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1.
Biomacromolecules ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31687811

RESUMO

In the recent decades, biodegradable and biocompatible polyphosphoesters (PPEs) have gained wide attention in the biomedical field as relevant substitutes for conventional aliphatic polyesters. These amorphous materials of low glass transition temperature offer promise for the design of soft scaffolds for tissue engineering. Advantageously, the easy variation of the nature of the lateral pendant groups of PPEs allows the insertion of pendent unsaturations valuable for their further cross-linking. In addition, varying the length of the pendent alkyl chains allows tuning their hydrophilicity. The present work aims at synthesizing PPE networks of well-defined hydrophilicity and mechanical properties. More precisely, we aimed at preparing degradable materials exhibiting identical hydrophilicity but different mechanical properties and vice versa. For that purpose, PPE copolymers were synthesized by ring-opening copolymerization of cyclic phosphate monomers bearing different pendent groups (e.g., methyl, butenyl, and butyl). After UV irradiation, a stable and well-defined cross-linked material is obtained with the mechanical property of the corresponding polymer films controlled by the composition of the starting PPE copolymer. The results demonstrate that cross-linking density could be correlated with the mechanical properties, swelling behavior, and degradation rate of the polymers network. The polymers were compatible to human skin fibroblast cells and did not exhibit significant cytotoxicity up to 0.5 mg mL-1. In addition, degradation products appeared nontoxic to skin fibroblast cells and showed their potential as promising scaffolds for tissue engineering.

2.
Int J Eat Disord ; 52(11): 1205-1223, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31512774

RESUMO

OBJECTIVE: Clinically, anorexia nervosa (AN) presents with altered body composition. We quantified these alterations and evaluated their relationships with metabolites and hormones in patients with AN longitudinally. METHOD: In accordance with PRISMA guidelines, we conducted 94 meta-analyses on 62 samples published during 1996-2019, comparing up to 2,319 pretreatment, posttreatment, and weight-recovered female patients with AN with up to 1,879 controls. Primary outcomes were fat mass, fat-free mass, body fat percentage, and their regional distribution. Secondary outcomes were bone mineral density, metabolites, and hormones. Meta-regressions examined relationships among those measures and moderators. RESULTS: Pretreatment female patients with AN evidenced 50% lower fat mass (mean difference [MD]: -8.80 kg, 95% CI: -9.81, -7.79, Q = 1.01 × 10-63 ) and 4.98 kg (95% CI: -5.85, -4.12, Q = 1.99 × 10-28 ) lower fat-free mass, with fat mass preferentially stored in the trunk region during early weight restoration (4.2%, 95% CI: -2.1, -6.2, Q = 2.30 × 10-4 ). While the majority of traits returned to levels seen in healthy controls after weight restoration, fat-free mass (MD: -1.27 kg, 95% CI: -1.79, -0.75, Q = 5.49 × 10-6 ) and bone mineral density (MD: -0.10 kg, 95% CI: -0.18, -0.03, Q = 0.01) remained significantly altered. DISCUSSION: Body composition is markedly altered in AN, warranting research into these phenotypes as clinical risk or relapse predictors. Notably, the long-term altered levels of fat-free mass and bone mineral density suggest that these parameters should be investigated as potential AN trait markers. RESUMENOBJETIVO: Clínicamente, la anorexia nervosa (AN) se presenta con alteraciones en la composición corporal. Cuantificamos estas alteraciones y evaluamos longitudinalmente su relación con metabolitos y hormonas en pacientes con AN. MÉTODO: De acuerdo con las pautas PRISMA, realizamos 94 meta-análisis en 62 muestras publicadas entre 1996-2019, comparando hasta 2,319 pacientes mujeres en pre-tratamiento, post-tratamiento, y recuperadas en base al peso con hasta 1,879 controles. Las principales medidas fueron masa grasa, masa libre de grasa, porcentaje de grasa corporal y su distribución regional. Las medidas secundarias fueron densidad mineral ósea, metabolitos y hormonas. Las meta-regresiones examinaron las relaciones entre esas medidas y moderadores. RESULTADOS: Las pacientes femeninas con AN pre-tratamiento mostraron un 50% menos de masa grasa (MD: -8.80 kg, CI 95%: -9.81, -7.79, Q = 1.01 × 10- 63 ) y 4.98 kg (CI 95%: -5.85, -4.12, Q = 1.99 × 10- 28 ) menos de masa libre de grasa, con masa grasa preferentemente almacenada en la región del tronco durante la recuperación temprana del peso (4.2%, CI 95%: -2.1, -6.2, Q = 2.30 × 10- 4 ). Aunque la mayoría de los rasgos regresaron a los niveles vistos en los controles sanos después de la restauración del peso, la masa libre de grasa (MD: -1.27 kg, CI 95%: -1.79, -0.75, Q = 5.49 × 10- 6 ) y la densidad mineral ósea (MD: -0.10 kg, CI 95%: -0.18, -0.03, Q = 0.01) permanecieron significativamente alteradas. DISCUSIÓN: La composición corporal es marcadamente alterada en la AN, lo que garantiza la investigación en estos fenotipos como predictores de riesgo clínico o de recaída. Notablemente, la alteración a largo plazo de los niveles de masa libre de grasa y densidad mineral ósea sugieren que estos parámetros debe ser investigados como potenciales rasgos indicadores de AN.

3.
Biol Psychiatry ; 86(8): 577-586, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31301758

RESUMO

BACKGROUND: Although attention-deficit/hyperactivity disorder (ADHD) and eating disorders (EDs) frequently co-occur, little is known about the shared etiology. In this study, we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs such as bulimia nervosa. METHODS: We applied different genetically informative designs to register-based information of a Swedish nationwide population (N = 3,550,118). We first examined the familial coaggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores and ED symptoms, and between AN polygenic risk scores and ADHD symptoms, in a genotyped population-based sample (N = 13,472). RESULTS: Increased risk of all types of EDs was found in individuals with ADHD (any ED: odds ratio [OR] = 3.97, 95% confidence interval [CI] = 3.81, 4.14; AN: OR = 2.68, 95% CI = 2.15, 2.86; other EDs: OR = 4.66, 95% CI = 4.47, 4.87; bulimia nervosa: OR = 5.01, 95% CI = 4.63, 5.41) and their relatives compared with individuals without ADHD and their relatives. The magnitude of the associations decreased as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with other EDs (.37, 95% CI = .31, .42) than with AN (.14, 95% CI = .05, .22). ADHD polygenic risk scores correlated positively with ED symptom measures overall and with the subscales Drive for Thinness and Body Dissatisfaction despite small effect sizes. CONCLUSIONS: We observed stronger genetic association with ADHD for non-AN EDs than for AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders.

4.
Nat Genet ; 51(8): 1207-1214, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31308545

RESUMO

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

5.
Dermatol Ther ; 32(4): e12993, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31175673

RESUMO

Doxepin is an old tricyclic antidepressant, whose efficacy in chronic urticaria had been well documented until 1990. However, over the past three decades, there has been limited data on its use. We aimed to assess the efficacy and safety of doxepin in the treatment of patients with chronic urticaria who were poorly responsive to antihistamines. In this retrospective, cross-sectional, single-center study from Turkey, data were examined from patients with chronic urticaria who had poor antihistamine responses and received doxepin therapy from 1998 to 2017. Patient data were analyzed with regard to the duration of the disease, age, sex, treatment outcomes using a weekly urticaria activity score (UAS7), and adverse effects of doxepin therapy. A reduction of ≥90% in UAS7 was defined as "complete response," 30-89% as "partial response" and <30% as "no significant response." Thirty-six patients were included in this study. Doxepin was effective in a majority (n = 27, 75%) of the patients with a short onset time. Sixteen patients (44.4%) showed a complete response. Mild sedative and anticholinergic side effects were well tolerated. Doxepin seems to be a reasonable, efficient, and affordable alternative for the treatment of chronic urticaria in patients who respond poorly to antihistamine therapy.

6.
Int J Eat Disord ; 52(6): 611-629, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30920679

RESUMO

OBJECTIVE: Alterations in blood lipid concentrations in anorexia nervosa (AN) have been reported; however, the extent, mechanism, and normalization with weight restoration remain unknown. We conducted a systematic review and a meta-analysis to evaluate changes in lipid concentrations in acutely-ill AN patients compared with healthy controls (HC) and to examine the effect of partial weight restoration. METHOD: A systematic literature review and meta-analysis (PROSPERO: CRD42017078014) were conducted for original peer-reviewed articles. RESULTS: Forty-eight studies were eligible for review; 33 for meta-analyses calculating mean differences (MD). Total cholesterol (MD = 22.7 mg/dL, 95% CI = 12.5, 33.0), high-density lipoprotein (HDL; MD = 3.4 mg/dL, CI = 0.3, 7.0), low-density lipoprotein (LDL; MD = 12.2 mg/dL, CI = 4.4, 20.1), triglycerides (TG; MD = 8.1 mg/dL, CI = 1.7, 14.5), and apolipoprotein B (Apo B; MD = 11.8 mg/dL, CI = 2.3, 21.2) were significantly higher in acutely-ill AN than HC. Partially weight-restored AN patients had higher total cholesterol (MD = 14.8 mg/dL, CI = 2.1, 27.5) and LDL (MD = 16.1 mg/dL, CI = 2.3, 30.0). Pre- versus post-weight restoration differences in lipid concentrations did not differ significantly. DISCUSSION: We report aggregate evidence for elevated lipid concentrations in acutely-ill AN patients compared with HC, some of which persist after partial weight restoration. This could signal an underlying adaptation or dysregulation not fully reversed by weight restoration. Although concentrations differed between AN and HC, most lipid concentrations remained within the reference range and meta-analyses were limited by the number of available studies.


Assuntos
Anorexia Nervosa/sangue , Lipídeos/sangue , Lipoproteínas/sangue , Adolescente , Adulto , Anorexia Nervosa/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
7.
J Am Acad Child Adolesc Psychiatry ; 58(2): 191-199, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30738546

RESUMO

OBJECTIVE: To examine whether childhood body mass index (BMI) trajectories are prospectively associated with later eating disorder (ED) diagnoses. METHOD: Using a subsample from the Avon Longitudinal Study of Parents and Children (N = 1,502), random-coefficient growth models were used to compare premorbid BMI trajectories of individuals who later developed anorexia nervosa (n = 243), bulimia nervosa (n = 69), binge-eating disorder (n = 114), and purging disorder (n = 133) and a control group without EDs or ED symptoms (n = 966). BMI was tracked longitudinally from birth to 12.5 years of age and EDs were assessed at 14, 16, and 18 years of age. RESULTS: Distinct developmental trajectories emerged for EDs at a young age. The average growth trajectory for individuals with later anorexia nervosa veered significantly below that of the control group before 4 years of age for girls and 2 years for boys. BMI trajectories were higher than the control trajectory for all other ED groups. Specifically, the mean bulimia nervosa trajectory veered significantly above that of controls at 2 years for girls, but boys with later bulimia nervosa did not exhibit higher BMIs. The mean binge-eating disorder and purging disorder trajectories significantly diverged from the control trajectory at no older than 6 years for girls and boys. CONCLUSION: Premorbid metabolic factors and weight could be relevant to the etiology of ED. In anorexia nervosa, premorbid low weight could represent a key biological risk factor or early manifestation of an emerging disease process. Observing children whose BMI trajectories persistently and significantly deviate from age norms for signs and symptoms of ED could assist the identification of high-risk individuals.

8.
Am J Psychiatry ; 176(6): 449-456, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30654643

RESUMO

OBJECTIVE: This study evaluated the benefits of olanzapine compared with placebo for adult outpatients with anorexia nervosa. METHODS: This randomized double-blind placebo-controlled trial of adult outpatients with anorexia nervosa (N=152, 96% of whom were women; the sample's mean body mass index [BMI] was 16.7) was conducted at five sites in North America. Participants were randomly assigned in a 1:1 ratio to receive olanzapine or placebo and were seen weekly for 16 weeks. The primary outcome measures were rate of change in body weight and rate of change in obsessionality, assessed with the Yale-Brown Obsessive Compulsive Scale (YBOCS). RESULTS: Seventy-five participants were assigned to receive olanzapine and 77 to receive placebo. A statistically significant treatment-by-time interaction was observed, indicating that the increase in BMI over time was greater in the olanzapine group (0.259 [SD=0.051] compared with 0.095 [SD=0.053] per month). There was no significant difference between treatment groups in change in the YBOCS obsessions subscale score over time (-0.325 compared with -0.017 points per month) and there were no significant differences between groups in the frequency of abnormalities on blood tests assessing potential metabolic disturbances. CONCLUSIONS: This study documented a modest therapeutic effect of olanzapine compared with placebo on weight in adult outpatients with anorexia nervosa, but no significant benefit for psychological symptoms. Nevertheless, the finding on weight is notable, as achieving change in weight is notoriously challenging in this disorder.

9.
Artigo em Inglês | MEDLINE | ID: mdl-30353925

RESUMO

BACKGROUND: Cross-sectional associations between anxiety disorders and eating disorders (EDs) have been well documented; however, limited research has examined whether symptoms of anxiety disorders are prospectively associated with EDs. Identifying these longitudinal associations can aid in discerning relationships among eating and anxiety disorders and point toward a mechanistic understanding of developmental psychopathology. This study investigated the prospective associations between parent-reported anxiety in mid-childhood (age 10) and child-reported ED behaviors and disorders in adolescence (at ages 14 and 16 years) in a population-based sample. METHODS: Participants were individuals enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based, prospective study of women and their children; 7,767 children whose parents provided data at age 10 were included in current analyses. An exploratory factor analysis identified latent anxiety factors at age 10, followed by a path analysis that evaluated associations between these factors and eating disorder symptoms and cognitions at age 14. RESULTS: Parent-reported anxiety symptoms at age 10 yielded 5 factors: obsessive-compulsive disorder (OCD) symptoms related to symmetry and checking (Factor 1); OCD symptoms associated with aversion to dirt and germs (Factor 2); physical anxiety symptoms (Factor 3); worries (Factor 4); and social phobia symptoms (Factor 5). Factors 3 and 4 showed the most consistent, positive associations with a range of ED symptoms at age 14. Factor 3 predicted diagnosis of bulimia nervosa by age 16 (OR = 1.11, p = .007), whereas Factor 4 predicted diagnoses of anorexia nervosa (OR = 1.10, p = .01) and disordered eating by age 16 (OR = 1.08, p = .001). CONCLUSIONS: Results indicate that symptoms of generalized anxiety in middle childhood may predict adolescent-onset ED symptoms and ED diagnoses.

10.
Contemp Clin Trials ; 74: 61-69, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30287268

RESUMO

BACKGROUND: Genetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13,000 individuals with AN and ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research. METHODS: ANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eating disorder questionnaire (ED100K-v1), 109 women also completed the Structured Clinical Interview for DSM-IV (SCID), Module H. RESULTS: Blood samples and clinical information were collected from 13,363 individuals with lifetime AN and from controls. Online diagnostic phenotyping was effective and efficient; the validity of the questionnaire was acceptable. CONCLUSIONS: Our multi-pronged recruitment approach was highly effective for rapid recruitment and can be used as a model for efforts by other groups. High online presence of individuals with AN rendered the Internet/social media a remarkably effective recruitment tool in some countries. ANGI has substantially augmented Psychiatric Genomics Consortium AN sample collection. ANGI is a registered clinical trial: clinicaltrials.govNCT01916538; https://clinicaltrials.gov/ct2/show/NCT01916538?cond=Anorexia+Nervosa&draw=1&rank=3.

11.
BMC Musculoskelet Disord ; 19(1): 345, 2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30249236

RESUMO

BACKGROUND: Baker's cyst is a benign lesion that results from degenerative or inflammatory diseases of the knee joint. When Baker's cyst ruptures, it may simulate deep vein thrombosis known as Pseudothrombophlebitis syndrome with calf pain, swelling and redness. Pseudothrombophlebitis syndrome without thrombus in popliteal veins has distinct treatment choice than deep vein thrombus. CASE PRESENTATION: In this report, we presented a 47 year-old male rheumatoid arthritis patient with complaints of redness, pain and swelling on his right calf. Pseudothrombophlebitis syndrome was diagnosed due to ruptured Baker's cyst. CONCLUSIONS: We used musculoskeletal ultrasound for both differential diagnosis and treatment of pseudothrombophlebitis syndrome. Ultrasonography revealed massive fluid collection within muscle layers. 280 cc inflammatory fluid was aspirated simultaneously. We also emphasized the importance of ultrasonography in diagnosis and treatment of Pseudothrombophlebitis syndrome with this report.

12.
Dermatol Ther ; 31(5): e12693, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30225952

RESUMO

Certolizumab-pegol is the first and only pegylated TNF-α antagonist approved in the treatment of Crohn's disease, rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. We herein present a case of certolizumab-pegol induced generalized psoriasiform eruption in a patient with ankylosing spondylitis. The diagnosis was based on typical clinical and histopathological findings and further confirmed with Naranjo Adverse Drug Reaction Probability Scale which revealed a total score of nine supporting a definite causal relationship between the drug and skin eruption. As an important finding, a significant improvement of the generalized plaque lesions was achieved upon a therapy including high-potency topical corticosteroid and oral antihistamine without discontinuation of certolizumab-pegol. Moreover, we also present a literature review of the previously published cases with certolizumab-pegol induced psoriasiform eruption. Since all of these cases had Crohn's disease or rheumatoid arthritis as the underlying disease, this is the first case report of certolizumab-pegol induced psoriasiform eruption in a patient with ankylosing spondylitis, to the best of our knowledge.

13.
Mol Psychiatry ; 2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-30087453

RESUMO

Anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a cross-disorder GWAS meta-analysis of 3495 AN cases, 2688 OCD cases, and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (rg = 0.49 ± 0.13, p = 9.07 × 10-7) and a sizable SNP heritability (SNP h2 = 0.21 ± 0.02) for the cross-disorder phenotype. Although no individual loci reached genome-wide significance, the cross-disorder phenotype showed strong positive genetic correlations with other psychiatric phenotypes (e.g., rg = 0.36 with bipolar disorder and 0.34 with neuroticism) and negative genetic correlations with metabolic phenotypes (e.g., rg = -0.25 with body mass index and -0.20 with triglycerides). Follow-up analyses revealed that although AN and OCD overlap heavily in their shared risk with other psychiatric phenotypes, the relationship with metabolic and anthropometric traits is markedly stronger for AN than for OCD. We further tested whether shared genetic risk for AN/OCD was associated with particular tissue or cell-type gene expression patterns and found that the basal ganglia and medium spiny neurons were most enriched for AN-OCD risk, consistent with neurobiological findings for both disorders. Our results confirm and extend genetic epidemiological findings of shared risk between AN and OCD and suggest that larger GWASs are warranted.

15.
Eur Eat Disord Rev ; 2018 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-30136346

RESUMO

OBJECTIVE: Anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are highly comorbid. However, the factors that account for this comorbidity are poorly understood. We examined the core dimensions of AN and OCD and psychological and personality factors shared by both disorders. METHOD: In path analyses (N = 732 women with either current AN or recovered from AN), we examined which factors were uniquely and independently associated with the core dimensions of AN and OCD. We also examined recovery from AN as a moderator. RESULTS: When individuals with AN reported greater concern over mistakes, they endorsed more severity in both AN and OCD core dimensions. These unique associations existed above and beyond all other transdiagnostic personality and psychological factors and regardless of AN recovery status. CONCLUSIONS: Concern over mistakes partially accounts for severity in the core dimensions of both AN and OCD. Concern over mistakes may represent an important target in the aetiology of AN and OCD.

16.
Int J Eat Disord ; 51(8): 835-841, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29693735

RESUMO

OBJECTIVE: Weight suppression (WS), the difference between highest past non-pregnancy weight and current weight, predicts negative outcomes in eating disorders, but the impact of WS and related weight constructs are understudied in nonclinical, midlife populations. We examined WS (current weight < highest weight) and weight elevation (WE), the opposite of WS (current weight > lowest weight) and their associations with eating psychopathology in women aged 50+. METHOD: Participants were a community-based sample (N = 1,776, Mage = 59) who completed demographic and eating psychopathology questions via online survey. WS, WE, and WS × WE were tested as predictors of outcome variables; BMI and medical conditions that affect weight were controlled for. RESULTS: Individuals that were higher on WS and WE were most likely to engage in current weight loss attempts, dieting in the past 5 years, and extreme lifetime restriction. Individuals with higher WS were more likely to experience binge eating, greater frequency of weight checking, overvaluation of shape and weight, and lifetime fasting. Individuals with higher WE were more likely to report negative life impacts of eating and dieting. Higher WS and WE each predicted higher levels of skipping meals over the lifetime. DISCUSSION: This novel study investigated WS in midlife women and introduced a new conceptualization of weight change (WE) that may be more relevant for aging populations given that women tend to gain weight with age. The findings implicate the utility of investigating both WS and WE as factors associated with eating psychopathology in midlife women.

17.
Tissue Cell ; 51: 68-76, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29622090

RESUMO

This study evaluated ulceroprotective and antioxidant effect of 1,25 dihydroxyvitamin D3 against gastric damage in rats. Rats were treated intraperitoneally with either 1,25 dihydroxyvitamin D3 (0.25 µg/kg) or saline for 14 days. On day-15, the non-selective cyclooxygenase inhibitor indomethacin (10 mg/kg; subcutaneously), the inhibitor of sulfhydryl groups N-ethylmaleimide (10 mg/kg; intraperitoneally) or ATP-sensitive K+ channel blocker glibenclamide (10 mg/kg; orally) was given prior to 1,25 dihydroxyvitamin D3. Animals were euthanized at 60 min post ulcerogenic challenge (0.3 M HCl and 60% ethanol (0.2 mL; orally). Stomach and blood were collected for biochemical and histological evaluations. HCl/Ethanol group revealed severely damaged mucous and glandular epithelium with diffuse hemorrhage and inflammatory cell infiltration (microscopic score: 10.67 ±â€¯0.67 and ulcer index: 33.13 ±â€¯5.09). 1,25 dihydroxyvitamin D3 decreased the extent of damage (microscopic score: 6.80 ±â€¯0.02 and ulcer index: 19.00 ±â€¯4.34; p < 0.05), and the elevations in gastric malondialdehyde level (p < 0.001), myeloperoxidase activity (p < 0.001), nuclear factor-κB expression (p < 0.05), and apoptotic index (p < 0.05) following HCl/Ethanol challenge. Decreased gastric glutathione following HCl/Ethanol administration was restored by 1,25 dihydroxyvitamin D3 (p < 0.01). These findings demonstrated protection of the gastric mucosa against HCl/Ethanol-induced injury by 1,25 dihydroxyvitamin D3 via attenuation of inflammatory reaction, oxidative stress and apoptosis.


Assuntos
Antioxidantes/farmacologia , Calcitriol/farmacologia , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Ácido Clorídrico/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle
18.
PLoS One ; 13(1): e0191153, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29370225

RESUMO

Oxidative phosphorylation within mitochondria is the main source of aerobic energy for neuronal functioning, and the key genes are located in mitochondrial DNA. Deficits in oxidative phosphorylation functioning have been reported for schizophrenia, but efforts in the identification of genetic markers within the mitochondrial DNA that predispose to schizophrenia have been limited. We genotyped a set of mitochondrial SNPs using Illumina HumanExome arrays and tested for association in the Swedish schizophrenia sample (N> 10,000). We developed a novel approach for mitochondrial DNA imputation in order to increase the number of common SNPs available for association analysis. The most significant findings were for the mitochondrial SNPs C15452A (GRCh38.p10; rs527236209; p = 0.007; gene MT-CYB; defining haplogroup JT); A11251G (rs869096886; p = 0.007; gene MT-ND4; defining haplogroup JT), and T4216C (rs1599988; p = 0.008, gene MT-ND1, defining haplogroup R2'JT). We also conducted rare variant burden analyses and obtained a p-value of 0.007. For multimarker haplotypes analysis, the most significant finding was for the J group (OR: 0.86, p = 0.02). We conducted the largest association study of mitochondrial DNA variants and schizophrenia but did not find an association that survived multiple testing correction. Analysis of a larger sample is required and will allow a better understanding of the role of mitochondria in schizophrenia.


Assuntos
DNA Mitocondrial/genética , Esquizofrenia/genética , Marcadores Genéticos , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Suécia
19.
Hematology ; 23(1): 25-29, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28583051

RESUMO

OBJECTIVES: Monoclonal B-cell lymphocytosis (MBL) is a precursor state of chronic lymphocytic leukemia (CLL) with peripheral lymphocytosis below 5 × 109/l. The diagnostic criteria exclude the presence of lymphadenopathy, organomegaly, infections, autoimmune diseases or any sign of a lymphoproliferative disorder. This prospective study was designed in order to evaluate the frequency of MBL in blood donors in Turkey. METHODS: The diagnosis of MBL was identified by flow cytometry method based on the International Familial CLL Consortium Report. A total of 999 volunteers [median age 34 (18-78) years; male/female: 705/294] were included in the study. RESULTS: Monoclonal B-cell lymphocytosis was demonstrated in 18 cases (1.8%). A total of 16 cases (1.6%) was evaluated as CLL-like MBL, while 2 (0.2%) had a non-CLL-like phenotype. The subjects were divided into three groups according to age, as <40 years, 40-60 years and >60 years. The prevalence of MBL was 1.1% below 40 years, 0.6% between 40 and 60 years and 0.1% in cases over 60 years, without statistical significance (p > 0.05). DISCUSSION: The sensitivity of the flow cytometry method is essential and may be responsible for the variations in the prevalence of MBL in different populations which can also be attributed to study design, higher detection rates in the elderly and families with genetic predisposition to CLL. CONCLUSION: Large population-based studies and standardized laboratory methods are needed to determine the potential risk factors of progression to CLL, including molecular markers and genetic profile.


Assuntos
Linfocitose/diagnóstico , Doadores de Sangue , Feminino , Humanos , Masculino , Turquia
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