Specific and Nonspecific Effects of Naltrexone on Goal-Directed and Habitual Models of Alcohol Seeking and Drinking

Abstract Background Adult vaccinations may reduce risk for dementia. However it has not been established whether tetanus, diphtheria, pertussis (Tdap) vaccination is associated with incident dementia. Methods Hypotheses were tested in a Veterans Health Affairs (VHA) cohort and replicated in a MarketScan medical claims cohort. Patients were ≥65 years of age and free of dementia for 2 years prior to index date. Patients either had or did not have a Tdap vaccination by the start of either of two index periods (2011 or 2012). Follow-up continued through 2018. Controls had no Tdap vaccination for the duration of follow-up. Confounding was controlled using entropy balancing. Competing risk (VHA) and Cox proportional hazard (MarketScan) models estimated the association between Tdap vaccination and incident dementia in all patients and in age sub-groups (65-69, 70-74, ≥75 years of age). Results VHA patients were, on average, 75.6 (SD±7.5) years of age, 4% female, and 91.2% were white race. MarketScan patients were 69.8 (SD±5.6) years of age, on average and 65.4% were female. After controlling for confounding, patients with, compared to without Tdap vaccination, had a significantly lower risk for dementia in both cohorts (VHA: HR=0.58; 95%CI:0.54 - 0.63 and MarketScan: HR=0.58; 95%CI:0.48 - 0.70). Conclusions Tdap vaccination was associated with a 42% lower dementia risk in two cohorts with different clinical and sociodemographic characteristics. Several vaccine types are linked to decreased dementia risk, suggesting that these associations are due to nonspecific effects on inflammation rather than vaccine-induced pathogen-specific protective effects.

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The Mesolimbic Dopamine Activity Signatures of Relapse to Alcohol-Seeking

Journal of Neuroscience ◽

10.1523/jneurosci.0724-20.2020 ◽

2020 ◽

Vol 40 (33) ◽

pp. 6409-6427 ◽

Cited By ~ 3

Author(s):

Yu Liu ◽

Philip Jean-Richard-dit-Bressel ◽

Joanna Oi-Yue Yau ◽

Alexandra Willing ◽

Asheeta A. Prasad ◽

...

Keyword(s):

Mesolimbic Dopamine ◽

Alcohol Seeking

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Evaluation of a commercially available radioimmunoassay kit for measurement of doxorubicin in plasma.

Clinical Chemistry ◽

10.1093/clinchem/28.1.119 ◽

1982 ◽

Vol 28 (1) ◽

pp. 119-121 ◽

Cited By ~ 5

Author(s):

E Piall ◽

G W Aherne ◽

V Marks

Keyword(s):

Human Serum ◽

Normal Human Serum ◽

Nonspecific Effects ◽

Normal Human ◽

Doxorubicin Concentration

Abstract We evaluated a commercially available (Diagnostic Biochemistry Inc.) doxorubicin 125I radioimmunoassay kit. This kit gave a high apparent doxorubicin concentration (greater than 12 micrograms/L), which was not linearly related to dilution, for two pools of normal human serum and plasma and also for samples collected from patients before they received the drug. In contrast, a doxorubicin 3H radioimmunoassay developed by us gave a low blank (2 micrograms/L), which was linearly related to dilution, for the same pools and patients' samples. Doxorubicin concentrations in the plasma of patients receiving the drug were compared by the two methods; the kit gave results five- to 10-fold those obtained with our assay. High nonspecific interference by serum and plasma as measured by the 125I radioimmunoassay must therefore be borne in mind by users of the kit, and we suggest that results should be corrected for these nonspecific effects.

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Chronopharmacology of β-Adrenoceptor-Blocking Drugs: Pharmacokinetic and Pharmacodynamic Studies in Rats

Journal of the American College of Toxicology ◽

10.3109/10915818309140723 ◽

1983 ◽

Vol 2 (6) ◽

pp. 347-358 ◽

Cited By ~ 26

Author(s):

B. Lemmer ◽

K. Bathe ◽

P. H. Lang ◽

G. Neumann ◽

H. Winkler

Keyword(s):

Treatment Time ◽

Human Subjects ◽

Temporal Variations ◽

Male Rats ◽

Pharmacokinetic Parameters ◽

Nonspecific Effects ◽

Elimination Half ◽

Receptor Blockers ◽

Β Receptor ◽

Kinetics Of

Specific and nonspecific effects and the pharmacokinetic behavior of β-adrenoceptor-blocking drugs of different Iipophilicity (atenolol, bupranolol, carazolol, metoprolol, ox-prenolol, practolol, propranolol, sotalol) were investigated in L-D-synchronized male rats as a function of treatment time. The studies revealed that pharmacodynamic effects on heart rate, cardiac noradrenaline turnover, and motor activity as well as pharmacokinetic parameters of racemic mixtures of β-receptor blockers display temporal variations with more pronounced pharmacological effects and shorter elimination half-lives in the dark span. Studies with the isomers of bupranolol and practolol indicate no stereospecificity in the central depressant effect; the kinetic behavior of, for example, propranolol, however, exhibits stereospecificity. The results demonstrate the importance of circadian rhythms in modifying the effects and kinetics of drugs. These findings may have therapeutic implication in human subjects.

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Nonspecific effects of the gap junction blocker mefloquine on fast hippocampal network oscillations in the adult rat in vitro

Neuroscience ◽

10.1016/j.neuroscience.2011.07.015 ◽

2011 ◽

Vol 192 ◽

pp. 11-19 ◽

Cited By ~ 20

Author(s):

C.J. Behrens ◽

R. ul Haq ◽

A. Liotta ◽

M.L. Anderson ◽

U. Heinemann

Keyword(s):

Gap Junction ◽

Adult Rat ◽

Network Oscillations ◽

Nonspecific Effects ◽

Hippocampal Network

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Matrix Metalloproteinase-9 and Synaptic Plasticity in the Central Amygdala in Control of Alcohol-Seeking Behavior

Biological Psychiatry ◽

10.1016/j.biopsych.2016.12.026 ◽

2017 ◽

Vol 81 (11) ◽

pp. 907-917 ◽

Cited By ~ 23

Author(s):

Marzena Stefaniuk ◽

Anna Beroun ◽

Tomasz Lebitko ◽

Olga Markina ◽

Szymon Leski ◽

...

Keyword(s):

Synaptic Plasticity ◽

Matrix Metalloproteinase ◽

Matrix Metalloproteinase 9 ◽

Central Amygdala ◽

Seeking Behavior ◽

Metalloproteinase 9 ◽

Alcohol Seeking

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Specific and Nonspecific Effects of Protein Kinase C on the Epithelial Na + Channel

The Journal of General Physiology ◽

10.1085/jgp.115.5.559 ◽

2000 ◽

Vol 115 (5) ◽

pp. 559-570 ◽

Cited By ~ 40

Author(s):

Mouhamed S. Awayda

Keyword(s):

Membrane Trafficking ◽

Expression System ◽

Na Channel ◽

Specific Effects ◽

Nonspecific Effects ◽

Oocyte Expression ◽

Xenopus Oocyte Expression ◽

Oocyte Expression System ◽

Baseline Values ◽

Epithelial Na Channel

The Xenopus oocyte expression system was used to explore the mechanisms of inhibition of the cloned rat epithelial Na+ channel (rENaC) by PKC (Awayda, M.S., I.I. Ismailov, B.K. Berdiev, C.M. Fuller, and D.J. Benos. 1996. J. Gen. Physiol. 108:49–65) and to determine whether human ENaC exhibits similar regulation. Effects of PKC activation on membrane and/or channel trafficking were determined using impedance analysis as an indirect measure of membrane area. hENaC-expressing oocytes exhibited an appreciable activation by hyperpolarizing voltages. This activation could be fit with a single exponential, described by a time constant (τ) and a magnitude (ΔI V). A similar but smaller magnitude of activation was also observed in oocytes expressing rENaC. This activation likely corresponds to the previously described effect of hyperpolarizing voltage on gating of the native Na+ channel (Palmer, L.G., and G. Frindt. 1996. J. Gen. Physiol. 107:35–45). Stimulation of PKC with 100 nM PMA decreased ΔIV in hENaC-expressing oocytes to a plateau at 57.1 ± 4.9% (n = 6) of baseline values at 20 min. Similar effects were observed in rENaC-expressing oocytes. PMA decreased the amiloride-sensitive hENaC slope conductance (gNa) to 21.7 ± 7.2% (n = 6) of baseline values at 30 min. This decrease was similar to that previously reported for rENaC. This decrease of g Na was attributed to a decrease of membrane capacitance (C m), as well as the specific conductance (gm/Cm ). The effects on gm/Cm reached a plateau within 15 min, at ∼60% of baseline values. This decrease is likely due to the specific ability of PKC to inhibit ENaC. On the other hand, the decrease of Cm was unrelated to ENaC and is likely an effect of PKC on membrane trafficking, as it was observed in ENaC-expressing as well as control oocytes. At lower PMA concentrations (0.5 nM), smaller changes of Cm were observed in rENaC- and hENaC-expressing oocytes, and were preceded by larger changes of gm and by changes of gm/Cm, indicating specific effects on ENaC. These findings indicate that PKC exhibits multiple and specific effects on ENaC, as well as nonspecific effects on membrane trafficking. Moreover, these findings provide the electrophysiological basis for assessing channel-specific effects of PKC in the Xenopus oocyte expression system.

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