Effects of Acute Arterial Bleeding on Renal Sympathetic Nerve Activity in Young and Old Anesthetized Rats

We compared the change in renal sympathetic nerve activity (RNA) during hemorrhage in young and old rats. Young (10 weeks) and old (80 weeks) male Wistar rats were anesthetized, and RNA together with arterial pressure (AP) and heart rate (HR) were measured under spontaneous respiration. Acute arterial bleeding, lm1Jl00g body weight, was carried out to induce hypotension and hypovolemia. With bleeding, mean AP (MAP) decreased from 110 ± 12 to 23 ± 11mmHg (mean ± SEM) and from 93 ± 15 to 15 ± 6mmHg in young and old rats, respectively. The difference in the change of MAP between the young and old rats was not significant. With bleeding, mean RNA increased by 46 ± 21 % and 20 ± 16% in young and old rats, respectively. The increase in mean RNA of the old rats was significantly lower than that of the young rats. We estimated the gain of the barocepter-renal sympathetic nervous system by using the formula ∆RNA/RNA/∆MAP/MAP. The gain was 0.61 ± 0.34 and 0.23 ± 0.18 in young and old rats, respectively. The difference in the gain was statistically significant (p<0.05). We concluded that the gain of baroceptor-sympathetic nerve system in acute arterial hemorrhage is attenuated with aging

Development of nuclear DNA markers to characterize genetically diverse groups of Misgurnus anguillicaudatus and its closely related species

Repetitive DNA sequences, ManDra and ManBgl, were isolated from the DraI and BglII digests of the genomic DNA of Misgurnus anguillicaudatus, respectively. A primer set of ManDra distinguished two genetically different groups (A and B) of M. anguillicaudatus by specific electrophoretograms. A primer set of ManBgl amplified the DNA of M. anguillicaudatus and M. mizolepis. The individuals of M. anguillicaudatus were divided into two groups depending on the fragment sizes, in which the groups A and B (B-1 and B-2) showed 400 and 460 bp, respectively. M. mizolepis was distinguished by a different pattern (400-, 460-, and 510-bp fragments). PCR-RFLP analyses of recombination activating gene 1 gave a clear difference between A or B-2 (443-bp fragment) and B-1 groups (296- and 147-bp fragments). Clonal lineages and hybrids between B-1 and B-2 groups could be identified by appearance of three fragments (443, 296, and 147 bp). The combined analyses using the above three nuclear markers discriminated among nuclear genomes of genetic groups (A, B-1 and B-2) of M. anguillicaudatus and M. mizolepis. In several localities, natural hybridizations between the group B-1 and B-2 loaches and introgressions of clonal mitochondrial genomes into the group B-1 loaches were detected

Predictors and impact of time to clinical stability in community-acquired pneumococcal pneumonia

SummaryBackgroundA clinical stability (CS) evaluation is thought to be important in community-acquired pneumonia (CAP) treatment, but evidence concerning the time to CS (TCS) remains lacking.MethodsAmong consecutive patients hospitalized with pneumococcal pneumonia, relationships between TCS and other clinical outcomes were examined, and predictors and a predictive TCS score were derived from patient characteristics on admission.ResultsA total of 144 patients were enrolled, including 46% and 27% with moderate and severe pneumonia, respectively, defined by the pneumonia severity index (PSI). The median TCS was 2 days, and was significantly correlated with the length of hospital stay (r = 0.595); a longer TCS was significantly associated with the more presence of poor clinical outcomes and ICU stays (adjusted odds ratios: 1.359 and 1.366, respectively). A multivariate Cox proportional hazard model revealed an absence of bilateral pneumonia (hazard rate (HR): 2.107) or bacteremia (HR: 2.520), and mild or moderate pneumonia (HR: 2.798 and 2.515, respectively, versus severe) as predictors of CS. A predictive score had moderate discriminating power for the prolonged TCS (area under the curve: 0.76), and provided similar predictive values for poor clinical outcomes and ICU stays. A score of 3 or more points indicated the prolonged TCS, with a sensitivity and specificity of 73.3% and 70.9%, respectively.ConclusionsBecause TCS has a significant relationship with other clinical outcomes of pneumococcal CAP, the prediction of TCS might lead to the prevention of complications or an earlier transition to oral therapy. Future studies are warranted to validate these results

Low frequency of intracranial progression in advanced NSCLC patients treated with cancer immunotherapies

Intracranial metastases are common in nonsmall-cell lung cancer (NSCLC) patients, whose prognosis is very poor. In addition, intracranial progression is common during systemic treatments due to the inability to penetrate central nervous system (CNS) barriers, whereas the intracranial effects of cancer immunotherapies remain unclear. We analyzed clinical data to evaluate the frequency of intracranial progression in advanced NSCLC patients treated with PD-1 blockade therapies compared with those treated without PD-1 blockade therapies, and found that the frequency of intracranial progression in advanced NSCLC patients treated with PD-1 blockade therapies was significantly lower than that in patients treated with cytotoxic chemotherapies. In murine models, intracranial rechallenged tumors after initial rejection by PD-1 blockade were suppressed. Accordingly, long-lived memory precursor effector T cells and antigen-specific T cells were increased by PD-1 blockade in intracranial lesions. However, intracranial rechallenged different tumors are not suppressed. Our results indicate that cancer immunotherapies can prevent intracranial progression, maintaining long-term effects intracranially as well as systemically. If intracranial recurrence occurs during the treatment with PD-1 blockade therapies, aggressive local therapies could be worthwhile