Leukotriene C4 biosynthesis in isolated August rat peritoneal leukocytes

The mixed leukocyte population obtained from the peritoneum of the August rat is a potentially important experimental model of inherent eosinophilia that has not been well characterized. In the present study, isolated cell preparations generated a concentration-dependent release of leukotriene (LT) C4 when exposed to the Ca2+ ionophore A23187, reaching maximal stimulation at 5.0 μM. This response was inhibited by the 5-lipoxygenase activating protein antagonist MK-886 (0.1 μM), nominally Ca2+ and Mg2+-free incubation media and by activation of protein kinase C via phorbol 12-myristate 13-acetate (50 nM). These findings establish a model system for investigating LTC4 profiles contingent with innate peritoneal eosinophilia and are consistent with the hypothesis that cellular LTC4 biosynthesis is phosphoregulated

Overlap of cognitive concepts in chronic widespread pain: An exploratory study

<p>Abstract</p> <p>Background</p> <p>A wide variety of cognitive concepts have been shown to play an important role in chronic widespread pain (CWP). Although these concepts are generally considered to be distinct entities, some might in fact be highly overlapping. The objectives of this study were to (i) to establish inter-relationships between self-efficacy, cognitive coping styles, fear-avoidance cognitions and illness beliefs in patients with CWP and (ii) to explore the possibility of a reduction of these cognitions into a more limited number of domains.</p> <p>Methods</p> <p>Baseline measurement data of a prospective cohort study of 138 patients with CWP were used. Factor analysis was used to study the associations between 16 different cognitive concepts.</p> <p>Results</p> <p>Factor analysis resulted in three factors: 1) negative emotional cognitions, 2) active cognitive coping, and 3) control beliefs and expectations of chronicity.</p> <p>Conclusion</p> <p>Negative emotional cognitions, active cognitive coping, control beliefs and expectations of chronicity seem to constitute principal domains of cognitive processes in CWP. These findings contribute to the understanding of overlap and uniqueness of cognitive concepts in chronic widespread pain.</p

Afdichtende functie van met waterglas geommobiliseerde afvalstoffen

De afdichtende werking van afdichtingslagen is onderzocht op de stortplaats Boeldershoek te Hengelo. De doorlatendheid volgens de falling-head-methode is bepaald aan ongestoorde monsters. De gemiddelde doorlatendheid van met waterglas geommobiliseerdemengsels van zuiveringsslib, zeefzand en vliegas is 0,61 nm/s; van zuiveringsslib/papierslib, zeefzand en vormzand 0,08 nm/s; en van mengsels van zuiveringsslib, zeefzand en koepelovenstof 0,18 nm/s. Als deze mengsels worden toegepast in een laagdikte van 0,5 m, voldoen de doorlatendheden ruimschoots aan de referentieafdichtingen van zand-bentoniet

Factors Associated With Sleep Quality in Patients With Chronic Widespread Pain Attending Multidisciplinary Treatment

Purpose: (1) To investigate the prevalence of poor sleep quality and (2) to explore the associations between clinical, cognitive, and emotional factors and quality of sleep in patients with chronic widespread pain (CWP) receiving multidisciplinary treatment. Method: Baseline data were used from 163 patients with CWP referred for multidisciplinary treatment. Linear regression models were used to assess the relationship of clinical (pain, fatigue, pain interference, and disability), emotional (anxiety, depression, and psychological distress), and cognitive factors (catastrophizing, acceptance, self-efficacy, kinesiophobia and illness beliefs) with sleep quality, as measured using the Pittsburgh Sleep Quality Index. Results: Poor sleep quality was found in 92% of the patients. The multivariable model showed that a higher level of fatigue (b = 1.77, standard error [SE] = 0.62, β = 0.21, t = 2.87, P < 0.01), psychological distress (b = 0.02, SE = 0.01, β = 0.27, t = 3.50, P < 0.01), and more concerns about the illness (b = 0.46, SE = 0.18, β = 0.20, t = 2.57, P = 0.01) were independently associated with poorer quality of sleep. The overall linear regression model explains 27.9% of sleep quality. Conclusions: The high prevalence of poor sleep quality in patients with CWP referred for multidisciplinary treatment emphasizes the need to target sleep during treatment. Further research is needed to disentangle the cause–effect relationship between fatigue, psychological distress, and concerns about the illness and poor sleep (note: this abstract has been published before [Ann Rheum Dis. 2018;77:A1788])

Oral treatment with etoposide in small cell lung cancer - dilemmas and solution

Background. Etoposide is a chemotherapeutic agent, widely used for the treatment of various malignancies, including small cell lung cancer (SCLC), an aggressive disease with poor prognosis. Oral etoposide administration exhibits advantages for the quality of life of the patient as well as economic benefits. However, widespread use of oral etoposide is limited by incomplete and variable bioavailability. Variability in bioavailability was observed both within and between patients. This suggests that some patients may experience suboptimal tumor cytotoxicity, whereas other patients may be atrisk for excess toxicity. Conclusions. The article highlights dilemmas as well as solutions regarding oral treatment with etoposide by presenting and analyzing relevant literature data. Numerous studies have shown that bioavailability of etoposide is influenced by genetic, physiological and environmental factors. Several strategies were explored to improve bioavailability and to reduce pharmacokinetic variability of oral etoposide, including desired and undesired drug interactions (e.g. with ketoconazole), development of suitable drug delivery systems, use of more water-soluble prodrug of etoposide, and influence on gastric emptying. In addition to genotype-based dose administration, etoposide is suitable for pharmacokinetically guided dosing, which enables dose adjustments in individual patient. Further, it is established that oral and intravenous schedules of etoposide in SCLC patients do not result in significant differences in treatment outcome, while results of toxicity are inconclusive. To conclude, the main message of the article is that better prediction of the pharmacokinetics of oral etoposide may encourage its wider use in routine clinical practice.Izhodišča. Etopozid je protitumorna učinkovina, ki jo pogosto uporabljamo za zdravljenje različnih rakavih obolenj, vključno z drobnoceličnim pljučnim rakom. Ta je agresivni rak s slabo napovedjo poteka bolezni. Peroralno vnašanje etopozida ima veliko prednosti tako z vidika kakovosti življenja bolnika kakor tudi z vidika obvladovanja stroškov. Uporaba etopozida pa je omejena zaradi nepopolne absorpcije ter velike intra- in inter-individualne spremenljivosti biološke uporabnosti. To lahko pri nekaterih bolnikih privede do zmanjšane učinkovitosti ali povečane toksičnosti. Zaključki. Članek s pregledom in analizo literaturnih podatkov predstavlja dileme in rešitve gledeperoralnega zdravljenja z etopozidom. Rezultati številnih raziskav so pokazali, da na biološko uporabnost etopozida vplivajo genetski, fiziološki in okoljski dejavniki. Poznamo številne pristope za izboljšanje biološke uporabnosti in zmanjšanje farmakokinetične spremenljivosti peroralnega etopozida. To so želene in neželene interakcije (npr. s ketokonazolom), razvojustreznih dostavnih sistemov, uporaba predzdravila, ki je bolj vodotopno od etopozida in vpliv na hitrost praznjenja želodca. Etopozid je primerna zdravilna učinkovina za odmerjanje na osnovi poznavanja farmakokinetike in genotipa, kar omogoča tudi prilagajanje odmerka pri posameznemu bolniku. Ugotovili so, da se učinkovitost peroralnega in intravenskega zdravljenja z etopozidom pri bolnikih z drobnoceličnim pljučnim rakom značilno ne razlikuje, medtem ko so si rezultati primerjav toksičnosti nasprotujoči. Glavno sporočilo članka je, da boljša napovedljivost farmakokinetike peroralnega etopozida omogoča večjo uporabo le-tega v rutinski klinični praksi