RESUMO
The epithelial-mesenchymal transition (EMT) is a phenomenon, in which epithelial cells acquire a mesenchymal cell phenotype. It is important during wound healing; however, chronic inflammation leads to excessive EMT and causes tissue barrier dysfunction with hyperplasia. EMT is induced by several cytokines, such as interleukin (IL)-4 and IL-13. Additionally, IL-4 and IL-13 are known to increase in atopic dermatitis (AD) characterized by intense itching and eczema. Therefore, we assumed that there was commonality between the respective EMT and AD phenotypes. Herein, we evaluated EMT marker expression in AD skin and demonstrated that EMT-maker Snai1 and Twist expression were increased in AD mice model and patients with AD. Moreover, the epithelial-marker keratin 5 and mesenchymal marker Vimentin were co-expressed in the skin epidermis of mice with AD, suggesting the existence of hybrid epithelial-mesenchymal (E/M) cells possessing both epithelial and mesenchymal characteristics. In fact, we found that ΔNp63a, a stabilizing factor for hybrid E/M cells, was upregulated in the skin epidermis of the AD model mouse. Interestingly, increased expression of EMT markers was observed even at a nonlesion site in a patient with AD without initial inflammation or scratching. Therefore, EMT-like phenomena may occur independently of wound healing in skin of patients with AD.
Assuntos
Dermatite Atópica , Humanos , Camundongos , Animais , Interleucina-13 , Epiderme , Transição Epitelial-Mesenquimal/genética , InflamaçãoRESUMO
An oxidative metabolite of lutein, 3'-hydroxy-ε,ε-caroten-3-one, inhibited the differentiation of 3T3-L1 cells to adipocytes and the subsequent triacylglycerol production, but lutein did not. The α,ß-unsaturated carbonyl structure of 3'-hydroxy-ε,ε-caroten-3-one was considered to participate in the inhibitory effect, suggesting that this lutein metabolite has the potential to prevent metabolic syndrome.
Assuntos
Adipócitos/citologia , Diferenciação Celular/efeitos dos fármacos , Luteína/análogos & derivados , Células 3T3-L1 , Animais , Cromatografia Líquida de Alta Pressão , Luteína/farmacologia , CamundongosRESUMO
We previously found that mice fed lutein accumulated its oxidative metabolites (3'-hydroxy-ε,ε-caroten-3-one and ε,ε-carotene-3,3'-dione) as major carotenoids, suggesting that mammals can convert xanthophylls to keto-carotenoids by the oxidation of hydroxyl groups. Here we elucidated the metabolic activities of mouse liver for several xanthophylls. When lutein was incubated with liver postmitochondrial fraction in the presence of NAD(+), (3'R,6'R)-3'-hydroxy-ß,ε-caroten-3-one and (6RS,3'R,6'R)-3'-hydroxy-ε,ε-caroten-3-one were produced as major oxidation products. The former accumulated only at the early stage and was assumed to be an intermediate, followed by isomerization to the latter. The configuration at the C3' and C6' of the ε-end group in lutein was retained in the two oxidation products. These results indicate that the 3-hydroxy ß-end group in lutein was preferentially oxidized to a 3-oxo ε-end group via a 3-oxo ß-end group. Other xanthophylls such as ß-cryptoxanthin and zeaxanthin, which have a 3-hydroxy ß-end group, were also oxidized in the same manner as lutein. These keto-carotenoids, derived from dietary xanthophylls, were confirmed to be present in plasma of normal human subjects, and ß,ε-caroten-3'-one was significantly increased by the ingestion of ß-cryptoxanthin. Thus, humans as well as mice have oxidative activity to convert the 3-hydroxy ß-end group of xanthophylls to a 3-oxo ε-end group.
Assuntos
Xantofilas/metabolismo , Animais , Carotenoides/química , Carotenoides/metabolismo , Criptoxantinas/química , Criptoxantinas/metabolismo , Humanos , Fígado/metabolismo , Luteína/análogos & derivados , Luteína/química , Luteína/metabolismo , Masculino , Mamíferos , Camundongos Endogâmicos ICR , Oxirredução , Xantofilas/química , Zeaxantinas/química , Zeaxantinas/metabolismoRESUMO
In the two cold-adapted monomeric isocitrate dehydrogenases from psychrophilic bacteria, Colwellia maris and Colwellia psychrerythraea (CmIDH and CpIDH, respectively), the combined substitutions of amino acid residues between the Leu693, Leu724 and Phe735 residues of CmIDH and the corresponding Phe693, Gln724 and Leu735 residues of CpIDH were introduced by site-directed mutagenesis. A double mutant of CmIDH substituted its Leu724 and Phe735 residues by the corresponding ones of CpIDH, CmL724Q/F735L, and the triple mutant of CpIDH, CpF693L/Q724L/L735F, showed the most decrease and increase of activity, respectively, of each wild-type and its all mutated enzymes. In the case of CmIDH, the substitutions of these three amino acid residues resulted in the decrease of catalytic activity and thermostability for activity, but the combined substitutions of amino acid residues did not necessarily exert additive effects on these properties. On the other hand, similar substitutions in CpIDH had quite opposite effects to CmIDH, and the effects of the combined substitutions were additive. All multiple mutants of CmIDH and CpIDH showed lower and higher catalytic efficiency (k(cat)/K(m)) values than the respective wild-type enzymes. Single and multiple mutations of the substituted amino acid residues in the CmIDH and CpIDH led to the increase and decrease of sensitivity to tryptic digestion, indicating that the stability of protein structure was decreased and increased by the mutations, respectively.
Assuntos
Alteromonadaceae/enzimologia , Proteínas de Bactérias/química , Isocitrato Desidrogenase/química , Sequência de Aminoácidos , Substituição de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Domínio Catalítico , Estabilidade Enzimática , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Dados de Sequência Molecular , Mutação , TemperaturaRESUMO
Early T-cell precursor acute lymphoblastic leukaemia (ETP-ALL) is a recently identified subtype of T-ALL with distinctive gene expression and cell marker profiles, poor response to chemotherapy and a very high risk of relapse. We determined the reliability of restricted panel of cell markers to identify EPT-ALL using a previously classified cohort. Then, we applied the cell marker profile that best discriminated ETP-ALL to a cohort of 91 patients with T-ALL enrolled in the Tokyo Children's Cancer Study Group L99-15 study, which included allogeneic stem cell transplantation (allo-SCT) for patients with poor prednisone response. Five of the 91 patients (5·5%) met the ETP-ALL criteria. There were no significant differences in presenting clinical features between these and the remaining 86 patients. Response to early remission induction therapy was inferior in ETP-ALL as compared with T-ALL. The ETP-ALL subgroup showed a significantly poorer event-free survival (4-year rate; 40%) than the T-ALL subgroup (70%, P=0·014). Of note, three of four relapsed ETP-ALL patients survived after allo-SCT, indicating that allo-SCT can be effective for this drug-resistant subtype of T-ALL.
Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia , Adolescente , Antígenos CD/análise , Antígenos de Neoplasias/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imunofenotipagem , Lactente , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/classificação , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/cirurgia , Prednisona/administração & dosagem , Indução de Remissão , Transplante de Células-Tronco , Transplante Homólogo , Resultado do TratamentoRESUMO
Childhood hearing impairment is a serious and relatively common condition. The earlier childhood hearing impairment is diagnosed, the less developmentally disadvantaged children become. Newborn hearing screening (NBS) programs have been implemented in Japan. NBS is important for identifying hearing loss at an early age and for adequate intervention at an early developmental stage. According to a survey questionnaire by the Japan Association of Obstetricians and Gynecologists, 62% of the newborn babies were audiologically and medically examined. The average age of examinees has become younger since the beginning of NBS. Here, we summarized the NBS programs in Japan including behavioral audiometry and examinations of auditory brainstem response, auditory-steady state response, and otoacoustic emissions. NBS can lead to advantages in terms of language developmental outcome for children with hearing impairment. However, there is no sufficient support system existing for children who are advised to undergo further auditory diagnostic tests after NBS. It is necessary for government agencies, medical and educational institutions to communicate together for clarifying their responsibilities in order to support the children with hearing impairment.
Assuntos
Testes Auditivos/tendências , Triagem Neonatal/tendências , Correção de Deficiência Auditiva , Previsões , Humanos , Recém-NascidoRESUMO
Chemoradiotherapy for head and neck cancer is associated with a high incidence of severe oral mucositis; an adverse, painful event. Oral mucositis also causes nutritional deficiency by making oral feeding difficult. This may lead to prolongation of hospitalization due to complications caused by malnutrition. However, an effective way to prevent oral mucositis completely, remains to be found. In this study, we evaluated the occurrence of oral mucositis, and nutritional conditions such as hypoalbuminemia, reduction of body weight, and length of hospital stay (days) when the mouth was rinsed using rebamipide solution (R solution), or Poraprezinc-alginate sodium solution (P-A solution) (both considered to be effective for oral mucositis). A mouth rinsed with sodium azulene sulfonate (S solution) was used as a control. The mouth was rinsed out six times per day continuously during chemoradiotherapy. In the study, 31 patients were assigned to rinse their mouths using R solution, 11 patients using PA solution, and 15 patients using S solution (reduction rate of body weight in 14 patients). For the evaluation, the criteria for adverse drug reactions CTCAE (v3. 0) were used. Grade 1 and over, oral mucositis occurred in 48% of the R solution group, 36% of the P-A solution group, and 80% of the S solution group, indicating that the P-A solution group significantly prevented the occurrence of oral mucositis as opposed to the S solution group. A reduction in body weight was observed in 81% of the R solution group, 82% of the P-A solution group, and 79% of the S solution group, indicating a similar weight reduction rate among individual solution groups. Hypoalbuminemia equal to grade 2 or higher occurred in 3% of the R solution group, 18% of the P-A solution group, and 29% of the S solution group, indicating that the R group significantly prevented the occurrence of hypoalbuminemia compared to the S solution group. In addition, the length of hospital stays were 44 ± 8. 0 days for the R solution group, 52 ± 18. 8 days for the P-A solution group, and 61 ± 19. 5 days for the S solution group, indicating that the R solution group significantly shortened the length of hospital stay compared to the S solution group. These results suggested that the use of an R or P-A solution may be effective in preventing oral mucositis and impaired nutrition of those undergoing chemoradiotherapy for head and neck cancer.
Assuntos
Alanina/análogos & derivados , Antineoplásicos/efeitos adversos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Antissépticos Bucais/uso terapêutico , Mucosite/prevenção & controle , Quinolonas/uso terapêutico , Alanina/uso terapêutico , Antineoplásicos/uso terapêutico , Terapia Combinada/efeitos adversos , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Mucosite/induzido quimicamenteRESUMO
The structure of the title compound, C27H22F2O4, at 193â K has triclinic (P ) symmetry. The hy-droxy and meth-oxy groups at the 1,2-positions of the acenaphthene core display a cis configuration. Both substituents are involved in the formation of a five-membered intra-molecular O-Hâ¯O hydrogen-bonded ring. The 4-fluoro-phenyl rings make dihedral angles of 87.02â (7) and 51.86â (8)° with the naphthalene ring system. In the crystal, a pair of non-classical C-Hâ¯O hydrogen bonds forms centrosymmetric dimeric structures. The dimeric aggregates are linked in the ac plane through non-classical C-Hâ¯F hydrogen bonds and C-Hâ¯π interactions.
RESUMO
Fucoxanthin, a xanthophyll present in brown algae consumed in Eastern Asia, can suppress carcinogenesis and obesity in rodents. We investigated the metabolism, tissue distribution, and depletion of fucoxanthin in ICR mice by comparison with those of lutein. The experiments comprised 14-d dietary supplementation with lutein esters or fucoxanthin, followed by 41- or 28-d, respectively, depletion periods with carotenoid-free diets. After lutein ester supplementation, 3'-hydroxy-ε,ε-caroten-3-one and lutein were the predominant carotenoids in plasma and tissues, accompanied by ε,ε-carotene-3,3'-dione. The presence of these keto-carotenoids in mouse tissues is reported here for the first time, to our knowledge. Lutein and its metabolites accumulated most in the liver (7.51 µmol/kg), followed by plasma (2.11 µmol/L), adipose tissues (1.01-1.44 µmol/kg), and kidney (0.87 µmol/kg). The half-life of the depletion (t(1/2)) of lutein metabolites varied as follows: plasma (1.16 d) < liver (2.63 d) < kidney (4.44 d) < < < adipose tissues (>41 d). Fucoxanthinol and amarouciaxanthin A were the main metabolites in mice fed fucoxanthin and partitioned more into adipose tissues (3.13-3.64 µmol/kg) than into plasma, liver, and kidney (1.29-1.80 µmol/kg). Fucoxanthin metabolites had shorter t(1/2) in plasma, liver, and kidneys (0.92-1.23 d) compared with those of adipose tissues (2.76-4.81 d). The tissue distribution of lutein and fucoxanthin metabolites was not associated with their lipophilicity, but depletion seemed to be slower for more lipophilic compounds. We concluded that mice actively convert lutein and fucoxanthin to keto-carotenoids by oxidizing the secondary hydroxyl groups and accumulate them in tissues.
Assuntos
Carotenoides/análise , Luteína/análogos & derivados , Luteína/farmacocinética , Xantofilas/farmacocinética , Tecido Adiposo/química , Animais , Carotenoides/sangue , Suplementos Nutricionais , Ésteres/administração & dosagem , Meia-Vida , Rim/química , Fígado/química , Luteína/administração & dosagem , Luteína/análise , Masculino , Camundongos , Camundongos Endogâmicos ICR , Xantofilas/administração & dosagemRESUMO
The retarding activity of 6-O-dodecanoyl-D-allose against rice growth was higher than that of the octanoate and the decanoate. The activities of 6-O-dodecanoyl-D-glucose, -D-mannose, and -D-galactose against rice seedlings were examined. 6-O-Dodecanoyl-D-allose exhibited the highest activity, suggesting the importance of the alpha-axial hydroxy group at C-3 of D-allose.
Assuntos
Glucose/farmacologia , Oryza/efeitos dos fármacos , Oryza/crescimento & desenvolvimento , Glucose/química , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimentoRESUMO
Immune checkpoint inhibition is associated with a broad spectrum of immune toxicities referred to as immune-related adverse events (irAEs). Myositis is known to be a potentially fatal irAE. Here, we report a case of immune-related myositis after the administration of durvalumab. A 60-year-old man with stage IIIA lung adenocarcinoma was treated with durvalumab after concurrent chemoradiation therapy. After the third dose of durvalumab, his serum CK level was elevated, and soon thereafter myalgia of the proximal muscles and blepharoptosis were observed. We diagnosed immune-related myositis based on the results of pathological examination and initiated systemic corticosteroid therapy. His symptoms then improved and the serum CK level immediately dropped to within a normal range. Clinicians should be aware of possible myositis during the early phase of durvalumab therapy.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Miosite/induzido quimicamente , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Delusional parasitosis is an uncommon psychiatric condition in which patients have the immutable conviction that small, living organisms, such as worms, insects, or larvae infest their skin or other organs. OBJECTIVE/METHOD: The authors describe a case of an unusual association of delusional parasitosis and thalamic pain syndrome after left-posterior thalamic hemorrhage. The patient initially suffered from dysesthesia and burning pain typical of thalamic pain syndrome and subsequently developed delusional oral parasitosis ("worms" infesting her mouth). RESULTS: Sulpiride 100 mg/day administered in addition to amitriptyline gradually improved her delusions within 3 months. DISCUSSION: The authors speculate that this specific type of delusion can be elicited by the disruption of the somatosensory pathway and that the subsequent cortical sensory deafferentiation and reorganization arising from this disruption may contribute to the development of delusional parasitosis.
Assuntos
Delusões/psicologia , Doenças Parasitárias/psicologia , Animais , Delusões/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Parasitárias/diagnóstico , Acidente Vascular Cerebral/psicologia , Síndrome , Tomografia Computadorizada por Raios XRESUMO
t(X;11) is a recurrent translocation in pediatric acute myeloid leukemia (AML). We showed that the MLL gene on 11q23 was fused to the SEPTIN6 gene on Xq24, a human homologue to mouse Septin6, in three de novo infant AML with complex chromosomal abnormalities involving 11q23 and Xq22-24. SEPTIN6 consisted of at least 12 exons and was predicted to encode at least two types of proteins by alternative splicing. Expression of approximately 2.3-, 3.1-, and 4.6-kb SEPTIN6 transcripts was simultaneously detected in fetal lung, liver, and brain, in all of the adult tissues except brain, and in acute lymphoblastic leukemia and AML cell lines. However, the expression of an approximately 2.7-kb transcript was detected alone in fetal heart and adult brain. The SEPTIN6 protein is homologous to septin family members including CDCREL1 and AF17q25/MSF, which generate fusion products with MLL. The MLL-SEPTIN6 fusion proteins contain almost the entire septin protein, similar to MLL-CDCREL1 and MLL-AF17q25/MSF. Notably, all three of the patients were diagnosed with M1 or M2. Combined present results and literatures suggest that AML with the MLL-SEPTIN6 fusion gene is a subset of infant AML, which differentiate into the myeloid lineage, although AML with other MLL fusion genes is capable of differentiating into the myelomonocytic or monocytic lineage.
Assuntos
Cromossomos Humanos Par 11 , Proteínas de Ligação a DNA/genética , Proteínas de Ligação ao GTP/genética , Leucemia Mieloide Aguda/genética , Proto-Oncogenes , Fatores de Transcrição , Translocação Genética , Cromossomo X , Adulto , Animais , Fusão Gênica Artificial , Clonagem Molecular , Proteínas do Citoesqueleto , DNA Complementar/genética , DNA de Neoplasias/genética , Feminino , Proteínas de Ligação ao GTP/biossíntese , Expressão Gênica , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Leucemia Mieloide Aguda/metabolismo , Masculino , Camundongos , Proteína de Leucina Linfoide-Mieloide , SeptinasRESUMO
Animal studies suggest that estrogen receptor ß (ERß)-agonists, but not ERα-agonists, are antidepressants. Several endogenous ligands for ERß have been proposed, including 5α-androstane-3ß, 17ß-diol (3ßAdiol), Androstenediol (Δ5-diol), and 7α-hydroxydehydroepiandrosterone (7α-OH-DHEA). The aim of this study was to determine the serum and salivary levels of natural ERß ligands in men and women with and without past depressive episodes in the elderly population. DHEA (a precursor of 3ßAdiol, Δ5-diol, and 7α-OH-DHEA), 17ß-estradiol (E2), and cortisol (F) were also measured. Samples were collected from 51 subjects and liquid chromatography tandem mass spectrometry was used for measurement. Comparisons were made between groups based on sex and depression history. E2, 3ßAdiol, and Δ5-diol levels were significantly lower in women than in men regardless of depression history. There were no significant differences between men and women in DHEA or 7α-OH-DHEA levels. DHEA was significantly lower in women with depression than in women without depression. Reduced DHEA levels may be related to depression vulnerability in women. Further studies are needed to determine the mechanism underlying sex differences in the prevalence of depression and increased risk of depression during menopause. Not only E2 but also two other estrogenic steroids (3ßAdiol and Δ5-diol) should be involved in these studies.
Assuntos
Desidroepiandrosterona/sangue , Depressão/sangue , Estradiol/sangue , Receptor beta de Estrogênio/metabolismo , Hidrocortisona/sangue , Idoso , Cromatografia Líquida , Depressão/metabolismo , Feminino , Humanos , Ligantes , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Espectrometria de Massas em TandemRESUMO
Imatinib, the ABL kinase inhibitor, is used not only for Philadelphia chromosome-positive (Ph + ) chronic myelogenous leukemia, but also for Ph + acute lymphoblastic leukemia (ALL), although resistance to the drug tends to develop in an early stage of the clinical course. We describe a childhood refractory Ph + ALL patient in whom progressive resistance to imatinib was correlated with the appearance of a mutation in the BCR-ABL kinase domain and in vitro drug resistance to imatinib as determined by the methyl-thiazol-tetrazolium (MTT) assay. A missense mutation of T to C (Y253H) of the ABL gene was identified in the resistant clone, suggesting that this mutation may play an etiological role in the rapid loss of drug sensitivity.
Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Genes abl/genética , Mutação de Sentido Incorreto , Piperazinas/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Pirimidinas/uso terapêutico , Benzamidas , Sobrevivência Celular/efeitos dos fármacos , Criança , Genes abl/fisiologia , Humanos , Mesilato de Imatinib , Masculino , Cromossomo Filadélfia , Piperazinas/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pirimidinas/farmacologiaRESUMO
Photodynamic therapy (PDT), which employs a combination of a tumor-localizing photosensitizer and visible light, has been used in the treatment of extramammary Paget's disease (EMPD). Two patients with EMPD were treated with PDT using 5-aminolevulinic acid (ALA). Histologically, in both cases, Paget's cells were present within the epidermis. Case 1 was a 92-year-old male who underwent total extirpation for treatment of EMPD. Two topical ALA-PDT treatments were applied to parts of the lesions at a total dose of 200J/cm2. Case 2 was a 73-year-old female, whose lesions in the right labia majora were treated with 3 topical ALA-PDT sessions at a total dose of 300 J/cm2. Clinical findings after the irradiation showed improvement in both patients, and elimination of tumor cells in the epidermis was confirmed histologically. Case 1 had no recurrence in the irradiation field at three months after PDT. Case 2 had a recurrence only in the periphery parts of the lesions at two months after PDT, but the periphery lesions remitted with two more PDT treatments. Topical ALA-PDT is an effective treatment for EMPD with tumor cells within the epidermis. It is noninvasive and achieves a cosmetically excellent outcome, especially in elderly patients and those in poor general condition.
Assuntos
Ácido Aminolevulínico/administração & dosagem , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Masculinos/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Doença de Paget Extramamária/tratamento farmacológico , Fármacos Fotossensibilizantes/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Masculinos/patologia , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Doença de Paget Extramamária/patologia , FotoquimioterapiaRESUMO
BACKGROUND: There are several treatments for wrinkles and depressed areas of the face, hands, and body. Hyaluronic acid is effective, but only for 6 months to 1 year. Autologous fat grafting may cause damage during tissue harvest. METHODS: In this study, patients were injected with platelet-rich plasma plus basic fibroblast growth factor (bFGF). Platelet-rich plasma was prepared by collecting blood and extracting platelets using double centrifugation. Basic fibroblast growth factor diluted with normal saline was added to platelet-rich plasma. There were 2005 patients who received platelet-rich plasma plus bFGF therapy. RESULTS: Of the 2005 patients treated, 1889 were female and 116 were male patients; patients had a mean age of 48.2 years. Treated areas inlcuded 1461 nasolabial folds, 437 marionette lines, 1413 nasojugal grooves, 148 supraorbital grooves, 253 midcheek grooves, 304 foreheads, 49 temples, and 282 glabellae. Results on the Global Aesthetic Improvement Scale indicated that the level of patient satisfaction was 97.3 percent and the level of investigator satisfaction was 98.4 percent. The period for the therapy's effectiveness to become apparent was an average of 65.4 days. Platelet-rich plasma plus bFGF therapy resulted in an improved grade on the Wrinkle Severity Rating Scale. Improvement was 0.55 for a Wrinkle Severity Rating Scale grade of 2, 1.13 for a Wrinkle Severity Rating Scale grade of 3, 1.82 for a Wrinkle Severity Rating Scale grade of 4, and 2.23 for a Wrinkle Severity Rating Scale grade of 5. CONCLUSIONS: Platelet-rich plasma plus bFGF is effective in treating wrinkles and depressed areas of the skin of the face and body. The study revealed that platelet-rich plasma plus bFGF is an innovative therapy that causes minimal complications. CLINCAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
Assuntos
Estética , Fator 2 de Crescimento de Fibroblastos/uso terapêutico , Plasma Rico em Plaquetas , Envelhecimento da Pele/efeitos dos fármacos , Pele/fisiopatologia , Idoso , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Humanos , Injeções Intradérmicas , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Sulco Nasogeniano , Satisfação do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Pele/efeitos dos fármacos , Envelhecimento da Pele/fisiologia , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
INTRODUCTION: Angiogenesis is an important factor in the development of osteoarthritis (OA). We investigated the efficacy of bevacizumab, an antibody against vascular endothelial growth factor and an inhibitor of angiogenesis, in the treatment of OA using a rabbit model of anterior cruciate ligament transection. METHODS: First, we evaluated the response of gene expression and histology of the normal joint to bevacizumab treatment. Next, in a rabbit model of OA induced by anterior cruciate ligament transection, we used macroscopic and histological evaluations and real-time polymerase chain reaction (PCR) to examine the responses to intravenous (systemic) administration of bevacizumab (OAB IV group). We also investigated the efficacy of intra-articular (local) administration of bevacizumab in OA-induced rabbits (OAB IA group). RESULTS: Histologically, bevacizumab had no negative effect in normal joints. Bevacizumab did not increase the expression of genes for catabolic factors in the synovium, subchondral bone, or articular cartilage, but it increased the expression of collagen type 2 in the articular cartilage. Macroscopically and histologically, the OAB IV group exhibited a reduction in articular cartilage degeneration and less osteophyte formation and synovitis compared with the control group (no bevacizumab; OA group). Real-time PCR showed significantly lower expression of catabolic factors in the synovium in the OAB IV group compared with the OA group. In articular cartilage, expression levels of aggrecan, collagen type 2, and chondromodulin-1 were higher in the OAB IV group than in the OA group. Histological evaluation and assessment of pain behaviour showed a superior effect in the OAB IA group compared with the OAB IV group 12 weeks after administration of bevacizumab, even though the total dosage given to the OAB IA group was half that received by the OAB IV group. CONCLUSIONS: Considering the dosage and potential adverse effects of bevacizumab, the local administration of bevacizumab is a more advantageous approach than systemic administration. Our results suggest that intra-articular bevacizumab may offer a new therapeutic approach for patients with post-traumatic OA.
Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Cartilagem Articular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Articulações/efeitos dos fármacos , Osteoartrite/prevenção & controle , Agrecanas/genética , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/farmacologia , Animais , Ligamento Cruzado Anterior/cirurgia , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Colágeno Tipo II/genética , Modelos Animais de Doenças , Humanos , Injeções Intra-Articulares , Injeções Intravenosas , Articulações/metabolismo , Articulações/patologia , Osteoartrite/genética , Osteoartrite/metabolismo , Osteófito/patologia , Osteófito/prevenção & controle , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/imunologiaRESUMO
Monomeric isocitrate dehydrogenases from psychrophilic bacteria, Colwellia maris and Colwellia psychrerythraea (CmIDH-II and CpIDH-M, respectively) are cold-adapted enzymes and show a high degree of amino acid sequential identity to each other (77%). However, maximum activity of CpIDH-M at optimum temperature is much less than that of CmIDH-II. In the C-terminal region 3 of these enzymes, which was suggested from previous study to be responsible for their distinct catalytic ability, several sequential differences of amino acid residue are present. Among them, ten amino acid residues were exchanged between them by site-directed mutagenesis and several properties of the mutated enzymes were examined in this study. The mutated enzymes of CmIDH-II substituted its Gln671, Leu724 and Phe735 residues with the corresponding residues of CpIDH-M (termed Q671K, L724Q and F735L, respectively) showed lower specific activity and thermostability for activity than the wild-type enzyme. Furthermore, the decreased specific activity was also observed in L693F. In contrast, the corresponding mutants of CpIDH-M, F693L, Q724L and L735F, showed the increased specific activity and thermostability for activity. The catalytic efficiency (k(cat)/K(m)) values of these mutated CmIDH-II and CpIDH-M were lower and higher than those of their wild-type IDHs, respectively. These results suggest that the Gln671, Leu693, Leu724 and Phe735 residues of CmIDH-II are important for exerting its high catalytic ability.
Assuntos
Alteromonadaceae/enzimologia , Temperatura Baixa , Isocitrato Desidrogenase/química , Isocitrato Desidrogenase/metabolismo , Alteromonadaceae/genética , Sequência de Aminoácidos , Estabilidade Enzimática/genética , Cinética , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Homologia de Sequência de AminoácidosRESUMO
In this study, we investigate the effects of treatment with layered chondrocyte sheets and synovial cell transplantation. An osteochondral defect was created of 48 Japanese white rabbits. In order to determine the effects of treatment, the following 6 groups were produced: (A) synovial cells (1.8 × 10(6) cells), (B)layered chondrocyte sheets (1.7 × 10(6) cells), (C) synovial cells (3.0 × 10(5) cells) + layered chondrocyte sheets, (D)synovial cells (6.0 × 10(5) cells) + layered chondrocyte sheets, (E)synovial cells (1.2 × 10(6) cells) + layered chondrocyte sheets, (F) osteochondral defect. Layered chondrocyte sheets and synovial cells were transplanted, sacrificed four and 12 weeks postoperatively. An incapacitance tester (Linton) was used to find trends in the weight distribution ratio of the damaged limbs after surgery. Sections were stained with Safranin-O. Repair sites were evaluated using ICRS grading system. In groups (A) to (E), the damaged limb weight distribution ratio had improved. The repair tissue stained positively with Safranin-O. Four and 12 weeks after surgery, groups (A) to (E) exhibited significantly higher scores than group (F), and groups (D) and (E) exhibited significantly higher scores than groups (A) and (B). This suggests the efficacy of combining layered chondrocyte sheets with synovial cells.