A well-functioning immune system requires balanced immune responses. In vitro studies have shown that plant stanols contribute to restoring the T-helper (Th)1/Th2 ratio when it is imbalanced. However, effects of plant stanols on healthy immune responses are unknown. Therefore, we studied effects of recommended (2·5 g/d) or high (9·0 g/d) plant stanol intakes on the Th1/Th2 cytokine balance in immunologically healthy subjects. In two RCTs, peripheral blood mononuclear cells (PBMCs) were isolated, cultured, and stimulated with 5 µg/ml Phytohemagglutinin-M to study ex vivo cytokine production. In the first study, twenty participants consumed margarines (2·5 g/d plant stanols) or control for three weeks. In the second study, nineteen participants consumed margarines and yogurts (9·0 g/d plant stanols) or control for four weeks. T-cell cytokine concentrations were measured in culture medium and in study 2 a standardized Th1/Th2 index was calculated. Serum lipids and non-cholesterol sterols were also measured. Compliance was confirmed by significant increases in serum total cholesterol (TC)-standardized sitostanol and campestanol levels in both studies. Changes in ex vivo cytokine production and Th1/Th2 index did not differ between intervention and control groups. In the first study, no statistically significant changes were observed in lipid and lipoprotein concentrations. In the second study, LDL cholesterol significantly decreased compared to control (–0·77 (–1·11, –0·42) mmol/l; P < 0·001). Recommended (2·5 g/d) or high (9·0 g/d) intakes of plant stanols did not alter PBMC ex vivo cytokine production in immunologically healthy subjects. This suggests that plant stanols might only affect immune function when Th1/Th2 immune responses are imbalanced.

In the US, research payments are technically taxable income. This article argues that tax liability is a form of possible economic and legal risk of paid research participation. Findings are presented from empirical research on Phase I healthy volunteer trials. The article concludes by discussing the implications of these findings for the informed consent process, as well as for broader ethical issues in whether and how payments for research participation should be regulated.

Complete nutrition drinks with a low glycemic index (GI) provide nutritional support and prevent hyperglycaemia. The present study identified GI and factors predicting individual glucose response to a new complete nutrition drink. A randomised cross-over controlled trial was conducted in eighteen healthy volunteers (FPG < 100 mg/dl). Complete nutrition drinks containing retrograded starch, glucose solution and white bread were assigned in a random sequence with 14-day wash-out intervals. Plasma glucose and insulin levels were measured from baseline to 180 min after consuming each food. Results show the adjusted GIs of the drink was 48.2 ± 10.4 and 46.7 ± 12.7 with glucose and white bread as the reference, respectively. While the drink has low GI (<55), the individual glucose responses varied (GI: 7–149). Comparing characters in individual GI < 55 (n = 12) and GI ≥ 55 (n = 6) groups revealed significantly higher baseline insulin in the low GI group (14.86 ± 16.51 μIU/ml v. 4.9 ± 3.4 μIU/ml, P < 0·05). The correlation matrix confirms only two predictive factors for having individual GI <55 were baseline insulin (r = 0·5, P = 0·03) and HOMA-IR (r = 0·55, P = 0·02). ROC curve reveals fasting insulin above 1.6 μIU/ml and HOMA-IR above 1.05 as the cut-off values. The findings suggest that the complete nutrition drink has a low GI, but there was wide variability in individual responses partly explained by fasting insulin levels and HOMA-IR. Screening for fasting insulin and HOMA-IR may be encouraged to maximise the functional benefit of the drink.

Modafinil is a new psychotropic compound with central α1, adrenergic-stimulant activity in animals. In the present study, its pharmacological activity in man was evaluated in the sleep-deprivation induced psychomotor and cognitive impairment paradigm. This was a double-blind placebo-controlled study involving 12 healthy volunteers. Standard psychomotor and memory tasks were used, including critical flicker fusion frequency determination (CFF), choice reaction time and short- and long-term memory evaluation. Results revealed a clear antagonism by modafinil of the psychomotor and cognitive impairment induced by sleep-deprivation in most tasks 6 h after drug administration, and marginal effects 18 h after. These results therefore support a psychostimulant activity of modafinil in man.

M.H. Pappworth's 1967 book, Human guinea pigs, was a major catalyst for change in the ethics and regulation of human research in the 1970s. Many of Pappworth's ethical concerns about the threats posed to human subjects are still valid today, yet the source of those threats has shifted from universities to industry sponsors.

Due to its low digestibility in the small intestine, a major fraction of the polyol isomalt reaches the colon. However, little is known about effects on the intestinal microflora. During two 4-week periods in a double-blind, placebo-controlled, cross-over design, nineteen healthy volunteers consumed a controlled basal diet enriched with either 30g isomalt or 30g sucrose daily. Stools were collected at the end of each test phase and various microbiological and luminal markers were analysed. Fermentation characteristics of isomalt were also investigated in vitro. Microbiological analyses of faecal samples indicated a shift of the gut flora towards an increase of bifidobacteria following consumption of the isomalt diet compared with the sucrose diet (P<0·05). During the isomalt phase, the activity of bacterial β-glucosidase decreased (P<0·05) whereas β-glucuronidase, sulfatase, nitroreductase and urease remained unchanged. Faecal polyamines were not different between test periods with the exception of cadaverine, which showed a trend towards a lower concentration following isomalt (P=0·055). Faecal SCFA, lactate, bile acids, neutral sterols, N, NH3, phenol and p-cresol were not affected by isomalt consumption. In vitro, isomalt was metabolized in several bifidobacteria strains and yielded high butyrate concentrations. Isomalt, which is used widely as a low-glycaemic and low-energy sweetener, has to be considered a prebiotic carbohydrate that might contribute to a healthy luminal environment of the colonic mucosa.

The polyol isomalt (Palatinit®) is a well established sugar replacer. The impact of regular isomalt consumption on metabolism and parameters of gut function in nineteen healthy volunteers was examined in a randomised, double-blind, cross-over trial with two 4-week test periods. Volunteers received 30 g isomalt or 30 g sucrose daily as part of a controlled diet. In addition to clinical standard diagnostics, biomarkers and parameters currently discussed as risk factors for CHD, diabetes or obesity were analysed. Urine and stool Ca and phosphate excretions were measured. In addition, mean transit time, defecation frequency, stool consistency and weight were determined. Consumption of test products was affirmed by the urinary excretion of mannitol. Blood lipids were comparable in both phases, especially in volunteers with hyperlipidaemia, apart from lower apo A-1 (P=0·03) for all subjects. Remnant-like particles, oxidised LDL, NEFA, fructosamine and leptin were comparable and not influenced by isomalt. Ca and phosphate homeostasis was not affected. Stool frequency was moderately increased in the isomalt phase (P=0·006) without changes in stool consistency and stool water. This suggests that isomalt is well tolerated and that consumption of isomalt does not impair metabolic function or induce hypercalciuria. In addition, the study data indicate that isomalt could be useful in improving bowel function.

In a double-blind cross-over study realized in 8 healthy volunteers, a bolus injection of yohimbine (0.15 mg/kg) followed by an infusion (0.0025 mg/kg/min) induced a raise of blood pressure without affecting selfratings. Total dose was 0.3 mg/kg. One subject out of 8 experienced a severe anxiety episode under yohimbine and dropped out.

In a preliminary study the effect of tyramine, used as eye-drops, was assessed in two different ethnical groups composed of healthy volunteers: 6 Africans and 6 Caucasians.

Tyramine-induced mydriasis in the Caucasian group was 5 times greater than in the African group.

Similar differences had already been observed for indirect sympathominetic amines (ephedrine and cocaine) used as mydriatics, as well as for the effects of alpha 1 blocking drugs on the vascular system.

Very few data are available in the literature concerning the CNS effects of drugs modulating the alpha adrenergic receptors.