IPP-rich milk protein hydrolysate lowers blood pressure in subjects with stage 1 hypertension a randomized controlled trial

Background. Milk derived peptides have been identified as potential antihypertensive agents. The primary objective was to investigate the effectiveness of IPP-rich milk protein hydrolysates (MPH) on reducing blood pressure (BP) as well as to investigate safety parameters and tolerability. The secondary objective was to confirm or falsify ACE...

Phenylalanine tolerance can already reliably be assessed at the age of 2 years in patients with PKU

Background: The clinical severity of phenylalanine hydroxylase deficiency is usually defined by either pre-treatment phenylalanine (Phe) concentration or Phe tolerance at 5 years of age. So far, little is known about the course of Phe tolerance or the ability of both pre-treatment Phe and Phe tolerance at early age to predict Phe tolerance at...

Doxycycline therapy for abdominal aneurysm: Improved proteolytic balance through reduced neutrophil content

Background: Matrix metalloproteinase-9 (MMP-9) is thought to play a central role in abdominal aortic aneurysm (AAA) initiation. Doxycycline, a tetracycline analogue, has direct MMP-9-inhibiting properties in vitro, and it effectively suppresses AAA development in rodents. Observed inhibition of AAA progression, and contradictory findings in...

Nonclinical testing of vaccines: Report from a workshop

Vaccine research and development is a heterogeneous and intensely active area, encompassing the development of many different kinds of novel preventive and therapeutic vaccines (eg, against infectious, allergic, and autoimmune diseases, cancer, etc). Included in this is the development of different types of vaccines (eg, DNA vaccines, novel...

Clinical trial of doxycycline for matrix metalloproteinase-9 inhibition in patients with an abdominal aneurysm doxycycline selectively depletes aortic wall neutrophils and cytotoxic t cells

Background-Doxycycline has been shown to effectively inhibit aneurysm formation in animal models of abdominal aortic aneurysm. Although this effect is ascribed to matrix metalloproteinase-9 inhibition, such an effect is unclear in human studies. We reevaluated the effect of doxycycline on aortic wall protease content in a inical trial and found...

Mannosylated self-peptide inhibits the development of experimental autoimmune encephalomyelitis via expansion of nonencephalitogenic T cells

Tolerance to experimental autoimmune encephalomyelitis (EAE) in SJL mice can be induced by immunization with a mannosylated form of the proteolipid protein (M-PLP139-151), despite the presence of CFA. The state of tolerance is characterized by poor delayed-type hypersensitivity responses and the absence of clinical EAE symptoms. In vivo...

Transdermal administration of radiolabelled [14C]rotigotine by a patch formulation: A mass balance trial

Background and objective: The dopamine agonist rotigotine has been formulated in a silicone-based transdermal system for once-daily administration. The objective of the present study was to characterise the mass balance of rotigotine in humans after administration of a single transdermal patch containing radiolabelled [14C]rotigotine and to...

Long-term gastrointestinal tolerance of NUTRIOSE®FB in healthy men

Objective: To determine the gastrointestinal (GI) tolerance of NUTRIOSE®FB in men. Design: A randomized, placebo-contro lled, parallel, double-blind study. Setting: The metabolic ward of TNO Quality of Life. Subjects: Forty-eight subjects started the study: 16 men participated in one of the three treatments. Subjects consumed either 22.5 g of...

The solvent-tolerant Pseudomonas putida S12 as host for the production of cinnamic acid from glucose

A Pseudomonas putida S12 strain was constructed that efficiently produced thefine chemical cinnamic acid from glucose or glycerol via the central metabolite phenylalanine. The gene encoding phenylalanine ammonia lyase from the yeast Rhodosporidium toruloides was introduced. Phenylalanine availability was the main bottleneck in cinnamic acid...

Synthesis and biological evaluation of disubstituted N6- cyclopentyladenine analogues: The search for a neutral antagonist with high affinity for the adenosine A1 receptor

Novel 3,8- and 8,9-disubstituted N6-cyclopentyladenine derivatives were synthesised in moderate overall yield from 6-chloropurine. The derivatives were made in an attempt to find a new neutral antagonist with high affinity for adenosine A1 receptors. N6-Cyclopentyl-9- methyladenine (N-0840) was used as a lead compound. Binding affinities of the...

Short-term digestive tolerance of different doses of NUTRIOSE®FB, a food dextrin, in adult men

Objective: To determine the tolerance of increasing dosages of an incompletely hydrolysed and/or incompletely absorbed food dextrin coming from wheat starch, NUTRIOSE®FB, at daily levels of 10 and 15 g up to 60 and 80 g, respectively. Design: A randomized, double-blind, multiple dose, placebo-controlled, combined crossover and parallel trial....

13-week oral toxicity study with stanol esters in rats

Plant sterols and their saturated derivatives, known as stanols, reduce serum cholesterol when consumed in amounts of approximately 2 g per day. Stanol fatty acid esters have been developed as a highly fat-soluble form that may lower cholesterol more effectively than stanols. Stanol esters occur naturally in human diets, but at levels far below...

On the development of behavioral tolerance to organophosphates IV: EEG and visual evoked responses

Several earlier studies showed that, in contrast with DFP, repeated injections with soman did not lead to behavioral tolerance in rats. The reason for the difference between the effects of these two organophosphate cholinesterase inhibitors was not clear and a neurophysiological approach was undertaken. Four experiments (A, B, C and D) were...

Antidotes to organophosphate poisoning. 2. Thiadiazole-5-carboxaldoximes

Three new nonquaternary oximes have been evaluated with respect to their antidotal activities against organophosphate poisoning. The oximes 1,2,3-thiadiazole-5-carboxaldoxime (1, pKa = 7.6), 2-methyl-1,3,4-thiadiazole-5-carboxaldoxime (2, pKa = 8.4), and 3-methyl-1,2,4-thiadiazole-5-carboxaldoxime (3, pKa = 7.0) were prepared in yields of 56, 24...