A new anti-ageing strategy focused on prevention of arterial ageing in the middle-aged population

Ageing is a progressive process that according to available knowledge cannot be effectively reversed, slowed or stopped. Here we propose a new anti-ageing approach that may lead to the design of effective therapeutic intervention. First, we hypothesize that the “organ system” oriented anti-ageing approach represents a better anti-ageing target than the “whole body” or “cellular ageing” concepts. The arterial system is the most suitable target, as it interconnects all the organs in the body, thus influencing them all. Second, we propose that an anti-ageing approach could be more successful in early than late ageing stages; middle-aged people seem to be the most appropriate candidates. Third, we believe that instead of searching for new medication, we should rely on already established medications with beneficial effects on the arterial wall. Renin-angiotensin system inhibitors and statins fulfill these criteria and are potential cornerstones of the new approach. The fourth hypothesis is based on the concept that in the early stages of arterial ageing only slight injury is present and therefore subtherapeutic, low-dose treatment would be effective. Fifth, we hypothesize that slight initial age-related arterial wall changes are reversible and could be corrected by a short-term (one month) treatment. Sixth, we hypothesize that the effects would be present for a certain period of time even after treatment termination. The listed assumptions combined represent the basis for a new, original anti-ageing approach – a subtherapeutic low-dose combination of a renin-angiotensin system inhibitor and a statin for one month (followed by approximately 6–12 months without treatment) could delay or even reverse the arterial ageing process and consequently decrease the incidence of cardiovascular disorders.     

A High-Fat Diet Increases IL-1, IL-6, and TNF-α Production by Increasing NF-κB and Attenuating PPAR-γ Expression in Bone Marrow Mesenchymal Stem Cells

It is well established that a high-fat diet (HFD) can lead to overweight and ultimately to obesity, as well as promoting low-grade chronic inflammation associated with increased levels of such mediators as TNF-α, IL-1, and IL-6. Bone marrow mesenchymal stem cells (MSCs), which are involved in hematopoietic niches and microenvironments, can be affected by these cytokines, resulting in induction of NF-κB and inhibition of PPAR-γ. Because this phenomenon could ultimately lead to suppression of bone marrow adipogenesis, we set out to investigate the effect of an HFD on the expression of PPAR-γ and NF-κB, as well as the production of IL-1, IL-6, and TNF-α in MSCs. Two-month-old male Wistar rats were fed a HFD diet and evaluated by means of leukograms and myelograms along with blood total cholesterol, triglyceride, and C-reactive protein levels. MSCs were isolated, and PPAR-γ and NF-κB were quantified, as well as IL-1, IL-6, and TNF-α production. Animals that were fed a HFD showed higher levels of blood total cholesterol, triglycerides, and C-reactive protein with leukocytosis and bone marrow hyperplasia. MSCs from HFD animals showed increased production of IL-1, IL-6, and TNF-α and increased NF-κB and reduced PPAR-γ expression. Therefore, ingestion of an HFD induces alterations in MSCs that may influence modulation of hematopoiesis.     

Headache Gauge: a real-life calendar-based tool for headache monitoring

Neurological Sciences - This study aimed to validate a semi-quantitative composite score tool, “Headache Gauge” (HG), to monitor the treatment effect in primary headaches in everyday...     

Progesterone as a morphological regulatory factor of the male and female gerbil prostate

Testosterone (T) and oestrogen are the main active steroid hormones in the male and female reproductive system respectively. In female rodents progesterone (P4), together with testosterone and oestrogen, has an essential role in the regulation of the oestrous cycle, which influences the prostate physiology through their oscillations. In this work we investigated how the male and female prostate gland of Mongolian gerbils responds to surgical castration at the start of puberty and what are the effects of T, oestradiol (E2) and P4 replacement, using both quantitative and qualitative methods. We also examined the location of the main steroid receptors present in the prostate. In the castrated animals of both sexes an intense glandular regression, along with disorganization of the stromal compartment, and abundant hyperplasia was observed. The replacement of P4 secured a mild recovery of the glandular morphology, inducing the growth of secretory cells and restoring the androgen receptor (AR) cells. The administration of P4 and E2 eliminated epithelial hyperplasia and intensified gland hypertrophy, favouring the emergence of prostatic intraepithelial neoplasia (PIN). In animals treated with T and P4, even though there are some inflammatory foci and other lesions, the prostate gland revealed morphology closer to that of control animals. In summary, through the administration of P4, we could demonstrate that this hormone has anabolic characteristics, promoting hyperplasia and hypertrophy, mainly in the epithelial compartment. When combined with E2 and T, there is an accentuation of glandular hypertrophy that interrupts the development of hyperplasia and ensures the presence of a less dysplastic glandular morphology.     

Supra and infratentorial massive strokes in previously healthy young patients with SARS-CoV-2. The role of neurosurgery

The coronavirus disease 2019 (COVID-19) has amazed by its distinct forms of presentation and severity.COVID-19 patients can develop large-scale ischemic strokes in previously healthy patients without risk factors, especially in patients who develop an acute respiratory distress syndrome (SARS-CoV-2).We hypothesize that ischemic events are usually the result of the combined process of a pro-inflammatory and pro-coagulant state plus vascular endothelial dysfunction probably potentiated by hypoxia, hemodynamic instability, and immobilization, as reported in other cases.To the best of our knowledge, we report the first case of partial obstruction of a vertebral artery in a patient with COVID-19.Decompressive surgery remains a life-saving maneuver in these patients (as in other non-COVID-19 strokes) and requires further investigation.     

Homogeneity of Trypanosoma cruzi I, II, and III populations and the overlap of wild and domestic transmission cycles by Triatoma brasiliensis in northeastern Brazil

The genetic variability of 24 Trypanosoma cruzi isolates from humans (11) and triatomines (13) in northeastern Brazil was analyzed by random amplified polymorphic DNA (RAPD) and compared with taxonomic groups, host, and geographical origin of the parasite. TcI (12.5 %), TcII (45.8 %), and TcIII (41.6 %) showed a similarity coefficient (SC) of 0.74 using the mean of three primers and 0.80, 0.75, and 0.66 for λgt11-F, M13-40F, and L15996 primers, respectively. The samples were clustered according to their phylogenetic origin in two polymorphic and divergent branches: one associated with TcI and the other with two subbranches corresponding to TcII and TcIII. TcI was only identified in humans and correlated with the Id homogenous group (0.80 SC). TcII from humans and Triatoma brasiliensis showed 0.86 SC and was clustered according monoclonal or polyclonal populations with similar RAPD profiles detected among the vector and/or humans in different municipalities. TcIII was isolated exclusively in sylvatic cycles from T. brasiliensis and Panstrongylus lutzi and showed low variability (0.84 SC) and high homology mainly among isolated populations at the same locality. The homology of T. cruzi among different hosts and locations suggests the distribution of principal clones circulating and reveals an overlapping between the sylvatic and domestic cycles in this area, where T. brasiliensis infected with TcII acts as link in both environments. This species is important to maintain TcII and TcIII in wild cycles and deserves particular attention due an emergent risk of these populations being introduced into the domestic cycle; moreover, its clinical and epidemiological implications remain unknown.