Pharmacogenomics and pharmacokinetics of efavirenz 400 or 600 mg in 184 treatment-naive HIV-infected patients in China

2020 ◽  
Vol 21 (13) ◽  
pp. 945-956
Author(s):  
Rong Chen ◽  
Jun Chen ◽  
Jingna Xun ◽  
Zhiliang Hu ◽  
Qiong Huang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Plasma Levels ◽  
Dose Group ◽  
Adverse Reactions ◽  
Standard Dose ◽  
Treatment Naïve ◽  
The Central Nervous System ◽  
To Receive

Background: The pharmacogenomics and pharmacokinetics/pharmacodynamics of 400 mg efavirenz have rarely been reported. Materials & methods: A total of 184 treatment-naive HIV-infected patients were randomly assigned (1:1) to receive a lower dose (tenofovir disoproxil 200 mg, efavirenz 400 mg and lamivudine) or a standard dose regimen. Relationships between pharmacogenomics and efavirenz pharmacokinetics/pharmacodynamics were explored at 48 weeks. Results: There was no relationship between pharmacogenomics and adverse reactions of the central nervous system and antiretoviral efficacy. CYP2B6 516G>T, 785A>G, 18492C>T and ABCB1 3435C>T T/C were associated with higher efavirenz plasma levels in the standard but not the lower dose group. No relationship was found between pharmacogenomics and antiretoviral efficacy. Patients who were <60 kg had higher efavirenz concentration compared with those with weight ≥60 kg when using 600 mg efavirenz, this was not observed with 400 mg efavirenz. Conclusion: The effect of pharmacogenomics and body weight on the efavirenz concentration was significant in the 600 mg group but not in the 400 mg group.

scholarly journals Oestrogenic effects of neonatal administration of raloxifene on hypothalamic-pituitary-gonadal axis in male and female rats

Reproduction ◽  
2001 ◽  
pp. 915-924 ◽  
Author(s):  
L Pinilla ◽  
LC Gonzalez ◽  
F Gaytan ◽  
M Tena-Sempere ◽  
E Aguilar
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Oestrogen Receptor ◽  
Female Rats ◽  
Male Rats ◽  
Selective Oestrogen Receptor Modulators ◽  
Male And Female Rats ◽  
The Central Nervous System ◽  
Neonatal Administration

Selective oestrogen receptor modulators constitute a family of drugs that are used increasingly in the management of oestrogen-associated pathology. Raloxifene is a selective oestrogen receptor modulator that is used to treat and prevent osteoporosis in post-menopausal women. The actions of raloxifene on bone, breast, uterus and serum cholesterol concentrations have been widely analysed, but very few studies have investigated the possible actions of this drug on the central nervous system. The central nervous system of the newborn rat is very sensitive to oestrogen action. In this study a series of experiments was conducted to analyse the effects of different doses of raloxifene (50, 100, 250 or 500 microg per rat per day) administered to neonatal rats on days 1-5 of age. Female rats treated with raloxifene showed decreased gonadotrophin secretion, hyperprolactinaemia, advanced vaginal opening, decreased body weight, persistent presence of cornified epithelial cells in vaginal smears, anovulation, inhibition of positive feedback between oestradiol and LH, and infertility. Male rats showed delayed balanopreputial separation, reduced body weight and hyperprolactinaemia. All these changes resemble those obtained after neonatal administration of oestradiol benzoate, thus indicating, for the first time, that raloxifene exerts an oestrogenic action on the hypothalamic-pituitary structures controlling reproductive function in rats.

Insulin: its relationship to the central nervous system and to the control of food intake and body weight

1985 ◽  
Vol 42 (5) ◽  
pp. 1063-1071 ◽  
Author(s):  
S C Woods ◽  
D Porte ◽  
E Bobbioni ◽  
E Ionescu ◽  
J F Sauter ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Food Intake ◽  
The Central Nervous System

scholarly journals CXCL13 levels are more increased in cerebrospinal fluid and plasma of patients with acute infectious than in non-infectious diseases of the central nervous system

2017 ◽  
Vol 25 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Brîndușa Țilea ◽  
Septimiu Voidăzan ◽  
Rodica Bălașa ◽  
Adina Huțanu ◽  
Andrea Fodor
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Infectious Diseases ◽  
Cell Count ◽  
Plasma Levels ◽  
Neurological Diseases ◽  
Protein Levels ◽  
Median Plasma ◽  
The Central Nervous System ◽  
Elisa Technique

Abstract Background: During the acute inflammatory process, the CXCL13 chemokine plays an important role in B cell recruitment within the central nervous system (CNS). Objective: The objective of the study consisted of the evaluation of CXCL13 chemokine cerebral spinal fluid (CSF) and plasma levels in patients with acute infectious and non-infectious neurological diseases correlated with pleocytosis and CSF protein levels. Material and method: This retrospective study was conducted over one year and included 72 patients. Thirty-eight patients (52.8%) suffering from infectious neurological disease, acute viral and bacterial meningitis, meningoencephalitis, and 34 patients (44.2%) diagnosed with non-infectious neurological diseases. CXCL13 chemokine CSF and plasma levels were determined through the ELISA technique with the Human CXCL13/BLC/BCA-1 kit. CSF cell count, glucose and protein levels, along with anti-Borrelia burgdorferi antibodies were monitored using the ELISA technique. Results: CXCL13 chemokine levels in the CSF of patients with acute infectious neurological diseases showed a median value of 23.07 pg/mL, which was significantly higher in comparison with the median value of 11.5 pg/mL of patients with noninfectious neurological diseases (p-0.03). CXCL13 median plasma concentration in patients with infectious neurological diseases was 108.1 pg/mL, in comparison with the second patient category, 50.7 pg/ml (p-0.001). We observed a statistically significant association between CXCL13 concentrations, CSF cell count and proteins. The higher the CXCL13 chemokine level, the more increased the cell count was. Conclusions: CXCL13 levels in the CSF was significantly increased in patients with acute infectious neurological diseases compared with patients with non-infectious diseases. Moreover, CXCL13 chemokine concentration was significantly correlated with the number of cells and proteins in the CSF of patients suffering from neuroinfections.

scholarly journals High doses of cefotaxime in treatment of adult meningitis due to Streptococcus pneumoniae with decreased susceptibilities to broad-spectrum cephalosporins.

1996 ◽  
Vol 40 (1) ◽  
pp. 218-220 ◽  
Author(s):  
P F Viladrich ◽  
C Cabellos ◽  
R Pallares ◽  
F Tubau ◽  
J Martínez-Lacasa ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Streptococcus Pneumoniae ◽  
Broad Spectrum ◽  
Adjunctive Therapy ◽  
Maximum Dose ◽  
Central Nervous System Infection ◽  
The Central Nervous System ◽  
High Doses

We treated nine patients (10 episodes) with meningitis caused by Streptococcus pneumoniae isolates with decreased susceptibilities to broad-spectrum cephalosporins with high doses of cefotaxime (300 mg/kg of body weight per day; maximum dose, 24 g/day). Early adjunctive therapy with dexamethasone was also administered. Cefotaxime MICs were 0.5 (three episodes), 1 (five episodes), and 2 (two episodes) micrograms/ml, and MBCs ranged from 1 to 4 micrograms/ml. Therapy was well tolerated, and all patients experienced prompt clinical improvement. One patient died 8 days after the end of therapy, the central nervous system infection had already been cured, and the remaining patients recovered without relapses.

Insulin in the Central Nervous System: A Regulator of Appetite and Body Weight

1987 ◽  
pp. 151-162 ◽  
Author(s):  
Dianne P. Figlewicz ◽  
Stephen C. Woods ◽  
Denis G. Baskin ◽  
Daniel M. Dorsa ◽  
Barbara J. Wilcox ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
System A ◽  
The Central Nervous System

scholarly journals Central nervous system: cholesterol turnover, brain development and neurodegeneration

2009 ◽  
Vol 390 (4) ◽  
Author(s):  
John M. Dietschy
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Brain Development ◽  
Cholesterol Synthesis ◽  
De Novo ◽  
Brain Size ◽  
Average Amount ◽  
Early Brain Development ◽  
The Central Nervous System

Abstract The average amount of cholesterol in the whole animal equals approximately 2100 mg/kg body weight, and 15% and 23% of this sterol in the mouse and human, respectively, is found in the central nervous system. There is no detectable uptake across the blood-brain barrier of cholesterol carried in lipoproteins in the plasma, even in the newborn. However, high rates of de novo cholesterol synthesis in the glia and neurons provide the sterol necessary for early brain development. Once a stable brain size is achieved in the adult, cholesterol synthesis continues, albeit at a much lower rate, and this synthesis is just balanced by the excretion of an equal amount of sterol, either as 24(S)-hydroxycholesterol or, presumably, as cholesterol itself.

Effects of protamine zinc insulin on chickens

1965 ◽  
Vol 208 (3) ◽  
pp. 589-592 ◽  
Author(s):  
S. Lepkovsky ◽  
R. Len ◽  
T. Koike ◽  
R. Bouthilet
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Feed Intake ◽  
Egg Production ◽  
Laying Hens ◽  
Protamine Zinc Insulin ◽  
The Central Nervous System

The injection of protamine zinc insulin into laying hens caused hypoglycemia as it does in other animals. While it increased feed intake and body weight in other animals, it did the opposite in chickens: it decreased feed intake, body weight, and egg production. Damage to the central nervous system in some of the chickens was indicated by their behavior. It was tentatively concluded that the aphagia in chickens following injection with protamine zinc insulin was due to the apparent damage to the nervous system.

Motivational and Perceptual Aspects of Subcortical Stimulation in Cats

1958 ◽  
Vol 194 (2) ◽  
pp. 427-432 ◽  
Author(s):  
Harold C. Nielson ◽  
Robert W. Doty ◽  
Lester T. Rutledge
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Electrical Stimulation ◽  
Minute Period ◽  
The Press ◽  
The Central Nervous System ◽  
Subcortical Stimulation ◽  
To Receive ◽  
Central Stimulation ◽  
Stimulation Of

Reports of others that animals will seek electrical stimulation of certain regions of the central nervous system are confirmed. A method is presented whereby these ‘motivational’ aspects of central stimulation can be analyzed and shown to be capable of change by training and to have a different threshold from the animal's ‘perception’ of this stimulation. Cats were trained to press a bar to receive pellets of meat. When each bar-press was accompanied by stimulation through electrodes implanted in the caudate nucleus or anterior hypothalamus, the animals continued pressing. If the press was paired with stimulation of the septal or habenular regions, pressing was abolished. Foot-shock paired with pressing also produced avoidance but pairing with a startling buzzer did not. Caudatal stimulation of 0.2 ma, 50/sec., 2-msec. pulses, was adequate as conditional stimulus to establish conditioned foreleg flexions to avoid an electric shock. Subsequent to the latter training two animals would no longer press the bar if pressing resulted in caudatal stimulation. Other cats would press as often as 1000 times in a 20-minute period to obtain caudatal stimulation if it were allowed at rapid rates and intensities five times that required to evoke conditioned flexion reflexes. The evidence suggests that avidity develops for stimulation of certain neural structures only if the stimulus is adequate to initiate some form of excessive, seizure-like activity.

scholarly journals Amylin Acts in the Central Nervous System to Increase Sympathetic Nerve Activity

Endocrinology ◽  
2013 ◽  
Vol 154 (7) ◽  
pp. 2481-2488 ◽  
Author(s):  
Caroline Fernandes-Santos ◽  
Zhongming Zhang ◽  
Donald A. Morgan ◽  
Deng-Fu Guo ◽  
Andrew F. Russo ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Food Intake ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Peripheral Tissues ◽  
Brown Adipose ◽  
The Central Nervous System

Abstract The pancreatic hormone amylin acts in the central nervous system (CNS) to decrease food intake and body weight. We hypothesized that amylin action in the CNS promotes energy expenditure by increasing the activity of the sympathetic nervous system. In mice, ip administration of amylin significantly increased c-Fos immunoreactivity in hypothalamic and brainstem nuclei. In addition, mice treated with intracerebroventricular (icv) amylin (0.1 and 0.2 nmol) exhibited a dose-related decrease in food intake and body weight, measured 4 and 24 hours after treatment. The icv injection of amylin also increased body temperature in mice. Using direct multifiber sympathetic nerve recording, we found that icv amylin elicited a significant and dose-dependent increase in sympathetic nerve activity (SNA) subserving thermogenic brown adipose tissue (BAT). Of note, icv injection of amylin also evoked a significant and dose-related increase in lumbar and renal SNA. Importantly, icv pretreatment with the amylin receptor antagonist AC187 (20 nmol) abolished the BAT SNA response induced by icv amylin, indicating that the sympathetic effects of amylin are receptor-mediated. Conversely, icv amylin-induced BAT SNA response was enhanced in mice overexpressing the amylin receptor subunit, RAMP1 (receptor-activity modifying protein 1), in the CNS. Our data demonstrate that CNS action of amylin regulates sympathetic nerve outflow to peripheral tissues involved in energy balance and cardiovascular function.

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