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1.
JAMA Surg ; 159(6): 606-614, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38506889

RESUMO

Importance: Surgical site infections (SSIs)-especially anastomotic dehiscence-are major contributors to morbidity and mortality after rectal resection. The role of mechanical and oral antibiotics bowel preparation (MOABP) in preventing complications of rectal resection is currently disputed. Objective: To assess whether MOABP reduces overall complications and SSIs after elective rectal resection compared with mechanical bowel preparation (MBP) plus placebo. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at 3 university hospitals in Finland between March 18, 2020, and October 10, 2022. Patients aged 18 years and older undergoing elective resection with primary anastomosis of a rectal tumor 15 cm or less from the anal verge on magnetic resonance imaging were eligible for inclusion. Outcomes were analyzed using a modified intention-to-treat principle, which included all patients who were randomly allocated to and underwent elective rectal resection with an anastomosis. Interventions: Patients were stratified according to tumor distance from the anal verge and neoadjuvant treatment given and randomized in a 1:1 ratio to receive MOABP with an oral regimen of neomycin and metronidazole (n = 277) or MBP plus matching placebo tablets (n = 288). All study medications were taken the day before surgery, and all patients received intravenous antibiotics approximately 30 minutes before surgery. Main Outcomes and Measures: The primary outcome was overall cumulative postoperative complications measured using the Comprehensive Complication Index. Key secondary outcomes were SSI and anastomotic dehiscence within 30 days after surgery. Results: In all, 565 patients were included in the analysis, with 288 in the MBP plus placebo group (median [IQR] age, 69 [62-74] years; 190 males [66.0%]) and 277 in the MOABP group (median [IQR] age, 70 [62-75] years; 158 males [57.0%]). Patients in the MOABP group experienced fewer overall postoperative complications (median [IQR] Comprehensive Complication Index, 0 [0-8.66] vs 8.66 [0-20.92]; Wilcoxon effect size, 0.146; P < .001), fewer SSIs (23 patients [8.3%] vs 48 patients [16.7%]; odds ratio, 0.45 [95% CI, 0.27-0.77]), and fewer anastomotic dehiscences (16 patients [5.8%] vs 39 patients [13.5%]; odds ratio, 0.39 [95% CI, 0.21-0.72]) compared with patients in the MBP plus placebo group. Conclusions and Relevance: Findings of this randomized clinical trial indicate that MOABP reduced overall postoperative complications as well as rates of SSIs and anastomotic dehiscences in patients undergoing elective rectal resection compared with MBP plus placebo. Based on these findings, MOABP should be considered as standard treatment in patients undergoing elective rectal resection. Trial Registration: ClinicalTrials.gov Identifier: NCT04281667.


Assuntos
Antibacterianos , Neoplasias Retais , Infecção da Ferida Cirúrgica , Humanos , Masculino , Feminino , Método Duplo-Cego , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Neoplasias Retais/cirurgia , Administração Oral , Antibioticoprofilaxia , Cuidados Pré-Operatórios/métodos , Neomicina/administração & dosagem , Neomicina/uso terapêutico , Catárticos/administração & dosagem , Metronidazol/administração & dosagem , Metronidazol/uso terapêutico , Protectomia/efeitos adversos , Reto/cirurgia , Deiscência da Ferida Operatória/prevenção & controle , Deiscência da Ferida Operatória/etiologia , Procedimentos Cirúrgicos Eletivos/efeitos adversos
2.
Eur J Dermatol ; 31(6): 741-743, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34911671

RESUMO

BACKGROUND: A patient received enoxaparin sodium subcutaneous injections for prophylaxis after surgery and developed inflammatory skin reactions on injection sites on Day 5 after the first administration. Patch test was performed with baseline series and low-molecular-weight heparins (LMWHs) at different concentrations and showed positive reactions to neomycin and LMWHs. Cross-reactivity between neomycin and LMWHs was suspected due to similar structure. OBJECTIVES: To establish the evidence of possible cross reaction between neomycin and LMWHs by patch testing. MATERIALS & METHODS: Patch testing of 12 individual controls with a history of neomycin contact allergy was performed. RESULTS: Positive patch test reactions to enoxaparin sodium, tinzaparin sodium, and neomycin sulphate were reported in the patients. None of the controls reacted to LMWHs. CONCLUSION: There was no proof of cross reaction between neomycin and LMWHs in this study, suggesting that the simultaneous reaction may be a coincidence. Since the number of individuals studied was low, allergy to LMWHs following injection in individuals with a history of neomycin allergy should be further investigated.


Assuntos
Antibacterianos/efeitos adversos , Anticoagulantes/efeitos adversos , Reações Cruzadas , Toxidermias/etiologia , Enoxaparina/análogos & derivados , Neomicina/efeitos adversos , Idoso , Antibacterianos/administração & dosagem , Anticoagulantes/administração & dosagem , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Humanos , Injeções Subcutâneas , Masculino , Neomicina/administração & dosagem , Testes do Emplastro
4.
BJS Open ; 5(2)2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33839753

RESUMO

BACKGROUND: In retrospective series, mechanical and oral antibiotic bowel preparation (MOABP) has been reported to reduce surgical-site infections (SSIs) after colectomy compared with no bowel preparation (NBP). METHOD: This was a subgroup analysis of a multicentre randomized trial that included patients scheduled for elective colectomy. The MOABP group underwent mechanical bowel preparation, and took 2 g neomycin and 2 g metronidazole orally during the day before surgery. The NBP group did not undergo bowel preparation. Patients were categorized according to the side of resection (right versus left colectomy), and these subgroups compared for postoperative outcomes. RESULTS: Among 217 patients undergoing right colectomy (106 in MOABP and 111 in NBP group), SSI was detected in seven (7 per cent) and 10 (9 per cent) patients (odds ratio (OR) 0.71, 95 per cent c.i. 0.26 to 1.95; P = 0.510), anastomotic dehiscence in two (2 per cent) and two (2 per cent) patients (OR 1.05, 0.15 to 7.58; P = 1.000), and the mean(s.d.) Comprehensive Complication Index (CCI) score was 9.4(12.9) and 10.5(18.0) (mean difference -1.09; 95 per cent c.i. -5.29 to 3.11; P = 0.608) in the MOABP and NBP groups respectively. Among 164 patients undergoing left colectomy (84 in MOABP and 80 in NBP group), SSI was detected in five (6 per cent) and eight (10 per cent) patients (OR 0.57, 0.18 to 1.82; P = 0.338), anastomotic dehiscence in four (5 per cent) and five (6 per cent) patients (OR 0.75, 0.19 to 2.90; P = 0.742), and the CCI score was 10.2(13.1) and 6.5(11.0) (mean difference 3.68, -0.06 to 7.42; P = 0.053) in the MOABP and NBP groups respectively. CONCLUSIONS: MOABP did not decrease the rate of SSI or complications in patients undergoing either right or left colectomy compared with NBP.


Assuntos
Antibacterianos/administração & dosagem , Catárticos/administração & dosagem , Colectomia/métodos , Infecção da Ferida Cirúrgica/prevenção & controle , Administração Oral , Idoso , Antibioticoprofilaxia/métodos , Procedimentos Cirúrgicos Eletivos , Feminino , Finlândia , Humanos , Masculino , Metronidazol/administração & dosagem , Pessoa de Meia-Idade , Neomicina/administração & dosagem , Cuidados Pré-Operatórios/métodos , Método Simples-Cego
5.
Clin Res Hepatol Gastroenterol ; 44(3): 356-367, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31420296

RESUMO

BACKGROUND: The gram-negative bacteria secreted endotoxin, Lipopolysaccharide (LPS), plays important roles in the formation and recurrence of hepatolithiasis and chronic biliary inflammation in patients of Southeast Asia. We aimed to elucidate the anti-inflammatory effect and mechanism of local antibiotics irrigation on chronic proliferative cholangitis (CPC) and hepatolithiasis. METHODS: Escherichia coli was injected into rabbit bile ducts to induce CPC. Rabbits were divided into sham operation (SO), povidone-iodine, Metronidazole plus chlorhexidine, ofloxacin, furacillin, Neosporin® G.U., and CPC groups. Local irrigation was performed for 28 days after CPC was established. Residual E. coli and LPS, and the expression of MCP-1, CD14, COX-2, VEGF, IL-6, NF-κB, TNF-α, Fas, TGF-ß1, α-SMA, Collagen-I, ß-glucuronidase, PKC, C-myc, and Mucin 5AC were assessed in bile duct tissues. RESULTS: The residual E. coli and LPS, and expression of MCP-1, CD14, COX-2, IL-6, NF-κB, TNF-α, Fas, TGF-ß1, α-SMA, ß-glucuronidase, PKC, C-myc, and Mucin 5AC in the SO, povidone-iodine, Metronidazole plus chlorhexidine, ofloxacin, and Neosporin® G.U. groups were significantly lower than those in the furacillin and CPC groups (P<0.05). VEGF and Collagen-I levels in the SO, povidone-iodine, metronidazole plus chlorhexidine, and ofloxacin groups were significantly lower than those in the furacillin, Neosporin® G.U., and CPC groups (P<0.05). CONCLUSIONS: LPS affects the pathophysiology of E. coli caused chronic proliferative cholangitis and hepatolithiasis recurrence. Local antibiotics irrigation could prevent chronic proliferative cholangitis and stones formation by decreasing LPS-induced proinflammatory and profibrotic cytokines release. Povidone iodine, metronidazole plus chlorhexidine, and ofloxacin were more effective than Neosporin® G.U. and furacillin.


Assuntos
Antibacterianos/administração & dosagem , Colangite/prevenção & controle , Infecções por Escherichia coli/tratamento farmacológico , Litíase/prevenção & controle , Hepatopatias/prevenção & controle , Animais , Bacitracina/administração & dosagem , Clorexidina/administração & dosagem , Colangite/metabolismo , Colangite/microbiologia , Doença Crônica , Colágeno Tipo I/sangue , Citocinas/sangue , Combinação de Medicamentos , Escherichia coli , Infecções por Escherichia coli/metabolismo , Lipopolissacarídeos , Litíase/metabolismo , Litíase/microbiologia , Hepatopatias/metabolismo , Hepatopatias/microbiologia , Metronidazol/administração & dosagem , Neomicina/administração & dosagem , Nitrofurazona/administração & dosagem , Ofloxacino/administração & dosagem , Polimixina B/administração & dosagem , Povidona-Iodo/administração & dosagem , Coelhos , Irrigação Terapêutica/métodos , Fator A de Crescimento do Endotélio Vascular/sangue
6.
N Z Vet J ; 68(2): 126-133, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31608795

RESUMO

Case history: Gradual onset of ocular opacity was observed in three gold-striped geckos (Woodworthia chrysosiretica), and five Pacific geckos (Dactylocnemis pacificus) held in two adjacent terrariums in a zoological institution located in the North Island of New Zealand. Ultraviolet light and heat had been provided for the previous 3-4 years by a fluorescent bulb, but in the last 4 weeks of winter a ceramic heat bulb had been added, situated 10 cm above the upper mesh of the cageClinical findings: All eight geckos presented with mostly bilateral lesions of varying severity confined to the central or upper quadrant of the spectacles. These lesions ranged from variable areas of opacity within the stroma of the spectacle to similarly distributed ulcers of the surface epithelium of both spectacles. The spectacle lesions in the Pacific geckos responded well to treatment with topical combined antimicrobial therapy, within 18-29 days. The gold-striped geckos suffered complications including dysecdysis, severe spectacle ulceration and perforation, mycotic spectaculitis, and widespread mycotic dermatitis resulting in death or leading to euthanasia.Pathological findings: In the three gold-striped geckos, there were extensive areas of deep ulceration and replacement of the spectacle with a thick serocellular crust containing large numbers of fungal elements. The affected areas of the stroma were expanded by large deposits of proteinaceous and mucinous material, pyknotic cellular debris and moderate numbers of heterophils and macrophages as well as infiltrating fungal hyphae.Diagnosis: Mycotic spectaculitis with ulceration and perforation, and disseminated mycotic dermatitis likely secondary to thermal burns.Clinical relevance: This is the first report of thermal burns of the spectacle in any reptile. There was species variation in the burn severity with gold-striped geckos showing more severe lesions, possibly due to a mix of behavioural and anatomical factors. The thermal burns to the spectacles in three cases were complicated by delayed healing, perforation, dysecdysis and severe mycotic infection.


Assuntos
Queimaduras/veterinária , Oftalmopatias/veterinária , Calefação/instrumentação , Abrigo para Animais , Lagartos , Animais , Animais de Zoológico , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Bacitracina/administração & dosagem , Bacitracina/uso terapêutico , Queimaduras/etiologia , Combinação de Medicamentos , Oftalmopatias/etiologia , Oftalmopatias/patologia , Meloxicam/uso terapêutico , Neomicina/administração & dosagem , Neomicina/uso terapêutico , Polimixina B/administração & dosagem , Polimixina B/uso terapêutico , Raios Ultravioleta
7.
J Pharm Biomed Anal ; 164: 630-635, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30471635

RESUMO

This work proposes a new method for the in vitro evaluation of the effect of UV irradiation on the production of free radicals and other reactive species during the photodecomposition of drugs. The method was based on the UV irradiation of antibiotics molecules to generate excited states that undergo to homolytic bond cleavages. These reactive species can be detected by their ability to oxidize the luminol, producing the electronically excited aminophtalate, which decays to the ground state releasing electromagnetic radiation in the visible zone of the spectrum. This method was applied to penicillin G, nafcillin, azlocillin and neomycin dissolved in water. It was found that the intensity of the luminol chemiluminescence emission (CL) was proportional to the concentration and dependent on the molecular structure of these drugs. Under the optimized conditions, it was found that penicillin and azlocillin were the most susceptible to photodegradation, while neomycin sulfate was the less affected by the UV light. It was observed that the addition to the antibiotics dissolutions of a hydro-alcoholic extract of petals of calyxes of Roselle reduced the CL intensity, indicating that the extract was able to scavenge the free radicals in the irradiated drugs. This result suggest that its addition to the antibiotics can help in the protection against the radicals formed during the exposition to solar light of patients treated with topic similar antibiotics.


Assuntos
Antibacterianos/efeitos da radiação , Sequestradores de Radicais Livres/farmacologia , Radicais Livres/antagonistas & inibidores , Hibiscus/química , Medições Luminescentes/métodos , Extratos Vegetais/farmacologia , Administração Tópica , Antibacterianos/administração & dosagem , Antibacterianos/química , Azlocilina/administração & dosagem , Azlocilina/química , Azlocilina/efeitos da radiação , Dermatite Fototóxica/etiologia , Dermatite Fototóxica/prevenção & controle , Flores/química , Radicais Livres/química , Radicais Livres/toxicidade , Substâncias Luminescentes/química , Luminol/química , Neomicina/administração & dosagem , Neomicina/química , Neomicina/efeitos da radiação , Oxirredução , Penicilinas/administração & dosagem , Penicilinas/química , Penicilinas/efeitos da radiação , Luz Solar/efeitos adversos , Raios Ultravioleta/efeitos adversos
8.
Braz Dent J ; 29(6): 555-561, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30517478

RESUMO

Bleaching gel containing hydrogen peroxide (H2O2) cause damages in pulp tissue. This study investigated the action of a topical anti-inflammatory, the Otosporin®, in rats' bleached teeth with the null hypothesis of which the Otosporin® is no able to minimize the pulp inflammation that bleaching gel generates. The rat's molars were divided into groups: BLE: bleached (35% H2O2 concentration /single application of 30 min); BLE-O: bleached followed by Otosporin® (10 min); and control: placebo gel. In the second day after dental bleaching, the rats were killed, and the jaws were processed for hematoxylin-eosin and immunohistochemistry analysis for tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-17. The data collected were subjected to Kruskal-Wallis and Dunn statistical tests with at a 5% level of significance (p<0.05). The BLE group had moderate to strong inflammation in the occlusal third of the coronary pulp, with necrotic areas; and BLE-O, mild inflammation (p<0.05). There was a significant difference in the occlusal and middle thirds of the coronary pulp between the BLE with BLE-O and control groups (p<0.05). There was no difference in the cervical third (p>0.05). The BLE group had a high immunoexpression of TNF-α than BLE-O and control groups (p<0.05), with moderate and mild immunoexpression, respectively. Regarding IL-6 and IL-17, the BLE group had higher immunoexpression than control (p<0.05); the BLE-O was similar to the control (p>0.05). The topical anti-inflammatory Otosporin® can reduce pulp inflammation after dental bleaching in the rat teeth.


Assuntos
Hidrocortisona/farmacologia , Neomicina/farmacologia , Polimixina B/farmacologia , Pulpite/induzido quimicamente , Pulpite/prevenção & controle , Clareamento Dental/efeitos adversos , Administração Tópica , Animais , Biomarcadores/análise , Combinação de Medicamentos , Hidrocortisona/administração & dosagem , Peróxido de Hidrogênio/efeitos adversos , Imuno-Histoquímica , Interleucina-17/análise , Interleucina-6/análise , Neomicina/administração & dosagem , Polimixina B/administração & dosagem , Ratos , Fator de Necrose Tumoral alfa/análise
9.
Medicine (Baltimore) ; 97(36): e12288, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30200175

RESUMO

We conducted this study to compare the effectiveness of combined oral nonabsorbable and intravenous antibiotics versus intravenous antibiotics alone in reducing the incidence of surgical site infections following elective colorectal surgery in pediatric patients.Between January 2010 and December 2016, patients from 0 to 14 who underwent elective colorectal surgery were retrospectively analyzed. Based on intravenous antibiotics with and without oral antibiotics, the patients were grouped as OA group (combination of oral nonabsorbable and intravenous antibiotics) or A group (the intravenous antibiotics alone). Neomycin combined with erythromycin was used in OA group. The data collected included demographic data, diagnosis, procedure being performed, operative time, time to first stool, time to removal of the nasogastric tube, time to full enteral feeds, hospital length of stay, and prophylactic antibiotics (days ±â€Šstandard deviation). The main outcome was the rate of postoperative infectious complications, such as wound infection, anastomotic leak, and intra-abdominal abscess formation.A total of 564 children who underwent elective colorectal surgery were enrolled which consist of OA group (combination of oral nonabsorbable and intravenous antibiotics) and A group (the intravenous antibiotics alone), the number of the former one was 216 and the latter one was 348. Postoperative complications were similar in both groups of patients. In the OA group, we observed 5 anastomotic leak, 6 wound infections, and 5 intra-abdominal abscesses. In the A group, we observed 13 anastomotic leak, 9 wound infections, and 11 intra-abdominal abscesses. Analysis with Fisher exact test revealed no statistically significant difference in the incidence of wound infection, anastomotic leak, and intra-abdominal abscess between the 2 groups.The results of our study suggest that omitting oral nonabsorbable antibiotics before elective colorectal surgery in infants and children carries no increased risk of infectious or anastomotic complications.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Cirurgia Colorretal , Procedimentos Cirúrgicos Eletivos , Infecção da Ferida Cirúrgica/prevenção & controle , Administração Intravenosa , Administração Oral , Pré-Escolar , Eritromicina/administração & dosagem , Feminino , Seguimentos , Humanos , Incidência , Lactente , Masculino , Neomicina/administração & dosagem , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Resultado do Tratamento
10.
Biochem Biophys Res Commun ; 500(2): 110-116, 2018 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-29571735

RESUMO

In hearing loss induced by aminoglycoside antibiotics, the outer hair cells (OHCs) in the basal turn are always more susceptible than OHCs in the apical turn, while the underlying mechanisms remain unknown. In this study, we reported that NAPDH oxidase 2 (NOX2) played an important role in the OHCs damage preferentially in the basal turn. Normally, NOX2 was evenly expressed in OHCs among different turns, at a relatively low level. However, after neomycin treatment, NOX2 was dominantly induced in OHCs in the basal turn. In vivo and in vitro studies demonstrated that inhibition of NOX2 significantly alleviated neomycin-induced OHCs damages, as seen from both the cleaved caspase-3 and TUNEL staining. Moreover, gp91 ds-tat delivery and DHE staining results showed that NOX2-derived ROS was responsible for neomycin ototoxicity. Taken together, our study shows that regional up-expression of NOX2 and subsequent increase of ROS in OHCs of the basal turn is an important factor contributing to the vulnerability of OHCs there, which should shed light on the prevention of hearing loss induced by aminoglycoside antibiotics.


Assuntos
Células Ciliadas Auditivas Externas/metabolismo , Células Ciliadas Auditivas Externas/patologia , NADPH Oxidase 2/metabolismo , Neomicina/efeitos adversos , Regulação para Cima , Animais , Apoptose/efeitos dos fármacos , Células Ciliadas Auditivas Externas/efeitos dos fármacos , Perda Auditiva/patologia , NADPH Oxidase 2/antagonistas & inibidores , Neomicina/administração & dosagem , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/efeitos dos fármacos
11.
Otolaryngol Head Neck Surg ; 158(5): 917-922, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29460666

RESUMO

Objective Ciprofloxacin + dexamethasone ear drops have been associated with higher rates of tympanic membrane perforations than ofloxacin. This was thought to be an effect of the steroid; however, ciprofloxacin (sans steroid) has been found to be more toxic to tympanic membrane fibroblasts than ofloxacin in vitro. This study aimed to compare the effect of these agents on tympanic membrane healing in vivo. Study Design Controlled animal study. Setting Academic research laboratory. Methods Perforations were created in 54 rats with a carbon dioxide laser. Rats were randomized to 6 groups (9/group), with 1 ear receiving ofloxacin, ciprofloxacin, dexamethasone, ofloxacin + dexamethasone, ciprofloxacin + dexamethasone, or neomycin, and the contralateral ear receiving saline twice daily for 10 days. Healing was assessed over 40 days. Results Ofloxacin did not delay healing relative to saline. All other treatments delayed healing relative to ofloxacin at day 10 ( P < .0001). Dexamethasone and ofloxacin + dexamethasone delayed healing up to day 14 ( P < .0001). Neomycin and ciprofloxacin + dexamethasone further delayed healing up to day 28 ( P = .009) and day 35 ( P = .043), respectively. All eardrums healed by day 10 with ofloxacin, day 20 with ciprofloxacin, day 28 for dexamethasone, and day 35 for ofloxacin + dexamethasone. At day 40, 2 of 9 ciprofloxacin + dexamethasone-treated eardrums had not healed. All saline-treated eardrums in the ofloxacin, ciprofloxacin, dexamethasone, and ofloxacin + dexamethasone groups were healed by day 14, but this was delayed to day 20 in the ciprofloxacin + dexamethasone group ( P = .007). Conclusions Ototopical quinolones delay rat tympanic membrane healing in a drug-specific manner, with ciprofloxacin having a greater impact than ofloxacin. This effect is potentiated by steroids.


Assuntos
Antibacterianos/administração & dosagem , Ciprofloxacina/administração & dosagem , Glucocorticoides/administração & dosagem , Ofloxacino/administração & dosagem , Perfuração da Membrana Timpânica/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Dexametasona/administração & dosagem , Instilação de Medicamentos , Masculino , Neomicina/administração & dosagem , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
12.
J Nutr Biochem ; 56: 65-73, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29459310

RESUMO

Vitamin D, 25hydroxyvitamin D (25D), and 24,25dihydroxyvitamin D (24,25D) were measured before and after broad spectrum antibiotic (Abx) treatment for 2 wks. Abx treatments increased 25D and 24,25D levels suggesting that the microbiota or Abx were altering vitamin D metabolism. Increased 25D, but not 24,25D, following Abx treatments were found to be dependent on toll like receptor signaling. Conversely, the effects of Abx on 24,25D levels required that the vitamin D receptor (VDR) be expressed in tissues outside of the hematopoietic system (kidney) and not the immune system. Fibroblast growth factor (FGF)23 increased following Abx treatment and the effect of Abx treatment on FGF23 (like the effect on 24,25D) was not present in VDR knockout (KO) mice. The Abx mediated increase in 24,25D was due to changes to the endocrine regulation of vitamin D metabolism. Conversely, 25D levels went up with Abx treatment of the VDR KO mice. Host sensing of microbial signals regulates the levels of 25D in the host.


Assuntos
Antibacterianos/farmacologia , Fatores de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica , Microbiota , Vitamina D/metabolismo , 24,25-Di-Hidroxivitamina D 3/metabolismo , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Ampicilina/administração & dosagem , Animais , Feminino , Fator de Crescimento de Fibroblastos 23 , Ligantes , Masculino , Metronidazol/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neomicina/administração & dosagem , Receptores de Calcitriol/metabolismo , Transdução de Sinais , Receptores Toll-Like/metabolismo , Vancomicina/administração & dosagem , Vitamina D/análogos & derivados
13.
JCI Insight ; 3(4)2018 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-29467322

RESUMO

Adoptive T cell therapy (ACT) is a promising new modality for malignancies. Here, we report that adoptive T cell efficacy in tumor-bearing mice is significantly affected by differences in the native composition of the gut microbiome or treatment with antibiotics, or by heterologous fecal transfer. Depletion of bacteria with vancomycin decreased the rate of tumor growth in mice from The Jackson Laboratory receiving ACT, whereas treatment with neomycin and metronidazole had no effect, indicating the role of specific bacteria in host response. Vancomycin treatment induced an increase in systemic CD8α+ DCs, which sustained systemic adoptively transferred antitumor T cells in an IL-12-dependent manner. In subjects undergoing allogeneic hematopoietic cell transplantation, we found that oral vancomycin also increased IL-12 levels. Collectively, our findings demonstrate an important role played by the gut microbiota in the antitumor effectiveness of ACT and suggest potentially new avenues to improve response to ACT by altering the gut microbiota.


Assuntos
Células Dendríticas/imunologia , Microbioma Gastrointestinal/imunologia , Transplante de Células-Tronco Hematopoéticas , Interações entre Hospedeiro e Microrganismos/imunologia , Imunoterapia Adotiva/métodos , Interleucina-12/imunologia , Neoplasias/terapia , Adulto , Idoso , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/imunologia , Bactérias/isolamento & purificação , Antígenos CD8/imunologia , Antígenos CD8/metabolismo , Linhagem Celular Tumoral/transplante , Estudos de Coortes , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Transplante de Microbiota Fecal , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Humanos , Interleucina-12/antagonistas & inibidores , Interleucina-12/genética , Interleucina-12/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Neomicina/administração & dosagem , Neoplasias/imunologia , Neoplasias/microbiologia , Linfócitos T/imunologia , Linfócitos T/transplante , Resultado do Tratamento , Vancomicina/administração & dosagem
15.
Genet Mol Res ; 14(2): 5642-51, 2015 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-26125762

RESUMO

The intestinal microflora affects inflammation and immunity, not only locally at the mucosal level but also systemically, raising the question of whether the microflora affects inflammatory processes that contribute to cancer and its therapy. Prebiotics have also been found to play an antitumor role that is not limited to the gut. We investigated the antitumor roles of the intestinal microbiota using the Lewis lung cancer mouse model. In mice treated with cisplatin combined with ABX (an antibiotic cocktail of vancomycin, ampicillin, and neomycin), which can destroy the host commensal microflora, the tumor size was larger than in mice on a single treatment of cisplatin. Moreover, the survival rate of mice treated with cisplatin combined with ABX was significantly reduced. In contrast, mice treated with cisplatin combined with Lactobacillus bacteria had smaller tumors and an improved survival rate. Further study on gene expression indicated that ABX can partially impair the function of cisplatin by upregulating the expression of VEGFA and downregulating the expression of BAX and CDKN1B. The expression of IFN-γ, GZMB, and PRF1 in the CD8(+) T cells of these mice was reduced by ABX, indicating an immuno-enhancement role of commensal microbiota. Conversely, Lactobacillus co-treatment mice showed an enhanced antitumor response with upregulated IFN-γ, GZMB, and PRF1 expression. We conclude that the commensal microbiota contributes to the anti-lung cancer response and probiotics co-treatment can enhance the antigrowth and proapoptotic effects of cisplatin.


Assuntos
Inflamação/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Microbiota/efeitos dos fármacos , Probióticos/administração & dosagem , Ampicilina/administração & dosagem , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cisplatino/administração & dosagem , Modelos Animais de Doenças , Humanos , Inflamação/microbiologia , Lactobacillus/efeitos dos fármacos , Lactobacillus/patogenicidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/microbiologia , Camundongos , Neomicina/administração & dosagem , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Vancomicina/administração & dosagem
16.
J Cataract Refract Surg ; 41(4): 724-31, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25840297

RESUMO

PURPOSE: To compare the efficacy of 2 prophylaxis regimens before cataract surgery using topical antibiotics (1 hour before surgery versus the day before), both with povidone-iodine, with regard to reducing the preoperative conjunctival bacterial load. SETTING: Tertiary ophthalmic referral center, Munich, Germany. DESIGN: Prospective comparative case series. METHODS: Eyes were treated with topical antibiotics and their conjunctival sac flush irrigated using 10 mL of povidone-iodine 1.0%. All eyes were randomized to receive either 4 applications of topical 3500 IU/mL neomycin sulfate/6000 IU/mL polymyxin-B sulfate within 1 hour preoperatively (Group 1) or on the day before surgery (Group 2). Conjunctival specimens were obtained at 4 timepoints: T0C untreated fellow eye (control), T0 surgery eye (after antibiotic prophylaxis but before povidone-iodine irrigation), T1 after povidone-iodine, and T2 at the conclusion of surgery. All specimens were inoculated onto blood and chocolate-blood agar and into thioglycollate broth. RESULTS: One hundred thirty-three eyes of 133 consecutive patients were included (Group 1, 64 eyes; Group 2, 69 eyes). The antibiotic regimens were equally effective in reducing the aerobic and microaerophilic conjunctival flora (Group 1, P=.028; Group 2, P=.000), but had no significant effect on anaerobic bacteria (Group 1, P=.201; Group 2, P=.117). Flush irrigation of the conjunctival sac using 10.0 mL povidone-iodine 1.0% significantly decreased the conjunctival bacterial load in both groups. CONCLUSION: Topical neomycin/polymyxin-B was equally effective in reducing the conjunctival bacterial load whether given 1 day or 1 hour before surgery. The greatest effect was achieved by irrigating the conjunctival sac using povidone-iodine. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia , Implante de Lente Intraocular , Neomicina/administração & dosagem , Facoemulsificação , Polimixina B/administração & dosagem , Administração Tópica , Idoso , Idoso de 80 Anos ou mais , Bactérias/isolamento & purificação , Carga Bacteriana , Túnica Conjuntiva/microbiologia , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Povidona-Iodo/administração & dosagem , Estudos Prospectivos , Fatores de Tempo
17.
Pan Afr Med J ; 17: 237, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25170381

RESUMO

UNLABELLED: Cushing syndrome is a hormonal disorder caused by prolonged exposure of body tissue to cortisol. We report two cases of iatrogenic Cushing's syndrome in two Nigerian children following intranasal administration of aristobed-N (Betamethasone + Neomycin) given at a private hospital where the children presented with feature of adenoidal hypertrophy. Two months into treatment children were noticed to have developed clinical and laboratory features of iatrogenic Cushing's syndrome with critical adrenal suppression. Serum cortisol (at presentation): 1(st) patient: 12nmol/L (reference range 240-618), 2(nd) PATIENT: 1.69nmol/L. Serum cortisol (3 months after weaning off steroid): 343.27 nmol/L (within normal range for the first patient; second patient newly presented and has just begun steroid weaning off process. The serum cortisol level one month into weaninig off process was 128 nmol/L). Unsupervised topical steroid administration in children can cause adrenal suppression with clinical features of Cushing's syndrome.


Assuntos
Betametasona/efeitos adversos , Síndrome de Cushing/induzido quimicamente , Glucocorticoides/efeitos adversos , Hidrocortisona/sangue , Neomicina/efeitos adversos , Administração Intranasal , Betametasona/administração & dosagem , Combinação de Medicamentos , Glucocorticoides/administração & dosagem , Humanos , Doença Iatrogênica , Lactente , Masculino , Neomicina/administração & dosagem , Nigéria
19.
Otolaryngol Head Neck Surg ; 150(2): 282-4, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24270164

RESUMO

OBJECTIVES: (1) To determine the safety of using a commercially available suspension of polymyxin B, neomycin, and hydrocortisone (PNH) in tympanoplasty surgery. (2) To apply evidence-based medicine to tympanoplasty surgery when considering potential ototoxicity. STUDY DESIGN: Case series with chart review. SETTING: Tertiary otology practice, single surgeon. METHODS: Approval for this study was obtained from the St. Dominic-Jackson Memorial Hospital Institutional Review Board. Data were gathered on 272 consecutive type 1, underlay tympanoplasties for which both pre- and postoperative audiometric data were available over a 10-year period. In each surgery, gelatin sponge saturated in a commercially available PNH suspension was placed in the middle ear to support the graft. Patients ranged in age from 3 years to 79 years. Preoperative and postoperative bone conduction thresholds were measured at 500, 1000, 2000, 3000, and 4000 Hz. RESULTS: The average change in sensorineural hearing as measured by bone conduction thresholds was negligible, with a slight improvement in all frequencies tested except 4000 Hz. The changes by frequencies were as follows: 500 Hz (-1.624 dB), 1000 Hz (-1.399 dB), 2000 Hz (-0.975 dB), 3000 Hz (-0.596 dB), and 4000 Hz (+0.560 dB). The 5-frequency average change was -0.545 dB. CONCLUSIONS: The commonly used otic solution containing polymyxin B, neomycin, and hydrocortisone demonstrates no ototoxicity in tympanoplasty surgery and is safe to use in this setting.


Assuntos
Antibacterianos/administração & dosagem , Audição/efeitos dos fármacos , Neomicina/administração & dosagem , Polimixina B/administração & dosagem , Timpanoplastia , Adolescente , Adulto , Idoso , Limiar Auditivo , Condução Óssea/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
20.
Otolaryngol Head Neck Surg ; 150(1): 121-5, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24225176

RESUMO

OBJECTIVE: Determine how the astroglial cells of the peripheral and central nervous system transitional zone (PCTZ) react to sensorineural hearing loss using a mouse cochlear nerve model. STUDY DESIGN: Prospective, basic science. SETTING: Research laboratory. SUBJECTS AND METHODS: Neomycin was injected into the mouse inner ear to cause chemically induced hearing loss. Auditory brainstem responses (ABRs) were used to determine hearing threshold shifts after neomycin treatment. Immunofluorescence was used to detect the expression of proteins specific for hair cells, spiral ganglion neurons, astrocytes, and the myelin components of both oligodendrocytes and Schwann cells. RESULTS: ABR threshold shifts and immunofluorescence results supported that hair cells and spiral ganglion neurons were damaged in neomycin-treated mice. Immunofluorescence showed the peripheral and central nervous system (PNS and CNS) transitional zone of the cochlear nerve at the interface of the myelin components of the PNS and CNS. In the control mice, the expression of glial fibrillary acidic protein (GFAP) was observed proximally to the PCTZ closer to the CNS, which is their normal location. However, in neomycin-treated animals the expression of GFAP was detected distally to the PCTZ and was found close to the spiral lamina level in the basal cochlear turn, suggesting that GFAP-expressing astrocytes migrated across the PCTZ and reached the PNS. CONCLUSION: The GFAP positive astrocyte processes extended across the PCTZ along the mouse cochlear nerve following chemically induced sensorineural hearing loss.


Assuntos
Astrócitos/patologia , Nervo Coclear/patologia , Perda Auditiva Neurossensorial/patologia , Animais , Astrócitos/efeitos dos fármacos , Nervo Coclear/efeitos dos fármacos , Orelha Interna/efeitos dos fármacos , Orelha Interna/patologia , Potenciais Evocados Auditivos do Tronco Encefálico , Imunofluorescência , Proteína Glial Fibrilar Ácida/análise , Células Ciliadas Auditivas/efeitos dos fármacos , Perda Auditiva Neurossensorial/induzido quimicamente , Camundongos , Neomicina/administração & dosagem , Estudos Prospectivos , Gânglio Espiral da Cóclea/efeitos dos fármacos
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