Low blood pressure,low mood?

OBJECTIVE--To determine whether a set of physical symptoms is associated with low blood pressure and to investigate the possible role of psychological factors in their occurrence. DESIGN--Analysis of data collected by questionnaire and physical screening from the first phase of the Whitehall II study, a cohort study of an employed population. SETTING--23 civil service departments in London. SUBJECTS--10,314 male and female London based civil servants aged between 35 and 55. MAIN OUTCOME MEASURES--Symptoms of dizziness-giddiness and unexplained tiredness; psychological functioning as measured by the 30 item general health questionnaire in which the response "no more than usual" to an item about disease was scored as indicating chronic illness. RESULTS--Dizziness-giddiness in men and unexplained tiredness in both men and women were significantly related to low systolic blood pressure. There was a highly significant inverse relation between general health questionnaire score and systolic blood pressure for both men and women, which persisted after controlling for potentially confounding variables, including age, body mass index, drug treatment, physical illness, and exercise. This association of low blood pressure with physical symptoms was no longer significant when general health questionnaire score was controlled for. CONCLUSIONS--There seems a strong relation between low systolic blood pressure and minor psychological dysfunction. Associated physical symptoms seem to be secondary to the primary disturbance in mental state.     

Phosphoproteomics identifies microglial Siglec‐F inflammatory response during neurodegeneration

Alzheimer’s disease (AD) is characterized by the appearance of amyloid‐β plaques, neurofibrillary tangles, and inflammation in brain regions involved in memory. Using mass spectrometry, we have quantified the phosphoproteome of the CK‐p25, 5XFAD, and Tau P301S mouse models of neurodegeneration. We identified a shared response involving Siglec‐F which was upregulated on a subset of reactive microglia. The human paralog Siglec‐8 was also upregulated on microglia in AD. Siglec‐F and Siglec‐8 were upregulated following microglial activation with interferon gamma (IFNγ) in BV‐2 cell line and human stem cell‐derived microglia models. Siglec‐F overexpression activates an endocytic and pyroptotic inflammatory response in BV‐2 cells, dependent on its sialic acid substrates and immunoreceptor tyrosine‐based inhibition motif (ITIM) phosphorylation sites. Related human Siglecs induced a similar response in BV‐2 cells. Collectively, our results point to an important role for mouse Siglec‐F and human Siglec‐8 in regulating microglial activation during neurodegeneration.     

Binge Drinking and Blood Pressure: Cross-Sectional Results of the HAPIEE Study

Objectives

To investigate whether binge drinking pattern influences blood pressure independently from drinking volume or whether it modifies the effect of volume of drinking.

Methods

We used cross-sectional data from population samples of 7559 men and 7471 women aged 45–69 years in 2002-05, not on antihypertensive medication, from Russia, Poland and Czech Republic. Annual alcohol intake, drinking frequency and binge drinking (≥100 g in men and ≥60 g in women in one session at least once a month) were estimated from graduated frequency questionnaire. Blood pressure was analysed as continuous variables (systolic and diastolic pressure) and a binary outcome (≥140/90 mm Hg).

Results

In men, annual alcohol intake and drinking frequency were strongly associated with blood pressure. The odds ratio of high blood pressure for binge drinking in men was 1.62 (95% CI 1.45–1.82) after controlling for age, country, body mass index, education and smoking; additional adjustment for annual alcohol intake reduced it to 1.20 (1.03–1.39). In women, the fully adjusted odds ratio of high blood pressure for binge drinking was 1.31 (1.05–1.63). Binge drinking did not modify the effect of annual alcohol intake. Consuming alcohol as wine, beer or spirits had similar effects.

Conclusions

The results suggest that the independent long-term effect of binge drinking was modest, that binge drinking did not modify the effect of alcohol intake, and that different alcoholic beverages had similar effects on blood pressure.     

Effect of cold acclimation on the photosynthetic performance of two ecotypes of Colobanthus quitensis (Kunth) Bartl

The effects of cold acclimation of two ecotypes (Antarctic and Andes) of Colobanthus quitensis (Kunth) Bartl. Caryophyllaceae on their photosynthetic characteristics and performance under high light (HL) were compared. Non-acclimated plants of the Antarctic ecotype exhibited a higher (34%) maximal rate of photosynthesis than the Andes ecotype. In cold-acclimated plants the light compensation point was increased. Dark respiration was significantly increased during the exposure to 4 degrees C in both ecotypes. Cold-acclimated Antarctic plants showed higher Phi(PSII) and qP compared with the Andes ecotype. In addition, the Antarctic ecotype exhibited higher heat dissipation (NPQ), especially in the cold-acclimated state, which was mainly associated with the fast relaxing component of non-photochemical quenching (NPQ(F)). By contrast, the Andes ecotype exhibited a lower NPQ(F) and a significant increase in the slowly relaxing component (NPQ(s)) at low temperature and HL, indicating higher sensitivity to low temperature-induced photoinhibition. Although the xanthophyll cycle was fully operational in both ecotypes, cold-acclimated Antarctic plants exposed to HL exhibited higher epoxidation state of the xanthophyll cycle pigments (EPS) compared with the cold-acclimated Andes ecotype. Thus, the photosynthetic apparatus of the Antarctic ecotype operates more efficiently than that of the Andes one, under a combination of low temperature and HL. The ecotype differences are discussed in relation to the different climatic conditions of the two Colobanthus.     

Cytotoxic effects of 2-arylbenzofuran phytoestrogens on human cancer cells: modulation by adrenal and gonadal steroids

Although 2-arylbenzofuran phytoalexins are known for decades, their anticancer activity has not been studied systematically. We have previously reported on the isolation and the estrogen receptor (ER) modulation properties of three new 2-arylbenzofurans from Onobrychis ebenoides, ebenfuran I [2-(2,4-dihydroxyphenyl)-5-hydroxy-6-methoxy-benzofuran], ebenfuran II [2-(2,4-dihydroxyphenyl)-3-formyl-4-hydroxy-6-methoxy-benzofuran] and ebenfuran III [2-(2,4-dihydroxyphenyl)-3-formyl-4-hydroxy-6-methoxy-5-(3-methyl-buten-2-yl)-benzofuran]. We now show that, while I and II could stimulate the proliferation of MCF-7 cells, III was inhibitory in a proliferation-dependent manner. III inhibited the growth of all human cancer cells examined, regardless of ER or multidrug resistance status. Estradiol rendered MCF-7 cells more sensitive to III, and this coincided with the ability of the hormone at concentrations ≥0.1 nM to bind to the ER of the cells and stimulate their proliferation in the presence of III. Cell proliferation stimulating concentrations of I and II also enhanced the effect of III on MCF-7 cells. However, dehydroepiandrosterone and dihydrotestosterone were ineffective in this respect. III-treated MCF-7 cells exhibited G1 phase arrest followed by detachment-induced cell death and/or apoptosis in the adherent fraction, pronounced induction of Bax and suppression of estradiol induction of Bcl-2. Our data indicate that the largely unexplored pool of benzofuran phytoalexins includes entities potentially suitable for chemoprevention and treatment of human cancer.     

New hydroxystilbenoid derivatives endowed with neuroprotective activity and devoid of interference with estrogen and aryl hydrocarbon receptor-mediated transcription

We have synthesized a series of new (E) stilbenoid derivatives containing hydroxy groups at ring positions identical or similar to those of trans-resveratrol and bearing one or two bulky electron donating groups ortho to 4′-OH and we have evaluated their neuroprotective activity using glutamate-challenged HT22 hippocampal neurons to model oxidative stress-induced neuronal cell death. The most active derivatives, 5-{(E)-2-[3,5-bis(1-ethylpropyl)-4-hydroxyphenyl]ethenyl}-1,3-benzenediol (2), 5-[(E)-2-(3,5-di-tert-butyl-4-hydroxyphenylethenyl)]-1,3-benzenediol (4) and 5-{(1E,3E)-4-[3,5-bis(1-ethylpropyl)-4-hydroxyphenyl]-1,3-butadienyl}-1,3-benzenediol (6), had EC₅₀ values of 30, 45 and 12 nM, respectively, and were ca. 100 to 400-fold more potent than resveratrol. Derivatives 2, 4 and 6 lacked cytotoxic activity against HT22 cells and estrogen receptor agonist or antagonist activity in estrogen response element-dependent gene expression and in estrogen-dependent proliferation of MCF-7 human breast cancer cells. In addition, they were incapable of interfering with aryl hydrocarbon receptor-mediated xenobiotic response element-dependent gene expression. Derivatives 2, 4 and 6 might assist in the development of lead candidates against oxidative stress-driven neurodegenerative diseases that will not increase endocrine cancer risk nor affect drug activation and detoxification mechanisms.