scholarly journals Caffeine intake increases plasma ketones: an acute metabolic study in humans

2017 ◽  
Vol 95 (4) ◽  
pp. 455-458 ◽  
Author(s):  
Camille Vandenberghe ◽  
Valérie St-Pierre ◽  
Alexandre Courchesne-Loyer ◽  
Marie Hennebelle ◽  
Christian-Alexandre Castellano ◽  
...  

Brain glucose uptake declines during aging and is significantly impaired in Alzheimer’s disease. Ketones are the main alternative brain fuel to glucose so they represent a potential approach to compensate for the brain glucose reduction. Caffeine is of interest as a potential ketogenic agent owing to its actions on lipolysis and lipid oxidation but whether it is ketogenic in humans is unknown. This study aimed to evaluate the acute ketogenic effect of 2 doses of caffeine (2.5; 5.0 mg/kg) in 10 healthy adults. Caffeine given at breakfast significantly stimulated ketone production in a dose-dependent manner (+88%; +116%) and also raised plasma free fatty acids. Whether caffeine has long-term ketogenic effects or could enhance the ketogenic effect of medium chain triglycerides remains to be determined.

2001 ◽  
Vol 91 (6) ◽  
pp. 2703-2712 ◽  
Author(s):  
Stephen M. Johnson ◽  
Julia E. R. Wilkerson ◽  
Daniel R. Henderson ◽  
Michael R. Wenninger ◽  
Gordon S. Mitchell

Brain stem preparations from adult turtles were used to determine how bath-applied serotonin (5-HT) alters respiration-related hypoglossal activity in a mature vertebrate. 5-HT (5–20 μM) reversibly decreased integrated burst amplitude by ∼45% ( P < 0.05); burst frequency decreased in a dose-dependent manner with 20 μM abolishing bursts in 9 of 13 preparations ( P < 0.05). These 5-HT-dependent effects were mimicked by application of a 5-HT1A agonist, but not a 5-HT1B agonist, and were abolished by the broad-spectrum 5-HT antagonist, methiothepin. During 5-HT (20 μM) washout, frequency rebounded to levels above the original baseline for 40 min ( P < 0.05) and remained above baseline for 2 h. A 5-HT3 antagonist (tropesitron) blocked the post-5-HT rebound and persistent frequency increase. A 5-HT3 agonist (phenylbiguanide) increased frequency during and after bath application ( P < 0.05). When phenylbiguanide was applied to the brain stem of brain stem/spinal cord preparations, there was a persistent frequency increase ( P < 0.05), but neither spinal-expiratory nor -inspiratory burst amplitude were altered. The 5-HT3receptor-dependent persistent frequency increase represents a unique model of plasticity in vertebrate rhythm generation.


2021 ◽  
Vol 14 (2) ◽  
pp. 139
Author(s):  
Mohammad Azam Ansari ◽  
Sarah Mousa Maadi Asiri ◽  
Mohammad A. Alzohairy ◽  
Mohammad N. Alomary ◽  
Ahmad Almatroudi ◽  
...  

The current study demonstrates the synthesis of fatty acids (FAs) capped silver nanoparticles (AgNPs) using aqueous poly-herbal drug Liv52 extract (PLE) as a reducing, dispersing and stabilizing agent. The NPs were characterized by various techniques and used to investigate their potent antibacterial, antibiofilm, antifungal and anticancer activities. GC-MS analysis of PLE shows a total of 37 peaks for a variety of bio-actives compounds. Amongst them, n-hexadecanoic acid (21.95%), linoleic acid (20.45%), oleic acid (18.01%) and stearic acid (13.99%) were found predominately and most likely acted as reducing, stabilizing and encapsulation FAs in LIV-AgNPs formation. FTIR analysis of LIV-AgNPs shows some other functional bio-actives like proteins, sugars and alkenes in the soft PLE corona. The zone of inhibition was 10.0 ± 2.2–18.5 ± 1.0 mm, 10.5 ± 2.5–22.5 ± 1.5 mm and 13.7 ± 1.0–16.5 ± 1.2 against P. aeruginosa, S. aureus and C. albicans, respectively. LIV-AgNPs inhibit biofilm formation in a dose-dependent manner i.e., 54.4 ± 3.1%—10.12 ± 2.3% (S. aureus), 72.7 ± 2.2%–23.3 ± 5.2% (P. aeruginosa) and 85.4 ± 3.3%–25.6 ± 2.2% (C. albicans), and SEM analysis of treated planktonic cells and their biofilm biomass validated the fitness of LIV-AgNPs in future nanoantibiotics. In addition, as prepared FAs rich PLE capped AgNPs have also exhibited significant (p < 0.05 *) antiproliferative activity against cultured HCT-116 cells. Overall, this is a very first demonstration on employment of FAs rich PLE for the synthesis of highly dispersible, stable and uniform sized AgNPs and their antibacterial, antifungal, antibiofilm and anticancer efficacy.


1993 ◽  
Vol 71 (5-6) ◽  
pp. 321-325 ◽  
Author(s):  
Morikuni Takigawa ◽  
Hiroshi Maeda ◽  
Kenichi Ueyama ◽  
Hidefumi Tominaga ◽  
Kei Matsumoto

The effect of long-term methamphetamine (MAP) treatment on intracranial self-stimulation of the lateral hypotholamus and locomotor traces was assessed. An attempt was made to provide a useful animal model for understanding anhedonia, stereotypy, and reoccurrence of liability, which are analogous to symptoms of schizophrenia. The frequency of intracranial self-stimulation (ICSS) as used as a measure of the animals' "hedonic–anhedonic" state. Following long-term MAP treatment (3 mg/kg), rats gradually showed stereotyped behavior, and became inactive and unresponsive to ICSS. These behavioral changes and decreased ICSS lasted several weeks after cessation of chronic MAP treatment and seemed to suggest post-MAP chronic psychosis and (or) anhedonia, two of the negative symptoms of schizophrenia. The traces of rat behavior affected by chronic MAP treatment were classified into three types, peripheral, mixed, and fixed, occurring in a dose-dependent manner. Reverse tolerance, similar to the reoccurrence of schizophrenic symptoms, was observed as a fixed stereotypy associated with loss of ICSS. These abnormal phenomena were suppressed by pretreatment with haloperidol. In the present study, the combination of ICSS and locomotor trace affected by chronic MAP treatment was proposed as an animal model of schizophrenia and as a useful technique for gauging the effect of neuroleptics.Key words: self-stimulation, anhedonia, stereotypy, reverse tolerance, animal disease model, schizophrenia, methamphetamine.


Blood ◽  
2010 ◽  
Vol 116 (25) ◽  
pp. 5716-5723 ◽  
Author(s):  
Petr Klement ◽  
Leslie R. Berry ◽  
Peng Liao ◽  
Henry Wood ◽  
Paul Tressel ◽  
...  

AbstractTranscranial Doppler-detected high-intensity transient signals (HITS) during cardiopulmonary bypass (CPB) surgery have been associated with postoperative neurocognitive dysfunction, suggesting microemboli in the brain could be a contributing factor. HITS occur despite administration of unfractionated heparin (UFH). This study was done to determine whether antithrombin-heparin covalent complex (ATH), a more potent anticoagulant than heparin, can reduce HITS during CPB. In a pig CPB model, ATH, UFH, or UFH + antithrombin (AT) was intravenously administered to female Yorkshire pigs after sternotomy. Twenty minutes later, hypothermic CPB was initiated and continued for 1.25 hours, then normothermia was re-established for 45 minutes. Protamine sulfate was given to neutralize the anticoagulants, and pigs were allowed to recover. HITS were monitored using an arterial flow probe placed over the carotid artery. Compared with UFH (300 or 1000 U/kg), ATH reduced the number of HITS during CPB in a dose-dependent manner. AT (3 mg/kg) + UFH (300 U/kg) resulted in an intermediate HITS rate between UFH and ATH (2 mg/kg in terms of AT). Examination of brain sections for emboli formation confirmed that, similar to HITS, number of thrombi decreased in direct proportion to ATH dosage. These results support the hypotheses that the majority of HITS represent thromboemboli and that ATH reduces emboli formation during CPB.


2021 ◽  
Vol 11 ◽  
Author(s):  
Orestis Stylianou ◽  
Frigyes Samuel Racz ◽  
Andras Eke ◽  
Peter Mukli

While most connectivity studies investigate functional connectivity (FC) in a scale-dependent manner, coupled neural processes may also exhibit broadband dynamics, manifesting as power-law scaling of their measures of interdependence. Here we introduce the bivariate focus-based multifractal (BFMF) analysis as a robust tool for capturing such scale-free relations and use resting-state electroencephalography (EEG) recordings of 12 subjects to demonstrate its performance in reconstructing physiological networks. BFMF was employed to characterize broadband FC between 62 cortical regions in a pairwise manner, with all investigated connections being tested for true bivariate multifractality. EEG channels were also grouped to represent the activity of six resting-state networks (RSNs) in the brain, thus allowing for the analysis of within- and between- RSNs connectivity, separately. Most connections featured true bivariate multifractality, which could be attributed to the genuine scale-free coupling of neural dynamics. Bivariate multifractality showed a characteristic topology over the cortex that was highly concordant among subjects. Long-term autocorrelation was higher in within-RSNs, while the degree of multifractality was generally found stronger in between-RSNs connections. These results offer statistical evidence of the bivariate multifractal nature of functional coupling in the brain and validate BFMF as a robust method to capture such scale-independent coupled dynamics.


2021 ◽  
Vol 12 ◽  
Author(s):  
Luping Zhang ◽  
Dengyuan Zhou ◽  
Qiuyan Li ◽  
Shuo Zhu ◽  
Muhammad Imran ◽  
...  

Flaviviruses are the major emerging arthropod-borne pathogens globally. However, there is still no practical anti-flavivirus approach. Therefore, existing and emerging flaviviruses desperately need active broad-spectrum drugs. In the present study, the antiviral effect of steroidal dehydroepiandrosterone (DHEA) and 23 synthetic derivatives against flaviviruses such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), and Dengue virus (DENV) were appraised by examining the characteristics of virus infection both in vitro and in vivo. Our results revealed that AV1003, AV1004 and AV1017 were the most potent inhibitors of flavivirus propagation in cells. They mainly suppress the viral infection in the post-invasion stage in a dose-dependent manner. Furthermore, orally administered compound AV1004 protected mice from lethal JEV infection by increasing the survival rate and reducing the viral load in the brain of infected mice. These results indicate that the compound AV1004 might be a potential therapeutic drug against JEV infection. These DHEA derivatives may provide lead scaffolds for further design and synthesis of potential anti-flavivirus potential drugs.


1987 ◽  
Vol 40 (4) ◽  
pp. 405
Author(s):  
David Mann ◽  
Audrey M Bersten

The incorporation of long-chain fatty acids into phospholipids has been detected in adipocyte ghosts that were incubated with [1_14 C] stearic, [1_14 C] linoleic or [l_14C] arachidonic acid. Adrenaline and adenosine activated this incorporation within 15 s of exposure of the ghosts to the hormones and the response was dose dependent. Maximum incorporation of labelled linoleic acid occurred at 10-5 M adrenaline and 10-7 M adenosine. The a-agonist phenylephrine and the ~-agonist isoproterenol were also shown to stimulate the incorporation of fatty acid in a dose dependent manner. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were each labelled preferentially with linoleic or arachidonic acid. p-Bromophenacylbromide, quinacrine and centrophenoxine inhibited the adrenaline-stimulated incorporation of fatty acids into ghost membrane phospholipids, and p-bromophenacylbromide also reduced the activation of adenylate cyclase by adrenaline. NaF, an activator of adenylate cyclase, like adrenaline, stimulated the incorporation of linoleic acid into ghost membrane phospholipids.


Author(s):  
MAHESWARI REDDY B ◽  
DHANAPAL CK ◽  
LAKSHMI BVS

Objective: The current study evaluates anti-Parkinson’s activity of aqueous extracts of leaves of Murraya koenigii (MK) (AEMK) against paraquat (PQ)-induced Parkinsonism in rats. Methods: In this study, effects of MK (100, 200, and 400 mg/kg, p.o.) were studied using in vivo behavioral parameters such as catalepsy, muscle rigidity, and locomotor activity and its effects on neurochemical parameters malondialdehyde, catalase (CAT), glutathione (GSH) reductase, GSH peroxidase, and GSH in rats. Results: Parkinson’s disease was induced by administering PQ 10 mg/kg b.w/i.p once in a week for 4 weeks. The increased cataleptic scores were significantly (p<0.001) found to be reduced, with the AEMK in a dose-dependent manner. Chronic administration of PQ significantly induced motor dysfunction (muscle rigidity and hypolocomotion), showed a significant increase in lipid peroxidation level, and depleted the levels of GSH, CAT, and reduced GSH. Daily administration of AEMK significantly improved motor performance and also significantly attenuated oxidative damage. Conclusion: The study proved that MK treatment significantly attenuated motor defects and also protected the brain from oxidative stress.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Monte S Willis ◽  
Jon Schisler ◽  
Holly McDonough ◽  
Cam Patterson

Previous work has suggested that MuRF1, a cardiac-specific protein, regulates metabolism by its interactions with proteins that regulate ATP transport, glycolysis, and the electron transport chain. We recently identified that MuRF1 is cardioprotective in ischemia reperfusion injury. In the current study, we investigated the effects of MuRF1 expression on metabolic substrate utilization and found that MuRF1 shifts substrate utilization from fatty acids to glucose in a dose-dependent manner. Isolated neonatal ventricular cardiomyocytes were treated with an adenovirus expressing MuRF1 (Ad.MuRF1) or GFP (Ad.GFP) at a range of 0–25 MOI (Multiplicity Of Infection). 14C-Oleate or 14C-glucose were added to cells for 1 hour and 14C-CO2 release was determined using the CO2-trapping method. Trapped 14CO2 and acid soluble metabolites were used to calculate total fatty acid oxidation. Cardiomyocytes treated with 5–25 MOI Ad.MuRF1 demonstrated a dose dependent decrease in fatty acid oxidation of 10.5 +/− 2.3(5 MOI), 8.5 +/− 1.9 (10 MOI), 6.6 +/− 1.6 (15 MOI), and 5.1 +/− 1.3 (25 MOI) nmol oleate/mg protein/h. Compared with control cardiomyocytes treated with 5–25 MOI Ad.GFP (average of 5–25 MOI=13.5 +/− 0.7 nmol oleate/mg protein/h), this represents a 22.2%– 62.2% decrease in fatty acid oxidation. Inversely, glucose oxidation increased with increasing MuRF1 expression. Cardiomyocytes infected with 25 MOI Ad.MuRF1 oxidized 184% more glucose (28.9 +/− 4.6 nmol glucose/mg protein/h) compared to control cells treated with 25 MOI Ad.GFP (15.7 +/− 1.3 nmol glucose/mg protein/h). Increasing MuRF1 expression resulted in no net gain or loss of calculated ATP production (1699 +/− 157 vs. 1480 +/− 188 nmol ATP/mg protein/h). The co-utilization of glucose and fatty acids as substrates for the production of ATP allows the heart to adapt to both environmental stress and disease. Increasing the relative proportion of glucose oxidation in relationship to fatty acids is a known protective mechanism during cardiac stress, and may represent one mechanism by which MuRF1 is cardioprotective.


2001 ◽  
Vol 21 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Gutemberg G. Alves ◽  
Luis Maurício T. R. Lima ◽  
Maely P. Fávero-Retto ◽  
Adriana P. Lemos ◽  
Carlos E. Peres-Sampaio ◽  
...  

The plasma membrane (Ca2++Mg2+)ATPase hydrolyzes pseudo-substrates such as p-nitrophenylphosphate. Except when calmodulin is present, Ca2+ ions inhibit the p-nitrophenylphosphatase activity. In this report it is shown that, in the presence of glycerol, Ca2+ strongly stimulates phosphatase activity in a dose-dependent manner. The glycerol- and Ca2+-induced increase in activity is correlated with modifications in the spectral center of mass (average emission wavenumber) of the intrinsic fluorescence of the enzyme. It is concluded that the synergistic effect of glycerol and Ca2+ is related to opposite long-term hydration effects on the substrate binding domain and the Ca2+ binding domain.


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