Cough occurs in 5% to 20% of patients treated with ACE inhibitors, recurring with reintroduction of the same or another ACE inhibitor. It is more common in women. The mechanism may involve accumulation of prostaglandins, kinins (such as bradykinin), or substance P (neurotransmitter present in respiratory tract C-fibers); both bradykinin and substance P are degraded by ACE. A 4-day trial of withdrawal of the ACE inhibitor or temporary substitution of another class of antihypertensive agent inexpensively and easily ascertains if the ACE inhibitor caused the cough. Change to another ACE inhibitor or additive therapy with nonsteroidal anti-inflammatory drugs is not recommended. Prompt recognition of ACE inhibitor-related cough can prevent unnecessary diagnostic testing and treatment. Angioedema occurs in 0.1% to 0.2% of patients receiving ACE inhibitors. The onset usually occurs within hours or, at most, 1 week after starting therapy. The mechanism may involve autoantibodies, bradykinin, or complement-system components. Treatment involves first protecting the airway, followed by epinephrine, antihistamines, and corticosteroids if needed. Therapy is then resumed with an alternate class of antihypertensive agent.

BackgroundToxoplasmosis is becoming a global health hazard as it infects 30–50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this ‘asymptomatic infection’ may also lead to development of other human pathologies.Aims of the StudyThe purpose of the study was to collect available geoepidemiological data on seroprevalence of toxoplasmosis and search for its relationship with mortality and disability rates in different countries.Methods and FindingsPrevalence data published between 1995–2008 for women in child-bearing age were collected for 88 countries (29 European). The association between prevalence of toxoplasmosis and specific disease burden estimated with age-standardized Disability Adjusted Life Year (DALY) or with mortality, was calculated using General Linear Method with Gross Domestic Product per capita (GDP), geolatitude and humidity as covariates, and also using nonparametric partial Kendall correlation test with GDP as a covariate. The prevalence of toxoplasmosis correlated with specific disease burden in particular countries explaining 23% of variability in disease burden in Europe. The analyses revealed that for example, DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and another 12 diseases showed positive trends (p<0.1). For several obtained significant correlations between the seroprevalence of toxoplasmosis and specific diseases/clinical entities, possible pathophysiological, biochemical and molecular explanations are presented.ConclusionsThe seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests however that possible role of toxoplasmosis as a triggering factor responsible for development of several clinical entities deserves much more attention and financial support both in everyday medical practice and future clinical research.

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For about half a century, the binding of drugs to plasma albumin, the "silent receptor," has been recognized as one of the major determinants of drug action, distribution, and disposition. In the last decade, the binding of drugs, especially but not exclusively basic entities, to another plasma protein, alpha 1-acid glycoprotein (AAG), has increasingly become important in this regard. The present review points out that hundreds of drugs with diverse structures bind to this glycoprotein. Although plasma concentration of AAG is much lower than that of albumin, AAG can become the major drug binding macromolecule in plasma with significant clinical implications. Also, briefly reviewed are the physiological, pathological, and genetic factors that influence binding, the role of AAG in drug-drug interactions, especially the displacement of drugs and endogenous substances from AAG binding sites, and pharmacokinetic and clinical consequences of such interactions. It can be predicted that in the future, rapid automatic methods to measure binding to albumin and/or AAG will routinely be used in drug development and in clinical practice to predict and/or guide therapy.

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Honey has been widely accepted as food and medicine by all generations, traditions, and civilizations, both ancient and modern. For at least 2700 years, honey has been used by humans to treat a variety of ailments through topical application, but only recently have the antiseptic and antimicrobial properties of honey been discovered. Honey has been reported to be effective in a number of human pathologies. Clinical studies have demonstrated that application of honey to severely infected cutaneous wounds rapidly clears infection from the wound and improves tissue healing. A large number of in vitro and limited clinical studies have confirmed the broad-spectrum antimicrobial (antibacterial, antifungal, antiviral, and antimycobacterial) properties of honey, which may be attributed to the acidity (low pH), osmotic effect, high sugar concentration, presence of bacteriostatic and bactericidal factors (hydrogen peroxide, antioxidants, lysozyme, polyphenols, phenolic acids, flavonoids, methylglyoxal, and bee peptides), and increase in cytokine release, and to immune modulating and anti-inflammatory properties of honey; the antimicrobial action involves several mechanisms. Despite a large amount of data confirming the antimicrobial activity of honey, there are no studies that support the systemic use of honey as an antibacterial agent.

A review of the clinical applications and of the disposition of probenecid in man, including drug interactions, is presented. Probenecid is the classical competitive inhibitor of organic acid transport in the kidney and other organs. There are 2 primary clinical uses for probenecid: as a uricosuric agent in the treatment of chronic gout and as an adjunct to enhance blood levels of antibiotics (such as penicillins and cephalosporins). Adsorption of probenecid is essentially complete following oral administration. The drug is extensively metabolised by glucuronide conjugation and by oxidation of the alkyl side chains; oxidation of the aromatic ring does not occur. The half-life of probenecid in plasma (4 to 12 hours) is dose-dependent. Renal excretion is the major route of elimination of the metabolites; excretion of the parent drug is minimal and is dependent on urinary pH. Probenecid and its oxidised metabolites are extensively bound to plasma proteins, mainly to albumin. Tissue concentrations (based on animal studies) are generally lower than plasma concentrations. Most of the drug-drug interactions involving probenecid are due to an effect on the kidney-block of transport of acidic drugs. Similarly probenecid affects the tubular secretion of a number of acidic endogenous substances by the kidney. Probenecid is also involved in the block of transport of acidic metabolites of catecholamines, for example homovanillic and hydroxyindoleacetic acids, in the brain. There are a number of analytical procedures for the assay of probenecid. These are based on spectrophotometry, spectrofluorometry, gas and liquid chromatography and radioimmunoassay.

There is a rising worldwide prevalence of diabetes, especially type 2 diabetes mellitus (T2DM), which is one of the most challenging health problems in the 21st century. The associated complications of diabetes, such as cardiovascular disease, peripheral vascular disease, stroke, diabetic neuropathy, amputations, renal failure, and blindness result in increasing disability, reduced life expectancy, and enormous health costs. T2DM is a polygenic disease characterized by multiple defects in insulin action in tissues and defects in pancreatic insulin secretion, which eventually leads to loss of pancreatic insulin-secreting cells. The treatment goals for T2DM patients are effective control of blood glucose, blood pressure, and lipids (if elevated) and, ultimately, to avert the serious complications associated with sustained tissue exposure to excessively high glucose concentrations. Prevention and control of diabetes with diet, weight control, and physical activity has been difficult. Treatment of T2DM has centered on increasing insulin levels, either by direct insulin administration or oral agents that promote insulin secretion, improving sensitivity to insulin in tissues, or reducing the rate of carbohydrate absorption from the gastrointestinal tract. This review presents comprehensive and up-to-date information on the mechanism(s) of action, efficacy, pharmacokinetics, pleiotropic effects, drug interactions, and adverse effects of the newer antidiabetic drugs, including (1) peroxisome proliferator-activated-receptor-γ agonists (thiazolidinediones, pioglitazone, and rosiglitazone); (2) the incretin, glucagon-like peptide-) receptor agonists (incretin-mimetics, exenatide. and liraglutide), (3) inhibitors of dipeptidyl-peptidase-4 (incretin enhancers, sitagliptin, and vildagliptin), (4) short-acting, nonsulfonylurea secretagogue, meglitinides (repaglinide and nateglinide), (5) amylin anlog-pramlintide, (6) α-glucosidase inhibitors (miglitol and voglibose), and (7) colesevelam (a bile acid sequestrant). In addition, information is presented on drug candidates in clinical trials, experimental compounds, and some plants used in the traditional treatment of diabetes based on experimental evidence. In the opinion of this reviewer, therapy based on orally active incretins and incretin mimetics with long duration of action that will be efficacious, preserve the β-cell number/function, and block the progression of diabetes will be highly desirable. However, major changes in lifestyle factors such as diet and, especially, exercise will also be needed if the growing burden of diabetes is to be contained.