Comparison of the effects of corneal and lacrimal gland denervation on the lacrimal functional unit of rats / Comparação dos efeitos da denervação da córnea e da glândula lacrimal na unidade funcional lacrimal de ratos

ABSTRACT Purpose: This study aimed to compare the changes in the lacrimal functional unit in the following two models of neurogenic dry eye syndrome: sensory denervation of the cornea versus autonomic denervation of the lacrimal gland. Methods: The neural network supports the lacrimal functional unit. It can be divided into afferent (sensory) and efferent (autonomic) pathways and is affected by severe diseases that compromise the lacrimal functional unit. Male Wistar, 8-week-old rats were divided into the following three groups: 1) control naïve (n=16 animals); 2) autonomic denervation: where rats were subjected to right lacrimal gland nerve ablation and evaluated after 1 and 2 months (1M and 2M) after the procedure (n=7 animals per subgroup, autonomic denervation 1M and autonomic denervation 2M, respectively); 3) sensory denervation induced by 0.2% benzalkonium chloride eye drops, twice a day for 7 days in the right eye (n=10 animals). The corneal sensitivity was measured using the eye wipe test with capsaicin (10 µM). The quantitative real-time PCR was performed to compare the mRNA expressions of proinflammatory cytokines, such as Il-1β, Il-6, Tnf, Mmp9, in the cornea, trigeminal ganglion, and lacrimal gland. In addition, the mRNA of the promitotic factors in the lacrimal gland, such as Bmp7, Runx1, Runx3, Fgf10, and Smad1, was compared. Results: Sensory denervation induced corneal hyperalgesia (p=0.001). Sensory denervation and autonomic denervation increased the mRNA of proinflammatory cytokines in the cornea and lacrimal gland (p<0.05), but only sensory denervation increased the mRNA levels of Il-1β and Tnf in the trigeminal ganglion (p<0.05) compared with the control naïve. Conclusions: Autonomic denervation and sensory denervation models can have common features, such as inflammation of different parts of the lacrimal functional unit. However, hyperesthesia and inflammatory markers in the trigeminal ganglion because of sensory denervation and the expression of regenerative mediators in the lacrimal gland owing to autonomic denervation are the distinguishing features of these diseases that can be explored in future studies assessing dry eye syndrome secondary to neural damage of the lacrimal functional unit.

RESUMO Objetivo: O nosso objetivo neste estudo foi comparar as alterações na unidade funcional lacrimal em dois modelos de síndrome do olho seco neurogênica: desnervação sensorial da córnea versus desnervação autonômica da glândula lacrimal. Métodos: A rede neural é um importante suporte para a unidade funcional lacrimal. Pode ser dividido em vias aferentes (sensoriais) e eferentes (autonômicas), sujeitas a doenças graves que comprometem a unidade funcional lacrimal. Ratos Wistar machos, com 8 semanas de idade, foram divididos em três grupos: 1) Controle naïve (n=16 animais); 2) Desnervação autonômica: onde os ratos foram submetidos à ablação do nervo da glândula lacrimal direita e avaliados após um e dois meses (1 M a 2 M) do procedimento (n=7 animais por subgrupo, desnervação autonômica 1M e desnervação autonômica 2M, respectivamente); 3) Desnervação sensorial induzida por colírio a 0,2% de cloreto de benzalcônio, duas vezes ao dia por 7 dias no olho direito (n=10 animais). A sensibilidade da córnea foi medida pelo teste de movimento pata-olho com capsaicina (10 µM). A PCR quantitativa em tempo real foi aplicada para comparar a expressão relativa de mRNA de citocinas pró-inflamatórias: Il1b, Il6, Tnf, Mmp9, na córnea, gânglio trigêmio e glândula lacrimal. O mRNA dos agentes pró-mitóticos Bmp7, Runx1, Runx3, Fgf10 e Smad1 foram comparados na glândula lacrimal. Resultados: A desnervação sensorial induziu hiperalgesia da córnea (p=0,001). Desnervação sensorial e desnervação autonômica aumentaram o mRNA de citocinas pró-inflamatórias no córnea e glândula lacrimal (p<0,05), mas apenas desnervação sensorial aumentou o mRNA de Il1b e Tnf no gânglio trigêmio (p<0,05) quando comparado ao controle naïve. Conclusões: Os modelos de desnervação autonômica e desnervação sensorial podem ter características comuns, como inflamação de diferentes partes da unidade funcional lacrimal. No entanto, a hiperestesia e os marcadores inflamatórios no gânglio trigêmio de desnervação sensorial e a expressão de mediadores regenerativos na glândula lacrimal na desnervação autonômica são características que distinguem essas doenças, podendo ser investigadas em estudos futuros que abordam o olho seco secundário ao dano neural da unidade funcional lacrimal.

Comparison of the effects of corneal and lacrimal gland denervation on the lacrimal functional unit of rats.

PURPOSE: This study aimed to compare the changes in the lacrimal functional unit in the following two models of neurogenic dry eye syndrome: sensory denervation of the cornea versus autonomic denervation of the lacrimal gland. METHODS: The neural network supports the lacrimal functional unit. It can be divided into afferent (sensory) and efferent (autonomic) pathways and is affected by severe diseases that compromise the lacrimal functional unit. Male Wistar, 8-week-old rats were divided into the following three groups: 1) control naïve (n=16 animals); 2) autonomic denervation: where rats were subjected to right lacrimal gland nerve ablation and evaluated after 1 and 2 months (1M and 2M) after the procedure (n=7 animals per subgroup, autonomic denervation 1M and autonomic denervation 2M, respectively); 3) sensory denervation induced by 0.2% benzalkonium chloride eye drops, twice a day for 7 days in the right eye (n=10 animals). The corneal sensitivity was measured using the eye wipe test with capsaicin (10 µM). The quantitative real-time PCR was performed to compare the mRNA expressions of proinflammatory cytokines, such as Il-1ß, Il-6, Tnf, Mmp9, in the cornea, trigeminal ganglion, and lacrimal gland. In addition, the mRNA of the promitotic factors in the lacrimal gland, such as Bmp7, Runx1, Runx3, Fgf10, and Smad1, was compared. RESULTS: Sensory denervation induced corneal hyperalgesia (p=0.001). Sensory denervation and autonomic denervation increased the mRNA of proinflammatory cytokines in the cornea and lacrimal gland (p<0.05), but only sensory denervation increased the mRNA levels of Il-1ß and Tnf in the trigeminal ganglion (p<0.05) compared with the control naïve. CONCLUSIONS: Autonomic denervation and sensory denervation models can have common features, such as inflammation of different parts of the lacrimal functional unit. However, hyperesthesia and inflammatory markers in the trigeminal ganglion because of sensory denervation and the expression of regenerative mediators in the lacrimal gland owing to autonomic denervation are the distinguishing features of these diseases that can be explored in future studies assessing dry eye syndrome secondary to neural damage of the lacrimal functional unit.

An Insight into the Role of Non-Porphyrinoid Photosensitizers for Skin Wound Healing.

The concept behind photodynamic therapy (PDT) is being successfully applied in different biomedical contexts such as cancer diseases, inactivation of microorganisms and, more recently, to improve wound healing and tissue regeneration. The effectiveness of PDT in skin treatments is associated with the role of reactive oxygen species (ROS) produced by a photosensitizer (PS), which acts as a "double agent". The release of ROS must be high enough to prevent microbial growth and, simultaneously, to accelerate the immune system response by recruiting important regenerative agents to the wound site. The growing interest in this subject is reflected by the increasing number of studies concerning the optimization of relevant experimental parameters for wound healing via PDT, namely, light features, the structure and concentration of the PS, and the wound type and location. Considering the importance of developing PSs with suitable features for this emergent topic concerning skin wound healing, in this review, a special focus on the achievements attained for each PS class, namely, of the non-porphyrinoid type, is given.

What is the role of general internists in the tertiary or academic setting?

The changing demography of European populations mandates a vital role for internists in caring for patients in each level of healthcare. Internists in the tertiary or academic setting are highly ranked in terms of their responsibilities: they are clinicians, educators, researchers, role models, mentors and administrators. Contrary to the highly focused approach of sub-specialties, general internists working in academic settings can ensure that coordinated care is delivered in the most cost-conscious and efficient way. Moreover, internal medicine is one of the most appropriate specialties in which to teach clinical reasoning skills, decision-making and analytical thinking, as well as evidence based, patient oriented medicine. Internists deal with challenging patients of the new millennium with a high burden of chronic diseases and polypharmacy; practice personalised medicine with a wide scientific background and so they are the perfect fit to establish and implement new tools for scientific research. In conclusion, internal medicine is developing a new identity as a specialty in its own right. The European Federation of Internal Medicine supports the concept of academic internists and calls upon the member countries to construct academic (general) internal medicine departments in their respective countries. As 'internal medicine is the cornerstone of every national healthcare system', academic (general) internal medicine should strive to be the cornerstone of every integrated, patient-centred, modern medical care and training system.

[Political issues in internal medicine in Europe. A position paper]. / Pozycja i przyszlosc medycyny wewn trznej w Europie. Prezentacja naszego stanowiska.

What will be the future of internal medicine in Europe? Because of rapidly growing concerns regarding the position of internal medicine in many European countries, the European Federation of Internal Medicine (EFIM) has established a working group to analyze the situation. Being well aware of the variation in working practices in the different countries, the members of the group used an "all-European" approach to answer the following questions: Are there problems for internal medicine? If so, what are these problems and why? Why do the health care systems in the European countries need internal medicine? Why do patients need internal medicine? What needs to be done? Internal medicine is the modern, clinical, and scientific medical discipline that is responsible for the care of adult patients with one or more complex, acute, or chronic illnesses. Internal medicine is the cornerstone of an integrated health care delivery service that is needed today. Decision-makers in politics and hospitals, insurers, journalists, and the general public need a better understanding of what internal medicine can offer to the health care system and to the individual patient.

Political issues in internal medicine in Europe.

What will be the future of Internal Medicine in Europe? Because of rapidly growing concerns regarding the position of Internal Medicine in many European countries, the European Federation of Internal Medicine has established a working group to analyze the situation. Being well aware of the variation of working practices in the different countries, the members of the group used an "all-European" approach to answer the following questions: Are there problems for Internal Medicine, what problems and why? Why do the health care systems of the European countries need Internal Medicine? Why do the patients need Internal Medicine? What needs to be done? Internal Medicine is the modern, clinical and scientific medical discipline taking care of adult patients with one or more complex, acute or chronic illnesses. Internal Medicine is the cornerstone of integrated health care delivery service that is needed today. Decision-makers in politics and hospitals, insurers, journalists and the general public need a better understanding of what Internal Medicine can offer to the health care system and to the individual patient.

Political issues in internal medicine in Europe. A position paper.

What will be the future of internal medicine in Europe? Because of rapidly growing concerns regarding the position of internal medicine in many European countries, the European Federation of Internal Medicine (EFIM) has established a working group to analyze the situation. Being well aware of the variation in working practices in the different countries, the members of the group used an "all-European" approach to answer the following questions: Internal medicine is the modern, clinical, and scientific medical discipline that is responsible for the care of adult patients with one or more complex, acute, or chronic illnesses. Internal medicine is the cornerstone of an integrated health care delivery service that is needed today. Decision-makers in politics and hospitals, insurers, journalists, and the general public need a better understanding of what internal medicine can offer to the health care system and to the individual patient.

[Acute disautonomia associated to Hodgkin lymphoma]. / Disautonomia aguda associada a linfoma de Hodgkin.

The case of a 31 man with acute disautonomia envolving the parasympathetic and sympathetic systems but sparing sympathetic cholinergic division is presented. A Hodgkin lymphoma was diagnosed allowing the diagnosis of a paraneoplastic syndrome.