Microdosing is a new concept in drug development that-if implemented in the pharmaceutical industry-would mean that new drugs can be tested earlier in humans than done today. The human microdosing concept-or 'Phase 0'-may offer improved candidate selection, reduced failure rates in the drug development line and a reduction in the use of laboratory animals in early drug development, factors which w

Background: Dizziness is a very common complaint. The frequency of dizziness increases with age. It affects quality of life negatively for older persons in several ways. Objectives: This study intended to investigate which variables (physical activity, loneliness, health complaints, need of help for daily living and falls) differed between those with and without dizziness and also to investigate w

Alzheimer's disease, the most common neurodegenerative disease, is characterized by a progressive loss of synapses and accumulation of amyloid-beta (Aβ) peptides in the brain. Previous studies demonstrated that acute increase in synaptic activity in cultured hippocampal slices and mouse brains (Cirrito et al. Neuron 48: 913-922, 2005; Kamenetz et al. Neuron 37: 925-937, 2003) enhanced secretion of

ABSTRACTBackground: This study was designed to determine the effectiveness of a psychosocial intervention for family caregivers in delaying nursing home placement of individuals with dementia.Methods: The participants comprised 153 family caregivers of persons with dementia who underwent intervention and 155 family caregivers who did not. The intervention consisted of five weekly counselling sessi

Knee joint replacement is an effective and cost-effective intervention for severe symptomatic osteoarthritis of the knee joint. However, utilisation rates vary hugely, there are no indications, it is difficult to know when (in the course of arthritis) it is best to operate, and some 10-20% of people who have this surgery are unhappy with the outcome, and have persistent pain. In this article we br

OBJECTIVES: To investigate the accuracy of the biochemical diagnosis of primary hyperparathyroidism (pHPT) in a consecutive series of patients with operatively verified disease. DESIGN AND SUBJECTS: Four hundred thirty-six patients with pHPT, 340 women and 96 men, were reviewed. Biochemical variables, including total calcium (Ca), ionized calcium (Cai) and PTH were analyzed and registered in a pro

Covalent inhibition is an efficient molecular mechanism for inhibiting enzymes or modulating the function of proteins and is found in the action of many drugs and biologically active natural products. However, it is has been less appreciated that the formation of covalent bonds can be reversible or irreversible. This review focuses on biologically active compounds that are Michael acceptors and ho

Intestinal-derived chemokines have a central role in orchestrating immune cell influx into the normal and inflamed intestine. Here, we identify the chemokine CCL6 as one of the most abundant chemokines constitutively expressed by both murine small intestinal and colonic epithelial cells. CCL6 protein localized to crypt epithelial cells, was detected in the gut lumen and reached high concentrations