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1.
Cureus ; 16(4): e58055, 2024 Apr.
Article En | MEDLINE | ID: mdl-38752050

BACKGROUND: Cyclical mastalgia, which is characterized by cyclic breast pain associated with the menstrual cycle, is a common condition among premenopausal women. Despite their prevalence, effective treatment options remain limited. Evening primrose oil (EPO) and vitamin E have been proposed as potential therapies for cyclical mastalgia; however, their efficacy remains uncertain, particularly when used in combination. OBJECTIVE: This study aimed to evaluate the efficacy of EPO, vitamin E, and their combination in alleviating breast pain associated with cyclical mastalgia through a randomized controlled trial. METHODS: Premenopausal women (n=126) with cyclical mastalgia were recruited from gynecology clinics and randomized to receive EPO (1000 mg twice daily), vitamin E (400 mg once daily), their combination, or a placebo for six months. Randomization was performed using computer-generated random numbers. Participants were assessed at baseline and monthly intervals for six months. The primary outcome was the change in breast pain severity measured using a validated pain questionnaire such as the short-form McGill Pain Questionnaire. The secondary outcomes included changes in breast pain characteristics, adverse effects, and treatment adherence. RESULTS: A total of 126 participants participated in this study. The combination of EPO and vitamin E demonstrated superior efficacy in reducing breast pain severity compared with individual treatments and placebo (p < 0.001). Participants in the combination group experienced a mean reduction in breast pain severity of 4.5 points on the pain scale, whereas those in the EPO and vitamin E groups experienced reductions of 2.5 and 3.0 points, respectively. Both EPO and vitamin E alone also showed significant improvements compared with placebo (p < 0.05), with mean reductions in breast pain severity of 2.0 and 2.5 points, respectively. Adverse effects were minimal and comparable across the treatment groups. CONCLUSION: Combination therapy with EPO and vitamin E appears to be an effective treatment option for cyclical mastalgia, offering superior pain relief compared with individual treatments and placebo.

2.
Cureus ; 16(1): e51734, 2024 Jan.
Article En | MEDLINE | ID: mdl-38318602

Actinomycosis is an uncommon bacterial infection, caused by the Actinomyces species, and it most commonly presents as cervicofacial actinomycosis. The most common risk factors for actinomycosis are poor dental hygiene, oral surgery, maxillofacial trauma, local tissue inflammation, and diabetes. We discuss a case of a male patient in his 50s with 30 years of poor dental hygiene, complicated by tobacco use, who presented with septic shock and was found to have cervicofacial actinomycosis and bacteremia. The treatment of severe actinomycosis often involves prolonged penicillin-based antibiotic therapy. This is the first case in the literature to describe the successful treatment of cervicofacial actinomycosis and bacteremia with intravenous cefepime (later narrowed to ceftriaxone) and oral metronidazole.

3.
Crit Pathw Cardiol ; 23(1): 1-11, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-37930224

BACKGROUND: Several studies have been conducted over the years to find an effective and safe therapeutic agent to treat hypercholesterolemia. Inclisiran is a novel drug being studied for its efficacy and safety in reducing low-density lipoprotein cholesterol levels in patients to reduce the risk of cardiovascular diseases. No previous study was done to review the trials for the serious adverse events of this drug. The primary objective of this research is to investigate the incidence of serious adverse events of this drug. DESIGN: A systematic review and meta-analysis of clinical trials is performed. METHODS: A systematic search of PubMed, Embase, and ClinicalTrials.gov, from their inception till July 3, 2023, was performed for ORION trials, studying the efficacy and safety of inclisiran. The random-effects model was used in the meta-analysis to provide a pooled proportion of serious adverse events. The risk of bias in each study was assessed by the Cochrane Risk of Bias Tool. RESULTS: From 319 studies searched from the databases, only 8 relevant articles remained after a detailed evaluation. These studies, having a total of 4981 patients, were involved in the analysis, with a pooled estimate showing a nonsignificant incidence of serious adverse events. Each adverse event was studied individually, and product issues and endocrine disorders had the highest odds ratio among them. All included studies were classified as moderate quality. CONCLUSION: Following systematic review and meta-analysis, we found no significant differences in any serious adverse events following the administration of inclisiran. However, larger ongoing trials will provide additional data to evaluate the safety profile of this agent.


Cardiovascular Diseases , Hypercholesterolemia , Humans , Hypercholesterolemia/drug therapy , Hypercholesterolemia/epidemiology , RNA, Small Interfering , Cardiovascular Diseases/epidemiology
5.
Cureus ; 15(11): e49325, 2023 Nov.
Article En | MEDLINE | ID: mdl-38143686

Background Medication adherence plays a vital role in managing blood sugar levels and preventing complications in individuals with diabetes. Patient adherence to antidiabetic medications and the factors associated with medication adherence were assessed. Objectives To assess the medication adherence among patients suffering from type 2 diabetes mellitus. To determine the various factors influencing medication adherence. Methods This cross-sectional study was conducted on patients with type 2 diabetes who were visiting the Internal Medicine Department of Thumbay University Hospital in the United Arab Emirates. A questionnaire was used to gather information about the medication adherence of a group of chosen consecutive patients. IBM SPSS Statistics for Windows, Version 27 (Released 2020; IBM Corp., Armonk, New York) was used for data analysis. A two-sided P-value <0.05 was regarded as significant when using the chi-square test to investigate the relationships between categorical variables. Results A total of 204 patients participated in the study: 112 (54.90%) males and 92 (45.09%) females. The mean age of the patients was 49 years. The adherence rates among males and females were 91% and 90%, respectively. Some of the common reasons for non-adherence to antidiabetic medications in our study included forgetfulness, unpleasant side effects, the use of multiple drugs, and long treatment duration. Conclusion Our study highlighted important factors associated with patients' non-adherence to their antidiabetic medications. Future research on methods to increase adherence rates should be taken into consideration.

6.
Cureus ; 15(12): e51395, 2023 Dec.
Article En | MEDLINE | ID: mdl-38292957

The increasing worldwide prevalence of cardiovascular diseases (CVDs) highlights the need to understand the complex relationships between lipid abnormalities and elevated cardiovascular risk. This review thoroughly investigates the complex terrain of lipid abnormalities, highlighting their crucial significance in developing CVDs. Dyslipidemia, which is closely connected to atherosclerosis, is a significant risk factor for CVDs, including coronary artery disease, myocardial infarction, and stroke. This review thoroughly examines the intricate relationship between lipoproteins, cholesterol metabolism, and the inflammatory cascade, providing a detailed comprehension of the mechanisms that contribute to atherogenic processes. An extensive analysis of the occurrence and distribution of lipid diseases worldwide indicates a concerning high frequency, which calls for a reassessment of public health approaches. Dyslipidemia is caused by a combination of genetic predispositions, lifestyle factors, and metabolic abnormalities, as supported by significant data. Moreover, investigating different types of lipoproteins and their specific functions in the development of atherosclerosis provides insight into the complex causes of CVDs. In addition to conventional lipid profiles, newly identified biomarkers and advanced imaging techniques are being carefully examined for their ability to improve risk classification and treatment strategies' effectiveness. From a critical perspective, the review thoroughly examines the current state of lipid-modifying medicines, specifically statins, fibrates, and new therapeutic approaches. The text discusses the emerging concept of precision medicine, which involves tailoring treatment approaches to individuals based on their genetic and molecular characteristics. This approach has the potential to improve treatment outcomes. In addition, this study critically assesses the effects of lifestyle changes and nutritional interventions on lipid homeostasis, offering a comprehensive view of preventive strategies. This review consolidates current viewpoints on lipid diseases and their complex correlation with cardiovascular risk. This review contributes to the ongoing cardiovascular disease prevention and management dialogue by clarifying the molecular mechanisms, exploring new therapeutic options, and considering broader societal implications.

7.
Ann Med Surg (Lond) ; 84: 104881, 2022 Dec.
Article En | MEDLINE | ID: mdl-36582878

Introduction: The new clinical and radiological entity of the myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is known as the FLAMES syndrome. It will add to the literature and enhance the understanding of this disease. Case presentation: Our case presented a 25-year-old male patient with no known comorbid presented with a generalized sudden headache of moderate intensity for 10 days who came to our hospital. A right-sided upper motor neuron facial palsy was found on the examination. The diagnosis was further confirmed utilizing the MRI scan and the presence of MOG-IgG antibodies. The patient was started on intravenous methylprednisolone which lead to improvement of his symptoms. In the follow-up contrast-enhancing MRI of the brain, the findings suggested near resolution as compared to the initial MRI. Discussion: The FLAMES have been categorized as a subtype of the MOGAD. It is commonly found in males as compared to females and the mean age in which it commonly affects is 29 years with the common age group of 11-46 years. The clinical symptoms and physical signs along with the findings of unilateral cortical FLAMES on MRI suggest the distinctive findings of the FLAMES syndrome. Patients commonly present with symptoms like fever, headache, and cortical symptoms like aphasia. Conclusion: There is a dire need of improving the understanding of this clinic-radiographic syndrome which makes it critically important to ensure the timely diagnosis and prompt consideration of the required medications.

8.
Ann Med Surg (Lond) ; 84: 104941, 2022 Dec.
Article En | MEDLINE | ID: mdl-36536713

Introduction: Ever since the world came into being different factors and circumstances contributed in a deteriorating fashion to mental health, and depression is the commonest of mental disturbance and incapability. We aimed to identify the risk factors for perinatal outcomes of maternal depression. Methods: Data extracted was from two important cities of Pakistan i.e Islamabad and Karachi, and the numbers are 500,000 and 800,000 respectively. The timeline of the information was from 2010 to 2020 to signify a decade. Women with active pregnancy and depression were included. Chisquare analysis was run to predict which factors had a significant impact on depression. Odds ratio was separately run on the significant factors. Regression analysis was done to describe the relationships between independent variables and each other. Results: The most preferred procedure of delivery was cesarean section in Islamabad and more than 500,000 in Karachi. Low-income women in Karachi had a mean depression score of 12.4 while men with the same socioeconomic class had a score of 23.4. 15.7 females in Islamabad reported medications taken during pregnancy & 34.9 females from major depression group. Mean of 87.9 individuals from Islamabad reported living with husband from no serious depression during pregnancy. In Population of Islamabad, Previous pregnancies and birth weight in comparison with depression is significant having p value 0.00. Maternal age, fetal sex & gestational age are also significant indicators of whether a woman is depressed or not. Apgar scores & violence in relation to depression are significant in Karachi Population having p values of 0.049 and 0.028. Conclusion: Female health and neonatal care should be a serious concern, but unfortunately in spite of progression in the field of medicine the low income or third world countries don't have sufficient awareness and due to that Pakistan still reports high maternal and neonatal mortality rates.

9.
Article En | MEDLINE | ID: mdl-36262504

Background and objective: Collagen protein, which is abundant in the cornea and has a triple helix form, may be found in almost every tissue matrix in the body. Natural cross connections between monomers provide the robustness of the helical protein structure. Wollensak and his colleagues developed the Dresden Protocol, a keratoconus treatment based on Corneal Cross-Linkage. We aimed to analyse and present the findings in individuals with progressive keratoconus using topographic and refractive results after corneal collagen crosslinking treatment (CXL) (KC) after 3 months. Methods: The study comprises a total of 100 patients who were diagnosed with progressive KC and who underwent CXL between 2021 and 2022 at KRL Hospital Islamabad, Pakistan. All eyes in this study had a preoperative topography within 1 month before CXL treatment and the follow-ups were conducted at 3 months interval. Results: In our investigation, 100 patients were added. The average age was 24.74 years. 77% of the patients were between the ages of 12 and 25 years, while 23% were between the ages of 26 and 50 years. In our survey, males made up 84% of the population, while females made up only 16%. The right eye was afflicted in 60% of cases, whereas the left eye was impacted in 40% of the population. Grade 2 Keratoconus affected 42% of patients, whereas Grade 1 Keratoconus affected 18%. Our findings were skewed toward men and the 12-25 age group, however in our recent study, we discovered considerable KC stability 3 months after CXL. Conclusion: Keratometric readings and visual acuity were stabilised or improved with CXL treatment. Keratoconus stability can be reached 3 months following the treatment, according to our findings.

10.
Cureus ; 14(7): e27320, 2022 Jul.
Article En | MEDLINE | ID: mdl-36044339

Background Surgical site infection (SSI) is the most commonly occurring infection in postoperative patients. This study is conducted to evaluate the prevalence of SSI in patients following gastrointestinal tract surgery and identify the risk factors. Method A cross-sectional study was conducted at the Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan, between December 2021 and May 2022. A total of 132 patients participated in the study who were at least 18 years older and had undergone the gastrointestinal surgical procedure. Patients who refused to give consent, died after the procedure, and were diagnosed with SSI after they were discharged were excluded from the study. We performed a chi-squared test. Result A total of 132 patients were included in the study, of which 63 (47.7%) were males, while 69 (52.3%) were females. SSI was more commonly found among the age group of 41-70 years with 29 (38.7%) patients. Presurgical features including hemoglobin of >11 mg/dL, albumin of >3.5 g/dL, blood glucose of <80 mg/dL, and emergency surgery were found to be associated with the SSI having a significant p-value. Similarly, the surgical and postsurgical features significantly associated with the SSI having a significant p-value were the presence of surgical trauma, wound irrigation with normal saline, malignancy, bowel preparation, longer duration of the surgery, intraoperative hypotension, operative site, drain insertion, and the absence of a second antibiotic. Conclusion The early identification and management of the demographical, presurgical, surgical, and postsurgical risk factors can help reduce the incidence of SSIs. Bowel preparation should be encouraged, and unnecessary delays during the surgical process leading to increased procedure time should be avoided. Extra precaution needs to be provided for the patients highly susceptible to SSIs.

11.
Biol Open ; 10(8)2021 08 15.
Article En | MEDLINE | ID: mdl-34342345

Conservation of genetic toolkits in disparate phyla may help reveal commonalities in organ designs transcending their extreme anatomical disparities. A male accessory sexual organ in mammals, the prostate, for instance, is anatomically disparate from its analogous, phylogenetically distant counterpart - the male accessory gland (MAG) - in insects like Drosophila. It has not been ascertained if the anatomically disparate Drosophila MAG shares developmental parallels with those of the mammalian prostate. Here we show that the development of Drosophila mesoderm-derived MAG entails recruitment of similar genetic toolkits of tubular organs like that seen in endoderm-derived mammalian prostate. For instance, like mammalian prostate, Drosophila MAG morphogenesis is marked by recruitment of fibroblast growth factor receptor (FGFR) - a signalling pathway often seen recruited for tubulogenesis - starting early during its adepithelial genesis. A specialisation of the individual domains of the developing MAG tube, on the other hand, is marked by the expression of a posterior Hox gene transcription factor, Abd-B, while Hh-Dpp signalling marks its growth. Drosophila MAG, therefore, reveals the developmental design of a unitary bud-derived tube that appears to have been co-opted for the development of male accessory sexual organs across distant phylogeny and embryonic lineages. This article has an associated First Person interview with the first author of the paper.


Drosophila Proteins/genetics , Drosophila/embryology , Drosophila/genetics , Gene Expression Regulation, Developmental , Prostate/metabolism , Animals , Biomarkers , Fluorescent Antibody Technique , Male , Morphogenesis/genetics , Signal Transduction
12.
J Obstet Gynaecol India ; 69(Suppl 2): 171-176, 2019 Oct.
Article En | MEDLINE | ID: mdl-31686752

INTRODUCTION: Abnormal uterine bleeding may be defined as bleeding pattern that differs in frequency, duration and amount from a pattern observed during a normal menstrual cycle or after menopause. AIM AND OBJECTIVE: The aim of this study was (1) to identify the different benign, premalignant and malignant conditions as the cause of abnormal uterine bleeding in perimenopausal and postmenopausal women and (2) to find out the different histopathological patterns of endometrium and cervix in these women. MATERIALS AND METHODS: This is a prospective study done in gynaecological oncology in 100 cases attending the OPD. Pap smear and cervical biopsy were done following clinical examination and then, the patients were sent for abdominal and pelvic ultrasound examination. Endometrial biopsy was done if endometrial thickness was increased with respect to age. The cut-off value of endometrial thickness in perimenopausal women was 11 mm, and for postmenopausal women, it was 4 mm, respectively. All the tissue specimens were sent for histopathological examination. RESULT: A total of 100 women were evaluated in which 50% were in the perimenopausal age group and 50% in the menopausal age group. Cervical pathology was present in 47% of cases, organic cause of uterine body like fibroid and adenomyosis was present in 26% of women, and thickened endometrium was seen in 24% of cases and endometrial polyp in 3 cases only. In this study, the incidence of benign cases was 49%, premalignant 9% and malignant condition 42%, respectively. Out of 42 malignant cases, 37 (88.09%) were cervical cancer, 3 (7.14%) endometrial carcinoma, 1 (2.38%) vulval cancer and 1 sarcoma of uterus. With regard to histology of endometrium, 34.48% had simple hyperplasia without atypia, 20.68% hyperplasia with atypia and secretory endometrium, and 10.34% endometrial carcinoma. Histologically, 94.59% of cervical cancer was squamous cell carcinoma and 5.40% was adenocarcinoma. CONCLUSION: Evaluation of cases of perimenopausal and postmenopausal bleeding differentiated premalignant and malignant lesions of the uterine body, endometrium and cervix. As our centre is a Regional Cancer Centre of Bihar, incidence of malignant lesions is higher in our centre.

13.
J Obstet Gynaecol India ; 69(Suppl 2): 177-181, 2019 Oct.
Article En | MEDLINE | ID: mdl-31686753

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) has tyrosine kinase activity and is a member of the epidermal growth factor receptor family. This initiates a variety of signal for pathways which leads to cell proliferation and tumourigenesis. In approximately 15-30% of breast cancers and 10-30% of gastric/gastroesophageal cancers, amplification or overexpression of HER2 occurs, and it serves as a prognostic and predictive biomarker. HER-2/neu is one of the most frequently studied molecular biological parameters in epithelial ovarian cancer (EOC), but its prognostic impact has not been fully assessed. The objective of the current study was firstly to analyse the presence of HER-2 overexpression in EOC patients and secondly to evaluate association between human epidermal growth factor receptor 2 (HER-2/neu) expression and progression-free survival in patients with EOC. METHOD: In this prospective study of 2 years in our department, 186 gynaecological cancers were operated out of which 98 cases were operated for epithelial ovarian cancer and rest for cervical cancer, endometrial cancer, and other subtypes of ovarian cancer. In this study, HER2 gene status was evaluated in EOC by immunohistochemistry analysis, and overall survival of these patients was evaluated. RESULTS: HER-2 overexpression was found in 22 of the 98 investigated cases (22.45%), in which 14 OC (14.29%) were weakly positive and 8 OC (8.16%) were moderately to intensely positive. In the study, increased HER2 expression was associated with decreased progression-free survival (PFS) and hence poor prognosis (P 0.054). CONCLUSIONS: The introduction of HER2-directed therapies has dramatically influenced the outcome of patients with HER2 positive breast and gastric/gastroesophageal cancers. The present study findings provided that HER-2/neu expression in patients with OC has an adverse impact on the PFS. Therefore, our results show that the decision algorithm usually used in breast cancer by HER2 may be appropriate in ovarian cancer.

15.
Indian J Cancer ; 55(1): 80-83, 2018.
Article En | MEDLINE | ID: mdl-30147099

BACKGROUND: Cervical cancer is the fourth leading cause of cancer in women in the world and it is the second most common cancer in women 15-44 years of age. Strict implementation of screening programs has led to a large decrease in cervical cancer incidence and mortality in the developed countries. In contrast, cervical cancer remains largely uncontrolled in high-risk developing countries because of ineffective or no screening programs. Conventional Pap smear method has been the mainstay of most of the screening programs for many decades. However, this technique is not without limitations, and the sensitivity and specificity of cervical cytology are relatively low. To overcome the limitations of conventional Pap smear (CPS), liquid-based cytology (LBC) was introduced in 1990s as a better tool for processing cervical samples. OBJECTIVES: This study was undertaken to compare CPS with liquid-based methods, to assess the effectiveness and feasibility of LBC over CPS in our setting, and also to evaluate the prevalence of human papillomavirus (HPV) in our population. MATERIALS AND METHODS: This study was conducted in Gynecological Oncology Unit of Regional Cancer Center at Indira Gandhi Institute of Medical Sciences, Patna, Bihar. About 310 women were enrolled in this study and the sample was taken for both conventional cytology and LBC. The smears were studied in detail and were interpreted as per the Bethesda system of reporting Pap smears. The results were compared and analyzed statistically. RESULTS: Unsatisfactory smears were more commonly reported by conventional method (7.1%) than with liquid-based method (1.61%), and this difference is statistically significant. There was no difference in the detection of epithelial cell abnormalities using both the methods. HPV DNA for high-risk oncogenic strains (16 and 18) was detected in 6.45% of women in this study. CONCLUSION: LBC has been found to be more superior to conventional smears only with respect to lesser number of unsatisfactory smears, but considering the economic implications of LBC, conventional Pap is more feasible in our setting.


Cytodiagnosis/methods , Mass Screening , Papanicolaou Test/methods , Uterine Cervical Neoplasms/diagnosis , Adolescent , Adult , Female , Humans , India/epidemiology , Tertiary Care Centers , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virology , Young Adult
16.
Indian J Cancer ; 55(1): 70-73, 2018.
Article En | MEDLINE | ID: mdl-30147097

OBJECTIVE: A retrospective analysis of all patients with cancer of the cervix attending regional cancer center of Indira Gandhi Institute of Medical Sciences, Patna, from June 2015 to June 2017. The aim of this study was to know patient demographics, histology, age, stage and status of presentation, compliance with treatment and follow-up. MATERIALS AND METHODS: Five hundred and eighteen consecutively registered patients with cancer of the cervix were included in the study. RESULTS: The prevalence of cervical cancer among gynecological malignancy was 52%. It is the second most common cancer after breast cancer at our center. Patients hailed from the various districts of Bihar (89%), India, and from Nepal (10.61%). The majority (>50%) were aged 40-59 years. Stage information was available for 71.81% of the patients, of which Stage I comprised 12.36%, Stage II, 35.21%; Stage III, 50%; and Stage IV, 2.41%. Squamous cell carcinoma was the most common reported histopathology (~90%). A significant proportion of the women defaulted after registration, or after undergoing investigations (17%). Of the 68% cases planned for treatment, 50% initiated it, but only 38% completed it, About 11% of cases underwent Wertheim's hysterectomy and rest of patients were treated by radiotherapy with or without chemotherapy. CONCLUSION: The incidence of cervical cancer is still unacceptably high at our center. Organized cervical cancer screening needs to be adopted for early diagnosis.


Adenocarcinoma/epidemiology , Carcinoma, Squamous Cell/epidemiology , Neoplasms, Second Primary/epidemiology , Uterine Cervical Neoplasms/epidemiology , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Cervix Uteri/pathology , Child , Female , Humans , Hysterectomy , India/epidemiology , Middle Aged , Neoplasm Staging , Neoplasms, Second Primary/pathology , Neoplasms, Second Primary/surgery , Nepal/epidemiology , Retrospective Studies , Tertiary Care Centers , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgery , Young Adult
17.
Front Immunol ; 6: 345, 2015.
Article En | MEDLINE | ID: mdl-26217339

The T-box transcription factor T-bet is expressed in a number of hematopoietic cell types in mammals and plays an essential role in the lineage determination of Th1 T-helper cells and is considered as an essential feature for both innate and adaptive immune responses in higher vertebrates. In the present study, we have identified and characterized the full-length Atlantic salmon T-bet cDNA (3502 bp). The putative primary structure of the polypeptide deduced from the cDNA sequence contained 612 aa, which possessed a T-box DNA binding domain. Phylogenetic study and gene synteny revealed it is as a homolog to mammalian T-bet. Quantitative PCR analysis of different tissues in healthy fish showed that salmon T-bet gene was highly expressed in spleen, followed by head kidney, and was expressed in intestine, skin, and liver at lower levels. Moreover, the time-dependent expression profile of T-bet, interferon gamma (IFNγ), interleukin-22 (IL-22), and natural killer enhancement factor in mucosal tissues during water-borne infection with live Aeromonas salmonicida, indicated the involvement of T-bet in mucosal immune response in Atlantic salmon.

19.
PLoS One ; 8(2): e55893, 2013.
Article En | MEDLINE | ID: mdl-23409078

Eomesodermin (Eomes), a T-bet homologue expressed in activated CD8+T cells was recently proposed to act as a master regulator of cytotoxic CD8+ T cell effector function and offers an exciting avenue for future exploration. Here, we have identified and characterized the full-length Atlantic salmon Eomes cDNA (2477 bp). Promoter analysis of the salmon Eomes showed the presence of important putative transcription binding sites like SP1, FOXO, Oct-1, SMAD, STAT, IRF, and Ets-1. The basal core region responsible for the promoter activity was located between base -199 and +59. Quantitative PCR analysis revealed that the Atlantic salmon Eomes was ubiquitously expressed in all the tissues studied but strongly expressed in the ovary, spleen, brain, and the head kidney. Moreover, the involvement of Eomes in Atlantic salmon immune response and its relation with the cytolytic activity was demonstrated by investigating the early time dependent expression profile of Eomes and CD8α followed by high interferon gamma (IFN-γ) and granzyme A expression during challenge with live Aeromonas salmonicida and Infectious Pancreatic Necrosis (IPN) virus. Therefore, we further analyzed the regulated expression and function of this transcription factor in spleen lymphocytes. Overexpression of Eomes induced IFN-γ, and granzyme A expression but not perforin expression, whereas small interfering RNA (siRNA) mediated suppression of Eomes expression led to significantly reduced IFN-γ production. Thus, Eomes may be critical in cytolytic gene expression and function in fish similar to mammals. Furthermore, IFN-α, and mitogens induced Eomes expression. Taken together, this is the first study on the promoter activity and regulatory role of Eomes in fish.


Salmo salar/genetics , Salmo salar/immunology , T-Box Domain Proteins/genetics , Amino Acid Sequence , Animals , Base Sequence , CD8-Positive T-Lymphocytes , Cell Line , Cloning, Molecular , Consensus Sequence , DNA, Complementary/chemistry , DNA, Complementary/genetics , Gene Expression Regulation , Granzymes , Humans , Interferon-gamma , Lymphocytes/immunology , Lymphocytes/metabolism , Molecular Sequence Data , Organ Specificity/genetics , Promoter Regions, Genetic , Spleen/immunology , Spleen/metabolism
20.
Fish Shellfish Immunol ; 27(5): 647-59, 2009 Nov.
Article En | MEDLINE | ID: mdl-19716422

IL-17 is a proinflammatory cytokine that plays an important role in the clearance of extracellular bacteria and contributes to the pathology of many autoimmune and allergic conditions. Much work on IL-17 has been done in humans and higher vertebrates while little work has been conducted in lower vertebrates including fish. In this study, we have cloned and characterized the full-length cDNA and genomic sequence of IL-17D from Atlantic salmon. The Atlantic salmon IL-17D (AsIL-17D) cDNA possessed an open reading frame of 621 bp encoding a putative protein of 206 aa with a predicted molecular weight of 23 kDa. The AsIL-17D gene has two exons and one intron showing the same (genome) organisation compared to zebrafish IL-17D. The encoded protein showed 97.6-48.8% identities to other IL-17D homologues, eight conserved cysteine residues were found within this group. Conserved residues believed to be important in receptor binding were also confirmed in salmon IL-17D by homology modelling. Phylogenetic analysis also confirmed the close relationship with other IL-17D homologues. Functional characterization of the 5' flanking region indicated that the region between -1552 and -150 contained sufficient elements for promoter activity. Tissue expression studies by real-time PCR showed a predominant expression of IL-17D transcript in gonads, skin, intestine, thymus of Atlantic salmon. The involvement of IL-17D during proinflammatory responses was demonstrated by investigating the time-dependent expression profile of IL-17D in head kidney and spleen following intraperitoneal injection of live Aeromonas salmonicida, LPS, and beta-glucan. This study provides further evidence for the existence of distinct homologue of IL-17D isoform in fish showing early expression induced by immunostimulants and bacterial infection that supports the fact that IL-17D is regulated by inflammatory processes in fish.


Interleukin-17/chemistry , Salmo salar/immunology , Aeromonas salmonicida/growth & development , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , Expressed Sequence Tags , Interleukin-17/genetics , Interleukin-17/metabolism , Interleukin-17/pharmacology , Models, Molecular , Molecular Sequence Data , Phylogeny , Promoter Regions, Genetic , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Random Amplified Polymorphic DNA Technique/veterinary , Salmo salar/genetics , Sequence Alignment
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