Modulation of two functionally distinct Ca2+ stores in astrocytes: Role of the plasmalemmal Na/Ca exchanger

Mechanisms that regulate the amount of releasable Ca²⁺ in intracellular stores of cultured mouse astrocytes were investigated using digital imaging of fura-2 loaded cells. At rest, the cytoplasmic Ca²⁺ concentration, [Ca²⁺]_cyt, was about 110 nM. In the absence of extracellular Ca²⁺, cyclopiazonic acid (CPA), an inhibitor of the endoplasmic reticulum (ER) Ca²⁺-ATPase, induced a transient, four-fold increase in [Ca²⁺]_cyt due to the release of Ca²⁺ from inositol triphosphate (IP₃) sensitive stores. Caffeine (CAF), which releases Ca²⁺ from Ca²⁺-sensitive stores, induced a two-fold increase in [Ca²⁺]_cyt. The CPA- and CAF-sensitive stores could be released independently. Changes in the amplitudes of the Ca²⁺ transients were taken as a measure of changes in store content. Removal of extracellular Na⁺ or addition of ouabain, which inhibit Ca²⁺ extrusion and promote Ca²⁺ entry across the plasmalemma via the Na/Ca exchanger, caused minimal increases in resting [Ca²⁺]_cyt but greatly potentiated both CPA- and CAF-induced Ca²⁺ transients. The amount of Ca²⁺ releasable from the IP₃ (CPA) sensitive store was directly proportional to cytosolic Na⁺ concentration (i.e., inversely proportional to the transmembrane Na⁺ electrochemical gradient). Under these reduced Na⁺ gradient conditions, little, if any, Ca²⁺ destined for the ER stores enters the cells through voltage-dependent Ca²⁺ channels. These results demonstrate that mouse astrocytes contain two distinct ER Ca²⁺ stores, the larger, IP₃- (CPA-) sensitive, and the smaller, Ca²⁺- (CAF-) sensitive. The Ca²⁺ content of both ER stores can be regulated by the Na/Ca exchanger. Thus, the magnitude of cellular responses to signals that are mediated by Ca²⁺ release induced by the two second messengers, IP₃ and Ca²⁺, can be modulated by factors that affect the net transport of Ca²⁺ across the plasmalemma. © 1996 Wiley-Liss, Inc.     

Effects of 3 mg/kg Body Mass of Caffeine on the Performance of Jiu-Jitsu Elite Athletes

The effects of caffeine were investigated in judo, boxing, taekwondo and Brazilian jiu-jitsu. However, this substance was never investigated regarding traditional jiu-jitsu. Therefore, the aim of this research was to analyze the effects of caffeine in the Special Judo Fitness Test (SJFT) and technical variables during combat in traditional jiu-jitsu elite athletes. Methods: Twenty-two young professionals of traditional jiu-jitsu, 11 men and 11 women (age = 22 ± 4 (18–33) years, body mass = 66.6 ± 10.8 (46.2–86.1) kg, height = 1.70 ± 0.9 (1.55–1.85) m) with 15 ± 7 years of experience in traditional jiu-jitsu, participated in a double-blind, counterbalanced, crossover study. In two different conditions, the traditional jiu-jitsu athletes ingested 3 mg/kg body mass of caffeine or a placebo. After 60 min, they performed the SJFT test to measure throwing performance, and subsequently, combat to analyze offensive and defensive hitting techniques. Results: Caffeine had a main effect on the number of throws during the SJFT test (P < 0.01). In addition, it was effective in sets 2 (13 ± 2 vs. 14 ± 2; p = 0.01) and 3 (12 ± 2 vs. 13 ± 1; p = 0.03). There was also a main effect during the test on heart rate when caffeine was ingested (F = 12.48, p < 0.01). The effects of caffeine were similar compared to the placebo condition regarding performance during combat both in offensive and defensive fighting variables Conclusions: the pre-exercise ingestion of 3 mg/kg body mass of caffeine increased performance in the SJFT test, decreased fatigue perception, and increased power and endurance perception in professionally traditional jiu-jitsu athletes. However, it did not seem to improve offensive and defensive technical actions during combat.     

Management of periorbital hyperpigmentation: An overview of nature‐based agents and alternative approaches

Periorbital hyperpigmentation (POH) is a common dermatological condition that presents as dark periorbital area beneath the lower eyelids, and it is commonly found in females belonging to the age group of 16 to 45 years. The data presented in this review include studies conducted on patients with a clinical/histological diagnosis of POH or melasma. Many diverse topical depigmenting agents comprising an array of naturally obtained actives such as arabinoxylans, α‐arbutin, asiaticoside, azelaic acid, beta‐carotene, boswellic acid, caffeine, chrysin, curcumin, cyanidin‐3‐glucoside, d ‐glucoronic acid, dihydrochalcone, dipalmitoyl‐hydroxyprolene, fucoxanthin, genistein, glabridin, b‐glucogallin, hyaluronic acid, lactic acid, lycopene, niacinamide, pycnogenol, retinol, salidroside, and xymenynic acid demonstrated significant benefits in the management of POH. An exhaustive literature search revealed that other techniques such as blepharoplasty, carboxytherapy, calcium hydroxylapatite fillers, tear trough implant, Q‐switched ruby laser, medicated tattoo, fat transfer, micro‐needling, chemical peels, nitrogen plasma skin regeneration, intense pulsed light, and radiofrequency have been evaluated and reported to be beneficial in the treatment of POH. The use of topical depigmenting agents is the most widely reported method in the clinical management of POH. Of these, α‐arbutin, caffeine, cyanidin‐3‐glucoside, and dihydrochalcone are reported to exhibit significant benefits. Combination products containing a blend of actives are reported to be better than single active containing products. This review aims to provide a comprehensive perspective on the role of several topical actives in the modulation of melanin and tyrosinase biosynthesis pathway involved in the complex pathophysiology of POH. It also presents the advantages of combination products and other alternative therapies used in the management of POH.     

Automated Detection of Caffeinated Coffee-Induced Short-Term Effects on ECG Signals Using EMD,DWT, and WPD

The effect of coffee (caffeinated) on electro-cardiac activity is not yet sufficiently researched. In the current study, the occurrence of coffee-induced short-term changes in electrocardiogram (ECG) signals was examined. Further, a machine learning model that can efficiently detect coffee-induced alterations in cardiac activity is proposed. The ECG signals were decomposed using three different joint time–frequency decomposition methods: empirical mode decomposition, discrete wavelet transforms, and wavelet packet decomposition with varying decomposition parameters. Various statistical and entropy-based features were computed from the decomposed coefficients. The statistical significance of these features was computed using Wilcoxon’s signed-rank (WSR) test for significance testing. The results of the WSR tests infer a significant change in many of these parameters after the consumption of coffee (caffeinated). Further, the analysis of the frequency bands of the decomposed coefficients reveals that most of the significant change was localized in the lower frequency band (<22.5 Hz). Herein, the performance of nine machine learning models is compared and a gradient-boosted tree classifier is proposed as the best model. The results suggest that the gradient-boosted tree (GBT) model that was developed using a db2 mother wavelet at level 2 decomposition shows the highest mean classification accuracy of 78%. The outcome of the current study will open up new possibilities in detecting the effects of drugs, various food products, and alcohol on cardiac functionality.     

N (L-Phenylisopropyl)adenosine (L-PIA) increases slow-wave sleep (S2) and decreases wakefulness in rats

Rats implanted with electrodes for polygraphic recording were administered with L-PIA (0.115 mg/kg, i.p.), caffeine (15 mg/kg, i.p.) or L-PIA (0.115 mg/kg, i.p.) + caffeine (15 mg/kg, i.p.) and recorded for 6 h. The results show that administration of L-PIA increased S₂ by 54 min suggesting that stimulation of adenosine receptors promotes deep sleep. Administration of L-PIA failed to produce the same effect in the presence of caffeine, a finding consistent with the hypothesis that the CNS stimulant effect of caffeine and other methylxanthines is due to their ability to antagonize depressant effects of endogenous adenosine.     

Relationship between plasma total homocysteine level and dietary caffeine and vitamin B6 intakes in pregnant women

A high total homocysteine (tHcy) level during pregnancy is a risk factor for adverse perinatal outcomes, such as fetal growth restriction and preeclampsia. Caffeine is assumed to increase tHcy levels by acting as a vitamin B₆ antagonist. The objective of this study was to examine a relationship between circulating tHcy levels and dietary caffeine and vitamin B₆ intakes in pregnant Japanese women. A total of 321 healthy women with singleton pregnancies were recruited in metropolitan Tokyo, from June to December 2008, resulting in the final number included in the study as 254. Dietary caffeine intakes did not correlate with plasma tHcy levels. When we analyzed the data according to caffeinated beverages, caffeinated tea consumption was positively associated with plasma tHcy levels only among the women with a high intake of vitamin B₆, after controlling for confounding factors (P = 0.029). No correlation between coffee consumption and plasma tHcy levels was found. Pregnant Japanese women might need to cut down the consumption of caffeinated tea as well as take sufficient vitamin B₆ in order to prevent the tHcy levels from increasing.     

Abortive Migraine Therapy With Oral Naproxen Sodium Plus Metoclopramide Plus Ergotamine Tartrate With Caffeine

The oral tablet combination, (550 mgs. of naproxen sodium plus 10 mgs. of metoclopramide plus 1 mg. of ergotamine tartrate plus 100 mgs. of caffeine), was retrospectively studied in 63 patients who used it to abort migraine headaches. On the average, 84% of the headaches were totally aborted; minor side effects occurred in 40% of the patients, and 87% of the patients considered the combination superior to all prior treatments.     

Stimulation of Na+, K+-pump activity in skeletal muscle by methylxanthines: evidence and proposed mechanisms

Evidence is presented to support the hypothesis that submillimolar concentrations of methylxanthines stimulate Na⁺, K⁺-ATPase activity in skeletal muscle. Administration of methylxanthines to skeletal muscle results in plasma membrane hyperpolarization and increased rates of K⁺ uptake and Na⁺ efflux. These effects are both dose- and time-dependent and inhibited by blockers of the Na⁺, K⁺ ATPase. The mechanisms for stimulation of Na⁺, K⁺-ATPase activity and the signal transduction pathways are not known. The methylxanthine concentrations required for stimulation of Na⁺, K⁺-ATPase activity are less than those required to cause a 50% inhibition of phosphodiesterase activity, and therefore increases in cyclic AMP due to inhibition of the enzyme are not involved. Possible mechanisms by which methylxanthines may increase Na⁺, K⁺-ATPase activity include: (1) a role for increased intracellular [Ca²⁺]; (2) Ca²⁺ or adenosine-receptor-mediated increases in intracellular cyclic AMP; and (3) a direct action of methylxanthines on the Na⁺, K⁺ ATPase.