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1.
Bioorg Chem ; 146: 107262, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38467092

RESUMO

Modern classes of antimicrobials are crucial because most drugs in development today are basically antibiotic derivatives. Even though a large number of metal-based compounds have been studied as antimicrobial agents, relatively few studies have examined the antimicrobial properties of Pd(II) and Pt(II) compounds. The [3+2] cycloaddition reactions of [M(N3)L]PF6 (M = Pd(II) and Pt(II); L = 4'-(2-pyridyl)-2,2':6',2″-terpyridine) with 4,4,4-trifluoro-2-butynoic acid ethyl ester gave the corresponding triazolate complexes. The reaction products were fully characterized with a variety of analytical and spectroscopic tools including X-ray crystallographic analysis. The crystal structure of [Pd(triazolatoCF3,COOCH2CH3)L]PF6 provided cut-off evidence that the kinetically formed N1-triazolato isomer favoured the isomerization to the thermodynamically stable N2-analogue. The experimental work was complemented with computational work to get an insight into the nature of the predominant triazolate isomer. The lysozyme binding affinity of the triazolate complexes was examined by mass spectrometry. An analysis of the lysozyme Pd(II) adducts suggests a coordinative covalent mode of binding via the loss of the triazolato ligand. The free ligand and its triazolate complexes displayed selective toxicity against Candida albicans and Cryptococcus neoformans, while no cytotoxicity was observed against the normal human embryonic kidney cell line.


Assuntos
Anti-Infecciosos , Muramidase , Humanos , Anti-Infecciosos/farmacologia , Reação de Cicloadição , Isomerismo , Ligantes , Platina/química , Chumbo/química
2.
BMC Vet Res ; 20(1): 276, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926724

RESUMO

BACKGROUND: Trace elements play a crucial role in fish nutrition, with zinc (Zn) being one of the most important elements. BIO-sourced zinc nanoparticles were synthesized using the green microalga Pediastrum boryanum (BIO-ZnNPs, 29.35 nm). 30 or 60 mg/ kg dry feed of the BIO-ZnNPs (BIO-ZnNPs30 and BIO-ZnNPs60) were mixed with the Nile tilapia (Oreochromis niloticus) basal diet and fed to the fish for 8 weeks to evaluate their impact on fish growth, digestion, intestinal integrity, antioxidative status, and immunity. RESULTS: A significant enhancement was observed in all investigated parameters, except for the serum protein profile. BIO-ZnNPs at 60 mg/kg feed elevated the activities of reduced glutathione (GSH) and catalase (CAT), enzymatic antioxidants, but did not induce oxidative stress as reflected by no change in MDA level. Fish intestinal immunity was improved in a dose-dependent manner, in terms of improved morphometry and a higher count of acid mucin-producing goblet cells. Interleukin-8 (IL-8) was upregulated in BIO-ZnNPs30 compared to BIO-ZnNPs60 and control fish groups, while no significant expressions were noted in tumor necrosis factor-alpha (TNFα), nuclear factor kappa B (NFkB), and Caspase3 genes. CONCLUSION: Overall, BIO-ZnNPs inclusion at 60 mg/kg feed showed the most advantage in different scenarios, compared to BIO-ZnNPs at 30 mg/kg feed. The positive effects on growth and intestinal health suggest that BIO-ZnNPs supplementation of aquafeeds has many benefits for farmed fish.


Assuntos
Ração Animal , Ciclídeos , Dieta , Intestinos , Zinco , Animais , Zinco/farmacologia , Zinco/administração & dosagem , Ração Animal/análise , Ciclídeos/imunologia , Ciclídeos/crescimento & desenvolvimento , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Dieta/veterinária , Suplementos Nutricionais , Nanopartículas Metálicas , Antioxidantes , Clorófitas/química , Microalgas
3.
J Cutan Med Surg ; 28(1): 44-50, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38156627

RESUMO

BACKGROUND: Pruritus is a common complaint in patients with end-stage renal disease. Indoxyl sulfate (IS) is a tryptophan end metabolite extremely renal excreted. Activated charcoal can interfere with IS intestinal absorption. OBJECTIVES: To evaluate the serum level of IS and the effect of activated charcoal on uremic pruritus. MATERIALS AND METHODS: In all, 135 participants were divided into 2 main groups. In total, 45 normal and healthy individuals as a control group and 90 patients on regular hemodialysis; 45 of these patients had uremic pruritus and the other 45 were not complaining of uremic pruritus. Serum IS was measured. Activated charcoal was used by patients with uremic pruritus. The severity of pruritus and Dermatology Life Quality Index (DLQI) were assessed. RESULTS: The serum IS was significantly elevated in uremic patients than in control subjects (P < .001) and significantly elevated in uremic patients without pruritus (P < .001). Furthermore, there were positive significant correlations between the serum IS and both severity of pruritus (P < .001) and DLQI (P < .001). After activated charcoal usage, there was a significant decrease in IS level with the improvement of pruritus and quality of life of patients. CONCLUSIONS: IS may play a role in uremic pruritus. Activated charcoal could be considered a treatment for uremic pruritus.


Assuntos
Carvão Vegetal , Uremia , Humanos , Carvão Vegetal/uso terapêutico , Uremia/complicações , Indicã , Qualidade de Vida , Prurido/tratamento farmacológico , Prurido/etiologia
4.
Chem Biodivers ; 21(5): e202400363, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38470083

RESUMO

Reactions between sodium tetrachloropalladate and 2- (or 4-) substituted 4-phenyl-3-thiosemicarbazone ligands (HLR), with various electron-donating and electron-withdrawing substituents (R = OCH3, NO2, and Cl), afford square-planar complexes of the general formula [Pd(LR)2]. Ground-state geometry optimization and the vibrational analysis of cis- and trans-isomers of the complexes were carried out to get an insight into the stereochemistry of the complexes. Natural bond orbital analysis was used to analyze how the nature of the substituent affects the natural charge of the metal center, the type of hybridization, and the strength of the M-N and M-S bonds. Using spectrophotometry, the stability of the complexes, and their DNA binding abilities were assessed. The Pd(II) complexes showed moderate cytotoxicity against MCF-7 and Caco-2 cell lines, two of the assessed malignant cell lines, resulting in all known cell death types, including early apoptotic bodies and late apoptotic vacuoles as well as evident necrotic bodies.


Assuntos
Antineoplásicos , Complexos de Coordenação , Paládio , Tiossemicarbazonas , Humanos , Paládio/química , Paládio/farmacologia , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia , Ligantes , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Células MCF-7 , Estrutura Molecular , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Relação Estrutura-Atividade , DNA/química , DNA/metabolismo , DNA/efeitos dos fármacos
5.
Molecules ; 29(2)2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38257319

RESUMO

Fatalities caused by infectious diseases (i.e., diseases caused by parasite, bacteria, and viruses) have become reinstated as a major public health threat globally. Factors such as antimicrobial resistance and viral complications are the key contributors to the death numbers. As a result, new compounds with structural diversity classes are critical for controlling the virulence of pathogens that are multi-drug resistant. Derivatization of bio-active organic molecules with organometallic synthons is a promising strategy for modifying the inherent and enhanced properties of biomolecules. Due to their redox chemistry, bioactivity, and structural diversity, organometallic moieties make excellent candidates for lead structures in drug development. Furthermore, organometallic compounds open an array of potential in therapy that existing organic molecules lack, i.e., their ability to fulfill drug availability and resolve the frequent succumbing of organic molecules to drug resistance. Additionally, metal complexes have the potential towards metal-specific modes of action, preventing bacteria from developing resistance mechanisms. This review's main contribution is to provide a thorough account of the biological efficacy (in vitro and in vitro) of metal-based complexes against infectious diseases. This resource can also be utilized in conjunction with corresponding journals on metal-based complexes investigated against infectious diseases.


Assuntos
Doenças Transmissíveis , Complexos de Coordenação , Humanos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico , Virulência , Desenvolvimento de Medicamentos , Saúde Pública
6.
BJU Int ; 132(1): 9-30, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36754376

RESUMO

OBJECTIVE: To assess the safety and feasibility of robot-assisted retroperitoneal lymph node dissection (R-RPLND) and to compare the perioperative outcomes of R-RPLND with open RPLND (O-RPLND), as RPLND forms an integral part of the management of testis cancer and R-RPLND is a minimally invasive treatment option for this disease. MATERIALS AND METHODS: The PubMed® , Scopus® , Cochrane Central Register of Controlled Trials, and Web of Science™ databases were searched for studies reporting perioperative outcomes of primary and post-chemotherapy R-RPLND and studies comparing R-RPLND with O-RPLND. RESULTS: The search yielded 42 articles describing R-RPLND, including five comparative studies. The systematic review included 4222 patients (single-arm studies, n = 459; comparative studies, n = 3763). Of 459 patients in the single-arm studies, 271 underwent primary R-RPLND and 188 underwent post-chemotherapy R-RPLND. For primary R-RPLND, the operative time ranged from 175 to 540 min and the major complication rate was 4.1%. For post-chemotherapy R-RPLND, the operative time ranged from 134 to 550 min and the major complication rate was 8.5%. The conversion rate to open surgery was 2.2% in primary R-RPLND and 9.0% in post-chemotherapy R-RPLND. In comparison with O-RPLND, R-RPLND was associated with a lower transfusion rate (14.5% vs 0.9%, P < 0.001) and a lower complication rate (18.5% vs 7.8%, P = 0.002). CONCLUSION: Robot-assisted RPLND has acceptable perioperative outcomes in both the primary and post-chemotherapy settings but a notable rate of conversion to open surgery in the post-chemotherapy setting. Compared with O-RPLND, R-RPLND is associated with a lower transfusion rate and fewer overall complications. Given the potential impact of selection bias, the optimal patient selection criteria for R-RPLND remain to be elucidated.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Robótica , Neoplasias Testiculares , Masculino , Humanos , Espaço Retroperitoneal/cirurgia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Excisão de Linfonodo , Neoplasias Testiculares/patologia , Estudos Retrospectivos , Resultado do Tratamento
7.
Phys Chem Chem Phys ; 25(43): 29718-29726, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37882732

RESUMO

The surface molecular doping of organic semiconductors can play an important role in the development of organic electronic or optoelectronic devices. Single-crystal rubrene remains a leading molecular candidate for applications in electronics due to its high hole mobility. In parallel, intensive research into the fabrication of flexible organic electronics requires the careful design of functional interfaces to enable optimal device characteristics. To this end, the present work seeks to understand the effect of surface molecular doping on the electronic band structure of rubrene single crystals. Our angle-resolved photoemission measurements reveal that the Fermi level moves in the band gap of rubrene depending on the direction of surface electron-transfer reactions with the molecular dopants, yet the valence band dispersion remains essentially unperturbed. This indicates that surface electron-transfer doping of a molecular single crystal can effectively modify the near-surface charge density, while retaining good charge-carrier mobility.

8.
Biol Pharm Bull ; 46(11): 1558-1568, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37914358

RESUMO

This study was designed to evaluate the potential protective impact of estrogen and estrogen receptor against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. The levels of liver injury serum biomarkers, liver content of interleukin-6 (IL-6), relative liver weight and distortion of liver histological pictures were significantly increased in ovariectomized (OVX) rats and SHAM rats that received DEN alone and were further exaggerated when DEN was combined with fulvestrant (F) compared to non-DEN treated rats. The OVX rats showed higher insults than SHAM rats. The tapering impact on these parameters was clear in OVX rats that received estradiol benzoate (EB), silymarin (S) or orlistat (ORS). The immunohistochemistry and/or Western blot analysis of liver tissues showed a prominent increase in fatty acid synthase (FASN) and cluster of differentiation 36 (CD36) expressions in OVX and SHAM rats who received DEN and/ or F compared to SHAM rats. In contrast to S, treatment of OVX rats with EB mitigated DEN-induced expression of FASN and CD36 in liver tissue, while ORS improved DEN-induced expression of FASN. In conclusion, the protective effect against HCC was mediated via estrogen receptor alpha (ER-α) which abrogates its downstream genes involved in lipid metabolism namely FASN and CD36 depriving the tumor from survival vital energy source. In addition, ORS induced similar mitigating effect against DEN-induced HCC which could be attributed to FASN inhibition and anti-inflammatory effect. Furthermore, S alleviated DEN-induced HCC, independent of its estrogenic effect.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Feminino , Ratos , Carcinoma Hepatocelular/metabolismo , Dietilnitrosamina/toxicidade , Dietilnitrosamina/metabolismo , Estrogênios/metabolismo , Ácido Graxo Sintases/metabolismo , Ácido Graxo Sintases/farmacologia , Interleucina-6/metabolismo , Fígado/metabolismo , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/prevenção & controle , Receptores de Estrogênio/metabolismo
9.
Ann Plast Surg ; 90(6S Suppl 5): S526-S532, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36921329

RESUMO

INTRODUCTION: An evaluation of complication rates in different abdominal lipectomy techniques with relationship to body mass index (BMI) and other risk factors. METHODS: We identified patients who underwent an abdominal lipectomy at our institution from January 2015 to July 2020. Those with concurrent hernia repair were excluded. Patients were classified into 2 groups: (1) horizontal lipectomy with or without umbilical translocation and (2) inverted-T lipectomy with translocation. Demographics, operative details, and postoperative complications were collected for 1 year postoperatively. Bivariate analyses were conducted to determine factors associated with type of procedure and complications. Crude and stratum-specific (based on BMI) odds ratios for complications were calculated for the inverted T as compared with the horizontal group. A replicate analysis using the national Tracking Operations and Outcomes for Plastic Surgeons (TOPS) as a single cohort was performed. RESULTS: At our institution, 362 patients (group 1 = 196, group 2 = 166) were included. A total of 40.9% of patients experienced at least one complication at 1 year postoperatively with the complication rate decreasing to 28.0% when analyzed at the 30-day postoperative period. Specifically, wound disruption rates were highest in group 2 (39.8%) compared with group 1 (15.6%; P < 0.0001). The odds of experiencing a complication were greater in the inverted-T group overall and within each stratum of BMI. When dividing the cohort based on BMI class (normal weight, overweight, class I, class II, and class III obesity), the incidence of wound disruption increased as did BMI (2.6%, 22.2%, 27.2%, 48.2%, and 56.3%, respectively; P < 0.0001). The TOPS data set included 23,067 patients and showed an overall complication rate of 13.1% at 30-day postop. Overall, wound disruption rate was 4.6%. Compared with normal weight patients, the odds of experiencing a complication trended higher with each stratum of BMI. Other factors associated with complications included BMI, tobacco use, diabetes, American Society of Anesthesiology, prior massive weight loss, and LOS. CONCLUSIONS: The increasing complication rate within each BMI stratum of the large sample size of the TOPS patient cohort, in addition to our similar institutional trends, suggests that a staged procedure may be more appropriate for higher BMI patients. Surgical technique modification with limited flap undermining in patients undergoing inverted-T lipectomy to preserve flap perfusion may also decrease overall complication rates.


Assuntos
Lipectomia , Cirurgiões , Humanos , Estados Unidos/epidemiologia , Lipectomia/efeitos adversos , Lipectomia/métodos , Índice de Massa Corporal , Incidência , Obesidade/complicações , Obesidade/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
10.
J Urol ; 208(2): 317-324, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35343252

RESUMO

PURPOSE: We sought to determine if absolute prostate specific antigen (PSA) value after 6 months of androgen deprivation therapy (ADT) is predictive of subsequent survival in patients with prostate adenocarcinoma. MATERIALS AND METHODS: We performed a retrospective review of men receiving care within the Veterans Health Administration who initiated ADT for prostate adenocarcinoma. We used low- (≤0.2 ng/ml), intermediate- (>0.2 to 4 ng/ml) and high-risk (>4 ng/ml) absolute PSA values after 6-9 months of ADT, previously described in Southwest Oncology Group trial 9346. The primary endpoints were all-cause mortality and prostate cancer-specific mortality (PCSM). Kaplan-Meier survival curves for each PSA category were estimated and log-rank test was conducted. We employed Cox regression analysis adjusted for covariates and inverse propensity score weights associated with PSA categories to estimate the PSA category association with PCSM and all-cause mortality. RESULTS: We identified 9,170 patients in our cohort. Following ADT induction, 3,508 patients had low, 3,419 had intermediate and 2,243 had high PSA values. Two- and 5-year survival rates for low, intermediate and high PSA groups were 93.9% and 85.2% vs 88.6% and 71.2% vs 63.6% and 38.6%, respectively (p <0.0001). Patients in the high and intermediate PSA categories had a 15-fold and 3-fold higher risk of PCSM compared to those with PSA <0.2 ng/ml (p <0.0001). CONCLUSIONS: Absolute PSA in hormone-sensitive prostate cancer after 6-9 months of ADT is a predictor of overall mortality and PCSM. This measure can rapidly assess the efficacy of new interventions in phase 2 clinical trials.


Assuntos
Adenocarcinoma , Neoplasias da Próstata , Adenocarcinoma/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Androgênios/uso terapêutico , Humanos , Masculino , Antígeno Prostático Específico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia
11.
J Urol ; 208(4): 821-829, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35574612

RESUMO

PURPOSE: We investigated the safety, preliminary efficacy, and immune effects of large surface area microparticle docetaxel (LSAM-DTX) administered by direct injection after transurethral resection of bladder tumor (TURBT), and by intravesical instillation in high-risk nonmuscle-invasive bladder cancer. MATERIALS AND METHODS: The trial followed an open-label 3+3 dose escalation with additional enrollment at the high dose. After TURBT, subjects received direct injection LSAM-DTX into the resection site and intravesical LSAM-DTX, followed by 6-week induction and 3-week maintenance intravesical LSAM-DTX courses. Tumor recurrence was evaluated by cytology, cystoscopy, or biopsy. Pharmacokinetic analysis of blood and multiplex immunofluorescence of tumor microenvironment occurred pre- and post-LSAM-DTX. RESULTS: Nineteen subjects were enrolled, 14 with prior bacillus Calmette-Guérin exposure and 16 with ≥1 prior TURBT. Direct injection and intravesical LSAM-DTX were well tolerated. In the 3 lowest dose escalation cohorts the median recurrence-free survival was 5.4 months (10 patients, median followup 8.6 months). In the high-dose and expansion cohorts median recurrence-free survival was significantly increased (p <0.05, hazard ratio 0.29) to 12.2 months (9 patients, median followup 12.4 months). Systemic docetaxel exposure was negligible and increases in antitumor immune cells were found in the tumor microenvironment along with elevations in the PD-1, PD-L1 and CTLA-4 immune checkpoint inhibitor targets. CONCLUSIONS: Post-TURBT direct injection and intravesical LSAM-DTX were well tolerated and demonstrated clinical response for patients with high-risk nonmuscle-invasive bladder cancer. Favorable immune cell infiltration and checkpoint receptor increases following LSAM-DTX treatment warrants investigation alone as well as in combination with immune checkpoint inhibitor therapy.


Assuntos
Neoplasias da Bexiga Urinária , Administração Intravesical , Vacina BCG/uso terapêutico , Docetaxel/uso terapêutico , Humanos , Inibidores de Checkpoint Imunológico , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Resultado do Tratamento , Microambiente Tumoral , Neoplasias da Bexiga Urinária/cirurgia
12.
J Urol ; 208(3): 542-560, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35762219

RESUMO

PURPOSE: Open radical nephrectomy with inferior vena cava thrombectomy (O-CT) is standard management for renal cell carcinoma with inferior vena cava thrombus. First reported a decade ago, robotic-assisted radical nephrectomy with inferior vena cava thrombectomy (R-CT) is a minimally invasive option for this disease. We aimed to perform a systematic review to assess the safety and feasibility of R-CT in terms of perioperative outcomes and compare the outcomes between R-CT and O-CT. MATERIALS AND METHODS: The PubMed®, Scopus®, Cochrane Central Register of Controlled Trials and Web of ScienceTM databases were searched using the free-text and MeSH terms "renal cell carcinoma," "inferior vena cava," "thrombosis" or "thrombus," "robot" and "thrombectomy." Studies reporting perioperative outcomes of R-CT and studies comparing R-CT with O-CT were included. The review was done in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS: The search retrieved 28 articles describing R-CT, including 7 comparative studies. This systematic review included 1,375 patients, out of which 329 patients were in single-arm studies and 1,046 patients were in comparative studies. Of the 329 patients who underwent R-CT, 14.7% were level I, 60.9% level II, 20.4% level III and 2.5% level IV thrombus. Operative time ranged from 150 to 530 minutes; blood transfusion was administered in 38.2% (126). The overall complication rate was 30.3% (99). R-CT, in comparison to O-CT, was associated with a lower blood transfusion rate (18.4% vs 64.3%, p=0.002) and a lower complication rate (14.5% vs 36.7%, p=0.005). Major complication and 30-day mortality rates were similar in both groups. CONCLUSIONS: R-CT has acceptable perioperative outcomes in carefully selected patients. Compared with O-CT, R-CT is associated with a lower blood transfusion rate and fewer overall complications. In experienced hands with carefully selected patients, R-CT is feasible and safe, with acceptable outcomes; however, selection bias limits definitive inference of these results, and optimal patient selection criteria remain to be described.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Trombose , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Trombectomia/efeitos adversos , Trombectomia/métodos , Veia Cava Inferior/patologia , Veia Cava Inferior/cirurgia
13.
Phys Chem Chem Phys ; 24(5): 3109-3118, 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35040854

RESUMO

Molecular doping is a key process to increase the density of charge carriers in organic semiconductors. Doping-induced charges in polymer semiconductors result in the formation of polarons and/or bipolarons due to the strong electron-vibron coupling in conjugated organic materials. Identifying the nature of charge carriers in doped polymers is essential to optimize the doping process for applications. In this work, we use Raman spectroscopy to investigate the formation of charge carriers in molecularly doped poly(3-hexylthiophene-2,5-diyl) (P3HT) for increasing dopant concentration, with the organic salt dimesityl borinium tetrakis(penta-fluorophenyl)borate (Mes2B+ [B(C6F5)4]-) and the Lewis acid tris(pentafluorophenyl)borane [B(C6F5)3]. While the Raman signatures of neutral P3HT and singly charged P3HT segments (polarons) are known, the Raman spectra of doubly charged P3HT segments (bipolarons) are not yet sufficiently understood. Combining Raman spectroscopy measurements on doped P3HT thin films with first-principles calculations on oligomer models, we explain the evolution of the Raman spectra from neutral P3HT to increasingly doped P3HT featuring polarons and eventually bipolarons at high doping levels. We identify and explain the origin of the spectral features related to bipolarons by tracing the Raman signature of the symmetric collective vibrations along the polymer backbone, which - compared to neutral P3HT - redshifts for polarons and blueshifts for bipolarons. This is explained by a planarization of the singly charged P3HT segments with polarons and rather high order in thin films, while the doubly charged segments with bipolarons are located in comparably disordered regions of the P3HT film due to the high dopant concentration. Furthermore, we identify additional Raman peaks associated with vibrations in the quinoid doubly charged segments of the polymer. Our results offer the opportunity for readily identifying the nature of charge carriers in molecularly doped P3HT while taking advantage of the simplicity, versatility, and non-destructive nature of Raman spectroscopy.

14.
J Asthma ; 59(11): 2135-2142, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34752186

RESUMO

OBJECTIVE: Asthma is a chronic disorder of the airways, in which chemokines coordinate airway inflammation and determine its severity. We aimed to study the chemokine interferonγ-inducible protein 10 kDa (IP10/CXCL10), a member of the CXC receptor 3 (CXCR3) ligand family, at the protein level in the serum of children, to evaluate the association between CXCL10 and exacerbations of childhood asthma. METHODS: Patients experiencing an asthma exacerbation (42 patients) and stable patients (43 patients) were investigated for serum CXCL10 levels. RESULTS: Patients with an asthma exacerbation expressed significantly higher CXCL10 levels in the serum than stable patients (p < 0.001). Additionally, CXCL10 values were elevated in severe asthma compared with moderate and mild disease (p < 0.001). In patients experiencing asthma exacerbations, higher values of CXCL10 were observed in atopic patients compared with non-atopic patients (p = 0.027) and in uncontrolled and partly controlled patients compared with controlled patients (p = 0.046). CONCLUSIONS: CXCL10 is proposed as an inflammatory serum marker for asthma exacerbations and worsening asthma symptoms. The levels of CXCL10 are representative of the clinical severity of asthma.


Assuntos
Asma , Quimiocina CXCL10 , Criança , Humanos , Inflamação , Ligantes , Sistema Respiratório
15.
Int J Clin Oncol ; 27(6): 1068-1076, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35319076

RESUMO

BACKGROUND: A recently reported phase III randomized trial comparing open and minimally invasive hysterectomy showed significantly higher rates of local recurrence after minimally invasive surgery (MIS) for cervical cancer. This raised concerns regarding patterns of recurrences and survival after MIS in general. This study aims to determine the effect of MIS on all-cause mortality among patients undergoing radical nephrectomy for Stage I and II renal cell carcinoma (RCC). METHODS: We utilized the National Cancer Database to identify patients diagnosed with clinical stage I-II RCCs between 2010 and 2013. Patients for whom a laparoscopic or robotic radical nephrectomy was attempted were compared to patients who underwent open radical nephrectomy (ORN). Adjusted regression models with inverse probability propensity score weighting (IPW) were utilized to identify independent predictors of receiving MIS. All-cause mortality rates were compared using IPW survival functions and log-rank tests. Adjusted Cox proportional hazard models were fitted to determine independent predictors of OS. RESULTS: 27,642 patients were identified; 11,524 (41.7%) had MIS, while 16,118 (58.3%) had ORN. Kaplan-Meier survival curves in the IPW cohort showed significant OS advantage for patients who underwent MIS (p < 0.001). Furthermore, length of hospital stays (3 vs. 4 days), 30 day readmission rates (2.4 vs. 2.87%), 30 day (0.53 vs. 0.96%) and 90 day mortality rates (1.04 vs. 1.77%) were significantly higher in the ORN group (p < 0.001). CONCLUSIONS: MIS was associated with better OS outcomes compared to ORN for stage I and II RCC. In addition, MIS had lower post-operative readmission, 30- and 90 day mortality rates.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Laparoscopia , Neoplasias do Colo do Útero , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Histerectomia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Estadiamento de Neoplasias , Nefrectomia , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia
16.
J Perinat Med ; 50(3): 294-299, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-34523303

RESUMO

OBJECTIVES: To compare between the effectiveness and safety of two different daily doses of vaginal progesterone (400 vs. 200 mg) in the prevention of preterm labor in twin pregnancy. METHODS: This is a prospective single-blinded randomized controlled trial conducted on 100 primi-gravida who had twin pregnancy and attended the antenatal clinic of a University hospital. They were equally and randomly allocated into two arms each containing 50 patients. Arm 1 received 400 mg and arm 2 received 200 mg vaginal progesterone daily at bed time starting from 14 weeks of pregnancy to 36 weeks. Transvaginal ultrasound was performed for assessment of the length of cervix at 14 and 22 weeks. RESULTS: Both arms of the current study were comparable regarding the cervical length at 14 and 22 weeks, mean gestational age at delivery, incidence of pre-term delivery, birth weight of the first twin. Second twin in addition to the average weight of both twins. No statistical significance differences between two arms regarding incidence of early neonatal death. NICU, mechanical ventilation, length of admission in NICU for the first twin. Second twin as well as both twins. CONCLUSIONS: Vaginal progesterone treatment with different doses was tolerable, but wasn't effective in the prevention of preterm labor in twin pregnancy.


Assuntos
Trabalho de Parto Prematuro/prevenção & controle , Gravidez de Gêmeos , Progesterona/administração & dosagem , Administração Intravaginal , Adulto , Medida do Comprimento Cervical , Relação Dose-Resposta a Droga , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos Prospectivos , Método Simples-Cego
17.
Int Orthop ; 46(12): 2765-2774, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35859214

RESUMO

BACKGROUND: Since femoral and horizontal offsets may be contributing factors to hip and pelvic balance, this study seeks to determine whether there is a correlation between pelvic obliquity (PO) after unilateral total hip arthroplasty (THA) and horizontal/vertical offset differences of the replaced and contralateral natural joints. METHODS: A cross-sectional study was performed on adult patients who underwent unilateral THA between 2017 and 2020. An expert orthopaedic resident measured PO angles and offset parameters. "Delta medial offset" is considered medial offset of the replaced hip minus the medial offset of the contralateral side. "Absolute delta medial offset" is considered the absolute value of the "Delta medial offset." RESULTS: Finally, 133 patients were included in the study with a mean (SD) age of 45.3 ± 14.8 years and 57.9% female. The PO values (median, IQR) changed from 3.2 (1.7-5.7) before THA to 3.0 (1.50-5.6) after THA, not significantly decreased (P = 0.31). The PO after THA is significantly correlated with PO before THA (correlation coefficient of 0.457, P < 0.001), the delta medial offset after THA (correlation coefficient of - 0.24, P = 0.006), and the absolute delta medial offset after THA (correlation coefficient of 0.284, P = 0.001). The amount of changes of delta medial offset, before and after surgery, was not significantly correlated to PO or PO changes after surgery. CONCLUSION: PO before the THA and medial offset discrepancy after THA are two important contributing factors for post-operative PO. Restoring the medial offset of the affected side and lowering the delta medial offset between the two sides can significantly decrease post-operative PO.


Assuntos
Artroplastia de Quadril , Doenças Ósseas , Prótese de Quadril , Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Masculino , Artroplastia de Quadril/efeitos adversos , Estudos Transversais , Fêmur/cirurgia , Extremidade Inferior/cirurgia , Pelve/cirurgia , Doenças Ósseas/cirurgia , Prótese de Quadril/efeitos adversos , Articulação do Quadril/cirurgia
18.
Molecules ; 27(7)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35408576

RESUMO

Biofilm control by essential oil (EO) application has recently increased to preclude biofilm production on foods and environmental surfaces. In this work, the anti-biofilm effects of garlic and thyme essential oils using the minimum inhibitory concentration (MIC) method against Salmonella typhimurium recovered from different abattoir samples were investigated along with the virulence genes (InvA, SdiA and Stn genes), and the antimicrobial susceptibility profile of S. typhimurium as well. The obtained results revealed that S. typhimurium contaminated abattoir samples to varying degrees. The InvA gene was investigated in all isolates, whereas the SdiA and Stn genes were observed in four and three isolates, respectively. Utilizing the disc diffusion method, S. typhimurium isolates demonstrated substantial resistance to most of the examined antibiotics with a high multiple antibiotic resistance index. S. typhimurium isolates demonstrated biofilm formation abilities to various degrees at varied temperatures levels (4 °C and 37 °C). In conclusion, the obtained samples from the research area are regarded as a potential S. typhimurium contamination source. Furthermore, garlic essential oil (GEO) has more potential to inhibit S. typhimurium biofilm at different sub-minimum inhibitory concentrations as compared to thyme essential oil (TEO). Therefore, these EOs are considered as potential natural antibacterial options that could be applied in food industry.


Assuntos
Alho , Óleos Voláteis , Thymus (Planta) , Antibacterianos/farmacologia , Biofilmes , Testes de Sensibilidade Microbiana , Óleos Voláteis/farmacologia , Salmonella typhimurium/genética
19.
Pharm Dev Technol ; 27(10): 1110-1124, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36458575

RESUMO

A 7%w/w ectoine formula, from natural source, is formulated to reduce melanomagenesis, enhance penetration by 3D printed microneedles (MNs), with specified length, diameter and tip to ensure painless effect. Ectoine gel formulations were prepared using Carbopol 940 and Pluronic (F127). The effect of the polymers on pH, viscosity, spreadability, and the in vitro, ex vivo release profiles was obtained. The physiochemical investigation showed uniform gel formulations. The formulations' in vitro and ex vivo drug release displayed a controllable drug release pattern, reaching 63.7-96% and 73-94.7% after 24 h. The permeation study of the in vitro and ex vivo release revealed that the drug release from gels followed diffusion mechanism. The selected formula was used, 3D printed MN array was applied to treat melanoma. Male rats were used for induction of melanoma using 0.5% of 7,12-dimethylbenz[a]anthracene three times weekly for 12 weeks, histopathology was applied to ensure development of carcinoma then rats were treated using the selected formula. Following treatment for continuous 6 weeks, histopathology showed a change in anatomy of skin, which started to return to its normal structure. The anti-melanogenesis activity of optimum formula of ectoine gel, enhanced by 3D printed MN, was found to be effective in reducing the severity of skin cancer reinforcing the efficacy of the promising treatment.


Assuntos
Melanoma , Absorção Cutânea , Ratos , Masculino , Animais , Administração Cutânea , Pele/metabolismo , Géis/química , Poloxâmero/química , Melanoma/tratamento farmacológico , Impressão Tridimensional
20.
Curr Issues Mol Biol ; 43(3): 1698-1714, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34698133

RESUMO

Autophagy has been demonstrated to have a beneficial effect on diabetic nephropathy (DN). Rapamycin, an inhibitor of mTOR, was shown to stimulate ß-cell autophagy. However, its effects on preventing or ameliorating DN is unclear, and its effects are worth studying. As fasting is now an attractive protective strategy, we aim to compare its effect to rapamycin effects on pancreatic and renal cells. Twenty-eight adult male Wistar Albino rats were randomly divided into four groups, using streptozotocin (STZ) to induce diabetes mellitus (DM). Autophagy was induced by two ways; rapamycin or fasting. The extent of autophagy and apoptosis were investigated by measuring the level of LC3B and p53 proteins, respectively, in pancreatic and kidney tissues using Western blotting (WB) technique and imaging the renal cells under transmission electron microscope. The efflux transporter P-glycoprotein was quantified by WB as well. Rapamycin-induced autophagy occurred concurrently with apoptosis. On the other hand, fasting supported P-glycoprotein recovery and renal cell survival together with disabling ß-cells apoptosis. In conclusion, this study provides a potential link between rapamycin or fasting for the cross-regulation of apoptosis and autophagy in the setting of cell stress as DN. Unlike rapamycin, fasting enhanced the active expression of ABCB1 efflux protein, providing insights on the potential ameliorative effects of fasting in DN that require further elucidation.


Assuntos
Autofagia/efeitos dos fármacos , Nefropatias Diabéticas/metabolismo , Jejum/metabolismo , Sirolimo/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagossomos/metabolismo , Autofagossomos/ultraestrutura , Biomarcadores , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Testes de Função Renal , Testes de Função Hepática , Estresse Oxidativo , Ratos
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