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1.
Biotechnol Biofuels Bioprod ; 17(1): 73, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822388

RESUMO

BACKGROUND: Lignin and xylan are important determinants of cell wall structure and lignocellulosic biomass digestibility. Genetic manipulations that individually modify either lignin or xylan structure improve polysaccharide digestibility. However, the effects of their simultaneous modifications have not been explored in a similar context. Here, both individual and combinatorial modification in xylan and lignin was studied by analysing the effect on plant cell wall properties, biotic stress responses and integrity sensing. RESULTS: Arabidopsis plant co-harbouring mutation in FERULATE 5-HYDROXYLASE (F5H) and overexpressing Aspergillus niger acetyl xylan esterase (35S:AnAXE1) were generated and displayed normal growth attributes with intact xylem architecture. This fah1-2/35S:AnAXE1 cross was named as hyper G lignin and hypoacetylated (HrGHypAc) line. The HrGHypAc plants showed increased crystalline cellulose content with enhanced digestibility after chemical and enzymatic pre-treatment. Moreover, both parents and HrGHypAc without and after pre-treating with glucuronyl esterase and alpha glucuronidase exhibited an increase in xylose release after xylanase digestion as compared to wild type. The de-pectinated fraction in HrGHypAc displayed elevated levels of xylan and cellulose. Furthermore, the transcriptomic analysis revealed differential expression in cell wall biosynthetic, transcription factors and wall-associated kinases genes implying the role of lignin and xylan modification on cellular regulatory processes. CONCLUSIONS: Simultaneous modification in xylan and lignin enhances cellulose content with improved saccharification efficiency. These modifications loosen cell wall complexity and hence resulted in enhanced xylose and xylobiose release with or without pretreatment after xylanase digestion in both parent and HrGHypAc. This study also revealed that the disruption of xylan and lignin structure is possible without compromising either growth and development or defense responses against Pseudomonas syringae infection.

2.
Cureus ; 16(2): e54619, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38523946

RESUMO

INTRODUCTION: The use of locally administered medication (LAM) agents such as minocycline, metronidazole, and tetracycline as antimicrobials has drawbacks, including the development of microorganism resistance, exorbitant pricing, and limited accessibility. Thus, there is a need for safer and more affordable alternatives. Numerous natural therapies have been found to be superior in this situation. In this study, the efficacy of tulsi extract as a LAM agent was assessed and it was compared with curcumin, which is currently used for the treatment of periodontal pockets. METHODS AND MATERIALS: There were three categories: each category had 30 sites. Category 1 sites underwent scaling along with root planing (SRP) solely, Category 2 sites received curcumin extract as LAM in the periodontal pocket in addition to SRP, and Category 3 sites received tulsi extract as LAM in the periodontal pocket in addition to SRP. The stent was used to ensure consistent and unbiased measurements on the 30th day after treatment. Clinical attachment level (CAL) and probing pocket depth (PPD) were measured at six points around each tooth.  Results: The reduction in values of periodontal parameters such as BAPNA (Nα-benzoyl-DL-arginine-p-nitroanilide) assays, modified sulcus bleeding index (mSBI), gingival index (GI), plaque index (PI), CAL, and PPD in sites within Category 1, Category 2, and Category 3 was statistically significant. The decrease in BAPNA assay results indicates that tulsi extract is more effective than curcumin gel at eradicating red-complex bacteria. Although not significantly different, the decrease in PI and GI was observed to be greater when curcumin jelly was used. This suggests that curcumin jelly has a stronger impact on reducing plaque, which in turn decreases gingival inflammation. CONCLUSION: Based on the overall results of the study, it can be said that both tulsi and curcumin have similar effectiveness in reducing periodontal markers.

4.
Bioinformation ; 19(1): 138-142, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37720288

RESUMO

The impact of inflammatory response on the biological characteristics of GMSCs has been the subject of studies, with conflicting findings. In order to more fully understand the effects of the localized inflammatory environment, the current study assessed the intensity and differentiating capacity of GMSCs derived from healthy periodontal tissues (H-GMSC) and GMSC derived from inflamed periodontal tissues (I-GMSC) tissues. Cells from every well were taken out and counted using a hemocytometer every three days for a total of 12 days. The findings of the cell proliferation assay, which involved quantifying the cells with the help of a hemocytometer at 0th day, 3rd day, 6th day, and 9th day, are shown. On day nine of culture, there was a considerable (P = 0.02) variation in the rate of multiplication between GMSCs from healthy gingival tissues and GMSCs from gingival tissues having inflammation. Additionally, I-GMSCs had a higher cell concentration on day twelve than that of H-GMSCs. However, there was no significant variance in PDT values comparing GMSCs from healthy gingival tissues and GMSCs from gingival tissues having inflammation (P > 0.05). The mean PDT findings of 66.7 h and 53.4 h have been documented for Healthy-GMSCs and Inflamed-GMSCs, respectively. In addition, compared to GMSCs from healthy gingival tissues, GMSCs from inflammatory tissues had decreased osteogenesis and increased adipogenic potential. To evaluate the efficacy of GMSCs derived from patients suffering periodontitis utilising human models for cell-based treatments, additional study is necessary.

5.
Eye (Lond) ; 37(15): 3213-3216, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36899109

RESUMO

BACKGROUND: Recurrent corneal erosion syndrome (RCES) is caused by repeated episodes of corneal epithelial breakdown due to improper adherence of the corneal epithelium to the underlying basement membrane. The most common aetiologies are corneal dystrophy or previous superficial ocular trauma. The incidence and prevalence of the condition is currently unknown. This study aimed to determine the incidence and prevalence of RCES within the London population over a 5-year period in order to better inform clinicians and evaluate how this condition affects ophthalmic service provision. METHODS: A retrospective cohort study over a 5-year period reviewed 487,690 emergency room patient attendances at Moorfields Eye Hospital (MEH) London between 1 January 2015 and 31 December 2019. MEH caters for a local population comprising of around ten regional clinical commissioning groups (CCGs). The data for this study were collected using OpenEyesTM electronic medical records including demographics and comorbidities. The CCGs encompass 41% (3,689,000) of London's total 8,980,000 inhabitants. Using these data the crude incidence and prevalence rates of disease were estimated with results reported per 100,000 population. RESULTS: Out of 330,684 patients, 3623 patients were given a new diagnosis of RCES by the emergency ophthalmology services, and from these, 1056 patients attended outpatient follow-up. The crude annual incidence of RCES was estimated at 25.4 per 100,000, with a crude prevalence rate of 0.96%. There was no statistical difference in annual incidence across the 5-year period. CONCLUSIONS: The period prevalence of 0.96% shows that RCES is not uncommon. There was also a stable annual incidence over the 5-year period, showing no changing trend over the study period. However, identifying the true incidence and period prevalence is a challenging task, as minor cases may heal prior to examination by an ophthalmologist. It is highly likely that RCES is underdiagnosed and therefore underreported.


Assuntos
Distrofias Hereditárias da Córnea , Edema da Córnea , Úlcera da Córnea , Humanos , Prevalência , Estudos Retrospectivos , Incidência , Londres/epidemiologia , Distrofias Hereditárias da Córnea/diagnóstico , Síndrome
6.
Clin Ophthalmol ; 16: 3973-3979, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36483187

RESUMO

Purpose: To investigate the quantitative and qualitative efficacy of finger-prick autologous blood (FAB) eye drops versus conventional medical therapy for the treatment of severe dry eye disease (DED). Methods: Two centre, single masked, randomised controlled trial. Sixty patients in total were recruited with thirty patients (sixty eyes) treated with FAB eye drops four times per day in addition to their conventional DED treatment, and thirty patients (fifty-eight eyes) served as control subjects on conventional treatment alone. Ocular surface disease index (OSDI), Schirmer's test, fluorescein ocular staining grade (OCSG) Oxford schema and fluorescein tear film break-up time (TBUT), were performed at baseline, at 4 and 8 weeks. Results: OSDI scores significantly decreased in the FAB arm by greater than -17.68 (-37.67 to -2.96, p=0.02) compared to the control arm. There were greater improvements in OCSG and TBUT in the FAB arm but these were non-significant (p>0.05). Conclusion: This feasibility study demonstrates adding FAB eye drops to conventional medical therapy for DED improves mean OSDI symptom score compared to conventional medical therapy alone. It may have particular use in settings where serum is unobtainable. An adequately powered and well-designed randomised trial is needed to further evaluate the long-term clinical benefit of FAB.

7.
J Pharm Bioallied Sci ; 14(Suppl 1): S841-S844, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36110722

RESUMO

Introduction: Periodontitis is a multifaceted disease that results from the intricate interplay of infectious pathogens and host factors. Periodontal surgical techniques may be required in moderate to severe cases of chronic periodontitis. As a result of the potential for postoperative infection to have a substantial impact on the surgical outcome, an attempt will be made in the study to assess the role of antibiotics in periodontal flap procedures in minimizing postoperative infections. Methodology: From the Department of Periodontics and Oral Implantology, 30 patients (male and female) with moderate to severe chronic periodontitis were chosen. Amoxicillin 500 mg three times a day for 5 days following surgery was given in the therapeutic group (15 patients). Antibiotics were not provided to the control group (15 patients) after surgery. Both groups were administered analgesics and antiseptic mouthwash. On the seventh day after suture removal, patients were assessed for pain (measured on a visual analogue scale [VAS]), modified gingival index, wound healing index, swelling, fever, ulceration, and delayed wound healing. Results: The VAS reported in the control group was 2.67, while the VAS recorded in the therapeutic group was 2.20. The mean modified gingival index score in the control group was 0.94, while it was 0.67 in the therapeutic group. The mean Wound Healing Index score in the control group was 3.80, whereas it was 3.97 in the therapeutic group. When antibiotics were administered to patients, they reported less pain and faster wound healing. Following flap surgery with or without antibiotics, however, there were no statistically significant variations in all clinical measures. Conclusion: The findings of our study imply that antibiotics for the sole goal of avoiding postsurgical infections may not be beneficial.

8.
Cureus ; 14(7): e27134, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36017283

RESUMO

Introduction Surface roughness encourages plaque retention and causes mechanical, chemical, and biological irritation to surrounding soft tissues. Hence, a smooth surface of restoration is preferred for optimal plaque control and the health of the periodontium. Aim The aim is to evaluate and compare the surface roughness of porcelain fused to metal and stainless-steel crowns following ultrasonic and hand scaling techniques. Material and methods An in-vitro study was conducted on 30 porcelain fused to metal crowns and 30 stainless-steel crowns. Their surface roughness following instrumentation was evaluated by scanning electron microscope (SEM) and profilometry. Results Evaluation by profilometry indicated that porcelain fused to metal following ultrasonic instrumentation has a statistically more significant surface roughness and indentation as compared to hand scaling with p-values < 0.05. Conclusion The surface roughness of any restoration may act as a plaque retentive factor which would affect the health of the periodontium. Ultrasonic scaling is capable of creating roughness to a more extent as compared to hand scaling and porcelain fused to the metal type of restorations is more vulnerable to roughness.

9.
Eur J Ophthalmol ; 32(4): NP115-NP119, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33736487

RESUMO

PURPOSE: To describe a case of malignant glaucoma following insertion of a Preserflo™ MicroShunt in a patient with primary open angle glaucoma (POAG). DESIGN: Case report. CASE: A 46-year-old Caucasian man with medically uncontrolled POAG developed malignant glaucoma 1 day after an uncomplicated insertion of a mitomycin C (MMC) augmented Preserflo MicroShunt (PMS). RESULTS: Initial medical treatment with aqueous suppressants and atropine 1% resulted in temporary resolution of the episode, although partial occlusion of the PMS with iris required a Nd:YAG laser iridotomy to open the inlet of the device. However, the malignant glaucoma recurred 6 days later. Temporary resolution was subsequently achieved with an Nd:YAG laser peripheral irido-zonulo-hyaloidotomy in combination with topical atropine, though a subsequent PMS revision was required due to bleb encapsulation. Unfortunately, the revision procedure was followed 2 days later, by a further recurrence of malignant glaucoma which was eventually resolved by left pars plana vitrectomy (PPV) in combination with clear lens extraction (CLE) and surgical irido-zonulo-hyaloidectomy. Subsequently, the eye remained stable, with a deep anterior chamber (AC), a partially functioning bleb, and an intraocular pressure (IOP) of 14 mmHg on one topical IOP-lowering agent, 8 months after the last procedure. CONCLUSIONS: The management of malignant glaucoma after PMS insertion and its subsequent clinical course is described. Apart from the propensity for a small tube such as the PMS to obstruct with iris when the AC is shallow, management is similar to other scenarios in which malignant glaucoma may develop.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Humanos , Masculino , Pessoa de Meia-Idade , Derivados da Atropina , Glaucoma/etiologia , Glaucoma/cirurgia , Glaucoma de Ângulo Aberto/etiologia , Glaucoma de Ângulo Aberto/cirurgia , Pressão Intraocular
11.
Br J Radiol ; 94(1121): 20201160, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33860674

RESUMO

OBJECTIVES: To evaluate the role of contrast-enhanced ultrasound (CEUS) quantitative parameters in predicting neoadjuvant chemotherapy (NACT) response in patients with locally advanced breast cancer (LABC). METHODS: 30 patients with histologically proven LABC scheduled for NACT were recruited. CEUS was performed using a contrast bolus of 4.8 ml and time intensity curves (TICs) were obtained by contrast dynamics software. CEUS quantitative parameters assessed were peak enhancement (PE), time-to-peak (TTP), area under the curve (AUC) and mean transit time (MTT). The parameters were documented on four consecutive instances: before NACT and 3 weeks after each of the three cycles. The gold-standard was pathological response using Miller Payne Score obtained pre NACT and post-surgery. RESULTS: A decrease in mean values of PE and an increase in mean values of TTP and MTT was observed with each cycle of NACT among responders. Post each cycle of NACT (compared with baseline pre-NACT), there was a statistically significant difference in % change of mean values of PE, TTP and MTT between good responders and poor responders (p-value < 0.05). The diagnostic accuracy of TTP post-third cycle was 87.2% (p = 0.03), and MTT post--second and third cycle was 76.7% (p = 0.004) and 86.7% (p = 0.006) respectively. CONCLUSION: In responders, a decrease in the tumor vascularity was reflected in the CEUS quantitative parameters as a reduction in PE, and a prolongation in TTP, MTT. ADVANCES IN KNOWLEDGE: Prediction of NACT response by CEUS has the potential to serve as a diagnostic modality for modification of chemotherapy regimens during ongoing NACT among patients with LABC, thus affecting patient prognosis.


Assuntos
Meios de Contraste , Terapia Neoadjuvante , Ultrassonografia/métodos , Neoplasias Unilaterais da Mama/diagnóstico por imagem , Neoplasias Unilaterais da Mama/tratamento farmacológico , Adulto , Área Sob a Curva , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Neoplasias Unilaterais da Mama/patologia , Neoplasias Unilaterais da Mama/cirurgia
12.
Curr Eye Res ; 46(11): 1762-1767, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33882770

RESUMO

Aims: To report spectral-domain optical coherence tomography (OCT) findings in cases of impending or occult central retinal artery occlusion (CRAO) in which a diagnosis other than CRAO was made on initial presentation.Methods: Retrospective, observational case series of patients diagnosed with CRAO for whom on initial presentation fundal examination and OCT findings were deemed unremarkable and/or a diagnosis other than CRAO was made. OCT images from the initial presentation were then reviewed for evidence of inner retinal ischaemia.Results: In total, 214 cases of CRAO were identified. Eleven patients (5.14%) had been given an alternative initial diagnosis at their first presentation in casualty and were included. The age range was 20-84 years and 81% (9/11) were male. On review of initial OCT imaging performed in casualty, all cases had evidence of inner retinal ischaemia.Conclusions: CRAO is an ophthalmic emergency which leads to vision loss which is often irreversible. Examination of the fundus may be normal early in the course of the disease and therefore a timely diagnosis may be missed. This case series reports the OCT findings of inner retinal ischaemia in patients with occult or impending CRAO which may aid in the early diagnosis and referral to stroke services.


Assuntos
Oclusão da Artéria Retiniana/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Diagnóstico Precoce , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acuidade Visual , Adulto Jovem
15.
Eye (Lond) ; 35(4): 1117-1139, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33514902

RESUMO

Emerging infectious diseases (EIDs) are an increasing threat to public health on a global scale. In recent times, the most prominent outbreaks have constituted RNA viruses, spreading via droplets (COVID-19 and Influenza A H1N1), directly between humans (Ebola and Marburg), via arthropod vectors (Dengue, Zika, West Nile, Chikungunya, Crimean Congo) and zoonotically (Lassa fever, Nipah, Rift Valley fever, Hantaviruses). However, specific approved antiviral therapies and vaccine availability are scarce, and public health measures remain critical. Patients can present with a spectrum of ocular manifestations. Emerging infectious diseases should therefore be considered in the differential diagnosis of ocular inflammatory conditions in patients inhabiting or returning from endemic territories, and more general vigilance is advisable in the context of a global pandemic. Eye specialists are in a position to facilitate swift diagnosis, improve clinical outcomes, and contribute to wider public health efforts during outbreaks. This article reviews those emerging viral diseases associated with reports of ocular manifestations and summarizes details pertinent to practicing eye specialists.


Assuntos
Doenças Transmissíveis Emergentes/diagnóstico , Infecções Oculares Virais/diagnóstico , Viroses/diagnóstico , Animais , Vetores Artrópodes , Doenças Transmissíveis Emergentes/epidemiologia , Surtos de Doenças , Infecções Oculares Virais/epidemiologia , Humanos , Vírus de RNA/patogenicidade , Zoonoses Virais , Viroses/epidemiologia
16.
Eye (Lond) ; 35(10): 2714-2718, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33184489

RESUMO

PURPOSE: To investigate outcomes for small versus large pupils in cataract surgery using different pupil expansion techniques. METHODS: Retrospective case-series reviewing 20,175 patients' cataract surgery electronic medical records at Moorfields Eye Clinic in Bedford Hospital NHS Trust from January 2010 to April 2020. Outcomes such as visual acuity (VA), intraocular pressure, intraoperative, post-operative complications were recorded and small pupil expansion device outcome. RESULTS: One thousand, four hundred twenty-six patients were identified as having small pupil (SP). Of these, 1110 patients (77.8%) had interventions to expand the pupil including 447 (31.3%) with intracameral phenylephrine (IC PE) alone, 194 (13.6%) with iris hooks and 469 (32.9%) with a Malyugin ring. The large pupil (LP) group had a statistically significant greater gain in VA than the SP group (p < 0.05). SPs had a significantly higher rate of intraocular complications including posterior capsular rupture (PCR) with vitreous loss (OR 2.75, p < 0.001). There was also a significantly higher rate of post-operative complications such as corneal oedema (OR 2.64, p < 0.001) and anterior uveitis (OR 2.11, p < 0.001) in the SP group. However, VA improvement and complications between the different pupil expansion groups showed no significant differences (p > 0.05) except for a greater rate of iris tears in the Malyugin group (p < 0.05). CONCLUSION: To date, this is the largest reported case-series comparing Malyugin rings and iris hooks with other pupil expansion techniques. The various techniques to expand pupil size appear to be safe and equally effective in improving VA with a similar rate of complications except for a greater rate of iris tears with Malyugin ring.


Assuntos
Catarata , Facoemulsificação , Humanos , Iris/cirurgia , Implante de Lente Intraocular , Miose/cirurgia , Fenilefrina , Estudos Retrospectivos
17.
J Family Med Prim Care ; 9(6): 2969-2974, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32984157

RESUMO

BACKGROUND: Interaction of various drugs and its effects on gingival and periodontal health is the area of concern; hence the aim of the present study was to explore factors affecting the awareness and practice of primary health care professionals towards the interaction of various medications used for systemic diseases on periodontal health. MATERIALS AND METHODS: It was a cross-sectional, descriptive, questionnaire study conducted among 203 primary health care professionals which include 94 medical officers and 109 nurses working in primary health centers in rural areas of Udaipur district. The study was conducted in December 2019. Sampling techniques was stratified random sampling technique. A close-ended questionnaire was prepared to conduct an interview schedule. RESULTS: The majority of health professionals had poor awareness (157 [77.33%]) and poor practice (168 [82.75%]) regarding the interaction of various medications used in systemic conditions and periodontal health. Factors that significantly affect awareness and practice of study participants were age (0.01*), degree (0.05*), and number of patients with oral problems seen in a week (0.05*), gender (0.05*), designation (0.05*). CONCLUSION: From above it was concluded that awareness and practice of primary care health professionals were poor. The factors that affect significantly affect awareness and knowledge of study participants was age, degree and number of patients with oral problems seen in a week, gender, designation, no. of patient attended in a day.

18.
Cornea ; 39(5): 594-597, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31868852

RESUMO

PURPOSE: Autologous hemoderivative eye drops have a role in the management of persistent epithelial defects (PEDs), but their use may be limited by cost and availability. Finger-prick autologous blood (FAB) treatment uses whole capillary blood, obtained from a sterilized fingertip, as an alternative form of hemoderivative eye drop therapy. To date, 1 report has described the safe and effective use of FAB for dry eye and PEDs. We report the results of 10 eyes (10 patients) treated with FAB for PEDs. METHODS: Ten patients with PEDs in 1 eye for a mean of 259 ± 201 days due to diabetic neurotrophic keratopathy (n = 3), herpetic keratitis (n = 3), postpenetrating keratoplasty (n = 1), keratoconjunctivitis sicca (n = 1), postradiotherapy (n = 1), and neuropathic ulcer (n = 1) were treated with FAB 4 times a day for 28 days in addition to conventional therapies. All patients had been unsuccessfully treated with conventional therapy before commencing on FAB. None of the patients had received any surgical treatment for PED. RESULTS: At day 28, the PED had healed in 60% (n = 6) of the eyes. In 1 eye, the PED reduced in size by half. Thirty percent (n = 3) of patients had incomplete follow-up data at the end of the study. CONCLUSIONS: FAB in combination with conventional treatment may be successfully used in the management of refractory PEDs. No adverse effects arising from FAB treatment were observed.


Assuntos
Doenças da Córnea/terapia , Epitélio Corneano/patologia , Idoso , Idoso de 80 Anos ou mais , Sangue , Doenças da Córnea/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Microscopia com Lâmpada de Fenda , Resultado do Tratamento
19.
PDA J Pharm Sci Technol ; 73(4): 320-330, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30770486

RESUMO

In our previously published work, we reported rapid polysorbate 80 (PS80) oxidation in a histidine buffer after brief exposure to stainless steel and the ability of citrate and EDTA to prevent this oxidation. The focus of our current study was to mechanistically understand PS80 oxidation by studying the impacts of temperature, light, and stainless steel and the role of citrate and EDTA. Additionally, PS80 oxidation was studied in three different buffer systems: histidine, citrate, and phosphate. When the PS80-containing buffers in glass containers were exposed to the elevated temperature of 50°C, no PS80 oxidation was observed in either the histidine or the citrate buffer systems after 30 days; however, PS80 oxidation was observed in the phosphate buffer system within 14 days. These results demonstrated that temperature does not initiate PS80 oxidation in the histidine or the citrate buffer systems, but it may be a factor in the phosphate buffer system. When the three buffer systems containing PS80 were exposed to 20%, 50%, or 100% ICH Q1B light conditions and subsequently incubated in the dark at 50°C, the PS80 in the phosphate buffer system underwent oxidation within 7 days, whereas the PS80 in the histidine and the citrate buffer systems showed oxidation products only after 14 and 35 days, respectively. PS80 in the phosphate buffer system seemed to be the most vulnerable to light as PS80 in both the histidine and the citrate buffer systems underwent oxidation to a lesser extent, with faster oxidation occurring in the histidine buffer system than in the citrate buffer system. Finally, the ability of citrate and EDTA to act as not only chelators but also radical quenchers/scavengers was demonstrated when a metal ion, Fe2+, was spiked into the histidine buffer containing PS80. While radicals could not be unambiguously identified by NMR or EPR, the observation of PS80 oxidation products indicated their presence.LAY ABSTRACT: In our previously published work, we reported rapid polysorbate 80 (PS80) oxidation in a histidine buffer after brief exposure to stainless steel and the ability of citrate and EDTA to prevent this oxidation. The focus of our current study was to mechanistically understand PS80 oxidation by studying the impacts of temperature, light, and stainless steel and the role of citrate and EDTA. Additionally, PS80 oxidation was studied in three different buffer systems: histidine, citrate, and phosphate. The temperature study demonstrated that PS80 oxidation in the histidine or the citrate buffer systems is not initiated by temperature, but may be a factor in the phosphate buffer system. PS80 in the phosphate buffer system seemed to be the most vulnerable to light, as PS80 in both the histidine and the citrate buffer systems underwent oxidation at a lower level, with the histidine buffer system showing more rapid oxidation than the citrate buffer system. Finally, the ability of citrate and EDTA to act as not only chelators but also radical quenchers/scavengers was demonstrated when a metal ion, Fe2+, was spiked into the histidine buffer containing PS80. While neither NMR nor EPR could definitively identify the presence of free radicals, the observation of PS80 oxidation products indicates that they were present.


Assuntos
Citratos/química , Histidina/química , Polissorbatos/química , Aço Inoxidável/química , Soluções Tampão , Radicais Livres/análise , Temperatura Alta , Luz , Modelos Teóricos , Oxirredução
20.
BMJ Open ; 8(10): e026770, 2018 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-30385451

RESUMO

INTRODUCTION: Patients with severe dry eye disease (DED) often have limited treatment options with standard non-surgical management focused on the use of artificial tears for lubrication and anti-inflammatory drugs. However, artificial tears do not address the extraordinary complexity of human tears. Crudely, human tears with its vast constituents is essentially filtered blood. Blood and several blood-derived products including autologous serum, have been studied as tear substitutes. This study proposes to test the use of whole, fresh, autologous blood obtained from a finger prick for treatment of severe DED. METHODS AND ANALYSIS: The research team at the two participating sites will approach patients with severe DED for this study. Recruitment will take place over 12 months and we expect to recruit 60 patients in total. The primary outcome of this feasibility study is to estimate the proportion of eligible patients approached who consent to and comply with study procedures including treatment regimen and completion of required questionnaires. The secondary outcome measures, although not powered for in this feasibility, include corneal inflammation (assessed by the Oxford corneal staining guide), patient pain and symptoms scores (assessed by the Ocular Surface Disease Index Score), and objective signs of DED as indicated by visual acuity (assessed by Schirmer's test, tear break-up time, lower and/or upper tear meniscus height measurement). Other secondary outcomes include patients' quality of life (assessed using the validated EQ-5D-5L Questionnaire), cost to the National Health Service (NHS) and patient (assessed via use of NHS services and privately purchased over-the-counter treatment related to DED) and safety measure of pressure within the eye (assessed by the Intraocular Pressure (IOP) Score). ETHICS AND DISSEMINATION: This protocol and any subsequent amendments, along with any accompanying material provided to the participant in addition to any advertising material used in this trial have been approved by the East of England - Cambridgeshire and Hertfordshire Research Ethics Committee (REC reference: 17/EE/0508). Written approval from the committee was obtained and subsequently submitted to the respective Trust's Research and Development (R&D) office with final NHS R&D approval obtained. Data obtained from this study will be published in a suitable peer-review journal and will also presented at international ophthalmic conferences including the American Academy of Ophthalmology, the Royal College of Ophthalmology Annual Congress, the Association for Research and Vision and Ophthalmology, and the European Society of Cataract and Refractive Surgery. Information will be provided to patient groups and charities such as the Sjogren's Society and the Royal National Institute of Blind People. This will also be shared with the study participants as well as with relevant patient groups and charities. TRIAL REGISTRATION NUMBER: NCT03395431; Pre-results.


Assuntos
Síndromes do Olho Seco/terapia , Lubrificantes Oftálmicos/uso terapêutico , Soro , Inglaterra , Estudos de Viabilidade , Humanos , Estudos Multicêntricos como Assunto , Soluções Oftálmicas/uso terapêutico , Modelos de Riscos Proporcionais , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Método Simples-Cego , Cloreto de Sódio/uso terapêutico , Acuidade Visual
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