Comparative pharmacology of chemically distinct NADPH oxidase inhibitors.

BACKGROUND AND PURPOSE: Oxidative stress [i.e. increased levels of reactive oxygen species (ROS)] has been suggested as a pathomechanism of different diseases, although the disease-relevant sources of ROS remain to be identified. One of these sources may be NADPH oxidases. However, due to increasing concerns about the specificity of the compounds commonly used as NADPH oxidase inhibitors, data obtained with these compounds may have to be re-interpreted. EXPERIMENTAL APPROACH: We compared the pharmacological profiles of the commonly used NADPH oxidase inhibitors, diphenylene iodonium (DPI), apocynin and 4-(2-amino-ethyl)-benzolsulphonyl-fluoride (AEBSF), as well as the novel triazolo pyrimidine VAS3947. We used several assays for detecting cellular and tissue ROS, as none of them is specific and artefact free. KEY RESULTS: DPI abolished NADPH oxidase-mediated ROS formation, but also inhibited other flavo-enzymes such as NO synthase (NOS) and xanthine oxidase (XOD). Apocynin interfered with ROS detection and varied considerably in efficacy and potency, as did AEBSF. Conversely, the novel NADPH oxidase inhibitor, VAS3947, consistently inhibited NADPH oxidase activity in low micromolar concentrations, and interfered neither with ROS detection nor with XOD or eNOS activities. VAS3947 attenuated ROS formation in aortas of spontaneously hypertensive rats (SHRs), where NOS or XOD inhibitors were without effect. CONCLUSIONS AND IMPLICATIONS: Our data suggest that triazolo pyrimidines such as VAS3947 are specific NADPH oxidase inhibitors, while DPI and apocynin can no longer be recommended. Based on the effects of VAS3947, NADPH oxidases appear to be a major source of ROS in aortas of SHRs.

Patients' anticipation of pain and pain-related side effects, and their perception of pain as a result of orthodontic treatment with fixed appliances.

The aim of this study was to investigate the relationship between (i) the pain and its side effects, anticipated by patients before orthodontic therapy, and (ii) the reported pain and its effects after the placement of initial archwires. Before treatment, 50 adolescent patients (median age 13.6 years, range 8.9-39.3 years, 28 female, 22 male) completed a questionnaire concerning their facial and dental appearance, and their expectations regarding pain, its influence on their daily lives, and changes in their facial and dental appearance as a result of orthodontic treatment. In the week following insertion of the initial archwires the patients completed a series of eight questionnaires, where they reported the level of pain experienced and its influence on their daily lives. In the week after archwire insertion, the maximum pain levels reported did not differ statistically from the anticipated pain levels. Patients significantly under-estimated the changes they would have to make in their diet as a response to pain after archwire insertion. Patients who anticipated a greater effect of pain on their leisure activities and those who had a history of frequent headaches reported higher levels of pain and more disruption of their daily lives as a result of pain. This pattern of response is consistent with a medical model where anxious patients and those with a history of chronic pain reported more pain after surgery.

Are cumulus cells necessary for the spontaneous maturation of germinal vesicle-stage oocytes to metaphase II.

PURPOSE: In this study we investigated the need of the support from cumulus cells for germinal-vesicle (GV) oocytes collected from stimulated ovaries to complete their maturation to metaphase II (MII). METHODS: We compared the maturation rate of GV oocytes after coculture with cumulus cells (study group) with their spontaneous maturation in culture medium alone (control group). RESULTS: Sixty-four and nine-tenths percent of the GV oocytes matured to metaphase II in the coculture group, and of these, 43.5% gave normal 2pn zygotes following intracytoplasmic sperm injection (ICSI), while 73.8% of the GV oocytes spontaneously matured to the MII stage and 30% of these reached the zygote stage after ICSI. CONCLUSIONS: It is probable that a follicular factor is responsible for this arrested maturation in the human and that maturation occurs spontaneously when the oocytes are separated from their follicular fluid environment after collection.

Perception of pain as a result of orthodontic treatment with fixed appliances.

The aims of this study were to investigate the intensity, location and duration of patients' discomfort following insertion of orthodontic appliances, and to examine for interactions between patient age, gender, appliance type and the perception of pain. After insertion of orthodontic appliances, 170 patients received eight questionnaires, one they completed and returned after 4 h, then one daily for 7 days. The respondents' ages ranged from 8-53 years (median age 13 years 7 months); 45 per cent were male and 55 per cent female. Of the patients, 65 per cent reported pain after 4 h and 95 per cent after 24 h. After 7 days, 25 per cent of the patients still reported discomfort. Patients' pain intensity scores were significantly higher for the anterior than for the posterior teeth. On day 1, 16 per cent took analgesics and 18 per cent reported being awakened the first night. Comparing a 2 x 4 appliance, a full appliance in one arch and in both arches, no statistical differences were found for reported pain frequency, general intensity of pain, pain at the teeth, discomfort when biting and chewing and analgesic consumption. The perception of general pain intensity, analgesic consumption, pain when eating and the influence of discomfort on daily life were all significantly greater in girls than in boys. Patients younger than 13 years reported pain significantly less frequently than the older patients. The highest frequency of pain was found in the group of 13-16 year olds. The pain intensity did not differ among the age groups.

Intracytoplasmic sperm injection (ICSI) with testicular sperm extraction (TESE) in non-obstructive azoospermia--two case reports.

Intracytoplasmic sperm injection (ICSI) with microsurgical epididymal sperm extraction (MESA) or testicular sperm extraction (TESE) can be offered to azoospermic men. We report our initial experience of two cases with ICSI-TESE in non-obstructive azoospermia. Both couples had a successful ICSI with embryo transfer. An ongoing triplet pregnancy at 21 weeks is observed.