Low-Dose Baclofen-Induced Encephalopathy in a Healthy Young Adult: Is Baclofen Toxicity Dose-Dependent?

Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. However, immunometabolic reprogramming involved in the regulation of IIM in microglia has not been fully addressed. Here, we evaluated the impact of dose-dependent microglial priming with ultra-low (ULP, 1 fg/mL) and high (HP, 100 ng/mL) lipopolysaccharide (LPS) doses on immunometabolic rewiring. Furthermore, we addressed the role of PI3Kγ on immunometabolic control using naïve primary microglia derived from newborn wild-type mice, PI3Kγ-deficient mice and mice carrying a targeted mutation causing loss of lipid kinase activity. We found that ULP-induced IIM triggered an enhancement of oxygen consumption and ATP production. In contrast, HP was followed by suppressed oxygen consumption and glycolytic activity indicative of immune tolerance. PI3Kγ inhibited glycolysis due to modulation of cAMP-dependent pathways. However, no impact of specific PI3Kγ signaling on immunometabolic rewiring due to dose-dependent LPS priming was detected. In conclusion, immunometabolic reprogramming of microglia is involved in IIM in a dose-dependent manner via the glycolytic pathway, oxygen consumption and ATP production: ULP (ultra-low-dose priming) increases it, while HP reduces it.

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A Single-Dose Bioequivalence and Food Effect Study With Aprepitant and Fosaprepitant Dimeglumine in Healthy Young Adult Subjects

Clinical Pharmacology in Drug Development ◽

10.1177/2160763x12447304 ◽

2012 ◽

Vol 1 (3) ◽

pp. 93-101 ◽

Cited By ~ 5

Author(s):

C. R. Shadle ◽

M. G. Murphy ◽

Y. Liu ◽

M. Ho ◽

D. Tatosian ◽

...

Keyword(s):

Single Dose ◽

Young Adult ◽

Food Effect ◽

Effect Study ◽

Healthy Young Adult

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Maternal Exposure to a Low Dose of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Suppressed the Development of Reproductive Organs of Male Rats: Dose-Dependent Increase of mRNA Levels of 5 -Reductase Type 2 in Contrast to Decrease of Androgen Receptor in the Pubertal Ventral Prostate

Toxicological Sciences ◽

10.1093/toxsci/60.1.132 ◽

2001 ◽

Vol 60 (1) ◽

pp. 132-143 ◽

Cited By ~ 94

Author(s):

S. Ohsako ◽

Y. Miyabara ◽

N. Nishimura ◽

S. Kurosawa ◽

M. Sakaue ◽

...

Keyword(s):

Androgen Receptor ◽

Low Dose ◽

Reproductive Organs ◽

Maternal Exposure ◽

Male Rats ◽

Ventral Prostate ◽

Mrna Levels ◽

Dose Dependent Increase ◽

Dose Dependent

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Enlargement of cerebrospinal fluid spaces in long-term benzodiazepine abusers

Psychological Medicine ◽

10.1017/s0033291700000660 ◽

1987 ◽

Vol 17 (4) ◽

pp. 869-873 ◽

Cited By ~ 37

Author(s):

C. Schmauss ◽

J.-C. Krieg

Keyword(s):

Low Dose ◽

Matched Control ◽

Control Group ◽

High Dose ◽

Withdrawal Therapy ◽

The Mean ◽

Dose Dependent ◽

Dose Dependent Effect ◽

Age And Sex

SynopsisIn 17 benzodiazepine (BDZ) dependent in-patients a CT scan was performed before initiation of withdrawal therapy. The evaluation of the ventricular to brain ratio (VBR) by standardized and computerized measurements revealed significantly higher mean VBRs for both high-and low-dose BDZ-dependent patients compared to the mean VBR of an age- and sex-matched control group. In addition, the mean VBR of high-dose BDZ-dependent patients (N = 8) was significantly higher than the mean VBR of low-dose BDZ-dependent patients (N = 9). This difference could not be accounted for by the age of the patients or duration of BDZ-dependency and, therefore, suggests a dose-dependent effect of BDZs on the enlargement of internal CSF-spaces. On the other hand, higher values for the width of external CSF-spaces were found to be related to increasing age of the patients and duration of BDZ-dependency.

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Islamic Wet Cupping and Risk Factors of Cardiovascular Diseases: Effects on Blood Pressure, Metabolic Profile and Serum Electrolytes in Healthy Young Adult Men

Alternative & Integrative Medicine ◽

10.4172/2327-5162.1000151 ◽

2014 ◽

Vol 03 (01) ◽

Cited By ~ 1

Author(s):

Bassem Refaat Adel Galal

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Young Adult ◽

Cardiovascular Diseases ◽

Metabolic Profile ◽

Healthy Young Adult ◽

Serum Electrolytes ◽

Adult Men

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Effectiveness of nasopalatine nerve block for anesthesia of maxillary central incisors after failure of the anterior superior alveolar nerve block technique

Brazilian Dental Journal ◽

10.1590/s0103-64402007000100015 ◽

2007 ◽

Vol 18 (1) ◽

pp. 69-73 ◽

Cited By ~ 9

Author(s):

Tufi Neder Meyer ◽

Leonardo Lima Lemos ◽

Carolina Neder Matuck do Nascimento ◽

William Ricardo Ribeiro de Lellis

Keyword(s):

Young Adult ◽

Nerve Block ◽

Thermal Sensitivity ◽

Dental Students ◽

Sensitivity Test ◽

Healthy Young Adult ◽

Cold Stimulus ◽

Single Operator ◽

The University ◽

Adult Volunteers

The purpose of this study was to assess the effectiveness of nasopalatine nerve block for anesthesia of maxillary central incisors after failure of the anterior superior alveolar nerve (ASAN) block technique. Secondarily, the possible innervation of the maxillary central incisors by the nasopalatine nerve was also investigated. Twenty-seven healthy, young adult volunteers (age: 17-26 years; gender: 9 males and 18 females) were enrolled in this study. All participants were undergraduate dental students of the University of Vale do Rio Verde de Três Corações. The volunteers had the anterior superior alveolar nerves anesthetized and a thermal sensitivity test (cold) was performed on the maxillary central incisors. The volunteers that responded positively to cold stimulus received a nasopalatine nerve block and the thermal sensitivity test was repeated. All participants were anesthetized by a single operator. Three patients presented sensitivity after both types of bilateral blocks and were excluded from the percentage calculations. In the remaining 24 patients, 16 had their maxillary central incisors anesthetized by the anterior superior alveolar block and 8 remained with sensitivity after the ASAN block. All these 8 patients had their maxillary central incisors successfully anesthetized by the nasopalatine block. In this study, 33.3% of the subjects had the innervation of one or both maxillary central incisors derived from the nasopalatine nerve, whilst most subjects (66.7%) had such teeth innervated by the anterior superior alveolar nerve. The nasopalatine nerve block was effective in anesthetizing the maxillary central incisors when the anterior superior alveolar nerve block failed.

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One-Year Delayed Recall Performance of the Rey-Osterrieth Complex Figure in a Healthy Young Adult Sample

Applied Neuropsychology ◽

10.1080/09084280802623064 ◽

2009 ◽

Vol 16 (2) ◽

pp. 141-143 ◽

Cited By ~ 1

Author(s):

Hikari Yamashita

Keyword(s):

Young Adult ◽

Recall Performance ◽

Healthy Young Adult ◽

Delayed Recall ◽

Adult Sample ◽

Complex Figure ◽

One Year

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Voice Onset Time of Velar Stop Productions in Aged Speakers

Perceptual and Motor Skills ◽

10.2466/pms.1993.76.1.83 ◽

1993 ◽

Vol 76 (1) ◽

pp. 83-88 ◽

Cited By ~ 15

Author(s):

Linda Petrosino ◽

Roger D. Colcord ◽

Karen B. Kurcz ◽

Robert J. Yonker

Keyword(s):

Standard Deviation ◽

Young Adult ◽

Voice Onset Time ◽

Onset Time ◽

Stop Consonants ◽

Physiological Changes ◽

Healthy Young Adult ◽

Apparent Increase ◽

Older Subjects

Voice onset time (VOT) was measured for voiced and voiceless velar stop consonants across three vowel contexts (/i, a, u/) in healthy young adult and older subjects. Analysis showed that mean VOT values for both /k/ and /g/ across the three vowel contexts did not differ between the two groups; however, differences in VOT variability (standard deviation) approached significance; the older subjects exhibited increased variability. This apparent increase in variability may be related to the subtle anatomical and physiological changes with age.

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