dl) were recorded for each patient. The patients were divided into 2 groups based on the total insulin dose they received over the 7 days (HG, n = 4: consisting of patients who required a higher insulin dose; LG, n = 4: patients who required a lower insulin dose). The data of the 2 groups were analyzed retrospectively. RESULTS: The blood glucose level before glucose control was 203.3 ± 9.9 mg/dl and could be controlled in all patients to within the target range. No hypoglycemia events were recorded for any of the patients. The insulin dose in the HG and LG groups was 21,824.8 ± 6,030.4 and 6,254.5 ± 3,402.3 mU/kg (p < 0.05). CONCLUSIONS: Accurate glucose control could be achieved with the artificial pancreas.

Potentiation of motilin-induced contraction by nitric oxide synthase inhibition in the isolated chicken gastrointestinal tract.

The present experiments were designed to determine whether or not endogenous nitric oxide (NO) modifies the contractile response to chicken motilin (ch-MT) in the gastrointestinal (GI) tract (proventriculus and small intestine) of the chicken. ch-MT (1 nmol L(-1)-1 micromol L(-1)) caused contractions of longitudinal muscle strips of the proventriculus through both myogenic and neurogenic (mostly cholinergic) mechanisms. On the other hand, ch-MT (0.1 nmol L(-1)-100 nmol L(-1)) contracted the small intestine (duodenum, jejunum and ileum) only through a myogenic mechanism. L-Nitroarginine methylester (L-NAME) potentiated, and L-arginine inhibited, the ch-MT- induced contraction without affecting the responsiveness of acetylcholine (ACh) or 5-hydroxytryptamine in the proventriculus. Electrical field stimulation (EFS)- and 1,1-dimethyl-4-phenylpiperazinium (DMPP)- induced contractions were also potentiated by L-NAME. The potentiation by L-NAME was prevented by L-arginine but not by D-arginine. However, in the presence of atropine or tetrodotoxin, neither L-NAME nor L-arginine modified the responses to ch-MT and DMPP. In contrast to the proventriculus, L-NAME and L-arginine were both ineffective in modifying the ch-MT-induced contraction in the small intestine. These results indicate that NO synthase inhibition potentiates the contractile response of ch-MT, EFS and DMPP in the chicken proventriculus through reduction of endogenous NO-mediated presynaptic inhibition on neural ACh release. However, NOS inhibition did not modify the myogenic (direct) action of ch-MT in gastric and intestinal smooth muscles of the chicken.

[Granulopoietic effects of lentinan, an antitumor polysaccharide in BALB/c nude mice].

The effect of lentinan on granulopoiesis in BALB/c nude mice (Nu/Nu) was compared with that in their heterozygotes (Nu/+). Lentinan-injected Nu/+ showed enhanced serum colony-stimulating activity (CSA), and increased diphasically granulocyte-macrophage colony forming cells (GM-CFC) in bone marrow and spleen (i.e., first peak on day 1-2 and second peak on day 6). On the other hand, in Nu/Nu, lentinan did not enhance serum CSA, although the control level was higher than the enhanced level in Nu/+. Monophasic increase in GM-CFC was observed in Nu/Nu, but the second peak seen in Nu/+ was not observed. Reconstitution of Nu/+ splenocytes to Nu/Nu increased GM-CFC on day 6, and the increase was augmented by lentinan administration. These results suggest that mature T-cells participate in regulation of granulopoiesis in vivo and that lentinan augments granulopoiesis at least in part via mature T-cell populations.

[Intravenous chronic toxicity of lentinan in rats: 6-month treatment and 3-month recovery (author's transl)].

Chronic toxicity of lentinan was studied in male and female JCL : SD rats. Lentinan was given intravenously into tail vein. Dosage levels employed were 0 (5% mannitol), 0.01, 0.1, 1 (with or without dextran), and 10 mg/kg/day for 6 months in a volume of 1 ml/100 g body weight. After 6 months, the treatment was discontinued and a recovery study was performed for 3 months. Rats receiving 10 mg/kg had redness and necrosis of the tail, the treatment was stopped at week 5, and the rats were sacrificed. Rats receiving 1 mg/kg showed redness of the ear, tail, and scrotum, which was remarkable in the 2nd and 3rd months. Body weight gains were not adversely affected. Laboratory examinations revealed an increase in leukocyte count, decreases in differential eosinophil count and platelet count, and an increase in serum beta-globulin level in drug-treated rats. At autopsy after 6 months, rats from the drug-treated groups had pulmonary hemorrhage and enlargements of the spleen and mesenteric lymph nodes. Histologic changes attributable to treatment included (1) activation of reticulo-endothelial system such as small epithelioid cell nodule in the liver, spleen, and mesenteric lymph nodes, and mobilization of Kupffer cells; (2) arteritis in various organs, especially notable in the spleen, testis, and epididymis ; (3) hemorrhage in the lung; and (4) hypospermatogenesis. All these changes described above had a propensity to recover. The maximum no effect level was estimated to be less than 0.01 mg/kg in the present study in male and female rats.

[Chronic toxicity test of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M73101) in beagle dogs (author's transl)].

Male and female dogs, aged 17--21 months, were administered orall M 73101 (0, 60, 120 and 240 mg/kg/day), a new analgesic and antiinflammatory drug, for 27 weeks, and following recovery test was carried out for 5 weeks. Dead animals were not found throughout the experimental period. Body weight gain, and food and water consumption were not affected due to M 73101 administration. Except for a slight increase of vomitting in the highest dose, there were no abnormal symptoms. Biochemical examination showed the slight increase in serum alkaline phosphatase activity and free cholesterol level. Pathological examination revealed a dose-dependent increase of liver weight and hypertrophy of hepatocytes due to proliferation of smooth endoplasmic reticulum. In addition, mitochondria became irregularly large in the highest dose. There were no abnormal findings in the gastro-intestinal tracts except for an erosion of gastric mucosa, which was noted in a female dog treated 240 mg/kg/day of M 73101. From these results, it was suggested that the maximum non-toxic dose was 60 mg/kg/day or less, and the greatest safety dose was 120 mg/kg/day in beagle dogs.