Lactoferrin is an iron-binding protein present in large quantities in colostrum and in breast milk, in external secretions and in polymorphonuclear leukocytes. Lactoferrin's main function is ...non-immune protection. Among several protective activities shown by lactoferrin, those displayed by orally administered lactoferrin are: (i) antimicrobial activity, which has been presumed due to iron deprivation, but more recently attributed also to a specific interaction with the bacterial cell wall and extended to viruses and parasites; (ii) immunomodulatory activity, with a direct effect on the development of the immune system in the newborn, together with a specific antinflammatory effects; (iii) a more recently discovered anticancer activity. It is worth noting that most of the protective activities of lactoferrin have been found, sometimes to a greater extent, also in peptides derived from limited proteolysis of lactoferrin that could be generated after lactoferrin ingestion. Lactoferrin could therefore be considered an ideal nutraceutic product because of its relatively cheap production from bovine milk and of its widely recognized tolerance after ingestion, along with its well demonstrated protective activities. The most important protective activities shown by orally administered bovine lactoferrin are reviewed in this article.
Randomized Trial of Thymectomy in Myasthenia Gravis Wolfe, Gil I; Kaminski, Henry J; Aban, Inmaculada B ...
New England journal of medicine/The New England journal of medicine,
08/2016, Letnik:
375, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus ...prednisone with prednisone alone.
We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period.
A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003).
Thymectomy improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.).
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•Lf and whey proteins are good candidates as antiviral and immunomodulatory drugs.•Lf exerts anti-SARS-CoV-2 activity in vitro, supporting evidence from in silico studies.•The ...combination of Lf with antiviral drugs improve recovery in COVID-19 patients.•A few clinical trials suggest that Lf help to prevent and treat COVID-19.
Native and chemically modified whey proteins and their peptide derivatives are encountering the interest of nutraceutical and pharmaceutical industries, due to the numerous properties, ranging from antimicrobial to immunological and antitumorigenic, that result in the possibility to employ milk and its protein components in a wide range of treatment and prevention strategies. Importantly, whey proteins were found to exert antiviral actions against different enveloped and non-enveloped viruses. Recently, the scientific community is focusing on these proteins, especially lactoferrin, since in vitro studies have demonstrated that they exert an important antiviral activity also against SARS-CoV-2. Up-to date, several studies are investigating the efficacy of lactoferrin and other whey proteins in vivo. Aim of this review is to shed light on the most relevant findings concerning the antiviral properties of whey proteins and their potential applications in human health, focussing on their application in prevention and treatment of SARS-CoV-2 infection.
Coumarin is an effective treatment for primary lymphoedema, as well as lymphoedema related to breast cancer radiotherapy or surgery. However, its clinical use is limited in several countries due to ...the possible occurrence of hepatotoxicity, mainly in the form of mild to moderate transaminase elevation. It is worth noting that only a few cases of severe hepatotoxicity have been described in the literature, with no reported cases of liver failure. Data available on coumarin absorption, distribution, metabolism, and excretion have been reviewed, focusing on hepatotoxicity studies carried out in vitro and in vivo. Finally, safety and tolerability data from clinical trials have been thoroughly discussed. Based on these data, coumarin-induced hepatotoxicity is restricted to a small subset of patients, probably due to the activation in these individuals of alternative metabolic pathways involving specific CYP450s isoforms. The aim of this work is to stimulate research to clearly identify patients at risk of developing hepatotoxicity following coumarin treatment. Early identification of this subset of patients could open the possibility of more safely exploiting the therapeutical properties of coumarin, allowing patients suffering from lymphoedema to benefit from the anti-oedematous activity of the treatment.
Galectin-3 binding protein (Gal-3BP) is a multifunctional glycoprotein involved in cell–cell and cell–matrix interactions known to be upregulated in cancer and various viral infections, including ...HIV-1, HCV, and SARS-CoV-2, with a key role in regulating the antiviral immune response. Studies have identified a direct correlation between circulating levels of Gal-3BP and the severity of disease and/or disease progression for some viral infections, including SARS-CoV-2, suggesting a role of Gal-3BP in these processes. Due to Gal-3BP’s complex biology, the molecular mechanisms underlying its role in viral diseases have been only partially clarified. Gal-3BP induces the expression of interferons (IFNs) and proinflammatory cytokines, including interleukin-6 (IL-6), mainly interacting with galectin-3, targeting the TNF receptor-associated factors (TRAF-6 and TRAF-3) complex, thus having a putative role in the modulation of TGF-β signaling. In addition, an antiviral activity of Gal-3BP has been ascribed to a direct interaction of the protein with virus components. In this review, we explored the role of Gal-3BP in viral infections and the relationship between Gal-3BP upregulation and disease severity and progression, mainly focusing on SARS-CoV-2. Augmented knowledge of Gal-3BP’s role in virus infections can be useful to evaluate its possible use as a prognostic biomarker and as a putative target to block or attenuate severe disease.
Bacterial resistance to antimicrobials is considered a major issue worldwide. This condition may account for treatment failure of urinary tract infections, which are among the most common infections ...both in community and healthcare settings. Therapy against uropathogens is generally administered empirically, possibly leading to unsuccessful therapy, recurrence and development of antibiotic resistance. The reduction in analytical time to obtain antimicrobial susceptibility test (AST) results could play a key role in reducing the cost of healthcare, providing information about antibiotic efficacy and thus preventing from either exploiting new and expensive antibiotics unnecessarily or using obsolete and ineffective ones. A more rational choice among treatment options would hence lead to more effective treatment and faster resolution. In this paper we evaluated the performance of a new Point Of Care Test (POCT) for the rapid prediction of antimicrobial susceptibility in urine samples performed without the need of a laboratory or specialized technicians. 349 patients were enrolled in two open-label, monocentric, non-interventional clinical trials in partnership with an Emergency Medicine ward and the Day Hospital of two large healthcare facilities in Rome. Antibiogram was carried out on 97 patients. Results from analysis of urine samples with the POCT were compared with those from routine AST performed on culture-positive samples, displaying high accuracy (>90%) for all tested antimicrobial drugs and yielding reliable results in less than 12 hours from urine collection thus reducing analytical and management costs.
The research and the individuation of tumour markers in biological fluids are currently one of the main tools to support diagnosis, prognosis, and monitoring of the therapeutic response in oncology. ...Although the identification of tumour markers in asymptomatic patients is crucial for early diagnosis, its application is still limited by the relatively low sensitivity and the complexity of existing methods (i.e. ELISA, mass spectrometry). We developed an easy, fast, and ultrasensitive surface-enhanced Raman scattering (SERS)–based system, for the detection and quantitation of the LGALS3BP (90K) biomarker that was used as a model, based on the development of antibody-functionalized nanostructured gold surfaces. The detection system was effective for the ultrasensitive detection and characterization of samples of different biochemical compositions. In conclusion, this work could provide the foundation for the development of a medical diagnostic device with the highest predictive power when compared with the methods currently used in cancer diagnostics.
Usnic acid (UA) is a dibenzofuran derivative naturally present in lichens, organisms resulting from the symbiosis between a fungus and a cyanobacterium, or an alga. UA shows antimicrobial, antitumor, ...antioxidant, analgesic, anti-inflammatory as well as UV-protective activities. Its use as pharmacological agent is widely described in traditional medicine, and in the past few years, the product has been marketed as a food supplement for the induction of weight loss. However, the development of severe hepatotoxicity in a limited number of subjects prompted the FDA to issue a warning letter, which led to the withdrawal of the product from the market in November 2001. Data published in literature on UA toxicology, genotoxicity, mutagenesis, and teratogenicity have been reviewed, as well as the case reports of subjects who developed hepatotoxicity following oral administration of UA as a slimming agent. Finally, we reviewed the most recent studies on the topical use of UA, as well as studies aimed at improving UA pharmacologic activity and reducing toxicity. Indeed, advancements in this field of research could open the possibility to reintroduce the use of UA as therapeutical agent.
Although classical trigeminal neuralgia (CTN) is frequently caused by neurovascular contact (NVC) at the trigeminal root entry zone (REZ), both anatomical and MRI studies have shown that NVC of the ...trigeminal nerve frequently occurs in individuals without CTN. To assess the accuracy of MRI in distinguishing symptomatic from asymptomatic trigeminal NVC, we submitted to high-definition MRI the series of CTN patients referred to our outpatient service between June 2011 and January 2013 (n=24), and a similar number of age-matched healthy controls. Two neuroradiologists, blinded to the clinical data, evaluated whether the trigeminal nerve displayed NVC in the REZ or non-REZ, whether it was dislocated by the vessel or displayed atrophy at the contact site, and whether the offending vessel was an artery or a vein. Our data were meta-analyzed with those of all similar studies published from January 1970 to June 2013. In our sample, REZ contact, nerve dislocation and nerve atrophy were independently associated with CTN (P=.027; P=.005; P=.035 respectively). Compared to a rather low sensitivity of each of these items (alone or in combination), their specificity was high. When REZ contact and nerve atrophy coexisted, both specificity and positive predictive value rose to 100%. Meta-analysis showed that REZ NVC was detected in 76% of symptomatic and 17% of asymptomatic nerves (P<.0001), whereas anatomical changes were detected in 52% of symptomatic and 9% of asymptomatic nerves (P<.0001). In conclusion, trigeminal REZ NVC, as detected by MRI, is highly likely to be symptomatic when it is associated with anatomical nerve changes.
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