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2.
J Health Serv Res Policy ; : 13558196241231191, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38329090

RESUMEN

OBJECTIVES: With high disease and disability burden in rural and remote regions, student-assisted clinics can be an effective workforce development tool to meet community health needs and workforce shortages. This research sought to identify the conditions under which student-assisted clinics can be successfully utilised as a workforce development strategy, with specific application to remote Queensland, Australia. METHODS: A rapid review of the international literature in English was conducted. This was the most appropriate type of review because the results of the review were time-sensitive, with the student-assisted clinic model being trialled in Queensland soon. A mixed methods design was applied, with the search strategy piloted with one database. RESULTS: Eleven studies met the inclusion criteria. Seven reported data on participant experiences, including consumers, students, services/clinics, and educators/supervisors/health professionals. Each of the studies operationalised student-assisted clinics through practice models (university-driven learning need), service delivery models (service driven need addressed through a student workforce), community need models (student delivered services primarily addressing a community health need), and blended models (practice need and community need). Some studies reported concerns about fragmentation of services, referral pathways and issues with follow-up, while others reported concerns about sustainable funding. All models reported successful outcomes when focused on service or consumer health outcomes, or student learning outcomes. CONCLUSIONS: Student-assisted clinics make an important contribution to the development of the rural and remote health workforce. Student-assisted clinics can complement and extend existing services, supporting workforce development in an overstretched health system impacted by an ongoing pandemic.

3.
Surgeon ; 22(1): 52-59, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37758556

RESUMEN

AIM: To investigate the effects of frailty and co-morbidities on short and medium-term outcome following emergency colorectal cancer surgery. METHODS: Data of patients who underwent emergency colorectal cancer operations between January 2013 and December 2016 were reviewed retrospectively. Collected data included demographic and operative variables, clinical frailty scale (CFS), Charlson comorbidity index (CCI) and cause of death with minimum 3 years follow-up. RESULTS: Three-hundred and six patients (median age 72, range 18-100 years) underwent emergency colorectal cancer surgery; Some 74 (24.2%) patients had metastatic cancer at the time of emergency surgery, 77 (25.2%) were frail (CFS ≥4), while 118 (38.6%) were comorbid (CCI of ≥8). Thirty-day mortality was 4.2% (13 patients) and a further 12 patients died within 90 days (8.2%). By 1 year 73 (23.9%) patients had died, and by 3 years 151 (49.3%) patients died. Frailty did not impact 30-day mortality (6.5% vs 3.5%, p = 0.26) but frail patients (CFS ≥4) had a higher mortality rate at 90 days (16.9% vs 5.2%, p < 0.05), 1 year (37.7% vs 19.2%, p < 0.05) and 3 years (61.0% vs 45.4%, p < 0.05). Similarly, higher comorbidity (CCI ≥8) did not impact 30-day mortality (5.9% vs 3.2%, p = 0.25), but they had a higher mortality rate at 90 days (14.4% vs 4.3%, p < 0.05), 1 year (40.7% vs 13.3%, p < 0.05), and 3 years (76.3% vs 32.4%, p < 0.05). CONCLUSION: Thirty-day mortality after emergency colorectal cancer surgery in frail and comorbid patients are similar to that of the general population.


Asunto(s)
Neoplasias Colorrectales , Fragilidad , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Fragilidad/complicaciones , Fragilidad/epidemiología , Estudios Retrospectivos , Comorbilidad , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/epidemiología , Morbilidad
4.
Eur J Surg Oncol ; 48(11): 2258-2262, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35086682

RESUMEN

Pelvic exenteration is a complex, technically challenging procedure requiring detailed anatomical knowledge. Understanding the complexity of the pelvis beyond TME is an essential requirement for both operative planning and execution. This paper highlights the key anatomical approaches to extended pelvic resection as relevant to the Colorectal Surgeon.


Asunto(s)
Carcinoma , Exenteración Pélvica , Neoplasias Pélvicas , Neoplasias del Recto , Humanos , Neoplasias Pélvicas/cirugía , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/patología , Exenteración Pélvica/métodos , Carcinoma/cirugía , Pelvis/patología , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología
5.
Infect Control Hosp Epidemiol ; 43(11): 1647-1655, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-34852866

RESUMEN

OBJECTIVE: To describe the cumulative seroprevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies during the coronavirus disease 2019 (COVID-19) pandemic among employees of a large pediatric healthcare system. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study open to adult employees at the Children's Hospital of Philadelphia, conducted April 20-December 17, 2020. METHODS: Employees were recruited starting with high-risk exposure groups, utilizing e-mails, flyers, and announcements at virtual town hall meetings. At baseline, 1 month, 2 months, and 6 months, participants reported occupational and community exposures and gave a blood sample for SARS-CoV-2 antibody measurement by enzyme-linked immunosorbent assays (ELISAs). A post hoc Cox proportional hazards regression model was performed to identify factors associated with increased risk for seropositivity. RESULTS: In total, 1,740 employees were enrolled. At 6 months, the cumulative seroprevalence was 5.3%, which was below estimated community point seroprevalence. Seroprevalence was 5.8% among employees who provided direct care and was 3.4% among employees who did not perform direct patient care. Most participants who were seropositive at baseline remained positive at follow-up assessments. In a post hoc analysis, direct patient care (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.03-3.68), Black race (HR, 2.70; 95% CI, 1.24-5.87), and exposure to a confirmed case in a nonhealthcare setting (HR, 4.32; 95% CI, 2.71-6.88) were associated with statistically significant increased risk for seropositivity. CONCLUSIONS: Employee SARS-CoV-2 seroprevalence rates remained below the point-prevalence rates of the surrounding community. Provision of direct patient care, Black race, and exposure to a confirmed case in a nonhealthcare setting conferred increased risk. These data can inform occupational protection measures to maximize protection of employees within the workplace during future COVID-19 waves or other epidemics.


Asunto(s)
COVID-19 , Virosis , Adulto , Humanos , Niño , Pandemias , COVID-19/epidemiología , SARS-CoV-2 , Estudios Seroepidemiológicos , Estudios Prospectivos , Virosis/epidemiología , Hospitales Pediátricos , Anticuerpos Antivirales , Personal de Salud
6.
Anat Rec (Hoboken) ; 305(2): 446-461, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-33890720

RESUMEN

Sperm characteristics, such as sperm morphology and sperm morphometry are important in assessing sperm quality. This is especially important for the management and conservation of endangered and exotic species, like the Florida manatee, where information of this nature is extremely limited. In this study, we fill this knowledge gap to better understand the reproductive physiology of Florida manatees by conducting the first extensive analysis of sperm morphometry and ultrastructure. Sperm were retrieved from the vas deferens of nine recently deceased Florida manatees. Computer-aided sperm morphology analysis (CASMA) was used for morphometric analysis and laser-scanning confocal microscopy and electron microscopy were used for structural and ultrastructural characterization. Our findings reveal new morphometric and structural data for the Florida manatee spermatozoon. Twelve morphometric features of Florida manatee sperm were quantified with some approximately 1.5-2 times larger than those previously reported. Ultrastructurally, the Florida manatee spermatozoon followed a mammalian structural pattern with an ovate-shaped head, midpiece containing 84-90 mitochondria, and a flagellum. However, unique ultrastructural features were identified. Distinct, rectangular-like enlargement of four outer dense fibers surrounding the axoneme was evident, which may provide additional tensile strength to counteract the forces on sperm transiting the female reproductive tract. Likewise, strong localization of F-actin fibers within the midpiece may function to maintain sperm integrity within the female reproductive tract. These findings highlight the potential effects of sexual selective pressures on sperm size and structure in the Florida manatee and provide avenues for research on the occurrence of sperm competition in this species.


Asunto(s)
Espermatozoides , Trichechus manatus , Animales , Femenino , Masculino , Mamíferos , Microscopía Electrónica , Mitocondrias
7.
Colorectal Dis ; 23(5): 1233-1238, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33544433

RESUMEN

BACKGROUND: The Versius surgical system, from CMR Surgical, is the first UK-based robotic platform to become commercially available. This is a prospective series in accordance with the IDEAL development framework for surgical innovation reporting the clinical implementation and initial experience using this robotic platform. METHODS: Patients with colorectal cancer were included. Exclusion criteria included T4 tumours, ultra-low rectal cancer and severe comorbidity (American Society of Anesthesiologists grade ≥ 3). Institutional ethical approval was obtained, and patients were counselled preoperatively with informed consent. Patients underwent colorectal resection using the Versius surgical system. Procedures were anticipated as hybrid operations (laparoscopic/robotic) consistent with a proof of concept/technical feasibility study. RESULTS: Main outcome measures included operative time, complication rates and pathological results. Thirty-two patients (15 men) underwent colorectal cancer resections. The mean age was 68 years (27-85 years). Estimated blood loss was 150 ml; range <100 to <500 ml. For right hemicolectomy, the average operative time was 221 min (183-323 min). The average console time was 111 min (64-213 min). For robotic anterior resection, the total operative time was on average 319 min (222-408 min) with an average console time of 204 min (85-242 min). Eight patients experienced Grade II morbidities (22%) with no serious morbidities and no mortalities. Mean return to bowel function was 2.9 days (1-6 days). The average length of stay was 5.3 days with a median of 4 days (2-20 days). All resections were R0 with an average lymph node yield of 20 nodes (8-46 nodes). CONCLUSION: Our initial experience with Versius demonstrates its safe adoption and implementation for colorectal resections.


Asunto(s)
Laparoscopía , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Anciano , Colectomía , Humanos , Masculino , Estudios Prospectivos , Neoplasias del Recto/cirugía , Resultado del Tratamiento
8.
Front Vet Sci ; 7: 569993, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33195557

RESUMEN

Limited information is available regarding male reproductive physiology in West Indian manatees (Trichechus manatus). Currently, only basic ultrastructural and morphometric descriptions of the spermatozoon exist; however, there are no reports evaluating any seminal characteristics in this species. Therefore, the aim of the study was to fill current gaps in knowledge regarding semen parameters in West Indian manatees by collecting and characterizing multiple ejaculate samples from a single, adult West Indian manatee. Samples were analyzed for the following semen parameters: volume, agglutination, pH, osmolality, viscosity, concentration, total sperm number, motility and kinematic parameters, morphology, plasma membrane integrity, acrosome integrity, chromatin maturation, and chromatin condensation. All macroscopic semen parameters varied to some extent between samples. Total and progressive motility was high for ejaculates 2 to 5, exceeding 97 and 89%, respectively; however, these parameters decreased dramatically throughout ejaculates 6 and 7. Across all samples, curvilinear velocity, straight-line velocity, and average pathway velocity represented the largest significant differences (p < 0.001) between each of the progression velocity subgroups (rapid, medium, slow). Sperm characteristics, including acrosome integrity (79.8%), chromatin condensation (93.1%), and chromatin maturation (99.5%) were very high; however, high numbers of morphologically abnormal sperm were present (52.9%) and plasma membrane integrity was low (45.1%). These results are the first of their kind for this species and suggest high semen quality, based on multiple ejaculates, in this male West Indian manatee.

12.
J Emerg Med ; 59(1): 1-11, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32389434

RESUMEN

BACKGROUND: Falls are among the leading cause of emergency department (ED) visits. OBJECTIVE: We set out to determine whether using a bedside decision aid could decrease falls. METHODS: This randomized controlled trial was conducted on those aged ≥ 65 years who were being discharged home and screened positive for a Centers for Disease Control and Prevention (CDC) fall risk factor. Control-arm subjects were given a CDC brochure about falls. The active-arm subjects received a personalized decision aid intervention. Both groups were followed up via telephone. RESULTS: A total of 200 subjects were enrolled and, after exclusions, 184 patients were analyzed. There were 76 male (41.3%) and 108 female (58.7%) subjects; 14% of the subjects chose to have their medications reviewed, 13.6% chose to have an eye examination, 22.8% chose to begin an exercise program, and the majority (44.6%) chose to have a home safety evaluation. Patients in the intervention arm chose more interventions to complete compared to control-arm subjects (p < 0.0001), but did not complete more interventions (p = 0.3387) and did not experience fewer falls compared to the control arm (p = 0.5675). At study conclusion, 73 subjects reported at least one fall during the study. CONCLUSIONS: Overall, in this study, subjects who had their fall-risk interventions facilitated by a decision tool chose to participate in interventions more than control subjects. However, they did not complete the interventions or fall less often than their counterparts in the control arm. Future study is needed to determine the effect of CDC screening guidelines and interventions facilitated by a decision aid on fall outcomes and their application in the ED population.


Asunto(s)
Accidentes por Caídas , Servicio de Urgencia en Hospital , Accidentes por Caídas/prevención & control , Anciano , Ejercicio Físico , Femenino , Humanos , Masculino , Alta del Paciente , Factores de Riesgo
13.
J Gastrointest Surg ; 24(7): 1663-1672, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32323252

RESUMEN

BACKGROUND: The most common complications after colorectal surgery, postoperative ileus, surgical site infections, and anastomotic leaks continue to occur despite advances in surgical technique and enhanced recovery pathways. Preclinical studies have documented that intestinal bacteria play a role in the development of these complication, yet human data is lacking. Here we hypothesized that patients that develop ileus, surgical site infection, and/or anastomotic leak following colorectal surgery harbor a specific preoperative gut microbiome. METHODS: We performed a prospective cohort study on 101 patients undergoing colon or rectal resection at the Mayo Clinic. Rectal samples were collected preoperatively and on the ward on postoperative day two. The bacterial community from each sample was characterized by 16S rRNA and associated with the development of complications. RESULTS: The rectal microbiome collected from patients in the operating room (p = .003) and on postoperative day two (p = .001) was significantly difference in patients whom later developed postoperative ileus compared with patients that had a normal return of bowel function. Patients whom developed ileus showed increased abundance of Bacteroides spp., Parabacteroides spp., and Ruminococcus spp., bacteria that are associated with promoting intestinal inflammation. There were no differences in the microbiome in patients that developed surgical site infections or anastomotic leaks. CONCLUSIONS: In this pilot study, patients that develop postoperative ileus harbor a specific gut microbiome during the perioperative period. These findings demonstrate that the preoperative bacterial composition may predispose patients to the development of ileus and that perioperative manipulation of the gut bacteria may provide a novel method to promote normal return of bowel function.


Asunto(s)
Cirugía Colorrectal , Ileus , Fuga Anastomótica/etiología , Procedimientos Quirúrgicos Electivos , Humanos , Ileus/etiología , Proyectos Piloto , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , ARN Ribosómico 16S/genética
14.
J Surg Educ ; 75(2): 465-470, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28720424

RESUMEN

OBJECTIVES: To determine whether involvement of colon and rectal fellows has an effect on short-term surgical and oncological outcomes in robotic rectal cancer surgery. PATIENTS AND METHODS: From a dataset of 263 robotic-assisted rectal cancer operations, 114 case-matched patients over a 5-year period (January 2010-December 2015) were included in the study. Patients who underwent resection with and without fellow involvement were compared. Cases were matched according to age, body mass index, neoadjuvant therapy, and tumor location. Intraoperative, postoperative, and pathological outcomes were compared between the 2 groups. RESULTS: There was no difference in tumor grade, type of surgical procedure, presence of an anastomosis, or diverting stoma between groups. In addition, there was no difference in the incidence of intraoperative or postoperative complications between the 2 groups. Estimated blood loss was higher in the fellow group compared to the consultant group (mean difference of 70mL, p = 0.007). For pathological outcomes, there was no difference in surrogate oncological quality indicators, specifically margin positivity and lymph node yield, between the 2 groups. Furthermore, fellow involvement did not adversely affect operative time. CONCLUSION: This study demonstrates that equivalent short-term surgical and oncological outcomes can be achieved with colorectal fellow participation in the field of robotic-assisted rectal cancer surgery.


Asunto(s)
Tempo Operativo , Proctoscopía/métodos , Neoplasias del Recto/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Centros Médicos Académicos , Adulto , Anciano , Estudios de Casos y Controles , Becas , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Neoplasias del Recto/diagnóstico , Estudios Retrospectivos , Medición de Riesgo , Estadísticas no Paramétricas , Resultado del Tratamiento
15.
F1000Res ; 6: 598, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28529719

RESUMEN

Historically, the 5-year survival rates for patients with stage 4 (metastatic) colorectal cancer were extremely poor (5%); however, with advances in systemic chemotherapy combined with an ability to push the boundaries of surgical resection, survival rates in the range of 25-40% can be achieved. This multimodal approach of combining neo-adjuvant strategies with surgical resection has raised a number of questions regarding the optimal management and timing of surgery. For the purpose of this review, we will focus on the treatment of stage 4 colorectal cancer with synchronous liver metastases.

16.
PLoS One ; 10(5): e0127726, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26011034

RESUMEN

BACKGROUND: Understanding retention and loss to follow up in HIV care, in particular the number of people with unknown outcomes, is critical to maximise the benefits of antiretroviral therapy. Individual-level data are not available for these outcomes in Australia, which has an HIV epidemic predominantly focused amongst men who have sex with men. METHODS AND FINDINGS: A network of the 6 main HIV clinical care sites was established in the state of Victoria, Australia. Individuals who had accessed care at these sites between February 2011 and June 2013 as assessed by HIV viral load testing but not accessed care between June 2013 and February 2014 were considered individuals with potentially unknown outcomes. For this group an intervention combining cross-referencing of clinical data between sites and phone tracing individuals with unknown outcomes was performed. 4966 people were in care in the network and before the intervention estimates of retention ranged from 85.9%-95.8% and the proportion with unknown outcomes ranged from 1.3-5.5%. After the intervention retention increased to 91.4-98.8% and unknown outcomes decreased to 0.1-2.4% (p<.01 for all sites for both outcomes). Most common reasons for disengagement from care were being too busy to attend or feeling well. For those with unknown outcomes prior to the intervention documented active psychiatric illness at last visit was associated with not re-entering care (p = 0.04). CONCLUSIONS: The network demonstrated low numbers of people with unknown outcomes and high levels of retention in care. Increased levels of retention in care and reductions in unknown outcomes identified after the intervention largely reflected confirmation of clinic transfers while a smaller number were successfully re-engaged in care. Factors associated with disengagement from care were identified. Systems to monitor patient retention, care transfer and minimize disengagement will maximise individual and population-level outcomes for populations with HIV.


Asunto(s)
Redes Comunitarias/estadística & datos numéricos , Atención a la Salud/métodos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Cooperación del Paciente , Atención a la Salud/estadística & datos numéricos , Infecciones por VIH/diagnóstico , Homosexualidad Masculina/estadística & datos numéricos , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud , Victoria/epidemiología , Carga Viral
17.
J Clin Gastroenterol ; 49(5): 358-69, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25811113

RESUMEN

Over the last decade there has been a striking shift in our understanding of the epidemiology, pathology, and management of diverticular disease. Indeed, many of the guidelines published in the late nineties and early 2000s are now redundant. High-fiber diets, avoidance of nuts and seeds, antibiotic treatment for mild diverticulitis, elective resection after 2 attacks of diverticulitis, Hartmann's procedure (HP), and aggressive management of young patients are all open to question. The more we challenge our understanding of diverticulitis it becomes apparent how little we know about this disease entity. This review aims update the reader on current hypotheses and evidencebased modern management strategies in diverticular disease.


Asunto(s)
Diverticulitis , Divertículo , Enfermedades Intestinales , Fibras de la Dieta , Diverticulitis/diagnóstico , Diverticulitis/epidemiología , Diverticulitis/etiología , Diverticulitis/terapia , Divertículo/diagnóstico , Divertículo/epidemiología , Divertículo/etiología , Divertículo/terapia , Humanos , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/epidemiología , Enfermedades Intestinales/etiología , Enfermedades Intestinales/terapia , Factores de Riesgo
18.
Best Pract Res Clin Gastroenterol ; 28(1): 175-82, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24485264

RESUMEN

A minimally invasive approach to the management of diverticular disease has gained acceptance over the last number of years. Certainly, in the elective setting, laparoscopic sigmoid resection compares favourably with open surgery. The use of laparoscopy in the context of emergency surgery for complicated diverticular disease remains controversial however recent studies have demonstrated a defined role for laparoscopy in the acute setting.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Diverticulitis/cirugía , Laparoscopía , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Diverticulitis/complicaciones , Diverticulitis/diagnóstico , Procedimientos Quirúrgicos Electivos , Urgencias Médicas , Humanos , Laparoscopía/efectos adversos , Resultado del Tratamiento
19.
PLoS One ; 8(7): e69050, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23935921

RESUMEN

Increased intestinal chloride secretion through chloride channels, such as the cystic fibrosis transmembrane conductance regulator (CFTR), is one of the major molecular mechanisms underlying enterotoxigenic diarrhea. It has been demonstrated in the past that the intracellular energy sensing kinase, the AMP-activated protein kinase (AMPK), can inhibit CFTR opening. We hypothesized that pharmacological activation of AMPK can abrogate the increased chloride flux through CFTR occurring during cholera toxin (CTX) mediated diarrhea. Chloride efflux was measured in isolated rat colonic crypts using real-time fluorescence imaging. AICAR and metformin were used to activate AMPK in the presence of the secretagogues CTX or forskolin (FSK). In order to substantiate our findings on the whole tissue level, short-circuit current (SCC) was monitored in human and murine colonic mucosa using Ussing chambers. Furthermore, fluid accumulation was measured in excised intestinal loops. CTX and forskolin (FSK) significantly increased chloride efflux in isolated colonic crypts. The increase in chloride efflux could be offset by using the AMPK activators AICAR and metformin. In human and mouse mucosal sheets, CTX and FSK increased SCC. AICAR and metformin inhibited the secretagogue induced rise in SCC, thereby confirming the findings made in isolated crypts. Moreover, AICAR decreased CTX stimulated fluid accumulation in excised intestinal segments. The present study suggests that pharmacological activation of AMPK effectively reduces CTX mediated increases in intestinal chloride secretion, which is a key factor for intestinal water accumulation. AMPK activators may therefore represent a supplemental treatment strategy for acute diarrheal illness.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Cloruros/metabolismo , Toxina del Cólera/farmacología , Mucosa Intestinal/metabolismo , Intestinos/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Animales , Regulador de Conductancia de Transmembrana de Fibrosis Quística/antagonistas & inhibidores , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Activación Enzimática , Humanos , Técnicas In Vitro , Mucosa Intestinal/efectos de los fármacos , Masculino , Ratones , Fosforilación , Ratas
20.
Eur J Pharmacol ; 696(1-3): 166-71, 2012 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-23022335

RESUMEN

Zinc's usefulness in the treatment of diarrhoea is well established as an addition to oral rehydration. Mechanisms of action of zinc have been explored in intestinal epithelia from rodents and in cell lines. The aim was to examine how zinc alters ion transport and signal transduction in human colon in vitro. Voltage clamped colonic sheets obtained at the time of surgical resection were used to quantify ion transport responses to established secretagogues. Nystatin permeabilisation was used to study basolaterally-sited ion channels. Direct actions of zinc were determined using preparations of colonic crypts isolated from human mucosal sheets. Electrophysiological measurements revealed zinc to be an inhibitor of electrogenic ion transport stimulated by forskolin, PGE(2), histamine and carbachol in isolated human colonic epithelium. Basolateral addition of zinc sulphate had no direct effect on the epithelium. To further outline the mechanism of action, levels of secondary intracellular messengers (3', 5'-cyclic adenosine monophosphate; cAMP) were determined in isolated colonic crypts, and were found to be reduced by zinc sulphate. Finally, indirect evidence from nystatin-permeabilised mucosae further suggested that zinc inhibits basolateral K(+) channels, which are critical for transepithelial Cl(-) secretion linked to water flux. Anti-secretory, and therefore anti-diarrhoeal, actions of exogenous zinc are due, at least in part, to direct basolateral epithelial K(+) channel inhibition.


Asunto(s)
Cloruros/metabolismo , Colon/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Sulfato de Zinc/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Colon/metabolismo , Femenino , Humanos , Técnicas In Vitro , Mucosa Intestinal/metabolismo , Masculino , Persona de Mediana Edad
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