Long-Term Methamphetamine Abuse Impairs Selective Inhibition

2005 ◽  
Author(s):  
Keyword(s):  
Selective Inhibition ◽  
Methamphetamine Abuse

scholarly journals Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 251 ◽  
Author(s):  
Bernadette Lázár ◽  
Gábor Brenner ◽  
András Makkos ◽  
Mihály Balogh ◽  
Szilvia László ◽  
...  
Keyword(s):  
Selective Inhibition ◽  
Mucosal Damage ◽  
Inhibitory Effect ◽  
Intestinal Dysbiosis ◽  
Bowel Diseases ◽  
Direct Inhibitory Effect ◽  
Cox 2 ◽  
Small Intestinal

Intestinal dysbiosis is linked to numerous gastrointestinal disorders, including inflammatory bowel diseases. It is a question of debate if coxibs, selective inhibitors of cyclooxygenase (COX)-2, cause dysbiosis. Therefore, in the present study, we aimed to determine the effect of long-term (four weeks) selective inhibition of COX-2 on the small intestinal microbiota in the rat. In order to avoid mucosal damage due to topical effects and inflammation-driven microbial alterations, rofecoxib, a nonacidic compound, was used. The direct inhibitory effect of rofecoxib on the growth of bacteria was ruled out in vitro. The mucosa-sparing effect of rofecoxib was confirmed by macroscopic and histological analysis, as well as by measuring the intestinal levels of cytokines and tight junction proteins. Deep sequencing of bacterial 16S rRNA revealed that chronic rofecoxib treatment had no significant influence on the composition and diversity of jejunal microbiota. In conclusion, this is the first demonstration that long-term selective inhibition of COX-2 by rofecoxib does not cause small intestinal dysbiosis in rats. Moreover, inhibition of COX-2 activity is not likely to be responsible per se for microbial alterations caused by some coxibs, but other drug-specific properties may contribute to it.

Strychnine poisoning causing generalized tetanic spasm

2020 ◽  
pp. 10.1212/CPJ.0000000000000943
Author(s):  
Simon Winzer ◽  
Kristian Barlinn
Keyword(s):  
Brain Activity ◽  
Selective Inhibition ◽  
Muscle Contractions ◽  
Whole Body ◽  
High Dose ◽  
Repeated Testing ◽  
Limited Effect ◽  
First Line Therapy ◽  
History Of

A 55-year old male presented with spontaneous and stimulus-triggered tetanic-like activity of the whole body without losing consciousness or orientation (video, http://links.lww.com/CPJ/A196). There was no history of trauma, and clinical examination did not reveal any tetanus-prone wound. Electroencephalography showed no significant alteration in brain activity. Serial intravenous benzodiazepines showed limited effect. Frequency and duration of muscle contractions increased over time and led to severe hypoxemia requiring intubation and sedation with propofol for almost 24 hours followed by continuous infusion of midazolam. Daily sedation pauses revealed ongoing generalized muscle spasm triggered by tactile and auditory stimuli and severe vegetative dysregulation. Tetanus antibody level suggested long-term protection. On day 6, toxicology revealed toxic levels of strychnine in serum (180 ng/ml [toxicity > 75 ng/ml]) and urine (514 ng/ml [no toxicity level defined]). Repeated testing showed markedly declined strychnine levels in serum (2.8 ng/ml) and urine (1.1 ng/ml) on day 11. Sedation was ultimately stopped on day 10. Subsequently, the patient recovered completely and was discharged on day 25. Strychnine ingestion mode remained unclear. Generalized tetanic spasm with sustained alertness, presumably caused by selective inhibition of post-synaptic glycine receptors in the spinal cord, should trigger testing for strychnine poisoning.1,2 High-dose intravenous benzodiazepines are considered first-line therapy for controlling muscle spasms; however, in patients whose muscle contractions are refractory to benzodiazepines, sedation with propofol or barbiturates is deemed necessary.1

352 LONG-TERM OUTCOMES FOR PHARMACOLOGICAL AND BEHAVIORAL TREATMENTS FOR METHAMPHETAMINE ABUSE.

2006 ◽  
Vol 54 (1) ◽  
pp. S140.5-S140
Author(s):  
S. Lohiya ◽  
J. Dang ◽  
X. Yang ◽  
S. Shoptaw ◽  
W. Ling
Keyword(s):  
Long Term Outcomes ◽  
Methamphetamine Abuse ◽  
Behavioral Treatments

Cellular mechanism of aminoglycoside tolerance in long-term gentamicin treatment

1997 ◽  
Vol 272 (4) ◽  
pp. C1309-C1318 ◽  
Author(s):  
D. P. Sundin ◽  
C. Meyer ◽  
R. Dahl ◽  
A. Geerdes ◽  
R. Sandoval ◽  
...  
Keyword(s):  
Apical Membrane ◽  
Fluid Phase ◽  
Selective Inhibition ◽  
Membrane Lipid ◽  
Immunofluorescent Staining ◽  
Morphological Studies ◽  
Gentamicin Treatment ◽  
Apical Membranes

In the rat, nephrotoxicity results from uptake of gentamicin at the apical membrane of proximal tubule (PT) cells. However, during continuous gentamicin treatment, the PT epithelium has been shown to recover. The mechanism(s) of cellular recovery and development of tolerance remains unknown. Therefore, we undertook studies designed to characterize cellular adaptations that occur during long-term gentamicin (LTG) treatment. After 19 days of gentamicin treatment, electron microscopy morphological evaluation revealed cellular recovery with an apparent mild decrease in height and number of microvilli. Enzymatic analysis of LTG PT membranes showed that apical and basolateral membranes had essentially returned to normal. Analysis of apical membrane lipid content revealed persistent statistically significant (P < 0.01) elevations in phosphatidylinositol (PI). In vivo immunogold morphological studies and biochemical studies in LTG rats revealed that endocytosis of gentamicin was selectively reduced, whereas the markers of fluid-phase (horseradish peroxidase) and receptor-mediated (beta2-microglobulin) endocytoses were unaffected or increased. Biochemical analysis showed that, although gentamicin binding to apical membranes isolated from LTG rats increased greater than twofold (P < 0.05) over membranes from untreated rats, in vivo cellular uptake, quantified with [3H]gentamicin, was reduced. Western blot analysis of LTG apical membranes and immunofluorescent staining of perfusion-fixed LTG kidneys showed no change in megalin levels or its apical membrane localization. These data imply that recovery of PT cells from and tolerance to LTG treatment involve a selective inhibition of gentamicin uptake across the apical membrane. They indicate that the mediators of gentamicin endocytosis were affected differently: PI levels increased, whereas megalin levels did not change. We conclude that selective inhibition of gentamicin uptake during LTG treatment is not affected by a reduction in PI or megalin levels. We postulate that trafficking of gentamicin and/or gentamicin-containing endocytic structures is reduced in LTG rats, allowing cells to develop tolerance to gentamicin.

scholarly journals Selective inhibition of COX-2 improves early survival in murine endotoxemia but not in bacterial peritonitis

2001 ◽  
Vol 281 (3) ◽  
pp. L537-L543 ◽  
Author(s):  
Raju C. Reddy ◽  
Gina H. Chen ◽  
Kazuhiro Tateda ◽  
Wan C. Tsai ◽  
Susan M. Phare ◽  
...  
Keyword(s):  
Cecal Ligation ◽  
Selective Inhibition ◽  
Lavage Fluid ◽  
Neutrophil Sequestration ◽  
Bacterial Peritonitis ◽  
Cytokine Levels ◽  
Cox 2 ◽  
And Control ◽  
Late Survival

Prostaglandins of the E series are believed to act as important mediators of several pathophysiological events that occur in sepsis. Studies were performed to evaluate the effect of cyclooxygenase (COX)-2-specific inhibition on the outcome in murine endotoxemia and cecal ligation and puncture (CLP). We observed a significant time-dependent upregulation of PGE2production in both blood and lung homogenates of mice administered lipopolysaccharide intraperitoneally, which was nearly completely suppressed by the administration of the COX-2 inhibitor NS-398. Treatment with NS-398 significantly improved early but not late survival in lipopolysaccharide-challenged mice. On the contrary, elevated PGE2levels were found in bronchoalveolar lavage fluid but not in plasma of mice subjected to CLP (21 gauge). Pretreatment with NS-398 failed to significantly improve survival in CLP mice. No significant differences were noted in plasma or lung homogenate proinflammatory cytokine levels or lung neutrophil sequestration between the NS-398-treated and control groups. These results demonstrate that selective COX-2 inhibition confers early but not long-term benefits without affecting the expression of proinflammatory cytokines or the development of lung inflammation.

scholarly journals An Interacting Systems Model of Infant Habituation

2004 ◽  
Vol 16 (8) ◽  
pp. 1352-1362 ◽  
Author(s):  
Sylvain Sirois ◽  
Denis Mareschal
Keyword(s):  
Selective Inhibition ◽  
Long Term Potentiation ◽  
Functional System ◽  
Systems Model ◽  
Age Related ◽  
Term Potentiation ◽  
Process Theories ◽  
Brain Circuitry ◽  
Interacting Systems

Habituation and related procedures are the primary behavioral tools used to assess perceptual and cognitive competence in early infancy. This article introduces a neurally constrained computational model of infant habituation. The model combines the two leading process theories of infant habituation into a single functional system that is grounded in functional brain circuitry. The HAB model (for Habituation, Autoassociation, and Brain) proposes that habituation behaviors emerge from the opponent, complementary processes of hippocampal selective inhibition and cortical long-term potentiation. Simulations of a seminal experiment by Fantz [Visual experience in infants: Decreased attention familiar patterns relative to novel ones. Science, 146, 668–670, 1964] are reported. The ability of the model to capture the fine detail of infant data (especially age-related changes in performance) underlines the useful contribution of neurocomputational models to our understanding of behavior in general, and of early cognition in particular.

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