Endocrine, metabolic & immune disorders drug targets最新文献

{"title":"Follow-up of Patients with Hereditary Metabolic Diseases during the 3 Years of the Pandemic in the Reference Center for Hereditary Metabolism Diseases of the Centro Hospitalar Universitário Lisboa Norte","authors":"Anabela Belo, Daniel Gomes, Patricia Nunes, Anabela Oliveira","doi":"10.2174/0118715303279331231123050015","DOIUrl":"https://doi.org/10.2174/0118715303279331231123050015","url":null,"abstract":"Introduction:: The adult unit of the Reference Center for Hereditary Metabolism Diseases of the Centro Hospitalar Universitário Lisboa Norte was created in 2002. The team that supports this unit is made up of several specialists, including 2 Internal Medicine Doctors and 2 Nutritionists. The unit carries out its activity mainly in an outpatient clinic on Fridays. Between March 2020 and December 2022, the team adapted the support given to this unit, transforming some external appointments into non-face-to-face appointments in order to maintain contact with patients and reduce the deslocation to the CHULN. Methods:: The analysis reported below reflects the activity in face-to-face and non-face-to-face appointment of the medical team and nutrition team in the critical period. Results/Case Report:: A total of 220 patients were evaluated, 56.4% female and 43.6% male. Regarding the evaluated pathologies, these were divided into 3 groups: aminoacidopathies – 40%, organic aciduria – 6.5% and other metabolic diseases – 53.5%. During these three years a total of 580 nutrition appointments were scheduled, 457 face-to-face and 123 non-face-to-face. 32% of patients scheduled did not attend the appointments or it was not possible to make telephone contact. This percentage is divided into 90% face-to-face appointments and 10% nonface- to-face appointments. Regarding medical appointments, the total was 797, 667 of which were face-to-face and 130 non-face-to-face. 16.8% of absences were registered in face-to-face and non-face-to-face appointments. 98.5% of absences concern non-face-to-face appointments. Conclusion:: Despite the troubled period worldwide, support for these patients was always ensured, both by the Medical team and the Nutrition team. Despite the solutions found to keep patients safe, in this specific period, the % of absences from the outpatient clinic is quite high, and one of the main justifications presented by the patients is related to the fact that they are afraid to go to the hospital. With regard to absences recorded in non-face-to-face appointments, there were several situations in which patients reported not being able to answer the phone during their working hours.","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"7 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138689714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eicosapentaenoic Acid as a Cardiovascular Benefit and a Risk of Atrial Fibrillation","authors":"Filippo Egalini, Mattia Rossi, Mauro Massussi, Giulia Gaggero, Guglielmo Beccuti, Andrea Benso, Massimo Francesco Piepoli, Fabio Broglio","doi":"10.2174/0118715303280825231122153024","DOIUrl":"https://doi.org/10.2174/0118715303280825231122153024","url":null,"abstract":": In recent years, scientific research has increasingly focused on the cardiovascular benefits of omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplements. The most promising results emerged from the new trials on high-dose eicosapentaenoic acid (EPA), which is the only approach instead of the previously prescribed therapy with EPA + docosahexaenoic acid (DHA). The evidence of the reduction of cardiovascular events in patients at high cardiovascular risk with EPA is intriguing. However, physicians have expressed concern about the potential high risk of atrial fibrillation [AF] occurrence due to such an approach. This study aims to investigate the current evidence on the cardiovascular benefits of EPA and its association with atrial arrhythmogenesis. Current guidelines consider EPA (as IPE) treatment for selected patients but with no specific indication regarding AF risk evaluation. We propose a flowchart that could be a starting point for the future development of an algorithm to help clinicians prescribe EPA safely and effectively, especially in patients at high risk of incipient AF.","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"84 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138580993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketosis-prone Diabetes presenting with Acute Esophageal Necrosis or “Black Esophagus”: An Intriguing New Clinical Association.","authors":"Riccardo Maria Pollis, Damiano Furlanetto, Elena Pagin, Carla Scaroni, Mattia Barbot, Giacomo Voltan","doi":"10.2174/0118715303279019231127065331","DOIUrl":"https://doi.org/10.2174/0118715303279019231127065331","url":null,"abstract":"Background:: Ketosis-prone diabetes (KPD) is an intermediate subtype of diabetes mellitus, usually affecting Afro-American adults, presenting with diabetic ketoacidosis (DKA), without the classic phenotype of autoimmune type 1 diabetes. Patients require insulin therapy at onset for the acute decompensation, then usually remain insulin-free for prolonged periods with diet alone or with other antidiabetic drugs. DKA can be rarely complicated by upper gastrointestinal bleeding and mucosal necrosis, a severe complication named acute esophageal necrosis (AEN) burdened by high mortality. The association of KPD presenting with DKA complicated by AEN is here reported for the first time, to the knowledge of the authors, in the medical literature. Case Presentation:: Here we report an interesting case of middle-aged African woman, newly diagnosed with KPD, presenting with DKA hematemesis. The patient was first treated at Intensive Care Unit for the ketoacidosis with intravenous fluids combined with continuous insulin infusion, and then switched to subcutaneous regimen. At the same time, esophagogastroduodenoscopy (EGD) was performed to diagnose acute esophageal necrosis, which was promptly managed with proton pump inhibitors infusion, fasting, and parenteral nutrition. After the correct clinical evaluation, the patient was switched to oral antidiabetic and basal insulin at discharge and an EGD follow-up was scheduled. Conclusions:: KPD remains an under-recognized and under-diagnosed type of diabetes which can present as DKA. Since DKA could be a possible trigger of AEN, a rare but potentially lifethreatening condition, that clinicians should be aware of, in patients presenting with upper gastrointestinal bleeding and ketoacidosis. The prompt management and classification of DKA, combined with the EGD execution for early AEN diagnosis and follow-up, is essential.","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"68 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138580995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle Quality and Risk of Metabolic Syndrome in Adult Patients with Inherited Metabolic Diseases","authors":"Luis Mguel Luengo-Pérez, Ana Ambrojo, Mercedes Fernández-Bueso, Marta Guijarro, Ana Ferreira, Goncalo Luzes, M. Pereira, Conceição Calhau, Júlio Cesar Rocha","doi":"10.2174/0118715303279040231129055755","DOIUrl":"https://doi.org/10.2174/0118715303279040231129055755","url":null,"abstract":": Adult patients with several Inherited Metabolic Diseases (IMD) follow diets controlled in proteins, rich in carbohydrates, and free amino acids formulae, which cause hyperinsulinism and ectopic fat. Previous studies showed IMD adult patients have a higher prevalence of metabolic syndrome and their complications [1]. Recently, ultrasound [US) has been validated for malnutrition, assessing muscle quality subjectively [2]. Higher echo intensity (EI) is associated with poorer muscle quality and functional results in aging [3] and other clinical settings, but it has never been evaluated in IMD. US measurements were conducted on 19 IMD patients and 6 healthy controls at Hospital Universitario de Badajoz (HUB) to assess EI, anthropometry, bioimpedance, and biochemistry. The HUB ethics committee approved the protocol and informed consent. Statistics were made with Jamovi. The mean age was 29.9 (range 18-47) in IMD patients vs. 33.7 (26-47) in controls. The distribution of IMD is shown in Figure 2. The mean EI in IMD was 56.9 (60.9 in PKU) vs. 54.4 in controls, NOT being the differences statistically significant (t- Student p =0.633; in PKU, p =0.246). The box plot is shown in Figure 3. IMD patients had excess body fat in a variable degree depending on the method (Figure 4): anthropometry, BIA, preperitoneal fat or myosteatosis. 40% had insulin resistance by HOMA, 20% prediabetes by HbA1c, 58.8% had low HDL-cholesterol levels, and 29.4% had hypertriglyceridemia. Insulin resistance status is shown in Figure 5. Obesity by anthropometry was significantly correlated with subcutaneous abdominal and preperitoneal fat by ultrasound and fat mass by BIA. Fat mass by BIA was correlated to preperitoneal fat, and fat-free mass by BIA with HOMA and degree of metabolic control of IMD. Muscle quality, by an objective tool, such as echo intensity, is worse in patients with IMD than in controls, reflecting poorer muscle metabolic condition and a higher risk of metabolic syndrome. It is not statistically significant, probably due to the small sample size. The prevalence of obesity and other metabolic syndrome components is higher in IMD patients than in the general population of the same age. Body composition analysis by BIA and nutritional ultrasound can help to identify patients at risk of metabolic syndrome before biochemical markers show.","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"8 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138580996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Umbilical Cord Mesenchymal Stem Cells Combined with Fufang Xueshuantong Capsule Attenuate Oxidative Stress and Vascular Lesions in Diabetic Rats by Activating Nrf-2/HO-1 Signaling Pathway","authors":"Yunchao Sun, Yongzhang Li, Xueliang Gao, Limin Gao, Bingqi Yang, Jianing Zhao","doi":"10.2174/0118715303251692231112150225","DOIUrl":"https://doi.org/10.2174/0118715303251692231112150225","url":null,"abstract":"Background:: Macrovascular lesions are the main cause of death and disability in diabetes mellitus, and excessive accumulation of cholesterol and lipids can lead to long-term and repeated damage of vascular endothelial cells. Umbilical cord mesenchymal stem cells (UCMSCs) can attenuate vascular endothelial damage in type 1 diabetic mice, while Fufang Xueshuantong capsule (FXC) has a protective effect on endothelial function; however, whether FXC in combination with UCMSCs can improve T2DM macrovascular lesions as well as its mechanism of action are not clear. Therefore, the aim of this study was to reveal the role of FXC + UCMSCs in T2DM vasculopathy and their potential mechanism in the treatment of T2DM. Methods:: The control and T2DM groups were intragastrically administered with equal amounts of saline, the UCMSCs group was injected with UCMSCs (1×106, resuspended cells with 0.5 mL PBS) in the tail vein, the FXC group was intragastrically administered with 0.58 g/kg FXC, and the UCMSCs + FXC group was injected with UCMSCs (1×106) in the tail vein, followed by FXC (0.58 g/kg), for 8 weeks. Results:: We found that FXC+UCMSCs effectively reduced lipid levels (TG, TC, and LDL-C) and ameliorated aortic lesions in T2DM rats. Meanwhile, Nrf2 and HO-1 expression were upregulated. We demonstrated that inhibition of Nrf-2 expression blocked the inhibitory effect of FXC+UCMSCs-CM on apoptosis and oxidative stress injury. Conclusion:: Our data suggest that FXC+UCMSCs may attenuate oxidative stress injury and macroangiopathy in T2DM by activating the Nrf-2/HO-1 pathway.","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"14 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138543263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Clinical Features, Pathogenic and Etiological Characteristics of Community-acquired Pneumonia with Type 2 Diabetes Mellitus in Early Diagnosis","authors":"Bai-Yi Liu, Dan Zhang, Zhu Fan, Jing-Jing Jin, Cai-Hong Li, Rui-Nan Guo, Xue-Juan Li, Yan Huang","doi":"10.2174/0118715303273741231117060753","DOIUrl":"https://doi.org/10.2174/0118715303273741231117060753","url":null,"abstract":"Objective:: To study the etiological characteristics of community-acquired pneumonia (CAP) combined with type 2 diabetes (T2D), providing a reference for early clinical diagnosis and treatment of the disease. Methods:: We selected a total of 93 patients with CAP and analyzed their metagenomics nextgeneration sequencing (mNGS) data. The case group comprised 46 patients with combined CAP/T2D, and the control group comprised 47 patients without diabetes. We analyzed the pathogenic findings of the two groups. Result:: There were statistically significant differences in age between the two groups (P = 0.001). Leukocytes (P = 0.012), blood platelets (P = 0.034), fibrinogen (P = 0.037), D-dimer (P = 0.000), calcitonin ogen (P = 0.015), ultrasensitive C-reactive protein or C-reactive protein (CRP) (P = 0.000), serum amyloid A (P = 0.000), and erythrocyte sedimentation rate (P = 0.003) were higher in the case group than in the control group. Albumin was lower in the case group than in the control group. All differences were statistically significant. The infection rates of Klebsiella pneumoniae (P = 0.030), Pseudomonas aeruginosa (P = 0.043), and Candida albicans (P = 0.032) were significantly different between the two groups. Conclusion:: Compared with those without diabetes, the infection rates of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans were higher in patients with combined CAP/T2D.","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"234 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138543264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Inorganic Nitrate Administration Increases the Expression of Genes Involved in the Browning of Gonadal Adipose Tissue in Ovariectomized Rats","authors":"Nasibeh Yousefzadeh, Sajad Jeddi, Asghar Ghasemi","doi":"10.2174/0118715303239481231030043730","DOIUrl":"https://doi.org/10.2174/0118715303239481231030043730","url":null,"abstract":"Background and Objective:: Nitrate, as nitric oxide (NO) donor, has been suggested as a nutrition-based treatment for decreasing the risk of menopause-related obesity. This study aimed to specify the effects of chronic inorganic nitrate administration on uncoupling protein-1 (UCP-1), peroxisome proliferator-activated-receptor-γ (PPAR-γ) coactivator-1α (PGC-1α), and PPAR-γ expression in gonadal adipose tissue (GAT) of ovariectomized (OVX) rats. Methods:: Female rats were assigned to 3 groups: Control, OVX, and OVX+nitrate (n=7/group), which consumed water containing inorganic nitrate (100 mg/L) for 9 months. At month 9, GAT was used for the measurement of NO metabolites (NOx), mRNA levels of NO synthases [endothelial (eNOS), inducible (iNOS), neuronal (nNOS)], and mRNA and protein levels of UCP-1, PGC-1α, and PPAR-γ. Conclusion:: In OVX rats, chronic nitrate administration increased gene and protein levels of UCP-1, PGC-1α, and PPAR-γ in GAT, indicating the anti-obesity effects of nitrate are partially mediated by the white adipose tissue (WAT) browning. Moreover, the stimulatory effect of inorganic nitrate on the WAT browning in OVX rats was associated with blunting the OVXinduced NO deficiency in GAT. result: OVX rats had lower NOx concentration (45%) and eNOS (38%) and nNOS (30%) expression in GAT that was restored to normal values following nitrate administration. OVX rats had significantly lower mRNA and protein levels of UCP-1 (83% and 30%), PGC-1α (65% and 39%), and PPAR-γ (66% and 34.5%) in OAT. Chronic inorganic nitrate administration in OVX-rats increased mRNA (236%, 115%, and 128%) and protein (38%, 43%, and 34%, respectively) levels of PPAR-γ, PGC-1α, and UCP-1, respectively.","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"13 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138532855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Metformin Treatment on Disease Control in Patients with Acromegaly","authors":"Humeyra Rekali Sahin, Serdar Sahin, Betul Sarac, Cem Sulu, Pinar Kadioglu, Hande Mefkure Ozkaya","doi":"10.2174/0118715303260084231102105149","DOIUrl":"https://doi.org/10.2174/0118715303260084231102105149","url":null,"abstract":"background: The increase in portal insulin levels has been shown to upregulate growth hormone receptor expression in the liver, leading to increased insulin-like growth hormone-1 levels. Metformin inhibits hepatic gluconeogenesis and reduces fasting insulin. objective: We evaluated the effect of metformin treatment in patients with acromegaly on growth hormone, insulin-like growth hormone-1, and pituitary adenoma size. method: Patients who were followed up with the diagnosis of acromegaly in Istanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty were evaluated. The patients were divided into three groups after pituitary adenectomy as those who received somatostatin receptor ligand and metformin treatment (group A), somatostatin receptor ligand treatment only (group B), and those who received metformin treatment only (group C). Groups A and B were compared with each other, and patients in group C were compared among themselves. result: Insulin-like growth factor-1 levels were significantly lower in group A than in group B (p=0.020). There was no significant difference in post-treatment growth hormone levels and residual adenoma sizes between groups A and B (p>0.005). In group C, there was no significant difference in growth hormone values pre-and post-metformin treatment (p=0.078); however, post-metformin treatment insulin-like growth factor-1 values were significantly lower than pre-treatment insulin-like growth factor-1 values (p=0.027). conclusion: Due to the effect of metformin treatment on insulin-like growth factor-1 values in patients with acromegaly, it can be used in disease control, as well as a diabetes treatment","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"7 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138532845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multi-dimensional Data Mining-based Study on the Prescriptions Developed by Professor Xu Zhiyin in Treating Thyroid Nodules","authors":"Hai-Jian Sun, Xiao-Man Wei, Ming Lu, Hong Zhu, Yao Zhu","doi":"10.2174/0118715303258346231101190843","DOIUrl":"https://doi.org/10.2174/0118715303258346231101190843","url":null,"abstract":"Objective:: In this study, we employed a multi-dimensional data mining approach to examine the clinical instances where Professor Xu Zhiyin treated thyroid nodules. Our aim is to understand the patterns of symptoms, underlying causes, and treatment approaches used for thyroid nodules. By doing so, the intention is to distill the essential aspects, compile Professor Xu Zhiyin's clinical insights, and investigate his scholarly perspectives. Methods:: Professor Xu Zhiyin's clinical diagnoses and treatments spanning from 2009 to 2019 were entered into Microsoft Excel. Subsequently, the collected data was imported into the Medcase V5.2 system to facilitate data mining. Various techniques, such as frequency-based method, association rule analysis, and clustering, including a decentralized system clustering approach, were employed on a set of 346 cases involving patients with thyroid nodules that conformed to the specified criteria. The primary focus was on extracting insights regarding symptoms and the underlying causes from the medical records. By integrating these findings with Professor Xu Zhiyin's clinical expertise, we examined and summarized the outcomes of the data mining process. Results:: The fundamental prescriptions were successfully extracted using the techniques for mining across multiple dimensions. Utilizing the scattered grouping of these prescriptions and with reference to the cluster analysis of the frequency-linked system, the fundamental prescriptions proposed by Professor Xu Zhiyin for addressing thyroid nodules encompass the following ingredients: Glycyrrhiza uralensis Fisch, Cortex Moutan, Paeoniae radix rubra, Curcuma longa L., Radix Curcumae, persica seed, Citri Reticulatae Viride Pericarpium, Pinellia ternata, Spica Prunellae, Ostreae concha, Gleditsia sinensis spine, Tuckahoe and Radix Codonopsis. Conclusion:: The fundamental prescriptions were acquired using the frequency approach, association rule technique, k-means clustering approach, and systematic clustering approach. The research findings corroborate one another, demonstrating that Professor Xu Zhiyin's approach to distinguishing and treating thyroid nodules is embodied in distinct prescriptions tailored to specific diseases.","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"31 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138532853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experience of Miglustat Therapy in Pediatric Patients with Niemann-pick Type C Disease","authors":"Claudia Monteiro, Anabela Bandeira, Joana Correira, Cristina Garrido, Teresa Temudo, Esmeralda Martins","doi":"10.2174/0118715303279407231006180056","DOIUrl":"https://doi.org/10.2174/0118715303279407231006180056","url":null,"abstract":"<p>Introduction: Niemann-Pick disease type C (NP-C) has an estimated incidence 1/100,000. Is an inherited neurovisceral lysosomal lipid storage disease characterized by progressive neurological deterioration. Different clinical forms have been defined based on patient age at onset: perinatal, early infantile (EI), late-infantile (Li), juvenile and adult. Approximately 95% of patients harbour mutations in NPC1, the remainder in NPC2. To date, miglustat is the only treatment specifically approved in the European Union for the treatment of progressive neurological manifestations in patients with NP-C. Methods: We have carried out a retrospective, descriptive study by reviewing the clinical histories, for all patients diagnosed with NP-C treated with miglustat followed in the Hereditary Metabolism Diseases Unit of Centro Materno Infantil do Norte – CHPorto. Results: A total of 6 NP-C patients (4 male and 2 female) were included. Two patients were sisters. The first patient to start treatment with miglustat was in 2009, the year the drug was approved in EU. Categorization of patients on clinical grounds according to age at onset of symptoms identified 1 patient with the EI form of the disease (case 1), 3 patients with the Li form, (case 3 and 4) and 2 patients with the juvenile form (case 5 and 6). The duration of miglustat treatment ranged between 4 months to 7 years; therapy was initiated at different ages of patient, depending on the clinical form. All patients were reported as having neurological manifestations. Among the neurological symptoms, vertical gaze palsy had been observed in all our cases except case 4. The gelastic cataplexy crises appeared in all cases except in the juvenile form. The brain MRI in case 1, 2 and 4 described an increased signal in the white matter and thinning of the corpus callosum only in case 1, none with alterations in brain spectroscopy. In the cases 1, 2 and 3, non-esterified cholesterol deposits were observed in fibroblasts by histochemical staining with filipin. The diagnosis was confirmed with the genetic study, finding mutations in the NPC1 gene in the 6 patients. Cases 1 and 5 died. Case 3 took miglustat for 2 years currently with a 5-domain NPC with a clinical severity scale of 19, whilecase 4 under therapy with the drug for 6 years with a clinical severity score of 18, both Li form. While the case 6 had been taking the medication for 30 months with a clinical severity score of 3. Conclusion: Sometimes it is difficult to discriminate which are the first neurological symptoms due to the NP-C disease. The progression of the disease is faster when the symptoms start early. Data indicating stabilization and a slower rate of progression of the disease; patients with later onset forms appear as better responders.","PeriodicalId":11614,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135758529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}