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Molecules (Basel, Switzerland) Feb 2024Zinc alumotitanate sorbents with various compositions were prepared through sol-gel synthesis with the use of ethyl acetoacetate as a chelating agent. The formation and...
Zinc alumotitanate sorbents with various compositions were prepared through sol-gel synthesis with the use of ethyl acetoacetate as a chelating agent. The formation and decomposition of chelates, providing insight into sol-gel process advancement, have been successfully monitored via H NMR, C NMR, and FTIR spectroscopy. It has been established that Al(OBu) and Ti(OBu) react completely with Eaa, forming chelates after 1 h, while after 24 h hydrolysis is already advanced. Hydrolysis is accelerated in the presence of Zn(NO)·6HO, supplying the water needed for hydrolysis. In dried gels, the amount of ethyl acetoacetate is greatly reduced, and it is mainly present unbound. According to XRD analysis, samples with none or less titania are composed of layered double hydroxide, while in samples with greater amounts of titania, crystal nitrates are present. In all samples except those without Al, the spinel phase with variable composition crystallizes.
PubMed: 38474477
DOI: 10.3390/molecules29050965 -
Animals : An Open Access Journal From... Mar 2024This review paper provides an in-depth analysis of three critical metabolic diseases affecting dairy cattle such as subacute ruminal acidosis (SARA), ketosis, and... (Review)
Review
This review paper provides an in-depth analysis of three critical metabolic diseases affecting dairy cattle such as subacute ruminal acidosis (SARA), ketosis, and hypocalcemia. SARA represents a disorder of ruminal fermentation that is characterized by extended periods of depressed ruminal pH below 5.5-5.6. In the long term, dairy herds experiencing SARA usually exhibit secondary signs of the disease, such as episodes of laminitis, weight loss and poor body condition despite adequate energy intake, and unexplained abscesses usually 3-6 months after an episode of SARA. Depressed milk-fat content is commonly used as a diagnostic tool for SARA. A normal milk-fat test in Holstein dairy cows is >4%, so a milk-fat test of <3% can indicate SARA. However, bulk tank testing of milk fat is inappropriate to diagnose SARA at the herd level, so when >4 cows out of 12 and <60 days in milk are suspected to have SARA it can be considered that the herd has a problem. The rapid or abrupt introduction of fresh cows to high-concentrate diets is the most common cause of SARA. Changes in ruminal bacterial populations when exposed to higher concentrate rations require at least about 3 weeks, and it is recommended that concentrate levels increase by no more than 400 g/day during this period to avoid SARA. Ketosis, a prevalent metabolic disorder in dairy cattle, is scrutinized with a focus on its etiological factors and the physiological changes leading to elevated ketone bodies. In total mix ration-fed herds, an increased risk of mastitis and reduced fertility are usually the first clinical signs of ketosis. All dairy cows in early lactation are at risk of ketosis, with most cases occurring in the first 2-4 weeks of lactation. Cows with a body condition score ≥3.75 on a 5-point scale at calving are at a greater risk of ketosis than those with lower body condition scores. The determination of serum or whole blood acetone, acetoacetate, beta-hydroxybutyrate (BHB) concentration, non-esterified fatty acids (NEFA), and liver biopsies is considered the best way to detect and monitor subclinical ketosis, while urine or milk cowside tests can also be used in on-farm monitoring programs. Concentrations >1.0 mmol/L or 1.4 mmol/L blood or serum BHB are considered diagnostic of subclinical ketosis. The standard threshold used for blood is 1.2 mmol/L, which corresponds to thresholds of 100 mcmol/L for milk and 15 mg/dL for urine. Oral administration of propylene glycol (250-400 g, every 24 h for 3-5 days) is the standard and most efficacious treatment, as well as additional therapy with bolus glucose treatment. Hypocalcemia is a disease of adult dairy cows in which acute hypocalcemia causes acute to peracute, afebrile, flaccid paralysis that occurs most commonly at or soon after parturition. Dairy cows are at considerable risk for hypocalcemia at the onset of lactation, when daily calcium excretion suddenly increases from about 10 g to 30 g per day. Cows with hypocalcemia have a more profound decrease in blood calcium concentration-typically below 5.5 mg/dL. The prevention of parturient paresis has been historically approached by feeding cows low-calcium diets during the dry period. Negative calcium balance triggers calcium mobilization before calving and better equips the cow to respond to the massive calcium needs at the onset of lactation. Calcium intake must be limited to <20 g per day for calcium restriction to be effective. The most practical and proven method for monitoring hypocalcemia is by feeding cows an acidogenic diet for ~3 weeks before calving. Throughout the review, emphasis is placed on the importance of early diagnosis and proactive management strategies to mitigate the impact of these metabolic diseases on dairy cattle health and productivity. The comprehensive nature of this paper aims to serve as a valuable resource for veterinarians, researchers, and dairy farmers seeking a deeper understanding of these prevalent metabolic disorders in dairy cattle.
PubMed: 38473200
DOI: 10.3390/ani14050816 -
Clinical Medicine Insights. Pediatrics 2024Hereditary Tyrosinemia Type 1 (HT1), a rare autosomal recessive metabolic disorder, arises from fumarylacetoacetate (FAH) enzyme deficiency, resulting in toxic...
BACKGROUND
Hereditary Tyrosinemia Type 1 (HT1), a rare autosomal recessive metabolic disorder, arises from fumarylacetoacetate (FAH) enzyme deficiency, resulting in toxic metabolite buildup. It manifests in acute, subacute, and chronic forms, with early diagnosis and Nitisinone treatment being vital.
OBJECTIVES
The study aims to highlight the different clinical presentations of Hereditary Tyrosinemia type 1 in a cohort of Pakistani children.
DESIGN
Retrospective observational study.
METHODOLOGY
All patients diagnosed with HT1 at Shifa International Hospital, Islamabad and Pak Emirates Military Hospital, Rawalpindi between 2010 and 2023 were included. Information was collected regarding age, gender, symptoms, physical signs, and laboratory results.
RESULTS
The study identified 6 cases of HT1. The average age at presentation was 8 months, with a mean delay in diagnosis of 26.8 months. Males were 4 (66.7%) and 2 (33.3%) were females. All patients had underlying liver disease presenting as abdominal distension with hepatosplenomegaly and accompanying growth failure. Four cases presented with rickets, 2 of which had hypophosphatemic rickets. Urine for succinylacetone was raised in all patients. Alpha fetoprotein was raised but hepatocellular carcinoma was diagnosed in 1 patient only. Low protein diet, and vitamin supplements were used for management. Five of the 6 patients died within 2 years of diagnosis.
CONCLUSION
Delayed referrals and unavailability of Nitisinone are the major challenges in diagnosing and treating HT1 in Pakistan.
PubMed: 38456192
DOI: 10.1177/11795565241236176 -
Frontiers in Chemistry 2024In this study, choline chloride/urea was used as a green deep eutectic solvent in the three-component reaction of hydrazine/phenylhydrazine, malononitrile, and aromatic...
Choline chloride/urea as a green and efficient deep eutectic solvent in three-component and four-component synthesis of novel pyrazole and pyrano[2,3-c] pyrazole derivatives with antibacterial and antifungal activity.
In this study, choline chloride/urea was used as a green deep eutectic solvent in the three-component reaction of hydrazine/phenylhydrazine, malononitrile, and aromatic aldehydes for synthesizing pyrazole derivatives, and in the four-component reaction of methyl/ethyl acetoacetate, hydrazine/phenylhydrazine, malononitrile, and aromatic aldehydes for synthesizing pyrano[2,3-c]pyrazole derivatives. Elemental analysis, H, and C NMR spectroscopy were used to confirm the structure of the synthesized pyrazole and pyrano[2,3-c] pyrazole derivatives. The antimicrobial effects of the synthesized pyrazole and pyrano[2,3-c] pyrazole derivatives were investigated. In antimicrobial tests, instructions from clinical and laboratory standards institutes were used. Antimicrobial study was done on pathogenic gram-positive and gram-negative species, and specialized aquatic strains and fungal species. Using choline chloride/urea, novel pyrazole derivatives and pyrano[2,3-c]pyrazole derivatives were synthesized, and other derivatives were synthesized with higher efficiency in less time than some previously reported methods. MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) obtained for derivatives were higher than some antibiotic drugs. Synthesis and reports of new derivatives of pyrazole and pyrano[2,3-c]pyrazole, and investigation and reports of their antimicrobial properties on gram-positive, gram-negative, and specialized aquatic and fungal species are among the novel and important findings of this study.
PubMed: 38435668
DOI: 10.3389/fchem.2024.1342784 -
Frontiers in Cellular and Infection... 2024is a versatile opportunistic pathogen which causes a variety of acute and chronic human infections, some of which are associated with the biofilm phenotype of the...
is a versatile opportunistic pathogen which causes a variety of acute and chronic human infections, some of which are associated with the biofilm phenotype of the pathogen. We hypothesize that defining the intracellular metabolome of biofilm cells, compared to that of planktonic cells, will elucidate the metabolic pathways and biomarkers indicative of biofilm inception. Disc-shaped stainless-steel coupons (12.7 mm diameter) were employed as a surface for static biofilm establishment. Each disc was immersed in a well, of a 24-well microtiter plate, containing a 1-mL Lysogeny broth (LB) suspension of ATCC 9027, a strain known for its biofilm prolificacy. This setup underwent oxygen-depleted incubation at 37°C for 24 hours to yield hypoxic biofilms and the co-existing static planktonic cells. In parallel, another planktonic phenotype of ATCC 9027 was produced in LB under shaking (200 rpm) incubation at 37°C for 24 hours. Planktonic and biofilm cells were harvested, and the intracellular metabolites were subjected to global untargeted metabolomic analysis using LC-MS technology, where small metabolites (below 1.5 kDa) were selected. Data analysis showed the presence of 324 metabolites that differed ( 0.05) in abundance between planktonic and biofilm cells, whereas 70 metabolites did not vary between these phenotypes ( > 0.05). Correlation, principal components, and partial least square discriminant analyses proved that the biofilm metabolome is distinctly clustered away from that of the two planktonic phenotypes. Based on the functional enrichment analysis, arginine and proline metabolism were enriched in planktonic cells, but butanoate metabolism was enriched in biofilm cells. Key differential metabolites within the butanoate pathway included acetoacetate, 2,3-butandiol, diacetyl, and acetoin, which were highly upregulated in the biofilm compared to the planktonic cells. Exogenous supplementation of acetoin (2 mM), a critical metabolite in butanoate metabolism, augmented biofilm mass, increased the structural integrity and thickness of the biofilm, and maintained the intracellular redox potential by balancing NADH/NAD ratio. In conclusion, hypoxic biofilm has a specialized metabolic landscape, and butanoate pathway is a metabolic preference and possibly required for promoting planktonic cells to the biofilm state. The butanoate pathway metabolites, particularly acetoin, could serve as markers for biofilm development.
Topics: Humans; Pseudomonas aeruginosa; Acetoin; Metabolomics; Metabolome; Hypoxia; Biofilms
PubMed: 38435305
DOI: 10.3389/fcimb.2024.1346813 -
IScience Mar 2024There are no blood-based biomarkers distinguishing patients with relapsing-remitting (RRMS) from secondary progressive multiple sclerosis (SPMS) although evidence...
There are no blood-based biomarkers distinguishing patients with relapsing-remitting (RRMS) from secondary progressive multiple sclerosis (SPMS) although evidence supports metabolomic changes according to MS disease severity. Here machine learning analysis of serum metabolomic data stratified patients with RRMS from SPMS with high accuracy and a putative score was developed that stratified MS patient subsets. The top differentially expressed metabolites between SPMS versus patients with RRMS included lipids and fatty acids, metabolites enriched in pathways related to cellular respiration, notably, elevated lactate and glutamine (gluconeogenesis-related) and acetoacetate and bOHbutyrate (ketone bodies), and reduced alanine and pyruvate (glycolysis-related). Serum metabolomic changes were recapitulated in the whole blood transcriptome, whereby differentially expressed genes were also enriched in cellular respiration pathways in patients with SPMS. The final gene-metabolite interaction network demonstrated a potential metabolic shift from glycolysis toward increased gluconeogenesis and ketogenesis in SPMS, indicating metabolic stress which may trigger stress response pathways and subsequent neurodegeneration.
PubMed: 38433900
DOI: 10.1016/j.isci.2024.109225 -
Viruses Feb 2024HIV-exposed, uninfected (HEU) children present with suboptimal growth and a greater susceptibility to infection in early life when compared to HIV-unexposed, uninfected...
HIV-exposed, uninfected (HEU) children present with suboptimal growth and a greater susceptibility to infection in early life when compared to HIV-unexposed, uninfected (HUU) children. The reasons for these findings are poorly understood. We used a metabolomics approach to investigate the metabolic differences between pregnant women living with HIV (PWLWH) and their HEU infants compared to the uninfected and unexposed controls. Untargeted metabolomic profiling was performed using H-NMR spectroscopy on maternal plasma at 28 weeks' gestation and infant plasma at birth, 6/10 weeks, and 6 months. PWLWH were older but, apart from a larger 28 week mid-upper-arm circumference, anthropometrically similar to the controls. At all the time points, HEU infants had a significantly reduced growth compared to HUU infants. PWLWH had lower plasma 3-hydroxybutyric acid, acetoacetic acid, and acetic acid levels. In infants at birth, threonine and myo-inositol levels were lower in the HEU group while formic acid levels were higher. At 6/10 weeks, betaine and tyrosine levels were lower in the HEU group. Finally, at six months, 3-hydroxyisobutyric acid levels were lower while glycine levels were higher in the HEU infants. The NMR analysis has provided preliminary information indicating differences between HEU and HUU infants' plasma metabolites involved in energy utilization, growth, and protection from infection.
Topics: Infant; Infant, Newborn; Child; Humans; Female; Pregnancy; HIV Infections; Mothers; Betaine; Metabolomics
PubMed: 38400088
DOI: 10.3390/v16020313 -
Cells Feb 2024Ketone bodies (KBs) are energy-efficient substrates utilized by the heart depending on its metabolic demand and substrate availability. Levels of circulating KBs have...
Ketone bodies (KBs) are energy-efficient substrates utilized by the heart depending on its metabolic demand and substrate availability. Levels of circulating KBs have been shown to be elevated in acute and chronic cardiovascular disease and are associated with severity of disease in patients with heart failure and functional outcome after myocardial infarction. To investigate whether this pattern similarly applies to patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB), we analysed prospectively collected pre- and postoperative blood samples from 192 cardiac surgery patients and compared levels and perioperative changes in total KBs with Troponin T as a marker of myocardial cell injury. We explored the association of patient characteristics and comorbidities for each of the two biomarkers separately and comparatively. Median levels of KBs decreased significantly over the perioperative period and inversely correlated with changes observed for Troponin T. Associations of patient characteristics with ketone body perioperative course showed notable differences compared to Troponin T, possibly highlighting factors acting as a "driver" for the change in the respective biomarker. We found an inverse correlation between perioperative change in ketone body levels and changes in troponin, indicating a marked decrease in ketone body concentrations in patients exhibiting greater myocardial cell injury. Further investigations aimed at better understanding the role of KBs on perioperative changes are warranted.
Topics: Humans; Cardiopulmonary Bypass; Troponin T; Ketone Bodies; Cardiac Surgical Procedures; Troponin; Biomarkers; Heart Injuries
PubMed: 38391907
DOI: 10.3390/cells13040294 -
Journal of Mass Spectrometry and... Jan 2024Ketone bodies (KBs) serve as important energy sources that spare glucose, providing the primary energy for cardiac muscle, skeletal muscle during aerobic exercise, and...
OBJECTIVES
Ketone bodies (KBs) serve as important energy sources that spare glucose, providing the primary energy for cardiac muscle, skeletal muscle during aerobic exercise, and the brain during periods of catabolism. The levels and relationships between the KBs are critical indicators of metabolic health and disease. However, challenges in separating isomeric KBs and concerns about sample stability have previously limited their clinical measurement.
METHODS
A novel 6.5-minute liquid chromatography-mass spectrometry-based assay was developed, enabling the precise measurement of alpha-, beta- and gamma-hydroxybutyrate, beta-hydroxyisobutyrate, and acetoacetate. This method was fully validated for human serum and plasma samples by investigating extraction efficiency, matrix effects, accuracy, recovery, intra- and inter-precision, linearity, lower limit of quantitation (LLOQ), carryover, specificity, stability, and more. From 107 normal samples, reference ranges were established for all analytes and the beta-hydroxybutyrate/acetoacetate ratio.
RESULTS
All five analytes were adequately separated chromatographically. An extraction efficiency between 80 and 120 % was observed for all KBs. Accuracy was evaluated through spike and recovery using 10 random patient samples, with an average recovery of 85-115 % for all KBs and a coefficient of variation of ≤ 3 %. Coefficients of variation for intra- and inter-day imprecision were < 5 %, and the total imprecision was < 10 %. No significant interferences were observed. Specimens remained stable for up to 6 h on ice or 2 h at room temperature.
CONCLUSIONS
The developed method is highly sensitive and robust. It has been validated for use with human serum and plasma, overcoming stability concerns and providing a reliable and efficient quantitative estimation of ketone bodies.
PubMed: 38375486
DOI: 10.1016/j.jmsacl.2024.01.004 -
Nutrition, Metabolism, and... Mar 2024The term "ketogenic diet" (KD) is used for a wide variety of diets with diverse indications ranging from obesity to neurological diseases, as if it was the same diet....
The term "ketogenic diet" (KD) is used for a wide variety of diets with diverse indications ranging from obesity to neurological diseases, as if it was the same diet. This terminology is confusing for patients and the medical and scientific community. The term "ketogenic" diet implies a dietary regimen characterized by increased levels of circulating ketone bodies that should be measured in blood (beta-hydroxybutyrate), urine (acetoacetate) or breath (acetone) to verify the "ketogenic metabolic condition". Our viewpoint highlights that KDs used for epilepsy and obesity are not the same; the protocols aimed at weight loss characterized by low-fat, low-CHO and moderate/high protein content are not ketogenic by themselves but may become mildly ketogenic when high calorie restriction is applied. In contrast, there are standardized protocols for neurological diseases treatment for which ketosis has been established to be part of the mechanism of action. Therefore, in our opinion, the term ketogenic dietary therapy (KDT) should be reserved to the protocols considered for epilepsy and other neurological diseases, as suggested by the International Study Group in 2018. We propose to adjust the abbreviations in VLCHKD for Very Low CarboHydrate Ketogenic Diet and VLEKD for Very Low Energy Ketogenic Diet, to clarify the differences in dietary composition. We recommend that investigators describe the researchers describing efficacy or side effects of KDs, to clearly specify the dietary protocol used with its unique acronym and level of ketosis, when ketosis is considered as a component of the diet's mechanism of action.
Topics: Humans; Diet, Ketogenic; Obesity; Epilepsy; Ketone Bodies; Ketosis
PubMed: 38326186
DOI: 10.1016/j.numecd.2024.01.014