Blood pressure lowering effects of Lactobacillus helveticus fermented milk containing bioactive peptides Ile-Pro-Pro and Val-Pro-Pro; mechanistic, kinetic and clinical studies

The purpose of the present study was to evaluate the effects of Lactobacillus helveticus fermented milk (peptide milk) containing the casein-derived tripeptides Isoleucyl-prolyl-proline (Ile-Pro-Pro) and Valyl-prolyl-proline (Val-Pro-Pro) on blood pressure and vascular function in hypertensive subjects. The peptide milk lowered systolic and diastolic blood pressure in long-term use in hypertensive subjects when blood pressure was measured by using 24-hour ambulatory blood pressure measurement (ABPM). The blood pressure lowering effect was seen with the dose of 50 mg of tripeptides, and a tendency for lowering blood pressure was also observed when the dose was 5 mg. No adverse effects compared to the placebo group were reported or detected in laboratory analysis. The effect of the peptide milk on arterial stiffness was shown using two different methods, the ambulatory arterial stiffness index (AASI) and pulse wave analysis (PWA). According to the AASI, arterial stiffness was significantly reduced in the peptide milk group compared to the baseline level, but the difference was not significant compared to the placebo group. PWA showed that the peptide milk reduced arterial stiffness significantly compared to the placebo group. Endothelium-independent relaxation (nitroglycerin) and endothelium-dependent relaxation (salbutamol) did not differ between the groups. The blood pressure lowering mechanisms of the tripeptides and the kinetics of Ile-Pro-Pro were investigated using spontaneously hypertensive rats (SHR) and Sprague-Dawley rats. Previous studies have suggested that the blood pressure lowering effect of the tripeptides Ile-Pro-Pro and Val-Pro-Pro is based on angiotensin-converting enzyme inhibition, but the present findings did not agree with these previous studies. It was shown in SHR that calcium, potassium and magnesium may also have an important role in attenuating the development of hypertension as part of the peptide milk effect. In addition, the present study suggests indirectly that improved endothelial nitric oxide release capacity is not the mechanism by which peptide milk mediates its favourable circulatory effects. The kinetics of Ile-Pro-Pro were studied using adult Sprague-Dawley rats. The results showed that orally administered Ile-Pro-Pro is absorbed at least partly intact from the gastrointestinal tract. Radiolabelled Ile-Pro-Pro was distributed in different tissues and considerable radioactivity levels were found in tissues related to the renin-angiotensin system (RAS), adrenals, aorta and kidneys. Ile-Pro-Pro does not bind to plasma proteins, and therefore it is possible that its blood pressure lowering effect is mediated by free Ile-Pro-Pro. In conclusion, consumption of the peptide milk lowers blood pressure and reduces arterial stiffness in hypertensive subjects. Ile-Pro-Pro can be absorbed partly intact from the gastrointestinal tract and might accumulate in tissues related to the RAS. The precise blood pressure lowering mechanism of peptide milk remains to be studied.

Attributes of clinical role models as described by senior veterinary students in Australia

Role models incite admiration and provide inspiration, contributing to learning as students aspire to emulate their example. The attributes of physician role models for medical trainees are well documented, but they remain largely unexplored in the context of veterinary medical training. The aim of the current study was to describe the attributes that final-year veterinary students (N=213) at the University of Queensland identified when reflecting on their clinical role models. Clinical role model descriptions provided by students were analyzed using concept-mapping software (Leximancer v. 2.25). The most frequent and highly connected concepts used by students when describing their role model(s) included clients, vet, and animal. Role models were described as good communicators who were skilled at managing relationships with clients, patients, and staff. They had exemplary knowledge, skills, and abilities, and they were methodical and conducted well-structured consultations. They were well respected and, in turn, demonstrated respect for clients, colleagues, staff, and students alike. They were also good teachers and able to tailor explanations to suit both clients and students. Findings from this study may serve to assist with faculty development and as a basis for further research in this area.

Clinical Escherichia coli isolates utilize alpha-hemolysin to inhibit in vitro epithelial cytokine production

Uropathogenic Escherichia coli is the primary cause of urinary tract infections, which affects over 60% of women during their lifetime. UPEC exhibits a number of virulence traits that facilitate colonization of the bladder, including inhibition of cytokine production by bladder epithelial cells. The goal of this study was to identify the mechanism of this inhibition. We observed that cytokine suppression was associated with rapid cytotoxicity toward epithelial cells. We found that cytotoxicity, cytokine suppression and alpha-hemolysin production were all tightly linked in clinical isolates. We screened a UPEC fosmid library and identified clones that gained the cytotoxicity and cytokine-suppression phenotypes. Both clones contained fosmids encoding a PAI II(J96)-like domain and expressed the alpha-hemolysin (hlyA) encoded therein. Mutation of the fosmid-encoded hly operon abolished cytotoxicity and cytokine suppression. Similarly, mutation of the chromosomal hlyCABD operon of UPEC isolate F11 also abolished these phenotypes, and they could be restored by introducing the PAI II(J96)-like domain-encoding fosmid. We also examined the role of alpha-hemolysin in cytokine production both in the murine UTI model as well as patient specimens. We conclude that E. coli utilizes alpha-hemolysin to inhibit epithelial cytokine production in vitro. Its contribution to inflammation during infection requires further study.

Integration of clinical information systems in Saudi Arabian health care contexts: A grounded theory exploration

This research examined the implementation of clinical information system technology in a large Saudi Arabian health care organisation. The research was underpinned by symbolic interactionism and grounded theory methods informed data collection and analysis. Observations, a review of policy documents and 38 interviews with registered nurses produced in-depth data. Analysis generated three abstracted concepts that explained how imported technology increased practice and health care complexity rather than enhance quality patient care. The core category, Disseminating Change, also depicted a hierarchical and patriarchal culture that shaped the implementation process at the levels of government, organisation and the individual.

The influence of HIV infection to the periodontium; a clinical, microbiological, and enzymological study

The main targets of human immunodeficiency virus (HIV) are CD4 receptors of CD4+ lymphocytes and many other cells such as monocytes/macrophages, megakaryocytes, peripheral blood dendritic cells, follicular dendritic cells (DC), epidermal Langerhans cells, and astrocytes. Infection and killing of CD4+ lymphocytes or false reaction of the body to HIV infection and the spontaneous apoptosis of CD4+ lymphocytes decrease CD4+ lymphocyte counts leading to immunosuppression, further disease progression, and appearance of opportunistic infections and malignancies. Oral manifestations are considered to be among the first signs of HIV infection. Enhanced degradation of extracellular matrix and basement membrane components in oral diseases including periodontitis is caused by Zn-dependent enzymes called matrix metalloproteinases (MMPs). The levels and degrees of activation of MMP-1, -2, -3, -7, -8, -9, -25, -26, tissue inhibitors of MMPs (TIMP)-1 and -2, and myeloperoxidase (MPO) and collagenolytic/gelatinolytic activities, and also Ig A, -G, and -M, total protein, and albumin levels in a two-year follow-up were studied from salivary samples. The expression of MMP-7, -8, -9, -25, and -26 immunoreactivities in gingival tissue specimens were studied. Healthy HIV-negative subjects served as controls. All studied clinical periodontal parameters and microbiological evaluation of the periodontopathogens showed that periodontal health of the HIV-positive patients was moderately decreased in comparison to the healthy controls. The levels of Candida in the periodontal pockets and salivary MPO increased with the severity of HIV infection. Immunoreactivities and levels of MMPs and TIMPs, and MMP activities (collagenase, gelatinase) were enhanced in the HIV-positive patient salivary samples relative to the healthy controls regardless of the phase of HIV infection. However, these parameters did not reflect periodontal status in a similar way as in the generally healthy periodontitis patients. Salivary total protein, albumin, IgA, -G, and -M levels were significantly higher in all phases of HIV infection compared to the controls, and salivary total protein, IgG and IgM levels remained higher after two years follow-up, partly correlating with the disease progression and which may reflect the leakage of serum components into the mouth and thus a decreased mucosal barrier. Salivary analyses of MMPs and TIMPs with immunohistochemical analyses showed that HIV infection could predispose to periodontal destruction when compared with healthy controls or the body s defence reactions associated with HIV infection may have been reflected or mediated by MMPs.

Temporomandibular disorders and related psychosocial factors in non-patients : A survey and a clinical follow-up study based on the RDC/TMD

Temporomandibular disorders (TMD) and psychosocial factors reportedly associate. The underlying factors remain partially obscure, however, and further studies are required to clarify the relationships. The aims of this study were thus to assess in a non-patient working population the prevalence of TMD and related symptoms, and to clinically diagnose and follow the natural courses of TMD over a one-year period. In addition, possible comorbidity of temporomandibular and/or neck muscle pain and perceived stress and their impact on work performance were investigated, as well as how various psychosocial aspects relate to TMD. A questionnaire was mailed to all 30- to 55-year-old employees of the Finnish Broadcasting Company Ltd. whose employment in the Helsinki area had lasted at least five years (n = 1784). Of the 1339 subjects, who returned the questionnaire, 241 were examined according to the RDC/TMD and standard neck muscle palpation methods. Clinical signs of temporomandibular and/or neck muscle pain were found in 118 subjects. One-year follow-up TMD examinations were conducted on 211 subjects. The prevalence of frequent painless TMJ-related symptoms was 10%, orofacial pain 7%, neck pain 38%, and headache 15%. TMD diagnoses were: myofascial pain (13%), disc displacements (16%), and arthralgia, osteoarthritis, osteoarthrosis (4%). Chronic myofascial pain was present in 7% and chronic disc displacement with reduction in 11% of the subjects. Symptoms were significantly associated with almost all the studied psychosocial symptoms. Reduced work performance was significantly positively associated with continuous pain, severity of pain, and health stress perception, and according to logistic regression, somatization with the probability of having chronic myofascial pain. It could be concluded based on the results of this study among a non-patient working population that TMD and related symptoms are common and associated with psychosocial factors. Moreover, myofascial pain and disc displacement with reduction are the most common diagnoses of TMD. In addition, self-reported health related stress, and continuous pain in temporomandibular and/or neck muscles are associated with reduced work performance, and somatization is significantly associated with chronic myofascial pain.

Algorithm of medication review in frail older people: Focus on minimizing the use of high-risk medications

Aim Frail older people typically suffer several chronic diseases, receive multiple medications and are more likely to be institutionalized in residential aged care facilities. In such patients, optimizing prescribing and avoiding use of high-risk medications might prevent adverse events. The present study aimed to develop a pragmatic, easily applied algorithm for medication review to help clinicians identify and discontinue potentially inappropriate high-risk medications. Methods The literature was searched for robust evidence of the association of adverse effects related to potentially inappropriate medications in older patients to identify high-risk medications. Prior research into the cessation of potentially inappropriate medications in older patients in different settings was synthesized into a four-step algorithm for incorporation into clinical assessment protocols for patients, particularly those in residential aged care facilities. Results The algorithm comprises several steps leading to individualized prescribing recommendations: (i) identify a high-risk medication; (ii) ascertain the current indications for the medication and assess their validity; (iii) assess if the drug is providing ongoing symptomatic benefit; and (iv) consider withdrawing, altering or continuing medications. Decision support resources were developed to complement the algorithm in ensuring a systematic and patient-centered approach to medication discontinuation. These include a comprehensive list of high-risk medications and the reasons for inappropriateness, lists of alternative treatments, and suggested medication withdrawal protocols. Conclusions The algorithm captures a range of different clinical scenarios in relation to potentially inappropriate medications, and offers an evidence-based approach to identifying and, if appropriate, discontinuing such medications. Studies are required to evaluate algorithm effects on prescribing decisions and patient outcomes.

Clinical tips: Bowel cancer screening

So, when was the last time you checked your poo? Checking your poo – it probably is not a conversation many patients want to have with their pharmacists. But bowel cancer screening remains an important tool in cancer detection...

Clinical tips: Treating addiction explained

Helping treat and manage addiction through pharmacotherapy is part of a complex process, write Dr Esther Lau and Professor Lisa Nissen, from the School of Clinical Sciences, Queensland University of Technology...

AJP clinical update: Eye health

For most people our eyes provide around 80% of the information from our surroundings, and pharmacists are perfectly placed to help consumers maintain good eye health.

Clinical tips: Diabetes explained

For many people, diabetes can start insidiously, without people knowing or being aware that they have diabetes. Signs and symptoms can just start with something very benign, such as feeling more thirsty than usual, or that they are going to the bathroom more because they are drinking more fluids from being thirsty...

Clinical tips: Mental health and Christmas explained

Christmas is usually a time for celebration, being with family and friends, opening presents, stuffing yourself silly with food at Christmas lunch – then doing it all over again at dinner. However, this may not be the case for some people. Relationships with family may be strained, or there may have been the loss of a loved one or significant other...

A taxonomic approach to understanding managerial ethical decision making approaches of clinically and non-clinically trained healthcare managers in Australia

Objective To understand differences in the managerial ethical decision-making styles of Australian healthcare managers through the exploratory use of the Managerial Ethical Profiles (MEP) Scale. Background Healthcare managers (doctors, nurses, allied health practitioners and non-clinically trained professionals) are faced with a raft of variables when making decisions within the workplace. In the absence of clear protocols and policies healthcare managers rely on a range of personal experiences, personal ethical philosophies, personal factors and organizational factors to arrive at a decision. Understanding the dominant approaches to managerial ethical decision-making, particularly for clinically trained healthcare managers, is a fundamental step in both increasing awareness of the importance of how managers make decisions, but also as a basis for ongoing development of healthcare managers. Design Cross-sectional. Methods The study adopts a taxonomic approach that simultaneously considers multiple ethical factors that potentially influence managerial ethical decision-making. These factors are used as inputs into cluster analysis to identify distinct patterns of influence on managerial ethical decision-making. Results Data analysis from the participants (n=441) showed a similar spread of the five managerial ethical profiles (Knights, Guardian Angels, Duty Followers, Defenders and Chameleons) across clinically trained and non-clinically trained healthcare managers. There was no substantial statistical difference between the two manager types (clinical and non-clinical) across the five profiles. Conclusion This paper demonstrated that managers that came from clinical backgrounds have similar ethical decision-making profiles to non-clinically trained managers. This is an important finding in terms of manager development and how organisations understand the various approaches of managerial decision-making across the different ethical profiles.

Feedback and clinical practice improvement: A tool to assist workplace supervisors and students

In work integrated learning, students may report difficulties applying theory learned at university to clinical practice. One contributing factor may be students' inability to engage in meaningful reflection and self-correcting behaviours. This paper reports the evaluation of a tool, process and resources developed to assist students to reflect on feedback and engage in self-assessment. Students were assisted to develop self-assessment skills by reflecting on, and engaging with feedback from previous workplace experiences to develop goals, learning outcomes and strategies to improve performance with mostly positive results. A secondary aim was to identify common learning strategies or barriers that impacted on student outcomes. Four themes emerged from the qualitative data: 1) preparing for clinical learning; 2) relationships and engagement levels; 3) shared awareness, and; 4) developing clinical practice. Overall students felt the tool assisted them to narrow their attention on what needed to be improved. While supervisors believed the tool helped them to focus on specific needs of each student. Common barriers to clinical practice improvement related to a lack of opportunity in some settings, and lack of staff willingness to support students to achieve identified goals. Students and supervisors found the use of the tools beneficial and assisted students to demonstrate a greater understanding of how to apply feedback received to support their learning in the clinical environment.