Effects of Pentoxifylline on TNF-Alpha and Lung Histopathology in HCl-Induced Lung Injury

OBJECTIVE: To evaluate the effects of pentoxifylline on hydrochloric acid-induced lung lesions in rats subjected to mechanical ventilation. METHODS: Twenty male, adult Wistar-EPM-1 rats were anesthetized and randomly grouped (n=5 animals per group) as follows: control-MV (mechanical ventilation, MV group); bilateral instillation of HCl (HCl group); bilateral instillation of HCl followed by pentoxifylline (50 mg/kg bw) infusion (HCl+PTX group) and pentoxifylline infusion followed by bilateral instillation of HCl (PTX+HCl group). At 20, 30, 90 and 180 min after treatments, the blood partial pressures of CO2 and O2 were measured. The animals were euthanized, and bronchoalveolar lavages were taken to determine the contents of total proteins, corticosterone and TNF-alpha. Samples of lung tissue were used for histomorphometric studies and determining the wet-to-dry (W/D) lung weight ratio. RESULTS: In the MV group, rats had alveolar septal congestion, and, in the HCl group, a remarkable recruitment of neutrophils and macrophages into the alveoli was noticed; these events were reduced in the animals with PTX+HCl. The partial pressure of oxygen increased in PTX+HCl animals (121±5 mmHg) as compared with the HCl (62±6 mmHg) and HCl+PTX (67±3 mmHg) groups within 30 minutes. TNF-alpha levels in bronchoalveolar lavage were significantly higher in the HCl group (458±50 pg/mL), reduced in the HCl+PTX group (329±45 pg/mL) and lowest in the PTX+HCl group (229±41 pg/mL). The levels of corticosterone in bronchoalveolar lavage were significantly lower in the HCl (8±1.3 ng/mL) and HCl+PTX group (16±2 ng/mL) and were highest in the PTX+HCl (27±1.9 ng/mL). CONCLUSION: Pretreatment with PTX improves oxygenation, reduces TNF-alpha concentration and increases the concentration of corticosterone in bronchoalveolar lavage upon lung lesion induced by HCl

Pentoxifylline decreases tumor necrosis factor and interleukin-1 during high tidal volume

Tumor necrosis factor-alpha (TNF-alpha) is one of the most important proinflammatory cytokines which plays a central role in host defense and in the acute inflammatory response related to tissue injury. The major source of TNF-alpha are immune cells such as neutrophils and macrophages. We tested the hypothesis that pentoxifylline, a methylxanthine derivative, down-regulates proinflammatory cytokine expression during acute lung injury in rats. Male Wistar rats weighing 250 to 450 g were anesthetized ip with 50 mg/kg sodium thiopental and randomly divided into three groups: group 1 (N = 7): tidal volume (V T) = 7 ml/kg, respiratory rate (RR) = 50 breaths/min and normal saline infusion; group 2 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and normal saline infusion; group 3 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and pentoxifylline infusion. The animals were ventilated with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 3 cmH2O, and normal saline or pentoxifylline injected into the left femoral vein. The mRNA of TNF-alpha rapidly increased in the lung tissue within 180 min of ventilation with a higher V T with normal saline infusion. The concentrations of inflammatory mediators were decreased in plasma and bronchoalveolar lavage (BAL) in the presence of higher V T with pentoxifylline infusion (TNF-alpha: plasma, 102.2 ± 90.9 and BAL, 118.2 ± 82.1; IL-1ß: plasma, 45.2 ± 42.7 and BAL, 50.2 ± 34.9, P < 0.05). We conclude that TNF-alpha produced by neutrophil influx may function as an alert signal in host defense to induce production of other inflammatory mediators.Universidade Federal de São Paulo (UNIFESP) Departamento de Doenças Infecciosas e Parasitárias Disciplina de PneumologiaUniversidade Federal de São Paulo (UNIFESP) Departamento de Doenças Infecciosas e Parasitárias Laboratório de Ginecologia MolecularUniversidade Federal de São Paulo (UNIFESP) Departamento de Doenças Infecciosas e Parasitárias Laboratório de ImunologiaUniversidade Estadual de Campinas Departamento de Clínica Médica Disciplina e Laboratório de Imunologia ClínicaUNIFESP, Depto. de Doenças Infecciosas e Parasitárias Disciplina de PneumologiaUNIFESP, Depto. de Doenças Infecciosas e Parasitárias Laboratório de Ginecologia MolecularUNIFESP, Depto. de Doenças Infecciosas e Parasitárias Laboratório de ImunologiaSciEL

RELATIONSHIP BETWEEN MOOD DISORDERS AND THYROID CHANGES

The thyroid gland, located at the base of the neck, produces hormones that regulate the body's metabolism, growth and development. Changes in the levels of these hormones, such as hypothyroidism (low production) and hyperthyroidism (high production), can have a significant impact on mental health, influencing the development of mood disorders. Studies demonstrate a strong association between thyroid dysfunction and disorders such as depression and bipolar disorder. In hypothyroidism, depressive symptoms may include fatigue, mental sluggishness, anhedonia, and weight gain. In hyperthyroidism, anxiety, insomnia and irritability are more frequent. The bidirectional relationship between thyroid and mood is complex and involves several mechanisms. Changes in thyroid hormone levels can affect brain neurotransmission, especially serotonin and dopamine, neurotransmitters directly related to mood. Furthermore, the hypothalamic-pituitary-thyroid axis, responsible for thyroid hormonal regulation, can also be influenced by psychological factors such as stress. Objective: To carry out a systematic review of the literature to evaluate the relationship between mood disorders and thyroid changes, investigating the prevalence of mood disorders in individuals with thyroid diseases, the underlying pathophysiological mechanisms and the impact of hormone replacement on mental health. Methodology: The review followed the PRISMA checklist guidelines. The PubMed, Scielo and Web of Science databases were searched using the following descriptors: "mood disorders", "hypothyroidism", "hyperthyroidism", "thyroid" and "mental health". Articles published in the last 10 years were selected. Inclusion criteria: studies that evaluate the relationship between mood disorders and thyroid diseases; Human studies; Published in Portuguese, English or Spanish; Published in the last 10 years. Exclusion: Animal studies; Studies with inadequate methodological designs; Studies that do not evaluate the relationship between mood and thyroid. Results: 15 studies were selected. The review identified that the prevalence of mood disorders is significantly higher in individuals with thyroid disease than in the general population. Hypothyroidism is associated with depression, while hyperthyroidism is more related to anxiety. The pathophysiological mechanisms underlying the relationship between mood and thyroid are complex and involve changes in cerebral neurotransmission, the hypothalamic-pituitary-thyroid axis and the response to stress. Adequate hormone replacement for thyroid disease can significantly improve symptoms of mood disorders in many cases. Conclusions: The systematic review confirmed the strong association between mood disorders and thyroid changes. Thyroid dysfunction can be a risk factor for the development of mood disorders, and adequate hormone replacement can be an important therapeutic tool.The thyroid gland, located at the base of the neck, produces hormones that regulate the body's metabolism, growth and development. Changes in the levels of these hormones, such as hypothyroidism (low production) and hyperthyroidism (high production), can have a significant impact on mental health, influencing the development of mood disorders. Studies demonstrate a strong association between thyroid dysfunction and disorders such as depression and bipolar disorder. In hypothyroidism, depressive symptoms may include fatigue, mental sluggishness, anhedonia, and weight gain. In hyperthyroidism, anxiety, insomnia and irritability are more frequent. The bidirectional relationship between thyroid and mood is complex and involves several mechanisms. Changes in thyroid hormone levels can affect brain neurotransmission, especially serotonin and dopamine, neurotransmitters directly related to mood. Furthermore, the hypothalamic-pituitary-thyroid axis, responsible for thyroid hormonal regulation, can also be influenced by psychological factors such as stress. Objective: To carry out a systematic review of the literature to evaluate the relationship between mood disorders and thyroid changes, investigating the prevalence of mood disorders in individuals with thyroid diseases, the underlying pathophysiological mechanisms and the impact of hormone replacement on mental health. Methodology: The review followed the PRISMA checklist guidelines. The PubMed, Scielo and Web of Science databases were searched using the following descriptors: "mood disorders", "hypothyroidism", "hyperthyroidism", "thyroid" and "mental health". Articles published in the last 10 years were selected. Inclusion criteria: studies that evaluate the relationship between mood disorders and thyroid diseases; Human studies; Published in Portuguese, English or Spanish; Published in the last 10 years. Exclusion: Animal studies; Studies with inadequate methodological designs; Studies that do not evaluate the relationship between mood and thyroid. Results: 15 studies were selected. The review identified that the prevalence of mood disorders is significantly higher in individuals with thyroid disease than in the general population. Hypothyroidism is associated with depression, while hyperthyroidism is more related to anxiety. The pathophysiological mechanisms underlying the relationship between mood and thyroid are complex and involve changes in cerebral neurotransmission, the hypothalamic-pituitary-thyroid axis and the response to stress. Adequate hormone replacement for thyroid disease can significantly improve symptoms of mood disorders in many cases. Conclusions: The systematic review confirmed the strong association between mood disorders and thyroid changes. Thyroid dysfunction can be a risk factor for the development of mood disorders, and adequate hormone replacement can be an important therapeutic tool

Use of the histopathology in the differential diagnosis of drowning in fresh and salty water: an experimental model establishment in rats Uso da histopatologia no diagnóstico diferencial de afogamento em água doce e água salgada: estabelecimento de modelo experimental em ratos

PURPOSE: To develop a method of differential diagnosis to drowning, due to analysis of the alveolar macrophages quantitative, in rats submitted to induced drowning in fresh water and salty water. METHODS: Were used 15 male adult rats Wistar EPM-1, weight 360g (SD=21,3), randomized in three groups: G1- Control; G2- Fresh water; G3- Salty water, each one with n=5. The animals have been anesthetized and tracheostomized to insert a cannula inside the trachea, for drowning induction. The lungs have been removed, weighed, prepared for histology and colored by immunohistochemistry. The macrophages have been counted in both lungs (right and left) of each animal. The statistical test used was ANOVA (SPSS.10) with p<0,05. RESULTS: The amount of macrophages was G3>G2>G1 with p=0,0001 in each comparison. The weight of lungs of G3 and G2 was higher than G1, with p>0,0001, however G3 and G2 do not possess difference statistics in the weight of lungs. CONCLUSION: The developed diagnostic method was efficient in rats. The results, if expanded, will be able to assist the Forensic Pathology for technique of low cost and high trustworthiness.<br>OBJETIVO: Desenvolver um método de diagnóstico diferencial de afogamento, pela análise quantitativa dos macrófagos alveolares, em ratos submetidos à afogamento induzido em água doce e água salgada. MÉTODOS: Foram utilizados 15 ratos adultos, machos Wistar EPM-1, pesando 360g (DP=21,3), randomizados em três grupos: G1 - controle; G2 - Água doce; G3 - Água salgada, cada um com n=5. Os animais foram anestesiados e traqueostomizados para inserção de uma cânula endotraqueal, para indução do afogamento. Os pulmões foram removidos, pesados, preparados para histologia e corados por imunohistoquímica. Os macrófagos foram contados em ambos os pulmões (direito e esquerdo) de cada animal. O teste estatístico utilizado foi o ANOVA (SPSS.10) com p<0,05. RESULTADOS: A quantidade de macrófagos foi G3>G2>G1 com p=0,0001, entretanto, G3 e G2 não possuem diferença estatística no peso dos pulmões. CONCLUSÃO: O método diagnóstico desenvolvido foi eficiente em ratos. Os resultados, se expandidos, serão capazes de auxiliar a Patologia Forense por uma técnica de baixo custo e alta confiabilidade

Effects of prone and supine position on oxygenation and inflammatory mediator in a hydrochloric acid-induced lung dysfunction in rats Efeitos da posição prona e supina na oxigenação e mediador inflamatório na disfunção pulmonar induzida por ácido clorídrico em ratos

PURPOSE: To compare the effectiveness of mechanical ventilation of supine versus prone position in hydrochloric acid (HCl)-induced lung dysfunction. METHODS: Twenty, adult, male, Wistar-EPM-1 rats were anesthetized and randomly grouped (n=5 animals per group) as follows: CS-MV (mechanical ventilation in supine position); CP-MV (mechanical ventilation in prone position); bilateral instillation of HCl and mechanical ventilation in supine position (HCl+S); and bilateral instillation of HCl and mechanical ventilation in prone position (HCl+P). All groups were ventilated for 180 minutes. The blood partial pressures of oxygen and carbon dioxide were measured in the time points 0 (zero; 10 minutes before lung injury for stabilization), and at the end of times acid injury, 60, 120 and 180 minutes of mechanical ventilation. At the end of experiment the animals were euthanized, and bronchoalveolar lavages (BALs) were taken to determine the contents of total proteins, inflammatory mediators, and lungs wet-to-dry ratios. RESULTS: In the HCl+P group the partial pressure of oxygen increased when compared with HCl+S (128.0±2.9 mmHg and 111.0±6.7 mmHg, respectively) within 60 minutes. TNF-&#945; levels in BAL do not differ significantly in the HCl+P group (516.0±5.9 pg/mL), and the HCl+S (513.0±10.6 pg/mL). CONCLUSION: The use of prone position improved oxygenation, but did not reduce TNF-&#945; in BAL upon lung dysfunction induced by HCl.<br>OBJETIVO: Comparar os efeitos da ventilação mecânica em posição prona versus supina na disfunção pulmonar induzida por ácido clorídrico (HCl). MÉTODOS: Vinte ratos, adultos, Wistar-EPM-1 foram anestesiados e distribuídos aleatoriamente em grupos (n=5 animais por grupo): CS-MV (controle, ventilado mecanicamente em posição supina); CP-MV (controle, ventilado mecanicamente em posição prona); instilação bilateral de HCl e ventilação mecânica em posição supina (HCl+S) ou ventilação em posição prona (HCl+P). Todos os grupos foram submetidos a ventilação mecânica por 180 minutos. As pressões parciais de oxigênio e dióxido de carbono no sangue arterial foram mensuradas nos tempos Injúria ácida (10 minutos após instilação de HCl), e ao final de cada período após lesão por HCl, 60, 120 e 180 minutos sob ventilação mecânica. Ao final do experimento os animais foram eutanasiados, os pulmões retirados para avaliação do peso úmido em relação ao peso seco do pulmão direito e realizamos o lavado broncoalveolar (BAL) para determinação de proteínas totais e o mediador inflamatório TNF-&#945;. RESULTADOS: No grupo HCl+P a pressão parcial de oxigênio, no tempo de 60 minutos, aumentou quando comparada com o grupo HCl+S (128.0±2.9 e 111.0±6.7 mmHg, respectivamente). Os níveis de TNF-&#945; no lavado broncoalveolar não diferiram de maneira estatisticamente significante quando comparamos os grupos HCl+S (513.0±10.6 pg/mL) versus HCl+P (516.0±5.9 pg/mL). CONCLUSÃO: O uso da posição prona melhora a oxigenação, mas não reduz os níveis de BAL após disfunção pulmonar induzida por HCl