Pregnancy: Atrial natriuretic peptide antagonizes the contractile effect of angiotensin II in the human uterine artery

The regulatory peptides angiotensin II (Ang II) and atrial natriureticpeptide (ANP) are believed to play important roles in the pathogenesisof pre-eclampsia. The interactions between Ang II, ANP and noradrenaline(NA) were studied in vitro on the human uterine artery. BothAng II and NA contracted the isolated vessel in a concentration-dependentway. At high doses a decrease in the contractile force inducedby Ang II but not NA was encountered. ANP inhibited the smoothmuscle activity elicited by Ang II, resulting in a dextroshiftof the concentration-response curve, and a decrease in bothE_max (the maximum contractile response) and pD2 (the negativelogarithm of the agonist concentration inducing 50% of the E_max)for Ang II. The results might indicate a specific antagonismbetween Ang II and ANP, probably at the post-receptor level.ANP did not induce any significant change in pD₂ of the concentration-responsecurve for NA. Only at the highest dose of ANP (10^–7 M)was E_max depressed. Thus, the results only indicate a weak antagonisticrelationship between NA and ANP in the human uterine artery.     

Schilddrüsenfunktionsuntersuchungen bei Säuglingsatrophie

Zusammenfassung Verfasser untersuchten bei 16 atrophischen und 10 eutrophen Säuglingen die an Serumeiweiß gebundenen Jodwerte, den Serumcholesterinspiegel sowie die Gesamteiweiß-, Albumin- und Globulinwerte.Die Durchschnittsmenge des an Serumeiweiß gebundenen Jods ist bei an schwerer Atrophie leidenden Säuglingen geringer als bei den eutrophen.Der Serumcholesterinspiegel sowie die Gesamteiweiß-, Albumin- und Globulinwerte zeigen hingegen im Vergleich zwischen atrophischen und eutrophen Säuglingen keine Abweichungen.     

ABCMdb: A database for the comparative analysis of protein mutations in ABC transporters,and a potential framework for a general application

To overcome the pathological phenomena caused by altered function of ABC (ATP Binding Cassette) proteins, their mechanisms of action are extensively investigated, often involving the design of mutant constructs for experiments. Designing mutagenetic constructs, interpreting the result of mutagenetic experiments, and finding individual genetic variants require an extensive knowledge of previously published mutations. To aid the recapitulation of mutations described in the literature, we set up a database of ABC protein mutations (ABCMdb) extracted from full‐text papers using an automatic mining approach. We have also developed a Web application interface to compare mutations in different ABC proteins using sequence alignments and to interactively map the mutations to 3D structural models. Currently our database contains protein mutations published for ABCB1, ABCB11, ABCC1, ABCC6, ABCC7, and the proteins of the ABCG subfamily. The database will be extended to include other members and subfamilies, and to provide information on whether or not a mutation is disease causing, represents a high‐incidence polymorphism, or was generated only in vitro. The ABCMdb database should already help to compare the effects of mutations at homologous positions in different ABC proteins, and its interactive tools aim to advance the design of experiments for a wider range of proteins. Hum Mutat 33:1547–1556, 2012. © 2012 Wiley Periodicals, Inc.     

Transatlantic Consensus Group on active surveillance and focal therapy for prostate cancer

Study Type – Prognosis (inception cohort) Level of Evidence 2a What's known on the subject? and What does the study add? There is little data on the utility of digital rectal examination (DRE) as a diagnostic tool in the era of prostate‐specific antigen (PSA) testing. Using a population‐based database, we found that detection of prostate cancer while still localized among men with high‐grade PSA‐occult disease may result in survival benefit.

OBJECTIVE

• ? To determine whether detection of high‐grade prostate cancer while still clinically localised on digital rectal examination (DRE) can improve survival in men with a normal prostate‐specific antigen (PSA) level.

PATIENTS AND METHODS

• ? From the Surveillance, Epidemiology and End Results database, 166 104 men with prostate cancer diagnosed between 2004 and 2007 were identified.
• ? Logistic regression was used to identify factors associated with the occurrence of palpable, PSA‐occult (PSA level of <2.5 ng/mL), Gleason score 8–10 prostate cancer.
• ? Fine and Gray's and Cox multivariable regressions were used to analyse whether demographic, treatment, and clinicopathological factors were associated with the risk of prostate cancer‐specific mortality (PCSM) and all‐cause mortality (ACM), respectively.

RESULTS

• ? Both increasing age (adjusted odds ratio [aOR] 1.02, 95% confidence interval (CI) 1.01–1.03; P < 0.001) and White race (aOR 1.26, 95% CI 1.03–1.54; P= 0.027) were associated with palpable, Gleason 8–10 prostate cancer. Of 166 104 men, 685 (0.4%) had this subset of prostate cancer.
• ? Significant factors associated with risk of PCSM included PSA level (adjusted hazard ratio [aHR] 0.71, 95% CI 0.51–0.99; P= 0.04), higher Gleason score (aHR 2.20, 95% CI 1.25–3.87; P= 0.006), and T3–T4 vs T2 disease (aHR 3.11, 95% CI 1.79–5.41; P < 0.001).
• ? Significant factors associated with risk of ACM included age (aHR 1.03, 95% CI 1.01–1.06; P= 0.006), higher Gleason score (aHR 2.05, 95% CI 1.36–3.09; P < 0.001), and T3–T4 vs T2 disease (aHR 2.11, 95% CI 1.38–3.25, P < 0.001)

CONCLUSIONS

• ? Clinically localised disease on DRE among men with PSA‐occult high‐grade prostate cancer was associated with improved PCSM and ACM, suggesting that DRE in this cohort (older age and White race) may have the potential to improve survival.