This study evaluated the effects of rosuvastatin in vivo on toxoplasmosis chronic infection. Thirty-five Swiss mice were orally infected (ME-49 strain). After 50 days, the mice were separated into five groups: GI – non-infected, GII – infected, GIII – infected and treated with pyrimethamine and sulfadiazine (12.5 + 50 mg kg−1 body weight day−1), GIV and GV – infected and treated with rosuvastatin 10 and 40 mg kg−1 body weight day−1, respectively. After 21 days, we collected blood, liver, lungs, femoral biceps and brain were removed for Toxoplasma gondii DNA quantification by qPCR and histopathological analysis. GIV and GV did not present premature death or clinical changes, and the hepatic enzyme levels were lower compared to GI. Toxoplasma gondii DNA was detected mainly in brain and muscle, but the parasite load was significantly lower in GV compared to GII brains (P < 0.05). Histopathological changes were observed in brains, with T. gondii cysts as well as an inflammatory condition, including necrosis areas in GII and GIII. These data confirm active infection with tissue injury. This inflammatory condition was attenuated in the groups treated with rosuvastatin, especially R40 (GV). Our findings demonstrated the in vivo action of rosuvastatin in reducing cerebral parasitic load and indicate that this drug may interfere in chronic toxoplasmosis.

This is the third in a series of three papers. In the first paper we describe a comprehensive stochastic model of an individual's lifetime that includes diagnosis with ischaemic heart disease and stroke and also the development of the major risk factors for these conditions. The second paper discusses in some detail models for changes in body mass index (BMI) and also the effects of these changes, in particular the current trend towards increasing prevalence of obesity, on diabetes, cardiovascular diseases and expected future lifetime. This paper is devoted to the following applications of the model described in the first paper:

(a) quantifying the effects of smoking and of changes in smoking habits, and,

(b) quantifying the effects of treatment with statins (drugs designed to lower cholesterol).

We construct a stochastic model of an individual's lifetime that includes diagnosis with ischaemic heart disease and stroke and also the development of the major risk factors for these conditions: hypercholesterolaemia, hypertension, diabetes and obesity. Smoking, another major risk factor, is treated deterministically. Mathematically, the model is a continuous time, finite state space Markov process, with the individual's age playing the rôle of time. The model is parameterised using data from the Framingham Heart Study, with parameter values adjusted so that the model is appropriate for UK conditions in the early 21st century. The model has been designed so that it can be used to quantify the effects of:

(i) trends, in particular increasing prevalence of obesity.

(ii) changes in behaviour, in particular smoking patterns, and

(iii) treatments, in particular statins for hypercholesterolaemia.

These applications are covered in two accompanying papers.

Although norovirus infection is generally known to be a mild disease, there is some evidence for severe outcome. An outbreak in a Dutch psychiatric institution, originating from pilgrims returning from Lourdes (France), provided an opportunity for performing a retrospective cohort study in order to identify risk factors for norovirus disease and excess mortality. Relative risks (RR) including 95% confidence intervals (CI) showed that attending the pilgrimage (RR 2·0, 95% CI 1·4–3·0) and age >70 (RR 1·7, 95% CI 1·2–2·2) were risk factors for symptomatic infection. In a subset of patients, for whom more detailed information was available, the use of statins was associated with norovirus disease when adjusted for underlying condition (adjusted odds ratio 3·9, 95% CI 1·2–13·0). Mortality was higher in cases infected during the pilgrimage compared to other residents (RR 20·9, 95% CI 4·7–93·8). Norovirus disease can lead to severe outcome. The newly identified risk of statins for contracting norovirus disease may have considerable consequences for the Western world and needs prospective confirmation.

Functional foods and dietary supplements might have a role in supporting drug therapy. These products may (1) have an additive effect to the effect that a drug has in reducing risk factors associated with certain conditions, (2) contribute to improve risk factors associated with the condition, other than the risk factor that the drug is dealing with, or (3) reduce drug-associated side effects, for example, by restoring depleted compounds or by reducing the necessary dose of the drug. Possible advantages compared with a multidrug therapy are lower drug costs, fewer side effects and increased adherence. In the present review we have focused on the support of statin therapy using functional foods or dietary supplements containing plant sterols and/or stanols, soluble dietary fibre, n-3 PUFA or coenzyme Q10. We conclude that there is substantial evidence that adding plant sterols and/or stanols to statin therapy further reduces total and LDL-cholesterol by roughly 6 and 10 %, respectively. Adding n-3 PUFA to statin therapy leads to a significant reduction in plasma TAG of at least 15 %. Data are insufficient and not conclusive to recommend the use of soluble fibre or coenzyme Q10 in patients on statin therapy and more randomised controlled trials towards these combinations are warranted. Aside from the possible beneficial effects from functional foods or dietary supplements on drug therapy, it is important to examine possible (negative) effects from the combination in the long term, for example, in post-marketing surveillance studies. Moreover, it is important to monitor whether the functional foods and dietary supplements are taken in the recommended amounts to induce significant effects.

Statins reduce cardiovascular mortality and related risks associated with pneumonia suggesting potentially beneficial use in influenza pandemics. We investigated the effect of current statin use on acute respiratory infections in primary care. Data from anonymized electronic medical records of persons aged ⩾45 years were examined for statin use, chronic morbidity, respiratory diagnoses, vaccination procedures, and immune suppression. Logistic regression models were used to calculate odds ratios (ORs) for statin users vs. non-users in respiratory infection outcomes. A total of 329 881 person-year observations included 18% statin users and 46% influenza vaccinees. Adjusted ORs for statin users vs. non-users were: influenza-like illness, 1·05 (95% CI 0·92–1·20); acute bronchitis, 1·08 (95% CI 1·01–1·15); pneumonia, 0·91 (95% CI 0·73–1·13); all acute respiratory infections, 1·03 (95% CI 0·98–1·07); and urinary tract infections, 0·91 (95% CI 0·85–0·98). We found no benefit in respiratory infection outcomes attributable to statin use, although uniformly higher ORs in non-vaccinated statin users might suggest synergism between statins and influenza vaccination.

Objectives: The aim of this study was to assess the trends and costs of statin use in Lithuania over a 3-year period and perform a cost-minimization and reference price analysis to rationalize the use of financial resources of the National Health Care System.

Methods: The defined daily dose (DDD) methodology was applied for assessment of statin use, which was expressed in DDD/1,000 inhabitants/day. Cost minimization and reference price calculations were used in the economic analysis.

Results: Over the 3-year period (2005–2007), the consumption and expenditures of statins in Lithuania doubled. The consumption went up from 3.87 DDD/1,000 inhabitants/day (in 2005) to 8.35 DDD/1,000 inhabitants/day (in 2007). Total expenses of statins increased during the same period from LTL6.186 million in 2005 to LTL12.418 million in 2007. Approximately 68 percent of the estimated costs for statins in 2007 were for atorvastatin. Provided that the calculated reference prices were fixed, the estimated savings would amount to a minimum of LTL1.371 million per year and could reach yearly savings in the order of LTL3.163 million. The total expenses would drop by at least 11 percent, and the decrease in costs could be as high as 25 percent (€1 = LTL3.4528).

Conclusions: Statins consumption is still very low in Lithuania in comparison with other European Union countries. Implementation of cholesterol education programs and changing reimbursement profile for statins therapy will increase consumption and expenditures. The introduction of reference-based pricing as an indirect cost control policy would help rationalizing the use of statins and their expenditures.

Consumption of plant sterol- or stanol-enriched margarines by statin users results in an additional LDL-cholesterol reduction of approximately 10 %, which may be larger than the average decrease of 3–7 % achieved by doubling the statin dose. However, whether this effect persists in the long term is not known. Therefore, we examined in patients already on stable statin treatment the effects of 85 weeks of plant sterol and stanol ester consumption on the serum lipoprotein profile, cholesterol metabolism, and bile acid synthesis. For this, a double-blind randomised trial was designed in which fifty-four patients consumed a control margarine with no added plant sterols or stanols for 5 weeks (run-in period). For the next 85 weeks, seventeen subjects continued with the control margarine and the other two groups with either a plant sterol (n 18) or plant stanol (n 19) (2·5 g/d each) ester-enriched margarine. Blood was sampled at the end of the run-in period and every 20 weeks during the intervention period. Compared with the control group, plant sterol and stanol ester consumption reduced LDL-cholesterol by 0·28 mmol/l (or 8·7 %; P = 0·08) and 0·42 mmol/l (13·1 %; P = 0·006) respectively after 85 weeks. No effects were found on plasma concentrations of oxysterols or 7α-hydroxy-4-cholesten-3-one, a bile acid synthesis marker. We conclude that long-term consumption of both plant sterol and stanol esters effectively lowered LDL-cholesterol concentrations in statin users.

We investigated the combined effect of dietary supplementation with l-arginine, which is the precursor of NO, and pharmacological treatment with atorvastatin, which is a 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitor, on the development of atherosclerosis in homozygous Watanabe heritable hyperlipidaemic rabbits. Rabbits were fed either standard rabbit chow (group C; n 9) as control, a 1·5 % l-arginine diet (group A; n 9), standard rabbit chow plus atorvastatin (2·5 mg/kg per d) in drinking water (group S; n 8), or standard rabbit chow plus a 1·5 % l-arginine diet with atorvastatin (group SA; n 8). Blood was sampled at 2-week intervals. After 8 weeks (T8), the aorta was harvested for topographic and histological analysis. Only the SA group showed decreases in total area of lesions (21 %) and the area of abdominal lesions (44 %) compared with the control group (P = 0·019). Furthermore, plaques in the SA group were smaller and less thick than those observed in the S group. Unexpectedly, plasma nitrite + nitrate levels were not modified under either the l-arginine diet alone or under l-arginine plus atorvastatin. The present study is the first to demonstrate that diet supplementation with l-arginine associated with a statin (atorvastatin) is more efficient in reducing lesion size than treatment with l-arginine or a statin alone. This is a relatively novel therapeutic approach associating a macronutrient and a drug.

During the past four decades, research efforts directed toward reducing shell egg cholesterol content have centred on genetic selection or alteration of the laying hens' diet with various nutrients, natural products, non-nutritive factors, or pharmacological agents. However, the vast majority of these experimental approaches elicited only minimal changes (<10%) at best or, as in the case of dietary azasterols and triparanol, resulted in the unacceptable replacement of yolk cholesterol by desmosterol. In contrast, when 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (‘statins’), garlic paste, or pharmacological amounts of copper were orally administered to chickens, yolk cholesterol levels were reduced by up to 46%, 32%, or 34%, respectively. The previous paper in this two-part series provided a justification for low-cholesterol egg production and reviewed cholesterol metabolism in the laying hen, avian embryonic cholesterol needs, and genetic and nutritional approaches to chicken egg cholesterol reduction. The present paper provides a comprehensive overview of the use of non-nutritive dietary factors and select pharmacological compounds as egg cholesterol-lowering agents, and discusses emerging strategies for lowering the cholesterol content of shell eggs. With the recent advances in avian genomics and transgenesis, it is anticipated that the greatest advances in the area of yolk cholesterol reduction will be attained through manipulation of key genes whose protein products mediate intestinal sterol absorption, hepatic cholesterol and lipoprotein synthesis, and/or lipoprotein uptake by growing oocytes. However, the future commercial availability of low-cholesterol eggs produced by transgenic hens ultimately will be influenced by the nature of the regulatory environment for bioengineered foods, public acceptance, and economics.