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1.
Trop Biomed ; 41(1): 36-44, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38852132

RESUMEN

Leishmaniasis causes significant morbidity and mortality worldwide. In our country, there has been a significant increase in the number of cases of leishmaniasis in the last decade. In our study, the effects of Hypericum thymbrifolium, Hypericum scabrum and Eryngium creticum plant extracts were tested on Leishmania major, Leishmania tropica and Leishmania infantum/donovani, which were clinically resistant by not responding to Glucantime® therapy. Cytotoxicity of these extracts were evaluated by XTT method in the human fibroblast cell line. Possible active ingredients were detected by GC-MS analysis from plant extracts. Glucantime® resistance was detected at concentrations of 50 µg/mL and lower in 4 of the 7 strains tested. No living leishmania parasites were found in leishmania strains treated with plant extracts at concentrations of 100 µg/mL or higher. The concentrations of plant extracts included in the study on the WI-38 human fibroblast cell line were not cytotoxic. According to the GC-MS analysis, several active substances with biological activities and anti-parasitic effects, such as Thiophene, Germacrene-D, trans-Geranylgeraniol, Pyridine, and Maleimides, were identified. Based on the findings of the study, it is believed that these identified active substances when supported by in-vivo studies, will pave the way for future research and have the potential to be developed as anti-leishmania drugs.


Asunto(s)
Eryngium , Hypericum , Leishmania infantum , Leishmania major , Leishmania tropica , Extractos Vegetales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Humanos , Hypericum/química , Leishmania infantum/efectos de los fármacos , Leishmania tropica/efectos de los fármacos , Leishmania major/efectos de los fármacos , Línea Celular , Eryngium/química , Antiprotozoarios/farmacología , Fibroblastos/efectos de los fármacos , Leishmania donovani/efectos de los fármacos , Cromatografía de Gases y Espectrometría de Masas
2.
BMC Pulm Med ; 24(1): 178, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622520

RESUMEN

BACKGROUND: Asthma is a common disease characterized by chronic inflammation of the lower airways, bronchial hyperactivity, and (reversible) airway obstruction. The Global Initiative of Asthma Guideline recommends a flowchart to diagnose asthma with first-step spirometry with reversibility and a bronchial challenge test (BPT) with histamine or methacholine as a second step [1]. The BPT is considered burdensome, time-consuming for patients and staff, can cause side effects, and is expensive. In addition, this test strongly encumbers lung function capacity. Elevated Nitric Oxide (NO) is associated with airway eosinophilic inflammation in asthma patients and can be measured in exhaled air with the Fractional exhaled (Fe) NO-test. This low-burden FeNO-test could be used as an 'add-on' test in asthma diagnostics [2, 3]. METHODS AND ANALYSIS: This multi-center prospective study (Trial number: NCT06230458) compares the 'standard asthma diagnostic work-up' (spirometry with reversibility and BPT) to the 'new asthma diagnostics work-up' (FeNO-test as an intermediate step between the spirometry with reversibility and the BPT), intending to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness and reduced burden to the patient and health care. The cost reduction of incorporating the FeNO-test in the new diagnostic algorithm will be established by the number of theoretically avoided BPT. The decrease in burden will be studied by calculating differences in the Visual Analogue Scale (VAS) -score and Asthma Quality of Life Questionnaire (AQLQ) -score after the BPT and FeNO-test with an independent T-test. The accuracy of the FeNO-test will be calculated by comparing the FeNO-test outcomes to the (gold standard) BPTs outcomes in terms of sensitivity and specificity. The intention is to include 171 patients. ETHICS AND DISSEMINATION: The local medical ethics committee approved the proposed study and is considered a low-burden and risk-low study. The local medical ethics committee registration number: R23.005. STRENGTHS AND LIMITATIONS OF THIS STUDY: Strengths: This is the first study that investigates the value of the FeNO-test (cut off ≥ 50 ppb) as an add-on test, to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness, and reduced burden on the patient and health care. LIMITATIONS: High FeNO levels may also be observed in other diseases such as eosinophilic chronic bronchitis and allergic rhinitis. The FeNO-test can be used to rule in a diagnosis of asthma with confidence, however, due to the poor sensitivity it is not suitable to rule out asthma.


Asunto(s)
Asma , Bronquitis Crónica , Humanos , Prueba de Óxido Nítrico Exhalado Fraccionado , Estudios Prospectivos , Calidad de Vida , Pruebas Respiratorias , Asma/tratamiento farmacológico , Óxido Nítrico , Inflamación , Estudios Multicéntricos como Asunto
3.
Tropical Biomedicine ; : 36-44, 2024.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1036532

RESUMEN

@#Leishmaniasis causes significant morbidity and mortality worldwide. In our country, there has been a significant increase in the number of cases of leishmaniasis in the last decade. In our study, the effects of Hypericum thymbrifolium, Hypericum scabrum and Eryngium creticum plant extracts were tested on Leishmania major, Leishmania tropica and Leishmania infantum/donovani, which were clinically resistant by not responding to Glucantime® therapy. Cytotoxicity of these extracts were evaluated by XTT method in the human fibroblast cell line. Possible active ingredients were detected by GC-MS analysis from plant extracts. Glucantime® resistance was detected at concentrations of 50 µg/mL and lower in 4 of the 7 strains tested. No living leishmania parasites were found in leishmania strains treated with plant extracts at concentrations of 100 µg/mL or higher. The concentrations of plant extracts included in the study on the WI-38 human fibroblast cell line were not cytotoxic. According to the GC-MS analysis, several active substances with biological activities and anti-parasitic effects, such as Thiophene, Germacrene-D, trans-Geranylgeraniol, Pyridine, and Maleimides, were identified. Based on the findings of the study, it is believed that these identified active substances when supported by in-vivo studies, will pave the way for future research and have the potential to be developed as anti-leishmania drugs.

4.
Eur Rev Med Pharmacol Sci ; 27(6): 2699-2705, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-37013789

RESUMEN

OBJECTIVE: COVID-19 may cause thrombosis in both venous and arterial systems. Familiarity with the signs and symptoms of thrombosis and its treatment is essential in treating COVID-19 infection and its complications. D-Dimer and mean platelet volume (MPV) are measurements related to the development of thrombosis. This study investigates whether MPV and D-Dimer values could be used to determine the risk of thrombosis and mortality in the COVID-19 early stages. PATIENTS AND METHODS: 424 patients who were COVID-19 positive, according to the World Health Organization (WHO) guidelines, were randomly and retrospectively included in the study. Demographic and clinical characteristics such as age, gender, and length of hospitalization were obtained from the digital records of participants. Participants were divided into living and deceased groups. The patients' biochemical, hormonal, and hematological parameters were analyzed retrospectively. RESULTS: White blood cells (WBC), neutrophils, and monocytes were significantly different in the two groups (p-value <0.001), and their values were lower in the living group than in the deceased group. MPV median values did not differ according to prognosis (p-value = 0.994). While the median value was 9.9 in the survivors, it was 10 in the deceased. Creatinine, procalcitonin, ferritin, and the number of hospitalization days in living patients were significantly lower than in patients who died (p-value <0.001). Median values of D-dimer (mg/L) differ according to prognosis (p-value <0.001). While the median value was 0.63 in the survivors, it was found as 438 in the deceased. CONCLUSIONS: Our results did not show any significant relationship between the mortality of COVID-19 patients and their MPV levels. However, a significant association between D-Dimer and mortality in COVID-19 patients was observed.


Asunto(s)
COVID-19 , Trombosis , Humanos , Volúmen Plaquetario Medio , Pronóstico , Estudios Retrospectivos
5.
Eur Rev Med Pharmacol Sci ; 26(22): 8612-8619, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36459042

RESUMEN

OBJECTIVE: This study aims at determining the significance of a novel inflammatory biomarker, presepsin, in predicting disease prognosis in patients with COVID-19. PATIENTS AND METHODS: This retrospective study was concluded at the University Hospital between April and August 2020. The study involved 88 COVID-19 patients (48 men and 40 women). The patients were categorized into two groups: the patients admitted to the COVID-19 clinic, described as the moderate COVID-19 patients (Group-1; n=44), and those admitted to the internal medicine outpatient clinic, who were the mild COVID-19 patients (Group-2; n=44). The groups were compared using inflammatory markers: presepsin, C-Reactive Protein to Albumin Ratio, Neutrophil to Lymphocyte Ratio, and procalcitonin. RESULTS: Serum presepsin levels (195.29 vs. 52.12 pg/ml) were significantly higher in the Group-1 compared to the Group-2 (p=0.001). The gender distribution and average age were similar in both groups (p > 0.05). While ferritin, lactate dehydrogenase, D-Dimer, platelet lymphocyte ratio, C-Reactive Protein to Albumin Ratio (p=0.001), erythrocyte sedimentation ratio, C-Reactive Protein and presepsin were significantly higher in the Group-1 compared to Group-2 (p<0.05), while hemoglobin and lymphocyte were significantly lower in the Group-1 than in Group-2 (p<0.05). CONCLUSIONS: Serum presepsin levels were found to be significantly higher in moderate clinical group COVID-19 patients compared to mild group. Presepsin, a new inflammatory biomarker, may be useful in predicting the prognosis and early treatment of COVID-19 infection.


Asunto(s)
Proteína C-Reactiva , COVID-19 , Masculino , Humanos , Femenino , COVID-19/diagnóstico , Estudios Retrospectivos , Pronóstico , Biomarcadores , Albúminas , Fragmentos de Péptidos , Receptores de Lipopolisacáridos
6.
Eur Rev Med Pharmacol Sci ; 26(21): 8180-8187, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36394767

RESUMEN

OBJECTIVE: Our study aimed at investigating the impacts of demographic, hematological, and biochemical factors on the clinical course and the prognostic outcome in adult COVID-19 patients. PATIENTS AND METHODS: This retrospective study was performed in the internal medicine departments of two hospitals, and data were extracted from the medical files of 1,700 adult COVID-19 patients (836 females, 49.2%; 864 males, 50.8%) with an average age of 48.23 ± 16.68 (range: 18-93). Clinical data included baseline descriptives, prior medical history, admission date, treatment, and hematological and biochemical blood test results. The relationship between the survival, length of hospitalization, hematological, and biochemical parameters was investigated. RESULTS: Advanced age (p<0.001), presence of at least on comorbid disease (p=0.045), increased length of hospitalization (p=0.006), elevated white blood cell (p=0.001) and neutrophil (p=0.002) counts, increased serum levels of glucose (p=0.027), blood urea nitrogen (p<0.001), AST (p=0.006), LDH (p<0.001), CRP (p>0.001), and D-dimer (p=0.001). In contrast, diminution of serum levels of albumin (p<0.001), ALT (p=0.028), calcium (p=0.022), and platelet count (p=0.010) were associated with increased mortality. There was a positive and weak relationship between serum D-dimer levels and length of hospitalization. CONCLUSIONS: Our data imply that identifying and validating indicators that predict COVID-19 disease progression to improve health outcomes is crucial. Age, comorbidities, immunological response, radiographic abnormalities, laboratory markers, and signs of organ dysfunction may all predict poor outcomes individually or collectively. Identifying characteristics that predict COVID-19 problems is critical to guiding clinical management, improving patient outcomes, and allocating limited resources.


Asunto(s)
COVID-19 , Masculino , Adulto , Femenino , Humanos , Persona de Mediana Edad , COVID-19/terapia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Pronóstico , Resultado del Tratamiento
7.
Eur Rev Med Pharmacol Sci ; 26(16): 5718-5728, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-36066145

RESUMEN

OBJECTIVE: The systemic immune inflammation (SII) index has been an excellent prognostic indicator in patients with acute ischemic stroke (AIS). In this study, we assessed the utility of the SII in predicting the prognosis and reperfusion status of patients with AIS who underwent endovascular treatment (EVT). PATIENTS AND METHODS: 123 consecutive AIS patients were enrolled in our study. The receiver-operating characteristics (ROC) curve was used to determine the cut-off value of SII for predicting unsuccessful cerebral reperfusion. Multivariate logistic regression analysis analyzed the association between SII and unsuccessful reperfusion rate after EVT. RESULTS: The median value of SII was significantly higher in patients with unsuccessful reperfusion compared to patients with successful reperfusion [2,029 (1,217-2,771) vs. 1,172 (680-2,145) respectively, p=0.003)]. A ROC curve analysis showed that the best cut-off value of SII for predicting unsuccessful reperfusion status was 1,690, with sensitivity and specificity of 71% and 69%, respectively. The area under the curve (AUC) was 0.673 (95% CI; 0.552-0.793). Multivariate analysis demonstrated that SII ≥ 1,690 value was an independent predictor of unsuccessful cerebral reperfusion and unfavorable clinical outcome after EVT (Hazard ratio - H.R.=3.713, 95% CI: 1.281-10.76, p=0.016, HR=2.28, 95% CI: 1.06-4.88, p=0.035, respectively). CONCLUSIONS: We suggested that SII is a potential indicator to predict the unsuccessful cerebral reperfusion and unfavorable clinical outcome for patients with AIS undergoing EVT.


Asunto(s)
Accidente Cerebrovascular Isquémico , Humanos , Inflamación , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/cirugía , Pronóstico , Modelos de Riesgos Proporcionales , Reperfusión , Estudios Retrospectivos
8.
Eur Rev Med Pharmacol Sci ; 26(15): 5568-5573, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35993654

RESUMEN

OBJECTIVE: SARS-CoV-2 infection primarily affects T-lymphocytes, particularly CD4+ and CD8+ T cells. However, there is a need for simpler and less expensive laboratory tests with predictive values comparable to CD4+ cell counts. Thus, the goal of this study was to investigate the role of neopterin levels in predicting intensive care and mortality in coronavirus disease patients in 2019. PATIENTS AND METHODS: This retrospective study included 87 hospitalized patients who were diagnosed with COVID-19. Patients were divided into two groups: those receiving intensive care (Severe COVID-19; S-COVID-19) and those receiving non-intensive care (Moderate COVID-19; M-COVID-19). Patients' clinical characteristics, serum neopterin levels, and other laboratory data were compared across groups. RESULTS: The average age was 63.9±155.2 years, and 44 (%) of the participants were male. WBC (p = 0.008), neutrophil (p = 0.002), HDL (p = 0.009), ferritin, calcium, albumin, LDH, APTT, lymphocyte, INR, D-dimer, troponin, prothrombin time sedimentation, and PaO2 (p = 0.001) were all associated with death. The neopterin level in the M-COVID-19 group was 3 (min-max; 3.1-5.9) and 3.2 (2.3-7) in the S-COVID-19 group, with no statistically significant difference (p = 0.456). Gender differences between groups were not significant (p = 0.183). According to the ROC analysis, if parameters such as age, D-Dimer, troponin, ferritin, albumin, LDH, CRP, procalcitonin, and PaO2 exceed the cut-off values and lymphocyte levels are below, it can predict the need for intensive care and mortality in COVID-19 patients. CONCLUSIONS: Although we did not find statistically significant results with neopterin in terms of mortality in COVID-19 individuals in our study, more thorough, prospective, randomized controlled studies with expanded patient populations at various phases of the disease are needed.


Asunto(s)
COVID-19 , Albúminas , Biomarcadores , COVID-19/diagnóstico , Femenino , Ferritinas , Humanos , Masculino , Neopterin , Oxígeno , Estudios Prospectivos , Estudios Retrospectivos , SARS-CoV-2 , Troponina
9.
Eur Rev Med Pharmacol Sci ; 26(8): 2900-2905, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35503633

RESUMEN

OBJECTIVE: Inflammation forms the basis of cancer development and progression. It causes changes in complete blood count parameters, such as neutrophil counts. Low albumin levels are associated with poor prognosis in cancer patients. We aimed to investigate the association between neutrophil to albumin ratio (NAR) and the stage of non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: 257 NSCLC patients (24 females and 198 males) were included in the study. Patients were divided into two groups. Group 1 (n=61) included patients with early stage cancer (stage 1 and 2), while group 2  (n=196) included those with advanced stage cancer (stage 3 and 4). Demographic data, neutrophil, lymphocyte, platelet, white blood cell counts (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin and albumin levels at the time of diagnosis were recorded. The NAR of 2 groups were compared. RESULTS: There were no significant differences between the lymphocyte count (2.0 vs. 2.0 103/mm3) and platelet count (291 vs. 311 103/mm3) of the two groups (p > 0.05). ESR (38.8 vs. 57.5 mm/h), CRP (158 vs. 57 mg/l), ferritin (85 vs. 261 ng/ml), WBC count (8.6 vs. 10.6 103/mm3), neutrophil count (5.6 vs. 7.5 103/mm3), albumin values (2.9 vs. 3.7 gr/dl), and (p < 0.05) NAR levels (1.6 vs. 2.3) (p < 0.05) were significantly higher in group 2. CONCLUSIONS: NAR can be used in predicting the stage of NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Albúminas , Proteína C-Reactiva/análisis , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Femenino , Ferritinas , Humanos , Recuento de Leucocitos , Neoplasias Pulmonares/diagnóstico , Recuento de Linfocitos , Linfocitos , Masculino , Neutrófilos , Estudios Retrospectivos
10.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 6787-6790, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34892666

RESUMEN

In this work, we present a case study to evaluate the connections between sleep, training load, and the perceptions of physical/emotional state of a collegiate, division 1 Women's basketball team. The study took place during the off- (3 weeks) and pre-season (6 weeks) while sleep was tracked using WHOOP wearable straps. Training load was recorded by the strength coach and athletes. Short Recovery and Short Stress (SRSS) questionnaire was used to evaluate the perceptions of athletes on their own emotional and physical states. Our results showed that heart rate measurements are associated with stress levels and recovery perception. We also discovered that the training load was not linked to the sleep variables without the considerations of athletic performance. However, training load may alter perceived stress and recovery which requires further exploration.


Asunto(s)
Rendimiento Atlético , Baloncesto , Atletas , Femenino , Humanos , Sueño , Universidades
11.
Eur Rev Med Pharmacol Sci ; 22(19): 6560-6566, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30338827

RESUMEN

OBJECTIVE: It is important to identify undesirable toxins and metabolites present in human milk that may be passed on to nursing infants. Such residues may derive from the antibiotics that are widely used to treat infectious diseases in both humans and food-producing animals. To the best of our knowledge, there are no reports in the literature on human milk antibiotic residue levels. PATIENT AND METHODS: As a part of the Human Milk Artificial Pollutants (HUMAP) study, we aimed to evaluate human milk antibiotic residues among mothers with 7 to 90-day-old babies. Pregnant women who had received antibiotic treatment during pregnancy were excluded. The use of antibiotic prophylaxis with cefazoline sodium during labor was noted among the study subjects. Human milk antibiotic residues were evaluated with the InfiniPlex for Milk Array (Randox Laboratories, London, United Kingdom), a semi-automated system with a multi-array biochip designed to detect antibiotic residues and toxins. RESULTS: The HUMAP study included 83 mothers, ranging in age from 17 to 41 years (mean 29.7 ± 6.2 years). Of these, 59% received cefazoline sodium shortly after birth, while 41% did not receive any antibiotics during the pregnancy, delivery or lactational periods. Testing revealed that 71/83 (85.5%) human milk samples were positive for beta-lactams and 12 (14.5%) samples were positive for quinolones. There was no difference in maternal age, gestational week, delivery type, sampling time, maternal dietary habits between the mothers with quinolones or beta-lactam residues in their milk and those without (p > 0.05 for both). Beta-lactam and quinolone residues were detected in 85.7% and 23.5%, respectively, of the human milk samples of mothers who did not receive antibiotics at birth and/or during the first seven days after birth. CONCLUSIONS: We found that the majority of human milk samples included beta-lactams or quinolones, even though the mothers did not receive these antibiotics during pregnancy and lactation. Antibiotic residues in human milk may affect early maintenance of the intestinal microbiota. Previous studies have shown that antimicrobials in food might increase the risks of allergies and could lead to the development of antibiotic-resistant bacterial strains. Effective policies on food safety and appropriate antibiotic use during pregnancy and lactation are needed.


Asunto(s)
Antibacterianos/análisis , Residuos de Medicamentos/análisis , Conducta Alimentaria , Contaminación de Alimentos , Lactancia , Fenómenos Fisiologicos Nutricionales Maternos , Leche Humana/química , Estado Nutricional , Parto , Adolescente , Adulto , Antibacterianos/efectos adversos , Cesárea , Estudios Transversales , Residuos de Medicamentos/efectos adversos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Exposición Materna , Medición de Riesgo , Adulto Joven
12.
Georgian Med News ; (252): 26-32, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27119831

RESUMEN

To investigate the effects of Vitamin D Analogs, paricalcitol and alphacalcidol, on hemoglobin levels and erythropoietin-stimulating agents' dosage in hemodialysis patients with chronic renal failure. A total of 310 patients under hemodialysis treatment for chronic renal failure were included in this retrospective multicenter study. Data on serum parathormone and hemoglobin levels, erythropoietin-stimulating agents' doses, C-reactive protein, calcium and phosphate levels were collected from medical records to comparatively evaluate paricalcitol, alphacalcidol and no treatment groups. Apart from significantly higher levels for hematocrit in patients treated with paricalcitol compared to pre-treatment values (32.3(3.8) vs. 34.1(3.1) p=0.007), pre-treatment and post-treatment values for biochemical parameters were similar in paricalcitol and alphacalcidol groups including ESA dose. A significant increase in parathormone levels (p=0.000 for each) while a significant decrease in calcium (p=0.003 and 0.040, respectively), Hb (p=0.001 and 0.009, respectively) and hematocrit (p=0.001 and 0.021, respectively) levels were determined in paricalcitol and alphacalcidol treated patients compared with untreated patients. Also, phosphate levels in alphacalcidol treated patients were significantly higher (p=0.018) than untreated patients. Our findings revealed insufficient suppression of parathormone levels and there of lower hemoglobin and hematocrit levels, but similar ESA dosage among CRF patients treated with Vitamin D analogs compared with untreated patients.


Asunto(s)
Anemia/tratamiento farmacológico , Ergocalciferoles/uso terapéutico , Hematínicos/administración & dosificación , Hidroxicolecalciferoles/uso terapéutico , Fallo Renal Crónico/terapia , Anciano , Anemia/sangre , Anemia/etiología , Femenino , Hemoglobinas/análisis , Humanos , Hiperparatiroidismo Secundario/tratamiento farmacológico , Hiperparatiroidismo Secundario/etiología , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Diálisis Renal , Estudios Retrospectivos
13.
Chem Sci ; 6(1): 804-815, 2015 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-25642316

RESUMEN

Aiming towards the development of novel nootropic therapeutics to address the cognitive impairment common to a range of brain disorders, we set out to develop highly selective small molecule inhibitors of HDAC2, a chromatin modifying histone deacetylase implicated in memory formation and synaptic plasticity. Novel ortho-aminoanilide inhibitors were designed and evaluated for their ability to selectively inhibit HDAC2 versus the other Class I HDACs. Kinetic and thermodynamic binding properties were essential elements of our design strategy and two novel classes of ortho-aminoanilides, that exhibit kinetic selectivity (biased residence time) for HDAC2 versus the highly homologous isoform HDAC1, were identified. These kinetically selective HDAC2 inhibitors (BRD6688 and BRD4884) increased H4K12 and H3K9 histone acetylation in primary mouse neuronal cell culture assays, in the hippocampus of CK-p25 mice, a model of neurodegenerative disease, and rescued the associated memory deficits of these mice in a cognition behavioural model. These studies demonstrate for the first time that selective pharmacological inhibition of HDAC2 is feasible and that inhibition of the catalytic activity of this enzyme may serve as a therapeutic approach towards enhancing the learning and memory processes that are affected in many neurological and psychiatric disorders.

14.
Eur Rev Med Pharmacol Sci ; 17(9): 1149-54, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23690182

RESUMEN

BACKGROUND: Epilepsy is one of the most important central nervous system disorder and 1% of the total world population suffers from this disorder which require a chronic drug treatment. Most of the researchers suggested that excessive calcium entry into neurons is the main triggering event in the initiation of epileptic discharges but the role of L type calcium channels has not been clarified in absence epilepsy. AIM: In this study, it is aimed to investigate the antiepileptic effects of nifedipine, an L type calcium channel blocker and BAY K8644, an L type calcium channel opener in a genetic model of absence epilepsy in WAG/Rij rats. MATERIALS AND METHODS: Thirty two WAG/Rij rats were allocated into four groups; sham (only saline injected), only nifedipine (an L type calcium channel blocker) injected group (40 µg/2 µl; 60 µg/2 µl; 80 µg/2 µl), only BAY K8644 (1,4 Dihydro-2,6-dimethyl-5-nitro-4-trifluoromethyl- phenyl-3-pyridine carboxylic acid methyl ester) (L-type Ca2+-channel activator) injected group (40 µg/2 µl; 60 µg/2 µl; 80 µg/2 µl) and combination of their most effective doses BAY K8644 (60 µg/2 µl) after nifedipine (60 µg/2 µl) injected group. All agents were given by intracerebroventricular injection. The beta, alpha, theta and delta wave ratios of electroencephalogram recordings and the frequency and duration of SWDs (spike and wave discharges) were analyzed and compared between four groups. RESULTS: Nifedipine increased the number and duration of spike wave discharges whereas BAY K8644 decreased both of them. When BAY K8644 was given after nifedipine, there was no significant difference with control group. CONCLUSIONS: L type calcium channels play an activator role on spike wave discharges and have positive effects on the duration and frequency.


Asunto(s)
Canales de Calcio Tipo L/fisiología , Electroencefalografía , Epilepsia Tipo Ausencia/fisiopatología , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Ritmo alfa/efectos de los fármacos , Animales , Ritmo beta/efectos de los fármacos , Agonistas de los Canales de Calcio/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Ritmo Delta/efectos de los fármacos , Nifedipino/farmacología , Ratas , Ratas Endogámicas
15.
Biopsychosoc Med ; 4(1): 1, 2010 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-20181219

RESUMEN

BACKGROUND: This study was performed to examine whether patients with type 2 diabetes have cognitive deficits associated with the prefrontal cortex (PFC). METHODS: Twenty-seven middle-aged patients with newly diagnosed type 2 diabetes and 27 healthy controls underwent physical measurements and neuropsychological tasks. Response inhibition, reward prediction, and executive function were assessed by the Go/NoGo task, the reversal and extinction tasks, and the Wisconsin Card Sorting Test (WCST). To examine the interactions of being overweight with diabetes on cognitive performance, performance data were analysed by two-way ANCOVA with diabetes and overweight as factors and age as a covariate. RESULTS: Patients with type 2 diabetes showed significantly decreased response inhibition in the Go/NoGo task (discriminability index: P = 0.001). There was an interaction of being overweight with diabetes on reaction time in the Go trials of the Go/NoGo task (P = 0.009). Being overweight was related to retained responses to the presentiment of reward in the extinction task (P = 0.029). The four groups showed normal cognitive performance in the WCST. CONCLUSIONS: Our results showed that middle-aged, newly diagnosed and medication-free patients with type 2 diabetes have a particular neuropsychological deficit in inhibitory control of impulsive response, which is an independent effect of diabetes apart from being overweight.

16.
Clin Exp Obstet Gynecol ; 36(2): 113-5, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19688955

RESUMEN

PURPOSE: Helicobacter pylori (H. pylori) is believed to play a role in several gynecological and obstetric pathologies since the cervical mucosa resembles the gastric environment. The microorganism is expected to infect the upper genital tract via the oral-genital and fecal-genital routes. METHODS: We studied 35 cases with benign, ASCUS, ASC-H, LSIL and HSIL pap-smear results. The presence of H. pylori in the uterine cervix and active infection were investigated with the H. pylori stool antigen test. Biopsy specimens were stained with hematoxylin-eosin and Warthin-Starry stains to find H. pylori in cervical tissue. Seroprevalence was investigated by using ELISA for H. pylori IgG and IgA. RESULTS: The H. pylori seroprevalence was 65.7%; further, 17.1% of the cases had an active infection. H. pylori was not found in the cervix or the cervicovaginal secretions. CONCLUSION: The cervix is not a reservoir for H. pylori, and the microorganism does not appear to be transmitted through the fecal-genital route.


Asunto(s)
Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/aislamiento & purificación , Displasia del Cuello del Útero/microbiología , Neoplasias del Cuello Uterino/microbiología , Adulto , Femenino , Infecciones por Helicobacter/microbiología , Humanos , Pruebas Serológicas , Adulto Joven
17.
Clin Exp Dermatol ; 34(8): e611-3, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19489863

RESUMEN

Incontinentia pigmenti (IP) is a rare genodermatosis caused by a mutation of nuclear factor kappa B essential modulator gene. There is no specific treatment for IP, therefore it has been claimed that there is no effective treatment to hasten resolution of any of the phases of IP. However, the initial vesiculobullous stage of IP is characterized histopathologically by eosinophilic inflammation, which is expected to respond to corticosteroids. An 18-day-old female neonate was seen, with vesicles on her trunk and limbs diagnosed as the vesiculobullous stage of IP. The patient was treated with a double-compound cream containing a potent corticosteroid (difluocortolone valerate 0.1%) and an antiseptic (chlorquinaldol 1%), to be applied to the lesions twice daily. Five days later, resolution of the lesions was almost complete. As chlorquinaldol has no known anti-inflammatory activity, we attribute this improvement to difluocortolone valerate. This case shows that early lesions of IP with eosinophilic inflammation are treatable.


Asunto(s)
Clorquinaldol/administración & dosificación , Diflucortolona/análogos & derivados , Glucocorticoides/administración & dosificación , Incontinencia Pigmentaria/tratamiento farmacológico , Administración Cutánea , Diflucortolona/administración & dosificación , Femenino , Humanos , Incontinencia Pigmentaria/patología , Recién Nacido
19.
Clin Rheumatol ; 27(9): 1119-25, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18357499

RESUMEN

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic, progressive, systemic inflammatory rheumatic diseases that lead to serious disability. The objective of this study was to investigate the demographic and clinical characteristics of the patients with RA and AS who were treated in tertiary hospitals in Turkey and to analyze their current medical management. A total of 562 RA and 216 AS patients were evaluated. The mean age of RA patients was 52.1 +/- 12.6 years. The female to male ratio was 3.7:1. Of the RA patients, 72.2% had positive rheumatoid factor (RF), 62.9% had high C-reactive protein, and 75.2% had radiological erosion. The ratio of patients with Disease Activity Score (DAS) 28 >3.2 was 73.9% and of those with Health Assessment Questionnaire (HAQ) > or =1.5 was 20.9%. There was a statistically significant increase in RF positivity and HAQ scores in the group with higher DAS 28 score. Frequency of extraarticular manifestations was 22.4%. The ratio of the patients receiving disease modifying antirheumatic drugs (DMARD) was 93.1%, and 6.9% of the patients were using anti-tumor necrosis factor (TNF) blocking agents. In AS, the mean age of the patients was 38.1 +/- 10.6, and the female to male ratio was 1:2.5. The time elapsed between the first symptom and diagnosis was 4.3 years. The ratio of peripheral joint involvement was 29.4%. Major histocompatibility complex, class I, B 27 was investigated in 31.1% of patients and the rate of positivity was 91%. In 52.4% of the patients, Bath AS Disease Activity Index (BASDAI) was > or =4. The erythrocyte sedimentation rate, Bath AS Functional Index, and peripheral involvement were significantly higher in the group with BASDAI > or =4. Frequency of extraarticular involvement was 21.2% in AS patients. In the treatment schedule, 77.5% of AS patients were receiving sulphasalazine, 15% methotrexate, and 9.9% anti-TNF agents. Despite widespread use of DMARD, we observed high disease activity in more than half of the RA and AS patients. These results may be due to relatively insufficient usage of anti-TNF agents in our patients and therefore these results mostly reflect the traditional treatments. In conclusion, analysis of disease characteristics will inform us about the disease severity and activity in RA and AS patients and could help in selecting candidate patients for biological treatments.


Asunto(s)
Artritis Reumatoide , Espondilitis Anquilosante , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/fisiopatología , Proteína C-Reactiva/análisis , Femenino , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Radiografía , Factor Reumatoide/análisis , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/diagnóstico por imagen , Espondilitis Anquilosante/tratamiento farmacológico , Sulfasalazina/uso terapéutico , Factor de Necrosis Tumoral alfa/inmunología
20.
Int Urol Nephrol ; 40(3): 691-9, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18327655

RESUMEN

AIMS: Several studies have reported evidence of hormonal abnormalities in 25-35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. In the present study, we examined purinergic relaxation responses in hypothyroidism in an experimental rabbit model and compared them with controls to evaluate the possible involvement of the purinergic pathway. MATERIALS AND METHODS: The study comprised 20 male New Zealand white rabbits. The rabbits were divided into two equal groups. We tested the effects of ATP, alpha beta ATP, and adenosine precontracted with phenylephrine on the isolated corpus cavernosum preparations from control and hypothyroid rabbits. We also evaluated the effects of ATP, alpha beta ATP, and adenosine on the cGMP levels in the isolated corpus cavernosum preparations from control and hypothyroid rabbits. RESULTS: T3, T4, and testosterone levels were significantly lower in hypothyroid rabbits. ATP, alpha beta ATP, carbachol, and electrical field stimulation (EFS)-induced frequency-dependent relaxation responses in the isolated rabbit corpus cavernosum strips precontracted with phenylephrine reduced significantly (P<0.05). Adenosine-induced relaxation responses did not change significantly in hypothyroid rabbits. CONCLUSION: Reduction of relaxation response in hypothyroid rabbits corpus cavernosum can depend on a decreased release of nitric oxide (NO) from nitrergic nerves and endothelium.


Asunto(s)
Hipotiroidismo/complicaciones , Hipotiroidismo/metabolismo , Impotencia Vasculogénica/etiología , Músculo Liso Vascular/metabolismo , Pene/metabolismo , Receptores Purinérgicos/fisiología , Adenosina/farmacología , Adenosina Trifosfato/farmacología , Análisis de Varianza , Animales , GMP Cíclico/metabolismo , Modelos Animales de Enfermedad , Estimulación Eléctrica , Femenino , Impotencia Vasculogénica/metabolismo , Masculino , Relajación Muscular/fisiología , Músculo Liso Vascular/fisiología , Testosterona/metabolismo , Hormonas Tiroideas/metabolismo , Tiroidectomía
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