Investigating the cardiovascular and metabolic effects of resistin

 Resistin is an adipokine, originally identified in adipose tissue and its plasma levels are elevated in obesity. Resistin induces insulin resistance and affects energy homeostasis by reducing food intake. Plasma levels of resistin are correlated with the development and severity of heart failure, hypertension and myocardial infarction, suggesting that resistin has cardiovascular effects, however, the mechanisms underlying such effects are unclear. Characteristics of obesity include impaired metabolic regulation and cardiovascular dysfunction such as increased sympathetic nerve activity (SNA) to the kidney and skeletal muscle vasculature. It is unknown whether resistin affects SNA. This thesis investigates the effect of centrally administered resistin on (i) blood pressure and heart rate, (ii) sympathetic nerve activity (SNA) targeting the kidney and skeletal muscle vasculature, (iii) SNA to brown adipose tissue (BAT) and thermogenesis and (iv) the intracellular signalling pathways mediating the changes in SNA affecting the kidney and BAT. Intracerebroventricular resistin (7µg) injected into overnight fasted, anaesthetised rats induced a significant increase in lumbar and renal SNA. The response in renal SNA was prevented when PI 3-Kinase was inhibited by intracerebroventricular administration of LY294002 (5µg). Resistin reduced BAT and body core temperature and BAT SNA, resulting in reduced thermogenesis. Consistent with these findings, resistin reduced the expression of thermogenesis markers in BAT. Inhibiting ERK1/2 by intracerebroventricular administration of U0126, delayed the action of resistin on BAT SNA. Finally, resistin did not significantly change the blood pressure or heart rate. The findings indicate that resistin has differential effects on sympathetic nerve activity to tissues involved in metabolic and cardiovascular regulation. The increased lumbar and renal SNA and the decreased thermogenesis in BAT elicited by resistin suggest that it may contribute to the sympathetic nerve over-activity to cardiovascular organs and reduced energy expenditure observed in obesity and metabolic syndrome

Effects of high fat diet on cognition and brain pathology

Consumption of a high fat diet in western countries has increased significantly over the past few decades, leading to major health issues. Recent evidence shows an association between obesity and cognitive decline. The present studies aimed to (i) determine whether high fat or western diet can affect working or spatial memory in rats (ii) investigate the changes that occur in brain areas important for memory regulation following the consumption of a higher percentage of fat in diet. Male Long Evan and Hooded-Wistar rats were fed normal chow, western diet (23% fat, 0.19% cholesterol) or high fat diet (60% fat) for 12 weeks. Body weight and food intake were measured twice weekly. Behavioural testing was carried out after 12 weeks of feeding by investigating (i) working memory performance in the novel object recognition test, (ii) spatial memory using a Y-maze and (iii) rewarded alternation using a T-maze. In one cohort of rats the Y-maze and novel object recognition tasks were repeated at the end of each month of feeding for three months to find out at what point during the feeding, the memory impairment begins. Immunohistochemistry was carried out in specific brain areas including those that are important in memory regulation in order to investigate the changes in the level of cholinergic markers, basal neuronal activity, astrocytes and insulin like growth factor 1 receptor. This research was the first to report an impairment of spatial memory using a Y-maze paradigm in rats following the consumption of a western or high fat diet for three months. Further investigation revealed that consumption of these diets is associated with changes in specific areas of the brain including those that are involved in memory regulation. These changes include the increased level of acetylcholinesterase in the striatum, the reduced number of GFAP-positive astrocytes in CA1 and dentate gyrus of the hippocampus besides the decreased level of basal neuronal activity in CA2&3 region of the hippocampus, prelimbic and infralimbic areas of the prefrontal cortex and in the paraventricular nucleus of thalamus in rats following consumption of high fat or western diets. Overall, these results suggest that higher percentage of fat in diet can affect specific regions of the brain that are important for memory regulation through various mechanisms and consequently may affect the memory

A comparative survey of abundance and biomass of Caspian Sea macrobenthos in coastal waters of Mazandaran Province

Caspian Sea macrobenthos was surveyed every two months from December 2007 to October 2008, in the west, east and central parts of Mazandaran province waters. Each area was sampled with 3 replicates at 2 depths of 5 and 10m by Van Veen grab. Five different classes were recognized, including Polychaeta (52.7%), Oligochaeta (27.8%), Bivalvia (12%), Cnistacea (7.5%) and Insects (0.07%). Total mean (LSD) abundance and biomass were 2727± 1303 individual/m2 and 88.9±22.93, respectively. The Polychaeta demonstrated the highest abundance and Bivalvia had the highest biomass. The highest abundance of macrobenthos was found in eastern and the highest biomass in western coasts of Mazandaran. In August 2008, macrobenthos abundance showed higher values. In October, remarkable difference was observed between the abundance of Polychaeta and other macrobenthos organisms. According to Kniskal-Wallis test, abundance and biomass of the entire macrobenthos classes except Insects, showed a significant difference between sampling months (P<0.05). Macrobenthos biomass had no significant difference among the three areas whereas abundance demonstrated a significant difference within these areas (P< 0.05)

Enhancement of in vitro production of volatile organic compounds by shoot differentiation in Artemisia spicigera

Callus initiation, shoot formation and plant regeneration were established for Artemisia spicigera, a traditional medicinal plant growing in Armenia, Middle-Anatolia and Iran, and pro- ducing valuable volatile organic compounds (VOCs) that are mostly represented by monoterpe- noids. Optimal callus initiation and shoot production were obtained by culture of hypocotyl and cotyledon explants on MS medium comprising 0.5 mg L−1 naphthalene acetic acid (NAA) and 0.5 mg L−1 6-benzyladenine (BA). Consequently, the shoots were transferred onto the MS media sup- plemented with 1 mg L−1 of indole-3-butyric acid (IBA) or 1 mg L−1 of NAA. Both types of auxin induced root formation on the shoots and the resulting plantlets were successfully grown in pots. The production of VOCs in callus tissues and regenerated plantlets was studied by gas chroma- tography–mass spectrometry (GC-MS) analysis. Although the potential of undifferentiated callus to produce VOCs was very low, an increased content of bioactive volatile components was ob- served at the beginning of shoot primordia differentiation. Intriguingly, the volatiles obtained from in vitro plantlets showed quantitative and qualitative variation depending on the type of auxins used for the rooting process. The acquired quantities based on total ion current (TIC) showed that the regenerated plantlets using 1 mg L−1 NAA produced higher amounts of oxygenated monoter- penes such as camphor (30.29%), cis-thujone (7.07%), and 1,8-cineole (6.71%) and sesquiterpene derivatives, namely germacrene D (8.75%), bicyclogermacrene (4.0%) and spathulenol (1.49%) compared with the intact plant. According to these findings, in vitro generation of volatile organic compounds in A. spicigera depends on the developmental stages of tissues and may enhance with the formation of shoot primordia and regeneration of plantlets

Resistin, an adipokine with non-generalized actions on sympathetic nerve activity

The World Health Organization has called obesity a global epidemic. There is a strong association between body weight gain and blood pressure. A major determinant of blood pressure is the level of activity in sympathetic nerves innervating cardiovascular organs. A characteristic of obesity, in both humans and in animal models, is an increase in sympathetic nerve activity to the skeletal muscle vasculature and to the kidneys. Obesity is now recognized as a chronic, low level inflammatory condition, and pro-inflammatory cytokines are elevated including those produced by adipose tissue. The most well-known adipokine released from fat tissue is leptin. The adipokine, resistin, is also released from adipose tissue. Resistin can act in the central nervous system to influence the sympathetic nerve activity. Here, we review the effects of resistin on sympathetic nerve activity and compare them with leptin. We build an argument that resistin and leptin may have complex interactions. Firstly, they may augment each other as both are excitatory on sympathetic nerves innervating cardiovascular organs; In contrast, they could antagonize each other&#039;s actions on brown adipose tissue, a key metabolic organ. These interactions may be important in conditions in which leptin and resistin are elevated, such as in obesity

General practice pharmacists in Australia:A systematic review

BACKGROUND: The inclusion of pharmacists into general practices in Australia has expanded in recent years. This systematic review aimed to synthesise the literature of qualitative and quantitative studies, and identify the knowledge gaps, related to pharmacists working in general practice in Australia. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, EBSCOhost, EMBASE, and the Cochrane Library were searched from the inception of databases to January 2021. The search was focused on studies investigating general practice pharmacists in Australia. The quality of each study was appraised using the Mixed Method Appraisal Tool criteria. The narrative synthesis approach was utilised to describe data due to the heterogeneity among study designs and measures. RESULTS: Twenty-five studies were included in this review. General practice pharmacists engaged in various non-dispensing patient care services, with medication management reviews being the primary activity reported. General practice pharmacists’ characteristics and an environment with a willingness of collaboration were the notable influencing factors for successfully including pharmacists in general practices. Factors that posed a challenge to the adoption of general practice pharmacists were lack of funding and other resources, poorly defined roles, and absence of mentoring/training. CONCLUSION: This review has summarised the characteristics, activities, benefits, barriers, and facilitators of including pharmacists in general practices in Australia. General practice pharmacists are well accepted by stakeholders, and they can engage in a range of patient-centred activities to benefit patients. There is a need for more robust research to explore the patient and economic outcomes related to clinical activities that a pharmacist can perform in general practice, as a foundation to developing an appropriate and sustainable funding model. The findings of this review will be beneficial for pharmacists, researchers, policymakers, and readers who wish to implement the role of general practice pharmacists in the future

Patients' opinions towards the services of pharmacists based in general practice

Pharmacists have been included in general practice teams to provide non-dispensing services for patients. In Australia, pharmacists' role in general practice has been slowly expanding. However, there is a paucity of research to explore patients' opinions toward pharmacist-led services in general practice. This study aimed to assess patient awareness, perceived needs, and satisfaction with these services. A cross-sectional survey was conducted with a purposeful sample of patients who visited six general practices in the Australian Capital Territory that included pharmacists in their team. The survey was informed by the literature and pre-tested. The survey was distributed to two samples: patients who had seen a pharmacist and those who had not seen a pharmacist. Of 100 responses received, 86 responses were included in the analysis: patients who had seen a pharmacist (n = 46) and patients who had not seen a pharmacist (n = 40). Almost all the patients who utilised pharmacist-led services were highly satisfied with those services. Among patients who had not seen a pharmacist, 50% were aware of the existence of general practice pharmacists. Patients who had visited the pharmacist rated higher scores for perceived needs. Patient satisfaction towards the pharmacist-led services in general practices was very high, and patients supported the expansion of these services. However, awareness of the availability of general practice pharmacist services could be improved

Identification of Risk of QT Prolongation by Pharmacists When Conducting Medication Reviews in Residential Aged Care Settings: A Missed Opportunity?

QT interval prolongation is associated with torsade de pointes and sudden cardiac death.QT prolongation can be caused by many drugs that are commonly prescribed in elderly residentialaged care populations. The aim of this study was to investigate the prevalence of use of QT-prolongingdrugs and to identify interventions made by pharmacists to reduce the risk of QT prolongationwhen conducting medication reviews in aged care. A retrospective analysis of 400 medicationreviews undertaken by Australian pharmacists in aged care settings was conducted. The assessmentincluded the risk of QT prolongation due to prescribed medications and other risk factors and therecommendations made by pharmacists to reduce the risk of QT prolongation. There was a highprevalence of the use of QT-prolonging medication, with 23% of residents (92 out of 400) takingat least one medication with a known risk of QT prolongation. Amongst the 945 prescribed drugswith any risk of QT prolongation, antipsychotics were the most common (n = 246, 26%), followedby antidepressants (19%) and proton pump inhibitors (13%). There appeared to be low awarenessamongst the pharmacists regarding the risk of QT prolongation with drugs. Out of 400 reviews,66 residents were categorised as high risk and were taking at least one medication associated with QTprolongation; yet pharmacists intervened in only six instances (9%), mostly when two QT-prolongingmedications were prescribed. There is a need to increase awareness amongst pharmacists conductingmedication reviews regarding the risk factors associated with QT prolongation, and further educationis generally needed in this area