Search results for: apocrine sweat gland
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 117

Search results for: apocrine sweat gland

117 A Case of Apocrine Sweat Gland Adenocarcinoma in a Tabby Cat

Authors: Funda Terzi, Elif Dogan, Ayse B. Kapcak

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In this report, clinical, radiological, macroscopic, and histopathological findings of apocrine sweat gland adenocarcinoma are presented in a 13-year-old male tabby cat. In clinical examination, soft tissue masses were detected in the caudal abdomen and left tuber coxae. On radiological examination, subcutaneous masses with soft tissue contrast appearance were detected, and the masses were surgically removed under general anesthesia. The sizes of the masses were approximately 2x2x3 cm in the caudal abdomen and approximately 1x1x2 cm in the tuber coxae region. The cross-section of the mass was whitish-yellow in color. After the masses were fixed in 10% formaldehyde solution, a routine histopathology procedure was applied. In histopathological examination, apocrine sweat glands in a cystic structure and extensions from the center of the cyst to the lumen were determined, and anisonucleosis, anisocytosis, and anaplastic cells with giant nuclei were observed in the epithelial cells of the gland facing the lumen. A diagnosis of papillary-cystic type apocrine sweat gland adenocarcinoma was made with these findings.

Keywords: apocrine sweat gland, carcinoma, cat, histopathology

Procedia PDF Downloads 178
116 Early Detection of Kidney Failure by Using a Distinct Technique for Sweat Analysis

Authors: Saba. T. Suliman, Alaa. H. Osman, Sara. T. Ahmed, Zeinab. A. Mustafa, Akram. I. Omara, Banazier. A. Ibraheem

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Diagnosis by sweat is one of the emerging methods whereby sweat can identify many diseases in the human body. Sweat contains many elements that help in the diagnostic process. In this research, we analyzed sweat samples by using a Colorimeter device to identify the disease of kidney failure in its various stages. This analysis is a non-invasive method where the sample is collected from outside the body, and then this sample is analyzed. Urea refers to the disease of kidney failure when its quantity is high in the blood and then in the sweat, and by experience, we found that the amount of urea for males differs from its quantity for females, where there is a noticeable increase for males in normal and pathological cases. In this research, we took many samples from a normal group that does not suffer from renal failure and another who suffers from the disease to compare the percentage of urea, and after analysis, we found that the urea percentage is high in people with kidney failure disease. with an accuracy of results of 85%.

Keywords: sweat analysis, kidney failure, urea, non-invasive, eccrine glands, mineral composition, sweat test

Procedia PDF Downloads 44
115 Visualization of Latent Sweat Fingerprints Deposit on Paper by Infrared Radiation and Blue Light

Authors: Xiaochun Huang, Xuejun Zhao, Yun Zou, Feiyu Yang, Wenbin Liu, Nan Deng, Ming Zhang, Nengbin Cai

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A simple device termed infrared radiation (IR) was developed for rapid visualization of sweat fingerprints deposit on paper with blue light (450 nm, 11 W). In this approach, IR serves as the pretreatment device before the sweat fingerprints was illuminated by blue light. An annular blue light source was adopted for visualizing latent sweat fingerprints. Sample fingerprints were examined under various conditions after deposition, and experimental results indicate that the recovery rate of the latent sweat fingerprints is in the range of 50%-100% without chemical treatments. A mechanism for the observed visibility is proposed based on transportation and re-impregnation of fluorescer in paper at the region of water. And further exploratory experimental results gave the full support to the visible mechanism. Therefore, such a method as IR-pretreated in detecting latent fingerprints may be better for examination in the case where biological information of samples is needed for consequent testing.

Keywords: forensic science, visualization, infrared radiation, blue light, latent sweat fingerprints, detection

Procedia PDF Downloads 497
114 Use of the SWEAT Analysis Approach to Determine the Effectiveness of a School's Implementation of Its Curriculum

Authors: Prakash Singh

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The focus of this study is on the use of the SWEAT analysis approach to determine how effectively a school, as an organization, has implemented its curriculum. To gauge the feelings of the teaching staff, unstructured interviews were employed in this study, asking the participants for their ideas and opinions on each of the three identified aspects of the school: instructional materials, media and technology; teachers’ professional competencies; and the curriculum. This investigation was based on the five key components of the SWEAT model: strengths, weaknesses, expectations, abilities, and tensions. The findings of this exploratory study evoke the significance of the SWEAT achievement model as a tool for strategic analysis to be undertaken in any organization. The findings further affirm the usefulness of this analytical tool for human resource development. Employees have expectations, but competency gaps in their professional abilities may hinder them from fulfilling their tasks in terms of their job description. Also, tensions in the working environment can contribute to their experiences of tobephobia (fear of failure). The SWEAT analysis approach detects such shortcomings in any organization and can therefore culminate in the development of programmes to address such concerns. The strategic SWEAT analysis process can provide a clear distinction between success and failure, and between mediocrity and excellence in organizations. However, more research needs to be done on the effectiveness of the SWEAT analysis approach as a strategic analytical tool.

Keywords: SWEAT analysis, strategic analysis, tobephobia, competency gaps

Procedia PDF Downloads 508
113 Sportband: An Idea for Workout Monitoring in Amateur and Recreational Sports

Authors: Kamila Mazur-Oleszczuk, Rafal Banasiuk, Dawid Krasnowski, Maciej Pek, Marcin Podgorski, Krzysztof Rykaczewski, Sabina Zoledowska, Dawid Nidzworski

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Workout safety is one of the most significant challenges of recreational sports. Loss of water and electrolytes is a consequence of thermoregulatory sweating during exercise. The rate of sweat loss and its chemical composition can fluctuate within and among individuals. That is why we propose our sportband 'Flow' as a device for monitoring these parameters. 'Flow' consists of two parts: an intelligent module and a mobile application. The application allows verifying the training progress and data archiving. The sportband intelligent module includes temperature, heart rate and pulse measurement (non-invasive, continuous methods of workout monitoring). Apart from the standard components, the device will consist of a sweat composition analyzer situated in sportband intelligent module. Sweat is a water solution of numerous compounds such as ions (sodium up to 1609 µg/ml, potassium up to 274 µg/ml), lactic acid (skin pH is between 4.5 - 6) and a small amount of glucose. Awareness of sweat composition allows personalizing electrolyte intake after training. A comprehensive workout monitoring (sweat composition, heart rate, blood oxygen level) will provide improvement in the training routine and time management, which is our goal for the development of the sweat composition analyzer.

Keywords: flow, sportband, sweat, workout monitoring

Procedia PDF Downloads 153
112 Reliability of Diffusion Tensor Imaging in Differentiation of Salivary Gland Tumors

Authors: Sally Salah El Menshawy, Ghada M. Ahmed GabAllah, Doaa Khedr M. Khedr

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Background: Our study aims to detect the diagnostic role of DTI in the differentiation of salivary glands benign and malignant lesions. Results: Our study included 50 patients (25males and 25 females) divided into 4 groups (benign lesions n=20, malignant tumors n=13, post-operative changes n=10 and normal n=7). 28 patients were with parotid gland lesions, 4 patients were with submandibular gland lesions and only 1 case with sublingual gland affection. The mean fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of malignant salivary gland tumors (n = 13) (0.380±0.082 and 0.877±0.234× 10⁻³ mm² s⁻¹) were significantly different (P<0.001) than that of benign tumors (n = 20) (0.147±0.03 and 1.47±0.605 × 10⁻³ mm² s⁻¹), respectively. The mean FA and ADC of post-operative changes (n = 10) were (0.211±0.069 and 1.63±0.20× 10⁻³ mm² s⁻¹) while that of normal glands (n =7) was (0.251±0.034and 1.54±0.29× 10⁻³ mm² s⁻¹), respectively. Using ADC to differentiate malignant lesions from benign lesions has an (AUC) of 0.810, with an accuracy of 69.7%. ADC used to differentiate malignant lesions from post-operative changes has (AUC) of 1.0, and an accuracy of 95.7%. FA used to discriminate malignant from benign lesions has (AUC) of 1.0, and an accuracy of 93.9%. FA used to differentiate malignant from post-operative changes has (AUC) of 0.923, and an accuracy of 95.7%. Combined FA and ADC used to differentiate malignant from benign lesions has (AUC) of 1.0, and an accuracy of 100%. Combined FA and ADC used to differentiate malignant from post-operative changes has (AUC) of 1.0, and an accuracy of 100%. Conclusion: Combined FA and ADC can differentiate malignant tumors from benign salivary gland lesions.

Keywords: diffusion tensor imaging, MRI, salivary gland, tumors

Procedia PDF Downloads 113
111 Analysis of Sweat Evaporation and Heat Transfer on Skin Surface: A Pointwise Numerical Study

Authors: Utsav Swarnkar, Rabi Pathak, Rina Maiti

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This study aims to investigate the thermoregulatory role of sweating by comprehensively analyzing the evaporation process and its thermal cooling impact on local skin temperature at various time intervals. Traditional experimental methods struggle to fully capture these intricate phenomena. Therefore, numerical simulations play a crucial role in assessing sweat production rates and associated thermal cooling. This research utilizes transient computational fluid dynamics (CFD) to enhance our understanding of the evaporative cooling process on human skin. We conducted a simulation employing the k-w SST turbulence model. This simulation includes a scenario where sweat evaporation occurs over the skin surface, and at particular time intervals, temperatures at different locations have been observed and its effect explained. During this study, sweat evaporation was monitored on the skin surface following the commencement of the simulation. Subsequent to the simulation, various observations were made regarding temperature fluctuations at specific points over time intervals. It was noted that points situated closer to the periphery of the droplets exhibited higher levels of heat transfer and lower temperatures, whereas points within the droplets displayed contrasting trends.

Keywords: CFD, sweat, evaporation, multiphase flow, local heat loss

Procedia PDF Downloads 68
110 The Impact of Prior Cancer History on the Prognosis of Salivary Gland Cancer Patients: A Population-based Study from the Surveillance, Epidemiology, and End Results (SEER) Database

Authors: Junhong Li, Danni Cheng, Yaxin Luo, Xiaowei Yi, Ke Qiu, Wendu Pang, Minzi Mao, Yufang Rao, Yao Song, Jianjun Ren, Yu Zhao

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Background: The number of multiple cancer patients was increasing, and the impact of prior cancer history on salivary gland cancer patients remains unclear. Methods: Clinical, demographic and pathological information on salivary gland cancer patients were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017, and the characteristics and prognosis between patients with a prior cancer and those without prior caner were compared. Univariate and multivariate cox proportional regression models were used for the analysis of prognosis. A risk score model was established to exam the impact of treatment on patients with a prior cancer in different risk groups. Results: A total of 9098 salivary gland cancer patients were identified, and 1635 of them had a prior cancer history. Salivary gland cancer patients with prior cancer had worse survival compared with those without a prior cancer (p<0.001). Patients with a different type of first cancer had a distinct prognosis (p<0.001), and longer latent time was associated with better survival (p=0.006) in the univariate model, although both became nonsignificant in the multivariate model. Salivary gland cancer patients with a prior cancer were divided into low-risk (n= 321), intermediate-risk (n=223), and high-risk (n=62) groups and the results showed that patients at high risk could benefit from surgery, radiation therapy, and chemotherapy, and those at intermediate risk could benefit from surgery. Conclusion: Prior cancer history had an adverse impact on the survival of salivary gland cancer patients, and individualized treatment should be seriously considered for them.

Keywords: prior cancer history, prognosis, salivary gland cancer, SEER

Procedia PDF Downloads 147
109 Misdiagnosed Mammary Analogue Secretory Carcinoma of the Salivary Gland: A Case Report with a Review of the Literature

Authors: Yaya Gao, Jifeng Liu, Yafeng Liu

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Objectives: This study aimed to improve clinicians' understanding and diagnosis of the Mammary analogue secretory carcinoma of the salivary gland(MASC). Methods: The clinical features of a MASC patient who was admitted to WestChina Hospital of Sichuan University in July 2020 were reviewed and analyzed. A 49-year-old woman with left upper neck pain for three months was admitted to the hospital. She underwent adenoma resection of the left submandibular gland 14 years ago and mucoepidermoid carcinoma resection surgery five years ago. Three months before admission, the patient developed pain in the left mandibular angle after "fatigue" and gradually developed radiation pain in the left ear, which could be relieved after rest. A mass of 1cm could be touched at the mandibular, with tenderness, poor mobility, and hard texture. No swelling, heat, pain, rupture, or pus was found on the surrounding skin. Color doppler ultrasonography of the salivary gland indicated a weak echo mass of 23*14*17mm in the left parotid gland. Results: Surgical excision was completed. Immunohistochemistry of the tumor samples after operation showed that P63(a few,+), CK7(+), S100(+), DOG1(-), Ki67(MIB-1)(+,5%),pan-TRK(+), PAS(+) . ETV-6 gene translocation was detected in FISH in postoperative pathology, which indicated MASC. After this diagnosis, the patient sent the postoperative specimen of the second submandibular tumor to our hospital for consultation. The morphology of the two was similar. FISH detected ETV-6 gene translocation, so the second pathological diagnosis was revised to MASC. Conclusion: MASC of the salivary gland is a rare salivary gland tumor whose diagnosis depends on the result of the ETV6-NTRK3 fusion gene.

Keywords: mammary analogue secretory carcinoma, ETV6-NTRK3, salivary gland, misdiagnosed

Procedia PDF Downloads 63
108 Phenotypical and Genotypical Diagnosis of Cystic Fibrosis in 26 Cases from East and South Algeria

Authors: Yahia Massinissa, Yahia Mouloud

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Cystic fibrosis (CF), the most common lethal genetic disease in the Europe population, is caused by mutations in the transmembrane conductance regulator gene (CFTR). It affects most organs including an epithelial tissue, base of hydroelectrolytic transepithelial transport, notably that aerial ways, the pancreas, the biliary ways, the intestine, sweat glands and the genital tractus. The gene whose anomalies are responsible of the cystic fibrosis codes for a protein Cl channel named CFTR (cystic fibrosis transmembrane conductance regulator) that exercises multiple functions in the cell, one of the most important in control of sodium and chlorine through epithelia. The deficient function translates itself notably by an abnormal production of viscous secretion that obstructs the execrator channels of this target organ: one observes then a dilatation, an inflammation and an atrophy of these organs. It also translates itself by an increase of the concentration in sodium and in chloride in sweat, to the basis of the sweat test. In order to do a phenotypical and genotypical diagnosis at a part of the Algerian population, our survey has been carried on 16 patients with evocative symptoms of the cystic fibrosis at that the clinical context has been confirmed by a sweat test. However, anomalies of the CFTR gene have been determined by electrophoresis in gel of polyacrylamide of the PCR products (polymerase chain reaction), after enzymatic digestion, then visualized to the ultraviolet (UV) after action of the ethidium bromide. All mutations detected at the time of our survey have already been identified at patients attained by this pathology in other populations of the world. However, the important number of found mutation with regard to the one of the studied patients testifies that the origin of this big clinical variability that characterizes the illness in the consequences of an enormous diversity of molecular defects of the CFTR gene.

Keywords: cystic fibrosis, CFTR gene, polymorphism, algerian population, sweat test, genotypical diagnosis

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107 Iontophoretic Drug Transport: An Non-Invasive Transdermal Approach

Authors: Ashish Jain, Shivam Tayal

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There has been great interest in the field of Iontophoresis since few years due to its great applications in the field of controlled transdermal drug delivery system. It is an technique which is used to enhance the transdermal permeation of ionized high molecular weight molecules across the skin membrane especially Peptides & Proteins by the application of direct current of 1-4 mA for 20-40 minutes whereas chemical must be placed on electrodes with same charge. Iontophoresis enhanced the delivery of drug into the skin via pores like hair follicles, sweat gland ducts etc. rather than through stratum corneum. It has wide applications in the field of experimental, Therapeutic, Diagnostic, Dentistry etc. Medical science is using it to treat Hyperhidrosis (Excessive sweating) in hands and feet and to treat other ailments like hypertension, Migraine etc. Nowadays commercial transdermal iontophoretic patches are available in the market to treat different ailments. Researchers are keen to research in this field due to its vast applications and advantages.

Keywords: iontophoresis, novel drug delivery, transdermal, permeation enhancer

Procedia PDF Downloads 255
106 Evaluation of Prevalence of the Types of Thyroid Disorders Using Ultrasound and Pathology of One-Humped Camel in Iran: Camelus dromedarius

Authors: M. Yadegari

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The thyroid gland is the largest classic endocrine organ that effects many organs of the body and plays a significant role in the process of Metabolism in animals. The aim of this study was to investigate the prevalence of thyroid disorders diagnosed by ultrasound and microscopic Lesions of the thyroid during the slaughter of apparently healthy One Humped Camels (Camelus dromedarius) in Iran. Randomly, 520 male camels (With an age range of 4 to 8 years), were studied in 2012 to 2013. The Camels’ thyroid glands were evaluated by sonographic examination. In both longitudinal and transverse view and then tissue sections were provide and stained with H & E and finally examined by light microscopy. The results obtained indicated the following: hyperplastic goiter (21%), degenerative changes (12%), follicular cysts (8%), follicular atrophy (4%), nodular hyperplasia (3%), adenoma (1%), carcinoma (1%) and simple goiter colloid (1%). Ultrasound evaluation of thyroid gland in adenoma and carcinoma showed enlargement and irregular of the gland, decreased echogenicity, and the heterogeneous thyroid parenchyma. Also, in follicular cysts were observed in the enlarged gland with no echo structures of different sizes and decreased echogenicity as a local or general. In nodular hyperplasia, increase echogenicity and heterogeneous parenchymal were seen. These findings suggest the use of Ultrasound as a screening test in the diagnosis of complications of thyroid disorders. Pathology also to be used for the diagnosis of thyroid problems and other side effects.

Keywords: thyroid gland, one humped camel, sonography, pathology

Procedia PDF Downloads 508
105 Adenoid Cystic Carcinoma of the Lacrimal Gland (About a Case)

Authors: H. Hadjeris, R. B. Ghoul, Lekhlaf, M. Nebbal

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Introduction: Adenoid cystic carcinomas of the lacrimal gland or orbital cylindroma constitute the second cause of epithelial tumors of this gland. It is a malignant tumor usually developed at the expense of the salivary glands; its orbital location is exceptional. It is a rare clinical entity, formidable by its malignancy and local aggressiveness; the recurrence rate is high. Materials and methods: Clinical case: 63 years old woman who presents with irreducible no pulsatile painful left exophthalmos with inflammatory chemosis and a decrease in visual acuity with a moderate intracranial hypertension syndrome that has been evolving for 03 months. Antecedent; a biopsy of the tumor was made; the histological examination was in favor of an adenoid cystic carcinoma of the lacrimal gland. Lesion assessment: computed tomography and brain MRI: show an intra and extra-conical mass; with sinus (ethmoido-frontal) and cerebral (left frontal) extension strongly enhanced after injection of contrast product surrounded by edema around the lesion, associated with left frontal bone lysis extension assessment: unremarkable treatment: Patient operated by left frontotemporal approach, a total exenteration was performed with macroscopically complete excision of the frontal lesion and wide frontal craniectomy with craniofacial reconstruction, followed by complementary radiotherapy. Results: The patient was seen again after 3 months in consultation; she does not present any signs in favor of a recurrence. Conclusion: Adenoid cystic carcinomas of the lacrimal gland are rare malignant tumors; they are very infiltrating and invasive. The prognosis is strongly linked to the treatment time.

Keywords: adenoid cystic, lacrimal gland, orbital location, fronto-temporal approac

Procedia PDF Downloads 71
104 Antitumor Activity of Gold Nanorods against Mammary Gland and Skin Carcinoma in Dogs and Cats

Authors: Abdoon A.S., El Ashkar E.A., Kandil O.M., Wael H. Eisa, Shaban A.M., Khaled H.M., El Ashkar M.R., El Shaer M., Hussein H., Shaalan A.H., El Sayed M.

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Cancer is a major obstacle to human health and development worldwide. Conventional strategies for cancer intervention include surgery, chemotherapy, and radiation therapy. Recently, plasmon photothermal therapy (PPTT) was introduced as a promising treatment for the management of cancer and several non-cancerous diseases that are generally characterized by overgrowth of abnormal cells. The present work was conducted to evaluate the cytotoxic efficacy and toxicity of gold nanorods (AuNRs) in dogs and cats suffering from spontaneous mammary gland. AuNRs was injected intratumoral (IT, n=10, dose of 75 p.p.m/kg body weight) or by using spray method after surgical removal of cancer tissue (n=2) in dogs and cats. Then exposed to laser light after 60 min. Treated animals were observed every 2 days and the morphological changes in tumor size and shape were recorded. Blood samples were collected before and after treatment for checking CBC, liver and kidney functions. Results revealed that AuNRs successfully treat mammary gland tumor in dogs and cats (adenocarcinoma type 1 to IV). AuNRs induced sloughing of carcinogenic tissue within 5 to 15 days. AuNRs have no toxic effect on blood profile and the toxicity studies still under evaluation. Conclusion, AuNRs can be used for treatment of mammary gland carcinoma in dogs and cats.

Keywords: pet animals, mammary gland tumor, AuNRs, photothermal therapy, toxicity studies

Procedia PDF Downloads 385
103 Criteria for Assessing Prostate Structure after Proton Radiotherapy for Prostate Cancer

Authors: Kuplevatsky V., Kuplevatskay, Cherkashin M., Berezina N.

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After 6 months, a violation of the differentiation of the structure of the gland due to edema in 100%. 20% retained signs of a tumor according to DWI/ADC data. By 12 months, the reduction in the size of the gland is 100%. In all cases, no diffusion restriction was observed. The study after 18 months showed no significant changes in all (100%) patients. In the study, 24 months after treatment, the size of the gland was stable in all cases (+/- up to 5%). Diffuse decrease in T2VI signals from peripheral zones, without signs of diffusion restriction in 100%. After 30 months, signs of recovery of adenomatous changes in the transient zone were revealed in 85%. After 36 and 42 months, the restoration of organ differentiation was observed in 93% of patients. In 4 patients, by the 48th month, signs of biochemical relapse were clinically noted. According to the MRI data, signs of a local relapse were revealed. After 48 months, there were signs of restoration of organ differentiation, which allowed the use of PI-RADS criteria. The study after 54 months showed no changes compared to the control. 60 months after treatment, 97% of patients showed a restoration of differentiation of the gland structure, which allows evaluating the organ according to PI-RADS criteria Conclusions: The beginning of restoration of the structure of the prostate gland began 24 months after proton radiation therapy, the PI-RADS criteria can be fully applied after 48 months of treatment. Control studies every 6 months without clinical signs of relapse are not advisable. Local control of the prostate tumor after proton radiation therapy was achieved in 95% of patients during the entire follow-up period ( 60 months).

Keywords: proton therapy, prostate cancer, MRI imaging, PI-RADS

Procedia PDF Downloads 103
102 The Role of the STAT3 Signaling for Melatonergic Synthetic Pathway in the Rat Pineal Gland

Authors: Simona Moravcova, Jiri Novotny, Zdenka Bendova

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The pineal gland of the vertebrate brain is a circumventricular organ which serves as a major neuroendocrine gland with the primary function of rhythmic secretion of neurohormone melatonin under the control of the hypothalamic suprachiasmatic nucleus (SCN). Soon after the onset of the darkness, the activity of the key rate-limiting enzyme for melatonin synthesis, arylalkylamine N-acetyltransferase (AANAT), raises due to the increased release of norepinephrine from sympathetic neurons terminating on the parenchymal cells where it binds to β-adrenergic receptors. Melatonin codes the length of the night, and it is well recognized for its anti-inflammatory effects. However, to our knowledge, less is known about the effect of the immune system on the melatonin biosynthesis and the precise role of the STAT3 in the signaling pathway leading to the expression of AANAT. Lipopolysaccharide (LPS) is the essential component in the outer surface membrane of gram-negative bacteria and acts as a strong stimulator of natural and innate immunity. STAT3 acts as an important factor in immune response. Here we investigated the effect of LPS on the components of the melatonergic synthetic pathway in the pineal gland. The experiments were performed both in vivo and in vitro. The changes in AANAT activity were determined by radioenzymatic assay. PCR analyses were carried out to detect aa-nat, icer, spi-3 and stat3 gene expression. From our results, it is apparent that the high basal level of phosphorylated forms of STAT3 can be elevated after systemic as well as in vitro administration of LPS. Our experiments have shown that LPS reduces melatonin synthesis, nevertheless, the activity of AANAT was increased. Moreover, the basal level of phosphorylated STAT3 counteracts β-adrenergic receptor-mediated aa-nat gene expression and sustains its own and spi-3 gene expression. In conclusion, LPS can affect immunomodulators such as melatonin in the pineal gland.

Keywords: AANAT, lipopolysaccharide, pineal gland, rat, STAT3

Procedia PDF Downloads 169
101 Mapping of Adrenal Gland Diseases Research in Middle East Countries: A Scientometric Analysis, 2007-2013

Authors: Zahra Emami, Mohammad Ebrahim Khamseh, Nahid Hashemi Madani, Iman Kermani

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The aim of the study was to map scientific research on adrenal gland diseases in the Middle East countries through the Web of Science database using scientometric analysis. Data were analyzed with Excel software; and HistCite was used for mapping of the scientific texts. In this study, from a total of 268 retrieved records, 1125 authors from 328 institutions published their texts in 138 journals. Among 17 Middle East countries, Turkey ranked first with 164 documents (61.19%), Israel ranked second with 47 documents (15.53%) and Iran came in the third place with 26 documents. Most of the publications (185 documents, 69.2%) were articles. Among the universities of the Middle East, Istanbul University had the highest science production rate (9.7%). The Journal of Clinical Endocrinology & Metabolism had the highest TGCS (243 citations). In the scientific mapping, 7 clusters were formed based on TLCS (Total Local Citation Score) & TGCS (Total Global Citation Score). considering the study results, establishment of scientific connections and collaboration with other countries and use of publications on adrenal gland diseases from high ranking universities can help in the development of this field and promote the medical practice in this regard. Moreover, investigation of the formed clusters in relation to Congenital Hyperplasia and puberty related disorders can be research priorities for investigators.

Keywords: mapping, scientific research, adrenal gland diseases, scientometric

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100 Cellulose Nanocrystals Suspensions as Water-Based Lubricants for Slurry Pump Gland Seals

Authors: Mohammad Javad Shariatzadeh, Dana Grecov

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The tribological tests were performed on a new tribometer, in order to measure the coefficient of friction of a gland seal packing material on stainless steel shafts in presence of Cellulose Nanocrystal (CNC) suspension as a sustainable, environmentally friendly, water-based lubricant. To simulate the real situation from the slurry pumps, silica sands were used as slurry particles. The surface profiles after tests were measured by interferometer microscope to characterize the surface wear. Moreover, the coefficient of friction and surface wear were measured between stainless steel shaft and chrome steel ball to investigate the tribological effects of CNC in boundary lubrication region. Alignment of nanoparticles in the CNC suspensions are the main reason for friction and wear reduction. The homogeneous concentrated suspensions showed fingerprint patterns of a chiral nematic liquid crystal. These properties made CNC a very good lubricant additive in water.

Keywords: gland seal, lubricant additives, nanocrystalline cellulose, water-based lubricants

Procedia PDF Downloads 185
99 Phenology and Size in the Social Sweat Bee, Halictus ligatus, in an Urban Environment

Authors: Rachel A. Brant, Grace E. Kenny, Paige A. Muñiz, Gerardo R. Camilo

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The social sweat bee, Halictus ligatus, has been documented to alter its phenology as a response to changes in temporal dynamics of resources. Furthermore, H. ligatus exhibits polyethism in natural environments as a consequence of the variation in resources. Yet, we do not know if or how H. ligatus responds to these variations in urban environments. As urban environments become much more widespread, and human population is expected to reach nine billion by 2050, it is crucial to distinguish how resources are allocated by bees in cities. We hypothesize that in urban regions, where floral availability varies with human activity, H. ligatus will exhibit polyethism in order to match the extremely localized spatial variability of resources. We predict that in an urban setting, where resources vary both spatially and temporally, the phenology of H. ligatus will alter in response to these fluctuations. This study was conducted in Saint Louis, Missouri, at fifteen sites each varying in size and management type (community garden, urban farm, prairie restoration). Bees were collected by hand netting from 2013-2016. Results suggest that the largest individuals, mostly gynes, occurred in lower income neighborhood community gardens in May and August. We used a model averaging procedure, based on information theoretical methods, to determine a best model for predicting bee size. Our results suggest that month and locality within the city are the best predictors of bee size. Halictus ligatus was observed to comply with the predictions of polyethism from 2013 to 2015. However, in 2016 there was an almost complete absence of the smallest worker castes. This is a significant deviation from what is expected under polyethism. This could be attributed to shifts in planting decisions, shifts in plant-pollinator matches, or local climatic conditions. Further research is needed to determine if this divergence from polyethism is a new strategy for the social sweat bee as climate continues to alter or a response to human dominated landscapes.

Keywords: polyethism, urban environment, phenology, social sweat bee

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98 Deep Learning Approach for Colorectal Cancer’s Automatic Tumor Grading on Whole Slide Images

Authors: Shenlun Chen, Leonard Wee

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Tumor grading is an essential reference for colorectal cancer (CRC) staging and survival prognostication. The widely used World Health Organization (WHO) grading system defines histological grade of CRC adenocarcinoma based on the density of glandular formation on whole slide images (WSI). Tumors are classified as well-, moderately-, poorly- or un-differentiated depending on the percentage of the tumor that is gland forming; >95%, 50-95%, 5-50% and <5%, respectively. However, manually grading WSIs is a time-consuming process and can cause observer error due to subjective judgment and unnoticed regions. Furthermore, pathologists’ grading is usually coarse while a finer and continuous differentiation grade may help to stratifying CRC patients better. In this study, a deep learning based automatic differentiation grading algorithm was developed and evaluated by survival analysis. Firstly, a gland segmentation model was developed for segmenting gland structures. Gland regions of WSIs were delineated and used for differentiation annotating. Tumor regions were annotated by experienced pathologists into high-, medium-, low-differentiation and normal tissue, which correspond to tumor with clear-, unclear-, no-gland structure and non-tumor, respectively. Then a differentiation prediction model was developed on these human annotations. Finally, all enrolled WSIs were processed by gland segmentation model and differentiation prediction model. The differentiation grade can be calculated by deep learning models’ prediction of tumor regions and tumor differentiation status according to WHO’s defines. If multiple WSIs were possessed by a patient, the highest differentiation grade was chosen. Additionally, the differentiation grade was normalized into scale between 0 to 1. The Cancer Genome Atlas, project COAD (TCGA-COAD) project was enrolled into this study. For the gland segmentation model, receiver operating characteristic (ROC) reached 0.981 and accuracy reached 0.932 in validation set. For the differentiation prediction model, ROC reached 0.983, 0.963, 0.963, 0.981 and accuracy reached 0.880, 0.923, 0.668, 0.881 for groups of low-, medium-, high-differentiation and normal tissue in validation set. Four hundred and one patients were selected after removing WSIs without gland regions and patients without follow up data. The concordance index reached to 0.609. Optimized cut off point of 51% was found by “Maxstat” method which was almost the same as WHO system’s cut off point of 50%. Both WHO system’s cut off point and optimized cut off point performed impressively in Kaplan-Meier curves and both p value of logrank test were below 0.005. In this study, gland structure of WSIs and differentiation status of tumor regions were proven to be predictable through deep leaning method. A finer and continuous differentiation grade can also be automatically calculated through above models. The differentiation grade was proven to stratify CAC patients well in survival analysis, whose optimized cut off point was almost the same as WHO tumor grading system. The tool of automatically calculating differentiation grade may show potential in field of therapy decision making and personalized treatment.

Keywords: colorectal cancer, differentiation, survival analysis, tumor grading

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97 Human Dental Pulp Stem Cells Attenuate Streptozotocin-Induced Parotid Gland Injury in Rats

Authors: Gehan ElAkabawy

Abstract:

Background: Diabetes mellitus causes severe deteriorations of almost all the organs and systems of the body, as well as significant damage to the oral cavity. The oral changes are mainly related to salivary glands dysfunction characterized by hyposalivation and xerostomia, which significantly reduce diabetic patients’ quality of life. Human dental pulp stem cells represent a promising source for cell-based therapies, owing to their easy, minimally invasive surgical access, and high proliferative capacity. It was reported that the trophic support mediated by dental pulp stem cells can rescue the functional and structural alterations of damaged salivary glands. However, potential differentiation and paracrine effects of human dental pulp stem cells in diabetic-induced parotid gland damage have not been previously investigated. Our study aimed to investigate the therapeutic effects of intravenous transplantation of human dental pulp stem cells (hDPSCs) on parotid gland injury in a rat model of streptozotocin (STZ)-induced type 1 diabetes. Methods: Thirty Sprague-Dawley male rats were randomly categorised into three groups: control, diabetic (STZ), and transplanted (STZ+hDPSCs). hDPSCs or vehicle was injected into the tail vein 7 days after STZ injection. The fasting blood glucose levels were monitored weekly. A glucose tolerance test was performed, and the parotid gland weight, salivary flow rate, oxidative stress indices, parotid gland histology, and caspase-3, vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA) expression in parotid tissues were assessed 28 days post-transplantation. Results: Transplantation of hDPSCs downregulated blood glucose, improved the salivary flow rate, and reduced oxidative stress. The cells migrated to, survived, and differentiated into acinar, ductal, and myoepithelial cells in the STZ-injured parotid gland. Moreover, they downregulated the expression of caspase-3 and upregulated the expression of VEGF and PCNA, likely exerting pro-angiogenetic and antiapoptotic effects and promoting endogenous regeneration. In addition, the transplanted cells enhanced the parotid nitric oxide (NO) -tetrahydrobiopterin (BH4) pathway. Conclusions: Our results show that hDPSCs can migrate to and survive within the STZ-injured parotid gland, where they prevent its functional and morphological damage by restoring normal glucose levels, differentiating into parotid cell populations, and stimulating paracrine-mediated regeneration. Thus, hDPSCs may have therapeutic potential in the treatment of diabetes-induced parotid gland injury.

Keywords: dental pulp stem cells, diabetes, streptozotocin, parotid gland

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96 Study and Melanocyte Adrenocorticotropic Effects on Sugar Metabolism and Immune Response in Rabbits Oryctolagus cuniculus

Authors: A. Bouaouiche, M. S. Boulakoud

Abstract:

The functioning of the pineal gland, the transducer body of environmental information to the neuroendocrine system is subject to a circadian rhythm. Melatonin is the main neuro-hormone expressing this operation. It is synthesized in the pinealocytes after conversion serotonin via N-acetyl-transferase enzyme, itself subject to a photoperiodic modulation (activation dark inhibition by light). Some authors have suggested that melatonin is involved in diabetic disease and found that it could have a diabetogenic effect. To this study the effect of this hormone on glucose metabolism has long been subject to controversy. Agreeing in effect and hyperinsulinemic hypoglycemic effect. In order to illustrate the level of interaction of melatonin with neuro-immune- corticotropin axis and its impact on carbohydrate metabolism, we studied the impact homeostatic (glucose) through the solicitation of two control systems (gland pineal and corticotropin axis). We then found that melatonin could have an indirect influence on insulin control (glucose metabolism) to the levels of the growth hormone axis (somatostatin) and adrenocorticotropic (corticotropin). In addition, we have suggested that melatonin might limit the hyperglycemic action of corticosteroids by direct action at peripheral level.

Keywords: pinéal gland, melatonin, neuro-immuno-corticotrop, metabolism

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95 Identification and Characterization of Novel Genes Involved in Quinone Synthesis in the Odoriferous Defensive Stink Glands of the Red Flour Beetle, Tribolium castaneum

Authors: B. Atika, S. Lehmann, E. Wimmer

Abstract:

The defense strategy is very common in the insect world. Defensive substances play a wide variety of functions for beetles, such as repellents, toxicants, insecticides, and antimicrobics. Beetles react to predators, invaders, and parasitic microbes with the release of toxic and repellent substances. Defensive substances are directed against a large array of potential target organisms or may function for boiling bombardment or as surfactants. Usually, Coleoptera biosynthesize and store their defensive compounds in a complex secretory organ, known as odoriferous defensive stink glands. The red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae), uses these glands to produce antimicrobial p-benzoquinones and 1-alkenes. In the past, the morphology of stink gland has been studied in detail in tenebrionid beetles; however, very little is known about the genes that are involved in the production of gland secretion. In this study, we studied a subset of genes that are essential for the benzoquinone production in red flour beetle. In the first phase, we selected 74 potential candidate genes from a genome-wide RNA interference (RNAi) knockdown screen named 'iBeetle.' All these 74 candidate genes were functionally characterized by RNAi-mediated gene knockdown. Therefore, they were selected for a subsequent gas chromatography-mass spectrometry (GC-MS) analysis of secretion volatiles in respective RNAi knockdown glands. 33 of them were observed to alter the phenotype of stink gland. In the GC-MS analysis, 7 candidate genes were noted to display a strongly altered gland, in terms of secretion color and chemical composition, upon knockdown, showing their key role in the biosynthesis of gland secretion. Morphologically altered stink glands were found for odorant receptor and protein kinase superfamily. Subsequent GC-MS analysis of secretion volatiles revealed reduced benzoquinone levels in LIM domain, PDZ domain, PBP/GOBP family knockdowns and a complete lack of benzoquinones in the knockdown of sulfatase-modifying factor enzyme 1, sulfate transporter family. Based on stink gland transcriptome data, we analyzed the function of sulfatase-modifying factor enzyme 1 and sulfate transporter family via RNAi-mediated gene knockdowns, GC-MS, in situ hybridization, and enzymatic activity assays. Morphologically altered stink glands were noted in knockdown of both these genes. Furthermore, GC-MS analysis of secretion volatiles showed a complete lack of benzoquinones in the knockdown of these two genes. In situ hybridization showed that these two genes are expressed around the vesicle of certain subgroup of secretory stink gland cells. Enzymatic activity assays on stink gland tissue showed that these genes are involved in p-benzoquinone biosynthesis. These results suggest that sulfatase-modifying factor enzyme 1 and sulfate transporter family play a role specifically in benzoquinone biosynthesis in red flour beetles.

Keywords: Red Flour Beetle, defensive stink gland, benzoquinones, sulfate transporter, sulfatase-modifying factor enzyme 1

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94 Uncommon Presentation of Iscahemic Heart Disease with Sheehan’s Syndrome at Mid-Level Private Hospital of Bangladesh and Its Management- A Case Report

Authors: Nazmul Haque, Syeda Tasnuva Maria

Abstract:

Sheehan's Syndrome (SS), also known as postpartum hypopituitarism, is a rare but potentially serious condition resulting from ischemic necrosis of the pituitary gland, often occurring during or after childbirth. This syndrome is characterized by hypopituitarism, leading to deficiencies in various hormones produced by the pituitary gland. The primary cause is typically severe postpartum hemorrhage, leading to inadequate blood supply and subsequent necrosis of the pituitary tissue. This chronic hypopituitarism sometimes plays the role of premature atherosclerosis, which may lead to cardiovascular disease. This abstract provides a comprehensive overview of Sheehan's Syndrome with ischaemic heart disease, encompassing its pathophysiology, clinical manifestations, and current management strategies. The disorder presents a wide spectrum of symptoms, including chest pain, fatigue, amenorrhea, lactation failure, hypothyroidism, and adrenal insufficiency. Timely diagnosis is crucial, as delayed recognition can lead to complications and long-term health consequences. We herein report a patient complaining of chronic fatigue symptoms, aggressiveness, chest pain, and breathlessness with repeated LOC that were diagnosed with SS with IHD. The patient was treated with antiplatelet, antianginal, steroids, and hormone replacement with marked improvement in his overall condition.

Keywords: ischaemic heart disease, Sheehan's syndrome, post-partum haemorrhage, pituitary gland

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93 A Sensitive Uric Acid Electrochemical Sensing in Biofluids Based on Ni/Zn Hydroxide Nanocatalyst

Authors: Nathalia Florencia Barros Azeredo, Josué Martins Gonçalves, Pamela De Oliveira Rossini, Koiti Araki, Lucio Angnes

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This work demonstrates the electroanalysis of uric acid (UA) at very low working potential (0 V vs Ag/AgCl) directly in body fluids such as saliva and sweat using electrodes modified with mixed -Ni0.75Zn0.25(OH)2 nanoparticles exhibiting stable electrocatalytic responses from alkaline down to weakly acidic media (pH 14 to 3 range). These materials were prepared for the first time and fully characterized by TEM, XRD, and spectroscopic techniques. The electrochemical properties of the modified electrodes were evaluated in a fast and simple procedure for uric acid analyses based on cyclic voltammetry and chronoamperometry, pushing down the detection and quantification limits (respectively of 2.3*10-8 and 7.6*10-8 mol L-1) with good repeatability (RSD = 3.2% for 30 successive analyses pH 14). Finally, the possibility of real application was demonstrated upon realization of unexpectedly robust and sensitive modified FTO (fluorine doped tin oxide) glass and screen-printed sensors for measurement of uric acid directly in real saliva and sweat samples, with no significant interference of usual concentrations of ascorbic acid, acetaminophen, lactate and glucose present in those body fluids (Fig. 1).

Keywords: nickel hydroxide, mixed catalyst, uric acid sensors, biofluids

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92 High Prevalence of Canine Mammary Gland Tumor in Nulliparous Compared with Multiparous Female Dogs

Authors: Sudson Sirivaidyapong, Ratthanan Sathienbumrungkit, Nongnapas Ruangpet, Nattanun Uaprayoon, Chawisa Wejjakul

Abstract:

Many factors initiate mammary gland tumor in female dogs such as age, breed, sex, estrous cycle, birth control and pseudopregnancy. Those factors are mostly associated with canine sex hormone. In this study, questionnaires and direct interviews were used to collect information from owners of female dogs that had been diagnosed as mammary tumors at our veterinary teaching hospital, during January 2015 to October 2016 to compare the prevalence of mammary tumor between nulliparous and multiparous female dogs. 200 dogs (from all 212 mammary tumor patients, some were excluded because of inadequate information) were included in the study, 72.5% were nulliparous and 27.5% were multiparous. The results revealed that breed, age, birth control age and birth control methods were not different in both groups; most dogs in both groups were various purebreds, geriatric age, and low incidence of hormonal contraception while 100% of multiparous dogs and 83.7% of nulliparous dogs had been neutered at over two years old. The significant differences between two groups were the frequency of pseudopregnancy and estrus which were much higher in nulliparous female dogs. It can be concluded from our study that nulliparous dogs may be more likely at higher risk of mammary tumor compared to multiparous dogs from various factors especially, the frequency of estrus and the occurrence of pseudopregnancy which related to more times of sex hormonal contact. This study was a preliminary data for further studies to determine the other risk factors of mammary gland tumors in dogs, and to our knowledge, it is the first report on a significantly higher prevalence of mammary tumor in nulliparous female dogs than that in multiparous dogs. This finding corresponds with the study of breast cancer in women but may be from different causes and factors due to the differences in estrous physiology.

Keywords: canine, female dogs, nulliparous, multiparous, mammary tumor, prevalence

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91 Concepts of Instrumentation Scheme for Thought Transfer

Authors: Rai Sachindra Prasad

Abstract:

Thought is physical force. This has been well recognized but hardly translated visually or otherwise in the sense of its transfer from one individual to another. In the present world of chaos and disorder with yawning gaps between right and wrong thinking individuals, if it is possible to transfer the right thoughts to replace the wrong ones it would indeed be a great achievement in the present situation of the world which is torn with violence with dangerous thoughts of individuals. Moreover, such a possibility would completely remove the barrier of language between two persons, which at times proves to be a great obstacle in realizing a desired purpose. If a proper instrumentation scheme containing appropriate transducers and electronics is designed and implemented to realize this thought ransfer phenomenon, this would prove to be extremely useful when properly used. Considering the advancements already made in recording the nerve impulses in the brain, which are electrical events of very short durations that move along the axon, it is conceivable that this may be used to good effect in implementing the scheme. In such a proposition one shoud consider the roles played by pineal body, pituitary gland and ‘association’ areas. Pioneer students of brain have thought that associations or connections between sensory input and motor output were made in these areas. It is currently believed that rather than being regions of simple sensory-motor connections, the association areas process and integrate sensory information relayed to them from the primary sensory areas of the cortex and from the thalamus, after the information has been processed, it may be sent to motor areas to be acted upon. Again, even though the role played by pineal body is not known fully to neurologists its interconnection with pituitary gland is a matter of great significance to the ‘Rishis’ and; Seers’ s described in Vedas and Puranas- the ancient Holy books of Hindus. If the pineal body is activated through meditation it would control the pituitary gland thereby the individual’s thoughts and acts. Thus, if thoughts can be picked up by special transducers, these can be connected to suitable electronics circuitry to amplify the signals. These signals in the form of electromagnetic waves can then be transmitted using modems for long distance transmission and eventually received by or passed on to a subject of interest through another set of electronics circuit and devices.

Keywords: modems, pituitary gland, pineal body, thought transfer

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90 Sensitivity of Staphylococcus aureus Isolated from Subclinical Bovine Mastitis to Ciprofloxacin in Dairy Herd in Tabriz during 2013

Authors: Alireza Jafarzadeh, Samad Mosaferi, Mansour Khakpour

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Mastitis is an inflammation of the parenchyma of mammary gland regardless of the causes. Mastitis is characterized by a range of physical and chemical changes in the glandular tissue. The most important change in milk includes discoloration, the presence of clots and large number of leucocytes. There is swelling, heat, pain and edema in mammary gland in many clinical cases. Positive coagulase S. aureus is a major pathogen of the bovine mammary gland and a common cause of contagious mastitis in cattle. The aim of this study was to evaluate the outbreaks of Staphylococcus aureus mastitis. This study is conducted in ten dairy herds about one thousand cows. After doing CMT and identifying infected cows, the milk samples obtained from infected teats and transported to microbiological laboratories. After microbial culture of milk samples and isolating S. aureus, antimicrobial, sensitivity test was performed with disk diffusion method by ciprofloxacin, co-amoxiclav, erythromycin, penicillin, oxytetracyclin, sulfonamides, lincomycin and cefquinome. The study defined that the outbreak of subclinical positive coagulase Staphylococcus mastitis in dairy herd was 13.11% (5.6% S. aureus and 7.51% S. intermedicus). The antimicrobial sensitivity test shown that 87.23% of Staphylococcus aureus isolated from bovine mastitis in dairy herd was susceptible to ciprofloxacin, 93.9% to cefquinome, 4.67% to co-amoxiclav, 12.16% to erythromycin 86.11% to sulfonamides (co-trimoxazole), 3.35% lincomycin, 12.7% to oxytetracyclin and 5.98% to penicillin. Results of present defined that ciprofloxacin has a great effect on Staphylococcus aureus isolated from subclinical bovine mastitis dairy herd. It seems that cefquinome sulfonamides has a great effect on isolated Staphylococcus aureus in vivo.

Keywords: ciprofloxacin, mastitis, Staphylococcus aureus, dairy herd

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89 Calculation of Secondary Neutron Dose Equivalent in Proton Therapy of Thyroid Gland Using FLUKA Code

Authors: M. R. Akbari, M. Sadeghi, R. Faghihi, M. A. Mosleh-Shirazi, A. R. Khorrami-Moghadam

Abstract:

Proton radiotherapy (PRT) is becoming an established treatment modality for cancer. The localized tumors, the same as undifferentiated thyroid tumors are insufficiently handled by conventional radiotherapy, while protons would propose the prospect of increasing the tumor dose without exceeding the tolerance of the surrounding healthy tissues. In spite of relatively high advantages in giving localized radiation dose to the tumor region, in proton therapy, secondary neutron production can have significant contribution on integral dose and lessen advantages of this modality contrast to conventional radiotherapy techniques. Furthermore, neutrons have high quality factor, therefore, even a small physical dose can cause considerable biological effects. Measuring of this neutron dose is a very critical step in prediction of secondary cancer incidence. It has been found that FLUKA Monte Carlo code simulations have been used to evaluate dose due to secondaries in proton therapy. In this study, first, by validating simulated proton beam range in water phantom with CSDA range from NIST for the studied proton energy range (34-54 MeV), a proton therapy in thyroid gland cancer was simulated using FLUKA code. Secondary neutron dose equivalent of some organs and tissues after the target volume caused by 34 and 54 MeV proton interactions were calculated in order to evaluate secondary cancer incidence. A multilayer cylindrical neck phantom considering all the layers of neck tissues and a proton beam impinging normally on the phantom were also simulated. Trachea (accompanied by Larynx) had the greatest dose equivalent (1.24×10-1 and 1.45 pSv per primary 34 and 54 MeV protons, respectively) among the simulated tissues after the target volume in the neck region.

Keywords: FLUKA code, neutron dose equivalent, proton therapy, thyroid gland

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88 Relevance of Dosing Time for Everolimus Toxicity on Thyroid Gland and Hormones in Mice

Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

Abstract:

Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

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