The effect of hyperbaric oxygen on apoptosis and proliferation in severe acute pancreatitis

Objectives:

This paper investigates the significance of apoptosis in severe acute pancreatitis (SAP) and the possible modulating effects of hyperbaric oxygen (HBO).

Methods:

Wistar rats (250–350 g) were induced with SAP by biliopancreatic infusion of 4% sodium taurocholate. Rats were randomized for HBO treatment. Pancreatic tissue was stained for apoptosis with immunohistochemistry (anti-CASPASE-3 antibody and TUNEL), and histopathology haematoxylin and eosin (H&E). Acini were stained for proliferation with an anti-KI67 antibody. ImageProPlus was used to quantify apoptosis and proliferation in acinar cells. Statistical analysis was performed with two-independent-sample t-test or non-parametric Mann–Whitney test.

Results:

In normal acini there is a low rate of apoptosis (0.165 ± 0.157%, 0.181 ± 0.168%, 0.130 ± 0.298% in CASPASE-3, H&E and TUNEL, respectively) and proliferation (0.951 ± 0.926%) (mean ± standard deviation [SD]). When compared with normal, apoptosis (CASPASE-3: 1.28 ± 1.12%, P= 0.008; 2.40 ± 3.04%, P= 0.101; 1.23 ± 0.87%, P= 0.091; H&E: 0.47 ± 0.36%, P= 0.051; 0.69 ± 0.63%, P= 0.001; 0.68 ± 0.28%, P= 0; TUNEL: 1.08 ± 1.42%, P= 0; 1.96 ± 1.87%, P= 0; 2.36 ± 2.26%, P= 0) and proliferation (1.96 ± 1.89%, P= 0.187; 1.73 ± 1.76%, P= 0.165; 1.36 ± 1.40%, P= 0.571) were increased on days 1, 2 and 3 post-induction, respectively. In comparison with the untreated controls, HBO increased apoptosis on day 1 (CASPASE-3: 3.11 ± 1.97%, P= 0.04; H&E: 0.97 ± 0.76%, P= 0.005) and day 2 (TUNEL: 3.61 ± 3.05%, P= 0.034). Treatment with HBO increased proliferation (3.04 ± 3.14%, P= 0.519; 7.33 ± 7.55%, P= 0.153) on days 2 and 3, respectively, compared with the untreated controls.

Conclusions:

During SAP, acini apoptosis and proliferation were increased. Hyperbaric oxygen therapy may improve the condition of SAP by promoting apoptosis and proliferation.     

Efficacy of lamivudine on hepatitis B viral status and liver function in patients with hepatitis B virus‐related hepatocellular carcinoma

Background/Aims: Treatment of patients with hepatocellular carcinoma (HCC) depends on the tumour extent and underlying liver function. Antiviral therapy with nucleoside/nucleotide analogues has been shown to be effective in improving the liver function of chronic hepatitis B (CHB) patients. We assessed whether lamivudine could induce biochemical and virological improvements in patients with hepatitis B virus‐related HCC. Patients/Methods: Of 148 CHB patients treated with 100 mg/day lamivudine for at least 6 months, 80 had HCC (CHB/HCC group) and 68 did not (CHB group). Biochemical and virological parameters were serially monitored. Results: Compared with the CHB group, the CHB/HCC group was older, had higher male predominance, bilirubin levels and liver cirrhosis rate, and lower albumin and hepatitis B virus (HBV) DNA levels and hepatitis B e antigen (HBeAg) positivity (P<0.05 each). The two groups showed similar cumulative rates of alanine aminotransferase normalization, HBV DNA seroconversion, HBeAg loss and viral breakthrough during 12 months of lamivudine treatment. After 12 months, the CHB/HCC group showed, relative to baseline, increased albumin levels (3.51±0.5 vs. 3.72±0.5 mg/ml) and decreased ascites scores (1.63±0.7 vs. 1.45±0.6) and Child–Pugh scores (6.92±1.9 vs. 6.02±1.38) (P<0.05 each). Conclusion: Lamivudine had comparable antiviral effects both in patients with CHB and CHB/HCC, and improved underlying liver function in the latter group. Treatment of HBV may increase the chance of curative treatments in patients with HBV‐related HCC.     

High prevalence and little change in TSH receptor blocking antibody titres with thyroxine and antithyroid drug therapy in patients with non-goitrous autoimmune thyroiditis

OBJECTIVE We have reevaluated the prevalence and pathogenetic importance of TSH receptor blocking antibodies (TRBAb) in autoimmune hypothyroidism, and investigated the changes in TRBAb activities during thyroxine and antithyroid drug treatment. DESIGN Serum TSH binding inhibitor immunoglobulin (TBII) and thyroid stimulation blocking antibody (TSBAb) were measured serially in all patients with non-goitrous autoimmune thyroiditis (AT) and measured monthly during methimazole treatment in 6 patients. PATIENTS Ninety patients with non-goitrous AT and 95 patients with goitrous AT were entered consecutively into this study. All patients with non-goitrous AT were treated with thyroxine and followed at intervals of 6 months for 2 years initially and then yearly intervals. The duration of follow-up was 1–8 years. Six patients from the TRBAb-positive non-goitrous AT group who were treated with thyroxine were randomly selected and given additional treatments with methimazole (40 mg per day) for 6 months. MEASUREMENTS Serum TBII was measured by 8 radioreceptor assay, TSBAb by using FRTL-5 cells, and antithyroid peroxidase and antithyroglobulin antibodies by radioimmunoassay. RESULTS The prevalences of TBII and TSBAb in non-goitrous AT were 47–8 and 58.9%, respectively, which were significantly higher than those in goitrous AT (6.3% for TBII, 10.5% for TSBAb). All but one patient showed persistent TBII and TSBAb activities during the thyroxine treatment for up to 8 years. A high dose of methimazole (40 mg per day) did not affect the titres of TBII and TSBAb in 5 out of 6 patients with non-goitrous AT tested. However, antithyroid peroxidase and antithyroglobulin antibodies activities were significantly decreased during the methimazole treatment. CONCLUSION The high prevalence of TSH receptor blocking antibodies (TRBAb) suggests that TRBAb may play a major role in the development of hypothyroidism and thyroid atrophy in the vast majority of patients with non-goitrous autoimmune thyroiditis. Most TRBAb activities are stable for at least 8 years and are not affected by thyroxine and antithyroid drug treatment.     

Higher circulating sphingosine 1-phosphate levels are associated with lower bone mineral density and higher bone resorption marker in humans

Context: Several in vivo and in vitro studies suggest that sphingosine-1-phosphate (S1P) is known to act as a coupling factor, to stimulate osteoclastogenesis, to control the migration of osteoclast precursors between the blood and bone, and to stimulate the proliferation, migration, and survival of osteoblasts. Objective: Using the determination of circulating S1P levels, we investigated which kinds of processes may be primarily affected by S1P in humans. Design and Setting: This was a cross-sectional study conducted in two clinical units in Korea. Participants: Men (n = 86), premenopausal women (n = 94), and postmenopausal women (n = 357) participated in the study. Main Outcome Measures: We measured S1P levels and their relationships with bone mineral density, biochemical bone turnover markers, and uncoupling indices. Results: S1P levels were significantly higher in the postmenopausal women than in the premenopausal women and men. High S1P concentrations were significantly associated with low bone mineral density values at some femur sites in the postmenopausal women (P = 0.015 to 0.049), at the lumbar spine in the premenopausal women (P = 0.017), and at all sites in men (P = 0.001 to 0.036) after adjustments with multiple covariates. S1P levels were positively correlated with bone resorption markers (P = 0.003 to 0.049), but not with formation markers in postmenopausal women. Higher S1P levels were associated with lower uncoupling indices (P = <0.001 to 0.048) in postmenopausal women. Conclusion: These findings suggest that S1P may primarily affect bone resorption, resulting in bone loss.     

Study on liver injury models induced by CCl4 D-Gal and ANIT in mice

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Effects of sera from burn patients on human hepatocytic viscoelasticity

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Comparison of clinical and self-reported diagnoses for participants on a community-based arthritis self-management programme

OBJECTIVE: With the advent of community-based arthritis education programmes, it is important to determine the accuracy of participants' self-reported diagnoses. The purpose of this study was to determine the level of agreement between general practitioner (GP)-recorded and self- reported diagnoses of participants attending an Arthritis Self- Management Programme (ASMP). METHODS: Participants enrolling on the ASMP were asked to (a) identify their type of arthritis via a self- administered postal questionnaire and (b) obtain a written confirmation of their diagnosis from their GP. The sample (n = 613) comprised mainly women (83%) with a mean age of 58.8 yr (S.D. 12.6) and a mean disease duration of 15.4 yr (S.D. 12.5). RESULTS: Participants' self-reported diagnoses were confirmed by GPs in 534 cases [87.1%, 95% confidence interval (CI): 84.4 89.8%]. Confirmed diagnoses were reported by 86.9% (95% CI: 83.1-90.7%) of those with osteoarthritis (OA) and 96.1% (95% CI: 93.6 98.6%) of those with rheumatoid arthritis (RA). The concordance rate for all other types of arthritis combined was lower at 60.5% (95% CI: 49.5-71.5%). There were no significant differences with respect to age, gender, education, physical functioning, duration of disease and number of GP visits between those who correctly identified their type of arthritis and those who did not. CONCLUSIONS: This study suggests that the majority of RA and OA participants attending an arthritis education programme can correctly identify their specific type of arthritis.      

Selecting the Best Noninvasive Imaging Test to Guide Treatment After an Inconclusive Exercise Test

The first step towards approaching a patient with an inconclusive stress test is to identify the initial reason why a stress test was ordered and examine what factors led to inconclusive test results. Next, it is important to ask whether the patient will benefit from further testing, as not all patients with inconclusive test results require additional testing. In patients who are at low-to-intermediate risk, it may be useful to perform coronary CT angiography (CTA) to exclude the presence of obstructive coronary atherosclerosis. Among individuals with no prior history of coronary artery disease, a possible advantage of CTA is that if subclinical atherosclerosis is identified, intensification of lifestyle interventions, and often pharmacotherapy, should be advocated. On the other hand, in high-risk patients or individuals that already have coronary artery disease, the primary objective is to quantify the presence and magnitude of ischemia in order to define the potential role of coronary revascularization procedures. This can be achieved by myocardial perfusion imaging using nuclear imaging or cardiac MRI. Alternatively, a functional evaluation to identify stress-induced wall motion abnormalities using stress echocardiography or MRI can be obtained. In selecting which test to obtain, it is important to understand the strengths and limitations of different imaging tests and to consider patient factors (e.g., body habitus) that may influence the accuracy of various tests. In addition, physicians should consider whether there are any other clinical questions that require imaging. For instance, cardiac MRI may be used to evaluate for infiltrative myocardial disease or pericardial disease whereas cardiac CT can evaluate for lung pathology or diseases of the aorta. Finally, any decision regarding what type of additional testing to obtain should also be based on knowing the local expertise and availability of various testing options.