The vitamin D receptor and the etiology of RANTES/CCL-expressive fatty-degenerative osteolysis of the jawbone: an interface between osteoimmunology and bone metabolism.

BACKGROUND: Recent research on vitamin D indicates that our current understanding of the factors leading to chronic inflammation should be revised. One of the key mechanisms by which microbial immunosuppression occurs is the suppression of one of the most common endogenous cell nucleus receptors: the vitamin D receptor (VDR). Autoimmune diseases may be correlated with VDR deactivation (VDR-deac) which occurs when the receptor is no longer able to transcribe antimicrobial agents. Excess 1,25-dihydroxyvitamin D (1,25D) is not converted to 25-hydroxyvitamin D (25D); thus, high 1,25D levels may be accompanied by low 25D values. PATIENTS AND METHODS: Since 1,25D promotes osteoclast activity and may thereby cause osteoporosis, fatty-degenerative osteolysis of the jaw (FDOJ), as described by our team, may also be associated with VDR-deac. In 43 patients, vitamin D conversion, immune system function and the quality of bone resorption and formation in the jawbone were related factors that may enhance chronic inflammatory processes. Here, we examine the relationship between immunology and bone metabolism among 43 FDOJ patients and those with immune system diseases (ISDs). RESULTS: We provide a link between FDOJ, RANTES/CCL5 overexpression and VDR-deac. CONCLUSION: The clinical data demonstrate the interaction between VDR-deac and proinflammatory RANTES/CCL5 overexpression in FDOJ patients.

Treatment satisfaction with zolmitriptan nasal spray for migraine in a real life setting: results from phase two of the REALIZE study.

In phase one of the REALIZE study, zolmitriptan nasal spray demonstrated a significant headache response from 10 min post-dose and total symptom relief from 30 min post-dose. The objective of phase two was to investigate patients' dosing patterns, satisfaction and preference following open-label treatment with the nasal spray. Up to 3 attacks were treated. The ITT population consisted of 851 patients. The median time from onset of symptoms to treatment was 1 h 15 min (primary endpoint). Most patients reported being satisfied or very satisfied with zolmitriptan nasal spray (75.7%). Furthermore, the majority of patients would be willing to use zolmitriptan nasal spray in the future (59.8%) and preferred zolmitriptan nasal spray over previous therapies (57.8%). Zolmitriptan nasal spray was well tolerated. Most patients were satisfied with zolmitriptan nasal spray, were willing to continue using it and preferred it to previous therapies.

Zolmitriptan 5 mg nasal spray: efficacy and onset of action in the acute treatment of migraine--results from phase 1 of the REALIZE Study.

OBJECTIVES: The objective of phase 1 (reported here) of this two-phase study was to assess the efficacy of zolmitriptan 5 mg nasal spray, in terms of ability to provide relief from all migraine symptoms, in a controlled setting, designed to replicate clinical practice. BACKGROUND: Zolmitriptan nasal spray has been shown to be fast acting and highly effective in the treatment of migraine, as assessed using standard endpoints, such as headache response and pain-free rates. METHODS: In the double-blind first phase of the study, patients with migraine were randomized to receive zolmitriptan 5 mg nasal spray or placebo to treat a single migraine attack. Attacks were treated according to patients' normal patterns of use, in order to closely reflect clinical practice; that is, no specific regimen was dictated in terms of time to treatment or at what level of pain intensity the headache should be treated. Patients could take a second dose of study medication or an agreed escape medication if adequate pain relief had not been achieved 2 hours after the first dose. The primary efficacy endpoint was total symptom relief (freedom from pain, nausea, photophobia, and phonophobia) 1 hour after the first dose. Secondary efficacy endpoints included headache response, pain-free status and sustained pain-free status, and ability to perform normal activities. RESULTS: The intention-to-treat population comprised 461 zolmitriptan nasal spray recipients and 451 placebo recipients. The total symptom relief rate 1 hour post-dose was significantly higher in the zolmitriptan 5 mg nasal spray group than in the placebo group (14.5% vs. 5.1%; P < .0001); the difference between the groups was significant from 30 minutes post-dose. Treatment with zolmitriptan nasal spray, compared with placebo, also produced a higher headache response rate from 10 minutes post-dose (15.1% vs. 9.1%; P = .0079) and a higher pain-free rate from 30 minutes post-dose (7.7% vs. 3.2%; P = .0039). Zolmitriptan nasal spray was also significantly superior to placebo in terms of sustained pain-free status and patients' ability to perform normal activities. Zolmitriptan nasal spray was well tolerated. CONCLUSIONS: These findings confirm the efficacy demonstrated by zolmitriptan nasal spray in previous clinical trials.

Circadian rhythms of locomotor activity in captive birds and mammals: Their variations with season and latitude.

1. The seasonal variations in time of daily onset and end of locomotor activity are described for 3 species of mammals and 5 species of birds kept in captivity at the arctic circle and at lower latitude. These variations are most pronounced at high latitude. 2. The duration of daily activity plotted versus the photoperiod can be described as an S-curve in all species studied so far, both in nature and in captivity. In both male and female fringillid birds activity times were longer before the summer solstice (spring) than after the summer solstice at equal photoperiods. 3. The seasonal changes in activity time result from roughly mirror-image changes in the times of onset and end of activity relative to sunrise and sunset, cancelling out each other. Therefore the midpoint of activity stays relatively stable; remaining minor changes in the midpoint of activity do not produce a general seasonal pattern. 4. At high latitude, a large seasonal fluctuation in the day-to-day variability (or precision) of activity timing is detected. These patterns of precision of the rhythm cannot be attributed to a single Zeitgeber property without complex assumptions. Onset and ends of activity become more precise when occurring during the civil twilight, i.e. at times of day with most rapid changes in light intensity. This may reflect direct action of light on the rhythm rather than a property of the entrainment mechanism. 5. The data do not give compelling evidence for any formal model of the oscillations driving the activity rhythms. Predictions concerning the relation between phase and activity time derived from a single oscillator model are not matched by the data. On the other hand, the general seasonal patterns can be easily described in terms of a two-oscillator model. 6. Seasonal variations in duration of activity are larger in birds than in mammals. Day-to-day variations in timing are larger in mammals than in birds. The implications for photoperiodic time measurement are discussed.

Phasenlage der Tagesperiodik in Abhängigkeit von Jahreszeit und Breitengrad.

The hypothesis is advanced that the regular seasonal changes of the phase relationship between circadian activity rhythms and the natural light-dark cycle can be explained on the basis of special mechanisms of synchronization. In part 1.1, all the endogenous and exogenous factors are discussed which theoretically may influence the phase. From these considerations, it is concluded that it is mainly the ligh-dark ratio and the duration of twilight that determine the phase. Experimental evidence is presented in Part 1.2. In part 2, field observations on onset and end of activity of birds are re-analyzed. These data, as well as data from laboratory records of activity (3), support the hypothesis. They all show maximal leading phases in mid-summer for diurnal species, and in mid-winter for a nocturnal species; minimal leading phases occur at the equinox. A few exceptions from this rule, mentioned in part 4, raise the question to what extent the results can be generalized. The paper also discusses the uniform seasonal changes of the duration of activity-time.