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[PMID]:29465589
[Au] Autor:Geng TT; Xu X; Huang M
[Ad] Endereço:Department of General Intensive Care Unit, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
[Ti] Título:High-dose tigecycline for the treatment of nosocomial carbapenem-resistant Klebsiella pneumoniae bloodstream infections: A retrospective cohort study.
[So] Source:Medicine (Baltimore);97(8):e9961, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI) has become increasingly frequent threat recently, especially in the intensive care unit (ICU). High-dose tigecycline (TGC) regimen is proposed due to the limitation of treatment options. We investigated the efficacy and safety of high-dose TGC combination regimens for treating CRKP BSI. Furthermore, the risk factors for mortality were also determined.This was a single center retrospective cohort study conducted from 2014 to 2016. A total of 40 patients with nosocomial CRKP BSI admitted to the ICU were included; they were classified into two groups according to the treatment regimens with high-dose TGC (HD group) or not (non-HD group). In-hospital mortality rates and microbiologic responses from both groups were reviewed and compared. Besides, the survival and non-survival groups were compared to identify the risk factors of mortality.Twenty-three patients constituted the HD group (high-dosage TGC regimen was administered as 200 mg loading dose followed by 100 mg every 12 h) and 17 patients constituted the non-HD group (standard dose TGC therapy as 100 mg loading dose followed by 50 mg every 12 h and other antibiotics). The in-hospital mortality was 52.2% in the HD group and 76.5% in the non-HD group (P = .117). The Kaplan-Meier test showed significantly longer survival times in the HD group (mean: 83 days vs 28 days; P = .027). Microbiological eradication was observed in 13 patients (56.5%) in the HD group and 6 patients (36.3%) in the non-HD group (P = .184). A smaller fraction of patients in the HD group were subjected to vasoactive therapy (52.2% vs 88.2%; P = .016) compared to the non-HD group. There was no significant difference in the manifestation of adverse effects between the two groups. In the multivariate analysis, multiple organ dysfunction syndrome (MODS), vasoactive therapy, and exposure to carbapenems were regarded as the independent predictors of mortality.A therapeutic regimen consisting of a high dose of TGC was associated with significantly longer survival time and numerically lower mortality in CRKP BSI. Adverse events were not increased with the double dose therapy.
[Mh] Termos MeSH primário: Antibacterianos/administração & dosagem
Bacteriemia/tratamento farmacológico
Infecção Hospitalar/tratamento farmacológico
Infecções por Klebsiella/tratamento farmacológico
Minociclina/análogos & derivados
[Mh] Termos MeSH secundário: Idoso
Bacteriemia/microbiologia
Bacteriemia/mortalidade
Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos
Infecção Hospitalar/microbiologia
Infecção Hospitalar/mortalidade
Feminino
Mortalidade Hospitalar
Seres Humanos
Estimativa de Kaplan-Meier
Infecções por Klebsiella/mortalidade
Klebsiella pneumoniae/efeitos dos fármacos
Masculino
Meia-Idade
Minociclina/administração & dosagem
Estudos Retrospectivos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 70JE2N95KR (tigecycline); FYY3R43WGO (Minocycline)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180222
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009961


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[PMID]:28456774
[Au] Autor:Salameh A; Greimann W; Vollroth M; Dhein S; Bahramsoltani M; Dahnert I
[Ad] Endereço:Clinic for Peadiatric Cardiology, University of Leipzig, Heart Centre, Leipzig, Germany. aida.salameh@medizin.uni-leipzig.de.
[Ti] Título:Lung protection in cardio-pulmonary bypass.
[So] Source:J Physiol Pharmacol;68(1):99-116, 2017 Feb.
[Is] ISSN:1899-1505
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:Since the invention of the heart-lung machine paediatric cardiac surgery developed rapidly. For correction of complex cardiac malformations the application of a cardio-pulmonary bypass (CPB) has become indispensable but possible negative effects of this technique should not be neglected. Especially, both bypassed organs i.e. heart and lung are not perfused during the procedure and therefore are threatened by ischemia and reperfusion injury. Additionally, CPB was developed with a non-pulsatile flow but there are clinical observations that pulsatile flow might be superior with improved patient outcomes. Thus, the aim of our study was to evaluate the effect of CPB on lung structure and to assess whether different flow modalities (pulsatile vs. non-pulsatile flow) or application of the antibiotic minocycline might be advantageous. Thirty five piglets of four weeks age were examined and divided into five experimental groups: control (no CPB) without or with minocycline, CPB (non-pulsatile flow) without or with minocycline and CPB with pulsatile flow. CPB was performed for 90 min followed by a 120 min reperfusion and recovery phase. Thereafter, adenosine triphosphate-content of lung biopsies and histology was carried out. We found that CPB was associated with a significant thickening of alveolar wall accompanied by an infiltration of neutrophil leucocytes. Moreover, markers for hypoxia, apoptosis, nitrosative stress, inflammation and DNA damage were significantly elevated after CPB. These cellular damages could be partially inhibited by minocycline or pulsatile flow. Both, minocycline and pulsatile flow attenuate lung damage after CPB.
[Mh] Termos MeSH primário: Lesão Pulmonar Aguda/prevenção & controle
Antibacterianos/uso terapêutico
Ponte Cardiopulmonar
Minociclina/uso terapêutico
Fluxo Pulsátil
[Mh] Termos MeSH secundário: Lesão Pulmonar Aguda/metabolismo
Lesão Pulmonar Aguda/patologia
Lesão Pulmonar Aguda/fisiopatologia
Trifosfato de Adenosina/metabolismo
Animais
Antibacterianos/farmacologia
Pulmão/efeitos dos fármacos
Pulmão/metabolismo
Pulmão/patologia
Pulmão/fisiopatologia
Minociclina/farmacologia
Infiltração de Neutrófilos
Suínos
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Tumor Necrosis Factor-alpha); 8L70Q75FXE (Adenosine Triphosphate); FYY3R43WGO (Minocycline)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


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[PMID]:29390528
[Au] Autor:Xu X; Zheng Y; Zhao Z; Zhang X; Liu P; Li C
[Ad] Endereço:Department of Dermatology.
[Ti] Título:Efficacy of photodynamic therapy combined with minocycline for treatment of moderate to severe facial acne vulgaris and influence on quality of life.
[So] Source:Medicine (Baltimore);96(51):e9366, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Acne vulgaris is a prevalent skin disorder impairing both physical and psychosocial health. This study was designed to investigate the effectiveness of photodynamic therapy (PDT) combined with minocycline in moderate to severe facial acne and influence on quality of life (QOL). METHODS: Ninety-five patients with moderate to severe facial acne (Investigator Global Assessment [IGA] score 3-4) were randomly treated with PDT and minocycline (n = 48) or minocycline alone (n = 47). All patients took minocycline hydrochloride 100 mg/d for 4 weeks, whereas patients in the minocycline plus PDT group also received 4 times PDT treatment 1 week apart. IGA score, lesion counts, Dermatology Life Quality Index (DLQI), and safety evaluation were performed before treatment and at 2, 4, 6, and 8 weeks after enrolment. RESULTS: There were no statistically significant differences in characteristics between 2 treatment groups at baseline. Minocycline plus PDT treatment led to a greater mean percentage reduction from baseline in lesion counts versus minocycline alone at 8 weeks for both inflammatory (-74.4% vs -53.3%; P < .001) and noninflammatory lesions (-61.7% vs -42.4%; P < .001). More patients treated with minocycline plus PDT achieved IGA score <2 at study end (week 8: 30/48 vs 20/47; P < .05). Patients treated with minocycline plus PDT got significant lower DLQI at 8 weeks (4.4 vs 6.3; P < .001). Adverse events were mild and manageable. CONCLUSIONS: Compared with minocycline alone, the combination of PDT with minocycline significantly improved clinical efficacy and QOL in moderate to severe facial acne patients.
[Mh] Termos MeSH primário: Acne Vulgar/tratamento farmacológico
Minociclina/uso terapêutico
Fotoquimioterapia/métodos
Qualidade de Vida
[Mh] Termos MeSH secundário: Acne Vulgar/diagnóstico
Acne Vulgar/psicologia
Adolescente
Adulto
Distribuição de Qui-Quadrado
Terapia Combinada
Dermatoses Faciais/diagnóstico
Dermatoses Faciais/tratamento farmacológico
Feminino
Seguimentos
Seres Humanos
Masculino
Estudos Prospectivos
Índice de Gravidade de Doença
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
FYY3R43WGO (Minocycline)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009366


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[PMID]:29369189
[Au] Autor:Bartal C; Sagy I; Barski L
[Ti] Título:Drug-induced eosinophilic pneumonia: A review of 196 case reports.
[So] Source:Medicine (Baltimore);97(4):e9688, 2018 Jan.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND OBJECTIVE: Eosinophilic pneumonia (EP) is an important subset of patients who present with pulmonary infiltrates and eosinophilia (PIE). EP is classified by chronicity and etiology and drug-induced EP is the main cause of secondary EP. The primary goal of this review was to examine all the case reports published since the syndrome was defined in 1990. It remains unclear whether acute or chronic EP (AEP or CEP) represent different diseases, and the secondary goal of this review is to determine if there are factors that may help distinguish these 2 entities. METHODS: PubMed (MEDLINE and Medical Subject Headings) was searched for case reports of drug-induced EP or PIE syndrome published between 1990 and 2017. Case reports were only included if the diagnostic criteria for AEP or CEP were fulfilled. For each case, data were extracted pertaining to age, sex, type of medication associated with the disease, time from the onset of symptoms to diagnosis, eosinophil counts in the blood, eosinophil fractions in bronchoalveolar lavage (BAL) fluid, initial chest radiograph and computed tomography results, use of mechanical ventilation, and use of steroid treatment and recurrence. RESULTS: We found 196 case reports describing drug-induced EP. The leading cause was daptomycin. From our review, we found that AEP is more common in younger patients with no gender preference. Eosinophilia in the blood at the time of diagnosis characterized only the CEP patients (80% in CEP vs. 20% in AEP). Abnormal findings on radiographic imagine was similar in both syndromes. A significant portion of AEP patients (20%) presented with acute respiratory failure requiring mechanical ventilation. Most patients with EP were treated with steroids with a higher rate of relapse observed in patients with CEP. CONCLUSION: AEP is a much more fulminant and severe disease than the gradual onset and slowly progressive nature of CEP. The pathogenesis of AEP and CEP remains unclear. However, there is significant clinical overlap among AEP and CEP that are associated with drug toxicity, suggesting the possibility that AEP and CEP are distinct clinical presentations that share a common pathogenic pathway.
[Mh] Termos MeSH primário: Antibacterianos/efeitos adversos
Anti-Inflamatórios não Esteroides/efeitos adversos
Eosinofilia Pulmonar/induzido quimicamente
[Mh] Termos MeSH secundário: Doença Aguda
Adulto
Doença Crônica
Daptomicina/efeitos adversos
Eosinófilos
Feminino
Seres Humanos
Masculino
Mesalamina/efeitos adversos
Meia-Idade
Minociclina/efeitos adversos
Eosinofilia Pulmonar/sangue
Sulfassalazina/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Anti-Inflammatory Agents, Non-Steroidal); 3XC8GUZ6CB (Sulfasalazine); 4Q81I59GXC (Mesalamine); FYY3R43WGO (Minocycline); NWQ5N31VKK (Daptomycin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180126
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009688


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[PMID]:29245350
[Au] Autor:Wu X; Zhao P; Dong L; Zhang X
[Ad] Endereço:aDepartment of Pharmacy, Ruijin Hospital Suzhou Branch Affiliated to Shanghai Jiaotong University School of MedicinebDepartment of Pharmacy, Jiangsu Shengze Hospital, SuzhoucDepartment of Critical Care MedicinedDepartment of Pharmacy, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, PR China.
[Ti] Título:A case report of patient with severe acute cholangitis with tigecycline treatment causing coagulopathy and hypofibrinogenemia.
[So] Source:Medicine (Baltimore);96(49):e9124, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Tigecycline is the first member of the glycylcycline family. There are rarely reports of tigecycline causing coagulopathy and hypofibrinogenemia until now. We report a case on tigecycline-associated coagulopathy and hypofibrinogenemia and discuss the characteristics of the adverse reaction. PATIENT CONCERNS: A 47-year-old male patient with severe acute cholangitis who developed sepsis was treated with a high dosage (100 mg twice daily) of tigecycline. He experienced coagulopathy and hypofibrinogenemia as substantiated by increased levels of prolonged prothrombin time (PT), the international normalized ratio (INR) and activated partial thromboplastin time (APTT), and in particular, the fibrinogen (FIB) levels obviously decreased. DIAGNOSES: Coagulopathy and hypofibrinogenemia. INTERVENTIONS: We discontinued tigecycline and gave the patient several blood products to prevent spontaneous bleeding. OUTCOMES: The adverse reaction disappeared after the withdrawal of tigecycline. After 30 days of hospitalization, the patient discharged with symptom free. LESSONS: We suggest that coagulation parameters should be closely monitored in patients treated with tigecycline, specifically in patients who may be renal insufficiency, female or use the high-dose.
[Mh] Termos MeSH primário: Antibacterianos/efeitos adversos
Transtornos da Coagulação Sanguínea/induzido quimicamente
Minociclina/análogos & derivados
[Mh] Termos MeSH secundário: Afibrinogenemia/induzido quimicamente
Antibacterianos/uso terapêutico
Colangite/complicações
Seres Humanos
Masculino
Meia-Idade
Minociclina/efeitos adversos
Minociclina/uso terapêutico
Sepse/tratamento farmacológico
Sepse/etiologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 70JE2N95KR (tigecycline); FYY3R43WGO (Minocycline)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009124


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[PMID]:27774567
[Au] Autor:Openshaw RL; Thomson DM; Penninger JM; Pratt JA; Morris BJ
[Ad] Endereço:Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, West Medical Building, Glasgow, G12 8QQ, UK.
[Ti] Título:Mice haploinsufficient for Map2k7, a gene involved in neurodevelopment and risk for schizophrenia, show impaired attention, a vigilance decrement deficit and unstable cognitive processing in an attentional task: impact of minocycline.
[So] Source:Psychopharmacology (Berl);234(2):293-305, 2017 Jan.
[Is] ISSN:1432-2072
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Members of the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein (MAP) kinases, and the upstream kinase MKK7, have all been strongly linked with synaptic plasticity and with the development of the neocortex. However, the impact of disruption of this pathway on cognitive function is unclear. OBJECTIVE: In the current study, we test the hypothesis that reduced MKK7 expression is sufficient to cause cognitive impairment. METHODS: Attentional function in mice haploinsufficient for Map2k7 (Map2k7 mice) was investigated using the five-choice serial reaction time task (5-CSRTT). RESULTS: Once stable performance had been achieved, Map2k7 mice showed a distinctive attentional deficit, in the form of an increased number of missed responses, accompanied by a more pronounced decrement in performance over time and elevated intra-individual reaction time variability. When performance was reassessed after administration of minocycline-a tetracycline antibiotic currently showing promise for the improvement of attentional deficits in patients with schizophrenia-signs of improvement in attentional performance were detected. CONCLUSIONS: Overall, Map2k7 haploinsufficiency causes a distinctive pattern of cognitive impairment strongly suggestive of an inability to sustain attention, in accordance with those seen in psychiatric patients carrying out similar tasks. This may be important for understanding the mechanisms of cognitive dysfunction in clinical populations and highlights the possibility of treating some of these deficits with minocycline.
[Mh] Termos MeSH primário: Atenção/fisiologia
Cognição/fisiologia
Haploinsuficiência/genética
MAP Quinase Quinase 7/genética
Minociclina/farmacologia
Esquizofrenia/genética
[Mh] Termos MeSH secundário: Animais
Atenção/efeitos dos fármacos
Comportamento de Escolha/efeitos dos fármacos
Comportamento de Escolha/fisiologia
Cognição/efeitos dos fármacos
Feminino
Seres Humanos
MAP Quinase Quinase 7/deficiência
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Minociclina/uso terapêutico
Tempo de Reação/efeitos dos fármacos
Tempo de Reação/genética
Fatores de Risco
Esquizofrenia/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.12.2 (MAP Kinase Kinase 7); EC 2.7.12.2 (Map2k7 protein, mouse); FYY3R43WGO (Minocycline)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171205
[Lr] Data última revisão:
171205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1007/s00213-016-4463-y


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[PMID]:28920959
[Au] Autor:Kuntz EM; Baquero P; Michie AM; Dunn K; Tardito S; Holyoake TL; Helgason GV; Gottlieb E
[Ad] Endereço:Cancer Research UK, Beatson Institute, Glasgow, UK.
[Ti] Título:Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemia stem cells.
[So] Source:Nat Med;23(10):1234-1240, 2017 Oct.
[Is] ISSN:1546-170X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second- and/or third-generation c-Abl-specific tyrosine kinase inhibitors (TKIs) has substantially extended patient survival. However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs). Therefore, targeting minimal residual disease to prevent acquired resistance and/or disease relapse requires identification of new LSC-selective target(s) that can be exploited therapeutically. Considering that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner, we searched for such vulnerabilities in CML LSCs. We performed metabolic analyses on both stem cell-enriched (CD34 and CD34 CD38 ) and differentiated (CD34 ) cells derived from individuals with CML, and we compared the signature of these cells with that of their normal counterparts. Through combination of stable isotope-assisted metabolomics with functional assays, we demonstrate that primitive CML cells rely on upregulated oxidative metabolism for their survival. We also show that combination treatment with imatinib and tigecycline, an antibiotic that inhibits mitochondrial protein translation, selectively eradicates CML LSCs both in vitro and in a xenotransplantation model of human CML. Our findings provide a strong rationale for investigation of the use of TKIs in combination with tigecycline to treat patients with CML with minimal residual disease.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Mesilato de Imatinib/farmacologia
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico
Minociclina/análogos & derivados
Mitocôndrias/efeitos dos fármacos
Células-Tronco Neoplásicas/efeitos dos fármacos
Fosforilação Oxidativa/efeitos dos fármacos
Inibidores de Proteínas Quinases/farmacologia
[Mh] Termos MeSH secundário: Animais
Western Blotting
Sobrevivência Celular/efeitos dos fármacos
Cromatografia Líquida
Quimioterapia Combinada
Feminino
Seres Humanos
Hipoglicemiantes/farmacologia
Mesilato de Imatinib/uso terapêutico
Técnicas In Vitro
Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo
Espectrometria de Massas
Metabolômica
Camundongos
Camundongos Endogâmicos NOD
Minociclina/farmacologia
Mitocôndrias/metabolismo
Células-Tronco Neoplásicas/metabolismo
Fenformin/farmacologia
Inibidores de Proteínas Quinases/uso terapêutico
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Células Tumorais Cultivadas
Ensaio Tumoral de Célula-Tronco
Regulação para Cima
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Hypoglycemic Agents); 0 (Protein Kinase Inhibitors); 70JE2N95KR (tigecycline); 8A1O1M485B (Imatinib Mesylate); DD5K7529CE (Phenformin); FYY3R43WGO (Minocycline)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170919
[St] Status:MEDLINE
[do] DOI:10.1038/nm.4399


  8 / 5261 MEDLINE  
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[PMID]:28887388
[Au] Autor:Fouda AY; Newsome AS; Spellicy S; Waller JL; Zhi W; Hess DC; Ergul A; Edwards DJ; Fagan SC; Switzer JA
[Ad] Endereço:From the Department of Neurology, Medical College of Georgia, Augusta (S.S., J.L.W., W.Z., D.C.H., A.E., J.A.S.); University of Georgia College of Pharmacy, Athens (A.Y.F., A.S.N., S.C.F.); and University of Waterloo, Ontario, Canada (D.J.E.).
[Ti] Título:Minocycline in Acute Cerebral Hemorrhage: An Early Phase Randomized Trial.
[So] Source:Stroke;48(10):2885-2887, 2017 Oct.
[Is] ISSN:1524-4628
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND PURPOSE: Minocycline is under investigation as a neurovascular protective agent for stroke. This study evaluated the pharmacokinetic, anti-inflammatory, and safety profile of minocycline after intracerebral hemorrhage. METHODS: This study was a single-site, randomized controlled trial of minocycline conducted from 2013 to 2016. Adults ≥18 years with primary intracerebral hemorrhage who could have study drug administered within 24 hours of onset were included. Patients received 400 mg of intravenous minocycline, followed by 400 mg minocycline oral daily for 4 days. Serum concentrations of minocycline after the last oral dose and biomarkers were sampled to determine the peak concentration, half-life, and anti-inflammatory profile. RESULTS: A total of 16 consecutive eligible patients were enrolled, with 8 randomized to minocycline. Although the literature supports a time to peak concentration (T ) of 1 hour for oral minocycline, the T was estimated to be at least 6 hours in this cohort. The elimination half-life (available on 7 patients) was 17.5 hours (SD±3.5). No differences were observed in inflammatory biomarkers, hematoma volume, or perihematomal edema. Concentrations remained at neuroprotective levels (>3 mg/L) throughout the dosing interval in 5 of 7 patients. CONCLUSIONS: In intracerebral hemorrhage, a 400 mg dose of minocycline was safe and achieved neuroprotective serum concentrations. However, oral administration led to delayed absorption in these critically ill patients and should not be used when rapid, high concentrations are desired. Given the safety and pharmacokinetic profile of minocycline in intracerebral hemorrhage and promising data in the treatment of ischemic stroke, intravenous minocycline is an excellent candidate for a prehospital treatment trial. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01805895.
[Mh] Termos MeSH primário: Hemorragia Cerebral/sangue
Hemorragia Cerebral/tratamento farmacológico
Minociclina/administração & dosagem
Minociclina/sangue
Fármacos Neuroprotetores/administração & dosagem
Fármacos Neuroprotetores/sangue
[Mh] Termos MeSH secundário: Doença Aguda
Administração Intravenosa
Hemorragia Cerebral/diagnóstico
Feminino
Seres Humanos
Masculino
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Neuroprotective Agents); FYY3R43WGO (Minocycline)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170910
[St] Status:MEDLINE
[do] DOI:10.1161/STROKEAHA.117.018658


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[PMID]:28878079
[Au] Autor:Quick ED; Seitz S; Clarke P; Tyler KL
[Ad] Endereço:Neuroscience Program, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA.
[Ti] Título:Minocycline Has Anti-inflammatory Effects and Reduces Cytotoxicity in an Spinal Cord Slice Culture Model of West Nile Virus Infection.
[So] Source:J Virol;91(22), 2017 Nov 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:West Nile virus (WNV) is a neurotropic flavivirus that can cause significant neurological disease. Mouse models of WNV infection demonstrate that a proinflammatory environment is induced within the central nervous system (CNS) after WNV infection, leading to entry of activated peripheral immune cells. We utilized spinal cord slice cultures (SCSC) to demonstrate that anti-inflammatory mechanisms may also play a role in WNV-induced pathology and/or recovery. Microglia are a type of macrophage that function as resident CNS immune cells. Similar to mouse models, infection of SCSC with WNV induces the upregulation of proinflammatory genes and proteins that are associated with microglial activation, including the microglial activation marker Iba1 and CC motif chemokines CCL2, CCL3, and CCL5. This suggests that microglia assume a proinflammatory phenotype in response to WNV infection similar to the proinflammatory (M1) activation that can be displayed by other macrophages. We now show that the WNV-induced expression of these and other proinflammatory genes was significantly decreased in the presence of minocycline, which has antineuroinflammatory properties, including the ability to inhibit proinflammatory microglial responses. Minocycline also caused a significant increase in the expression of anti-inflammatory genes associated with alternative anti-inflammatory (M2) macrophage activation, including interleukin 4 (IL-4), IL-13, and FIZZ1. Minocycline-dependent alterations to M1/M2 gene expression were associated with a significant increase in survival of neurons, microglia, and astrocytes in WNV-infected slices and markedly decreased levels of inducible nitric oxide synthase (iNOS). These results demonstrate that an anti-inflammatory environment induced by minocycline reduces viral cytotoxicity during WNV infection in CNS tissue. West Nile virus (WNV) causes substantial morbidity and mortality, with no specific therapeutic treatments available. Antiviral inflammatory responses are a crucial component of WNV pathology, and understanding how they are regulated is important for tailoring effective treatments. Proinflammatory responses during WNV infection have been extensively studied, but anti-inflammatory responses (and their potential protective and reparative capabilities) following WNV infection have not been investigated. Minocycline induced the expression of genes associated with the anti-inflammatory (M2) activation of CNS macrophages (microglia) in WNV-infected SCSC while inhibiting the expression of genes associated with proinflammatory (M1) macrophage activation and was protective for multiple CNS cell types, indicating its potential use as a therapeutic reagent. This culture system can uniquely address the ability of CNS parenchymal cells (neurons, astrocytes, and microglia) to respond to minocycline and to modulate the inflammatory environment and cytotoxicity in response to WNV infection without peripheral immune cell involvement.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Ativação de Macrófagos/efeitos dos fármacos
Macrófagos/imunologia
Minociclina/farmacologia
Coluna Vertebral/imunologia
Febre do Nilo Ocidental/tratamento farmacológico
Vírus do Nilo Ocidental/imunologia
[Mh] Termos MeSH secundário: Animais
Biomarcadores
Proteínas de Ligação ao Cálcio/imunologia
Citocinas/imunologia
Macrófagos/patologia
Camundongos
Proteínas dos Microfilamentos/imunologia
Microglia/imunologia
Microglia/patologia
Microglia/virologia
Óxido Nítrico Sintase Tipo II/imunologia
Coluna Vertebral/patologia
Coluna Vertebral/virologia
Febre do Nilo Ocidental/imunologia
Febre do Nilo Ocidental/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aif1 protein, mouse); 0 (Anti-Inflammatory Agents); 0 (Biomarkers); 0 (Calcium-Binding Proteins); 0 (Cytokines); 0 (Microfilament Proteins); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 1.14.13.39 (Nos2 protein, mouse); FYY3R43WGO (Minocycline)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE


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[PMID]:28865218
[Au] Autor:Jasiecka-Mikolajczyk A; Jaroszewski JJ
[Ad] Endereço:.
[Ti] Título:Determination of tigecycline in turkey plasma by LC-MS/MS: validation and application in a pharmacokinetic study.
[So] Source:Pol J Vet Sci;20(2):241-249, 2017 Mar 01.
[Is] ISSN:1505-1773
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Tigecycline (TIG), a novel glycylcycline antibiotic, plays an important role in the management of complicated skin and intra-abdominal infections. The available data lack any description of a method for determination of TIG in avian plasma. In our study, a selective, accurate and reversed-phase high performance liquid chromatography-tandem mass spectrometry method was developed for the determination of TIG in turkey plasma. Sample preparation was based on protein precipitation and liquid-liquid extraction using 1,2-dichloroethane. Chromatographic separation of TIG and minocycline (internal standard, IS) was achieved on an Atlantis T3 column (150 mm × 3.0 mm, 3.0 µm) using gradient elution. The selected reaction monitoring transitions were performed at 293.60 m/z → 257.10 m/z for TIG and 458.00 m/z → 441.20 m/z for IS. The developed method was validated in terms of specificity, selectivity, linearity, lowest limit of quantification, limit of detection, precision, accuracy, matrix effect, carry-over effect, extraction recovery and stability. All parameters of the method submitted to validation met the acceptance criteria. The assay was linear over the concentration range of 0.01-100 µg/ml. This validated method was successfully applied to a TIG pharmacokinetic study in turkey after intravenous and oral administration at a dose of 10 mg/kg at various time-points.
[Mh] Termos MeSH primário: Cromatografia Líquida/métodos
Minociclina/análogos & derivados
Espectrometria de Massas em Tandem/métodos
Perus/sangue
[Mh] Termos MeSH secundário: Animais
Antibacterianos/sangue
Antibacterianos/farmacocinética
Limite de Detecção
Minociclina/sangue
Minociclina/farmacocinética
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 70JE2N95KR (tigecycline); FYY3R43WGO (Minocycline)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170903
[St] Status:MEDLINE



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