Structural determinants of agonist-induced signaling and regulation of the angiotensin AT1 receptor

Angiotensin II (Ang II) regulates aldosterone secretion by stimulating inositol phosphate production and Ca(2+) signaling in adrenal glomerulosa cells via the G(q)-coupled AT(1) receptor, which is rapidly internalized upon agonist binding. Ang II also binds to the heptahelical AT(2) receptor, which neither activates inositol phosphate signaling nor undergoes receptor internalization. The differential behaviors of the AT(1) and AT(2) receptors were analyzed in chimeric angiotensin receptors created by swapping the second (IL2), the third (IL3) intracellular loops and/or the cytoplasmic tail (CT) between these receptors. When transiently expressed in COS-7 cells, the chimeric receptors showed only minor alterations in their ligand binding properties. Measurements of the internalization kinetics and inositol phosphate responses of chimeric AT(1A) receptors indicated that the CT is required for normal receptor internalization, and IL2 is a determinant of G protein activation. In addition, the amino-terminal portion of IL3 is required for both receptor functions. However, only substitution of IL2 impaired Ang II-induced ERK activation, suggesting that alternative mechanisms are responsible for ERK activation in signaling-deficient mutant AT(1) receptors. Substitution of IL2, IL3, or CT of the AT(1A) receptor into the AT(2) receptor sequence did not endow the latter with the ability to internalize or to mediate inositol phosphate signaling responses. These data suggest that the lack of receptor internalization and inositol phosphate signal generation by the AT(2) receptor is a consequence of its different activation mechanism, rather than the inability of its cytoplasmic domains to couple to intracellular effectors.     

A cross-sectional study of newborns over a 20-year period in Szeged,Hungary

Objective: Records of metric data of birth, serve not only the medical needs of the newborn baby, but are also indicators to assess the status of public health.

Methods: This is a retrospective study of 4946 newborns (singleton: 2508 boys and 2365 girls) born in 1989 and in 2009 at the Department of Obstetrics and Gynaecology of the University of Szeged. We aimed as to compare and map the metrical changes over 20 years, and to describe the averages of four body parameters of the normal birth weight (2500–4000?g) subgroup (3993 singleton babies) in both years. Statistical analysis was performed with SPSS 17.0.

Results: In 1989, the mean birth weight was 3223.770?±?559.595?g, birth length 49.551?±?2.729?cm, chest circumference 32.181?±?2.231?cm, and head circumference 34.122?±?1.688?cm. In 2009, the birth weight was 3309.673?±?582.630?g, birth length 49.515?±?2.658?cm, chest circumference 32.736?±?2.392?cm and head circumference 33.854?±?1.768?cm. The mean birth weight, chest circumference and the maximum value of birth weight have thus increased. The mean maternal age shifted to 30.21?±?4.863 years, which is an increase of 3.57 years in 20 years.

Conclusion: The body parameters of newborns changed significantly between 1989 and 2009. As underlying causes changes in eating habits and lifestyle of the mother are to be mentioned.     

Benefits of implementing a rapid access clinic in a high-volume inflammatory bowel disease center:Access,resource utilization and outcomes

BACKGROUND Emergency situations in inflammatory bowel diseases(IBD)put significant burden on both the patient and the healthcare system.AIM To prospectively measure Quality-of-Care indicators and resource utilization after the implementation of the new rapid access clinic service(RAC)at a tertiary IBD center.METHODS Patient access,resource utilization and outcome parameters were collected from consecutive patients contacting the RAC between July 2017 and March 2019 in this observational study.For comparing resource utilization and healthcare costs,emergency department(ED)visits of IBD patients with no access to RAC services were evaluated between January 2018 and January 2019.Time to appointment,diagnostic methods,change in medical therapy,unplanned ED visits,hospitalizations and surgical admissions were calculated and compared.RESULTS 488 patients(Crohn’s disease:68.4%/ulcerative colitis:31.6%)contacted the RAC with a valid medical reason.Median time to visit with an IBD specialist following the index contact was 2 d.Patients had objective clinical and laboratory assessment(C-reactive protein and fecal calprotectin in 91%and 73%).Fast-track colonoscopy/sigmoidoscopy was performed in 24.6%of the patients,while computed tomography/magnetic resonance imaging in only 8.1%.Medical therapy was changed in 54.4%.ED visits within 30 d following the RAC visit occurred in 8.8%(unplanned ED visit rate:5.9%).Diagnostic procedures and resource utilization at the ED(n=135 patients)were substantially different compared to RAC users:Abdominal computed tomography was more frequent(65.7%,P<0.001),coupled with multiple specialist consults,more frequent hospital admission(P<0.001),higher steroid initiation(P<0.001).Average medical cost estimates of diagnostic procedures and services per patient was$403 CAD vs$1885 CAD comparing all RAC and ED visits.CONCLUSION Implementation of a RAC improved patient care by facilitating easier access to IBD specific medical care,optimized resource utilization and helped avoiding ED visits and subsequent hospitalizations.