Transitioning a home telehealth project into a sustainable, large-scale service: a qualitative study.

BACKGROUND: This study was a component of the Flinders Telehealth in the Home project, which tested adding home telehealth to existing rehabilitation, palliative care and geriatric outreach services. Due to the known difficulty of transitioning telehealth projects services, a qualitative study was conducted to produce a preferred implementation approach for sustainable and large-scale operations, and a process model that offers practical advice for achieving this goal. METHODS: Initially, semi-structured interviews were conducted with senior clinicians, health service managers and policy makers, and a thematic analysis of the interview transcripts was undertaken to identify the range of options for ongoing operations, plus the factors affecting sustainability. Subsequently, the interviewees and other decision makers attended a deliberative forum in which participants were asked to select a preferred model for future implementation. Finally, all data from the study was synthesised by the researchers to produce a process model. RESULTS: 19 interviews with senior clinicians, managers, and service development staff were conducted, finding strong support for home telehealth but a wide diversity of views on governance, models of clinical care, technical infrastructure operations, and data management. The deliberative forum worked through these options and recommended a collaborative consortium approach for large-scale implementation. The process model proposes that the key factor for large-scale implementation is leadership support, which is enabled by 1) showing solutions to the problems of service demand, budgetary pressure and the relationship between hospital and primary care, 2) demonstrating how home telehealth aligns with health service policies, and 3) achieving clinician acceptance through providing evidence of benefit and developing new models of clinical care. Two key actions to enable change were marketing telehealth to patients, clinicians and policy-makers, and building a community of practice. CONCLUSIONS: The implementation of home telehealth services is still in an early stage. Change agents and a community of practice can contribute by marketing telehealth, demonstrating policy alignment and providing potential solutions for difficult health services problems. This should assist health leaders to move from trials to large-scale services.

The islet-acinar axis of the pancreas: more than just insulin.

Although the role of the islets in the regulation of acinar cell function seemed a mystery to investigators who observed their dispersion among pancreatic acini, over time an appreciation for this intricate and unique structural arrangement has developed. The last three decades have witnessed a steadily growing understanding of the interrelationship of the endocrine and the exocrine pancreas. The islet innervation and vascular anatomy have been more fully characterized and provide an appropriate background for our current understanding. The interrelationship between the endocrine and exocrine pancreas is mediated by islet-derived hormones such as insulin and somatostatin, other humoral factors including pancreastatin and ghrelin, and also neurotransmitters (nitric oxide, peptide YY, substance P, and galanin) released by the nerves innervating the pancreas. Although considerable progress has been achieved, further work is required to fully delineate the complex interplay of the numerous mechanisms involved. This review aims to provide a comprehensive update of the current literature available, bringing together data gleaned from studies addressing the actions of individual hormones, humoral factors, and neurotransmitters on the regulation of amylase secretion from the acinar cell. This comprehensive view of the islet-acinar axis of the pancreas while acknowledging the dominant role played by insulin and somatostatin on exocrine secretion sheds light on the influence of the various neuropeptides on amylase secretion.

Aquaporin-1 in blood vessels of rat circumventricular organs.

Although the water channel protein aquaporin-1 (AQP1) is widely observed outside the rat brain in continuous, but not fenestrated, vascular endothelia, it has not previously been observed in any endothelia within the normal rat brain and only to a limited extent in the human brain. In this immunohistochemical study of rat brain, AQP1 has also been found in microvessel endothelia, probably of the fenestrated type, in all circumventricular organs (except the subcommissural organ and the vascular organ of the lamina terminalis): in the median eminence, pineal, subfornical organ, area postrema and choroid plexus. The majority of microvessels in the median eminence, pineal and choroid plexus, known to be exclusively fenestrated, are shown to be AQP1-immunoreactive. In the subfornical organ and area postrema in which many, but not all, microvessels are fenestrated, not all microvessels are AQP1-immunoreactive. In the AQP1-immunoreactive microvessels, the AQP1 probably facilitates water movement between blood and interstitium as one component of the normal fluxes that occur in these specialised sensory and secretory areas. AQP1-immunoreactive endothelia have also been seen in a small population of blood vessels in the cerebral parenchyma outside the circumventricular organs, similar to other observations in human brain. The proposed development of AQP1 modulators to treat various brain pathologies in which AQP1 plays a deleterious role will necessitate further work to determine the effect of such modulators on the normal function of the circumventricular organs.

Octreotide negates the benefit of galantide when used in the treatment of caerulein-induced acute pancreatitis in mice.

BACKGROUND: We have previously shown that galantide, a non-specific galanin receptor antagonist, ameliorates acute pancreatitis (AP) induced in mice. Octreotide, a somatostatin analogue, has been used in the treatment of AP with inconsistent outcomes. This study set out to compare the efficacy of a combined treatment of galantide and octreotide with the efficacy of each agent individually in experimental AP. METHODS: Acute pancreatitis was induced in mice with 7-hourly caerulein injections. Galantide and/or octreotide were co-administered with each caerulein injection commencing with the first injection. Control animals received galantide, octreotide or saline alone. Pancreata were harvested for histological examination and estimation of myeloperoxidase (MPO) activity. Plasma amylase and lipase activities were measured. RESULTS: Galantide significantly reduced AP-induced hyperenzymaemia by 39-45%. Octreotide alone, or in combination with galantide, did not significantly alter AP-induced hyperenzymaemia. Plasma enzyme activity in the control groups was comparable with pre-treatment activity. Galantide and octreotide administered individually reduced MPO activity by 79% and 50%, respectively; however their combination was without effect. Galantide, octreotide and their combination significantly reduced the percentage of abnormal acinar cells by 28-45%. CONCLUSIONS: Treatment with galantide alone ameliorated most of the indices of AP studied, whereas treatment with octreotide reduced pancreatic MPO activity and acinar cell damage. Combining the two peptides appears to negate their individual benefits, which suggests an interaction in their mechanism of action.

Galanin potentiates supramaximal caerulein-stimulated pancreatic amylase secretion via its action on somatostatin secretion.

Galanin inhibits pancreatic amylase secretion from mouse lobules induced by physiological concentrations of caerulein via an insulin-dependent mechanism. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on pancreatic amylase secretion induced by supramaximal concentrations of caerulein. Amylase secretion from isolated murine pancreatic lobules was measured. Lobules were coincubated with galanin (10(-12)-10(-7) M) and caerulein (10(-7) M). Lobules were preincubated with atropine (10(-5) M), tetrodotoxin (10(-5) M), diazoxide (10(-7) M), or the galanin antagonist galantide (10(-12)-10(-7) M) for 30 min followed by incubation with caerulein alone, or combined with galanin (10(-12) M). Lobules were also coincubated with combinations of galanin (10(-12) M), caerulein, octreotide (10(-12)-10(-7) M) or cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[BZL]), a somatostatin receptor antagonist (10(-9) M). Amylase secretion was expressed as percent of total lobular amylase. Caerulein stimulated amylase secretion to 124% of control. Diazoxide pretreatment abolished the caerulein-stimulated amylase secretion, whereas atropine or tetrodotoxin caused a partial inhibition. Galanin (10(-12)-10(-7) M) potentiated caerulein-stimulated amylase secretion to 160% of control. Preincubation with a combination of atropine and diazoxide abolished the potentiating effect of galanin, indicating muscarinic receptor and insulin mediation. Preincubation with galantide abolished the galanin effect, implying galanin receptor involvement. Coincubation with caerulein, galanin, and octreotide significantly reduced the potentiating effect galanin. However, coincubation with the somatostatin receptor antagonist, alone or in combination with galanin, significantly increased caerulein-stimulated amylase secretion to a level comparable to the galanin potentiation. Taken together, these data suggest that, at supramaximal caerulein concentrations, galanin acts via its receptors to further increase caerulein-stimulated amylase secretion by inhibiting the caerulein-induced release of somatostatin.

Galanin inhibits caerulein-stimulated pancreatic amylase secretion via cholinergic nerves and insulin.

Pancreatic exocrine secretion is affected by galanin, but the mechanisms involved are unclear. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on basal and stimulated pancreatic amylase secretion in vitro. The effect of galanin on basal-, carbachol-, and caerulein-stimulated amylase secretion from isolated murine pancreatic lobules was measured. Carbachol and caerulein concentration-response relationships were established. Lobules were coincubated with galanin (10(-12) M to 10(-7) M), carbachol (10(-6) M), or caerulein (10(-10) M). Lobules were preincubated with atropine (10(-5) M), tetrodotoxin (10(-5) M), hexamethonium (10(-5) M), or diazoxide (10(-7) M and 10(-4) M) for 30 min followed by incubation with caerulein (10(-10) M) alone or combined with galanin (10(-12) M). Amylase secretion was expressed as percent of total lobular amylase. Immunohistochemical studies used the antigen retrieval technique and antisera for galanin receptor (GALR) 1, 2, and 3. Carbachol and caerulein stimulated amylase secretion in a concentration-dependent manner with maximal responses of two- and 1.7-fold over control evoked at 10(-6) M and 10(-10) M, respectively. Galanin (10(-12) M) completely inhibited caerulein-stimulated amylase secretion but had no effect on carbachol-stimulated or basal secretion. Atropine and tetrodotoxin pretreatment abolished the caerulein-stimulated amylase secretion, whereas hexamethonium had no significant effect. Diazoxide significantly reduced caerulein-stimulated amylase secretion by approximately 80%. Galanin did not affect caerulein-stimulated amylase secretion in the presence of hexamethonium or diazoxide. Glucose-stimulated amylase secretion was also inhibited by galanin. Immunohistochemistry revealed islet cells labeled for GALR2. These data suggest that galanin may modulate caerulein-stimulated amylase secretion by acting on cholinergic nerves and/or islet cells possibly via GALR2 to regulate insulin release.

It's important, but not important enough: eHealth as a curriculum priority in medical education in Australia.

Information and communications technology has become central to the way in which health services are provided. Technology-enabled services in healthcare are often described as eHealth, or more recently, digital health. Practitioners may require new knowledge, skills and competencies to make best use of eHealth, and while universities may be a logical place to provide such education and training, a study in 2012 found that the workforce was not being adequately educated to achieve competence to work with eHealth. We revisited eHealth education and training in Australian universities with a focus on medical schools; we aimed to explore the progress of eHealth in the Australian medical curriculum. We conducted a national interview study and interpretative phenomenological analysis with participants from all 19 medical schools in Australia; two themes emerged: (i) consensus on the importance of eHealth to current and future clinical practice; (ii) there are other priorities, and no strong drivers for change. Systemic problems inhibit the inclusion of eHealth in medical education: the curriculum is described as 'crowded' and with competing demands, and because accrediting bodies do not expect eHealth competence in medical graduates, there is no external pressure for its inclusion. Unless and until accrediting bodies recognise and expect competence in eHealth, it is unlikely that it will enter the curriculum; consequently the future workforce will remain unprepared.

Theoretical frameworks in telemedicine research.

The purposive use of theory is a foundational component of research, which underpins the design, methodology, measures, interventions, and interpretation of the research project. This should be considered from the time the nascent idea of the research is born, until the final interpretation of results and write up of the discussion. Several theories relevant to telemedicine are described, discussed, and linked to typical research questions in the field.

Quantifying shape changes of silicone breast implants in a murine model using in vivo micro-CT.

A major complication of silicone breast implants is the formation of a capsule around the implant known as capsular contracture which results in the distortion of the implant. Recently, a mouse model for studying capsular contracture was examined using micro-computed tomography (micro-CT), however, only qualitative changes were reported. The aim of this study was to develop a quantitative method for comparing the shape changes of silicone implants using in vivo micro-CT. Mice were bilaterally implanted with silicone implants and underwent ionizing radiation to induce capsular contracture. On day 28 post-surgery mice were examined in vivo using micro-CT. The reconstructed cross-section images were visually inspected to identify distortion. Measurements were taken in 2D and 3D to quantify the shape of the implants in the normal (n = 11) and distorted (n = 5) groups. The degree of anisotropy was significantly higher in the distorted implants in the transaxial view (0.99 vs. 1.19, p = 0.002) and the y-axis lengths were significantly shorter in the sagittal (9.27 mm vs. 8.55 mm, p = 0.015) and coronal (9.24 mm vs. 8.76 mm, p = 0.031) views, indicating a deviation from the circular cross-section and shortening of the long axis. The 3D analysis revealed a significantly lower average thickness (sphere-fitting method) in distorted implants (6.86 mm vs. 5.49 mm, p = 0.002), whereas the volume and surface area did not show significant changes. Statistically significant differences between normal and distorted implants were found in 2D and 3D using distance measurements performed via micro-CT. This objective analysis method can be useful for a range of studies involving deformable implants using in vivo micro-CT. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1447-1452, 2017.

Investigating the preferences of older people for telehealth as a new model of health care service delivery: A discrete choice experiment.

Introduction Telehealth approaches to health care delivery can potentially improve quality of care and clinical outcomes, reduce mortality and hospital utilisation, and complement conventional treatments. However, substantial research into the potential for integrating telehealth within health care in Australia, particularly in the provision of services relevant to older people, including palliative care, aged care and rehabilitation, is lacking. Furthermore, to date, no discrete choice experiment (DCE) studies internationally have sought the views and preferences of older people about the basic features that should make up a telehealth approach to these services. Methods Using a DCE, we investigated the relative importance of six salient features of telehealth (what aspects of care are to be pursued during telehealth sessions, distance to the nearest hospital or clinic, clinicians' attitude to telehealth, patients' experience of using technology, what types of assessments should be conducted face-to-face versus via telehealth sessions and the costs associated with receiving telehealth). Data were obtained from an online panel of older people aged 65 years and above, drawn from the Australian general population. Results The mean age for 330 study participants was 69 years. In general, individuals expressed strong preferences for telehealth services that offered all aspects of care, were relatively inexpensive and targeted specifically at individuals living in remote regions without easy access to a hospital or clinic. Participants also preferred telehealth services to be offered to individuals with some prior experience of using technology, provided by clinicians who were positive about telehealth but wanted all or some pre-telehealth health assessments to take place in a hospital or clinic. Preferences only differed by gender. Additionally, respondents did not feel that telehealth led to loss of privacy and confidentiality. Discussion Our findings indicate a preference amongst respondents for face-to-face pre-telehealth health assessments and, thereafter, a comprehensive telehealth model (in terms of services offered) targeted at those with some technological know-how as a substitute for attendance at hospitals and clinics, especially where these health facilities were far away from older people's homes. The findings may be usefully incorporated into the design of future telehealth models of service delivery for older people.

Technology support to a telehealth in the home service: Qualitative observations.

INTRODUCTION: The Flinders University Telehealth in the Home (FTH) trial was an action research initiative that introduced and evaluated the impact of telehealth services on palliative care patients living in the community, home-based rehabilitation services for the elderly, and services to the elderly in residential aged care. The aim of this study was to understand the issues encountered during the provision of technology services that supported this trial. METHODS: A mixed methods approach was undertaken to analyse the roles of information and communication technology (ICT) and clinical staff in design, technology management and training. The data sources were staff observations and documents including job logs, meetings, emails and technology descriptions. RESULTS: Use of consumer technology for telehealth required customisation of applications and services. Clinicians played a key role in definition of applications and the embedding of workflow into applications. Usability of applications was key to their subsequent use. Management of design creep and technology services, coupled with support and training for clinicians were important to maintenance of a telehealth service. DISCUSSION: In the setting described, an iterative approach to the development of telehealth services to the home using consumer technologies was needed. The efficient management of consumer devices in multiple settings will become critical as telehealth services grow in scale. Effective collaboration between clinical and technical stakeholders and further workforce education in telehealth can be key enablers for the transition of face-to-face care to a telehealth mode of delivery.

Home Telehealth Video Conferencing: Perceptions and Performance.

BACKGROUND: The Flinders Telehealth in the Home trial (FTH trial), conducted in South Australia, was an action research initiative to test and evaluate the inclusion of telehealth services and broadband access technologies for palliative care patients living in the community and home-based rehabilitation services for the elderly at home. Telehealth services at home were supported by video conferencing between a therapist, nurse or doctor, and a patient using the iPad tablet. OBJECTIVE: The aims of this study are to identify which technical factors influence the quality of video conferencing in the home setting and to assess the impact of these factors on the clinical perceptions and acceptance of video conferencing for health care delivery into the home. Finally, we aim to identify any relationships between technical factors and clinical acceptance of this technology. METHODS: An action research process developed several quantitative and qualitative procedures during the FTH trial to investigate technology performance and users perceptions of the technology including measurements of signal power, data transmission throughput, objective assessment of user perceptions of videoconference quality, and questionnaires administered to clinical users. RESULTS: The effectiveness of telehealth was judged by clinicians as equivalent to or better than a home visit on 192 (71.6%, 192/268) occasions, and clinicians rated the experience of conducting a telehealth session compared with a home visit as equivalent or better in 90.3% (489/540) of the sessions. It was found that the quality of video conferencing when using a third generation mobile data service (3G) in comparison to broadband fiber-based services was concerning as 23.5% (220/936) of the calls failed during the telehealth sessions. The experimental field tests indicated that video conferencing audio and video quality was worse when using mobile data services compared with fiber to the home services. As well, statistically significant associations were found between audio/video quality and patient comfort with the technology as well as the clinician ratings for effectiveness of telehealth. CONCLUSIONS: These results showed that the quality of video conferencing when using 3G-based mobile data services instead of broadband fiber-based services was less due to failed calls, audio/ video jitter, and video pixilation during the telehealth sessions. Nevertheless, clinicians felt able to deliver effective services to patients at home using 3G-based mobile data services.

Interferon-γ suppresses intestinal epithelial aquaporin-1 expression via Janus kinase and STAT3 activation.

Inflammatory bowel diseases are associated with dysregulated electrolyte and water transport and resultant diarrhea. Aquaporins are transmembrane proteins that function as water channels in intestinal epithelial cells. We investigated the effect of the inflammatory cytokine, interferon-γ, which is a major player in inflammatory bowel diseases, on aquaporin-1 expression in a mouse colonic epithelial cell line, CMT93. CMT93 monolayers were exposed to 10 ng/mL interferon-γ and aquaporin-1 mRNA and protein expressions were measured by real-time PCR and western blot, respectively. In other experiments, CMT93 cells were pretreated with inhibitors or were transfected with siRNA to block the effects of Janus kinases, STATs 1 and 3, or interferon regulatory factor 2, prior to treatment with interferon-γ. Interferon-γ decreased aquaporin-1 expression in mouse intestinal epithelial cells in a manner that did not depend on the classical STAT1/JAK2/IRF-1 pathway, but rather, on an alternate Janus kinase (likely JAK1) as well as on STAT3. The pro-inflammatory cytokine, interferon-γ may contribute to diarrhea associated with intestinal inflammation in part through regulation of the epithelial aquaporin-1 water channel via a non-classical JAK/STAT receptor signalling pathway.

Telerehabilitation for older people using off-the-shelf applications: acceptability and feasibility.

We investigated the feasibility of providing telerehabilitation in the home as an alternative to conventional ambulatory rehabilitation. Two groups of patients were accepted for telerehabilitation. The first group were community patients who needed rehabilitation, e.g. following a stroke, a fracture or prolonged hospital admission. The second group was from two rural nursing homes where residents were identified with a recent injury, fall or hospitalisation. Telerehabilitation employed a coaching model, with fewer therapist home visits, more feedback and "homework" for the patient. Patients had a tablet computer loaded with a videoconferencing app to connect with therapists and relevant therapeutic apps. Multidisciplinary care was provided for up to 8 weeks. The majority (86%) of eligible patients consented to receive telerehabilitation in their own home (n = 61) or in the country nursing home where they lived (n = 17). Most services were delivered using the 3G and 4G wireless networks with few technical problems. On average participants felt that they had achieved 75% of the goals set at the beginning of the programme. High levels of satisfaction were recorded. There was a 50% reduction in home visits by staff, or 10 visits per patient. Speech therapists were able to double occasions of service and direct patient contact time, whilst halving their travel time. Previous experience with technology and age were not barriers to this method of delivery but did affect recruitment. Telerehabilitation using off-the-shelf technology is feasible for post-acute treatment.

The efficacy of combining feG and galantide in mild caerulein-induced acute pancreatitis in mice.

We have previously shown that galantide ameliorates mild acute pancreatitis (AP), and the salivary tripeptide analogue, feG, ameliorates severe AP in mice. In this study, we compared the efficacy of combining galantide and feG with that of the individual agents in treating mild AP induced in mice with 7-hourly caerulein injections. Galantide was co-administered with each caerulein injection commencing with the first injection. feG was co-administered with the first injection of caerulein as a single intraperitoneal injection. Combination of the agents was also administered. Control animals received galantide, feG, or saline alone. Pancreata were harvested for histological examination and estimation of myeloperoxidase (MPO) activity. Plasma enzyme activities were measured. Galantide significantly reduced AP-induced hyperenzymemia by 41-49%. The combination of galantide and feG significantly reduced AP-induced hyperenzymemia by 39-40%, whereas feG alone was without effect. Plasma enzyme activity in the control groups was comparable with pre-treatment activity. Galantide, feG, and their combination significantly reduced MPO activity by 83, 44 and 74% respectively, and % abnormal acinar cells by 32, 29 and 36% respectively. This study demonstrates for the first time the beneficial effect of feG in mild caerulein-induced AP. Moreover the data indicate that the hyperenzymemia in mild caerulein-induced AP at 12h possibly reflect a larger secretory component as compared to enzyme release due to neutrophil-mediated acinar cell damage. The effects of the treatment with both peptides indicate a possible role for galantide in modulating neutrophil chemotaxis/activation and supports the hypothesis that galantide may influence neurogenic inflammation in AP.

The combination of neurokinin-1 and galanin receptor antagonists ameliorates caerulein-induced acute pancreatitis in mice.

Both galanin and substance P have been separately implicated in the pathogenesis of acute pancreatitis. We compared the efficacy of the combination of the galanin antagonist galantide and the neurokinin-1 receptor antagonist L703,606 with that of either alone in the treatment of acute pancreatitis. Acute pancreatitis was induced in mice with 7-hourly caerulein injections. Galantide was co-administered with each caerulein injection commencing with the first injection (prophylactic) or 2h after the first injection (therapeutic). L703,606 was administered either 30 min before (prophylactic), or 2h after the first caerulein injection (therapeutic). Combination of the two agents was also administered. Control groups received galantide, L703,606, or saline, without caerulein. Pancreata were harvested for histological examination and estimation of myeloperoxidase activity. Plasma amylase activity was measured. Prophylactic and therapeutic administration of galantide reduced the hyperamylasemia by 37% and 30% respectively whereas only prophylactic L703,606 reduced hyperamylasemia (by 34%). Prophylactic administration of the combined antagonists reduced the hyperamylasemia by 44%. In contrast, therapeutic administration of the combination significantly increased plasma amylase levels by 27%. The plasma amylase activity in the control groups was similar to basal levels. Prophylactic and therapeutic administration of either antagonist or the combination significantly reduced myeloperoxidase activity. Galantide and L703,606 individually, and in combination, significantly reduced the acute pancreatitis-induced necrosis score. The administration of the combined antagonists does not offer any further benefit as compared to galantide alone. An interaction between neurokinin-1 and galanin receptors may occur to modulate amylase secretion.

Galanin mediates the pathogenesis of cerulein-induced acute pancreatitis in the mouse.

OBJECTIVES: Acute pancreatitis (AP) is characterized by pancreatic microcirculatory and secretory disturbances. As galanin can modulate pancreatic vascular perfusion, we sought to determine if galanin plays a role in AP. METHODS: Acute pancreatitis was induced in wild-type and galanin gene knockout mice by intraperitoneal injections of cerulein. The severity of AP was evaluated (plasma amylase and lipase, myeloperoxidase activity, and acinar cell necrosis) with and without treatment with galanin or the antagonist galantide. Galanin receptor messenger RNA expression in mouse pancreas was measured by reverse transcription-polymerase chain reaction and Western blot analysis. RESULTS: Galantide ameliorated AP, reducing all indices by 25% to 40%, whereas galanin was without effect. In galanin knockout mice, all indices of AP were reduced 25% to 50% compared with wild-type littermates. Galanin administration to the knockout mice exacerbated AP such that it was comparable with the AP induced in the wild-type mice. Conversely, administration of galantide to the galanin knockout mice did not affect the AP, whereas AP was ameliorated in the wild-type mice. The 3 galanin receptor subtypes are expressed in mouse pancreas, with receptor subtype 3 expression predominating. CONCLUSIONS: These data implicate a role for galanin in AP and suggest a potential clinical application for galanin antagonists in treatment.

Galanin in the regulation of pancreatic vascular perfusion.

OBJECTIVES: Acute pancreatitis is associated with compromised pancreatic microcirculation. Galanin is a vasoactive neuropeptide, but its role in the regulation of pancreatic vascular perfusion (PVP) is unclear. METHODS: Localization of galanin immunoreactivity was investigated by immunohistochemistry, and the effects of bolus doses of galanin or the antagonist galantide on blood pressure (BP) and PVP (by laser Doppler fluxmetry) were determined in anesthetized possums. RESULTS: Galanin immunoreactivity was abundant in the possum pancreas particularly around blood vessels. Galanin (0.001-10 nmol) produced a dose-dependent increase in BP (to 177% of baseline) and a complex PVP response consisting of a transient increase, then a fall below baseline with recovery to above baseline. Galantide (0.003-30 nmol) caused a dose-dependent biphasic response in BP, with a reduction, recovery, then a further fall, followed by recovery, whereas PVP increased (178%) then fell (to 56%) of baseline. Similar effects were produced by continuous intravenous infusion of galanin (1 and 10 nmol) or galantide (3 and 30 nmol). The second-phase response of these agents is probably a passive response of the pancreatic vasculature to systemic cardiovascular effects. CONCLUSIONS: These data suggest that galanin acutely reduces PVP, whereas galantide increases it, implying galanin may be important in the regulation of PVP.

The tripeptide analog feG ameliorates severity of acute pancreatitis in a caerulein mouse model.

Acute pancreatitis (AP) is associated with significant morbidity and mortality; however, there is no specific treatment for this disease. A novel salivary tripeptide analog, feG, reduces inflammation in several different animal models of inflammation. The aims of this study were to determine whether feG reduced the severity of AP and modifies the expression of pancreatic ICAM-1 mRNA during AP in a mouse model. AP was induced in mice by hourly (x12) intraperitoneal injections of caerulein. A single dose of feG (100 microg/kg) was coadministered with caerulein either at time 0 h (prophylactic) or 3 h after AP induction (therapeutic). Plasma amylase and pancreatic MPO activities and pancreatic ICAM-1 mRNA expression (by RT-PCR) were measured. Pancreatic sections were histologically assessed for abnormal acinar cells and interstitial space. AP induction produced a sevenfold increase in plasma amylase, a tenfold increase in pancreatic MPO activity, and a threefold increase in interstitial space, and 90% of the acinar cells were abnormal. Prophylactic treatment with feG reduced the AP-induced plasma amylase activity by 45%, pancreatic MPO by 80%, the proportion of abnormal acinar cells by 30%, and interstitial space by 40%. Therapeutic treatment with feG significantly reduced the AP-induced abnormal acinar cells by 10% and the interstitial space by 20%. Pancreatic ICAM-1 mRNA expression was upregulated in AP and was reduced by 50% with prophylactic and therapeutic treatment with feG. We conclude that feG ameliorates experimental AP acting at least in part by modulating ICAM-1 expression in the pancreas.