Biomedical subjects

Anniina Alakuijala

Publications and source records attributed to Anniina Alakuijala.

5 recordsLinked to original sources

PubMed2006

Efficacy and safety of pramipexole in idiopathic restless legs syndrome: a polysomnographic dose-finding study--the PRELUDE study.

BACKGROUND AND PURPOSE: To evaluate the effects of pramipexole (0.125-0.75 mg/d) on polysomnographic (PSG) measures and patient and clinician ratings of restless legs syndrome (RLS). PATIENTS AND METHODS: Patients (n=109) with moderate to severe RLS were randomized to placebo or fixed doses of pramipexole during a 3-week, double-blind, placebo-controlled, dose-finding study. RESULTS: In each pramipexole dose group, the periodic limb movements during time in bed index (PLMI) decreased significantly, compared with placebo (adjusted mean difference in log-transformed data: 0.125 mg, -1.54; 0.25 mg, -1.93; 0.50 mg, -1.89; and 0.75 mg, -1.52; P<0.0001). At all doses, International RLS Study Group Rating Scale (IRLS) scores were also significantly reduced, with the greatest adjusted mean reduction in the 0.50mg group (-17.01). At all but the lowest pramipexole dose, the percentage of responders (> or =50% reduction of IRLS score) was substantially higher than for placebo (61.9-77.3, vs 33.3%). In the pramipexole groups, 50.0-77.3% of patients rated their condition as 'much better' or 'very much better', compared with 38.1% of patients in the placebo group (P=0.0139 for the 0.50 mg dose). Clinical global impressions (CGI) scale ratings of 'much improved' or 'very much improved' were given to 61.9-86.4% of patients in the pramipexole groups, compared with 42.9% in the placebo group (P<0.05 for the 0.25, 0.50, and 0.75 mg groups). Pramipexole was well tolerated and did not produce somnolence at any dose. CONCLUSION: Pramipexole is effective and safe in the treatment of both objective and subjective facets of RLS.

Adult↗

PubMed2006

Evidence for a functional role of GABA receptors in the rat mature hippocampus.

Both gamma-aminobutyric acid (GABA)(C) receptor subunit mRNA and protein are expressed in the stratum pyramidale in the CA1 area of the adult rat hippocampus, but so far no conclusive evidence about functional hippocampal GABA(C) receptors has been presented. Here, the contribution of GABA(C) receptors to stimulus-evoked postsynaptic potentials was studied in the hippocampal CA1 area with extracellular and intracellular recordings at the age range of 21-47 postnatal days. Activation of GABA(C) receptors with the specific agonist cis-4-aminocrotonic acid (CACA) suppressed postsynaptic excitability and increased the membrane conductance. The GABA(C) receptor antagonist 1,2,5,6-tetrahydropyridine-4-ylmethylphosphinic acid (TPMPA), but not the GABA(A) receptor antagonist bicuculline, inhibited the effects of CACA. GABA-mediated long-lasting depolarizing responses evoked by high-frequency stimulation of local inhibitory interneurons in the CA1 area in the presence of ionotropic glutamate receptor and GABA(B) receptor blockers were prolonged by TPMPA, indicating that GABA(C) receptors are activated under these conditions. For weaker stimulation, the effect of TPMPA was enhanced after GABA uptake was inhibited. Our data demonstrate that GABA(C) receptors can be activated by endogenous synaptic transmitter release following strong stimulation or under conditions of reduced GABA uptake. The lack of GABA(C) receptor activation by less intensive stimulation under control conditions suggests that these receptors are extrasynaptic and activated via spillover of synaptically released GABA.

Action Potentials↗

PubMed2005

GABA receptor rho subunit expression in the developing rat brain.

Ionotropic GABA(C) receptors are composed of rho1, rho2 and rho3 subunits. Although the distribution of rho subunit mRNAs in the adult brain has been studied, information on the developmental regulation of different rho subunits in the brain is scattered and incomplete. Here, GABA(C) receptor rho subunit expression was studied in the developing rat brain. In situ hybridization on postnatal brain slices showed rho2 mRNA expression from newborn in superficial gray layer (SGL) of superior colliculus (SuC), and from the first postnatal week in the hippocampal CA1 region and pretectal nucleus of the optic tract. rho2 mRNA was also expressed in the adult dorsal lateral geniculate nucleus. Quantitative RT-PCR revealed expression of all three rho subunits in the hippocampus and superior colliculus from the first postnatal day. In the hippocampus, rho2 mRNA expression clearly dominated over rho1 and rho3, whereas in the superior colliculus, rho1 mRNA expression levels were similar to rho2. In both areas, a clear up-modulation of rho2 and rho3 mRNA during the first postnatal week was detected. GABA(C) receptor protein expression was confirmed in adult hippocampus, superior colliculus and dorsal lateral geniculate nucleus by immunohistochemistry. Our results demonstrate for the first time the expression of all three rho subunit mRNAs in several regions of the developing and adult rat brain. Our quantitative data allows assessment of putative subunit combinations in the superior colliculus and hippocampus. From the selective distribution of rho subunits, it may be hypothesized that GABA(C) receptors are specifically involved in aspects of visual image motion processing in the rat brain.

Animals↗

PubMed2005

Perceived orofacial pain and its associations with reported bruxism and insomnia symptoms in media personnel with or without irregular shift work.

A standardized questionnaire was mailed to all employees of the Finnish Broadcasting Company with irregular shift work (n = 750) and to an equal number of randomly selected controls in the same company with regular 8-hour daytime work. The aims were to investigate the prevalence and severity of perceived orofacial pain (Research Diagnostic Criteria for Temporomandibular Disorders Axis II) and to analyze whether current orofacial pain was associated with reported bruxism and insomnia symptoms (Diagnostic and Statistical Manual of Mental Disorders-IV and the International Classification of Sleep Disorders Revised). The response rate in the irregular shift-work group was 82.3% (56.6% men) and in the regular daytime-work group 34.3% (46.7% men). Current orofacial pain was found overall in 19.6%, of which 88.3% had experienced the pain over 6 months. All claimed that their pain fluctuated. No subjects with chronic orofacial pain reported disabling pain, and grades III and IV were not found. Insomnia symptoms and frequent bruxism were significantly more prevalent in chronic pain grade II than in lower grades. According to logistic regression, current orofacial pain was significantly positively associated with frequent bruxism (p < 0.001), female gender (p < 0.001), and disrupted sleep (p < 0.01), and significantly negatively associated with age over 45 years (p < 0.01). Our results revealed a clear-cut association between perceived orofacial pain and reported bruxism. The association held with both chronic orofacial pain intensity and current pain. Based on the multivariate analyses, it can be concluded that disrupted sleep and bruxism may be concomitantly involved in the development of orofacial pain.

Adult↗

PubMed2005

Functional characterization of rat rho2 subunits expressed in HEK 293 cells.

GABA(C) receptors are thought to be homo- or heteropentamers composed of rho1, rho2 and rho3 subunits. Previous work on rat rho2 subunits expressed in Xenopus oocytes has suggested that they do not form functional homo-oligomeric GABA(C) receptors, but do combine with rho1 or rho3 subunits to form hetero-oligomers. These findings are difficult to interpret because both human and mouse rho2 subunits do form functional homo-oligomeric receptors. Also, many regions of the rat brain express solely rho2 subunit transcripts which, according to presently available evidence, would not result in expression of functional GABA(C) receptors. We show here that homomeric rat rho2 receptors can be expressed in HEK 293 cells. Homo-oligomeric rat rho2 receptors expressed in mammalian cells matured slowly and displayed small but detectable GABA-induced currents with slow kinetics. Rat rho2 receptors also had a decreased sensitivity to picrotoxin and a marked sensitivity to the GABA(C) receptor agonist cis-aminocrotonic acid. Our results demonstrate for the first time the expression of functional homomeric rat rho2 receptors, and suggest that rho(2) subunits may contribute to brain function, including in areas not expressing other rho subunits.

Animals↗