Current Clinical Pharmacology - Volume 11, Issue 3, 2016

Background: Post-operative atrial fibrillation (POAF) is a major and frequent complication occurring after cardiac surgery, contributing to prolonged intensive care and hospital stays and is associated with several cardiovascular complications. The exact mechanisms and signaling pathways involved in the development of POAF seem to be multifactorial and remain to date incompletely understood. β-blockers and amiodarone are the first line preventive drugs but are partially effective and near 30% of POAF resist to these strategies. Objective and Method: In this work, we review the current knowledge about pathophysiological POAF mechanisms and preventive pharmacological strategies. We also discuss the rational for the use of pre-operative plasma aldosterone and galectin-3 (Gal-3) levels as predictive biomarkers of POAF and the potential role of aldosterone antagonists in the POAF preventive strategy. Conclusion: POAF is a major complication occurring after cardiac surgery. In this context, there is some evidence indicating that renin–angiotensin–aldosterone system and Gal-3 could be very useful predictive biomarkers of POAF and potentially interesting therapeutic target to prevent POAF occurrence. We present the rationale and the design of the ALDO-POAF trial (ALDOsterone for prediction of Post- Operative Atrial Fibrillation, NCT 02814903).

Background: The toxicity of lead and its compounds is well known, causing anemia by inhibiting the synthesis of porphyrins. The neurotoxic effects, particularly in the young, alter the structure of cell membranes and DNA. Chronic exposure to lead has adverse effects on the body by disrupting the mechanisms of energy production and tissue damage, in particular in its links with thiol groups and competition for binding sites with zinc. Objective: This review is therefore a description of the mechanism of lead toxicity as well as of possible interventions for the detoxification of the body. Part of the clinical intervention is the provision of chelates that form insoluble complexes with lead and eliminate the load in tissues. Most of these chelating agents have a number of side effects. It is therefore not surprising that active compounds with distinctive antioxidant and chelating properties are being sought after. Conclusion: The possibility of administering lower amounts, and the corresponding decrease in side effects, would be important for clinical practice. Both prospective studies and our initial studies on humic acids have highlighted positive effects based on their antioxidant and chelating properties.

Background: Drug delivery across the deeper layers of skin to make it systemically available is a considerable challenge in the development of a carrier. Numerous efforts have been put forward to find ways to overcome the formidable barrier of stratum corneum. Various lipid based vesicles viz liposomes, transfersomes, and invasomes have gained prominent deliberations across the globe. More recently, ethosomes have been investigated for their potential for transdermal delivery of several drugs. Objective: In the present review an attempt has been made to illustrate preclinical and clinical studies depicting enhanced safety and efficacy of drugs delivered via ethosomes. Further, patents on transdermal delivery have been highlighted specifying the effectiveness of ethosomes in the transport of therapeutic actives. Methods: Through the search engine “Scopus” literature on therapeutic categories such as antimicrobials, anti-inflammatory, and drugs acting on CNS has been collected. Results: Preclinical and clinical studies that have been carried out by various researchers affirm the potentiality of ethosomes for delivering wide variety of drugs belonging to different therapeutic categories. In vitro and in vivo permeability analyses delineated the enhancement of permeability. Consequently, enhanced transdermal flux was reported and in vivo confocal laser scanning microscopy depicted the quantity as well as depth of penetrability via ethosomes. Conclusion: From various research reports, it can be concluded that ethosomes are the competent and efficient vesicles to provide better drug transport via transdermal route.

Endothelin-1, (ET-1, EDN1) is an endogenous polypeptide which demonstrates dominant vasoconstriction activity and mitogenic effect. It has positive inotropic and chronotropic effects on the heart, stimulates the sympathetic and the renin-angiotensin-aldosterone systems and modifies homeostasis. The human ET-1 gene which consists of 6836 nucleotides located on chromosome 6p23-p24 produces Pre-pro-ET-1, which is consequently cleaved to big-ET-1. The mature 21-amino acid ET-1 is generated by subsequent enzymatic cleavage of the big-ET-1. A comprehensive review of the literature on the consequences of different ET-1 gene variants on ET-1 linked diseases has not been accomplished. Many variants of ET-1 gene, including transversion, transition, insertion, and repeated nucleotide polymorphisms, which influence the hereditary risk of cardiovascular and other related diseases have already been located, genotyped, and examined. Among them ten polymorphisms including transversion; -1370 (T-1370G) (rs1800541), +5665 (Lys198Asn) (rs5370), G2288T polymorphisms (rs2070699), and -974 C>A (rs3087459) polymorphism, transition; +3660 (Glu106Glu) (rs5369), G(8002)A (rs2071942), rs1476046 polymorphism , rs2071943 polymorphism, and rs9296345 polymorphism, and insertion/delete; +138 (+138/ex1ins/delA) (rs1800997) were studied and phenotyped extensively. Some significant associations with many different diseases (phenotypes) especially those related to cardiovascular system diseases such as hypertension, ischemic diseases, angina, and acute coronary syndrome have been described in the literature. Some are associated with other diseases such as asthma, pulmonary edema, hearing impairment, obesity and sleep apnea. Moreover, some are modifying the course and adverse effects of several drugs. Many of these polymorphisms were studied, thus some inner complex association manner was also described.

Remineralizing agents represent a new frontier in dentistry. They may be classified as fluoride agents, calcium and phosphate based agents, herbal agents or combinations. The modes of delivery of remineralizing agents may be as dentifrices, mouth rinses, lozenges or chewing gums. The applications of remineralizing agents may be extrapolated to virtually every branch of dentistry ranging from pediatric to geriatric dentistry.

Background: There is still speculative data regarding the role of spinal dopaminergic neurotransmission in restless leg syndrome (RLS). Methods: We evaluated the therapeutic role of pramipexole in a patient with cervical disc prolapsus who exceptionally presented with neck restlessness. Results: We have found that pramipexole leads to a significant improvement in restlessness symptoms in the neck region. Discussion: The therapeutic role of pramipexole may not only suggest secondary deficits due to spinal pathologies but also indicate that specialized spinal dopaminergic neurons may play an important role in the pathogenesis of region specific restlessness symptomatology.