COVID-19 vaccination and transmission patterns among pregnant and postnatal women during the fifth wave of COVID-19 in a tertiary hospital in Hong Kong.

INTRODUCTION: Vaccination is a key strategy to control the coronavirus disease 2019 (COVID-19) pandemic. Safety concerns strongly influence vaccine hesitancy. Disease transmission during pregnancy could exacerbate risks of preterm birth and perinatal mortality. This study examined patterns of vaccination and transmission among pregnant and postnatal women during the fifth wave of COVID-19 in Hong Kong. METHODS: The Antenatal Record System and Clinical Management System of the Hospital Authority was used to retrieve information concerning the demographic characteristics, vaccination history, COVID-19 status, and obstetric outcomes of women who were booked for delivery at Queen Mary Hospital in Hong Kong and had attended the booking antenatal visit from 1 July 2021 to 30 June 2022. RESULTS: Among 2396 women in the cohort, 2006 (83.7%), 1843 (76.9%), and 831 (34.7%) had received the first, second, and third doses of COVID-19 vaccine, respectively. Among 1012 women who had received the second dose, 684 (67.6%) women were overdue for their third dose. There were 265 (11.1%) reported COVID-19 cases. Women aged 20 to 29 years had a low vaccination rate but the highest disease rate (19.1%). The disease rate was more than tenfold higher in women who had no (20.3%) or incomplete (18.8%) vaccination, compared with women who had complete vaccination (2.1%; P<0.001). CONCLUSION: Acceptance of COVID-19 vaccination was low in pregnant women. Urgent measures are needed to promote vaccination among pregnant women before the next wave of COVID-19.

Pictorial Blood Loss Assessment Chart for evaluating heavy menstrual bleeding in Asian women.

INTRODUCTION: Heavy menstrual bleeding is a common gynaecological problem, but some women may prefer not to articulate their menstrual problems. The objective of this study was to evaluate the usefulness and acceptability of the Pictorial Blood Loss Assessment Chart (PBAC) as a selfscreening tool in evaluation of menstrual blood loss among Asian women in Hong Kong. METHODS: This prospective cohort study recruited 206 women from the general gynaecology ward and out-patient clinic: 118 had self-perceived heavy menstrual bleeding and 88 had self-perceived normal menstrual flow. Participants were asked to fill in the PBAC for one menstrual cycle. RESULTS: Compared with women who had self-perceived normal menstrual flow, women with self-perceived heavy menstrual bleeding had significantly higher total PBAC scores and numbers of flooding episodes, larger clot sizes and numbers, more days of bleeding, and lower haemoglobin levels. Receiver-operating characteristic curve analysis demonstrated good pairwise associations of self-perceived symptoms with PBAC score and haemoglobin level. CONCLUSIONS: The PBAC can be used to differentiate self-perceived heavy and normal menstrual bleeding in Asian women in Hong Kong. It can also serve as an additional indicator of possible heavy menstrual bleeding to alert women of the need to seek early medical attention.

Comparison of antral follicle count and serum anti Müllerian hormone level for determination of gonadotropin dosing in in-vitro fertilization: randomized trial.

OBJECTIVE: To compare the proportion of women achieving a desired ovarian response following ovarian stimulation when gonadotropin dosing was determined based on antral follicle count (AFC) vs serum anti-Müllerian hormone (AMH) level, in women undergoing in-vitro fertilization (IVF) using the gonadotropin-releasing hormone (GnRH) antagonist protocol. METHODS: This was a randomized double-blind trial carried out in a university-affiliated assisted reproduction unit. A total of 200 women undergoing their first IVF cycle using the GnRH-antagonist protocol between April 2016 and February 2018 were randomized to determination of gonadotropin dosing based on either AFC or serum AMH level measured in the pretreatment cycle 1 month before the IVF cycle. Patients underwent IVF as per our center's standard protocol. The proportion of subjects achieving a desired ovarian response, defined as retrieval of six to 14 oocytes, was compared between the two study arms. Subgroup analysis of patients with baseline AFC > 5 and those with baseline AFC ≤ 5 was performed. Concordance in AFC and AMH categorization between the pretreatment cycle and the ovarian-stimulation cycle was assessed using Cohen's kappa (κ). RESULTS: There was no significant difference in the proportion of patients achieving a desired ovarian response between the AFC (54%) and AMH (49%) groups (P = 0.479). The median number of oocytes retrieved was nine vs seven (P = 0.070), and the median follicular output rate was 0.54 vs 0.55 (P = 0.764) in the AFC and AMH groups, respectively. Similar findings were observed on subgroup analysis of subjects with AFC ≤ 5 and AFC > 5 at the start of ovarian stimulation (P > 0.05 for all comparisons). There was moderate concordance between AFC and AMH measured in the pretreatment cycle and the stimulation cycle (κ = 0.478 and 0.587, respectively). CONCLUSION: The proportion of women achieving a desired ovarian response following ovarian stimulation using the GnRH-antagonist protocol is similar when the gonadotropin-dosing algorithm used is based on AFC or serum AMH level. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Comparación del recuento de folículos sinusales y el nivel de la hormona antimulleriana en el suero para la determinación de la dosis de gonadotrofina en la fecundación in vitro: ensayo aleatorizado OBJETIVO: Comparar la proporción de mujeres que logran una respuesta ovárica deseada tras la estimulación del ovario cuando se determinó la dosis de gonadotrofina en función del recuento de folículos sinusales (AFC, por sus siglas en inglés) frente al nivel de la hormona antimulleriana (HAM) en el suero, en mujeres que se sometieron a una fecundación in vitro (FIV) mediante el protocolo de antagonistas de la hormona liberadora de gonadotropina (GnRH, por sus siglas en inglés). MÉTODOS: Se trata de un ensayo aleatorizado doble ciego realizado en una unidad de reproducción asistida afiliada a una universidad. Un total de 200 mujeres que se sometieron a su primer ciclo de FIV y utilizaron el protocolo de antagonistas de la GnRH entre abril de 2016 y febrero de 2018 fueron asignadas al azar a la determinación de la dosis de gonadotrofina basada en el nivel de AFC o de HAM en suero, medidos en el ciclo de pretratamiento un mes antes del ciclo de FIV. Las pacientes se sometieron a una FIV según el protocolo estándar de nuestro centro. La proporción de mujeres que lograron una respuesta ovárica deseada, definida como la recuperación de seis a 14 ovocitos, se comparó entre las dos ramas del estudio. Se realizó un análisis de subgrupos de las pacientes con AFC de base >5 y de aquellas con AFC de base ≤5. La concordancia en la categorización del AFC y la HAM entre el ciclo de pretratamiento y el ciclo de estimulación ovárica se evaluó utilizando la medida estadística kappa de Cohen (κ). RESULTADOS: No hubo diferencias significativas en la proporción de pacientes que lograron una respuesta ovárica deseada entre los grupos de AFC (54%) y HAM (49%) (P=0,479). La mediana del número de ovocitos recuperados fue de nueve frente a siete (P=0,070), y la mediana de la tasa de producción folicular fue de 0,54 frente a 0,55 (P=0,764) en los grupos AFC y HAM, respectivamente. Se observaron hallazgos similares en el análisis de subgrupos de pacientes con AFC ≤5 y AFC >5 al comienzo de la estimulación ovárica (P>0,05 para todas las comparaciones). Se observó una concordancia moderada entre el AFC y la HAM medidos en el ciclo de pretratamiento y el ciclo de estimulación (κ=0,478 y 0,587, respectivamente). CONCLUSIÓN: La proporción de mujeres que logran una respuesta ovárica deseada después de la estimulación ovárica utilizando el protocolo de antagonistas de la GnRH es similar cuando el algoritmo de dosificación de gonadotrofina utilizado se basa en el nivel del AFC o de la HAM en suero.

Adaptive cytoprotection and the brain-gut axis.

Adaptive cytoprotection is a concept to counteract against the gastric mucosal injury caused by stress, strong irritants and drugs such as non-steroidal anti-inflammatory drugs. The process is mediated through diverse mediators and mechanisms. Studies on adaptive cytoprotection began from the discovery of prostaglandin (PG)-dependent and PG-independent pathways, followed by the investigation on the types and concentrations of mild irritants to be used. Upon the confirmation on the importance of the vagus nerve and the vago-vagal pathway in regulating the mucosal protective actions of the mild irritants, individual participating mediators for the neuronal modulatory processes were explored, including peptide neurotransmitters such as calcitonin gene-related peptide and substance P. Further correlation with the sympathetic nervous system, the sensory afferent neurons and the enteric nervous system of the gastric mucosa had been made. A close working relationship between the hypothalamic-pituitary-adrenal axis, the autonomic nervous system and the enteric nervous system was then proposed, with concurrent regulation of PG, nitric oxide and sensory neuropeptides by different mild irritants. Apart from these conventional concepts, there are now contemporary ideas on newer forms of adaptive cytoprotection such as ischemic preconditioning and heat-shock proteins, which will cast new light to novel approaches in facilitating gastric mucosal protection.

Intrapulmonary shunt in the course of pediatric liver transplantation.

The hepatopulmonary syndrome occurs when an intrapulmonary shunt (IPS) causes hypoxemia in patients with cirrhosis. Because IPS has not been clearly defined in children, we investigated the prevalence, clinical characteristics, and outcomes of IPS in children undergoing liver transplantation (OLT). Of the 107 pediatric OLT recipients between December 1994 and March 2005, 18 (16.8%) had IPS, as evaluated by contrast-enhanced echocardiography (CEE) at 9 months to 16 years of age. The degree of IPS was classified into five grades according to the extent of microbubbles in the left ventricle, with significant IPS defined as grade II or higher. Baseline characteristics, including serum total bilirubin, albumin, aminotransferase, and prothrombin time, did not differ in patients with or without IPS. The patients with IPS had significantly lower Pao2 and Sao2, longer duration of mechanical ventilation and hospital stay, and higher postoperative morbidity and mortality than patients without IPS (P < .05 each), but there were no other significant differences between the groups. The six patients with significant IPS (one grade II, three grade III, and two grade IV) showed a significantly greater morbidity and mortality than patients with grade I IPS (P < .05). Most of the positive CEE findings of IPS regressed within 6 months after OLT. These findings indicated that IPS is not uncommon among children undergoing OLT, but is reversible. Because severe IPS may increase patient morbidity and mortality, early assessment of IPS status using CEE is essential for pediatric OLT candidates.

Pathogenesis, Experimental Models and Contemporary Pharmacotherapy of Irritable Bowel Syndrome: Story About the Brain-Gut Axis.

BACKGROUND: Although the precise pathophysiology of irritable bowel syndrome (IBS) remains unknown, it is generally considered to be a disorder of the brain-gut axis, representing the disruption of communication between the brain and the digestive system. The present review describes advances in understanding the pathophysiology and experimental approaches in studying IBS, as well as providing an update of the therapies targeting brain-gut axis in the treatment of the disease. METHODS: Causal factors of IBS are reviewed. Following this, the preclinical experimental models of IBS will be introduced. Besides, both current and future therapeutic approaches of IBS will be discussed. RESULTS: When signal of the brain-gut axis becomes misinterpreted, it may lead to dysregulation of both central and enteric nervous systems, altered intestinal motility, increased visceral sensitivity and consequently contributing to the development of IBS. Interference of the brain-gut axis can be modulated by various psychological and environmental factors. Although there is no existing animal experiment that can represent this complex multifactorial disease, these in vivo models are clinically relevant readouts of gastrointestinal functions being essential to the identification of effective treatments of IBS symptoms as well as their molecular targets. Understanding the brain-gut axis is essential in developing the effective therapy for IBS. Therapies include improvement of GI motor functions, relief of visceral hypersensitivity and pain, attenuation of autonomic dysfunctions and suppression of mucosal immune activation. CONCLUSION: Target-oriented therapies that provide symptomatic, psychological and physiological benefits could surely help to improve the quality of life of IBS patients.

Coadministration of angiopoietin-1 and vascular endothelial growth factor enhances collateral vascularization.

Using growth factors to induce vasculogenesis is a promising approach in the treatment of ischemic legs and myocardium. Because the vasculogenesis requires a cascade of growth factors, their receptors, and intracellular signals, such therapies may require the application of more than a single growth factor. We examined the effect of 2 endothelial cell-specific growth factors, angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF), on primary cultured porcine coronary artery endothelial cells. VEGF, but not Ang1, increased DNA synthesis and cell number. Ang1 or VEGF induced migration and sprouting activity, increased plasmin and matrix metalloproteinase-2 secretion, and decreased tissue inhibitors of metalloproteinase type 2 secretion. A combination of the submaximal doses of Ang1 and VEGF enhanced these effects and was more potent than the maximal dose of either alone. In a rabbit ischemic hindlimb model, a combination of Ang1 and VEGF gene delivery produced an enhanced effect on resting and maximal blood flow and capillary formation that was greater than that of either factor alone. Angiographic analyses revealed that larger blood vessels were formed after gene delivery of Ang1 or Ang1 plus VEGF than after VEGF gene delivery. These results suggest that combined treatment of Ang1 and VEGF could be used to produce therapeutic vascularization.

The role of exercise training for patients with heart failure.

Heart failure (HF) is characterized by dyspnea and fatigue leading to exercise intolerance. HF patients have been advised to avoid exercise because of concerns about detrimental cardiac effects. However, in many studies on the effects of exercise training HF patients have demonstrated beneficial outcomes. Furthermore, exercise training has been found to be safe. Recent studies have demonstrated that exercise training might reduce morbidity and mortality. Although these data are promising, confirmation is required from a large clinical trial powered to examine the effects of exercise training on mortality and morbidity. The "Heart Failure - A Controlled Trial Investigating Outcomes of Exercise TraiNing" (HF-ACTION) trial, a large randomized controlled clinical trial, will answer that question. Standardized guidelines for exercise training HF patients have not been established. Exercise training should be individualized according to the results of the exercise test. Ideally, the exercise program should be initiated in the setting of a supervised program followed by a home-based program. Each patient should have a tailored activity program based on a prescription for the frequency of each session, the intensity, duration of each session, and modalities to be used. Exercise training should involve aerobic exercise. Resistance exercise and interval training might be an acceptable method for HF patients; however, more studies are required for these types of exercise programs.

The correlation of the weakening effect on gastric mucosal integrity by 5-HT with neutrophil activation.

The effects of 5-hydroxytryptamine (5-HT) on ethanol-induced gastric mucosal damage and on epithelial and vascular integrity were investigated. Male Sprague-Dawley rats were administered with 5-HT (5 or 10 mg/kg, IP) 30 min prior to the challenge with ethanol (40% v/v, 10 ml/kg, PO). 5-HT dose dependently aggravated ethanol-induced injury in the gastric mucosa. Both xanthine oxidase (XO) and myeloperoxidase (MPO) activities in the mucosa were significantly increased with the high dose of 5-HT, which also potentiated the elevation of these enzyme activities by ethanol. However, the mucosal superoxide dismutase activity was left unaltered. In neutropenic (antineutrophil serum-treated) animals, the ethanol-induced gastric mucosal injury was significantly ameliorated, with or without the pretreatment of 5-HT (10 mg/kg). In addition, the effect of 5-HT on the activity of MPO, but not of XO, was also attenuated in these animals. In the ex vivo gastric chamber study on pentobarbital-anesthetized animals, volume of gastric secretion was significantly decreased in the 5-HT-treated groups, with further reduction after ethanol incubation. Transmucosal potential difference (PD) was significantly reduced in 5-HT-treated rats, which also potentiated the ethanol-induced drop in PD. Nevertheless, 5-HT dose dependently increased mucosal vascular permeability and further enhanced during ethanol incubation. These findings suggest that 5-HT adversely affects the defense mechanisms of the gastric mucosa by reducing the secretory function of the mucosal cells and to weaken the epithelial and vascular integrity. Neutrophil activation appears to be responsible for the detrimental effects of 5-HT partly through the elevation in MPO activity. The increase in mucosal XO activity by 5-HT may induce free radical production and possibly modulate the ulcerogenic processes.

Supraventricular tachycardia mechanisms and their age distribution in pediatric patients.

To better define the natural history of supraventricular tachycardia (SVT) in young patients, age distribution of SVT mechanisms was examined in 137 infants, children and adolescents. Patients with a history of cardiac surgery or neuromuscular diseases were excluded. An electrophysiologic study was performed in each patient: transesophageal (110 patients) or transvenous (14 patients) or both (13 patients). Mechanisms were classified as SVT using accessory atrioventricular (AV) connection (SVT using accessory connection, including orthodromic and antidromic reciprocating tachycardia), primary atrial tachycardia (including chaotic, automatic and reentrant atrial tachycardia), and tachycardia due to reentry within the AV node. SVT using accessory connection occurred in 100 of 137 patients (73%) and was the most prevalent mechanism. Primary atrial tachycardia and reentry within the AV node were present in 19 of 137 (14%) and 18 of 137 (13%) patients, respectively. Using a multinomial logit model, relative probabilities for tachycardia mechanisms for 5 age groups--prenatal, less than 1, 1 to 5, 6 to 10 and greater than 10 years--were determined. Primary atrial tachycardia (11 to 16%) and SVT using accessory connection (58 to 84%) appeared throughout infancy, childhood and adolescence. On the other hand, tachycardia due to reentry within the AV node (0 to 31%) rarely appeared before age 2 years. Mechanisms of SVT appear to have age-dependent distributions. SVT using accessory connection is the most common mechanism in young patients. We speculate that the propensity to tachycardia due to reentry within the AV node occurs during postnatal development.

The vascular and glandular organoprotective properties of metronidazole in the rodent stomach.

BACKGROUND: The gastroprotective action of metronidazole, an antimicrobial used in the therapy against Helicobacter pylori infection, is unclear. Thus, the aim of the present investigation was to study the organoprotective action and antiulcer mechanisms of this drug in rodents. METHODS AND RESULTS: Metronidazole (10 mg/kg), given either per os or intraperitoneally, 30 min beforehand, reduced ethanol (40%, 10 mL/kg, p.o.)-induced gastric mucosal damage in male rats. Likewise, oral administration of metronidazole dose-dependently attenuated the indomethacin (30 mg/kg, p.o.)-induced gastric lesion formation and the concurrent depletion of mucosal mucus. However, metronidazole did not affect the basal mucosal prostaglandin E2 content. In an ex vivo gastric chamber preparation, 40% ethanol incubation markedly lowered transmucosal potential difference and increased mucosal vascular permeability in rat stomachs. Incubation with all doses of metronidazole did not modulate gastric mucosal blood flow nor transmucosal potential difference, either before or after ethanol treatment. Nevertheless, the increase in vascular permeability by 40% ethanol was significantly alleviated by either p.o. or i.p. metronidazole pretreatment. In addition, exposure of the isolated rabbit gastric gland preparation to metronidazole (10(-5) and 10(-4) M) significantly attenuated the damaging action of 10% ethanol. CONCLUSION: It is concluded that metronidazole possesses a direct vascular and glandular organoprotective property in the rodent stomach. However, the anti-ulcer action does not appear to involve prostaglandins nor act through the improvement of gastric mucosal blood flow. Preservation of intramucosal mucus may partly contribute to the prevention of indomethacin-induced ulceration in rats.

Protective role of cyclooxygenase inhibitors in the adverse action of passive cigarette smoking on the initiation of experimental colitis in rats.

Clinical and experimental findings had indicated that cigarette smoke exposure, and cyclooxygenase-2, are strongly associated with inflammatory bowel disease. The present study aimed to evaluate the role of cyclooxygenase-2 in the pathogenesis of experimental inflammatory bowel disease as well as in the adverse action of cigarette-smoke exposure. Rats were pretreated with different cyclooxygenase-2 inhibitors (indomethacin, nimesulide, or SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide)) along with cigarette-smoke exposure before 2,4,6-trinitrobenzenesulfonic acid-enema. Results indicated that pretreatment with cyclooxygenase-2 inhibitors not only protected against 2,4,6-trinitrobenzenesulfonic acid-induced inflammatory bowel disease, but also attenuated the potentiating effect of cigarette-smoke exposure on colonic damage. Furthermore, the colonic cyclooxygenase-2 protein and mRNA expression was markedly induced by 2,4,6-trinitrobenzenesulfonic acid-enema, and it was potentiated further by cigarette-smoke exposure, while the cyclooxygenase-1 expression was not changed. The present study suggests that the highly induced cyclooxygenase-2 expression not only plays a pathogenic role in 2,4,6-trinitrobenzenesulfonic acid-induced inflammatory bowel disease, but also contributes to the adverse action of cigarette-smoke exposure on this disorder.

Endogenous mediators in adaptive cytoprotection against ethanol-induced gastric gland damage in rabbits.

The present study determined the participation of different endogenous mediators in adaptive cytoprotection against gastric gland damage caused by ethanol in rabbits. Using the isolated gland preparation, pretreatment with 10(-5)M of either indomethacin, Nw-nitro-L-arginine methyl ester (L-NAME) or N-ethylmaleimide (NEM), but not of substance P antagonist, intensified the 10% (v/v) ethanol-induced gastric gland damage and lessened the degree of cytoprotection evoked by 2% (v/v) ethanol to a significant level. Co-administration with 10(-4)M of prostaglandin E2, L-arginine or glutathione to the respective groups completely reversed the above adverse effects. These results demonstrate the involvement of endogenous prostaglandins, nitric oxide and glutathione in gastric adaptive cytoprotection against the damaging action of ethanol in the rabbit gastric glands.

Co-regulation of mucosal prostanoids and substance P by indomethacin in rat stomachs.

The present investigation examined the correlation between the regulation of mucosal prostaglandin (PG) biosynthesis and the release of the neuropeptide substance P (SP) in rat stomachs by indomethacin, a cyclooxygenase inhibitor. When given subcutaneously at the dose of 5 mg/kg, indomethacin reduced mucosal biosynthesis of PGE2 and concurrently lowered mucosal SP level. The inter-relationship between mucosal generation of PG and SP was further demonstrated by using [D-Pro2, D-Trp7,9]-SP, which also inhibited PGE2 production besides its suppression on SP release. Co-administration of either arachidonic acid, the PGE2 precursor, or SP reversed the inhibitory actions of indomethacin and [D-Pro2, D-Trp7,9]-SP, respectively, on mucosal levels of PGE2 and SP. Our findings suggest that indomethacin, aside from its depletion of endogenous PG, also exerts a secondary action in regulating the release of SP, which is mediated indirectly through PG in the gastric mucosa. These actions may play a role in the modulation of gastric mucosal integrity.

Contributions of physical and chemical properties of mild irritants to gastric cytoprotection in rats.

The present study demonstrated the cytoprotective abilities of low concentrations of ethanol, NaCl and HCl, against the gastric mucosal damage caused by 100% ethanol, and the contributions of the physical and chemical properties of these mild irritants to their protective actions. The results have shown the differential protective effects of ethanol (10-40%), NaCl (2.5-12.5%) and HCl (0.15-0.45M), with the optimal cytoprotective concentrations being 20% ethanol, 5% NaCl and 0.3M HCl, respectively. Solutions of KCl and NaCl with similar osmolarity, and H2SO4 and HCl of similar acidity and osmolarity, all showed similar protective protective potentials as compared to the osmotic agent mannitol, which possessed a concentration- and tonicity-dependent protective action against 100% ethanol-induced mucosal damage. Some concentration of methanol, propan-2-ol and ethanol, having similar osmolarity with deionized water, exerted indifferent protective effects. It is therefore concluded that adaptive cytoprotection induced by low concentrations of NaCl and HCl could depend on their physical properties, while that of ethanol could act through its unique chemical property.

Rare variants of divided right ventricle with sequestered apical trabecular component.

The right ventricle may be divided into two or more compartments by various structures in various ways. Rarely, the apical trabecular component may be sequestered from the rest of the right ventricle. We report 4 cases with different underlying lesions that share a common pathology of apical sequestration of the right ventricle resulting in diverse hemodynamic consequences. Case 1 had pulmonary valve stenosis. The apical sequestration of the right ventricle resulted in no significant hemodynamic consequence. Case 2 had multiple defects in the muscular ventricular septum. The volume of left-to-right shunt seemed to be reduced because of the commitment of some of the defects to the sequestered cavity. Case 3 had a large defect in the trabecular septum. As the defect involved the whole septum that was related to the sequestered right ventricular apex, the left ventricle together with the sequestered right ventricle formed a boot-shaped chamber. Hemodynamically, the muscular shelf was an interventricular septum. Case 4 had a coronary artery fistula to an isolated cavity that occupied the apical region of the right ventricle. The pathology was similar to the case that was reported as a five-chambered heart. The abnormal cavity was, in fact, the sequestered right ventricular apex.

Beneficial intervention of experimental colitis by passive cigarette smoking through the modulation of cytokines in rats.

BACKGROUND: Epidemiologic observations have indicated that cigarette smoking decreases the risk of ulcerative colitis, but the modes of action remain anonymous. The present study aimed to investigate the beneficial effects of passive cigarette smoking using an animal colitis model. We hypothesized that the underlying mechanisms may involve immunoregulation of cytokines. METHODS: Experimental colitis was induced in rats by enema administration of 2,4-dinitrobenzene sulfonic acid (DNBS). Passive cigarette smoking by rats was performed for 1 hour once daily, from 3 days before DNBS enema until they were sacrificed on day 8. Other groups of DNBS-treated rats received therapeutic treatment of cyclosporin A or pentoxifylline, a tumor necrosis factor (TNF)-alpha inhibitor. Macroscopic and histologic damage were graded, and the colonic levels of different cytokines and the levels/activities of parameters related to neutrophil activation were also measured. RESULTS: DNBS-induced colonic damage was improved in passive-cigarette-smoking rats. This was accompanied by attenuation of the elevated colonic myeloperoxidase and inducible nitric oxide synthase activities and leukotriene B4 level. Likewise, the augmentation in colonic levels of TNF-alpha, interleukin (IL)-1 beta, and IL-6 in colitis rats was also alleviated by passive cigarette smoking. In contrast, the deprivation of colonic IL-10 during colitis was preserved in cigarette-smoking rats. These effects were similarly accomplished by pentoxifylline and, to some degree, by cyclosporin A. CONCLUSIONS: The results support the idea that the beneficial effects of passive cigarette smoking in experimental colitis involved immunoregulation of cytokines in colonic tissues.

The vagus nerve and its non-cholinergic mechanism in the modulation of ethanol-induced gastric mucosal damage in rats.

The role of the cholinergic pathway in the vagus nerve in modulating gastric lesion formation by ethanol was examined, using an ex-vivo stomach chamber preparation. Subdiaphragmatic vagotomy significantly increased the lesion areas but lowered acid secretion and gastric mucosal blood flow (GMBF). Atropine had no effect, whereas pirenzepine antagonized ethanol-induced mucosal damage. All three procedures showed similar potencies in depressing acid secretion, but only pirenzepine reversed the fall in the GMBF produced by ethanol. These differential effects of vagotomy, atropine and pirenzepine on gastric function suggest that the cholinergic component in the vagus nerve may not be important in the formation of ethanol-induced gastric damage. The persistent protective action as well as the restoration of ethanol-induced GMBF drop by pirenzepine in vagotomized animals further support this hypothesis. The worsening effect of vagotomy is probably modulated by a non-cholinergic mechanism, the abolition of which makes the gastric mucosa more susceptible to damage by ethanol. The acid-independent protective action of pirenzepine and its influence on the GMBF, which were not exhibited by atropine, are indeed unique and perhaps may be attributed to this non-cholinergic pathway.