TMTHSI, a superior 7-membered ring alkyne containing reagent for strain-promoted azide-alkyne cycloaddition reactions.

We describe the development of TMTH-ulfoxmine (TMTH) as a superior click reagent. This reagent combines a great reactivity, with small size and low hydrophobicity and compares outstandingly with existing click reagents. TMTHSI can be conveniently functionalized with a variety of linkers allowing attachment of a diversity of small molecules and (peptide, nucleic acid) biologics.

Water and heat transport in boreal soils: implications for soil response to climate change.

Soil water content strongly affects permafrost dynamics by changing the soil thermal properties. However, the movement of liquid water, which plays an important role in the heat transport of temperate soils, has been under-represented in boreal studies. Two different heat transport models with and without convective heat transport were compared to measurements of soil temperatures in four boreal sites with different stand ages and drainage classes.

Complications of the intrauterine device in nulliparous and parous women.

Objectives: The intrauterine device (IUD) is still related to pelvic inflammatory disease (PID), pregnancy, expulsion, perforation and menstrual problems, particularly in nulliparous women. We aimed to study the complications and symptoms of the intrauterine device in general practice, particularly in nulliparous women.

Methods: We used a retrospective cohort study in four general practices participating in the Nijmegen Continuous Morbidity Registration.

Intrauterine contraception: the role of general practitioners in four Dutch general practices.

The intrauterine device (IUD) use in the Netherlands and the United States is limited to a small group of women, though the risk of infection and pregnancy is small. Therefore, it was of interest to investigate the characteristics of women who choose an IUD as contraceptive method and the influence of general practitioners concerning IUD insertion. The aim of this retrospective cohort study was to assess differences between general practices and to investigate the characteristics of IUD users.

Rearrangement of O-cinnamoyltaxicin I to a novel C-13 spiro-taxane.

During the large-scale synthesis of an O-cinnamoyltaxicin I acetonide, an intermediate for the semisynthesis of 7-deoxypaclitaxel derivatives, side-product 3 was formed via a vinylogous retro-aldol reaction and a long-range hydride shift from O-cinnamoyltaxicin I (1) under alkaline reaction conditions. Compound 3 has two hemi-acetal bridges at C-1,C-9 and C-10,C-13. Compound 4 was formed from side-product 3 under acidic reaction conditions and is the first C-13 spiro-taxane described in the literature.

Anatomic consideration for preventive implantation.

The aim of preventive implant therapy is to prevent or delay loss of alveolar ridge bone mass. For use in an anatomic study of 60 mandibles, resorption of the alveolar ridge was classified into four preventive stages: (1) after extraction of teeth; (2) after initial resorption; (3) when the ridge has atrophied to a knife-edge shape; and (4) when only basal bone remains. Implantation in stage 3 necessitates removal of the knife-edge ridge to create space for cylindrical implants.

Effect of serotonin re-uptake inhibition by fluoxetine on body weight and spontaneous food choice in obesity.

The effect of fluoxetine on body weight and spontaneous food choice was studied in twenty-three healthy, non-depressed, obese females on an outpatient basis. After a one week placebo run-in period, subjects were randomized to receive either fluoxetine (FXT) 60 mg daily (n = 11) or placebo (P) (n = 12) for 6 weeks in a double blind study design. BMI (35.

Effects of pituitary beta-endorphin secretagogues on the concentration of beta-endorphin in rat cerebrospinal fluid: evidence for a role of vasopressin in the regulation of brain beta-endorphin release.

The concentration of beta-endorphin-immunoreactivity (beta E-IR) in cerebrospinal fluid (CSF) and plasma of rats was determined following intracerebroventricular (ICV) treatment of conscious animals with substances known to stimulate the release of beta E and other pro-opiomelanocortin (POMC)-derived peptides at the level of the anterior and intermediate lobes of the pituitary. The beta-adrenoceptor agoinst isoproterenol (ISO) did not influence the concentration of beta E-IR in CSF collected 5-60 min after ICV administration of doses ranging from 3 to 30,000 pg/rat. Plasma beta E-IR levels, however, were significantly increased 20 min following ICV injection of 30,000 pg ISO.

All porcelain anterior veneer bridges.

The introduction of new porcelain materials used in combination with vastly improved bonding materials and techniques have virtually revolutionized the use of conservative esthetic bonded prosthetic restorations fabricated without the need for metal substructures. Missing anterior teeth in selected cases may be replaced by all porcelain veneer bridges that are accomplished with more conservation of natural tooth structure of the abutment teeth as compared to traditional procedures. A total of 12 all porcelain veneer bridges were monitored for varying periods up to 24 months postoperatively, during which time no fractures occurred.

Differential effects of cisterna magna cannulation on beta-endorphin levels in rat plasma and cerebrospinal fluid.

The concentration of beta-endorphin-like immunoreactivity (beta-ELIR) was determined in plasma and cerebrospinal fluid (CSF) of rats at various times following the implantation under Hypnorm anesthesia of a permanent cannula into the cisterna magna. Plasma beta-ELIR levels were highly increased immediately after the operation, and gradually returned to basal within 6 h. The beta-ELIR concentration in CSF followed a completely different pattern.

Antiglucocorticoid RU 38486 attenuates retention of a behaviour and disinhibits the hypothalamic-pituitary adrenal axis at different brain sites.

Adrenalectomized rats displayed a deficiency in retention of an immobility response acquired during an initial 15-min forced swimming procedure (Porsolt swimming test) and measured 24 h later in a 5-min retest session. The deficit could be restored dose dependently with the glucocorticoid dexamethasone (microgram range) administered 15 min after the initial test. The antiglucocorticoid RU 38486 administered subcutaneously (1 and 10 mg/kg) inhibited the dexamethasone effect and caused a parallel shift in the dose-response curve of dexamethasone.

Corticosteroid effects on morphine-induced antinociception as a function of two types of corticosteroid receptors in brain.

The antinociceptive effect of parenterally and intracerebroventricularly injected morphine and beta-endorphin in adrenalectomized rats and in adrenalectomized rats treated with adrenal steroids was examined employing the hot-plate method. (1) Adrenalectomy sensitized the rats to an analgesic effect of morphine and beta-endorphin. (2) Replacement therapy (chronic and acute) with corticosterone, dexamethasone or RU 28362 (glucocorticoid receptor agonist) effectively reversed the increase in the sensitivity to the analgesic effect of peripherally injected morphine (5 mg/kg i.

Microinjection of anti-vasopressin serum into limbic structures of the rat brain: effects on passive avoidance responding and on local catecholamine utilization.

Rats which had received bilateral microinjections of 1:50 diluted anti-vasopressin serum into the dorsal or ventral hippocampus, immediately after the learning trial of a one-trial passive avoidance test, showed a reduction in avoidance latency scores during subsequent retention tests 24 and 48 h later. Postlearning microinjection of anti-vasopressin serum into either the dorsolateral septum or the caudate nucleus was without effect on the retention of passive avoidance behavior. Microinjection of anti-vasopressin serum 1 h before the 24-h retention session into either the dorsal hippocampus, the ventral hippocampus or the dorsolateral septum attenuated avoidance responding during both the 24-h and 48-h retention sessions, whereas preretention microinjection of the serum into the caudate nucleus was not effective.

Modulation of the immune response by emotional stress.

The influence of mild, emotional stress was investigated for its effect on the immune system by subjecting rats to the one-trial-learning passive avoidance test. The reactivity of the immune system was tested by determining the proliferative response after mitogenic stimulation in vitro as well as the capacity to generate a primary antibody response in vivo after immunization with sheep red blood cells. Our results demonstrate that exposure of rats to a single electric footshock (learning trial) or habituation to the passive avoidance apparatus, induces an increase of the immune response in vitro and in vivo.

Substantia nigra lesions attenuate the development of hypertension and behavioural hyperreactivity in spontaneously hypertensive rats.

The possible relation between changes in behaviour and the development of hypertension was investigated. Depletion of striatal dopamine by lesions in the substantia nigra of Spontaneously Hypertensive Rats (SHR) was associated with an inhibition of the development of hypertension. In the open field a decrease in rearing score was found with no effect on other parameters.

Facilitation of avoidance behavior by vasopressin fragments microinjected into limbic-midbrain structures.

Effects of arginine vasopressin (AVP1-9) and its behaviorally active fragments [Cyt6]AVP5-9 and [Cyt6]AVP5-8 were studied on the retention of one-trial learning passive avoidance behavior in rats. Peptides were microinjected into various limbic and midbrain structures (ventral or dorsal hippocampus or the dorsal raphe nucleus) and were administered either immediately after the learning trial (post-learning treatment) or shortly before the 24 h retention session (pre-retention treatment). Doses for intracerebral microinjections were selected after preliminary experiments with subcutaneous and intracerebroventricular peptide administration.

Vasopressin and oxytocin. Their presence in the central nervous system and their functional significance in brain processes related to behaviour and memory.

Vasopressin and oxytocin exert pronounced effects on behaviour by a direct action on the brain. A single injection of vasopressin results in a long-term inhibition of extinction of a conditioned avoidance response suggesting that vasopressin triggers a long-term effect on the maintenance of a learned response, probably by facilitation of memory processes. In addition vasopressin improves passive avoidance behaviour, delays extinction of appetitive discrimination tasks, affects approach behaviour to an imprinting stimulus in ducklings, improves copulation rewarded behaviour of male rats in a T-maze, prevents or reverses amnesia induced by electroconvulsive shock, CO2 inhalation, pentylenetetrazol or puromycin.

Central 6-OHDA affects both open-field exploratory behaviour and the development of hypertension in SHR.

To investigate the possible relation between changes in behaviour and the development of hypertension in the spontaneously hypertensive rat (SHR), the effect of intracerebroventricular (ICV) administration of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) on blood pressure and spontaneous behaviour was studied. In addition to an attenuation of the rise in blood pressure in SHR, 6-OHDA induced a marked decrease in rearing activity in the open field towards levels found in WKY. Other parameters were either not changed (stereotyped sniffing) or influenced in a comparable way in SHR and WKY (increase in locomotion).

Behavioural factors contribute to the development of spontaneous hypertension in rats.

The relationship was studied between brain catecholamine systems, open-field behaviour and the development of hypertension in spontaneously hypertensive rats (SHR). Both the rise in blood pressure and the increased open-field rearing activity of SHR were inhibited by central dopamine depletion. Antihypertensive treatment with hydralazine or captopril did not change behaviour, however.

Glucocorticoids facilitate the retention of acquired immobility during forced swimming.

The adrenalectomy-induced decrease in the level of immobility during a 5 min retest period in the Porsolt swimming test could be reversed by glucocorticoids administered s.c. 15 min after the initial forced swimming exposure.

Beneficial effect of chronic treatment with Org 2766 and alpha-MSH on impaired reversal learning of rats with bilateral lesions of the parafascicular area.

The effects of chronic treatment with the ACTH-(4-9) analogue Org 2766, alpha-MSH, and gamma 2-MSH were studied on T-maze reversal learning and on behavior assessed on the basis of open-field and other gross behavioral activities, grasping responses, inspection of various reflexes and electrical footshock sensitivity of rats with parafascicular lesions or sham-lesions. Repeated administration of Org 2766 and alpha-MSH to parafascicular area-lesioned rats resulted in functional recovery of impaired T-maze reversal learning. The structurally related neuropeptide gamma 2-MSH was without any effect.

Vasopressin: site of behavioral action and role in human mental performance.

Diminishment of endogenous vasopressin in various brain areas (dorsal and ventral hippocampus, dorsal septum) by local application of diluted anti-vasopressin serum results in attenuation of passive avoidance behavior of rats. Both post-learning or pre-retention treatment results in impaired behavior when the anti-vasopressin serum was applied in the dorsal or ventral hippocampus, whereas only pre-retention but not post-learning application of the antiserum in the dorsal septum induced behavioral impairment. Only injection of less diluted antiserum into the lateral ventricle results in attenuation of passive avoidance behavior.

Differential behavioral actions of corticotropin-releasing factor (CRF).

In order to elucidate the involvement of the 41 amino-acid residue corticotropin-releasing factor (CRF) in the modulation of brain functioning, the behavioral profile of the releasing hormone was determined using tests for spontaneous behavior, grooming, active and passive avoidance behavior. Intracerebroventricular (ICV) administration of CRF in a dose that does not stimulate the pituitary-adrenal axis, resulted in an activation of open-field behavior, as measured by ambulation and rearing activities. Also grooming activity was significantly enhanced after central application of CRF.