Sympatheticregulationofvascularfunctioninhealthanddisease

Thesympatheticnervoussystem(SNS)isknowntoplayapivotalroleinshort-andlong-termregulationofdifferentfunctionsofthecardiovascularsystem.Inthepastdecadesincreasingevidencedemonstratedthatsympatheticneuralcontrolisinvolvednotonlyinthevasomotorcontrolofsmallresistanearteriesbutalsoinmodulationoflargearteryfunction.Sympatheticactivityandvascularfunction,bothofwhicharekeyfactorsinthedevelopmentandprognosisofcardiovasculareventsanddisease,arelinkedatseverallevels.EvidencefromexperimentalstudiesindicatesthattheSNSiscriticallyinfluenced,atthecentralandalsoattheperipherallevel,bythemostrelevantfactorsregulatingvascularfunction,suchasnitricoxide(NO),reactiveoxygenspecies(ROS),endothelin(ET),therenin-angiotensinsystem.Additionally,thereisindirectevidenceofareciprocalrelationshipbetweenendothelialfunctionandactivityoftheSNS.Anumberofcardiovascularriskfactorsanddiseasesarecharacterizedbothbyincreasedsympatheticoutflowanddecreasedendothelialfunction.Inhealthysubjects,musclesympatheticnerveactivity(MSNA)appearstoberelatedtosurrogatemarkersofendothelialfunction,andanacuteincreaseinsympatheticactivityhasbeenassociatedwithadecreaseinendothelialfunctioninhealthysubjects.However,directevidenceofacause-effectrelationshipfromhumanstudiesisscanty.Inhumanslargearterystiffnesshasbeenassociatedwithincreasedsympatheticdischarge,bothinhealthysubjectsandinrenaltransplantrecipients.Peripheralsympatheticdischargeisalsoabletomodulatewavereflection.Ontheotherhand,largearterystiffnesscaninterferewithautonomicregulationbyimpairingcarotidbaroreflexsensitivity

the clinical significance and application of vascular stiffness measurements

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Antimicrobial peptides for novel antiviral strategies in the current post-COVID-19 pandemic

The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted how urgent and necessary the discovery of new antiviral compounds is for novel therapeutic approaches. Among the various classes of molecules with antiviral activity, antimicrobial peptides (AMPs) of innate immunity are among the most promising ones, mainly due to their different mechanisms of action against viruses and additional biological properties. In this review, the main physicochemical characteristics of AMPs are described, with particular interest toward peptides derived from amphibian skin. Living in aquatic and terrestrial environments, amphibians are one of the richest sources of AMPs with different primary and secondary structures. Besides describing the various antiviral activities of these peptides and the underlying mechanism, this review aims at emphasizing the high potential of these small molecules for the development of new antiviral agents that likely reduce the selection of resistant strains

Biomarcatori ecografici di funzione e struttura vascolare nell'uomo Imaging biomarkers of vascular function and structure in humans

Cardiovascular (CV) disease is the first cause of mortality and morbidity in the world. Prevention of this condition, which is responsible of more than 2200 deaths per day only in United States, is a public health priority. Thus in the last decades great efforts have been made in the search of non-invasive biomarkers, able to identify the individual at risk for CV events in the asymptomatic, subclinical stage. Some biomarkers are currently recommended in order to improve stratification of CV risk, whereas other are considered useful only for research purposes. In particular, increased intima-media thickness of the common carotid artery (C-IMT), representing a marker of early atherosclerosis significantly correlated with coronary or cerebrovascular disease, has been considered as an intermediate stage in the continuum of vascular disease and as a predictor of CV risk. Current guidelines also introduced other vascular parameters evaluating mechanical and functional arterial properties of peripheral and central arteries. Increased aortic stiffness has been shown to predict future CV events and it has been recognized as a marker of subclinical target organ damage in hypertensive patients. Earlier vascular abnormalities, such as endothelial dysfunction in the peripheral arteries, have been also mentioned for their possible use in future. However, several questions in this field are still open, limiting the wide use of these tools in the clinical practice. The open issues concern methodological as well as pathophysiological and prognostic aspects, and in this thesis we will discuss only a small part of these ones. First, C-IMT and arterial stiffness represent two sides of vascular aging, atherosclerosis and arteriosclerosis respectively, and are generally considered structural alterations. The identification of a “functional” component in these alterations would be of interest, since it will suggest a possibility of reversibility of vascular aging. Second, vascular aging is a process involving the whole organism, while different techniques explore different districts. The quantification of the impact of different CV risk factors on different vascular districts might indicate the most adequate biomarker to use for future studies and suggest specific mechanisms of disease in different conditions. Third, vascular aging is often accompanied by cardiac and renal damage, but the relationship between organ damage in different districts is still largely unexplored. Fourth, while hypertension and diabetes have become the main cause of end-stage renal disease, and chronic kidney disease has been recognized as a main cause of CV events, to date early markers of renal vascular damage have not been developed. For this PhD thesis I examined cross-sectionally a cohort of healthy subjects and patients with traditional CV risk factors in order to elucidate some of the abovementioned aspects. My original contribution to the knowledge in this field consists in: - the demonstration of a “functional” component in aortic stiffness, that is present only in diabetic patients and relies on endothelium-mediated mechanisms; - the demonstration of a differential impact of different CV risk factors on carotid and aortic stiffness; - the demonstration, in hypertensive patients, of an additive role of carotid and aortic stiffness in determining cardiac organ damage; - the identification of a new marker of renal vascular damage. In the second part of the PhD thesis, I sought to demonstrate the usefulness of imaging biomarkers of vascular function and structure not only for risk stratification in patients with traditional CV risk factors, but also to explore CV consequences of non primarily CV diseases and conditions. We hypothesized that a comprehensive, multiparametric approach would be the best strategy to detect early vascular damage in one or more districts, possibly in a subclinical, reversible stage. This approach could allow identifying the “CV footprint” characterizing each condition, with a double aim: to elucidate the pathophysiology of CV complications in non-CV diseases and to propose the most useful test to be used in the clinical practice for screening and follow-up. During my PhD thesis I applied this strategy to some primarily non-CV conditions that might qualify as emerging CV risk factors, such as exposure to environmental and iatrogenic radiation doses, obstructive sleep apnea syndrome (OSAS) in the absence of traditional CV risk factors, and chronic exposure to hypobaric hypoxia at high altitude. My original contribution to the knowledge in this field consisted in: - the demonstration of a selective reduction of circulating endothelial progenitor cells, in the presence of preserved vascular function and structure, in young adults exposed during childhood to environmental radiation doses after the Chernobyl disaster and to therapeutic radioiodine treatment after thyroid cancer; - the demonstration that conduit artery endothelial dysfunction and impaired renal vasodilating capacity are part of the vascular phenotype of OSAS per se, since they are present even in the absence of traditional CV risk factors, while structural alterations such as arterial stiffness and increased C-IMT characterized only obese and/or hypertensive OSAS patients; - the demonstration that Himalayan high altitude dwellers, chronically living above 2500 meters of altitude, present a mainly microcirculatory endothelial dysfunction and a maladaptive carotid remodeling even in the absence of traditional CV risk factors

Laparoscopic Approach of a Unicornuate Uterus with Noncommunicating Rudimentary Horns

Background. Müllerian duct malformations delineate a miscellaneous group of congenital anomalies that result from arrested development, abnormal formation, or incomplete fusion of the mesonephric ducts. Case. This paper describes the diagnosis and management of a noncommunicating rudimentary horn complicated by severe pelvic pain and associated endometriosis. Conclusion. This condition was diagnosed by laparoscopy and hysteroscopy examination. Operative videolaparoscopy proved to be a successful approach for the treatment of this congenital Müllerian anomaly

Necrotizing amebic colitis in an elder patient: an unexpected autopsy finding

Necrotizing amebic colitis is an uncommon amebiasis complication associated with high mortality. We present a case of necrotizing amebic colitis in an old patient whose diagnosis was revealed at postmortem examination. An 81-year-old man died at home without medical attention. The postmortem examination revealed ulcers involving the entire colon and intestinal perforation. The ulcers were large, geographic, and necrotizing, extending from the cecum to the rectum. The histological examination disclosed the infectious etiology by showing amebic trophozoites at the base of the ulcers. No extra-intestinal lesions were found. No information about previous episodes of dysentery or travel could be obtained. The potential role of aging or drug-causing immunosuppression and the evolution of chronic and latent intestinal infection to a severe and invasive form of amebiasis is discussed. This case reinforces the value of postmortem examination for diagnosing diseases not clinically identified

The collection of Brendel Botanical Models at the Botanical Garden of Naples, Italy

The Botanical Garden of Naples has a collection of papier-mâché models that reproduce plant structures, whole plants, or fungi. They are known as Brendel Models, named after the German Company that built and supplied them to the Botanical Garden in the early nineteenth century. For their state of decay, due to time and continuous use for educational purposes, the models have undergone recovery interventions. Given their historical and artistic interest, and in order to preserve them, the models are no longer used today. In order not to completely lose such a cultural heritage for didactics, a CD-ROM has been created which includes, for each species reproduced by the models, photos in nature of the plants represented and didactic cards re-porting all the useful information for the use of models in computer mode

TCD4pos lymphocytosis in rheumatoid and psoriatic arthritis patients following TNFα blocking agents

BACKGROUND: Lymphocyte expansion and true lymphocytosis are commonly observed in the everyday clinical practice. The meaning of such phenomenon is often poorly understood so that discrimination between benign and malignant lymphocytosis remains difficult to establish. This is mainly true when lymphocytosis rises in patients affected by immune-mediated chronic inflammatory diseases under immunosuppressive treatment, conditions potentially associated with lymphomagenesis. In this brief report the development of mild T CD4pos lymphocytosis in a group of patients with chronic arthritis under anti-TNF-α treatment is described. METHODS: Two hundred eight rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients have been evaluated longitudinally for at least 1-year before and 2-years after anti-TNF-α therapy introduction for the possible appearance of a lymphocyte expansion. In patients who developed lymphocyte expansion, T, B and NK cells were analysed. RESULTS: Twenty-five out of 208 (12%) subjects developed a mild T CD4pos lymphocytosis, during anti-TNF-α therapy, which reverted after its interruption. Higher lymphocyte count, more frequent use of steroids and shorter disease duration, before biological therapy start, have emerged as risk factors for lymphocytosis development. CONCLUSIONS: This is the first longitudinal cohort study evaluating the onset of lymphocytosis in RA and PsA patients under anti-TNF-α treatment and its possible clinical relevance. A mild T CD4pos lymphocytosis has been observed in 12% of RA and PsA patients probably related to anti-TNF-α treatment as previously reported by anecdotal cases. Patients with higher baseline lymphocyte count, use of steroids and shorter disease duration before the introduction of biologic therapy, seem to be prone to develop this laboratory reversible abnormality

Influxo de Ca2+ mediado por canais TRP em células secretoras de insulina

Dissertação de mestrado em Bioquímica apresentada ao Departamento Ciências da Vida da Faculdade de Ciências e Tecnologia da Universidade de Coimbra.A célula-β está equipada com um mecanismo de influxo de Ca2+ distinto do mediado por canais CaV. Pretendeu-se neste trabalho identificar este mecanismo, recorrendo a técnicas de microscopia quantitativa de fluorescência para monitorizar a [Ca2+]i em ilhéus únicos de ratinho. A estimulação do influxo de Ca2+ foi efectuada, na maior parte dos casos, aumentando a [Ca2+]o para 7 mM (doravante designada como „pulso de Ca2+‟). A aplicação de um pulso de Ca2+ na presença de 3 mM glicose aumentou a [Ca2+]i. O efeito não foi afectado por hiperpolarização com o agonista de canais KATP diazóxido (100 μM), mas foi muito potenciado pelo bloqueador de canais CaV1.0 nifedipina (10 μM). Nifedipina aumentou a [Ca2+]i e acelerou o quenching da fluorescência de FURA-2 por Mn2+ no ponto isosbéstico do indicador. Os efeitos dos pulsos de Ca2+ na presença de nifedipina foram bloqueados por dois fenamatos, difenilamina-2-carboxilato (DPC, 500 μM) e ácido mefenâmico (3-80 μM; IC50=10.3 μM). O ácido mefenâmico é um inibidor aparentemente selectivo de canais TRPM3, uma sub-classe de canais TRP activada pelo esteróide neuroactivo pregnenolona. DPC aumentou a [Ca2+]i acentuadamente na ausência de nifedipina, pondo em evidência acções colaterais indesejáveis noutros transportadores de Ca2+; o efeito correspondente de ácido mefenâmico foi negligenciável. O ácido mefenâmico não afectou os aumentos da [Ca2+]i induzidos por pulsos de Ca2+ na ausência de nifedipina, indicando que os canais subjacentes são diferentes dos canais TRPM3. Também foram avaliados os efeitos de pulsos de Ca2+ utilizando células BRIN-BD11 únicas. Os pulsos de Ca2+ induziram respostas compostas por vários aumentos rápidos e transitórios, com latências variáveis, um padrão que era notoriamente diferente do registado em ilhéus. Esta observação sugere que, em células BRIN-BD11, o mecanismo subjacente ao efeito dos pulsos de Ca2+ é manifestamente diferente do que ocorre em ilhéus. Conclui-se que as células-β de ratinho estão equipadas com canais TRPM3 sensíveis a pregnenolona, nifedipina e ácido mefenâmico. Sendo estes canais permeáveis a outros catiões divalentes, é provável que sejam responsáveis por IV recapturar iões Zn2+, que são necessários para a estabilização da insulina nos grânulos da célula-β.There is evidence for the operation of a Ca2+ influx pathway distinct from CaV channels in pancreatic beta cells. I aimed at identifying this pathway, using quantitative FURA-2 fluorescence microscopy to monitor global [Ca2+]i from single mouse islets. Stimulation of Ca2+ influx was effected mostly by raising [Ca2+]o to 7 mM (henceforth designated as a „Ca2+ pulse‟). Applying a Ca2+ pulse in presence of 3 mM glucose raised the [Ca2+]i. The effect was insensitive to further hyperpolarization with the KATP channel opener diazoxide (100 μM) but was greatly enhanced by the CaV1.0 blocker nifedipine (10 μM). Nifedipine itself raised the [Ca2+]i and accelerated Mn2+ quenching of FURA-2 fluorescence at the dye‟s isosbestic point. The effects of Ca2+ pulses in presence of nifedipine were blocked by two fenamates, diphenylamine-2-carboxylate (DPC, 500 μM) and mefenamic acid (3-80 μM; IC50: 10.3 μM). Mefenamic acid is a seemingly selective inhibitor of TRPM3 channels, a TRP channel sub-class activated by the neuroactive steroid pregnenolone. DPC raised the [Ca2+]i markedly in absence of nifedipine, highlighting unwanted actions of the drug on Ca2+ transport mechanisms unrelated to TRPM3 channels; the corresponding effect of mefenamic acid was negligible. Mefenamic acid did not affect the [Ca2+]i rises evoked by Ca2+ pulses in absence of nifedipine, indicating that the underlying channels are distinct from TRPM3 channels. I have also assessed the effects of Ca2+ pulses using single insulin-secreting BRIN-BD11 cells. Ca2+ pulses elicited multi-spike responses with variable lag-times, a pattern that contrasted markedly with that in islets, suggesting that the underlying mechanism is different. It is concluded that mouse beta-cells are equipped with pregnenolone-, nifedipine- and mefenamic acid-sensitive TRPM3 channels. Since these channels are permeant to other divalent cations, they may provide the re-uptake of Zn2+ ions, required to stabilize insulin in the beta-cell granules

Cyclic fatigue resistance, torsional resistance, and metallurgical characteristics of M3 Rotary and M3 Pro Gold NiTi files

Objectives: To evaluate the mechanical properties and metallurgical characteristics of the M3 Rotary and M3 Pro Gold files (United Dental). Materials and Methods: One hundred and sixty new M3 Rotary and M3 Pro Gold files (sizes 20/0.04 and 25/0.04) were used. Torque and angle of rotation at failure (n = 20) were measured according to ISO 3630-1. Cyclic fatigue resistance was tested by measuring the number of cycles to failure in an artificial stainless steel canal (60° angle of curvature and a 5-mm radius). The metallurgical characteristics were investigated by differential scanning calorimetry. Data were analyzed using analysis of variance and the Student-Newman-Keuls test. Results: Comparing the same size of the 2 different instruments, cyclic fatigue resistance was significantly higher in the M3 Pro Gold files than in the M3 Rotary files (p < 0.001). No significant difference was observed between the files in the maximum torque load, while a significantly higher angular rotation to fracture was observed for M3 Pro Gold (p < 0.05). In the DSC analysis, the M3 Pro Gold files showed one prominent peak on the heating curve and 2 prominent peaks on the cooling curve. In contrast, the M3 Rotary files showed 1 small peak on the heating curve and 1 small peak on the cooling curve. Conclusions: The M3 Pro Gold files showed greater flexibility and angular rotation than the M3 Rotary files, without decrement of their torque resistance. The superior flexibility of M3 Pro Gold files can be attributed to their martensite phase