Methodological problems in the measurement of drug-induced rotational behaviour: Continuous recording reveals time-course differences undetected by previous techniques

1978 ◽  
Vol 58 (2) ◽  
pp. 153-155 ◽  
Author(s):  
John L. Waddington ◽  
Timothy J. Crow
2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Elizabeth W Hunsaker ◽  
Chen-Hsin Albert Yu ◽  
Katherine J Franz

Abstract The ability of pathogens to maintain homeostatic levels of essential biometals is known to be important for survival and virulence in a host, which itself regulates metal availability as part of its response to infection. Given this importance of metal homeostasis, we sought to address how the availability of copper in particular impacts the response of the opportunistic fungal pathogen Candida albicans to treatment with the antifungal drug fluconazole. The present study reports whole transcriptome analysis via time-course RNA-seq of C. albicans cells exposed to fluconazole with and without 10 µM supplemental CuSO4 added to the growth medium. The results show widespread impacts of small changes in Cu availability on the transcriptional response of C. albicans to fluconazole. Of the 2359 genes that were differentially expressed under conditions of cotreatment, 50% were found to be driven uniquely by exposure to both Cu and fluconazole. The breadth of metabolic processes that were affected by cotreatment illuminates a fundamental intersectionality between Cu metabolism and fungal response to drug stress. More generally, these results show that seemingly minor fluctuations in Cu availability are sufficient to shift cells’ transcriptional response to drug stress. Ultimately, the findings may inform the development of new strategies that capitalize on drug-induced vulnerabilities in metal homeostasis pathways.


1995 ◽  
Vol 7 (5) ◽  
pp. 905-914 ◽  
Author(s):  
Corinna Fohlmeister ◽  
Wulfram Gerstner ◽  
Raphael Ritz ◽  
J. Leo van Hemmen

As a simple model of the cortical sheet, we study a locally connected net of spiking neurons, Refractoriness, noise, axonal delays, and the time course of excitatory and inhibitory postsynaptic potentials are taken into account explicitly. In addition to a low-activity state and depending on the synaptic efficacy, four different scenarios evolve spontaneously, viz., stripes, spirals, rings, and collective bursts. Our results can be related to experimental observations of drug-induced epilepsy and hallucinations.


1998 ◽  
Vol 44 (3) ◽  
pp. 16-19
Author(s):  
T. I. Rodionova ◽  
M. Yu. Ledvanov

sIСАМ-1 was measured in the sera of 156 patients with diffuse toxic goiter (DTG). The majority (105) of these patients presented with clinical signs of autoimmune ophthalmopathy (AO), and the above parameter was measured in order to assess the probability of using it as a criterion of preclinical diagnosis of AO and assessment of the efficacy of its therapy. Five groups of patients were distinguished in the course of study: 1) DTG without AO (n = 27); 2) zero stage of AO (no clinical manifestations) (n = 24); 3) stage I AO (n — 22); 4) stage II AO (n = 60); and 5) stage III AO (n = 23). All patients were in a state of drug-induced euthyrosis; AO of the first-third stages wasttreated traditionally (nonsteroid antiinflammatory drugs, glucocorticoids, radiotherapy of the orbits). Significant changes in sICAM-1 concentration were recorded in DTG patients as early as during the zero stage of AO without apparent clinical signs and confirmed only by computer- aided tomography of the orbits; this result recommends this parameter as an early marker of AO. Serum sICAM-1 content was notably increased in DTG patients with AO, the increase depending on the severity of AO. Changes of si CAM-1 correlated with the clinical picture of the condition (time course of the orbital and muscle index and size of the orbit) and can be used as an additional criterion for assessing the efficacy of treatment of AO.


Lupus ◽  
2020 ◽  
pp. 096120332098114
Author(s):  
Eliana Figueredo Zamora ◽  
Jeffrey P Callen ◽  
Courtney R Schadt

Numerous drugs have been linked to the induction or exacerbation of systemic cutaneous lupus erythematosus (SCLE). This report presents the third case of the biologic abatacept as an exacerbating medication for SCLE. A 73-year old woman with a remote history of subacute cutaneous lupus and rheumatoid arthritis, well controlled on hydroxychloroquine, presented with worsening annular erythematous, slightly scaly plaques on her forearms and hands. She had been started on abatacept a month prior. She was diagnosed with SCLE exacerbated by abatacept given the clinical findings, time course, and skin biopsy with interface dermatitis. Her skin eruption cleared completely several months later after discontinuing abatacept and switching to tociluzumab, while remaining on hydroxychloroquine. This case highlights the need to consider abatacept as a potential exacerbating medication for SCLE in any patient with a new photodistributed papulosquamous eruption.


1959 ◽  
Vol 196 (5) ◽  
pp. 1049-1052 ◽  
Author(s):  
Sydney M. Friedman ◽  
James D. Jamieson ◽  
J. A. M. Hinke ◽  
Constance L. Friedman

By means of a glass-to-silver sodium electrode, the pattern of change in plasma sodium concentration following the administration of pressor and depressor drugs was recorded as a continuous function in a series of seven dogs. The electrode was connected into the femoral artery and its output fed into a Cary vibrating reed electrometer recording through a Grass Polygraph. The pressor response to norepinephrine, epinephrine and angiotonin was regularly accompanied by a fall in electrode potential, indicating a fall in sodium concentration. In terms of degree of change, time course, and duration of effect, each agent produced its own characteristic pattern. The depressor response to acetylcholine, histamine and isopropylnorepinephrine was accompanied by oscillations in the electrode tracing which, in general, tended to be inverse to those observed with pressor agents. The experiments demonstrate that shifts in blood pressure accompany shifts in sodium as recorded by the electrode and thus complement previous observations using blood sampling procedures.


1985 ◽  
Vol 85 (5) ◽  
pp. 621-647 ◽  
Author(s):  
A Uehara ◽  
J R Hume

Inhibition of whole-cell calcium currents in enzymatically dispersed frog atrial myocytes by D-600, diltiazem, and nifedipine was studied using a single-micropipette voltage-clamp technique. The objective of these experiments was to test the applicability of a modulated-receptor hypothesis similar to that proposed for local anesthetic interactions with sodium channels to account for the tonic and frequency-dependent interactions of these organic compounds with myocardial calcium channels. Data consistent with such a hypothesis include: (a) prominent use-dependent block of iCa by D-600 and diltiazem, which are predominantly charged at physiological pH; (b) iCa block by an externally applied, permanently charged dihydropyridine derivative is greatly attenuated; (c) all three antagonists produce large negative shifts in the voltage dependence of iCa availability; (d) block of iCa by these compounds is state-dependent; (e) reactivation of iCa in the presence of all three antagonists is biexponential, which suggests that drug-free channels recover with a normal time course and drug-bound channels recover more slowly; and (f) the kinetics of the drug-induced slow iCa recovery process may be determined largely by factors such as size and molecular weight, in addition to lipid solubility of the compounds. Experiments in which the pH was modified, however, reveal some important differences for the interaction of organic calcium antagonists with myocardial calcium channels. Acidification, in addition to changing the proportion of charged and neutral antagonist in solution, was found to selectively antagonize tonic inhibition of iCa by diltiazem and nifedipine, without changing the kinetics of the drug-induced slow iCa reactivation process. It is concluded that two distinct receptor sites may be involved in block of iCa by some of these compounds: a proton-accessible site and a proton-inaccessible site.


Sign in / Sign up

Export Citation Format

Share Document