Involvement of prolactin in the REM sleep-promoting activity of systemic vasoactive intestinal peptide (VIP)

The involvement of pituitary prolactin (PRL) in systemic vasoactive intestinal peptide (VIP)-induced sleep was studied. Male rats were implanted with electrodes for EEG-recording, with brain thermistors to record cortical temperature (T_crt) and with chronic intracardial catheters to obtain blood samples and to deliver substances. One group of rats (n = 8) received normal rabbit serum (NS) + physiological saline (SAL) on the baseline day and was injected with NS + VIP on the experimental day. In the other group of rats (n = 6), the baseline day was followed by administration of PRL-antiserum (PRL-AS) + VIP on the experimental day. The sera and VIP or SAL were injected 30 min before and at light onset, respectively. Sleep-wake activity was then recorded for the next 12-h light period. Systemic VIP-stimulated PRL secretion as measured by RIA in serial samples obtained hour 1 postinjection. VIP also elicited selective increases in REM sleep (REMS) in the rats pretreated with NS. T_crt was not affected by VIP. Administration of PRL-AS blocked the increase in circulating levels of free (non-IgG-bound) PRL and prevented VIP-enhanced REMS. Comparisons of the sleep effects of PRL-AS + VIP with the previously reported changes in sleep after PRL-AS alone indicate that PRL has a major role in the mediation of the REMS-promoting activity of systemic VIP. The results suggest that an increased release of endogenous pituitary PRL modulates REMS.     

Increase of prolactin mRNA in the rat hypothalamus after intracerebroventricular injection of VIP or PACAP

Vasoactive intestinal peptide (VIP), the structurally homologous pituitary adenylate cyclase-activating peptide (PACAP) and the pituitary hormone, prolactin (PRL) enhance rapid eye movement sleep (REMS). VIP and PACAP are both inducers of PRL gene expression and release in the pituitary gland. Little is known about PRL regulation in the brain although it is hypothesized that the REMS-promoting activity of i.c.v. administered VIP may be mediated via the activation of cerebral PRL. To test whether VIP or PACAP in fact increase intracerebral mRNA, the peptides (VIP: 30 or 300 pmol; PACAP: 220 pmol) were injected i.c.v. into rats at dark onset. 1 h later, cDNA was synthesized from purified hypothalamic mRNA. Standardized amounts were analysed for PRL using the polymerase chain reaction followed by Southern blotting and hybridization. Compared with β-actin mRNA levels, both VIP and PACAP increased PRL mRNA levels in a dose-dependent fashion though VIP was more effective on a molar basis. The previously reported alternatively spliced PRL mRNA (lacking exon 4) was not detected. The data support the hypothesis that the REMS-promoting activity of central VIP and PACAP might be mediated by cerebral PRL.     

Topical application of fluorides on teeth

Abstract Prevention of caries in exposed root surfaces constitutes an important clinical problem. It is thus important that clinicians involved with periodontology have an insight into fluoride prophylaxis. The understanding of the cariostatic mechanism of fluoride has improved during recent years. The aim of the present review is to give a short account of the present concept. Calcium fluoride appears to be the only product which is formed on enamel, dentin or cementum during brief topical treatments with fluoride or use of toothpaste containing fluoride. This calcium fluoride is stable in the oral environment: this is contrary to what was believed until recently. The calcium fluoride constitutes a pH-dependant reservoir of fluoride which releases fluoride when pH drops. The practical consequences of this concept is discussed.     

Synergistic actions of the vitamin D analogue MC 1288 and 15-deoxyspergualin in xenotransplantation

Abstract: The vitamin D analogue MC 1288 (20-epi-1α,25-dihydroxycholecalciferol) effectively postpones rejection of cardiac, intestinal, skin, and aortic allografts. MC 1288 binds to the vitamin D receptor and is thus assumed to exert its immunosuppressive effects via the same mechanisms as 1α,25-dihydroxycholecalciferol, the active form of vitamin D. 1α,25-Dihydroxycholecalciferol has been demonstrated to inhibit the production of various cytokines (interleukin-2, interferon-γ, granulocyte macrophage colony-stimulating factor, and interleukin-12) and to prevent B lymphocyte secretion of immunoglobulins. In the present study MC 1288 was evaluated for its ability to prevent rejection of mouse-to-rat cardiac xenografts, alone and in combination with 15-deoxyspergualin (DSG). Combined treatment with MC 1288 (given days -1 to 9) and DSG (given day -1 and onward) postponed rejection from day 3.0 (untreated recipients) until day 19.5. In rats treated with MC 1288 or DSG as monotherapy, rejection occurred after 3.0 and 7.5 days, respectively. Functioning grafts, obtained on day 9 from recipients treated with MC 1288 and DSG in combination, displayed an almost normal morphology without any obvious deposition of immunoglobulins in the vessels of the grafts and with just a few infiltrating cells. Thus, we have demonstrated synergistic actions of MC 1288 and DSG in delaying rejection of xenografts. Analysis of cellular infiltration, immunoglobulin deposition and graft survival times in the various treatment groups indicate a combined inhibitory effect of these two drugs on the level of macrophage effector function, direct or indirect via T lymphocytes, as well as on antibody production.     

Bone loss detection in rats using a mouse densitometer.

Estrogen-depletion bone-loss studies often use ovariectomized (ovx) rats and measure bone mineral density in vivo or ex vivo using DXA. Recently, a portable densitometer (PIXImus) was developed for mouse research; however, its use in rats is unclear. This study compared the ability of PIXImus and a standard densitometer (DPXL) to detect ovx-induced bone loss in rats both in vivo and ex vivo. Additionally, instrument accuracy was assessed by comparing measured bone mass with ash weight. Finally, the use of two distal femur regions of interest (ROI) to detect ovx-induced bone loss was evaluated. Twenty-three 6-month-old nulliparous female Sprague-Dawley rats were randomly assigned to sham or ovx groups. Distal femur bone mineral density was assessed at baseline and at 1 and 2 months postoperatively, using a PIXImus and DPXL densitometer. At 3 months postoperatively, all animals were killed, and ex vivo femur scans obtained. Distal femur bone loss was demonstrable by 1 month post-ovx using either densitometer. With the PIXImus, a 4-mm ROI demonstrated greater bone loss (p < 0.05) than an 8-mm ROI. Using the 4-mm ROI, similar amounts of bone loss were detected by the PIXImus and DPXL: 22.2% and 22.4%, respectively, at 2 months post-ovx. Total femur bone mineral content was overestimated by the PIXImus but highly correlated with the DPXL measurement (r = 0.988) and ash weight (r = 0.998). Given its comparability to standard DXA plus its rapid scan speed and portability, the PIXImus is useful in evaluating ovx-induced osteopenia in rats.     

CSF testosterone in 43 male suicide attempters.

Several studies have shown a relationship between high testosterone and violent aggressive behaviour. The general aim of this study was to gain knowledge of the importance of testosterone in suicide attempters. Testosterone in cerebrospinal fluid (CSF) was analysed in men with a recent suicide attempt, diagnostically subdivided into groups according to DSM-III-R axis I and II diagnosis and mode of suicidal behaviour. In general, our patients had lower CSF testosterone levels than aggressive violent patients in other studies. Patients with depression NOS or dysthymia showed higher CSF testosterone levels than the rest. Significant positive correlation between testosterone and irritability or a negative correlation with social desirability was found in diagnostic subgroup of patients, specifically axis II, cluster B personality disorders. The results suggest that suicide attempts may be mediated by different biological variables than aggression.     

The Remittive Effects of Alefacept

The duration of response to treatment with alefacept has been assessed in patients with moderate to severe chronic plaque psoriasis who responded to alefacept therapy in phase 2 and phase 3 clinical studies. In a phase 2 trial, duration of response was based on time to retreatment with alefacept. In two phase 3 studies, the more objective measure of maintenance of a ≥50% reduction from baseline Psoriasis Area and Severity Index (PASI 50) was used. Two patient subsets were analyzed: (1) those who achieved a PASI 75 at any time during the trials and (2) those who achieved a Physician Global Assessment of “clear” or “almost clear” at any time during the trials. Regardless of the criterion used or the route of alefacept administration (intravenous or intramuscular), the median duration of response to alefacept therapy ranged from 7 to 10 months across the three studies. Alefacept is a remittive therapy for psoriasis.     

Does the nature of the solvent affect the anti-inflammatory capacity of triclosan? An experimental study

Abstract The anti-inflammatory properties of triclosan have been revealed in several recent studies, including an effect on histamine-induced inflammation. In other studies, the nature of the solvent has been shown to be of importance for the plaque inhibiting as well as the antibacterial potential of triclosan. This study was aimed at examining whether the nature of the solvent also may influence the anti-inflammatory capacity of triclosan and further to study a possible dose/response relationship. The study was performed as 3 separate, double-blind experiments, comprising 10, 11 and 12 healthy females. In all 3 experiments, 5 sites on the lower part of the back of the volunteers were intradermally exposed to one drop of 1% histamine dihydrochloride for 15 min. The size of the resulting wheals was recorded before and after 40 min of triclosan treatment. In experiment I. 4 different concentrations of triclosan in 2-fold dilutions in absolute alcohol (0.125%-1%) were applied on the histamine-induced wheals. In experiments 2 and 3, 4 different solutions containing 0.5% triclosan and a saline solution as negative control were used. The solvents in experiment 2 were as follows: (1) absolute alcohol (positive control). (2) propylene glycol (PG), (3) polyethylene glycol (PEG). (4) olive oil, and in experiment 3: (1) absolute alcohol (positive control). (2) Tween 80. (3) sodium carbonate, (4) soy oil. The results showed a dose/ response effect of triclosan and further that the solvent may be of importance for its anti-inflammatory potential.