Assessment of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and other antidiabetic agents in Alzheimer's disease: A population-based study.

The lack of effective treatments for dementia has led to explore the potential of antidiabetic agents as a possible approach. This cross-sectional and population-based study aimed to investigate the relationship between each antidiabetic drug and their defined daily doses (DDDs) and the use of anti-Alzheimer's disease (AD) drugs in order to establish new possible hypotheses about the role of antidiabetic drugs in AD. For that purpose, a database containing information on medications prescribed to 233183 patients aged 50 years or older between 2018 and 2020 was used. DDDs were calculated according to the ATC/DDD index 2023. Statistical analyses, with logistic regression, were carried out to assess antidiabetic and anti-AD drugs consumption. A total of 91836 patients who were prescribed at least one antihypertensive, antidiabetic, or lipid-modifying agent were included in the study; specifically, 29260 patients were prescribed antidiabetic medication. Among the antidiabetic agents, glucagon-like peptide-1 analogs (GLP-1) DDDs were likely to have a positive association with anti-AD drugs in people aged between 70 and 80 years. Additionally, sodium-glucose cotransporter 2 inhibitors (SGLT2i) were prone to have a positive association with anti-AD drug usage across almost every age. However, insulin usage was associated with an increased usage of anti-AD agents. In conclusion, there is evidence suggesting a correlation between certain antidiabetic agents and dementia. Specifically, GLP-1 and SGLT2i might be associated with lower odds of anti-AD drugs usage, while insulins might be linked to higher odds of using anti-AD drugs.

Cost Evaluation of Professional Services in a Rural Community Pharmacy: A Monocentric Exploratory Approach.

The increasing pressure on healthcare systems (HCSs) is a cause for concern worldwide. Rising costs, uncertainty about sustainability, and aging populations are the main issues that make it challenging to allocate scarce resources to the needs of HCSs. Clinical professional pharmacy services (PSs) have been shown to help alleviate system stress and to reach the entire population, although a cost of provision is borne. The objective of this study was to evaluate the provision costs of three PSs, a medicine-dispensing service (MDS), a multicompartmental compliance aid system service (MCAS), and a cognitive impairment screening service (CISS), in a rural community pharmacy. A cost analysis was performed using a time-driven activity-based costing model. The time dedicated to PS provision was appropriately recorded, and the corresponding expenses were extracted from the accounting records. A provision time of 4.80 min and a cost of EUR 2.24 were estimated for the MDS, while 18.33 min and EUR 8.73 were calculated for the MCAS, and 122.20 min and EUR 56.72 were calculated for the CISS. The total provision time represented 85% of the pharmacist's effective working time. Tailored cost analysis is a useful tool for making decisions on the implementation of a PS. Larger studies including a variety of pharmacies and locations are necessary to accurately assess costs and engage in discussions on funding and remuneration.

The A-to-Z factors associated with cognitive impairment. Results of the DeCo study.

Introduction: Cognitive impairment (CI) is known to be mediated by several risk and protective factors, many of which are potentially modifiable. Therefore, it is important to have up-to-date studies that address a standard assessment of psychosocial, clinical and lifestyle variables. Materials and methods: We conducted a cross-sectional observational study, with a 24-month timeframe, to estimate the relationship between risk and protective factors associated with dementia, according to the A-to-Z Dementia Knowledge. Participants were considered at CI risk if they tested positive for at least one of three validated CI screening tests: The Memory Impairment Screening, Short Portable Mental State Questionnaire, and Semantic Verbal Fluency. The A-to-Z data Collection included Mediterranean Diet Adherence Screener and Geriatric Depression Scale. Results: The estimated prevalence of CI was 22.6% in a sample of 709 patients with an average of 69.3±10.3 years. The risk factors gradually associated with cognitive decline were hypertension, loneliness, and depression. In contrast, the protective factors gradually associated with less cognitive decline were internet use, reading, and intellectually stimulating jobs. Finally, living alone, having diabetes, taking benzodiazepines, and sleeping more than 9 h were statistically significant associated with CI, whereas to do memory training or a family history of dementia was characteristic of patients without CI. Conclusion: A joint assessment of the influence of psychosocial, clinical, and lifestyle-related factors is needed to develop dementia prevention strategies.

The effect of an anti-inflammatory diet on chronic pain: a pilot study.

Objective: Rheumatic diseases result in chronic pain (CP) and require treatment with drugs whose prolonged administration is associated with side effects. However, publications in the academic literature have suggested that diet modification and food supplementation can play a crucial role in alleviating the symptoms of inflammatory disease. Thus, it is hoped that the use of an anti-inflammatory diet for pain management might result in improved quality of life. Hence, here we aimed to investigate the effect of anti-inflammatory foods in patients with CP caused by rheumatic diseases. Methods: After an exhaustive bibliography search, we designed a 13-item anti-inflammatory dietary guide based on a Mediterranean diet without red meat, gluten, or cow's milk (the AnMeD-S). We then conducted a pilot study to evaluate the efficacy of this anti-inflammatory diet in patients with CP. A food consumption score (with a maximum of 156 points) was then applied to evaluate patient adhesion to the proposed diet. Forty-five patients with CP were followed-up for 4 months. Variables related with quality of life (including pain perception, depression status, and sleep satisfaction) were measured using 9 validated questionnaires and anthropometric measurements were recorded before and after the participants followed the anti-inflammatory diet. Results: We found a correlation between increased anti-inflammatory food intake and improved physical characteristics, stress, and pain in the patients we assessed. Moreover, decreased consumption of pro-inflammatory foods was positively correlated with sleep satisfaction. Following the AnMeD-S was associated with improved physical characteristics and quality-of-life in patients with CP. Conclusion: The AnMeD-S, includes anti-inflammatory foods and restricts the consumption of certain pro-inflammatory foods (such as those containing gluten). This dietary pattern could provide relief from CP and improve the symptoms of stress and depression, as well as reducing sleep disturbances.

Bridging the Generational Digital Divide in the Healthcare Environment.

Increasing technological advances have generated a digital dependency in the population, resulting in a group of digitally excluded vulnerable people that lack basic digital skills. The aim of this study was to assess the digital divide in patients in relation to the healthcare environment. We explored the extent and effects of the digital health divide by undertaking a systematic review of the academic literature and comparing our findings with the results of a cross-sectional in-person survey answered by 881 people at four community pharmacies. In terms of the sociodemographic profile of the patients, we collected data regarding their gender, age, education level, and location (periphery or urban). The parameters evaluated were use of the internet to search for health information, use of telemedicine, use of different medical/healthcare applications, understanding explanations given by physicians regarding health, and asking pharmacists for help about newly prescribed treatments. Moreover, 168 pharmacists answered an online survey about how often they helped patients to make health center appointments or to download their COVID-19 vaccination certificate. Gender did not influence these results, but age, education level, and population location did. Those with the lowest levels of education required more help to request a health center appointment. People with high education levels and those living in an urban environment more often searched the internet for information about treatments that were new to them. Finally, people living in periphery areas received more help from their pharmacists, 60% of which said they had helped patients to download their COVID-19 vaccination certificate, with 24% of them saying they helped patients with this on a daily basis.

CRIDECO Anticholinergic Load Scale: An Updated Anticholinergic Burden Scale. Comparison with the ACB Scale in Spanish Individuals with Subjective Memory Complaints.

The increase in life expectancy has also been accompanied by an increase in the use of medication to treat chronic diseases. Polypharmacy is associated with medication-related problems such as the increase in the anticholinergic burden. Older people are more susceptible to anticholinergic effects on the central nervous system and this, in turn, may be related to cognitive impairment. In this paper, we develop an updated anticholinergic burden scale, the CRIDECO Anticholinergic Load Scale (CALS) via a systematic review of the literature and compare it with the currently most used Anticholinergic Burden Scale (ACB). Our new scale includes 217 different drugs with anticholinergic properties, 129 more than the ACB. Given the effect that anticholinergic medications have on cognitive performance, we then used both scales to investigate the relationship between anticholinergic burden and cognitive impairment in adult Spanish subjects with subjective memory complaint. In our population, we observed an association between cognitive impairment and the anticholinergic burden when measured by the new CALS, but not when the ACB was applied. The use of a more comprehensive and upgraded scale will allow better discrimination of the risk associated with the use of anticholinergic medications on cognitive impairment. CALS can help raise awareness among clinicians of the problems associated with the use of medications, or combinations of them, with large anticholinergic effect, and promote a better personalized pharmacological approach for each patient.

Addressing Psychosocial Factors in Cognitive Impairment Screening from a Holistic Perspective: The DeCo-Booklet Methodology Design and Pilot Study.

Cognitive impairment (CI), an intermediate phase between the decline in physiological cognition and dementia, is known to be mediated by a variety of risk and protective factors, with age being the most influential of these. The multifactorial nature of CI and the worldwide phenomenon of an aging population makes decoupling old age from disease through the concept of healthy aging (HA) a matter of major interest. Focusing on psychosocial variables and psychological constructs, here we designed and piloted a data collection booklet (DeCo-B) to assess CI and HA from a holistic perspective. The DeCo-B comprises six sections: sociodemographic factors, CI, meaning in life, psychosocial factors, health problems, and lifestyle. The estimated prevalence of CI and HA in our cohort were 24.4% and 6.6%, respectively. Spearman correlations mainly identified pairwise associations between the meaning in life domains and psychosocial variables. Moreover, age, marital status, purpose in life, resilience, chronic pain, cognitive reserve, and obstructive sleep apnea were significantly associated with an increased risk of CI. Our results showed that DeCo-B is a suitable tool for researching how modifiable risk and protective factors influence cognitive status. The complex interrelationships between variables should be further investigated and, for practical reasons, the questionnaire should be optimized in future work.

Lifestyle Variables Such as Daily Internet Use, as Promising Protective Factors against Cognitive Impairment in Patients with Subjective Memory Complaints. Preliminary Results.

Subjective memory complaints (SMCs) may be important markers in the prediction of cognitive deterioration. The aim of this study was to find associations between individual lifestyle factors, which may contribute to cognitive impairment (CI) in people with SMCs and to conduct a literature review on the relationship between internet use and CI in subjects over 50 years old, as a related factor. This was a case-controlled study that included 497 subjects aged over 50 years with SMCs who were recruited from 19 community pharmacies. Three screening tests were used to detect possible CIs, and individuals with at least one test result compatible with a CI were referred to primary care for evaluation. Having self-referred SMC increased the odds of obtaining scores compatible with CI and this factor was significantly related to having feelings of depression (OR = 2.24, 95% CI [1.34, 3.90]), taking anxiolytics or antidepressants (OR = 1.93, 95% CI [1.23, 3.05]), and being female (OR = 1.83, 95% CI [1.15, 2.88]). Thirty percent of our sample obtained scores compatible with CI. Age over 70 years increased the odds of obtaining scores compatible with CI. A high-level education, reading, and daily internet use were factors associated with a reduced risk of positive scores compatible with CI (37-91%, 7-18%, and 67-86%, respectively), while one extra hour television per day increased the risk by 8-30%. Among others, modifiable lifestyle factors such as reading, and daily internet usage may slow down cognitive decline in patients over 50 with SMCs. Four longitudinal studies and one quasi-experimental study found internet use to be beneficial against CI in patients over 50 years of age.

Pharmacists' Knowledge of Factors Associated with Dementia: The A-to-Z Dementia Knowledge List.

Dementia is a neurodegenerative disease with no cure that can begin up to 20 years before its diagnosis. A key priority in patients with dementia is the identification of early modifiable factors that can slow the progression of the disease. Community pharmacies are suitable points for cognitive-impairment screening because of their proximity to patients. Therefore, the continuous training of professionals working in pharmacies directly impacts the public health of the population. The main purpose of this study was to assess community pharmacists' knowledge of dementia-related factors. Thus, we conducted a cross-sectional study of 361 pharmacists via an online questionnaire that quizzed their knowledge of a list of dementia-related factors, which we later arranged into the A-to-Z Dementia Knowledge List. We found that younger participants had a better knowledge of risk factors associated with dementia. The risk factors most often identified were a family history of dementia followed by social isolation. More than 40% of the respondents did not identify herpes labialis, sleep more than 9 h per day, and poor hearing as risk factors. A higher percentage of respondents were better able to identify protective factors than risk factors. The least known protective factors were internet use, avoidance of pollution, and the use of anti-inflammatory drugs. Pharmacists' knowledge of dementia-related factors should be renewed with the aim of enhancing their unique placement to easily implement cognitive-impairment screening.

Pharmacist-Physician Interprofessional Collaboration to Promote Early Detection of Cognitive Impairment: Increasing Diagnosis Rate.

The increased pressure on primary care makes it important for other health care providers, such as community pharmacists, to collaborate with general practitioners in activities related to chronic disease care. Therefore, the objective of the present project was to develop a protocol of action that allows close pharmacist-physician collaboration to carry out a coordinated action for very early detection of cognitive impairment (CI). Methods: A comparative study to promote early detection of CI was conducted in 19 community pharmacies divided into two groups: one group with interprofessional collaboration (IPC) and one group without interprofessional collaboration (NonIPC). IPC was defined as an interactive procedure involving all pharmacists, general practitioners and neurologists. A total of 281 subjects with subjective memory complaints were recruited. Three tests were used in the community pharmacies to detect possible CI: Memory Impairment Screening, Short Portable Mental State Questionnaire, and Semantic Verbal Fluency. Individuals with at least one positive cognitive test compatible with CI, were referred to primary care, and when appropriate, to the neurology service. Finally, we evaluated the differences in clinical and diagnostic follow-up in both groups after six months. Results: The NonIPC study group included 38 subjects compatible with CI referred to primary care (27.54%). Ten were further referred to a neurology department (7.25%) and four of them (2.90%) obtained a confirmed clinical diagnosis of CI. In contrast, in the IPC group, 46 subjects (32.17%) showed results compatible with CI and were referred to primary care. Of these, 21 (14.68%) were subsequently referred to a neurology service, while the remaining 25 were followed up by primary care. Nineteen individuals out of those referred to a neurology service obtained a confirmed clinical diagnosis of CI (13.29%). The percentage of subjects in the NonIPC group referred to neurology and the percentage of subjects diagnosed with CI, was significantly lower in comparison to the IPC group (p-value = 0.0233; p-value = 0.0007, respectively). Conclusions: The creation of IPC teams involving community pharmacists, general practitioners, and neurologists allow for increased detection of patients with CI or undiagnosed dementia and facilitates their clinical follow-up. This opens the possibility of diagnosis in patients in the very early stages of dementia, which can have positive implications to improve the prognosis and delay the evolution of the disease.

A Machine Learning Approach to Design an Efficient Selective Screening of Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is the first sign of dementia among elderly populations and its early detection is crucial in our aging societies. Common MCI tests are time-consuming such that indiscriminate massive screening would not be cost-effective. Here, we describe a protocol that uses machine learning techniques to rapidly select candidates for further screening via a question-based MCI test. This minimizes the number of resources required for screening because only patients who are potentially MCI positive are tested further. This methodology was applied in an initial MCI research study that formed the starting point for the design of a selective screening decision tree. The initial study collected many demographic and lifestyle variables as well as details about patient medications. The Short Portable Mental Status Questionnaire (SPMSQ) and the Mini-Mental State Examination (MMSE) were used to detect possible cases of MCI. Finally, we used this method to design an efficient process for classifying individuals at risk of MCI. This work also provides insights into lifestyle-related factors associated with MCI that could be leveraged in the prevention and early detection of MCI among elderly populations.

The impact of alpha1-adrenoceptors up-regulation accompanied by the impairment of beta-adrenergic vasodilatation in hypertension.

In human and animal hypertension models, increased activity of G-protein-coupled receptor kinase (GRK) 2 determines a generalized decrease of beta-adrenergic vasodilatation. We analyzed the possibility of differential changes in the expression and functionality of alpha(1A), alpha(1B), alpha(1D), beta(1), beta(2), and beta(3)-ARs also being involved in the process. We combined the quantification of mRNA levels with immunoblotting and functional studies in aortas of young and adult spontaneously hypertensive rats (SHRs) and their controls (Wistar Kyoto). We found the expression and function of beta(1)-adrenoceptors in young prehypertensive SHRs to be higher, whereas a generalized increase in the expression of the six adrenoceptors and GRK2 was observed in aortas of adult hypertensive SHRs. alpha(1D)- and beta(3)-adrenoceptors, the subtypes that are more resistant to GRK2-mediated internalization and mostly expressed in rat aorta, exhibited an increased functional role in hypertensive animals, showing two hemodynamic consequences: 1) an increased sensitivity to the vasoconstrictor stimulus accompanied by a decreased sensitivity to the vasodilator stimulus (alpha(1D)-ARs are the most sensitive to agonists, and beta(3)-ARs are the least sensitive to agonists); and 2) a slower recovery of the basal tone after adrenergic stimulus removal because of the kinetic characteristic of the alpha(1D) subtype. These functional changes might be involved in the greater sympathetic vasoconstrictor tone observed in hypertension.

Importance of Increasing Modifiable Risk Factors Knowledge on Alzheimer's Disease Among Community Pharmacists and General Practitioners in Spain.

Community pharmacists and general practitioners have daily contact with patients with Alzheimer's disease (AD) but the number of positive cases constantly increases every day. Thus, the aim of this research is to describe the level of AD knowledge among community pharmacists and general practitioners in Spain, in order to see where the biggest gaps in the knowledge are. Therefore, a cross-sectional study has been carried out, using the Alzheimer's disease knowledge survey (ADKS), among members of the Spanish Society of Primary Care Physicians and the Spanish Society of Family and Community Pharmacy to report the differences in AD knowledge in both professional collectives. The ADKS has been responded by 578 community pharmacists and 104 general practitioners and consists of a battery of 30 questions, whose possible answers are true or false. It assesses the AD knowledge in seven areas (impact on the disease, risk factors, course of the disease, diagnosis, care, treatment and symptoms). Results indicate that Spanish pharmacists and general practitioners have a high personal knowledge of AD, nevertheless, it is not associated with greater awareness. Both scored above 80% at the categories: diagnostic, treatment and symptoms. However, lower knowledge level (60% of correct answers) was found in those related to risk factors, such as the ignorance about hypercholesterolemia or hypertension as risk factors for the disease. Community pharmacists are already acting to control cardiovascular risk factors, but a wider knowledge of the relationship of these factors to AD is needed to act against these silent risk factors. Thus, pharmacists may also be involved in the management of AD that includes recognizing early symptoms for early detection of cognitive impairment. Hence, knowledge about risk factors is very important in developing this expanding role.

Decision Tree for Early Detection of Cognitive Impairment by Community Pharmacists.

Purpose: The early detection of Mild Cognitive Impairment (MCI) is essential in aging societies where dementia is becoming a common manifestation among the elderly. Thus our aim is to develop a decision tree to discriminate individuals at risk of MCI among non-institutionalized elderly users of community pharmacy. A more clinically and patient-oriented role of the community pharmacist in primary care makes the dispensation of medication an adequate situation for an effective, rapid, easy, and reproducible screening of MCI. Methods: A cross-sectional study was conducted with 728 non-institutionalized participants older than 65. A total of 167 variables were collected such as age, gender, educational attainment, daily sleep duration, reading frequency, subjective memory complaint, and medication. Two screening tests were used to detect possible MCI: Short Portable Mental State Questionnaire (SPMSQ) and the Mini-Mental State Examination (MMSE). Participants classified as positive were referred to clinical diagnosis. A decision tree and predictive models are presented as a result of applying techniques of machine learning for a more efficient enrollment. Results: One hundred and twenty-eight participants (17.4%) scored positive on MCI tests. A recursive partitioning algorithm with the most significant variables determined that the most relevant for the decision tree are: female sex, sleeping more than 9 h daily, age higher than 79 years as risk factors, and reading frequency. Moreover, psychoanaleptics, nootropics, and antidepressants, and anti-inflammatory drugs achieve a high score of importance according to the predictive algorithms. Furthermore, results obtained from these algorithms agree with the current research on MCI. Conclusion: Lifestyle-related factors such as sleep duration and the lack of reading habits are associated with the presence of positive in MCI test. Moreover, we have depicted how machine learning provides a sound methodology to produce tools for early detection of MCI in community pharmacy. Impact of findings on practice: The community of pharmacists provided with adequate tools could develop a crucial task in the early detection of MCI to redirect them immediately to the specialists in neurology or psychiatry. Pharmacists are one of the most accessible and regularly visited health care professionals and they can play a vital role in early detection of MCI.

Dexamethasone Preconditioning in Cardiac Procedures Reduces Decreased Antithrombin Activity and Is Associated to Beneficial Outcomes: Role of Endothelium.

Introduction: Decreased antithrombin (AT) activity in patients scheduled for cardiovascular surgery under cardiopulmonary bypass (CPB) is related to increased postoperative complications and hospitalization time. Indirect evidence suggests that glucocorticoids mitigate this decreased AT activity. To better understand the beneficial effects of AT we have analyzed: (i) the clinical relevance of acute dexamethasone (DX) administration before cardiac surgery on AT activity, (ii) the modulation by DX of AT expression in human endothelial cells (hECs), (iii) the activity of AT on migration and angiogenesis of hECs, or on angiogenesis of rat aorta. Methods: A retrospective cohort study in patients undergoing aortic valve replacement surgery was designed to evaluate the effect of DX administration on AT activity at five separate time points: preoperatively, during CPB, at intensive care unit admission and at 12 and 24 h post-intervention. We have analyzed also clinical differences in postoperative outcomes as safety and the length of stay in hospitalization. Changes in mRNA levels of AT induced by DX were determined by qRT-PCR in human coronary (hCEC), aorta (hAEC) and cardiac microvasculature (hCMEC) endothelial cells. AT activity on migration and angiogenesis were also assayed. Angiogenic growth of rat aortic rings incubated in Matrigel® was determined in presence and absence of AT. Results: The cohort comprised 51 patients in the control group and 29 patients in the group receiving dexamethasone. Preoperative DX supplementation reduced intraoperative decrease of AT activity (67.71 ± 10.49% DX treated vs. 58.12 ± 9.11% untreated, p < 0.001) that could be related to a decrease in the hospitalization time (7.59 ± 4.08 days DX treated vs. 13.59 ± 16.00 days untreated, p = 0.014). Treatment of hECs with 500 nM DX slightly increased AT expression. Incubation with 0.5 and 1 IU/mL of AT increased migration and angiogenesis in hCAECs and hAECs, but not in hCMECs. The same concentrations of AT potentiated angiogenic sprouting of new vessels from rat aorta. Conclusion: Preoperative DX supplementation could be an interesting procedure to avoid excessive decrease in AT levels during cardiac surgery. Positive outcomes associated with maintaining adequate AT levels could be related to its potential beneficial effect on endothelial function (migration and angiogenesis).

Glucocorticoids as modulators of expression and activity of Antithrombin (At): potential clinical relevance.

INTRODUCTION: An inverse relationship has been reported between decreased postoperative Antithrombin (AT) plasmatic levels and the incidence of complications. We hypothesized that Nuclear Hormone Receptors could modulate the expression of SERPINC1, encoding AT, through a Hormone Regulatory Element present in its promoter, and thus hormone analogs could be a pharmacological complement in surgical procedures to activate endogenous AT synthesis. MATERIALS AND METHODS: The expression of SERPINC1 was analyzed in HepG2 cells by quantitative RT-PCR and Western Blot. Two studies were conducted with (a) patients submitted to cardiac surgery with cardiopulmonary bypass receiving (n =17) or not (n=321) glucocorticoids (GCs) as part of their pharmacological treatment, and (b) patients who received (n =20) or not (n=16) GCs as part of their surgery (exodontia or knee arthroscopic, respectively). AT activity in plasma was determined by Innovance Antithrombin Test on a BCS XP System hemostasis analyzer. RESULTS: 13 nuclear hormone receptor ligands were assayed, being GW4064 (FXR ligand) the most potent activator. Retinoids, activating RXR, and GCs (Dexamethasone, cortisone and methylprednisolone) also resulted in increased AT expression. Chronic GC treatment mitigates the decreased AT activity observed after cardiac surgery. In patients who received two acute GC doses, pre-operative and post-operative AT activity was similar, whereas a significant decrease was observed after surgery in untreated patients. CONCLUSIONS: Whereas retinoids and FXR ligands are investigational compounds, regulation of AT by GCS could have a higher potential for translation to clinical practice, pre-conditioning the patient against complications related to reduced AT levels. Larger prospective studies are needed to define the exact role of GCs and their potential clinical utility in cardiac surgery.

Antithrombin activity and outcomes in patients undergoing cardiac surgery with cardiopulmonary bypass.

We recently reported prospective results from a cohort of patients scheduled for elective cardiac surgery with cardiopulmonary bypass (CPB) in which most baseline clinical parameters of patients and surgery outcomes failed to demonstrate relationships with post-CPB antithrombin (AT) activity. In this extension study, a larger sample size (250 patients) was analyzed following general linear models. Patients' sociodemographic and pre-CPB clinical data as well as pre/post-CPB AT activity and outcomes were collected. There was a significant decrease of post-CPB AT activity (95.6 ± 13.7-64.6 ± 12.1%; P < 0.001). Univariate and multivariate analyses revealed that a decrease of approximately 1% post-CPB AT activity may be expected per 3 years increase in patient's age. Univariate analysis showed that post-CBP AT activity was inversely related to the need for transfusions, acute renal failure and occurrence of any complication (re-intervention, low cardiac output, arrhythmia, lung dysfunction, stroke, acute renal failure, mesenteric ischemia and re-hospitalization; P < 0.05). Multivariate analysis adjusted for age and pre-CPB AT did not show statistical significance. Odds ratio (OR) less than 1 was observed in most outcomes (0.8 on average), which suggested a reduction of the probability for an increase of 10% in post-CBP AT. Our results confirm the role of low postsurgery AT activity influencing outcomes in patients undergoing CPB.

Correlation between mRNA levels and functional role of alpha1-adrenoceptor subtypes in arteries: evidence of alpha1L as a functional isoform of the alpha1A-adrenoceptor.

The mRNA levels for the three alpha1-adrenoceptor subtypes, alpha1A, alpha1B, and alpha1D, were quantified by real-time RT-PCR in arteries from Wistar rats. The alpha1D-adrenoceptor was prominent in both aorta (79.0%) and mesenteric artery (68.7%), alpha1A predominated in tail (61.7%) and small mesenteric artery (73.3%), and both alpha1A- and alpha1D-subtypes were expressed at similar levels in iliac artery. The mRNA levels of the alpha1B-subtype were a minority in all vessels (1.7-11.1%). Concentration-response curves of contraction in response to phenylephrine or relaxation in response to alpha1-adrenoceptor antagonists on maximal sustained contraction induced by phenylephrine were constructed from control vessels and vessels pretreated with 100 micromol/l chloroethylclonidine (CEC) for 30 min. The significant decrease in the phenylephrine potency observed after CEC treatment together with the inhibitory potency displayed by 8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-8-azaspiro (4,5) decane-7-dionedihydrochloride} (BMY-7378, an alpha1D-adrenoceptor antagonist) confirm the relevant role of alpha1D-adrenoceptors in aorta and iliac and proximal mesenteric arteries. The potency of 5-methylurapidil (an alpha1A-adrenoceptor antagonist) and the changes in the potency of both BMY-7378 and 5-methylurapidil after CEC treatment provided evidence of a mixed population of alpha1A- and alpha1D-adrenoceptors in iliac and distal mesenteric arteries. The low potency of prazosin (pIC50 < 9) as well as the high 5-methylurapidil potency in tail and small mesenteric arteries suggest the main role of alpha1A/alpha1L-adrenoceptors with minor participation of the alpha1D-subtype. The mRNA levels and CEC treatment corroborated this pattern and confirmed that the alpha1L-adrenoceptor could be a functional isoform of the alpha1A-subtype.

Pharmacological properties of the methanol extract from Mentha suaveolens Ehrh.

The present study analyses the pharmacological activity in in vivo and in vitro models of the methanol extract obtained from the leaves and steams of Menta suaveolens Ehrh. This extract lacked toxicity, but exhibited a central nervous system depressant action; an analgesic effect in models of chemical and mechanical stimulation suggesting the induction of a peripheral analgesic response. The extract also exhibited an antiinflammatory action inhibiting the rat paw oedema induced by carrageenin. Moreover, the in vitro studies showed a significant diminution in the contractile effects induced by histamine, serotonin and acetylcholine.

Globularia alypum L. extracts reduced histamine and serotonin contraction in vitro.

The present study analyses in in vitro models the pharmacological activity of methanol and dichloromethane extracts (1, 10 and 100 microg/mL) obtained from the leaves and stems of Globularia alypum L. Preincubation of the guinea-pig ileum and rat uterus with both extracts produced a dose dependent abolition of the contractile effects of histamine and serotonin, respectively. At the same doses, neither methanol nor dichloromethane extract reduced the contractile effects of acetylcholine on rat duodenum or noradrenaline on rat vas deferens.