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1.
Support Care Cancer ; 28(1): 261-269, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31037378

RESUMO

PURPOSE: Local/systemic symptoms during cancer therapy may be exacerbated by dysregulated inflammation and its downstream toxic effects. Minocycline can suppress proinflammatory cytokine release; therefore, we investigated its potential to reduce patient-reported symptom severity during radiotherapy (RT) for head and neck cancer (HNC). METHODS: Eligible patients for this blinded, placebo-controlled trial were adults with T0-3, N-any, and M0 HNC receiving single-modality RT. Participants were randomized 1:1 to either minocycline (200 mg/day) or placebo during RT. The primary endpoint was the area under the curve (AUC) of 5 prespecified symptoms (pain, fatigue, disturbed sleep, poor appetite, difficulty swallowing/chewing) during RT, assessed with the MD Anderson Symptom Inventory for HNC (MDASI-HN). RESULTS: We analyzed data from 20 evaluable patients per arm. Overall, 75% had oropharyngeal cancer and 78% were male. No grade 3+ adverse events potentially related to study medication were observed. Two minocycline patients required a feeding tube during RT vs 5 placebo patients (P = 0.21). The average daily AUC during RT for the 5 MDASI-HN symptoms was 3.1 (SD = 1.0) for minocycline and 3.7 (SD = 1.7) for placebo (P = 0.16); the 0.37 effect size was less than our 0.70 target. AUC comparisons for several individual symptoms and symptom interference favored minocycline but were not statistically significant. The greatest numerical differences occurred for systemic symptoms, larger toward treatment end, and in early post-RT recovery. CONCLUSIONS: Minocycline was feasible, well tolerated, and achieved a positive signal toward reducing patient-reported symptom severity during RT for HNC, particularly for systemic symptoms. This justifies additional study and informs future trial design.


Assuntos
Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Minociclina/uso terapêutico , Radiodermatite/prevenção & controle , Idoso , Terapia Combinada , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Fadiga/epidemiologia , Fadiga/etiologia , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Dor/epidemiologia , Dor/etiologia , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia , Resultado do Tratamento
2.
Int J Radiat Oncol Biol Phys ; 106(1): 100-107, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31627177

RESUMO

PURPOSE: In patients with non-small cell lung cancer (NSCLC), concurrent chemoradiation therapy (CRT) exacerbates a cluster of difficult-to-manage symptoms, especially cancer-related fatigue. Minocycline is a readily available, low-cost antibiotic with antiinflammatory properties. We conducted a phase 2 randomized, double-blinded, placebo-controlled trial to investigate the effect of minocycline in reducing CRT-symptom burden in NSCLC. METHODS AND MATERIALS: Patients with NSCLC scheduled to receive CRT provided consent and were randomized to receive either minocycline (100 mg twice daily) or a matching placebo during 6 to 7 weeks of CRT. Patient-reported fatigue and other symptoms were assessed on MD Anderson Symptom Inventory weekly from the start of CRT for 12 weeks. The primary outcome was 12-week (±2 days) area under the curve for symptom burden, which was compared between treatment groups. RESULTS: Forty of 49 enrolled patients (80%) were evaluable (19 on minocycline and 21 on placebo). There were no grade 3 + adverse events related to the study medication. Fatigue was significantly reduced in the minocycline group compared with placebo group during the 12-week trial period (area under the curve = 31.2 ± 14.2 vs 45.0 ± 20.9, P = .011), with a large effect size (Cohen's d = 0.77). Pain (Cohen's d = 0.54) and shortness of breath (Cohen's d = 0.55) were also significantly reduced in the minocycline group (all P < .05). CONCLUSIONS: Minocycline during CRT for NSCLC was feasible, had a low toxicity profile, and yielded a clinically and statistically significant positive signal in reducing symptom burden related to NSCLC and CRT. This study is a proof of concept so a larger trial in CRT patients is warranted.


Assuntos
Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Quimiorradioterapia/efeitos adversos , Fadiga/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Minociclina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carcinoma Pulmonar de Células não Pequenas/complicações , Método Duplo-Cego , Dispneia/tratamento farmacológico , Fadiga/etiologia , Feminino , Humanos , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Estudos Prospectivos , Qualidade de Vida
3.
Undersea Hyperb Med ; 46(5): 709-712, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31683371

RESUMO

We describe the emergency management of a man who experienced acute vision loss diagnosed as direct traumatic optic neuropathy (TON) in his right eye (no light perception) after falling from a height. TON is caused by a high-impact mechanism of injury. Clinical findings include acute vision loss, which is typically immediate, afferent pupillary defect, decreased color vision, and visual field defects. Treatment is controversial because of the lack of strong evidence supporting intervention over observation. In this case report, our treatment strategy comprised immediate hyperbaric oxygen (HBO2) and daily high doses of a steroid. On the second day, minocycline was added to the treatment regimen for its neuroprotective effects. The patient was discharged after receiving six HBO2 treatments and six days of intravenous solumedrol transitioned to oral prednisone. After the third HBO2 treatment, his vision improved to 20/100; after the fourth treatment, it was 20/40 and plateaued. At the time of discharge, it was 20/40. At two-month follow-up, his corrected visual acuity was 20/60+2 in the affected eye. Immediate HBO2 for ischemic and mechanical injury to the optic nerve following trauma is a therapeutic option.


Assuntos
Cegueira/terapia , Glucocorticoides/administração & dosagem , Hemissuccinato de Metilprednisolona/administração & dosagem , Minociclina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Traumatismos do Nervo Óptico/terapia , Acidentes por Quedas , Doença Aguda , Adulto , Cegueira/etiologia , Terapia Combinada/métodos , Tratamento de Emergência/métodos , Humanos , Masculino , Traumatismos do Nervo Óptico/complicações , Prednisona/administração & dosagem , Recuperação de Função Fisiológica
4.
BMJ Case Rep ; 12(9)2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570343

RESUMO

Dipeptidyl peptidase 4 (DPP-4) inhibitors are increasingly used these days in management of diabetes. There has been reported in a few case reports of increasing association between DPP-4 inhibitor use and bullous pemphigoid (BP). We report a case of association between linagliptin use and BP and subsequent treatment with rituximab.


Assuntos
Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Erupção por Droga/patologia , Linagliptina/efeitos adversos , Penfigoide Bolhoso/induzido quimicamente , Rituximab/uso terapêutico , Idoso , Antibacterianos/uso terapêutico , Clobetasol/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Erupção por Droga/tratamento farmacológico , Humanos , Linagliptina/administração & dosagem , Masculino , Minociclina/uso terapêutico , Penfigoide Bolhoso/patologia , Prednisona/uso terapêutico , Resultado do Tratamento
5.
BMC Infect Dis ; 19(1): 720, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416441

RESUMO

BACKGROUND: Non-tuberculous mycobacteria cause chronic pulmonary infection, but pleuritis and pleural effusion are rarely associated with infection with non-tuberculous mycobacteria, especially rapid-growing mycobacteria. CASE PRESENTATION: A 68-year-old woman with rheumatoid arthritis who was using prednisone, azathioprine, and certolizumab pegol presented complaining of fever, dry cough, and night sweats for the past 2 weeks. Chest examination revealed bilateral opacity that was more pronounced on her right side. Bronchoalveolar lavage fluid and pleural effusion fluid were obtained, and revealed coinfection with Mycobacterium fortuitum and Mycobacterium mageritense. Imipenem/cilastatin, levofloxacin, and minocycline were prescribed for 6 months, and the patient was well and asymptomatic for the subsequent 6 months. CONCLUSIONS: This is the first case report describing pleural effusion associated with coinfection with two different mycobacterial species. If the species cannot be identified, the possibility of mycobacterial coinfection should be considered.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Micobactéria não Tuberculosa/tratamento farmacológico , Infecções por Micobactéria não Tuberculosa/microbiologia , Micobactérias não Tuberculosas/patogenicidade , Derrame Pleural/microbiologia , Idoso , Líquido da Lavagem Broncoalveolar/microbiologia , Combinação Imipenem e Cilastatina/uso terapêutico , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Feminino , Humanos , Levofloxacino/uso terapêutico , Minociclina/uso terapêutico , Infecções por Micobactéria não Tuberculosa/etiologia , Mycobacterium fortuitum/patogenicidade , Derrame Pleural/tratamento farmacológico
6.
Eur J Pharmacol ; 858: 172446, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31202800

RESUMO

Lipopolysaccharide (LPS) increases inflammatory cytokines of the brain and deregulates the mitochondrial function, thus could increase the seizure susceptibility. Studies have shown that minocycline has neuroprotective and antioxidant properties. In this study, we aimed to evaluate the anticonvulsant properties of minocycline in LPS-treated animals and the possible involvement of nitric oxide and mitochondrial pathways. In a PTZ model of seizure in mice, minocycline was administrated to LPS-treated mice. Then followed by co-injection of its sub-effective dose and NOS inhibitors including 7-Nitroindazole (7-NI), aminoguanidine (AG) and L-NG-Nitroarginine methyl ester (L-NAME) to evaluate the changes in seizure threshold and the possible involvement of nitrergic system. Molecular assessments were used to evaluate the effects of each treatment on inflammation and mitochondrial function in the brain. LPS-treated animals had lower seizure threshold compared to intact animals; injection of minocycline (80 mg/kg) to LPS-treated mice reversed this effect. Co-injection of sub-effective doses of minocycline (40 mg/kg) and L-NAME to LPS-treated animals significantly increased seizure threshold. We observed that co-treatment of minocycline and AG dissimilar to 7-NI could increase the seizure threshold of LPS-treated animals. L-arginine reversed the anticonvulsant effect of minocycline. Also, molecular evaluations showed that LPS could increase the ATP levels, GSH levels, and reactive oxygen species formation. However, minocycline at both doses significantly reversed the effect of LPS. Minocycline counteracts the proconvulsant effects of LPS through regulating of mitochondrial function and decreasing of neuro-inflammation. Also, co-administration of minocycline and i-NOS inhibitors could intensify anticonvulsant effects of minocycline.


Assuntos
Lipopolissacarídeos/farmacologia , Minociclina/farmacologia , Mitocôndrias/efeitos dos fármacos , Óxido Nítrico/metabolismo , Convulsões/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Masculino , Camundongos , Minociclina/uso terapêutico , Mitocôndrias/metabolismo , Mitocôndrias/patologia , NG-Nitroarginina Metil Éster/farmacologia , Convulsões/metabolismo , Convulsões/patologia
7.
BMC Infect Dis ; 19(1): 460, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118048

RESUMO

BACKGROUND: The multidrug therapy (MDT) for leprosy treatment adopted by Brazil in the 1990s was important for reducing leprosy in the country; however, recurrent cases remained problematic. Mechanisms involved in leprosy recurrence are heterogeneous and can be sorted into three groups: insufficient therapy, bacillary persistence and new infections. This study aimed to analyse the time interval of leprosy recurrence in relation to the therapeutic scheme in the state of Acre. The hypotheses were as follows: 1) treatments (a) rifampicin, ofloxacin and minocycline (ROM) and (b) dapsone (DDS) have a short leprosy recurrence time, 2) treatments based on MDT have a long leprosy recurrence time, 3) there is a dose-response relationship between MDT and the time interval between leprosy episodes. METHODS: This retrospective cohort study included 201 patients with a second episode of clinical leprosy at the reference centers for leprosy control in the state of Acre. Exposure was the type of therapeutic scheme as follows: 1) ROM, 2) DDS, 3) MDT0-9 doses, 4) MDT10-19 doses, 5) MDT20-29 doses, and 6) MDT30+ doses. Outcome was the time interval between release from treatment and a diagnosis of a recurrent leprosy case. Incidence rate ratios and relative risk Poisson regressions adjusted by age and sex were calculated with 95% confidence intervals. RESULTS: The 201 patients studied during this retrospective follow-up resulted in a total of 224 cases of recurrent leprosy. Incidence rate ratios within this therapeutic scheme were as follows: 3.3 (2.39, 4.2; ROM/MDT30+), 1.12 (0.33, 1.92; DDS/MDT30+), 2.17 (1.39, 2.94; MDT0-9/MDT30+), 1.94 (1.13, 2.75; MDT10-19/MDT30+) and 1.26 (0.47, 2.05; MDT20-29/MDT30+). Relative risk Poisson regressions showed a protective effect of MDT30+ in comparison with ROM (0.22; 0.07, 0.72), MDT0-9 (0.42; 0.21, 0.85), and MDT10-19 (0.44; 0.21, 0.92). No differences among MDT30+ and DDS (0.71; 0.36, 1.41) and MDT20-29 (0.76; 0.38, 1.49) were observed. CONCLUSIONS: New infection is an important-yet neglected-mechanism in leprosy recurrence in the state of Acre and can challenge the leprosy elimination plan in Brazil. MDT with few doses might be associated with leprosy recurrence due to insufficient therapy or bacillary persistence.


Assuntos
Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Hanseníase/etiologia , Adulto , Brasil/epidemiologia , Estudos de Coortes , Dapsona/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Hanseníase/epidemiologia , Masculino , Pessoa de Meia-Idade , Minociclina/uso terapêutico , Ofloxacino/uso terapêutico , Recidiva , Estudos Retrospectivos , Rifampina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
8.
Neurobiol Dis ; 127: 591-604, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31028873

RESUMO

We tested a biomaterial-based approach to preserve the critical phrenic motor circuitry that controls diaphragm function by locally delivering minocycline hydrochloride (MH) following cervical spinal cord injury (SCI). MH is a clinically-available antibiotic and anti-inflammatory drug that targets a broad range of secondary injury mechanisms via its anti-inflammatory, anti-oxidant and anti-apoptotic properties. However, MH is only neuroprotective at high concentrations that cannot be achieved by systemic administration, which limits its clinical efficacy. We have developed a hydrogel-based MH delivery system that can be injected into the intrathecal space for local delivery of high concentrations of MH, without damaging spinal cord tissue. Implantation of MH hydrogel after unilateral level-C4/5 contusion SCI robustly preserved diaphragm function, as assessed by in vivo recordings of compound muscle action potential (CMAP) and electromyography (EMG) amplitudes. MH hydrogel also decreased lesion size and degeneration of cervical motor neuron somata, demonstrating its central neuroprotective effects within the injured cervical spinal cord. Furthermore, MH hydrogel significantly preserved diaphragm innervation by the axons of phrenic motor neurons (PhMNs), as assessed by both detailed neuromuscular junction (NMJ) morphological analysis and retrograde PhMN labeling from the diaphragm using cholera toxin B (CTB). In conclusion, our findings demonstrate that local MH hydrogel delivery to the injured cervical spinal cord is effective in preserving respiratory function after SCI by protecting the important neural circuitry that controls diaphragm activation.


Assuntos
Medula Cervical/lesões , Hidrogéis/uso terapêutico , Minociclina/uso terapêutico , Rede Nervosa/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Medula Cervical/efeitos dos fármacos , Medula Cervical/fisiopatologia , Diafragma/efeitos dos fármacos , Diafragma/fisiopatologia , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Feminino , Hidrogéis/administração & dosagem , Minociclina/administração & dosagem , Rede Nervosa/fisiopatologia , Fármacos Neuroprotetores/administração & dosagem , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Respiração/efeitos dos fármacos , Traumatismos da Medula Espinal/fisiopatologia
9.
Dermatol Ther ; 32(4): e12945, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31012213

RESUMO

Hailey-Hailey disease is a hereditary blistering disorder characterized by episodic vesicles, pustules, erosions, and maceration mainly in intertriginous areas with generalized eruptions encountered rarely. We present a case of generalized HHD with keratotic papules over flexural areas along with its dermoscopic features; treated successfully with minocycline alone.


Assuntos
Antibacterianos/uso terapêutico , Minociclina/uso terapêutico , Pênfigo Familiar Benigno/tratamento farmacológico , Dermoscopia , Feminino , Humanos , Pessoa de Meia-Idade , Pênfigo Familiar Benigno/patologia , Resultado do Tratamento
10.
Int J STD AIDS ; 30(5): 512-514, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30999836

RESUMO

Mycoplasma genitalium (MG) infection is a sexually transmitted infection that causes up to 25% of nongonococcal urethritis (NGU). MG strains carrying genetic markers of antimicrobial resistance that may affect treatment outcomes are increasingly recognized as a public health concern. We present two cases of persistent MG NGU with strains carrying both macrolide and quinolone resistance-associated mutations that were eradicated successfully by an extended course of minocycline.


Assuntos
Antibacterianos/uso terapêutico , Disuria/etiologia , Minociclina/uso terapêutico , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma genitalium/isolamento & purificação , Uretrite/etiologia , Adulto , Homossexualidade Masculina , Humanos , Masculino , Infecções por Mycoplasma/diagnóstico , Mycoplasma genitalium/efeitos dos fármacos , Resultado do Tratamento
11.
Oral Health Prev Dent ; 17(2): 167-171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30968072

RESUMO

PURPOSE: To retrospectively evaluate the clinical outcomes of subgingival debridement (e.g. scaling and root planing, SRP) and application of either a chlorhexidine chip (PerioChip, PC) or Arestin (AR) minocycline microspheres in patients with chronic periodontitis during supportive periodontal treatment (SPT). MATERIALS AND METHODS: Patients diagnosed with moderate to severe chronic periodontitis who were treated with SRP and a slow-release device during SPT were evaluated (total n = 53; n = 37 received PC, n = 16 received AR). Clinical measurements at baseline, 3, 6 and 12 months included changes in probing pocket depth (PD), bleeding on probing (BOP) and clinical attachment level (CAL). RESULTS: Both treatments led to a reduction in PD and gain of CAL. AR showed higher improvements in pockets of ≥7 mm compared with PC. In contrast, PC was more effective in 5-6 mm PD. At one year following treatment, both treatments reduced the need-for-surgery index (95% to 100%) of the sites at baseline to 30% for AR and 42% for PC, with no differences between PC and AR. CONCLUSIONS: In patients enrolled in SPT, the use of both PC and AR in conjunction with subgingival mechanical debridement represents an effective treatment modality for improving the clinical outcomes and reducing the need for surgery.


Assuntos
Antibacterianos/uso terapêutico , Anti-Infecciosos Locais/uso terapêutico , Clorexidina/análogos & derivados , Periodontite Crônica/terapia , Minociclina/uso terapêutico , Desbridamento Periodontal/métodos , Aplainamento Radicular/métodos , Idoso , Clorexidina/uso terapêutico , Raspagem Dentária/métodos , Feminino , Humanos , Masculino , Microesferas , Pessoa de Meia-Idade , Perda da Inserção Periodontal , Índice Periodontal , Bolsa Periodontal , Estudos Retrospectivos
12.
J Drugs Dermatol ; 18(3): 240-244, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30909327

RESUMO

Oral antibiotics are well established treatments for acne vulgaris but are associated with undesirable side effects. Topical antibiotics offer an improved safety profile but have led to an alarming rise in worldwide P. acnes resistance. Fortunately, a new class of topical minocycline products has been developed for the treatment of acne and rosacea that decreases the risk for antibiotic resistance while maintaining safety and efficacy. Recent clinical studies have demonstrated that a hydrophilic minocycline gel (BPX-01) and a lipophilic minocycline foam (FMX101) both reduced acne lesion counts with negligible systemic absorption. Head-to-head studies have yet to be completed, but the hydrophilic gel studies reported greater treatment efficacy than the lipophilic foam studies. J Drugs Dermatol. 2019;18(3):240-244.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/farmacologia , Minociclina/farmacologia , Propionibacterium acnes/efeitos dos fármacos , Acne Vulgar/microbiologia , Acne Vulgar/patologia , Administração Cutânea , Antibacterianos/uso terapêutico , Ensaios Clínicos como Assunto , Farmacorresistência Bacteriana , Humanos , Minociclina/uso terapêutico , Pele/efeitos dos fármacos , Pele/patologia , Resultado do Tratamento
13.
J Am Acad Dermatol ; 81(2): 456-462, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30905802

RESUMO

BACKGROUND: Cycline antibiotics (CAs) are commonly used to treat acne, blepharitis, and dry eye syndrome. Prescribers or patients may hesitate to use Cas because they may increase the risk of pseudotumor cerebri syndrome (PTCS). OBJECTIVE: We sought to assess whether CA use is associated with an increased risk of PTCS or papilledema and whether the risk depends upon dosage or duration of CA intake. METHODS: We studied patients 12 to 65 years of age who were diagnosed with acne, blepharitis, or dry eye syndrome, who were enrolled in a nationwide managed care network between January 1, 2001 and December 31, 2015, and who had no preexisting diagnosis of papilledema or PTCS. Multivariable Cox regression modeling was used to assess the risk of developing papilledema or PTCS from exposure to CAs. RESULTS: Among the 728,811 eligible enrollees (mean age, 34.7 years; 72% female), 42.0% filled ≥1 CA prescription. Of the 305,823 CA users, 170 (0.06%) were diagnosed with papilledema or PTCS. By comparison, of the 57.0% with no record of CA use, 121 (0.03%) were diagnosed with papilledema or PTCS (P < .0001). In the unadjusted model, every additional year of CA use was associated with a 70% (doxycycline: hazard ratio, 1.70 [95% confidence interval 0.98-2.97]; P = .06) or 91% (minocycline: hazard ratio, 1.91 [95% confidence interval 1.11-3.29]; P = .02) increased hazard of papilledema/PTCS relative to nonusers of CAs. After adjustment for confounders, the increased hazard of PTCS/papilledema with CA use was no longer statistically significant (P = .06, doxycycline; P = .08, minocycline). LIMITATIONS: This study relies on claims data, which lack clinical data. CONCLUSION: This study offers some evidence that CAs may increase the risk of PTCS/papilledema. However, after accounting for confounding factors in our multivariable models, we found no statistically significant association between CA use and the development of PTCS. Moreover, there was no dose-response effect whereby greater CA use was associated with a higher PTCS risk.


Assuntos
Antibacterianos/uso terapêutico , Doxiciclina/uso terapêutico , Minociclina/uso terapêutico , Papiledema/epidemiologia , Pseudotumor Cerebral/epidemiologia , Acne Vulgar/tratamento farmacológico , Demandas Administrativas em Assistência à Saúde , Adolescente , Adulto , Antibacterianos/administração & dosagem , Blefarite/tratamento farmacológico , Doxiciclina/administração & dosagem , Síndromes do Olho Seco/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minociclina/administração & dosagem , Adulto Jovem
15.
Asian J Psychiatr ; 40: 100-102, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30776665

RESUMO

Preclinical evidence shows that the minocycline and N-acetylcysteine (NAC) combination synergistically improved cognition. Meta-analyses of randomized controlled trials (RCTs) with minocycline and NAC have shown some efficacy signal for positive, cognitive, and negative symptoms of schizophrenia. Hence, the combination may be more effective than either medication alone. The objective of this article is to highlight the potential role of the minocycline-NAC combination for the treatment of schizophrenia. The antipsychotic-minocycline-NAC combination is promising and has the potential to concurrently treat positive, cognitive, and primary negative symptoms. RCTs are warranted with the minocycline-NAC combination to address the unmet clinical need in schizophrenia.


Assuntos
Acetilcisteína/uso terapêutico , Antibacterianos/uso terapêutico , Antipsicóticos/uso terapêutico , Depuradores de Radicais Livres/uso terapêutico , Minociclina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Animais , Quimioterapia Combinada , Humanos , Esquizofrenia/fisiopatologia
16.
J Neuroinflammation ; 16(1): 6, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30626393

RESUMO

BACKGROUND: Altered neuronal connectivity in peri-infarct tissue is an important contributor to both the spontaneous recovery of neurological function that commonly develops after stroke and improvements in recovery that have been induced by experimental treatments in animal models. Microglia and astrocytes are primary determinants of the environment in peri-infarct tissue and hence strongly influence the potential for neuronal plasticity. However, the specific roles of these cells and the timing of critical changes in their function are not well understood. Minocycline can protect against ischemic damage and promote recovery. These effects are usually attributed, at least partially, to the ability of this drug to suppress microglial activation. This study tested the ability of minocycline treatment early after stroke to modify reactive responses in microglia and astrocytes and improve recovery. METHODS: Stroke was induced by photothrombosis in the forelimb sensorimotor cortex of Sprague-Dawley rats. Minocycline was administered for 2 days after stroke induction and the effects on forelimb function assessed up to 28 days. The responses of peri-infarct Iba1-positive cells and astrocytes were evaluated using immunohistochemistry and Western blots. RESULTS: Initial characterization showed that the numbers of Iba1-positive microglia and macrophages decreased in peri-infarct tissue at 24 h then increased markedly over the next few days. Morphological changes characteristic of activation were readily apparent by 3 h and increased by 24 h. Minocycline treatment improved the rate of recovery of motor function as measured by a forelimb placing test but did not alter infarct volume. At 3 days, there were only minor effects on core features of peri-infarct microglial reactivity including the morphological changes and increased density of Iba1-positive cells. The treatment caused a decrease of 57% in the small subpopulation of cells that expressed CD68, a marker of phagocytosis. At 7 days, the expression of glial fibrillary acidic protein and vimentin was markedly increased by minocycline treatment, indicating enhanced reactive astrogliosis. CONCLUSIONS: Early post-stroke treatment with minocycline improved recovery but had little effect on key features of microglial activation. Both the decrease in CD68-positive cells and the increased activation of astrogliosis could influence neuronal plasticity and contribute to the improved recovery.


Assuntos
Astrócitos/efeitos dos fármacos , Infarto Encefálico , Microglia/efeitos dos fármacos , Minociclina/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/complicações , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/etiologia , Infarto Encefálico/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Membro Anterior/fisiopatologia , Trombose Intracraniana/complicações , Masculino , Proteínas dos Microfilamentos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , Fatores de Tempo
18.
Nano Lett ; 19(2): 829-838, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30605619

RESUMO

Spinal cord injury (SCI) routinely causes the immediate loss and disruption of neurons followed by complicated secondary injuries, including inflammation, oxidative stress, and dense glial scar formation. Inhibitory factors in the lesion scar and poor intrinsic neural regeneration capacity restrict functional recovery after injury. Minocycline, which has neuroprotective activity, can alleviate secondary injury, but the long-term administration of this drug may cause toxicity. Polysialic acid (PSA) is a large cell-surface carbohydrate that is critical for central nervous system development and is capable of promoting precursor cell migration, axon path finding, and synaptic remodeling; thus, PSA plays a vital role in tissue repair and regeneration. Here, we developed a PSA-based minocycline-loaded nanodrug delivery system (PSM) for the synergistic therapy of spinal cord injury. The prepared PSM exerted marked anti-inflammatory and neuroprotective activities both in vitro and in vivo. The administration of PSM could significantly protect neurons and myelin sheaths from damage, reduce the formation of glial scar, recruit endogenous neural stem cells to the lesion site, and promote the regeneration of neurons and the extension of long axons throughout the glial scar, thereby largely improving the locomotor function of SCI rats and exerting a superior therapeutic effect. The findings might provide a novel strategy for SCI synergistic therapy and the utilization of PSA in other central nervous system diseases.


Assuntos
Antibacterianos/uso terapêutico , Portadores de Fármacos/uso terapêutico , Minociclina/uso terapêutico , Regeneração Nervosa/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Ácidos Siálicos/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Micelas , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia
19.
J Dent Res ; 98(3): 288-295, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30626263

RESUMO

The purpose of this study was to determine the clinical, microbial, and radiographic effects of local minocycline combined with surgical treatment of peri-implantitis. Fifty patients with peri-implantitis were recruited, and surgical treatment with the local application of either minocycline or placebo ointment was performed. The application of minocycline was repeated with supragingival debridement at 1, 3, and 6 mo postoperatively. Plaque index, gingival index (GI), probing pocket depth (PPD), and bleeding/suppuration on probing were measured at baseline and 1-, 3-, and 6-mo evaluations. The change in supporting bone level (SBL) measured with cone beam computed tomography was analyzed between baseline and 6 mo. Microbial analysis was performed with real-time polymerase chain reaction. Both groups exhibited improvements in clinical and radiographic measurements after surgical treatment. There was a significant difference in the changes of mean PPD between the test and control groups (2.68 ± 1.73 and 1.55 ± 1.86 mm, respectively, P = 0.039). The changes of mean GI and SBL differed significantly between the groups (ΔGI: 0.83 ± 0.60 and 0.40 ± 0.68; ΔSBL: 0.72 ± 0.56 and 0.31 ± 0.49 mm, respectively, P = 0.026 and 0.014). Treatment success rates (defined as PPD <5 mm, absence of bleeding/suppuration on probing, and no further bone loss) were 66.7% and 36.3% in the test and control groups, respectively. The count of red complex bacteria tended to decrease in both groups until 6 mo; however, no significant intergroup difference was found. None of the patients in the test group carried Porphyromonas gingivalis or Tannerella forsythia at 6 mo. These findings indicate that the repeated local delivery of minocycline combined with surgical treatment provides significant benefits in terms of clinical parameters and radiographic bone fill, with a higher treatment success rate in the short healing period (cris.nih.go.kr KCT0002844).


Assuntos
Antibacterianos/uso terapêutico , Implantes Dentários , Minociclina/uso terapêutico , Peri-Implantite/cirurgia , Desbridamento , Índice de Placa Dentária , Humanos , Peri-Implantite/tratamento farmacológico , Índice Periodontal
20.
Clin Microbiol Infect ; 25(4): 489-495, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29933049

RESUMO

OBJECTIVES: Nocardia, a Gram-positive bacterium, is responsible for rare and severe infections. Accurate microbiological data are essential to guide antibiotic treatment. Our primary objective was to describe species identification and results of antimicrobial susceptibility testing (AST) for Nocardia isolates analysed over a 6-year period. Secondary objectives were to study temporal trends in species distribution and AST results. METHODS: We retrospectively analysed results from Nocardia isolates sent between January 2010 and December 2015 to a French laboratory dedicated to Nocardia (Observatoire Français des Nocardioses). Species identification was obtained by amplification and sequencing of a 600-bp fragment of the 16S rRNA gene (for all isolates) and of hsp65 (when required). AST was performed using disk diffusion. RESULTS: We included 793 Nocardia isolates, mostly from the lungs (53.8%). The most frequent species were Nocardia farcinica (20.2%), Nocardia abscessus complex (19.9%) and Nocardia nova complex (19.5%). The proportion of N. farcinica increased significantly over time from 13% in 2010 to 27.6% in 2014. Linezolid, amikacin, trimethoprim-sulfamethoxazole, minocycline and imipenem were the most frequently identified active antibiotics with, respectively, 0% (0/734), 2.9% (21/730), 5.4% (40/734), 9.4% (69/734) and 19.5% (143/732) of isolates not susceptible. Nocardia farcinica was frequently not susceptible to cefotaxime (118/148, 79.7% of the isolates), but only about 5% of Nocardia cyriacigeorgica and N. abscessus complex isolates were not susceptible to cefotaxime. CONCLUSIONS: In this first epidemiological study of Nocardia isolated from human samples in France, N. farcinica was the species most frequently identified and its prevalence increased over time.


Assuntos
Antibacterianos/uso terapêutico , Nocardiose/tratamento farmacológico , Nocardiose/epidemiologia , Nocardia/classificação , Nocardia/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amicacina/uso terapêutico , Proteínas de Bactérias/genética , Criança , Pré-Escolar , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Feminino , França/epidemiologia , Humanos , Imipenem/uso terapêutico , Linezolida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Minociclina/uso terapêutico , Nocardia/genética , Nocardiose/microbiologia , RNA Ribossômico 16S/genética , Estudos Retrospectivos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adulto Jovem
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