Eduardo José Caldeira

Prostatic stromal microenvironment and experimental diabetes.

The diabetes causes alterations in various organ systems, including the male accessory sex glands. The prostate is very important in the reproductive process and it is a frequent target of malignant changes. The aim of this work was to demonstrate the histochemical and ultrastructural alterations in the prostate of diabetic animals. Two groups of animals were utilized: control and non-obese diabetic mice (NOD). Twelve days after the characterization of diabetic status the ventral prostate was collected, fixed in Karnovsky and paraformaldehyde, processed for histochemistry and TEM associated to stereology. The results showed reduction of the epithelial area and increasing of the stromal area with muscular and collagen hypertrophy in the prostatic gland. It was characterized the development of prostatic intraepithelial neoplasia, inflammatory processes and dilation of the organelles involved in the secretory process. It was concluded that diabetes besides damaging the reproductive process, affects the glandular homeostasis favoring the development of prostatic pathologies.

IGF-I and INS receptor expression in the salivary glands of diabetic Nod mice submitted to long-term insulin treatment

This work aimed to characterize the IGF‐I and INS receptor expression in the salivary glands of Nod mice, correlating to therapeutic effects of insulin treatment on these receptors. Nod mice were divided into: Groups 1 and 2 (diabetic), Groups 3 and 4 (diabetic with insulin treatment) and Group 5 (non‐diabetic). Fragments from the salivary glands were processed for immunohistochemical analysis. The results showed that the prolonged diabetic state led to a steadily increased IGF‐I receptor expression. INS receptor expression was gradually decreased. It was concluded that not only was the IGF‐I receptor expression affected by the diabetic state but also the INS receptor expression. The period of the diabetic state was directly related to changes in the expression of these receptors. In spite of the insulin treatment having recovered the glycaemic levels, the expression of INS and the IGF‐I receptors did not reach the standard level, which certainly hampered glandular function.

Epithelial-stromal interactions in salivary glands of rats exposed to chronic passive smoking

OBJECTIVES Cigarette smoke leads to precancerous and cancerous lesions in the mouth even when the exposure is passive. The salivary glands are amongst the tissues exposed to the smoke but it is unclear whether or not passive cigarette exposure is related to detectable changes in these tissues. The objective of this study was to observe the tissue architecture of the parotid and submandibular glands in rats after passive cigarette exposure and to measure any changes that occurred. DESIGN Twenty Wistar rats were divided into 10 non-smoking animals and 10 animals exposed to cigarette smoke. After 6 months of smoke exposure samples were collected from both exposed and unexposed salivary glands for histological examination under both transmitted and polarized light microscopy. RESULTS Changes in the glands of exposed animals included involution of the cytoplasm and nucleus of the acinar cells and the presence of an inflammatory infiltrate. There was an abnormal accumulation of type I collagen in the stroma and an enlarged interacinar space filled with extracellular matrix. CONCLUSION Passive smoking led to substantial structural changes in the salivary glands which could significantly affect function.

Estrogen and Insulin Replacement Therapy Modulates the Expression of Insulin‐Like Growth Factor‐I Receptors in the Salivary Glands of Diabetic Mice

Diabetes mellitus results in various complications, also compromising the salivary glands. Hormone levels and interactions with cellular receptors are altered, intensifying the damage caused by this disease. Hormone replacement therapy alone or combined with other treatments may reverse this damage, but doubts still exist regarding the efficacy of this procedure. The objective of this study was to evaluate the effect of estrogen replacement therapy combined with insulin treatment on salivary secretory cells and on the expression of insulin‐like growth factor (IGF)‐I receptors in salivary glands of spontaneously diabetic (NOD) mice. Twenty‐five mice were divided into five groups of five animals each: group I (NOD diabetic), group II (NOD diabetic treated with insulin), group III (NOD diabetic treated with estrogen), group IV (NOD diabetic treated with insulin and estrogen), and group V (control Balb/c mice). Group II received insulin, group III received estrogen, and group IV received insulin plus estrogen administered daily for 20 days. Groups I and V received saline for the same period of time to simulate treatment. Glucose and estrogen levels were monitored during treatment, and salivary gland samples were collected at the end of treatment for stereological analysis and immunofluorescence detection of IGF‐I receptors. Tissue restructuring and regulation of IGF‐I receptors expression were observed in animals submitted to estrogen replacement therapy plus insulin. Estrogen effectively promoted the recovery of salivary secretory cells, demonstrating that this hormone alone, and especially when combined with insulin, might be important for the reversal of hyperglycemia‐induced tissue injury. Anat Rec, 2011.

Recovery of INS-R and ER-alpha expression in the salivary glands of diabetic mice submitted to hormone replacement therapy

The interaction between proteins and cell receptors is related to tissue homeostasis such as in salivary glands. In this respect, alterations in hormone levels caused by hyperglycaemic conditions may interfere with this interaction, intensifying the damage caused by diabetes mellitus. Hormone replacement therapy is an option to reverse this damage, but doubts still exist regarding the efficacy of this procedure. The objective of this study was to evaluate the effect of oestrogen replacement therapy combined with insulin treatment on the expression of oestrogen (ER-alpha) and insulin receptors (INS-R) in the salivary glands of spontaneously diabetic mice. Twenty-five mice were divided into five group of 5 animals each: group I (NOD diabetic), group II (NOD diabetic treated with insulin), group III (NOD diabetic treated with oestrogen), group IV (NOD diabetic treated with insulin and oestrogen), and group V (control BALB/c mice). Group II received insulin, group III received oestrogen, and group IV received insulin plus oestrogen administered daily for 20 days. Groups I and V received saline for the same period of time to simulate treatment. Glucose and oestrogen levels were monitored during the experimental period and salivary gland samples were collected at the end of the experiment for fluorescence microscopy analysis of ER-alpha and INS-R. Animals receiving oestrogen replacement therapy plus insulin showed regulation of the expression of oestrogen and insulin receptors. Oestrogen treatment alone contributed to the recovery of these cell receptors. These results indicate that oestrogen replacement therapy alone, and especially when combined with insulin, is important for the recovery of the interaction between functional proteins and their receptors, thus contributing to the reestablishment of tissues damaged by the hyperglycaemic condition.

Subcutaneous Immunotherapy Improves the Symptomatology of Allergic Rhinitis

Introduction The relevance of allergic rhinitis is unquestionable. This condition affects peoples quality of life and its incidence has increased over the last years. Objective Thus, this study aims to analyze the effectiveness of subcutaneous injectable immunotherapy in cases of nasal itching, sneeze, rhinorrhea and nasal congestion in allergic rhinitis patients. Methods In the present study, the same researcher analyzed the records of 281 patients. Furthermore, the researchers identified allergens through puncture cutaneous tests using standardized extracts containing acari, fungi, pet hair, flower pollen, and feathers. Then, the patients underwent treatment with subcutaneous specific immunotherapy, using four vaccine vials for desensitization, associated with environmental hygiene. The authors analyzed conditions of nasal itching, sneeze, rhinorrhea, and nasal congestion throughout the treatment, and assigned them with a score ranging from zero (0), meaning absence of these symptoms to three (3), for severe cases. The symptoms were statistically compared in the beginning, during, and after treatment. Results In this study, authors analyzed the cases distribution according to age and the evolution of symptomatology according to the scores, comparing all phases of treatment. The average score for the entire population studied was 2.08 before treatment and 0.44 at the end. These results represent an overall improvement of ∼79% in symptomatology of allergic rhinitis in the studied population. Conclusion The subcutaneous immunotherapy as treatment of allergic rhinitis led to a reduction in all symptoms studied, improving the quality of life of patients, proving itself as an important therapeutic tool for these pathological conditions.

Effects of anti‐CD3 monoclonal antibody in salivary glands of spontaneously diabetic mice

Background: Diabetes mellitus results in many complications, also compromising the salivary glands. The current treatment for this condition should be a substituting method to exogenous insulin. In this aspect, the immunotherapy has been tested, but, it can be inefficient as an agent for the control of damage caused by diabetes. Thus, the aim of this study was to evaluate the anti‐CD3 monoclonal antibody as alternative immunotherapy in the recovery of salivary glands of spontaneously diabetic NOD (nonobese diabetic) mice. Methods: NOD mice were divided into two groups of 10 animals: group I (untreated diabetic mice) and group II (anti‐CD3‐treated diabetic mice). After treatment, the samples of salivary glands were collected for histological examination under both transmitted and polarized light microscopy. Results: Alterations in tissue architecture; increase in extracellular matrix and presence of inflammatory process were observed in untreated animals. Recovery of the salivary acinar cells occurred in treated animals. The parotid glands demonstrated a smaller amount of collagen fibers and were not observed severe inflammatory processes. Conclusion: These results indicate that immunotherapy contributed to reestablishment of tissue damaged by the hyperglycemic condition, demonstrating that the immunomodulation plays an important role in the recovery of salivary glands. Microsc. Res. Tech., 2012.

The immunomodulation to diabetes control: New proposals for the reversion of this disease

The diabetes mellitus is a metabolic disorder, characterized by the hyperglycemia with deficiency in the use of carbohydrates, fats and proteins, resultant of the impairment in secretion and/or insulin action. Severely, the type 1 diabetes provokes the compromise of several organs, causing different disorders and until death of patient. In this way, the literature has shown the general treatments for the type 1 diabetes and currently the focus in immunotherapy and/or immunomodulation, to control of this hyperglycemic condition. The use of new therapies is necessary due to the high increase of incidence of this disease around the world. Recent studies showed an increase of 40% in the cases since 1997. This disease affects different organs, including the glandular tissues, mainly the pancreas. Despite all therapies for diabetes control, the damages occurred remain irreversible. Thus, in addition to general treatments, the use of immunotherapy may open new perspectives for treatment of this disease. Within this aspect, the anti-CD3 monoclonal antibodies may be effective, mainly by protect and maintain the pancreatic acinar cells. Thus, these treatments based in the immunomodulation can be an option for diabetes control and to reverse the damage caused by this disease.

Dipeptidyl peptidase IV inhibitor improves the salivary gland histology of spontaneously diabetic mice

OBJECTIVES The incretin-based therapy might be effective in patients possessing certain levels of preserved pancreatic beta-cells. However, doubts still exist regarding the efficacy of this atment in the recovery of tissues damaged by type 1 diabetes. Thus, the objective of this study was to evaluate the treatment with MK0431 in salivary glands of spontaneously diabetic mice, focusing mainly on the possible therapeutic and hypoglycaemic effects of this dipeptidyl peptidase IV inhibitor in the recovery of these salivary tissues. METHODS AND RESULTS Twenty mice were divided into two groups of 10 animals each: group I (NOD diabetic/untreated) and group II (NOD diabetic MK0431/treated). The group II was treated during 4 weeks with MK0431 mixed in the food. The group I was maintained in the same way without receiving, however, any treatment. Glucose levels were monitored during treatment and salivary glands samples were collected at the end of treatment for the histological examination under both transmitted and polarized light microscopy. High glucose levels were observed in untreated animals, while in animals with treatment, reduction of these levels was observed. Tissue restructuring was also observed in animals submitted to therapy with MK0431, mainly in relation to the attempt to extracellular matrix reorganization. CONCLUSIONS According to results, the treatment with this dipeptidyl peptidase IV inhibitor contributed to the general homeostasis of the organism and to the reestablishment of both epithelial and stromal compartments which were damaged by the hyperglycaemic condition, demonstrating that the incretin-based therapy may be an important complementary treatment for the type 1 diabetic condition.

High-fat diet suppresses the positive effect of creatine supplementation on skeletal muscle function by reducing protein expression of IGF-PI3K-AKT-mTOR pathway

High-fat (HF) diets in combination with sedentary lifestyle represent one of the major public health concerns predisposing to obesity and diabetes leading to skeletal muscle atrophy, decreased fiber diameter and muscle mass with accumulation of fat tissue resulting in loss of muscle strength. One strategy to overcome the maleficent effects of HF diet is resistance training, a strategy used to improve muscle mass, reverting the negative effects on obesity-related changes in skeletal muscle. Together with resistance training, supplementation with creatine monohydrate (CrM) in the diet has been used to improve muscle mass and strength. Creatine is a non-essential amino acid that is directly involved in the cross-bridge cycle providing a phosphate group to ADP during the initiation of muscle contraction. Besides its antioxidant and anti-inflammatory effects CrM also upregulates IGF-1 resulting in hyperthophy with an increase in muscle function. However, it is unknown whether CrM supplementation during resistance training would revert the negative effects of high-fat diet on the muscle performance. During 8 weeks we measured muscle performance to climb a 1.1m and 80° ladder with increasing load on trained rats that had received standard diet or high-fat diet, supplemented or not with CrM. We observed that the CrM supplementation up-regulated IGF-1 and phospho-AKT protein levels, suggesting an activation of the IGF1-PI3K-Akt/PKB-mTOR pathway. Moreover, despite the CrM supplementation, HF diet down-regulated several proteins of the IGF1-PI3K-Akt/PKB-mTOR pathway, suggesting that diet lipid content is crucial to maintain or improve muscle function during resistance training.