Objectives: Most cases of caffeine intoxication result from the excessive intake of over-the-counter drugs and energy drinks. However, few cases of caffeine intoxication due to the excessive ...consumption of bottled coffee products have been reported. Herein, we present a case report of caffeine intoxication.Patient: A 39-year-old man experienced numbness and weakness in the extremities for three nights over five days.Results: Blood tests revealed hypophosphatemia and low 25-OH vitamin D concentration. The symptoms disappeared the next day without any additional treatment. A lifestyle interview revealed that he regularly consumed bottled coffee like it was water and had approximately 1 L of it from evening to night. He was diagnosed with weakness in the extremities due to hypophosphatemia caused by caffeine intoxication. Upon investigating some bottled coffee products, we found that only a few of them had labels disclosing caffeine content and warnings of the risks of excessive caffeine intake.Conclusion: We encountered a case of caffeine intoxication via coffee. Although rare in the past, caffeine intoxication might increase owing to the widespread use of bottled coffee products. The caffeine content of coffee products should be indicated on labels to warn consumers.
Background and Purpose
The ω‐3 polyunsaturated fatty acids exert antinociceptive effects in inflammatory and neuropathic pain; however, the underlying mechanisms remain unclear. Docosahexaenoic ...acid‐induced antinociception may be mediated by the orphan
GPR
40, now identified as the free fatty acid receptor 1 (
FFA
1 receptor). Here, we examined the involvement of supraspinal FFA1 receptor signalling in the regulation of inhibitory pain control systems consisting of serotonergic and noradrenergic neurons.
Experimental Approach
Formalin‐induced pain behaviours were measured in mice. Antinociception induced by FFA1 receptor agonists was examined by intrathecal injections of a catecholaminergic toxin, 5‐HT lowering drug or these antagonists. The expression of FFA1 receptor protein and c‐
F
os was estimated by immunohistochemistry, and the levels of noradrenaline and 5‐HT in the spinal cord were measured by
LC
‐
MS
/
MS
.
Key Results
FFA1 receptors colocalized with
N
eu
N
(a neuron marker) in the medulla oblongata and with tryptophan hydroxylase (
TPH
; a serotonergic neuron marker) and dopamine β‐hydroxylase (
DBH
; a noradrenergic neuron marker). A single i.c.v. injection of
GW
9508, a FFA1 receptor agonist, increased the number of c‐
F
os‐positive cells and the number of neurons double‐labelled for c‐
F
os and
TPH
and/or
DBH
. It decreased formalin‐induced pain behaviour. This effect was inhibited by pretreatment with 6‐hydroxydopamine,
DL
‐p‐chlorophenylalanine, yohimbine or
WAY
100635. Furthermore,
GW
9508 facilitated the release of noradrenaline and 5‐HT in the spinal cord. In addition,
GW
1100, a FFA1 receptor antagonist, significantly increased formalin‐induced pain‐related behaviour.
Conclusion and Implications
Activation of the FFA1 receptor signalling pathway may play an important role in the regulation of the descending pain control system.
Repeated IP injections of 2 mg/kg methamphetamine (MA) or 20 mg/kg cocaine at 48-h intervals induced reverse tolerance to their ambulation-enhancing effects (behavioral sensitization). Furthermore, ...the reappearance of the sensitized state was observed at the time of readministration of MA or cocaine even after a 30-day discontinuation of drug administration. A concomitant injection of ginseng extract (GE), 200 mg/kg, IP, suppressed the development of reverse tolerance and the reappearance of sensitization to MA and cocaine. Conditioned place preference to MA (1, 2, and 4 mg/ kg, IP) and cocaine (1, 4, 10, and 20 mg/kg, IP), was completely blocked by GE, 200 mg/kg, IP combined treatment with MA or cocaine. Meanwhile, spontaneous motor activity and place preference were not affected by GE alone. These results provide evidence that GE may be useful clinically for the prevention of adverse actions of MA and cocaine.
An actinomycete, strain DMKUA 245(T), isolated from soil, was investigated using a polyphasic approach. The isolate formed longitudinally paired spores on the tips of short sporophores that branched ...alternately from aerial hyphae. The morphological and chemotaxonomic properties clearly demonstrated that the new isolate belonged to the genus Microbispora. 16S rRNA gene sequence analysis supported the assignment of the novel strain to the genus Microbispora. The gene sequence similarity values between the novel strain and the closely related species Microbispora corallina, Microbispora rosea subsp. rosea, Microbispora rosea subsp. aerata and Microbispora amethystogenes were 98.4 %, 97.4 %, 97.0 % and 96.9 %, respectively. The DNA-DNA hybridization values and some physiological and biochemical properties indicated that strain DMKUA 245(T) could be distinguished from its phylogenetically closest relatives. Based on these genotypic and phenotypic data, strain DMKUA 245(T) represents a novel species in the genus Microbispora for which the name Microbispora siamensis sp. nov. is proposed. The type strain is strain DMKUA 245(T) (=BCC 14407(T)=NBRC 104113(T)). In addition, DNA-DNA relatedness values in reciprocal hybridization experiments showed that M. amethystogenes was a separate genomic species from M. rosea subsp. rosea. A combination of genotypic and phenotypic data supported the classification of M. amethystogenes as a separate species.
Altered expression of P-glycoprotein (P-gp), a drug efflux transporter expressed by brain capillary endothelial cells (BCECs), may contribute to the development of opioid analgesic tolerance, as ...demonstrated by cumulative evidence from research. However, the detailed mechanism by which chronic morphine treatment increases P-gp expression remains unexplained. Ezrin/radixin/moesin (ERM) are scaffold proteins that are known to regulate the plasma membrane localization of some drug transporters such as P-gp in peripheral tissues, although a few reports suggest its role in the central nervous system as well. In this study, we investigated the involvement of ERM in the development of morphine analgesic tolerance through altered P-gp expression in BCECs. Repeated treatment with morphine (10mg/kg/day, s.c. for 5 days) decreased its analgesic effect in the tail-flick test and increased P-gp protein expression in BCECs, as determined by Western blotting. Furthermore, moesin protein expression increased in the same fraction whereas that of ezrin decreased; no change was observed in the radixin expression. Furthermore, immunoprecipitation and immunofluorescence assays revealed interaction between moesin and P-gp molecules, along with co-localization, in BCECs. In conclusion, an increase in moesin expression may contribute to the increased expression of P-gp in BCECs, leading to the development of morphine analgesic tolerance.
Objectives Opioids and anticancer compounds such as etoposide (ETP) are substrates of P‐glycoprotein (P‐gp), an ATP‐dependent efflux pump. Chemotherapy compounds may impact on the analgesic effect ...of opioids such as morphine when the two drugs are co‐administered. In this study, we used a mouse model to determine if there is a pharmacological interaction between ETP and morphine, focusing on the involvement of intestinal P‐gp.
Methods P‐gp drug efflux activity was measured by an in‐situ closed loop method with Rhodamine 123, a P‐gp substrate. The analgesic effect of morphine was determined by the tail‐flick test. Intestinal P‐gp expression levels were determined by Western blot.
Key findings ETP and morphine significantly decreased the intestinal Rhodamine 123 efflux activity of P‐gp. Oral morphine analgesia was significantly enhanced when co‐administered with ETP. However, repeated pretreatment (7 days) with oral ETP significantly decreased the oral morphine‐induced analgesia, in a cyclosporine A (a P‐gp inhibitor) reversible manner. Furthermore, repeated ETP significantly up‐regulated intestinal P‐gp expression.
Conclusions It may be important to consider aspects of therapeutic design such as the administration route or scheduling of drugs in patients receiving concurrent chemotherapy and opioid therapy to avoid pharmacokinetic interactions between the two agents.
Pharmacological and physiological effects of ginseng on actions induced by opioids and psychostimulants are summarized. Analgesic effects of opioids, such as morphine and U-50, 488H, were blocked by ...ginseng in a nonopioid dependent manner. Furthermore, ginseng inhibited the tolerance to and dependence on morphine, and eliminated the suppressive effect of the development of morphine tolerance by coexposure to footshock stress, but not psychological stress. On the other hand, behavior sensitization (reverse tolerance to their ambulation-accelerating effect) to morphine, methamphetamine and cocaine was also inhibited by ginseng. Interestingly, ginseng also inhibited the appearance of the recurrent phenomenon (reappearance of the sensitized state was observed at the time of readministration of methamphetamine and cocaine even after a 30-day discontinuation of drug administration) of the effect of methamphetamine and cocaine. The conditioned place preference of methamphetamine and cocaine was completely blocked by ginseng. These findings provide evidence that ginseng may be useful clinically for the prevention of abuse and dependence of opioids and psychostimulants.
It is known that opioid analgesics given systemically have limited distribution into the brain because of their interaction with P-glycoprotein (P-gp), an ATP-dependent efflux pump acting at the ...blood-brain barrier (BBB). We previously found that morphine and fentanyl showed higher analgesic potencies in P-gp–deficient mice compared with those in wild-type mice, suggesting that their analgesic effects are considerably dependent on P-gp expression. In this study, we focused on individual differences in the analgesic effectiveness of morphine, in cortical P-gp expression, and in basal P-gp ATPase activity in male ICR mice. We found that there were 3- to 10-fold differences between the magnitude of morphine analgesia (3 mg /kg, s.c.; tail-pinch method) in mice. Furthermore, there was a significant negative correlation between morphine’s analgesic effects and individual P-gp expression in the cortex as estimated by western blot analysis. In addition, basal P-gp ATPase activities in isolated membrane preparations of brain capillary endothelial cells (BCECs) were negatively correlated with the magnitude of the analgesic effect of morphine. These results indicate that the individual differences in morphine analgesia may be due to some functional or quantitative differences in individual P-gp in BCECs, acting at the BBB.
A novel enzyme, N-acylamino acid racemase (acylamino acid racemase) which catalyzes the interconversion of the enantiomers of N-acylamino acid, but does not act on amino acids, was found in an ...actinomycete strain Y-53 isolated from soil. A taxonomic study on the strain identified Y-53 as a strain of Streptomyces atratus. This strain also produced L- and D-aminoacylases simultaneously. Furthermore, another 13 strains of actinomycetes with the enzyme activity from the type culture collection of the Institute for Fermentation, Osaka (IFO) were observed
1. The effect of 2,2'-dipyridyl ketone and 2,2'-dipyridyl amine on the induction of hepatic microsomal cytochrome P450 (P450) and heme oxygenase was compared, and their effects on five different P450 ...isoforms (P4501A1, 3A2, 2B1, 2E1 and 2C11) in rat were examined. 2. Treatment of rat with 2,2-dipyridyl amine resulted in the marked induction of haem oxygenase to about seven-fold of the controls with a decrease in P450 content. 2,2-'Dipyridyl ketone produced concomitant induction of both P450 and haem oxygenase activity in a dose- and time-dependent manner without showing any sex differences. 3. Immunoblot analysis revealed that 2,2'-dipyridyl ketone slightly increased CYP2E1 and CYP3A2 at low doses, but not at high dose levels. There was no effect on P4502C11. P4502B1 was induced by the treatment with 2,2'-dipyridyl ketone in a dose-dependent manner. 4. These results indicate that dipyridyl compounds having different bridges between two aromatic moieties act as differential inducers of hepatic microsomal P450s and haem oxygenase.
PDF
