Comparison of the Effect of Proanthocyanidin Surface Treatments on Shear Bond Strength of Different Cements.

This study aimed to compare the effect of proanthocyanidin-rich grape seed extract (Pa-rich GSE) in two different concentrations on the bond strength to dentin tissue for four different cement groups (resin cement (P), resin modified glass ionomer cement (K), calcium aluminate glass ionomer cement (C), glass ionomer cement (G)). One hundred and eighty dentin surfaces of the extracted molar teeth placed on acrylic cylinders were divided into 12 groups randomly (n = 15). Each cement group was further divided into control (CP, CC, CK, CG), 6.5% Pa-rich GSE (P6.5, C6.5, K6.5, G6.5) and 12.5% Pa-rich GSE (P12.5, C12.5, K12.5, G12.5) subgroups. In accordance with the manufacturer's recommendations the cements were applied. After shear bond tests, surfaces were examined under a stereomicroscope. Median shear bond strength (in MPa) of CP, CK, CC, CG groups were 14.13, 7.05, 4.87, 3.86; for the P6.5, G6.5, C6.5, K6.5 groups they were 13.98, 13.42, 6.21, 3.27; and for the P12.5, C12.5, K12.5, G12.5 groups they were 15.08, 5.40, 3.10, 0.00, respectively. CK and K6.5 groups showed a significant difference from the K12.5 group (p < 0.05). Also, CG, G6.5 and G12.5 groups were found statistically different from each other (p < 0.05). Applied to the dentin surface, 6.5% Pa-rich GSE enhanced the bond strength of glass ionomer cements.

Pre- and post-surgery treatments in rectal cancer: a long-term single-centre experience.

BACKGROUND: Our study evaluated long-term survival outcomes in rectal cancer patients treated with preoperative radiotherapy, and the impact on survival of concomitant and postoperative adjuvant chemotherapy (ctx), among other prognostic factors. METHODS: The study included 196 patients [median age: 58 years (range: 20-86 years); 63.0% men] with locally advanced rectal carcinoma and, in some cases, resectable liver metastasis. Rates of distant metastasis and local recurrence and of 5-year distant metastasis-free survival (dmfs) and overall survival (os) were determined. RESULTS: The 5-year os rate was 57.0%, with a median duration of 81.5 months (95% confidence interval: 73.7 months to 89.4 months), and the 5-year dmfs rate was 54.1%, with a median duration of 68.4 months (95% confidence interval: 40.4 months to 96.4 months). Prognostic factors for higher os and dmfs rates were downstaging (p = 0.013 and p = 0.005 respectively), radiotherapy dose (50 Gy vs. 56 Gy or 45-46 Gy, both p = 0.002), and concomitant ctx use (p = 0.004 and p = 0.001) and type (5-fluorouracil-leucovorin-folinic acid vs. tegafur-folinic acid, p = 0.034 and p = 0.043). Adjuvant ctx after neoadjuvant long-term concomitant chemoradiotherapy (ccrt) and surgery was associated with better 5-year os rates for postoperative T0-T3 disease (p = 0.003) and disease at all lymph node stages (p = 0.001). CONCLUSIONS: Our findings revealed a favourable survival outcome with long-term fractionated irradiation and concomitant 5-fluorouracil-based ctx, achieving 5-year os and dmfs rates of 57.0% and 54.1% respectively. Preoperative administration of radiotherapy (50 Gy) and postoperative adjuvant ctx were associated with a significant survival benefit. Radiation doses above 50 Gy and the interval between ccrt and surgery had no significant effect on survival.

Quercetin protects radiation-induced DNA damage and apoptosis in kidney and bladder tissues of rats.

Ionizing radiation (IR) can induce cell damage and cell death through the reactive oxygen species generated by radiolytic hydrolysis. The present study was aimed to determine the possible protective effects of quercetin, a well-known antioxidant agent, against IR-induced bladder and kidney damage in rats. Sprague-Dawley rats were exposed to 8-Gy whole-abdominal IR and given either vehicle or quercetin (20 mg/kg, ip). Rats were decapitated at either 36 h or 10 days following IR, where quercetin or vehicle injections were repeated once daily, and kidney and bladder samples were obtained for the determination of myeloperoxidase and caspase-3 activities, an index of tissue neutrophil infiltration and apoptosis, respectively. Radiation-induced inflammation was evaluated through tissue cytokine, TNF-α levels. In order to examine oxidative DNA damage, tissue 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. All tissues were also examined microscopically. In the saline-treated irradiation groups, myeloperoxidase and caspase-3 activities, 8-OHdG and TNF-α levels were found to be increased in both tissues (p < 0.05). In the quercetin-treated-IR groups, all these oxidant responses were prevented significantly (p < 0.05). The present data demonstrate that quercetin, through its free radical scavenging and antioxidant properties, attenuates irradiation-induced oxidative organ injury, suggesting that quercetin may have a potential benefit in radiotherapy by minimizing the adverse effects and will improve patient care.

Investigation into the role of the cholinergic system in radiation-induced damage in the rat liver and ileum.

It has been previously shown that acetylcholine (ACh) may affect pro-inflammatory and anti-inflammatory cytokines. The role of the cholinergic system in radiation-induced inflammatory responses and tissue damage remains unclear. Therefore, the present study was designed to determine the radio-protective properties of the cholinergic system in the ileum and the liver of rats. Rats were exposed to 8-Gy single-fraction whole-abdominal irradiation and were then decapitated at either 36 h or 10 d post-irradiation. The rats were treated either with intraperitoneal physiological saline (1 ml/kg), physostigmine (80 µg/kg) or atropine (50 µg/kg) twice daily for 36 h or 10 d. Cardiac blood samples and liver and ileal tissues were obtained in which TNF-α, IL-1ß and IL-10 levels were assayed using ELISA. In the liver and ileal homogenates, caspase-3 immunoblots were performed and myeloperoxidase (MPO) activity was analyzed. Plasma levels of IL-1ß and TNF-α increased significantly following radiation (P < 0.01 and P < 0.001, respectively) as compared with non-irradiated controls, and physostigmine treatment prevented the increase in the pro-inflammatory cytokines (P < 0.01 and P < 0.001, respectively). Plasma IL-10 levels were not found to be significantly changed following radiation, whereas physostigmine augmented IL-10 levels during the late phase (P < 0.01). In the liver and ileum homogenates, IL-1ß and TNF-α levels were also elevated following radiation, and this effect was inhibited by physostigmine treatment but not by atropine. Similarly, physostigmine also reversed the changes in MPO activity and in the caspase-3 levels in the liver and ileum. Histological examination revealed related changes. Physostigmine experiments suggested that ACh has a radio-protective effect not involving the muscarinic receptors.

Comparative performance analysis of 4 different anti-citrullinated protein assays in the diagnosis of rheumatoid arthritis.

OBJECTIVE: To evaluate the diagnostic performances of 2 recently developed assays, third-generation anti-cyclic citrullinated peptide (anti-CCP3) and anti-mutated citrullinated vimentin (anti-MCV), in comparison to conventional second-generation anti-cyclic citrullinated peptide (anti-CCP2) assay; and to assess a novel fully automated, random-access AxSYM anti-CCP assay for early diagnosis of rheumatoid arthritis (RA). METHODS: A cohort of 176 patients was enrolled in our study; 93 were diagnosed as having RA. The non-RA group consisted of 83 patients including 38 with systemic lupus erythematosus, 17 with primary Sjögren's syndrome, 11 with osteoarthritis, and 17 healthy controls. All were tested for presence of anti-CCP2, anti-CCP3, AxSYM anti-CCP, anti-MCV, and rheumatoid factor (RF)-IgM according to the manufacturers' instructions. RESULTS: Diagnostic performance of the assays revealed the highest area under the curve for the novel AxSYM anti-CCP [89.1; 95% confidence interval (CI) 84.3-93.8], followed by anti-CCP3 (86.7; 95% CI 81.6-91.9), anti-CCP2 (82; 95% CI 75.8-88.3), and anti-MCV (71.9; 95% CI 64.4-79.5). The sensitivities and specificities were 60.2% and 98.8% for anti-CCP2, 61.3% and 97.6% for anti-CCP3, 80.6% and 84.3% for AxSYM anti-CCP, 49.8% and 91.6% for anti-MCV, and 67.8% and 91.6% for RF-IgM, respectively. CONCLUSION: At cutoff of 5 U/ml, AxSYM anti-CCP emerged as a highly sensitive first-line early diagnostic tool for RA, with the greatest discrimination power, above 16 U/ml, in case of positive result. Using a single easily performed automated assay at 2 determined decision limits we were able to diagnose 81% of cases of RA and missing only 1.2%.

Intra-articular hyaluronic acid compared to exercise therapy in osteoarthritis of the ankle. A prospective randomized trial with long-term follow-up.

OBJECTIVE: The goal of this study has been to determine whether hyaluronic acid (HA) or exercise therapy can improve functional parameters in patients with osteoarthritis (OA) of the ankle. METHODS: In a prospective clinical trial, 43 ankles (30 patients) with radiographic Kellgren Lawrence grade III OA were randomized to receive three intra-articular HA injections, with one-week interval of or exercise therapy for six weeks. Patients were evaluated by the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale and followed-up after 12 months. RESULTS: Total AOFAS Ankle-Hindfoot score of OA patients has improved in both groups, varying from 61.6+/-16.8 to 90.1+/-9.7 with HA treatment and from 72.1+/-16.6 to 87.5+/-17.5 using exercise therapy at the end of the trial (p<0.01). There were no statistically significant differences between the groups. CONCLUSION: This prospective randomized trial confirmed that, both HA injections and exercise therapy provide functional improvement. However, larger trials with longer follow-up are necessary for more definite conclusions.

Clinical trial: insulin-sensitizing agents may reduce consequences of insulin resistance in individuals with non-alcoholic steatohepatitis.

BACKGROUND: Currently, although only a few therapies normalize the liver test abnormalities with/without improving the liver histology, no pharmacologic therapy has proved to be effective for the treatment of non-alcoholic steatohepatitis. AIM: To investigate the role of insulin sensitizers in the treatment of individuals with non-alcoholic steatohepatitis (NASH). METHODS: A total of 74 individuals with NASH (male/female, 44/30; mean age, 47.2 +/- 9.0 years) were enrolled. Participants were divided into two distinct groups: group 1 (n = 25) participants were administered a conventional diet and exercise programme while those in group 2 (n = 49) were administered the diet and exercise programme plus insulin sensitizers. RESULTS: With respect to baseline metabolic, biochemical and histological parameters, no significant differences were observed between the two groups (P > 0.05). Insulin sensitizers significantly improved metabolic parameters (homeostasis model assessment-insulin resistance score, P < 0.05), serum aminotransferase levels [aspartate aminotransferase (AST): 45.9 +/- 24.2 to 33.3 +/- 17.7 IU/L, P < 0.01; alanine aminotransferase (ALT): 78.2 +/- 46.3 to 47.3 +/- 34.5 IU/L, P < 0.001] and histological features (median non-alcoholic fatty liver disease activity score: 5.0-3.0, P = 0.01), while diet and exercise improved serum aminotransferase levels (AST: 39.3 +/- 11.1 to 30.0 +/- 8.6 IU/L, P < 0.01; ALT: 66.9 +/- 28.9 to 42.0 +/- 16.2 IU/L, P < 0.001) at the end of the 48 weeks when compared to baseline. Insulin sensitizers improved the high-sensitivity C-reactive protein levels (P < 0.01). No serious adverse effects of insulin sensitizers were observed. CONCLUSION: Insulin sensitizers can lead to improvement in metabolic, biochemical and histological abnormalities of NASH as a result of improved insulin sensitivity.

Treatment of chronic delta hepatitis with lamivudine vs lamivudine + interferon vs interferon.

Chronic delta hepatitis is the most severe form of chronic viral hepatitis for which interferon (IFN) is the only available treatment. In 39 patients (25 were treatment-naïve, 14 had previously used IFN), efficacy of 1-year treatment with IFN (9 MU, t.i.w.) or lamivudine (LAM; 100 mg, q.d.) alone was compared with IFN and LAM combination (2 months of LAM to be followed by combination treatment). IFN monotherapy was given only to treatment-naïve patients. In both treatment-naïve and previous IFN users, end of treatment virological and biochemical responses were similar with IFN-LAM combination and superior to LAM monotherapy (P < 0.05). Improvement in liver histology occurred more often with IFN +/- LAM than with LAM alone (P < 0.05). In treatment-naïve patients, combination treatment was not superior to IFN monotherapy. After treatment discontinuation, virological and biochemical response rates decreased in LAM and IFN combination and IFN monotherapy. On treatment virological response at month 6 of treatment predicted sustained virological response. The results of this study suggest that addition of LAM to IFN for the treatment of delta hepatitis is of no additional value and that both treatment modalities are superior to LAM monotherapy.

Comparison of the Sit-to-Stand Test with 6 min walk test in patients with chronic obstructive pulmonary disease.

OBJECTIVE: To discuss the utility of Sit-to-Stand Test (STST) compared to the 6min walking test (6MWT) for the evaluation of functional status in patients with chronic obstructive pulmonary disease (COPD). SUBJECTS: Fifty-three patients with stable COPD (mean forced expiratory volume in 1s (FEV(1)) 46+/-9% predicted, mean age 71+/-12 year) and 15 healthy individuals (mean FEV(1) 101+/-13% predicted and mean age 63+/-8) were included. INTERVENTIONS: Functional performance was evaluated by STST and 6MWT. During the tests, severity of dyspnea (by Modified Borg Scale), heart rate, pulsed oxygen saturation (SpO(2), by Modified Borg Scale) (by pulse oxymeter), blood pressure were measured. The pulmonary function (by spirometry), quadriceps femoris muscle strength (by manual muscle test) and quality of life (by Nottingham Health Profile Survey) were evaluated. RESULTS: The STST and 6MWT results were lower in COPD group than the healthy group (P<0.05). During the 6MWT the rise in the heart rate, systolic blood pressure and the decrease in SpO(2) were statistically significant according to STST in COPD groups (P<0.05). The STST and 6MWT were strongly correlated with each other in both groups (P<0.05). Similarly, they were correlated with age, quality of life, peripheral muscle strength and dyspnea severity in COPD groups (P<0.05). CONCLUSION: Similar to 6MWT, STST is also able to determine the functional state correctly. Additionally, it produces less hemodynamical stress compared to the 6MWT. In conclusion, STST can be used as an alternative of the 6MWT in patients with COPD.

Sexual dysfunctions in HCV patients and its correlations with psychological and biological variables.

The frequency of sexual dysfunction (SD) is not very well known in patients with chronic hepatitis C. In this study, the prevalence of SD and its correlations with psychological and biological variables was assessed in 46 HCV positive patients. The mean age of patients was 46.4+/-9.4 y; the mean duration of HCV infection was 43.4+/-34.0 months; 52% were male; 89% were living with a spouse. SD was assessed using the Arizona Sexual Experiences Scale (ASEX), the level of anxiety and depression measured with the Hospital Anxiety and Depression Scale (HADS). Biochemical parameters were also assessed. Overall, as indicated by ASEX criteria, SD was observed in 35% of our patients. Of 24 males, 21% described SD; problems with drive (25%), arousal (17%) and erection (17%) were the most frequent complaints. Of 22 female patients, 50% described SD; problems with drive (55%) arousal (50%), and reaching orgasm (59%) were the most frequent complaints. Total ASEX scores were correlated with age (P<0.07, significant at trend level), education (P<0.001), and was higher in female patients (P<0.02). After controlling for the effects of age, sex, education, duration of HCV and marital status, depression levels could still significantly predict the SD (P<0.05). Moreover, even after controlling the effects of all other variables, gamma glutamyl transpeptidase (GGT) levels could predict the SD status of the patients (P<0.05). Our results indicate that the prevalence of SD was 35% in HCV-infected patients and the level of depression and GGT levels were predictive of patients SD status.

Lamivudine prophylaxis for prevention of chemotherapy-induced hepatitis B virus reactivation in hepatitis B virus carriers with malignancies.

Although hepatitis B virus (HBV) reactivation in HBV carriers undergoing immunosuppressive therapy is clearly documented, the role of antiviral prophylaxis in such individuals is still controversial. The aim of this study was to determine the efficacy of lamivudine prophylaxis in HBV carriers with haemato/oncological malignancies, who receive chemotherapy. Eighteen HBV carriers with malignancy, who were candidates for chemotherapy, were enrolled. Eight subjects (three with leukaemia, four with lymphoma and one with multiple myeloma) were enrolled for prophylactic lamivudine therapy. The remaining 10 patients (six with leukaemia, three with lymphoma and one with breast cancer) were not treated with lamivudine and were used as a control. Lamivudine was administered beginning on the same day as the chemotherapy and was maintained for a year after chemotherapy was discontinued. No HBV-related mortality was observed in either group. In the lamivudine-treated group, none of the subjects had clinical, biochemical or serological evidence of HBV reactivation during the time they were receiving chemotherapy and after their chemotherapy was discontinued. In contrast, five of the 10 HBV carriers not receiving lamivudine therapy experienced a reactivation of HBV infection. This reactivation of HBV was observed during the chemotherapy in four with one individual experiencing a HBV activation 12 months after chemotherapy was discontinued. No lamivudine-related major adverse effects were observed. Hence prophylactic lamivudine treatment in HBV carriers with haemato/oncological malignancy receiving chemotherapy prevents chemotherapy-induced HBV reactivation.

The status of antimicrobial resistance of Helicobacter pylori in eastern Europe.

OBJECTIVE: To evaluate the primary, secondary and combined resistance to five antimicrobial agents of 2340 Helicobacter pylori isolates from 19 centers in 10 countries in eastern Europe. METHODS: Data were available for centers in Bulgaria, Croatia, the Czech Republic, Estonia, Greece, Lithuania, Poland, Russia, Slovenia and Turkey. Susceptibility was tested by agar dilution (seven countries), E test (five countries) and disk diffusion (three countries) methods. Resistance breakpoints (mg/L) were: metronidazole 8, clarithromycin 1, amoxicillin 0.5, tetracycline 4, and ciprofloxacin 1 or 4 in most centers. Primary and post-treatment resistance was assessed in 2003 and 337 isolates respectively. Results for 282 children and 201 adults were compared. RESULTS: Primary resistance rates since 1998 were: metronidazole 37.9%, clarithromycin 9.5%, amoxicillin 0.9%, tetracycline 1.9%, ciprofloxacin 3.9%, and both metronidazole and clarithromycin 6.1%. Isolates from centers in Slovenia and Lithuania exhibited low resistance rates. Since 1998, amoxicillin resistance has been detected in the southeastern region. From 1996, metronidazole resistance increased significantly from 30.5% to 36.4%, while clarithromycin resistance increased slightly from 8.9% to 10.6%. In centers in Greece, Poland, and Bulgaria, the mean metronidazole resistance was slightly higher in adults than in children (39% versus 31.2%, P > 0.05); this trend was not found for clarithromycin or amoxicillin (P > 0.20). Post-treatment resistance rates exhibited wide variations. CONCLUSIONS: In eastern Europe, primary H. pylori resistance to metronidazole is considerable, and that to clarithromycin is similar to or slightly higher than that in western Europe. Resistance to amoxicillin, ciprofloxacin and tetracycline was detected in several centers. Primary and post-treatment resistance rates vary greatly between centers.

Preliminary evaluation of salivary pellicle on nickel-chromium alloy in vivo.

OBJECTIVE: The composition of the salivary interface (pellicle) between dental restorations and oral mucosa may be critical to the biocompatibility of the restoration. The purpose of this study was to examine the molecular composition of the salivary pellicle on nickel-chromium alloy in vivo. METHOD AND MATERIALS: The molecular components of nickel-chromium pellicle was examined with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analyses. RESULTS: Only limited numbers of salivary proteins were found to participate in the formation of nickel-chromium pellicle in vivo. Salivary amylase and secretory immunoglobulin A were among the proteins identified in the pellicle. CONCLUSION: In vivo, nickel-chromium pellicle consists of selectively adsorbed salivary proteins. Because both salivary amylase and secretory immunoglobulin A are antimicrobial proteins, it is possible that they play a role in modulating the microbial flora on the nickel-chromium prosthesis.

The effect of trimetazidine on the survival of rat island skin flaps subjected to ischemia-reperfusion injury.

The effect of trimetazidine (TMZ) on flap ischemia-reperfusion injury was investigated in rat inferior epigastric artery flaps. Twenty-six rats, divided into four experimental groups-nonischemic group (group 1, N = 5), ischemic control group (group 2, N = 7), preischemic TMZ-treated group (group 3, N = 7), and postischemic TMZ-treated group (group 4, N = 7)-were used. Rat inferior epigastric artery flaps were rendered ischemic by occluding the feeding femoral artery, and they were reperfused by releasing the clamps after 11 hours in groups 2 through 4. Group 3 rats were given TMZ (3 mg per kilogram, intravenously) diluted in saline before application of the clamp, and group 4 rats were given TMZ before clamp removal. Flap survival was scored on postoperative day 8. All flaps in the nonischemic control group (group 1) survived completely. The ischemic control group (group 2) demonstrated a 6.3 +/- 4.3% survival area. In the preischemic TMZ group (group 3) the mean survival area was 76.9 +/- 6.1%, and in the postischemic TMZ group (group 4) it was 76.8 +/- 5.6%. TMZ-treated flaps showed a significant increase in survival area regardless of the time of administration (p = 0.001, group 3 vs. group 2; p = 0.001, group 4 vs. group 2). This finding suggests that TMZ has a beneficial effect on the prevention or treatment of arterial ischemic flaps.

Antithrombin III reduces renal ischemia-reperfusion injury in rats.

Few studies have pointed out the relationship between ischemia-reperfusion (IR) injury and the coagulation system. Antithrombin III (AT) has anti-inflammatory effects in IR injury. We investigated the effect of AT supplementation on renal IR injury in rats achieved by clamping of the left renal pedicle for 60 min and subsequent 24-h reperfusion after right nephrectomy. Sprague-Dawley rats were divided into three groups: sham-operated (no IR injury), ischemic controls, and an AT-treated group (250 U/kg before reperfusion). Creatinine values, tissue malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and histopathological damage were investigated after 24 h of reperfusion. In addition, the 7-day survival rates in each group were evaluated. Creatinine and MDA levels and MPO activity were significantly elevated and histopathological damage was more severe in controls than in the sham group (P<0.05). Creatinine and MDA levels and MPO activity were significantly lower and there was less histopathological damage in the AT group than in controls. Accumulation of lipid peroxidation products and neutrophils were significantly inhibited by AT treatment. We conclude that AT may attenuate renal IR injury in rats.

Vacuolating cytotoxic activity of 40 Helicobacter pylori strains isolated from Turkish patients.

In this study we examined the in vitro vacuolating cytotoxic activity of Helicobacter pylori, which is a gram-negative microaerophilic curved bacterium and a causative agent of gastritis, peptic ulcer and gastric ulcer. A vacuolating cytotoxin assay was performed to assess the vacuolating activity of 40 strains (20 gastritis, 11 gastric ulcer, and 9 duodenal ulcer), which were obtained from patients undergoing upper gastrointestinal endoscopy. The Vero cell line was used in the cytotoxic assay. Of the 40 isolates, 24 (12 gastritis, 6 gastric ulcer, 6 duodenal ulcer) were cytotoxic for the Vero cell line at 1:4 and 1:8 dilutions. Thus, vacuolating cytotoxin of H. pylori affects the Vero cell line, but it seems there is no correlation between the positivity of the strains and the risk of any particular H. pylori disease.

Cytoprotective effect of trimetazidine on 60 minutes of intestinal ischemia-reperfusion injury in rats.

Trimetazidine (TMZ), a potent antioxidant agent, has been used to protect the myocardium, liver and kidney from ischemia reperfusion (IR) injury. We investigated the effect of TMZ, a cellular anti-ischemic agent and a free radical scavenger, on 60 min of warm intestinal IR injury in rats. Sprague-Dawley rats were divided into three groups: a sham-operated group (no IR injury, n = 8), an ischemic control group (control, n = 8), and a TMZ-treated group (3 mg/kg, n = 8). Malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and mucosal damage were investigated after 120 min of reperfusion. MDA levels and MPO activity were more elevated and histopathological damage more severe in the control group than in the sham group (P < 0.05). MDA levels and MPO activity were lower and there was less histopathological damage in the TMZ group than in the control group (P < 0.05). Accumulation of lipid peroxidation products and neutrophils in mucosal tissues were significantly inhibited by TMZ treatment. We conclude that pretreatment of rats with TMZ before intestinal ischemia attenuates but does not prevent, histological damage.