Effects of Cilastatin on the Pharmacokinetics of a New Carbapenem, DA-1131, in Rats, Rabbits, and Dogs

DA-1131, a new carbapenem antibiotic, undergoes renal metabolism by renal dehydropeptidase I (DHP-I), located on the brush border of the proximal tubular cell. Species differences with regard to the effects of cilastatin, a renal DHP-I inhibitor, were investigated after a 1-min intravenous infusion of DA-1131, with or without cilastatin, to rats, rabbits, and dogs. After intravenous infusion, the nonrenal clearance (CL(NR)) of DA-1131 was significantly slower in rats (3.00 versus 8.01 ml/min/kg) and rabbits (2.41 versus 6.77 ml/min/kg) when the drug was coadministered with cilastatin; this could be due to the slower metabolism of DA-1131 by rat and rabbit kidney DHP-I. This indicated that renal metabolism of DA-1131 by renal DHP-I was inhibited by cilastatin. However, coadministration with cilastatin to dogs did not affect the CL(NR) of DA-1131.     

Hypoglycemic effect of Chlorella vulgaris intake in type 2 diabetic Goto-Kakizaki and normal Wistar rats

The aim of this study was to examine the hypoglycemic effect of chlorella in 6 week-old type 2 diabetic Goto-Kakizaki (GK, n=30) rats and 6 week-old normal Wistar (n=30) rats. Animals were randomly assigned to 3 groups respectively, and were fed three different experimental diets containing 0%, 3% or 5% (w/w) chlorella for 8 weeks. In diabetic GK rats, the insulinogenic-indices were not significantly different among the groups. The concentrations of fasting plasma glucagon and hepatic triglyceride, and the insulin/glucagon ratios of the GK-3% chlorella and GK-5% chlorella groups were significantly lower than those of the GK-control group. The HOMA-index and the concentrations of fasting blood glucose and plasma insulin of the GK-3% chlorella and GK-5% chlorella groups were slightly lower than those of the GK-control group. In normal Wistar rats, the insulinogenic-indices were not significantly different among the normal groups, but that of the Wistar-5% chlorella group was slightly higher than the other groups. The concentrations of fasting blood glucose and plasma insulin, and the HOMA-index of the Wistar-5% chlorella group were a little higher, and the fasting plasma glucagon concentration and the insulin/glucagon ratio of the Wistar-5% chlorella group were significantly higher than those of the Wistar-control and Wistar-3% chlorella groups. In conclusion, this study shows that the glucose-stimulated insulin secretion was not affected by the intake of chlorella, which could be beneficial, however, in improving insulin sensitivity in type 2 diabetic GK and normal Wistar rats.     

The effect of surfactant therapy associated with high frequency jet ventilation on oxygenation in canine lavaged lungs

The effects of exogenous surfactant (SF) replacement therapy associated with high frequency jet ventilation (HFJV) on blood gas changes, pulmonary and hemodynamic variables were studied in canine lavaged lungs. The lungs were lavaged repeatedly with physiological saline until PaO2 decreased to 100 mmHg under intravenous pentobarbital anesthesia with 100% oxygen. SF (50 mg.kg-1) in the experimental group (n = 12) and saline in the control group (n = 8) were administered to the trachea using HFJV with a duration of 10 min. HFJV was further continued for 1 hour to make surfactant distribute evenly. Then respiration was controlled by the conventional mechanical ventilator for 3 hrs. During the administration of SF (10 min). PaCO2 was not altered. In the surfactant group, PaO2 improved significantly (200 mmHg) at the end of HFJV and was maintained for the next 3 hrs at this level, but it did not improve in the saline group. Therefore, we suggest that HFJV can be used safely for the treatment of acute respiratory failure and is an effective method for the administration of the pulmonary surfactant into the alveoli.     

Treatment of mediastinitis using video-assisted thoracoscopic surgery

Background: Mediastinitis remains a life-threatening disease that is difficult to manage and has a poor prognosis. This is especially true of descending necrotizing mediastinitis, which before the 1990s era had a mortality of approximately 40% despite the use of antibiotics, surgical techniques, and intensive care monitoring. Several authors have recommended that aggressive surgical approaches for mediastinitis are more effective than simple surgical approaches; however the best surgical option for mediastinitis remains controversial. Materials and methods: In a retrospective analysis between January 2000 and June 2006, 17 patients who underwent surgical debridement and drainage using video-assisted thoracoscopic surgery are included in this report. Data extracted from medical records included sex, age, origin of infection, surgical intervention, progress, and outcome including cause of death. There were eight men and nine women. The mean age was 52 years old (range, 20-72). Results: The origins of infection included esophageal perforation in nine patients and odontogenic or peritonsillar abscesses in the remaining eight patients. Among them, two patients required conversion to thoracotomy during operation in cases of mediastinitis due to esophageal perforation, so excluding the two patients, we calculated next five data for 15 patients. The mean duration from onset of symptoms to surgery was 12.4+/-13.1 days (range, 0-43) and the mean duration from the initial operation to discharge was 43.6+/-24.4 days (range, 8-113). There was serial operation in one case. There were three cases of postoperative mortality. Conclusion: Mediastinal drainage using video-assisted thoracoscopic surgery with or without cervical drainage can be a feasible and effective surgical option. This less invasive technique seems to have an outcome similar to more aggressive open surgical approaches for patients with mediastinitis previously reported in the literature, although it has not been directly compared.     

In Vitro Cytotoxicity of Mokko Lactone in Human Leukemia HL-60 Cells: Induction of Apoptotic Cell Death by Mitochondrial Membrane Potential Collapse

We studied the effect of mokko lactone (ML) isolated from the roots of Saussurea lappa (Compositae), a plant that is used for medicinal purposes in Korea, on the induction of apoptosis in human leukemia HL-60 cells. ML was cytotoxic to HL-60 cells, and this cytotoxic effect of ML appears to be attributable to its induction of apoptotic cell death, as ML induced nuclear morphologic changes and internucleosomal DNA fragmentation and increased the proportion of Annexin V-positive cells and the activity of caspase-3. Further studies revealed that the induction of apoptosis by ML was associated with the loss of mitochondrial membrane potential. Collectively, our results suggest that apoptosis induced by ML in HL-60 cells was executed by a collapse of mitochondrial membrane potential followed by the activation of caspase-3. This is the first report on the mechanism of apoptosis-inducing effect of ML.     

The alteration of enterochromaffin cell,mast cell,and lamina propria T lymphocyte numbers in irritable bowel syndrome and its relationship with psychological factors

Background/Aims: Psychological factors and subtle histopathological changes have been implicated in irritable bowel syndrome (IBS). The aims of the present study were to investigate whether the numbers of enterochromaffin (EC) cells, mast cells, and lamina propria T lymphocytes are altered in IBS, and evaluate the relationship of such alterations with psychological factors. Methods: Forty‐two consecutive IBS patients (M : F = 17:25, mean age 48 years) fulfilling the Rome III criteria and twelve asymptomatic healthy controls underwent rectal biopsy. Immunostaining was performed for EC cells, mast cells, and lamina propria T lymphocytes. Results: The IBS group included five post‐infectious (PI) IBS and 37 non‐PI IBS patients. Significantly more EC cells, mast cells and lamina propria T lymphocytes were observed in PI IBS patients. Mast cells significantly increased in non‐PI IBS‐D (diarrhea) patients, but not in non‐PI IBS‐C (constipation) and non‐PI IBS‐M (mixed) patients. Enterochromaffin cell numbers were not significantly altered in non‐PI IBS patients. Anxiety and depression scores did not differ between IBS patients with and without abnormal increase in EC cell or mast cell counts, defined as more than the mean of controls + 2 standard deviations. Enterochromaffin cell, mast cell, or lamina propria T lymphocyte numbers were poorly correlated with anxiety and depression scores in the IBS group. Conclusions: Enterochromaffin cells, mast cells, and lamina propria T lymphocytes significantly increase in PI IBS, whereas only mast cells significantly increase in non‐PI IBS‐D. Such histopathological changes do not seem to be directly associated with psychological factors.     

Pericardium Plug in the Repair of the Corneoscleral Fistula After Ahmed Glaucoma Valve Explantation

We report four cases in which a pericardium (Tutoplast®) plug was used to repair a corneoscleral fistula after Ahmed Glaucoma Valve (AGV) explantation. In four cases in which the AGV tube had been exposed, AGV explantation was performed using a pericardium (Tutoplast®) plug to seal the defect previously occupied by the tube. After debridement of the fistula, a piece of processed pericardium (Tutoplast®), measured 1 mm in width, was plugged into the fistula and secured with two interrupted 10-0 nylon sutures. To control intraocular pressure, a new AGV was implanted elsewhere in case 1, phaco-trabeculectomy was performed concurrently in case 2, cyclophotocoagulation was performed postoperatively in case 3 and anti-glaucomatous medication was added in case 4. No complication related to the fistula developed at the latest follow-up (range: 12~26 months). The pericardium (Tutoplast®) plug seems to be an effective method in the repair of corneoscleral fistulas resulting from explantation of glaucoma drainage implants.