The symptomatology of Attention-Deficit/Hyperactivity Disorder and the genetic control of vitamin D levels.

OBJECTIVES: Vitamin D deficiency has been associated with psychiatric disorders and behavioral phenotypes such as Attention-Deficit/Hyperactivity Disorder (ADHD). Considering that vitamin D levels are polygenic, we aim to evaluate the overall effects of its genetic architecture on symptoms of inattention, hyperactivity, and impulsivity and on the serum levels of vitamin D in two independent samples of adults, as well as the specific effects of five relevant polymorphisms in vitamin D-related genes. METHODS: We evaluated 870 subjects from an ADHD sample (407 cases and 463 controls) and 319 subjects from an academic community (nutrigenetic sample). Vitamin D serum levels were obtained through Elisa test and genetic data by TaqMan™ allelic discrimination and Infinium PsychArray-24 BeadChip genotyping. Polygenic Scores (PGS) were calculated on PRSice2 based on the latest GWAS for Vitamin D and statistical analyses were conducted at Plink and SPSS software. RESULTS: Vitamin D PGSs were associated with inattention in the ADHD sample and with hyperactivity when inattention symptoms were included as covariates. In the nutrigenetic sample, CYP2R1 rs10741657 and DHCR7 rs12785878 were nominally associated with impulsivity and hyperactivity, respectively, and both with vitamin D levels. In the clinical sample, RXRG rs2134095 was associated with impulsivity. DISCUSSION: Our findings suggest a shared genetic architecture between vitamin D levels and ADHD symptoms, as evidenced by the associations observed with PGS and specific genes related to vitamin D levels. Interestingly, differential effects for vitamin D PGS were found in inattention and hyperactivity, which should be considered in further studies involving ADHD.

Detection of Spinal Cord Multiple Sclerosis Lesions Using a 3D-PSIR Sequence at 1.5 T.

PURPOSE: Multiple sclerosis (MS) is a prevalent autoimmune inflammatory disease. Besides cerebral manifestations, an affection of the spinal cord is typical; however, imaging of the spinal cord is difficult due to its anatomy. The aim of this study was to assess the diagnostic value of a 3D PSIR pulse sequencing at a 1.5 T magnetic field strength for both the cervical and thoracic spinal cord. METHODS: Phase sensitive inversion recovery (PSIR), short tau inversion recovery (STIR) and T2-weighted (T2-w) images of the spinal cord of 50 patients were separately evaluated by three radiologists concerning the number and location of MS lesions. Furthermore, lesion to cord contrast ratios were determined for the cervical and thoracic spinal cord. RESULTS: Of the lesions 54.81% were located in the cervical spinal cord, 42.26% in the thoracic spinal cord and 2.93% in the conus medullaris. The PSIR images showed a higher sensitivity for lesion detection in the cervical and thoracic spinal cord (77.10% and 72.61%, respectively) compared to the STIR images (58.63% and 59.10%, respectively) and the T2-w images (59.95% and 59.52%, respectively). The average lesion to cord contrast ratio was significantly higher in the PSIR images compared to the STIR images (p < 0.001) and the T2-w images (p < 0.001). CONCLUSION: Evaluation of the spinal cord with a 3D PSIR sequence at a magnetic field strength of 1.5 T is feasible with a high sensitivity for the detection of spinal MS lesions for the cervical as well as the thoracic segments. In combination with other pulse sequences it might become a valuable addition in an advanced imaging protocol.

Contour device implantation for treatment of intracranial aneurysms in the basilar tip.

INTRODUCTION: Treatment of basilar apex aneurysms will remain challenging regarding the nobility of the parent vessel and their often wide-necked configuration. With endovascular techniques being the treatment approach of choice, novel intrasaccular flow-disruption devices constitute an endovascular embolization option. In this research, we report our experiences in embolizing basilar tip aneurysms with the novel Contour device. MATERIAL AND METHODS: Retrospective analysis of eight patients after Contour implantation into a basilar apex aneurysm. Periprocedural data on intervention times, radiation dose, procedural success and complications were gathered. All patients received follow-up digital subtraction angiography after six months. Further follow-up examination results were analysed given their availability. RESULTS: Contour implantation was successful in all patients. The mean device instrumentation time was 18.8 ± 7.7 min with a mean full intervention time of 100 ± 65.8 min. The mean full procedure radiation dose was 1917 (421-5107) cGy/cm2. After six months, six aneurysms were occluded (Raymond Roy Scale (RRS) 1/2), one showed perfusion inside the device (RRS 3a) and one patient had undergone reintervention due to progression. The aneurysm with constant perfusion at six months was seen to be occluded after 24 months. CONCLUSION: Contour device implantation is a promising feasible alternative endovascular method for embolization of intracranial aneurysms located in the basilar tip with short intervention times and low radiation dosages. Short- and medium-term follow-ups show promising results concerning aneurysm occlusion and reinterventions, however further research is needed to show long-term stability.

Compartment Syndrome Secondary to Bothrops spp. Envenomation in Triângulo Mineiro, Region, Minas Gerais, Brazil.

BACKGROUND: Snakebite is a neglected global health problem with high morbidity. We describe compartment syndrome (CS) cases related to snakebites by Bothrops spp. METHODS: The medical records of patients admitted with snakebites envenomation were reviewed. RESULTS: Of 47 patients with Bothrops spp. envenomation (4 male; mean age: 42 years), 7 (15%) developed CS. The mean time to antivenom administration was 9.5 hours. The time to fasciotomy was variable. Seven patients developed infection and four had acute kidney injury. CONCLUSIONS: The incidence of CS is higher than that reported previously. This may be due to the clinical severity and long delay before administering antivenom.

Intra-cranial aneurysm treatment with contour or WEB - a single center comparison of intervention times and learning curves.

BACKGROUND AND PURPOSE: Treating aneurysms with intra-saccular flow disruption is a feasible alternative to coil-embolization. Besides the established WEB device, the novel Contour Neurovascular System has emerged as a potentially easier alternative regarding sizing and deployment. We report the learning curve experienced at our center from the first 48 patients treated with Contour and compared it with 48 consecutive WEB cases. METHODS: Both groups were compared concerning intervention time, sizing failures leading to device changes and radiation dose. Additionally, we analyzed potential learning effects by comparing the first 24 Contour cases with our last 24 Contour cases and WEB cases respectively. RESULTS: Patient demographics, acute vs. incidental cases and aneurysm localization were comparable in both groups. The deployment time was faster in our 48 Contour cases (median: 22.0 ± 17.0 min), than in the WEB group (median: 27.5 ± 24.0 min). Total intervention time was similar for Contour (median: 68.0 ± 46.9 min) and WEB cases (median: 69.0 ± 38.0 min). Device implantation times in our WEB cases were slightly shorter in the later cases (median: 25.5 ± 24.1 min) than in the earlier (median: 28.0 ± 24.4 min) cases. In the Contour cohort, deployment times were similar for the first 24 cases (median: 22.0 ± 14.5 min) and the final 24 (median: 22.0 ± 19.4 min). Radiation dose was lower in the Contour group (1469.0 ± 1718 mGy*cm2 vs. 1788.0 ± 1506 mGy*cm2 using the WEB device). Less intra-procedural device changes were performed in the Contour cohort (6 of 48 cases, 12.5%), than in the WEB group (8 of 48 cases, 16.7%). CONCLUSION: Aneurysm occlusion times and consequently radiation doses, as well as the amount of device changes were lower in the Contour group. Occlusion times did not differ in the first and last 24 Contour cases, leading to the assumption that the handling of Contour does not require extended training. A short training effect in occlusion times was noted, however, between the first and last WEB cases as shorter procedure times were seen in the latter cases.

Contour device implantation versus coil embolization for treatment of narrow neck intracranial aneurysms.

The novel Contour device is an intrasaccular flow disruption device designed for treatment of intracranial wide-neck bifurcation aneurysms. Outside its original purpose, Contour implantation can be used to treat aneurysms with a higher dome-to-neck ratio which would be suitable for conventional unassisted coil embolization. We compared both techniques in a retrospective single-center analysis. A total of 42 aneurysms from 42 patients with a dome-to-neck ratio of 1.6 or higher were included in this study. Data on technical success, implantation times, radiation dosages, procedural complications, reinterventions and recurrences were gathered and compared. Technical success was achieved in all cases with both techniques. Aneurysm embolization was achieved significantly faster in the Contour group compared to coiling (Overall p = 0.0002; r = 0.580; acute setting: p = 0.005, r = 0.531; elective setting: p = 0.002, r = 0.607). Significantly less radiation dosage was applied in the Contour group (Overall p = 0.002; r = 0.478; acute group p = 0.006; r = 0.552; elective group p = 0.045; r = 0.397). The number of complications was higher in the coiling group compared to the Contour group (Coiling 7/21 (33,3%); Contour 3/21 (14.3%). There was a higher rate of reinterventions in the coiling group (7.6% vs 21.4%). Outside its original intention, the Contour device seems to be a safe and fast alternative to coil embolization for the treatment of narrow-neck-aneurysms.

Physical capacity, body composition and immune-inflammatory markers are associated with risk of cardiovascular disease in sedentary people living with HIV.

BACKGROUND: People living with HIV (PLHIV) are experiencing a high level of non-HIV-related disease mainly related to cardiovascular system however the factors associated with this scenario are widely discussed and indefinite so far. The purpose was to investigate the association of physical capacities, body composition, and immune-inflammatory markers with the Framingham risk score (FRS) in PLHIV. METHODS: Volunteers were recruited and data on age, the time of HIV infection diagnosis and the time of HAART use were collected. The volunteers performed upper limb strength (ULS), lower limb strength (LLS) and cardiorespiratory fitness (VO2peak) tests, body composition evaluation, and blood collection to immune-inflammatory marker markers and the FRS was calculated. Partial age- and sex-adjusted correlation was used to verify associations between factors and multiple linear regression analysis was performed to identify an independent association of FRS and the variables. RESULTS: 113 PLHIV met the eligible criteria and were observed a negative correlation between CD4+ (r=-0.615), time of HIV infection diagnosis (r=-0.237), time of HAART use (r=-0.239), ULS (r=-0.274), LLS (r=-0.213), and VO2peak (r=-0.207) with FRS. There was a positive correlation between fibrinogen and FRS (r=0.363; P<0.001). The TCD4+ count cells were significantly associated with FRS (P=0.001). CONCLUSIONS: Environmental and biological HIV-related factors are inversely associated with FRS while immune-inflammation markers have a positive association.

Compartment Syndrome Secondary to Bothrops spp. Envenomation in Triângulo Mineiro, Region, Minas Gerais, Brazil

ABSTRACT Background: Snakebite is a neglected global health problem with high morbidity. We describe compartment syndrome (CS) cases related to snakebites by Bothrops spp. Methods: The medical records of patients admitted with snakebites envenomation were reviewed. Results: Of 47 patients with Bothrops spp. envenomation (4 male; mean age: 42 years), 7 (15%) developed CS. The mean time to antivenom administration was 9.5 hours. The time to fasciotomy was variable. Seven patients developed infection and four had acute kidney injury. Conclusions: The incidence of CS is higher than that reported previously. This may be due to the clinical severity and long delay before administering antivenom.

Clinical Evaluation of Non-Contrast-Enhanced Radial Quiescent-Interval Slice-Selective (QISS) Magnetic Resonance Angiography in Comparison to Contrast-Enhanced Computed Tomography Angiography for the Evaluation of Endoleaks after Abdominal Endovascular Aneurysm Repair.

PURPOSE: Contrast-enhanced (CE) angiographic techniques, such as computed tomographic angiography (CE-CTA), are most commonly used for follow-up imaging after endovascular aneurysm repair. In this study, CE-CTA and non-CE QISS-MRA were compared for the first time for assessing endoleaks and aneurysms at follow-up after abdominal EVAR. METHODS: Our study included 20 patients (17 male, median age 79.8 years) who underwent radial QISS-MRA and CE-CTA after EVAR at their first follow-up examination. Two interventional radiologists evaluated datasets from both techniques in each patient concerning presence of endoleaks, types of endoleaks, aneurysm diameter, and image quality. Interobserver and intermodal agreement were assessed with Cohen's Kappa. RESULTS: Image quality was rated as excellent or good for both modalities by both observers. Ferromagnetic embolization materials cause hyperdense artifacts in CE-CTA causing aneurysm sac diameter measurements to be inaccurate by up to 1 cm. Type 2 endoleaks with low-flow characteristics in CE-CTA were overlooked compared to radial QISS-MRA. Compared to CE-CTA, all endoleaks after abdominal EVAR were detected and classified correctly on QISS-MRA. The interobserver agreement between CE-CTA and QISS-MRA was almost perfect, except for type 2 endoleaks, where agreement was substantial. Intermodal aneurysm diameter correlate "very strongly" for both observers. CONCLUSIONS: Radial QISS-MRA is a contrast agent free technique for diagnosing and monitoring all types of endoleaks and aneurysms in patients after abdominal EVAR. It provides information about specific clinical questions concerning aneurysm diameter and presence and types of endoleaks without radiation exposure and the side effects associated with iodine-based contrast agents.

Effects of Two Different Exercise Training Programs Periodization on Anthropometric and Functional Parameters in People Living with HIV: A Randomized Clinical Trial.

The purpose of this study was to investigate the effects of two different exercise training programs periodization on anthropometric and functional parameters in people living with HIV (PLHIV). This was a randomized clinical trial that involved participants (n = 31) living with HIV aged over 18 years and undergoing antiretroviral therapy which were randomized to periodized exercise training (PET; n = 13), non-periodized exercise training (NPET; n = 13), or control group (CON; n = 15). The PET and NPET groups performed 12 weeks of combined training while the CON group maintained the usual activities. Before and after 12 weeks of intervention were measured body composition and perimeters, muscle strength, Short Physical Performance Battery (SPPB) and Timed Up and Go (TUG) test time. Results: The PET and NPET groups increased fat-free mass (p < 0,001), right (p < 0,001) and left thigh perimeter (p < 0,001), muscle strength (p < 0,001), handgrip force (p < 0,001), and reduced the fat mass (p < 0,001), neck perimeter (p < 0,001), chair stand (p < 0,001), and time-up and go test time (p < 0,001) compared to CON. Furthermore, PET was significantly different to increase right thigh and muscle strength (p < 0,05) compared to NPET. Conclusion: Both exercise training periodization protocols were effective to improve body composition and functional outcomes; however, seems that PET presents better results compare to NPET in PLHIV.

Daily Undulating Periodization Is More Effective Than Nonperiodized Training on Maximal Strength, Aerobic Capacity, and TCD4+ Cell Count in People Living With HIV.

ABSTRACT: Soares, VL, Soares, WF, Zanetti, HR, Neves, FF, Silva-Vergara, ML, and Mendes, EL. Daily undulating periodization is more effective than nonperiodized training on maximal strength, aerobic capacity, and TCD4+ cell count in people living with HIV. J Strength Cond Res 36(6): 1738-1748, 2022-The aim of this study was to evaluate the effects of daily undulating periodization (DUP) and nonperiodized training (NPT) programs on maximal muscle strength, body composition, aerobic capacity, muscle power, and immune markers in people living with HIV (PLWHIV). A total of 41 PLWHIV were randomly assigned to control (CON [n = 15]), DUP (n = 13), and NPT (n = 13) groups. The DUP and NPT groups performed combined training 3 times a week on nonconsecutive days during 12 weeks, whereas the CON group was asked to maintain their current level of activity. After the 12-week training program, DUP produced greater gains in muscle strength (except for bench press), V̇o2peak, and muscle power than NPT (p < 0.05). Compared to CON, the training groups showed significantly (p < 0.05) increased muscle strength (DUP = 31.0 ± 13.9 kg; NPT = 17.7 ± 9.2 kg; CON = -0.3 ± 1.5 kg), fat-free mass (DUP = 1.9 ± 1.5 kg; NPT = 1.4 ± 1.9 kg; CON = -0.1 ± 1.2 kg), and metabolic equivalent (DUP = 2.3 ± 1.3; NPT = 1.8 ± 1.9), and decreased body fat mass (DUP = -2.1 ± 1.6 kg; NPT = -1.4 ± 1.5 kg; CON = 0.1 ± 0.2) and functional aerobic impairment (DUP = -35.9 ± 17.0%; NPT = -25.8 ± 22.0%; CON = 0.8 ± 3.0%). There was an increase in TCD4+ cells only in the DUP group (p < 0.05). The training effect generally provided a positive correlation between change in leg press strength (r = 0.393, p < 0.05), triceps pulley strength (r = 0.417, p < 0.05), lat pull-down strength (r = 0.459, p < 0.05), and muscle power (r = 0.324, p < 0.05) with changing CD4 + lymphocyte count. Daily undulating periodization protocol showed to be safe, applicable, and more efficient for increasing strength, aerobic capacity, and TCD4+ cells compared to NPT in PLWHIV.

Effects of exercise training and statin on hemodynamic, biochemical, inflammatory and immune profile of people living with HIV: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The aim of this study is to evaluate the effect of exercise training (ET) and statins on the hemodynamic, biochemical, inflammatory and immune profile of people living with HIV (PLHIV). METHODS: This was a randomized, double-blind, placebo-controlled clinical trial in which 83 PLHIV were assigned to either placebo (PL), statins (STA), placebo + ET (PLET), or statins + ET (STAET) groups. Volunteers assigned to STA and STAET groups were administered 10 mg of rosuvastatin, whereas the PL and PLET groups were administered a placebo. The PLET and STAET groups performed ET three times a week. Before and after the 12-week follow-up, volunteers underwent blood collection to assess the biochemical, inflammatory, and immune profile. RESULTS: There were significant time x group interaction effects (P<0.05) for all variables except for diastolic blood pressure. The PLET and STAET groups had significantly (P<0.05) decreased systolic blood pressure, resting heart rate, fasting glucose, glycated hemoglobin, fasting insulin, homeostatic model assessment for insulin resistance, creatine kinase, lactate, and TNF-α levels, and increased adiponectin, CD4+, and CD8+ levels. There was also a significant group effect (P<0.05) for CK levels among the exercised (PLET and STAET) and STA groups. The latter had a significant increase in fasting glucose (P<0.05) and creatine kinase (P<0.05). CONCLUSIONS: ET improved the hemodynamic, biochemical, inflammatory, and immune profile of PLHIV and this effect was not dependent on the use of statins.

Effects of Exercise Training and Statin Use in People Living with Human Immunodeficiency Virus with Dyslipidemia.

PURPOSE: To evaluate the effects of the combination of exercise training (ET) and statins in people living with human immunodeficiency virus. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial. Eighty-three people living with human immunodeficiency virus were assigned to either placebo (PL), statins (STA), PL + ET (PLET) or STA + ET (STAET) groups. Volunteers assigned to STA and STAET groups were administered 10 mg of rosuvastatin, whereas the PL and PLET groups were administered a placebo. The PLET and STAET groups performed ET three times a week. Before and after the 12-wk follow-up, the volunteers underwent to anthropometric assessment and blood collection to evaluate lipid profile, cardiovascular markers, inflammatory profile; a Doppler ultrasound examination, muscle strength (MS) and cardiorespiratory fitness (CF) tests were performed. RESULTS: There was a decrease in total cholesterol, triglycerides, low-density lipoprotein, C-reactive protein, fibrinogen, interleukin (IL)-1ß and right carotid intima-media thickness in the STA, PLET, and STAET groups compared with PL group (P < 0.001). Furthermore, there was a decrease in total cholesterol, triglycerides, low-density lipoprotein, IL-1ß, IL-6, and IL-8 levels and in left and right carotid intima-media thickness and an increase in HDL-c levels in the STAET groups compared with the STA (P ≤ 0.001) and PLET groups (P ≤ 0.001). There was an increase in IL-10 levels, peak-systolic velocity, end-diastolic velocity, wall shear rate in the PLET and STAET groups compared with the PL (P ≤ 0.001) and STA groups (P ≤ 0.001). The PLET and STAET groups reduced body fat mass, body fat percentage and increased lean body mass, MS and CF compared with PL (P ≤ 0.001) and STA (P ≤ 0.001) groups. CONCLUSIONS: The combination of ET and statins is useful to enhance lipid and inflammatory profiles, reduce cardiovascular disease markers, and improve Doppler ultrasound findings, MS and CF in people living with HIV.

The combined polymorphisms of interleukin-6-174GG genotype and interleukin-10 ATA haplotype are associated with a poor quality of life in patients with chronic hepatitis C.

PURPOSE: Chronic hepatitis C (CHC) is associated with a decreased health-related quality of life (HRQOL). More recent studies have pointed toward a genetic basis of patient-reported quality of life outcomes. Taking into account that the influence of single-nucleotide polymorphisms (SNPs) on the HRQOL of CHC patients has not been studied, we investigated the combined IL10-1082G/A, - 819C/T, and - 592C/A SNPs, and IL6-174G/C SNP. We also evaluated the association between demographic, clinical, psychiatric, virological, and genetic variables with domains and summaries of HRQOL in CHC patients. METHODS: 132 consecutive CHC patients and 98 controls underwent psychiatric evaluation by using the Mini International Neuropsychiatric Interview. HRQOL was assessed by a generic questionnaire, the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), and by the specific Liver Disease Quality of Life Questionnaire (LDQOL). IL6 and IL10 polymorphisms were evaluated by Taqman SNP genotyping assay. Multivariate analysis was used to evaluate the associations. RESULTS: Major depressive disorder was associated with lower SF-36 and LDQOL scores in seven and ten domains, respectively. Diabetes and hypertension were also associated with reduced HRQOL. CHC patients carrying the combination of IL10 ATA haplotype/IL6-GG genotype had lower scores in the SF-36-physical functioning domain, and reduced scores in the LDQOL effects of liver disease on activities of daily living, quality of social interaction, and sexual function domains than the non-carriers of the combined haplotype/genotype. CONCLUSION: This is the first study to demonstrate that combined IL6 high-producer GG genotype and IL10 low-producer ATA haplotype is associated with poorer HRQOL in CHC patients.

Periodontal condition and levels of bacteria associated with periodontitis in individuals with bipolar affective disorders: A case-control study.

OBJECTIVE: To evaluate the epidemiological and microbiological aspects of the potential association between bipolar affective disorder (BAPD) and periodontitis. METHODOLOGY: The present case-control study comprised 176 individuals with BAPD and 176 controls. All individuals underwent a complete full-mouth periodontal examination and microbiological sampling. Data on bleeding on probing, probing depth, and clinical attachment level in all present teeth were recorded. Quantification of total bacterial load and Aggregatibacter actinomycetemcomitans, Treponema denticola, and Porphyromonas gingivalis counts were performed through qPCR. Data were analyzed using univariate analysis, Spearman correlation and multivariate logistic regression. RESULTS: The prevalence of periodontitis was 39.7% among controls and 58.5% among individuals with BAPD (OR = 2.13; 95% CI 1.39-3.27). A. actinomycetemcomitans and P. gingivalis counts were significantly higher in individuals with BPAD and periodontitis. The final multivariate logistic regression revealed that periodontitis was strongly associated with the total bacterial load (OR = 1.91; 95% IC = 1.0-1.99; P < 0.001) and the depressive phase of BPAD (OR = 28.94; 95% IC = 4.44-177.27; P < 0.001). CONCLUSION: BAPD was associated with increased risk for periodontitis. Individuals with BPAD presented higher levels of A. actinomycetemcomitans and P. gingivalis, suggesting that periodontitis could be a co-morbidity frequently found in individuals with BAPD.

Interleukin-10 promoter gene polymorphisms are associated with the first major depressive episode in chronic hepatitis C patients.

AIMS: To investigate the association of IL10 SNPs in chronic hepatitis C (CHC) patients with and without the first major depressive episode (MDE), as well as their association with plasma levels of target cytokines. METHODS: A hundred and thirty two CHC patients (32 with and 100 without first MDE) and 98 controls were prospectively enrolled in this cross-sectional study. MDE was diagnosed by a psychiatrist, using the Mini International Neuropsychiatric Interview Plus 5.0. IL10 polymorphisms (-1082 G/A, -819C/T and -592C/A IL10 SNPs) were evaluated by Taqman SNP genotyping assay. Plasma concentrations of IL-2, IL-6, IL-10, IFN-γ and TNF-α were determined using the Human Th1/Th2 Cytometric Bead Array kit. The associations were investigated by logistic models. RESULTS: The frequencies of the studied IL10 SNPs did not differ between the CHC patients and controls. The first MDE was positive and independently associated with the IL10-1082*A, IL10-819*T and IL10-592*A (ATA) low producer haplotype (OR = 1.50; 95% CI = 1.11-2.04; P = 0.009) and current alcohol misuse (OR = 4.29; 95% CI = 1.22-15.05; P = 0.02), and inversely associated with increasing age (OR = 0.94; 95% CI = 0.91-0.98; P = 0.006). In addition, plasma level of TNF-α was significantly higher in the carriers than in the non-carriers of the IL10 ATA haplotype in patients with the first MDE. The IL-10 and IL-2 plasma levels were significantly higher in the carriers than in non-carriers of the IL10 GCC high producer haplotype, demonstrating the functionality of the studied IL10 polymorphisms. CONCLUSIONS: This is the first study to demonstrate that the IL10 low producer ATA haplotype is associated with the first MDE in patients with CHC.

Avaliação de cinco excipientes no perfil de dissolução de cápsulas magistrais de naproxeno / Evaluation of five excipients in the profile of dissolution of naproxen magisterial capsules

Introdução: o naproxeno é um anti-inflamatório não esteroidal (AINE) encontrado nas formas farmacêuticas cápsulas e comprimidos. A análise do efeito de diferentes tipos de excipientes na formulação representa uma importante ferramenta no que diz respeito à influência na dissolução. Objetivo: analisar o efeito de diferentes tipos e quantidades de excipientes no perfil de dissolução de cápsulas de naproxeno. Material e Método: foram manipuladas 4 fórmulas de cápsulas de naproxeno na concentração de 250 mg, com variações de excipientes quanto às concentrações de diluentes, molhantes e desintegrantes. No teste de dissolução, foram avaliadas 6 unidades de cada formulação, em tampão fosfato pH 7,4 (900mL), aparato pá + sinker, 50 rpm, em 6 diferentes tempos de coleta, com leitura das amostras obtidas em 332 nm. Para a determinação da porcentagem de princípio ativo liberado em função do tempo no teste de perfil de dissolução, foi previamente construída uma curva de calibração com 5 concentrações diferentes. Segundo USP (2013), a porcentagem mínima de dissolução de comprimidos de naproxeno aos 45 minutos é de no mínimo 80%. Resultados: todas as formulações se encontram dentro das especificações farmacopéicas, sendo que a formulação 1 apresentou melhor perfil de dissolução do naproxeno, além de ser a formulação com menor custo de preparo, constatando a influência da quantidade e do tipo de excipiente. Conclusão: a melhor combinação dos tipos e quantidades de excipientes em uma formulação magistral é essencial para garantir a qualidade e a eficácia dos fármacos manipulados, especialmente os Classe II no Sistema de Classificação Biofarmacêutica.

Introduction: Naproxen is a Nonsteroidal Anti-Inflammatory drugs (NSAIDs) found in pharmaceutical forms capsules and tablets. The analysis of the effect with different kinds of excipients in magistral formulation represents an important tool to the influence on the dissolution. Purpose: to analyze the effect of different kinds and amounts of excipients on the dissolution profile of naproxen capsules. Material and Method: 4 naproxen capsule formulations in the 250 mg concentration were manipulated, with excipient variations regarding concentrations of diluents, wetting agents and disintegrants. In the dissolution test, 6 units of each formulation were evaluated in phosphate buffer pH 7.4 (900mL), paddle + sinker apparatus, 50 rpm, in 6 different collection times, with a reading of the samples obtained at 332 nm. For percentage determination of active principle released in function of time in dissolution profile test, a calibration curve with 5 different concentrations was previously constructed. According to USP (2013), the minimum dissolution rate of naproxen tablets at 45 minutes is at least 80%. Results: all formulations are within pharmacopoeial specifications, and formulation 1 presented a better dissolution profile of naproxen, besides being the formulation with the lowest preparation cost, noting the influence of the amount and type of excipient. Conclusion: The best combination of the kinds and amounts of excipients in a magistral formulation is essential to ensure the quality and efficacy of the drugs handled, especially Class II in the Biopharmaceutical Classification System.

Avaliação da equivalência farmacêutica de comprimidos de Ibuprofeno por meio do teste perfil de dissolução / Evaluation of the pharmaceutical equivalence of ibuprofen tablets by dissolution profile test

Introdução: Em formas farmacêuticas sólidas orais como comprimidos, o perfil de dissolução comparativo representa o principal teste de avaliação da equivalência farmacêutica. Objetivo: comparar os perfis de dissolução de comprimidos de ibuprofeno 600mg nas formas de referência, genérico e similar. Material e método: Uma curva de calibração de ibuprofeno foi construída com cinco pontos (2, 3, 5, 10 e 15 ppm) com o objetivo de se obter os coeficientes linear, angular e de correção. A partir disto, foram realizados os ensaios de perfil de dissolução em sextuplicata, segundo parâmetros farmacopéicos com 900 mL de tampão fosfato pH 7,2, cesta como aparato, velocidade de rotação de 150 rpm e amostras coletadas em intervalos de 5, 10, 15, 20 e 30 minutos. As alíquotas obtidas foram filtradas e diluídas para a concentração adequada e analisadas em comprimento de onda de 221 nm, para a determinação da porcentagem de dissolução em cada intervalo de tempo amostrado. Resultados: Todos os tipos de medicamentos estavam de acordo com as especificações farmacopeias quanto à porcentagem de dissolução (mínimo 60%) em até 30 minutos. Além disso, segundo os parâmetros da RDC nº 31 de 11 de agosto de 2010 da Agência Nacional de Vigilância Sanitária, os valores de coeficiente de variação no tempo de 10 minutos não excederam a 10%, indicando assim equivalência farmacêutica entre as amostras avaliadas. Conclusão: Com base nos resultados obtidos através dos valores de coeficiente de variação, conclui-se que há equivalência farmacêutica entre as amostras.

Introduction: in solid oral dosage forms as tablets, the comparative dissolution profile represents the main test for the evaluation of pharmaceutical equivalence. Objective: compare the dissolution profiles of ibuprofen 600mg tablets in reference, generic and similar forms. Material and method: a calibration curve of ibuprofen was constructed with five points (2, 3, 5, 10 and 15 ppm) in order to obtain the linear, angular and correction coefficients. From this, dissolution profile assays were carried out in sixfold, according to pharmacopoeial parameters with 900 mL of pH 7.2 phosphate buffer, basket as apparatus, rotation speed of 150 rpm and samples collected at intervals of 5, 10, 15 , 20 and 30 minutes. The obtained aliquots were filtered and diluted to the appropriate concentration and analyzed at a wavelength of 221 nm to determine the percent dissolution at each sampled time interval. Results: all drug types were in accordance with the pharmacopoeial specifications for percent dissolution (minimum 60%) within 30 minutes. In addition, according to the parameters of the RDC nº 31 of August 11, 2010 of the National Agency of Sanitary Surveillance the values of coefficient of variation in the time of 10 minutes did not exceed 10%, thus indicating pharmaceutical equivalence among the evaluated samples. Conclusion: based on the results obtained through the coefficient of variation values, it is concluded that there is a pharmaceutical equivalence between the samples.

Avaliação Da Atividade Antifúngica Dos Extratos Etanólicos Do Melão-De-São Caetano (momordica charantia l) frente a diferentes espécies de cândida / Evaluation of the antifungal activity of ethanolic extracts of the bitter melon (Momordica Charantia L.) Against different species of candida

Introdução: Leveduras do gênero Candida são reconhecidas por serem as espécies mais comuns envolvidas na etiologia das micoses. Objetivo: avaliar a atividade antifúngica dos extratos etanólicos do Melão-de-São-Caetano (Momordica charantia L.) frente a diferentes espécies de Candida. Metodologia: após aprovação pelo Comitê de Ética em Pesquisa, a coleta dos frutos e das folhas do Melão-de-SãoCaetano foi realizada na região da zona rural de Bauru-SP. Os frutos in natura e as folhas foram levados à estufa com circulação forçada de ar por 96 horas a 45°C, sendo, após esse período, submetidos ao processo de moagem em turbólise. Os triturados foram pesados e a cada 10g foram acrescentados 85mL de álcool 70%. Os macerados foram armazenados em erlemeyer, ficaram em repouso por 21 dias, foram devidamente embalados para que a luz não penetrasse na solução. Na sequência, o líquido foi filtrado a vácuo e o solvente evaporado em capela para obtenção dos extratos etanólicos. Os testes foram realizados em triplicata. Resultados: o extrato do fruto não apresentou capacidade fungistática (CIM) nem fungicida (CFM) na máxima concentração avaliada (1250µg/mL) sob as espécies de Candida utilizadas. Já o extrato da folha demonstrou ação fungistática (CIM) frente a todas as espécies de Candida, mostrando padrões diferentes nas concentrações (312,5µg/mL para C. albicans e 625µg/ mL para C. krusei, C. tropicalis e C. glabrata). O mesmo extrato demonstrou capacidade fungicida (CFM) nas espécies C. albicans e na C. tropicalis, nas concentrações 625µg/mL e 1250µg/mL respectivamente. Conclusão: o extrato da folha do Melão-de-SãoCaetano foi eficaz sobre todas as linhagens de Candida ensaiadas, sugerindo uma ótima alternativa terapêutica.

Introduction: Yeast of the candida gender are mostly related to etiology of mycosis. Objective: evaluate the antifungal activity of ethanolic extracts of the Bitter melon (Momordica charantia L.) against different species of Candida. Methodology: after the approval by the Research Ethics Committee, fruits and leaves of the Bitter melon were collected in the rural area of Bauru-SP. The fruits and leaves were taken to a greenhouse and kept with forced air circulation for 96 hours at the temperature of 45 °C. After that period, the samples were submitted to a grinding process in turbolysis. The grindings were weighed and each 10g received 85mL of alcohol 70%. The macerates were stored in an Erlenmeyer flask and were kept at rest for 21 days; after that, they were appropriately packed so that no light would penetrate in the solution. In the sequence, the liquid suffered a vacuum filtration and the solvent was evaporated in a hood to obtain the ethanolic extracts. The tests were performed in triplicate. Results: The extract of the fruit did not show fungistatic (CIM) nor fungicidal capacity (CFM) in the maximum concentration evaluated (1250µg/mL) against the species of Candida used. On the other hand, the extract of the leave showed fungistatic activity (CIM) against the other species of Candida, presenting different patterns in the concentrations (312.5µg/mL for C. albicans and 625µg/mL for C. krusei, C. tropicalis and C. glabrata). The same extract showed fungicidal capacity (CFM) in the species C. albicans and C. tropicalis, in the concentrations 625µg/mL and 1250µg/mL, respectively. Conclusion: the extract of the leave of the Bitter melon was effective against all Candida strains studied, suggesting this is a great therapeutic alternative.