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1.
Nucleic Acids Res ; 52(12): 7063-7080, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38808662

RESUMO

Cohesin plays a crucial role in the organization of topologically-associated domains (TADs), which influence gene expression and DNA replication timing. Whether epigenetic regulators may affect TADs via cohesin to mediate DNA replication remains elusive. Here, we discover that the histone demethylase PHF2 associates with RAD21, a core subunit of cohesin, to regulate DNA replication in mouse neural stem cells (NSC). PHF2 loss impairs DNA replication due to the activation of dormant replication origins in NSC. Notably, the PHF2/RAD21 co-bound genomic regions are characterized by CTCF enrichment and epigenomic features that resemble efficient, active replication origins, and can act as boundaries to separate adjacent domains. Accordingly, PHF2 loss weakens TADs and chromatin loops at the co-bound loci due to reduced RAD21 occupancy. The observed topological and DNA replication defects in PHF2 KO NSC support a cohesin-dependent mechanism. Furthermore, we demonstrate that the PHF2/RAD21 complex exerts little effect on gene regulation, and that PHF2's histone-demethylase activity is dispensable for normal DNA replication and proliferation of NSC. We propose that PHF2 may serve as a topological accessory to cohesin for cohesin localization to TADs and chromatin loops, where cohesin represses dormant replication origins directly or indirectly, to sustain DNA replication in NSC.


Assuntos
Proteínas de Ciclo Celular , Proteínas Cromossômicas não Histona , Coesinas , Replicação do DNA , Proteínas de Ligação a DNA , Células-Tronco Neurais , Animais , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas Cromossômicas não Histona/metabolismo , Proteínas Cromossômicas não Histona/genética , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Camundongos , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Cromatina/metabolismo , Origem de Replicação , Histona Desmetilases/metabolismo , Histona Desmetilases/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Genoma/genética , Fator de Ligação a CCCTC/metabolismo , Fator de Ligação a CCCTC/genética , Camundongos Knockout
2.
Emerg Infect Dis ; 30(4): 807-809, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38437706

RESUMO

We describe a case of tinea genitalis in an immunocompetent woman in Pennsylvania, USA. Infection was caused by Trichophyton indotineae potentially acquired through sexual contact. The fungus was resistant to terbinafine (first-line antifungal) but improved with itraconazole. Clinicians should be aware of T. indotineae as a potential cause of antifungal-resistant genital lesions.


Assuntos
Antifúngicos , Trichophyton , Feminino , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Farmacorresistência Fúngica , Itraconazol/uso terapêutico , Testes de Sensibilidade Microbiana , Terbinafina/farmacologia , Terbinafina/uso terapêutico
3.
Gastroenterology ; 164(5): 828-840, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36702360

RESUMO

The central role of the gut microbiota in the regulation of health and disease has been convincingly demonstrated. Polymicrobial interkingdom interactions between bacterial (the bacteriome) and fungal (the mycobiome) communities of the gut have become a prominent focus for development of potential therapeutic approaches. In addition to polymicrobial interactions, the complex gut ecosystem also mediates interactions between the host and the microbiota. These interactions are complex and bidirectional; microbiota composition can be influenced by host immune response, disease-specific therapeutics, antimicrobial drugs, and overall ecosystems. However, the gut microbiota also influences host immune response to a drug or therapy by potentially transforming the drug's structure and altering bioavailability, activity, or toxicity. This is especially true in cases where the gut microbiota has produced a biofilm. The negative ramifications of biofilm formation include alteration of gut permeability, enhanced antimicrobial resistance, and alteration of host immune response effectiveness. Natural modulation of the gut microbiota, using probiotic and prebiotic approaches, may also be used to affect the host microbiome, a type of "natural" modulation of the host microbiota composition. In this review, we discuss potential bidirectional interactions between microbes and host, and we describe the changes in gut microbiota induced by probiotic and prebiotic approaches as well as their potential clinical consequences, including biofilm formation. We outline a systematic approach to designing probiotics capable of altering the host microbiota in disease states, using Crohn's disease as a model chronic disease. Understanding how the effective changes in the microbiome may enhance treatment efficacy may unlock the possibility of modulating the gut microbiome to improve treatment using a natural approach.


Assuntos
Doença de Crohn , Microbioma Gastrointestinal , Microbiota , Probióticos , Humanos , Doença de Crohn/tratamento farmacológico , Probióticos/uso terapêutico , Prebióticos
4.
World J Urol ; 42(1): 384, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909142

RESUMO

PURPOSE: Transurethral resection of the prostate (TURP) is one of the surgical options for treating enlarged prostates with lower urinary symptoms (LUTS). In this older group of patients, concomitant prostate cancer is not uncommon. However, the fibrosis and distortion of the prostate anatomy by prior TURP can potentially hinder surgical efficacy at robotic-assisted radical prostatectomy (RARP). We aim to evaluate functional, and oncologic outcomes of RARP in patients with and without previous TURP. METHODS: 231 men with previous TURP underwent RARP (TURP group). These men were propensity score matched using clinicopathological characteristics to men without previous TURP who underwent RARP (Control group). Perioperative and postoperative variables were analysed for significant differences in outcomes between groups. Variables analysed included estimated blood loss (EBL), operative time, catheter time, hospitalization time, postoperative complications, positive surgical margins (PSM) rates, cancer status, biochemical recurrence (BCR), potency, and continence rates. RESULTS: Patients in the TURP group showed no statistically significant differences in operative safety measures including median EBL, operative time, catheter time, hospitalization time or postoperative complications. No significant difference between the groups in terms of potency rates and continence rates. Furthermore, there were no statistically significant differences in oncological outcomes, including PSM rates (15% vs 18%, P = 0.3) and BCR. CONCLUSION: In RARP after TURP there is often noticeable distortion of the surgical anatomy. For an experienced team the procedure is safe and provides similar oncologic control and functional outcomes to RARP in patients without previous TURP.


Assuntos
Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Ressecção Transuretral da Próstata , Humanos , Masculino , Prostatectomia/métodos , Idoso , Ressecção Transuretral da Próstata/métodos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Pessoa de Meia-Idade , Resultado do Tratamento , Estudos Retrospectivos , Hiperplasia Prostática/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
5.
Am J Dermatopathol ; 46(3): 185-188, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38153289

RESUMO

ABSTRACT: In a retrospective analysis of biopsies from January 1, 2019 to December 31, 2020, at University Hospitals Cleveland Medical Center, we aimed to determine the frequency of dermatologic conditions biopsied in African Americans (AA). Given that AAs constitute 13.4% of the US population, understanding the skin disease profile within this significant demographic is crucial. From a total of 1701 biopsies collected from 1442 AA patients, benign neoplasms emerged as the most common diagnosis, accounting for 26.7%, predominantly in females. Notably, cutaneous T-cell lymphoma was the most frequently biopsied malignancy, whereas pigmentary disorders were the least common at 1.4%. The study highlighted the higher occurrence of squamous cell carcinoma compared with basal cell carcinoma in AA, contrasting trends in other racial demographics. Moreover, recognizing the unique presentations of skin disorders in different racial backgrounds is essential, especially because disparities have been reported in skin of color training among dermatology residency programs. Understanding these racial differences in skin diseases can assist clinicians in refining their diagnostic approach. Future research could further explore the potential gaps between clinical expectations and histologic findings, improving diagnostic accuracy.


Assuntos
Negro ou Afro-Americano , Neoplasias Cutâneas , Humanos , Biópsia , Estudos Retrospectivos , Pele/patologia , Neoplasias Cutâneas/patologia
6.
Clin Oral Investig ; 28(1): 71, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38172458

RESUMO

OBJECTIVES: The present study goal was to assess clinically and radiographically using simvastatin (SMV) loaded xenograft for guided bone regeneration (GBR) around simultaneously placed implants with alveolar ridge splitting in patients with horizontally atrophic jaw defect. MATERIALS AND METHODS: Randomized distribution of the twenty-two patients into two groups (11 patients each) was performed. Group I participants received alveolar ride splitting (ARS) with GBR using SMV gel mixed bone graft and a barrier membrane with simultaneous implant placement. Group II received the same treatment protocol without SMV gel. At the baseline, 6- and 9-months post-surgery, clinical and radiological alterations were assessed. RESULTS: Six months after therapy, PES records of group I were statistically significantly improved than those of group II (P < .001). Group I exhibited statistically significant expansion of the alveolar ridge over group II after 6 and 9 months (P < .001). When compared to group II over the evaluation interval between 6 and 9 months, group I demonstrated statistically substantially minimal loss of the mean marginal bone level (P < .001). At the 6- and 9-month observation periods, bone density gain was considerably higher in group I than that in group II (P < .001). CONCLUSION: Alveolar ridge splitting along with GBR-augmented SMV improve the clinical and radiographical outcomes around dental implant over GBR alone. CLINICAL RELEVANCE: Augmenting GBR with SMV in alveolar ridge splitting could boost implant osseointegration and enhance peri-implant tissue changes. CLINICAL TRIAL REGISTRATION: NCT05020405.


Assuntos
Aumento do Rebordo Alveolar , Implantes Dentários , Humanos , Implantação Dentária Endóssea/métodos , Xenoenxertos , Aumento do Rebordo Alveolar/métodos , Processo Alveolar/cirurgia , Regeneração Óssea
7.
Int Orthop ; 48(3): 865-884, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37867166

RESUMO

PURPOSE: This study conducts a comprehensive comparative analysis of bone pathologies between ancient Egypt and today. We aim to elucidate the prevalence, types, and potential aetiological factors influencing skeletal disorders in these two distinct temporal and cultural contexts. METHODS: The research employs a multidisciplinary approach, integrating osteological, paleopathological, and historical data to understand bone pathologies in mummies and the actual world. Applying radiographs and CT scans as noninvasive techniques has shed new light on past diseases such as fractures, dysplasia, osteoarthritis, surgery, and tuberculosis. Virtual inspection has almost replaced classical autopsy and is essential, especially when dealing with museum specimens. RESULTS: Findings indicate no significant disparities in the prevalence and types of bone pathologies through 4300 years of evolution. Moreover, this study sheds light on the impact of sociocultural factors on bone health. Examination of ancient Egypt's burial practices and associated cultural beliefs provides insights into potential behavioral and ritualistic influences on bone pathologies and the prevalence of specific pathologies in the past and present. CONCLUSION: This comparative analysis illuminates the dynamic of bone pathologies, highlighting the interplay of biological, cultural, and environmental factors. By synthesizing archeological and clinical data, this research contributes to a more nuanced understanding of skeletal health's complexities in ancient and modern societies, offering valuable insights for anthropological and clinical disciplines.


Assuntos
Múmias , Ortopedia , Humanos , Antigo Egito , Múmias/diagnóstico por imagem , Osso e Ossos , Radiografia
8.
Int Braz J Urol ; 502024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787614

RESUMO

INTRODUCTION: Robot-assisted radical prostatectomy (RARP) has become a popular surgical approach for localized prostate cancer due to its favorable oncological and functional outcomes, as well as lower morbidity. In cases of intermediate- and high-risk prostate cancer, bilateral pelvic lymphadenectomy (PLND) is recommended as an adjunct to RARP (1-3). Despite its benefits, PLND can lead to surgical complications, with postoperative lymphocele formation being the most common. Most postoperative lymphoceles are clinically insignificant with variable incidence, reaching up to 60% of cases 4. However, a small percentage of patients 2-8% may experience symptomatic lymphoceles (SL), which can cause significant morbidity (4, 5). SURGICAL TECHNIQUE: We perform our RARP technique with our standard approach in all patients (6). After vesicourethral anastomosis a modified PF created to prevent symptomatic lymphocele. We start by suturing the peritoneal fold on the right side, medially to the vas deferens, followed by a similar stitch on the left side to approximate the edges in the midline. A running suture bunches the bladder peritoneum from both sides, passing through the pubic bone periosteum to secure it in place (7). This approach keeps the lateral pelvic gutters open for lymphatic drainage, while allowing fluid drainage from the true pelvis into the abdomen. A pelvic ultrasound was done for all patients at 6 weeks post operative, and additional clinical follow-up was carried out at 3 months following surgery. CONSIDERATIONS: We have demonstrated a modified technique of peritoneal flap (PBFB) with an initial decrease in postoperative symptomatic lymphoceles, the technique is feasible, safe, does not add significant morbidity, and does not require a learning curve.

9.
Int Braz J Urol ; 50(1): 65-79, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38166224

RESUMO

OBJECTIVE: In the following years after the United States Preventive Service Task Force (USPSTF) recommendation against prostate cancer screening with PSA in 2012, several authors worldwide described an increase in higher grades and aggressive prostate tumors. In this scenario, we aim to evaluate the potential impacts of USPSTF recommendations on the functional and oncological outcomes in patients undergoing robotic-assisted radical prostatectomy (RARP) in a referral center. MATERIAL AND METHODS: We included 11396 patients who underwent RARP between 2008 and 2021. Each patient had at least a 12-month follow-up. The cohort was divided into two groups based on an inflection point in the outcomes at the end of 2012 and the beginning of 2013. The inflection point period was detected by Bayesian regression with multiple change points and regression with unknown breakpoints. We reported continuous variables as median and interquartile range (IQR) and categorical variables as absolute and relative percent frequencies. RESULTS: Group 1 had 4760 patients, and Group 2 had 6636 patients, with a median follow-up of 109 and 38 months, respectively. In the final pathology, Group 2 had 9.5% increase in tumor volume, 24% increase on Gleason ≥ 4+3 (ISUP 3) , and 18% increase on ≥ pT3. This translated to a 6% increase in positive surgical margins and 24% reduction in full nerve sparing in response to the worsening pathology. There was a significant decline in post-operative outcomes in Group 2, including a 12-month continence reduction of 9%, reduction in potency by 27%, and reduction of trifecta by 22%. CONCLUSIONS: The increasing number of high-risk patients has led to worse functional and oncologic outcomes. The initial rapid rise in PSM was leveled by the move towards more partial nerve sparing. Among some historical changes in prostate cancer diagnosis and management in the period of our study, the USPSTF recommendation coincided with worse outcomes of prostate cancer treatment in a population who could benefit from PSA screening at the appropriate time.


Assuntos
Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Teorema de Bayes , Detecção Precoce de Câncer , Antígeno Prostático Específico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Resultado do Tratamento
10.
Dermatol Surg ; 49(3): 247-252, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36735798

RESUMO

BACKGROUND: Treating infraorbital dark circles is one of the commonest aesthetic demands worldwide. Autologous fat transfer is commonly used to treat dark circles by filling the grooves, without effect on skin quality. Platelet-rich plasma has been reported to improve skin quality. Autologous fat can be emulsified and filtered to produce nanofat, which is then injected superficially in the dark circles to improve skin quality and discoloration. OBJECTIVE: To compare the efficacy of platelet-rich plasma versus combined fat transfer and nanofat in treating infraorbital dark circles. MATERIALS AND METHODS: 30 patients with infraorbital dark circles of combined etiological factors were randomized into 2 equal groups: Group A treated with platelet-rich plasma and Group B treated with autologous fat transfer with emulsified fat injection. RESULTS: Excellent and moderate responses were observed in 3 (20%) and 2 (13%) patients in group A versus 7 (46.7%) and 4 (27%) in group B, respectively. Nonresponders were 8 (53.3%) in group A and only 1 patient (6.7%) in group B. The difference was statistically significant regarding improvement ( p = .048) and patient satisfaction ( p = .032). CONCLUSION: Autologous fat transfer with nanofat is significantly superior to platelet-rich plasma in improvement and satisfaction.


Assuntos
Terapia com Luz de Baixa Intensidade , Plasma Rico em Plaquetas , Humanos , Satisfação do Paciente , Pele , Resultado do Tratamento
11.
Clin Oral Investig ; 27(7): 3949-3960, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37083985

RESUMO

OBJECTIVES: This study evaluated clinically and histologically the efficacy of modified perforated collagen membrane (PCM) and/or leukocyte- and platelet-rich fibrin (L-PRF) in combination with xenogeneic block bone graft in the vertical alveolar ridge augmentation. MATERIALS AND METHODS: Six adult mongrel dogs were enrolled in this randomized blinded study. After defect preparation, xenogeneic screw-fixed block graft was covered by an occlusive collagen membrane in group 1 that represented the control group (Block + CM). In group 2, L-PRF membrane was added first before top coverage by occlusive collagen membrane (Block + L-PRF + CM). Groups 3 (Block + PCM) and 4 (Block + L-PRF + PCM) were identical to the first two groups except that the occlusive collagen membrane was replaced by a perforated one. Following a healing period of 2 months, the dogs were submitted to the surgical reentry phase for clinical and histological evaluation. RESULTS: Clinically, no significant differences were found among all groups regarding vertical and horizontal ridge dimensions (p = 0.155, 0.492, respectively). Histomorphometric analysis revealed that the percentage of the total bone area and mature bone was significantly higher in group 4 (69.36 ± 2.72, 33.11 ± 5.18) compared to the control group (59.17 ± 4.27, 21.94 ± 2.86) (p = 0. 027, p = 0.029). CONCLUSION: The use of xenogenic block grafts in combination with a double-layered perforated collagen L-PRF membrane in vertical ridge augmentation appeared to improve the inductive power of this challenging defect type. CLINICAL RELEVANCE: Size and number of perforations may affect the mechanical and handling properties of the membrane.


Assuntos
Aumento do Rebordo Alveolar , Fibrina Rica em Plaquetas , Animais , Cães , Aumento do Rebordo Alveolar/métodos , Regeneração Óssea , Transplante Ósseo/métodos , Colágeno
12.
BMC Oral Health ; 23(1): 631, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37667213

RESUMO

BACKGROUND: The innovation of leukocyte platelet-rich fibrin (L-PRF) has added enormous impact on wound healing dynamics especially the field of periodontal regeneration. The release of growth factors (GF) is thought to improve the clinical outcomes in infrabony defects. The aim of this study was to evaluate the clinical effect of covering L-PRF contained infrabony defects with collagen membranes (CM), and to compare their GF release profile to uncovered L-PRF defects and open flap debridement (OFD). METHODS: Thirty non- smoking patients with infrabony pockets participated to be randomly assigned to OFD group (n = 10), L-PRF group (n = 10), or L-PRF protected CM group (n = 10). Plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL) and the radiographic defect base fill (DBF) were measured at baseline and at 6 month following surgical intervention. Gingival crevicular fluid samples were obtained on days 1, 3, 5, 7, 14, 21 and 30 days following surgery for the Platelet Derived Growth Factor-BB (PDGF-BB) and Vascular Endothelial Growth Factors (VEGF) release profile evaluation. RESULTS: For all patients, a statistically significant (P ≤ 0.05) reduction in PI, GI, PD and CAL were reported throughout the study period. Differences between the three treatment modalities were not statistically significant. PRF + CM showed a statistically significant DBF compared to OFD and L-PRF groups at follow up. Quantitative analysis of PDGF-BB and VEGF levels demonstrated a statistically significant (P < 0.001) decline between measurement intervals for all groups with no statistically significant differences between the three groups. CONCLUSION: Within the limitations of this study, L-PRF coverage with CM may augment defect base fill through its mechanical protective effect without enhancement in the release profile of VEGF and PDGF. The non-significant intergroup differences question the validity of the claimed extra physiologic concentration of GF offered by L-PRF harvests. TRIAL REGISTRATION: The present study was registered at ClinicalTrials.gov (NCT05496608), (11/08/2022).


Assuntos
Fibrina Rica em Plaquetas , Humanos , Fator A de Crescimento do Endotélio Vascular , Becaplermina , Colágeno/uso terapêutico , Leucócitos
13.
Arch Virol ; 167(1): 85-97, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34738153

RESUMO

Silver nanoparticles (AgNPs) are a potentially effective tool for preventing viral plant diseases. This study was carried out to evaluate the effectiveness of AgNPs for managing bean yellow mosaic virus (BYMV) disease in faba bean plants from the plant-virus-vector interaction side. AgNPs were evaluated as foliar protective and curative agents. In addition, the effect of AgNPs on virus acquisition and transmission by its vector aphid was investigated. The results indicated that AgNPs exhibited curative viricidal activity and were able to inactivate BYMV when applied 48 hours after virus inoculation. The occurrence of disease was prevented using an AgNP concentration as low as 100 mg L-1, whereas virus infection was completely inhibited when plants were preventatively treated with AgNPs at a concentration of to 200 mg L-1 24 h before virus inoculation. AgNPs proved to be highly bio-reactive, binding to viral particles and suppressing their replication and accumulation within plant tissues. Moreover, AgNPs, at all concentrations tested, were found to upregulate the pathogenesis-related gene PR-1 and induce the production of defense-related oxidizing enzymes in treated plants. Exposure of aphids to AgNPs-treated plants before virus acquisition reduced BYMV acquisition and transmission efficiency by 40.65 to 100% at 24 h post-application, depending on the AgNP dosage. At 10 days after treatment, virus acquisition was reduced by 36.82% and 79.64% upon exposure to AgNPs at a concentration of 250 and 300 mg L-1, respectively. These results suggest that AgNPs have curative viricidal activity due to targeting the virus coat protein and affecting virus-vector interactions. Accordingly, AgNPs may contribute to alleviating the natural disease and virus transmission under field conditions. This is the first report on the activity of nanomaterials against plant virus acquisition and transmission by insects.


Assuntos
Afídeos , Nanopartículas Metálicas , Vírus de Plantas , Animais , Doenças das Plantas , Prata/farmacologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-33846131

RESUMO

Antifungal activity of AmBisome against Candida auris was determined in vitro and in vivo AmBisome showed MIC50 and MIC90 values of 1 and 2 µg/ml, respectively. Unlike conventional amphotericin B, significant in vivo efficacy was observed in the AmBisome 7.5 mg/kg treatment group in survival and reduction of kidney tissue fungal burden compared to the untreated group. Our data show that AmBisome has significant antifungal activity against C. auris infection in vitro and in vivo.


Assuntos
Anfotericina B , Fluconazol , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida , Candidíase Invasiva , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana
15.
Antimicrob Agents Chemother ; 65(9): e0054921, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34228541

RESUMO

Antifungal activity of anidulafungin, voriconazole, isavuconazole, and fluconazole in the treatment of Candida auris was determined in vitro and in vivo. MICs for anidulafungin, voriconazole, isavuconazole, fluconazole, and amphotericin B were 0.5, 1, >64, 0.25, and 4 µg/ml, respectively. Significant in vivo efficacy was observed in the anidulafungin- and voriconazole-treated groups in survival and reduction in kidney tissue fungal burden compared to that in the untreated group (P values of <0.001 and 0.044, respectively). Our data showed that anidulafungin and voriconazole had comparable efficacies against C. auris, whereas isavuconazole did not show significant in vivo activity.


Assuntos
Candidíase , Fluconazol , Anidulafungina , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida , Candidíase/tratamento farmacológico , Modelos Animais de Doenças , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Camundongos , Testes de Sensibilidade Microbiana , Nitrilas , Piridinas , Triazóis , Voriconazol/farmacologia , Voriconazol/uso terapêutico
16.
Int Orthop ; 45(8): 2141-2147, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34189622

RESUMO

INTRODUCTION: Refracture of the tibia after union is a challenging problem for the patients and the surgeons. The purpose of the current study is to present our experience in conservative management of such patients with refracture of infected ununited tibia after successful treatment by Ilizarov external fixator and bone transport. MATERIAL AND METHODS: We reviewed the files of 812 patients with infected ununited tibia who were treated by debridement, corticotomy, and bone transport using Ilizarov methods in our institute between 1997 and 2017. Inclusion criteria were patients with refracture after union and removal of the Ilizarov apparatus. Twenty-two patients with 23 refracture tibia were included in the study. All the 23 tibias were treated conservatively by above knee cast that was converted to Sarmiento below knee cast after early callus formation, except in the case of upper tibial fracture that continued in above knee cast till union. Afterwards, a protective splint was used for additional two months. RESULTS: There were 19 males (86.4%) and three females (13.6%), the mean age of the patients was 38.39 years, the mean time of Ilizarov external fixator application was 10.86 months (range, 6-17), and the mean time of refracture after fixator removal was 2.33 months. Union was achieved in 19 tibias (82.6%), with a mean time of 7.2 months (range, 4-12). Complications included five cases of skin irritation that was treated by large windows in the cast and changing the casts more frequently, three cases developed DVT (deep venous thrombosis), and axial deviation occured in four tibias (17.3%). CONCLUSION: Conservative treatment of refractured tibia after removal of Ilizarov external fixator following treatment of infected non-union tibia by above knee cast is effective in achieving union. However, complications as skin irritation, DVT (deep venous thrombosis), and axial deviation can be anticipated.


Assuntos
Fraturas não Consolidadas , Técnica de Ilizarov , Fraturas da Tíbia , Fixadores Externos/efeitos adversos , Feminino , Consolidação da Fratura , Humanos , Lactente , Masculino , Tíbia/cirurgia , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Resultado do Tratamento
17.
Int J Mol Sci ; 22(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34638761

RESUMO

Niclosamide is an oral anthelmintic drug, approved for use against tapeworm infections. Recent studies suggest however that niclosamide may have broader clinical applications in cancers, spurring increased interest in the functions and mechanisms of niclosamide. Previously, we reported that niclosamide targets a metabolic vulnerability in p53-deficient tumours, providing a basis for patient stratification and personalised treatment strategies. In the present study, we functionally characterised the contribution of the aniline 4'-NO2 group on niclosamide to its cellular activities. We demonstrated that niclosamide induces genome-wide DNA damage that is mechanistically uncoupled from its antitumour effects mediated through mitochondrial uncoupling. Elimination of the nitro group in ND-Nic analogue significantly reduced γH2AX signals and DNA breaks while preserving its antitumour mechanism mediated through a calcium signalling pathway and arachidonic acid metabolism. Lipidomics profiling further revealed that ND-Nic-treated cells retained a metabolite profile characteristic of niclosamide-treated cells. Notably, quantitative scoring of drug sensitivity suggests that elimination of its nitro group enhanced the target selectivity of niclosamide against p53 deficiency. Importantly, the results also raise concern that niclosamide may impose a pleiotropic genotoxic effect, which limits its clinical efficacy and warrants further investigation into alternative drug analogues that may ameliorate any potential unwanted side effects.


Assuntos
Dano ao DNA , Mitocôndrias/metabolismo , Neoplasias , Niclosamida , Células HCT116 , Humanos , Mitocôndrias/patologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Niclosamida/análogos & derivados , Niclosamida/farmacologia
18.
Environ Geochem Health ; 43(10): 4089-4104, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33772385

RESUMO

The River Nile is the primary source of freshwater for drinking, irrigation, and industrial purposes in Egypt. Thus, the water quality in this river concerns the health of local inhabitants. The present study reveals seasonal variations of various physicochemical and heavy metals parameters and microbial load of water at 15 sites from Qena to Sohag cities, Egypt. The water is fresh with TDS ≤ 270 and 410 mg L-1 in summer and winter, respectively. Fe, Mn, Cd, Cr, Cu, Ni, and Zn concentrations were within drinking water specification in both seasons except Cr and Cd in summer. Viable numbers of total coliform, fecal coliform, and fecal streptococci were recorded in both seasons with fecal streptococci's disappearing in winter. The concentrations of salts and ions in winter were higher than summer due to decreased water quantity and flow rate in this season. On the other hand, heavy metals and bacteria were higher in summer owing to the rain and weathering of upstream rocks and increasing of human activities during the summer. The calculated water quality index (WQI) depicted that the chemical quality of water was poor for drinking and treatment, especially biological treatment, which is required before the water is supplied for drinking. Human health risk assessment factors such as probable daily intake, hazard quotient, and carcinogenic risk indicated high risks of Cr, Cd, and Ni for adults and children in both seasons. The non-carcinogenic and carcinogenic risks are mainly posed by Cr. The WQI values for the other water uses indicated the marginal quality for aquatic life, fair for irrigation, and fair in summer to good in winter for livestock consumption. The irrigation water quality parameters indicated that the water could be used to irrigate all soils and crops except the hazard of biological contamination. The water-rock interaction controls water chemistry besides the contribution of human activities. The agricultural, industrial, and municipal wastewaters were the main contributors to water pollution and should be treated before discharge into the Nile River. Source and drinking water should be monitored continuously to prevent related human waterborne diseases.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Adulto , Bactérias , Criança , Egito , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Metais Pesados/toxicidade , Medição de Risco , Rios , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Qualidade da Água
19.
J Periodontal Res ; 55(1): 85-95, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31448832

RESUMO

BACKGROUND: Perforated barrier membranes (PBM) were suggested to enhance periodontal regeneration by allowing positive charity of wanted elements from the gingival tissue side. The present study was designed to evaluate clinically and biochemically the use of PBM combined with simvastatin (SMV) gel with and without an associated EDTA gel root surface etching as a suggested option that could improve SMV availability and clinical outcomes of PBM. METHODS: Forty patients having moderate-to-severe chronic periodontitis with 40 intrabony defects were randomly divided into four treatment groups (10 sites each). Patients in group 1 received 1.2% SMV gel and covering the defect with occlusive membrane (OM). Patients in group 2 received 1.2% SMV gel and covering the defect with PBM. Group 3 received 24% EDTA root surface etching, 1.2% SMV gel, and defect coverage with OM (eOM). Patients in group 4 were treated as in group 3 but the defect was covered with PBM (ePBM). Clinical parameters were recorded at baseline before surgical procedures and were reassessed at 6 and 9 months after therapy. The mean concentration of SMV in gingival crevicular fluid (GCF) was estimated by reverse-phase high-performance liquid chromatography at days 1, 7, 14, 21, and 30. RESULTS: At 6- and 9-month observation periods, groups 3 and 4 showed a statistically significant improvement in PD reduction and CAL gain compared with groups 1 and 2. Group 4 showed a statistically significant more defect fill compared with groups 1, 2, and 3 (P ≤ .05). Group 2 showed statistically significant higher defect fill compared with group 1 and group 3 (P < .05). Bone density was significantly increased with no significant difference between the four groups at 6- and 9-month observation periods. SMV-GCF concentration in group 4 showed the highest mean concentration with no significant difference than that of group 3. CONCLUSION: The use of perforated barrier membranes in association with SMV enhances the clinical hard tissue parameters compared with occlusive ones in treating intrabony periodontal defects. Moreover, EDTA root surface treatment could enhance SMV availability in the defect area.


Assuntos
Perda do Osso Alveolar/terapia , Regeneração Tecidual Guiada Periodontal , Membranas Artificiais , Sinvastatina/uso terapêutico , Adulto , Perda do Osso Alveolar/cirurgia , Ácido Edético , Feminino , Seguimentos , Líquido do Sulco Gengival , Humanos , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal , Bolsa Periodontal , Estudos Prospectivos , Resultado do Tratamento
20.
J Periodontal Res ; 55(3): 441-452, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32080858

RESUMO

BACKGROUND: Defective cellular elements constitute an important challenge to achieve predictable periodontal regeneration. In an attempt to improve the cellularity of periodontal defects, gingival fibroblasts were implanted without their associated extracellular elements in periodontal defects to expose them to periodontal tissue mediators. In order to investigate the regenerative potential of gingival fibroblasts translocated into periodontal defects, the present study was designed to clinically and biochemically investigate the use of gingival fibroblasts (GF) and their associated mesenchymal stem cells (GMSC) in the treatment of intrabony periodontal defects. METHODS: A total of 20 subjects were randomly divided into two groups (n = 20). Group I: ten patients were included with ten intrabony periodontal defects that received ß-calcium triphosphate (ß-TCP) followed by collagen membrane defect coverage, while group II: (10 patients) ten periodontal defects received cultured gingival fibroblasts (GF) on the ß-TCP scaffold and covered by a collagen membrane. The clinical evaluation was carried out at the beginning and at 6 months. Gingival crevicular fluid (GCF) samples were collected directly from the test sites for the quantitative measurement of PDGF-BB and BMP-2 using the ELISA kit at 1, 7, 14, and 21 days after surgery. RESULTS: Group II reported a significantly greater reduction in vertical pocket depth (VPD) and CAL gain compared with group I after 6 months. Radiographic bone gain was statistically higher in group II compared with group I. A significantly higher concentration of PDGF-BB was observed in group II on days 1, 3, and 7 compared with group I. CONCLUSIONS: Translocation of gingival fibroblasts from gingival tissue to periodontal defects could be a promising option that increases cellular elements with regeneration potential. The concept of total isolation of gingival fibroblasts using occlusive membranes must be re-evaluated.


Assuntos
Perda do Osso Alveolar/terapia , Fibroblastos/citologia , Regeneração Tecidual Guiada Periodontal , Seguimentos , Gengiva/citologia , Humanos , Membranas Artificiais , Resultado do Tratamento
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