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1.
Biotechnol J ; 19(4): e2300466, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581094

RESUMO

The bacterium Sporosarcina pasteurii is the most commonly used microorganism for Microbial Induced Calcite Precipitation (MICP) due to its high urease activity. To date, no proper fed-batch cultivation protocol for S. pasteurii has been published, even though this cultivation method has a high potential for reducing costs of producing microbial ureolytic biomass. This study focusses on fed-batch cultivation of S. pasteurii DSM33. The study distinguishes between limited fed-batch cultivation and extended batch cultivation. Simply feeding glucose to a S. pasteurii culture does not seem beneficial. However, it was exploited that S. pasteurii is auxotrophic for two vitamins and amino acids. Limited fed-batch cultivation was accomplished by feeding the necessary vitamins or amino acids to a culture lacking them. Feeding nicotinic acid to a nicotinic acid deprived culture resulted in a 24% increase of the specific urease activity compared to a fed culture without nicotinic acid limitation. Also, extended batch cultivation was explored. Feeding a mixture of glucose and yeast extract results in OD600 of ≈70 at the end of cultivation, which is the highest value published in literature so far. These results have the potential to make MICP applications economically viable.


Assuntos
Carbonato de Cálcio , Ácidos Nicotínicos , Sporosarcina , Carbonato de Cálcio/química , Urease/metabolismo , Biomassa , Ureia/química , Ureia/metabolismo , Vitaminas , Aminoácidos , Glucose
2.
Int J Biol Macromol ; 262(Pt 1): 129903, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325694

RESUMO

In the present study, chitosan-bentonite biocomposites were synthesised by ultrasonication, characterized using spectral techniques and assessed for their effectiveness in removing imazethapyr and imazamox from aqueous solution. The response surface methodology based box behnken design was utilized to generate optimum conditions viz. pH (1 to 9), adsorbent dose (0.01 to 1.0 g), contact time (0.5 to 48 h) and temperature (15 to 55 °C) for adsorption of herbicides on biocomposites. Based on model predictions, 60.4 to 91.5 % of imazethapyr and 31.7 to 46.4 % of imazamox was efficiently removed under optimal conditions. Adsorption data exhibited a strong fit to pseudo-second-order kinetic (R2 > 0.987) and Freundlich isotherm (R2 > 0.979). The adsorption capacity ranged from 3.88 to 112 µg1-ng-1mLn and order of adsorption was: low molecular weight chitosan-bentonite> medium molecular weight chitosan-bentonite> high molecular weight chitosan-bentonite> bentonite. Thermodynamic experiments suggested a spontaneous, exothermic process, reducing the system randomness during adsorption. Desorption experiments revealed successful desorption ranging from 91.5 to 97.0 % using 0.1 M NaOH. The adsorption mechanism was dominated by synergistic electrostatic interactions and hydrogen bonding. These results collectively indicated the potential environmental remediation application of chitosan-bentonite biocomposites to adsorb imazethapyr and imazamox from wastewaters.


Assuntos
Quitosana , Imidazóis , Ácidos Nicotínicos , Poluentes Químicos da Água , Quitosana/química , Bentonita/química , Adsorção , Concentração de Íons de Hidrogênio , Termodinâmica , Cinética , Poluentes Químicos da Água/química
3.
J Drugs Dermatol ; 23(2): 50-53, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306148

RESUMO

INTRODUCTION: Moisturizers are often used as adjuvant therapy for psoriasis to assist with rehydration and skin barrier restoration. Fixed-combination halobetasol propionate 0.01% and tazarotene 0.045% lotion (HP/TAZ) is indicated for the topical treatment of plaque psoriasis in adults, with a demonstrated clinical profile in two phase 3 trials. However, the effect of application order with HP/TAZ has yet to be explored. This study evaluated the clinical profile of HP/TAZ applied before versus after a ceramide-containing moisturizer in adults with mild-to-moderate plaque psoriasis. METHODS: Sixteen participants were randomized to apply HP/TAZ followed by moisturizer on one side and moisturizer followed by HP/TAZ on the other side once daily for 12 weeks. Tolerability, safety, efficacy, and quality of life endpoints were assessed.  Results: Significant Investigator's Global Assessment improvement was observed across all time points (P≤0.003) regardless of application order. Total Dermatology Life Quality Index scores significantly improved at all time points (P≤0.003), and visual analog scale for itch significantly improved at weeks 4, 8, and 12 (P<0.008). Four moderate adverse events were experienced by 3 participants. Two participants reported itching/irritation, which was worse when HP/TAZ was applied first. CONCLUSIONS: The application order of moisturizer did not decrease therapeutic efficacy of HP/TAZ. Moisturizer application before HP/TAZ may reduce incidence of application site adverse events, ultimately increasing tolerability and supporting the real-world recommendation that applying a ceramide-containing moisturizer before HP/TAZ, versus after, results in a safe and effective therapeutic option for plaque psoriasis. J Drugs Dermatol. 2024;23(2):50-53.     doi:10.36849/JDD.7928.


Assuntos
Fármacos Dermatológicos , Ácidos Nicotínicos , Psoríase , Adulto , Humanos , Combinação de Medicamentos , Qualidade de Vida , Resultado do Tratamento , Índice de Gravidade de Doença , Creme para a Pele , Clobetasol/efeitos adversos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Prurido/induzido quimicamente , Prurido/tratamento farmacológico , Ceramidas/uso terapêutico , Método Duplo-Cego
4.
J Agric Food Chem ; 72(7): 3445-3455, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38325393

RESUMO

As representatives of allelopathy, weeds consistently coexist with crops, exhibiting mutual growth inhibition. At the same time, herbicides are usually employed to control weeds. However, few studies have investigated how herbicides will affect allelopathy between crops and their neighboring weeds. Our findings suggested that allelopathic-induced phenotypic variations in ryegrass were reduced in the presence of the herbicide imazethapyr (IM), consistent with the antioxidant system analysis results. Additionally, IM affected the levels of allelochemical hydroxamic acid (Hx) in both plants. Hydroponic experiments revealed that this impact was due to the accelerated transportation of Hx from wheat to ryegrass, driven by ryegrass-secreted jasmonic acid. This study holds paramount significance for comprehending the effects of herbicides on the allelopathic interactions between nontargeted crops and neighboring weeds, contributing to an enhanced understanding of herbicides on plant species interactions.


Assuntos
Herbicidas , Lolium , Ácidos Nicotínicos , Triticum , Herbicidas/farmacologia , Alelopatia , Plantas Daninhas , Produtos Agrícolas
5.
Nanoscale ; 16(7): 3243-3268, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38265094

RESUMO

A key role in lessening humanity's continuous fight against cancer could be played by photodynamic therapy (PDT), a minimally invasive treatment employed in the medical care of a range of benign disorders and malignancies. Cancerous tissue can be effectively removed by using a light source-excited photosensitizer. Singlet oxygen and reactive oxygen species are produced via the photosensitizer as a result of this excitation. In the recent past, researchers have put in tremendous efforts towards developing photosensitizer molecules for photodynamic treatment (PDT) to treat cancer. Conjugated polymers, characterized by their efficient fluorescence, exceptional photostability, and strong light absorption, are currently under scrutiny for their potential applications in cancer detection and treatment through photodynamic and photothermal therapy. Researchers are exploring the versatility of these polymers, utilizing sophisticated chemical synthesis and adaptable polymer structures to create new variants with enhanced capabilities for generating singlet oxygen in photodynamic treatment (PDT). The incorporation of photosensitizers into conjugated polymer nanoparticles has proved to be beneficial, as it improves singlet oxygen formation through effective energy transfer. The evolution of nanotechnology has emerged as an alternative avenue for enhancing the performance of current photosensitizers and overcoming significant challenges in cancer PDT. Various materials, including biocompatible metals, polymers, carbon, silicon, and semiconductor-based nanomaterials, have undergone thorough investigation as potential photosensitizers for cancer PDT. This paper outlines the recent advances in singlet oxygen generation by investigators using an array of materials, including graphene quantum dots (GQDs), gold nanoparticles (Au NPs), silver nanoparticles (Ag NPs), titanium dioxide (TiO2), ytterbium (Yb) and thulium (Tm) co-doped upconversion nanoparticle cores (Yb/Tm-co-doped UCNP cores), bismuth oxychloride nanoplates and nanosheets (BiOCl nanoplates and nanosheets), and others. It also stresses the synthesis and application of systems such as amphiphilic block copolymer functionalized with folic acid (FA), polyethylene glycol (PEG), poly(ß-benzyl-L-aspartate) (PBLA10) (FA-PEG-PBLA10) functionalized with folic acid, tetra(4-hydroxyphenyl)porphyrin (THPP-(PNIPAM-b-PMAGA)4), pyrazoline-fused axial silicon phthalocyanine (HY-SiPc), phthalocyanines (HY-ZnPcp, HY-ZnPcnp, and HY-SiPc), silver nanoparticles coated with polyaniline (Ag@PANI), doxorubicin (DOX) and infrared (IR)-responsive poly(2-ethyl-2-oxazoline) (PEtOx) (DOX/PEtOx-IR NPs), particularly in NIR imaging-guided photodynamic therapy (fluorescent and photoacoustic). The study puts forward a comprehensive summary and a convincing justification for the usage of the above-mentioned materials in cancer PDT.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Neoplasias , Ácidos Nicotínicos , Fotoquimioterapia , Succinimidas , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/química , Polímeros/química , Ouro/química , Prata , Neoplasias/tratamento farmacológico , Nanopartículas/uso terapêutico , Nanopartículas/química , Doxorrubicina/uso terapêutico , Ácido Fólico
6.
Chemosphere ; 351: 141178, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38218236

RESUMO

Excessive or inappropriate applications of imazethapyr cause severe ecological deteriorations and health risks in human. A novel bacterial strain, i.e., Bacillus marcorestinctum YN1, was isolated to efficiently degrade imazethapyr, with the degradation pathways and intermediates predicted. Protein mass spectrometry analysis identified enzymes in strain YN1 potentially involved in imazethapyr biodegradation, including methylenetetrahydrofolate dehydrogenase, carbon-nitrogen family hydrolase, heme degrading monooxygenase, and cytochrome P450. The strain YN1 was further immobilized with biochar (BC600) prepared from mushroom waste (i.e., spent mushroom substrate) by pyrolysis at 600 °C to evaluate its degrading characteristics of imazethapyr. Scanning electron microscope observation showed that strain YN1 was adsorbed in the rich pore structure of BC600 and the adsorption efficiency reached the maximum level of 88.02% in 6 h. Both energy dispersive X-ray and Fourier transform infrared spectroscopy analyses showed that BC600 contained many elements and functional groups. The results of liquid chromatography showed that biochar-immobilized strain YN1 (IBC-YN1) improved the degradation rate of imazethapyr from 79.2% to 87.4%. The degradation rate of imazethapyr by IBC-YN1 could still reach 81.0% in the third recycle, while the bacterial survival rate was 67.73% after 180 d storage at 4 °C. The treatment of IBC-YN1 significantly shortened the half-life of imazethapyr in non-sterilized soil from 35.51 to 11.36 d, and the vegetative growth of imazethapyr sensitive crop plant (i.e., Cucumis sativus L.) was significantly increased in soil remediated, showing that the inhibition rate of root length and fresh weight were decreased by 12.45% and 38.49% respectively. This study exhanced our understanding of microbial catabolism of imazethapyr, and provided a potential in situ remediation strategy for improving the soil environment polluted by imazethapyr.


Assuntos
Bacillus , Carvão Vegetal , Herbicidas , Ácidos Nicotínicos , Poluentes do Solo , Humanos , Herbicidas/análise , Solo/química , Biodegradação Ambiental , Bactérias/metabolismo , Poluentes do Solo/análise
7.
Photodiagnosis Photodyn Ther ; 44: 103818, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37788794

RESUMO

The rational design of photosensitizers with rapid cellular uptake and dual-organelle targeting ability is essential for enhancing the efficacy of photodynamic therapy (PDT). However, achieving this goal is a great challenge. In this paper, a novel axial piperazine substituted (PIP) silicon phthalocyanine (PIP-SiPc) has been synthesized. The PIP substitution significantly improved the cellular uptake of PIP-SiPc in MCF-7 breast cancer cells, as demonstrated by two-photon fluorescence imaging combined with fluorescence correlation spectroscopy. Additionally, PIP-SiPc was able to target both mitochondria and lysosomes simultaneously. Notably, PIP-SiPc exhibited remarkable singlet oxygen generation ability, leading to apoptosis in cancer cells upon irradiation, with an IC50 value of only 0.2 µM. These findings highlight the effectiveness of PIP-SiPc as a multifunctional photosensitizer for PDT.


Assuntos
Isoindóis , Ácidos Nicotínicos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Succinimidas , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Mitocôndrias , Piperazinas/farmacologia
8.
BMC Biotechnol ; 23(1): 25, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37507713

RESUMO

BACKGROUND: One critical parameter in microbial cultivations is the composition of the cultivation medium. Nowadays, the application of chemically defined media increases, due to a more defined and reproducible fermentation performance than in complex media. In order, to improve cost-effectiveness of fermentation processes using chemically defined media, the media should not contain nutrients in large excess. Additionally, to obtain high product yields, the nutrient concentrations should not be limiting. Therefore, efficient medium optimization techniques are required which adapt medium compositions to the specific nutrient requirements of microorganisms. RESULTS: Since most Paenibacillus cultivation protocols so far described in literature are based on complex ingredients, in this study, a chemically defined medium for an industrially relevant Paenibacillus polymyxa strain was developed. A recently reported method, which combines a systematic experimental procedure in combination with online monitoring of the respiration activity, was applied and extended to identify growth limitations for Paenibacillus polymyxa. All cultivations were performed in microtiter plates. By systematically increasing the concentrations of different nutrient groups, nicotinic acid was identified as a growth-limiting component. Additionally, an insufficient buffer capacity was observed. After optimizing the growth in the chemically defined medium, the medium components were systematically reduced to contain only nutrients relevant for growth. Vitamins were reduced to nicotinic acid and biotin, and amino acids to methionine, histidine, proline, arginine, and glutamate. Nucleobases/-sides could be completely left out of the medium. Finally, the cultivation in the reduced medium was reproduced in a laboratory fermenter. CONCLUSION: In this study, a reliable and time-efficient high-throughput methodology was extended to investigate limitations in chemically defined media. The interpretation of online measured respiration activities agreed well with the growth performance of samples measured in parallel via offline analyses. Furthermore, the cultivation in microtiter plates was validated in a laboratory fermenter. The results underline the benefits of online monitoring of the respiration activity already in the early stages of process development, to avoid limitations of medium components, oxygen limitation and pH inhibition during the scale-up.


Assuntos
Ácidos Nicotínicos , Paenibacillus polymyxa , Paenibacillus , Paenibacillus polymyxa/metabolismo , Reatores Biológicos , Fermentação , Meios de Cultura/química , Ácidos Nicotínicos/metabolismo
10.
J Drugs Dermatol ; 22(2): 223-225, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36745373

RESUMO

Copy: Palmoplantar psoriasis is a chronic, difficult-to-treat localized variant of psoriasis that affects the palms and soles, significantly affecting patient's quality of life. OBJECTIVE: To evaluate the synergistic effect of a fixed-combination topical lotion composed of halobetasol propionate 0.01% and tazarotene 0.045% in the treatment of palmoplantar psoriasis. METHODS: This was an open-label investigator-initiated trial involving 21 patients with moderate-to-severe palmoplantar plaque-type psoriasis who underwent treatment with halobetasol propionate 0.01% and tazarotene 0.045%. Subjects were assessed for disease severity using the palmoplantar Physician Global Assessment and the mean difference over time was compared using the Wilcoxon signed-rank test. RESULTS: 5 patients (24%) achieved a palmoplantar Physician Global Assessment of 0 or 1 after week 24 or last observation carried forward. The mean palmoplantar Physician Global Assessment significantly decreased from baseline (3.57) to week 24/last observation carried forward (2.38) (P<0.001). DISCUSSION: Halobetasol propionate 0.01% and tazarotene 0.045% lotion demonstrated efficacy in adult patients with moderate-to-severe palmoplantar plaque-type psoriasis through significant improvement in palmoplantar Physician Global Assessment. The complementary mechanisms of action of the corticosteroid and tazarotene may be of benefit compared to monotherapeutic agents. J Drugs Dermatol. 2023;22(2): 223-225. doi:10.36849/JDD.7067.


Assuntos
Fármacos Dermatológicos , Ácidos Nicotínicos , Psoríase , Adulto , Humanos , Resultado do Tratamento , Emulsões/uso terapêutico , Qualidade de Vida , Combinação de Medicamentos , Índice de Gravidade de Doença , Creme para a Pele , Clobetasol , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Método Duplo-Cego
11.
J Drugs Dermatol ; 22(2): 132-138, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36745378

RESUMO

Discordance between patient and clinician treatment goals and expectations can present a challenge to implementation of effective therapeutic plans. Because topical treatments are commonly used for plaque psoriasis, both as monotherapy and adjuncts to other treatment modalities, providers need to understand the concerns of patients with psoriasis regarding use of topical products. Psoriasis is a complex and chronic disease with treatment needs that may change over time, influencing patient treatment goals and expectations of efficacy. When these expectations are not met and patient concerns are unaddressed, dissatisfaction may lead to nonadherence, which in turn can prevent patients from achieving relief from the signs and symptoms of psoriasis that affect their quality of life. Here, we detail how current topical treatments meet patient expectations and needs, with particular attention given to combination regimens using corticosteroids. This review shows that once-daily application of halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) not only has a rapid onset of treatment effect and proven efficacy, but also has a remittive effect. In addition, HP/TAZ has a favorable safety profile, with low rates of irritation and local skin reactions in clinical studies. The dual mechanisms of action related to 2 active ingredients, once-daily use, and the favorable clinical findings suggest that HP/TAZ may address patient concerns and promote treatment adherence.J Drugs Dermatol. 2023;22(2):132-138. doi:10.36849/JDD.7367.


Assuntos
Fármacos Dermatológicos , Ácidos Nicotínicos , Psoríase , Humanos , Combinação de Medicamentos , Motivação , Qualidade de Vida , Resultado do Tratamento , Índice de Gravidade de Doença , Creme para a Pele , Clobetasol , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/etiologia , Emolientes/uso terapêutico , Emulsões/uso terapêutico
12.
J Drugs Dermatol ; 22(1): 3446174-34461710, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36607764

RESUMO

Psoriasis is a complex inflammatory disease, which can be triggered by the interplay among keratinocytes, various immune cells, and even dermal vascular endothelial cells. Understanding of the key players and cytokine/chemokine messengers involved in the initiation and maintenance of psoriasis has significantly evolved and led to numerous systemic biologic therapies targeting those specific components. These therapies, despite their successes, do not ubiquitously affect all pathogenic cellular pathways. They also carry their risks and may be contraindicated in certain patient populations. Therefore, other therapeutics are still necessary. Tazarotene, a decades-old topical retinoid, has been successfully used for treating cutaneous psoriasis. Its retinoid effect via binding to retinoic acid receptors (RAR)/retinoic X receptors (RXR) alters cellular gene expression of numerous pathogenic cells and leads to a long-standing maintenance effect despite discontinuation - a phenomenon known as remittance. Concurrent use of tazarotene with topical corticosteroids results in reduced incidence of treatment-related adverse events. A fixed-combination lotion containing halobetasol propionate (HP) and tazarotene (HP 0.01%/TAZ 0.045%, Duobrii, Ortho Dermatologics) was developed implementing polymeric emulsion technology that demonstrates efficacy in psoriasis while mitigating adverse events associated with each component alone as monotherapy. In this paper, we review the pathogenesis of psoriasis and illuminate the effect of tazarotene and HP on key cellular pathways. In addition, we review the clinical efficacy of fixed-combination HP 0.01%/TAZ 0.045% lotion in psoriasis as well as its long-term treatment maintenance, applicability in skin of color, and beneficial economic impact for patients and healthcare stakeholders. As HP 0.01%/TAZ 0.045% lotion is safe and exhibits excellent efficacy, it should be within the therapeutic toolbox for every psoriasis patient.J Drugs Dermatol. 2023;22:1(Suppl 1):s3-10.


Assuntos
Fármacos Dermatológicos , Ácidos Nicotínicos , Psoríase , Humanos , Administração Cutânea , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Combinação de Medicamentos , Emolientes/uso terapêutico , Emulsões/uso terapêutico , Células Endoteliais , Psoríase/tratamento farmacológico , Retinoides/uso terapêutico , Índice de Gravidade de Doença , Creme para a Pele , Resultado do Tratamento
13.
J Drugs Dermatol ; 21(10): 1061-1069, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36219057

RESUMO

BACKGROUND: While topical retinoids are a mainstay of acne treatment, acne can manifest differently in various skin types. The objective of these post hoc analyses from two pooled phase 3 studies was to examine efficacy and safety of tazarotene 0.045% and quality of life improvements in self-identified Caucasian adults with moderate-to-severe acne. METHODS: In two phase 3, double-blind, 12-week studies (NCT03168334; NCT03168321), participants aged ≥9 years with moderate-to-severe acne were randomized (1:1) to tazarotene 0.045% lotion or vehicle lotion (N=1,614); a subset of adults (≥18 years) who self-reported Caucasian (White) race (n=645) were examined. Coprimary endpoints were inflammatory/noninflammatory lesion counts and treatment (endpoint) success (≥2-grade reduction from baseline in Evaluator's Global Severity Score and a score of 0 [clear] or 1 [almost clear]). Quality of life, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability were also assessed. RESULTS: At week 12, tazarotene lotion significantly reduced lesion counts by ~60% (least-squares mean percent changes from baseline, tazarotene vs vehicle: inflammatory, -61.2% vs -51.1%; noninflammatory, -59.7% vs -49.3%; P<0.001, both). Significantly more participants achieved treatment success with tazarotene lotion versus vehicle (P<0.001). Numerical improvements in quality-of-life domains were observed from baseline to week 12. Most TEAEs were unrelated to treatment, and rates of moderate-to-severe erythema decreased from baseline to week 12 with tazarotene treatment. CONCLUSIONS: Tazarotene 0.045% lotion was efficacious and well tolerated over 12 weeks and led to quality-of-life improvements in Caucasian adults with moderate-to-severe acne. These results, along with those from patients with skin of color, demonstrate that once daily tazarotene 0.045% lotion is an effective and well-tolerated treatment option regardless of race or skin color.J Drugs Dermatol. 2022;21(10):1061-1069. doi:10.36849/JDD.6834.


Assuntos
Acne Vulgar , Fármacos Dermatológicos , Ácidos Nicotínicos , Acne Vulgar/diagnóstico , Acne Vulgar/tratamento farmacológico , Acne Vulgar/etiologia , Administração Cutânea , Adulto , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Emolientes/uso terapêutico , Emulsões/uso terapêutico , Humanos , Qualidade de Vida , Retinoides/uso terapêutico , Índice de Gravidade de Doença , Creme para a Pele/efeitos adversos , Resultado do Tratamento
14.
Org Biomol Chem ; 20(36): 7270-7277, 2022 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-35972402

RESUMO

Ligand release from silicon phthalocyanine (SiPc) dyes triggered by near-infrared (NIR) light is a key photochemical reaction involving caged compounds based on SiPc. Although NIR light is relatively permeable compared with visible light, this light can be attenuated by tissue absorption and scattering; therefore, using light to induce photochemical reactions deep inside the body is difficult. Herein, because X-rays are highly permeable and can produce radicals through the radiolysis of water, we investigated whether the axial ligands of SiPcs can be cleaved using X-ray irradiation. SiPcs with different axial ligands (alkoxy, siloxy, oxycarbonyl, and phenoxy groups) were irradiated with X-rays under hypoxic conditions. We found that the axial ligands were cleaved via reactions with hydrated electrons (e-aq), not OH radicals, generated from water in response to X-ray irradiation, and SiPc with alkoxy groups exhibited the highest cleavage efficiency. A quantitative investigation revealed that X-ray-induced axial ligand cleavage proceeds via a radical chain reaction. The reaction is expected to be applicable to the molecular design of X-ray-activatable functional molecules in the future.


Assuntos
Corantes , Água , Álcoois , Indóis , Ligantes , Ácidos Nicotínicos , Compostos de Organossilício , Succinimidas , Água/química , Raios X
15.
Biotechnol Bioeng ; 119(12): 3421-3431, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36042572

RESUMO

Nitrilases are promising biocatalysts to produce high-value-added carboxylic acids through hydrolysis of nitriles. However, since the enzymes always show low activity and sometimes with poor reaction specificity toward 2-chloronicotinonitrile (2-CN), very few robust nitrilases have been reported for efficient production of 2-chloronicotinic acid (2-CA) from 2-CN. Herein, a nitrilase from Paraburkholderia graminis (PgNIT) was engineered to improve its catalytic properties. We identified the beneficial residues via computational analysis and constructed the mutant library. The positive mutants were obtained and the activity of the "best" mutant F164G/I130L/N167Y/A55S/Q260C/T133I/R199Q toward 2-CN was increased from 0.14 × 10-3  to 4.22 U/mg. Its reaction specificity was improved with elimination of hydration activity. Molecular docking and molecular dynamics simulation revealed that the conformational flexibility, the nucleophilic attack distance, as well as the interaction forces between the enzyme and substrate were the main reason alternating the catalytic properties of PgNIT. With the best mutant as biocatalyst, 150 g/L 2-CN was completely converted, resulting in 2-CA accumulated to 169.7 g/L. When the substrate concentration was increased to 200 g/L, 203.1 g/L 2-CA was obtained with yield of 85.7%. The results laid the foundation for industrial production of 2-CA with the nitrilase-catalyzed route.


Assuntos
Aminoidrolases , Burkholderiaceae , Ácidos Nicotínicos , Aminoidrolases/química , Aminoidrolases/genética , Aminoidrolases/metabolismo , Burkholderiaceae/genética , Burkholderiaceae/metabolismo , Simulação de Acoplamento Molecular , Especificidade por Substrato , Ácidos Nicotínicos/biossíntese , Ácidos Nicotínicos/metabolismo , Catálise
16.
Skin Therapy Lett ; 27(4): 1-3, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35857858

RESUMO

Topical retinoids are recommended as first line therapy for the treatment of acne. Despite this recommendation, topical retinoids are underutilized, in part because of their tendency to cause cutaneous irritation. Tazarotene 0.045% lotion was developed using polymeric emulsion technology to provide an effective, well tolerated topical retinoid for the treatment of acne.


Assuntos
Acne Vulgar , Fármacos Dermatológicos , Acne Vulgar/tratamento farmacológico , Administração Cutânea , Fármacos Dermatológicos/efeitos adversos , Emolientes/uso terapêutico , Emulsões/uso terapêutico , Humanos , Ácidos Nicotínicos , Retinoides , Índice de Gravidade de Doença , Resultado do Tratamento
17.
Sci Rep ; 12(1): 11414, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35794139

RESUMO

This study aims to deliver Tazarotene (TZR) in a controlled manner to reduce adverse effects in the form of a microsponge-based gel. It adopts the methodology of a similar study by the undersigned authors with respect to the drug Clindamycin. Under both studies, the methodology used is emulsion solvent diffusion. Accordingly, we altered the concentrations of polymer and emulsifier to generate four formulations of TZR microsponges. Additionally, we used two types of emulsifiers and two types of solvents to develop two further microsponge formulations. We then studied the physical properties of each formulation, as well as drug-polymer interactions. Echoing findings from our prior study of Clindamycin, we found that microsponge formulations coded by T1 and T3 had superior production yield and entrapment efficiency, and their particle size was suitable for dermal application. As in the prior Clindamycin study, each of the T1 and T3 microsponge formulations were incorporated into a Carbopol gel and evaluated in vitro. The optimal formulation was found to be the microsponge formulation gel T8, which released 87.63% of TZR over 12 h. No significant interactions between the drug and excipients were found through Fourier transform infrared spectroscopy and differential scanning calorimetry.


Assuntos
Sistemas de Liberação de Medicamentos , Ácidos Nicotínicos , Clindamicina , Sistemas de Liberação de Medicamentos/métodos , Emulsificantes , Polímeros/química
18.
J Drugs Dermatol ; 21(7): 713-716, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35816073

RESUMO

BACKGROUND: Although truncal acne is thought to have the same pathophysiology as facial acne, treatment response may differ based on body area involvement. Traditionally, prescribers have relied on oral therapies for the management of truncal acne, possibly because oral therapy has been considered more convenient than topical application of medication to the chest and back. A lotion formulation may be particularly well-suited for the treatment of truncal acne. Tazarotene lotion, 0.045% is FDA approved for treatment of acne vulgaris in individuals 9 years of age or older. This pilot study was designed to investigate the efficacy and safety of Arazlo lotion for the treatment of truncal acne. STUDY FINDINGS: A total of 19 subjects ranging in age from 12 to 58 years completed the 12-week study. There were significant reductions in truncal IGA (the primary endpoint) at each of the study follow-up visits. At week 12, 89% of subjects were clear or almost clear, as assessed by truncal IGA score. There were statistically significant reductions in inflammatory, non-inflammatory, and total lesion counts from baseline to week 12. Treatment with tazarotene lotion 0.045% was well-tolerated, with erythema, dryness, peeling, oiliness, pruritis, and burning generally rated as trace or mild. Most subjects (64% or more) rated the lotion as “Good” or “Excellent” in general and in comparison to their prior medications. CONCLUSIONS: Tazarotene lotion, 0.045% is shown to be effective and well-tolerated for the management of truncal acne in this pilot study. Further studies with placebo control and larger populations are warranted. J Drugs Dermatol. 2022;21(7):713-716. doi:10.36849/JDD.6967.


Assuntos
Acne Vulgar , Fármacos Dermatológicos , Ácidos Nicotínicos , Acne Vulgar/diagnóstico , Acne Vulgar/tratamento farmacológico , Acne Vulgar/patologia , Administração Cutânea , Adolescente , Adulto , Criança , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Emolientes/uso terapêutico , Emulsões/uso terapêutico , Humanos , Imunoglobulina A/uso terapêutico , Pessoa de Meia-Idade , Ácidos Nicotínicos/efeitos adversos , Projetos Piloto , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
19.
J Drugs Dermatol ; 21(6): 587-595, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35674760

RESUMO

BACKGROUND: Females aged ≥25 years may have acne with different etiology, presentation, burden, and treatment response than females 18–24 years. This post hoc analysis investigated efficacy and safety of tazarotene 0.045% lotion in females ≥18 years or ≥25 years of age. METHODS: In two phase 3 double-blind studies, participants 9 years of age and older with moderate-to-severe acne were randomized (1:1) to once-daily tazarotene 0.045% lotion or vehicle lotion for 12 weeks. Pooled data were analyzed for females aged ≥18 years (n=744) or ≥25 years (n=335). Assessments included inflammatory/noninflammatory lesion counts, treatment success (≥2-grade reduction from baseline in Evaluator’s Global Severity Score and score of 0 [clear] or 1 [almost clear]), Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability. RESULTS: At week 12, tazarotene-treated females in both age groups had greater reductions from baseline versus vehicle in inflammatory (≥18 years: 60.6% vs 53.7% [P<0.01]; ≥25 years: 60.9% vs 57.3% [P>0.05]) and noninflammatory lesions (59.0% vs 48.4% and 61.1% vs 48.8%; P<0.01, both). Rates of treatment success were greater with tazarotene versus vehicle; this difference was significant for females ≥18 years. Acne-QoL improvements were similar across age groups and generally greater with tazarotene than vehicle. TEAEs were mostly mild to moderate in severity. No age-related trends for safety or tolerability were observed. CONCLUSIONS: Tazarotene 0.045% lotion demonstrated comparable efficacy, improvement in quality of life, and safety in adult females aged ≥18 or ≥25 years with moderate-to-severe acne. This cosmetically elegant lotion is a well-studied and important treatment option for all patients, particularly adult females. J Drugs Dermatol. 2022;21(5):587-595. doi:10.36849/JDD.6876.


Assuntos
Acne Vulgar , Fármacos Dermatológicos , Ácidos Nicotínicos , Acne Vulgar/diagnóstico , Acne Vulgar/tratamento farmacológico , Acne Vulgar/etiologia , Administração Cutânea , Adolescente , Adulto , Criança , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Emolientes/uso terapêutico , Emulsões/uso terapêutico , Excipientes , Feminino , Humanos , Ácidos Nicotínicos/efeitos adversos , Qualidade de Vida , Índice de Gravidade de Doença , Creme para a Pele/efeitos adversos , Resultado do Tratamento
20.
Cutis ; 109(2): 103-109, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35659807

RESUMO

Not all patients with psoriasis achieve a satisfactory response to their initial biologic monotherapy. Switching to a new biologic may be associated with new safety issues and additional costs. In this study, we assessed the effectiveness and safety of adjunctive halobetasol propionate (HP) 0.01%-tazarotene (TAZ) 0.045% lotion in adult patients with moderate to severe plaque psoriasis who had been receiving biologic monotherapy for 24 weeks or more but had inadequate responses. All participants received HP-TAZ lotion once daily for 8 weeks, then once every other day for 4 weeks, in addition to their ongoing biologics. This real-world study demonstrated that HP-TAZ lotion adjunctive to ongoing biologics is safe and effective and potentially a more economical alternative to switching biologics for patients with psoriasis with inadequate responses to biologic monotherapy.


Assuntos
Produtos Biológicos , Fármacos Dermatológicos , Ácidos Nicotínicos , Psoríase , Administração Cutânea , Adulto , Produtos Biológicos/uso terapêutico , Clobetasol/análogos & derivados , Clobetasol/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Combinação de Medicamentos , Emolientes/uso terapêutico , Humanos , Ácidos Nicotínicos/uso terapêutico , Propionatos/uso terapêutico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Creme para a Pele , Resultado do Tratamento
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