Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis

Effect of storage time on falling number and apparent viscosity of wheat flour gruels

Celem przeprowadzonych badań było określenie wpływu czasu składowania na zmiany liczby opadania oraz lepkości pozornej kleików mąk pszennych. Mąkę uzyskano w wyniku laboratoryjnego przemiału pszenicy, uprawianej przy dwu poziomach agrotechniki: podstawowym (A1) oraz zaawansowanym (A2 –zwiększone nawożenia azotowe, zaawansowana ochrona chemiczna). W szczególności badania miały na celu ustalenie zależności pomiędzy liczbą opadania a lepkością pozorną. Pomiary lepkości pozornej zawiesin wykonano stosując lepkościomierz rotacyjny – MettlerRheomat RM 180 o współosiowym układzie cylindrów. Wykazano, że maksymalna oraz końcowa lepkość kleików ulegały zmianie w czasie składowania, a kierunek i intensywność przemian zależały od rodzaju mąki. W czasie składowania wykazano wzrost wartości liczby opadania i zmniejszenie lepkości pozornej kleików mąk pszennych, otrzymanych z przemiału ziarna pochodzącego z podstawowego poziomu agrotechniki (A1). Mąki pozyskane z przemiału ziarna z zaawansowanego poziomu agrotechniki charakteryzowały się bardziej stabilnymi właściwościami reologicznymi w czasie leżakowania. Stwierdzono istotną korelację liniową (Pearsona, p < 0,05) pomiędzy lepkością maksymalną oraz końcową kleików pszennych a wartością liczby opadania.The objective of the research study was to determine the effect of storage time on changes in the falling number and apparent viscosity of wheat flour gruels. The flour was obtained by milling wheat in a laboratory whereas the wheat used was grown using two different levels of agrotechnology: basic (A1) and advanced (A2 - increased nitrogen fertilizing, advanced chemical protection). In particular, the research conducted aimed at the determination of the correlation between the falling number and apparent viscosity. The rheological properties of water slurries were measured using a spindle-type rotational rheometer with coaxial cylinders i.e. a MettlerRheomat RM 180 model. It was proved that the maximum and final viscosity changed during storage, and the direction and intensity of the transformation depended on the type of flour. During storage, an increase was confirmed in the falling number and a decrease in apparent viscosity of gruels made of wheat flour types obtained by milling the grain produced using the basic level of agrotechnology (A1). The flour types obtained by milling grain produced using the advanced level of agrotechnology were characterized by a more stable rheological properties during storage. A significant linear correlation (Pearson’s correlation, p < 0.05) was found between the maximum and final viscosity of wheat gruels and the value of falling number

Sklad florystyczny upraw rzepaku ozimego i ochrona przed chwastami

W pracy przedstawiono wyniki dotyczące zachwaszczenia łanów i gleb przeprowadzone na polach produkcyjnych rzepaku ozimego w kilku Rolniczych Zakładach Doświadczalnych SGGW w trzech okresach wegetacji 1997-2000. W uprawach rzepaku dominowały gatunki krótkotrwałe: Stellaria media, Viola arvensis, Chenopodium album oraz samosiewy zbóż. Zapas nasion chwastów w badanych glebach wahał się od 5 704 do 81 807 szt.·m⁻², a najczęściej występującymi gatunkami były nasiona chwastów dominujących w łanie. Zastosowane herbicydy bardzo dobrze niszczyły większość gatunków chwastów (ponad 90%), jedynie Viola arvensis pozostawał w łanie w znacznym stopniu. Posiewny termin opryskiwania Butisanem Star 416 SC był skuteczniejszy niż powschodowy.The experiment was conducted on the winter oilseed rape fields during three vegetation periods of 1997-2000 in several experimental stations of Warsaw Agricultural University. The studies concerned the estimation of weeds in the winter oilseed rape canopies and soil under rape plants. In the winter oilseed rape the annual species such as: Stellaria media, Viola arvensis, Chenopodium album were predominant. The number of weed seeds in the soil varied (from 5704 to 81807 pecies per m²) and it was found that most often weed seeds were similar to predominate species observed in the canopy of winter oilseed rape. The applied herbicides controlled very well most weed species in winter oilseed rape but not Viola arvensis. The best weed control were obtained with the preemergence treatments of Butisan Star 416 SC application as compared to the postemergence