Green coffee bean extract attenuates gentamicin induced acute nephrotoxicity in rats

Gentamicin induced acute nephrotoxicity (GIAN) is considered as one of the important causes of acute renal failure. In recent years’ great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of GIAN. Hence, the current study was designed to investigate the effect of green coffee bean extract (GCBE) on GIAN in rats. Results of the present study showed that rat groups that received oral GCBE for 7 days after induction of GIAN (by a daily intraperitoneal injection of gentamicin for 7days), reported a significant improvement in renal functions tests when compared to the GIAN model groups. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE-treated groups when compared to GIAN model group. These results indicate that GCBE has a potential role in ameliorating renal damage involved in GIAN.

Novel Insight into the Mechanism of Metabolic Surgery Causing the Diversity in Glycemic Status in Type 2 Diabetes

Metabolic surgery results in diverse glycemic status in patients with type 2 diabetes (T2D), including hyperglycemia without remission, significant amelioration of hyperglycemia with partial remission, complete restoration of euglycemia, or with prolonged remission, hyperglycemia recurrence in relapses after remission, or post-bariatric hypoglycemia. Unfortunately, it is not known how metabolic surgery leads to this diverse consequence. Here, we discuss the diversity of glycemic status associated with metabolic surgery and the potential mechanisms of T2D remission. We also highlight the relationship between the change in low-grade inflammation and T2D remission after metabolic surgery. We hypothesize that the level of inflammatory and anti-inflammatory cytokines controls the efficacy of metabolic surgery in patients with T2D. This hypothesis may provide further insight into the mechanism of the beneficial effects of metabolic surgery patients with T2D.

Idiopathic dilated cardiomyopathy as cor bovinum in infancy: “A foggy road in winter”

Dilated cardiomyopathy, when diagnosed in infancy, poses an array of difficulties from reaching an etiological diagnosis to prognosticating the long-term outcome. Here, we report a case of idiopathic dilated cardiomyopathy in a 6-month-old child who responded well to beta-blocker (Carvedilol) in optimum dosage and revealed favorable cardiac remodeling over 6 months with substantial improvement in ejection fraction (EF) (EF of 22–44%) with significant amelioration of child’s symptoms. Our case has a unique message that while treating idiopathic dilated cardiomyopathy (DCM) in infancy, optimized use of the beta-blockers is most often the only way to clear the foggy road of idiopathic DCM and obtain a favorable outcome.

Endovascular Thrombolysis in Hypothenar Hammer Syndrome: A Systematic Review

Objectives: Hypothenar hammer syndrome (HHS) is a rare vascular disease caused by blunt trauma of the hypothenar region. The optimal therapeutic strategy remains debatably since no large comparative studies are available yet. We want to evaluate the effectiveness of intra-arterial thrombolysis on angiographic and clinical outcome parameters in patients with HHS by performing a systematic review of the existing literature.Methods: A literature search of PUBMED/MEDLINE and SCIENCE DIRECT databases was performed up to May 2021.Results: In total, 16 manuscripts with 43 patients were included in the systematic review. Intra-arterial thrombolysis led to angiographic improvement in 29 patients (67.4%) and to clinical improvement in 34 patients (79.1%). Deterioration of arterial perfusion or clinical symptoms after thrombolysis were absent. Post-interventional complications were reported in only one patient (2.3%) without any bleeding complication. Logistic regression analyses demonstrated that a combined administration of fibrinolytics and heparin was associated with a significantly improved arterial patency [OR 12.57 (95% CI 2.48–97.8), p = 0.005] without significant amelioration of clinical symptoms [OR 3.20 (95% CI 0.6–18.9), p = 0.172]. The use of rt-PA compared to other fibrinolytics and a prolonged thrombolysis duration of more than 24 h did not show statistically significant effects. Intra-arterial thrombolysis was significantly less effective in patients who had undergone thrombolysis with a delay of more than 30 days regarding clinical improvement [OR 0.07 (95% CI 0.00–0.54), p = 0.024].Conclusions: Intra-arterial thrombolysis with a combination of fibrinolytics and heparin is an effective and safe therapeutic option in patients with acute HHS.

Prism Adaptation and Optokinetic Stimulation Comparison in the Rehabilitation of Unilateral Spatial Neglect

Prism adaptation (PA) is one of the most effective treatments for the rehabilitation of unilateral spatial neglect. Optokinetic stimulation (OKS) has also been demonstrated to be effective in ameliorating symptoms of neglect. The aim of this study is to compare the effectiveness of these two methods in a group of neglect patients using a crossover design. A group of 13 post-acute brain-damaged patients with unilateral spatial neglect, who had never been rehabilitated, were treated using PA and OKS. Each treatment was applied for 10 sessions, twice a day, to all patients with both treatments in crossed order (i.e., PA followed by OKS or vice versa). Neuropsychological assessments were performed: before the first (T1), at the end of the first/beginning of the second (T2) and at the end of the second training sessions (T3), and two weeks after the end of treatment (T4). Both procedures produced a significant improvement in clinical tests at T2, independent of the type of training. The results suggest that either PA or OKS induces a significant amelioration of neglect in right brain-damaged patients, mainly in the first block of treatment. Since no differences between treatments were found, they could be applied in clinical practice, according to the requirements of the individual patient.

Cognitive, behavioral, and psychological manifestations of COVID-19 in post-acute rehabilitation setting: preliminary data of an observational study

Psychological, emotional, and behavioral domains could be altered in COVID-19 patients and measurement of variables within these domains seems to be mandatory. Neuropsychological assessment could detect possible cognitive impairment caused by COVID-19 and the choice of appropriate tools is an important question. Aim of this exploratory study was to verify the effectiveness of an assessment model for patients with COVID-19. Twelve patients were enrolled and tested with Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Anxiety and Depression Short Scale (AD-R), and the Neuropsychiatry Inventory (NPI), at the time of their entrance (T0) and discharge (T1) from a rehabilitative unit. Moreover, a follow-up evaluation after 3 months (T2) has been conducted on eight patients. Results showed that at baseline (T0), 58.3% of the patients reported a score below cut-off at MMSE and 50% at MoCA. Although a significant amelioration was found only in NPI scores, a qualitative improvement has been detected at all tests, except for MoCA scores, in the T0-T1 trend analysis. A one-way repeated measures analysis of variance showed a significant variation in AD-R depression score, considering the three-assessment time (T0, T1, and T2). The evaluation and tracking over time of the impact of COVID-19 on cognitive, psychological, and behavioral domains has relevant implications for rehabilitation and long-term assistance needs planning. The choice of assessment tools should consider patients vulnerability and match the best compromise among briefness, sensitivity, and specificity.

The proSAAS chaperone provides neuroprotection and attenuates transsynaptic α–synuclein spread in rodent models of Parkinson’s disease

ABSTRACTParkinson’s disease is a devastating motor disorder involving the aberrant aggregation of the synaptic protein synuclein (aSyn) and degeneration of the nigrostriatal dopaminergic tract. We previously showed that proSAAS, a small secreted chaperone protein widely expressed in neurons within the brain, is able to block aSyn-induced dopaminergic cytotoxicity in primary nigral neuron cultures. We show here that coinjection of proSAAS-encoding lentivirus profoundly reduced the motor asymmetry caused by unilateral nigral AAV-mediated human aSyn overexpression. This positive functional outcome was accompanied by significant amelioration of the human aSyn-induced loss of both nigral tyrosine hydroxylase-positive cells and striatal tyrosine hydroxylase-positive terminals, demonstrating clear proSAAS-mediated protection of the nigro-striatal tract. ProSAAS overexpression also reduced the content of human aSyn protein in both the nigra and striatum and reduced the loss of tyrosine hydroxylase protein in both regions. Since proSAAS is a secreted protein, we tested the possibility that proSAAS is able to block the transsynaptic spread of aSyn from the periphery to the central nervous system, increasingly recognized as a potentially significant pathological mechanism. The number of human aSyn-positive neurites in the pons and caudal midbrain of mice following administration of human aSyn-encoding AAV into the vagus nerve was considerably reduced in mice coinjected with proSAAS-encoding AAV, supporting proSAAS-mediated blockade of transsynaptic aSyn transmission. We suggest that proSAAS may represent a promising target for therapeutic development in Parkinson’s disease.SignificanceThis paper describes two independent avenues of research that both provide support for the in vivo neuroprotective function of this small chaperone protein. In the first approach, we show that proSAAS overexpression provides remarkably effective protection against dopaminergic neurotoxicity in a rat model of Parkinson’s disease. This conclusion is supported both by three independent assays of motor function as well as by quantitative analysis of surviving dopaminergic neurons in brain areas involved in the control of motor function. In the second line of research, we show that in mice, the spread of human synuclein across synapses can be blunted by proSAAS overexpression.

The Anti-Atherosclerotic Action of FFAR4 Agonist TUG-891 in ApoE–Knockout Mice Is Associated with Increased Macrophage Polarization towards M2 Phenotype

Background: Over the past few years, a better understanding of the biology of G-protein coupled receptors (GPRs) has led to the identification of several receptors as novel targets for free fatty acids (FFAs). FFAR4 has received special attention in the context of chronic inflammatory diseases, including atherosclerosis, obesity and NAFLD, through to its anti-inflammatory effect. Methods: The present study investigates the influence of prolonged treatment with TUG-891-FFAR4 agonist on the development of atherosclerosis plaque in apoE-knockout mice, using morphometric and molecular methods. Results: TUG-891 administration has led to the reduction of atherosclerotic plaque size and necrotic cores in an apoE-knockout mice model. TUG-891-treated mice were administered subcutaneously at a dose of 20 mg/kg three times a week for 4 months. The FFAR4 agonist reduced the content of pro-inflammatory M1-like macrophages content in atherosclerotic plaques, as evidenced by immunohistochemical phenotyping and molecular methods. In atherosclerotic plaque, the population of smooth muscle cells increased as evidenced by α-SMA staining. We observed changes in G-CSF and eotaxin markers in the plasma of mice; changes in the levels of these markers in the blood may be related to macrophage differentiation. Importantly, we observed a significant increase in M2-like macrophage cells in atherosclerotic plaque and peritoneum. Conclusions: Prolonged administration of TUG-891 resulted in significant amelioration of atherogenesis, providing evidence that the strategy based on macrophage phenotype switching toward an M2-like activation state via stimulation of FFAR4 receptor holds promise for a new approach in the prevention or treatment of atherosclerosis.

Ions and Organic Solutes as Implicated in the Ameliorative Effect of Exogenous Application of Calcium on Salt Stressed Tomato (Lycopersicon esculentum Mill.) Plants

Aims: This study evaluated the role of sodium, potassium, proline and soluble sugars accumulation in the ameliorative effect of an exogenous application of calcium on the detrimental effect of salinity on tomato plants. Study Design: The experiment was implemented as a Completely Randomized Design (RCD) with four treatments and three replications. Place and Duration of Study: The experiment was realized in a green house of the Faculty of Agronomical Sciences, University of Abomey-Calavi, Benin Republic from June to July 2020. Methodology: Three weeks old plants of the tomato cultivar “Padma” was submitted in pots to four treatments comprising the control (without NaCl); salt stress (120 mM NaCl) and a combination of 120 mM NaCl and exogenous application of 40 mM CaSO4 or Ca (NO3)2 by irrigation every two days. Plants growth, sodium (Na) and potassium (K) as well as proline and soluble sugars contents of leaves and roots were determined after two weeks. Results: Salt effect reduced significantly plant growth at P =.05, root K content at P =.05 and leaf K/Na ratio at P =.01 whereas it increased significantly leaf Na at P =.05 and root soluble sugars content at P =.05. The application of exogenous calcium (Ca) induced a significant amelioration of plant growth at P =.01 more marked with CaSO4 than with Ca (NO3)2. This treatment induced a significant decrease at P =.01 in leaf and root Na content and a significant increase at P =.05 in root K content only for CaSO4, a significant increase at P =.01 in leaf K/Na ratio and a significant increase at P =.01 in leaf and root proline content only for Ca(NO3)2. Conclusion: The ameliorative effect of both forms of calcium was due mainly to sodium (Na) exclusion from leaves and potassium (K) accumulation associated to a maintain of high K/Na ratio mainly in leaves. The importance of proline accumulation as an indicator of this ameliorative effect was associated only to Ca(NO3)2.

ILB® Attenuates Clinical Symptoms and Serum Biomarkers of Oxidative/Nitrosative Stress and Mitochondrial Dysfunction in Patients with Amyotrophic Lateral Sclerosis

Oxidative/nitrosative stress and mitochondrial dysfunction is a hallmark of amyotrophic lateral sclerosis (ALS), an invariably fatal progressive neurodegenerative disease. Here, as an exploratory arm of a phase II clinical trial (EudraCT Number 2017-005065-47), we used high performance liquid chromatography(HPLC) to investigate changes in the metabolic profiles of serum from ALS patients treated weekly for 4 weeks with a repeated sub-cutaneous dose of 1 mg/kg of a proprietary low molecular weight dextran sulphate, called ILB®. A significant normalization of the serum levels of several key metabolites was observed over the treatment period, including N-acetylaspartate (NAA), oxypurines, biomarkers of oxidative/nitrosative stress and antioxidants. An improved serum metabolic profile was accompanied by significant amelioration of the patients’ clinical conditions, indicating a response to ILB® treatment that appears to be mediated by improvement of tissue bioenergetics, decrease of oxidative/nitrosative stress and attenuation of (neuro)inflammatory processes.