piperidines and Uterine-Diseases

Patients with inflammatory gynecological/obstetrical problems often complain of irritable bowel syndrome. The authors examined whether acute uterus irritation reflexively provokes colonic motility in rat preparations.. A modified colon manometry and striated abdominal muscle electromyogram activity in response to mustard oil (MO) instillation into the uterine horn were continuously recorded in anesthetized rats. The lumbosacral (L6-S1) dorsal horn was dissected to assess the level and the cellular location of phosphorylated NR2B subunit using Western blotting and immunofluorescence analysis, respectively. Finally, the uterine transient receptor potential A1 or spinal NR2B subunit was pharmacologically blocked to elucidate its roles.. MO (0.1%, 0.2 ml) injected into the lower uterine horn dramatically provoked colonic hypermotility characterized by rhythmic colonic contractions (about 3-4 contractions per 10 min, n = 7) accompanied by synchronized electromyogram firing in the abdominal muscle (about 4-5 folds of control, n = 7). In addition to provoking colonic hypermotility, MO administration also up-regulated phosphorylated (about 2-3 folds of control, n = 7), but not total, NR2B expression in the dorsal horn neurons. Both intrathecal Ro 25-6981 (a selective NR2B subunit antagonist; 10 μM, 10 μl) and intrauterine HC-030031 (a selective transient receptor potential A1 receptor antagonist; 30 mg/kg, 0.2 ml) injected before the MO instillation attenuated the MO-induced colonic hypermotility and spinal NR2B phosphorylation.. The comorbidity of gynecological/obstetrical and gastrointestinal problems is not coincidental but rather causal in nature, and clinicians should investigate for gynecological/urological diseases in the setting of bowel problems with no known pathological etiology.

Topics: Acetanilides; Acetic Acid; Animals; Blood Proteins; Blotting, Western; Colon; Dose-Response Relationship, Drug; Electromyography; Excitatory Amino Acid Antagonists; Female; Fluorescent Antibody Technique; Gastrointestinal Motility; Ghrelin; Irritants; Mustard Plant; Phenols; Phosphorylation; Piperidines; Plant Oils; Posterior Horn Cells; Pressure; Purines; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Spinal Cord; TRPA1 Cation Channel; TRPC Cation Channels; Uterine Diseases; Uterus

Our objective was to determine whether coating the amniotic membrane with halofuginone, a type 1 collagen synthase inhibitor, with or without the hemostasis-inducing substance chitosan, reduced the number and severity of adhesions in the rat uterine horn injury model. Sixty retired breeder Sprague-Dawley rats underwent midline laparotomy and a zone of ischemia was created in the left uterine horn of each animal. Rats were randomized to one of six treatment groups: (1) untreated control, (2) oxidized regenerated cellulose (Interceed®) (ORC), (3) plain amnion, (4) amnion coated on both sides with 0.5% solution of halofuginone (HAH), (5) amnion coated on one side with 0.5% halofuginone and on the other side with chitosan (CAH), or (6) amnion coated on both sides with chitosan (CAC). The zone of ischemia in each left uterine horn was wrapped in each treatment. Rats were sacrificed 2 weeks after laparotomy, and adhesions were counted and scored for severity. Data were analyzed using Chi square and a p < 0.05 was considered significant. Our results showed that there were no differences in the percentage of animals with adhesions in the untreated, ORC, plain amnion, or CAC groups. No adhesions formed in any animal in the HAH group and only 14% of the animals developed adhesions to the uterine horn in the CAH group (p < 0.05). The percentage of animals with moderate and severe adhesions did not differ between untreated controls and the ORC groups, but were significantly reduced in all four of the amnion groups: plain amnion, HAH, CAH, and CAC (p < 0.05). Amnion coated with halofuginone alone or in combination with chitosan reduced the percentage of animals with adhesions, as well as the percentage of animals with moderate and severe adhesions compared to untreated controls and the ORC group in the rat uterine horn injury model. Amnion alone or coated with chitosan reduced the percentage of rats with moderate and severe adhesions, but not the percentage of rats with adhesions of any type compared to both untreated controls and the ORC group in the rat uterine horn injury model.

Topics: Abdomen; Amnion; Angiogenesis Inhibitors; Animals; Cellulose, Oxidized; Chitosan; Female; Ischemia; Laparotomy; Piperidines; Postoperative Complications; Quinazolinones; Random Allocation; Rats; Rats, Sprague-Dawley; Tissue Adhesions; Treatment Outcome; Uterine Diseases; Uterus

The objective of this study was to evaluate the effects of halofuginone-a specific inhibitor of collagen type I synthesis-in preventing uterine horn adhesion formation in rats.. Adhesions were induced by scraping the rat uterine horns until capillary bleeding occurred. Halofuginone was either injected intraperitoneally or administered orally. The number and severity of the adhesions were scored. Collagen alpha1(I) gene expression was evaluated by in situ hybridization; total collagen was estimated by sirius red staining. Collagen synthesis in response to halofuginone was evaluated in cells cultured from the adhesions.. Regardless of the administration procedure, halofuginone reduced significantly the number and severity of the adhesions in a dose-dependent manner. Halofuginone prevented the increase in collagen alpha1(I) gene expression observed in the rats that underwent this procedure, thus affecting only the newly synthesized collagen but not the resident collagen. In cells derived from rat uterine horn adhesions, halofuginone induced dose-dependent inhibition of collagen synthesis.. Upregulation of collagen synthesis appears to play a critical role in the pathophysiologic mechanism of adhesion formation. Halofuginone could be used as an important means of understanding the role of collagen in adhesion formation and might become a novel and promising antifibrotic agent for preventing adhesion formation after pelvic surgery.

Topics: Administration, Oral; Animals; Collagen; Female; Gene Expression; In Situ Hybridization; Injections, Intraperitoneal; Piperidines; Protein Synthesis Inhibitors; Quinazolines; Quinazolinones; Rats; Rats, Sprague-Dawley; Tissue Adhesions; Uterine Diseases

Topics: Adult; Aged; Anesthesia, Endotracheal; Anesthesia, Epidural; Blood Pressure Determination; Chlorpromazine; Cholecystectomy; Diphenhydramine; Electrocardiography; Ether; Female; Humans; Hydroxybutyrates; Intestines; Liver; Meperidine; Middle Aged; Neuroleptanalgesia; Piperidines; Preanesthetic Medication; Propionates; Sodium; Solutions; Tetracaine; Urologic Diseases; Uterine Diseases; Uterine Neoplasms