ABSTRACT
Progesterone is a steroidal hormone that is produced from the corpus luteum of the ovaries and from the placenta. The main function of progesterone is to promote the secretory differentiation in the endometrium of the uterus and to maintain pregnancy by inhibiting uterine contractions throughout pregnancy. Progesterone performs its actions by activating the classical progesterone nuclear receptors that affect gene transcription and by the non-classical activation of cell surface membrane receptors that accounts for the rapid actions of progesterone. Besides the reproductive roles of progesterone, it exerts functions in many tissues and systems such as the nervous system, the bone, the vascular system, and the gastrointestinal (GI) tract. This review will summarize the recent literature that investigated the role of progesterone in GI tract motility. Most literature indicates that progesterone exerts an inhibitory role on gut smooth muscle cells in part by elevating nitric oxide synthesis which induces relaxation in smooth muscle. Moreover, progesterone inhibits the signaling pathways that lead to contraction such as Rho kinase inhibition. These data serve as a quick resource for the future directions of progesterone research that could lead to better understanding and more effective treatment of gender-related GI tract motility disorders.
Subject(s)
Progesterone , Receptors, Progesterone , Endometrium/metabolism , Female , Gastrointestinal Motility , Humans , Pregnancy , Progesterone/metabolism , Progesterone/pharmacology , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism , Uterus/metabolismABSTRACT
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is marked by destruction of alveolar architecture. Preclinical modelling for COPD is challenging. Chronic cigarette smoke exposure, the reference animal model of COPD, is time-inefficient, while exposure to waterpipe smoke (WPS), a surging smoking modality, was not fully tested for its histopathological pulmonary consequences. Since alveolar damage and pulmonary vascular endothelial dysfunction are integral to COPD pathology, lung histopathological effects of WPS were temporally evaluated, alone or in combination with vascular endothelial growth factor receptor (VEGFR) inhibition in mice. MATERIALS AND METHODS: Mice were exposed to WPS, 3 hours/day, 5 days/week, for 1, 2, 3, or 4 months. Another group of mice was exposed to WPS for 1 month, while being subjected to injections with the VEGFR blocker Sugen5416 (SU, 20 mg/kg) 3 times weekly. Control mice were exposed to fresh air in a matching inhalation chamber. Histopathological assessment of COPD was performed. Alveolar destructive index (DI) was counted as the percentage of abnormally enlarged alveoli with damaged septa per all alveoli counted. Mean linear intercept (MLI) was calculated as a measure of airspace enlargement. RESULTS: Exposure to WPS resulted in significant increases in alveolar DI and MLI only after 4 months. Lung inflammatory score was minimal across all time-points. Importantly, combination of WPS and SU resulted in significantly increased DI, MLI, and inflammatory scores as early as 1 month post exposure. CONCLUSIONS: Combined exposure to WPS and SU results in COPD picture, highlighting the role of pulmonary vascular endothelial dysfunction in the disease.
Subject(s)
Endothelium, Vascular , Pulmonary Alveoli , Pulmonary Disease, Chronic Obstructive , Receptors, Vascular Endothelial Growth Factor/metabolism , Water Pipe Smoking , Animals , Disease Models, Animal , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Mice , Mice, Inbred BALB C , Pulmonary Alveoli/metabolism , Pulmonary Alveoli/pathology , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/pathology , Water Pipe Smoking/metabolism , Water Pipe Smoking/pathologySubject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Nasal Polyps/complications , Pregnadienediols/administration & dosage , Rhinitis/drug therapy , Sinusitis/drug therapy , Administration, Topical , Adult , Chronic Disease , Cohort Studies , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Mometasone Furoate , Nebulizers and Vaporizers , Rhinitis/complications , Sinusitis/complicationsABSTRACT
BACKGROUND: Ano-rectal disorders are common in the general population. Although they are not life threatening conditions, they do represent a social stigma and a reduced quality of life for the sufferer. The underlying physiology of muscle function contributing to ano-rectal competence is complex and there is room for a much better understanding so that treatments can improve. METHODS: A cylindrically shaped, liquid filled bag (12 cm long), mounted on a catheter was inserted into the anus and positioned straddling the ano-rectal region in 20 healthy volunteers (10 females). Series of volume-controlled distensions (40 mL min(-1) to 40 mL) were carried out and data on 16 CSA at 5 mm apart and bag pressure were recorded. Provocative tests using squeeze and cough at bag volumes of 20, 30, and 40 mL were carried out. KEY RESULTS: Ramp distension of the anal canal showed that the opening pressure for females (mean, 11 mmHg) was higher than for males (mean, 5 mmHg) (P < 0.001). Geometric profile of the anal canal at low distension volumes showed narrow bands at proximal and distal ends of the anal profile and shortening of a middle narrow zone at higher volumes. Inter-individual differences were observed in the behavior of the proximal end and the distal end of the anal profile during squeeze. CONCLUSIONS & INFERENCES: This distensibility technique provides an important new way of studying the anal canal and hence may have a role in testing sphincter competence in patients with disorders.
