The promise of PROMIS(®) for addiction

The field of addiction treatment has a measurement problem that pervades efforts to help patients achieve self-sustainable recovery. The impact of using older measurement technology has increased the measurement burden on both service providers and patients, while at the same time limiting the scope and frequency of measurement. The resulting burden can affect provider performance, patient access, and addiction recovery. This paper underscores the need for applying modern measurement theory techniques to reduce the measurement burden currently affecting most if not all major aspects of treatment and recovery. It is currently possible to obtain information more precisely, over a broad spectrum of recovery-oriented domains, faster and at lower cost than current measurement practices allow. However, a persistent research effort will be necessary to achieve that goal.     

Food–drug interactions: effect of capsaicin on the pharmacokinetics of galantamine in rats

1. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide, CAP) is a naturally occurring alkaloid extracted from the fruit of Capsicum plant family. It represents an important ingredient in spicy foods consumed throughout the world. However, little is known about the metabolic interactions between CAP and clinically used drugs.

2. This study attempted to investigate the effect of CAP on the pharmacokinetics of galantamine, a competitive and reversible cholinesterase inhibitor. CAP, dexamethasone or sodium salt of carboxymethyl cellulose (CMC-Na) was given to rats for seven consecutive days and on the seventh day galantamine (10 mg/kg) was administered orally. Dexamethasone was used as a CYP inducer and CMC-Na was used as a vehicle.

3. The results showed that the pretreatment of rats with CAP resulted in a decrease in the AUC_0–∞ of galantamine of about 49.70% (p < 0.01) compared with the control group. After oral administration of galantamine (10 mg/kg), the apparent oral clearance of galantamine was raised by 2.05-fold by pretreatment with CAP (p < 0.05). These results demonstrate that the chronic ingestion of high doses of CAP will decrease the bioavailability of galantamine to a significant extent in rats.

     

The effect of a secreted form of β-amyloid-precursor protein on intracellular Ca2+ increase in rat cultured hippocampal neurones

1. The effects of secreted forms of β-amyloid-precursor proteins (APP^Ss) on the intracellular Ca²⁺ concentration ([Ca²⁺]_i) were investigated in rat cultured hippocampal neurones. APP695^S, a secretory form of APP695, attenuated the increase in [Ca²⁺]_i evoked by glutamate. In addition, APP695^S itself evoked an increase in [Ca²⁺]_i in 1 or 2 day-cultured hippocampal cells, but not in 7 to 13 day-cultured cells.
2. Eighty-one percent of neurones which were immunocytochemically positive for microtubule-associated protein 2 responded to APP695^S with an increase in [Ca²⁺]_i.
3. APP695^S induced a transient rise in [Ca²⁺]_i even in the absence of extracellular Ca²⁺ and produced an elevation in inositol-1,4,5-trisphosphate (IP₃) in a concentration-dependent manner from 100 to 500 ng ml⁻¹. In the presence of extracellular Ca²⁺, APP695^S caused a transient rise in [Ca²⁺]_i followed by a sustained phase at high [Ca²⁺]_i, suggesting Ca²⁺ entry from the extracellular space.
4. The [Ca²⁺]_i elevation was mimicked by amino terminal peptides of APP^S, but not by carboxy terminal peptides.
5. These results taken together suggest that APP695^S induces an increase in [Ca²⁺]_i in hippocampal neurones through an IP₃-dependent mechanism that changes according to the stage of development.

     

Nanoprobing of misfolding and interactions of amyloid β 42 protein

The assembly of amyloid β (Aβ) proteins into nanostructures is currently considered a major pathway of Alzheimer’s disease development, but the molecular mechanisms of this self-assembly process remains unclear. Recently, we showed that single-molecule AFM force spectroscopy (SMFS) is capable of probing the dynamics and interaction between Aβ40 peptides, and these studies allowed us to shed new light on transiently existing Aβ40 misfolding states. In this study, we applied the same SMFS approach to characterize the misfolding of Aβ42 peptide, the most toxic Aβ alloform. The quantitative analysis of SMFS data demonstrated that Aβ interaction leads to the formation of dimers with a lifetime in the range of a second. Interaction via C-terminal segments prevailed at pH 7, but interaction within the peptide center prevailed at acidic pH levels. The difference in the misfolding properties for Aβ40 and Aβ42 peptides and the mechanisms of amyloid nanoassembly are discussed.From the Clinical EditorDespite decades of intense research, Alzheimer's disease still remains incurable. This novel study focuses on the assembly of amyloid β proteins into nanostructures, which is a key mechanism in Alzheimer's disease development. Single molecule atomic force spectroscopy is utilized to shed light on the molecular mechanisms of this self-assembly process.     

The effect of (±)-dobutamine on adrenergic nerve endings

Summary Possible effects of (±)-dobutamine on adrenergic nerve endings were determined in experiments with ghosts of bovine chromaffin granules, with rat phaeochromocytoma (PC-12) cells and with the rat vas deferens. Dobutamine inhibited the vesicular uptake of a mixture of 70% adrenaline + 30% ³H-noradrenaline into ghosts, with an IC₅₀ of 1.7 mol/l. Dobutamine inhibited uptake, of ³H-noradrenaline in PC-12 cells (with an IC₅₀ of 0.38 mol/l) without being a substrate. However, dobutamine easily entered PC-12 cells by diffusion. After inhibition of MAO, COMT and vesicular uptake dobutamine (15 and 45 mol/l) released tritium from rat vasa deferentia preloaded with ³H-noradrenaline. Equi-inhibitory concentrations of dobutamine and desipramine (against uptake₁) were equireleasing. On the other hand, when MAO and vesicular uptake were intact, dobutamine (15 mol/l) increased the efflux of tritium from preloaded vasa deferentia much more than did an equi-inhibitory concentration of desipramine. Most of the released tritium was then ³H-DOPEG.Dobutamine is a potent inhibitor of uptake₁ as well as of vesicular uptake; moreover, it easily diffuses into adrenergic nerve endings. Hence, it blocks the neuronal and the vesicular re-uptake of noradrenaline; consequently, when MAO and vesicular uptake are intact, dobutamine increases the net leakage of noradrenaline from the storage vesicles, thereby leading to an efflux of deaminated metabolites. However, dobutamine is virtually unable to release noradrenaline into the extracellular space.Abbreviations COMT catechol-O-methyl transferase - DOPEG dihydroxyphenylglycol - DOMA dihydroxymandelic acid - MAO monoamine oxidase Supported by the Deutsche Forschungsgemeinschaft (Gr 490/5 and SFB 176) Send offprint requests to P. Fischer at the above address     

Supppressive effect of the immuno-suppressive protein induced by stress on arterrial blood pressure rat

To study the effect of partially purified immune suppressive protein of stress on the normal arterial blood pressure in rots.The immune suppressive protein of stress was partially purified from the lymph node of the restraint stressed rat with salting-out, extra-filtration and HPLC gel filtration.The protein was intravenously injected into normal SD rats.Blood pressure, heart rate and respiration were recorded with MacLab system.It was found that intravenous injection of the protein (200, 400, and 800 μg per     

The effect of spironolactone on the levels of GATA4 protein and hypoxia inducible factor-1α in patients receiving coronary stent implantation

In the present study, we aimed to explore the protective effect of spironolactone on cardiac function in patients undergoing coronary stent implantation by determining the serum levels of GATA4 and hypoxia-inducible factor-1α (HIF-1α) proteins before and after the coronary stent implantation. A total of 134 patients undergoing coronary stent implantation in our hospital from March 2019 to March 2020 were retrospectively selected using the propensity score matching (PSM) method. Of the 134 patients, 67 patients taking spironolactone were used as a test group, and the other 67 patients without taking spironolactone were used as a control group. In all patients, the levels of serum GATA4, HIF-1α, and troponin I proteins were determined before as well as 24 h and 6 months after the coronary stent implantation. Left ventricular ejection fraction (LVEF) and left ventricular systolic global longitudinal strain (GLS) were determined before and 6 months after the coronary stent implantation. There were no significant differences in the HIF-1α level between the two groups before and 6 months after the operation, while the HIF-1α level was significantly lower in the test group compared with the control group at 24 h after the operation (P < 0.01). There were no significant differences in the GATA4 protein level between the two groups before and 24 h after the operation, while the GATA4 protein level was significantly lower in the test group compared with the control group at 6 months after the operation (P < 0.01). There was no significant difference in LVEF between the two groups before and 6 months after the operation. GLS was significantly improved at 6 months after the operation compared with that before the operation in both groups, while GLS was significantly better in the test group compared with the control group at 6 months after the operation (P < 0.01). Collectively, spironolactone could protect cardiac function probably by improving myocardial hypoxia and inhibiting myocardial remodeling.     

The effect of mandatory generic substitution on the safety of alendronate and patients’ adherence

Abstract

Objective:

Generic medicines are often used in public hospitals. However, data on the quality of generic alendronate, its efficacy, side-effects and medication adherence in clinical practice is scarce. Therefore, this study aimed to compare the side-effects and medication adherence of generic (apo-alendronate) and proprietary alendronate (Fosamax).     

The effect of chlorpromazine on the electrical activity of the “cerveau isolé”

Zusammenfassung Chlorpromazin (Largactil; Megaphen) verursachte in Dosen von 0,2–0,5 mg/kg (intravenös) ausgeprägte Veränderungen des Elektrocorticogramms des thalamo-corticalen Systems (cerveau isolé — Präparation von Bremer). Die für diese Präparation charakteristischen Spindeln (12–15 per sec) und langsamen Wellen (2–3 per sec) verschwanden innerhalb weniger Minuten nach der Injektion; in einigen Experimenten wurden vorübergehend spikes and waves im Anschluß an die intravenöse Injektion von Chlorpromazin beobachtet.Die Beobachtungen werden dahingehend interpretiert, daß Chlorpromazin die Spontanaktivität des thalamocorticalen Systems beeinflußt; diese Wirkung zusammen mit der früher beschriebenen blockierenden Wirkung auf die formatio reticularis des Hirnstammes vermag zu erklären, auf welche Weise Chlorpromazin den Zustand des Wachseins beeinflußt und dabei Veränderungen des Verhaltens verursacht.

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With 2 figures in the text.