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1.
Iran J Pathol ; 17(2): 166-173, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463722

RESUMO

Background & Objective: The existence of eosinophils in the gastric mucosal epithelium is unusual, while the term "eosinophilic gastritis" has become overused due to the increased numbers of eosinophils found in gastric specimens. Thus, we aimed to assess the number and distribution of eosinophils in gastric specimens in Shahid Beheshti University of Medical Sciences hospitals. Methods: This study was performed on 318 patients with gastric diseases who had undergone endoscopic biopsy or gastrectomy in the hospitals affiliated with Shahid Beheshti University from 2016 to 2018. By referring to the archives of pathology departments, patients' demographic and clinical information, endoscopic and histopathological findings were collected. The data was then statistically analyzed using SPSS software version 24 with a significance level of P-value< 0.05 in all tests. Results: The participants were 157 men and 161 women, with an average age of 51.21 years. There was no significant correlation between eosinophil distribution and age, gender, or primary gastric locations. However, there was a strong correlation between the count of eosinophils in the lamina propria and intestinal metaplasia. Mean eosinophil count per high power field (HPF) was 12, 23, and 14 in mild, moderate, and severe degrees of intestinal metaplasia, respectively. An increase in eosinophil count was seen along with lymphoplasma cells infiltration up to 8/HPF in mild cases, 13/HPF in moderate cases, and 14/HPF in severe cases. Conclusion: Eosinophil counts in the lamina propria layer show a significant positive relationship with the eosinophil sheet, presence of Heliobacter pylori microorganism, intestinal metaplasia, and lymphoplasma cells infiltration.

2.
Iran J Pathol ; 17(2): 136-142, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463734

RESUMO

Background & Objective: Eosinophils are normally found in different parts of the gastrointestinal tract and with less prevalence in the esophagus. Eosinophilic infiltration is increased as part of inflammatory reactions in various diseases. The aim of this study was to determine the count and distribution of eosinophils in esophageal specimens obtained for different causes. Methods: Endoscopy and pathology reports of esophageal specimens in Shahid Beheshti University related hospitals, Tehran, Iran, were extracted from 2016 to 2019. The prevalence of gastroesophageal reflux disease (GERD), malignancy, eosinophilic esophagitis, and asymptomatic patients were determined as the percentages of total resection and biopsy specimens. Each group was calculated and randomly selected according to the inclusion criteria. All data were analyzed statistically using SPSS software. Results: A total of 258 biopsy and resection specimens were evaluated in this study. Fourty three cases (16.7%) diagnosed as normal esophageal mucosa , 42 cases (16.3%) as non-specific esophagitis, 155 cases (60.1%) diagnosed as gastroesophageal reflux disease, 4 cases (1.6%) showed malignancy and other diagnoses were recorded for 14 cases (5.4%). The numbers of eosinophils in the epithelium and lamina propria in the normal group were 0.1±0.5 and 2.08±2.33, respectively. The eosinophil count in different groups and its relation to different histopathologic findings were diverse. Conclusion: The number of eosinophils within the lamina propria was significantly higher than those found within other layers. . The highest mean eosinophil count was observed in the epithelium and the lamina propria of cases diagnosed as GERD.

3.
Iran J Pathol ; 16(4): 448-450, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567196

RESUMO

The incidence of pericardial epithelioid angiosarcoma is rare. Angiosarcoma of pericardium may coat the pericardium in a diffuse fashion. Diagnosis of an angiosarcoma is challenging and may be easily mistaken as constrictive pericarditis. Herein, a case of primary pericardial angiosarcoma is reported in a 16-year-old female. Patient presented with chest pain and dyspnea on exertion, regarded as constrictive pericarditis. Pericardectomy was performed and histopathologic examination showed pleomorphic epithelioid cells exhibiting hyperchromatic nuclei, prominent nucleoli and eosinophilic cytoplasm arranged in sheets and occasionally lined irregular vascular spaces. Moreover, immunohistochemical staining revealed that tumor cells were positive for CD31 and vimentin. The patient received chemotherapy with adriamycin, ifosfamide, and mesna. Unfortunately, the patient died of cardiac involvement and pleural metastases less than three months following the operation. Primary pericardial angiosarcoma is rare and difficult to diagnose, especially epithelioid variant. Immunohistochemical assessment is required to confirm the final diagnosis.

4.
Iran J Pathol ; 15(3): 167-174, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32754211

RESUMO

BACKGROUND & OBJECTIVE: Most colorectal cancers (CRCs) arise from adenomatous polyps, and clinical management of this type of polyp is highly dependent on the reliability and validity of the pathological diagnosis. The aim of this study was to examine the interobserver agreement of five pathologists in assessing dysplasia in adenomatous polyps. METHODS: In this study, a total of 146 adenomatous polyps of patients undergoing colonoscopy were selected from hospitals of Shahid Beheshti University of Medical Sciences, Tehran, Iran between 2017 and 2018. Five pathologists independently classified adenomatous polyps according to histologic type, nuclear pseudostratification, mitotic activity, nuclear polarity, nuclear pleomorphism, nuclear shape, nucleolus, chromatin pattern, cytology grade, architectural features, dysplasia, and final diagnosis. The overall kappa statistic (k) was used to assess agreement among pathologists. RESULTS: The mean age of the patients was 62.06 ± 13.06 (mean ± SD) with a male-to-female ratio of 2.2:1. The most common site of resection was the sigmoid colon (28.1%). The highest agreement was found for dysplasia grade (k=0.415) and histologic type (k=0.401), whereas the lowest agreement was found for mitotic activity (k=0.185), nuclear shape (k=0.187), and nucleolus (k=0.196). CONCLUSION: Our findings indicate that agreement among pathologists in assessing dysplasia in adenomatous polyps is within fair to moderate levels of agreement. Therefore, there is a vital need to better clarify the current diagnostic criteria.

5.
Asian Pac J Cancer Prev ; 21(1): 133-137, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31983175

RESUMO

INTRODUCTION: Breast cancer (BC) is the most common malignancy affecting females worldwide. Various risk factors play a role in the developing of BC. Infectious agents like viruses have been proposed for this cancer and Epstein-Barr virus (EBV) is a widely researched candidate virus. This study detects the presence of EBV-DNA in breast cancer patients. METHODS: The study was conducted on 59 formalin-fixed paraffin-embedded (FFPE) tissue blocks samples of women with breast carcinoma and 11 non-neoplastic breast controls. The DNA was extracted for all the samples. Then detection of EBNA1 EBV was done by polymerase chain reaction (PCR). RESULTS: EBV was detected in 6.7% (4/59) of patients while all breast control samples were negative. All patients with positive EBV-DNA were high tumor grades (II, and III). Also, they had a low level of educations. CONCLUSIONS: According to our findings, it can be suggested that EBV may have a potential role in breast cancer development. However, this study provides substantial but not conclusive evidence for the involvement of viruses in BC disease development. Therefore, future investigations are needed to elucidate the exact role of EBV in breast cancer.
.


Assuntos
Neoplasias da Mama/epidemiologia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Lobular/epidemiologia , Infecções por Vírus Epstein-Barr/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/virologia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/virologia , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/virologia , DNA Viral/análise , DNA Viral/genética , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Irã (Geográfico)/epidemiologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Prevalência , Prognóstico
6.
Urol J ; 17(2): 156-163, 2020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-30882175

RESUMO

PURPOSE: Autophagy plays a critical role in PCa development. DAXX has a potent pro-survival effect by enhancing cell growth in PCa via suppression of autophagy. Here, we depicted a network governed by DAXX and SPOP by which the autophagy pathway is suppressed through the ubiquitination and modulation of key cellular signaling pathways mediators including LAMP2 and RARRES1. MATERIALS AND METHODS: Through network-based bioinformatics approaches, the expression levels of DAXX, RARRES1, LAMP2, and SPOP genes was assessed in 50 PCa tissues and 50 normal adjacent from the same sample as well as 50 benign prostatic hyperplasia (BPH) tissues by quantitative RT-PCR. The normal adjacent tissues were taken from regions more than 5mm away from the bulk of those tumor tissues with clearly distinct margins. RNA extraction, cDNA synthesis and Real-time Quantitative RT-PCR were done for assessment of gene expression. To evaluate the primary gene network centered on autophagy pathway, according to the Query-dependent weighting algorithm, these two networks were integrated with Cytoscape 3.4 software. RESULTS: We found that in PCa tissues the DAXX expression level was significantly increased (P < 0.001) and the expressions of SPOP, RARRES1, and LAMP2 were significantly down-regulated, when compared to both control groups including normal adjacent and BPH tissues. Moreover, significant correlations were observed between expression levels of all four genes. Additionally, ROC curve analysis revealed that LAMP2 had the most sensitivity and specificity. CONCLUSION: These findings suggest that the contribution of SPOP, DAXX, RARRES1, and LAMP2 together could be a putative regulatory element acting as a prognostic signature and therapeutic target in PCa.


Assuntos
Autofagia/fisiologia , Proteínas Correpressoras/genética , Proteína 2 de Membrana Associada ao Lisossomo/genética , Proteínas de Membrana/genética , Chaperonas Moleculares/genética , Proteínas Nucleares/genética , Hiperplasia Prostática , Neoplasias da Próstata , Proteínas Repressoras/genética , Biologia Computacional/métodos , Correlação de Dados , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Prognóstico , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo
7.
J Relig Health ; 59(1): 19-28, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30644042

RESUMO

Given the prevalence of Heart Failure (HF), the current study was conducted, aiming to determine the relationship between praying and self-care in the patients with HF in Iran in 2018. The type of the study is descriptive-analytical, which has been conducted in patient group of more than 65, suffering HF. The population of study has consisted of HF patients, referring to Shahid Mostafa Khomeini Hospital of Ilam province. Therefore, the patients, referring to this hospital for medical treatments, were included in this study. The study data were analyzed using software SPSS16. The findings showed there was a significant relationship between the severity of prayer and the demographic variables, such as gender (p < 0.004), education (p < 0.03), and duration of the disease (p < 0.001). The findings also showed that there was a relationship between self-care and gender (p < 0.001), education (p < 0.004), and duration of disease (p < 0.001). Also, the findings showed that there is a relationship between self-care and prayer (r = 727), so that increasing the amount of prayer will increase self-care. The mean (SD) of total prayer is 167.33 (10.49) and total self-care is 35.86 (10.60). With the increase in the rate of praying, their self-care increased. Based upon this, religious interventions are recommended to be held for this group of patients, focusing on praying.


Assuntos
Insuficiência Cardíaca/terapia , Autocuidado , Espiritualidade , Idoso , Estudos Transversais , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/psicologia , Humanos , Irã (Geográfico)/epidemiologia , Religião , Religião e Medicina , Autocuidado/psicologia
8.
J Family Med Prim Care ; 8(2): 717-721, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30984701

RESUMO

INTRODUCTION: Skin cancer, the melanoma type of which causes high mortality, is the most common malignancy in Iran and all over the world. UV is the most important cause of the incidence of this disease. This study evaluates the frequency of different types of cancer and their trajectory in Ilam province from 2012 to 2011. MATERIALS AND METHODS: This analytical-descriptive study covered and evaluated all skin cancer patients who were registered in Ilam Province Cancer Registry during 20002 to 2011. Required information of each individual patient, such as age, sex, residence, pathological type of skin cancer, the location of the incidence of the disorder, and the year, was collected and studied. FINDINGS: Out of total 347 cases, 240 cases (69.2%) were diagnosed with basal cell carcinoma (BCC), 63 cases (18.2%) with squamous cell carcinoma (SCC), 16 cases (4.6%) with malignant melanoma (MM), 8 cases (2.3%) with metastatic cancer, and 20 cases (37.7%) with other skin cancers. Mean age of patients was 62/42 ± 16/11 years, and the majority of them (37.7%) were men and lived in the city. Face was the most common place of the incidence of this disease (81.6%) and hand was the least common one (1.7%). The rate of incidence of cancer has experienced considerable growth in men and a slight decrease in the case of women between 2002 and 2011 in Ilam. CONCLUSION: According to the results of this study, the rate of skin cancer has increased among men during the studied period; thus, necessary measures are required to prevent and reduce the incidence of this disease, especially in people who are exposed to the sun's ultraviolet rays because of their jobs.

9.
J Family Med Prim Care ; 7(6): 1314-1318, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30613518

RESUMO

BACKGROUND: Diabetes mellitus is the most common metabolic disease around the world. The present study aims at studying hemoglobin A1C (HbA1C) and vitamin D serum levels in diabetic patients. MATERIALS AND METHODS: A descriptive study was conducted on 102 diabetic patients presenting to the diabetic clinic of a tertiary care hospital in West of Iran in 2016 (Shahid Mostafa Khomeini Hospital of Ilam city). The data collected were inserted into the SPSS-20 software, and it was then analyzed by using the relevant statistical tests. For describing the quantitative variables, mean and standard deviation were used. Moreover, for describing the qualitative variables, number and percentage were applied. The mean serum levels of HbA1C and vitamin D were compared for different variables using the Chi-square and ANOVA. RESULTS: There is a positive and statistically significant relationship between the HbA1C and fasting blood sugar (FBS). Moreover, there is a statistically significant relationship between the serum level of vitamin D with smoking and body mass index (BMI). There is also an inverse linear relationship between vitamin D with HbA1C, FBS, BMI, and disease duration. The relationship between HbA1C with FBS and disease duration is a linear direct one. Their relationship between HbA1C and BMI is an inverse linear one, yet not significant. CONCLUSION: Given the role of this vitamin in secretion and the effect of insulin, it seems useful to monitor the serum level of vitamin D in a diabetic patient and prescribe its supplements if necessary.

10.
Iran J Pathol ; 13(2): 212-219, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30697292

RESUMO

BACKGROUND & OBJECTIVE: Increase in intraand extracellular glucose levels can cause oxidative stress, and theprolonged imbalance between prooxidants and antioxidantscan lead to cell damage and the associated complications in patients with diabetes. Vitamin D acts as a strong antioxidant in the body and several studies emphasized on its important role to preventoxidative stress in prediabeticand diabetic subjects. The current study aimed at determining and comparingthe total antioxidant capacity (TAC) in individuals with hemoglobin A1c(HbA1c) below and above 6.5%, and its correlation with vitamin D levels. METHODS: The current cross sectional study was conducted on a total of 107patients with diabetes (HbA1c >6.5%) and 107 non-diabetic subjects (HbA1c<6.5%)referred toRassoolAkram Hospital, Tehran, Iranfrom2015 to 2016, as the sample population. The two groups were compared regarding their TAC and vitamin D serum levels and the association between vitamin D concentration and TAC was evaluated. RESULTS: Age and body mass index (BMI)were significantly higher in patients with diabetes,comparedwiththe serum levels of vitamin D and TAC (P<0.001 for both). Both TAC and vitamin D levels were significantly lower in the group with diabetesand a weak significant correlation was observedbetween the two factors (r=0.2, P=0.003). In multivariate regression model, the duration of diabetes was also significantly associated with TAC level (beta coefficient=-0.82, P <0.001). CONCLUSION: The low serum levels of TAC and vitamin D in patients with diabetescould be indicative of oxidative stress in the presence of high blood glucose levels. Supplementation of vitamin D in patients with diabetes might be effective to control thenegative impacts of the disease and decreasecells' exposure to oxidative environment in prediabetes.

11.
Iran J Pathol ; 12(4): 392-396, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29563936

RESUMO

BACKGROUND & OBJECTIVE: Beta-lactam antibiotics resistance specifically Imipenem and Meropenem, the last choices of treatment, causes fatal events in patients with P.aeruginosa infection. The aim of this study was to detect the VIM and IMP of metallo-beta-lactamase genes in 103 isolates of P. aeruginosa in two Iranian hospitals. METHODS: In this study, we evaluated the susceptibility of P. aeruginosa to a range of ß-lactam antibiotics using disk diffusion method as a standard biochemical test. Combined disk test of Imipenem (IMP) and Imipenem plus Ethylenediaminetetraacetic acid (EDTA) was performed as a phenotypic method to find metallo-beta-lactamase producing isolates.Using conventional PCR method; we evaluated VIM and IMP of metallo-beta-lactamase (MBL) genes in 103 isolates of P.aeruginosa. RESULTS: Twenty six (25.2%) out of 103 isolates were resistant to Imipenem and 26 (25.2%) to Meropenem. Among 26 Imipenem and Meropenem-resistant strains (25.2%), 19 cases (73.0%) were MBL producing. Using PCR method, we detected the blaVIM and blaIMP genes in 6 (5.8%) and 2(1.9%) of 19 MBL producing isolates, respectively. CONCLUSIONS: Evaluation of these carbepenemases genes improve epidemiologic researches and also, can be used as a diagnostic tool for discriminating between antibiotics resistant and sensitive strains of P.aeruginosa as well as follow-up the patients after treatment.

12.
J Family Med Prim Care ; 6(4): 770-774, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29564261

RESUMO

INTRODUCTION: Recently, hepatoma-derived growth factor (HDGF) has been considered as a significantly important factor in determining the prognosis and estimating the probability of tumor cell invasions, recurrence, and lymph node metastasis in different cancers, including breast malignancies. MATERIALS AND METHODS: Immunohistochemistry (IHC) study for HDGF was performed on paraffin-embedded blocks of patients with breast carcinoma in Modarres hospital, Tehran, Iran, since 1387-1390 (74 cases); three separate pathologists read the slides after complete IHC staining. Thereafter, necessary information was recorded from patient files, and eventually, findings were analyzed by SPSS program. RESULTS: Expression of nuclear HDGF has significant statistical correlation with tumor grade according to Nottingham grading scheme; this correlation is also seen with nuclear pleomorphism of tumor cells and mitotic count. No correlation between age and tumor size with expression of HDGF is found. Lymph node metastasis is in inverse ratio to nuclear HDGF staining. CONCLUSION: Nuclear expression of HDGF in tumor cells is increased concordantly to tumor grade, which implies us to the role of this marker in determining the prognosis and choosing the most suitable treatment plan.

13.
Turk J Gastroenterol ; 25(3): 253-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25141312

RESUMO

BACKGROUND/AIMS: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein with vital function during human embryogenesis in terms of cellular growth and migration. Although it has minimum and undetectable expression in human adult tissues, it is highly expressed in various types of cancer. Few studies have recommend application of IMP3 expression to diagnose challenging cases of esophageal adenocarcinoma. This survey was aimed to evaluate the benefit of IMP3 expression detection in the diagnosis of esophageal adenocarcinoma and high-grade dysplasia by using immunohistochemistry (IHC). MATERIALS AND METHODS: An immunohistochemistry study of IMP3 oncofetal protein was performed on paraffin-embedded blocks of 76 cases, including Barrett's esophagus, esophageal squamous epithelium, Barrett's esophagus with low-grade dysplasia, Barrett's esophagus with high-grade dysplasia, moderately differentiated esophageal adenocarcinoma, and poorly differentiated esophageal adenocarcinoma. Two pathologists reevaluated the diagnosis and evaluated the positivity and intensity of the IHC staining as well. RESULTS: Insulin-like growth factor II mRNA-binding protein 3 expression was intensely positive in all cases of esophageal adenocarcinoma and Barrett's esophagus with HGD. Only mild positivity in 30% of Barrett's esophagus with LGD was seen. However, Barrett's esophagus and esophageal squamous epithelium had, in fact, no IMP3 expression. CONCLUSION: The percentage and intensity of IP3 IHC staining showed a significant difference between high-grade dysplasia and adenocarcinoma versus Barrett's esophagus with low-grade dysplasia, Barrett's esophagus, and esophageal squamous epithelium. Therefore, IMP3 oncofetal protein could be a very useful marker for the diagnosis of high-grade dysplasia and adenocarcinoma. However, to test the validation, a larger number samples is required.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/diagnóstico , Proteínas de Ligação a RNA/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Esôfago de Barrett/metabolismo , Esôfago de Barrett/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Humanos , Imuno-Histoquímica , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia
14.
J Obstet Gynaecol Res ; 39(1): 446-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22845423

RESUMO

Extramedullary spread of multiple myeloma is extremely rare. This paper reports a case of bilateral ovarian involvement in plasma cell myeloma. The patient was a 48-year-old Persian woman who experienced constitutional symptoms, bone pain and flashing for one year. Her condition showed multiple myeloma with lytic lesions of the skull, plasma cell infiltration in bone marrow and positive light chain lambda type in serum. Workup showed huge bilateral ovarian masses, and ovarian metastasis from plasma cell myeloma was confirmed after pathologic assessment. Multiple myeloma spread to ovary is rare and according to our knowledge, this is the fourth reported case of bilateral ovarian involvement in extramedullary multiple myeloma.


Assuntos
Mieloma Múltiplo/patologia , Neoplasias Ovarianas/patologia , Feminino , Humanos , Pessoa de Meia-Idade
15.
EXCLI J ; 11: 163-75, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-27385956

RESUMO

This study investigated the effects of acute and chronic psychological stress on glucose-stimulated insulin secretion from isolated pancreatic islets. Male Wistar rats were divided into two control and stressed groups; each further was allocated into fed and fasted groups. Stress was induced by communication box for one (acute), fifteen and thirty (chronic) days. After islet isolation, their number, size and insulin output were assessed. Plasma corticosterone level was determined. In fasted animals, acute stress increased basal and post stress plasma corticosterone level, while 30 days stress decreased it compared to day 1. In fed rats, acute stress increased only post stress plasma corticosterone concentration, however, after 15 days stress, it was decreased compared to day 1. Acute stress did not change insulin output; however, the insulin output was higher in the fed acutely stressed rats at 8.3 and 16.7 mM glucose than fasted ones. Chronic stress increased insulin output on day 15 in the fasted animals but decreased it on day 30 in the fed animals at 8.3 and 16.7 mM glucose. In the fasted control rats insulin output was lower than fed ones. In the chronic stressed rats insulin output at 8.3 and 16.7 mM glucose was higher in the fasted than fed rats. The number of islets increased in the fasted rats following 15 days stress. This study indicated that the response of the isolated islets from acute and chronically stressed rats are different and depends on the feeding status.

16.
J Mol Neurosci ; 41(1): 156-64, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19936637

RESUMO

Maternal morphine consumption has been shown to result in physical and neurobehavioral defects in fetus and offspring, but the underlying molecular mechanisms of these defects remain unclear. Regarding the critical role of apoptosis in normal development of central nervous system, the present study was designed to investigate the effect of intrauterine morphine exposure on programmed cell death of neuroblasts during the early development of neural system. Pregnant Wistar rats received morphine sulfate through drinking water at the concentration of 0.01 mg/ml (20 ml water per day for each rat) from the first day of gestation to the time of sampling. Control groups received tap water. Control and morphine-treated pregnant rats, each in five separated groups, were killed on gestational days 9.5 to 13.5, and the embryos were taken out, fixed, and embedded in paraffin. Immunohistochemical assay was used to reveal the protein expression of Bax, Bcl2, and the activation of caspase 3. The results showed a significant increase in Bax immunoreactivity in all of the mentioned embryonic days (E9.5 to E13.5) and a significant decrease in Bcl-2 immunoreactivity at days E10.5 and E12.5 in morphine-treated groups compared with control. Data analysis revealed that Bax/Bcl2 ratio was increased in all of the morphine-exposed groups. Consistent with these results, immunostaining of cleaved caspase 3 showed a significant increase at days E11.5 to E13.5. These findings suggest that morphine exposure during the first embryonic days may enhance the susceptibility of neuroblasts to apoptosis by upregulating the ratio of Bax to Bcl-2 protein expression and increasing downstream caspase-3 activity. The increased probability of neuroblast apoptosis may be the cause of morphine-induced defects in the central nervous system development and its structural and neurobehavioral consequences.


Assuntos
Caspase 3/metabolismo , Sistema Nervoso Central , Embrião de Mamíferos , Morfina/farmacologia , Efeitos Tardios da Exposição Pré-Natal , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Administração Oral , Animais , Caspase 3/genética , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/embriologia , Embrião de Mamíferos/anatomia & histologia , Embrião de Mamíferos/efeitos dos fármacos , Embrião de Mamíferos/fisiologia , Feminino , Idade Gestacional , Masculino , Exposição Materna , Morfina/administração & dosagem , Gravidez , Distribuição Aleatória , Ratos , Ratos Wistar
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