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Hepatic metabolomics and transcriptomics to study susceptibility to ketosis in response to prepartal nutritional management

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Journal of Animal Science and Biotechnology 2020年第1期11卷 194-210页

作者： Khuram Shahzad Vincenzo Lopreiato Yusheng Liang Erminio Trevisi Johan S.Osorio Chuang Xu Juan J.Loor COMSATS Institute of Information Technology ChakShahzadIslamabad 44000Pakistan Department of Animal Sciences and Division of Nutritional Sciences University of IllinoisUrbanaIL 61801USA Istituto di Zootecnica Facoltàdi Scienze AgrarieAlimentari e AmbientaliUniversitàCattolica del Sacro Cuore29122 PiacenzaItaly Department of Dairy Science South Dakota State UniversityBrookingsSD 57006USA College of Animal Science and Veterinary Medicine Heilongjiang Bayi Agricultural UniversityXinyang Rd.5Daqing 163319China.

Background:ketosis in dairy cows is associated with body fat mobilization during the peripartal ***-clinical and clinical ketosis arise more frequently in cows that are overfed energy during the entire dry(last 50 to 45 days prior to parturition)or close-up period(last^28 days prepartum).Methods:A retrospective analysis was performed on 12 cows from a larger cohort that were fed a higher-energy diet[1.54 Mcal/kg of dry matter(DM);35.9%of DM corn silage and 13%of DM ground corn]during the close-up dry period,of which 6 did not develop clinical ketosis(OVE,0.83 mmol/L plasma hydroxybutyrate;BHB)and 6 were diagnosed with clinical ketosis(KET,1.4 mmol/L BHB)during the first week postpartum.A whole-transcriptome bovine microarray(Agilent Technologies)and metabolomics(GC-MS,LC-MS;Metabolon~?Inc.)were used to perform transcript and metabolite profiling of liver tissue harvested at-10 days relative to parturition which allowed to establish potential associations between prepartal transcriptome/metabolome profiles and susceptibility to clinical ketosis ***:Cows in KET had greater(P=0.01)overall body weight between-2 and 1 week around parturition,but similar body condition score than *** dry matter intake(DMI)did not differ prepartum,KET cows had lower(P<0.01)DMI and similar milk yield as OVE cows during the first week *** analysis revealed a total of 3065 differentially expressed genes(DEG;P≤0.05)in *** identified 15 out of 313 total biochemical compounds significantly affected(P≤0.10)in *** those,greater concentrations(P≤0.06,+2.3-fold)of glycochenodeoxycholate in KET cows also have been detected in humans developing non-alcoholic fatty liver *** analysis using the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database and the DEG revealed that,among the top 20 most-impacted metabolic pathway categories in KET,65%were overall *** included’Metabolism of cofactors

关键词： Bioinformatics ketosis Metabolomics Transition cow

Sirtuin 3 regulation:a target to alleviateβ-hydroxybutyric acid-induced mitochondrial dysfunction in bovine granulosa cells

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Journal of Animal Science and Biotechnology 2023年第4期14卷 1377-1394页

作者： Shanjiang Zhao Jianfei Gong Yi Wang Nuo Heng Huan Wang Zhihui Hu Haoyu Wang Haobo Zhang Huabin Zhu State Key Laboratory of Animal Nutrition Key Laboratory of Animal GeneticsBreeding and Reproduction of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina

Background During the transition period,the insufficient dry matter intake and a sharply increased in energy consumption to produce large quantities of milk,high yielding cows would enter a negative energy balance(NEB)that causes an increase in ketone bodies(KBs)and decrease in reproduction *** excess concentrations of circulating KBs,represented byβ-hydroxybutyric acid(BHBA),could lead to oxidative damage,which potentially cause injury to follicular granulosa cells(fGCs)and delayed follicular *** 3(Sirt3)regulates mitochondria reactive oxygen species(mitoROS)homeostasis in a beneficial manner;however,the molecular mechanisms underlying its involvement in the BHBA-induced injury of fGCs is poorly *** aim of this study was to explore the protection effects and underlying mechanisms of Sirt3 against BHBA overload-induced damage of *** Our findings demonstrated that 2.4 mmol/L of BHBA stress increased the levels of mitoROS in bovine *** investigations identified the subsequent mitochondrial dysfunction,including an increased abnormal rate of mitochondrial architecture,mitochondrial permeability transition pore(MPTP)opening,reductions in mitochondrial membrane potential(MMP)and Ca^(2+)release;these dysfunctions then triggered the caspase cascade reaction of apoptosis in ***,the overexpression of Sirt3 prior to treatment enhanced mitochondrial autophagy by increasing the expression levels of Beclin-1,thus preventing BHBA-induced mitochondrial oxidative stress and mitochondrial dysfunction in ***,our data suggested that the AMPK-mTOR-Beclin-1 pathway may be involved in the protective mechanism of Sirt3 against cellular injury triggered by BHBA *** These findings indicate that Sirt3 protects fGCs from BHBA-triggered injury by enhancing autophagy,attenuating oxidative stress and mitochondrial *** study provides new strategies to mitigate the fGCs injury caused by excess

关键词： BHBA Dairy cows Granulosa cells ketosis Mitochondrial function Sirt3

Investigation of HCAR2 antagonists as a potential strategy to modulate bovine leukocytes

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Journal of Animal Science and Biotechnology 2024年第4期15卷 1567-1577页

作者： Laman K.Mamedova Kirby C.Krogstad Paiton O.McDonald Laxman Pokhrel Duy H.Hua Evan C.Titgemeyer Barry J.Bradford Department of Animal Science Michigan State UniversityEast LansingMichigan 48824USA Department of Animal Sciences and Industry Kansas State UniversityManhattanKS 66506USA Comparative Medicine and Integrative Biology East LansingMI 48824USA Department of Chemistry Kansas State UniversityManhattanKS 66506USA

Background Dairy cows experiencing ketosis after calving suffer greater disease incidence and are at greater risk of leaving the herd. In vitro administration of beta-hydroxybutyric acid(BHBA;the primary blood ketone) has inhibitory effects on the function of bovine leukocytes. BHBA is a ligand of HCAR2 and the activation of these receptors promotes an anti-inflammatory response which may be related with immunosuppression observed in transition dairy cattle. The objective of this study was to identify and test antagonists for HCAR2 in bovine immune cells cultured with *** We observed expression of HCAR2 at the protein level within lymphocytes, monocytes, and granulocytes. The proportion of cells expressing HCAR2 tended to be greater in mid-lactation compared to early lactation cows;the increase was a result of increased proportion of T and B cells expressing HCAR2. Stimulation of HCAR2 with niacin or BHBA promoted Ca^(2+) mobilization in neutrophils and mononuclear cells. Mononuclear cells treated with BHBA had diminished intracellular Ca^(2+) responses when HCAR2 was knocked down by si RNA silencing, indicating Ca^(2+) mobilization was mediated by HCAR2 signaling. Two candidate antagonists for HCAR2, synthesized from niacin(NA-1 and NA-5), were tested;monocytes and neutrophils pre-treated with NA-1 and NA-5 had reduced Ca^(2+) mobilization after incubation with BHBA. Furthermore, NA-5 but not NA-1 prevented BHBA-associated reductions in cyclic *** We demonstrated that HCAR2 is present on bovine leukocytes and has greater expression later in lactation. We confirmed that BHBA and niacin derived HCAR2 antagonists alter bovine leukocyte activity. Our results demonstrate that both BHBA and niacin affect bovine leukocyte Ca^(2+) mobilization in a HCAR2-dependent manner.

关键词： Flow cytometry GPR109A HM74A ketosis

Early vs late oral nutrition in patients with diabetic ketoacidosis admitted to a medical intensive care unit

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World Journal of Diabetes 2019年第1期10卷 57-62页

作者： Kirill Lipatov Kevin K Kurian Courtney Shaver Heath D White Shekhar GhamANDe AlejANDro C Arroliga Salim Surani Department of Internal Medicine Division of Pulmonary Critical Care and Sleep MedicineBaylor Scott and White Health Department of Biostatistics Baylor Scott and White Health Department of Medicine Texas A and M University

BACKGROUND Diabetic ketoacidosis(DKA) has an associated mortality of 1% to 5%. Upon admission, patients require insulin infusion and close monitoring of electrolyte and blood sugar levels with subsequent transitioning to subcutaneous insulin and oral nutrition. No recommendations exist regarding the appropriate timing for initiation of oral *** To assess short-term outcomes of oral nutrition initiated within 24 h of patients being admitted to a medical intensive care unit(MICU) for *** A retrospective observational cohort study was conducted at a single academic medical center. The patient population consisted of adults admitted to the MICU with the diagnosis of DKA. Baseline characteristics and outcomes were compared between patients receiving oral nutrition within(early nutrition group) and after(late nutrition group) the first 24 h of admission. The primary outcome was 28-d mortality. Secondary outcomes included 90-d mortality, MICU and hospital lengths of stay(LOS), and time to resolution of *** There were 128 unique admissions to the MICU for DKA with 67 patientsreceiving early nutrition and 61 receiving late nutrition. The APACHE(Acute Physiology and Chronic Health Evaluation) IV mortality and LOS scores and DKA severity were similar between the groups. No difference in 28-or 90-d mortality was found. Early nutrition was associated with decreased hospital and MICU LOS but not with prolonged DKA resolution, anion gap closure, or greater rate of DKA *** In patients with DKA, early nutrition was associated with a shorter MICU and hospital LOS without increasing the rate of DKA complications.

关键词： Diabetes mellitus Diabetic ketoacidosis Diabetic complications Acidosis ketosis Critical care

Euglycemic diabetic ketoacidosis:A missed diagnosis

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World Journal of Diabetes 2021年第5期12卷 514-523页

作者： Prashant Nasa Sandeep Chaudhary Pavan Kumar Shrivastava Aanchal Singh Department of Critical Care Medicine NMC Specialty HospitalDubai 7832United Arab Emirates Department of Endocrinology NMC Specialty HospitalDubai 7832United Arab Emirates Department of Internal Medicine NMC Specialty HospitalDubai 7832United Arab Emirates

Euglycemic diabetic ketoacidosis(DKA)is an acute life-threatening metabolic emergency characterized by ketoacidosis and relatively lower blood glucose(less than 11 mmol/L).The absence of hyperglycemia is a conundrum for physicians in the emergency department and intensive care units;it may delay diagnosis and treatment causing worse *** DKA is an uncommon diagnosis but can occur in patients with type 1 or type 2 diabetes *** the addition of sodium/glucose cotransporter-2 inhibitors in diabetes mellitus management,euglycemic DKA incidence has *** other causes of euglycemic DKA include pregnancy,fasting,bariatric surgery,gastroparesis,insulin pump failure,cocaine intoxication,chronic liver disease and glycogen storage *** pathophysiology of euglycemic DKA involves a relative or absolute carbohydrate deficit,milder degree of insulin deficiency or resistance and increased glucagon/insulin *** DKA is a diagnosis of exclusion and should be considered in the differential diagnosis of a sick patient with a history of diabetes mellitus despite lower blood glucose or absent urine *** diagnostic workup includes arterial blood gas for metabolic acidosis,serum ketones and exclusion of other causes of high anion gap metabolic *** DKA treatment is on the same principles as for DKA with correction of dehydration,electrolytes deficit and insulin *** dextrosecontaining fluids should accompany intravenous insulin to correct metabolic acidosis,ketonemia and to avoid hypoglycemia.

关键词： Diabetic Ketoacidosis Sodium/glucose co-transporter-2 inhibitors Pregnancy with diabetic ketoacidosis Diabetes complications Pregnancy in diabetes ketosis Metabolic acidosis

Preserving finger length in a patient with symmetric digital gangrene under local anesthesia:A case report

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World Journal of Clinical Cases 2023年第27期11卷 6640-6645页

作者： Keun Hyung Kim In Chang Ko Hoon Kim Soo Yeon Lim Department of Plastic and Reconstructive Surgery Konyang University Medical CenterKonyang University of College of MedicineDaejeon 35365South Korea Department of Plastic and Reconstructive Surgery Konyang University HospitalKonyang University of College of MedicineMyunggok Medical Research CenterDaejeon 35365South Korea

BACKGROUND Case reports of symmetric digital gangrene resulting from high-dose vasopressors use in patients with alcoholic ketoacidosis,leading to cardiac arrest,are *** date,no specific treatment method for autolysis or surgical amputation or guidelines for determining the level of amputation have been *** SUMMARY In this case report,we describe a treatment method that effectively preserved the function of fingers by surgical treatment under local anesthesia with a minimum operative time,while also preserving finger length to the maximum possible *** Our approach may contribute to improved postoperative quality of life by preserving finger length.

关键词： Acidosis Disseminated intravascular coagulation ketosis Purpura fulminans Surgical amputation Case report

Use of sodium bicarbonate and blood gas monitoring in diabetic ketoacidosis: A review

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World Journal of Diabetes 2018年第11期9卷 199-205页

作者： Mit P Patel Ali Ahmed Tharini Gunapalan Sean E Hesselbacher Department of Internal Medicine Eastern Virginia Medical School Medicine Service Hampton Veterans Affairs Medical Center

Diabetic ketoacidosis(DKA) is a severe and toocommon complication of uncontrolled diabetes mellitus. Acidosis is one of the fundamental disruptions stemming from the disease process, the complications of which are potentially lethal. Hydration and insulin administration have been the cornerstones of DKA therapy; however, adjunctive treatments such as the use of sodium bicarbonate and protocols that include serial monitoring with blood gas analysis have been much more controversial. There is substantial literature available regarding the use of exogenous sodium bicarbonate in mild to moderately severe acidosis; the bulk of the data argue against significant benefit in important clinical outcomes and suggest possible adverse effects with the use of bicarbonate. However, there is scant data to support or refute the role of bicarbonate therapy in very severe acidosis. Arterial blood gas(ABG) assessment is an element of some treatment protocols, including society guidelines, for DKA. We review the evidence supporting these recommendations. In addition, we review the data supporting some less cumbersome tests, including venous blood gas assessment and routine chemistries. It remains unclear that measurement of blood gas pH, via arterial or venous sampling, impacts management of the patient substantially enough to warrant the testing, especially if sodium bicarbonate administration is not being considered. There are special circumstances when serial ABG monitoring and/or sodium bicarbonate infusion are necessary, which we also review. Additional studies are needed to determine the utility of these interventions in patients with severe DKA and pH less than 7.0.

关键词： Diabetic ketoacidosis Sodium bicarbonate Blood gas analysis Acidosis ketosis Ketone bodies Hyperglycemia

“酮粉法”连续一年监测大群奶牛酮病试验简报

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安徽科技学院学报 1989年第1期15卷 48-50页

作者：吴齐鸿商常发李光辉刘士喜陈会良安徽农业技术师范学院合肥市奶牛公司

为探寻监测奶牛酮病的方法,试验用“酮粉法”快速检验酮病的效果,探讨安徽省奶牛酮病的发病规律,为防治本病提供科学依据,在一年时间内,连续对安徽合肥保健奶牛场和淮南奶牛一场、二场的泌乳母牛,进行了全面的,每月一次的监测。通过对... 详细信息

为探寻监测奶牛酮病的方法,试验用“酮粉法”快速检验酮病的效果,探讨安徽省奶牛酮病的发病规律,为防治本病提供科学依据,在一年时间内,连续对安徽合肥保健奶牛场和淮南奶牛一场、二场的泌乳母牛,进行了全面的,每月一次的监测。通过对近一万头次的监测发现,这几个场奶牛酮病的发病率在头年的十一月份到第二年的四月份发病率较高(平均为3.7%),其中二月份发病率最高(6.62%)。

关键词： Tongfen" method (invented in this test) ketosis inci-dence

Study of the Management of Diabetic Metabolic Emergency in the National Teaching Hospital HKM of Cotonou

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Journal of Diabetes Mellitus 2014年第4期4卷 359-370页

作者： Annelie Kerekou Eugene Zoumenou Medard Agbantey Corneille Tiomon Daniel Amoussou-Guenou Francois Djrolo Martin Chobli Clinical Service of Endocrinology and Metabolism National Teaching Hospital HKM of CotonouUniversity of AbomeyCalaviBenin Clinical Service of Emergency Aid National Teaching Hospital HKM of CotonouUniversity of AbomeyCalaviBenin

Objective: To study the epidemiological, clinical and therapeutic profile of diabetic metabolic emergencies. Patients and methods: This was a prospective study in descriptive and analytical referred conducted over a period of 6 months in the National Teaching Hosptial HKM of Cotonou December 1, 2011 to May 31, 2012. The patients included in the case of our study were those who, conscious or comatose, had submitted a diabetic hypoglycemia or abnormal blood sugar (2.5 g/l), with a positive glycosuria and ketonuria positive or not. All patients gave their consent for this study. Results: 2786 patients were admitted to the emergency room, 57 (2%) of acute metabolic decompensation of diabetes. DKA accounted for 1.1%, hyperosmolar hyperglycemic syndrome 0.5% and 0.4% hypoglycemia. For hyperglycemic decompensation, sex ratio was 0.8 for females with a mean age of 50.7 ± 16.9 (16-84). For hypoglycemia, male gender was predominant. As decompensation factors for hyperglycemia, infection was found in 54% (n = 30) of cases and stroke by 29% hypertension (n = 15). As for hypoglycemia triggers were dominated by dietary error (50%) and therapeutic errors (25%). 63% (n = 36) of patients underwent resuscitation. More than 3 out of 4 patients were resuscitated to insulin. 98% of patients were rehydrated. The outcome was favorable in 56% of cases. The death rate was 25 % (n = 14). Conclusion: Diabetes mellitus is a serious condition and its severity is mainly due to complications which can be acute or chronic.

关键词： Ketoacidosis Diabetes Decompensation ketosis