Zofenopril: Blood pressure control and cardio-protection

Current hypertension guidelines suggest various strategies to reduce blood pressure levels, thereby reducing cardiovascular events: combinations of drugs with different mechanisms of action, such as an angiotensin converting enzyme inhibitors (ACEIs) and a diuretic, are the cornerstone of the modern treatment of hypertension, also as initial therapy. Among ACEIs, zofenopril has been shown to be effective in the management of hypertension both as monotherapy and in combination with a diuretic: zofenopril/hydrochlorothiazide fixed dose combination is particularly useful to improve treatment adherence through simplification of treatment regimen. Moreover, thanks to the sulfhydryl group, zofenopril has some peculiar properties (higher lipophilicity and tissue penetration, lower bradykinin-dependent effect, higher affinity for, and more persistent binding to, tissue ACE, significant antioxidant effect), which may account for the cardioprotective effects of the drug demonstrated in both pre-clinical studies and randomized clinical trials. The positive impact of zofenopril on clinical outcomes has been extensively documented by the SMILE program, including several clinical trials in patients with different conditions of myocardial ischemia treated with zofenopril: the results of the SMILE program, demonstrating the benefits of zofenopril vs. placebo and other ACEIs, emphasize the importance of a differentiated approach to patients with ischemic heart disease, based on a careful choice of the adopted agent, in order to improve the overall impact of pharmacological treatment on clinical outcomes

A study of the remarkable galaxy system AM 546-324 (the core of Abell S0546)

We report first results of an investigation of the tidally disturbed galaxy system AM\,546-324, whose two principal galaxies 2MFGC 04711 and AM\,0546-324 (NED02) were previously classified as interacting doubles. This system was selected to study the interaction of ellipticals in a moderately dense environment. We provide spectral characteristics of the system and present an observational study of the interaction effects on the morphology, kinematics, and stellar population of these galaxies. The study is based on long-slit spectrophotometric data in the range of $\sim$ 4500-8000 $\AA$ obtained with the Gemini Multi-Object Spetrograph at Gemini South (GMOS-S). We have used the stellar population synthesis code STARLIGHT to investigate the star formation history of these galaxies. The Gemini/GMOS-S direct r-G0303 broad band pointing image was used to enhance and study fine morphological structures. The main absorption lines in the spectra were used to determine the radial velocity. Along the whole long-slit signal, the spectra of the Shadowy galaxy (discovered by us), 2MFGC 04711, and AM\,0546-324 (NED02) resemble that of an early-type galaxy. We estimated redshifts of z= 0.0696, z= 0.0693 and z= 0.0718, corresponding to heliocentric velocities of 20\,141 km s$^{-1}$, 20\,057 km s$^{-1}$, and 20\,754 km s$^{-1}$ for the Shadowy galaxy, 2MFGC 04711 and AM\,0546-324 (NED02), respectively. ..

Spatiotemporal dynamics of cortical representations during and after stimulus presentation

Visual perception is a spatiotemporally complex process. In this study, we investigated cortical dynamics during and after stimulus presentation. We observed that visual category information related to the difference between faces and objects became apparent in the occipital lobe after 63 ms. Within the next 110 ms, activation spread out to include the temporal lobe before returning to residing mainly in the occipital lobe again. After stimulus offset, a peak in information was observed, comparable to the peak after stimulus onset. Moreover, similar processes, albeit not identical, seemed to underlie both peaks. Information about the categorical identity of the stimulus remained present until 677 ms after stimulus offset, during which period the stimulus had to be retained in working memory. Activation patterns initially resembled those observed during stimulus presentation. After about 200 ms, however, this representation changed and class-specific activity became more equally distributed over the four lobes. These results show that, although there are common processes underlying stimulus representation both during and after stimulus presentation, these representations change depending on the specific stage of perception and maintenance. </p

Effects of hyperoxia and cardiovascular risk factors on myocardial ischemia reperfusion injury: a randomized, sham and placebo controlled parallel study

peer reviewedRecent studies on O2 supplementation in acute coronary syndrome patients are equivocal. We tested the hypothesis that oxidative stress (OS) is increased in rodents with cardiovascular risk factors and enhances ischemia reperfusion injury in the presence of hyperoxia. Forty-three Wistar rats (WR), 30 spontaneous hypertensive rats (SHR) and 33 obese Zucker rats (ZR) were randomized in a sham procedure (1/3rd) or a left anterior descending ligation for 60 minutes (2/3rd). This was followed by 3 hours of reperfusion while animals were randomised either in a hyperoxic (HR) or a normoxic reperfusion group (NR). Baseline troponin (cTnT) was larger in SHR and ZR than WR (both p &lt; 0.001). HR was associated with a lesser troponin rise in SHR and ZR than in NR (both p &lt; 0.001); while the reverse occurred in WR (p &lt; 0.001). In SHR, HR limited total MPO (myeloperoxydase) increase as compared to NR (p = 0.0056) to the contrary of total MPO in WR (p = 0.013). NR was associated with a drastic reduction of total thiols as compared to HR both in SHR and in ZR (both p &lt; 0.001). Despite a heightened baseline OS, HR rather restrained myocardial necrosis and anti/pro-oxidant imbalance in SHR and ZR, to the reverse of healthy WR

Current management and prognostic factors in physiotherapy practice for patients with shoulder pain: Design of a prospective cohort study

Background: Shoulder pain is disabling and has a considerable socio-economic impact. Over 50% of patients presenting in primary care still have symptoms after 6 months; moreover, prognostic factors such as pain intensity, age, disability level and duration of complaints are associated with poor outcome. Most shoulder complaints in this group are categorized as non-specific. Musculoskeletal ultrasound might be a useful imaging method to detect subgroups of patients with subacromial disorders.This article describes the design of a prospective cohort study evaluating the influence of known prognostic and possible prognostic factors, such as findings from musculoskeletal ultrasound outcome and working alliance, on the recovery of shoulder pain. Also, to assess the usual physiotherapy care for shoulder pain and examine the inter-rater reliability of musculoskeletal ultrasound between radiologists and physiotherapists for patients with shoulder pain. Methods. A prospective cohort study including an inter-rater reliability study. Patients presenting in primary care physiotherapy practice with shoulder pain are enrolled. At baseline validated questionnaires are used to measure patient characteristics, disease-specific characteristics and social factors. Physical examination is performed according to the expertise of the physiotherapists. Follow-up measurements will be performed 6, 12 and 26 weeks after inclusion. Primary outcome measure is perceived recovery, measured on a 7-point Likert scale. Logistic regression analysis will be used to evaluate the association between prognostic factors and recovery. Discussion. The ShoCoDiP (Shoulder Complaints and using Diagnostic ultrasound in Physiotherapy practice) cohort study will provide information on current management of patients with shoulder pain in primary care, provide data to develop a prediction model for shoulder pain in primary care and to evaluate whether musculoskeletal ultrasound can improve prognosis

Competitive repopulation and allo-immunologic pressure determine chimerism kinetics after T Cell-depleted allogeneic stem cell transplantation and donor lymphocyte infusion

After allogeneic stem cell transplantation (alloSCT), patient-derived stem cells that survived the pretransplantation conditioning compete with engrafting donor stem cells for bone marrow (BM) repopulation. In addition, donor-derived alloreactive T cells present in the stem cell product may favor establishment of complete donor-derived hematopoiesis by eliminating patient-derived lymphohematopoietic cells. T cell-depleted alloSCT with sequential transfer of potentially alloreactive T cells by donor lymphocyte infusion (DLI) provides a unique opportunity to selectively study how competitive repopulation and allo-immunologic pressure influence lymphohematopoietic recovery. This study aimed to determine the relative contribution of competitive repopulation and donor-derived anti-recipient alloimmunologic pressure on the establishment of lymphohematopoietic chimerism after alloSCT. In this retrospective cohort study of 281 acute leukemia patients treated according to a protocol combining alemtuzumab-based T cell-depleted alloSCT with prophy-lactic DLI, we investigated engraftment and quantitative donor chimerism in the BM and immune cell subsets. DLI-induced increase of chimerism and development of graft-versus-host disease (GVHD) were analyzed as complementary indicators for donor-derived anti-recipient alloimmunologic pressure. Profound suppression of patient immune cells by conditioning sufficed for sustained engraftment without necessity for myeloablative conditioning or development of clinically significant GVHD. Although 61% of the patients without any DLI or GVHD showed full donor chimerism (FDC) in the BM at 6 months after alloSCT, only 24% showed FDC in the CD4+ T cell compartment. In contrast, 75% of the patients who had received DLI and 83% of the patients with clinically significant GVHD had FDC in this compartment. In addition, 72% of the patients with mixed hematopoiesis receiving DLI converted to complete donor-derived hematopoiesis, of whom only 34% developed clinically significant GVHD. Our data show that competitive repopulation can be sufficient to reach complete donor-derived hematopoiesis, but that some alloimmunologic pressure is needed for the establishment of a completely donor-derived T cell compartment, either by the development of GVHD or by administration of DLI. We illustrate that it is possible to separate the graft-versus-leukemia effect from GVHD, as conversion to durable complete donor-derived hematopoiesis following DLI did not require induction of clinically significant GVHD. (c) 2023 The American Society for Transplantation and Cellular Therapy. Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Are luminous radio-loud active galactic nuclei triggered by galaxy interactions?

We present the results of a comparison between the optical morphologies of a complete sample of 46 southern 2Jy radio galaxies at intermediate redshifts (0.05<z<0.7) and those of two control samples of quiescent early-type galaxies: 55 ellipticals at redshifts z<0.01 from the Observations of Bright Ellipticals at Yale (OBEY) survey, and 107 early-type galaxies at redshifts 0.2<z<0.7 in the Extended Groth Strip (EGS). Based on these comparisons, we discuss the role of galaxy interactions in the triggering of powerful radio galaxies (PRGs). We find that a significant fraction of quiescent ellipticals at low and intermediate redshifts show evidence for disturbed morphologies at relatively high surface brightness levels, which are likely the result of past or on-going galaxy interactions. However, the morphological features detected in the galaxy hosts of the PRGs (e.g. tidal tails, shells, bridges, etc.) are up to 2 magnitudes brighter than those present in their quiescent counterparts. Indeed, if we consider the same surface brightness limits, the fraction of disturbed morphologies is considerably smaller in the quiescent population (53% at z<0.2 and 48% at 0.2<z<0.7) than in the PRGs (93% at z<0.2 and 95% at 0.2<z<0.7 considering strong-line radio galaxies only). This supports a scenario in which PRGs represent a fleeting active phase of a subset of the elliptical galaxies that have recently undergone mergers/interactions. However, we demonstrate that only a small proportion (<20%) of disturbed early-type galaxies are capable of hosting powerful radio sources.Comment: 20 pages, 7 figures, accepted for publication in MNRA

Hydroxychloroquine in rheumatic autoimmune disorders and beyond

Initially used as antimalarial drugs, hydroxychloroquine (HCQ) and, to a lesser extent, chloroquine (CQ) are currently being used to treat several diseases. Due to its cost-effectiveness, safety and efficacy, HCQ is especially used in rheumatic autoimmune disorders (RADs), such as systemic lupus erythematosus, primary Sjögren's syndrome and rheumatoid arthritis. Despite this widespread use in the clinic, HCQ molecular modes of action are still not completely understood. By influencing several cellular pathways through different mechanisms, CQ and HCQ inhibit multiple endolysosomal functions, including autophagy, as well as endosomal Toll-like receptor activation and calcium signalling. These effects alter several aspects of the immune system with the synergistic consequence of reducing pro-inflammatory cytokine production and release, one of the most marked symptoms of RADs. Here, we review the current knowledge on the molecular modes of action of these drugs and the circumstances under which they trigger side effects. This is of particular importance as the therapeutic use of HCQ is expanding beyond the treatment of malaria and RADs