Search results for: parathyroid gland

Authors: Branka Milicic Stanic, Romana Mijovic

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In primary hyperparathyroidism, an increased risk of developing cardiovascular disease may exist due to increased activity of the renin-angiotensin-aldosterone system (RAAS). In adenomatous altered tissue of parathyroid gland, compared to normal tissue, there are two to fourfold increase in the expression of type 1 angiotensin II receptors. As there is a clear evidence of the independent role of aldosterone on the cardiovascular system, the aim of this study was to evaluate the existence of an association between aldosterone secretion and parathyroid hormone in patients with primary hyperparathyroidism. This study included 48 patients with elevated parathyroid hormone who had come to the Departement of Nuclear Medicine, Clinical Center of Vojvodina, for Parathyroid Scintigraphy. The control group consisted of 30 healthy subjects who matched age and gender to the study group. All the results were statistically processed by statistical package STATISTICA 14 (Statsoft Inc,Tulsa, OK, USA). The survey was conducted between February 2017 and April 2018 at the Departement of Nuclear Medicine and at the Departement for Endocinology Diagnoistics, in Clinical Center of Vojvodina, Novi Sad. Compared to the control group, the study group had statistically significantly higher values of aldosterone (p=0.028), total calcium (p=0.01), ionized calcium (p=0.003) and parathyroid hormone (N-TACT PTH) (p=0.00), while statistically a significant lower levels in the study group were for phosphorus (p=0.003) and vitamin D (p=0.04). A linear correlation analysis in the study group revealed a statistically significant degree of positive correlation between renin and N-TACT PTH (r=0.688, p<0.05); renin and calcium (r=0.673, p<0.05) and renin and ionized calcium (r=0.641, p<0.05). Serum aldosterone and parathyroid hormone levels (N-TACT) were correlated positively in patients with primary hyperparathyroidism (r=0.509, p<0.05). According to the linear correlation analysis in the control group, aldosterone showed no positive correlation with N-TACT PTH (r=-0.285, p>0.05), as well as total and ionized calcium (r=-0.200, p>0.05; r=-0.313, p>0.05). In multivariate regression analysis of the study group, the strongest predictive variable of aldosterone secretion was N-TACT PTH (p=0.011). Aldosterone correlated positively to PTH levels in patients with primary hyperparathyroidism, and the fact is that in these patients aldosterone might be a key mediator of cardiovascular symptoms. All this knowledge should help to find new treatments to prevent cardiovascular disease.

Keywords: aldosterone, hyperparathyroidism, parathyroid hormone, parathyroid gland

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Authors: Antarip Bhattacharya, Dhritiman Maitra

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Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia due to autonomous production of parathormone (PTH) and the third most common endocrine disorder. Upto 2% of postmenopausal women could have this condition. Primary hyperparathyroidism is characterized by hypercalcemia with a high or insufficiently suppressed level of parathyroid hormone and is caused by a solitary parathyroid adenoma in 85-90% of patients. PHPT may also be caused by parathyroid hyperplasia (involving multiple glands) or parathyroid carcinoma. Associated morbidities and sequelae include decreased bone mineral density, fractures, kidney stones, hypertension, cardiac comorbidities and psychiatric disorder which entail huge costs for treatment. In the year 2021, by virtue of running a Breast and Endocrine Surgery clinic in a Tier 1 city at a tertiary care hospital, the opportunity to be associated with patients of hyperparathyroidism came our way. Here, we shall describe the spectrum of clinical presentations and customisation of treatment for parathyroid diseases with reference to the above patients. A retrospective analysis of the data of all patients presenting with symptoms of parathyroid diseases was made and classified according to the cause. 13 patients had presented with symptoms of hyperparathyroidism and each case presented with unique symptoms and necessitated detailed evaluation. The treatment or surgery offered to each patient was tailored to his/her individual disease and led to favourable outcomes. Diseases affecting parathyroid are not as rare as we believe. Each case merits detailed clinical evaluation, investigations and tailoring of suitable treatment with regard to medical management and extent of surgery. Intra-operative frozen section/iOPTH monitoring are really useful adjuncts for intra-operative decision making.

Keywords: hyperparathyroidism, parathyroid adenoma, parathyroid surgery, PTH

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Authors: Augustina Konadu Larbi-Ampofo, Ekemini Umoinwek

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Background: Hypercalcaemia is a common electrolyte imbalance that increases mortality if poorly controlled. Primary hyperparathyroidism often presents like this with a prevalence of 0.1-0.3%. Management due to an ectopic parathyroid adenoma in the mediastinum is challenging, especially in a patient with a pacemaker. Case Presentation: A 79-year-old woman with a history of a previous cardiac arrest, permanent pacemaker, ischaemic heart disease, bilateral renal calculi, rectal polyps, liver cirrhosis, and a family history of hyperthyroidism presented to the emergency department with acute back pain. Management and Outcome: The patient was diagnosed with primary hyperparathyroidism due to her elevated corrected calcium and parathyroid hormone levels. Parathyroid investigations consisting of an NM MIBI scan, SPECT-CT, 4D parathyroid scan, and an ultrasound scan of the neck and thorax confirmed an ectopic parathyroid adenoma in the mediastinum at the level of the aortic arch, along with benign thyroid nodules. The location of the adenoma warranted a thoracoscopic surgical approach; however, the presence of her pacemaker and other cardiovascular conditions predisposed her to a potentially poorer post-operative outcome. Discussion: Mediastinal ectopic parathyroid adenomas are rare and difficult to diagnose and treat, often needing a multimodal imaging approach for accurate localisation. Surgery is a definitive treatment; however, in this patient, long-term medical treatment with cinacalcet was the only next suitable treatment option. The difficulty with this is that cinacalcet tackles the biochemical markers of the disease entity and not the disease itself, leaving room for what happens next if there is refractory/uncontrolled hypercalcaemia in this patient with a pacemaker. Moreover, the coexistence of her multiple conditions raises the suspicion of an underlying multisystemic or multiple endocrine disorder, with multiple endocrine neoplasia coming to mind, necessitating further genetic or autoimmune investigations. Conclusion: Mediastinal ectopic parathyroid adenomas are rare, with diagnostic and management challenges.

Keywords: mediastinal ectopic parathyroid adenoma, hyperparathyroidism, SPECT/CT, nuclear medicine, multimodal imaging

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Authors: Awf A. Al-Khan, Michael J. Day, Judith Nimmo, Mourad Tayebi, Stewart D. Ryan, Samantha J. Richardson, Janine A. Danks

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Osteosarcoma (OS) is the most common type of malignant primary bone tumour in dogs. In addition to their critical roles in bone formation and remodeling, parathyroid hormone-related protein (PTHrP) and its receptor (PTHR1) are involved in progression and metastasis of many types of tumours in humans. The aims of this study were to determine the localisation and expression levels of PTHrP and PTHR1 in canine OS tissues using immunohistochemistry and to investigate if this expression is correlated with survival time. Formalin-fixed, paraffin-embedded tissue samples from 44 dogs with known survival time that had been diagnosed with primary osteosarcoma were analysed for localisation of PTHrP and PTHR1. Findings showed that both PTHrP and PTHR1 were present in all OS samples. The dogs with high level of PTHR1 protein (16%) had decreased survival time (P<0.05) compared to dogs with less PTHR1 protein. PTHrP levels did not correlate with survival time (P>0.05). The results of this study indicate that the PTHR1 is expressed differently in canine OS tissues and this may be correlated with poor prognosis. This may mean that PTHR1 may be useful as a prognostic indicator in canine OS and could represent a good therapeutic target in OS.

Keywords: dog, expression, osteosarcoma, parathyroid hormone receptor 1 (PTHR1), parathyroid hormone-related protein (PTHrP), survival

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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

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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

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Authors: Rajish Shil, Mohammad Ali Houri, Mohammad Milad Ismail, Fatimah Al Kaabi

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The clinical presentation of Primary hyperparathyroidism can vary from simple asymptomatic hypercalcemia to severe life-threatening hypercalcemic crisis with multi-organ dysfunction, which can be due to parathyroid adenoma or sometimes with malignant cancer. This cascade of clinical presentation can lead to a diagnostic and therapeutic challenge for treating the disease. We are presenting a case of severe hypercalcemic crisis due to parathyroid adenoma with an emphasis on early management, diagnosis, and interventions to prevent any lifelong complications and any permanent organ dysfunction. A 30 years old female with a history of primary Infertility, admitted to Al Ain Hospital critical care unit with Acute Severe Necrotizing Pancreatitis. She initially had a 1-month history of abdominal pain on and off, for which she was treated conservatively with no much improvement, and later on, she developed life-threatening severe pancreatitis, which required her to be admitted to the critical care unit. She was transferred from a private healthcare facility, where she was found to have a very high level of calcium up to 15mmol/L. She received systemic Zoledronic Acid, which lowered her calcium level transiently and later was increased again. She went on to develop multiple end-organ damages along with multiple electrolytes disturbances. She was found to have high levels of Parathyroid hormone, which was correlated with a parathyroid mass on the neck via radiological imaging. After a long course of medical treatment to lower the calcium to a near-normal level, parathyroidectomy was done, which showed parathyroid adenoma on histology. She developed hungry bone syndrome after the surgery and pancreatic pseudocyst after resolving of pancreatitis. She required aggressive treatment with Intravenous calcium for her hypocalcemia as she received zoledronic acid at the beginning of the disease. Later on, she was discharged on long term calcium and other electrolytes supplements. In patients presenting with hypercalcemia, it is prudent to investigate and start treatment early to prevent complications and end-organ damage from hypercalcemia and also to treat the primary cause of the hypercalcemia, with conscious follow up to prevent hypocalcemic complications after treatment. It is important to follow up patients with parathyroid adenomas for a long period in order to detect any recurrence of the tumor or to make sure if the primary tumor is either benign or malignant.

Keywords: hypercalcemia, pancreatitis, hypocalcemia, hyperparathyroidism

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Authors: Sara Ataei, Mohammad Bagher Oghazian, Mania Radfar

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We describe a patient with hypercalcemia associated with the injection of high doses vitamin D as supplement for a period of six months. A 76-year-old woman had been taking an intramuscular injection of vitamin D 300,000 IU every ten days for six months. She was hospitalized with symptoms of hypercalcemia: chronic constipation, unstable gait, a chronic generalized musculoskeletal pain and increased fatigue. On admission her 25 (OH) vitamin D and Calcium levels were 559 nmol/L and 13.85 mg/dL respectively, and Parathyroid Hormone (PTH) level was 7.1 pg/mL. Immediately she received diuresis therapy with saline and furosemide in conjunction with calcitonin and pamidronate. At discharge her serum calcium level was 11.5 mg/dL. To lower endogenous overproduction of calcitriol, prednisolone 20 mg/day for 10 days was administered at discharge time.

Keywords: vitamin D, hypercalcemia, vitamin D toxicity, parathyroid hormone

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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

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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

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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

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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

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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

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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

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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

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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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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

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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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Authors: Gehan ElAkabawy

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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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Authors: A. Bouaouiche, M. S. Boulakoud

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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

Procedia PDF Downloads 476

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

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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

Procedia PDF Downloads 155

Authors: Nazmul Haque, Syeda Tasnuva Maria

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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

Procedia PDF Downloads 58

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

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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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Authors: Rai Sachindra Prasad

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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

Procedia PDF Downloads 372

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

Procedia PDF Downloads 634

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

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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

Procedia PDF Downloads 425

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

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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

Procedia PDF Downloads 349

Authors: H. El-Messiry, M. El-Zainy, D. Ghazy

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Diabetes is a metabolic disease that results in a variety of oral health complications. Green tea is a natural antioxidant proved to have powerful effects against diabetes. The aim of this study was to compare between the effect of insulin and green tea on the Parotid gland of streptozotocin induced diabetic Albino rats by using light and transmission electron microscopy. Forty male Albino rats were divided into control group and diabetic groups. The diabetic group received a single injection of 40 mg/kg of streptozotocin intra-peritoneal under anesthesia and was further subdivided into three subgroups: The diabetic untreated subgroup which was untreated for two weeks, the insulin treated subgroup which has received insulin subcutaneously in a daily dose of 5 IU/kg body weight/day for two weeks and a green tea treated subgroup received a daily dose of 1 ml/ 100 gm body weight intragastrically for two weeks. Rats were terminated and parotid glands were dissected and processed for light and transmission electron microscopic examination. Histological examination of the diabetic untreated subgroup revealed acinar cells with pyknotic and hyperchromatic nuclei with cytoplasmic vacuolations. Ultrastructurally, acinar cells showed nuclear pleomorphism, dilated rough endoplasmic reticulum and swollen mitochondria with damaged cristae. Inflammatory cell infiltration was detected both histologically and ultrastructurally. Ducts showed signs of degeneration with loss of their normal outline and stagnated secretion within the lumen. However, insulin and green tea treated subgroups showed minimal degenerative damage and were almost similar to the control with minimal changes. Treatment of the parotid gland of the streptozotocin induced diabetic rats with GT was closely comparable to the traditional insulin therapy in reducing signs of histological and ultrastructural damage.

Keywords: diabetes, green tea, insulin, parotid

Procedia PDF Downloads 177

Authors: Antonela Matana, Dubravka Brdar, Vesela Torlak, Marijana Popovic, Ivana Gunjaca, Ozren Polasek, Vesna Boraska Perica, Maja Barbalic, Ante Punda, Caroline Hayward, Tatijana Zemunik

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Parathyroid hormone (PTH) plays a critical role in the regulation of bone mineral metabolism and calcium homeostasis. Higher PTH levels are associated with heart failure, hypertension, coronary artery disease, cardiovascular mortality and poorer bone health. A twin study estimated that 60% of the variation in PTH concentrations is genetically determined. Only one GWAS of PTH concentration has been reported to date. Identified loci explained 4.5% of the variance in circulating PTH, suggesting that additional genetic variants remain undiscovered. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels in a general population. We have performed a GWAS meta-analysis on 2596 individuals originating from three Croatian cohorts: City of Split and the Islands of Korčula and Vis, within a large-scale project of “10,001 Dalmatians”. A total of 7 411 206 variants, imputed using the 1000 Genomes reference panel, with minor allele frequency ≥ 1% and Rsq ≥ 0.5 were analyzed for the association. GWAS within each data set was performed under an additive model, controlling for age, gender and relatedness. Meta-analysis was conducted using the inverse-variance fixed-effects method. Furthermore, to identify sex-specific effects, we have conducted GWAS meta-analyses analyzing males and females separately. In addition, we have performed biological pathway analysis. Four SNPs, representing one locus, reached genome-wide significance. The most significant SNP was rs11099476 on chromosome 4 (P=1.15x10-8), which explained 1.14 % of the variance in PTH. The SNP is located near the protein-coding gene RASGEF1B. Additionally, we detected suggestive association with SNPs, rs77178854 located on chromosome 2 in the DPP10 gene (P=2.46x10-7) and rs481121 located on chromosome 1 (P=3.58x10-7) near the GRIK1 gene. One of the top hits detected in the main meta-analysis, intron variant rs77178854 located within DPP10 gene, reached genome-wide significance in females (P=2.21x10-9). No single locus was identified in the meta-analysis in males. Fifteen biological pathways were functionally enriched at a P<0.01, including muscle contraction, ion homeostasis and cardiac conduction as the most significant pathways. RASGEF1B is the guanine nucleotide exchange factor, known to be associated with height, bone density, and hip. DPP10 encodes a membrane protein that is a member of the serine proteases family, which binds specific voltage-gated potassium channels and alters their expression and biophysical properties. In conclusion, we identified 2 novel loci associated with PTH levels in a general population, providing us with further insights into the genetics of this complex trait.

Keywords: general population, genome-wide association analysis, parathyroid hormone, single nucleotide polymorphisms.

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Authors: Ritesh Verma, Manisha Rathi, Chand Singh Dhull, Sumit Sachdeva, Jitender Phogat

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A Rathke's cleft cyst is a benign growth found on the pituitary gland in the brain, specifically a fluid-filled cyst in the posterior portion of the anterior pituitary gland. It occurs when the Rathke's pouch does not develop properly and ranges in size from 2 to 40mm in diameter. A 38-year-old male presented to the outpatient department with loss of vision in the inferior quadrant of the left eye since 15 days. Visual acuity was 6/6 in the right eye and 6/9 in the left eye. Visual field analysis by HFA-24-2 revealed an inferior field defect extending to the supero-temporal quadrant in the left eye. MRI brain and orbit was advised to the patient and it revealed a well defined cystic pituitary adenoma indenting left optic nerve near optic chiasm consistent with the diagnosis of Rathke’s cleft cyst (RCC). The patient was referred to neurosurgery department for further management. Symptoms vary greatly between individuals having RCCs. RCCs can be non-functioning, functioning, or both. Besides headaches, neurocognitive deficits are almost always present but have a high rate of immediate reversal if the cyst is properly treated or drained.

Keywords: pituitary tumors, rathke’s cleft cyst, visual field defects, vision loss

Procedia PDF Downloads 205