Short- and long-term effects of zinc treatment on lacrimal gland histopathology and tear functions tests in radioiodine-administered rats / Efeitos de curto e longo prazo do tratamento com zinco na histopatologia da glândula lacrimal e funções lacrimais em ratos que receberam iodo radioativo

ABSTRACT Purpose: To investigate the short-term (1 week) and long-term (8 weeks) protective effects of zinc administration on radioiodine (RAI)-induced lacrimal gland damage of rats. Methods: A total of 40 rats were divided into two groups: an RAI group (n=20), which was administrated a single dose of 3 mCi of 131I and 1 mL physiologic saline for 7 days by gastric gavage, and a zinc group (n=20), which received a single dose of 3 mCi of 131I and 1 mL of physiologic saline containing zinc sulfate at a concentration of 10 mg/kg concentration for 7 days by gastric gavage. All rats underwent tear function tests before and 1 week after RAI administration. About 1 week after irradiation, half of the animals in each group were sacrificed and the extraorbital lacrimal glands were removed for histopathological examination. The remaining animals of the groups underwent the same procedures at 8 weeks after irradiation. Results: In the RAI and zinc groups, the mean tear production was 3.75 ± 1.55 and 3.65 ± 1.53 mm at baseline, 2.10 ± 1.07 and 3.30 ± 1.34 mm at week 1 (p=0.004), and 3.22 ± 1.48 and 3.50 ± 1.78 mm at week 8, respectively; further, the mean corneal fluorescein staining scores were 4.65 ± 2.16 and 4.80 ± 2.21 points at baseline, 7.85 ± 1.90 and 5.45 ± 2.06 points at week 1 (p=0.001), and 5.44 ± 2.13 and 4.90 ± 2.08 at week 8, respectively. The histopathological changes in rat lacrimal glands at weeks 1 and 8 were consistent with the tear function test results. Conclusions: Zinc treatment seems to be protective against RAI-induced lacrimal gland damage of rats, particularly in the acute period.

RESUMO Objetivo: Investigar se o tratamento com zinco tem efeito protetor, no curto prazo (1 semana) e longo prazo (8 semanas), sobre os danos induzidos na glândula lacrimal por iodo radiotativo (RAI) em ratos. Métodos: Quarenta ratos foram divididos em dois grupos. No grupo RAI (n=20) foi administrada uma única dose de 3 mCi 131I e 1 cc de solução salina fisiológica durante 7 dias, por gavagem gástrica. O grupo zinco (n=20) recebeu uma dose única de 3 mCi 131I e 1 cc de solução salina fisiológica contendo sulfato de zinco na concentração de 10 mg/kg durante 7 dias por gavagem gástrica. Os testes de função lacrimal foram realizadas para todos os animais antes e após uma semana da administração da RAI. Em seguida, após 1 semana da administração, metade dos animais de cada grupo foi sacrificada e as glândulas lacrimais extraorbitais foram removidas para exame histopatológico. Os animais remanescentes dos grupos foram submetidos aos mesmos procedimentos após 8 semanas a radiação. Resultados: As médias de produção lacrimal foram de 3,75 ± 1,55 e 3,65 ± 1,53 mm na linha de base, 2,10 ± 1,07 e 3,30 ± 1,34 mm na 1a semana (p=0,004), e 3,22 ± 1,48 e 3,50 ± 1,78 mm na 8a semana, para os grupos RAI e zinco, respectivamente. As pontuações médias de coloração fluoresceína foram 4,65 ± 2,16 e 4,80 ± 2,21 no início do estudo, 7,85 ± 1,90 e 5,45 ± 2,06 na primeira semana (p=0,001), 5,44 ± 2,13 e 4,90 ± 2,08 pontos na 8a semana, para os grupos RAI e zinco, respectivamente. As alterações histopatológicas das glândulas lacrimais em 1 e 8 semanas foram consistentes com os testes de função lacrimal resultados. Conclusões: O tratamento de zinco parece ser protetor sobre os danos glândula lacrimal induzidos por RAI em ratos, especialmente no período agudo.

Influence of hyperprolactinemia on collagen fibers in the lacrimal gland of female mice

OBJECTIVE:To quantify the collagen fibers in the lacrimal gland of female mice with hyperprolactinemia.METHODS:Forty adult female mice were randomly divided into two groups with 20 animals each: nonpregnant control (CTR1, control group, 0.2 mL of saline solution) and nonpregnant experimental (HPRL1, experimental group, 200 µg/day metoclopramide). Treatments lasted for 50 consecutive days. On day 50, 10 females from each group (control and experimental) were euthanized in the proestrus phase; then, the blood was collected and the lacrimal glands were removed. Thereafter, the remaining females were placed with the mates and continued to receive treatment with saline solution or metoclopramide. On the 6th post-coital day, 10 pregnant females from the control group (CTR2) and 10 pregnant females from the experimental group (HPRL2) were euthanized, after which blood was collected and the lacrimal glands removed. The lacrimal glands were processed for morphological analyses and collagen quantification, and prolactin and sex steroid levels were measured in the blood samples. Data were statistically analyzed using an unpaired Student t test (p<0.05).RESULTS:Morphological analysis revealed greater structural tissue disorganization of the lacrimal glands in the metoclopramide-treated groups. The total collagen content was significantly higher in the HPRL1 group than in the CTR1 group (p<0.05), whereas the difference between the CTR2 and HPRL2 groups was not significant.CONCLUSION:Our data suggest an impairment in the functioning of the lacrimal gland as a consequence of increased prolactin levels and decreased serum levels of estrogen and progesterone.

Insulin replacement restores the vesicular secretory apparatus in the diabetic rat lacrimal gland / Reposição de insulina restaura o mecanismo secretório da glândula lacrimal de ratos diabéticos

ABSTRACT Purpose: In the lacrimal gland (LG) acinar cells, signaling regulates the release of secretory vesicles through specific Rab and SNARE exocytotic proteins. In diabetes mellitus (DM), the LGs are dysfunctional. The aim of this work was to determine if secretory apparatus changes were associated with any effects on the secretory vesicles (SV) in diabetic rats as well as the expression levels of constituent Rab and members of the SNARE family, and if insulin supplementation reversed those changes. Methods: DM was induced in male Wistar rats with an intravenous dose of streptozotocin (60 mg/kg). One of the two diabetic groups was then treated every other day with insulin (1 IU). A third control group was injected with vehicle. After 10 weeks, Western blotting and RT-PCR were used to compared the Rab and SNARE secretory factor levels in the LGs. Transmission electron microscopy evaluated acinar cell SV density and integrity. Results: In the diabetes mellitus group, there were fewer and enlarged SV. The Rab 27b, Rab 3d, and syntaxin-1 protein expression declined in the rats with diabetes mellitus. Insulin treatment restored the SV density and the Rab 27b and syntaxin expression to their control protein levels, whereas the Vamp 2 mRNA expression increased above the control levels. Conclusions: Diabetes mellitus LG changes were associated with the declines in protein expression levels that were involved in supporting exocytosis and vesicular formation. They were partially reversed by insulin replacement therapy. These findings may help to improve therapeutic management of dry eye in diabetes mellitus. .

RESUMO Objetivo: Células acinares da glândula lacrimal (GL) sinalizam a regulação da liberação através de vesículas secretórias específicas Rab proteínas exocitóticas SNARE. No diabetes mellitus (DM), as glândulas lacrimais são disfuncionais. O objetivo deste trabalho foi determinar se em ratos diabéticos, alterações dos aparatos secretórios estão associados a efeitos sobre vesículas secretoras (VS) e sobre os níveis de expressão do constituinte Rab, bem como membros da família SNARE, e se a suplementação de insulina reverte as alterações. Métodos: DM foi induzido em ratos Wistar machos com uma dose intravenosa de estreptozotocina (60 mg/kg). Um dos dois grupos diabéticos foi então tratado a cada dois dias com insulina (1 UI). Um terceiro grupo controle foi injetado com o veículo. Após 10 semanas, western blot e RT-PCR comparou níveis de fatores secretórios de Rab e SNARE na glândula lacrimal. Microscopia eletrônica de transmissão (MET) avaliaram a densidade e integridade de VS de célula acinar. Resultados: No grupo diabetes mellitus , houve poucas e alargadas VS. Rab27b, Rab 3d e Sintaxina-1 diminuiu a expressão da proteína em ratos com Diabetes Mellitus. O tratamento com insulina restaurou a densidade das VS e expressão de Rab 27b e Sintaxina para seus níveis de proteína controle, enquanto a expressão de Vamp 2 RNAm aumentou em relação aos controles. Conclusões: Alterações na glândula lacrimal de diabetes mellitus estão associadas a reduções nos níveis de expressão de proteínas envolvidas no apoio a exocitose e formação vesicular. Eles são, em parte, revertida por terapia de reposição de insulina. Estes resultados podem ajudar a melhorar a conduta terapêutica do olho seco no diabetes mellitus. .

Influência da toxina botulínica tipo A na função lacrimal de pacientes com distonias faciais / Botulinum toxin type A influence on the lacrimal function of patients with facial dystonia

OBJETIVO: Avaliar a influência da toxina botulínica na função lacrimal de pacientes com distonias faciais. MÉTODOS: Pacientes com diagnóstico de espasmo hemifacial ou blefaroespasmo essencial em atividade foram clinicamente avaliados e responderam questionário de desconforto ocular (OSDI) e foram submetidos aos testes de Schirmer I e basal, tempo de ruptura do filme lacrimal e clearance da lágrima para avaliação da função lacrimal. No dia seguinte, os pacientes receberam tratamento padronizado com toxina botulínica. O questionário e todos os exames iniciais foram repetidos 30 dias após o tratamento pelo mesmo examinador. RESULTADOS: Foram incluídos 26 pacientes no estudo, sendo 15 (57,7 por cento) com espasmo hemifacial e 11(42,3 por cento) com blefaroespasmo essencial. Nos pacientes com espasmo hemifacial a média de idade foi 70,9 ± 13,3 anos e a relação masculino/feminino foi de 1:1,5. Nos pacientes com blefaroespasmo essencial a mé­dia de idade foi 68,9 ± 8,4 anos com predomínio do sexo feminino (90,9 por cento). Após o tratamento o escore do OSDI e os valores dos testes de Schirmer I e basal diminuíram significantemente nos dois grupos. O valor médio da ruptura do filme lacrimal aumentou significantemente nos dois grupos. No teste do clearance da lágrima houve um aumento no número de olhos que apresentaram drenagem completa da lágrima após o tratamento nos dois grupos. CONCLUSÃO: O tratamento com toxina botulínica melhorou os sintomas de olho seco em pacientes com distonias faciais. Apesar da porção aquosa da lágrima ter diminuído, as alterações no piscar aumentaram a estabilidade e melhoraram a drenagem da lágrima.

PURPOSE: To analyze the influence of botulinum toxin on the lacrimal function of patients with facial dystonias. METHODS: Patients with the diagnosis of hemifacial spasm or benign essential blepharospasm were evaluated and invited to answer the Ocular Surface Index Disease (OSID) questionnaire. All patients underwent Schirmer I and basal tests; break-up time (BUT) test and lacrimal clearance evaluation. On the following day, the patients were treated with botulinum toxin. The Ocular Surface Index Disease questionnaire and all the initial tests were reapplied 30 days after the treatment by the same examiner. RESULTS: Twenty-six patients were enrolled in this study, 15 (57.7 percent) with hemifacial spasm and 11 (42.3 percent) with benign essential blepharospasm. The mean age of patients with hemifacial spasm was 70.9 ± 13.3 years and the male:female ratio was 1:1.5. In the group of patients with benign essential blepharospasm, the mean age was 68.9 ± 8.4 years with a female preponderance (90.0 percent). After the treatment, the Ocular Surface Index Disease score, Schirmer I and basal tests score decreased in both groups. The mean of Break-up time test increased significantly in both groups. The lacrimal clearance evaluation showed a greater number of eyes that achieved a complete drainage of the tears after the treatment in both groups. CONCLUSION: The treatment with botulinum toxin improved dry eye symptoms in patients with facial dystonia. Despite of the aqueous portion of tear have decreased, blink modifications improved the tear stability and drainage.

role of hormone replacement therapy on structural integrity of lacrimal gland in ovariectomized albino rats [histological and immunohistochemical study]

Sex steroid hormones are important regulators of lacrimal gland functions. In addition, dry eye syndrome is conmion in menopausal women. This work was conducted to demonstrate the role of hormone replacement therapy [HRT] on structural integrity of the lacrimal gland of ovariectomized rats. Thirty six adult female albino rats, were used in the present work divided into three equal groups: Group I [control] and group II [bilaterally ovariectomized rats] sacrificed 1 and 12 weeks following ovariectomy. The third group contained ovariectomized rats receiving HRT was subdivided into: Subgroup lila received estradiol benzoate and subgroup III b received androgen. Small pieces of the gland were obtained and processed for different histological and immunohistochernical stains. One week after ovariectomy the connective tissue septa was thickened. Collagen fibers were abundant with extensive cellular infiltration around dilated ducts and congested blood vessels. Some acinar cells were vacuolated and others contained darkly stained nuclei. Twelve weeks after ovarictomy, the acini were lined with low cuboidal cells and their lumina were widened with increased collagen fibers inbetween. In hormone treated group, the gland nearly regained its normal architecture, however few acinar cell nuclei showed hyperchrornatism. In estrogen treated group some interlobular septa were widened. Concerning fiRs inimunoreactivity, in group 11, the acinar cell nuclei showed strong positive reaction in the first week then the reaction was negative after 12 weeks. The immune reaction for ERs remained negative after the HRT. One week after ovariectomy, the immune reaction for bcl-2 was weak in the cytoplasm of ductal cells and moderate in interstitial cells. After 12 weeks, they became immune negative and after estrogen and androgen treatment marked rise in their bcl-2 immune reactivity was observed. Sex hormone balance was proved to be a crucial factor in maintaining structural and functional integrity of lacrirnal gland. So, future clinical therapeutic strategies based on estrogen and/or androgen replacement therapy for aged women and patients with premature ovarian failure could help in preventing or curing dry eye syndrome associated with lacrimal deficiency is adivsed

Tear film and ocular surface alterations in chronic users of antiglaucoma medications

PURPOSE: Tear film can be altered by chronic medications that may disrupt the equilibrium responsible for the functioning of the lacrimal gland and ocular surface. The purpose of this study was to determine if antiglaucomatous chronic treatment induced alterations in the tear film and ocular surface. METHODS: After informed consent, 21 patients using antiglaucomatous eye drops for more than 8 months and 20 age- and sex-matched volunteers without eye and systemic medications (control group) were enrolled. The data of ocular discomfort, fluorescein and lisamine green staining, tear film break-up time and Schirmer test were collected and compared by Student's t test. The impression cytology data were graded and compared by chi-square test. RESULTS: Patients chronically using antiglaucomatous medications presented with significant higher fluorescein staining (p=0.003), lisamine green staining (p=0.02) and lower TFBUT (p=0.001). The other comparedparameters, including impression cytology were similar between the treated and control group (p>0.05). CONCLUSIONS: The present study shows that the tear film and the ocular surface are altered in patients under antiglaucomatous medications. In common, all medications were preserved with benzalkonium chloride. Efforts to minimize the adverse effects of chronic use of antiglaucomatous drugs must be addressed.

OBJETIVO: O filme lacrimal pode ser alterado por medicações crônicas, que podem comprometer o equilíbrio responsável pela função da glândula lacrimal e da superfície ocular. O objetivo desse estudo foi determinar se o tratamento crônico com drogas antiglaucomatosas induz alterações no filme lacrimal e superfície ocular. MÉTODOS: Após o consentimento informado, 21 pacientes usando drogas antiglaucomatosas por mais de 8 meses e 20 voluntários com similar distribuição etária e por sexo, não usuários de medicação ocular ou sistêmica (grupo controle) foram incluídos. Os dados do desconforto ocular, coloração com fluoresceína e lissamina verde, tempo de ruptura do filme lacrimal e teste de Schirmer foram colhidos e analisados pelo teste t de Student. A citologia de impressão foi avaliada e comparada pelo teste de qui-quadrado. RESULTADOS: Pacientes usando cronicamente medicação antiglaucomatosa apresentaram ignificativamente maior coloração por fluoresceína (p=0,003), lissamina verde (p=0,02) e menor TRFL (p=0,001). Os outros parâmetros comparados, incluindo a citologia de impressão foram similares entre o grupo tratado e controle (p>0,05). CONCLUSÕES: Esse estudo demonstra que o filme lacrimal e a superfície ocular estão alterados em usuários de medicação antiglaucomatosa. Essas medicações apresentam em comum o cloreto de benzalcônio como conservante. Esforços para minimizar efeitos adversos do uso crônico de drogas antiglaucomatosas devem ser considerados.

Effect of pinealectomy and 5-methoxyindoles on Harderian gland activity of the Indian Jungle bush quail Perdicula asiatica.

The present study reveals that the annual Harderian gland weight cycle of P. asiatica has a direct relationship with the testicular cycle and an inverse relationship with the pineal gland cycle. Pinealectomy resulted in a significant decrease of the Harderian gland weight during the recurdescence (March-May) and active (April-June) phases. Subcutaneous implantation of melatonin (aMT) and 5-methoxytryptamine (MT) brought about a significant reduction during the recrudescence and active phases whereas subcutaneous injections of aMT, MT and 5-methoxytryptophol (ML) reduced Harderian gland weight effectively during the morning as well as in the evening hours in the active and inactive phases.

Da existência de receptores beta-adrenérgicos na glândula lacrimal do cäo / Beta-adrenergic receptors in the lacrimal gland of the dog

Estudo em glândulas lacrimais de cäes, das modificaçöes do fluxo lacrimal, bem como das alteraçöes histológicas induzidas por drogas alfa e ß-adrenérgicas, sem e com bloqueio destes receptores pelo propranolol. Os resultados mostraram que as drogas ß-estimulantes induziram ao aumento do fluxo, lacrimal, bloqueável pelo propranolol. Quanto às drogas estimulantes, aquele efeito näo ocorreu. A administraçäo crônica de drogas ß-estimulantes ocasionou aumento do volume nuclear na glândula lacrimal