Effect of antimycotics and rifampicin on the pharmacokinetics of buprenorphine and the feasibility of sublingual fentanyl for procedural sedation

Buprenorphine and fentanyl are opioids, which have been clinically used for decades. Buprenorphine is traditionally prescribed for maintenance therapy in opioid dependent patients and to a lesser extent in the treatment of acute pain. Fentanyl is the most widely used perioperative opioid. In recent years new dosage forms have been introduced for both of these drugs. The use of buprenorphine in the treatment of chronic pain has increased with the introduction of sublingual and transdermal formulations. Good results have been obtained with the administration of sublingual fentanyl in the treatment of cancer breakthrough pain. Some interaction studies have been made using high-dose buprenorphine and antiretrovirals, but there are few studies evaluating the drug-drug interactions between low-dose buprenorphine and known CYP3A4 inhibitors and inducers. In this thesis three studies were conducted to study the interactions between buprenorphine, using three different administration routes, and two CYP3A4 inhibitors, voriconazole and posaconazole and the CYP3A4 inducer, rifampicin. Voriconazole increased significantly the plasma concentration of sublingually and orally administered buprenorphine. Posaconazole also increased the plasma concentration of sublingually administered buprenorphine but the effect was not as evident as that encountered with voriconazole. Rifampicin decreased the plasma concentrations of sublingually administered buprenorphine, but it had no effect after the opioid’s intravenous administration. The aim of the fourth study was to evaluate the efficacy and safety of a sublingually administered fentanyl tablet in patients having colonoscopy. Patients often experience colonoscopy painful and unpleasant. Intravenous sedation increases the costs of colonoscopy significantly because patients need monitoring during sedation and recovery. The use of the sublingual administration route could offer a cost-effective alternative to intravenous sedation. This study showed that 100 micrograms of sublingual fentanyl was ineffective for the treatment of pain during colonoscopy. Nonetheless, it was observed that very few procedures had to be interrupted and the pain that patients experienced was mostly moderate. This raises the question of whether we should treat patients for anxiety and distress instead of pain

Performance of silver contacts in III-V solar cells

The development of solar cells with higher efficiencies is paramount when future global energy demands are to be met with renewable energy sources. The largest efficiency has been achieved with a multijunction solar cell manufactured from group III-V semiconductors. In order to improve the cells efficiency parasitic power losses manifesting in the cell should be reduced. This can be done by reducing the series resistance of the front metal contact. The aim for this thesis was to fabricate solar cells with smaller series resistances by changing the conductive metal in the front contact from gold to a silver-based structure. Silver has higher conductivity when compared to gold and it is also cheaper with a downside of being less chemically stable. This material change was studied in three different experiments which measured the properties of the fabricated silver such as conductivity, chemical stability and overall functionality in the process. In addition to the tests for the material properties multiple CPV solar cells with silver contacts were fabricated and their performance was compared to identical solar cells with gold contacts. The material tests proved that the silver-based structure is workable in the fabrication process and its conductivity was higher than gold. The performance of the fabricated silver cells was satisfactory, and it was identical to the gold cells when their performance was measured with a solar simulator in concentrations of 1, 100, 250, 500, 750 and 900 suns. However, when subjected to a high-power laser performance test it was observed that the silver cells had more resistive losses than the gold ones. The reason for performance decrease was estimated to be related to chemical degradation of silver during the manufacturing process as the structure was not completely protected. However, future developments for the silver contacts seem quite promising and with some adjustments to the fabrication process the contact structure could be protected from degradation. This could be done by utilizing alternative etchants which won’t react with the silver structure or utilizing a metallization process that covers the silver contact from its’ sides where it is most vulnerable for process chemicals. In conclusion, this thesis answered all the research questions provided sufficiently and it could function as a base for further silver contact development in III-V solar cells

Peruskoulua vai omaa elämää? Peruskoulun kuvataideopinnot ei-kuvataideopiskelijoiden ajatuksissa nykypäivänä

Tämän tutkimuksen tarkoituksena oli selvittää, minkälaisia merkityksiä peruskoulun kuvataideopinnot herättivät ei-kuvataideopiskelijoiden ajatuksissa nykypäivänä. Nyky-yhteiskunnan suorituskeskeinen ja tietopohjainen ote on vaikuttanut merkittävästi perusopetuksen opetettaviin sisältöihin ja tuntijakojen muodostumiseen. Kuvataiteen opetettava osuus muiden taito- ja taideaineiden rinnalla, on siten laajempien yhteiskunnallisten tavoitteiden saavuttamisessa nähty yhä epäoleellisemmaksi kokonaisuudeksi. Kuvataiteen yhtenäisen opetuksen määrä on vähentynyt peruskoulukontekstissa merkittävästi, jolloin myös opetuksen oppilasta eri tavalla kasvattava merkitys ja tietoteoreettinen punainen lanka on vaarassa kadota. Tämä tutkimus pyrkiikin tarkastelemaan peruskoulun kuvataideopintojen kautta syntyneitä merkityksiä myös oppiaineen tulevaisuuden näkymien kannalta. Kuvataiteen merkityksien käsittelyä lähestytään tutkimuksessa neljän keskeisimmän opetuksellisen tavoitteen (kuvailmaisu, luovuus, identiteetti ja tunnetaidot) toteutumisen kautta. Sosiaalinen konstruktionismi toimii tutkimuksessa laajempana teoreettisena viitekehyksen ja tarkastelee erityisesti opetuksellisen tavan vaikutuksia oppiaineen merkitysten rakentajana ja tavoitteiden toteutumisen edistäjänä. Tutkimustuloksien tarkoituksena on tuottaa tietoa opetussuunnitelman ja opettajankoulutuksen kehitystyötä varten. Tutkimuksen aineisto kerättiin teemahaastatteluna viideltä eri alan korkeakouluopiskelijalta. Opiskelijoiden tieteenaloja oli: kauppatiede, kasvatustiede, yhteiskuntatiede, biolääketiede ja tuotantotalous. Tutkimusaineiston analyysi toteutettiin pragmaattisena sisällönanalyysinä, jonka avulla eri tavoitesisältöihin liittyviä mainintoja ja niiden välisiä merkityksiä voitiin tarkastella osana laajempaa kuvataideopetuksellista kokonaisuutta. Luokittelun apuna toimi kuvataiteen tavoitekokonaisuuksia käsittelevät tieteelliset määritelmät. Tutkimustulosten mukaan, peruskoulun kuvataideopinnot näyttäytyivät kaikille eri alojen korkeakouluopiskelijoille mielekkäinä ja merkityksellisinä oppiaineellisena kokonaisuutena, jolla tulee olla paikka tulevaisuudessa osana perusopetuksen oppisisältöjä. Oppianeellisessa syvällisemmässä merkitysten rakentumisessa ja keskeisten opetuksellisten tavoitteiden toteutumisessa nähtiin kuitenkin selkeänä esteenä opettajan ainedidaktisesti uupuva ja oppiaineelle sopimaton opetuksellinen lähestymistapa. Opetuksen kaikki keskeisimmät tavoitteet toteutuivat vain yhden opiskelijan kohdalla, jolla opetus oli voimakkaimmin sosiaalisen konstruktionismin pedagogisiin periaatteisiin pohjautuvaa. Sosiaalisen konstruktionismin pedagogiset periaatteet voitaisiinkin siten nähdä oppiaineen opetuksellisia tavoitteita edistävänä tekijänä. Oppiainekohtaisten tavoitteiden toteutumisen vähyys ja opetuksellisten käsitysten ero toisaalta myös vahvistaa oppiaineen yhtenäisen opetuksellisen merkityskäsityksen puutteellisuutta

Extremely viscous stool in a newborn leading to an early diagnosis of a life-long disease

A female infant, born at 37+3 gestational weeks after an uncomplicated pregnancy, was referred to level III neonatal intensive care unit at the age of 24 hours due to a suspected bowel obstruction, with a history of not having passed meconium and some non-bilious emesis. Physical examination showed considerable abdominal distension with visible bowel loops. Abdominal X-ray identified dilated bowel loops, with no evidence of perforation.</p

Voriconazole greatly increases the exposure to oral buprenorphine

PurposeBuprenorphine has low oral bioavailability. Regardless of sublingual administration, a notable part of buprenorphine is exposed to extensive first-pass metabolism by the cytochrome P450 (CYP) 3A4. As drug interaction studies with buprenorphine are limited, we wanted to investigate the effect of voriconazole, a strong CYP3A4 inhibitor, on the pharmacokinetics and pharmacodynamics of oral buprenorphine.MethodsTwelve healthy volunteers were given either placebo or voriconazole (orally, 400mg twice on day 1 and 200mg twice on days 2-5) for 5days in a randomized, cross-over study. On day 5, they ingested 0.2mg (3.6mg during placebo phase) oral buprenorphine. We measured plasma and urine concentrations of buprenorphine and norbuprenorphine and monitored their pharmacological effects. Pharmacokinetic parameters were normalized for a buprenorphine dose of 1.0mg.ResultsVoriconazole greatly increased the mean area under the plasma concentration-time curve (AUC(0-18)) of buprenorphine (4.3-fold, PPeer reviewe

Feasibility of a transmucosal sublingual fentanyl tablet as a procedural pain treatment in colonoscopy patients: a prospective placebo-controlled randomized study

Since patients often experience pain and unpleasantness during a colonoscopy, the present study aimed to evaluate the efficacy and safety of sublingually administered fentanyl tablets for pain treatment. Furthermore, since the use of intravenous drugs significantly increases colonoscopy costs, sublingual tablets could be a cost-effective alternative to intravenous sedation. We conducted a prospective placebo-controlled randomized study of 158 patients to evaluate the analgesic effect of a 100 µg dose of sublingual fentanyl administered before a colonoscopy. Pain, sedation, nausea, and satisfaction were assessed during the colonoscopy by the patients as well as the endoscopists and nurses. Respiratory rate and peripheral arteriolar oxygen saturation were monitored throughout the procedure. There were no differences between the fentanyl and placebo groups in any of the measured variables. The median pain intensity values, as measured using a numerical rating scale, were 4.5 in the fentanyl group and 5 in the placebo group. The sedation and oxygen saturation levels and the respiratory rate did not differ between the groups. The majority of the colonoscopies were completed.Our results indicate that a 100 µg dose of sublingual fentanyl is not beneficial compared to the placebo in the treatment of procedural pain during a colonoscopy.</p

Rifampicin decreases exposure to sublingual buprenorphine in healthy subjects

Fam3c, a cytokine-like protein, is a member of the Fam3 family (family with sequence similarity 3) and has been implicated to play a crucial role in Epithelial-to- mesenchymal transition (EMT) and subsequent metastasis during cancer progression. A few independent genome-wide association studies on different population cohorts predicted the gene locus of Fam3c to be associated with bone mineral density and fractures. In this study, we examined the role of Fam3c during osteoblast differentiation. Fam3c was found to be expressed during osteogenic differentiation of both primary bone marrow stromal cells and MC3T3-E1 pre-osteoblasts. In differentiating osteoblasts, knockdown of Fam3c increased alkaline phosphatase expression and activity whereas overexpression of Fam3c reduced it. Furthermore, overexpression of Fam3c caused reduction of Runx2 expression at both mRNA and protein levels. Fam3c was localized in the cytoplasm and it was not secreted outside the cell during osteoblast differentiation and therefore, may function intracellularly. Furthermore, Fam3c and TGF-β1 were found to regulate each other reciprocally. Our findings therefore suggest a functional role of Fam3c in the regulation of osteoblast differentiation.</p

Optimized molecular beam epitaxy process for lattice-matched narrow-bandgap (0.8 eV) GaInNAsSb solar junctions

High performance narrow-bandgap GaInNAsSb solar cells are instrumental for the development of lattice-matched GaAs-based solar cells with more than four junctions. To this end a comprehensive optimization process including the effects of growth temperature, As/III beam equivalent pressure ratio, and Sb flux on the performance of 0.8 eV GaInNAsSb solar cells grown by molecular beam epitaxy is reported. For this, sets of GaInNAsSb p-i-n solar cell structures with 5–6% nitrogen compositions were fabricated, while varying the key growth parameters. The quantum efficiency and current generation increased significantly when the narrow gap materials were grown at elevated growth temperatures, close to phase separation. A further improvement in the current generation was observed by employing lower As/III beam equivalent pressure ratios. The best GaInNAsSb cell exhibited about 94% peak external quantum efficiency and generated a short-circuit current of 17.7 mA/cm2 with AM1.5D (1000 W/m2) illumination at wavelengths above 900 nm without employing a back surface reflector. Our analysis indicates that the best cell is already close to being absorption limited. While the N composition should be kept as low as possible (i.e., ≲5%) to achieve high performance, increasing the Sb flux generally results in improved the material quality, i.e., leading to a slight improvement for the open-circuit voltages and fill factors. In addition, it was found that the phase separation observed at the growth temperature of 480 °C could effectively be inhibited by employing higher Sb fluxes.publishedVersionPeer reviewe

Voriconazole more likely than posaconazole increases plasma exposure to sublingual buprenorphine causing a risk of a clinically important interaction

This study aimed to determine possible effects of voriconazole and posaconazole on the pharmacokinetics and pharmacological effects of sublingual buprenorphine.We used a randomized, placebo-controlled crossover study design with 12 healthy male volunteers. Subjects were given a dose of 0.4 mg (0.6 mg during placebo phase) sublingual buprenorphine after a 5-day oral pretreatment with either (i) placebo, (ii) voriconazole 400 mg twice daily on the first day and 200 mg twice daily thereafter or (iii) posaconazole 400 mg twice daily. Plasma and urine concentrations of buprenorphine and its primary active metabolite norbuprenorphine were monitored over 18 h and pharmacological effects were measured.Compared to placebo, voriconazole increased the mean area under the plasma concentration-time curve (AUC(0-a)) of buprenorphine 1.80-fold (90 % confidence interval 1.45-2.24; P < 0.001), its peak concentration (C-max) 1.37-fold (P < 0.013) and half-life (t (A1/2) ) 1.37-fold (P < 0.001). Posaconazole increased the AUC0(0-a) of buprenorphine 1.25-fold (P < 0.001). Most of the plasma norbuprenorphine concentrations were below the limit of quantification (0.05 ng/ml). Voriconazole, unlike posaconazole, increased the urinary excretion of norbuprenorphine 1.58-fold (90 % confidence interval 1.18-2.12; P < 0.001) but there was no quantifiable parent buprenorphine in urine. Plasma buprenorphine concentrations correlated with the pharmacological effects, but the effects did not differ significantly between the phases.Voriconazole, and to a minor extent posaconazole, increase plasma exposure to sublingual buprenorphine, probably via inhibition of cytochrome P450 3 A and/or P-glycoprotein. Care should be exercised in the combined use of buprenorphine with triazole antimycotics, particularly with voriconazole, because their interaction can be of clinical importance

Rifampicin decreases exposure to sublingual buprenorphine in healthy subjects

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