The Protective Role of Glutathione, Cysteine and Vitamin C against Oxidative DNA Damage Induced in Rat Kidney by Potassium Bromate

The roles of glutathione (GSH), cysteine, vitamin C., liposome-encapsulated superoxide dismutase (L-SOD) and vitamin E in preventing oxidative DNA damage and cytotoxicity in the rat kidney after administration of potassium bromate (KBrO₃) to male F344 rats were investigated by measuring 8-hydroxydeoxyguanosine (8-OH-dG), an oxidative DNA product, lipid peroxidation (LPO) levels and relative kidney weight (RKW). Combined pre- and posttreatment of animals with 2 × 800 mg/kg GSH i.p. inhibited the increase of 8-OH-dG, LPO levels and RKW caused by 80 mg/kg KBrO₃ i.p. administration. In contrast, pretreatment with 0.3 ml/kg diethylmaleate (DEM) i.p., a depletor of tissue GSH, was associated with elevation of 8-OH-dG, LPO levels and RKW after a 20 mg/kg KBrO₃ i.p. treatment, which itself caused no change. Administration of KBrO₃ itself reduced renal non-protein thiol levels, but this was inhibited by the two doses of exogenous GSH. Combined treatment with DEM and KBrO₃ lowered the non-protein thiol level in the kidney more than did DEM treatment alone. Protective effects against the oxidative damage caused by KBrO₃ were also observed for pre- and posttreatment with 400 mg/kg cysteine i.p., another sulfhydryl compound, and daily i.g. application of 200 mg/kg vitamin C for 5 days. However, no influence was evident after pre- and posttreatment with 18,000 U/kg L-SOD i.p. or daily i.g. 100 mg/kg of vitamin E for 5 days. The results suggest that intracellular GSH plays an essential protective role against renal oxidative DNA damage and nephrotoxicity caused by KBrO₃.     

Aortic arch replacement with proximal first technique.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) without retrograde cerebral perfusion (RCP) has a strict time limit. We modified a surgical technique for anastomosis to shorten the period of DHCA and unilateral cerebral perfusion (UCP). METHODS: Between March 1993 and August 2001, retrospective analysis was done on 23 consecutive patients, who underwent aortic arch replacement with branches. The patients were divided into two groups: DHCA group and UCP group. The DHCA group, in which DHCA alone and without additional cerebral perfusion was performed, comprised of nine patients. Proximal aortic anastomosis was performed first during systemic cooling; then both the brachiocephalic artery and left carotid artery were reconstructed with the branches of the artificial graft during circulatory arrest; thereafter, cerebral and coronary perfusions were resumed. The UCP group, in which DHCA was not used but right hemisphere perfusion during deep hypothermia was performed when the origin of brachiocephalic artery was safely clamped, consisted of 14 patients. RESULTS: Mean time of DHCA was 18.8+/-4.2 minutes and that of right hemisphere perfusion time was 11.0+/-3.8 minutes, respectively. Twenty-one patients survived the surgery (91.3%), and two (8.7%) died during hospitalization. Transient cerebral complication occurred in four patients in the DHCA group and all recovered. Logistic regression analysis revealed that DHCA was the only parameter to significantly influence temporary neurological dysfunction. There was no other significant difference between the two groups. CONCLUSION: With our modified and simple surgical technique for aortic arch repair, we were able to successfully shorten the DHCA time and right hemisphere perfusion time. However, because DHCA was the only parameter to significantly influence temporary neurological dysfunction, some form of continuous cerebral perfusion at deep hypothermia may be a safer method to preserve cerebral function.     

Outcomes in patients with interrupted aortic arch and associated anomalies: a 20-year experience.

OBJECTIVE: The surgical results for the repair of interrupted aortic arch (IAA) have evolved in recent years. We report our results for staged repair of this complex congenital malformation. METHODS: Sixty-five patients (mean age, 16.9+/-41.7 days) were diagnosed with IAA and referred for surgical therapy. The surgical management strategy at our institution between 1982 and 2005 has been one-stage complete repair (n=13) or staged repair (n=52) in selected patients. Non-complex patients (group I, n=51) had a ventricular septal defect (87%), aortopulmonary window (8%), and left ventricular outflow tract obstruction (27%). Group II (n=14) were patients with Taussig-Bing double outlet right ventricle (n=6) or truncus arteriosus (n=8). Method of staged repair of IAA was to transect and turn down the left carotid artery and anastomosis it to the descending aorta (n=41) or graft interposition (n=2) combined with a pulmonary artery (PA) banding followed in a few months by delayed ventricular septal defect (VSD) closure and PA de-banding. RESULTS: There were 5 early and 10 late deaths. The actuarial survival including early mortality was 92% at 1 year, 81% at 5 years, and 76% at 10 and 15 years. There was an 81% 15-year survival for children in group I compared with a 54% for children in group II (p<0.001). Risk factors for increased mortality by univariate analysis were as follows: (1) primary aortic anastomosis (p=0.03), (2) presence of complex anomalies (p=0.05), and (3) initial IAA repair performed before 1994 (p=0.05). Actuarial freedom from any type of aortic reoperation or intervention was 86% at 1 year, 69% at 5 years, and 60% at 10 and 15 years. Univariate and multivariate analyses identified no tested variables as risk factors for reoperation. The majority (86%) was in New York Heart Association (NYHA) class I, and 14% remained in NYHA class II. During the postoperative course there were no neurologic deficits, seizures, and growth disturbances in any patient. CONCLUSION: Staged repair of IAA using a left carotid artery turn down can be safely applied in IAA patients with and without other intracardiac anomalies with good results. Use of the left carotid artery for arch reconstruction did not result in any detectable neurological events or growth disturbances later in life. Associated anomalies played an important role in outcomes. The long-term probability for reoperation and/or reintervention remains high regardless of operative technique.     

Chromosome analysis of brain tumors in childhood

We performed a chromosome analysis of 26 pediatric brain tumors, including 20 primitive neuroectodermal tumors (PNETs), 5 astrocytomas, and I immature teratoma. Specimens were treated with collagenase, placed in overnight or short-term cultures, and harvested for chromosome analysis. Numerical and/or structural abnormalities were noted in 14 of the 20 PNETs and 4 of the 5 astrocytomas. In 13 PNETs, so-called medulloblastoma in the cerebellum, an i(17q) was the most frequent structural abnormality, accounting for 30% (4/13). Double minute chromosomes (dmin) were observed in one tumor. Near-diploidy was demonstrated in three of these PNETs, hyperdiploidy in three, and near-tetraploidy in three. We could not find any correlation of these cytogenetic findings with the prognosis. In the remaining seven PNETs other than medulloblastoma, the karyotypes of five PNETs demonstrated a variety of numerical and structural abnormalities. As to the astrocytomas, losses of chromosomes 7 and 9 with dmin were observed in two, and structural abnormalities of chromosomes 1 and 17 were also observed in two tumors. In our limited cases, however, we could not find the same chromosome abnormalities that are well known in adult astrocytomas. A congenital immature teratoma showed hyperdiploidy with increased numbers of chromosomes 3, 6, and 12. We conclude that i(17_q) is an important chromosome abnormality in medulloblastomas, and that the oncogenesis of pediatric astrocytomas might be different cytogenetically from that of adult astrocytomas.     

Influence of ileal pouch capacity and anal sphincteric function on the clinical outcome after ileal pouch-anal anastomosis

This study was designed to determine the influence of ileal pouch capacity and anal sphincteric function on the clinical outcome after ileal pouch-anal anastomosis. A total of 24 patients who had undergone ileal pouch-anal anastomosis (J pouch) for ulcerative colitis were studied. The 24-hour stool frequency was found to be inversely correlated with the sensitivity threshold volume (STV), maximal tolerance volume (MTV), and distensibility, but was independent of the maximal resting pressure and maximal squeeze pressure. Patients experiencing nocturnal fecal incontinence had maximal resting pressures that were significantly lower than those of nocturnally continent patients. Among the patients with fecal incontinence, those with frequent soiling had lower resting pressures, STV, and distensibility than the patients with intermittent spotting. In addition, the STV in patients needing nocturnal evacuation were lower than those of patients who did not evacuate after falling asleep. The conclusions are as follows. Both stool frequency and the need for nocturnal pouch evacuation correlated directly with pouch volume. Anal incontinence was more common in patients with low internal sphincteric function. In addition, frequent and gross nocturnal incontinent patients demonstrate a worse function in both the anal sphincter and reservoir than those with intermittent spotting.     

Time after excision and temperature alter ex vivo tissue relaxation time measurements

Previously unreported effects of tissue storage were recently observed in the authors' experimental magnetic resonance (MR) studies. To evaluate the effect of elapsed time after excision and storage temperature on tissue relaxation time measurements, tissue samples from the liver, pancreas, kidney, testis, spleen, and brain were obtained in rats. T1 and T2 were first measured within 5 minutes of excision, and between subsequent measurements, tubes were kept in a water bath at 40°C, at room temperature (28°C), or in an ice bath (4°C). Cellular and organellar integrity was assessed with electron microscopy and correlated with the MR findings. At 40°C (20-MHz spectrometer), the T1 of liver decreased from 280 msec ± 8 to 212 msec ± 10 during the first 60 minutes; the T1 of pancreas decreased from 276 msec ± 3 to 208 msec ± 2. Other tissues showed less than a 5% decrease in T1. T2 changes were smaller than T1 changes in all tissues. Electron microscopy of pancreatic acinar cells showed postmortem changes in mitochondria evolving over the first 60 minutes after death. Manganese loading experiments implicated mitochondrial manganese stores in the observed enhanced postmortem decrease in T1. This study calls into question reported relaxation time data for liver and pancreas. MR studies of excised tissues must account for time and temperature to prevent systematic experimental errors.     

Effects of Peak Inspiratory Flow on Development of Ventilator-induced Lung Injury in Rabbits

Background: A lung-protecting strategy is essential when ventilating acute lung injury/acute respiratory distress syndrome patients. Current emphasis is on limiting inspiratory pressure and volume. This study was designed to investigate the effect of peak inspiratory flow on lung injury.

Methods: Twenty-four rabbits were anesthetized, tracheostomized, ventilated with a Siemens Servo 300, and randomly assigned to three groups as follows: 1) the pressure regulated volume control group received pressure-regulated volume control mode with inspiratory time set at 20% of total cycle time, 2) the volume control with 20% inspiratory time group received volume-control mode with inspiratory time of 20% of total cycle time, and 3) the volume control with 50% inspiratory time group received volume-control mode with inspiratory time of 50% of total cycle time. Tidal volume was 30 ml/kg, respiratory rate was 20 breaths/min, and positive end-expiratory pressure was 0 cm H2O. After 6 h mechanical ventilation, the lungs were removed for histologic examination.

Results: When mechanical ventilation started, peak inspiratory flow was 28.8 +/- 1.4 l/min in the pressure regulated volume control group, 7.5 +/- 0.5 l/min in the volume control with 20% inspiratory time group, and 2.6 +/- 0.3 l/min in the volume control with 50% inspiratory time group. Plateau pressure did not differ significantly among the groups. Gradually during 6 h, Pao2 in the pressure regulated volume control group decreased from 688 +/- 39 to a significantly lower 304 +/- 199 mm Hg (P < 0.05) (mean +/- SD). The static compliance of the respiratory system for the pressure regulated volume control group also ended significantly lower after 6 h (P < 0.05). Wet to dry ratio for the pressure regulated volume control group was larger than for other groups (P < 0.05). Macroscopically and histologically, the lungs of the pressure regulated volume control group showed more injury than the other groups.