RESUMO
BACKGROUND/AIMS: To investigate a possible association between the use of hydrochlorothiazide (HCT) and/or angiotensin-converting enzyme inhibitors (ACE inhibitors) and the occurrence of periocular non-melanoma skin cancer. METHODS: The files of 929 patients from the University Medical Center Hamburg-Eppendorf who were surgically treated for suspected periocular malignancy were evaluated retrospectively regarding the occurrence of non-melanoma skin cancer and concomitant medication. To be able to put the data in an overall context, we also analyzed age-matched routine data of the DAK-Gesundheit (DAK-G), a nationwide operating German health insurance company. RESULTS: Of the 929 patient records examined, who underwent surgical excision for suspected non-melanotic malignancy, non-melanocytic skin cancer could actually be determined by histology in 199 patients. In total, 176 patients (103 women, 72 men) had a basal cell carcinoma and 23 patients (16 women, 7 men) suffered from squamous cell carcinoma. The rate of intake of HCT or ACE inhibitors in our patient collective with non-melanotic skin cancer is significantly higher than in the general age-matched population (ORACE: 2.51, p < 0.001; ORHCT: 7.24, p < 0.001, ORBOTH: 4.61, p < 0.001). CONCLUSION: The rate of intake of HCT or ACE inhibitors is significantly higher in our patient collective with non-melanotic skin cancer compared to the group from the age-matched general population (DAK insured (p < 0.001)) compared to the routine data of the DAK-G. This leads us to the conclusion that taking the medication is associated with an increased risk for non-melanotic skin cancer. We recommend regular skin cancer screening, moderate ordination of photosensitizing medication, but above all comprehensive clarification of possible risks.
Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Carcinoma Basocelular/induzido quimicamente , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/epidemiologia , Feminino , Humanos , Hidroclorotiazida , Masculino , Estudos Retrospectivos , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/epidemiologiaRESUMO
Read-across and grouping is one of the most commonly used alternative approaches for data gap filling in registrations submitted under the REACH Regulation as defined by the European Chemicals Agency (ECHA) in their 'Read-Across Assessment Framework' (RAAF, 2017). At the same time, the application of read-across is rejected by ECHA frequently due to various reasons. As a major reason hereof, applicants fail to reduce the level of 'remaining uncertainty' intrinsical to every read-across approach compared to testing a substance experimentally. Recently, the use of metabolomics to support read-across cases with biological information has been reported in a case study with phenoxy herbicides (Ravenzwaay et al., 2016). In the present case-study a 'weight-of-evidence' read-across approach from 2-aminoethanol (MEAâ¯=â¯'source') to 3-aminopropanol (3APâ¯=â¯'target') with metabolomics as 'supporting evidence' reducing the remaining uncertainties is reported. We demonstrate the high structural similarity of the two analogous substances based on the available data and we report how metabolome data add confidence concerning mechanistic similarity in this read-across approach. Finally, the herein described read-across case supported by metabolomics is used to cover the data gaps in repeated dose and reproductive toxicity endpoint of 3AP via weight of evidence for the REACH-registration.
Assuntos
Etanolamina/toxicidade , Metaboloma/efeitos dos fármacos , Propanolaminas/toxicidade , Animais , Feminino , Masculino , Metabolômica , Ratos Wistar , Medição de Risco , Testes de ToxicidadeRESUMO
New technologies, such as metabolomics, can address chemical grouping and read across from a biological perspective. In a virtual case study, we selected MCPP as target substance and MCPA and 2,4-DP as source substances with the goal to waive a 90-day study with MCPP. In order to develop a convincing case to show how biological data can substantiate read across, we used metabolomics on blood samples from the 28-day studies to show the qualitative and quantitative similarity of the substances. The 28-day metabolome evaluation of source substances and the target substance indicate liver and kidneys as target organs. 2,4-DP was identified as the best source substance. Using the information of the 90-day 2,4-DP study, we predicted MCPP's toxicity profile at 2500 ppm: reduced food consumption and body weight gain, liver and kidney weight increases with clinical-pathology changes and a moderate red blood cell parameter reduction. NOEL prediction for MCPP was below that of 2,4-DP (<500 ppm), and similar to that of MCPA (≥150 ppm). Qualitatively, these predictions are comparable to the results of the real MCPP 90-day study in rats (reduced food consumption and body weight gain, weight increases and clinical-pathology changes in liver and kidneys, reduced red blood cells values). Quantitatively, the predicted NOAEL (150 ppm) is similar to the actual study (NOEL = 75 ppm, NOAEL ≤ 500 ppm). Thus, the 90-day rat toxicity study of MCPP could have been waived and substituted by the 90-day results of 2,4-DP by using metabolome data of 28 day studies.
Assuntos
Herbicidas/metabolismo , Metabolômica , Fenóis/metabolismo , Animais , Disponibilidade Biológica , Eritrócitos/efeitos dos fármacos , Feminino , Herbicidas/farmacocinética , Herbicidas/toxicidade , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Estrutura Molecular , Fenóis/farmacocinética , Fenóis/toxicidade , Ratos , Ratos Wistar , Fatores de TempoRESUMO
BACKGROUND: This study focuses on the refractive implications of albinism in Malawi, which is mostly associated with the burden of visual impairment. The main goal was to describe the refractive errors and to analyze whether patients with albinism in Malawi, Sub-Saharan Africa, benefit from refraction. METHODS: Age, sex, refractive data, uncorrected and best-corrected visual acuity (UCVA, BCVA), colour vision, contrast sensitivity, and the prescription of sunglasses and low vision devices were collected for a group of 120 albino individuals with oculocutaneous albinism (OCA). Refractive errors were evaluated objectively and subjectively by retinoscopy, and followed by cycloplegic refraction to reconfirm the results. Best-corrected visual acuity (BCVA) was also assessed binocularly. RESULTS: One hundred and twenty albino subjects were examined, ranging in age from 4 to 25 years (median 12 years), 71 (59 %) boys and 49 (41 %) girls. All exhibited horizontal pendular nystagmus. Mean visual acuity improved from 0.98 (0.33) logMAR to 0.77 (0.15) logMAR after refraction (p < 0.001). The best improvement of VA was achieved in patients with mild to moderate myopia. Patients with albinism who were hyperopic more than +1.5 D hardly improved from refraction. With the rule (WTR) astigmatism was more present (37.5 %) than against the rule (ATR) astigmatism (3.8 %). Patients with astigmatism less than 1.5 D improved in 15/32 of cases (47 %) by 2 lines or more. Patients with astigmatism equal to or more than 1.5 D in any axis improved in 26/54 of cases (48 %) by 2 lines or more. CONCLUSIONS: Refraction improves visual acuity of children with oculocutaneous albinism in a Sub-Saharan African population in Malawi. The mean improvement was 2 logMAR units.
Assuntos
Albinismo Oculocutâneo/complicações , Erros de Refração/etiologia , Auxiliares Sensoriais/estatística & dados numéricos , Baixa Visão/etiologia , Pessoas com Deficiência Visual/reabilitação , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Malaui , Masculino , Nistagmo Patológico/diagnóstico , Refração Ocular/fisiologia , Erros de Refração/fisiopatologia , Erros de Refração/terapia , Retinoscopia , Estudos Retrospectivos , Baixa Visão/fisiopatologia , Baixa Visão/terapia , Acuidade Visual/fisiologia , Adulto JovemRESUMO
PURPOSE: The aim of this study was to determine the anatomic sites of severe visual impairment and blindness in children in an integrated school for the blind in Malawi, and to compare the results with those of previous Malawian blind school studies. METHODS: Children attending an integrated school for the blind in Malawi were examined in September 2011 using the standard WHO/PBL eye examination record for children with blindness and low vision. Visual acuity [VA] of the better eye was classified using the standardised WHO reporting form. RESULTS: Fifty-five pupils aged 6 to 19 years were examined, 39 (71 %) males, and 16 (29 %) females. Thirty eight (69%) were blind [BL], 8 (15 %) were severely visually impaired [SVI], 8 (15 %) visually impaired [VI], and 1 (1.8 %) was not visually impaired [NVI]. The major anatomic sites of visual loss were optic nerve (16 %) and retina (16 %), followed by lens/cataract (15 %), cornea (11 %) and lesions of the whole globe (11 %), uveal pathologies (6 %) and cortical blindness (2 %). The exact aetiology of VI or BL could not be determined in most children. Albinism accounted for 13 % (7/55) of the visual impairments. 24 % of the cases were considered to be potentially avoidable: refractive amblyopia among pseudophakic patients and corneal scaring. CONCLUSIONS: Optic atrophy, retinal diseases (mostly albinism) and cataracts were the major causes of severe visual impairment and blindness in children in an integrated school for the blind in Malawi. Corneal scarring was now the fourth cause of visual impairment, compared to being the commonest cause 35 years ago. Congenital cataract and its postoperative outcome were the commonest remedial causes of visual impairment.
Assuntos
Doenças da Córnea/epidemiologia , Doenças do Cristalino/epidemiologia , Doenças do Nervo Óptico/epidemiologia , Doenças Retinianas/epidemiologia , Estudantes/estatística & dados numéricos , Transtornos da Visão/epidemiologia , Pessoas com Deficiência Visual/estatística & dados numéricos , Adolescente , Causalidade , Criança , Comorbidade , Doenças da Córnea/diagnóstico , Feminino , Humanos , Incidência , Doenças do Cristalino/diagnóstico , Malaui/epidemiologia , Masculino , Doenças do Nervo Óptico/diagnóstico , Fatores de Risco , Doenças da Úvea/diagnóstico , Doenças da Úvea/epidemiologia , Transtornos da Visão/diagnóstico , Adulto JovemRESUMO
BACKGROUND: Open and minimally invasive tear duct surgery are among the common surgical indications; however, little is known so far about the respective influences on the quality of life. OBJECTIVE: The aim of this study was to compare the subjective influence on the quality of life of patients after open and minimally invasive surgical techniques for recanalization of dacryostenosis. MATERIAL AND METHODS: From the collective of patients who were surgically treated at the University Medical Center Hamburg-Eppendorf from 2015 to 2018, a total of 169 patients (111 dacryocystorhinostomy, DCR, 58 endoscopy) took part in the survey and answered 9 questions about subjective satisfaction, which were evaluated also comparatively. RESULTS: When asked about postoperative satisfaction, the patients were significantly more satisfied after DCR (pâ¯= 0.001) than the patients who underwent a lacrimal endoscopy. There was no significant difference in terms of postoperative complications (pâ¯= 0.348). The rate of reoperations, however, was significantly higher in the patient group who underwent lacrimal endoscopy (χ2-test, pâ¯= 0.004). CONCLUSION: In summary it can be said that DCR is not inferior to lacrimal endoscopy in terms of patient satisfaction.
Assuntos
Dacriocistorinostomia , Aparelho Lacrimal , Obstrução dos Ductos Lacrimais , Constrição Patológica , Endoscopia , Humanos , Aparelho Lacrimal/cirurgia , Obstrução dos Ductos Lacrimais/diagnóstico , Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: There is largely a lack of clarity on the question of whether refraction or topography changes are to be expected after blepharoplasty, levator resection, or a lateral tarsal strip procedure. MATERIALS AND METHODS: Therefore, in the present study, objective refraction, anterior eye segment tomography, and visual acuity tests were carried out pre- and postoperatively in 78 patients and then analyzed. The examination was carried out preoperatively, at suture removal after 10 days, and after 3 months. RESULTS: Neither after blepharoplasty nor after a lateral tarsal strip procedure were significant changes in vision or refraction seen in the topography. In contrast, the Wilcoxon sign test 10 days after levator resection showed a significant increase in the cylinder after 10 days compared to the preoperative level (pâ¯= 0.042). However, this change was no longer detectable after 3 months. CONCLUSION: The authors postulate that extensive patient education with regard to temporary visual changes, particularly in the case of levator resections, is essential and that additional refraction and topography control can be useful postoperatively.
Assuntos
Astigmatismo , Blefaroplastia , Córnea , Topografia da Córnea , Pálpebras/cirurgia , Humanos , Refração OcularRESUMO
BACKGROUND: The question of whether refractive or topographic changes are to be expected after eye muscle surgery is largely unanswered. MATERIALS AND METHODS: Results of pre- and postoperative objective refraction, Pentacam (Oculus, Menlo Park, CA, USA), and visual acuity tests of 229 eyes are included in the present analysis. The examinations took place preoperatively, on the first postoperative day, and after 3 months. RESULTS: After surgery on one or two extraocular recti muscle, there are significant changes in the cylinder (pâ¯< 0.001) on the first postoperative day, although values returned to normal after 3 months. Similar changes also appeared in combined operations of extraocular and oblique muscles. CONCLUSION: The authors postulate that extensive patient education with regard to temporary changes in the cylinder is necessary, particularly when the extraocular muscles are involved, and that additional refraction and topography control can be useful postoperatively if visual rehabilitation is inadequate.
Assuntos
Astigmatismo , Músculos Oculomotores , Astigmatismo/cirurgia , Córnea/cirurgia , Topografia da Córnea , Humanos , Músculos Oculomotores/cirurgia , Refração Ocular , Acuidade VisualRESUMO
BACKGROUND: Intravitreal injections of triamcinolone are not only an important therapeutic tool for a variety of vitreo-retinal disorders, but can also be employed for visualisation of the vitreous during pars plana vitrectomy. Triesence® is a preservative-free triamcinolone suspension that has been approved for visualisation during vitrectomy via intravitreal administration and as intravitreal therapy for certain rare ocular diseases. However, the differences between Triesence® and purified (and thus also preservative-free) triamcinolones such as Volon A® or Kenalog® are not well specified, although the manufacturer of Triesence® advertises the product as "specifically formulated for the eye". METHODS: The publicly available FDA application material and information provided by the manufacturer for Triesence®, Kenalog® and Volon A® were analysed with respect to the differences between Triesence® and older triamcinolone preparations. RESULTS: According to the publicly available FDA documents the approval of Triesence mainly was based on studies that have been conducted with the older triamcinolone preparations Kenalog® or purified Volon A®. Apart from the absence of preservative the differences between Triesence® and the "older" triamcinolone preparation seem marginal. Published experimental or clinical studies in respect to the possible advantages of Triesence® compared to Kenalog® or Volon A® are lacking. Triesence® has been approved for sympathetic ophthalmia, temporal arteriitis, uveitis unresponsive to topical corticosteroids and for enhancing tissue visualisation during vitrectomy. Recently, the manufacturer of Kenalog® added a warning label ("not for intraocular use") on each vial of Kenalog®. The motifs for this re-labelling of Kenalog® remain unclear. CONCLUSION: Apart from the intraoperative use during vitrectomy Triesence® has only been approved for sympathetic ophthalmia, temporal arteriitis, and ocular conditions unresponsive to topical steroids. Consequently, the use of Triesence® like the older triamcinolone preparations (Kenalog® or Volon A®) for diabetic macular oedema, for Irivine-Gass syndrome, for neovascular AMD or after retinal vein occlusion is off-label.
Assuntos
Oftalmia Simpática/tratamento farmacológico , Conservantes Farmacêuticos/química , Doenças Retinianas/tratamento farmacológico , Triancinolona Acetonida/química , Triancinolona Acetonida/uso terapêutico , Feminino , Humanos , Masculino , Conservantes Farmacêuticos/efeitos adversos , Triancinolona Acetonida/efeitos adversosRESUMO
BACKGROUND: Behçet's disease is a systemic vasculitis disorder of unknown aetiology. Ocular involvement, especially with vasculitis, is detected in up to 80 % of the cases. Anterior segment involvement such as cataract is also seen in the follow-up of patients who are then treated surgically. In this study, we aimed to analyze the outcomes of cataract surgery in patients with Behçet's disease retrospectively. PATIENTS AND METHODS: The records of 9 patients (12 eyes) with Behçet's disease who underwent phacoemulsification with IOL implantation in 11 eyes and extracapsular cataract extraction (ECCE) with IOL implantation in one eye between June 2001 and September 2009 were evaluated retrospectively. The visual outcome and complications were analysed. RESULTS: The mean follow-up was 33.8 months (range 3 to 88 months). The mean preoperative LogMAR BCVA was 1.15 ± 0.53 (95 % CI: 0.81 - 1.49) and increased to 0.36 ± 0.32 (95 % CI: 0.15 - 0.56) at last medical visit (p < 0.001). The most frequent postoperative complication was posterior capsular opacification, which developed in 2 eyes (17 %). Other complications were mild fibrinous reaction in 1 eye (8 %). CONCLUSIONS: The outcomes of cataract surgery in patients with Behçet's disease were satisfactory. The great majority of the patients regained and retained a good visual outcome and had fewer postoperative complications.
Assuntos
Síndrome de Behçet/cirurgia , Lentes Intraoculares , Adulto , Anti-Inflamatórios/administração & dosagem , Azatioprina/administração & dosagem , Extração de Catarata/métodos , Feminino , Humanos , Imunossupressores/administração & dosagem , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Complicações Pós-Operatórias/etiologia , Prednisolona/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Retinal detachment is an ophthalmological emergency. Delayed diagnostics and treatment increase the risk of permanent loss of vision. Current media reports have suggested that patients with medical emergencies delay seeking treatment out of fear of being infected with the corona virus SARS-CoV2. This study analyzed data from a German university hospital to determine if the coronavirus pandemic had an impact on treatment and visual outcomes of patients with retinal detachment. METHODS: In this study 60 patients treated for rhegmatogenous retinal detachment in the eye hospital of the University Hospital Hamburg-Eppendorf between 15 March and 5 May 2020 were retrospectively analyzed. Patients from the corresponding period of the previous year acted as a control group. Significant differences between the groups were investigated by hypothesis testing. RESULTS: When compared to the period in the previous year there were no significant differences for sex, age, eye, length of symptoms, previous visit to doctor, visual acuity, macula status, degree of retinal detachment, proliferative vitreoretinopathy and type or length of procedure during the coronavirus pandemic. Of the patients with retinal detachment 29% had general health concerns due to the coronavirus pandemic. CONCLUSION: Medical treatment for retinal detachment was not influenced by the coronavirus pandemic. In contrast to other medical emergencies the morbidity of retinal detachment did not increase and admitted cases did not decrease during the pandemic when compared to the same period in the previous year.
Assuntos
COVID-19 , Descolamento Retiniano , Hospitais Universitários , Humanos , Pandemias , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/epidemiologia , Descolamento Retiniano/terapia , Estudos Retrospectivos , SARS-CoV-2 , Resultado do Tratamento , VitrectomiaRESUMO
BACKGROUND: Postoperative endophthalmitis is among the most feared complications encountered after intraocular surgery. A prompt diagnosis and initiation of treatment are crucial for the visual prognosis, which also depends on the causative microorganism. Despite advances in prevention and the availability of more epidemiological data, most of the evidence for treatment dates back to a single study, the early vitrectomy study (EVS) carried out in the early 1990s. The EVS showed that vitrectomy with intravitreal antibiotics was superior to intravitreal antibiotics alone, only when visual acuity was light perception or below. The addition of systemic antibiotics did not have any benefits. Over the last 30 years, however, surgical techniques have continued to evolve and the medicinal options have also been expanded. Moreover, the EVS examined only endophthalmitis after cataract surgery and strictly speaking the results cannot be transferred to endophthalmitis from other causes. OBJECTIVE: This review discusses the current evidence for the different treatment modalities of the most important types of postoperative endophthalmitis. CONCLUSION: The EVS provided important guidelines for the initial management of endophthalmitis and these guidelines remain relevant to this day; however, in view of the refinement of surgical techniques, novel treatment options, especially the nowadays continuously growing number of intravitreal injections and even some new antibiotics, it would be desirable if new controlled trials addressing the treatment of endophthalmitis would be performed.
Assuntos
Extração de Catarata , Endoftalmite , Infecções Oculares Bacterianas , Antibacterianos/uso terapêutico , Endoftalmite/diagnóstico , Endoftalmite/tratamento farmacológico , Endoftalmite/etiologia , Infecções Oculares Bacterianas/tratamento farmacológico , Humanos , Injeções Intravítreas , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , VitrectomiaRESUMO
A laterally located sound source stimulates the two ears at slightly different times, generating interaural phase disparities (IPDs) that are used for sound localization. Under natural conditions, such interaural cues are likely to be constantly changing, or dynamic. In the inferior colliculus of gerbils and cats, the nonlinearities in the coding of dynamic interaural phase cues are demonstrated. Responses to ecologically realistic phase cues are more reflective of the change of IPD than of the absolute IPDs over which that change occurs. This observation is inconsistent with the established view that directional information is coded in terms of absolute IPD.
Assuntos
Colículos Inferiores/fisiologia , Mesencéfalo/fisiologia , Neurônios/fisiologia , Localização de Som , Estimulação Acústica , Animais , Gatos , GerbillinaeRESUMO
Despite major improvements of vitreo-retinal surgical techniques proliferative vitreoretinopathy (PVR) remains a major challenge. Surgical therapy alone may not be sufficient in complicated cases of PVR. A combination of standard techniques such as pars plana vitrectomy with a vitreous substitute and a simultaneous adjuvant pharmacological treatment for the suppression of undesired proliferation of retinal cells and retinal scarring may be a promising therapeutic approach. However, due to the narrow therapeutic range and the short biological half-life of most anti-proliferative or anti-inflammatory drugs in the vitreous cavity, intravitreal slow-release systems for extended drug delivery are desirable. Vitrectomy for PVR normally requires a vitreous substitute. Consequently, a vitreous substitute that could also serve as a slow-release system for anti-proliferative or anti-inflammatory drugs would provide several advantages. This review gives an overview of recent developments of slow-release systems that may also be suitable as vitreous substitutes. Even standard internal tamponades such as silicone oils or gases may serve as extended drug-release systems under certain conditions. In the mean time polymerised hydrogels have been developed, which apart from providing an adequate tamponade effect, may facilitate an extended intravitreal release of various anti-proliferative and anti-inflammatory drugs for several weeks.
Assuntos
Materiais Biomiméticos/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Óleos de Silicone/uso terapêutico , Vitrectomia/métodos , Vitreorretinopatia Proliferativa/terapia , Corpo Vítreo/química , Materiais Biomiméticos/química , Terapia Combinada , Preparações de Ação Retardada/química , Humanos , Descolamento Retiniano/complicações , Descolamento Retiniano/terapia , Óleos de Silicone/química , Gravidade Específica , Vitreorretinopatia Proliferativa/etiologia , Descolamento do Vítreo/complicações , Descolamento do Vítreo/terapiaRESUMO
INTRODUCTION: The aim of this study was an analysis of the feasibility of a picosecond infrared laser fiber-assisted sclerostomy (PIRL-FAST) using a novel sapphire fiber and different energy levels of the picosecond laser. METHOD: The laser-assisted sclerostomy was carried out with a newly generated sapphire fiber of the PIRL-HP2-1064 OPA-3000 (Attodyne, Canada). Immediately after the intervention, the eyes were fixed in phosphate-buffered 3.5% formaldehyde. For subsequent histological analysis the eyes were cut into 4⯵m thick sections and stained with hematoxylin and eosin (H&E, Merck, Darmstadt, Germany). All preparations were then scanned and digitalized using the MIRAX SCAN (Carl Zeiss Microimaging GmbH, Jena, Germany). RESULTS: The pulse energies 150 µJ (Nâ¯= 4), 175 µJ (Nâ¯= 6), 200 µJ (Nâ¯= 7) and 250 µJ (Nâ¯= 6) were selected. Within the framework of this first feasibility analysis 400⯵m (10 sequential sections) of the sclerotomies were evaluated. The mean area of PIRL-FAST showed a dependency on the pulse energy applied. The diameter of the collateral damage zone (CDZ) depended on the pulse energy used. The largest CDZ could be measured using the highest pulse energy in this experiment (250⯵J). The environmental scanning electron microscope (ESEM) results revealed circular smooth sclerostomy wall with only minimal change of tissue ultrastructure. CONCLUSION: The PIRL-FAST using sapphire fibers is a new minimally invasive instrument to provide robust stenting from the anterior chamber to the subconjunctival space. Since the PIRL has proven to work efficiently in sectioning several tissues with minimal collateral damage these first proof of principle experiments might pave the way for a new minimally invasive glaucoma surgery strategy. We have already initiated experiments to analyze the wound healing and scar formation in vivo.
Assuntos
Terapia a Laser , Esclerostomia , Cicatriz , Alemanha , Humanos , LasersRESUMO
We have previously shown that capsaicin, noxious heat, protons and potassium ions (K(+)) induce a graded, calcium- and receptor-dependent increase of immunoreactive calcitonin gene-related peptide (iCGRP) release from isolated rat sciatic axons. Morphological evidence for axonal vesicular exocytosis has also been presented. Here we determine the differential contribution of voltage-gated calcium and sodium channels to high extracellular potassium and capsaicin-induced iCGRP secretion. Blockade of L-type calcium channels significantly decreased the K(+)-induced axonal response (nimodipine (10 microM) by 66% and methoxyverapamil, D600 (50 microM), by 77%). Interestingly, however, D600 was unable to reduce the capsaicin-induced iCGRP release. Omega-Conotoxin GVIA (1 microM), a N-type blocker, and omega-agatoxin TK (0.1 microM), a P/Q-type blocker, had no significant effect. Also the anticonvulsant gabapentin (50 microM and 100 microM), reported to impede calcium channels, was ineffective. Inhibition of low threshold T-type calcium channels by mibefradil (10 microM) significantly reduced potassium (by 47%) but not capsaicin-stimulated iCGRP release. Reduction of total sodium channel conductance by tetrodotoxin (1 microM), lidocaine (10 microM, 50 microM or 500 microM) or by replacement of extracellular sodium with choline-chloride did not result in a reduction of either potassium- or capsaicin-induced axonal iCGRP release. These results suggest that slow depolarization by high extracellular potassium activates axonal low threshold (T-type) as well as high threshold-activated (L-type) voltage-gated calcium channels to mediate iCGRP release, and that capsaicin-induced release is largely dependent on calcium influx through TRPV1. Action potential generation and propagation are not required for axonal release mechanisms.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Canais de Cálcio Tipo L/fisiologia , Canais de Cálcio Tipo T/fisiologia , Capsaicina/farmacologia , Líquido Extracelular/efeitos dos fármacos , Potássio/farmacologia , Canais de Cátion TRPV/fisiologia , Aminas/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Ácidos Cicloexanocarboxílicos/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Antagonistas de Aminoácidos Excitatórios/farmacologia , Gabapentina , Técnicas Imunoenzimáticas/métodos , Técnicas In Vitro , Masculino , Ratos , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismo , Bloqueadores dos Canais de Sódio/farmacologia , Canais de Sódio/fisiologia , Estatísticas não Paramétricas , Ácido gama-Aminobutírico/farmacologiaRESUMO
The human visual system uses texture information to segment visual scenes into figure and ground. We developed a computational model of human texture processing [Thielscher A, Neumann H (2003) Neural mechanisms of cortico-cortical interaction in texture boundary detection: a modeling approach. Neuroscience 122:921-939] which allows us to examine the functional roles of early and intermediate stages of the ventral visual pathway in figure-ground segmentation. In particular, the model highlights the central role of cells in mid-level areas (such as V4) with larger receptive fields in the robust identification of texture boundaries and pop-out stimuli even under noisy conditions. A straightforward prediction of the model is that the activity of cells in mid-level, but not early visual areas directly co-varies with the saliency of the texture borders in the visual scene. Consequently, their activity should directly correlate with the saliency of pop-out texture regions as accessed in psychophysical studies [Nothdurft HC (1991) Texture segmentation and pop-out from orientation contrast. Vision Res 31:1073-1078]. This prediction explicitly derived from the model was tested using functional magnetic resonance imaging. The saliency of texture bars composed of oriented line items was varied by parametrically changing the defining orientation contrast between fore- and background lines. Consistent with the model, increasing contrast at texture boundaries resulted in a monotonic increase of blood oxygen level dependent responses in mid-level, but not early visual areas. Our modeling and imaging results indicate that mid-level visual areas form a key stage in figure-ground segregation by gradually signaling the salience of region boundaries defined by orientation contrast.
Assuntos
Percepção de Forma/fisiologia , Imageamento por Ressonância Magnética , Modelos Neurológicos , Reconhecimento Visual de Modelos/fisiologia , Córtex Visual/irrigação sanguínea , Adulto , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Oxigênio/sangue , Estimulação Luminosa/métodos , Tempo de Reação , Córtex Visual/fisiologiaRESUMO
Visuospatial navigation in animals and human subjects is generally studied using maze exploration. We used functional MRI to observe brain activation in male and female subjects as they searched for the way out of a complex, three-dimensional, virtual-reality maze. Navigation activated the medial occipital gyri, lateral and medial parietal regions, posterior cingulate and parahippocampal gyri as well as the right hippocampus proper. Gender-specific group analysis revealed distinct activation of the left hippocampus in males, whereas females consistently recruited right parietal and right prefrontal cortex. Thus we demonstrate a neural substrate of well established human gender differences in spatial-cognition performance.