BACKGROUND Congenital hypothyroidism(CH)is a common condition in both preterm and term infants characterized by either thyroid gland absence or hypofunctionality.The clinical association of refractory lactic acidosis ...BACKGROUND Congenital hypothyroidism(CH)is a common condition in both preterm and term infants characterized by either thyroid gland absence or hypofunctionality.The clinical association of refractory lactic acidosis and heart failure has rarely been observed in cases of pediatric patients with CH pathology.Here,we explored the etiological relationship between CH,heart failure,and refractory lactic acidosis to reflect the importance of thyroid function screening in neonates with heart disease.CASE SUMMARY A 33-day-old extremely premature female infant presented with tachypnea,respiratory distress,recurrent infections,and abdominal distension postnatal.On admission to our facility,she had cardiomegaly,hepatomegaly,and lactic acidosis(revealed on blood gas analysis),with lactate progressively rising to 25 mmol/L.Chest radiographs showed pulmonary congestion,while echocardiography revealed cardiac enlargement,left ventricular wall thickening,and pericardial effusion.Initial management aimed at correcting acidosis and treating heart failure proved ineffective.After reassessment,thyroid function tests showed significantly decreased triiodothyronine,free triiodothyronine,thyroxine,and free thyroxine levels,with a significantly increased thyroidstimulating hormone level,confirming a CH diagnosis.Levothyroxine was administered,resulting in rapid correction of lactic acidosis and gradual improvement of thyroid function and systemic symptoms,culminating in full recovery and discharge.We also reviewed the relevant literature on thyroid and cardiac dysfunctions in order to explore their deeper association.CONCLUSION This case links CH-induced heart failure with refractory lactic acidosis,urging prompt thyroid screening in affected neonates to reduce mortality.展开更多
BACKGROUND Renal tubular acidosis(RTA)refers to a group of kidney disorders characterized by defective acid excretion or bicarbonate reabsorption,leading to metabolic acidosis.This case series presents three cases of ...BACKGROUND Renal tubular acidosis(RTA)refers to a group of kidney disorders characterized by defective acid excretion or bicarbonate reabsorption,leading to metabolic acidosis.This case series presents three cases of RTA with distinct etiologies and clinical manifestations.These cases emphasize the necessity of a comprehensive evaluation of RTA,considering both renal and systemic origins.CASE SUMMARY The first case describes a female patient with osteopetrosis-related RTA,diagnosed with Guibaud-Vainsel syndrome,emphasizing the importance of genetic assessment.The second case delineates RTA secondary to focal segmental glomerulosclerosis,associating tubular dysfunction with glomerular pathology.In the first two cases whole exome sequencing confirmed genetic diagnosis.The third case illuminates RTA as a complication of Graves’disease,highlighting autoimmune implications.CONCLUSION These cases underscore the interdisciplinary approach essential in RTA management.Understanding the diverse pathophysiology of RTA aids in tailored therapeutic strategies and improved patient outcomes.展开更多
Background Subacute rumen acidosis(SARA)is a common metabolic disorder in ruminants that disrupts the rumen microbiome and animal health,but diagnosis is challenging due to subtle symptoms and invasive testing require...Background Subacute rumen acidosis(SARA)is a common metabolic disorder in ruminants that disrupts the rumen microbiome and animal health,but diagnosis is challenging due to subtle symptoms and invasive testing require-ments.This study explores the potential of the buccal(oral)microbiome as a diagnostic indicator for SARA,hypoth-esizing an interaction with the rumen microbiome.Results The study involved 47 dairy goats,including 11 on a control diet and 36 on high-concentrate diets with increasing rumen-degradable starch.Animals were grouped based on dietary exposure and ruminal pH:Control,Low-RDS Tolerance/SARA(LRDST/LRDSS),and High-RDS Tolerance/SARA(HRDST/HRDSS).Transcriptomics of rumen epithelium showed heightened inflammatory pathway gene expression in SARA-susceptible goats compared to controls and tolerant groups.Alpha diversity of ruminal bacteria showed lower Shannon diversity in HRDSS goats compared to HRDST whereas buccal bacteria displayed significantly lower Chao1 diversity in LRDSS goats compared to HRDST.Beta diversity analyses revealed distinct patterns between SARA-affected goats and healthy controls in both ruminal and buccal microbiomes.Prevotellaceae_UCG-003 emerged as a candidate biomarker,with reduced abundance in SARA-susceptible goats in both rumen and buccal samples.Machine learning classifiers achieved high accuracy in distinguishing SARA-susceptible goats using this genus(rumen AUC=0.807;buccal AUC=0.779).Source tracking analysis illustrated diminished cross-population of bacteria from the buccal to rumen(2.86%to 0.25%)and vice versa(8.59%to 1.17%),signifying compromised microbial interchange in SARA-affected goats.A microbiota transplant experiment verified SARA microbiota’s ability to induce pH decline,escalate inflammation-related gene expression(MAPK10,IL17B,FOSB,SPP1),disrupt microbial transfer,and reduce Prevotellaceae_UCG-003 in recipients.Conclusion Our findings highlight SARA’s dual impact on ruminal and buccal microbiota,exacerbating epithelial inflammation gene expression.Shifts in the buccal microbiome,specifically reductions in Prevotellaceae_UCG-003,mirror ruminal changes and can be influenced by inter-compartmental bacterial transmission,thereby offering a non-invasive diagnostic approach for SARA.展开更多
BACKGROUND Kidney dysfunction and reduced filtration capacity due to chronic kidney disease(CKD)lead to a shift in the body's acid-base balance,ultimately causing metabolic acidosis(MA).Sodium bicarbonate has been...BACKGROUND Kidney dysfunction and reduced filtration capacity due to chronic kidney disease(CKD)lead to a shift in the body's acid-base balance,ultimately causing metabolic acidosis(MA).Sodium bicarbonate has been used as a supplement to alleviate the symptoms and reverse the acidosis,and it may even slow the progression of CKD.However,its safety profile and overall effectiveness are uncertain.AIM To conduct a systematic review and meta-analysis of clinical trials assessing sodium bicarbonate's safety and efficacy for treating CKD-induced MA.METHODS Medline,Scopus,EMBASE,and Cochrane Central were systematically searched from inception until May 2024 to select all relevant randomized control trials(RCTs)and non-RCT(NRCTs)evaluating the effectiveness of sodium bicarbonate in correcting MA in end-stage renal disease patients.In addition,ClinicalTrials.gov,Medrxiv.org,and Google Scholar were searched for other literature.A random-effects meta-analysis was performed to derive mean differences(MD)and risk ratios(RR)with their 95%CI for continuous and dichotomous outcomes respectively.RESULTS Following a systematic search of the databases,20 RCTs and 2 and NRCTs comprising 2932 patients were included in our study.The results revealed that sodium bicarbonate significantly increased serum bicarbonate in CKD patients(MD:2.59,95%CI:0.95-4.22;P=0.02;I2=95%).However,there was a non-significant increase in estimated glomerular filtration rate(eGFR)in patients on sodium bicarbonate therapy(MD:0.93,95%CI:-1.88-3.75;P=0.52;I2=93%).Upon assessment of the safety profile of sodium bicarbonate,no significant association was found in the outcomes of death/prolonged hospitalization(RR:1.05,95%CI:0.84-1.32;P=0.66;I2=0%),or gastrointestinal disorders(RR:1.64,95%CI:0.35-7.66;P=0.53;I2=76%),or worsening edema(RR:1.26,95%CI:0.94-1.68;P=0.12;I2=37%)when compared to control.CONCLUSION Sodium bicarbonate therapy may halt worsening kidney function by correcting serum bicarbonate levels and treating MA.Although sodium bicarbonate does not significantly improve the eGFR,it may potentially prevent CKD progression while maintaining an overall favorable safety profile.展开更多
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 f...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 outcomes.Euglycemic DKA is an uncommon diagnosis but can occur in patients with type 1 or type 2 diabetes mellitus.With the addition of sodium/glucose cotransporter-2 inhibitors in diabetes mellitus management,euglycemic DKA incidence has increased.The other causes of euglycemic DKA include pregnancy,fasting,bariatric surgery,gastroparesis,insulin pump failure,cocaine intoxication,chronic liver disease and glycogen storage disease.The pathophysiology of euglycemic DKA involves a relative or absolute carbohydrate deficit,milder degree of insulin deficiency or resistance and increased glucagon/insulin ratio.Euglycemic 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 ketones.The diagnostic workup includes arterial blood gas for metabolic acidosis,serum ketones and exclusion of other causes of high anion gap metabolic acidosis.Euglycemic DKA treatment is on the same principles as for DKA with correction of dehydration,electrolytes deficit and insulin replacement.The dextrosecontaining fluids should accompany intravenous insulin to correct metabolic acidosis,ketonemia and to avoid hypoglycemia.展开更多
Diabetes affects approximately 30 million persons in the United States. Diabetes ketoacidosis is one of the most serious and acute complications of diabetes. At the time of presentation and during treatment of diabeti...Diabetes affects approximately 30 million persons in the United States. Diabetes ketoacidosis is one of the most serious and acute complications of diabetes. At the time of presentation and during treatment of diabetic ketoacidosis(DKA), several metabolic and electrolyte derangements can ultimately result in respiratory compromise. Most commonly, hypokalemia, hypomagnesemia and hypophosphatemia can eventually lead to respiratory muscles failure.Furthermore, tachypnea, hyperpnea and more severely, Kussmaul breathing pattern can develop. Also, hydrostatic and non-hydrostatic pulmonary edema can occur secondary to volume shifts into the extracellular space and secondary to increased permeability of the pulmonary capillaries. The presence of respiratory failure in patients with DKA is associated with higher morbidity and mortality. Being familiar with the causes of respiratory compromise in DKA, and how to treat them, may represent better outcomes for patients with DKA.展开更多
Diabetic ketoacidosis(DKA)and hyperosmolar hyperglycemia state(HHS)are two life-threatening metabolic complications of diabetes that significantly increase mortality and morbidity.Despite major advances,reaching a uni...Diabetic ketoacidosis(DKA)and hyperosmolar hyperglycemia state(HHS)are two life-threatening metabolic complications of diabetes that significantly increase mortality and morbidity.Despite major advances,reaching a uniform consensus regarding the diagnostic criteria and treatment of both conditions has been challenging.A significant overlap between these two extremes of the hyperglycemic crisis spectrum poses an additional hurdle.It has well been noted that a complete biochemical and clinical patient evaluation with timely diagnosis and treatment is vital for symptom resolution.Worldwide,there is a lack of large-scale studies that help define how hyperglycemic crises should be managed.This article will provide a comprehensive review of the pathophysiology,diagnosis,and management of DKA-HHS overlap.展开更多
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 pot...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.展开更多
Renal tubular acidosis(RTA)can lead to renal calcification in children,which can cause various complications and impair renal function.This review provides pediatricians with a comprehensive understanding of the relat...Renal tubular acidosis(RTA)can lead to renal calcification in children,which can cause various complications and impair renal function.This review provides pediatricians with a comprehensive understanding of the relationship between RTA and renal calcification,highlighting essential aspects for clinical manage-ment.The article analyzed relevant studies to explore the prevalence,risk factors,underlying mechanisms,and clinical implications of renal calcification in children with RTA.Results show that distal RTA(type 1)is particularly associated with nephrocalcinosis,which presents a higher risk of renal calcification.However,there are limitations to the existing literature,including a small number of studies,heterogeneity in methodologies,and potential publication bias.Longitudinal data and control groups are also lacking,which limits our understanding of longterm outcomes and optimal management strategies for children with RTA and renal calcification.Pediatricians play a crucial role in the early diagnosis and management of RTA to mitigate the risk of renal calcification and associated complications.In addition,alkaline therapy remains a cornerstone in the treatment of RTA,aimed at correcting the acid-base imbalance and reducing the formation of kidney stones.Therefore,early diagnosis and appropriate therapeutic interventions are paramount in preventing and managing renal calcification to preserve renal function and improve long-term outcomes for affected children.Further research with larger sample sizes and rigorous methodologies is needed to optimize the clinical approach to renal calcification in the context of RTA in the pediatric population.展开更多
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...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 nutrition.AIM To assess short-term outcomes of oral nutrition initiated within 24 h of patients being admitted to a medical intensive care unit(MICU) for DKA.METHODS 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 DKA.RESULTS 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 complications.CONCLUSION In patients with DKA, early nutrition was associated with a shorter MICU and hospital LOS without increasing the rate of DKA complications.展开更多
All oral nucleoside analogues against hepatitis B virus,with an exception of telbivudine,have been reported causing lactic acidosis(LA).Here we report the first case of chronic hepatitis B developing severe refractory...All oral nucleoside analogues against hepatitis B virus,with an exception of telbivudine,have been reported causing lactic acidosis(LA).Here we report the first case of chronic hepatitis B developing severe refractory LA during telbivudine monotherapy.A 36-year-old man of Chinese origin received telbivudine antiviral treatment for chronic hepatitis B.After 11 mo of therapy,he developed anorexia,nausea,and vomiting with mild muscle weakness.The patient was found with elevated serum creatine phosphokinase up to 3683 U/L(upper limit of normal 170 U/L)and marked LA.LA did not resolve immediately following discontinuation of telbivudine.His condition began to improve after hemodialysis treatment for 16 times and usage of glucocorticosteroid.The patient fully recovered after 16 wk of treatment.This is the first documented case with severe LA caused by telbivudine monotherapy.Besides serum creatine phosphokinase,blood lactate level should also be closely monitored in patients receiving telbivudine.展开更多
Type A lactic acidosis resulted from hypoxic mitochondrial dysfunction is an independent predictor of mortality for critically ill patients. However, current therapeutic agents are still in shortage and can even be ha...Type A lactic acidosis resulted from hypoxic mitochondrial dysfunction is an independent predictor of mortality for critically ill patients. However, current therapeutic agents are still in shortage and can even be harmful. This paper reviewed data regarding lactic acidosis treatment and recommended that pyruvate might be a potential alkalizer to correct type A lactic acidosis in future clinical practice. Pyruvate is a key energy metabolic substrate and a pyruvate dehydrogenase(PDH) activator with several unique beneficial biological properties, including anti-oxidant and antiinflammatory effects and the ability to activate the hypoxia-inducible factor-1(HIF-1α)-erythropoietin(EPO) signal pathway. Pyruvate preserves glucose metabolism and cellular energetics better than bicarbonate, lactate, acetate and malate in the efficient correction of hypoxic lactic acidosis and shows few side effects. Therefore, application of pyruvate may be promising and safe as a novel therapeutic strategy in hypoxic lactic acidosis correction accompanied with multi-organ protection in critical care patients.展开更多
BACKGROUND： Early diagnosis of postoperative pancreatic fistula （POPF） is important for proper interventions. The pre- operative, intraoperative and early postoperative biochemical markers have predictive value of ...BACKGROUND： Early diagnosis of postoperative pancreatic fistula （POPF） is important for proper interventions. The pre- operative, intraoperative and early postoperative biochemical markers have predictive value of POPF. The present study was to evaluate several simple biochemical parameters in the pre- diction of POPF.展开更多
Diabetic keto acidosis(DKA) is the major cause for mortality in children with Diabetes mellitus(DM). With increasing incidence of type 1 DM worldwide, there is an absolute increase of DM among children between 0-14 ye...Diabetic keto acidosis(DKA) is the major cause for mortality in children with Diabetes mellitus(DM). With increasing incidence of type 1 DM worldwide, there is an absolute increase of DM among children between 0-14 year age group and overall incidence among less than 30 years remain the same. This shift towards younger age group is more of concern especially in developing countries where mortality in DKA is alarmingly high. Prior to the era of insulin, DKA was associated with 100% mortality and subsequently mortality rates have come down and is now, 0.15%-0.31% in developed countries. However the scenario in developing countries like India, Pakistan, and Bangladesh are very different and mortality is still high in children with DKA. Prospective studies on DKA in children are lacking in developing countries. Literature on DKA related mortality are based on retrospective studies and are very recent from countries like India, Pakistan and Bangladesh. There exists an urgent need to understand the differences between developed and developing countries with respect to mortality rates and factors associated with increased mortality in children with DKA. Higher mortality rates, increased incidence of cerebral edema, sepsis, shock and renal failure have been identified among DKA in children from developing countries.Root cause for all these complications and increased mortality in DKA could be delayed diagnosis in children from developing countries. This necessitates creating awareness among parents, public and physicians by health education to identify symptoms of DM/DKA in children, in order to decrease mortality in DKA. Based on past experience in Parma, Italy it is possible to prevent occurrence of DKA both in new onset DM and in children with established DM, by simple interventions to increase awareness among public and physicians.展开更多
The objectives of this study were to 1） determine the variation of nutrient digestion, plasma metabolites and oxidative stress parameters triggered by induced subacute ruminal acidosis （SARA）; and 2） evaluate the ...The objectives of this study were to 1） determine the variation of nutrient digestion, plasma metabolites and oxidative stress parameters triggered by induced subacute ruminal acidosis （SARA）; and 2） evaluate the ability of pelleted beet pulp （BP） as a replacement for ground corn to alleviate SARA. Eight Holstein-Friesian cows were fed four diets during four successive17 day periods： 1） total mixed ration （TMR） containing 0% finely ground wheat （FGW） （WO）; 2） TMR containing 10% FGW （W10）; 3） TMR containing 20% FGW （W20）; and 4） TMR containing 10% BP as a replacement for 10% ground corn （BP10）. The SARA induction protocol reduced the mean ruminal pH from 6.37 to 5.94, and the minimum ruminal pH decreased from 5.99 to 5.41 from baseline to challenge period. Mean ruminal pH increased from 5.94 to 6.05, and minimum daily ruminal pH increased from 5.41 to 5.63, when BP was substituted for corn. The apparent digestibility of nutrients was not affected by the dietary treatments, except that the digestibility of neutral detergent fibre （NDF） and acid detergent fibre （ADF） was reduced in cows fed the W20 diet compared with cows fed the W0 and W10 diets, and cows fed the BP10 diet had higher NDF and ADF digestibility than the cows fed the W20 diet. Cows fed the W20 diet had a lower plasma concentration of 13-hydroxybutyrate （BHBA）, non-esterified fatty acids （NEFA）, cholesterol, triglyceride, and total antioxidative capacity （TAC）, and a higher plasma concentration of glucose, insulin, malonaldehyde （MDA）, super oxygen dehydrogenises （SOD）, and glutathione peroxidase （GSH-Px） than cows fed the W0 diet. Substitution of BP for corn increased concentrations of plasma BHBA and TAC, but decreased concentrations of plasma MDA. Our results indicate that reduction of fibre digestion; the concomitant increase of plasma glucose and insulin; the decrease of plasma BHBA, NEFA, cholesterol, and triglyceride; and changes of plasma oxidative stress parameters are highly related to SARA induced by W20 diets. These variables may be alternative candidates for SARA diagnosis. We also suggest that the substitution of BP for corn could reduce the risk of SARA, increase fibre digestion, and improve the antioxidant status in dairy cows.展开更多
Objective To study the characteristics of spectra on proton magnetic resonance spectroscopy （^1H-MRS） and its value in patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes （ME...Objective To study the characteristics of spectra on proton magnetic resonance spectroscopy （^1H-MRS） and its value in patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes （MELAS）. Methods Seven clinically diagnosed patients with MELAS underwent magnetic resonance imaging （MRI） and ^1H-MRS examinations. The ^1H-MRS techniques, characteristics of the spectra, and its correlation with the laboratory tests were analyzed. Reaults Cerebral abnormalities were revealed in all 7 patients on conventional MR images, and most abnormal signals were observed in bilateral occipital, parietal, and temporal lobes. We found 4 cases with basal ganglia involvement, 2 cases with mild frontal lobe lesions, and 1 case with involvement of lateral cerebral peduncles and thalami. Additionally, 1 patient was involved with left insular lobe. Spectra from prominent lesions in brain parenchyma showed lactate doublet peak in 6 patients, 3 of whom were also noted lactate peak in ventricular cerehrospinal fluid （CSF）. Conclusion ^1H-MRS may provide more direct information about the metabolism changes, which aids to affirm the diagnosis, and may replace the conventional invasive method of quantifying lactate in CSF.展开更多
Grain-induced subacute ruminal acidosis(SARA)impairs rumen epithelial barrier function,but it is yet to be determined if SARA can cause persistent damage to the morphology and function of the rumen epithelial barrier....Grain-induced subacute ruminal acidosis(SARA)impairs rumen epithelial barrier function,but it is yet to be determined if SARA can cause persistent damage to the morphology and function of the rumen epithelial barrier.The objective of the present study was to investigate if SARA has persistent effects on the morphological structure and permeability of ruminal epithelium and the expression of the genes involved in epithelial barrier function using a lactating goat model.Twelve mid-lactating Saanen goats with rumen cannulas were randomly assigned to 1 of 2 groups:control group(Ctrl,n=4)fed a basal diet with a non-fiber carbohydrate(NFC)to neutral detergent fiber(NDF)ratio of 1.40,and SARA group(SARA,n=8)fed the same basal diet but with increasing NFC to NDF ratio from 1.4 to 1.79,2.31,and 3.23 overtime to induce SARA.At the end of the SARA challenge(post-SARA),4 goats were randomly selected from the SARA group and fed only hay mixture ad libitum for another 4 weeks to allow for restitution(post-SARA).Ruminal pH was continuously recorded to monitor the severity of SARA.Samples of the ventral ruminal epithelium were collected after slaughter to examine the structural and functional changes of the ruminal epithelium using transmission electron microscopy(TEM),Ussing chambers,qRT-PCR,and Western bolt analyses.Compared with the Ctrl group,ruminal papilla length,width,surface area and thickness of stratum corneum increased(P<0.05),while stratum spinosum and basale thickness,and total depth of the epithelium decreased(P<0.05)in the SARA group.These changes diminished or tended to return to the levels of the Ctrl group in the post-SARA group(P>0.05).The SARA challenge also decreased cellular junction and widened the intercellular space between epithelial cells.Rumen transepithelial short-circuit current(Isc),tissue conductance(Gt),and mucosa-to-serosa flux of paracellular horseradish peroxidase(HRP)all increased(P<0.05)both in the SARA and post-SARA groups,which indicates that SARA can induce a sustained increase in epithelial permeability and barrier dysfunction.Moreover,the mRNA and protein expressions of CLDN1,OCLN and ZO-1 were down-regulated(P<0.01)in both the SARA and post-SARA groups.The results of this study showed that SARA could result in sustained epithelial barrier dysfunction,at both structural and functional levels,which is associated with decreased expression of rumen epithelial tight junction proteins,and the restitution of rumen epithelial barrier function is slower than that of its morphology.展开更多
This report presents a case of massive mucosal necrosis of the small intestine in a patient with mitochondrial myopathy,encephalopathy,lactic acidosis,and stroke-like episodes(MELAS),which particularly affects the bra...This report presents a case of massive mucosal necrosis of the small intestine in a patient with mitochondrial myopathy,encephalopathy,lactic acidosis,and stroke-like episodes(MELAS),which particularly affects the brain,nervous system and muscles.A 45-year-old Japanese female,with an established diagnosis of MELAS,presented with vomiting.Computed tomography showed portomesenteric venous gas and pneumatosis intestinalis.She underwent a resection of the small intestine.A microscopic study showed necrosis of the mucosa and vacuolar degeneration of smooth muscle cells in the arterial wall.Immunohistochemistry showed anti-mitochondrial antibody to be highly expressed in the crypts adjacent the necrotic mucosa.The microscopic and immunohistochemical findings suggested the presence of a large number of abnormal mitochondria in MELAS to be closely linked to mucosal necrosis of the small intestine.展开更多
Glucose is the main energy substrate for neurons, however, at certain conditions, e.g. in starvation, these cells could also use ketone bodies. This approach is used in clinical conditions as the ketogenic diet. The k...Glucose is the main energy substrate for neurons, however, at certain conditions, e.g. in starvation, these cells could also use ketone bodies. This approach is used in clinical conditions as the ketogenic diet. The ketogenic diet is actually a biochemical model of fasting. It includes replacing carbohydrates by fats in daily meal. Synthesis of ketone bodies β-hydroxubutirate, acetoacetate and acetone begins once glycogen stores have depleted in the liver. The ketogenic diet can be used to treat clinical conditions, primarily epilepsy. The mechanism of neuroprotective action of ketogenic diet is not very clear. It is shown that ketone bodies influence neurons at three different levels, namely, metabolic, signaling and epigenetic levels. Ketone bodies are not always neuroprotective. Sometimes they can be toxic for the brain. Ketoacidosis which is a very dangerous complication of diabetes mellitus or alcoholism can be taken as an example. The exact mechanism of how neuroprotective properties of ketone bodies reverse to neurotoxic is yet to be established.展开更多
文摘BACKGROUND Congenital hypothyroidism(CH)is a common condition in both preterm and term infants characterized by either thyroid gland absence or hypofunctionality.The clinical association of refractory lactic acidosis and heart failure has rarely been observed in cases of pediatric patients with CH pathology.Here,we explored the etiological relationship between CH,heart failure,and refractory lactic acidosis to reflect the importance of thyroid function screening in neonates with heart disease.CASE SUMMARY A 33-day-old extremely premature female infant presented with tachypnea,respiratory distress,recurrent infections,and abdominal distension postnatal.On admission to our facility,she had cardiomegaly,hepatomegaly,and lactic acidosis(revealed on blood gas analysis),with lactate progressively rising to 25 mmol/L.Chest radiographs showed pulmonary congestion,while echocardiography revealed cardiac enlargement,left ventricular wall thickening,and pericardial effusion.Initial management aimed at correcting acidosis and treating heart failure proved ineffective.After reassessment,thyroid function tests showed significantly decreased triiodothyronine,free triiodothyronine,thyroxine,and free thyroxine levels,with a significantly increased thyroidstimulating hormone level,confirming a CH diagnosis.Levothyroxine was administered,resulting in rapid correction of lactic acidosis and gradual improvement of thyroid function and systemic symptoms,culminating in full recovery and discharge.We also reviewed the relevant literature on thyroid and cardiac dysfunctions in order to explore their deeper association.CONCLUSION This case links CH-induced heart failure with refractory lactic acidosis,urging prompt thyroid screening in affected neonates to reduce mortality.
文摘BACKGROUND Renal tubular acidosis(RTA)refers to a group of kidney disorders characterized by defective acid excretion or bicarbonate reabsorption,leading to metabolic acidosis.This case series presents three cases of RTA with distinct etiologies and clinical manifestations.These cases emphasize the necessity of a comprehensive evaluation of RTA,considering both renal and systemic origins.CASE SUMMARY The first case describes a female patient with osteopetrosis-related RTA,diagnosed with Guibaud-Vainsel syndrome,emphasizing the importance of genetic assessment.The second case delineates RTA secondary to focal segmental glomerulosclerosis,associating tubular dysfunction with glomerular pathology.In the first two cases whole exome sequencing confirmed genetic diagnosis.The third case illuminates RTA as a complication of Graves’disease,highlighting autoimmune implications.CONCLUSION These cases underscore the interdisciplinary approach essential in RTA management.Understanding the diverse pathophysiology of RTA aids in tailored therapeutic strategies and improved patient outcomes.
基金supported by the National Key Research and Development Program for International Science and Technology Innovation Cooperation between Governments(2023YFE0111800)the Shaanxi Province’s San Qin Talent Attraction Program for Regional Youth Talents.
文摘Background Subacute rumen acidosis(SARA)is a common metabolic disorder in ruminants that disrupts the rumen microbiome and animal health,but diagnosis is challenging due to subtle symptoms and invasive testing require-ments.This study explores the potential of the buccal(oral)microbiome as a diagnostic indicator for SARA,hypoth-esizing an interaction with the rumen microbiome.Results The study involved 47 dairy goats,including 11 on a control diet and 36 on high-concentrate diets with increasing rumen-degradable starch.Animals were grouped based on dietary exposure and ruminal pH:Control,Low-RDS Tolerance/SARA(LRDST/LRDSS),and High-RDS Tolerance/SARA(HRDST/HRDSS).Transcriptomics of rumen epithelium showed heightened inflammatory pathway gene expression in SARA-susceptible goats compared to controls and tolerant groups.Alpha diversity of ruminal bacteria showed lower Shannon diversity in HRDSS goats compared to HRDST whereas buccal bacteria displayed significantly lower Chao1 diversity in LRDSS goats compared to HRDST.Beta diversity analyses revealed distinct patterns between SARA-affected goats and healthy controls in both ruminal and buccal microbiomes.Prevotellaceae_UCG-003 emerged as a candidate biomarker,with reduced abundance in SARA-susceptible goats in both rumen and buccal samples.Machine learning classifiers achieved high accuracy in distinguishing SARA-susceptible goats using this genus(rumen AUC=0.807;buccal AUC=0.779).Source tracking analysis illustrated diminished cross-population of bacteria from the buccal to rumen(2.86%to 0.25%)and vice versa(8.59%to 1.17%),signifying compromised microbial interchange in SARA-affected goats.A microbiota transplant experiment verified SARA microbiota’s ability to induce pH decline,escalate inflammation-related gene expression(MAPK10,IL17B,FOSB,SPP1),disrupt microbial transfer,and reduce Prevotellaceae_UCG-003 in recipients.Conclusion Our findings highlight SARA’s dual impact on ruminal and buccal microbiota,exacerbating epithelial inflammation gene expression.Shifts in the buccal microbiome,specifically reductions in Prevotellaceae_UCG-003,mirror ruminal changes and can be influenced by inter-compartmental bacterial transmission,thereby offering a non-invasive diagnostic approach for SARA.
文摘BACKGROUND Kidney dysfunction and reduced filtration capacity due to chronic kidney disease(CKD)lead to a shift in the body's acid-base balance,ultimately causing metabolic acidosis(MA).Sodium bicarbonate has been used as a supplement to alleviate the symptoms and reverse the acidosis,and it may even slow the progression of CKD.However,its safety profile and overall effectiveness are uncertain.AIM To conduct a systematic review and meta-analysis of clinical trials assessing sodium bicarbonate's safety and efficacy for treating CKD-induced MA.METHODS Medline,Scopus,EMBASE,and Cochrane Central were systematically searched from inception until May 2024 to select all relevant randomized control trials(RCTs)and non-RCT(NRCTs)evaluating the effectiveness of sodium bicarbonate in correcting MA in end-stage renal disease patients.In addition,ClinicalTrials.gov,Medrxiv.org,and Google Scholar were searched for other literature.A random-effects meta-analysis was performed to derive mean differences(MD)and risk ratios(RR)with their 95%CI for continuous and dichotomous outcomes respectively.RESULTS Following a systematic search of the databases,20 RCTs and 2 and NRCTs comprising 2932 patients were included in our study.The results revealed that sodium bicarbonate significantly increased serum bicarbonate in CKD patients(MD:2.59,95%CI:0.95-4.22;P=0.02;I2=95%).However,there was a non-significant increase in estimated glomerular filtration rate(eGFR)in patients on sodium bicarbonate therapy(MD:0.93,95%CI:-1.88-3.75;P=0.52;I2=93%).Upon assessment of the safety profile of sodium bicarbonate,no significant association was found in the outcomes of death/prolonged hospitalization(RR:1.05,95%CI:0.84-1.32;P=0.66;I2=0%),or gastrointestinal disorders(RR:1.64,95%CI:0.35-7.66;P=0.53;I2=76%),or worsening edema(RR:1.26,95%CI:0.94-1.68;P=0.12;I2=37%)when compared to control.CONCLUSION Sodium bicarbonate therapy may halt worsening kidney function by correcting serum bicarbonate levels and treating MA.Although sodium bicarbonate does not significantly improve the eGFR,it may potentially prevent CKD progression while maintaining an overall favorable safety profile.
文摘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 outcomes.Euglycemic DKA is an uncommon diagnosis but can occur in patients with type 1 or type 2 diabetes mellitus.With the addition of sodium/glucose cotransporter-2 inhibitors in diabetes mellitus management,euglycemic DKA incidence has increased.The other causes of euglycemic DKA include pregnancy,fasting,bariatric surgery,gastroparesis,insulin pump failure,cocaine intoxication,chronic liver disease and glycogen storage disease.The pathophysiology of euglycemic DKA involves a relative or absolute carbohydrate deficit,milder degree of insulin deficiency or resistance and increased glucagon/insulin ratio.Euglycemic 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 ketones.The diagnostic workup includes arterial blood gas for metabolic acidosis,serum ketones and exclusion of other causes of high anion gap metabolic acidosis.Euglycemic DKA treatment is on the same principles as for DKA with correction of dehydration,electrolytes deficit and insulin replacement.The dextrosecontaining fluids should accompany intravenous insulin to correct metabolic acidosis,ketonemia and to avoid hypoglycemia.
文摘Diabetes affects approximately 30 million persons in the United States. Diabetes ketoacidosis is one of the most serious and acute complications of diabetes. At the time of presentation and during treatment of diabetic ketoacidosis(DKA), several metabolic and electrolyte derangements can ultimately result in respiratory compromise. Most commonly, hypokalemia, hypomagnesemia and hypophosphatemia can eventually lead to respiratory muscles failure.Furthermore, tachypnea, hyperpnea and more severely, Kussmaul breathing pattern can develop. Also, hydrostatic and non-hydrostatic pulmonary edema can occur secondary to volume shifts into the extracellular space and secondary to increased permeability of the pulmonary capillaries. The presence of respiratory failure in patients with DKA is associated with higher morbidity and mortality. Being familiar with the causes of respiratory compromise in DKA, and how to treat them, may represent better outcomes for patients with DKA.
文摘Diabetic ketoacidosis(DKA)and hyperosmolar hyperglycemia state(HHS)are two life-threatening metabolic complications of diabetes that significantly increase mortality and morbidity.Despite major advances,reaching a uniform consensus regarding the diagnostic criteria and treatment of both conditions has been challenging.A significant overlap between these two extremes of the hyperglycemic crisis spectrum poses an additional hurdle.It has well been noted that a complete biochemical and clinical patient evaluation with timely diagnosis and treatment is vital for symptom resolution.Worldwide,there is a lack of large-scale studies that help define how hyperglycemic crises should be managed.This article will provide a comprehensive review of the pathophysiology,diagnosis,and management of DKA-HHS overlap.
文摘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.
文摘Renal tubular acidosis(RTA)can lead to renal calcification in children,which can cause various complications and impair renal function.This review provides pediatricians with a comprehensive understanding of the relationship between RTA and renal calcification,highlighting essential aspects for clinical manage-ment.The article analyzed relevant studies to explore the prevalence,risk factors,underlying mechanisms,and clinical implications of renal calcification in children with RTA.Results show that distal RTA(type 1)is particularly associated with nephrocalcinosis,which presents a higher risk of renal calcification.However,there are limitations to the existing literature,including a small number of studies,heterogeneity in methodologies,and potential publication bias.Longitudinal data and control groups are also lacking,which limits our understanding of longterm outcomes and optimal management strategies for children with RTA and renal calcification.Pediatricians play a crucial role in the early diagnosis and management of RTA to mitigate the risk of renal calcification and associated complications.In addition,alkaline therapy remains a cornerstone in the treatment of RTA,aimed at correcting the acid-base imbalance and reducing the formation of kidney stones.Therefore,early diagnosis and appropriate therapeutic interventions are paramount in preventing and managing renal calcification to preserve renal function and improve long-term outcomes for affected children.Further research with larger sample sizes and rigorous methodologies is needed to optimize the clinical approach to renal calcification in the context of RTA in the pediatric population.
文摘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 nutrition.AIM To assess short-term outcomes of oral nutrition initiated within 24 h of patients being admitted to a medical intensive care unit(MICU) for DKA.METHODS 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 DKA.RESULTS 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 complications.CONCLUSION In patients with DKA, early nutrition was associated with a shorter MICU and hospital LOS without increasing the rate of DKA complications.
基金Supported by National Natural Science Foundation of ChinaNo.81071354 and 81271833+4 种基金National "973’ ’ProjectNo.2012CB519001National Science and Technology Major Project of ChinaNo.2012ZX10002007-001-002No.2013ZX10002001
文摘All oral nucleoside analogues against hepatitis B virus,with an exception of telbivudine,have been reported causing lactic acidosis(LA).Here we report the first case of chronic hepatitis B developing severe refractory LA during telbivudine monotherapy.A 36-year-old man of Chinese origin received telbivudine antiviral treatment for chronic hepatitis B.After 11 mo of therapy,he developed anorexia,nausea,and vomiting with mild muscle weakness.The patient was found with elevated serum creatine phosphokinase up to 3683 U/L(upper limit of normal 170 U/L)and marked LA.LA did not resolve immediately following discontinuation of telbivudine.His condition began to improve after hemodialysis treatment for 16 times and usage of glucocorticosteroid.The patient fully recovered after 16 wk of treatment.This is the first documented case with severe LA caused by telbivudine monotherapy.Besides serum creatine phosphokinase,blood lactate level should also be closely monitored in patients receiving telbivudine.
基金supported by the National Natural Science Foundation of China(No.81700181,No.81600148)
文摘Type A lactic acidosis resulted from hypoxic mitochondrial dysfunction is an independent predictor of mortality for critically ill patients. However, current therapeutic agents are still in shortage and can even be harmful. This paper reviewed data regarding lactic acidosis treatment and recommended that pyruvate might be a potential alkalizer to correct type A lactic acidosis in future clinical practice. Pyruvate is a key energy metabolic substrate and a pyruvate dehydrogenase(PDH) activator with several unique beneficial biological properties, including anti-oxidant and antiinflammatory effects and the ability to activate the hypoxia-inducible factor-1(HIF-1α)-erythropoietin(EPO) signal pathway. Pyruvate preserves glucose metabolism and cellular energetics better than bicarbonate, lactate, acetate and malate in the efficient correction of hypoxic lactic acidosis and shows few side effects. Therefore, application of pyruvate may be promising and safe as a novel therapeutic strategy in hypoxic lactic acidosis correction accompanied with multi-organ protection in critical care patients.
文摘BACKGROUND： Early diagnosis of postoperative pancreatic fistula （POPF） is important for proper interventions. The pre- operative, intraoperative and early postoperative biochemical markers have predictive value of POPF. The present study was to evaluate several simple biochemical parameters in the pre- diction of POPF.
文摘Diabetic keto acidosis(DKA) is the major cause for mortality in children with Diabetes mellitus(DM). With increasing incidence of type 1 DM worldwide, there is an absolute increase of DM among children between 0-14 year age group and overall incidence among less than 30 years remain the same. This shift towards younger age group is more of concern especially in developing countries where mortality in DKA is alarmingly high. Prior to the era of insulin, DKA was associated with 100% mortality and subsequently mortality rates have come down and is now, 0.15%-0.31% in developed countries. However the scenario in developing countries like India, Pakistan, and Bangladesh are very different and mortality is still high in children with DKA. Prospective studies on DKA in children are lacking in developing countries. Literature on DKA related mortality are based on retrospective studies and are very recent from countries like India, Pakistan and Bangladesh. There exists an urgent need to understand the differences between developed and developing countries with respect to mortality rates and factors associated with increased mortality in children with DKA. Higher mortality rates, increased incidence of cerebral edema, sepsis, shock and renal failure have been identified among DKA in children from developing countries.Root cause for all these complications and increased mortality in DKA could be delayed diagnosis in children from developing countries. This necessitates creating awareness among parents, public and physicians by health education to identify symptoms of DM/DKA in children, in order to decrease mortality in DKA. Based on past experience in Parma, Italy it is possible to prevent occurrence of DKA both in new onset DM and in children with established DM, by simple interventions to increase awareness among public and physicians.
基金financially supported by funds from the National Key Basic Research Program of China(Project No.2011CB100801)
文摘The objectives of this study were to 1） determine the variation of nutrient digestion, plasma metabolites and oxidative stress parameters triggered by induced subacute ruminal acidosis （SARA）; and 2） evaluate the ability of pelleted beet pulp （BP） as a replacement for ground corn to alleviate SARA. Eight Holstein-Friesian cows were fed four diets during four successive17 day periods： 1） total mixed ration （TMR） containing 0% finely ground wheat （FGW） （WO）; 2） TMR containing 10% FGW （W10）; 3） TMR containing 20% FGW （W20）; and 4） TMR containing 10% BP as a replacement for 10% ground corn （BP10）. The SARA induction protocol reduced the mean ruminal pH from 6.37 to 5.94, and the minimum ruminal pH decreased from 5.99 to 5.41 from baseline to challenge period. Mean ruminal pH increased from 5.94 to 6.05, and minimum daily ruminal pH increased from 5.41 to 5.63, when BP was substituted for corn. The apparent digestibility of nutrients was not affected by the dietary treatments, except that the digestibility of neutral detergent fibre （NDF） and acid detergent fibre （ADF） was reduced in cows fed the W20 diet compared with cows fed the W0 and W10 diets, and cows fed the BP10 diet had higher NDF and ADF digestibility than the cows fed the W20 diet. Cows fed the W20 diet had a lower plasma concentration of 13-hydroxybutyrate （BHBA）, non-esterified fatty acids （NEFA）, cholesterol, triglyceride, and total antioxidative capacity （TAC）, and a higher plasma concentration of glucose, insulin, malonaldehyde （MDA）, super oxygen dehydrogenises （SOD）, and glutathione peroxidase （GSH-Px） than cows fed the W0 diet. Substitution of BP for corn increased concentrations of plasma BHBA and TAC, but decreased concentrations of plasma MDA. Our results indicate that reduction of fibre digestion; the concomitant increase of plasma glucose and insulin; the decrease of plasma BHBA, NEFA, cholesterol, and triglyceride; and changes of plasma oxidative stress parameters are highly related to SARA induced by W20 diets. These variables may be alternative candidates for SARA diagnosis. We also suggest that the substitution of BP for corn could reduce the risk of SARA, increase fibre digestion, and improve the antioxidant status in dairy cows.
文摘Objective To study the characteristics of spectra on proton magnetic resonance spectroscopy （^1H-MRS） and its value in patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes （MELAS）. Methods Seven clinically diagnosed patients with MELAS underwent magnetic resonance imaging （MRI） and ^1H-MRS examinations. The ^1H-MRS techniques, characteristics of the spectra, and its correlation with the laboratory tests were analyzed. Reaults Cerebral abnormalities were revealed in all 7 patients on conventional MR images, and most abnormal signals were observed in bilateral occipital, parietal, and temporal lobes. We found 4 cases with basal ganglia involvement, 2 cases with mild frontal lobe lesions, and 1 case with involvement of lateral cerebral peduncles and thalami. Additionally, 1 patient was involved with left insular lobe. Spectra from prominent lesions in brain parenchyma showed lactate doublet peak in 6 patients, 3 of whom were also noted lactate peak in ventricular cerehrospinal fluid （CSF）. Conclusion ^1H-MRS may provide more direct information about the metabolism changes, which aids to affirm the diagnosis, and may replace the conventional invasive method of quantifying lactate in CSF.
基金supported by the National Natural ScienceFoundation of China(31472124)the Natural Science Foundation of Inner Mongolia,China(2019MS03031)+2 种基金the earmarked fund for China Agriculture Research System(CARS-36)the Innovation Fund of Inner Mongolia Agricultural and Animal Husbandry,China(2021CXJJM02)a China Scholarship Council(Beijing)fellowship to Hu Honglian for training at the Ohio State University,USA(201909150001)。
文摘Grain-induced subacute ruminal acidosis(SARA)impairs rumen epithelial barrier function,but it is yet to be determined if SARA can cause persistent damage to the morphology and function of the rumen epithelial barrier.The objective of the present study was to investigate if SARA has persistent effects on the morphological structure and permeability of ruminal epithelium and the expression of the genes involved in epithelial barrier function using a lactating goat model.Twelve mid-lactating Saanen goats with rumen cannulas were randomly assigned to 1 of 2 groups:control group(Ctrl,n=4)fed a basal diet with a non-fiber carbohydrate(NFC)to neutral detergent fiber(NDF)ratio of 1.40,and SARA group(SARA,n=8)fed the same basal diet but with increasing NFC to NDF ratio from 1.4 to 1.79,2.31,and 3.23 overtime to induce SARA.At the end of the SARA challenge(post-SARA),4 goats were randomly selected from the SARA group and fed only hay mixture ad libitum for another 4 weeks to allow for restitution(post-SARA).Ruminal pH was continuously recorded to monitor the severity of SARA.Samples of the ventral ruminal epithelium were collected after slaughter to examine the structural and functional changes of the ruminal epithelium using transmission electron microscopy(TEM),Ussing chambers,qRT-PCR,and Western bolt analyses.Compared with the Ctrl group,ruminal papilla length,width,surface area and thickness of stratum corneum increased(P<0.05),while stratum spinosum and basale thickness,and total depth of the epithelium decreased(P<0.05)in the SARA group.These changes diminished or tended to return to the levels of the Ctrl group in the post-SARA group(P>0.05).The SARA challenge also decreased cellular junction and widened the intercellular space between epithelial cells.Rumen transepithelial short-circuit current(Isc),tissue conductance(Gt),and mucosa-to-serosa flux of paracellular horseradish peroxidase(HRP)all increased(P<0.05)both in the SARA and post-SARA groups,which indicates that SARA can induce a sustained increase in epithelial permeability and barrier dysfunction.Moreover,the mRNA and protein expressions of CLDN1,OCLN and ZO-1 were down-regulated(P<0.01)in both the SARA and post-SARA groups.The results of this study showed that SARA could result in sustained epithelial barrier dysfunction,at both structural and functional levels,which is associated with decreased expression of rumen epithelial tight junction proteins,and the restitution of rumen epithelial barrier function is slower than that of its morphology.
文摘This report presents a case of massive mucosal necrosis of the small intestine in a patient with mitochondrial myopathy,encephalopathy,lactic acidosis,and stroke-like episodes(MELAS),which particularly affects the brain,nervous system and muscles.A 45-year-old Japanese female,with an established diagnosis of MELAS,presented with vomiting.Computed tomography showed portomesenteric venous gas and pneumatosis intestinalis.She underwent a resection of the small intestine.A microscopic study showed necrosis of the mucosa and vacuolar degeneration of smooth muscle cells in the arterial wall.Immunohistochemistry showed anti-mitochondrial antibody to be highly expressed in the crypts adjacent the necrotic mucosa.The microscopic and immunohistochemical findings suggested the presence of a large number of abnormal mitochondria in MELAS to be closely linked to mucosal necrosis of the small intestine.
基金supported by the Belorussian Republican Foundation of Fundamental Research(grant No.B17-006)
文摘Glucose is the main energy substrate for neurons, however, at certain conditions, e.g. in starvation, these cells could also use ketone bodies. This approach is used in clinical conditions as the ketogenic diet. The ketogenic diet is actually a biochemical model of fasting. It includes replacing carbohydrates by fats in daily meal. Synthesis of ketone bodies β-hydroxubutirate, acetoacetate and acetone begins once glycogen stores have depleted in the liver. The ketogenic diet can be used to treat clinical conditions, primarily epilepsy. The mechanism of neuroprotective action of ketogenic diet is not very clear. It is shown that ketone bodies influence neurons at three different levels, namely, metabolic, signaling and epigenetic levels. Ketone bodies are not always neuroprotective. Sometimes they can be toxic for the brain. Ketoacidosis which is a very dangerous complication of diabetes mellitus or alcoholism can be taken as an example. The exact mechanism of how neuroprotective properties of ketone bodies reverse to neurotoxic is yet to be established.
