Silymarin and Inflammation: Food for Thoughts.

Inflammation is a vital defense mechanism, creating hostile conditions for pathogens, preventing the spread of tissue infection and repairing damaged tissues in humans and animals. However, when inflammation resolution is delayed or compromised as a result of its misregulation, the process proceeds from the acute phase to chronic inflammation, leading to the development of various chronic illnesses. It is proven that redox balance disturbances and oxidative stress are among major factors inducing NF-κB and leading to over-inflammation. Therefore, the anti-inflammatory properties of various natural antioxidants have been widely tested in various in vitro and in vivo systems. Accumulating evidence indicates that silymarin (SM) and its main constituent silibinin/silybin (SB) have great potential as an anti-inflammation agent. The main anti-inflammatory mechanism of SM/SB action is attributed to the inhibition of TLR4/NF-κB-mediated signaling pathways and the downregulated expression of pro-inflammatory mediators, including TNF-α, IL-1ß, IL-6, IL-12, IL-23, CCL4, CXCL10, etc. Of note, in the same model systems, SM/SB was able to upregulate anti-inflammatory cytokines (IL-4, IL-10, IL-13, TGF-ß, etc.) and lipid mediators involved in the resolution of inflammation. The inflammatory properties of SM/SB were clearly demonstrated in model systems based on immune (macrophages and monocytes) and non-immune (epithelial, skin, bone, connective tissue and cancer) cells. At the same time, the anti-inflammatory action of SM/SB was confirmed in a number of in vivo models, including toxicity models, nonalcoholic fatty liver disease, ischemia/reperfusion models, stress-induced injuries, ageing and exercising models, wound healing and many other relevant model systems. It seems likely that the anti-inflammatory activities of SM/SB are key elements on the health-promoting properties of these phytochemicals.

Identifying mental health training needs of general practice pharmacy workforce to advance practice: a training needs analysis survey.

BACKGROUND: Mental health problems are commonly treated in general practice. Pharmacy roles are evolving in general practice; however it is unknown what mental health training the pharmacy workforce needs. AIM: To identify and prioritise general practice clinical pharmacists' (GPCPs) and technicians' mental health and psychotropic prescribing learning needs within general practice. METHOD: All 353 GPCPs and technicians, in one health board, were invited to participate in an online survey, September 2021. The validated Hennessy-Hicks Training Needs Assessment Questionnaire, was embedded in the survey. Participants rated 26 tasks with regard to their confidence in performing the task, and importance to their role. Clinical knowledge was assessed against clinical guidelines and literature. RESULTS: Response rate was 26% (92/353); 27% (68/256) GPCPs and 25% (24/97) technicians. Respondents prioritised 'appraising own performance' and 'assessing suicide/deliberate self-harm risk' as high training needs. There were significant variations in prioritisation between GPCPs and technicians; substantial pharmacist agreement (inter-rater correlation 0.713, 95% CI 0.376-0.870, p = 0.001). Depression was a priority training need followed by anxiety, dementia, bipolar, attention deficit (hyperactivity) disorder and schizophrenia. For depression treatment, 2 in 3 respondents were unaware of early antidepressant response, dose-response effects for efficacy, and would wait 8-12 weeks before optimising treatment. The majority were aware of individual lithium and antipsychotic cardiometabolic monitoring parameters; 25% identifying the correct monitoring care-bundle. CONCLUSION: Respondents identified a range of training needs which varied between technicians and pharmacist, and staff banding. Addressing these learning needs may help pharmacy staff to better support practices and patients.

Antioxidant Defences and Redox Homeostasis in Animals.

For many years reactive oxygen species (ROS) production in biological systems has been considered to be detrimental [...].

The standards of practice for delivery of polypharmacy and chronic disease medication reviews by general practice clinical pharmacists: a consensus study.

Background General practice in the UK is experiencing a crisis. Greater multidisciplinary working is a potential solution. The new general practice contract in Scotland encourages this and includes a new pharmacotherapy service to be delivered by General Practice Clinical Pharmacists (GPCPs). Consensus is lacking for the standards of practice for delivery of pharmacotherapy medication reviews (which are polypharmacy and chronic medication reviews) as part of this service. Aim To identify and validate standards of practice for polypharmacy and chronic disease medication (pharmacotherapy level 3) reviews conducted by GPCPs. Method A two-phased mixed-methods consensus methodology was used. Phase 1: An expert group of GPCPs (n = 4) and clinical pharmacist managers (n = 2) responsible for delivering the pharmacotherapy service used a Modified Nominal Group Technique to generate potential standards. Phase 2: Two-round Delphi survey involving GPCPs with ≥ 1 year of experience of working in general practice (n = 159). Results The expert group identified 44 potential standards of practice for polypharmacy and chronic disease reviews. Practicing GPCPs indicated during the Delphi phase that the 44 standards were applicable to practice. The standards of practice covered seven main categories: skills, environment, qualifications, qualities and behaviours, knowledge, process and experience. Conclusion Practicing GPCPs indicated that the standards identified by the expert group are acceptable and valid for current practice and the delivery of polypharmacy and chronic medication reviews. The application of these standards to practice may help GPCPs and general practices to ensure equitable delivery of patient care.

Taurine as a Natural Antioxidant: From Direct Antioxidant Effects to Protective Action in Various Toxicological Models.

Natural antioxidants have received tremendous attention over the last 3 decades. At the same time, the attitude to free radicals is slowly changing, and their signalling role in adaptation to stress has recently received a lot of attention. Among many different antioxidants in the body, taurine (Tau), a sulphur-containing non-proteinogenic ß-amino acid, is shown to have a special place as an important natural modulator of the antioxidant defence networks. Indeed, Tau is synthesised in most mammals and birds, and the Tau requirement is met by both synthesis and food/feed supply. From the analysis of recent data, it could be concluded that the direct antioxidant effect of Tau due to scavenging free radicals is limited and could be expected only in a few mammalian/avian tissues (e.g., heart and eye) with comparatively high (>15-20 mM) Tau concentrations. The stabilising effects of Tau on mitochondria, a prime site of free radical formation, are characterised and deserve more attention. Tau deficiency has been shown to compromise the electron transport chain in mitochondria and significantly increase free radical production. It seems likely that by maintaining the optimal Tau status of mitochondria, it is possible to control free radical production. Tau's antioxidant protective action is of great importance in various stress conditions in human life, and is related to commercial animal and poultry production. In various in vitro and in vivo toxicological models, Tau showed AO protective effects. The membrane-stabilizing effects, inhibiting effects on ROS-producing enzymes, as well as the indirect AO effects of Tau via redox balance maintenance associated with the modulation of various transcription factors (e.g., Nrf2 and NF-κB) and vitagenes could also contribute to its protective action in stress conditions, and thus deserve more attention.

A Right Ventricular Mass in a Patient with Squamous Cell Lung Cancer: A Case Report and Review of Literature.

Cardiac metastasis is much more common than primary cardiac tumors. Lung cancer is one of the most common primary malignancies to metastasize to the heart. It is not common for metastasis in the heart to present as a cavitary mass. To our knowledge, four cases have been reported in the literature showing metastatic lung cancer to the heart, presenting as a right ventricular mass.

Clues from hands/Part 2. Personal details about patients revealed by hand examination.

This is the second part of a two-part article on personal details revealed by hand examination. Examining hands to determine daily activities was the focus of Part 1 in the July/August 2014 Missouri Medicine. Personal traits and preferences, including pets, nutrition and psychology are presented here. These articles serve as a guide for visual clues on the hands to discern a patient's daily activities and personal preference, thereby providing social information that may help establish rapport between patient and physician and may have medical significance.

Clues from hands Part 1: personal details about patients revealed by hand examination.

This is the first part of a two-part article on personal details revealed by the hand examination. Daily activities revealed by hand examination are the focus of Part 1, while personal details including nutrition and psychological assessment are presented in Part 2. These clues enable the examiner to discern hobbies, vocation, sporting activities, dietary information, and psychosocial information of the patient. We describe signs that may aid the clinician in determining these activities, enabling us to provide better patient care by establishing good patient rapport. Part 1, presented here, focuses on detection of visible traces on the hands of sporting activities, hobbies, and vocation. The patient through long familiarity may be oblivious to these features or may find them too insignificant to mention, yet they can provide meaningful social details for the

Extreme pain from brown recluse spider bites: model for cytokine-driven pain.

IMPORTANCE: Bites from the brown recluse spider (BRS) can cause extreme pain. We propose cytokine release as a cause of the discomfort and a central mechanism through glial cell upregulation to explain measured pain levels and time course. OBSERVATIONS: Twenty-three BRS bites were scored at a probable or documented level clinically, and an enzyme-linked immunosorbent assay was used to confirm the presence of BRS venom. The mean (SD) pain level in these cases 24 hours after the spider bite was severe: 6.74 (2.75) on a scale of 0 to 10. Narcotics may be needed to provide relief in some cases. The difference in pain level by anatomic region was not significant. Escalation observed in 22 of 23 cases, increasing from low/none to extreme within 24 hours, is consistent with a cytokine pain pattern, in which pain increases concomitantly with a temporal increase of inflammatory cytokines. CONCLUSIONS AND RELEVANCE: These findings in BRS bites support the hypothesis of cytokine release in inflammatory pain. A larger series is needed to confirm the findings reported here. The extreme pain from many BRS bites motivates us to find better prevention and treatment techniques.

The pink rim sign: location of pink as an indicator of melanoma in dermoscopic images.

Background. In dermoscopic images, multiple shades of pink have been described in melanoma without specifying location of these areas within the lesion. Objective. The purpose of this study was to determine the statistics for the presence of centrally and peripherally located pink melanoma and benign melanocytic lesions. Methods. Three observers, untrained in dermoscopy, each retrospectively analyzed 1290 dermoscopic images (296 melanomas (170 in situ and 126 invasive), 994 benign melanocytic nevi) and assessed the presence of any shade of pink in the center and periphery of the lesion. Results. Pink was located in the peripheral region in 14.5% of melanomas and 6.3% of benign melanocytic lesions, yielding an odds ratio of 2.51 (95% CI: 1.7-3.8, P < 0.0001). Central pink was located in 12.8% of melanomas and 21.8% of benign lesions, yielding an odds ratio of 0.462 (95% CI: 0.67, P = 0.204). Pink in melanoma in situ tended to be present throughout the lesion (68% of pink lesions). Pink in invasive melanoma was present in 17% of cases, often presenting as a pink rim. Conclusions. The presence of pink in the periphery or rim of a dermoscopic melanocytic lesion image provides an indication of malignancy. We offer the "pink rim sign" as a clue to the dermoscopic diagnosis of invasive melanoma.

Obtundation and Myocardial Infarction in a Case of Systemic Loxoscelism.

We report an atypical course of a likely brown recluse spider bite in a 79-year-old male. The Rader scale and Loxosceles reclusa venom detection by ELISA provide supporting evidence for a loxoscelism diagnosis. Obtundation and myocardial infarction occurred following a drop in hemoglobin to 6.5g/dL. The rapid loss of blood volume was considered a significant etiologic factor for both the obtundation and myocardial infarction. The neurological symptoms reversed rapidly after packed red blood cell transfusion.

Beta3 integrin haplotype influences gene regulation and plasma von Willebrand factor activity.

The Leu33Pro polymorphism of the gene encoding beta(3) integrin (ITGB3) is associated with acute coronary syndromes and influences platelet aggregation. Three common promoter polymorphisms have also been identified. The aims of this study were to (1) investigate the influence of the ITGB3 -400C/A, -425A/C and -468G/A promoter polymorphisms on reporter gene expression and nuclear protein binding and (2) determine genotype and haplotype associations with platelet alpha(IIb)beta(3) receptor density. Promoter haplotypes were introduced into an ITGB3 promoter-pGL3 construct by site directed mutagenesis and luciferase reporter gene expression analysed in HEL and HMEC-1 cells. Binding of nuclear proteins was assessed by electrophoretic mobility shift assay. The association of ITGB3 haplotype with platelet alpha(IIb)beta(3) receptor density was determined in 223 subjects. Species conserved motifs were identified in the ITGB3 promoter in the vicinity of the three polymorphisms. The GAA, GCC, AAC, AAA and ACC constructs induced approximately 50% increased luciferase expression relative to the GAC construct in both cell types. Haplotype analysis including Leu33Pro indicated five common haplotypes; no associations between ITGB3 haplotypes and receptor density were found. However, the GCC-Pro33 haplotype was associated with significantly higher vWF activity (128.6 [112.1-145.1]%) compared with all other haplotypes (107.1 [101.2-113.0]%, p=0.02). In conclusion, the GCC-Pro33 haplotype was associated with increased vWF activity but not with platelet alpha(IIb)beta(3) receptor density, which may indicate ITGB3 haplotype influences endothelial function.

Regulatory mechanisms to control tissue alpha-tocopherol.

To test the hypothesis that hepatic regulation of alpha-tocopherol metabolism would be sufficient to prevent overaccumulation of alpha-tocopherol in extrahepatic tissues and that administration of high doses of alpha-tocopherol would up-regulate extrahepatic xenobiotic pathways, rats received daily subcutaneous injections of either vehicle or 0.5, 1, 2, or 10 mg alpha-tocopherol/100 g body wt for 9 days. Liver alpha-tocopherol increased 15-fold in rats given 10 mg alpha-tocopherol/100 g body wt (mg/100 g) compared with controls. Hepatic alpha-tocopherol metabolites increased with increasing alpha-tocopherol doses, reaching 40-fold in rats given the highest dose. In rats injected with 10 mg/100 g, lung and duodenum alpha-tocopherol concentrations increased 3-fold, whereas alpha-tocopherol concentrations of other extrahepatic tissues increased 2-fold or less. With the exception of muscle, daily administration of less than 2 mg/100 g failed to increase alpha-tocopherol concentrations in extrahepatic tissues. Lung cytochrome P450 3A and 1A levels were unchanged by administration of alpha-tocopherol at any dose. In contrast, lung P-glycoprotein (MDR1) levels increased dose dependently and expression of this xenobiotic transport protein was correlated with lung alpha-tocopherol concentrations (R(2)=0.88, p<0.05). Increased lung MDR1 may provide protection from exposure to environmental toxins by increasing alveolar space alpha-tocopherol.