Counterfeit or substandard drugs are pharmaceutical formulations in which the active pharmaceutical ingredients (APIs) have been replaced or ingredients do not comply with the drug leaflet. With the ...outbreak of the COVID-19 pandemic, fraud associated with the preparation of substandard or counterfeit drugs is expected to grow, undermining health systems already weakened by the state of emergency. Analytical chemistry plays a key role in tackling this problem, and in implementing strategies that permit the recognition of uncompliant drugs. In light of this, the present work represents a feasibility study for the development of a NIR-based tool for the quantification of dexamethasone in mixtures of excipients (starch and lactose). Two different regression strategies were tested. The first, based on the coupling of NIR spectra and Partial Least Squares (PLS) provided good results (root mean square error in prediction (RMSEP) of 720 mg/kg), but the most accurate was the second, a strategy exploiting sequential preprocessing through orthogonalization (SPORT), which led (on the external set of mixtures) to an R
of 0.9044, and an RMSEP of 450 mg/kg. Eventually, Variable Importance in Projection (VIP) was applied to interpret the obtained results and determine which spectral regions contribute most to the SPORT model.
Some reports have suggested that inflammation in perivascular adipose tissue (PVAT) may be implicated in vascular dysfunction by causing the disappearance of an anticontractile effect. The aim of ...this study was to investigate the effects of chronic melatonin treatment on the functional responses of the small mesenteric arteries and on the expression of markers of inflammation/oxidative stress in the aortas of senescence-accelerated prone mice (SAMP8), a model of age-related vascular dysfunction. We investigated seven SAMP8 and seven control senescence-accelerated resistant mice (SAMR1) treated for 10 months with melatonin, as well as equal numbers of age-matched untreated SAMP8 and SAMR1. The mesenteric small resistance arteries were dissected and mounted on a wire myograph, and the concentration-response to norepinephrine was evaluated in vessels with intact PVAT and after the removal of the PVAT. The expression of markers of oxidative stress, inflammation and aging in the aortas was evaluated by immunostaining. In addition, the adiponectin content and the expression of adiponectin receptor 1 were evaluated in the visceral adipose tissue. In untreated SAMP8 mice, we observed an overexpression of oxidative stress and inflammatory markers in the vasculature compared with the controls. No anticontractile effect of the PVAT was observed in untreated SAMP8 mice. Long-term treatment of SAMP8 mice with melatonin increased the expression of some markers of vasoprotection, decreased oxidative stress and inflammation and restored the anticontractile effect of the PVAT. Decreased expression of adiponectin and adiponectin receptor 1 was also observed in visceral fat of untreated SAMP8, whereas a significant increase was observed after melatonin treatment.
It has been previously demonstrated that T lymphocytes may be involved in the development of hypertension and microvascular remodeling, and that circulating T effector lymphocytes may be increased in ...hypertension. In particular, Th1 and Th 17 lymphocytes may contribute to the progression of hypertension and microvascular damage while T-regulatory (Treg) lymphocytes seem to be protective in this regard. However, no data is available about patients with severe obesity, in which pronounced microvascular alterations were observed.
We have investigated 32 severely obese patients undergoing bariatric surgery, as well as 24 normotensive lean subjects and 12 hypertensive lean subjects undergoing an elective surgical intervention. A peripheral blood sample was obtained before surgery for assessment of CD4+ T lymphocyte subpopulations. Lymphocyte phenotype was evaluated by flow cytometry in order to assess T-effector and Treg lymphocytes.
A marked reduction of several Treg subpopulations was observed in obese patients compared with controls, together with an increased in CD4+ effector memory T-effector cells.
In severely obese patients, Treg lymphocytes are clearly reduced and CD4+ effector memory cells are increased. It may be hypothesized that they might contribute to the development of marked microvascular alterations previously observed in these patients.
The regular practice of physical activity helps in the prevention and control of several non-communicable diseases. However, evidence on the role of physical activity in mitigating worsening clinical ...outcomes in people with COVID-19 is still unclear. The aim of this study was to verify whether different levels of physical activity provide protection for clinical outcomes caused by SARS-CoV-2 infection. A cross-sectional study was conducted with 509 adults (43.8 ± 15.71 years; 61.1% female) with a positive diagnosis of COVID-19 residing in Ribeirão Preto, São Paulo, Brazil. Participants were interviewed by telephone to determine the severity of the infection and the physical activity performed. Binary logistic regression was used to indicate the odds ratio (OR) of active people reporting less harmful clinical outcomes from COVID-19. Active people had a lower chance of hospitalization, fewer hospitalization days, less respiratory difficulty and needed less oxygen support. The results suggest that active people, compared to sedentary people, have a lower frequency of hospitalization, length of stay, breathing difficulty and need for oxygen support. These results corroborate the importance of public policies to promote the practice of physical activity, in order to mitigate the severity of the clinical outcomes of COVID-19.
INTRODUCTIONIntroduction: functional limitation is a result of sarcopenia and is associated with loss of skeletal muscle mass (SMM). Cost-effective methods are important for the identification of ...sarcopenia. Objective: to propose cutoff points for normalized calf circumference (CC) in order to identify low SMM in older women based on their functional limitation. Methods: in this descriptive, cross-sectional study the CC values of a young female sample (n = 78) were used to establish cutoff points (-2 SD) for low SMM in older women (n = 67). Functional limitation was identified by the six-minute walk test (≤ 400 m). CC was normalized by body mass, height, and BMI. The diagnostic accuracy of CC was calculated with a ROC curve, using functional limitation as standard. Results: cutoff points and area under the curve (AUC) were: CC (≤ 28.5; 0.62); CC·body mass-1 (≤ 0.40; 0.63); CC·height-2 (≤ 8.52; 0.55) and CC·BMI-1 (≤ 1.10; 0.73). Only CC·BMI-1 achieved a desirable accuracy (AUC > 0.7) to distinguish functional limitation. Conclusion: the accuracy attained supports the use of CC·BMI-1 to identify low SMM in older women. In the clinical context it is possible to predict the risk of sarcopenia when sophisticated methods for determining SMM are not available.
People living with HIV (PWH) experience an accelerated aging process. There is no anthropometric predictive model for appendicular skeletal muscle mass (ASM) in PWH. This study develops ...anthropometric models to predict and validate ASM measured by dual energy x-ray absorptiometry (DXA) in PWH; DXA scans were obtained for 125 PWH (male = 74; age >18 years) on antiretroviral therapy. Fat mass ratio was used for lipodystrophy diagnosis. A multiple stepwise linear regression considered ASM DXA as the dependent variable and validated by PRESS method. A high power of determination and low standard estimate error were found for ASM DXA -predicted (adjusted r2 = 0.84 to 0.87, standard estimate error = 1.7-1.6 kg) and high PRESS validation coefficients (Q 2PRESS = 0.84-0.86, S PRESS = 1.7-1.6 kg). The variables included were lipodystrophy diagnosis, medial calf circumference, sex, and total body weight. We present novel, reliable, and validated anthropometric models to predict ASM DXA in PWH.
Introduction: currently, there is no consensus regarding accurate and low-cost methods for diagnosing lipodystrophy in people living with HIV/AIDS (PLWHA). The aim of this study was to propose ...anthropometric cutoff points for the diagnosis of lipodystrophy among PLWHA. Methods: we included 106 PLWHA (men = 65, women = 41) who are under antiretroviral therapy and have been clinically classified into either a "lipodystrophy" or "non-lipodystrophy" group. Anthropometric measurements included 19 regions of body perimeters and 6 skinfold thickness measures. The Youden index was used to establish anthropometric cutoff points for the diagnosis of lipodystrophy, using the mean values of the anthropometric data (referred to as "original") along with the "Z index" (ZI) values, which were adjusted by the "Phantom Strategy." The cutoff points were proposed when "original" anthropometric measurements and ZI values had a statistical significance of p < 0.01 and an area under the curve (AUC) higher than 70%. The size effect was assessed to verify the influence of lipodystrophy on each anthropometric measure. Results: our data analysis proposes sex-specific cutoff points for the diagnosis of lipodystrophy in PLWHA - 17 points using the "original" anthropometric measurements, and 20 using the ZI values (average effect size between 1.0 and 1.1, and AUC = 76.7% and 78%). Conclusions: our study proposes accurate cutoff points for the diagnosis of lipodystrophy using "original" anthropometric measurements and ZI values adjusted by the "Phantom Strategy." Our findings support the use of anthropometric measurements as a simplified method for diagnosing lipodystrophy and monitoring body composition alterations in people living with HIV/AIDS.
The evaluation of microvascular alterations might provide clinically useful information for patients with an increased cardiovascular (CV) risk, such as those with rheumatoid arthritis (RA), being ...the small artery remodeling the earliest form of target organ damage in primary CV diseases, such as arterial hypertension. The evaluation of retinal arterioles is a non-invasive technique aimed to identify an early microvascular damage, represented by the increase of the wall-to-lumen ratio (WLR) index. Abatacept (ABA), a T-cell co-stimulator blocker, is used to treat RA. A CV protective action was hypothesized for its peculiar mechanism of action in the modulation of T-cells, potentially involved in the pathogenesis of CV comorbidity. The study aimed to non-invasively investigate morphological characteristics of retinal arterioles in a cohort of RA patients treated with ABA.
Seventeen RA patients median (25th-75thpercentile) age = 58 (48-64) years, baseline 28-joint Disease Activity Score DAS28-C-reactive protein (DAS28-CRP) = 4.4 (3.9-4.6), body mass index (BMI) = 24.2 (23.4-26) kg/m
, rheumatoid factor positive:52.9%, anti-citrullinated peptide autoantibodies positive:76.5% without known CV risk factors (arterial hypertension, diabetes, hypercholesterolemia, previous CV events, smoking) were evaluated by the adaptive optics imaging system of retinal arterioles before and every 6 months of therapy with ABA (T0, T6 and T12). Office blood pressure evaluation, 24-h ambulatory blood pressure monitoring and tissue-doppler echocardiography were also performed.
A progressive significant reduction of the WLR of retinal arterioles was observed T0 = 0.28 (0.25-0.30), T6 = 0.27 (0.24-0.31), T12 = 0.23 (0.23-0.26); p T0 vs. T6 = 0.414; p T6 vs. T12 = 0.02; p T0 vs. T12 = 0.009, without significant variations in other parameters. The T0-T12 reduction of WLR was correlated with that of DAS28-CRP (r:0.789;
= 0.005). Moreover, a significant reduction of diastolic office blood pressure and a trend for reduction of daily pressure measured by ambulatory monitoring were observed.
In a cohort of RA patients without known CV risk factors, a reduction of retinal microvascular alterations was demonstrated after treatment for 12 months with ABA, in parallel with the reduction of disease activity. These results might suggest the possibility of microvascular abnormalities regression induced by the immune system modulation.
Introduction: appropriate appendicular lean soft tissue (ALST) parameters to identify sarcopenia in Brazil are scarce. The use of international references may lead to a false positive diagnosis. The ...objective was to propose cut-off points to identify sarcopenia in older men and women using DXA-derived ALST values from a young adult population. Methods: this was an observational study with a cross-sectional analysis. University students of both sexes (n = 125), aged 20 to 30 years, underwent anthropometric measurements and DXA scanning to obtain their ALST (kg). Cut-off points for sarcopenia were set at -2 standard deviations (-2SDs) away from the mean ALST of a young sample. Absolute values and indices (ALST/height2, ALST/weight, and ALST/body mass index BMI) were considered as recommended by international consensus. Results: compared to women, men presented higher values of weight, height, BMI, bone mineral content, lean soft tissue, ALST, and ALST index (kg/m²). Only fat mass was higher in women, and age was not different between genders. The -2SD ALST indices obtained were ≤ 6.56 kg/m² for men and ≤ 4.67 kg/m² for women. They were below international and national values, which tended to classify false positives. Conclusions: the -2SD ALST values proposed here are validated cut-offs for identifying low muscle in older adults and to prevent misdiagnosis with sarcopenia. In addition, they contribute to efficient monitoring and control of this disease in geriatric populations.
Background: In the development of hypertensive microvascular remodeling, a relevant role may be played by changes in extracellular matrix proteins. Aim of this study was the to evaluate some ...extracellular matrix components within the tunica media of subcutaneous small arteries in 9 normotensive subjects and 12 essential hypertensive patients, submitted to a biopsy of subcutaneous fat from the gluteal or the anterior abdominal region.
Patients and Methods: Subcutaneous small resistance arteries were dissected and mounted on an isometric myograph, and the tunica media to internal lumen ratio was measured. In addition, fibronectin, laminin, transforming growth factor-beta-1 (TGF-β1) and emilin-1 contents within the tunica media were evaluated by immunofluorescence and relative immunomorphometrical analysis (immunopositivity % of area). The total collagen content and collagen subtypes within the tunica media were evaluated using both Sirius red staining (under polarized light) and immunofluorescence assay.
Results: Normotensive controls had less total and type III collagen in respect with hypertensive patients. Fibronectin and TGF-β1 tunica media content was significantly greater in essential hypertensive patients, compared with normotensive controls, while laminin and emilin-1 tunica media content was lesser in essential hypertensive patients, compared with normotensive controls. A significant correlation was observed between fibronectin tunica media content and media to lumen ratio.
Conclusions: Our results indicate that, in small resistance arteries of patients with essential hypertension, a relevant fibrosis may be detected; fibronectin and TGF-β1 tunica media content is increased, while laminin and emilin-1 content is decreased; these changes might be involved in the development of small resistance artery remodeling in humans.
PDF
