RESUMO
The aim of this longitudinal study was to examine changes in COVID-19 and illness-related perceptions, gastrointestinal symptoms, coping, catastrophising, psychological distress, and QoL during the COVID-19 pandemic. A total of 831 adults with a gastrointestinal condition completed an online questionnaire at baseline (May-October 2020). Of those, 270 (32.5%) participants (85.2% female, mean age = 47.3 years) provided follow-up data (March-May 2021). Repeated-measures multiple analysis of variance and a cross-lagged panel model were used to test the study hypotheses. Gastrointestinal symptoms and COVID-19 perceptions at follow-up were strongly predicted by their baseline values, while illness perceptions were predicted by baseline gastrointestinal symptoms. Cross-lagged relationships indicated a reciprocal relationship between gastrointestinal symptoms and psychological distress. Moreover, gastrointestinal symptoms had substantial predictive utility, strongly predicting future gastrointestinal symptoms, and to a lesser extent, more negative illness perceptions, greater psychological distress, and greater use of adaptive coping strategies across time.
Assuntos
COVID-19 , Angústia Psicológica , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estresse Psicológico/psicologia , Qualidade de Vida/psicologia , Estudos Longitudinais , Pandemias , Adaptação Psicológica , Inquéritos e QuestionáriosRESUMO
Nearly 20% of elderly patients suffer from constipation, but the age-related changes in the gastrointestinal (GI) tract remain insufficiently elucidated. In this study, the alterations within the endogenous opioid system (EOS) as a potential cause of constipation in the elderly were evaluated. The GI functions were assessed in vitro and in vivo and compared between 6-, 12- and 18-month old mice. Moreover, the effect of opioid receptor (MOP, DOP, KOP) agonists on the mouse GI tract functions and the EOS components expression in mouse tissues and colonic biopsies from patients with functional constipation were determined. In the oldest mice, the GI peristalsis was significantly impaired as compared to the younger groups. The tissue response to MOP and DOP, but not KOP, agonists weakened with age in vitro; for DOP, it was confirmed in vivo. In the mouse upper GI tract, Oprm1, Oprd1, Oprk1 expression decreased with age; in the colon, Oprm1 expression increased. There were no differences in the expression of these genes in the colonic biopsies from patients >50 years old as compared to the younger group. In conclusion, the age-related impairment of the GI peristalsis may result from reduced MOP and DOP response to the activation with opioid agonists or the alterations in the EOS expression.
Assuntos
Analgésicos Opioides , Receptores Opioides , Idoso , Envelhecimento/genética , Analgésicos Opioides/farmacologia , Animais , Constipação Intestinal , Trato Gastrointestinal/metabolismo , Humanos , Camundongos , Peptídeos Opioides , Receptores Opioides/genética , Receptores Opioides/metabolismo , Receptores Opioides mu/metabolismoRESUMO
This study aimed to explore the association between perceived isolation and symptoms of distress in people with GI disorders at the time of the pandemic; and to examine factors which moderate this relationship. This online cross-sectional survey was advertised in May-September 2020 via patient organisations and associated social media. Overall, 831 people (82% female, mean age 49 years) from 27 countries participated. A significant relationship between social isolation and psychological distress was noted (r = .525, p < .001). GI symptoms moderated the association between isolation and distress (B = .047, t = 2.47, p = .015). Interventions targeting these factors may help to reduce distress in people with GI disorders at the time of major stressors such as the COVID-19 pandemic.
Assuntos
COVID-19 , Gastroenteropatias , Estudos Transversais , Feminino , Gastroenteropatias/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2RESUMO
The aim of this cross-sectional study was to use an extended common sense model (CSM) to evaluate the impact of fear of COVID-19 on quality of life (QoL) in an international inflammatory bowel disease cohort. An online study involving 319 adults (75% female, mean (SD) 14.06 (15.57) years of symptoms) completed the Gastrointestinal Symptom Rating Scale, Brief Illness Perceptions Questionnaire, Fear of Contracting COVID-19 Scale, Brief-COPE, Depression, Anxiety and Stress Scale, and the EUROHIS-QOL. The extended CSM had an excellent fit (χ2 (9) = 17.06, p = .05, χ2/N = 1.90, RMSEA = 0.05, SRMR = 0.04, CFI = .99, TLI = .97, GFI = 0.99), indicating the influence of gastrointestinal symptoms on QoL was mediated by illness perceptions, fear of COVID-19, adaptive and maladaptive coping, and psychological distress. Interventions targeting the fear of COVID-19 in the context of an individual's perceptions will likely enhance QoL during the pandemic.
Assuntos
COVID-19 , Doenças Inflamatórias Intestinais , Adulto , Doença Crônica , Estudos Transversais , Medo , Feminino , Humanos , Doenças Inflamatórias Intestinais/psicologia , Masculino , Qualidade de Vida/psicologiaRESUMO
The pathogenesis of inflammatory bowel diseases (IBD) seems to be associated with alterations of immunoregulation. Several lines of evidence suggest that estrogens play a role in the modulation of immune responses and may be related to the etiology of IBD. The purpose of this work was to examine the involvement of G protein-coupled estrogen receptor (GPER), estrogen receptor α (ERα), estrogen receptor ß (ERß) and ERα spliced variants ERα36 and ERα46 in Crohn's disease (CD) and ulcerative colitis (UC). The studied group included 73 patients with IBD and 31 sex and age-related controls. No differences in serum levels of 17ß-estradiol nor of CYP1A1 and SULT1E1 enzymes involved in estrogen catabolism were stated. The expression pattern of estrogen receptors in tissue samples was quantified using real-time PCR and Western blotting. Statistically significant up-regulation of GPER and ERα in both CD and UC as well as down-regulation of ERß in CD patients was found. However, differences in the expression of estrogen receptors in CD and UC have been identified, depending on the sex and age of patients. In men, up-regulation of GPER, ERα and ERα46 expression was shown in CD and UC patients. In women under 50 years of age, GPER protein level increased in UC whereas ERß expression tended to decrease in CD and UC patients. In turn, in women over 50 the protein level of ERα increased in UC while ERß expression decreased in CD patients. Dysregulation of estrogen receptors in the intestinal mucosa of patients with CD and UC indicates that estrogen signaling may play a role in the local immune response and maintain epithelial homeostasis in a gender- and age-dependent manner.
Assuntos
Colite Ulcerativa/metabolismo , Doença de Crohn/metabolismo , Estrogênios/metabolismo , Receptores de Estrogênio/metabolismo , Transdução de Sinais , Fatores Etários , Idoso , Colite Ulcerativa/patologia , Doença de Crohn/patologia , Estradiol/sangue , Estradiol/metabolismo , Estrogênios/sangue , Feminino , Humanos , Mucosa Intestinal/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores de Estrogênio/genética , Fatores SexuaisRESUMO
Protease inhibition has become a possible new approach in inflammatory bowel disease (IBD) therapy. A serine exopeptidase, dipeptidyl peptidase IV (DPP IV), is responsible for the inactivation of incretin hormone, glucagon-like peptide 2 (GLP-2), a potent stimulator of intestinal epithelium regeneration and growth. Recently, we showed that the novel peptide analog of endomorphin-2, Tyr-Pro-D-ClPhe-Phe-NH2 (EMDB-1) is a potent blocker of DPP IV and has an inhibitory effect on gastrointestinal (GI) smooth muscle contractility. The aim of this study was to characterize the anti-inflammatory effect and mechanism of action of EMDB-1 in the mouse GI tract. We used two models of experimental colitis (induced by TNBS and DSS). The anti-inflammatory effect of EMDB-1 was assessed by the determination of macroscopic score, ulcer score, colonic wall thickness, as well as myeloperoxidase activity. Additionally, we measured the expression of GLP-2, GLP2R, and DPP IV in the colon of control and colitic animals treated with the test compound. The expression of GLP-2 and GLP2R in the serum and colon of IBD patients and healthy control subjects has been assessed. We showed that EMDB-1 elevates the half-life of GLP-2 in vitro and attenuates acute, semichronic, and relapsing TNBS as well as DSS-induced colitis in mice after topical administration. The anti-inflammatory action of EMDB-1 is associated with changes in the level of colonic GLP-2 but not DPP IV expression. Our results validate DPP IV as a pharmacological target for the anti-IBD drugs, and its inhibitors based on natural substrates, such as EMDB-1, have the potential to become valuable anti-inflammatory therapeutic agents.
Assuntos
Colite/tratamento farmacológico , Colite/metabolismo , Dipeptidil Peptidase 4/metabolismo , Peptídeo 2 Semelhante ao Glucagon/metabolismo , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacologia , Administração Tópica , Adulto , Idoso , Sequência de Aminoácidos , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Doença de Crohn/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Inibidores da Dipeptidil Peptidase IV/química , Inibidores da Dipeptidil Peptidase IV/farmacologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Receptor do Peptídeo Semelhante ao Glucagon 2/metabolismo , Meia-Vida , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Oligopeptídeos/química , Oligopeptídeos/uso terapêutico , Proteólise/efeitos dos fármacos , Adulto JovemRESUMO
The nociceptin receptors (NOPs) are expressed in the gastrointestinal (GI) tract on muscle cell membranes and neurons, as well as the immune cells that infiltrate the mucosa. The involvement of NOPs in the pathophysiology of GI inflammation has been suggested, but due to the lack of selective NOP agonists, it never fully elucidated. Our aim was to characterize the anti-inflammatory and antinociceptive effect of the NOP agonist, SCH 221510 [3-endo-8-[bis(2-methylphenyl)methyl]-3-phenyl-8-azabicyclo [3.2.1]octan-3-ol], as a potential therapeutic strategy in the treatment of inflammatory bowel diseases (IBD). The anti-inflammatory action of SCH 221510 was determined after intraperitoneal, oral, and intracolonic administration of SCH 221510 (0.1-3.0 mg/kg once or twice daily) in mice treated with 2,4,6-trinitrobenzenesulfonic acid (TNBS). Antinociceptive action of SCH 221510 was evaluated in the mouse model of mustard oil (MO)-induced abdominal pain. Relative NOP mRNA expression was assessed in patients with IBD using real-time reverse transcriptase-polymerase chain reaction. We found that the expression of NOP mRNA was significantly decreased in patients with IBD. The administration (0.1 and 1.0 mg/kg i.p. twice daily and 3 mg/kg p.o. twice daily) of SCH 221510 attenuated TNBS colitis in mice. This effect was blocked by a selective NOP antagonist [J-113397 [(±)-1-[(3R*,4R*)-1-(cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one]]. The intracolonic injections of SCH 221510 did not improve colitis in mice. The antinociceptive effect of SCH 221510 was observed after oral administration of SCH 221510 in MO-induced pain tests in mice with acute colitis. In conclusion, our results show a potent anti-inflammatory and antinociceptive effect upon selective activation of NOP receptors and suggest that the NOP agonist SCH 221510 is a promising drug candidate for future treatment of IBD.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Compostos Azabicíclicos/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Receptores Opioides/agonistas , Dor Abdominal/induzido quimicamente , Dor Abdominal/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Estudos de Casos e Controles , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo/metabolismo , Colo/patologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Mostardeira , Óleos de Plantas , Receptores Opioides/metabolismo , Ácido Trinitrobenzenossulfônico , Adulto Jovem , Receptor de NociceptinaRESUMO
BACKGROUND: Histopathologic differentiation between the stages of Barrett's carcinogenesis is often challenging. Liver-intestine (LI)-cadherin, an intestine-specific marker, is involved in intestinal metaplasia development in gastric and colon cancers and could be of value in diagnosis and differentiation. AIMS: To examine the expression of LI-cadherin in the sequence of Barrett's carcinogenesis and to evaluate its association with clinicopathological data. METHODS: LI-cadherin expression was immunohistologically investigated, by use of anti-CDH17 antibody, in gastric mucosa (GM) biopsies taken from the cardia (n = 9), in Barrett's esophagus (BE) without intraepithelial neoplasia (without IEN) (n = 9) and BE with low-grade IEN (n = 11), and in esophageal adenocarcinoma (ADC) (n = 13). RESULTS: The immunoreactivity score was highest in adenocarcinoma (mean IRS = 4.0), and dropped gradually from BE with IEN and BE without IEN (mean IRS = 2.0) to cardia mucosa (IRS = 0). Similarly, the intensity of staining and the percentage of positive cells increased during the sequential stages of BE carcinogenesis. Comparative analysis showed that LI-cadherin expression was significantly different between cardiac epithelium and ADC. Also, percentage of positive cells in GM was significantly different from that in BE with IEN. LI-cadherin IRS was lower for tumors with poor differentiation than for moderately differentiated tumors, but the difference was not statistically significant. CONCLUSIONS: LI-cadherin is a sensitive marker of intestinal metaplasia and can be helpful for early histologic diagnosis of Barrett's esophagus; it is, however, not significantly different between BE with and without IEN, and cannot be used to distinguish between these.
Assuntos
Esôfago de Barrett/metabolismo , Esôfago de Barrett/patologia , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/genética , Caderinas/genética , Cárdia/metabolismo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Mucosa Gástrica/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND/AIMS: Esophageal adenocarcinoma (ADC) incidence has been increasing dramatically in the past 3 decades despite the surveillance programs in patients with Barrett's esophagus (BE). Therefore, markers of early neoplastic progression are required to predict of cancer risk in BE patients. The aim of this study was to investigate the frequency of Her2/neu amplification in different stages during Barrett's-related carcinogenesis. METHODOLOGY: Her2/neu amplification analysis in 39 patients with gastroesophageal reflux disease (GERD), in 34 with BE, in 11 with dysplasia and 13 with ADC were performed with PCR. RESULTS: Her2/neu amplification was detected in 8% (3/39) GERD patients, 15% (5/34) with BE, 41% (7/17) with dysplasia and in 54% (7/13) with ADC. We observed an increasing trend in the frequency of Her2/neu alteration between BE-carcinogenesis stages (p=0.001). This finding was confirmed in the logistic regression analysis showing gradient in odds ratios between BE (2.07; 95% CI: 0.46-9.39), dysplasia (8.4; 95% CI: 1-83-38.53) and ADC (14.0; 95% CI: 2.81-69.69) compared to GERD; it was even higher after adjustment for age and gender. CONCLUSIONS: Her2/neu alterations may occur early and increasingly during Barrett's malignant progression. We suggest that it may be useful to stratify the risk of adenocarcinoma in patients with Barrett's esophagus.
Assuntos
Adenocarcinoma/genética , Esôfago de Barrett/genética , Neoplasias Esofágicas/genética , Refluxo Gastroesofágico/genética , Amplificação de Genes , Genes erbB-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. METHODS: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. FINDINGS: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. INTERPRETATION: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. FUNDING: German Research Foundation (DFG).
Assuntos
Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Estudo de Associação Genômica Ampla , Heterogeneidade Genética , Esôfago de Barrett/genética , Adenocarcinoma/patologia , Neoplasias Esofágicas/genética , Fatores de RiscoRESUMO
BACKGROUND/AIMS: Central obesity is a risk factor for GERD, Barrett's esophagus and esophageal adeno-carcinoma. Recent studies have suggested that adipocytokines are the possible link between adiposity and Barrett's carcinogenesis. To determine the adiponectin, resistin and leptin concentration as well as the central adiposity parameters in BE patients with and without intestinal metaplasia (IM) in comparison to GERD and healthy controls. METHODOLOGY: Total of 77 patients (30 patients with GERD, 26 BE with IM and 21 BE without IM) and 30 healthy controls were investigated for the central obesity parameters. Serum levels of adipocytokines were measured with ELISA. RESULTS: The serum concentration of adiponectin was significantly lower in BE compared to those in GERD and to controls (p<0.001). Levels of leptin was slightly higher in BE than in GERD and controls (NS). Level of resistin was significantly higher in GERD compared to both control and BE patients (p<0.001). Waist circumference, WHR and WTR were significantly higher in BE patients compared to GERD (p<0.001) and to control group (p<0.001). CONCLUSIONS: Features of central obesity rather than BMI are associated with BE development. Adipokines may be important at the early step of BE development, before the IM occurrence.
Assuntos
Adiponectina/sangue , Adiposidade , Esôfago de Barrett/etiologia , Neoplasias Esofágicas/etiologia , Esôfago/patologia , Refluxo Gastroesofágico/etiologia , Leptina/sangue , Obesidade Abdominal/complicações , Resistina/sangue , Adulto , Idoso , Esôfago de Barrett/sangue , Esôfago de Barrett/patologia , Esôfago de Barrett/fisiopatologia , Biomarcadores/sangue , Índice de Massa Corporal , Estudos de Casos e Controles , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/fisiopatologia , Feminino , Refluxo Gastroesofágico/sangue , Refluxo Gastroesofágico/patologia , Refluxo Gastroesofágico/fisiopatologia , Humanos , Masculino , Metaplasia , Pessoa de Meia-Idade , Obesidade Abdominal/sangue , Obesidade Abdominal/patologia , Obesidade Abdominal/fisiopatologia , Circunferência da Cintura , Relação Cintura-QuadrilRESUMO
BACKGROUND: Although several studies have reported the impact of fears relating to coronavirus-19 on several chronic illnesses, there are few studies focused on gastrointestinal conditions. Therefore, the aim of this study was to compare the fear of coronavirus-19 in patients with inflammatory bowel disease to other gastrointestinal conditions and how the fear of COVID-19 manifests across different demographical backgrounds among inflammatory bowel disease respondents. METHODS: Participants with gastrointestinal conditions (age ≥ 18) were recruited from 27 countries. Demographic, clinical, and psychosocial information was collected. An adapted scale for inflammatory bowel disease patients measuring the fear of coronavirus-19 and gastrointestinal-specific fear of coronavirus-19 was used. RESULTS: In 831 participants (312 inflammatory bowel disease), only significant increases in gastrointestinal-fear of coronavirus-19 were found in between inflammatory bowel disease and other gastrointestinal conditions (mean [standard deviation]: 13.5 [5.5] vs 10.9 [5.0], P < .01). Among inflammatory bowel disease respondents, persons on sick leave had significantly more fear of coronavirus-19 than those employed (median [IQR], 31.0 [28.5-39.5] vs 26.0 [20.0-33.0], P = .035) and significantly more gastrointestinal-fear of coronavirus-19 compared to the employed (18.0 [14.5-22.0] vs 13.0 [9.0-17.0], P = .033) or respondents outside of the labor market (12.0 [7.0-16.0], P = .022). Persons living in a rural setting had significantly more fear of coronavirus-19 compared to persons living in regional setting (29.5 [22.0-37.8] vs 25.0 [20.0-31.3], P = .007) and gastrointestinal-fear of coronavirus-19 (15.0 [11.0-19.8] vs 12.0 [9.0-16.0], P = .02). CONCLUSION: Respondents with inflammatory bowel disease are more afraid of coronavirus-19 regarding their disease; especially, persons on sick leave or persons living in a rural setting. This should be taken into consideration to personalize the support that health care providers can offer in mitigating fear related to coronavirus-19.
Assuntos
COVID-19 , Doenças Inflamatórias Intestinais , COVID-19/epidemiologia , Doença Crônica , Medo , Humanos , Doenças Inflamatórias Intestinais/psicologiaRESUMO
BACKGROUND: The mental health response to the coronavirus (COVID-19) pandemic-related product shortages in those living with chronic gastrointestinal (GI) disorders has received little attention. We aimed to explore the association between the pandemic-related product shortages and psychological distress in people with GI disorders. METHODS: This online cross-sectional survey was nested within an ongoing, international, prospective study of well-being in people with GI disorders. The study was advertised in multiple countries in May-September 2020 via patient organizations and social media. The primary outcome measure was distress, evaluated by the Depression Anxiety Stress Scale. We utilized linear regressions, adjusting for covariates and testing individual moderation effects. KEY RESULTS: Overall, 831 people completed the survey from 27 countries, of whom 82% were female (mean age = 49 years). The most common disorders included inflammatory bowel disease (n = 322), celiac disease (n = 273), and irritable bowel syndrome (n = 260). Significant problems accessing food were reported by 19.8%, non-medical therapies by 16%, toilet paper by 10.8%, and essential medication by 8.9% of the sample (>5% pain medication). There was a positive association between toilet paper and pain medication shortages and distress, and a negative association between food shortages and distress. Significant moderation effects were identified for COVID-19 prevalence and toilet paper and food shortages, and between COVID-19 fear and pain medication shortages. CONCLUSIONS AND INFERENCES: The study documented a significant relationship between product shortages and psychological distress, which were associated with COVID-19 prevalence and fear. Strategies addressing COVID-19 fear could potentially modify the relationship between shortages and distress.
Assuntos
COVID-19/prevenção & controle , Gastroenteropatias/psicologia , Pandemias , Equipamento de Proteção Individual , Angústia Psicológica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/psicologia , COVID-19/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Quality of life (QOL) has increasingly become a factor in management decisions in patients with chronic diseases. Chronic pancreatitis (CP) is a debilitating disorder that causes not only pain and endo/exocrine insufficiency but is also connected with some social issues. The aim of this study was to assess QOL in patients with chronic pancreatitis in correlation with the disease activity or the environmental/social factors that can influence their well-being. MATERIAL/METHODS: The study group comprised 43 patients with CP: M/F 37/6; mean age 47.9 ± 8.6; range: 30-74 yrs. The control group consisted of 40 healthy volunteers of comparable demographics. Different degrees of CP activity were defined using the Cambridge classification. Pain intensity and frequency were assessed using a pain index. QOL was assessed using the Short-Form-36 questionnaire. RESULTS: Mean QOL scores in CP were lower compared to the control group in all SF-36 domains, particularly in general health perception, physical functioning, role-physical (p<0.001) and vitality (p<0.05). We observed correlation of QOL results and pain index in all domains, and number of the disease relapses and body weight in 5 out of 8 domains (p<0.001 and p<0.05, respectively). The worst QOL scores were obtained in retired patients, as well as in unemployed persons in almost all SF-36 domains (p<0.001). CONCLUSIONS: Chronic pancreatitis significantly impairs patients' quality of life. Severity of abdominal pain, low body weight, and loss of work were the factors most closely associated with poor health status perception.
Assuntos
Medição da Dor/psicologia , Pancreatite Crônica/patologia , Qualidade de Vida/psicologia , Adulto , Idoso , Peso Corporal/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/estatística & dados numéricos , Polônia , Inquéritos e Questionários , Desemprego/psicologiaRESUMO
The pathogenesis and course of inflammatory bowel diseases are related to both immune system disorders and dysfunction of colon permeability. Moreover, co-existing diseases in patients with Crohn's disease and ulcerative colitis are identified. Currently, there are some therapeutic strategies that affect the function of cytokine/s causing inflammation in the intestinal wall. However, additional approaches which target other components of inflammatory bowel diseases pathogenesis are still needed. Accumulating evidence suggests that proteases and protease-activated receptors seem to be responsible for colitis progression. Experimental and observational studies showed alteration of protease-activated receptors expression in the colon of patients with Crohn's disease and ulcerative colitis. Furthermore, it was suggested that the expression of protease-activated receptors correlated with inflammatory bowel diseases activity. Moreover, regulation of protease-activated receptors seems to be responsible for the modulation of colitis and clinical manifestation of inflammatory bowel diseases. In this review, we present the current state of knowledge about the contribution of protease-activated receptors to Crohn's disease and ulcerative colitis and its implications for diagnosis and treatment.
RESUMO
BACKGROUND: The role of the incretin hormone, glucagon-like peptide (GLP-1), in Crohn's disease (CD), is still poorly understood. The aim of this study was to investigate whether colitis is associated with changes in blood glucose levels and the possible involvement of the incretin system as an underlaying factor. METHODS: We used a murine model of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Macroscopic and microscopic score and expression of inflammatory cytokines were measured. The effect of colitis on glucose level was studied by measurement of fasting glucose and GLP-1, dipeptidyl peptidase IV (DPP IV) levels, prohormone convertase 1/3 (PC 1/3) and GLP-1 receptor (GLP-1R) expression in mice. We also measured the level of GLP-1, DPP IV and expression of glucagon (GCG) and PC 1/3 mRNA in serum and colon samples from healthy controls and CD patients. RESULTS: Fasting glucose levels were increased in animals with colitis compared to controls. GLP-1 was decreased in both serum and colon of mice with colitis in comparison to the control group. DPP IV levels were significantly increased in serum, but not in the colon of mice with colitis as compared to healthy animals. Furthermore, PC 1/3 and GLP-1R expression levels were increased in mice with colitis as compared to controls. In humans, no differences were observed in fasting glucose level between healthy subjects and CD patients. GLP-1 levels were significantly decreased in the serum. Interestingly, GLP-1 level was significantly increased in colon samples of CD patients compared to healthy subjects. No significant differences in DPP IV levels in serum and colon samples were observed between groups. CONCLUSIONS: Changes in the incretin system during colitis seem to contribute to the impaired glucose levels. Differences in incretin levels seem to be modulated by degrading enzyme DPP-IV and PC 1/3. Obtained results suggest that the incretin system may become a novel therapeutic approach in the treatment of CD.
Assuntos
Glicemia/metabolismo , Colite/patologia , Doença de Crohn/patologia , Incretinas/metabolismo , Adulto , Animais , Estudos de Casos e Controles , Dipeptidil Peptidase 4/metabolismo , Modelos Animais de Doenças , Feminino , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Pró-Proteína Convertase 1/genética , Ácido Trinitrobenzenossulfônico , Adulto JovemRESUMO
BACKGROUND: GPR18 is a recently deorphanized receptor which was reported to act with several endogenous cannabinoid ligands. Here, we aimed to describe the role of GPR18 in intestinal inflammation and inflammatory pain. METHODS: The anti-inflammatory activity of selective GPR18 agonist, PSB-KK-1415, and antagonist, PSB-CB5, was characterized in semi-chronic and chronic mouse models of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). The extent of inflammation was evaluated based on the macroscopic and microscopic scores, quantification of myeloperoxidase (MPO) activity, and Western blot analyses of tumor necrosis factor-α (TNF-α) and interleukin-6 in colonic tissue. The expression of GPR18 in colonic samples from patients with Crohn's disease (CD) was quantified using real-time PCR. The anti-nociceptive potential of the agonist in intestinal inflammation was evaluated in the mouse model of inflammatory pain. KEY RESULTS: In semi-chronic colitis, PSB-KK-1415 reduced macroscopic score (1.79 ± 0.22 vs. 2.61 ± 0.48), expression of TNF-α (1.89 ± 0.36 vs. 2.83 ± 0.64), and microscopic score (5.00 ± 0.33 vs. 6.45 ± 0.40), all compared to mice with colitis. In chronic colitis, PSB-KK-1415 decreased macroscopic score (3.33 ± 1.26 vs. 4.00 ± 1.32) and MPO activity (32.23 ± 8.51 vs. 41.33 ± 11.64) compared to inflamed mice. In the mouse model of inflammatory pain, PSB-KK-1415 decreased the number of pain-induced behaviors in both, controls (32.60 ± 2.54 vs. 58.00 ± 6.24) and inflamed mice (60.83 ± 2.85 vs. 85.00 ± 5.77) compared to animals without treatment with PSB-KK-1415 (P < 0.005 for both). Lastly, we showed an increased expression of GPR18 in CD patients compared to healthy controls (3.77 ± 1.46 vs. 2.38 ± 0.66, p = 0.87). CONCLUSIONS & INFERENCES: We showed that GPR18 is worth considering as a potential treatment target in intestinal inflammation and inflammatory pain.
Assuntos
Colite/metabolismo , Doença de Crohn/genética , Inflamação/metabolismo , Nociceptividade/efeitos dos fármacos , Dor Nociceptiva/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Casos e Controles , Colite/fisiopatologia , Doença de Crohn/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/fisiopatologia , Masculino , Camundongos , Pessoa de Meia-Idade , Dor Nociceptiva/fisiopatologia , Peroxidase/metabolismo , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismoRESUMO
OBJECTIVE: The COVID-19 pandemic has had a significant impact on mental health across the globe. People living with a chronic gastrointestinal (GI) disorder might be particularly at risk of mental health complications given higher rates of comorbid anxiety and depression compared to the healthy population. As GI disorders affect up to 40% of the population worldwide, this international collaborative study seeks to evaluate the extent of the impact of the COVID-19 pandemic on GI symptoms specifically and more generally on the well-being of those living with chronic GI conditions. METHODS: A longitudinal survey with three time points (baseline, 6-month, and 12-month) will be conducted online. Adult participants with GI disorders from multiple countries will be recruited via patient associations, social media advertising, utilizing snowball sampling. Participants will be invited to complete a battery of questionnaires including demographic and health parameters, and measures of gastrointestinal symptoms, fear of COVID-19, perceived impact of COVID-19, illness perceptions, coping, depression, anxiety, stress, catastrophizing, and quality of life, using validated measures where available. Statistical analyses will include univariate descriptive models, multivariate models utilizing regression, mediation, and moderation, and latent growth models. CONCLUSIONS: This project may present novel information to the field of psychogastroenterology and may provide crucial information regarding the areas of impact for individuals with GI disorders during and following the pandemic. Further, this information can guide healthcare providers and patient associations on how to target support related to the pandemic mental health sequelae for these patients.
Assuntos
COVID-19/epidemiologia , Gastroenteropatias/epidemiologia , Gastroenteropatias/psicologia , Inquéritos Epidemiológicos , Cooperação Internacional , Projetos de Pesquisa , Ansiedade/epidemiologia , Depressão/epidemiologia , Gastroenteropatias/fisiopatologia , Humanos , Estudos Longitudinais , Pandemias , Qualidade de Vida , Reprodutibilidade dos Testes , Estresse Psicológico/epidemiologiaRESUMO
BACKGROUND: Resistin and visfatin, hormones produced by adipose tissue, have pro-inflammatory potential; however, their role in acute pancreatitis (AP) has been investigated only rarely. METHODS: The study group comprised 32 patients with alcoholic AP and 30 controls. In all cases AP was classified as C according to Balthazar's CT score and as severe according to Ranson's criteria. The serum level of visfatin, resistin, and interleukin(IL)-8 immunoassays were measured by ELISA on admission and on the third and fifth day of hospitalization. RESULTS: On the admission day serum resistin and IL-8 concentrations in AP patients were significantly higher than in controls and they further increased on the third and fifth day of hospitalization. On the admission day serum visfatin levels in AP patients were significantly higher than in controls and further increased on the third day of hospitalization. On the fifth day the levels decreased; however, they were still higher than on admission. The correlation between visfatin and resistin as well as between C-reactive protein and visfatin, resistin and IL-8 levels has been found. CONCLUSION: In the course of AP, visfatin and resistin levels increase in parallel with C-reactive protein. We speculate that those parameters may provide an additional tool for the prognosis and monitoring of AP. and IAP.
Assuntos
Citocinas/sangue , Interleucina-8/sangue , Nicotinamida Fosforribosiltransferase/sangue , Pancreatite Alcoólica/sangue , Resistina/sangue , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite Alcoólica/patologia , PrognósticoRESUMO
BACKGROUND/AIMS: Inflammatory bowel disease (IBD) represents the heterogeneous group of disorders with a wide variety of clinical manifestations. The Montreal classification has been developed recently and its accuracy in categorizing of IBD phenotypes needs to be investigated. The aim of the study was to assess the usefulness of the Montreal classification compared to CAI and CDAI in various disease activity, serological and clinical manifestations of IBD. METHODOLOGY: The study was performed in 125 IBD patients: 71 patients with ulcerative colitis, 31 with Crohn's disease and 23 with IBD unclassified (indeterminate colitis). Disease activity and clinical course were assessed using Montreal classification, Clinical Activity Index and Crohn's Disease Activity Index. pANCA and ASCA were measured with ELISA, using widely used, commercial antibody panel (Cogent Diagnostics and Genesis Diagnostics and MedTek kits). RESULTS: No significant correlation has been found between pANCA/ASCA presence and disease activity using CAI and CDAI. ASCA and pANCA-/ASCA+ antibodies pattern had been detected more often in patients with Crohn's disease after surgery, with localization in small or small and large intestine, without perianal lesions and with early disease onset. CONCLUSIONS: Correlations between serotype and certain clinical phenotype are present, which could potentially be of value in the classification of patients particular treatment regimen. We have noticed that clinical course assessment using Montreal classification shows precisely real CD patients state.