Cardiovascular and hepatic toxicity of cocaine: potential beneficial effects of modulators of oxidative stress

Oxidative stress (OS) is thought to play an important role in the pharmacological and toxic effects of various drugs of abuse. Herein we review the literature on the mechanisms responsible for the cardiovascular and hepatic toxicity of cocaine with special focus on OS-related mechanisms. We also review the preclinical and clinical literature concerning the putative therapeutic effects of OS modulators (such as N-acetylcysteine, superoxide dismutase mimetics, nitroxides and nitrones, NADPH oxidase inhibitors, xanthine oxidase inhibitors, and mitochondriotropic antioxidants) for the treatment of cocaine toxicity. We conclude that available OS modulators do not appear to have clinical efficacy

1972 Otterbein Football Roster

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Stati d’animo in persone con malattie croniche

ItNell’ambito della psicologia della salute è di rilievo la rappresentazione della propria malattia per le persone affette da disturbi invalidanti, cronici che, per effetto di un continuo trauma, comportano una ridefinizione del proprio Sé. Questo trauma nell’esperienza della persona è cumulativo (Khann, 1963) ed anche il tempo cronologico diviene permeato di micro traumi,che sono collegati a perdite che riguardano la propria autostima e la capacità di fronteggiare le difficoltà e la propria identità corporea Per questi motivi l’indagine ha teso ad esplorare la rappresentazione della malattia degenerativa cronica in persone con malattia di Parkinson ed Artrite Reumatoide, disturbi che investono non solo lo psicofisico, ma anche la realtà psicosociale della persona. La ricerca ha avuto l’obiettivo di conoscere quanto le due malattie si differenziano, pur avendo in comune cronicità, invalidità e degenerazione, ipotizzando che vi siano espressioni linguistiche comuni e tipiche di ciascuna malattia. Con la somministrazione di tre strumenti (M.M.S.E., Beck Depression Inventory, Scala di Hoehn&Yahr e Scala di Hockberg) abbiamo selezionato e caratterizzato i due gruppi di soggetti a cui abbiamo successivamente applicato un Questionario Anamnestico ed un aggregato di 35 parole stimolo, per descrivere il proprio stato d’animo. Dai risultati è emerso che le persone (adulti-anziani), con un’età media di 54 anni, considerano il proprio stato soprattutto in termini negativi. Per quanto riguarda i sintomi il tremore è quello più citato dai parkinsoniani, seguito dalle le problematiche motorie, mentre le persone con Artrite puntualizzano soprattutto il dolore e le difficoltà psicologiche. La percezione della malattia è legata all’entità del sintomo e le parole scelte (10 su 35) sono simili per i due gruppi , ma la distribuzione del grado di importanza attribuita è risultata diversa in modo significativo La conoscenza della diversa distribuzione delle parole permette all’altro di facilitare il rapporto con coloro che sono spesso sopraffatti dal disagio e dalla sofferenza.EnIn the area of health psychology, the way in which a disorder is represented is important, especially by people suffering from two incapacitating and chronic disorders, as these lead to self-redefinition because of constant trauma. People experience this suffering as being cumulative (Khann M.M.R.1963) and over time it becomes permeated with micro-traumas that are associated with the loss of self-esteem and the ability to cope with difficulties, and identifying with their own body. For these reasons, the research aimed at exploring the way in which chronic degenerative disorders are represented by people with Parkinson’s disease and rheumatoid arthritis: disorders that affect not only psychophysical aspects, but also the person’s psychosocial circumstances. The research also aimed at finding out the extent to which the two disorders differ. Although they are both chronic, incapacitating and degenerative, we investigated whether there may be linguistic expressions that are common to, and typical of, the two pathologies that would describe a state of mind and contribute to representing the two chronic, degenerative disorders. We administrated three tools (M.M.S.E., Beck. Depression Inventory, Hoehn &Yahr Scale, Hockberg Scale) to select and describe two groups of people to whom we then gave the following tests: an Anamnestic Questionnaire and a list of 35 suggested words to be used to describe their state of mind. The results showed that those (adultselderly) with an average age of 54 were primarily negative about their condition. In terms of symptoms, trembling is the most frequent in Parkinson’s sufferers, followed by impeded movement and, in particular, pain and psychological problems for those with arthritis. The perception of the disorder is linked to the extent of the symptoms and the words chosen (10 out of 35) were similar in both groups, but the distribution of the importance ascribed was significantly different. Knowing about the different distribution of the words also facilitates the relationship with those who are frequently overwhelmed by discomfort and suffering.FrDans le cadre de la psychologie de la santé un rôle important est donné à la représentation de la pathologie, en particulier chez les patients souffrant de deux affections invalidantes et chroniques, qui, en raison du caractère constant du traumatisme, entraînent une redéfinition de Soi. Dans l’expérience personnelle ce traumatisme est cumulatif (Khann M.M.R.1963) et le temps chronologique s’imprègne de microtraumatismes associés à la perte de l’auto estime, de la capacité de faire face aux difficultés et de l’identité corporelle. Pour ces raisons, l’étude explore la représentation de la maladie dégénérative chronique chez les personnes atteintes de la maladie de Parkinson et d’Arthrite Rhumatoïde: des troubles qui affectent non seulement la dimension psychophysique, mais aussi la réalité psychosociale de la personne. La recherche vise à explorer la manière dont ces deux pathologies – qui ont des traits communs, comme la chronicité, l’invalidité et le caractère dégénératif – peuvent donner lieu à des expressions linguistiques communes et typiques de deux maladies, en rapport avec le tableau pathologique, permettant d’établir des descriptions de l’état d’âme qui contribuent à une représentation des deux pathologies chroniques dégénératives. Par l’administration de trois protocoles (M.M.S.E., Beck. Depression Inventory Echelle Hoehn &Yahr- Echelle Hockberg) nous avons sélectionné les deux groupes de patients auxquels ont été par la suite administrés les tests suivants: le Questionnaire Anamnestique et une liste de 35 mots les incitant à décrire leur état d’âme. Les résultats ont mis en évidence que les patients (adultes – personnes âgées) dont l’âge moyen était de 54 ans, décrivent leur état surtout en termes négatifs. En ce qui concerne les symptômes, la Trémulation apparaît comme le plus répandu, suivi par l’Empêchement de la capacité motrice et surtout par la Douleur et les Difficultés psychologiques. Pour les personnes souffrant d’Arthrite Rhumatoïde, la perception de la maladie est liée à la gravité du symptôme. Les mots choisis (10 sur 35) sont pareills pour les deux groupes, mais l’attribution de l’importance diffère de manière significative. La connaissance de l’attribution différente contribue à faciliter la relation avec ces patients, souvent accablés par l’angoisse et la souffrance

Effect of a 16-month exercise training program on functional capacities in a centenarian male master athlete: A case study

The effects of exercise training have never been investigated in centenarians. This single-subject research study aimed to assess the effects of a structured training protocol on functional capacities in a centenarian master athlete. A 99.5 years old male subject participated in the study. Before and after a 16-month training intervention the participant underwent a test battery for flexibility (YMCA sit and reach), balance (single leg stance), upper limb strength (hand grip and pinch strength), and lower limb power (counter movement jump) and muscular endurance (horizontal leg press with 85 kg load). After training, sit and reach (-3 cm) and counter movement jump (-0.5 cm) scores decreased, whereas single leg stance (+1.3 s), left hand grip (+2.0 kg), right hand pinch (+0.5 kg), and horizontal leg press (+2 repetitions) scores increased. Right hand grip strength and left-hand pinch strength did not change after training. When pre- and post-training scores were compared to gender-matched normative values, flexibility resulted well below average, maybe because of a relatively broad age category (>65 years). When more specific age categories were available, the participant's balance resulted slightly below average (age category 80-99 years) and upper limb strength above average (age category >85 years). No normative values were found for lower limb power and muscular endurance. In conclusion, this study highlights that structured exercise training may play a role in maintaining – and even in increasing – functional capacities in the oldest old age

Cardiovascular and Hepatic Toxicity of Cocaine: Potential Beneficial Effects of Modulators of Oxidative Stress

Oxidative stress (OS) is thought to play an important role in the pharmacological and toxic effects of various drugs of abuse. Herein we review the literature on the mechanisms responsible for the cardiovascular and hepatic toxicity of cocaine with special focus on OS-related mechanisms. We also review the preclinical and clinical literature concerning the putative therapeutic effects of OS modulators (such as N-acetylcysteine, superoxide dismutase mimetics, nitroxides and nitrones, NADPH oxidase inhibitors, xanthine oxidase inhibitors, and mitochondriotropic antioxidants) for the treatment of cocaine toxicity. We conclude that available OS modulators do not appear to have clinical efficacy

Do changes in Lactuca sativa metabolic performance, induced by mycorrhizal symbionts and leaf UV-B irradiation, play a role towards tolerance to a polyphagous insect pest?

: The increased ultraviolet radiation (UV) due to the altered stratospheric ozone leads to multiple plant physiological and biochemical adaptations, likely affecting their interaction with other organisms, such as pests and pathogens. Arbuscular mycorrhizal fungi (AMF) and UV-B treatment can be used as eco-friendly techniques to protect crops from pests by activating plant mechanisms of resistance. In this study, we investigated plant (Lactuca sativa) response to UV-B exposure and Funneliformis mosseae (IMA1) inoculation as well as the role of a major insect pest, Spodoptera littoralis. Lettuce plants exposed to UV-B were heavier and taller than non-irradiated ones. A considerable enrichment in phenolic, flavonoid, anthocyanin, and carotenoid contents and antioxidant capacity, along with redder and more homogenous leaf color, were also observed in UV-B-treated but not in AMF-inoculated plants. Biometric and biochemical data did not differ between AMF and non-AMF plants. AMF-inoculated plants showed hyphae, arbuscules, vesicles, and spores in their roots. AMF colonization levels were not affected by UV-B irradiation. No changes in S. littoralis-feeding behavior towards treated and untreated plants were observed, suggesting the ability of this generalist herbivore to overcome the plant chemical defenses boosted by UV-B exposure. The results of this multi-factorial study shed light on how polyphagous insect pests can cope with multiple plant physiological and biochemical adaptations following biotic and abiotic preconditioning

Multidisciplinary Approach on Characterizing a Mechanochemically Activated Composite of Vinpocetine and Crospovidone

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Significant improvement of solubilization kinetics of poorly soluble vinpocetine was obtained through amechanochemical activation process in presence ofmicronized crospovidone. Drug-to-polymer weight ratio and milling time variables resulted to have statistically significant impacts on the activation of the product. The complete amorphization was obtained in the coground with the highest crospovidone contents (>80% wt), milled for the longest time (180 min). An ad hoc software was then used to calculate the dimensions of the drug crystallites in the samples on the basis of the calorimetric data. The thermal analyses were then accompanied and confirmed by an extensive solid-state characterization, performing X-ray diffraction, Raman imaging/spectroscopy, DRIFT, and SS-NMR spectroscopy, followed by laser diffraction and solubilization kinetics tests. All the analyses agreed on attesting the progressive loosing of crystalline structure of the drug when increasing milling time and amount of polymer in the formulations. This activated status of the drug, which resulted to be homogeneously distributed on the coground sample and stable for at least 1 year, was reflected on favorable solubilization kinetics. The in vivo studies on rats revealed that coground systems promoted a fivefold higher oral bioavailability enhancement in comparison to a commercial formulation (VimpocetinR 5mg Capsules, Pharma

Predicting respiratory failure in patients infected by SARS-CoV-2 by admission sex-specific biomarkers

Background: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. Methods: Plasma levels of sex hormones (testosterone and 17β-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. Results: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. Conclusions: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring

Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations

: Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) were evaluated. Patients who were FH-mutation negative had lower mean levels of pretreatment LDL-C than patients who were FH-mutation positive (217.14±55.49 versus 270.52±68.59 mg/dL, P<0.0001). The mean value (±SD) of the polygenic LDL-C risk score was 1.00 (±0.18) in patients who were FH-mutation negative and 0.94 (±0.20) in patients who were FH-mutation positive (P<0.0001). In the receiver operating characteristic analysis, the area under the curve for recognizing subjects characterized by polygenic hypercholesterolemia was 0.59 (95% CI, 0.56-0.62), with sensitivity and specificity being 78% and 36%, respectively, at 0.905 as a cutoff value. Higher mean polygenic LDL-C risk score levels were observed among patients who were FH-mutation negative having pretreatment LDL-C levels in the range of 150 to 350 mg/dL (150-249 mg/dL: 1.01 versus 0.91, P<0.0001; 250-349 mg/dL: 1.02 versus 0.95, P=0.0001). A positive correlation between polygenic LDL-C risk score and pretreatment LDL-C levels was observed among patients with FH independently of the presence of causative mutations. Conclusions This analysis confirms the role of polymorphisms in modulating LDL-C levels, even in patients with genetically confirmed FH. More data are needed to support the use of the polygenic score in routine clinical practice