Use of ATP bioluminescence to survey the spread of aerosol and splatter during dental treatments.

Aerosol and splatter produced during dental treatments (ultrasonic scaling and professional mechanical tooth cleaning) are potential sources of infection. Contamination patterns on the mask, goggles, chest and gowned right arm of operators, and on the goggles of patients before and after dental treatments were investigated using ATP bioluminescence analysis. Contamination on every surface tested increased significantly after dental treatment. Maximum contamination was found on the goggles of patients. Aerosol and splatter produced during dental treatments therefore have the potential to spread infection to operators and patients. ATP bioluminescence is a useful tool for monitoring surface contamination.

Hypoxic volume evaluated by 18F-fluoromisonidazole positron emission tomography (FMISO-PET) may be a prognostic factor in patients with oral squamous cell carcinoma: preliminary analyses.

Tumour hypoxia can be detected by 18F-fluoromisonidazole positron emission tomography (FMISO-PET). Few studies have assessed the relationships of new PET parameters, including hypoxic volume (HV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG), with 5-year survival of patients treated surgically for oral squamous cell carcinoma (OSCC). This study evaluated the relationships between these PET parameters and 5-year survival in OSCC patients. Twenty-three patients (age 42-84 years; 15 male, eight female) with OSCC underwent FMISO- and 18F-fluoro-2-deoxyglucose (FDG)-PET computed tomography before surgery. All of them underwent radical surgery and were followed up for more than 5 years. The FDG-PET maximum standardized uptake value (SUVmax), HV, MTV, and TLG were measured. The ability of PET parameters to predict disease-free survival (DFS) and loco-regional recurrence (LR) was evaluated using receiver operating characteristic curve analysis. During the follow-up period, five of the 23 patients (22%) died and six (26%) experienced LR. Although FDG-PET SUVmax was not significantly associated with DFS or LR, HV correlated significantly with both DFS and LR. TLG, but not MTV, was significantly associated with DFS; however neither MTV nor TLG was related significantly to LR. In conclusion, tumour HV may predict outcomes in patients with OSCC.

Hepatitis B surface antigen reduction by switching from long-term nucleoside/nucleotide analogue administration to pegylated interferon.

Hepatitis B surface antigen (HBsAg) reduction during nucleoside/nucleotide analogue (NA) therapy is slow and an alternative strategy for patients receiving ongoing NA to facilitate HBsAg reduction is required. We investigated whether switching to pegylated interferon (PEG-IFN) after long-term NA administration enhances HBsAg reduction. Forty-nine patients who switched from long-term NA to 48 weeks of PEG-IFN alfa-2a were studied. The mean duration of previous NA was 48 months (sequential group). A total of 147 patients who continued NA and matched for baseline characteristics were analysed for comparison (NA continuation group). The treatment response was defined as HBsAg reduction ≥1.0 logIU/mL at the end of PEG-IFN. HBsAg reduction at week 48 was 0.81±1.1 logIU/mL in the sequential group, which was significantly higher than that in the NA continuation group (0.11±0.3 logIU/mL, P < .001). The treatment response was achieved in 29% and 2% of the sequential group and NA continuation group (P < .001), and the odds ratio of sequential therapy for the treatment response was 19 compared with the NA continuation (P < .001). In patients tested positive for hepatitis B e antigen (HBeAg), HBeAg seroconversion was higher in the sequential group (44% vs 8%, P < .001). In HBeAg-negative patients, only patients in the sequential group achieved HBsAg loss. No patient needed to resume NA administration because of HBV DNA increase accompanied by alanine aminotransferase flares. In summary, sequential therapy with PEG-IFN after long-term NA enhances the reduction of HBsAg and may represent a treatment option to promote HBsAg loss.

Monitoring of bacterial contamination of dental unit water lines using adenosine triphosphate bioluminescence.

Bacterial contamination of dental unit waterlines (DUWLs) was evaluated using ATP bioluminescence analysis and a conventional culture method. Water samples (N=44) from DUWLs were investigated for heterotrophic bacteria by culture on R2A agar, which gave counts ranging from 1.4×103 to 2.7×105 cfu/mL. The ATP bioluminescence results for DUWL samples ranged from 6 to 1189 relative light units and could be obtained within 1min; these correlated well with the culture results (r=0.727-0.855). We conclude that the results of the ATP bioluminescence assay accurately reflect the results of conventional culture-based testing. This method is potentially useful for rapid and simple monitoring of DUWL bacterial contamination.

Oxidative stress and antibody levels to periodontal bacteria in adults: the Nagasaki Islands study.

OBJECTIVE: Periodontitis is a chronic inflammatory disease of the tissues supporting the teeth and is caused by subgingival plaque. Systemic increases in reactive oxygen species are involved in pathogenesis of periodontitis. This study addressed the relationship between levels of serum oxidative stress and antibodies against putative periodontopathic bacteria and their association with periodontal conditions, in a community-based study. SUBJECTS AND METHODS: Serum samples were measured for reactive oxygen metabolite (ROM) levels and anti-oxidant capacity. The serum levels of immunoglobulin G (IgG) antibodies to Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Aggregatibacter actinomycetemcomitans (Aa), and Eikenella corrodens (Ec) were determined by ELISA. RESULTS: The participants with greater clinical attachment loss had higher serum ROM levels and IgG antibody titers to Pg. Serum ROM levels were positively correlated with antibody titers to Pg, Pi, and Ec. When the participants with greater probing pocket depth and clinical attachment loss were used as the dependent variables, high ROM levels showed a statistically significant associations in multivariate logistic analyses; the adjusted odds ratios were 2.9 (95% confidence interval = 1.0-8.5) and 6.0 (95% confidence interval = 2.0-17.6), respectively. CONCLUSIONS: It was concluded that an increased oxidative stress may be detrimental to periodontitis in Japanese community-dwelling adults.

Noninvasive estimation of fibrosis progression overtime using the FIB-4 index in chronic hepatitis C.

The FIB-4 index is a simple formula to predict liver fibrosis based on the standard biochemical values (AST, ALT and platelet count) and age. We here investigated the utility of the index for noninvasive prediction of progression in liver fibrosis. The time-course alteration in the liver fibrosis stage between paired liver biopsies and the FIB-4 index was examined in 314 patients with chronic hepatitis C. The average interval between liver biopsies was 4.9 years. The cases that showed a time-course improvement in the fibrosis stage exhibited a decrease in the FIB-4 index, and those that showed deterioration in the fibrosis stage exhibited an increase in the FIB-4 index with a significant correlation (P < 0.001). Increase in the ΔFIB-4 index per year was an independent predictive factor for the progression in liver fibrosis with an odds ratio of 3.90 (P = 0.03). The area under the receiver operating characteristic curve of the ΔFIB-4 index/year for the prediction of advancement to cirrhosis was 0.910. Using a cut-off value of the ΔFIB-4 index/year <0.4 or ≥ 0.4, the cumulative incidence of fibrosis progression to cirrhosis at 5 and 10 years was 34% and 59%, respectively in patients with the ΔFIB-4 index/year ≥0.4, whereas it was 0% and 3% in those with the ΔFIB-4 index/year <0.4 (P < 0.001). In conclusion, measurement of the time-course changes in the FIB-4 index is useful for the noninvasive and real-time estimation of the progression in liver fibrosis.

Cilostazol versus aspirin therapy in patients with chronic dizziness after ischemic stroke.

BACKGROUND: Chronic dizziness is frequently reported by patients in the chronic stage after ischemic stroke. The aim of this study was to determine the efficacy of cilostazol versus that of aspirin for the chronic dizziness that follows ischemic stroke. METHODS: We performed a prospective, randomized, open-label, blinded endpoint trial. One hundred six patients who suffered supratentorial ischemic stroke within the previous 1-6 months and subsequently complained of persistent dizziness without other obvious sequelae were enrolled. Patients were randomly given cilostazol (200mg/day) or aspirin (100mg/day) for 6 months. Rates of improvement in the dizziness were then evaluated. Changes in fixation suppression of the vestibulo-ocular reflex (an indicator of cerebral control over the brainstem reflex related to balance), regional cerebral blood flow (CBF) in the cerebrum, cerebellum, and brainstem; and the Zung Self-Rating Depression Scale (SDS) were also evaluated. RESULTS: Dizziness was significantly improved in the cilostazol group versus the aspirin group (P<0.0001) after the 6-month therapy. The capacity for fixation suppression of the vestibulo-ocular reflex was improved (P<0.0001), and regional CBF in the cerebrum (relative to that in the brainstem [P=0.003] and to that in the cerebello-brainstem [P=0.012]) was increased only in the cilostazol group. There was no statistical difference in the change in SDS scores between the two groups. CONCLUSION: Cilostazol improves the chronic dizziness that follows ischemic stroke and increases supratentorial CBF and cerebral function for adaptation of the brainstem reflex related to the sense of balance.

Relationship between periodontal condition and arterial properties in an adult population in Japan.

UNLABELLED: Oral Diseases (2010) 16, 781-787 OBJECTIVE: This study addressed the relationship between periodontal condition and second derivative of the finger photoplethysmogram (SDPTG) in Japanese adults. SUBJECT AND METHODS: The Community Periodontal Index (CPI) and SDPTG were recorded in 415 subjects (mean age: 44.0 years). For assessing SDPTG, we mainly focused on the ratio of the absolute value of the height of the early negative 'b' wave and ratio of the late re-decreasing 'd' wave to the height of the initial positive 'a' wave, namely the b/a and d/a ratios. RESULTS: The CPI score was positively correlated with the b/a ratio (P < 0.001), and negatively correlated with the d/a ratio (P < 0.001). Logistic regression analysis showed that subjects with CPI scores ≥ 3 were more likely to have a higher level (male > -0.69, female > -0.64) of b/a ratio (Odds ratio = 1.7, P = 0.026) and lower level (male ≤ -0.29, female ≤ -0.32) of d/a ratio (Odds ratio = 2.2, P =0.001) than those with CPI scores 0-2, after adjusting for age, gender, smoking status, pulse rate and presence of hypertension. CONCLUSION: There was a statistical association between the CPI scores and SDPTG indices in Japanese adults.

Effects of topical application of lipopolysaccharide and proteases on hepatic injury induced by high-cholesterol diet in rats.

BACKGROUND AND OBJECTIVE: Topical application of lipopolysaccharide and proteases to the gingival sulcus induced not only periodontal inflammation but also detectable liver changes in rats fed a normal diet. However, these changes in the liver were not sufficient to induce pathological consequences. The purpose of the present study was to investigate whether gingival inflammation-induced liver change would have more dramatic pathological consequences in rats fed a high-cholesterol diet compared with the effect of the high-cholesterol diet alone. MATERIAL AND METHODS: Twenty-four male Wistar rats were divided into four groups. During an 8 week experimental period, two groups were fed a normal diet and the other two were fed a high-cholesterol diet containing 1% cholesterol (w/w) and 0.5% cholic acid (w/w). Four weeks prior to the end of the experimental period, one of each of the dietary groups received daily topical application of lipopolysaccharide and proteases to the gingival sulcus, while the other was treated with pyrogen-free water. RESULTS: In the rats without application of lipopolysaccharide and proteases, the serum level of hexanoyl-lysine, scores of steatosis and inflammation, and concentration of 8-hydroxydeoxyguanosine in liver of rats fed a high-cholesterol diet were higher than in those fed a normal diet. In rats fed a high-cholesterol diet, the scores of steatosis and inflammation and the concentration of 8-hydroxydeoxyguanosine in the liver of rats with application of lipopolysaccharide and proteases were higher than in those without. CONCLUSION: In a rat model, application of lipopolysaccharide and proteases to the gingival sulcus augmented the effect of a high-cholesterol diet on steatosis, inflammation and oxidative damage in the liver.

Relation of dietary preference to bite force and occlusal contact area in Japanese children.

The purpose of this study was to examine the relationship of dietary preference to bite force and occlusal contact area in Japanese elementary school children. A total of 348 children, aged 7-12 years, from two public elementary schools located in Okayama Prefecture, Japan, participated in the study. Clinical examination included decayed, missing and filled teeth (dmft and DMFT), and total numbers of deciduous and permanent teeth. Bite force and occlusal contact area were measured using a pressure-detecting sheet. Dietary preference was assessed using a questionnaire in which the answers were given in like/dislike form. Mann-Whitney U-test and multiple logistic regression analysis were applied to analyse the data. In multiple logistic regression analysis after adjustment for age, gender and total number of teeth present, children who liked cabbage and celery showed significantly higher bite force (P = 0.05 and P < 0.01, respectively) than those who disliked these. Children who liked cabbage and celery also showed higher occlusal contact area (P < 0.05 and P < 0.01, respectively) than those who disliked these. The Japanese elementary school children who liked hard foods such as cabbage and celery showed higher bite force and higher occlusal contact area than those who disliked these foods. A positive attitude towards harder food items might contribute to healthy development of the masticatory apparatus.

Periodontitis-induced lipid peroxidation in rat descending aorta is involved in the initiation of atherosclerosis.

BACKGROUND AND OBJECTIVE: Periodontitis is a risk factor for the development of atherosclerosis. Recent studies indicate that oxidative mechanisms, including lipid peroxidation, are involved not only in periodontitis but also in atherosclerosis. Lipid peroxidation may play an important role in the pathogenesis of atherosclerosis, particularly during its earliest stages. The purpose of this study was to investigate the relationship between lipid peroxidation induced by periodontitis and the initiation of atherosclerosis. MATERIAL AND METHODS: Sixteen rats were randomly divided into two groups of eight rats each. Periodontitis was ligature-induced for 4 wk in the experimental group, whereas the control group was left untreated. After the experimental period, the mandibular first molar regions were resected and then subjected to histological analysis and measurement of hexanoyl-lysine expression as an indicator of lipid peroxidation. Descending aorta was used for measuring the levels of hexanoyl-lysine, reactive oxygen species and lipid deposits, and for real-time polymerase chain reaction microarray analysis. The level of hexanoyl-lysine was also measured in serum. RESULTS: In the experimental group, the levels of hexanoyl-lysine in periodontal tissue and serum increased. Only aorta samples in the experimental group showed lipid accumulation, with increased expression of hexanoyl-lysine, reactive oxygen species and oxidative stress-related genes (including nitric oxide synthases 2 and 3), whereas the superoxide dismutase 1 gene level was down-regulated. CONCLUSION: In a ligature-induced periodontitis rat model, increased lipid peroxidation was found in serum and aorta as well as in periodontal tissue. Atherosclerosis-related gene expression and histological changes were also stimulated. Periodontitis-induced lipid peroxidation in the aorta may be involved in the early stage of atherosclerosis.

Effects of ethanol consumption on periodontal inflammation in rats.

Studies suggest a correlation between ethanol consumption and periodontal disease. We hypothesized that elevated levels of blood reactive oxygen species following ethanol consumption may increase inflammation in periodontal tissue. Rats were divided into 4 groups (6-7 rats/group). Two groups were fed an ethanol-containing liquid diet, and 2 groups were fed a pair-fed control diet. In one of each dietary group, periodontitis was ligature-induced, while the other group was left unligated. Chronic ethanol feeding alone decreased the ratio of reduced/oxidized glutathione and increased 8-hydroxydeoxy-guanosine and tumor necrosis factor (TNF)-alpha levels in the gingiva. Blood hydroperoxides were also increased. In ligature-induced periodontitis lesions, ethanol feeding enhanced polymorpho-nuclear leukocyte infiltration and TNF-alpha expression. The results suggest that chronic alcohol consumption increased periodontal inflammation, oxidative damage, and TNF-alpha production and had an additive effect on polymorphonuclear leukocyte infiltration and gingival oxidative damage, increasing the severity of periodontal inflammation in the ligature model.

SPET in cardiology. Diagnosis, prognosis, and management of patients with coronary artery disease.

Stress myocardial perfusion imaging has been considered as a most valuable means for diagnosis and treatment strategy in patients with suspected and known coronary artery disease. (99m)Tc perfusion imaging agents provide excellent myocardial perfusion images. In addition, greater photon flux from the tracer permits simultaneous assessment of regional perfusion and function with use ECG-gated acquisition. Gated SPET imaging technique has a potential for higher diagnostic accuracy for diagnosis of coronary artery disease and assessment of the disease severity. In addition, radionuclide imaging plays an important role to differentiate reversible ischemic myocardium which may improve LV function after revascularization from irreversible scar in patients with history of myocardial infarction. While FDG-PET is considered as a most reliable means for myocardial assessment, SPET imaging has been widely used for the viability assessment, with gaining higher accuracy for predicting reversible ischemia. Recently a variety of new radiopharmaceutical agents have been introduced to probe myocardial function in vivo. [(123)I]BMIPP, a branched fatty acid analog, has been used for metabolic imaging using SPET. Less uptake of BMIPP than perfusion is often observed in the ischemic myocardium. Such a perfusion metabolic mismatch which seems to be similarly observed in FDG-PET is identified in the stunned or hibernating myocardium with regional dysfunction. Severe ischemia is identified as reduced BMIPP uptake at rest, suggesting its role as an ischemic memory imaging. These new techniques will provide insights into new pathological states in the ischemic heart disease and enable to select optimal treatment of these patients.

Isolation and characterization of aminopeptidase from Capnocytophaga granulosa ATCC 51502.

There is evidence that enzymes from the genus Capnocytophaga play a role in dental calculus formation. Although most of the species in the genus produce aminopeptidases, there is a paucity of data on the purification and characterization of the enzyme, except in the case of Capnocytophaga gingivalis. The aim of this study was to purify aminopeptidase from culture supernatant of Capnocytophaga granulosa ATCC 51502, a new species of the genus. Purification was performed using ammonium sulfate fractionation and two chromatographic steps. The aminopeptidase was purified 158,433-fold with a yield of 12.0%. The enzyme appeared to be a trimer with a molecular mass of 270 kDa. The optimal pH of the aminopeptidase was 6.5 and its activity was completely inhibited by incubation at 50 degrees C for 10 min. The enzyme showed maximum specificity for basic amino acids (Arg and Lys) and also hydrolyzed noncharged amino acids (Met, Leu and Ala). Ca(2+), Zn(2+) and Fe(3+) activated the enzyme, while EDTA, Ag(+), Hg(+) and Cu(2+) inhibited it. These results suggest that aminopeptidase of C. granulosa is different from that of C. gingivalis but similar to aminopeptidase B.

Preparation and pharmaceutical evaluation for clinical application of high specific activity S-(-)[11C]CGP-12177, a radioligand for beta-adrenoreceptors.

BACKGROUND: Although S-(-)[C]CGP-12177 is a useful positron emission tomography (PET) ligand for beta-adrenoreceptors, the difficulty in radiolabelling the compound has prevented its extensive clinical application. Recently, we have developed a simple synthesis method for S-(-)[C]CGP-12177. In the present study, we attempted to prepare S-(-)[C]CGP-12177 with a high specific activity for intravenous injection which is feasible for the clinical evaluation of beta-adrenoreceptors. METHODS: The [C]methane produced during irradiation of a N2--H2 (95/5) mixture with an 18 MeV proton beam (20 microA, 30 min) was chlorinated using Cl2 to yield [C]carbon tetrachloride. S-(-)[C]CGP-12177 was synthesized by reacting the diamino precursor with [C]phosgene produced by oxidizing [C]carbon tetrachloride on a Fe--Fe2O3 column. The product was purified by using reversed phase, high-performance liquid chromatography (RP-HPLC) and the radioactive fraction containing S-(-)[C]CGP-12177 was collected and evaporated to dryness. S-(-)[C]CGP-12177 dissolved in physiological saline was sterilized through a 0.22 microm membrane filter. The radiochemical purity and the mass of the compound were determined with RP-HPLC. The residual organic solvents were determined with GC. Tests for sterility and the presence of bacterial endotoxins were also performed. RESULTS: S-(-)[C]CGP-12177 for intravenous injection was prepared in 25 min after the end of bombardment with a yield of 1.5+/-0.2 GBq. Specific activity was found to be 385.4+/-133.0 GBq/ micromol at the end of synthesis (EOS) (n=3). Radiochemical purity was found to be more than 99%. Toluene was not detected in the solution. The ethanol concentration was determined to be 60.3+/-52.5 ppm. Tests for sterility and bacterial endotoxins showed negative results. CONCLUSION: We successfully prepared S-(-)[C]CGP-12177 formulated for intravenous injection with high purity and high specific activity, which is feasible for the clinical evaluation of beta-adrenoreceptors.

Effect of steroids on [18F]fluorodeoxyglucose uptake in an experimental tumour model.

BACKGROUND: It is well known that blood glucose level affects the uptake of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in tumours. Thus, the action of steroids on glucose metabolism may alter blood glucose levels and may affect FDG uptake in tumours in patients treated with steroids. To clarify this point, we determined the effects of steroids on FDG uptake in tumours in a rat model of a malignant tumour. METHODS: Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle. They were fasted overnight and divided into three groups (n=5 in each group): (1) dexamethasone (DEX) pretreated (0.8 mg.kg(-1) body weight, i.m. injection 4 h before FDG i.v. injection); (2) prednisolone (PRE) pretreated (8 mg.kg(-1) body weight, i.m. injection 20 h before FDG i.v. injection); and (3) control (untreated) groups. Radioactivity in tissues was determined 1 h after i.v. injection of FDG. FDG uptake in the tumour was expressed as the percentage of injected dose per gram of tissue after normalization to animal's weight (%ID/g tissue/kg body weight). RESULTS: DEX and PRE pretreatments significantly increased the blood glucose levels to 128% and 145% of the control value. The levels of FDG uptake in the tumour were not significantly affected by DEX and PRE pretreatment (90% and 87% of the control value, respectively) (P=NS). CONCLUSIONS: These results demonstrate that FDG uptake in the tumour was not affected by pretreatment with steroids, in spite of a slight elevation in blood glucose level.

Prediction of functional recovery after coronary bypass surgery using quantitative gated myocardial perfusion SPECT.

Previous studies have demonstrated that myocardial perfusion imaging using 99mTc-tetrofosmin at rest allows viability assessment similar to that obtained with 201Tl imaging and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). The simultaneous assessment of perfusion and regional function is now available by quantitative gated myocardial perfusion single-photon emission computed tomography (SPECT). This study was designed to evaluate the utility of quantitative values of wall motion and wall thickening, calculated by quantitative gated myocardial perfusion SPECT, for the prediction of functional recovery after coronary bypass grafting (CABG). Fifty-six patients with coronary artery disease scheduled for CABG were included prospectively. All patients underwent 99mTc-tetrofosmin gated SPECT imaging at rest preoperatively and 3 months after CABG. The myocardium was divided into nine segments and the average quantitative values of regional perfusion (percentage uptake) (%), wall motion (mm) and wall thickening (%) were determined automatically using quantitative gated SPECT (QGS) software. The wall motion score was defined visually using a four-point scale (0, normal; 3, akinesis), and segments with severe asynergy (score of 2 or 3) with patent grafts were assessed. Of 77 segments with severe asynergy, 56 segments showed improved wall motion and 21 segments did not improve after CABG. The area under the receiver operating characteristic curve of wall thickening for the prediction of functional recovery was significantly higher (0.92) than that of the percentage uptake (0.77, P<0.017) or wall motion (0.60, P<0.0001). When each analysis used the optimal threshold, the wall thickening analysis (>or=10%) had a sensitivity of 95% and a specificity of 81%. These values tended to be higher than those of the percentage uptake (sensitivity, 86%; specificity, 67%). The wall motion analysis (>or=1.5 mm) had a significantly lower sensitivity of 75% and specificity of 43% than the wall thickening analysis (P=0.0038 and P=0.011, respectively). The results indicate that wall thickening, calculated by QGS software, may be more useful than regional perfusion or wall motion analysis for the prediction of functional recovery after CABG. The areas of asynergy with relatively preserved wall thickening may have the potential for improved function despite severely decreased perfusion.

Transient left ventricular dysfunction in ischaemic myocardium after stress: comparative study with exercise and pharmacological stress gated myocardial single photon emission computed tomography.

In ischaemic heart disease patients, transient left ventricular dysfunction is observed due to post-exercise stunning. The aim of this study was to determine whether transient left ventricular dysfunction could also be seen after short-acting pharmacological stress (adenosine triphosphate). A 1 day rest/stress gated myocardial single photon emission computed tomography was performed on 362 patients suspected of having ischaemic heart disease by exercise (n=199) or short-acting pharmacological stress (n=163). Left ventricular ejection fraction were estimated both at rest and stress. Based on perfusion findings, patients were subdivided into ischaemia, fixed defect and normal group. For the ischaemia and fixed defect group, left ventricular ejection fraction after stress was significantly decreased compared with the resting value by exercise stress (ischaemia group, 57.5+/-11.0 vs 60.4+/-10.4; fixed defect group, 47.7+/-16.7 vs 49.6+/-16.8; P<0.01), but not by pharmacological stress (ischaemia group, 55.8+/-13.4 vs 57.1+/-13.8; fixed defect group, 50.8+/-13.5 vs 50.6+/-13.1; P=NS). In the normal group, left ventricular ejection fraction after stress was not significantly changed by either exercise (65.7+/-10.4 vs 66.8+/-10.2; P=NS) or pharmacological stress (63.0+/-11.7 vs 64.0+/-12.1; P=NS). It is concluded that a transient decrease in left ventricular ejection fraction after stress was observed following post-exercise, not following a short-acting pharmacological stress in patients showing perfusion abnormalities. Transient left ventricular dysfunction may be the result of post-exercise stunning, not from subendocardial hypoperfusion induced by short-acting pharmacological stress.

Quantitative analysis of hyperosmotic and hypothermic blood-brain barrier opening.

Hyperosmotic opening of the blood-brain barrier (BBB) by mannitol is being used to enhance drug transport in human brains. Recently, cooling of the solution has been reported to have potential to open the BBB. However, the mechanism in barrier opening and closure remains elusive. We studied the rapid changes in cerebrovascular permeability after hyperosmotic and hypothermic BBB opening in rats, and then demonstrated that the Na+/Ca++ exchange blocker (KB-R7943) prolongs opening. BBB opening was attained by using intra-arterial infusion of hyperosmotic mannitol (1.6 M) and 1.1 M mannitol (which is less hyperosmotic than commonly used mannitol) at 4 degrees in Sprague-Dawley (SD) rats. To measure the changes in cerebrovascular permeability, perfusate-containing [14C]-sucrose was infused intra-arterially at different time points following hyperosmotic and hypothermic stress. Cerebrovascular permeability was then measured with the in situ brain perfusion technique. 1.6 M Mannitol produced opening of the BBB but the duration of the opening was less than 30 minutes. Use of 1.1 M Mannitol at 4 degrees indicated the same results. We then investigated the effect of a Na/Ca ion exchange blocker (KB-R7943) in both hyperosmotic and hypothermic BBB opening. KB-R7943 extended BBB opening up to 30 min without affecting the peak level of BBB permeability at 5 minutes. Our findings represent important experimental information regarding pharmacological manipulation of BBB opening. The possibility of prolonging the transient opening of the BBB has major clinical implications.