RESUMO
1,8-dihydroxy-9-anthrone are tricyclic compounds with a ketone group in the middle ring and two hydroxyl groups substituted in the side-aromatic rings what results in formation of two intramolecular hydrogen bonds in which the oxygen atom from the ketone group is the proton acceptor. 1,8-dihydroxy-9-anthrones in which intramolecular proton transfer between C10 and CO in the middle ring occurs, can exist in a tautomeric keto-enol equilibrium. For anthralin, the most important representative of this group, this equilibrium has been studied previously, but it has not been studied for its derivatives. Substituents in the middle ring change the geometry of 1,8-dihydroxy-9-anthrones so they are also expected to affect the keto-enol equilibrium. It is also important to study the effect of intramolecular hydrogen bonds on the structure of both tautomeric forms. It was found that the nature of the substituent in the middle ring could affect the antioxidant properties of the investigated compound.
Assuntos
Antralina , Prótons , Antralina/química , Elétrons , Antracenos/química , Álcoois , CetonasRESUMO
The geometry of dibenzoazepine analogues-typical multifunctional drugs-was investigated to find the geometrical parameters sensitive to the substitution of the central seven-membered ring. Exploration of the crystal structure database (CSD) shows that the geometrical parameter sensitive to the substitution of the carbon atom distance of the central ring not included in the aromatic rings to the plane through the carbon atoms common for the central ring and the aromatic side rings. Presence of the double bond in the central ring was reflected in its partial aromaticity expressed by the HOMED parameter. Some derivatives of 5H-dibenzo[b,f]azepine with flat conformation of the central ring are characterized by mobility of the electron density comparable to the mobility in the aromatic side rings. Influence of the surrounding on the investigated compounds was confirmed by comparison of the optimized molecules and the molecules in the crystal state where the packing forces can influence the molecular geometry.
Assuntos
Azepinas/química , Modelos Químicos , Azepinas/farmacologia , Ciclização , Teoria da Densidade Funcional , Estrutura Molecular , TermodinâmicaRESUMO
BACKGROUND: Type 1 diabetes (T1D) may coexist with primary immunodeficiencies, indicating a shared genetic background. OBJECTIVE: To evaluate the prevalence and clinical characteristics of immunoglobulin deficiency (IgD) among children with T1D. METHODS: Serum samples and medical history questionnaires were obtained during routine visits from T1D patients aged 4-18 years. IgG, IgA, IgM, and IgE were measured by nephelometry and enzyme-linked immunosorbent assay (ELISA). IgG and IgM deficiency (IgGD, IgMD) were defined as IgG/IgM >2 standard deviations (SD) below age-adjusted mean. IgE deficiency was defined as IgE <2 kIU/L. IgA deficiency (IgAD) was defined as IgA >2 SD below age-adjusted mean irrespective of other immunoglobulin classes (absolute if <0.07 g/L, partial otherwise) and as selective IgAD when IgA >2 SD below age-adjusted mean with normal IgG and IgM (absolute if <0.07 g/L, partial otherwise). RESULTS: Among 395 patients (53.4% boys) with the median age of 11.2 (8.4-13.7) and diabetes duration 3.6 (1.1-6.0) years, 90 (22.8%) were found to have hypogammaglobulinemia. The IgGD and IgAD were the most common each in 40/395 (10.1%). Complex IgD was found in seven patients. Increased odds of infection-related hospitalization (compared to children without any IgD) was related to having any kind of IgD and IgAD; OR (95%CI) = 2.1 (1.2-3.7) and 3.7 (1.8-7.5), respectively. Furthermore, IgAD was associated with having a first-degree relative with T1D OR (95%CI) = 3.3 (1.4-7.6) and suffering from non-autoimmune comorbidities 3.3 (1.4-7.6), especially neurological disorders 3.5 (1.2-10.5). CONCLUSIONS: IgDs frequently coexist with T1D and may be associated with several autoimmune and nonimmune related disorders suggesting their common genetic background.
Assuntos
Diabetes Mellitus Tipo 1 , Síndromes de Imunodeficiência , Adolescente , Idade de Início , Criança , Estudos de Coortes , Diabetes Mellitus Tipo 1/classificação , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/patologia , Feminino , Humanos , Deficiência de IgG/complicações , Deficiência de IgG/epidemiologia , Deficiência de IgG/patologia , Imunoglobulina A/análise , Imunoglobulina A/sangue , Imunoglobulina G/análise , Imunoglobulina G/sangue , Síndromes de Imunodeficiência/classificação , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/patologia , Masculino , Fenótipo , Polônia/epidemiologia , PrevalênciaRESUMO
The geometry of anthrone and anthraquinone-natural substances of plant origin-was investigated under the substitution of hydrogen atoms in side aromatic ring and, for anthrone, also in the central ring. A significant influence of substitution on geometry expressed by the angle between the side rings was shown. The geometry changes are connected with the changes of electron density and aromaticity of the anthrone and anthraquinone rings. The flexibility of the investigated compounds was confirmed by comparison of the optimized molecules and the molecules in the crystal state where the packing forces can influence the molecular geometry.
Assuntos
Antracenos/química , Antraquinonas/química , Hidrogênio/química , Modelos Moleculares , Conformação MolecularRESUMO
As the influence of transformer-based approaches in general and generative artificial intelligence (AI) in particular continues to expand across various domains, concerns regarding authenticity and explainability are on the rise. Here, we share our perspective on the necessity of implementing effective detection, verification, and explainability mechanisms to counteract the potential harms arising from the proliferation of AI-generated inauthentic content and science. We recognize the transformative potential of generative AI, exemplified by ChatGPT, in the scientific landscape. However, we also emphasize the urgency of addressing associated challenges, particularly in light of the risks posed by disinformation, misinformation, and unreproducible science. This perspective serves as a response to the call for concerted efforts to safeguard the authenticity of information in the age of AI. By prioritizing detection, fact-checking, and explainability policies, we aim to foster a climate of trust, uphold ethical standards, and harness the full potential of AI for the betterment of science and society.
RESUMO
INTRODUCTION: Type 1 diabetes (T1D) may be associated with numerous complications including bone metabolism disorders. The aim of the study was to evaluate the bone metabolism markers twice in children with a newly diagnosed T1D and after an average of seven months of its duration in relation to parameters of the clinical course of diabetes. MATERIAL AND METHODS: In 100 T1D patients and 52 control subjects, the following bone turnover markers were evaluated: osteocalcin - OC, osteoprotegerin - OPG, sRANKL, and deoxypyridoline in urine - DPD and DXA examination was also performed. RESULTS: Lower OC concentration at T1D onset in comparison to controls (p < 0.001) and its increase during follow-up (p < 0.001) was ob-served. The OPG concentration was elevated at T1D onset as compared to the control group (p = 0.024) and decreased thereafter (p < 0.001). The s-RANKL level increased during follow-up (p < 0.001) and was lower than in controls (p < 0.001). Urine DPD con-centration also increased during follow-up in the T1D patient group (p < 0.001) and was higher in comparison to the control group (p = 0.021). BMD-TBLH was higher in the control group as compared to patients both at T1D onset (p = 0.025) and in follow-up ob-servation (p = 0.034). Moreover, OPG correlated positively with glycated haemoglobin (HbA1c) (p = 0.004) and negatively with fasting C-peptide level (p = 0.046) and BMI Z-score (p = 0.003), whereas s-RANKL correlated positively with both fasting (p < 0.001) and stimulated C-peptide levels (p < 0.001). CONCLUSIONS: Bone metabolism disorders observed at T1D onset in children and modified after reaching the metabolic control of the disease seem to be most strongly associated with preserved insulin secretion.
Assuntos
Diabetes Mellitus Tipo 1/sangue , Secreção de Insulina , Osteocalcina/sangue , Osteoprotegerina/sangue , Ligante RANK/sangue , Adolescente , Densidade Óssea , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: The aim of the study was to compare the selected markers in children with and without partial clinical remission (CR) of newly diagnosed type 1 diabetes (T1D). METHODS: The study group consisted of 186 patients (F/M; 87/99) at onset of T1D and 24 months of follow-up. Partial CR was defined as insulin requirement <0.5 IU/kg and glycated hemoglobin (HbA1c) <7%. RESULTS: Partial CR was observed in 115/186 (61.83%) of patients. At diagnosis body mass index standard deviation (BMI SDS) was higher among remitters than in non-remitters (p=0.0051) and remitters were younger (p=0.0029). In the follow-up a higher triglyceride concentration in non-remitters compared to remitters (p=0.0455) and a lower high density lipoprotein (HDL) cholesterol level (p=0.0119) were noticed. CONCLUSIONS: Younger age and higher BMI at diagnosis of T1D can predispose to partial CR in children. In patients with CR of T1D after 2 years of follow-up a lipid profile improvement is observed.
Assuntos
Biomarcadores/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Hipoglicemiantes/uso terapêutico , Índice de Massa Corporal , Criança , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Seguimentos , Humanos , Insulina/uso terapêutico , Masculino , Prognóstico , Indução de RemissãoRESUMO
INTRODUCTION AND OBJECTIVE: The aim of the study was to evaluate the influence of age and gender on the prevalence of overweight and obesity, body composition and fatty tissue distribution in young adults with type 1 diabetes. MATERIAL AND METHODS: 197 patients with type 1 diabetes aged 20-40 years participated in the study. The control group consisted of 138 healthy adults. Body weight, height, waist and hip circumferences were measured. Analysis of body mass composition was performed using the bioimpedance. Study groups were stratified into cohorts aged <30 and 30+ years. RESULTS: Overweight and obesity were diagnosed in 35.5% and 13.2% of diabetic patients and in 26.1% and 7.3% of the control group, respectively (p=0.016). In the whole study group, advanced age (OR=1.10; p<0.001) and diabetes mellitus (OR=2.25; p=0.001) predisposed patients to excess body weight. Women had a lower prevalence of overweight and obesity, but a trend toward excessive body mass was observed in diabetic females (OR=1.18; p=0.181). Diabetic females more often had abdominal obesity than control females (mean difference - 19.2%; p=0.020). Higher total body fat mass was found in the diabetic group (p=0.037). Diabetic females had a higher amount of absolute (p<0.001) and relative body fat mass (p=0.002), fat free mass (p=0.007), relative arm (p=0.007), leg (0<0.001) and trunk (p-=0.006) fat mass than control females. Diabetic males showed only higher relative fat mass of the lower limbs compared to control males (p=0.018). CONCLUSIONS: Patients with type 1 diabetes develop overweight and obesity in early adulthood more frequently than the general population and are characterized by higher body fat mass. Gender-related differences in body weight and composition in young type 1 diabetic adults were found.
Assuntos
Composição Corporal , Diabetes Mellitus Tipo 1/epidemiologia , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Adulto , Fatores Etários , Distribuição da Gordura Corporal , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/etiologia , Feminino , Humanos , Masculino , Obesidade/etiologia , Sobrepeso/etiologia , Polônia/epidemiologia , Prevalência , Fatores Sexuais , Adulto JovemRESUMO
The accumulation of Nxi-(carboxymethyl)lysine (CML), a product of glycoxidation and lipoxidation reactions, on tissue proteins is related to the formation and acceleration of diabetic and nondiabetic atherosclerotic lesions. Yet, little is known about the levels of circulating serum CML-containing protein in nondiabetic patients with clinical symptoms of advanced atherosclerosis. We measured the levels of immunoreactive CML in sera from non-diabetic patients with accelerated symptoms of coronary heart disease, from diabetic patients with no late complications, and from healthy individuals. Serum CML was significantly higher in non-diabetic patients with coronary heart disease than in healthy control subjects and was comparable to serum CML in patients with type 2 diabetes mellitus without late complications and coronary heart disease. In nondiabetic patients with coronary heart disease, a significant inverse correlation was found between serum levels of CML and proinsulin C-peptide, a marker of pancreatic beta cells activity that affects microvascular function. Serum levels of CML and high density lipoprotein (HDL) were positively correlated in this group. We conclude that glycoxidation and lipoxidation are associated with serum HDL levels and the secretive capacity of pancreatic beta cells in nondiabetic patients with coronary heart disease.
Assuntos
Doença das Coronárias/sangue , Lisina/análogos & derivados , Lisina/sangue , Arteriosclerose/sangue , Peptídeo C/sangue , Metabolismo dos Carboidratos , HDL-Colesterol/sangue , Diabetes Mellitus/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Glucose/metabolismo , Humanos , Ilhotas Pancreáticas/metabolismo , Metabolismo dos Lipídeos , Lipoproteínas HDL/sangue , Masculino , Pessoa de Meia-Idade , OxirreduçãoRESUMO
In recent years a great deal of discussion has focused on postprandial hyperglycaemia as a risk factor for cardiovascular mortality. Routinely used parameters of metabolic control such as fasting plasma glucose (FPG) and HbA1c are not useful for determination of daily glucose excursions. 1,5-Anhydro-D-glucitol (1,5-AG) in human plasma has been proposed for several years as a short-term, retrospective marker of glycaemic control and seems to be the most suitable parameter for monitoring glucose excursions. The plasma level of 1,5-AG reflects acute episodes of hyperglycaemia more sensitively than HbA1c does and is correlated with FPG and postprandial hyperglycaemic peaks. The maximal glycaemic value observed in a patient ultimately determines the plasma 1,5-AG level. 1,5-AG could be helpful in detection of hyperglycaemic excursions, even in those patients with diabetes who self-monitor blood glucose and in those patients who are monitored routinely for FPG and HbA1c. In non-diabetic patients the plasma 1,5-AG level may serve as a screening marker for postprandial hyperglycaemia-associated cardiovascular risk.
Assuntos
Glicemia/análise , Desoxiglucose/sangue , Diabetes Mellitus Tipo 2/sangue , Hiperglicemia/diagnóstico , Biomarcadores/análise , Angiopatias Diabéticas/prevenção & controle , Hemoglobinas Glicadas/análise , Humanos , Período Pós-Prandial/fisiologiaRESUMO
Sudden sensorineural hearing loss is rarely the first manifestation of multiple sclerosis (MS). In the presented case of a 31-year-old woman, sudden hearing loss in the left ear was the first monosymptomatic manifestation of the disease. Based on clinical evaluation and MRI, we diagnosed the relapsing-remitting variant of MS. The several-month long observation of the patient included noting the fluctuations in the patient's hearing capability in correlation with the continuously abnormal auditory brainstem responses.