The aim of this study was to identify the characteristics of human excited electroencephalogram and the excited location in brain. The subjects were excited by taking a fixed quantity of caffeine. Electroencephalographic signals were collected using with 128 channels Phoenix Digital EEG and compared before and after the subjects drank coffee. The results showed obvious differences and compared with the ones before being excited electroencephalogram. After being excited we found that the lower frequency composition was restrained in the region below 10 Hz, the high frequency composition was increased significantly,and a wave crest of 38 Hz was produced in every acquisition point with the height around 200. Then the excited region was located in brain with the software of ASA 3 Course (designed by ANT company of Germany) and found that the excited location was focused on the area of the middle abdomen in the pons' side near bulbar when a person was exciting.
Adult ; Brain ; drug effects ; physiology ; Caffeine ; administration & dosage ; Electroencephalography ; drug effects ; Female ; Humans ; Male ; Models, Biological ; Signal Processing, Computer-Assisted

OBJECTIVETo evaluate the effectiveness and safety of different doses of caffeine in treatment of primary apnea in preterm infants.

METHODA total of 164 preterm infants (<32 weeks gestation), presented with primary apnea, were recruited in Tianjin Central Hospital of Gynecology and Obstetrics from October 2013 to December 2014. The patients were prospectively allocated into low-dose (loading 20 mg/kg and maintenance of 5 mg/(kg·d) after 24 h, n=82) and high-dose (loading 20 mg/kg and maintenance of 15 mg/(kg·d) after 24 h, n=82) groups of caffeine citrate treatment by using a random number table. The treatment effects, side effects of caffeine, and the clinical outcome of the preterm infants were compared between groups by χ(2) test or nonparametric test.

RESULTThe patients in low-dose group had birth weight of (1,237 ± 338) g, male gender of 43 (52%) and gestational age of (29.8 ± 3.4) weeks. The patients in high-dose group had birth weight of (1 262 ± 296) g, male gender of 45 (55%) and gestational age of (29.9 ± 2.7) weeks. The baseline characteristics including birth weight, gender and gestational age were comparable between the two groups. Frequency of apnea was significantly lower in high-dose group compared with low-dose group (10 (8, 15) vs.18 (13, 22), Z = -2.610, P = 0.009), and the success rate of removal of the ventilator was significantly higher in high-dose group compared with low-dose group (85% (70/82) vs.70% (57/82), χ(2) = 5.898, P = 0.015). The effective rate of caffeine treatment was significantly higher in high-dose group compared with low-dose group (82% (67/82) vs.61% (50/82), χ(2)=8.619, P = 0.003). No significant differences were observed concerning the incidence of caffeine-associated side effects including tachycardia, irritability, difficulty in feeding, hyperglycemia, hypertension, digestive disorders and electrolyte disturbances between two groups (P all > 0.05). There were no significant differences in the clinical outcomes of the preterm infants including death during hospitalization, chronic lung disease, other complications and duration of hospital stay between two groups (P all > 0.05).

CONCLUSIONA therapeutic regimen consisting of a loading dose of 20 mg/kg and maintenance dose of 15 mg/(kg·d) of caffeine citrate could improve the treatment effects and keep safety for primary apnea in preterm infants, and will not cause more adverse events.

Apnea ; drug therapy ; Birth Weight ; Caffeine ; administration & dosage ; Citrates ; administration & dosage ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; drug therapy ; Male ; Pregnancy ; Treatment Outcome

AIMTo test the enhancing activity and the mechanism of oleyl pyroglutamate used as transdermal enhancer.

METHODSThe penetration-enhancing effects of oleyl pyroglutamate, oleyl alcohol and oleic acid on the three drugs (caffeine, tinidazole and cortisone) were observed; the transdermal enhancing mechanism of oleyl pyroglutamate was studied with the attenuated total reflectance Fourier-transfer infrared spectroscopy(ATR-FTIR) of the human stratum corneum in vivo.

RESULTSThe penetration-enhancing ratio of the three drugs was 7.9 fold, 41.8 fold and 2.8 fold, respectively. The absorptions at 2,800-2,950 cm-1 and 1,642-1,646 cm-1 (amide-I) in the ATR-FTIR spectrum of the stratum were found to be shifted differently following removal of the stratum corneum which was treated with oleyl pyroglutamate.

CONCLUSIONOleyl pyroglutamate showed better penetration-enhancing effect on the penetration of drugs. Its transdermal enhancing mechanism may be that oleyl pyroglutamate induced not only disordering of the stratum corneum lipid, but also change of the secondary structure of keratin.

Administration, Cutaneous ; Adult ; Animals ; Caffeine ; administration & dosage ; pharmacokinetics ; Cortisone ; administration & dosage ; pharmacokinetics ; Fatty Alcohols ; pharmacology ; Humans ; Male ; Mice ; Oleic Acid ; pharmacology ; Pyrrolidonecarboxylic Acid ; analogs & derivatives ; chemistry ; pharmacology ; Skin Absorption ; drug effects ; Tinidazole ; administration & dosage ; pharmacokinetics

OBJECTIVES: To investigate whether caffeine intake is associated with urinary incontinence (UI) among Japanese adults. METHODS: A total of 683 men and 298 women aged 40 to 75 years were recruited from the community in middle and southern Japan. A validated food frequency questionnaire was administered face-to-face to obtain information on dietary intake and habitual beverage consumption. Urinary incontinence status was ascertained using the International Consultation on Incontinence Questionnaire-Short Form. RESULTS: Mean daily caffeine intake was found to be similar between incontinent subjects (men 120 mg, women 94 mg) and others without the condition (men 106 mg, women 103 mg), p=0.33 for men and p=0.44 for women. The slight increases in risk of UI at the highest level of caffeine intake were not significant after adjusting for confounding factors. The adjusted odds ratios (95% confidence interval) were 1.36 (0.65 to 2.88) and 1.12 (0.57 to 2.22) for men and women, respectively. CONCLUSIONS: No association was evident between caffeine intake and UI in middle-aged and older Japanese adults. Further studies are required to confirm the effect of caffeine in the prevention of UI.
Adult ; Aged ; Caffeine/*administration & dosage/*adverse effects ; Female ; Health Surveys ; Humans ; Japan/epidemiology ; Male ; Middle Aged ; Odds Ratio ; Questionnaires ; Risk Assessment ; Urinary Incontinence/*chemically induced/*epidemiology/physiopathology

The use of caffeine citrate for treatment of apnea in very low birth weight infants showed short-term and long-term benefits. A systematic review and meta-analysis of the literature was undertaken to document the effect providing caffeine early (0-2 days of life) compared to providing caffeine late (> or =3 days of life) in very low birth weight infants on several neonatal outcomes, including bronchopulmonary dysplasia (BPD). We searched MEDLINE, the EMBASE database, the Cochrane Library, and KoreaMed for this meta-analysis. The quality of the included studies was assessed using the Newcastle-Ottawa Scale and Jadad's scale. Studies were included if they examined the effect of the early use of caffeine compared with the late use of caffeine. Two reviewers screened the candidate articles and extracted the data from the full-text of all of the included studies. We included a total of 59,136 participants (range 58,997-59,136; variable in one study) from a total of 5 studies. The risk of death (odds ratio [OR], 0.902; 95% confidence interval [CI], 0.828 to 0.983; P=0.019), bronchopulmonary dysplasia (BPD) (OR, 0.507; 95% CI, 0.396 to 0.648; P<0.001), and BPD or death (OR, 0.526; 95% CI, 0.384 to 0.719; P<0.001) were lower in the early caffeine group. Early caffeine use was not associated with a risk of necrotizing enterocolitis (NEC) and NEC requiring surgery. This meta-analysis suggests that early caffeine use has beneficial effects on neonatal outcomes, including mortality and BPD, without increasing the risk of NEC.
Apnea/*drug therapy ; Bronchopulmonary Dysplasia/drug therapy ; Caffeine/*administration & dosage/adverse effects ; Citrates/*administration & dosage/adverse effects ; Enterocolitis, Necrotizing/etiology ; Humans ; Infant ; Infant Mortality ; Infant, Newborn ; Infant, Very Low Birth Weight ; Risk Factors ; Treatment Outcome

Scutellaria baicalensis is one of the most widely used herbal medicines in East Asia. Because baicalein and baicalin are major components of this herb, it is important to understand the effects of these compounds on drug metabolizing enzymes, such as cytochrome P450 (CYP), for evaluating herb-drug interaction. The effects of baicalin and baicalein on activities of ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), benzyloxyresorufin O-debenzylase (BROD), p-nitrophenol hydroxylase and erythromycin N-demethylase were assessed in rat liver microsomes in the present study. In addition, the pharmacokinetics of caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) in baicalin-treated rats were compared with untreated control. As results, EROD, MROD and BROD activities were inhibited by both baicalin and baicalein. However, there were no significant differences in the pharmacokinetic parameters of oral caffeine and its three metabolites between control and baicalin-treated rats. When the plasma concentration of baicalin was determined, the maximum concentration of baicalin was below the estimated IC50 values observed in vitro. In conclusion, baicalin had no effects on the pharmacokinetics of caffeine and its metabolites in vivo, following single oral administration in rats.
Administration, Oral ; Animals ; Caffeine* ; Cytochrome P-450 CYP1A1 ; Cytochrome P-450 CYP2B1 ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System ; Drug Interactions ; Far East ; Herb-Drug Interactions ; Inhibitory Concentration 50 ; Microsomes, Liver ; Pharmacokinetics* ; Plasma ; Rats* ; Scutellaria baicalensis ; Theobromine

OBJECTIVETo study the effect of ferment powder caterpillar fungus on cytochrome P450 isozymes CYP1A2, CYP3A4 and CYP2E1.

METHODThe methods of Cocktail probe drugs were used. The rats were randomly divided into two groups. One group were given ferment powder caterpillar fungus once daily orally for ten days. Another group received orally normal saline one daily as the blank control. After ten days of treatment, the rats were given probe drugs of coffine, dapsone and chlorzoxazone and the blood was taken out by femoral catheterization. The plasma concentration of probe drugs were determined by HPLC. Data of plasma drug level-time were disposed with DAS Ver 2.0.

RESULTThe metabolism of caffeine and dapsone speeded up after receiving ferment powder caterpillar fungus, but the metabolism of chlorzoxazone was hardly changed.

CONCLUSIONIt suggested that ferment powder caterpillar fungus tended to be the inducer of CYP1A2 and CYP3A4. But the CYP2E1 was hardly affected.

Animals ; Caffeine ; metabolism ; Chlorzoxazone ; metabolism ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System ; metabolism ; Dapsone ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Fermentation ; Male ; Random Allocation ; Rats ; Rats, Wistar

The knowledge on the pathogenetic mechanisms of bronchopulmonary dysplasia (BPD) has increased considerably over recent years. However, the incidence of the disease has not substantially been changed by our therapeutic approaches. This review summarizes the existing evidence for a number of respiratory and medical strategies to prevent or ameliorate the disease and gives recommendations for clinical practice. Oxygen plays an important pathogenetic and therapeutic role for BPD. Targeting infants at lower oxygen saturation levels than traditionally used seems to confer major advantages. There is no sufficient evidence for a routine use of respiratory strategies like permissive hypercapnia or inhaled nitric oxide to prevent BPD. Diuretics can ameliorate lung function transiently. High intramuscular doses of vitamin A can reduce the risk of BPD. Early or prophylactic surfactant might also be advantageous. Postnatal corticosteroids are effective but, due to their severe side effects, should be restricted to the severest cases. Alpha1-proteinase inhibitor and superoxide dismutase have no proven benefits for BPD. The role of erythromycin has not been completely elucidated yet. Innovative strategies like Clara Cell 10 kD protein still have to be assessed in future trials.
Antioxidants ; therapeutic use ; Bronchopulmonary Dysplasia ; prevention & control ; therapy ; Caffeine ; therapeutic use ; Diuretics ; therapeutic use ; Erythromycin ; therapeutic use ; Humans ; Incidence ; Infant, Newborn ; Nitric Oxide ; administration & dosage ; Oxygen ; therapeutic use ; Ureaplasma urealyticum ; drug effects

With the increase in the rescue success rate of critically ill preterm infants and extremely preterm infants, the incidence rate of bronchopulmonary dysplasia (BPD) is increasing year by year. BPD has a high mortality rate and high possibility of sequelae, which greatly affects the quality of life of preterm infants and brings a heavy burden to their families, and so the treatment of BPD is of vital importance. At present, no consensus has been reached on the treatment measures for BPD. However, recent studies have shown that early application of caffeine can prevent BPD. With reference to the latest studies on the effect of caffeine in the prevention of BPD, this article reviews the mechanism of action of caffeine in reducing pulmonary inflammation, improving morphological abnormalities of lung injury, reducing oxidative stress injury, and improving pulmonary function.
Animals ; Bronchopulmonary Dysplasia ; genetics ; metabolism ; physiopathology ; prevention & control ; Caffeine ; administration & dosage ; Humans ; Infant, Premature ; growth & development ; metabolism ; Infant, Premature, Diseases ; genetics ; metabolism ; physiopathology ; prevention & control ; Oxidative Stress ; drug effects

To study the effect of Tibetan medicine Zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2, three different doses (1.2, 3.8 and 12 mg x kg(-1)) of Zuotai were administrated orally to rats once a day or once daily for twelve days, separately. Rats were administrated orally caffeine (CF) on the second day after Zuotai administration, and the urine concentration of CF metabolite 5-acetylamino-6-formylamino-3-methyl-uracil (AFMU), 1-methyluric acid (1U), 1-methylxanthine (1X), 1, 7-dimethylxanthine (17U) at 5 h after study drug administration was determined by RP-HPLC. The activity of CYP1A2 and NAT2 was evaluated by the ratio of metabolites (AFMU+1X+1U)/17U and the ratio of AFMU/(AFMU+1X+1U), respectively. The protein and mRNA expression of CYP1A2 and NAT2 were determined by ELISA and RT-PCR method, respectively. After single administration of Zuotai 3.8 mg x kg(-1) and repeated administration of Zuotai 3.8 and 12 mg x kg(-1), the activity of CYP1A2 and NAT2 decreased significantly compared with control group and there was no significant difference between other dose group and control group. The protein expression of CYP1A2 was significant lower than that in control group after repeated administration of Zuotai 12 mg x kg(-1), and the mRNA expression of CYP1A2 decreased significantly compared with that of control group after single administration of Zuotai 3.8 mg x kg(-1) and repeated admistration of Zuotai 12 mg x kg(-1), separately. The protein expression of NAT2 decreased significantly compared with that of control group after single and repeated administration of Zuotai 3.8 mg x kg(-1), respectively, and the mRNA expression of CYP1A2 decreased significantly compared with control group after single administration of Zuotai 3.8 mg x kg(-1). This study found that Tibetan medicine Zuotai had significant effect on the activity, protein and mRNA expression of CYP1A2 and NAT2.
Administration, Oral ; Animals ; Arylamine N-Acetyltransferase ; genetics ; metabolism ; Caffeine ; metabolism ; urine ; Cytochrome P-450 CYP1A2 ; genetics ; metabolism ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Female ; Male ; Medicine, Tibetan Traditional ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Theophylline ; urine ; Uracil ; analogs & derivatives ; urine ; Uric Acid ; analogs & derivatives ; urine ; Xanthines ; urine