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References: Laxative

Masui. 1998 Jul;47(7):817-23.
[Pharmacokinetics of PF-402, sustained-release morphine capsule, in cancer patients with pain]

[Article in Japanese]

Ogawa H, Hiraga K, Takeda F.

Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical College.

A once-daily dose of PF-402 60 mg and twice-daily doses of sustained-release morphine sulfate tablets (MSC) 30 mg were repeatedly administered in cancer patients in a cross-over design. Their plasma concentrations were measured, and the pharmacokinetics of PF-402 and MSC were compared. A total of 7 subjects in the study were taking commercially sold MSC 60 mg daily (30 mg twice-daily) prior to the study and had "mild" or "no" pain at the start of the study. Plasma morphine concentrations of PF-402 were longer-lasting and showed smaller fluctuations than those of MSC. Repeated administration of the same daily doses of PF-402 and MSC produced similar plasma concentrations for periods of 24 hr and 12 hr. PF-402 administration produced a Tmax of 7.4 hr, and an MRT of 9.8 hr, all longer than those with MSC. Moreover, no significant difference was observed in AUC between PF-402 and MSC. These results indicate that the sustained-release characteristics of PF-402 are superior to those of MSC, and that the two drugs have a similar absorption pattern. Adverse drug reactions (ADRs) were observed in all 7 subjects and consisted of 6 incidences of constipation, 3 incidences of nausea, 2 incidences of itching, and 1 incidence each of vomiting and somnolence. Study drug administration was not discontinued in any case due to ADRs, and no symptoms indicating physical or psychic drug dependence were observed. No abnormal laboratory values related to study drug administration were observed. The above results indicate that once-daily administration of PF-402 is sufficient to maintain plasma concentrations obtained with twice-daily administration of MSC. As the safety of PF-402 is confirmed, the drug is considered to be

Br J Pharmacol. 1998 Aug;124(7):1516-22.
Glycodermorphins: opioid peptides with potent and prolonged analgesic activity and enhanced blood-brain barrier penetration.

Negri L, Lattanzi R, Tabacco F, Scolaro B, Rocchi R.

Institute of Medical Pharmacology, University La Sapienza, Rome, Italy.

1. In order to improve the in vivo stability of the opioid peptide dermorphin we synthesized O-betaglucosylated analogs ([Ser7-O-betaGlc]dermorphin and [Ser7-O-betaGlc(Ac)4]-dermorphin) and C-alphagalactosylated analogs ([Ala7-C-alphaGal]dermorphin and [Ala7-C-alphaGal(Ac)4]-dermorphin). 2. O- and C-glycosylation of dermorphin halved the peptide affinity for brain mu-opioid receptors and the biological potency in guinea-pig ileum assay (GPI). Despite their lower opioid receptor affinity, when administered intracerebroventricularly (i.c.v., 8-40 pmol) and subcutaneously (s.c., 0.5-3 micromol kg(-1)) in rats, glycosylated analogs were two times more potent than dermorphin in reducing the nociceptive response to radiant heat. Acetylation of sugar hydroxyl groups reduces 5-10 times both biological activity on GPI and mu-receptor affinity, whereas the antinociceptive potency was equal to (i.c.v.) or only two-three times lower (s.c.) than dermorphin potency. 3. Blood-Brain Barrier Permeability Index (BBB-PI) of the glycodermorphins was significantly higher than that of dermorphin, indicating a facilitated entry into the brain: O-beta-linked glucoconiugates are expected to enter CNS by the glucose transporter GLUT-1 of the endothelial barrier. However the calculated BBB-PI for the C-alphagalactoside was about two times higher than that of the O-betaglucoside, excluding the implication of GLUT-1 that is known to be selective for O-beta-links and preferring for the exose glucose. 4. The enhanced brain permeability with the subsequent decrease in peripheral dosage of these opioid peptides did not result in lowering constipation.

Laxative online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9723966&dopt=Abstract constipation laxative colon cleansing

Dig Dis Sci. 1998 Aug;43(8):1794-9.
Abnormal vagal cholinergic function and psychological behaviors in irritable bowel syndrome patients: a hospital-based Oriental study.

Lee CT, Chuang TY, Lu CL, Chen CY, Chang FY, Lee SD.

Department of Medicine and Rehabilitation, Veterans General Hospital-Taipei, National Yang-Ming University School of Medicine, Taiwan.

Irritable bowel syndrome (IBS) patients in Western countries usually manifest autonomic nerve dysfunctions and abnormal psychological behaviors. The purpose of this study was to assess whether Oriental IBS patients with predominant bowel symptoms also exhibited similar abnormalities. We enrolled 40 IBS patients from the outpatient clinic and 20 controls with normal daily bowel habit for study. The IBS patients were further divided according to their predominant bowel habit: 20 were constipation-predominant and 20 were diarrhea-predominant. Sympathetic function was evaluated by sympathetic skin response (SSR) while vagal cholinergic function was determined by measuring R-R interval variation (RRIV) in electrocardiography during rest and deep breathing. Psychological parameters were assessed by scales of the Minnesota Multiphasic Personality Inventory (MMPI) and the Hopkins Symptom Checklist (HSCL-90). IBS patients, despite their bowel habit, showed normal SSR response. RRIV during deep breathing was significantly lower in constipation-predominant IBS patients than in controls or diarrhea-predominant IBS patients (16.5+/-3.1% vs 20.5+/-4.8% and 21.5+/-4.6%, P < 0.001). IBS patients also exhibited abnormal MMPI measuring scores on depression, hysteria, paranoia, and masculinity/femininity scales. In addition, they also had more severe psychological distress in the items of HSCL-90 measurement. In conclusion, vagal dysfunction characterizes Oriental constipation-predominant IBS patients seeking medical help. Abnormal psychoneurotic profiles also exist in these IBS patients, irrespective of their bowel habits.

Laxative online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9724171&dopt=Abstract constipation laxative [PubM

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