Hasil untuk "Diseases of the endocrine glands. Clinical endocrinology"

Ahmed Y. Azzam, Muhammed Amir Essibayi, Nathan Farkas et al.

ABSTRACT Introduction Idiopathic intracranial hypertension (IIH) is a neurological disorder characterised by elevated intracranial pressure (ICP), predominantly affecting obese women of reproductive age. While GLP‐1 receptor agonists have shown promise in IIH management, the potential of dual GIP/GLP‐1 receptor activation through tirzepatide remains unexplored. This study aimed to evaluate tirzepatide's efficacy as an adjunctive therapy in IIH management. Methods We conducted a retrospective cohort analysis using the TriNetX Global Health Research Network, analysing data through November 2024. Through propensity score matching, we compared 193 tirzepatide‐exposed IIH patients with 193 controls receiving standard care. Primary outcomes included papilledema severity, visual function, headache frequency, and treatment resistance, monitored at multiple follow‐up timepoints. Results Our analysis revealed significant improvements across all measured outcomes in the tirzepatide group. At 24 months, we observed a 68% reduction in papilledema risk (RR 0.320, 95% CI 0.189–0.542, p < 0.001), a 73.9% reduction in visual disturbance and blindness risk (RR 0.261, 95% CI 0.143–0.477, p < 0.001), and a 19.7% reduction in headache risk (RR 0.803, 95% CI 0.668–0.966, p = 0.019). The tirzepatide group demonstrated significant body‐mass index reductions, reaching −1.147 kg/m2 (95% CI [−1.415, −0.879], p < 0.001) at 24 months compared to controls. Conclusions Our results demonstrate that tirzepatide, when used as an adjunctive therapy, provides significant therapeutic benefits in IIH management, particularly in improving papilledema and visual outcomes. Our findings suggest that dual GIP/GLP‐1 receptor activation may offer advantages over traditional single‐receptor therapies, potentially through enhanced metabolic regulation and direct effects on ICP dynamics.

Lía Nattero‐Chávez, Jorge Bondía, Héctor F. Escobar‐Morreale et al.

Zhiliang Mai, Zhiliang Mai, Hua Mao

BackgroundPrevious studies have highlighted changes in the cerebral cortical structure and cognitive function among nonalcoholic fatty liver disease (NAFLD) patients. However, the impact of NAFLD on cerebral cortical structure and specific affected brain regions remains unclear. Therefore, we aimed to explore the potential causal relationship between NAFLD and cerebral cortical structure.MethodsWe conducted a Mendelian randomization (MR) study using genetic predictors of alanine aminotransferase (ALT), NAFLD, and percent liver fat (PLF) and combined them with genome-wide association study (GWAS) summary statistics from the ENIGMA Consortium. Several methods were used to assess the effect of NAFLD on full cortex and specific brain regions, along with sensitivity analyses.ResultsAt the global level, PLF nominally decreased SA of full cortex; at the functional level, ALT presented a nominal association with reduced SA of parahippocampal gyrus, TH of pars opercularis, TH of pars orbitalis, and TH of pericalcarine cortex. Besides, NAFLD presented a nominal association with reduced SA of parahippocampal gyrus, TH of pars opercularis, TH of pars triangularis and TH of pericalcarine cortex, but increased TH of entorhinal cortex, lateral orbitofrontal cortex and temporal pole. Furthermore, PLF presented a nominal association with reduced SA of parahippocampal gyrus, TH of pars opercularis, TH of cuneus and lingual gyrus, but increased TH of entorhinal cortex.ConclusionNAFLD is suggestively associated with atrophy in specific functional regions of the human brain.

Indraneel Banerjee, Klaus Mohnike

Peijuan Wu, Ying Zhu, Junjie Li et al.

Objective To investigate the potential molecular mechanism of traditional Chinese medicine Guizhi Fuling Wan (GZFLW) inhibiting granulosa cells (GCs) autophagy in polycystic ovary syndrome (PCOS).Methods Control GCs and model GCs were cultured and treated with blank serum or GZFLW-containing serum. The levels of H19 and miR-29b-3p in GCs were detected using qRT-PCR, target genes of miR-29b-3p were identified using luciferase assay. The protein expressions of Phosphatase and tensin homolog (PTEN), Matrix Metalloproteinase (MMP)-2, and Bax were measured using western blot. The level of autophagy was detected via MDC staining, the degree of autophagosomes and autophagic polymers was observed using dual fluorescence-tagged mRFP-eGFP-LC3.Results GZFLW intervention reduced the expression of autophagy-related proteins PTEN, MMP-2 and Bax, by upregulating the expression of miR-29b-3p and downregulated the expression of H19 (p < .05 or p < .01). The number of autophagosomes and autophagy polymers was significantly decreased by GZFLW treatment. However, the inhibition of miR-29b-3p and overexpression of H19 induced a significant increase in the number of autophagosomes and autophagic polymers, which attenuated the inhibitory effect of GZFLW on autophagy (p < .05 or p < .01). In addition, inhibition of miR-29b-3p or overexpression of H19 can attenuate the effect of GZFLW on the expression of PTEN, MMP-2 and Bax proteins (p < .05 or p < .01).Conclusion Our study found that GZFLW inhibits autophagy in PCOS GCs via H19/miR-29b-3p pathway.

Belinda Pletzer, Erika Comasco, Esmeralda Hidalgo-Lopez et al.

Caroline S. Johnson, Paul E Micevych, Paul G. Mermelstein

Estrogen receptors were initially identified in the uterus, and later throughout the brain and body as intracellular, ligand-regulated transcription factors that affect genomic change upon ligand binding. However, rapid estrogen receptor signaling initiated outside of the nucleus was also known to occur via mechanisms that were less clear. Recent studies indicate that these traditional receptors, estrogen receptor-α and estrogen receptor-β, can also be trafficked to act at the surface membrane. Signaling cascades from these membrane-bound estrogen receptors (mERs) not only rapidly effect cellular excitability, but can and do ultimately affect gene expression, as seen through the phosphorylation of CREB. A principal mechanism of neuronal mER action is through glutamate-independent transactivation of metabotropic glutamate receptors (mGluRs), which elicits multiple signaling outcomes. The interaction of mERs with mGluRs has been shown to be important in many diverse functions in females, including, but not limited to, reproduction and motivation. Here we review membrane-initiated estrogen receptor signaling in females, with a focus on the interactions between these mERs and mGluRs.

Xudong Huang, Zhou Zhou, Yingyi Zheng et al.

BackgroundModified Duhuo Jisheng Decoction (MDHJSD) is a traditional Chinese medicine prescription for the treatment of osteoporosis (OP), but its mechanism of action has not yet been clarified. This study aims to explore the mechanism of MDHJSD in OP through a combination of network pharmacology analysis and experimental verification.MethodsThe active ingredients and corresponding targets of MDHJSD were acquired from the Traditional Chinese Medicine System Pharmacology (TCMSP) database. OP-related targets were acquired from databases, including Genecards, OMIM, Drugbank, CTD, and PGKB. The key compounds, core targets, major biological processes, and signaling pathways of MDHJSD that improve OP were identified by constructing and analysing the relevant networks. The binding affinities between key compounds and core targets were verified using AutoDock Vina software. A rat model of ovariectomized OP was used for the experimental verification.ResultsA total of 100 chemical constituents, 277 targets, and 4734 OP-related targets of MDHJSD were obtained. Subsequently, five core components and eight core targets were identified in the analysis. Pathway enrichment analysis revealed that overlapping targets were significantly enriched in the tumour necrosis factor-alpha (TNF-α) signaling pathway, an inflammation signaling pathway, which contained six of the eight core targets, including TNF-α, interleukin 6 (IL-6), transcription factor AP-1, mitogen-activated protein kinase 3, RAC-alpha serine/threonine-protein kinase, and caspase-3 (CASP3). Molecular docking analysis revealed close binding of the six core targets of the TNF signaling pathway to the core components. The results of experimental study show that MDHJSD can protect bone loss, inhibit the inflammatory response, and downregulate the expression levels of TNF-α, IL-6, and CASP3 in ovariectomized rats.ConclusionThe mechanism of MDHJSD in the treatment of OP may be related to the regulation of the inflammatory response in the bone tissue.

Caroline de Gouveia Buff Passone, Caroline de Gouveia Buff Passone, Gaëlle Vermillac et al.

Aims/HypothesisCaused by biallelic mutations of the gene encoding the transcription factor RFX6, the rare Mitchell–Riley syndrome (MRS) comprises neonatal diabetes, pancreatic hypoplasia, gallbladder agenesis or hypoplasia, duodenal atresia, and severe chronic diarrhea. So far, sixteen cases have been reported, all with a poor prognosis. This study discusses the multidisciplinary intensive clinical management of 4 new cases of MRS that survived over the first 2 years of life. Moreover, it demonstrates how the mutations impair the RFX6 function.MethodsClinical records were analyzed and described in detail. The functional impact of two RFX6R181W and RFX6V506G variants was assessed by measuring their ability to transactivate insulin transcription and genes that encode the L-type calcium channels required for normal pancreatic beta-cell function.ResultsAll four patients were small for gestational age (SGA) and prenatally diagnosed with duodenal atresia. They presented with neonatal diabetes early in life and were treated with intravenous insulin therapy before switching to subcutaneous insulin pump therapy. All patients faced recurrent hypoglycemic episodes, exacerbated when parenteral nutrition (PN) was disconnected. A sensor-augmented insulin pump therapy with a predictive low-glucose suspension system was installed with good results. One patient had a homozygous c.1517T&gt;G (p.Val506Gly) mutation, two patients had a homozygous p.Arg181Trp mutation, and one patient presented with new compound heterozygosity. The RFX6V506G and RFX6R181W mutations failed to transactivate the expression of insulin and genes that encode L-type calcium channel subunits required for normal pancreatic beta-cell function.Conclusions/InterpretationMultidisciplinary and intensive disease management improved the clinical outcomes in four patients with MRS, including adjustment of parenteral/oral nutrition progression and advanced diabetes technologies. A better understanding of RFX6 function, in both intestine and pancreas cells, may break ground in new therapies, particularly regarding the use of drugs that modulate the enteroendocrine system.

S. Y. Rybakov

Chronic insufficiency of the cortical substance of the adrenal glands or hypocorticism until recently belonged to rare forms of endocrine pathology. This included a few cases of Addison’s disease of tuberculous etiology, a relatively small number of patients after bilateral adrenalectomy for Cushing’s disease, removal of bilateral, sometimes unilateral, hormonally active tumors of the cortex and medulla of the adrenal glands. Bilateral adrenalectomy is also practiced for some types of hormone‑dependent tumors of the mammary glands, ovaries, prostate, and malignant hypertension. The evolution of ideas about the pathophysiology of adrenal glands contributed to a significant expansion and increase in the number of patients suffering from hypocorticism. A decrease in the incidence of tuberculosis contributed to a decrease in the number of patients with classic Addison’s disease. However, an increasing number of patients with hypocorticism of autoimmune, genetically determined and other genesis are currently being discovered. The improvement of diagnostic methods contributes to the increase in the number of operations for adrenal glands tumors and, accordingly, the number of cases of post‑adrenalectomy hypocorticism. Operations on the pituitary gland for various types of tumors, the number of which is steadily increasing, also contribute to the increase in the number of cases of hypothyroidism. In the mid‑70s of the XX century. a new direction in the treatment of various forms of endocrine insufficiency by the method of transplanting cultures of cells and tissues of endocrine glands took shape. Disorders of the endocrine glands seem to be particularly suitable for the transplantation method of treatment, since it is expected that living and functionally active donor endocrine tissue, transplanted into a patient with endocrine insufficiency, will secrete hormones and provide the body’s physiological needs and clinical compensation of the insufficiency. Similar experimental studies have been conducted since the beginning of the 20th century. The methods of obtaining cultures of cells and tissues of various endocrine organs were developed in detail, the issue of their viability, morphological and hormonal characteristics, and the possibility of compensation of certain forms of endocrine insufficiency were studied.&#x0D;

The Endocrine Society

Abstract Rising costs have made access to affordable insulin far more difficult for people with diabetes, especially low-income individuals, those on high deductible health plans, beneficiaries using Medicare Part B to cover insulin delivered via pump, Medicare beneficiaries in the Part D donut hole, and those who turn 26 and must transition from their parents’ insurance, to manage their diabetes and avoid unnecessary complications and hospitalizations. For many patients with diabetes, insulin is a life-saving medication. Policymakers should immediately address drivers of rising insulin prices and implement solutions that would reduce high out-of-pocket expenditures for patients. The Endocrine Society recommends policy options to expand access to lower cost insulin in this paper.

Weie Zhou, Xuefeng Zhou, Yuan Zhang et al.

Diabetic nephropathy (DN) is one of the common and severe microvascular complications of diabetes mellitus (DM). The occurrence and development of DN are related to multiple factors in the human body, which makes DN a complex disease, and the pathogeneses of DN have not yet been fully illustrated. Furthermore, DN lacks effective drugs for treatment nowadays. Chinese herbal medicine (CHM) often shows the feature of multicomponents, multitargets, multipathways, and synergistic effects and shows a promising source of new therapeutic drugs for DN. As a CHM, Tangshen Formula (TSF) was used to treat DN patients in China. However, its bioactive compounds and holistic pharmacological mechanisms on DN are both unclear. A network pharmacology approach was firstly applied to explore multiple active compounds and multiple key pharmacological mechanisms for TSF treating DN by drug-targeted interaction databases, herb-compound-target network, protein-protein interaction network, compound-target-pathway network, and analysis methods. And the results showed that TSF have the characteristic of multicomponents, multitargets, multipathways, and synergistic effects for treating DN. The quercetin, naringenin, kaempferol, and isorhamnetin as key active compounds and the PI3K-Akt signaling pathway, TNF signaling pathway, nonalcoholic fatty liver disease (NAFLD), focal adhesion, rap1 signaling pathway, T cell receptor signaling pathway, MAPK signaling pathway, and insulin resistance as the key molecular mechanisms play important roles in TSF treating DN. Moreover, quercetin, naringenin, kaempferol, and isorhamnetin were successfully detected in TSF by the UHPLC-MS/MS analysis method. And their concentrations were 0.224, 8.295, 0.0564, and 0.0879 mg·kg-1, respectively. The present findings not only provide new insights for a deeper understanding of the constituent basis and pharmacology of TSF but also provide guidance for further pharmacological studies on TSF.

Asif Alam Khan, Inam Malkani, Junaid Jameel Khattak et al.

Renal stones are the third most common problem affecting about 10% of global population. The management of nephrolithiasis has undergone a complete transformation since the 1980s. Percutaneous nephrolithotomy (PCNL) has established itself an effective and safe technique that delivers high stone-free rate as well as overall shorter treatment time. We aim to compare the outcome of mini-PCNL with standard-PCNL in patients presenting with renal stones. In all, 90 patients fulfilled the selection criteria and randomized into two groups. Group A underwent mini-PCNL whereas Group B underwent standard-PCNL. Pre-operative hemoglobin level was recorded. Duration of procedure as well as drop in hemoglobin level was also recorded. A kidney, ureter, and bladder (KUB) X-ray was performed to confirm the presence of of stone and stone-free status. The mean age of patients in mini-PCNL group was 43.11 years and in standard-PCNL group, it was 36.91 years. The mean stone size in patients of mini-PCNL group was 29.53 mm and 31.58 mm in standard-PCNL group. The mean duration of renal stone in mini-PCNL group was 1.91 years and that in standard-PCNL group 1.80 years. The mean operative time in mini-PCNL group was 59.56 min and 61.22 min in standard-PCNL group. The mean fall in hemoglobin in mini-PCNL group was 0.38 g/dL and that in standard-PCNL group 0.51 g/dL. In mini-PCNL group, stone clearance was observed in 42 (93.3%) patients, while in standard-PCNL group, it was observed in 45 (100%) patients. This difference was insignificant (P > 0.05). Mini-PCNL and standard-PCNL have no significant differences in terms of outcome, operative time, and stone clearance, although fall in hemoglobin level was less in mini-PCNL group, which showed less blood loss in this group, thereby making it a more appropriate method for renal stone removal.

Paloma Almeda-Valdés, Israel Lerman-Garber, Elisa Nishimura-Meguro

Con el advenimiento de la insulina, la diabetes mellitus tipo 1 (DM1) dejó de ser una enfermedad fatal para convertirse en una enfermedad crónica, asociada a descompensaciones agudas e importantes complicaciones microvasculares y macrovasculares. A lo largo de los años los importantes avances tecnológicos han facilitado lograr los objetivos terapéuticos con menor riesgo de hipoglucemias y reducción significativa en el riesgo de desarrollar complicaciones. Estos avances, sin embargo, aún no son accesibles a la gran mayoría de los pacientes. En este capítulo se presenta en forma breve la evolución del tratamiento de la DM1 en nuestro país y permite hacer un repaso a la historia del manejo de la DM1.

Margherita Sisto

Salivary glands (SGs) are of the utmost importance for maintaining the health of the oral cavity and carrying out physiological functions such as mastication, protection of teeth, perception of food taste, and speech [...]

Peter Godsk Jørgensen

Wenqian Gu, Andreas Rebsdorf, Camilla Anker et al.

Abstract Aims Steviol glycosides are the sweet components extracted from medicinal plant Stevia rebaudiana Bertoni, which have antihyperglycaemic effects. Steviol glucuronide (SVG) is the metabolite excreted in human urine after oral administration of steviol glycosides. We aimed to clarify whether SVG exerts direct insulin stimulation from pancreatic islets and to explore its mode of action. Materials and Methods Insulin secretion was measured after 60 minutes static incubation of isolated mouse islets with (a) 10−9‐10−5 mol/L SVG at 16.7 mmol/L glucose and (b) 10−7 mol/L SVG at 3.3‐16.7 mmol/L glucose. Islets were perifused with 3.3 or 16.7 mmol/L glucose in the presence or absence of 10−7 mol/L SVG. Gene transcription was measured after 72 hours incubation in the presence or absence of 10−7 mol/L SVG. Results SVG dose‐dependently increased insulin secretion from mouse islets with 10−7 mol/L exerting the maximum effect in the presence of 16.7 mmol/L glucose (P < .001). The insulinotropic effect of SVG was critically dependent on the prevailing glucose concentration, and SVG (10−7 mol/L) enhanced insulin secretion at or above 11.1 mmol/L glucose (P < .001) and showed no effect at lower glucose concentrations. During perifusion of islets, SVG (10−7 mol/L) had a long‐acting and apparently reversible insulinotropic effect in the presence of 16.7 mmol/L glucose (P < .05). Gene‐transcript levels of B2m and Gcgr were markedly altered. Conclusion This is the first report to demonstrate that SVG stimulates insulin secretion in a dose‐ and glucose‐dependent manner from isolated mouse islets of Langerhans. SVG may be the main active metabolite after oral intake of steviol glycosides.

Fang Wang, Yuxing Liu, Jingjing Yuan et al.

Objectives. The aim of this study was to investigate the effects of compound C on an in vivo mouse model of high-fat diet- (HFD-) induced obesity and hepatosteatosis. Methods. C57BL/6 mice were fed with a standard diet (n = 5) for 16 weeks and then injected saline once a day for 4 weeks as the normal chow group. Mice (n = 10) were fed with HFD for 16 weeks to induce obesity and hepatosteatosis and then divided into two groups: HFD + vehicle group injected with the vehicle solution (saline) and HFD + compound C group injected with compound C in saline (5 mg/kg i.p., once a day) for 4 weeks. Liver histology was observed. The expression levels of genes related to lipid metabolism and proinflammation in liver tissue were examined. NLRP3 inflammasome expression in liver tissue was detected by the western blot assay. HepG2 cells were pretreated with compound C and/or AICAR for 1 h and then treated with palmitic acid (PA) for 3 h. The cells were collected, and mRNA levels were determined. Results. There was a significant reduction in body-weight gain and daily food intake in the HFD + compound C group compared with the HFD + vehicle group (p<0.05). The glucose tolerance test (GTT) and insulin tolerance test (ITT) showed that compound C alleviated insulin resistance. Histology analysis showed a significant reduction of hepatic steatosis by compound C. Compound C also significantly decreased fatty acid synthesis genes, while increased fatty acid oxidation genes. Furthermore, compound C significantly reduced the expression of proinflammatory markers and NLRP3 inflammasome (p<0.05). Compound C enhanced mRNA levels of SOD1, SOD2, catalase, GPx1, and GPx4 and reduced the p-AMPK/AMPK ratio, which were stimulated by palmitic acid (PA). The effect was enhanced by AICAR. Conclusion. Our data suggest that compound C is a potent NAFLD suppressor and an attractive therapeutic target for hepatic steatosis and related metabolic disorders.

Callum Livingstone, Anwar Borai

SummaryInsulin‐like growth factor‐II (IGF‐II) is a widely expressed 7·5 kDa mitogenic peptide hormone. Although it is abundant in serum, understanding of its physiological role is limited compared with that of IGF‐I. IGF‐II regulates foetal development and differentiation, but its role in adults is less well understood. Evidence suggests roles in a number of tissues including skeletal muscle, adipose tissue, bone and ovary. Altered IGF‐II expression has been observed in metabolic conditions, notably obesity, diabetes and the polycystic ovary syndrome. This article summarizes what is known about the actions of IGF‐II and its dysregulation in metabolic and endocrine diseases. The possible causes and consequences of dysregulation are discussed along with the implications for diagnostic tests and future research.

Sanjay Kalra, Ameya Joshi, Bharti Kalra et al.

This communication presents verses from the Bhagavad Gita which help define a good clinician's skills and behavior. Using the teachings of Lord Krishna, these curated verses suggest three essential skills that a physician must possess: Excellent knowledge, equanimity, and emotional attributes. Three good behaviors are listed (Pro-work ethics, Patient-centered care, and Preceptive leadership) and supported by thoughts written in the Gita.