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Int J Toxicol. 2003 May-Jun;22(3):207-13.
An in vitro bioassay for xenobiotics using the SXR-driven human CYP3A4/lacZ reporter gene.

Lee MR, Kim YJ, Hwang DY, Kang TS, Hwang JH, Lim CH, Kang HK, Goo JS, Lim HJ, Ahn KS, Cho JS, Chae KR, Kim YK.

Division of Laboratory Animal Resources, National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul, Korea.

The dose and time effect of nine xenobiotics, including 17beta-estradiol, corticosterone, dexamethasone, progesterone, nifedipine, bisphenol A, rifampicin, methamphetamine, and nicotine were investigated, in vitro, using human steroid and xenobiotics receptor (SXR)-binding sites on the human CYP3A4 promoter, which can enhance the linked lacZ reporter gene transcription. To test this, liver-specific SAP (human serum amyloid P component)-SXR (SAP/SXR) and human CYP3A4 promoter-regulated lacZ (hCYP3A4/lacZ) constructs were transiently transfected into HepG2 and NIH3T3 cells to compare the xenobiotic responsiveness between human and nonhuman cell lines. In the HepG2 cells, rifampicin, followed by corticosterone, nicotine, methamphetamine, and dexamethasone, exhibited enhanced levels of the lacZ transcript, whereas those of bisphenol A and nifedipine were found to be reduced. No significant responses were observed with 17beta-estradiol or progesterone. In addition, 17beta-estradiol and progesterone did not change the levels of the lacZ transcripts in the HepG2 cells, but did induce significant increases in the transcripts of the NIH3T3 cells. Treatment with corticosterone and dexamethasone, which were highly expressed in the HepG2 cells, did not affect the levels of the lacZ transcript in NIH3T3 cells. These results show that lacZ transcripts can be measured, rapidly and reproducibly, using reverse transcriptase-polymerase chain reaction (RT-PCR) based on the expression of the hCYP3A4/lacZ reporter gene, and was mediated by the SXR. Thus, this in vitro reporter gene bioassay is useful for measuring xenobiotic activities, and is a means to a better relevant bioassay, using human cells, human genes and human promoters, in order to get a closer look at actual human exposure.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12851153&dopt=Abstract [PubMed - in process]

Methods Find Exp Clin Pharmacol. 2003 Jun;25(5):383-5.
Transdermal nicotine increases heart rate after endotracheal intubation.

Puura A.

Department of Anesthesiology, Valkeakoski District Hospital, Kangasala, Finland. arto.puurshp.fi

Transdermal nicotine reduces perioperative withdrawal symptoms when smoking is forbidden. We evaluated the influence of a transdermal nicotine system on cardiovascular response after endotracheal intubation. The study design was prospective, randomized, double-blind and placebo- controlled. Sixty healthy smokers scheduled for minor surgery under general anesthesia were divided into two groups. The first group received a 21 mg/day transdermal nicotine system while the second group received a placebo transdermal system. After induction with standardized doses of fentanyl, thiopental and atracurium, the patients were intubated immediately when EMG-response decreased to 10% of the initial control. Heart rate and noninvasive arterial pressures were recorded 1 min and 5 min after intubation. The transdermal nicotine system significantly increased heart rate compared with the control group without nicotine substitution. Since the transdermal nicotine system increases heart rate it should not be used if tachycardia is potentially dangerous, such as in patients with ischemic heart disease. (c) 2003 Prous Science. All rights reserved.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12851662&dopt=Abstract [PubMed - in process]

Acta Pharmacol Sin. 2003 Jul;24(7):657-62.
Muscarinic receptor activities potentiated by desensitization of nicotinic receptors in rat superior cervical ganglia.

Wan Q, Luo ZP, Wang H.

Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.

AIM: The influences of desensitized nicotinic acetylcholine receptors (nAChR) on the activities of muscarinic acetylcholine receptors (mAChR) were investigated in single cultured rat superior cervical ganglion. METHODS: Whole-cell patch-clamp techniques were used. RESULTS: An inward current was induced by nicotine 80 micromol/L in the sympathetic neurons and desensitized rapidly after the prolonged exposure to nicotine. An outward current was induced by oxotremorine 100 micromol/L or pilocarpine 100 micromol/L and it showed no desensitization after exposure to its agonists. After nAChR desensitized completely, the current evoked by oxotremorine was increased significantly compared with its control. There were (42 38) % (n=8, P<0.05) and (165 66) % (n=5, P<0.01) increases induced by 100 and 500 micromol/L oxotremorine, respectively. Similar results were also obtained from pilocarpine and the current evoked by 100 micromol/L pilocarpine increased by (66 33) % (n=6, P<0.05) after nAChR desensitization. Once nicotine was removed, nAChR recovered from desensitization gradually and the enhanced mAChR activity also subsided along with it. Furthermore, the facilitatory effect of desensitized nAChR on mAChR activity could be prevented by mecamylamine. CONCLUSION: The activities of mAChR to its agonists were potentiated by the desensitization of nAChR in rat sympathetic neurons

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12852831&dopt=Abstract [PubMed - in process]

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Saw palmetto berry is a widely known herbal supplement for hair loss problems. However, there are a number of great anecdotal herbs that people used for thousands of years stop hair loss and start hair growth. Numerous anecdotal cases have demonstrated that this herbal formula based on Chinese herbs actually improves the age-related hair thinning and hair loss for a significant fraction of people who take it diligently. It is unknown how Hair Million herbs actually stop hair loss, and promote hair growth, No scientific research or placebo controlled clinical trials have been conducted. Nonetheless, a number of people agree that it works.

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