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On implications of somatostatin in diabetic retinopathy

Neural Regeneration Research 2024年第9期19卷 1984-1990页

作者： Yanhong Fang Qionghua Wang Youjian Li Li Zeng Jian Liu Kepeng Ou Department of Ophthalmology Chongqing University Jiangjin HospitalChongqingChina College of Pharmacy National&Local Joint Engineering Research Center of Targeted and Innovative TherapeuticsIATTIChongqing University of Arts and SciencesChongqingChina Shandong Provincial Hospital Shandong Laboratory Animal CenterScience and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinanShandong ProvinceChina Academic Unit of Ophthalmology Bristol Medical SchoolUniversity of BristolBristolUK

somatostatin,a naturally produced neuroprotective peptide,depresses excitatory neurotransmission and exerts anti-proliferative and anti-inflammatory effects on the retina.In this review,we summarize the progress of somatostatin treatment of diabetic retinopathy through analysis of relevant studies published from February 2019 to February 2023 extracted from the PubMed and Google Scholar databases.Insufficient neuroprotection,which occurs as a consequence of declined expression or dysregulation of retinal somatostatin in the very early stages of diabetic retinopathy,triggers retinal neurovascular unit impairment and microvascular damage.somatostatin replacement is a promising treatment for retinal neurodegeneration in diabetic retinopathy.Numerous pre-clinical and clinical trials of somatostatin analog treatment for early diabetic retinopathy have been initiated.In one such trial(EUROCONDOR),topical administration of somatostatin was found to exert neuroprotective effects in patients with pre-existing retinal neurodysfunction,but had no impact on the onset of diabetic retinopathy.Overall,we concluded that somatostatin restoration may be especially beneficial for the growing population of patients with early-stage retinopathy.In order to achieve early prevention of diabetic retinopathy initiation,and thereby salvage visual function before the appearance of moderate non-proliferative diabetic retinopathy,several issues need to be addressed.These include the needs to:a)update and standardize the retinal screening scheme to incorporate the detection of early neurodegeneration,b)identify patient subgroups who would benefit from somatostatin analog supplementation,c)elucidate the interactions of somatostatin,particularly exogenously-delivered somatostatin analogs,with other retinal peptides in the context of hyperglycemia,and d)design safe,feasible,low cost,and effective administration routes.

关键词： diabetes retinopathy excitotoxicity growth hormone insulin like growth factor irisin neurodegeneration neuroinflammation neuroprotection neurovascular unit octreotide oxidative stress somatostatin

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Computerized tomography-guided therapeutic percutaneous puncture catheter drainage-combined with somatostatin for severe acute pancreatitis: An analysis of efficacy and safety

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 59-66页

作者： Xue-Lan Zheng Wan-Ling Li Yan-Ping Lin Ting-Long Huang Department of Critical Care Medicine The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina CT Room The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina

BACKGROUND Severe acute pancreatitis(SAP),a condition with rapid onset,critical condition and unsatisfactory prognosis,poses a certain threat to human health,warranting optimization of relevant treatment plans to improve treatment efficacy.AIM To evaluate the efficacy and safety of computerized tomography-guided the-rapeutic percutaneous puncture catheter drainage(CT-TPPCD)combined with somatostatin(SS)in the treatment of SAP.METHODS Forty-two SAP patients admitted to The Second Affiliated Hospital of Fujian Medical University from June 2020 to June 2023 were selected.On the basis of routine treatment,20 patients received SS therapy(control group)and 22 patients were given CT-TPPCD plus SS intervention(research group).The efficacy,safety(pancreatic fistula,intra-abdominal hemorrhage,sepsis,and organ dysfunction syndrome),abdominal bloating and pain relief time,bowel recovery time,hospital stay,inflammatory indicators(C-reactive protein,interleukin-6,and pro-calcitonin),and Acute Physiology and Chronic Health Evaluation(APACHE)II score of both groups were evaluated for comparison.RESULTS Compared with the control group,the research group had a markedly higher total effective rate,faster abdominal bloating and pain relief and bowel recovery,INTRODUCTION Pancreatitis,an inflammatory disease occurring in the pancreatic tissue,is classified as either acute or chronic and is associated with high morbidity and mortality,imposing a socioeconomic burden[1,2].The pathogenesis of this disease involves early protease activation,activation of nuclear factor kappa-B-related inflammatory reactions,and infiltration of immune cells[3].Severe acute pancreatitis(SAP)is a serious condition involving systemic injury and subsequent possible organ failure,accounting for 20%of all acute pancreatitis cases[4].SAP is also characterized by rapid onset,critical illness and unsatisfactory prognosis and is correlated with serious adverse events such as systemic inflammatory response syn-drome and acute lung injury,threatening the health of pa

关键词： Computerized tomography guidance Therapeutic percutaneous puncture catheter drainage somatostatin Severe acute pancreatitis Efficacy and safety

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Excitatory somatostatin interneurons in the dentate gyrus drive a widespread seizure network in cortical dysplasia

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Signal Transduction and Targeted Therapy 2023年第6期8卷 3111-3122页

作者： Yang Zheng Cenglin Xu Jinyi Sun Wenjie Ming Sijie Dai Yuying Shao Xiaoyun Qiu Menghan Li Chunhong Shen Jinghong Xu Fan Fei Jiajia Fang Xuhong Jiang Guoqing Zheng Weiwei Hu Yi Wang Shuang Wang Meiping Ding Zhong Chen Department of Neurology Zhejiang Provincial Hospital of Chinese MedicineThe First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou310060China Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province School of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou310053China Institute of Pharmacology and Toxicology College of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China Epilepsy Center Department of NeurologySecond Affiliated Hospital Zhejiang University School of MedicineHangzhou310009China Department of Neurology Fourth Affiliated Hospital of Zhejiang University School of MedicineYiwu322000China

Seizures due to cortical dysplasia are notorious for their poor prognosis even with medications and surgery,likely due to the widespread seizure network.Previous studies have primarily focused on the disruption of dysplastic lesions,rather than remote regions such as the hippocampus.Here,we first quantified the epileptogenicity of the hippocampus in patients with late-stage cortical dysplasia.We further investigated the cellular substrates leading to the epileptic hippocampus,using multiscale tools including calcium imaging,optogenetics,immunohistochemistry and electrophysiology.For the first time,we revealed the role of hippocampal somatostatin-positive interneurons in cortical dysplasia-related seizures.somatostatin-positive were recruited during cortical dysplasia-related seizures.Interestingly,optogenetic studies suggested that somatostatin-positive interneurons paradoxically facilitated seizure generalization.By contrast,parvalbumin-positive interneurons retained an inhibitory role as in controls.Electrophysiological recordings and immunohistochemical studies revealed glutamate-mediated excitatory transmission from somatostatin-positive interneurons in the dentate gyrus.Taken together,our study reveals a novel role of excitatory somatostatin-positive neurons in the seizure network and brings new insights into the cellular basis of cortical dysplasia.

关键词： somatostatin dysplasia seizure

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Parvalbumin neuroplasticity compensates for somatostatin impairment, maintaining cognitive function in Alzheimer’s disease

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Translational Neurodegeneration 2022年第1期11卷 566-587页

作者： Christopher Daniel Morrone Aaron Yenhsin Lai Jossana Bishay Mary Elizabeth Hill JoAnne McLaurin Biological Sciences Sunnybrook Research InstituteTorontoON M4N 3M5Canada Department of Laboratory Medicine and Pathobiology Temerty Faculty of MedicineUniversity of TorontoTorontoON M5S 1A8Canada

Background: Patient-to-patient variability in the degree to which β-amyloid, tau and neurodegeneration impact cognitive decline in Alzheimer’s disease (AD) complicates disease modeling and treatment. However, the underlying mechanisms leading to cognitive resilience are not resolved. We hypothesize that the variability in cognitive function and loss relates to neuronal resilience of the hippocampal GABAergic network. Methods: We compared TgF344-AD and non-transgenic littermate rats at 9, 12, and 15 months of age. Neurons, β-amyloid plaques and tau inclusions were quantified in hippocampus and entorhinal cortex. somatostatin (SST) and parvalbumin (PVB) interneurons were traced to examine hippocampal neuroplasticity and cognition was tested in the Barnes maze. Results: The 9-month-old TgF344-AD rats exhibited loss of neurons in the entorhinal cortex and hippocampus. Hippocampal neuronal compensation was observed in 12-month TgF344-AD rats, with upregulation of GABAergic interneuronal marker. By 15 months, the TgF344-AD rats had robust loss of excitatory and inhibitory neurons. β-Amyloid and tau pathology accumulated continuously across age. SST interneurons exhibited tau inclusions and atrophy from 9 months, whereas PVB interneurons were resilient until 15 months. The hippocampal PVB circuit underwent neuroplastic reorganization with increased dendritic length and complexity in 9- and 12-month-old TgF344- AD rats, before atrophy at 15 months. Strikingly, 12-month-old TgF344-AD rats were resilient in executive function and cognitive flexibility. Cognitive resilience in TgF344-AD rats occurred as maintenance of function between 9 and 12 months of age despite progressive spatial memory deficits, and was sustained by PVB neuroplasticity. Conclusions: Our results demonstrate the inherent neuronal processes leading to cognitive maintenance, and describe a novel finding of endogenous cognitive resilience in an AD model.

关键词： Alzheimer’s disease TgF344-AD rat GABAergic interneuron Parvalbumin somatostatin Barnes maze Hippocampus Neuronal compensation Cognitive resilience

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Association between serum somatostatin levels and glucose-lipid metabolism in the Jino ethnic minority and Han Chinese population

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Science China(Life Sciences) 2018年第11期61卷 1382-1388页

作者： Shiyun Wang Rong Zhang Xuhong Hou Fusong Jiang Jie Wang Zhen He Feng Jiang Cheng Hu Weiping Jia Shanghai Diabetes Institute Shanghai Key Laboratory of Diabetes MellitusShanghai Clinical Center for DiabetesShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai 200233China Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus Shanghai 200233China

We aim to investigate the relationship between serum somatostatin(SST) levels and glucose-lipid metabolism at various stages of glucose tolerance in the Jino ethnic minority(n=111) and Han population(n=113) of Yunnan Province, southwest China.Anthropometric parameters and biochemical traits were measured. Serum SST and plasma glucagon levels were tested. Participants were divided into three subgroups: isolated fasting hyperglycemia(IFH), isolated post challenge hyperglycemia(IPH)and normal glucose tolerance(NGT). SST levels were found lower while glucagon levels were significantly higher in the Jino ethnic with IPH(P=0.0026 and P=0.0069, respectively). Fasting glucose and high density lipoprotein-cholesterol(HDL-C)levels were higher(P=0.0055 and P=0.0021, respectively) and fasting insulin levels and homeostasis model assessments β-cell function were lower(P=0.0479 and P=0.0007, respectively) in the Jino population. After adjusting for confounding factors, the serum SST level was associated with glucagon(P<0.0001) in both populations. The SST level was correlated with fasting Cpeptide(P=0.0267) in Jino and HDL-C levels in Han(P=0.0079). Our findings suggest that serum SST levels and plasma glucagon levels may vary in subjects with IPH between two ethnics.

关键词： somatostatin glucagon hyperglycemia Jino ethnic Han Chinese

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Downregulation of endothelin-1 by somatostatin improves liver function of recipients undergoing adult-to-adult living donor liver transplantation

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Chinese Medical Journal 2010年第15期123卷 1961-1966页

作者： FENG Zhi-ying XU Xiao WU Ling-jiao WU Jian ZHU Sheng-mei ZHENG Shu-sen Department of Anesthesiology the First Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310003China Division of Hepatobiliary and Pancreatic Surgery Department of Surgery the First Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310003China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Institute of Infectious Diseases the First Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310003China

Background The aim of this study was to investigate the possible effect of somatostatin on the liver function of recipients undergoing living donor liver transplantation.Methods Forty recipients were randomized into group A （n=20） and group B （n=20）. Recipients in group A received no somatostatin whereas somatostatin was administrated for recipients in group B perioperatively. Liver function, the plasma concentration of endothelin-1 and nitric oxide, the intragraft expressions of endothelin-1 and inducible nitric oxide syntheses at 2 hours after declamping of the portal vein were compared between the two groups.Results Compared to group A, alanine transaminase values in group B were significantly reduced at 2 hours after portal vein declamping, at the end of the operation and postoperation day 1 （P 〈0.05）, whereas aspartate aminotransferase values in group B decreased at 30 minutes after portal vein clamping, at 2 hours after portal vein declamping and at the end of the operation （P 〈0.05）. Total bilirubin values in group B were reduced significantly at 2 hours after portal vein declamping and at the end of the operation when compared to group A （P 〈0.05）. Intragraft expression of endothelin-1 was significantly downregulated at 2 hours after declamping of the portal vein accompanied with a reduction of plasma concentration of endothelin-1 in the peripheral blood （P 〈0.05）.Conclusions somatostatin had a protective effect on liver function during the early phase after declamping of portal vein for recipients undergoing living donor liver transplantation, and the possible mechanism might be partially attributed to the downregulation of endothelin-1.

关键词： somatostatin endothelin-1 liver function tests liver transplantation

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Is prophylactic somatostatin effective to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis or hyperamylasemia？ A randomized, placebo-controlled pilot trial

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Chinese Medical Journal 2013年第13期126卷 2403-2408页

作者： WANG Zi-kai YANG Yun-sheng CAI Feng-chun WANG Yong-hua SHI Xiao-lin DING Chen LI Wen Department of Gastroenterology and Hepatology Chinese People'sLiberation Army (Jeneral Hospital Bmjing 100853 China

Background Effects of prophylactic somatostatin on post-endoscopic retrograde cholangiopancreatography （ERCP） pancreatitis （PEP） and hyperamylasemia remain inconclusive. This study aimed to examine whether high-dose, long-term continuous infusion of somatostatin can reduce the incidence of PEP and post-ERCP hyperamylasemia. Methods This was a randomized, placebo-controlled pilot trial. One hundred and twenty-four patients scheduled for ERCP from December 2008 to May 2010 randomly received one of the following three interventions： pre-ERCP somatostatin （0.5 mg/h for 24 hours, starting 1 hour prior to ERCP; n=36）, post-ERCP somatostatin （0.5 mg/h for 24 hours, starting 1 hour after ERCP; n=47）, or placebo （saline for 24 hours, starting 1 hour prior to ERCP; n=41）. Serum amylase and lipase concentrations were measured 1 to 3 hours prior to ERCP and 6, 24, and 48 hours after ERCP. Results The three groups did not differ in age, gender, medical history, or ERCP procedure （catheterization using contrast or guidewire, pancreatic duct visualization, procedure time, or procedure type）. The rate of PEP was 13.7% （17/124） in the overall study sample and 16.7% （6/36）, 10.6% （5/47）, and 14.6% （6/41） in the pre-ERCP somatostatin, post- ERCP somatostatin, and placebo groups, respectively （P=0.715）. The rate of post-ERCP hyperamylasemia was 19.4% （7/36）, 21.3% （10/47）, and 46.3% （19/41） in the pre-ERCP somatostatin, post-ERCP somatostatin, and placebo groups, respectively （P=0.011）. Conclusions High-dose, long-term continuous infusion （0.5 mg/h for 24 hours） of somatostatin, performed as either a pre- or post-ERCP, can reduce the incidence of hyperamylasemia, but not PEP.

关键词： somatostatin endoscopic retrograde cholangiopancreatography post-endoscopic retrogradecholangiopancreatography pancreatitis hyperamylasemia

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somatostatin involved in transmission of nociceptive information induced by substance P in the spinal cord

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Chinese Science Bulletin 1997年第5期42卷 426-429页

作者： Ruan, HZ Li, XC Cai, WQ Department of Physiology China Department of Histology and Embryology Third Military Medical College Chongqing China

SUBSTANCE P (SP) and somatostatin (SOM), which were believed to have relation with the transmission of nociceptive information, were distributed commonly in the spinal cord. In the previous study, we observed that SP mainly functioned as an algogenesia in spinal cord and could enhance noxious stimulus-evoked pain response. It was reported that SOM was also

关键词： somatostatin substance P in situ hybridization immunohistochemistry spinal cord.

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Successful management of chylous ascites with total parenteral nutrition,somatostatin,and fibrin glue

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Chinese Medical Journal 2007年第20期120卷 1847-1849页

作者： HUANG Qi GE Bu-jun LIU Li-ming TU Zhi-yuan ZHANG Guo-fen FAN Yue-zu Department of General Surgery Tongji Hospital Tongji University Shanghai 200065 China

Chylous ascites, an uncommon disease usually caused by obstruction or rupture of the peritoneal or retroperitoneal lymphatic glands, is defined as the accumulation of chyle in the peritoneal cavity. It is a difficult management problem due to the serious mechanical, nutritional, and immunological consequences of the constant loss of protein and lymphocytes. Most investigators believe that the incidence of chylous ascites is increasing because of more aggressive thoracic and retroperitoneal surgery and also because of the prolonged survival of patients with cancer. Although the incidence of chylous ascites has increased in recent years, treatment remains unsatisfactory. The standard conservative treatments include paracentesis, a medium chain triglyceride （MCT） based diet, total parenteral nutrition （TPN）, and recently recommended somatostatin, are preferable in most cases, but usually need several weeks to cure chyloperitonum. Open or laparoscopic ligation of ruptured lymph ducts, a commonly used procedure for persistent chylous ascites, may fail in patients without visible chylous leak. Fibrin glue, a widely used approach to treat various kinds of fistulae, has recently been reported to seal chylous leak during operation. Here we present two cases of chylous ascites who were successfully treated with fibrin glue in different settings.

关键词： chylous ascites fibrin glue somatostatin ovarian cancer tuberculous peritonitis

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VIP immunoreactive nerves and somatostatin and serotonin containing cellsin Crohn′s disease

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World Journal of Gastroenterology 1999年第6期5卷 541-543页

作者： Lu SJ Liu YQ Lin JS Wu HJ Sun YH Tan YB Weifang Med Coll Dept Pathol Weifang 261042 Peoples R China Tianjin Med Univ Dept Pathol Tianjin 300070 Peoples R China

INTRODUCTIONWith the progress of the studies on neuroendocrine and immunology in the gastrointestinal tract, it has been recognized that the intestinal neuroendocrine system and the immune system can influence and modulate each other and a neuroendocrine immunomodulation network in the intestine has been established[1]. Neuropeptides, such as vasoactive intestinal peptide (VIP), substance P (SP), somatostatin (SS) etc. are widely distributed in the gastrointestinal tract and they play an important role in the immunomodulation of the intestinal mucosa.

关键词： vasoactive intestinal peptide somatostatin serotonin Crohn′s disease immunohistochemistry histomorphometry

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