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Objective: In order to understand the epidemic trend of COVID-19 and evaluate the effect of prevention and control, this study aims to evaluate the epidemic dynamics of COVID-19 in Chinese mainland from January 16 to February 14, 2020. Methods: The daily number of new confirmed COVID-19 cases detected by nucleic acid was collected from the National Health Commission from January 16, 2020 to February 14, 2020. The analysis included the epidemic curve of the new confirmed cases, multiple of the new confirmed cases for period-over-period, multiple of the new confirmed cases for fixed-base, and the period-over-period growth rate of the new confirmed cases. Results: From January 16 to February 14, 2020, the cumulative number of new confirmed cases of COVID-19 in Chinese mainland was 50 031, including 37 930 in Hubei Province, 22 883 in Wuhan city and 12 101 in other provinces outside Hubei. The peak of new confirmed cases in other provinces outside Hubei was from January 31 to February 4, 2020, and the peak of new confirmed cases in Wuhan city and Hubei Province was from February 5 to February 9, 2020. The number of new confirmed cases in other provinces outside Hubei showed a significant decline (23% compared with the peak) from February 5 to February 9, 2020, while the number of new confirmed cases in Wuhan city (30% compared with the peak) and Hubei Province (37% compared with the peak) decreased significantly from February 10 to February 14, 2020. Conclusion: The epidemic prevention and control measures taken by the state and governments at all levels have effectively curbed the spread of the COVID-19 epidemic in Chinese mainland.
Assuntos
Infecções por Coronavirus/epidemiologia , Epidemias , Pneumonia Viral/epidemiologia , COVID-19 , China/epidemiologia , Cidades/epidemiologia , Humanos , PandemiasRESUMO
To study the effect of internal particle size on the microstructure properties and thermal decomposition characteristics of site mixed emulsion explosive at different altitudes. Site mixed emulsion explosive was prepared with different shear rate. The particle size, viscosity, sensitized bubbles, detonation velocity and peak pressure of the emulsion explosive were tested after stored at different simulated altitudes. The thermal decomposition characteristics of emulsion matrix prepared at three different rotational speeds were measured by thermogravimetric analyzer and kinetic analysis was performed by non-isothermal model Kissinger-Akah-Sunose (KAS) method. The results show that with the increase in altitude, the internal phase size showed a trend of first increasing and then decreasing, and the number of sensitized bubbles within the emulsion explosive decreases. At an altitude of 0 m, the detonation velocity and peak overpressure of the emulsion explosive prepared by 1600 r min-1 increased 4.78% and 29.09%, respectively compared with 1200 r min-1, and at an altitude of 4500 m, the detonation velocity increased 11.87%, the peak overpressure increased 43.98%. The thermal decomposition activation energy of the emulsion matrix at 1600 r min-1 increased 13.14% compared to 1200 r min-1. It shows that in the production of site mixed emulsion explosive at high altitude, reducing the particle size of the internal phase of emulsion explosives in a certain range can effectively improve the performance of emulsion explosives.
RESUMO
We studied the effect of iron saturation level on the osteogenic activity of lactoferrin (LF) in vitro and in vivo. Different iron saturation levels of LF (1.0, 9.0, 38, 58, and 96%) were prepared as the following samples: apo-LF, LF-9, LF-38, LF-58, and holo-LF. Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we observed that the stimulating osteoblast proliferation activity of LF in vitro decreased with increasing iron saturation level at 100 and 1,000 µg/mL. In vivo, 4-wk-old ICR Swiss male mice were randomly divided into 4 groups: blank control (physiological saline), negative control (BSA), apo-LF, and holo-LF. Four groups of mice were injected subcutaneously with physiological saline, BSA, apo-LF, or holo-LF over the calvarial surface twice a day for 5 consecutive days at a dose of 4 mg/kg per day. Bone histomorphometry showed that new bone formation (assessed using tetracycline-HCl labels) tended to be stronger with apo-LF than with holo-LF. Using fluorescence spectroscopy and circular dichroism measurements, we found that exposure of tryptophan increased, α-helix content increased, but ß-structure content decreased with increasing iron saturation level. These findings indicated that the osteogenic activity of LF decreases with increasing iron saturation level in vitro and in vivo, which may be related to conformational changes in LF.
Assuntos
Ferro/farmacologia , Lactoferrina/farmacologia , Osteogênese/efeitos dos fármacos , Animais , Dicroísmo Circular , Técnicas In Vitro , Ferro/química , Lactoferrina/química , Masculino , Camundongos , Camundongos Endogâmicos ICR , Conformação Proteica , Espectrometria de FluorescênciaRESUMO
A new approach of utilizing microwave to pattern gradient concentric silver nanoparticle ring structures has been presented. The width and height of a single ring and the space between adjacent rings can be adjusted by changing the silver colloidal concentration and the microwave output power. By simply enhancing the ambient vapour pressure to the saturated value during microwave-assisted evaporation, sub-100 nm rings can be deposited in between adjacent micro-rings over a distance of millimetres. Combined with microwave sintering, this approach can also create conductive silver tracks in a single step, showing huge potential in fabricating micro- and nano-electronic devices in an ultra-fast and cost-effective fashion.
Assuntos
Coloides/química , Micro-Ondas , Nanoestruturas/química , Nanotecnologia/métodos , Prata/química , Nanoestruturas/ultraestruturaRESUMO
A facile while flexible approach to size-controllable high-purity colloidal gold nanoplates has been presented. By adjusting the quantity of seeds and I(-) through a seed-mediated, cetyltrimethylammonium bromide (CTABr)-assisted synthetic system, the edge length of the gold nanoplates can be adjusted from 140 to 30 nm without changing their thickness or crystal structure. By simply increasing the ion concentration of the reaction solution, the as-prepared gold nanoplates can be deposited due to the different electrostatic aggregation effects between nanoplates and spherical nanoparticles. Effective storage methods to keep the structural and optical stability of these gold nanoplates are also proposed.
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Burn rehabilitation in China started from compression therapy in the mid-1970s, which showed the dual effects of prevention and treatment of hypertrophic scars. It not only promoted functional rehabilitation but also strengthened the confidence of patients in rehabilitation treatment. Thereafter, more therapies were brought into practice, such as intra-scar injection of triamcinolone acetonide, application of plastic splints, hydrotherapy, exercises with equipment, skin care, local therapeutic massage, active and passive exercises, as well as external use of drugs for inhibiting scars and pigments. Since the beginning of the 21st century, rehabilitation therapies have been gradually increasing. Psychological rehabilitation, occupational therapy, external use of silicone gel, wax therapy and sound, light, electricity, and radiation therapy have been carried out. Many hospitals have established foundations and held summer camps for children. As far as the whole country is concerned, compared with the huge demand, we still face a number of problems such as shortage of working staff, limited working space, capital chain rupture, lack of multi-disciplinary cooperation, untimely treatment, and incomplete rehabilitation. Nowadays, with increasing knowledge of burn rehabilitation and number of practitioners, improvement of equipment and economic situation, the pace of rehabilitation has accelerated, and the overall implementation of burn rehabilitation therapy has shown great vitality. Patients with burn injury involving over 80% total burn surface area (TBSA) of total burn area or full-thickness burn over 60% TBSA were cured and recovered in different levels of hospitals nationwide, which not only reflects the superb level of burn treatment in China but also reflects the overall improvement of rehabilitation level of the country.
Assuntos
Unidades de Queimados/organização & administração , Queimaduras/reabilitação , Cicatriz Hipertrófica/reabilitação , Queimaduras/complicações , Criança , China , Cicatriz Hipertrófica/etiologia , Humanos , Unidades de Terapia Intensiva/organização & administraçãoRESUMO
Objective: To investigate the association between ten single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors and pulse pressure (PP) as well as the relationships between gene-gene interaction between PPARα/δ/γ genes and PP. Methods: A total of 820 subjects, with 550 females and 270 males, were recruited from a cohort study of "Prevention of Metabolic Syndrome and Multi-metabolic Disorders in Jiangsu Province of China Study (PMMJS)" . Ten SNPs of PPARα/δ/γ genes were selected. GMDR software (version 1.0.1) was used to evaluate the gene-gene interactions among PPARs SNPs associated with PP. Results: The mean levels of PP in people with mutant genotype of rs1805192 in PPARγ genes (PA+AA) showed a significant increase by 1.341 mmHg (95%CI: 0.431-2.252 mmHg) when compared to the persons with wild genotype (PP). In the subgroup of subjects with more than 30 mmHg levels of PP, a six-locus model comprised rs135539 of PPARα, rs2016520 of PPARδ, rs10865710, rs1805192, rs709158 and rs3856806 of PPARγ showed a highest level of prediction accuracy (0.577) and displayed a better cross-validation consistency (10/10). In the subgroup of subjects with less than 40 mmHg levels of PP, a two-locus model was statistically associated with PP with 0.628 of prediction accuracy and 10/10 of cross-validation consistency. Conclusion: PPARγ rs1805192 was associated with the occurrence of PP. Gene-gene interactions among rs135539 of PPARα, rs2016520 of PPARδ, rs10865710, rs1805192, rs709158 and rs3856806 of PPARγ were all significantly related to PP.
Assuntos
Pressão Sanguínea/genética , Epistasia Genética , Predisposição Genética para Doença , Receptores Ativados por Proliferador de Peroxissomo/genética , Polimorfismo de Nucleotídeo Único/genética , Pressão Sanguínea/fisiologia , China , Estudos de Coortes , Feminino , Frequência do Gene , Genótipo , Humanos , Síndrome Metabólica , PPAR alfa/genética , PPAR delta/genética , PPAR gama/genéticaRESUMO
The blood pressure (BP) fluctuation was first noticed in the 18th century. However, its clinical significance did not get attention until recent years. The increase in BP variability (BPV) is possibly more valuable than the increase in BP level for predicting damages in target organs. Moreover, attenuating BPV is more important than decreasing the BP level. However, the concept of BPV was not used in any related guideline for diagnosing, defining, and grading the risk of hypertension, which is due to the understanding of BPV is not profound, and blind areas and misunderstanding still exist in the definition, features, and classification of BPV. In this paper, the doubts and difficulties in studying BPV are analyzed, which may conduce to understand BPV and thus help for the clinical diagnosis and treatment of hypertension.
Assuntos
Determinação da Pressão Arterial , Pressão Sanguínea , Humanos , Hipertensão/tratamento farmacológicoRESUMO
The inhibitory action of a set of 4,5-diamino-1,2-dihydro-2,2-dimethyl-1-(3-substituted-phenyl)-s-triazines on Lactobacillus casei dihydrofolate reductase is compared with their action on methotrexate-resistant and methotrexate-sensitive cell cultures by means of quantitative structure-selectivity analysis. The analysis uncovers major differences in the steric and hydrophobic interactions of the substituents X with the three different systems. Correlation analysis is used to define the hydrophobic binding site for 3-X in the isolated enzyme. This is shown to be similar to that of the sensitive cells but different from that in the resistant cells, which have a larger hydrophobic binding site. When X has the general structure 3-CH2ZC6H4-Y (Z = O or NH), it is shown that Y does not interact with the isolated enzyme, but in the living cells, Y interacts with a molecular barrier in a way that can be quantitatively related to the molar refractivity of X. The methotrexate-resistant cells are resistant to highly hydrophilic inhibitors such as methotrexate but are not able to resist hydrophobic inhibitors. The results with the inhibition of L. casei dihydrofolate reductase are compared with the inhibition of enzyme from bovine liver.
Assuntos
Antagonistas do Ácido Fólico , Lacticaseibacillus casei/enzimologia , Triazinas/farmacologia , Resistência a Medicamentos , Lacticaseibacillus casei/crescimento & desenvolvimento , Metotrexato/farmacologia , Relação Estrutura-AtividadeRESUMO
The inhibition of dihydrofolate reductase from chicken liver and from Lactobacillus casei has been studied with 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(substituted-phenyl)-s-triazines. It was found that for the chicken enzyme, inhibitor potency for 101 triazines was correlated by the following equation: log 1/Kiapp = 0.85 sigma tau' - 1.04 log (beta X 10 sigma tau' + 1) + 0.57 sigma + 6.36. The parameter tau' indicates that for certain substituents, tau = 0. In the case of the L. casei DHFR results, meta and para derivatives could not be included in the same equation. For 38 meta-substituted compounds, it was found that log 1/Kiapp = 0.38 tau'3-0.91 log (beta X 10 tau'3 + 1) + 0.71I + 4.60 and for 32 para-substituted phenyltriazines log 1/Kiapp = 0.44 tau'4-0.65 log (beta tau'4 + 1') - 0.90 upsilon + 0.69I + 4.67. In the L. casei equation, I is an indicator variable for substituents of the type CH2ZC6H4-Y and ZCH2C6H4-Y, where Z = O, NH, S, or Se. The parameter upsilon is Charton's steric parameter, which is similar to Taft's Es. The mathematical models obtained from correlation analysis are compared with stereo color graphics models.
Assuntos
Galinhas/metabolismo , Antagonistas do Ácido Fólico , Lacticaseibacillus casei/enzimologia , Fígado/enzimologia , Triazinas/farmacologia , Animais , Computadores , Matemática , Modelos Moleculares , Conformação Molecular , Ligação Proteica , Relação Estrutura-Atividade , Tetra-Hidrofolato Desidrogenase/metabolismo , Triazinas/metabolismo , Difração de Raios XRESUMO
The inhibitory activity of 101 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(substituted-phenyl)-s-triazines against purified dihydrofolate reductase from human lymphoblastoid cell (WIL 2) has been studied. From the obtained Kiapp values, quantitative structure-activity relationships (QSAR) have been derived. The QSAR from human dihydrofolate reductase are compared with QSAR for triazines inhibiting bovine and murine tumor DHFR, as well with QSAR for their inhibitory action on murine tumor cell culture.
Assuntos
Antagonistas do Ácido Fólico , Triazinas/farmacologia , Animais , Bovinos , Linhagem Celular , Humanos , Linfócitos/enzimologia , Matemática , Camundongos , Conformação Molecular , Relação Estrutura-Atividade , Triazinas/síntese químicaRESUMO
The relationships between 210 aliphatic group dipole moments (mu) and Taft polar constants (sigma *) are explored, and they are shown to be correlated by a general equation: mu = -a X sigma * -b X n' -c, where a, b, and c are constants. The value n' is a parameter reflecting the attenuating factor due to the number and electronic nature of the interval atoms between the most electronegative atom and the first atom connected to the acetate in the measurement of sigma *. The mu and sigma * values of over 214 aliphatic substituents are compiled for future correlation studies. Comparative examples using sigma * and mu in quantitative structure-activity relationships are presented.
Assuntos
Relação Estrutura-Atividade , Anticonvulsivantes , Antifúngicos , Fenômenos Químicos , Físico-Química , Elétrons , Peso MolecularRESUMO
Pulmonary oedema was produced in isolated lung lobes with steam and provided direct continuous measurements of transudation as it occurred. Transvascular flux (Qf) and weight gain (Gw) of the lobe increased immediately and the transudation reached its peak within half an hour after inhalation injury. Studies of protein content, colloid osmotic pressure of bronchial exudate and water content of lung, reconfirmed the increase in pulmonary capillary permeability. Marked haemoconcentration was revealed. Plasma leaked 113 g (25 per cent), plasma protein leaked 1.96 g (9.7 per cent) during the experiment. Based on the measured arterial pressure (Pa), vein pressure (Pv), arterial occlusion (Pao), venous occlusion (Pvo), double occlusion (Pdo) and blood flow through the lobe (Qt), the total vascular (Rt), arterial (Ra), middle compartment (Rmid) and venous (Rv) resistances were calculated. All the resistances were increased and the Qt showed a decrease after inhalation injury.
Assuntos
Queimaduras por Inalação/complicações , Edema Pulmonar/etiologia , Animais , Proteínas Sanguíneas/análise , Permeabilidade Capilar , Coloides/análise , Modelos Animais de Doenças , Cães , Pulmão/patologia , Tamanho do ÓrgãoRESUMO
In a group of eight burn patients with a mean of 65.3 +/- 17.4 per cent TBSA burn injury (range 50-90 per cent TBSA), accompanied by a mean of 43.5 +/- 18.9 per cent TBSA full-thickness injury, it was shown that the evidence of global hypovolaemia had disappeared at 12 h after the injury following aggressive fluid resuscitation, while there was still a subnormal pHi of stomach at 48 h. As a prolonged period of inadequacy of oxygen delivery to the intestine might result in impairment of the intestinal mucosal barrier function, and then endogenous endotoxaemia might ensue, it seems to be important to correct intestinal hypoxia as early as possible. Since the inadequate perfusion to the gut wall is due to selective vasoconstriction of the mesenteric vasculature, logic dictates that the use of a vasodilator is in order. Anisodamine, an anticholinergic drug, was then given in six burn patients with comparable burn size and amount of fluid replenishment with the eight patients in the control group. It was clearly demonstrated that gastric pHi returned to normal before 48 h after injury. Plasma endotoxin and TNF contents were measured, and they were significantly lower than control values after 72 h. In conclusion, it is believed that anisodamine might be a valuable adjunct to the resuscitation regime of burn shock, and, therefore, a promising drug to abate endogenous endotoxaemia subsequent to splanchnic vasoconstriction due to hypovolaemia. The shortcomings of the drug were a mild abdominal distention and tachycardia after its administration.
Assuntos
Queimaduras/tratamento farmacológico , Choque/tratamento farmacológico , Alcaloides de Solanáceas/uso terapêutico , Circulação Esplâncnica/efeitos dos fármacos , Vasodilatadores/uso terapêutico , Adulto , Queimaduras/complicações , Endotoxinas/análise , Hemodinâmica/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Injeções Intravenosas , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Soluções para Reidratação/administração & dosagem , Choque/complicações , Alcaloides de Solanáceas/administração & dosagem , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Vasodilatadores/administração & dosagemRESUMO
In this study, we examined the relationship of plasma endotoxin levels to the development of multiple organ failure (MOF), and the outcome in patients with thermal injury. A prospective cohort study of 17 patients admitted with burns covering more than 70 per cent of body surface area was undertaken. Circulating endotoxin concentrations were measured by modified limulus amoebocyte lysate assay in serial samples of plasma. Seven out of 17 burned patients developed MOF according to multiple criteria. The plasma endotoxin concentrations of patients with MOF were 0.512-1.127 EU/ml, which were significantly higher than that of 10 patients without MOF (0.216-0.553 EU/ml), on 3, 14, 21 and 28 days postburn (p < 0.05-0.01). A significantly higher incidence of positive endotoxin tests (> or = 0.120 EU/ml) was found in patients who developed MOF as compared to those patients who did not develop MOF during the observation period (p < 0.05). As the mean endotoxin levels increased, the incidence of MOF and death rate also increased, and persistent endotoxemia carried a poor prognosis. The present investigation provides further evidence that endotoxemia in severely burned patients commonly occurs. Circulating endotoxin has also been found to be strongly associated with the development of MOF and mortality following major burn injury.
Assuntos
Queimaduras/sangue , Endotoxinas/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Adulto , Queimaduras/complicações , Queimaduras/microbiologia , Queimaduras/mortalidade , Feminino , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Positivas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/mortalidade , Prognóstico , Estudos ProspectivosRESUMO
In order to reduce excessive plasma loss, to alleviate the effects of devitalized tissues on the body, and to shorten the time in hospital, we attempted to perform extensive escharectomy during the shock period in extensively burned patients. Group A consisted of 21 patients, aged 9-45 years, with a mean total burn area of 63.2 +/- 18.1 per cent TBSA, and full-thickness injury involving 35.9 +/- 19.6 per cent TBSA. The first escharectomy was performed at 24.1 +/- 13.9 h postburn. The excision area averaged 32.3 +/- 6.7 per cent TBSA (range 24-96 per cent). In 15 patients a Swan-Ganz catheter was introduced to monitor haemodynamic changes. It was found that RAP, PAP, PAWP, ABP, HR, CO and CI were all stable during and after the operation. Group B consisted of 29 patients, and escharectomy was begun 4-5 days postburn. The mean healing time of the patients in group A was 33.1 days, which was shorter than that in group B (40.1 days). The period of haemoconcentration was shorter in group A and the amount of blood required during the first 2 weeks was almost 700 ml less in group A. There were fewer visceral complications in group A and smaller amounts of antibiotics were required in this group. The authors believe that escharectomy during the shock stage is feasible.
Assuntos
Queimaduras/cirurgia , Choque Traumático/cirurgia , Doença Aguda , Adolescente , Adulto , Antibacterianos/uso terapêutico , Transfusão de Sangue , Queimaduras/sangue , Queimaduras/complicações , Queimaduras/fisiopatologia , Queimaduras/terapia , Criança , Terapia Combinada , Feminino , Hemodinâmica , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Cuidados Pós-Operatórios , Choque Traumático/sangue , Choque Traumático/etiologia , Choque Traumático/fisiopatologia , Choque Traumático/terapia , Transplante de Pele , Procedimentos Cirúrgicos Operatórios/métodos , Fatores de Tempo , CicatrizaçãoRESUMO
We have given whole blood as one of the main constituents of burn shock resuscitation for the past 28 years. To appraise the value of using whole blood, we have summarized the clinical experience of 2630 burn patients. Overall mortality was 4.18%. The lethal area of the burn were 50% of the population is expected to die was 82.8% total body surface area and 57.4% third-degree burns. The incidence of renal failure, pulmonary edema, and gastrointestinal bleeding was 0.9%, 0.4%, and 0.6% respectively. To confirm the advantage of transfusion of whole blood, we have carried out a series of experimental studies. Two groups of 25 dogs with 25% total body surface area full-thickness burns were treated with two resuscitation regimens. Group I was treated with whole blood, and group II with no blood, during the shock phase. After 48 hours, the infusions were stopped. Measurements were made before the burn and 2, 24, 48, 72, and 144 hours after the burn injury. The animals were then killed for histologic studies. From our data, we concluded that whole blood used in burn shock did not increase hemoconcentration or viscosity; it improved anemia, oncotic pressure, hypoproteinemia, acid-base balance, oxygenation, hemodynamics, and myocardial contractility, promoted cardionatrin secretion, reduced edema of tissue, and protected viscera from degenerative changes and bacterial colonization.
Assuntos
Transfusão de Sangue , Queimaduras/terapia , Choque Traumático/terapia , Animais , Queimaduras/complicações , Soluções Cristaloides , Dextranos/uso terapêutico , Cães , Humanos , Soluções Isotônicas , Plasma , Substitutos do Plasma/uso terapêutico , Ressuscitação , Choque Traumático/etiologiaRESUMO
Twenty seven women with mild, moderate or severe cervical dysplasia proven by pathology were treated by retinamide RII suppository. Retinamide RII suppository, 10 mg QD, was given intravaginally for six months (three months as a course). Clinical examination, Papanicolaou cytology and tissue biopsy under colposcope were carried out before and after treatment. The results indicated that after the second course, 26 out of 27 patients responded; of them, precancerous lesions disappeared in 24 and even normal squamous epithelium was observed in 3. The overall response rate was 96.29% and the marked response rate was 88.89%. The general side effects were mild. There was little cervical and vaginal irritation which was well tolerated. The results of this clinical trial make available a practical base for chemoprevention of cervical cancer.
Assuntos
Antineoplásicos , Lesões Pré-Cancerosas/tratamento farmacológico , Tretinoína/análogos & derivados , Neoplasias do Colo do Útero/prevenção & controle , Colo do Útero/patologia , Feminino , Humanos , Hiperplasia , Lesões Pré-Cancerosas/patologia , Supositórios , Tretinoína/administração & dosagem , Tretinoína/uso terapêutico , Neoplasias do Colo do Útero/patologiaRESUMO
AIM: To build a model of two series of PPAR gamma agonists--thiazolidinedione and aryketo-acid derivatives using 3D-QSAR method, and to reveal the structural features affecting the binding activity to PPAR gamma, which relates to antihyperglycemic and antihyperlipidemic activity and has a potential application to the treatment of type II diabetes. METHODS AND RESULTS: 48 agonists with selective activity for PPAR gamma were analyzed using CoMFA. Based upon the active conformation of rosiglitazone (BRL) extracted from its complex with PPAR gamma all agonists were aligned. The model from CoMFA showed a high ability to explain and predict the activity of PPAR gamma agonists with cross-validation correlation coefficient R2 = 0.656, that of non-cross-validation R2 = 0.982, F10,37 = 201.1, and SE = 0.115. CONCLUSION: The CoMFA contour map indicates that the steric fields mainly contribute to the binding effect, and especially a bulk group in the arylketo-acid series favors in the increase of affinity for PPAR gamma, as compared to the thiazolidinedione.
Assuntos
Benzofenonas/química , Fenilpropionatos/química , Relação Quantitativa Estrutura-Atividade , Receptores Citoplasmáticos e Nucleares/agonistas , Tiazóis/química , Tiazolidinedionas , Fatores de Transcrição/agonistas , Conformação Molecular , Estrutura Molecular , Receptores Citoplasmáticos e Nucleares/química , Fatores de Transcrição/químicaRESUMO
AIM: To build a three dimensional structure model that correlates the biological activities and the structures of a series of farnesyl protein transferase (FPT) inhibitors exemplified by the compound of 2, 3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-4-(2-biphenylylcarbonyl)-1H-1, 4-benzodiazepine. METHODS AND RESULTS: Thirty-two FPT inhibitors with two types of scaffold were analyzed. Active conformations of which were studied using system search, a 3D-QSAR model were constructed using the method of comparative molecular field analysis (CoMFA). The resulting of cross-validated RCV2 = 0.602, non-cross-validated R2 = 0.958, SE = 0.270 and F = 124.5 indicate that the 3D-model possesses an ability to predict activities of new inhibitors. CONCLUSION: The information of CoMFA model offers an approach to designing new FPT inhibitors.