Effect of chronic exposure to aluminium on isoform expression and activity of rat (Na+/K+)ATPase.

The ability of aluminum to inhibit the (Na(+)/K(+))ATPase activity has been observed by several investigators. The (Na(+)/K(+))ATPase is characterized by a complex molecular heterogeneity that results from the expression and differential association of multiple isoforms of both catalytic (alpha) and regulatory (beta) subunits. For instance, three main alpha (alpha(1), alpha(2) and alpha(3)) and three beta (beta(1), beta(2) and beta(3)) subunit isoforms exist in vertebrate nervous tissue, whereas only alpha(1) and beta(1) have been identified in kidney. However, no studies have focused on determining the change in (Na(+)/K(+))ATPase isoforms caused by chronic exposure to aluminum and its relation with aluminum toxicity. In this study, adult male Wistar rats were submitted to chronic dietary AlCl(3) exposure (0.03 g/day of AlCl(3) for 4 months), and the activity and protein expression of (Na(+)/K(+))ATPase isozymes were studied in brain cortex synaptosomes and in kidney homogenates. The intracellular levels of adenine nucleotides, plasma membrane integrity, and aluminum accumulation were also studied in brain synaptosomes. Aluminum accumulation upon chronic dietary AlCl(3) administration significantly decreased the (Na(+)/K(+))ATPase activity measured in the presence of nonlimiting Mg-ATP concentrations, without compromising protein expression of alpha-subunit isoforms in brain and kidney. Aluminum-induced synaptosomal (Na(+)/K(+))ATPase inhibition was due to a reduction in the activity of isozymes containing alpha(1)-alpha(2) and alpha(3)-subunits. The onset of enzyme inhibition was accompanied by a decrease of the (Na(+)/K(+))ATPase sensitivity to submicromolar concentrations of ouabain, and it preceded major damage in plasma membrane integrity and energy supply, as revealed by the analysis of lactate dehydrogenase leakage and endogenous adenine nucleotides. The data suggest that, during chronic dietary exposure to AlCl(3), brain (Na(+)/K(+))ATPase activity drops, even if no significant alterations of catalytic subunit protein expression, cellular energy depletion, and changes in cell membrane integrity are observed. Implications regarding underlying mechanisms of aluminum neurotoxicity are discussed.     

Induction of p53 up-regulated modulator of apoptosis messenger RNA by chemotherapeutic treatment of locally advanced breast cancer.

PURPOSE: In biopsies of patients with locally advanced breast cancer, we investigated the in vivo changes of the gene expression pattern induced by chemotherapy to find genes that are potentially responsible for the efficacy of the drug. EXPERIMENTAL DESIGN: Early cellular responses to chemotherapy-induced damage, both in vivo and in vitro, were investigated by analyzing chemotherapy-induced changes in gene expression profiles. Core biopsies were taken from nine patients with locally advanced breast cancer, before and at 6 hours after initiation of doxorubicin-based chemotherapy. Both samples were cohybridized on the same microarray containing 18,000 cDNA spots. RESULTS: The analysis revealed marked differences in gene expression profile between treated and untreated samples. The gene which was most frequently found to be differentially expressed was p53 up-regulated modulator of apoptosis (PUMA). This gene was up-regulated in eight of nine patients with an average factor of 1.80 (range, 1.36-2.73). In vitro MCF-7 breast cancer cells exposed to clinically achievable doxorubicin concentrations for 6 hours revealed marked induction of PUMA mRNA, as well. CONCLUSIONS: This is the first report describing PUMA mRNA to be up-regulated as a response to chemotherapy in patients. Because PUMA is a known member of the family of BH3-only proapoptotic proteins, this finding suggests PUMA's potential importance for the response to anticancer drugs.     

Effect of reminder cards on compliance with antihypertensive medication

Objective Poor compliance to antihypertensive medications has been identified as a primary cause of uncontrolled blood pressure (BP), with consequent increases in hypertension‐related morbidity and mortality. Therefore, any measure known to improve compliance should be encouraged. This study assessed the impact of reminder cards on compliance to antihypertensive therapy. Method A field trial was undertaken in pharmacies located in the districts of Lisbon and Porto. Eligible participants comprised those aged 30–74 years, prescribed an angiotensin‐converting enzyme inhibitor (ACEI) in monotherapy, and taken on a once‐daily regimen. Patients were allocated to control group (CG) or intervention group (IG), the latter being provided with a reminder card, an alarm‐type device due to remind the patient of the time to take his medication. Patients were monitored monthly during 3 months for compliance and blood pressure control. Key findings Seventy‐one patients participated in the study (intervention: 35; control group: 36). Compliance was similar between the groups in the first 2 months of follow‐up (97.1% IG vs 94.9% CG at first follow‐up and 97.5% IG vs 94.2% CG at second follow‐up) and higher in the intervention group at the end of the study (97.3% IG vs 87.3% CG; P = 0.011). There were no mean blood pressure differences between compliant and non‐compliant subjects at the end of the study (P value for differences in systolic BP (P_syst) = 0.580; and P value for differences in diastolic BP (P_dlast) = 0.175). Conclusion This small‐scale study indicates a possible positive impact on patients' compliance resulting from the use of reminder cards. However, this needs confirming in larger scale studies with longer monitoring periods.     

Patterns and determinants of psychoactive drug use in Lisbon University students – a population-based study

OBJECTIVE: To study the patterns and determinants of psychoactive drug use by Lisbon University students. MATERIALS AND METHODS: A cross-sectional survey was conducted, from January to April 2000, in a probabilistic sample of 1,147 students. Information about use of psychoactive drugs and co-variates was collected by a questionnaire administered by trained interviewers. Psychoactive drugs were considered to be all medicines classified in group N (nervous system) of the ATC system except the anesthetics (subgroup N01) and the analgesics (subgroup N02). RESULTS: 91 students (7.9%) had taken psychoactive drugs during the fortnight before the interview, 39 of whom (42.8%) mentioned continuous use. The prevalence of use was significantly higher in females (9.6%), older than 25 years (13.1%), married (16%), who considered themselves to have a weak health status (21.7%), as under intense stress (15.5%). After adjustment by multivariate analysis the variables sex, self-evaluation of health status and daily stress retained a higher significant association with psychoactive drug use. A total of 132 drugs were reported as being used in that period. Tranquilizers (ATC = N05B or N05C) were used by 82 students (7.2%), while 22 (1.9%) consumed psychoactive stimulants (N06B) and 19 (1.7%) antidepressants (N06A). In all of these therapeutical subgroups, females had higher consumption prevalence than males, but the difference was statistically significant only for tranquilizers (P < 0.001). Anxiety, depression and insomnia were the most frequently stated health problems. More than 90% of drug consumers considered they had a compliant attitude and about 60% considered themselves well-informed about adverse effects of the drug used. The reported prevalence of self-medication for psychoactive drugs used was 12.8%. CONCLUSIONS: The prevalence of psychoactive drug use among students of Lisbon University was higher than expected, considering age group and the usual health status of this population. The administration of a questionnaire was a very useful tool to characterise the pattern of use and the consumer's knowledge about the drugs consumed.     

The Impact of Dense Breasts on the Stage of Breast Cancer at Diagnosis: A Review and Options for Supplemental Screening

The purpose of breast cancer screening is to find cancers early to reduce mortality and to allow successful treatment with less aggressive therapy. Mammography is the gold standard for breast cancer screening. Its efficacy in reducing mortality from breast cancer was proven in randomized controlled trials (RCTs) conducted from the early 1960s to the mid 1990s. Panels that recommend breast cancer screening guidelines have traditionally relied on the old RCTs, which did not include considerations of breast density, race/ethnicity, current hormone therapy, and other risk factors. Women do not all benefit equally from mammography. Mortality reduction is significantly lower in women with dense breasts because normal dense tissue can mask cancers on mammograms. Moreover, women with dense breasts are known to be at increased risk. To provide equity, breast cancer screening guidelines should be created with the goal of maximizing mortality reduction and allowing less aggressive therapy, which may include decreasing the interval between screening mammograms and recommending consideration of supplemental screening for women with dense breasts. This review will address the issue of dense breasts and the impact on the stage of breast cancer at the time of diagnosis, and discuss options for supplemental screening.     

Factors associated with early uptake of COVID‐19 vaccination among healthcare workers in Azerbaijan, 2021

IntroductionWe evaluated uptake and factors associated with COVID‐19 vaccination among health workers (HWs) in Azerbaijan.ResultsAmong 1575 HWs, 73% had received at least one dose, and 67% received two doses; all received CoronaVac. Factors associated with vaccination uptake included no previous COVID‐19 infection, older age, belief in the vaccine''s safety, previous vaccination for influenza, having patient‐facing roles and good or excellent health by self‐assessment.ConclusionThese findings could inform strategies to increase vaccination uptake as the campaign continues.     

Characterization of Healthcare-Associated and Community-Associated Clostridioides difficile Infections among Adults,Canada, 2015–2019

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015–2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015–2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control.     

Investigation of the in vitro and ex vivo acetylcholinesterase and antioxidant activities of traditionally used Lycopodium species from South America on alkaloid extracts

Ethnopharmacological relevance

The study was aimed at evaluating medicinal and therapeutic potentials of two Lycopodiaceae species, Lycopodium clavatum (L.) and Lycopodium thyoides (Humb. & Bonpl. ex Willd), both used in South American folk medicine for central nervous system conditions. Alkaloid extracts were evaluated for chemical characterization, acetylcholinesterase and antioxidant activities.

Materials and methods

The alkaloid extracts obtained by alkaline extraction were determined for each species by GC/MS examination. The evaluation of the anticholinesterase and the antioxidant activities of the extracts were tested by determining in vitro and ex vivo models. Effects on acetylcholinesterase (AChE) were tested in vitro using rat brain homogenates and ex vivo after a single administration (25, 10 and 1 mg/kg i.p.) of the alkaloid extracts in mice. The in vitro antioxidant effects were tested for the 2-deoxyribose degradation, nitric oxide (NO) interaction, 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging activity and total reactive antioxidant potential (TRAP). After an acute administration (25 and 10 mg/kg i.p.) of the extracts in middle-aged (12 months) mice, the antioxidant effects were estimated through the thiobarbituric acid reactive substances test (TBARS), and the antioxidant enzymes activities for catalase (CAT) and superoxide dismutase (SOD) were measured.

Results

AChE activity was inhibited in vitro by the alkaloid-enriched extracts of both Lycopodium species in a dose and time-dependent manner in rat cortex, striatum and hippocampus. A significant inhibition was also observed in areas of the brain after acute administration of extracts, as well as decreased lipid peroxidation and increased CAT activity in the cortex, hippocampus and cerebellum. A moderate antioxidant activity was observed in vitro for the extracts. Chemically, the main alkaloids found for the two species were lycopodine and acetyldihidrolycopodine.

Conclusion

This study showed that the biological properties of the folk medicinal plants Lycopodium clavatum and Lycopodium thyoides include AChE inhibitory activity and antioxidant effects, two possible mechanisms of action in Alzheimer's related processes.