Increased blood-brain barrier permeability and altered tight junctions in experimental diabetes in the rat: contribution of hyperglycaemia and matrix metalloproteinases.

AIMS/HYPOTHESIS: Although diabetes mellitus is associated with peripheral microvascular complications and increased risk of neurological events, the mechanisms by which diabetes disrupts the blood-brain barrier (BBB) are not known. Matrix metalloproteinase (MMP) activity is increased in diabetic patients, is associated with degradation of tight junction proteins, and is a known mediator of BBB compromise. We hypothesise that diabetes leads to compromise of BBB tight junctions via stimulation of MMP activity. MATERIALS AND METHODS: Diabetes was induced in the rat with streptozotocin. At 14 days after injection, BBB function was assessed by in situ brain perfusion. Tight junction proteins were assessed by immunoblot and immunofluorescence. Plasma MMP activity was quantified by fluorometric gelatinase assay and gel zymography. RESULTS: In streptozotocin-treated animals, permeability to [(14)C]sucrose increased concurrently with decreased production of BBB tight junction proteins occludin (also known as OCLN) and zona occludens 1 (ZO-1, also known as tight junction protein 1 or TJP1). Insulin treatment, begun on day 7, normalised blood glucose levels and attenuated BBB hyperpermeability to [(14)C]sucrose. Neither acute hyperglycaemia in naive animals nor acute normalisation of blood glucose in streptozotocin-treated animals altered BBB permeability to [(14)C]sucrose. Plasma MMP activity was increased in streptozotocin-treated animals. CONCLUSIONS/INTERPRETATION: These data indicate that diabetes increases BBB permeability via a loss of tight junction proteins, and that increased BBB permeability in diabetes does not result from hyperglycaemia alone. Increased plasma MMP activity is implicated in degradation of BBB tight junction proteins and increased BBB permeability in diabetes. Peripheral MMP activity may present a novel target for protection of the BBB and prevention of neurological complications in diabetes.

Health care system utilization for chronic facial pain.

Because physician utilization is only partly related to physical health status, it was hypothesized that high utilization associated with chronic pain should correlate with other nonpain factors. One hundred consecutive patients were given a battery of tests and rated by clinicians for the severity of psychological factors, stress, and chronicity. The patients were divided into high- and low-utilization groups on the basis of their scores on the Health Care Utilization Index. The high-utilization patients were found to be more focused on bodily symptoms and to be more convinced that they had a physical illness. This contrasted with the clinicians' opinion that the high-utilization patients had higher levels of psychological factors and stress.

TMD symptomology among denture patients.

The relationship between denture wearing and symptoms of temporomandibular disorder (TMD) was assessed with a psychometric test specifically developed to measure TMD symptoms. The subjects were 278 denture patients and 36 elderly patients with a diagnosed TMD. Denture wearers were found to have a higher prevalence of TMD symptoms than the normal population, but the average level of symptoms was of low intensity and not clinically significant. Denture wearers reported fewer TMD symptoms and less stress and psychological distress than TMD patients. Responses to test items assessing perceived malocclusion apparently were not affected by denture wearing.

Stress in patients with pain in the muscles of mastication and the temporomandibular joints.

This study examined the role of stress in subjects having combined muscle and temporomandibular joint pain compared to subjects having only muscle pain or only joint pain. It was found that the combined pain (n = 39) and muscle pain (n = 24) groups had comparable levels of pain intensity and activity impairment. The combined pain group, however, had the lowest level of stress and was rated lower than the muscle group in clinicians ratings of psychological factors, stress and chronicity. The combined pain group and joint pain group (n = 28) were found to be comparable in terms of the clinician's ratings. This data does not support the concept of a progression of symptoms from muscle pain to combined muscle and joint pain that would be expected from a stress-induced muscle hyperactivity model of temporomandibular disorders.

Stress as a factor in muscle and temporomandibular joint pain.

Stress-induced muscle hyperactivity has been proposed as a major aetiological factor in the production of pain in the muscles of mastication and the temporomandibular joints. In the present study, a total of fifty-two patients with joint or muscle pain were evaluated for stress with the Derogatis Stress Profile (DSP). The muscle pain group (n = 24) had higher clinician ratings of psychological factors, stress and chronicity. The muscle-pain group also had higher Environmental Stress scores on the DSP, more intense pain, and more activity impairment than the joint-pain group (n = 28). The results of multiple regression analysis suggest an association between pain, depression, and impairment of activity in the muscle-pain group but not in the joint-pain group. The overall results further suggest that muscle pain develops at 'normal' levels of stress.

Correlates of dental student stress.

The purpose of this study is to identify correlates of dental student stress. Associations between characteristics of dental students and their stress levels are examined, along with the association of stress with drug use and health problems. A total of 300 out of 315 dental students completed a questionnaire that measured the frequency and stressfulness of 31 stressors; drug use; health problems; and student characteristics including Type A behavior, career commitment, demographics, and lifestyle variables. Characteristics that were associated with a higher stress level were a higher level of Type A behavior and lower level of career commitment. Greater stress was also associated with a greater frequency of health problems. The results suggest an interactional stress model in which the personalities and attitudes of students are important mediators of the stress response.