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1.
Int J Mol Sci ; 25(15)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39126093

RESUMO

The history of effective anti-cancer medications begins with the discovery of cisplatin's anti-cancer properties. Second-generation analogue, carboplatin, with a similar range of effectiveness, made progress in improving these drugs with fewer side effects and better solubility. Renewed interest in platinum-based drugs has been increasing in the past several years. These developments highlight a revitalized enthusiasm and ongoing exploration in platinum chemotherapy based on the series of dinuclear platinum(II) complexes, [{Pt(L)Cl}2(µ-bridging ligand)]2+, which have been synthesized and evaluated for their biological activities. These complexes are designed to target various cancerous conditions, exhibiting promising antitumor, antiproliferative, and apoptosis-inducing activities. The current work aims to shed light on the potential of these complexes as next-generation platinum-based therapies, highlighting their enhanced efficacy and reduced side effects, which could revolutionize the approach to chemotherapy.


Assuntos
Antineoplásicos , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Ligantes , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/química , Compostos Organoplatínicos/síntese química , Apoptose/efeitos dos fármacos , Platina/química , Platina/farmacologia , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/síntese química , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/patologia
2.
Sensors (Basel) ; 24(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-39000831

RESUMO

Conventional air quality monitoring networks typically tend to be sparse over areas of interest. Because of the high cost of establishing such monitoring systems, some areas are often completely left out of regulatory monitoring networks. Recently, a new paradigm in monitoring has emerged that utilizes low-cost air pollution sensors, thus making it possible to reduce the knowledge gap in air pollution levels for areas not covered by regulatory monitoring networks and increase the spatial resolution of monitoring in others. The benefits of such networks for the community are almost self-evident since information about the level of air pollution can be transmitted in real time and the data can be analysed immediately over the wider area. However, the accuracy and reliability of newly produced data must also be taken into account in order to be able to correctly interpret the results. In this study, we analyse particulate matter pollution data from a large network of low-cost particulate matter monitors that was deployed and placed in outdoor spaces in schools in central and western Serbia under the Schools for Better Air Quality UNICEF pilot initiative in the period from April 2022 to June 2023. The network consisted of 129 devices in 15 municipalities, with 11 of the municipalities having such extensive real-time measurements of particulate matter concentration for the first time. The analysis showed that the maximum concentrations of PM2.5 and PM10 were in the winter months (heating season), while during the summer months (non-heating season), the concentrations were several times lower. Also, in some municipalities, the maximum values and number of daily exceedances of PM10 (50 µg/m3) were much higher than in the others because of diversity and differences in the low-cost sensor sampling sites. The particulate matter mass daily concentrations obtained by low-cost sensors were analysed and also classified according to the European AQI (air quality index) applied to low-cost sensor data. This study confirmed that the large network of low-cost air pollution sensors can be useful in providing real-time information and warnings about higher pollution days and episodes, particularly in situations where there is a lack of local or national regulatory monitoring stations in the area.

3.
J Biol Inorg Chem ; 29(1): 51-73, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38099936

RESUMO

Platinum-based drugs are widely recognized efficient anti-tumor agents, but faced with multiple undesirable effects. Here, four dinuclear platinum(II) complexes, [{Pt(1,2-pn)Cl}2(µ-pydz)]Cl2 (C1), [{Pt(ibn)Cl}2(µ-pydz)]Cl2 (C2), [{Pt(1,3-pn)Cl}2(µ-pydz)]Cl2 (C3) and [{Pt(1,3-pnd)Cl}2(µ-pydz)]Cl2 (C4), were designed (pydz is pyridazine, 1,2-pn is ( ±)-1,2-propylenediamine, ibn is 1,2-diamino-2-methylpropane, 1,3-pn is 1,3-propylenediamine, and 1,3-pnd is 1,3-pentanediamine). Interactions and binding ability of C1-C4 complexes with calf thymus DNA (CT-DNA) has been monitored by viscosity measurements, UV-Vis, fluorescence emission spectroscopy and molecular docking. Binding affinities of C1-C4 complexes to the bovine serum albumin (BSA) has been monitored by fluorescence emission spectroscopy. The tested complexes exhibit variable cytotoxicity toward different mouse and human tumor cell lines. C2 shows the most potent cytotoxicity, especially against mouse (4T1) and human (MDA-MD468) breast cancer cells in the dose- and time-dependent manner. C2 induces 4T1 and MDA-MD468 cells apoptosis, further documented by the accumulation of cells at sub-G1 phase of cell cycle and increase of executive caspase 3 and caspase 9 levels in 4T1 cells. C2 exhibits anti-proliferative effect through the reduction of cyclin D3 and cyclin E expression and elevation of inhibitor p27 level. Also, C2 downregulates c-Myc and phosphorylated AKT, oncogenes involved in the control of tumor cell proliferation and death. In order to measure the amount of platinum(II) complexes taken up by the cells, the cellular platinum content were quantified. However, C2 failed to inhibit mouse breast cancer growth in vivo. Chemical modifications of tested platinum(II) complexes might be a valuable approach for the improvement of their anti-tumor activity, especially effects in vivo.


Assuntos
Antineoplásicos , Neoplasias da Mama , Complexos de Coordenação , Piridazinas , Humanos , Animais , Camundongos , Feminino , Platina/farmacologia , Platina/química , Soroalbumina Bovina/química , Simulação de Acoplamento Molecular , Ligantes , DNA/química , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Piridazinas/farmacologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química
4.
J Exp Child Psychol ; 233: 105688, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37156081

RESUMO

According to the processing efficiency theory (PET), math anxiety would interfere with working memory resources, negatively affecting mathematical abilities. To date, few studies have explored how the interaction between math anxiety and working memory would affect different types of math tasks, especially in primary school children. Therefore, the purpose of this study was to explore whether the interplay between math anxiety and working memory would influence performance in numerical operations (i.e., math fluency task) and mathematical reasoning (i.e., math reasoning task) in a group of primary school children (N = 202). Results showed that visuospatial working memory appeared to moderate the relationship between math anxiety and math performance when the math fluency task was considered, indicating that participants with higher levels of working memory were more negatively affected by math anxiety. No interaction effect was found for the math reasoning task in which students' scores were explained only by visuospatial working memory. The findings suggest that math anxiety and visuospatial working memory interact to influence performance in the math fluency task and that this effect may vary depending on the strategies used to complete the task. On the other hand, results on the math reasoning task showed that visuospatial working memory continues to have a positive effect on the math performance independently of math anxiety. The implications in the educational setting are discussed, pointing to the importance of monitoring and intervention studies on affective factors.


Assuntos
Ansiedade , Memória de Curto Prazo , Criança , Humanos , Ansiedade/psicologia , Cognição , Resolução de Problemas , Estudantes/psicologia
5.
Eur J Oral Sci ; 130(6): e12896, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36250548

RESUMO

The goal of this study was to examine the prevalence of WNT10A and RUNX2 mutations and assess their potential impact on the phenotype of non-syndromic tooth agenesis. The study included 30 participants with non-syndromic tooth agenesis, divided into hypodontia (n = 24) and oligodontia forms (n = 6), and 42 unaffected family members. Genomic DNA from buccal epithelial cells was used for polymerase chain reaction amplification of functionally important exons of the WNT10A and RUNX2 genes. Direct sequencing reactions were performed to confirm the presence of mutations. The trend of increasing prevalence of WNT10A mutations and a slight increase in the prevalence of RUNX2 mutations were revealed in tooth agenesis cases compared to unaffected family members. There was a higher prevalence of hypodontia than oligodontia, increased frequency of females over males with missing teeth, and a wide phenotypic variability was observed in individuals and families analyzed. The common missense mutations (p.Phe228Ile, p.Arg113Cys, p.Asp217Asn, and p.Gly165Arg) and c.114-56T>C in the WNT10A gene and in-frame-deletion/insertions (11A, 24Q, 30Q), synonymous variant c.240G>A, and 424-33dupC in the RUNX2 gene were identified. These findings highlight an important role of WNT10A and RUNX2 mutations in the genetic etiology of non-syndromic tooth agenesis.

6.
Int J Esthet Dent ; 17(3): 252-253, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047883
7.
Br J Dev Psychol ; 40(3): 438-452, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35394078

RESUMO

Previous studies mainly investigated working memory (WM) and math anxiety (MA) leaving almost unexplored other aspects of executive functions (EFs) in middle school period. Filling the gap in the literature, the aims of this study were: (1) to better examine the relationship between MA and math performance, (2) to better examine the relationship between EFs and math performance and (3) to investigate the interplay between EFs and MA on math performances. This study confirmed a significant and negative relationship between MA and math performance, indicates a significant and positive relationship between visuospatial WM and math performance, shifting and math performance and highlight a scarcely investigated indirect influence of MA through the measure of shifting on math performance. Our findings shed further light on the mediating role of EFs between MA and math performance and underline some future perspectives.


Assuntos
Função Executiva , Memória de Curto Prazo , Ansiedade , Humanos , Matemática , Estudantes
8.
J Inorg Biochem ; 231: 111773, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35279446

RESUMO

Four Pt(II) complexes of the general formula [Pt(L)(5,6-epoxy-1,10-phen)], where L is an anion of either malonic acid (mal, Pt1), 2-methylmalonic acid (Me-mal, Pt2), 2,2-dimethylmalonic acid (Me2-mal, Pt3) or 1,1-cyclobutanedicarboxylic acid (CBDCA, Pt4) and 5,6-epoxy-1,10-phen is 5,6-epoxy-5,6-dihydro-1,10-phenanthroline, were synthesized and characterized by elemental microanalysis and different spectroscopic techniques. The crystal structure of anhydrous Pt3 complex was determined by single crystal X-ray diffraction. The in vitro anticancer activity of the platinum(II) complexes was investigated in human and murine cancer cell lines as well as in a normal murine cell line by MTT assay. The results show that the investigated platinum(II) complexes exhibit potent cytotoxic activity against murine breast carcinoma cells (4T1), human (HCT116) and murine (CT26) colorectal carcinoma cells. The Pt3 complex shows stronger selectivity against cancer cells compared to other platinum(II) complexes tested and thus exhibits beneficial antitumor activity, mainly by inducing apoptosis and inhibiting cell proliferation and migration. The Pt3 complex also exhibits significant in vivo antitumor activity in the orthotopical 4T1 tumor model without detected liver, kidney, lung, and heart toxicity. All the results indicate that these novel platinum(II) complexes have good antitumor activity on breast and colorectal cancer and have the potential to become possible candidates for cancer treatment.


Assuntos
Antineoplásicos , Complexos de Coordenação , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Complexos de Coordenação/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Malonatos/farmacologia , Camundongos , Platina/química , Platina/farmacologia
9.
J Biol Inorg Chem ; 27(1): 65-79, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34714401

RESUMO

The mechanism of action of most approved drugs in use today is based on their binding to specific proteins or DNA. One of the achievements of this research is a new perspective for recognition of binding modes to DNA by monitoring of changes in measured and stoichiometric values of absorbance at 260 nm. UV-Vis and IR spectroscopy, gel electrophoresis and docking study were used for investigation of binding properties of three dinuclear platinum(II) complexes containing different pyridine-based bridging ligands, [{Pt(en)Cl}2(µ-4,4'-bipy)]Cl2·2H2O (Pt1), [{Pt(en)Cl}2(µ-bpa)]Cl2·4H2O (Pt2) and [{Pt(en)Cl}2(µ-bpe)]Cl2·4H2O (Pt3) to DNA (4,4'-bipy, bpa and bpe are 4,4'-bipyridine, 1,2-bis(4-pyridyl)ethane and 1,2-bis(4-pyridyl)ethene, respectively). In contrast to the system with well-known intercalated ligand (EtBr), covalently bound ligand (cis-Pt) and with minor groove binder (Hoechst 33258), which do not have significant differences in measured and stoichiometric values, the most pronounced deviations are recorded for two dinuclear platinum(II) complexes (Pt1 and Pt2), as a consequence of complex binding to the phosphate backbone and bending of DNA helix. The hydrolysis of complexes and changes in DNA conformation were also analysed as phenomena that may have an impact on the changes in absorbance.


Assuntos
Antineoplásicos , Platina , Antineoplásicos/química , DNA/química , Ligantes , Fosfatos , Platina/química
10.
J Inorg Biochem ; 225: 111619, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34597886

RESUMO

The antitumour potential of nine dinuclear platinum(II) complexes of the type [{Pt(L)Cl}2(µ-X)]2+(where L represents two NH3 or different bidentantly coordinated diamine ligand - ethylenediamine, en; (±)-1,2-propylenediamine, 1,2-pn; isobutylenediamine, ibn; trans-(±)-1,2-diaminocyclohexane, dach; 1,3-propylenediamine, 1,3-pd; 2,2-dimethyl-1,3-propylenediamine, 2,2-diMe-1,3-pd; (±)-1,3-pentanediamine,1,3-pnd, and X is a bridging pyrazine (pz) or pyridazine (pydz) ligand) were determined by in vitro and in vivo assays using the CT26 cell line and a murine model of heterotopic colon cancer tumour induced in immunocompetent BALB/c mice. This study concludes that complexes Pt1, Pt2 and Pt7 possess significant in vitro cytotoxic activity against mouse colon carcinoma CT26 cells, while all these complexes show moderate apoptotic effect. Complexes Pt1 and Pt7 arrested CT26 cells in G2/M phase of cell cycle, while, evaluated by detection of Ki67 expressing cells, complexes Pt5 and Pt6 exerted the highest antiproliferative effect. Complexes Pt1 and Pt2 exerted significant in vivo antitumour effects. These complexes reduced the growth of primary tumour and the incidence of lung and liver metastases without causing the significant hepato- and nephro- toxicity. Our data indicate considerable antitumour activity of platinum(II) complexes against CT26 cells in vitro and in vivo and imply possible further investigations on their role as potential chemotherapeutic agents.


Assuntos
Antineoplásicos/uso terapêutico , Complexos de Coordenação/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Ligantes , Masculino , Camundongos Endogâmicos BALB C , Estrutura Molecular , Metástase Neoplásica/prevenção & controle , Platina/química
11.
J Inorg Biochem ; 210: 111158, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32622215

RESUMO

Three new dinuclear palladium(II) complexes with general formula [{Pd(en)Cl}2(µ-L)]2+ (L is pyridine-based bridging ligand 4,4'-bipyridine (4,4'-bipy, 1), 1,2-bis(4-pyridyl)ethane (bpa, 2), 1,2-bis(4-pyridyl)ethylene (bpe, 3) and en is bidentate coordinated ethylenediamine) were synthesized and characterized by elemental microanalyses, NMR (1H and 13C), IR and UV-Vis spectroscopy. In vitro cytotoxic activity of these complexes against human A549 and murine LLC1 lung cancer cells, as well as two human HCT116 and SW480 and one murine CT26 colon cancer cells was investigated using MTT assay (MTT is 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). The potential of complexes 1-3 to induce apoptosis was tested by flow cytometric analysis of Annexin V and propidium iodide stained treated cells, while their antiproliferative activity was analyzed by detection of Ki67 expression in treated cancer cells. The DNA binding affinity of complexes 1-3 was evaluated by UV-Vis, fluorescence emission spectroscopy and by viscosity measurements in aqueous phosphate buffer solution at pH 7.40. Furthermore, interaction of these complexes with bovine serum albumin was investigated by fluorescence spectrometry. The present study showed that the nature of pyridine-based bridging ligand (L) in dinuclear [{Pd(en)Cl}2(µ-L)]2+ complex has an influence on the complex preference for the cytotoxic activity and CT-DNA/BSA (CT-DNA is calf thymus DNA and BSA is bovine serum albumin) binding affinity.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , DNA/metabolismo , Piridinas/farmacologia , Soroalbumina Bovina/metabolismo , Animais , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Bovinos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Estabilidade de Medicamentos , Humanos , Ligantes , Camundongos , Paládio/química , Ligação Proteica , Piridinas/metabolismo
12.
J Biol Inorg Chem ; 25(3): 395-409, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32162071

RESUMO

New anticancer platinum(II) compounds simultaneously targeting tumor cells and tumor-derived neoangiogenesis, with new DNA interacting mode and large therapeutic window are appealing alternative to improve efficacy of clinical platinum chemotherapeutics. Herein, we describe three novel dinuclear [{Pt(en)Cl}2(µ-L)]2+ complexes with different pyridine-like bridging ligands (L), 4,4'-bipyridine (Pt1), 1,2-bis(4-pyridyl)ethane (Pt2) and 1,2-bis(4-pyridyl)ethene (Pt3), which highly, positively charged aqua derivatives, [{Pt(en)(H2O)}2(µ-L)]4+, interact with the phosphate backbone forming DNA-Pt adducts with an unique and previously undescribed binding mode, called a minor groove covering. The results of this study suggested that the new binding mode of the aqua-Pt(II) complexes with DNA could be attributed to the higher anticancer activities of their chloride analogues. All three compounds, particularly complex [{Pt(en)Cl}2(µ-4,4'-bipy)]Cl2·2H2O (4,4'-bipy is 4,4'-bipyridine) (Pt1), overcame cisplatin resistance in vivo in the zebrafish-mouse melanoma xenograft model, showed much higher therapeutic potential than antiangiogenic drug sunitinib malate, while effectively blocking tumor neovascularization and melanoma cell metastasis. Overall therapeutic profile showed new dinuclear Pt(II) complexes could be novel, effective and safe anticancer agents. Finally, the correlation with the structural characteristics of these complexes can serve as a useful tool for developing new and more effective anticancer drugs.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , DNA/química , Neovascularização Patológica/tratamento farmacológico , Compostos Organoplatínicos/farmacologia , Piridinas/farmacologia , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Sítios de Ligação/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Simulação de Acoplamento Molecular , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química , Piridinas/química , Viscosidade , Peixe-Zebra
13.
J Biol Inorg Chem ; 24(7): 1009-1022, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31385067

RESUMO

Three new dinuclear Pd(II) complexes with general formula [{Pd(en)Cl}2(µ-L)](NO3)2 [L is bridging ligand quinoxaline (Pd1), quinazoline (Pd2) and phthalazine (Pd3)] were synthesized and characterized by elemental microanalyses, UV-Vis, IR and NMR (1H and 13C) spectroscopy. The interaction of dinuclear Pd1-Pd3 complexes with calf thymus DNA (CT-DNA) has been monitored by viscosity measurements, UV-Vis and fluorescence emission spectroscopy in aqueous phosphate buffer solution (PBS) at pH 7.40 and 37 °C. In addition, these experimental conditions have been applied to investigate the binding affinities of Pd1-Pd3 complexes to the bovine serum albumin (BSA) by fluorescence emission spectroscopy. In vitro antiproliferative and apoptotic activities of the dinuclear Pd(II) complexes have been tested on colorectal and lung cancer cell lines. All tested Pd(II) complexes had lower cytotoxic effect than cisplatin against colorectal cancer cells, but also had similar or even higher cytotoxicity than cisplatin against lung cancer cells. All complexes induced apoptosis of colorectal and lung cancer cells, while the highest antiproliferative effect exerted Pd2 complex.


Assuntos
DNA/metabolismo , Compostos Heterocíclicos/química , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Paládio/química , Soroalbumina Bovina/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Ligantes , Modelos Moleculares , Conformação Molecular , Compostos Organometálicos/metabolismo
14.
J Diabetes Sci Technol ; 13(2): 171-175, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30132685

RESUMO

AIMS: The aim of the study was to evaluate Facebook group as possible communication tool to improve glucose control in adolescents and young people with type 1 diabetes (T1D). METHODS: This retrospective and cross-sectional study included 728 T1D patients (age 11-25) on continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) treated at the center for insulin pump and glucose sensor in Skopje from January 2012 to December 2017. Data were collected through the electronic medical record system and cross-sectional analysis (telephone, social media (Facebook and Viber) or email). Patients were analyzed in two groups: (a) non-Internet group, with 398 patients treated using standard medical protocol with regular clinic visits; (b) Internet group, with 330 patients who, besides standard medical protocol, were active members of a national closed Facebook group on diabetes. Both the non-Internet and Internet groups had regular visits every 2-3 months. Patients from the Internet group were members of the closed Facebook group "Diabetes Macedonia" and had an opportunity to interact with questions, answers, and comments on diabetes care. An additional analysis was performed of the Internet group on combined use of Facebook and Viber. Average HbA1c levels were compared in both groups. RESULTS: Each patient from the Facebook group had 1.5 ± 3.5 posts per day. Hba1c was significantly lower in patients from the Internet group (7.1 ± 3.2%; 54 ± 35 mmol/mol) compared to patients from the non-Internet group (7.6 ± 2.8%; 60 ± 31 mmol/mol). CONCLUSIONS: Social media like Facebook and Viber can be additional communication tool in adolescents and young people with T1D and can significantly lower HbA1c compared to patients without social media use. CSII patients are more likely to use both social media (Facebook and Viber) compared with MDI patients (Facebook only).


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Processos Grupais , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Mídias Sociais , Adolescente , Adulto , Atitude Frente aos Computadores , Biomarcadores/sangue , Glicemia/metabolismo , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/psicologia , Feminino , Hemoglobinas Glicadas/metabolismo , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Hipoglicemiantes/efeitos adversos , Infusões Subcutâneas , Injeções Subcutâneas , Insulina/efeitos adversos , Relações Interpessoais , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
Dalton Trans ; 47(42): 15091-15102, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30303498

RESUMO

The synthesis, spectroscopic characterization, cytotoxic activity and DNA binding evaluation of seven new dinuclear platinum(ii) complexes Pt1-Pt7, with the general formula [{Pt(L)Cl}2(µ-1,5-nphe)](ClO4)2 (1,5-nphe is 1,5-naphthyridine; while L is two ammines (Pt1) or one bidentate coordinated diamine: ethylenediamine (Pt2), (±)-1,2-propylenediamine (Pt3), trans-(±)-1,2-diaminocyclohexane (Pt4), 1,3-propylenediamine (Pt5), 2,2-dimethyl-1,3-propylenediamine (Pt6), and 1,3-pentanediamine (Pt7)), were reported. In vitro cytotoxic activity of these complexes was evaluated against three tumor cell lines, murine colon carcinoma (CT26), murine mammary carcinoma (4T1) and murine lung cancer (LLC1) and two normal cell lines, murine mesenchymal stem cells (MSC) and human fibroblast (MRC-5) cells. The results of the MTT assay indicate that all investigated complexes have almost no cytotoxic effects on 4T1 and very low cytotoxicity toward LLC1 cell lines. In contrast to the effects on LLC1 and 4T1 cells, complexes Pt1 and Pt2 had significant cytotoxic activity toward CT26 cells. Complex Pt1 had a much lower IC50 value for activity on CT26 cells compared with cisplatin. In comparison with cisplatin, all dinuclear Pt1-Pt7 complexes showed lower cytotoxicity toward normal MSC and MRC-5 cells. In order to measure the amount of platinum(ii) complexes taken up by the cells, we quantified the cellular platinum content using inductively coupled plasma mass spectrometry (ICP-QMS). Molecular docking studies performed to evaluate the potential binding mode of dinuclear platinum(ii) complexes Pt1-Pt7 and their aqua derivatives W1-W7, respectively, at the double stranded DNA showed that groove spanning and backbone tracking are the most stable binding modes.


Assuntos
Antineoplásicos/farmacologia , DNA/química , Naftiridinas/farmacologia , Compostos Organoplatínicos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Sítios de Ligação/efeitos dos fármacos , Bovinos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Naftiridinas/química , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química
16.
Bioinorg Chem Appl ; 2018: 3294948, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29853829

RESUMO

Dinuclear platinum(II) complexes, [{Pt(en)Cl}2(µ-qx)]Cl2·2H2O (1), [{Pt(en)Cl}2(µ-qz)](ClO4)2 (2), and [{Pt(en)Cl}2(µ-phtz)]Cl2·4H2O (3), were synthesized and characterized by different spectroscopic techniques. The crystal structure of 1 was determined by single-crystal X-ray diffraction analysis, while the DFT M06-2X method was applied in order to optimize the structures of 1-3. The chlorido Pt(II) complexes 1-3 were converted into the corresponding aqua species 1a-3a, and their reactions with an equimolar amount of Ac-L-Met-Gly and Ac-L-His-Gly dipeptides were studied by 1H NMR spectroscopy in the pH range 2.0 < pH < 2.5 at 37°C. It was found that, in all investigated reactions with the Ac-L-Met-Gly dipeptide, the cleavage of the Met-Gly amide bond had occurred, but complexes 2a and 3a showed lower catalytic activity than 1a. However, in the reactions with Ac-L-His-Gly dipeptide, the hydrolysis of the amide bond involving the carboxylic group of histidine was observed only with complex 1a. The observed disparity in the catalytic activity of these complexes is thought to be due to different relative positioning of nitrogen atoms in the bridging qx, qz, and phtz ligands and consequent variation in the intramolecular separation of the two platinum(II) metal centers.

18.
Diabetes Technol Ther ; 19(12): 739-743, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28976785

RESUMO

BACKGROUND: Subcutaneous insulin infusion (CSII) therapy is a challenge for both patients and healthcare providers. The long-term CSII use is scarce. The aim of this study is to describe the impact of CSII therapy for 10 years of use at our center. METHODS: This single-center retrospective study includes 162 type 1 diabetes patients using CSII for >3 years during October 2004 until October 2014. Data were collected through the electronic medical record system, cross-sectional analysis (telephone, e-mail, or social media), and CSII reports generated by Carelink Therapy Management Software (Medtronic, Northridge, CA). RESULTS: Patients were analyzed in three age groups: 12-18, 19-24, and >25 years. All patients were treated with CSII for >3 years. Total daily dose of insulin was >0.9 U/(kg·day) in age group 12-18 years old, which was significantly higher than other two age groups (P < 0.05). Basal ratio was lower in younger age (<40%) and showed trend of increasing with age and longer diabetes duration (up to 44%). Younger patients used bolus wizard on regular basis (>75%), which was significantly higher than other age groups (P < 0.05). More than 50% of patients achieved glycated hemoglobin (HbA1c) <7.0% and >70% of patients achieved HbA1c <7.5%. HbA1c level significantly changed from baseline in all groups (P < 0.05). CONCLUSION: Our study shows improved glucose control in long-term CSII users. A reduction of HbA1c levels by -1.1% was maintained during the study period.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Masculino , República da Macedônia do Norte , Estudos Retrospectivos , Adulto Jovem
20.
Bioorg Chem ; 72: 190-198, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28460361

RESUMO

Two dinuclear palladium(II) complexes, [{Pd(en)Cl}2(µ-pz)](NO3)2 and [{Pd(en)Cl}2(µ-pydz)](NO3)2, have been synthesized and characterized by elemental microanalysis and spectroscopic (1H and 13C NMR, IR and UV-vis) techniques (en is ethylenediamine; pz is pyrazine and pydz is pyridazine). The square planar geometry of palladium(II) metal centers in these complexes has been predicted by DFT calculations. The chlorido complexes were converted into the corresponding aqua complexes, [{Pd(en)(H2O)}2(µ-pz)]4+ and [{Pd(en)(H2O)}2(µ-pydz)]4+, and their reactions with N-acetylated l-histidylglycine (Ac-l-His-Gly) and l-methionylglycine (Ac-l-Met-Gly) were studied by 1H NMR spectroscopy. The palladium(II)-aqua complexes and dipeptides were reacted in 1:1 M ratio, and all reactions performed in the pH range 2.0

Assuntos
Amidas/química , Dipeptídeos/química , Histidina/química , Metionina/química , Compostos Organometálicos/química , Dimerização , Relação Dose-Resposta a Droga , Hidrólise , Estrutura Molecular , Paládio/química , Platina/química , Pirazinas/química , Piridazinas/química , Relação Estrutura-Atividade
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