Natural antioxidants in Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by severe cognitive impairment that ultimately leads to death. Current drugs used in AD are acetylcholinesterase inhibitors and antagonists to the NMDA receptors. These drugs may only slightly improve cognitive functions but have only very limited impact on the clinical course of the disease. In the past several years, based on in vitro and in vivo studies in laboratory animals, natural antioxidants, such as resveratrol, curcumin and acetyl-L-carnitine have been proposed as alternative therapeutic agents for AD. An increasing number of studies demonstrated the efficacy of primary antioxidants, such as polyphenols, or secondary antioxidants, such as acetylcarnitine, to reduce or to block neuronal death occurring in the pathophysiology of this disorder. These studies revealed that other mechanisms than the antioxidant activities could be involved in the neuroprotective effect of these compounds. This paper discusses the evidence for the role of acetylcarnitine in modulating redox-dependent mechanisms leading to the upregulation of vitagenes. Furthermore, future development of novel antioxidant drugs targeted to the mitochondria should result in effectively slowing disease progression. The association with new drug delivery systems may be desirable and useful for the therapeutic use of antioxidants in human neurodegenerative diseases.     

New lanthanide complexes of 4-methyl-7-hydroxycoumarin and their pharmacological activity.

Complexes of cerium(III), lanthanum(III) and neodymium(III) with 4-methyl-7-hydroxycoumarin (Mendiaxon, Hymecromone) were synthesized by the mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, (1)H and (13)C NMR spectroscopies and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and the most active complex was investigated for spasmolytic activity. The complexes of cerium(III) and neodymium(III) showed marginal cytotoxic activity against transformed leukemic cell lines (P3HR1 and THP-1) as compared to the inorganic salts.     

Ruthenium complexes as anticancer agents

Cancer is one of the major cases of death in the world. Current treatment of cancer is limited to surgery, radiotherapy, and the use of cytotoxic agents, despite their well known side effects and problems associated with the development of resistance. For most forms of disseminated cancer, however, no curative therapy is available, and the discovery and development of novel active chemotherapeutic agents is largely needed. Since the development of cisplatin, an inorganic platinum complex, numerous platinum and non-platinum metal complexes were synthesized and tested for anticancer activity. Very few match the clinical efficacy of cisplatin. Ruthenium complexes were prepared to ameliorate cisplatin activity, particularly on resistant tumours, or to reduce host toxicity at active doses. Since many years a lot of scientific groups have actively worked in the field of inorganic antitumor drugs and have developed a number of Ru(II) and Ru(III) complexes, which were shown to possess good antitumor and, above all, antimetastatic properties against animal models. Ruthenium complexes are presently an object of great attention in the field of medicinal chemistry, as antitumor agents with selective antimetastatic properties and low systemic toxicity. Ruthenium compounds appear to penetrate reasonably well the tumor cells and bind effectively to DNA. In this review, the achievements in the field of medicinal chemistry, DNA binding modes, and the development status of Ru(II) and Ru(III) complexes as anticancer agents are discussed. The aim of this review is therefore that of critically examining the past and the actual work on ruthenium compounds with emphasis on their proposed role in cancer therapy.     

Coumarins as inhibitors of HIV reverse transcriptase

Acquired immunodeficiency syndrome (AIDS), a degenerative disease of the immune and central nervous systems, is an enormous world-wide health threat. No cure has been found, and research is aimed at developing chemotherapy against the causative agent, human immunodeficiency virus (HIV). Chemotherapy for AIDS has progressed steadily in the past decade. However, new, effective, and less toxic chemotherapeutic agents are still needed. Plants, particularly anti-infective or immunomodulating herbal medicines, can serve as sources of new active leads to be further developed as anti-AIDS drug candidates. A lot of structurally different natural coumarins were found to display potent anti-HIV activity and continued progress is anticipated in the discovery of new leads and in the development of these agents as potential anti-AIDS drug candidates. Recent studies based on the account of various coumarins from plant sources and their analogs--synthetic coumarins, indicate that some of them serve as potent nonnucleoside RT-inhibitors, another as inhibitors of HIV-integrase or HIV-protease. The current review demonstrates the variety of coumarins of natural plant origin and synthetic coumarins having unique mechanism of action to one of the most important stage of HIV replication (RT-inhibition). The merits of selecting potential anti-HIV agents to be used in rational combination drugs design and structure-activity relationships are discussed. The scientific community is looking actively for new drugs and combinations for treatment of HIV infection effective for first-line treatment, as well as against drug-resistant mutants.     

The migrant clinicians network: connecting practice to need and patients to care

Migrant Clinicians Network advocates for migrants and clinicians, develops appropriate resources, engages outside partners, conducts translational research, and runs programs that support clinical care on the front line of migrant health. Migrant Clinicians Network's goal is to improve health care for migrants by providing support, technical assistance, and professional development to clinicians in Federally Qualified Health Centers and other healthcare delivery sites with the ultimate purpose of providing quality health care that increases access and reduces disparities for migrant farmworkers and other mobile underserved populations. In this article the authors examine the migrant population in the United States, a brief history of clinicians working in migrant health, and the scope of current Migrant Clinicians Network activities, including occupational and environmental health.     

The Cost-Effectiveness of Hyperlipidemia Medication in Low- and Middle-Income Countries: A Review

Hyperlipidemia is a risk factor for cardiovascular disease – the leading cause of death globally. Increased understanding of the cost-effectiveness of hyperlipidemia treatment in low- and middle-income countries can guide approaches to hyperlipidemia management in resource-limited environments. We conducted a systematic review of the evidence on the cost-effectiveness of hyperlipidemia medication treatment in low- and middle-income countries using studies published between January 2010 and April 2020. We abstracted study details, including study design, treatment setting, intervention type, health metrics, costs standardized to constant 2019 US dollars, and cost-effectiveness measures including average and incremental cost-effectiveness ratios. Comparisons across studies suggested that treatment via polypill is generally more cost-effective than statin-only therapy, and that primary prevention is more cost-effective than secondary prevention. Treating hyperlipidemia at a threshold of 5.7 mmol/l comes at a higher cost per disability-adjusted life-years averted than at a threshold of 6.2 mmol/l. Most pharmacological treatment strategies for hyperlipidemia were found to be cost-effective in most of the examined low- and middle-income countries.     

Increase in aortic pulse wave velocity is associated with abnormal postprandial triglyceride response

BACKGROUND: Aortic pulse wave velocity (aPWV), an index of aortic distensibility, and postprandial hypertriglyceridemia are recognized as independent cardiovascular risk factors. HYPOTHESIS: The aim of this study was to evaluate the relationship between postprandial hypertriglyceridemia and changes in aPWV. METHODS: We prospectively studied 45 patients (mean age 48 [14] years, 28.9% men), who were submitted to a standardized fat meal (FM) test. According to their triglyceride (TG) levels 2, 4, 6, and 8 h after the FM, the patients were divided into two groups: Group 1 (31 patients) with postprandial TG levels < or = 219 mg/dl, and Group 2 (14 patients) with TG levels > 219 mg/dl at one of the aforementioned time intervals. Before and 6 h after the FM, aPWV was measured noninvasively. RESULTS: Baseline characteristics in the two groups were similar, except for higher TG, pulse pressure, waist-to-hip ratio, percentage of patients who smoked or had arterial hypertension, and lower high-density lipoprotein cholesterol levels in Group 2. Postprandially, aPWV was higher in Group 2 [11.2(2.7) vs. 9.1(2.1) m/s, p = 0.004]. Changes in aPWV correlated with TG changes from baseline to 6 h after FM (r = 0.539, p < 0.001) and with the areas under the TG curve (r = 0.617, p < 0.001). A postprandial TG increase of 100 mg/dl resulted in a 0.88 m/s rise of aPWV. CONCLUSION: An increase in aPWV 6 h after an FM test correlates positively with abnormal postprandial hypertriglyceridemia. These relationships, reported here for the first time, could be of practical use for better evaluation of patient prognosis.     

An electrophysiologic study: can semantic context processes be mobilized in patients with thought-disordered schizophrenia?

OBJECTIVE: The aim of this study was to test the hypothesis that reinforcing the structuring of verbal material may bring about an improvement in contextualization processes in patients with formal thought-disordered schizophrenia. METHOD: A total of 38 schizophrenia patients with formal thought disorders and 24 matched healthy control subjects performed 2 lexical decision tasks, involving 2 levels of contextual structuring (with 16.7% and 33% of related words, respectively). The event-related potentials, N400 and late positive component (LPC), and behavioural variables (reaction times and error percentages) were analyzed. RESULTS: A context-structuring effect was observed on LPC, but not on N400. In subjects with schizophrenia, the N400 anomalies (that is, increase in amplitude for the related words and reduction of the N400 effect) persisted in both context-structuring conditions. Similarly, a reduction in LPC amplitude for the unrelated word category, as well as a decrease in the LPC effect, was observed in these patients. CONCLUSIONS: The schizophrenia patients with formal thought disorders did not benefit from the structuring of the context to implement context integration strategies. This deficit appears to be stable. The results are discussed within the framework of a previously published model of language comprehension.