The effect of overt and subclinical hypothyroidism on the development of non-dipper blood pressure

Introduction: ′Non-dippers′ are individuals without the anticipated nocturnal decrease in blood pressure. An increased incidence of target organ damage and a worse outcome in terms of cardiovascular events have been reported in this group of people. The pathogenesis of non-dipper hypertension is not clear at present. We aimed to investigate the effects of overt and subclinical hypothyroidism on the development of a non-dipper blood pressure pattern via 24-hour ambulatory blood pressure monitoring. Material and methods: 109 normotensive patients with overt and subclinical hypothyroidism were evaluated, and 95 of these patients without reverse dipping and masked hypertension were included in the study. The control group consisted of 75 gender- and age-matched, normotensive, euthyroid healthy individuals. Results: Median serum TSH levels were 7.61 and 1.59 mUmL in patient and control groups, respectively. The number of non-dippers according to systolic, diastolic and mean blood pressure was significantly higher in the patients with hypothyroidism compared to the control group. In linear regression analysis, TSH had a negative effect on the night/day ratio of the systolic, diastolic and mean blood pressures. Conclusion: Despite the fact that the effect of hypothyroidism on non-dipper blood pressure pattern is not known, the present study has revealed that elevated TSH levels are likely to increase the risk of non-dipping in normotensive patients with either overt or subclinical hypothyroidism. (Pol J Endocrinol 2012; 63 (2): 97–103)Wstęp: U osób określanych jako non-dippers nie występuje fizjologiczne obniżenie ciśnienia tętniczego w godzinach nocnych. Jak wynika z doniesień, w tej grupie chorych częściej dochodzi do zmian narządowych i zdarzeń sercowo-naczyniowych. Patogenezy nadciśnienia tętniczego typu non-dipper dotychczas nie wyjaśniono. Celem autorów było zbadanie wpływu jawnej i subklinicznej niedoczynności tarczycy na rozwój profilu dobowej zmienności ciśnienia tętniczego typu non-dipper metodą całodobowego automatycznego pomiaru ciśnienia tętniczego. Materiał i metody: Spośród 109 chorych z prawidłowym ciśnieniem i z jawną lub subkliniczną niedoczynnością tarczycy do analizy włączono 95 osób, u których nie występował nocny wzrost ciśnienia tętniczego (reverse dipping) ani utajone nadciśnienie tętnicze. Grupa kontrolna składała się z 75 zdrowych osób z prawidłowym ciśnieniem tętniczym i prawidłową czynnością tarczycy odpowiednio dobranych pod względem płci i wieku. Wyniki: Mediany stężeń TSH w surowicy w grupach badanej i kontrolnej wynosiły odpowiednio 7,61 i 1,59 mUml. Liczba osób, u których nie występował nocny spadek wartości skurczowego, rozkurczowego i średniego ciśnienia tętniczego, był istotnie wyższy w grupie chorych z niedoczynnością tarczycy niż w grupie kontrolnej. W analizie regresji liniowej wykazano istnienie odwrotnej zależności między stężeniem TSH a stosunkiem między nocnymi i dziennymi wartościami ciśnienia skurczowego, rozkurczowego i średniego ciśnienia tętniczego. Wnioski: Mimo że nie wiadomo, jaki jest mechanizm oddziaływania niedoczynności tarczycy na rozwój dobowego profilu ciśnienia tętniczego typu non-dipper, w niniejszym badaniu wykazano, że podwyższone stężenie TSH może zwiększać ryzyko wystąpienia takiego profilu ciśnienia tętniczego u osób z prawidłowym ciśnieniem tętniczym i jawną lub subkliniczną niedoczynnością tarczycy. (Endokrynol Pol 2012; 63 (2): 97–103

Peptidylarginine Deiminase Inhibitors Reduce Bacterial Membrane Vesicle Release and Sensitize Bacteria to Antibiotic Treatment

Outer membrane and membrane vesicles (OMV/MV) are released from bacteria and participate in cell communication, biofilm formation and host-pathogen interactions. Peptidylarginine deiminases (PADs) are phylogenetically conserved enzymes that catalyze post-translational deimination/citrullination of proteins, causing structural and functional changes in target proteins. PADs also play major roles in the regulation of eukaryotic extracellular vesicle release. Here we show phylogenetically conserved pathways of PAD-mediated OMV/MV release in bacteria and describe deiminated/citrullinated proteins in E. coli and their derived OMV/MVs. Furthermore, we show that PAD inhibitors can be used to effectively reduce OMV/MV release, both in Gram-negative and Gram-positive bacteria. Importantly, this resulted in enhanced antibiotic sensitivity of both E. coli and S. aureus to a range of antibiotics tested. Our findings reveal novel strategies for applying pharmacological OMV/MV-inhibition to reduce antibiotic resistance

Cannabidiol Is a Novel Modulator of Bacterial Membrane Vesicles

Membrane vesicles (MVs) released from bacteria participate in cell communication and host-pathogen interactions. Roles for MVs in antibiotic resistance are gaining increased attention and in this study we investigated if known anti-bacterial effects of cannabidiol (CBD), a phytocannabinoid from Cannabis sativa, could be in part attributed to effects on bacterial MV profile and MV release. We found that CBD is a strong inhibitor of MV release from Gram-negative bacteria (E. coli VCS257), while inhibitory effect on MV release from Gram-positive bacteria (S. aureus subsp. aureus Rosenbach) was negligible. When used in combination with selected antibiotics, CBD significantly increased the bactericidal action of several antibiotics in the Gram-negative bacteria. In addition, CBD increased antibiotic effects of kanamycin in the Gram-positive bacteria, without affecting MV release. CBD furthermore changed protein profiles of MVs released from E. coli after 1 h CBD treatment. Our findings indicate that CBD may pose as a putative adjuvant agent for tailored co-application with selected antibiotics, depending on bacterial species, to increase antibiotic activity, including via MV inhibition, and help reduce antibiotic resistance

Grain and phase stress criteria for behaviour and cleavage in duplex and bainitic steels

Stress analyses by X-ray diffraction are performed on a cast duplex (32% ferrite) stainless steel elbow and a bainitic (95% ferrite) pressure vessel steel. During an in situ tensile test, micrographic observations are made (visible glides and microcracks) and related to the stress state determined in the individual ferritic grains (aged duplex) and the ferritic phase (bainite loaded at low temperatures). Several material parameters have been identified at different scales, as for example, the critical resolved shear stress of 245 MPa for the aged ferritic grain (duplex) or 275 MPa for bainite (–60 ◦C), a crystallographic cleavage propagation criterion of 465 MPa (stress normal to {100} planes), and a fracture stress of approximately 700 MPa in the ferritic phase. Even though the two steels are different in many respects, the macroscopic fracture strains and stresses are well predicted by the polycrystalline model developed for bainite, whatever the temperatures tested (considering 7% of the grains reaching the local criterion)

Circulating endothelial cell-derived extracellular vesicles mediate the acute phase response and sickness behaviour associated with CNS inflammation.

Brain injury elicits a systemic acute-phase response (APR), which is responsible for co-ordinating the peripheral immunological response to injury. To date, the mechanisms responsible for signalling the presence of injury or disease to selectively activate responses in distant organs were unclear. Circulating endogenous extracellular vesicles (EVs) are increased after brain injury and have the potential to carry targeted injury signals around the body. Here, we examined the potential of EVs, isolated from rats after focal inflammatory brain lesions using IL-1β, to activate a systemic APR in recipient naïve rats, as well as the behavioural consequences of EV transfer. Focal brain lesions increased EV release, and, following isolation and transfer, the EVs were sequestered by the liver where they initiated an APR. Transfer of blood-borne EVs from brain-injured animals was also enough to suppress exploratory behaviours in recipient naïve animals. EVs derived from brain endothelial cell cultures treated with IL-1β also activated an APR and altered behaviour in recipient animals. These experiments reveal that inflammation-induced circulating EVs derived from endothelial cells are able to initiate the APR to brain injury and are sufficient to generate the associated sickness behaviours, and are the first demonstration that EVs are capable of modifying behavioural responses