Abnormal Secretion Research Articles

The Effect of Family Support in Nutrition Education on Dietary Adherence and Blood Glucose Levels of Type 2 Diabetes Mellitus Inpatients at Panti Rapih Hospital Yogyakarta

Diabetes mellitus is included in the group of metabolic diseases with characteristics of hyperglycemia that occurs due to abnormalities in insulin secretion and function or both. According to the Association of Diabetes Care and Education Specialists, there are 7 pillars of diabetes mellitus management that can be done, one of which is providing nutritional education. The purpose of this study was to determine an effect of family support in nutritional education on dietary compliance and blood glucose levels of type 2 diabetes mellitus at Panti Rapih Hospital, Yogyakarta. This study used a quantitative research design with a quasy experiment design with an accidental sampling method with a sample size of 34 diabetes mellitus inpatients divided into control and experimental groups. The variables of this study will be analyzed using SPSS, with the T-Paired Test and T-Independent Sample Test. Based on the statistical results, the effect of education on dietary compliance in the control and experimental groups showed a p value of 0.000 <0.05. While the statistical results of the effect of education on blood glucose levels in the control group showed a p value of 0.002 <0.05, in the experimental group the results of the p value were 0.001 <0.05. However, based on the results of the statistical test on the difference in compliance scores, a p value of 0.000 <0.05 was obtained. While the results of the statistical test of blood glucose levels obtained a p value of 0.315> 0.05. It can be concluded that family support in providing nutritional education can influence the increase in compliance scores for following a diet but does not affect blood glucose levels in type 2 diabetes mellitus patients at Panti Rapih Hospital, Yogyakarta.

Targeting RACGAP1 suppresses growth hormone pituitary adenoma growth.

Growth hormone pituitary adenoma (GHPA) is a major subtype of pituitary adenoma (PA), with tumor enlargement and abnormal secretion of growth hormone (GH) often causing complications. Rac GTPase-activating protein 1 (RACGAP1), a member of the guanine triphosphatase-activating protein family, is highly overexpressed in multiple tumors and promotes tumor growth. However, the role of RACGAP1 in GHPA remains unelucidated. Besides, specific inhibitors targeting RACGAP1 have not yet been developed. In this study, we aimed to determine the expression and function of RACGAP1 in GHPA and identify effective inhibitors against RACGAP1. Immunohistochemistry was used to detect the expression of RACGAP1 in GHPA and normal pituitary tissues. The effect of RACGAP1 on cell proliferation, apoptosis, and cell cycle was evaluated by knockdown of RACGAP1 in GH3 cells in vitro and xenograft models of GHPA in vivo. The downstream mechanism of RACGAP1 was explored by RNA sequencing, bioinformatic analysis, and Western blot. Inhibitors targeting RACGAP1 were screened and verified through a structure-based virtual docking method, cell viability assays, and surface plasmon resonance (SPR) experiments. RACGAP1 expression was increased in GHPA compared with normal pituitary tissues. Knocking down RACGAP1 suppressed cell growth in vitro and in vivo. Preliminary mechanism studies indicated that inhibition of RACGAP1 led to the upregulation of p21 and the downregulation of several genes involved in the cell cycle signaling pathway, such as Cyclin A, CDK1, and CDK2. Moreover, DB07268 was identified for the first time as an effective RACGAP1 inhibitor that could prominently restrain the proliferation of GH3 cells. This study demonstrates that RACGAP1 plays a critical role in GHPA, highlighting the novel inhibitor DB07268 as a promising therapeutic approach.

Dysregulation of dopamine neurotransmission in drug addicts: implications for criminal behavior and corrective interventions

Drug addiction often correlates with criminal behavior. When investigating criminal behavior among individuals grappling with drug addiction, it becomes crucial to scrutinize the influence of dopamine. Substances such as heroin, morphine, methamphetamine and other drugs can cause abnormal dopamine secretion when people are addicted to them, which promotes changes in the brain’s reward circuit and emotional balance, thereby increasing susceptibility to criminal behavior. The pivotal role of dopamine within the reward pathway and its regulatory function in emotional processes exert profound influence on behavior following drug simulation. These influences are primarily manifested by three distinct attributes: a singular criminal motive and objective, lack of moral sense, and impulsive decision-making processes. Drawing upon the distinctive dopaminergic dynamics inherent in individuals afflicted by drug addiction, this study advocates for targeted corrective interventions. The preventive paradigm encompasses the cultivation of supportive community environments, the establishment of comprehensive databases, and providing legal education and protection, among other initiatives. In terms of treatment, along with judicial sanctions and protections, exercise regimens and psychotherapeutic interventions are advocated. The corrective endeavor necessitates a synergistic integration of community-based and legalistic frameworks. The objective is to furnish guiding principles for tackling criminal behavior precipitated by aberrant dopamine secretion, underpinned by a scientifically informed approach.

Acupoint injection inhibiting abnormal secretion of mucin and inflammatory reaction of nasal mucosa in rats with allergic rhinitis through the p38 mitogen-activated protein kinase pathway

To observe the effects of acupoint injection on the expression of p38 mitogen-activated protein kinase (MAPK), phosphorylated (p)-p38 MAPK, mucin 5 subtype AC (MUC5AC) in the nasal mucosa, and serum inflammatory factors of rats with allergic rhinitis, so as to explore the mechanism of acupoint injection in improving inflammatory reactions in the nasal mucosa of rats with allergic rhinitis. SD rats were randomly divided into the normal group, model group, acupoint injection group, and non-acupoint group, with 7 rats in each group. The allergic rhinitis rat model was established using ovalbumin sensitization. Intervention was performed by injecting dexamethasone and 1% lidocaine mixture (0.05 mL) into the bilateral "Yingxiang"(LI20) and "Yintang"(GV24+) acupoints, with injection at non-acupoints for non-acupoint group as the control, once every 3 days for a total of 4 times. Allergic symptoms in the rat nose were evaluated using a cumulative scoring method；histopathological changes in the nasal mucosa were observed after HE staining；serum histamine (HA), interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-α) contents were detected using ELISA；real-time fluorescent quantitative PCR was used to detect the expression of MUC5AC mRNA in the nasal mucosa；Western blot was used to detect the expression of p38 MAPK, p-p38 MAPK, and MUC5AC protein in the nasal mucosa. Compared with the normal group, nasal allergic symptom score, serum HA, IL-6, IL-8, and TNF-α contents, nasal mucosal p38 MAPK, p-p38 MAPK proteins expression, MUC5AC mRNA and protein expression were significantly increased(P<0.01) in the model group. Compared with the model group and non-acupoint group, nasal allergic symptom score, serum HA, IL-6, IL-8, and TNF-α contents, nasal mucosal p38 MAPK and p-p38 MAPK proteins expression, MUC5AC mRNA and protein expression were significantly reduced (P<0.01, P<0.05) in the acupoint injection group. Acupoint injection can reduce nasal allergic symptom, and MUC5AC secretion in rats with allergic rhinitis, alleviate nasal mucosal inflammatory reactions, and its mechanism of action may be related to the inhibition of p38 MAPK phosphorylation, thereby reducing the release of inflammatory factors.

Transforming growth factor-β3/Smad2/Smad3 signaling pathway inhibition and autophagy by the Yunpi-Xiefei-Huatan decoction ameliorated airway inflammation and mucus hypersecretion in asthmatic rats

Ethnopharmacological relevanceThe Yunpi-Xiefei-Huatan decoction (YXHD) is a traditional Chinese medicine that can improve asthma-related symptoms, including cough, phlegm in the throat, and shortness of breath. However, the YXHD mechanism on asthma has not yet been elucidated. Study aimThe aim of this study is to investigate the effect of YXHD on airway inflammation, mucus hypersecretion, and autophagy modulation in asthma. Materials and methodsThe YXHD chemical constituents were observed and analyzed using high-performance liquid chromatography-mass spectrometry. Ovalbumin sensitization and stimulation were used to establish an asthma rat model. A total of 80 Sprague-Dawley (SD) rats were segmented into eight groups at random: a Normal (NC) group, a Model (Mod) group, a YXHD low-dose group (10 g/kg/d), a YXHD moderate-dose group (20 g/kg/d), a YXHD high-dose group (40 g/kg/d), a Rapamycin group (4 mg/kg/d), a 3-methyladenine (3-MA) group (15 mg/kg/d), and a Dexamethasone (DEX) group (0.5 mg/kg/d). Whole-body plethysmography (WBP) detection was used to evaluate airway hyperresponsiveness. An enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory factors in the peripheral blood. Inflammatory cells in the bronchoalveolar lavage fluid (BALF) were also counted. Pathological changes in the lung tissues were marked using hematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining. The localization of MUC5AC and the co-localization of LC3B + MUC5AC were observed using immunofluorescence. The expressions of autophagy and the TGF-β3/Smad2/Smad3 pathway in the lung tissues were detected using a Western blot assay (WB) and qPCR, and the autophagosomes in the lung tissues were detected using a transmission electron microscope (TEM). ResultsTwenty signal peaks were identified using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) technology. The TGF-β3/Smad2/Smad3 signal pathway activation was induced using ovalbumin (OVA) exposure in the rats. The upregulated expression of autophagy, enhanced MUC5AC fluorescence and LC3B fluorescence, and their co-localized expression in the airway epithelium indicated inflammatory cell infiltration and excessive mucus secretion in the lungs. This resulted in airway hyper-responsiveness. The YXHD inhibited the activation of the TGF-β3/Smad2/Smad3 signaling pathway, and autophagy expression reduced inflammatory factors, abnormal mucus secretion, and airway hyperresponsiveness. ConclusionThe YXHD improved lung function, relieved lung inflammation, and inhibited airway mucus secretions in asthmatic rat models. Its mechanism may have been related to the blockage of the TGF-β3/Smad2/Smad3 signaling pathway and autophagy downregulation.

Adipose Tissues Have Been Overlooked as Players in Prostate Cancer Progression.

Obesity is a common risk factor in multiple tumor types, including prostate cancer. Obesity has been associated with driving metastasis, therapeutic resistance, and increased mortality. The effect of adipose tissue on the tumor microenvironment is still poorly understood. This review aims to highlight the work conducted in the field of obesity and prostate cancer and bring attention to areas where more research is needed. In this review, we have described key differences between healthy adipose tissues and obese adipose tissues, as they relate to the tumor microenvironment, focusing on mechanisms related to metabolic changes, abnormal adipokine secretion, altered immune cell presence, and heightened oxidative stress as drivers of prostate cancer formation and progression. Interestingly, common treatment options for prostate cancer ignore the adipose tissue located near the site of the tumor. Because of this, we have outlined how excess adipose tissue potentially affects therapeutics' efficacy, such as androgen deprivation, chemotherapy, and radiation treatment, and identified possible drug targets to increase prostate cancer responsiveness to clinical treatments. Understanding how obesity affects the tumor microenvironment will pave the way for understanding why some prostate cancers become metastatic or treatment-resistant, and why patients experience recurrence.

TMOD-06. ESTABLISHMENT OF PITUITARY NEUROENDOCRINE TUMOR (PITNET) ORGANOID MODELS

Abstract Pituitary neuroendocrine tumors (PitNETs) are tumors that originate from the anterior pituitary gland. While they are mostly benign, they can cause various clinical symptoms due to hormonal secretion abnormalities. PitNET can be broadly categorized into three lineages, each of which has its differentiation controlled by specific transcription factors. Treatment options for PitNET include surgical resection and pharmacotherapy, but available drugs are limited, and their efficacy markers remain unclear. To develop novel drugs for PitNET and identify their efficacy markers, it is necessary to develop new research models. In recent years, organoid models have garnered attention as novel research models for various cancer types. In this study, we established novel organoid models derived from PitNET patients and analyzed their histological and endocrinological characteristics. Surgical specimens from 4 cases of somatotroph adenoma, 1 case of double adenoma, 1 case of gonadotroph adenoma, and 1 case of corticotroph adenoma were minced in dissection medium and embedded in Matrigel basement membrane matrix respectively. The organoids were cultured under 5% CO2 at 37°C using media supplemented with various growth factors. After 28 days of culture, formalin-fixed paraffin-embedded sections were prepared to examine histological homology with patient tumors. Hematoxylin and eosin staining results showed that all organoids maintained cell morphology and tissue structure similar to the original tumors. Immunohistochemical staining for markers specific to each PitNET revealed similar staining patterns between the organoids and the original tumors. Furthermore, analysis of hormone levels in the culture medium showed that hormone production capabilities, such as growth hormone and follicle stimulating hormone, were maintained even after long-term culture. In this study, we successfully established PitNET organoid models that retain histological and endocrinological characteristics. These models are expected to serve as useful research tools for elucidating the molecular mechanisms of PitNET and developing novel therapies targeting critical molecular abnormalities.

AKK-derived outer membrane vesicles alleviate indomethacin-induced mucin secretion reduction in LS174T cells by inhibiting endoplasmic reticulum stress.

AKK-derived outer membrane vesicles (AKK-OMVs) have shown potential in modulating intestinal mucosal immunity by increasing the number of intestinal goblet cells. However, it remains unclear whether AKK-OMVs can directly regulate MUC2 secretion in goblet cells exposed to indomethacin in vitro and the underlying mechanisms involved. The abnormal mucin secretion model in LS174T cells was established using indomethacin, with treatment including Akkermansia muciniphila (AKK) supernatant, AKK-OMVs, and extracellular vesicle removal supernatant. The effects of these treatment on MUC2 expression were observed. Transcriptomic sequencing analysis was used to explore the underlying regulatory mechanisms, which were further validated through qRT-PCR and western blotting. The treatment with AKK supernatant and AKK-OMVs alleviated the indomethacin-induced reduction in MUC2 secretion in goblet cells. Mechanistically, transcriptomic analysis showed that the gene expression associated with endoplasmic reticulum (ER) stress were upregulated after indomethacin treatment in LS174T cells. This suggests that AKK-OMVs, as the active component in the supernatant, improved MUC2 expression by inhibiting ER stress. AKK-OMVs can directly stimulate goblet cells to promote MUC2 secretion, providing potential for further in vivo studies to confirm their protective effects against indomethacin-induced intestinal injury.

Biofilm Forming Intestinal Escherichia coli as a Risk Factor for Increasing BMI in Type 2 Diabetic Patients

Biofilm Forming Intestinal Escherichia coli as a Risk Factor for Increasing BMI in Type 2 Diabetic Patients

Hubungan Antara Kadar HbA1c dengan Kadar Trigliserida terhadap Pasien Prolanis Diabetes Melitus Tipe 2 di Laboratorium Klinik Kimia Farma Depok

Diabetes Mellitus (DM) is a group of metabolic disorders characterized by elevated blood glucose levels resulting from abnormalities in insulin secretion, insulin action, or both. Patients with Type 2 DM are at a higher risk of developing cardiovascular diseases, often indicated by dyslipidemia, which is characterized by elevated triglyceride levels, increased Low-Density Lipoprotein (LDL) levels, and decreased High-Density Lipoprotein (HDL) levels. This study employs an analytical observational design. The data obtained shows that controlled and uncontrolled HbA1c levels with normal triglyceride levels were found in 24.7% of the patients, while 75.3% had high triglyceride levels. The data were further analyzed using the Statistical Package for the Social Sciences 25 (SPSS 25) with a non-parametric test, specifically the Chi-Square continuity correction test, with a significance level of p 0.05. The Chi-Square test results indicated that H0 was rejected and Ha was accepted, with a p-value of 0.036 for the relationship between HbA1c and triglycerides. These results suggest a correlation between HbA1c levels and triglyceride levels in Prolanis Type 2 DM patients at Kimia Farma Clinical Laboratory in Depok. These findings can serve as an evaluation material for Prolanis DM Type 2 patients to control their glycemic levels by routinely monitoring their HbA1c and triglyceride levels.

Negative pressure assisted rubbing suction technique for the treatment of axillary osmidrosis based on minimally invasive principle

BackgroundAxillary Osmidrosis is highly prevalent and occurr in adolescents, bilateral onset, its pathogenesis is related to abnormal secretion function of apocrine glands, with a significant genetic predisposition, the patient's bilateral armpit area can smell a spicy pungent odor, although it does not affect the health, but it is inconvenient to life, socialize. Patients are often accompanied by low self-esteem and urgently require treatment, and most of them have the requirement of minimally invasive treatment and minimal scarring. MethodIn this study, we aimed to evaluate the efficacy of minimally invasive treatment of axillary osmidrosis with refined negative pressure-assisted rubbing suction technique. From August 2022 to August 2023, 50 patients (28 females and 22 males) with axillary osmidrosis were treated with refined negative pressure-assisted rubbing suction technique. HE staining of the tissue rubbed out of six of these patients showed a large amount of apocrine gland. ResultsIn the subjective evaluation of 50 (100 sides) patients, 66 sides (66 %) were very satisfied with the results of the treatment, 30 sides (30 %) were satisfied, and 4 sides (4 %) were dissatisfied. Clinical efficacy evaluation showed that 74 sides (74 %) of patients rated the results as cured, 18 sides (18 %) as significantly effective, 4 sides (4 %) as effective, and 4 sides (4 %) as ineffective. No serious surgical complications occurred except for the occurrence of Subcutaneous hydrops and hematoma on 6 sides. ConclusionsRefined negative pressure-assisted rubbing suction technique is an easy and effective method for minimally invasive treatment of axillary hyperhidrosis and deserves clinical promotion.

7574 Diabetes Stem Cells: A Common Target for Abnormal Insulin Secretion and Insulin Resistance

Abstract Disclosure: H. Kojima: None. M. Katagi: None. J. Okano: None. T. Nakagawa: None. Diabetes is based on chronic inflammation and cannot be cured using only drugs that lower blood glucose levels. A culprit was lurking there that was hindering healing. We discovered abnormal hematopoietic stem cells that caused persistent chronic inflammation in the bone marrow of diabetic model animals. The real culprit is born after several days of hyperglycemia, never dies, and each time glycemic control deteriorates, it moves its progeny in large numbers throughout the body, fusing with unique cells in various organs and producing TNF-α from the organ cells. We have named these worst stem cells, which resemble cancer stem cells, "diabetes stem cells," and attempted to induce complete remission in diabetic model animals by eliminating them with drugs. In this study, we used streptozotocin (STZ)-induced insulin-deficient diabetes model mice. "Diabetes stem cells" were included in the CD106-positive short-term hematopoietic stem cell fraction, in which progenitor cells that play an important role in the regeneration of the thymus and peripheral tissues, and were characterized by abnormal expression of proinsulin and TNF-α. Furthermore, like cancer cells, the expression of histone deacetylases (HDACs) increased, and once the cells were born, they would not disappear. Therefore, we aimed to eliminate diabetes by administering an HDAC inhibitor and subcutaneously injecting insulin pellets to temporarily correct blood glucose levels. We treated diabetic mice with HDAC inhibitor for 8 weeks, along with several weeks of insulin therapy. Insulin aims to prevent the formation of new abnormal cells in the bone marrow and to prevent the inhibition of pancreatic islet wasting due to the forced insulin secretion caused by hyperglycemia. The combination therapy allowed the beta cells to regenerate and produce enough insulin to normalize blood glucose levels and maintain them even after treatment was discontinued. It also solved the mystery of how the abnormal cell population evades attacks from the T cells. In STZ diabetes, the supply of normal CD106-positive progenitor cells from the bone marrow for thymic regeneration was completely blocked, resulting in marked thymic atrophy. As a result, the thymus, which had lost its progenitor cells, was unable to establish an immune surveillance system to eliminate mutated cells throughout the body. In other words, the combination therapy completely broke the vicious cycle caused by atrophies in both the islet and the thymus. Moreover, when the thymus was surgically removed along with the adventitia to prevent regeneration, diabetes remission was completely inhibited, supporting the importance of thymic normalization. Diabetes is a hematopoietic stem cell disease accompanied by thymic dysfunction, and the removal of "diabetes stem cells" paves the way for the cure of diabetes. Presentation: 6/2/2024

7822 Mild Autonomous Cortisol Secretion In High Suspicious Adrenal Incidentaloma

Abstract Disclosure: N. Zavrashvili: None. N. Margvelashvili: None. K. Chanturishvili: None. Mild Autonomous Cortisol Secretion in High Suspicious Adrenal IncidentalomaIntroduction: Incidentally discovered adrenal masses are common and mostly benign and non-functioning adenomas. However, evolving evidence suggests that a notable proportion of these adrenal adenomas may demonstrate mild autonomous cortisol secretion (MACS), which has been associated with an increased risk for hypertension, hyperglycemia, obesity, dyslipidemia, vertebral fractures, adverse cardiovascular events, and mortality. 55-year-old women with 5-year history of hypertension and hyperlipidemia. She was treated with a three-drug program: verapamil 250 mg daily, combined B-blocker, atenolol 100 mg and chlorthalidone 25 mg daily. Blood pressure control remained suboptimal. Her body mass index was 29,5 kg/m2. She had no signs or symptoms of overt Cushing syndrome.She was referred to CT coronary angiogram by her cardiologist, which revealed adrenal incidentaloma.Adrenal dedicated CT showed left-sided 3,4 cm high density node (41HU), with absolute washout &amp;lt;60. She was consulted by oncologist to exclude adrenal metastasis. The baseline laboratory test results excluded PA and Pheochromocytoma. The diagnosis of glucocorticoid secretory autonomy was based on positive low-dose dexamethasone suppression test (DST), low serum ACTH concentration, low-normal DHEA-S and lack of complete suppression of serum cortisol with an overnight 8-mg DST. Patient was referred to left-sided laparoscopic adrenalectomy with perioperative glucocorticoid coverage (100 mg hydrocortisone administered IV and again 8 hours later). Conclusion: Mild autonomous cortisol secretion is a term used to describe biochemical evidence of abnormal cortisol secretion in patients with adrenal incidentaloma, but without the classical external manifestations of overt CS, such as central muscle weakness, adipose tissue redistribution, and skin fragility. The management of patients with an incidentally discovered adrenal adenoma who do not have overt Cushing’s syndrome but who have MACS is more controversial as the available studies comparing outcomes of adrenalectomy vs conservative management have been generally small. It is associated with an increased risk of Type 2 diabetes mellitus, HBP, obesity, dyslipidemia, and global cardiovascular risk. Therefore, it is of great importance to correctly identify these patients. There are different tests for the screening of hypercortisolism. However, in the absence of a single test considered as the gold standard, it is necessary to combine the different tests to reach an adequate diagnostic capacity. The indication of surgery in ACS patients should be based mainly on the hormonal evaluation and the comorbidities potentially mediated by cortisol. Presentation: 6/1/2024

8686 scRNA-seq of pituitary from letrozole-induced PCOS mouse model reveals abnormal prolactin secretion

Abstract Disclosure: G. De Robles: None. N. Ujagar: None. Z. Del Mundo: None. D. Nicholas: None. Polycystic ovary syndrome (PCOS) has a complex pathophysiology and is the most common endocrine disorder among reproductive-aged women. Ovarian hormonal dynamics are regulated via the secretion of the gonadotropin-releasing hormone (GnRH), which stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gland. High serum levels of LH in PCOS patients indicate an increase in GnRH levels, but the mechanisms within the anterior pituitary at a cellular level are unclear. We performed single-cell mRNA sequencing (scRNA-seq) on the pituitaries of the letrozole-induced (LET) mouse model of PCOS to profile the functional genomics of endocrine cell populations relative to serum hormone levels. The population percentage of lactotropes significantly decreased; in contrast, two gonadotrope populations significantly increased in the LET mice compared to the placebo-treated mice. Consistent with these changes, an increasing trend of serum LH levels and a decreasing trend of serum prolactin (PRL) levels were observed in the LET mice, while no change occurred in serum growth hormone levels. A gene set enrichment analysis (GSEA) on the differentially expressed genes (DEGs) from the lactotropes revealed an association with negative regulation of protein kinase activity. These DEGs included Hspb1, Park7, Pcp4, and Ppia, which all share the function of mediating stress-induced apoptosis. A GSEA on the DEGs between the two gonadotrope clusters in the LET mice also confirmed a variation in biological pathways linked to ribosomal subunits, transcription regulation, and the regulation of steroid metabolic processes. Based on the scRNA-seq results of the anterior pituitaries of LET mice, alterations in the proportions of hormone-secreting cells may be a response to hyperandrogenism, in which functionally diverse gonadotropes could contribute to heterogeneity in reproductive phenotypes. Changes in the lactotrope population and PRL serum levels also support further research on the lactation hormone and its role in PCOS. PRL is involved in metabolic homeostasis and reproduction, and understanding its dysregulations may provide additional insight into the pathophysiology of PCOS. Presentation: 6/3/2024

7247 Adrenal Insufficiency In Advanced Cirrhosis: A ‘Shocky’ Clinical Dilemma

Abstract Disclosure: L. Aboishava: None. A. Pareek: None. A. Mertens: None. A. Erokhin: None. Background: In patients with advanced cirrhosis, profound hypoproteinemia can complicate the laboratory assessment of the hypothalamic-pituitary-adrenal axis, but a clinical phenotype of persistent hypotension and suboptimal cortisol response to ACTH stimulation raises the question of whether adrenal insufficiency could also be a contributing factor. Clinical Case: A 65-year-old man with a history of cirrhosis complicated by esophageal varices, ascites, encephalopathy and hepatorenal syndrome was admitted to the ICU with worsening fatigue, profound hypotension, and respiratory arrest. He was started on pressors, antibiotics and was also intubated for a short time. A broad workup was negative for cardiac or infectious causes of shock and showed decreased total protein and albumin (1.6 g/dl (3.5-5.2), with normal serum sodium and potassium. The patient had no previous history of adrenal disease or corticosteroid use. Workup for adrenal insufficiency was initiated and showed decreased morning blood serum cortisol (10.6 ug/dl (2.5-19.5)) and ACTH (&amp;lt;5.0 pg/ml (7.2-63)), as well as suboptimal cortisol response on ACTH stimulation testing (12.5 ug/dl initially, 16.7 ug/dl after stimulation). Head CT on admission was negative for intracranial pathology, and lab results showed normal TSH and mildly increased prolactin of 36.2 ng/ml (4.0-15.0). Pt was started on IV hydrocortisone 50 mg TID. Glucocorticoid therapy didn’t improve his state significantly but was continued with a gradual tapering down of the dose. After intense treatment in the ICU the patient’s state was stabilized. Unfortunately, an endoscopy performed for worsening anemia and blood in stools showed gastric cancer. The patient was transferred to comfort care after a discussion of goals of treatment and died within the next 24 hours. Conclusion: The nature of decreased cortisol levels in patients with cirrhosis is most likely multifactorial, due to impaired hepatic synthetic function, dysregulation of hormone-binding protein balance, abnormal ACTH secretion, and other factors. Impaired corticosteroid-binding globulin synthesis might affect the ratio of globulin-bound and free hormone fractions and alter the accuracy of cortisol assays. Whether adrenal insufficiency is truly one of the complications of advanced cirrhosis contributing to persistent hypotension, or a mere laboratory finding is difficult to answer. It is also yet to be determined whether patients with advanced cirrhosis might benefit from screening and treatment of adrenal insufficiency in circumstances of persistent hypotension, and studies are needed to decide on optimal diagnostic tests to recognize the disease and develop treatment algorithms. Presentation: 6/3/2024

Risk factors of pancreatic fistula after distal pancreas resections: an observational retrospective study

BACKGROUND: The main complication of surgical pancreas interventions is the pancreatic fistula (PF) — abnormal secretion of pancreatic secretions into the abdominal cavity, which can lead to more severe complications. At the same time, some predictors of PF remain poorly understood. AIM: To investigate the risk factors for the development of PF after distal pancreatic resection. MATERIALS AND METHODS: The study included 40 patients who underwent distal resection. The influence of various clinical parameters on the development of PF after surgery was evaluated. Methods of mathematical modeling and correlation analysis were used. Mathematical modeling was carried out using the Random forest machine learning algorithm, and the indicator of the relative importance of the “importance” parameters was evaluated. RESULTS: According to the Random forest model, on day 1 after surgery, the most significant predictors of the development of PF were: the volume of neoplasm, age and stage of the oncological process, for which “importance” was 53.2, 13.7 and 12.5 (AUC ROC=62%); on day 3–5, “importance” was 61.7, 11.5 and 5.2 (AUC ROC=79%). An increase in the concentration of pancreatic amylase in blood plasma for 2–3 and 3–5 days correlated with its increase in the drainage discharge for 5-7 days after the intervention (r=0.48 and 0.76; p 0.05). A correlation was found between the level of amylase in the drainage discharge on 3–5 days after the intervention and the level of leukocytes according to the general blood test (r=0.62, p 0.05). CONCLUSION: An increase in plasma amylase levels is the main risk factor for the development of PF. An increase in the concentration of amylase in the drainage discharge can be considered as a potential risk factor for the development of pancreatic fistulas with clinical manifestations in the following days. The stage of the oncological process, the size of the neoplasm and the age of the patient are also risk factors.

Evaluation of the Choroid Plexus Epithelium Inflammation TLR4/NF-κB/NKCC1 Signal Pathway Activation in the Development of Hydrocephalus.

Hydrocephalus is characterized by secretion, circulation, and absorption disorder of cerebrospinal fluid (CSF) with high morbidity and complication rate. The relationship between inflammation and abnormal secretion of CSF by choroid plexus epithelium (CPE) had received more attention. In this study, we aim to detect the role of Toll-like receptor 4/nuclear factor-kappa B/Na+/K+/2Cl-cotransporter 1(TLR4/NF-κB/NKCC1) signal pathway in the development of hydrocephalus. Hydrocephalus was induced in adult rats (8 weeks) by intracisternal kaolin injection, then pyrrolidinedithiocarbamate (PDTC) and bumetanide were administrated to the rats mode. Then the rat model was evaluated, and ventricular volume was calculated at different time points. Then CPE, cortex, preventricular tissue, and CSF were obtained. Protein expressions of TLR-4, NKCC/serine-threonine STE20/SPS1-related, proline-alanine-rich kinase (SPAK), pNKCC1, pSPAK, GFAP, AQP1, and AQP4 were measured by RT-PCR, western blot, and immunofluorescence (IF) stains in CPE, respectively. Our data showed that inflammation factors tumor necrosis factor-(TNF-α), interleukin 18(IL-18), and glial fibrillary acidic protein (GFAP) concentrations were significantly higher in the model group than in controls. The TLR4/NF-κB/NKCC1 signal pathway were actived by NF-κB-p65, NKCC1, pNKCC1- pSPAK complex, and Aquaporin1 (AQP1) high expression. PDTC and bumetanide use can help regular TLR4/NF-κB/NKCC1 expression and reduced AQP1 expression by down-regulate NF-B-p65 and inhibiting NKCC1, respectively. As a result, the treatment groups alleviated CPE abnormal secretion and ventricle enlargement. These results confirmed that the inflammatory reaction contributes TLR4/NF-κB/NKCC1 mediated CPE abnormal secretion and consequent hydrocephalus. Regulation of TLR4/NF-κB/NKCC1 and AQP1 can prevent this process. Our study provides a strong rationale for further exploring alleviating CPE abnormal secretion as a therapeutic perspective of hydrocephalus.

A comparison of the Anti-diabetic Potential of Magnetized Water, Metformin, and Their Combination in A Rat Model of Type II Diabetes

DM is a collection of metabolic disorders brought on by abnormalities in secretion, action, or combination of both of insulin. Nowadays, many efforts are made to change lifestyles to get a moderate outcome with the fewest possible side effects and reduce complications. Although magnetized water (MW) has been promoted since 1930s, it has not received wide approbation since its effectiveness is still in question; however, the therapeutic potential of MW on the body has been reported. This study investigated the impact of MW supplementation on glucose, insulin, antioxidant status, inflammatory condition, DNA fragmentation and gene expression associated with the metabolism of glucose in STZ-induced diabetes in rats. Adult female Wistar rats (6 groups) were used in this study: G1: Control group+ tap water (TW); G2: Control group+ MW; G3: Diabetic group+ TW; G4: Diabetic group+ MW; G5: Diabetic group+ metformin (Met)+ TW; G6: Diabetic group+ Met+ MW. Additionally, lowering serum glucose and raising insulin level, MW consumption repaired DNA damage, enhanced antioxidant status, reduced inflammatory response, and upregulated genes linked to glucose metabolism. Furthermore, as shown by the histological analysis of pancreatic tissue sections, supplementation with MW could reverse the detrimental effects of STZ on the pancreas. This study offers novel insights into how MW consumption can help reduce T2DM by reducing hyperglycemia, restoring the equilibrium between antioxidants and oxidants, reducing inflammatory responses, and altering genes involved in glucose metabolism. Therefore, MW may be used as an adjuvant in T2DM management.

PHARMACODYNAMIC OF METFORMIN IN TYPE 2 DIABETES MELLITUS PATIENTS: REVIEW OF THE PRKAA2 AND SLC22A3 GENES

Type 2 diabetes mellitus (type 2 DM) is a disease including on metabolic disorder that characterized by an increase in glucose levels above normal. This glucose increase is caused by reduced insulin function which can be in the form of abnormalities in insulin secretion, impaired insulin action in peripheral tissues, or both. Metformin is one of the recommended therapies for type 2 DM. AMPK is the main pathway of metformin's mechanism. AMPKa2 encoded by PRKAA2 gene is an AMPK subunit that plays an important role in AMPK activation. OCT3 encoded by SLC22A3 plays a role in the metformin transport mechanism. OCT3 is needed in the metformin pharmacokinetic like absorption and elimination, this process determines metformin bioavailability, clearance, and its pharmacological effects. Mutations in PRKAA2 and SLC22A3 cause variations in the pharmacodynamic effects and pharmacokinetic of metformin in individuals directly. These changes will ultimately affect the effectiveness of metformin in type 2 DM patients.

Irritable Bowel Syndrome - current state of knowledge

Introduction and objective: Irritable bowel syndrome (IBS) is a common gastroenterological disorder affecting 9% to 23% of the population worldwide. The disease causes recurrent abdominal pain and abnormal bowel movements without visible anatomical or biochemical changes and diagnosis is often difficult. The purpose of this paper is to analyze the current knowledge of the pathophysiology, risk factors, diagnosis and treatment of IBS. Review methods: The literature available in the PubMed database was reviewed using the following key words: "irritable bowel syndrome," "constipation," "diarrhea", "abdominal pain", "diagnostics", "treatment". 49 articles were included in the review and 80% were from 2016-2024. Current state of knowledge: The pathophysiology of IBS is not fully understood, but it is recognized that the disease is a disorder of the gut-brain axis. It can lead to abnormal secretion of serotonin and dopamine, which affects symptoms. The diagnosis of IBS is based on the Rome IV Criteria, defining the characteristics and severity of symptoms. Summary: IBS is a disorder that significantly affects quality of life. Diagnosis is based on the exclusion of organic diseases and meeting certain criteria. Treatment includes both dietary modification and pharmacotherapy aimed at relieving symptoms. Despite advances in research, the pathophysiology of IBS is still not fully understood, making it difficult to develop effective treatments.