The impact of an interprofessional care transitions clinic on readmission rates and costs.

The objective of this study was to assess the effectiveness of the Interprofessional Care Transitions Clinic (ICTC) in reducing preventable readmissions and their associated costs among Medicare/Medicaid patients. A prospective cohort study was conducted among adults who were discharged from the University of Maryland Prince George's Hospital Center to assess the comparative effectiveness of a clinic-based intervention in terms of readmission events, potentially avoidable utilization, length of stay, and hospital charges. Outcomes were evaluated at 1 month, 3 months, and 6 months post-discharge. There were statistically significant differences in the following outcomes (follow-up period): proportion of readmissions (3 months), potentially avoidable utilization (1 month), and mean medical charges for ICTC patients compared to non-ICTC patients (1 month). This program was aimed at testing the impact of having an interprofessional team focused on providing holistic patient-centered care.

Impact of pharmacist-led program on knowledge of college students about pre-exposure prophylaxis.

OBJECTIVE: This study's primary objective was to evaluate the impact of a pharmacist-led educational program on undergraduate college students' knowledge about PrEP. METHODS: This was a cross-sectional, pre- and postprogram survey study. The study included undergraduate students at least 18 years old at a university in Washington, DC. Graduate students, pharmacy students, and those not enrolled at the university were excluded. Before the educational program, the participants completed an anonymous preprogram survey to assess their perception and knowledge of HIV prevention and PrEP as well as their willingness to obtain a prescription for PrEP. A pharmacist delivered a 30-minute educational program to students regarding HIV prevention and PrEP in small groups. After the program, the participants completed a postprogram survey to evaluate the changes from the baseline responses. Paired t tests and chi-square tests detected the associations between the pre- and postprogram surveys. RESULTS: One-hundred sixteen students participated in the program, and 102 surveys were included in the data analysis. Students' perception of their knowledge of HIV (4.2 vs. 4.6; P < 0.001), perception of their knowledge of PrEP (3.1 vs. 4.5; P < 0.001), and their willingness to obtain a prescription for PrEP (3.8 vs. 4.5; P < 0.001) was statistically significant after the education. There was a statistically significant increase in the participants' actual knowledge of HIV risk factors (62.4% correct vs. 90.2% correct; P < 0.001) and knowledge of PrEP effectiveness (26.3% vs. 75.0%; P < 0.001). CONCLUSION: These findings demonstrated that a pharmacist-led educational program may have an impact on undergraduate students' perception and knowledge of HIV and PrEP. This study may help to further guide pharmacists' PrEP initiatives in this targeted population.

Impact of pharmacist-led program on knowledge of college students about pre-exposure prophylaxis.

OBJECTIVE: This study's primary objective was to evaluate the impact of a pharmacist-led educational program on undergraduate college students' knowledge about PrEP. METHODS: This was a cross-sectional, pre- and postprogram survey study. The study included undergraduate students at least 18 years old at a university in Washington, DC. Graduate students, pharmacy students, and those not enrolled at the university were excluded. Before the educational program, the participants completed an anonymous preprogram survey to assess their perception and knowledge of HIV prevention and PrEP as well as their willingness to obtain a prescription for PrEP. A pharmacist delivered a 30-minute educational program to students regarding HIV prevention and PrEP in small groups. After the program, the participants completed a postprogram survey to evaluate the changes from the baseline responses. Paired t tests and chi-square tests detected the associations between the pre- and postprogram surveys. RESULTS: One-hundred sixteen students participated in the program, and 102 surveys were included in the data analysis. Students' perception of their knowledge of HIV (4.2 vs. 4.6; P < 0.001), perception of their knowledge of PrEP (3.1 vs. 4.5; P < 0.001), and their willingness to obtain a prescription for PrEP (3.8 vs. 4.5; P < 0.001) was statistically significant after the education. There was a statistically significant increase in the participants' actual knowledge of HIV risk factors (62.4% correct vs. 90.2% correct; P < 0.001) and knowledge of PrEP effectiveness (26.3% vs. 75.0%; P < 0.001). CONCLUSION: These findings demonstrated that a pharmacist-led educational program may have an impact on undergraduate students' perception and knowledge of HIV and PrEP. This study may help to further guide pharmacists' PrEP initiatives in this targeted population.

Patient perception of community pharmacists prescribing pre-exposure prophylaxis for HIV prevention.

OBJECTIVE: The primary objective of this study was to determine patients' perceptions of pharmacists prescribing pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) prevention. DESIGN: An anonymous, 26-item, cross-sectional survey was administered to individuals and data collection occurred during a 12-week period from January to March 2019. SETTING AND PARTICIPANTS: Individuals were recruited to complete the survey in person at 5 locations of a large grocery-chain pharmacy in Washington, D.C. and Maryland. Inclusion criteria included individuals who were at least 18 years old and able to read and write English. Exclusion criteria included persons living with HIV or acquired immunodeficiency syndrome. OUTCOME MEASURES: In order to measure perception, participants were asked on the survey to select their level of agreement using a Likert scale from 1 to 5 (1 = strongly disagree, 5 = strongly agree). Researchers analyzed overall perception in addition to differences in perception based on various demographic characteristics. RESULTS: In total, 117 surveys were collected and analyzed. Most participants were comfortable with pharmacists prescribing PrEP. Notable statistically significant findings included participants who interacted with pharmacists through medication therapy review (4.4, 3.1 [P < 0.05]) and vaccinations (4.3, 3.1 [P < 0.05]) were more likely to agree with pharmacists prescribing PrEP than participants who had no previous interactions with pharmacists. Participants who had previously used PrEP were more likely to agree with pharmacists prescribing PrEP than those who had not used PrEP before. CONCLUSION: This study provided a glimpse into patients' perceptions of pharmacists prescribing PrEP. Patients were generally favorable of pharmacists prescribing PrEP; however, there are still barriers to overcome before prescribing PrEP for HIV prevention can feasibly occur in the community setting.

Mice that express farnesylated versions of prelamin A in neurons develop achalasia.

Neurons in the brain produce lamin C but almost no lamin A, a consequence of the removal of prelamin A transcripts by miR-9, a brain-specific microRNA. We have proposed that miR-9-mediated regulation of prelamin A in the brain could explain the absence of primary neurological disease in Hutchinson-Gilford progeria syndrome, a genetic disease caused by the synthesis of an internally truncated form of farnesyl-prelamin A (progerin). This explanation makes sense, but it is not entirely satisfying because it is unclear whether progerin-even if were expressed in neurons-would be capable of eliciting neuropathology. To address that issue, we created a new Lmna knock-in allele, Lmna(HG-C), which produces progerin transcripts lacking an miR-9 binding site. Mice harboring the Lmna(HG-C) allele produced progerin in neurons, but they had no pathology in the central nervous system. However, these mice invariably developed esophageal achalasia, and the enteric neurons and nerve fibers in gastrointestinal tract were markedly abnormal. The same disorder, achalasia, was observed in genetically modified mice that express full-length farnesyl-prelamin A in neurons (Zmpste24-deficient mice carrying two copies of a Lmna knock-in allele yielding full-length prelamin A transcripts lacking a miR-9 binding site). Our findings indicate that progerin and full-length farnesyl-prelamin A are toxic to neurons of the enteric nervous system.

A hypomorphic Egfr allele does not ameliorate the palmoplantar keratoderma caused by SLURP1 deficiency.

Mutations in SLURP1, a secreted protein of keratinocytes, cause a palmoplantar keratoderma (PPK) known as mal de Meleda. Slurp1 deficiency in mice faithfully recapitulates the human disease, with increased keratinocyte proliferation and thickening of the epidermis on the volar surface of the paws. There has long been speculation that SLURP1 serves as a ligand for a receptor that regulates keratinocyte growth and differentiation. We were intrigued that mutations leading to increased signalling through the epidermal growth factor receptor (EGFR) cause PPK. Here, we sought to determine whether reducing EGFR signalling would ameliorate the PPK associated with SLURP1 deficiency. To address this issue, we bred Slurp1-deficient mice that were homozygous for a hypomorphic Egfr allele. The hypomorphic Egfr allele, which leads to reduced EGFR signalling in keratinocytes, did not ameliorate the PPK elicited by SLURP1 deficiency, suggesting that SLURP1 deficiency causes PPK independently (or downstream) from the EGFR pathway.

Evaluating health outcomes following a pharmacist-provided comprehensive pretravel health clinic in a supermarket pharmacy.

OBJECTIVES: To evaluate health outcomes and acceptance of pharmacists' recommendations of travel health including prevalance of immunizations, sunburn, insect-borne diseases, traveler's diarrhea, and altitude sickness, and assess patient satisfaction with the pretravel health clinic. DESIGN: Retrospective cross-sectional study design. SETTING: Central Virginia, July 2011 to June 2012. PARTICIPANTS: Patients 18 years and older who had an appointment with the pharmacist for pretravel health. INTERVENTION: Interview/survey administered to patients by telephone. MAIN OUTCOME MEASURES: Health outcomes, acceptance rates of pharmacist's travel health recommendations, and patient satisfaction. RESULTS: Of 356 patients eligible to participate in the study, 103 patients participated, 30 patients declined, and 223 patients could not be reached by telephone (29% response rate). Pharmacists' recommendations for travel immunizations (100% acceptance rate for yellow fever and 82% for Typhoid) and nonpharmacologic preventive measures (prevention of sunburn, traveler's diarrhea, insect bites, and altitude sickness) were well accepted by respondents, and occurrence of these adverse events was low. Patients were satisfied overall with the education and services that the pharmacist delivered in the pretravel health clinic. CONCLUSION: Pharmacists providing services in pretravel health clinics can have substantial impact on the health of patients traveling internationally.

Implementation of longitudinal thematic course design across four institutions.

INTRODUCTION: The objective of this study was to describe thematic course design utilized in pharmacy courses at four different institutions. Best practices and lessons learned are shared. METHODS: Four institutions independently incorporated a longitudinal Harry Potter (HP) theme into their courses. Faculty collaborated to share course experiences and determine similar concepts present at all four institutions. A mixed-methods approach was used to analyze available data. Thematic analysis was used for qualitative course evaluation comments. Quantitative course evaluation data from two institutions was also analyzed. RESULTS: Similar concepts identified as important elements of longitudinal thematic course design included creation of new groups, incorporation of thematic activities (e.g., adding HP characters to patient cases), and gamification. Qualitative analysis of student course evaluation comments found three emerging themes: increased student engagement, enjoyment of thematic course design, and appreciation for the gaming aspect. Quantitative course evaluation data demonstrated that students liked the HP theme to facilitate learning and it increased student engagement in the course. CONCLUSIONS: A thematic course design at four institutions was well received by students and potentially increased student engagement with the course material longitudinally.

Cost-effectiveness of routine type and screens in select urological surgeries.

PURPOSE: To evaluate the cost-effectiveness of obtaining a preoperative type and screen (T/S) for common urologic procedures. METHODS: A decision tree model was constructed to track surgical patients undergoing two preoperative blood ordering strategies as follows: obtaining a preoperative T/S versus not doing so. The model was applied to the National (Nationwide) Inpatient Sample (NIS) data, from January 1, 2006 to September 30, 2015. Cost estimates for the model were created from combined patient-level data with published costs of a T/S, type and crossmatch (T/C), a unit of pRBC, and one unit of emergency-release transfusion (ERT). The primary outcome was the incremental cost per ERT prevented, expressed as an incremental cost-effectiveness ratio (ICER) between the two preoperative blood ordering strategies. A cost-effectiveness analysis determined the ICER of obtaining preoperative T/S to prevent an emergency-release transfusion (ERT), with a willingness-to-pay threshold of $1,500.00. RESULTS: A total of 4,113,144 surgical admissions from 2006 to 2015 were reviewed. The overall transfusion rate was 10.54% (95% CI, 10.17-10.91) for all procedures. The ICER of preoperative T/S was $1500.00 per ERT prevented. One-way sensitivity analysis demonstrated that the risk of transfusion should exceed 4.12% to justify preoperative T/S. CONCLUSION: Routine preoperative T/S for radical prostatectomy (rate = 3.88%) and penile implants (rate = .91%) does not represent a cost-effective practice for these surgeries. It is important for urologists to review their institution T/S policy to reduce inefficiencies within the preoperative setting.

Assessment of drug utilization review activities within United States colleges of pharmacy.

INTRODUCTION: Limited literature exists regarding current practices in teaching and assessment of drug utilization review (DUR) skills in pharmacy schools. This manuscript aimed to: (1) examine how assessment is conducted for DUR activities using survey results and (2) summarize the assessment strategies of DUR activities via analysis of tools in colleges of pharmacy. METHODS: A survey was administered to members of the American Association of Colleges of Pharmacy Laboratory Instructors Special Interest Group via Qualtrics. Descriptive statistics were used to evaluate survey results and the assessment tools (i.e. rubrics/checklists) collected were analyzed qualitatively to determine common content areas. RESULTS: Out of the 113 institutions emailed, 48 (42.5%) responses were complete and represented individual colleges. Thirty-four of those 48 both implemented and assessed DUR activities. Fourteen institutions (41%) utilized one DUR assessment tool throughout the entire curriculum. The majority (62%) used the assessment tool in the first professional year, with a paper tool being the most frequently utilized (74%). "Identification of drug-related problems" (97%) and "determination of the pharmacist's action" (85%) were listed as important components of the assessment tool. Faculty noted that the assessment tool was easy to use (55%) and adequately assessed students' knowledge/skills (55%). A validated assessment tool (85%) and inclusion of technology (50%) would improve delivery of student feedback. CONCLUSIONS: Wide variability existed in how schools incorporated and assessed DUR activities. Developing a standardized method of teaching and assessing DUR is important to adequately prepare the next generation of pharmacists.

Aggressive angiomyxoma of left buttock.

Aggressive angiomyxoma (AA) is a rare mesenchymal tumour that is characterised by increased incidence in women compared with men, local invasion to the surrounding tissue and high recurrence rate. A premenopausal woman presented to clinic with pelvic pressure, intermittent tingling in the thigh and pressure emptying the bladder. CT scan, vaginal and gluteal biopsies, and MRI scan were performed to conclude a final diagnosis of AA. The patient underwent complete resection of the mass. The mass tested positive for oestrogen receptor and progesterone receptor. The patient received leuprolide postoperatively to prevent recurrence. AA should be considered as a differential diagnosis for a pelvic and perineal mass. Patients should be warned of high recurrence rate, necessity of surgical removal and long-term hormonal treatment.

Recurrent Hyperhemolysis Syndrome in Sickle Cell Disease.

Sickle cell disease is a disorder of hemoglobin. The abnormal hemoglobin S disrupts blood flow, thereby resulting in acute painful sickle cell crisis. These episodes frequently prompt packed red blood cell transfusions to replace a patient's functional hemoglobin stores. Production of alloantibodies and autoantibodies to these transfusions can result in a rare, but serious, complication known as hyperhemolysis syndrome. Hyperhemolysis syndrome presents several challenges in regard to its acute management and the consequent difficulties in finding future compatible blood products. We report a case of recurrent hyperhemolysis syndrome. Both episodes occurred following orthopedic procedures, and the recurrent episode proved refractory to multiple treatments.

Improving the Remediation Process for Skills-based Laboratory Courses in the Doctor of Pharmacy Curriculum.

When students fail to meet minimum competence standards on summative pharmacy skills-based assessments, remediation can be used to ensure student readiness for progression. Skills-based remediation is challenging as a high volume of resources is required to develop an action plan that addresses the heterogeneity in student needs and to create and execute another assessment equivalent to the initial assessment. Although many Doctor of Pharmacy (PharmD) programs face these same challenges, there is no consensus on how to best address them. Recently, faculty from six PharmD programs convened to share ideas and approaches to overcoming these challenges. This commentary aims to define remediation as it pertains to summative skills-based assessments, share our consensus views regarding remediation best practices, and highlight areas where there is more work to be done. Our intent is to advance the ongoing conversation and empower institutions to develop their own effective and impactful skills-based remediation policies, procedures, and activities.

Changes to summative skills-based assessments within the Big Ten Academic Alliance Performance-Based Assessment Collaborative (BTAA-PBAC) due to COVID-19.

Background: In Spring 2020 many academic institutions transitioned to remote learning in response to the developing COVID-19 pandemic. These changes affected skills-based training, as schools of pharmacy were forced to transition traditionally in-person assessments to a remote setting. The purpose of this article is to describe the experience of pharmacy skills lab coordinators when transitioning summative skills-based assessments (SSBA). Methods: A web-based survey instrument administered through QualtricsXM was sent to all institutions in the Big Ten Academic Alliance-Performance Based Assessment Collaborative. Only one member from each institution completed the survey on behalf of the institution. The survey consisted of four sections: changes made to skills evaluated; changes made to the delivery of those evaluations; challenges to and strategies used by the skills lab program when switching to remote learning; and recommendations for incorporating remote learning within future SSBAs. Survey respondents were invited to participate in an optional unstructured interview regarding survey answers. Results: Nine of ten invited institutions responded to the survey. Of the nine respondents, three participated in the post-survey interview. Overall, 79.5% (93/117) of skills planned to be assessed were assessed with or without modification, with 8.5% (10/117) of skills canceled and 10.3% (12/117) of skills assessments postponed. The most common challenges mentioned were the lack of preparation time, inability to assess certain skills virtually, and student barriers. The most common recommendations made were to prioritize lab components and incorporate flexibility in planning and scheduling. Discussion: The results indicate that most skills were still assessed during the Spring 2020 semester. Though the transition to remote learning was challenging and unique for each institution, common strategies and recommendations identified here provide opportunities for academics to analyze and prioritize learning objectives and to rethink how to develop and deliver SSBAs as remote assessments.

Building confidence: Three-year evaluation of systematic progression of prescription verification on students' confidence during IPPE.

INTRODUCTION: To determine how a progression in community pharmacy prescription verification activities (PVAs) in a skills-based laboratory series impacts student confidence during community-based introductory pharmacy practice experiences (IPPEs). METHODS: Motivated by the 2016 Accreditation Council for Pharmacy Practice Education Standards, a progression of PVAs was implemented. As students progressed through three semesters of laboratory courses, the scope and verification error types expanded. A web-based survey was administered after students completed their IPPE. The survey was conducted over three years to collect data from students who completed one, two, or three semesters of PVAs. Two-way Analysis of Variance and Tukey-Kramer tests were used to analyze data. RESULTS: Over the three-year period, 395 students completed the survey. Students with two or three semesters of PVAs were significantly more confident than those with one semester of PVAs in verifying prescriptions on IPPEs, identifying legal concerns with prescriptions, and identifying and correcting prescription labels and expiration/discard dates. Students without professional pharmacy experience strongly agreed that PVAs prepared them for IPPEs compared to those with experience. CONCLUSIONS: This is the first study evaluating the impact of PVAs in the didactic curriculum on student confidence during IPPEs. Systematic progression of multiple semesters of PVAs may have helped students prepare for IPPEs and may have influenced student confidence in several aspects of prescription verification. This study lays the foundation for further investigation into the impact of building confidence and examining if confidence leads to improved accuracy in patient care.

Implementation of systematic progression of community pharmacy-based prescription verification into the skills-based laboratory curriculum.

BACKGROUND AND PURPOSE: To describe the design, implementation, and evaluation of systematic progressive community pharmacy-based prescription verification activities across a skills-based laboratory course series. EDUCATIONAL ACTIVITY AND SETTING: Community pharmacy-based prescription verification activities were implemented into three laboratory courses, Abilities Lab (ABL) 1, 2, and 4. During each activity, students practiced prescription verification using a handout with two components. First, a checklist outlining an eight-step verification process serves as a student resource. In the second handout component, students are required to identify which step contains a prescription error(s), the appropriate pharmacist action, and the recommendation needed in order to correct the error(s). After verifying and completing the handout, the students participate in a facilitator-led discussion on the recommendations necessary to dispense the prescription. As students progressed through ABL 1, 2, and 4, both the error type and scope of the verification process expanded. Class verification exercises culminated in a final practical assessment at the end of each semester. FINDINGS: In ABL 1 students scored an average of 99.5% (n = 161, standard deviation (SD) = 1.92) on the final practical assessment. In ABL 2, students scored an average of 97.6% (n = 166, SD = 3.07). In ABL 4, students scored an average of 90.3% (n = 159, SD = 11.2). SUMMARY: This manuscript adds value to the current literature by describing the implementation of progressive community pharmacy-based prescription verification activities across a skills-based laboratory course series.

Cholesterol Point-of-Care Testing for Community Pharmacies: A Review of the Current Literature.

OBJECTIVE: To summarize the literature on cholesterol point-of-care tests (POCTs). This article would serve as a resource to assist community pharmacists in developing cholesterol point-of-care (POC) pharmacy services. DATA SOURCES: A literature search was performed in MEDLINE Ovid, PubMed, EMBASE, and Cochrane database using the following medical subject headings (MeSH) terms: point-of-care test, cholesterol, blood chemical analysis, rapid testing, collaborative practice, community pharmacy, and ambulatory care. Additional resources including device manufacturer web sites were summarized to supplement the current literature. STUDY SELECTION AND DATA EXTRACTION: All human research articles, review articles, meta-analyses, and abstracts published in English through September 1, 2014, were considered. DATA SYNTHESIS: A total of 36 articles were applicable for review. Information was divided into the following categories to be summarized: devices, pharmacists' impact, and operational cost for the pharmacy. CONCLUSIONS: The current literature suggests that POCTs in community pharmacies assist with patient outcomes by providing screenings and referring patients with dyslipidemia for further evaluation. The majority of studies on cholesterol POC devices focused on accuracy, revealing the need for further studies to develop best practices and practice models with successful reimbursement. Accuracy, device specifications, required supplies, and patient preference should be considered when selecting a POC device for purchase.

Palmoplantar Keratoderma in Slurp2-Deficient Mice.

SLURP1, a member of the lymphocyte antigen 6 protein family, is secreted by suprabasal keratinocytes. Mutations in SLURP1 cause a palmoplantar keratoderma (PPK) known as mal de Meleda. SLURP2, another secreted lymphocyte antigen 6 protein, is encoded by a gene located ?20 kb downstream from SLURP1. SLURP2 is produced by suprabasal keratinocytes. To investigate the importance of SLURP2, we first examined Slurp2 knockout mice in which exon 2-3 sequences had been replaced with lacZ and neo cassettes. Slurp2(-/-) mice exhibited hyperkeratosis on the volar surface of the paws (i.e., palmoplantar keratoderma), increased keratinocyte proliferation, and an accumulation of lipid droplets in the stratum corneum. They also exhibited reduced body weight and hind limb clasping. These phenotypes are similar to those of Slurp1(-/-) mice. To solidify a link between Slurp2 deficiency and palmoplantar keratoderma and to be confident that the disease phenotypes in Slurp2(-/-) mice were not secondary to the effects of the lacZ and neo cassettes on Slurp1 expression, we created a new line of Slurp2 knockout mice (Slurp2X(-/-)) in which Slurp2 was inactivated with a simple nonsense mutation. Slurp2X(-/-) mice exhibited the same disease phenotypes. Thus, Slurp2 deficiency and Slurp1 deficiencies cause the same disease phenotypes.

Cathelicidin suppresses colon cancer development by inhibition of cancer associated fibroblasts.

BACKGROUND: Cathelicidin (LL-37 in humans and mCRAMP in mice) represents a family of endogenous antimicrobial and anti-inflammatory peptides. Cancer-associated fibroblasts can promote the proliferation of colon cancer cells and growth of colon cancer tumors. METHODS: We examined the role of cathelicidin in the development of colon cancer, using subcutaneous human HT-29 colon-cancer-cell-derived tumor model in nude mice and azoxymethane- and dextran sulfate-mediated colon cancer model in C57BL/6 mice. We also determined the indirect antitumoral mechanism of cathelicidin via the inhibition of epithelial-mesenchymal transition (EMT) of colon cancer cells and fibroblast-supported colon cancer cell proliferation. RESULTS: Intravenous administration of cathelicidin expressing adeno-associated virus significantly reduced the size of tumors, tumor-derived collagen expression, and tumor-derived fibroblast expression in HT-29-derived subcutaneous tumors in nude mice. Enema administration of the mouse cathelicidin peptide significantly reduced the size and number of colonic tumors in azoxymethane- and dextran sulfate-treated mice without inducing apoptosis in tumors and the adjacent normal colonic tissues. Cathelicidin inhibited the collagen expression and vimentin-positive fibroblast expression in colonic tumors. Cathelicidin did not directly affect HT-29 cell viability, but did significantly reduce tumor growth factor-ß1-induced EMT of colon cancer cells. Media conditioned by the human colonic CCD-18Co fibroblasts promoted human colon cancer HT-29 cell proliferation. Cathelicidin pretreatment inhibited colon cancer cell proliferation mediated by media conditioned by human colonic CCD-18Co fibroblasts. Cathelicidin disrupted tubulin distribution in colonic fibroblasts. Disruption of tubulin in fibroblasts reduced fibroblast-supported colon cancer cell proliferation. CONCLUSION: Cathelicidin effectively inhibits colon cancer development by interfering with EMT and fibroblast-supported colon cancer cell proliferation.

Anti-fibrogenic effects of the anti-microbial peptide cathelicidin in murine colitis-associated fibrosis.

BACKGROUND AND AIMS: Cathelicidin (LL-37 in human and mCRAMP in mice) represents a family of endogenous antimicrobial peptides with anti-inflammatory effects. LL-37 also suppresses collagen synthesis, an important fibrotic response, in dermal fibroblasts. Here we determined whether exogenous cathelicidin administration modulates intestinal fibrosis in two animal models of intestinal inflammation and in human colonic fibroblasts. METHODS: C57BL/6J mice (n=6 per group) were administered intracolonically with a trinitrobenzene sulphonic acid (TNBS) enema to induce chronic (6-7 weeks) colitis with fibrosis. mCRAMP peptide (5 mg/kg every 3 day, week 5-7) or cathelicidin gene (Camp)-expressing lentivirus (107 infectious units week 4) were administered intracolonically or intravenously, respectively. 129Sv/J mice were infected with Salmonella typhimurium orally to induce cecal inflammation with fibrosis. Camp expressing lentivirus (107 infectious units day 11) was administered intravenously. RESULTS: TNBS-induced chronic colitis was associated with increased colonic collagen (col1a2) mRNA expression. Intracolonic cathelicidin (mCRAMP peptide) administration or intravenous delivery of lentivirus-overexpressing cathelicidin gene significantly reduced colonic col1a2 mRNA expression in TNBS-exposed mice, compared to vehicle administration. Salmonella infection also caused increased cecal inflammation associated with collagen (col1a2) mRNA expression that was prevented by intravenous delivery of Camp-expressing lentivirus. Exposure of human primary intestinal fibroblasts and human colonic CCD-18Co fibroblasts to transforming growth factor-beta1 (TGF-beta1) and/or insulin-like growth factor 1 induced collagen protein and mRNA expression, that was reduced by LL-37 (3-5 µM) through a MAP kinase-dependent mechanism. CONCLUSION: Cathelicidin can reverse intestinal fibrosis by directly inhibiting collagen synthesis in colonic fibroblasts.