Ascorbic acid prevents ischemia-reperfusion injury in the rat small intestine

Ischemia-reperfusion injury by free radicals and lipid peroxides is observed in various organs. Ascorbic acid (AsA) or glutathione (GSH) in various doses (AsA:2, 0.5, 0.1 mmol/kg, GSH:2 mmol/kg) was intraperitoneally administered to male Wistar rats. The entire small intestines were resected just before ischemia, after ischemia, and after 20 min of reperfusion (n = 7–10 at each time point). At each time point, the specimens were subjected to assays of lipid peroxides, GSH, and glutaminase activity of the tissues; they were also examined histologically. In the AsA group, the production of lipid peroxides after reperfusion was significantly suppressed in a dose-dependent manner, and the ratio of oxidized GSH to total GSH was also significantly low. Tissue glutaminase activity decreased to a lesser extent, and the degree of injury was apparently less marked in the AsA group. This study indicates that AsA acts as an antioxidant against peroxidative tissue injury, possibly by scavenging radicals, preserving reduced GSH, and reducing the peroxidative reaction. Received: 21 June 1996 Received after revision: 8 October 1996 Accepted: 12 November 1996     

Radiotherapy for pediatric brain stem glioma: radiation dose, response, and survival.

An analysis of 39 patients under 20 years of age with brain stem glioma treated with radiotherapy between 1977 and 1991 was undertaken. Twenty-eight (71.2%) of the patients responded well to initial radiotherapy, and 11 (28.8%) responded poorly. Median survival for the total patient population was 10 months. Response rates and median survivals were influenced by radiation dose: 45.5% and 9 months at doses less than 4499 cGy (n = 11), 83.3% and 13 months at doses between 4500 and 5499 cGy (n = 12), 66.7% and 11.5 months at doses between 5500 and 6499 cGy (n = 9), and 100% and 10 months at doses more than 6500 cGy (n = 7). Multivariate analysis revealed the response to initial radiotherapy was the only predictor of survival with radiation doses up to 6499 cGy. Four of the patients who responded well demonstrated radiological and/or histological calcification within or around the tumor at the time of clinical deterioration. Radiation injury was confirmed in two autopsy cases. The possibility that intratumoral radiation injury causes clinical deterioration is suggested.     

Comparison of circulatory and respiratory responses between supplementary epidural buprenorphine and eptazocine administration during and immediately after total intravenous anesthesia

Opioid supplements are often required in total intravenous anesthesia (TIVA). Most ϰ-opiate receptors are found in the spinal cord, wherea μ-opiate receptors are widespread throughout the brain and spinal cord. Buprenorphine has a strong μ-action with a minute ϰ-action, while eptazocine stimulates ϰ-receptors only. From these, epidural eptazocine is expected to exert strong spinal analgesia by ϰ-stimulation without μ-action, which produces circulatory and respiratory depression. Therefore, the clinical effects of epidural opioids on circulation, respiration, and analgesia were compared. Continuous epidural administration of eptazocine or buprenorphine was combined with TIVA in patients scheduled for elective abdominal surgery. Epidural opioid administration was continued throughout and for 72h after anesthesia. A significant analgesic effect (P<0.01) of epidural eptazocine without circulatory and respiratory depression was observed. With epidural buprenorphine, circulatory and respiratory depression during and immediately after anesthesia were significant (P<0.05). These results suggest that medullary μ-stimulation by an epidural opioid induces circulatory (hypervagotonicity and hypervagosensitivity) and respiratory depression, while ϰ-stimulation produces only minimal effects on circulatory and respiratory systems.     

Identification of 16 novel mutations in the argininosuccinate synthetase gene and genotype-phenotype correlation in 38 classical citrullinemia patients

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron-exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are "private" and are distributed throughout the gene, except for exons 5 and 12-14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype-phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease.     

The Influence of Dysphagia on Nutritional and Frailty Status among Community-Dwelling Older Adults

Malnutrition is a core symptom of the frailty cycle in older adults. The purpose of this study was to investigate whether dysphagia influences nutrition or frailty status in community-dwelling older adults. The study participants were 320 Japanese community-dwelling older adults aged ≥65 years. All participants completed a questionnaire survey that included items on age, sex, family structure, self-rated health, nutritional and frailty status, and swallowing function. Nutritional status was categorized as malnourished, at risk of malnutrition, and well-nourished based on the Mini Nutrition Assessment-Short Form. The participants were then classified into a malnutrition (malnourished/at risk) or a well-nourished group (well-nourished). Frailty was assessed using the Cardiovascular Health Study criteria. The participants were then divided into a frailty (frail/pre-frail) or a non-frailty group (robust). Dysphagia was screened using the 10-item Eating Assessment Tool. Multiple logistic regression analysis was conducted to determine whether dysphagia was associated with nutritional or frailty status. The results revealed that dysphagia influenced both nutrition (odds ratio [OR]: 4.0; 95% confidence interval [CI]: 1.9–8.2) and frailty status (OR: 2.3; 95% CI: 1.0–5.2); therefore, the swallowing function would be an important factor for community-dwelling older adults on frailty prevention programs.     

Posterior subtemporal transtentorial approach for a lower basilar trunk aneurysm (author's transl)]

A lower basilar trunk aneurysm is rare and it has been difficult to operate on this kind of aneurysm which is located in so-called "no man's land". We have recently operated on the aneurysm which was located between the vertebrobasilar junction and the origin of AICA. The aneurysm was approached posterior-subtemporal-transtentorially and wrapped with a muscle piece because of its broad neck. After the operation the patient developed amnestic aphasia which, however, disappeared 4 months postoperatively. The advantage of this approach is that it enables a better visualization of the lower basilar trunk, the lateroventral portion of the pons, the distal part (5 mm) of both vertebral arteries and the upper portion of the medulla oblongata than any other approaches hitherto reported. The retraction of the temporal lobe and subsequent brain damage may be minimized by using intraoperative ventricular drainage and microtechnical maneuver.     

Clinical utility of monitoring sialyl Lewis(X) (CD15S) antigen on peripheral lymphocytes for the diagnosis and treatment of rejection after renal transplantation

BACKGROUND: In organ transplantation, the grafts must be carefully monitored, but it is often difficult to make a quick and accurate diagnosis of unusual changes. Extensive research has failed to identify a useful marker for rejection. We investigated the clinical utility of sialyl Lewis(X) (CD15s) monitoring in 17 renal transplant patients with acute rejection. METHODS: The expression of CD15s on peripheral lymphocytes was examined using flow cytometry in renal transplant recipients with rejection (n=17), without rejection (n=23), recipients infected with cytomegalovirus (n=7), recipients with other diseases (n=7), and healthy volunteers (n=18). CD15s expression was compared with histological findings, and was also examined before and after steroid pulse therapy to investigate the effects of steroids on CD15s antigen expression on the surface of the peripheral lymphocytes. RESULTS: CD15s was strongly expressed in all patients with rejection, but was not expressed in any of the patients without rejection or in any healthy volunteers. Histologically, cell infiltration into the rejected graft was moderate or severe in all patients with strong expression of CD15s. In contrast, no or only mild infiltration was observed in patients with weak expression of CD15s. In addition, 14 of 17 patients (14/17, 82%) with strong CD15s expression improved upon administration of steroid pulse therapy, although there was no benefit from steroids in any of the patients with weak expression of CD15s. CONCLUSIONS: The CD15s antigen is expressed strongly on the peripheral lymphocytes at the time of rejection. It is interesting that the efficacy of steroid therapy in the patients with elevated creatinine could be predicted by CD15s expression on the peripheral lymphocytes before graft biopsy. There have been only few reports showing the relationship between CD markers and the efficacy of the treatment in patients with elevated creatinine. We report that the detection of CD15s on the peripheral lymphocytes by flow cytometry was an easy, helpful, and noninvasive means for the diagnosis and treatment of patients with elevated creatinine after renal transplantation.     

Serum levels of S-glutathionylated proteins as a risk-marker for arteriosclerosis obliterans.

BACKGROUND: Oxidative stress plays a role in the development of chronic peripheral arterial disease (PAD) because under these conditions redox regulation is impaired, inducing the S-glutathionylation of proteins. A method of estimating the levels of S-glutathionylated proteins has been developed using biotinylated glutathione S-transferase, which allows the study of their crucial role in the oxidative stress-related progression of PAD. METHODS AND RESULTS: The serum levels of S-glutathionylated proteins were examined in 41 patients with arteriosclerosis obliterans (ASO) and 38 age-matched non-ASO patients using biotinylated glutathione S-transferase. The levels were higher in the patients with ASO, even early on, and positively correlated with the ankle/brachial index. In vitro, the levels of S-glutathionylated proteins were reduced in the presence of glutathione and glutaredoxin. CONCLUSIONS: Serum levels of S-glutathionylated proteins are a sensitive risk-marker for ASO at an early stage.