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1.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39000130

RESUMO

Prenatal stress (PNS), which alters the hypothalamic-pituitary-adrenal axis function in the offspring, predisposes to insulin resistance (IR) in later life and is associated with numerous disorders, including cognitive and memory impairments. At present, our main goal is to assess the effects of chronic piromelatine (Pir) administration, a melatonin analogue, on PNS-provoked IR in the periphery and the hippocampus in male and female offspring. Pregnant Sprague-Dawley rats were exposed to chronic stress (one short-term stressor on a daily basis and one long-term stressor on a nightly basis) from the first gestation week until birth. Vehicle or Pir 20 mg/kg were administered intraperitoneally for 21 days. Plasma glucose, serum insulin levels, and the homeostasis model assessment of insulin resistance (HOMA-IR) were determined as markers of peripheral IR. For the hippocampal IR assessment, insulin receptors (IRs) and glucose transporter 4 (GLUT4) were examined. Prenatally stressed offspring of both sexes indicated enhanced plasma glucose and serum insulin concentrations, increased HOMA-IR, and decreased hippocampal GLUT4 only in male rats. The PNS-induced changes were corrected by chronic treatment with Pir. The present results suggest that the melatoninergic compound Pir exerts beneficial effects on altered glucose/insulin homeostasis in PNS-exposed offspring.


Assuntos
Hipocampo , Resistência à Insulina , Insulina , Efeitos Tardios da Exposição Pré-Natal , Ratos Sprague-Dawley , Animais , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Feminino , Gravidez , Masculino , Ratos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Insulina/metabolismo , Insulina/sangue , Glicemia/metabolismo , Estresse Psicológico/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Receptor de Insulina/metabolismo , Melatonina/farmacologia
2.
Biomedicines ; 11(6)2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37371675

RESUMO

Metabolic syndrome (MetS) is a constellation of several associated cardiometabolic risk factors that increase the risk of developing type 2 diabetes mellitus (T2DM), cardiovascular diseases, and mortality. The role of hormonal factors in the development of MetS is assumed. In women, an insulin-resistant state that is associated with polycystic ovarian syndrome and increased deposition of intra-abdominal adipose tissue promotes the development of MetS and increases cardiovascular risk. The neuroendocrine hormone melatonin is secreted mainly at night under the regulatory action of the suprachiasmatic nucleus in the hypothalamus. Melatonin secretion is influenced by exogenous factors such as light and seasons and endogenous factors such as age, sex, and body weight. At present, the role of melatonin in metabolic disorders in humans is not fully understood. In this review, we set out to analyze the relationship of melatonin with the main features of MetS in women. Data from experimental and clinical studies on the role of melatonin in glucose metabolism and on the involvement of melatonin in lipid disturbances in MetS are reviewed. The complex influence of melatonin on hypertension is discussed. The changes in melatonin, leptin, and ghrelin and their relation to various metabolic processes and vascular dysfunction are discussed.

3.
Biomedicines ; 11(6)2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37371817

RESUMO

Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide, its complex pathogenesis remains incompletely understood. The currently stated hypotheses cannot fully clarify the interrelationships between individual pathogenetic mechanisms of the disease. No appropriate health strategies have been developed for treating NAFLD. NAFLD is characterized by an accumulation of triglycerides in hepatic cells (steatosis), with the advanced form known as nonalcoholic steatohepatitis. In the latter, superimposed inflammation can lead to fibrosis. There are scientific data on NAFLD's association with components of metabolic syndrome. Hormonal factors are thought to play a role in the development of metabolic syndrome. Endogenous melatonin, an indoleamine hormone synthesized by the pineal gland mainly at night, is a powerful chronobiotic that probably regulates metabolic processes and has antioxidant, anti-inflammatory, and genomic effects. Extrapineal melatonin has been found in various tissues and organs, including the liver, pancreas, and gastrointestinal tract, where it likely maintains cellular homeostasis. Melatonin exerts its effects on NAFLD at the cellular, subcellular, and molecular levels, affecting numerous signaling pathways. In this review article, we discuss the experimental scientific data accumulated on the involvement of melatonin in the intimate processes of the pathogenesis of NAFLD.

4.
J Clin Med ; 10(2)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33450923

RESUMO

Endometrial cancer (EC) has been associated with an increased risk of cardiovascular disease, including atrial fibrillation (AF). We performed a prospective, case-controlled analysis among 310 Bulgarian women with new-onset, histologically confirmed EC, free of AF at the baseline survey, and women with normal (senile) endometrium/endometrial hyperplasia as a control group (n = 205). The risk of AF as well as relationship of adiponectin (APN) and high sensitivity C-reactive protein (hs-CRP) levels with AF in women with EC were calculated by Cox proportional hazards models. During the mean follow-up of 2.5 ± 0.5 years, new-onset AF had occurred in 11.7% of women with EC vs. 5.8% in the control group (p < 0.01). The risk of AF was highest in the first 6 months after new-onset EC, with an incidence rate ratio (IRR) of 1.19 (95% CI 1.10-1.29; p = 0.01). Women with EC, who were obese (body mass index (BMI) > 30 kg/m2) and younger (age < 60) were found to be more likely to develop AF (HR 1.95; 95% CI 1.18-3.32; p = 0.05). APN levels were not significantly associated with new-onset AF (95% CI 0.87-1.21; p = 0.063). However, the secondary analysis showed evidence of APN-AF association when adjusted for BMI (2.05; 95% CI 1.04-4.04; p = 0.037). We conclude that EC was significantly associated with the incidence of AF.

5.
Folia Med (Plovdiv) ; 63(5): 692-696, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-35851203

RESUMO

INTRODUCTION: Primary membranous nephropathy (PMN) is one of the most common causes of nephrotic syndrome in adults. The disease process is probably initiated by the binding of circulating autoantibodies to target podocyte antigens. In 2009, Beck et al. found that phospholipase A2 receptor (PLA2R1) was expressed on human podocytes in patients with PMN. Recent evidence suggests that PLA2R1 autoantibodies play an important role in the diagnosis of PMN. AIM: The aim of the present study was to compare the serum levels of anti-PLA2R1 in patients with PMN, second MN (SMN), other nephropathies (ON), and healthy controls (HC). MATERIALS AND METHODS: The study included 52 patients with PMN, 12 patients with SMN, 49 patients with ON, and 50 healthy controls. The serum concentration of anti-PLA2R1 was determined with ELISA kit (Anti-PLA2R ELISA, IgG, EUROIMMUN, Lübeck, Germany) using MR-96A microplate Reader (MINDRAY). Statistical analysis was performed with SPSS v.22.0. RESULTS: There was significant difference in the serum anti-PLA2R1 concentrations between patient groups and HC (p<0.0001). Compared to HC, the median anti-PLA2R1 level in the PMN group was significantly higher (4.8 RU/ml vs. 34.9 RU/ml, p=0.001), in the ON group it was lower (2.1 RU/ml, p=0.002) and did not differ in patients with SMN (2.9 RU/ml, p=0.193). The anti-PLA2R1 serum levels were significantly higher in the PMN group than in the SMN (p=0.015) and ON (p<0.001) groups. CONCLUSIONS: Our results showed that anti-PLA2R1 is significantly increased in patients with PMN. We can conclude that the anti-PLA2R1 serum concentration may be used as a beneficial biomarker for distinguishing PMN from other membranous nephropathies.


Assuntos
Glomerulonefrite Membranosa , Adulto , Autoanticorpos , Biomarcadores , Ensaio de Imunoadsorção Enzimática , Glomerulonefrite Membranosa/diagnóstico , Humanos , Receptores da Fosfolipase A2
6.
Folia Med (Plovdiv) ; 61(1): 76-83, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31237842

RESUMO

BACKGROUND: The glucagon-like peptide-1 (GLP-1) and the glucose- dependent Insulinotropic peptide (GIP) are natural incretin hormones, which are secreted respectively by the L- and K-cells of the intestinal mucosa in response to the physiological gastrointestinal glucose absorption. In patients with type 2 diabetes mellitus, the incretin effect is reduced, whereas the results in type 1 diabetes mellitus (T1DM) are heterogeneous, in some patients normal incretin response is observed. AIM: Comparative analysis of the basal serum levels of the incretin hormones GLP-1 and GIP in patients with type 1 DM and in individuals without carbohydrate disorders. MATERIALS AND METHODS: The study included 27 patients with diagnosed T1DM and a control group of 39 individuals without carbohydrate disorders. All participants in the study were subjected to the following clinical measurements and laboratory tests - height, weight, bioimpedance analysis of body composition, fasting blood sugar (BS 0'), postprandial blood sugar (PPBS), glycated haemoglobin (HbA1c) in T1DM patients, total cholesterol (TC), HDL cholesterol (HDL chol), triglycerides (TG), transaminase (AST and ALT), basal serum levels of GLP-1 and GIP. RESULTS: The serum levels of GIP in the patients with type T1DM were significantly higher, compared to the individuals without carbohydrate disorders (P<0.05), while there was no statistically significant difference in the GLP-1 levels. CONCLUSION: The significantly higher GIP levels and the similar GLP-1 levels in our patients with type 1 DM, compared to the individuals without carbohydrate disorders, support the hypothesis of intact incretin effect in this type of diabetes mellitus Key Words: Glucagon-like peptide-1, Glucose-dependent insulinotropic peptide, Type 1 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Adulto , Glicemia/análise , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade
7.
Behav Brain Res ; 370: 111963, 2019 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-31116960

RESUMO

Aerobic training has a neuroprotective effect, reduces the risk of developing neurodegenerative diseases and facilitates functional recovery. The present study assesses the effect of aerobic training on cognitive functions, hippocampal BDNF/TrkB ligand receptor system expression and serum levels of BDNF and corticosterone in intact rats after chronic treatment with Lacosamide (LCM). Male Wistar rats were randomly divided into two groups. One group was exercised on a treadmill (Ex) and the other one was sedentary (Sed). Half of the rats from each group received saline (veh) while the other half - LCM. The rats underwent a month-long training and LCM treatment before being subjected to one active and two passive avoidance tests. Both trained groups increased significantly the number of avoidances compared with the sedentary animals during the learning session and on memory retention tests, while the number of avoidances of the LCM-treated rats was significantly lower in comparison with the saline-treated animals. Both passive avoidance tests revealed that trained animals spent more time in the lighted compartment or caused longer stay on the platform than did the sedentary rats during acquisition and short- and long-term memory retention tests. Aerobic training increased BDNF and TrkB hippocampal immunoreactivity. We found no significant difference between BDNF serum levels but corticosterone levels of the Sed-LCM rats were lower than those of the Sed-veh animals. Our results show that aerobic training increases the hippocampal BDNF/TrkB expression suggesting a role in preventing the negative effect of Lacosamide on cognitive functions in rats.


Assuntos
Aprendizagem/fisiologia , Memória/fisiologia , Condicionamento Físico Animal/fisiologia , Animais , Fator Neurotrófico Derivado do Encéfalo/sangue , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição , Corticosterona/sangue , Corticosterona/metabolismo , Hipocampo/metabolismo , Lacosamida/farmacologia , Masculino , Condicionamento Físico Animal/métodos , Ratos , Ratos Wistar , Receptor trkB/metabolismo , Transdução de Sinais
8.
Pharmacol Biochem Behav ; 169: 1-9, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29605232

RESUMO

Cognitive impairment is considered a frequent side effect in the drug treatment of epilepsy. The objective of the present study was to investigate the effects of lacosamide (LCM) on learning and memory processes in rats, on the serum level of brain-derived neurotrophic factor (BDNF) and BDNF/TrkB ligand receptor system expression in the hippocampal formation. Male Wistar rats underwent long-term treatment with three different doses of lacosamide - 3 mg/kg (LCM 3), 10 mg/kg (LCM 10) and 30 mg/kg (LCM 30). All rats were subjected to one active and one passive avoidance tests. The BDNF/TrkB immunohistochemical expression in the hippocampus was measured and serum BDNF was determined. The LCM-treated rats made fewer avoidance responses than controls during acquisition training and in the memory retention test. The number of escapes in the LCM 10 and LCM 30 groups decreased throughout the test, while the rats in the LCM 3 group showed fewer escapes only in the memory test in the active avoidance task. In the step-down test, the latency time of the LCM-30 treated rats was reduced as compared with the controls during the learning session and the short- and long-term memory retention tests. Lacosamide induced a dose-dependent reduction of the hippocampal expression of BDNF and its receptor TrkB. We found no significant difference between BDNF serum levels in the test animals and controls. The results of the study suggest that LCM suppresses the learning and memory processes in rats, with the inhibition of hippocampal BDNF/TrkB ligand receptor system being one of the possible mechanisms causing this effect.


Assuntos
Anticonvulsivantes/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Lacosamida/farmacologia , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Receptor trkB/metabolismo , Animais , Anticonvulsivantes/administração & dosagem , Fator Neurotrófico Derivado do Encéfalo/sangue , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Imuno-Histoquímica , Lacosamida/administração & dosagem , Masculino , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Receptor trkB/sangue
9.
Folia Med (Plovdiv) ; 60(4): 546-552, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31188770

RESUMO

BACKGROUND: There is a dose-dependent relationship between chronically increased cortisol levels and the number of metabolic syndrome (MetS) components. Both cortisol and MetS are linked to various brain abnormalities. AIM: To investigate an association of MetS components and salivary cortisol levels with cortical thickness in middle-aged Bulgarian patients with MetS. MATERIALS AND METHODS: We examined 26 healthy volunteers (mean age 50, 16±3.1 yrs) divided into two groups depending on whether or not they were diagnosed with MetS. Salivary cortisol was sampled and tested at two time points -morning and evening. Cortical thickness measures were obtained from structural T1-images using FreeSurfer software. We performed vertex-wise analysis across entire cortex and for preselected brain regions in frontal, temporal and cingulate cortex partial correlation analysis, accounting for gender. RESULTS: The control group consisted of 12 women; in the MetS group there were 6 men and 8 women. The whole brain analysis showed that waist circumference (WC) was negatively correlated with cortical thickness in rostro-lateral area in left frontal lobe and the right lateral orbito-frontal cortex. Morning cortisol levels, accounting for sex and WC, correlated negatively with thickness in left superior temporal area (r = -0.477, p = 0.039) and entorhinal area (r = -0.465, p = 0.045) and left mediotemporal cortex (r = -0.477, p = 0.038). CONCLUSION: Our pilot study confirmed that WC is associated with brain atrophic changes mainly in the frontal lobe. Our finding that cortisol levels negatively correlate with thinning of the cortex in temporal lobe should be further explored in subsequent study.


Assuntos
Hidrocortisona/metabolismo , Síndrome Metabólica/diagnóstico por imagem , Síndrome Metabólica/metabolismo , Adulto , Atrofia/diagnóstico por imagem , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Mapeamento Encefálico , Bulgária , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Projetos Piloto , Saliva/metabolismo , Circunferência da Cintura
10.
Folia Med (Plovdiv) ; 59(1): 91-97, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28384105

RESUMO

AIM: The objective of the present study was to investigate the effect of treadmill training at lactate threshold intensity on maximum time to exhaustion (MTE) and heart rate (HR) as well as behavioral changes after kainate (KA)-induced status epilepticus (SE) of spontaneously hypertensive rats (SHRs). MATERIALS AND METHODS: Male SHRs were divided in four groups: two sedentary (vehicle- and KA-treated) and two exercised (vehicle- and KA-treated), respectively. The exercised rats were trained on a treadmill at a speed of 20 m.min-1 and 0° elevation for 40 min.d-1, for 4 wk. Maximal time to exhaustion and HR was measured at the beginning and at the end of the training period. Status epilepticus was evoked in half of the sedentary and trained rats by a repetitive intraperitoneal injection of KA in low subconvulsive doses. The other half of the groups received saline. Sucrose preference test (SPT) for depression-like behavior and hole board test (HBT) for impulsivity were performed a month after KA/veh injection. RESULTS: The maximum time of exhaustion was elongated in the SHRs at the end of the training period in comparison with the beginning. However, no effect on HR was detected in trained rats. Kainate treatment after one month of training alleviated the SE-induced anhedonia in SPT and stereotyped behavior in HBT, respectively. CONCLUSIONS: Taken together, these results demonstrate that exercise exerts a beneficial influence on physical working capacity, depression and impulsive behavior in a co-morbid model of essential hypertension and SE.


Assuntos
Ansiedade/psicologia , Comportamento Animal/fisiologia , Depressão/psicologia , Fadiga , Frequência Cardíaca , Condicionamento Físico Animal/fisiologia , Animais , Comorbidade , Modelos Animais de Doenças , Hipertensão Essencial , Agonistas de Aminoácidos Excitatórios/toxicidade , Hipertensão , Comportamento Impulsivo/fisiologia , Ácido Caínico/toxicidade , Ácido Láctico/metabolismo , Masculino , Condicionamento Físico Animal/psicologia , Ratos , Ratos Endogâmicos SHR , Estado Epiléptico/induzido quimicamente , Fatores de Tempo
11.
Asian J Androl ; 19(4): 444-448, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27030085

RESUMO

The aim of the study was to assess the effects of androgen receptor antagonists on the physical working capacity and activity of some of the key muscle enzymes for the energy supply in rats. Young adult male Wistar rats were divided into two groups. One group received 15 mg kg-1 of flutamide daily for 6 days a week and the other group served as control for 8 weeks. At the beginning and at the end of the experiment, all rats were subjected to submaximal running endurance (SRE), maximum time to exhaustion (MTE), and maximal sprinting speed (MSS) tests. At the end of the trial, maximum oxygen consumption (VO2max) test was performed and the levels of testosterone, erythrocytes, hemoglobin as well as enzyme activity of succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), and NAD.H2-cytochrome-c reductase (NAD.H2) of the gastrocnemius muscle were measured. Serum testosterone of the flutamide-treated rats was higher than that of the controls, which verifies the effectiveness of the dose chosen. MTE and SRE of the anti-androgen-treated group were lower compared with the initial values. Flutamide treatment decreased the activity of SDH and NAD.H2 compared with the controls. We found no effect of the anti-androgen treatment on MSS, VO2max, running economy, LDH activity, and hematological variables. Our findings indicate that the maintenance of the submaximal and maximal running endurance as well as the activity of some of the key enzymes associated with muscle oxidative capacity is connected with androgen effects mediated by androgen receptors.


Assuntos
Antagonistas de Androgênios/farmacologia , Metabolismo Energético/efeitos dos fármacos , Flutamida/farmacologia , Mitocôndrias Musculares/enzimologia , Resistência Física/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Masculino , Mitocôndrias Musculares/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/enzimologia , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Wistar , Corrida/fisiologia , Testosterona/sangue
12.
Folia Med (Plovdiv) ; 55(2): 10-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24191394

RESUMO

UNLABELLED: There has been a surge of interest in recent years in studying the changes of serum melatonin concentrations in disorders that are associated with insulin resistance such as diabetes mellitus type 2 and polycystic ovary syndrome (PCOS). AIM: The present study was designed to investigate the day-time and night-time levels of serum melatonin and the cortisol rhythm in women with PCOS and compare them with those of healthy women. PATIENTS AND METHODS: This is a case-control study which included 30 women with PCOS and 25 healthy women. All hormonal measurements in both the study group and controls were carried out between days 3 and 5 counted from the beginning of the last regular menstrual cycle; they included serum levels of melatonin and cortisol at 03:00 a.m and 08:00 a.m, total testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), follicle stimulating hormone (FSH), and immunoreactive insulin at 08:00 a.m. RESULTS: Women with PCOS were found to have a significantly higher melatonin level at 08:00 a.m. and smaller mean night-day difference in the concentrations of melatonin in comparison with those of healthy women (natural log (Ln) night-day difference 0.60 +/- 0.10 pg/ml versus 1.15 +/- 0.14, p < 0.002). Melatonin to cortisol ratios at 03:00 a.m. and 08:00 a.m. showed no statistically significant differences between the two groups (Ln melatonin/cortisol 03:00 a.m., 1.01 +/- 0.06 versus 1.05 +/- 0.05; Ln melatonin/cortisol at 08:00 a.m., 0.62 +/- 0.01 versus 0.56 +/- 0.03, p > 0.05). CONCLUSION: The results we obtained about the changes of melatonin in women with PCOS could help in elucidating the complex pathophysiological pattern of this disease.


Assuntos
Melatonina/sangue , Síndrome do Ovário Policístico/sangue , Adolescente , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Ritmo Circadiano , Feminino , Humanos , Hidrocortisona/sangue
13.
Folia Med (Plovdiv) ; 54(4): 45-52, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23441469

RESUMO

UNLABELLED: Data on cytomegalovirus infection (CMV) prevalence and course in hospitalized infants are rather scarce, obsolete and considerably inconsistent. AIM: to determine the prevalence, rate of clinical manifestations, risk factors and predictive capacity of clinical manifestations of CMV infection in hospitalized infants during their first year of life. PATIENTS AND METHODS: All 163 infants hospitalized in the Pediatric Ward for Nonrespiratory Pathology in a tertiary hospital were serologically screened for cytomegalovirus infection for 10 months. In infants up to 6 months old that were CMV IgG (+) and CMV IgM (-) we followed up the CMV IgG concentration or compared it with that of their mothers. RESULTS: The CMV prevalence for the entire study sample was 33.1 +/- 3.7% (54 seropositive out of 163 examined infants); in newborns it was 19.4 +/- 6.7% (7 of 36), in infants aged 1-3 months--23.8 +/- 5.4% (15 of 63), in 4-6-month olds--28.1 +/- 8.1% (9 of 32), and in 7-12-month old--71.9 +/- 8.1% (23 of 32). The rates of clinically apparent infections in the respective groups was 33.3 +/- 6.5%, 57.01 +/- 20.2%, 53.3 +/- 13.3%, 33.3 +/- 16.6%, and 13.0 +/- 7.17%. The overall rate of clinically apparent CMV infection in all 163 children was between 11.0 +/- 2.5% and 17.2 +/- 2.9%. The probability of CMV infection increased with age and duration of breastfeeding. Hepatitis, cerebral vasculopathy and pneumonia (alone or combined) turned out to be predictors of CMV infection, but none of these symptoms had a frequency greater than 22%. CONCLUSIONS: We found a high rate of cytomegalovirus infections in hospitalized infants less than one year of age. This infection is the reason why at least 10% of the newborns and 12% of the children aged 1 to 3 months were hospitalised. The course was clinically apparent in over half of the infected children of up to 3 months of age.


Assuntos
Criança Hospitalizada/estatística & dados numéricos , Infecções por Citomegalovirus/epidemiologia , Bulgária/epidemiologia , Citomegalovirus/imunologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Risco , Centros de Atenção Terciária/estatística & dados numéricos
14.
Folia Med (Plovdiv) ; 53(2): 44-50, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21797106

RESUMO

AIM: The aim of this study was to analyze the correlation between serum levels of inflammatory cytokines IL-1beta, IL-6, TNF-alpha and VEGF and the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM). PATIENTS AND METHODS: In this prospective study we included 38 healthy volunteers (group 1) and 39 patients with type 2 DM (group 2). All participants underwent routine ophthalmological examination and laboratory analysis of the serum cytokines IL-1beta, IL-6, TNF-alpha and VEGF. Group 2 patients were additionally examined by colour fundus photography and fluorescein angiography to determine the DR stage. We studied the correlation of IL-1beta, IL-6, TNF-alpha and VEGF with the presence of DM, the presence and severity of DR, the duration of DM and DR, the serum levels of glycosylated haemoglobin, as well as with hyperlipidemia and the general indicators of inflammation - erythrocyte sedimentation rate (ESR) and fibrinogen. RESULTS: The group 2 patients had statistically significantly higher levels of IL-1beta (p = 0.01) and IL-6 (p = 0.029) and elevated TNF-alpha and VEGF levels in comparison with group 1 patients. Group 2 patients were divided into 5 subgroups depending on the severity of DR: patients without DR (n = 11), patients with mild non-proliferative DR (n = 10), patients with moderate non-proliferative DR (n = 5), and patients with severe non-proliferative DR (n = 2) (total number of non-proliferative DR (n = 17)) and patients with proliferative DR (n = 11). The comparative analysis showed statistically significant differences in the serum levels of IL-1beta (p = 0.003), TNF-alpha (p = 0.002) and VEGF (p = 0.005) between the different subgroups. Patients with proliferative DR showed significantly higher values of serum IL-1beta (p < 0.0001), IL-6 (p = 0.007), TNF-alpha (p = 0.002) and VEGF (p < 0.0001) compared with the patients with non-proliferative DR. The cytokine serum levels did not correlate with the duration of DM, the duration of DR (except for IL-1beta, p = 0.045), and hyperlipidemia (except for TNF-alpha, p = 0.05). TNF-alpha(p = 0.05) and VEGF (p = 0.047) serum levels correlated with the levels of glycosylated hemoglobin, and IL-1beta, TNF-alpha and VEGF correlated with the general indicators of inflammation (ESR and fibrinogen). CONCLUSION: Serum concentrations of IL-1beta, TNF-alpha and VEGF have an effect on the development and progression of DR. They correlate with the presence and severity of the disease. Whether serum cytokines can play the role of a prognostic factor or serve as a means to choose a proper therapeutic agent for the treatment of diabetic retinopathy should be analyzed by further more extensive prospective longitudinal studies in future.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/etiologia , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Diabetes Mellitus Tipo 2/sangue , Retinopatia Diabética/sangue , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Inflamação/sangue , Interleucina-1beta/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
15.
Echocardiography ; 26(9): 1060-8, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19558516

RESUMO

BACKGROUND: The aim was to establish the predictors of early functional and structural vascular alterations (using intima-media thickness (IMT)) and flow-mediated vasodilation (%FMD) as well as to investigate the interrelationship between IMT and %FMD in asymptomatic, never-treated, severe hypercholesterolemia (HH). METHODS: One hundred and twenty patients with asymptomatic, severe, untreated HH and 100 controls were included. ELISA was used for asymmetric dimethylarginine (ADMA) and cellular adhesion molecules, and fluid chromatography for total homocysteine (tHcy). Hewlett Packard SONOS 5500 with a 7.5 MHz transducer and MedicaSoft IMT software were used for evaluation of %FMD and IMT of common carotid artery (CCA). RESULTS: Patients and controls differ with respect to all tested biomarkers (P < 0.05), except for P-selectin and E-selectin (P < 0.05). %FMD was lower in patients (P < 0.001). The IMT of the CCA was higher in patients (P < 0.001). Inverse correlations were found between %FMD and IMT mean and age, ADMA, Apo-B, Apo-B/Apo-A(1), and tHcy. ADMA was established as the most important factor related to %FMD. Age and Apo-B were established as the most important factors related to IMT mean. An inverse correlation was established between %FMD and IMT mean (r(xy)= 0.546; P < 0.001)). If cases with IMT mean > or =1 were excluded, the correlation weakened. In patients with IMT mean > or =1 mm, the correlation did not change. CONCLUSION: In conclusion, asymptomatic, untreated patients with severe hypercholesterolemia are at high risk of having increased IMT of the CCA, especially if there is endothelial dysfunction, verified by %FMD of the brachial artery.


Assuntos
Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etiologia , Hipercolesterolemia/complicações , Hipercolesterolemia/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , Vasodilatação , Adulto , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ultrassonografia
16.
Clin Lab ; 55(9-10): 359-61, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20099572

RESUMO

We determined melatonin reference limits in blood serum of 129 healthy volunteers, aged 21 to 70 years, using enzyme-linked immunosorbent assay (IBL ELISA kit, Hamburg, Germany). At 3:00 AM, in almost full dark, the reference limits were found to be 18.3-134 pg/ml in males, 19.0-197 pg/ml in females and 18.5-180 pg/ml in the whole group. At 8:00 AM, they were statistically lower (5.63-61.8, 3.30-93.2 and 3.83-80.4 pg/ml respectively) possibly due to the light.


Assuntos
Ritmo Circadiano/fisiologia , Melatonina/sangue , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Adulto Jovem
17.
Folia Med (Plovdiv) ; 48(3-4): 79-85, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17668702

RESUMO

INTRODUCTION: Tacrine is an acetylcholinesterase inhibitor. It has an indirect cholinomimetic effect inducing contractions of the gastric smooth muscles. The contractions are related to the effect of the accumulated acetylcholine in tissues on the respective choline receptors. There is a well defined direct correlation between tacrine concentrations and the inhibition of cholinesterase activity. That suggest simultaneous increase of the strength of tacrine-induced contractions. Instead, at concentrations above 1 x 10(-5) mol/l, tacrine causes permanent relaxation with yet unknown causing mechanism. AIM: The aim of this study was to investigate if tacrine induces reduction of calcium ions through chelation and/or inhibits directly calmodulin's participation in the contractile processes, thus causing smooth muscle relaxation which is not characteristic of a typical acetylcholinesterase blocker. METHODS: The contractile activity of smooth muscle preparations was measured isometrically with a Microtechna (Czech Republic) amplifier and recorded by a Linseis (Germany) recorder. The absorption electron spectrum of tacrine (1 x 10(-4) mol/l) was determined with a Cary 1 (Varian, Australia) spectrophotometer. The concentration of ionized CaCa2+ was measured with the ISE-block of a clinical-chemical analyzer Konelab 60 (Finland). RESULTS: The presence of Ca2+ (10(-2) mol/l) does not alter tacrine characteristic absorption spectrum at pH values corresponding to the SM cell cytosolic pH. The presence of 1 x 10(-4) mol/l tacrine does not affect Ca2+ concentration in the Krebs solution (pH = 7.4). In the presence of trifluoperazine (a calmodulin blocker) 1 x 10(-4) mol/l tacrine causes relaxation which is commensurable with that in the controls. CONCLUSIONS: Tacrine-induced smooth muscle relaxation is not a result of the reduction of the effective Ca2+ concentrations as a result of chelation between tacrine and Ca2+ and it is not related to the tacrine effects on calmodulin.


Assuntos
Cálcio/metabolismo , Calmodulina/metabolismo , Inibidores da Colinesterase/farmacologia , Citosol/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Tacrina/farmacologia , Animais , Quelantes , Citosol/metabolismo , Relação Dose-Resposta a Droga , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Técnicas In Vitro , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Relaxamento Muscular/efeitos dos fármacos , Relaxamento Muscular/fisiologia , Músculo Liso/metabolismo , Músculo Liso/fisiopatologia , Ratos , Ratos Wistar , Trifluoperazina/farmacologia
18.
Folia Med (Plovdiv) ; 47(3-4): 40-5, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16761393

RESUMO

AIM: The aim of the present study was to evaluate the role of the preoperative antithyroid drug treatment and hormonal status in the development of early postoperative hypothyroidism after subtotal thyroidectomy in patients with Graves' disease. MATERIAL AND METHODS: Eighty-five patients with Graves' disease (males : females ratio 1:5.54, age range 19 to 64, 37.52 +/- 1.09 yrs) who had previously undergone surgical treatment were enrolled in the study. All patients underwent bilateral subtotal thyroidectomy with the amount of remnant tissue of 2-3 g for each lobe (total 4-6 g). Development of early (within one year after the operation) postoperative hypothyroidism was analyzed regarding the type of the antithyroid drug, preoperative dose, duration of the preoperative medical treatment, FT3, FT4, FT3/FT4 and hTSH. RESULTS: Forty six percent of all examined patients (54.12%) were euthyroid and 39 (45.88%/)--hypothyroid. Postoperative hypothyroidism was developed by 33.33% of the patients that had received preoperatively propylthiouracil compared with 50.82% of those treated with methymazol (p > 0.05). The duration of the preoperative treatment was 38.36 +/- 3.53 months for the hypothyroid patients and 30.11 +/- 2.34 months for the euthyroid patients (p < 0.05). Postoperative hypothyroidism developed in 58.70% of the patients with preoperatively suppressed thyroid-stimulating hormone (hTSH) and in 33.33% of those with normalized values of hTSH (p < 0.05). No statistically significant between-group difference was found in the preoperative dose of antithyroid agent, mean values of free triiodothyronine (FT3), free thyroxine (FT4), FT3/FT4, thyrotropic hormone (TSH). CONCLUSIONS: Longer preoperative antithyroid drug treatment and suppression of hTSH in the preoperative period correlated with higher risk of hypothyroidism after subtotal thyroidectomy. The type and the preoperative dose of the antithyroid agent, as well as the mean values of thyroid hormones before the operation have no prognostic significance for postoperative thyroid hypofunction.


Assuntos
Doença de Graves/cirurgia , Hipotireoidismo/etiologia , Hipotireoidismo/prevenção & controle , Tireoidectomia/efeitos adversos , Adulto , Antitireóideos/uso terapêutico , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Estatísticas não Paramétricas , Tireotropina/análise , Tiroxina/análise , Tri-Iodotironina/análise
19.
Folia Med (Plovdiv) ; 47(3-4): 46-52, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16761394

RESUMO

AIM: To compare serum levels of interleukin-6, interleukin-8 and interleukin-10 in bacteremic and non-bacteremic episodes of febrile neutropenia in children with malignant diseases, and determine their changes and correlation with C-reactive protein (CRP). MATERIAL AND METHODS: Between January 2003 and June 2004, we examined 41 episodes of febrile neutropenia in 24 children with malignant diseases who were receiving polychemotherapy. C-reactive protein was measured at the onset of febrile episodes and on days 3 and 5 from beginning of therapy. The soluble interleukins-6, -8, and -10 were determined in the serum using enzyme bound immunosorbent analysis at the onset of fever and at 24 and 72 hours after initiation of an empiric antibiotic therapy. RESULTS: The CRP baseline levels differentiated the patients with unexplained fever from those with local infection but did not differentiate them from those with bacteremia. Interleukin-8 at 24 hours differentiated bacteremic from non-bacteremic episodes (P < 0.05) and at a cut-off value of 130 pg/ml it had a sensitivity of 72% and a specificity of 84% to differentiate bacteremia. Interleukin-10 at 24 hours yielded higher values in Gram (-) bacteremia in comparison with the non-bacteremic episodes (P < 0.001) and Gram (+) bacteremia (P < 0.05). Interleukin-6 at 24 hours had significantly higher values in febrile episodes of more than 3 days duration (P < 0.05). CONCLUSIONS: Interleukin-8 could differentiate in the first 24 hours bacteremic from non-bacteremic episodes in febrile neutropenia, while interleukin-10 is perhaps a more accurate marker for Gram (-) bacteremia.


Assuntos
Proteína C-Reativa/metabolismo , Interleucina-10/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Neoplasias/sangue , Neutropenia/sangue , Adolescente , Adulto , Análise de Variância , Bacteriemia/etiologia , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Febre/sangue , Febre/complicações , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Humanos , Lactente , Masculino , Neoplasias/tratamento farmacológico , Neutropenia/complicações , Estatísticas não Paramétricas
20.
Folia Med (Plovdiv) ; 47(3-4): 59-62, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16761396

RESUMO

INTRODUCTION: Chromium deficiency in diabetic patients is a debatable problem. The prevailing opinion suggests the presence of low serum concentrations in such patients and therefore an early, long-term addition of chromium to the standard therapy is recommended. PURPOSE: The aim of the present study was to evaluate the effect of chromium on the insulin resistance in diabetic patients with type II diabetes mellitus. MATERIAL AND METHODS: We have studied a total of 34 overweight patients with type II diabetes mellitus, who were distributed in two study sub-groups--patients with very good metabolic control and patients with bad control. For sixty days the patients of both groups received 30 microg of chromium picolinate as food additive. We measured the serum concentration of chromium (using atom-absorption methods), immune-reactive insulin and the insulin resistance index at baseline and at the end of the two-month period. RESULTS: The serum concentrations of chromium was significantly lower in diabetic patients than in the healthy individuals used as controls (2.18 +/- 0.87 nmol/l versus 4.03 +/- 0.96 nmol/l; p < 0.001). We found a significant decrease of the immune-reactive insulin and the insulin resistance index after a two-month application of chromium 30 microg daily (1 tablet of chrome picolinate). The effects of this trace element are analysed in the light of an improved first phase of secretion of insulin or facilitated post-receptor insulin sensibility as a way of potentiating the insulin action. CONCLUSION: Chromium included early in the complex therapy of diabetes is beneficial in the reduction of the degree of insulin resistance.


Assuntos
Cromo/administração & dosagem , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Adulto , Idoso , Cromo/sangue , Cromo/deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso , Resultado do Tratamento
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