Treatment Of Ketosis Research Articles

Propylene Glycol Alleviates Oxidative Stress and Enhances Immunity in Ketotic Cows through Modulating Amino Acid and Lipid Metabolism.

This study investigates the impact of propylene glycol (PRG) on ketotic cows, focusing on alleviating oxidative stress and enhancing immunity through modulating amino acid and lipid metabolism. Ketosis, a prevalent metabolic disease in dairy cows, negatively affects productivity and health. PRG, known for its gluconeogenic properties, was administered to cows with ketosis daily for three days and compared to an untreated group. Serum samples were taken to measure the biochemical parameters, and metabolomic and lipidomic analyses were performed with ultra-high-performance liquid chromatography-mass spectrometry. The results showed significant reductions in serum non-esterified fatty acids, beta-hydroxybutyrate, and C-reactive protein levels, alongside increased glucose, anti-inflammatory factor interleukin-10, superoxide dismutase, and glutathione peroxidase activities. Metabolomic and lipidomic analyses revealed significant alterations, including increased levels of glucogenic amino acids like glutamate and proline, and decreased levels of ceramide species. A pathway analysis indicated that PRG affects multiple metabolic pathways, including alanine, aspartate, glutamate metabolism, and sphingolipid metabolism. These findings suggest that PRG not only mitigates oxidative stress, but also enhances immune function by restoring metabolic homeostasis. This study provides valuable insights into the biochemical mechanisms underlying PRG's therapeutic effects, offering potential strategies for the effective management and treatment of ketosis in dairy cows.

The relationship between sodium glucose co-transporter 2 inhibitors and diabetic ketosis/infection: single center retrospective experiences

Aims: Diabetes is a serious social problem in our country and around the world. Beyond hyperglycemia, it causes common and potentially life-threatening complications in all systems. For this reason, beyond the regulation of blood glucose, a holistic approach and combating complications are important in diabetes management. Sodium glucose co-transporter 2 inhibitors (SGLT2-i) are one of many antidiabetic drug families and stand out with their strong blood sugar regulation and cardiac and renal protective effects independent of blood sugar decrease. Despite its strong effectiveness, it is seen as risky in terms of diabetic ketosis and infection, which limits its use. We aimed to investigate the legitimacy of concerns by examining the relationship between SGLT-2 inhibitors and diabetic ketosis/infection. Methods: Our study was designed single-center and retrospectively. 152 patients over the age of 18 who were treated as inpatients in our clinic with diabetic ketosis between January 2020 and June 2023 were included in the study. In these patients, ketosis and the severity of the infection clinic, if any, were examined through various parameters among Type 2 diabetic patients using SGLT-2 inhibitors, Type 2 diabetic patients not using SGLT-2 inhibitors, and Type 1 diabetes patients. These parameters were determined by the patient's blood and urine biochemistry tests at admission and discharge, the duration of ketosis treatment, the duration of intravenous antibiotic use, and the duration of hospitalization. Results: Within the scope of the study, type 2 diabetic patients using SGLT-2 inhibitors were compared with type 2 diabetic patients not using SGLT-2 inhibitors and type 1 diabetic patients. In patients using SGLT-2 inhibitors, the leukocyte in urine, an indicator of urinary tract infection, was found to be significantly higher (p<0.002). When the blood biochemistry tests of the patients at the time of admission were compared in terms of ketosis severity, no significant difference was detected between the groups. No significant difference was detected in terms of ketosis treatment duration, intravenous antibiotic use duration, and hospitalization duration. Conclusion: We believe that we have obtained data showing that ketoacidosis and infection complications associated with SGLT-2 inhibitors are manageable and controllable. Based on this, we recommend that further research be conducted on the side effects of SGLT-2 inhibitors, emphasizing their additional systemic benefits, and that the place of these agents in diabetic treatment should be discussed.

Lipolysis inhibition as a treatment of clinical ketosis in dairy cows: Effects on adipose tissue metabolic and immune responses

Dairy cows with clinical ketosis (CK) exhibit excessive adipose tissue (AT) lipolysis and systemic inflammation. Lipolysis in cows can be induced by the canonical (hormonally induced) and inflammatory lipolytic pathways. Currently, the most common treatment for CK is oral propylene glycol (PG); however, PG does not reduce lipolysis or inflammation. Niacin (NIA) can reduce the activation of canonical lipolysis, whereas cyclooxygenase inhibitors such as flunixin meglumine (FM) can limit inflammation and inhibit the inflammatory lipolytic pathway. The objective of this study was to determine the effects of including NIA and FM in the standard PG treatment for postpartum CK on AT function. Multiparous Jersey cows [n = 18; 7.1 (SD = 3.8) DIM] were selected from a commercial dairy. Inclusion criteria were CK symptoms (lethargy, depressed appetite, and drop in milk yield) and high blood levels of β-hydroxybutyrate (BHB ≥ 1.2 mmol/L). Cows with CK were randomly assigned to one of 3 treatments: 1) PG: 310 g administered orally once per d for 5 d, 2) PG+NIA: 24 g administered orally oral once per d for 3 d, 3) PG+NIA+FM: 1.1 mg/kg administered IV once per day for 3 d. Healthy cows (HC; n = 6) matched by lactation and DIM (±2 d) were sampled. Subcutaneous AT explants were collected at d 0 (d0) and 7 (d7) relative to enrollment. To assess AT insulin sensitivity, explants were treated with insulin (INS = 1 µL/L) during lipolysis stimulation with a β-adrenergic receptor agonist (isoproterenol, ISO = 1 µM). Lipolysis was quantified by glycerol release in the media. Lipid mobilization and inflammatory gene networks were evaluated using real-time qPCR. Protein biomarkers of lipolysis, insulin signaling, and AT inflammation, including HSL, AKT, and ERK1/2, were quantified by capillary immunoassays. Flow cytometry of AT cellular components was used to characterize macrophage inflammatory phenotypes. Statistical significance was determined by a non-parametric t-test when 2 groups (HC vs CK) were analyzed and an ANOVA test with Tukey adjustment when 3 treatment groups (PG vs PGNIA vs PGNIAFM) were evaluated. At d0, AT from CK cows showed higher mRNA expression of lipolytic enzymes ABHD5, LIPE, and LPL, as well as increased phosphorylation of the lipase HSL (pHSL) compared with HC. At d0, INS reduced lipolysis by 41 ± 8% in AT from HC, while CK cows were unresponsive (-2.9 ± 4%). AT from CK cows exhibited reduced Akt phosphorylation compared with HC. CK had increased AT expression of inflammatory gene markers, including CCL2, IL8, IL10, TLR4, and TNF, along with ERK1/2 phosphorylation. AT from CK cows showed increased macrophage infiltration compared with HC. By d7, AT from PGNIAFM cows had a more robust response to INS, as evidenced by reduced glycerol release (36.5 ± 8% compared with PG, 26.9 ± 7%, and PGNIA, 7.4 ± 8%) and enhanced phosphorylation of Akt. By d7, PGNIAFM cows presented lower inflammatory markers, including ERK1/2 phosphorylation and reduced macrophage infiltration, compared with PG and PGNIA. These data suggest that including NIA and FM in CK treatment improves AT insulin sensitivity and reduces AT inflammation and macrophage infiltration.

Evaluation of a novel dipotassium phosphate bolus for treatment of metabolic disorders in dairy cattle.

A dipotassium phosphate bolus (K Phos-Boost) has been developed to treat both hypophosphatemia and hypokalemia, as the clinical signs of both conditions are similar and occur in the early post-partum period. The objective of this research was to evaluate the efficacy and application of the bolus for prevention and treatment of metabolic diseases that are common in dairy production systems. Study 1 (Pharmacokinetic study): Healthy post-partum cows were either untreated or received two K Phos-Boost boluses at times 0, 24, and 48 h. Blood was taken at t = 0, 2-, 4-, 6-, 8-, 10-, 24-, and 52-h post-treatment for analysis of total serum minerals. There was an increase in serum phosphorous to normal levels within 2 h of treatment with the bolus, but control cows remained hypophosphatemic. Serum potassium was significantly elevated 2 h after bolus administration relative to control, while calcium, magnesium, sodium, and chloride levels were not affected by the K Phos-Boost bolus. Study 2 (Downer Cow Treatment): K Phos-Boost boluses were provided to cows that were unresponsive to intravenous calcium therapy and had been unable to stand for over 24 h ("downer cows"). Most cows (16 of 19) treated with two boluses were standing without assistance between 1 and 24 h after treatment and the serum phosphorous was increased to normal levels in five of five tested animals. Study 3 (Ketosis Treatment): cows with clinical ketosis were provided with propylene glycol and K Phos-Boost boluses (n = 29) or only propylene glycol (n = 23). Cows treated with the K Phos-Boost bolus showed a more rapid recovery by increased milk production (3.9 kg/day) and rumination rate (97 min/day). Study 4 (Health Promotion): cows in herds with >40% post-partum hypophosphatemia received K Phos-Boost boluses (n = 130) or no treatment (n = 146) following calving. There was a trend for treated 2nd-lactation animals to have higher milk production after 30 DIM (49.1 vs. 46.2 kg/day; P = 0.09). There were no significant differences between control and bolus treated animals in the incidence of subclinical ketosis, post-calving total health events, or culling rates. The K Phos-Boost bolus is a novel product and has the potential to treat and prevent several important metabolic diseases in dairy cattle. The studies described in this paper are early investigations and further research should be conducted to demonstrate the applications of a dipotassium phosphate bolus in dairy cows.

Lipolysis inhibition as a treatment of clinical ketosis in dairy cows: A randomized clinical trial

Excessive and protracted lipolysis in adipose tissues of dairy cows is a major risk factor for clinical ketosis (CK). This metabolic disease is common in postpartum cows when lipolysis provides fatty acids as an energy substrate to offset negative energy balance. Lipolysis in cows can be induced by the canonical (hormonally induced) and inflammatory pathways. Current treatments for CK focus on improving glucose in blood (i.e., oral propylene glycol [PG], or i.v. dextrose). However, these therapies do not inhibit the canonical and inflammatory lipolytic pathways. Niacin (NIA) can reduce activation of the canonical pathway. Blocking inflammatory responses with cyclooxygenase inhibitors such as flunixin meglumine (FM) can inhibit inflammatory lipolytic activity. The objective of this study was to determine the effects of including NIA and FM in the standard PG treatment for postpartum CK on circulating concentrations of ketone bodies. A 4-group, parallel, individually randomized trial was conducted in multiparous Jersey cows (n = 80) from a commercial dairy in Michigan during a 7-mo period. Eligible cows had CK symptoms (lethargy, depressed appetite, and milk yield) and hyperketonemia (blood β-hydroxybutyrate [BHB] ≥1.2 mmol/L). Cows with CK were randomly assigned to 1 of 3 groups where the first group received 310 g of oral PG once per day for 5 d; the second group received PG for 5 d + 24 g of oral NIA once per day for 3 d (PGNIA); and the third group received PG for 5 d + NIA for 3 d + 1.1 mg/kg i.v. FM once per day for 3 d (PGNIAFM). The control group consisted of cows that were clinically healthy (HC; untreated; BHB <1.2 mmol/L, n = 27) matching for parity and DIM with all 3 groups. Animals were sampled at enrollment (d 0), and d 3, 7, and 14 to evaluate ketone bodies and circulating metabolic and inflammatory biomarkers. Effects of treatment, sampling day, and their interactions were evaluated using mixed effects models. Logistic regression was used to calculate the odds ratio (OR) of returning to normoketonemia (BHB <1.2 mmol/L). Compared with HC, enrolled CK cows exhibited higher blood concentrations of dyslipidemia markers, including nonesterified fatty acids (NEFA) and BHB, and lower glucose and insulin levels. Cows with CK also had increased levels of biomarkers of pain (substance P), inflammation, including lipopolysaccharide-binding protein, haptoglobin, and serum amyloid A, and proinflammatory cytokines IL-4, MCP-1, MIP-1α, and TNFα. Importantly, 72.2% of CK cows presented endotoxemia and had higher circulating bacterial DNA compared with HC. By d 7, the percentage of cows with normoketonemia were higher in PGNIAFM = 87.5%, compared with PG = 58.33%, and PGNIA = 62.5%. At d 7 the OR for normoketonemia in PGNIAFM cows were 1.5 (95% CI, 1.03-2.17) and 1.4 (95% CI, 0.99-1.97) relative to PG and PGNIA, respectively. At d 3, 7, and 14, PGNIAFM cows presented the lowest values of BHB (PG = 1.36; PGNIA = 1.24; PGNIAFM = 0.89 ± 0.13 mmol/L), NEFA (PG = 0.58; PGNIA = 0.59; PGNIAFM = 0.45 ± 0.02 mmol/L), and acute phase proteins. Cows in PGNIAFM also presented the highest blood glucose increment across time points and insulin by d 7. These data provide evidence that bacteremia or endotoxemia, systemic inflammation, and pain may play a crucial role in CK pathogenesis. Additionally, targeting lipolysis and inflammation with NIA and FM during CK effectively reduces dyslipidemia biomarkers, improves glycemia, and improves overall clinical recovery.

Prevention of subclinical ketosis in cows during drying off and after calving

Research of the frequency of increased ketone bodies in cows during the transition period three weeks before calving and three weeks after calving should determine the tendency of the Holstein breed to ketosis. It is also important to investigate the relationship between changes in blood biochemical parameters and the development and treatment of ketosis. The purpose of the study was to determine the effectiveness of using a probiotic strain of bacteria in subclinical ketosis in cows during drying off and after calving. The following methods were used: testing for determining the level of beta-ketones in the blood of cows; biochemical method of blood testing; clinical method; statistical method. A study of cows in the drying off group showed that the level of β-ketones ranged from 0.2 to 1.0 mmol/L. Application efficiency of Bacillus Pumilus L. A 56 in a concentration of 1×109 , CFU/g at a dose of 30 g per animal was determined to be 100%. In the study of metabolic changes in the body of cows after calving patients with ketosis, the content of total protein, albumins globulins of the enzyme aspartate aminotransferase, and urea at the beginning of the study was increased and went beyond the maximum permissible limits of the reference level. After seven days of using the probiotic, the content of ketone bodies and biochemical parameters decreased to normal. It was proved that at the end of the study, the activity of alanine aminotransferase increased, the level of potassium, vitamins A and E increased. Thus, it was determined that the enzyme alanine aminotransferase is one of the metabolites, an increase in the level of which indicates the accumulation of lipids in the liver. In addition, the content of Ca, P, and vitamin D decreased during treatment, which indicates the risk of hypocationemia. In the group of cows after calving, the incidence of ketosis was 27%. The therapeutic efficacy of a probiotic of 35 g per animal in the postcalving distribution group was 73%. The practical value of the study lies in the prevention of subclinical ketosis in cows in deep drying off and after calving, reducing the cost of treating concomitant diseases, and culling animals

Breath Analysis in Children with Ketogenic Glycogen Storage Diseases

(1) Background: The treatment goal of ketogenic glycogen storage diseases (GSDs) is appropriate control of hypoglycemia and other disturbances such as dyslipidemia. Monitoring and treatment of ketosis are known to improve outcomes. We used breath analysis to identify volatile organic compounds (VOCs) that correlate with serum ketones in order to provide a non-invasive method of monitoring ketosis. (2) Methods: Consecutive children with ketogenic GSDs were recruited from a single center during routine admission to monitor serum glucose and ketone levels. Five breath samples were collected from every patient at the same time of blood draws. SIFT-mass spectrometry was used to analyze breath samples. Univariate linear mixed-effects regression models for 22 known VOCs and either serum ketones or glucose were performed. (3) Results: Our cohort included 20 patients aged 5–15 years with a mean BMI of 20 kg/m2 (72% tile). Most patients had GSD type 0 (35%), while 25% had type IX. VOCs that showed a significant correlation with serum ketone levels included acetone (p &lt; 0.0001), trimethylamine (p &lt; 0.0001), pentane (p = 0.0001), 3-methylhexane (p = 0.0047), and carbon disulfide (p = 0.0499). No correlation was found between serum glucose and any VOC. (4) Conclusions: Breath analysis is a promising noninvasive tool that can be used to predict ketone serum levels in patients with GSD.

PSXIII-B-13 Investigation of Genetic Markers That may be Associated with Responses of Dairy Cows to Ketosis Treatment

Abstract The objective of this study was to investigate genetic markers associated with different responses to ketosis treatment when compared to ketosis-free Holstein cows. Holstein cows (N=964) from four commercial farms, located in New York State/USA, were included in a randomized controlled trial for ketosis treatment for a period of 2 months (5/19/2019 to 7/20/2019). The cows were screened for BHB (β-hydroxybutyrate ≥1.2 mmol/L) in the first two weeks postpartum (0-14 DIM). Cows with negative results (BHB &amp;lt; 1.2 mmol/L) in the first week (0-7 DIM) were retested in the second week of lactation (8-14 DIM), if negative at both screening tests, cows were categorized as ketosis-free (control group). The cows with positive results in the screening period (0-14 DIM) were treated as detailed in Capel et al. (2020) and reassessed in the following two weeks. According to the cow`s response to the treatment, they were classified as CURED, RECURRENT, SEVERE, and CHRONIC. Out of the 964 cows, 489 were genotyped using the 50k Illumina Bead Chip array. A mixed linear model-based genome-wide association study (GWAS) was carried out in GCTA software. The GWAS was performed for each ketosis outcome compared to the control group. Several potential genomic regions were identified on chromosomes 1, 3, 4, 7, 8, 14, and 17. Overall, the highlighted genes included COL1A1, NEDD4l, DIP2A, CARD6, ITGA7, and MMP19, which have shared functions with genes previously associated with ketosis (e.g., CASP9, ACACA, and Interleukins) in pathways such as the transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds, Cell adhesion_ECM remodeling Pathway, TGF-beta signaling, Nucleotide-binding Oligomerization Domain (NOD), and Mesodermal commitment. These findings contribute to a better understanding of the mechanisms that trigger response to ketosis treatment and warrant further investigation.

Ketosis Alters Transcriptional Adaptations of Subcutaneous White Adipose Tissue in Holstein Cows during the Transition Period.

Simple SummaryKetosis in dairy cows is one of the common nutritional metabolic diseases during the perinatal period. We conducted the present subcutaneous white adipose tissue transcriptome-based study to investigate the pathogenesis of ketosis in dairy cows. The transcriptome results showed that the expression of PCK1 and PCK2, key enzymes of the glyceroneogenesis, was simultaneously downregulated post-partum compared to pre-partum, possibly resulting in impaired lipid storage in the adipose tissue of ketotic cows. Integrating the GO enrichment analysis and published gene expression traits, the inflammatory response biological process inhibiting PCK1 and PCK2 expression in adipose tissue may be important in the development of ketosis in dairy cows. The findings of the present study provided important clues for the therapeutic and preventive targets for ketosis.Ketosis is a common nutritional, metabolic disease during the perinatal period in dairy cows characterized by elevated blood β-hydroxybutyrate (BHBA). In this study, RNA sequencing (RNA-seq) was performed to investigate adaptive changes in adipose tissue during the perinatal period of dairy cows. Blood and tailhead subcutaneous white adipose tissue (sWAT) were obtained from ketotic cows (Ket = 8, BHBA ≥ 1.4 mmol/L) and non-ketotic cows (Nket = 6, BHBA < 1.4 mmol/L) 21 d pre-partum and 10 d post-partum. Compared with pre-partum, decreased lipid synthesis due to down-regulation of PCK1 may be in a strong association with clinical ketosis. Simultaneously, PCK2 was downregulated in the Ket postnatally compared to its expression prenatally, and the expression of PCK2 was 2.7~4.2 times higher than that of PCK1, implying a more severe lipid storage impairment in the Ket. Moreover, compared to pre-partum, the upregulated differentially expressed genes post-partum in the Ket were enriched in the inflammatory response biological process. The higher expression of TNC (tenascin C) in the post-partum Ket relative to the Nket suggested that the adipose tissue of ketotic cows might also be accompanied by tissue fibrosis. Notably, pre-partum CD209 was higher in the Ket than in the Nket, which might be used as a candidate marker for the pre-partum prediction of ketosis. Combined with published gene expression traits, these results suggested that inflammation leads to a more widespread downregulation of the lipid synthesis gene network in adipose tissue in ketotic cows. Additionally, sWAT in post-partum cows with ketosis might also be accompanied by tissue fibrosis which could make the treatment of ketosis more difficult.

EFFECT OF PROPYLENE GLYCOL ON BLOOD METABOLITES, RUMINAL AND PRODUCTIVE PARAMETERS OF GROWING-FINISHING LAMBS

&lt;p class="Default"&gt;&lt;strong&gt;Background. &lt;/strong&gt;Propylene glycol has been used successfully since the 1950’s for him acute and prophylactic treatment of ketosis in dairy cows however; its use has been poorly evaluated in beef cattle and meat sheep.&lt;strong&gt; Objective&lt;/strong&gt;. Evaluate the effects of different doses of propylene glycol on the productive parameters, blood metabolites and ruminal parameters in fattening lambs. &lt;strong&gt;Methodology&lt;/strong&gt;. Twenty lambs 14.70 ±0.57 kg of weigh, 2 months old, males and Katahdin-Black Belly breed, were randomly assigned to one of four treatments, a control mixed ration and an experimental diet with three different levels of propylene glycol: 1.0, 1.5 and 2.0 g/20 kg live weight/day. The effects of propylene glycol on blood metabolites, ruminal and productive parameters were assessed. &lt;strong&gt;Results&lt;/strong&gt;. Propylene glycol supplementation did not affect (P&amp;gt;0.05) glucose, total lipids, triglycerides and cholesterol concentration as well as increased (P&amp;lt;0.05) the concentration of beta hydroxybutyrate. In addition, its inclusion resulted in an increase in pH and protozoa population and in a decrease of reductive activity (P&amp;lt;0.05). No effect was observed (P&amp;gt;0.05) on feed intake, weight gain and feed conversion ratio of lambs but carcass yield was improved without increasing the feeding cost of production. &lt;strong&gt;Implications&lt;/strong&gt;. Propylene glycol is a viable option as an energy source in fattening lambs. &lt;strong&gt;Conclusion&lt;/strong&gt;. Inclusion of PPG increased the pH and the population of ruminal protozoa, reduced the formation of ketone bodies and improved the carcass yield of lambs without increasing the meat production cost.&lt;/p&gt;

Evaluation of intraperitoneal administration of glucose solution using in the treatment of ketosis in dairy cows

Ketosis in high‐yielding dairy cows is the most common metabolic pathology during late dryness and early lactation. This work aims to establish the possibility and effectiveness of therapy for ketosis in dairy cows through the intraperitoneal injection of a 20% glucose solution. For the experiment, on days 21‐30 of lactation, two groups of black‐and‐white cows with a β‐hydroxybutyrate level above 1.0 mmol / l were formed. Animals of the first group (n = 10) were injected four times with an interval of 24 hours intraperitoneally with 1000 ml of 20% dextrose solution. Cows of the second group (n = 10) in a similar regimen were injected dextrose intravenously. Blood for research was obtained before the start of injections, after 5, 30 minutes, 1, 2, 3 hours after the first injection of the solution, and one day and seven days after the end of therapy. It was found that a single intravenous injection of dextrose during the first 5 minutes is accompanied by an increase in the concentration of the monosaccharide in the blood by 2.2 times (from 5.1 to 11.4 mmol / L; P &lt;0.001). The level decreases to the initial values within 1 hour, and intraperitoneal infusion does not cause hyperglycemia. A redistribution of protein fractions accompanies therapy of cows with ketosis: a decrease in the albumin‐globulin coefficient by 16.8% (P &lt;0.05) with intraperitoneal administration and by 26.9% (P &lt;0.01) with intravenous administration. The activity of AST after intracavitary injections of dextrose decreased by 36.5% (P &lt;0.05). The loading of erythrocytes with substances of low and medium molecular weight was 19.4% (P &lt;0.05) with the intraperitoneal injection. It was not observed with the intravascular route of administration. The morphological composition of blood after intravenous administration of dextrose was characterized by an increase in the level of leukocytes by 34.8% (P &lt;0.05), a decrease in erythrocytes by 11.9% (P &lt;0.05), hemoglobin by 11.6% (P &lt;0, 05), hematocrit by 12.3% (P &lt;0.05). Therapy via intraperitoneal injection did not cause pronounced changes in these parameters. The intravenous administration of glucose promoted a more rapid elimination of ketone bodies, which decreased by 2 times one day after the end of therapy (P &lt;0.05), but after 7 days, their level began to increase again (by 21.1%). It did not have significant differences with indicators at the time of diagnosis. Intraperitoneal infusions were accompanied by a slight decrease (by 16.3%) in the level of β‐hydroxybutyrate one day after the end of therapy, followed by a pronounced decrease in the concentration of ketones by day 7 (2.3 times; P &lt;0.01). The dynamics of fructosamine indicate that intracavitary injections do not cause glycosylation of plasma proteins, while intravenous infusions increase the values by 37.0 ‐ 39.4% (P &lt;0.001). Thus, intraperitoneal administration of glucose during ketosis in dairy cows has a more favorable effect on the morphobiochemical composition of the blood and provides a more prolonged therapeutic effect.

Reducing milking frequency from twice to once daily as an adjunct treatment for ketosis in lactating dairy cows—A randomized controlled trial

This randomized controlled trial investigated the effects of temporarily reducing milking frequency (MF) on the resolution of ketosis and milk production in dairy cows in early lactation. To detect ketosis [blood β-hydroxybutyrate (BHB) ≥1.2 mmol/L], Holstein cows were screened daily from 3 to 16 d in milk using a cow-side meter. Cows diagnosed with ketosis (n = 104) were randomly assigned to twice-daily milking (TDM) or reduced to once-daily milking (ODM) for 2 wk, then returned to twice-daily milking. Both treatment groups received a 5-d treatment of an oral propylene glycol drench (PG; 300 g) beginning on the afternoon of the diagnosis; cows received additional 5-d PG treatments if they had a ketotic test result (blood BHB ≥1.2 mmol/L) at least 4 d after finishing the first PG treatment. Blood BHB tests were conducted for the first 3 d after ketosis diagnosis, and then once every 3 d for 21 d of trial (DOT). Milk and milk component data were collected weekly for 15 wk following trial enrollment. The ODM group showed rapidly and markedly decreased blood BHB concentrations (primiparous cows: 1 DOT, 0.92 ODM vs. 1.22 TDM, 15 DOT, 0.55 vs. 0.81 mmol/L; multiparous cows: 1 DOT, 1.01 vs. 1.40, 15 DOT, 0.78 vs. 1.65 mmol/L). In addition, a logistic regression model indicated that ODM cows were less likely to have blood BHB concentrations ≥1.2 mmol/L [primiparous cows: 3 DOT: ODM 1% (95% confidence interval: 0-10%) vs. TDM 43% (30-58%), 15 DOT ODM 0% (0-0.2%) vs. TDM 22% (13-36%); multiparous cows: 3 DOT: ODM 33% (24-44%) vs. TDM 59% (48-69%), 15 DOT ODM 20.9% (13-31%) vs. TDM 64% (53-74%)]. The proportion of ODM cows that required additional treatments of PG were substantially lower than the TDM group (ODM: 39%; TDM: 64%) than the TDM cows during the initial 21-d period. However, during the 2-wk treatment period, cows in the ODM group produced 26% less milk and 25% less energy-corrected milk than the TDM cows. During wk 3 to 15, when all cows were milked twice daily, ODM cows produced less milk (-14%) and energy-corrected milk (-12%) compared with the TDM group. Milk protein percentage was greater, and milk fat percentage and linear score tended to be greater in the ODM group over 15 wk. In conclusion, a 2-wk reduction of MF in ketotic cows from twice to once daily with treatment with PG resolved ketosis and decreased blood BHB concentrations more effectively than treating TDM cows with PG alone. However, the 2-wk MF reduction had immediate and long-term (up to 13 wk after cessation of MF reduction) negative effects on milk production.

USE OF BACILLUS PUMILUS FOR PREVENTION OF KETOSIS IN COWS

The paper considers the effectiveness of Bacillus pumilus (109 CFU / g) for dairy cows for the treatment and prevention of ketosis. The causes of ketosis in the farm were also studied. The research was conducted in LTD "Agrofirma Lan", v. Kindrativka, Sumy district, Sumy region. Healthy and ill on ketosis cows were used for the experiment. The total number of experimental animals was 15 heads. Animals with ketosis received compound feed with the addition of Bacillus pumilus (109 CFU / g) at a dose of 15-35 g per animal. Healthy cows in the control group had a normal diet for their production group. The studies were performed for 30 days. The aim of the study was to investigate the mechanism of acetonemia in farm animals and to determine the effectiveness of Bacillus pumilus (109 CFU / g) in ketosis of dairy cows. During the study it was found that cows at different times of the year productivity was largely related to the way they were kept. Thus, in the warm season, cows with an average daily milk yield of more than 35 kg and younger cows of the first lactation had better clinical indicators compared to other animals. According to the results of the studies, it was found that the level of urea and urea nitrogen in the cows of the experimental group before treatment was 77.8 % higher than in healthy animals in the control. Aspartate aminotransferase (AST) at the beginning of the study in cows with ketosis was 78.8 % higher than in healthy animals. An increase in the level of this metabolite in the blood indicates liver damage and increases and decreases simultaneously with urea and β-ketones in the blood of sick animals. In addition, serum protein levels, including globulins and albumins, in experimental and control cows were within the reference value for cows throughout the experimental period. Feeding cows that ill on ketosis Bacillus pumilus (109 CFU / g) at a dose of 35 g per animal helps to reduce serum β-ketones and return to physiological norm. The use of probiotic strain Bacillus pumilus does not cause toxic effects on organs and systems of the body. Contributes to the normalization of metabolic processes in the body.

Ketone bodies - causes and effects of their increased presence in cows' body fluids: A review.

Ketosis is the most common metabolic disease in high-performance dairy cows during the first 6-8 weeks of lactation. Its main symptoms include an excessive amount of so-called ketone bodies in a cow’s body fluids. Ketone bodies consist of β-hydroxybutyric acid (βHBA), acetoacetic acid, and acetone. βHBA is the main component with its share of the total volume of ketone bodies in the blood of about 70%. Clinical symptoms of ketosis in cows include loss of appetite, preference for forage to concentrated feed, and acetone odor in their mouth and urine. Those symptoms are accompanied by a production drop, an increase of concurrent illness (mastitis, metritis, and displaced abomasum), and poor reproductive performance. One of the ketosis characteristic effects is an increase in the level of fat in milk (>5%), while protein levels decrease (<2.9%). In the case of subclinical ketosis (SCK), the fat–protein ratio in milk is increased to above 1.4:1. The current consensus for SCK is to consider a cutoff point of βHBA to be at least 1.2 mmol/L in blood plasma. Ketosis prevention is based on keeping perinatal cows in good condition, that is, with around 3.5 points in the five-point body condition scoring, carefully balancing food doses during the first 2 months of lactation with the correct energy–protein ratio. Glucose precursor products should be administered orally, in particular to at-risk herds. Ketosis occurs in 7-14% on average of the total number of cows in a herd. In general, data on the prevalence of SCK vary considerably, depending on their source. Moreover, the problem is mostly observed in poorly-fed animals with high milk production potential. The objectives of this review are to reveal the current situation of ketosis prevalence, the possibility of diagnosis, consequences in dairy cows and to provide some recommendations for ketosis treatment and prevention.

Comparison of Protocols to Reduce Diabetic Ketoacidosis in Patients With Type 1 Diabetes Prescribed a Sodium-Glucose Cotransporter 2 Inhibitor.

OBJECTIVE | Sodium-glucose cotransporter 2 (SGLT2) inhibitors are approved for type 1 diabetes in Europe and Japan, with off-label use in type 1 diabetes in the United States. Although there were no consistent approaches to risk mitigation in clinical trials of these agents, protocols have been developed to try to reduce the risk of diabetic ketoacidosis (DKA). However, a validated risk mitigation strategy does not exist. We reviewed available DKA risk mitigation protocols to better understand the various strategies currently in use. METHODS | We conducted a search of the published medical literature and other medical information sources, including conference presentations, for protocols. We then categorized the information provided into guidance on patient selection, initiation of SGLT2 inhibitors, ketone monitoring, necessary patient action in the event of ketosis or DKA, and inpatient treatment of ketosis or DKA. RESULTS | Patient selection is generally similar among the protocols, although some require a minimum BMI and insulin dose. All protocols advocate routine measurement of ketones, although some insist on blood ketone tests. Although action steps for ketosis varies, all protocols advocate rapid patient intervention. The importance of evaluating ketones and acid-base balance even in the absence of hyperglycemia is emphasized by all protocols, as is the need to continue administering insulin until ketosis has resolved. CONCLUSION | DKA risk mitigation must be pursued systematically in individuals with type 1 diabetes, although the best strategy remains to be determined. Given the ongoing need for adjunctive therapies in type 1 diabetes and current use of SGLT2 inhibitors for this purpose, additional education and research are crucial, especially in the hospital environment, where DKA may not be diagnosed promptly and treated appropriately.

Некоторые аспекты применения препарата Катобевит при субклиническом кетозе у коров

Ratio of active ingredients in combined cyanocobalamin and butafosfan injectable solution has to remain constant in storage; otherwise, the distorted ratio would lead to diminished efficacy in the treatment of subclinical ketosis in dairy cattle. It has been found that efficacy of Catobevit (fixed combination of cyanocobalamine and butafosfan) in the treatment of subclinical ketosis in lactating cows is superior as compared to reference combination having slightly different vehicles composition.

Effect of Elevated Ketone Body on Maternal and Infant Outcome of Pregnant Women with Abnormal Glucose Metabolism During Pregnancy.

Ketone bodies are one of the products of fat metabolism which can be used as an alternative energy source for the human body in states of glucose deficiency. Normal pregnant women may develop ketosis due to physiological changes during pregnancy, while pregnant women with abnormal glucose metabolism are more likely to develop ketosis due to abnormal insulin secretion. Animal experiments and clinical studies have shown that exposure to high-ketone environments during pregnancy is closely related to adverse maternal and infant outcomes. However, there is no unified conclusion on whether ketone bodies should be routinely monitored during pregnancy. This review summarizes the existing studies on ketone body levels and pregnancy outcomes in the case of abnormal blood glucose during pregnancy, elaborates the current guidelines on the level of ketone bodies, provides the detection and treatment of ketosis in pregnant women with abnormal blood glucose in the clinical practice.

Metabolism, Ketosis Treatment and Milk Production after Using Glycerol in Dairy Cows: A Review.

Simple SummaryGlycerol, as well as being an attractive feed ingredient for cattle, is also a by-product of a wide range of industrial applications. Glycerol has potential value in farming since it improves metabolism, feed efficiency, and can alleviate the symptoms of ketosis. Data indicate that glycerol can be a suitable partial grain replacement in the diet of cows during the transition period and at the beginning of lactation. The impact on milk yield is not significant, but glycerol mostly decreases milk fat content. The inclusion of dietary glycerol in the ration of dairy cows has an affect on ruminal fermentation patterns. Glycerol is rapidly fermented in the rumen into propionate, and it is metabolized to glucose in the liver through the process of glycogenolysis. Additionally, glycerol administration to ruminants can reduce greenhouse gas emissions. The purpose of this review is to highlight the potential benefits and drawbacks related to the use of glycerol in cattle.The aim of this paper is to review and systematize the current state of knowledge on glycol metabolism in cattle. Glycerol, derived from biodiesel production, must be purified in order to be a useful product for feeding livestock. The use of glycerol in the feeding of ruminants can be justified for several reasons: (i) it is a source of energy in the ration, (ii) it is a glucogenic precursor, and (iii) it may have an effect on milk composition. The high energy value of glycerol provides the opportunity to use this raw material as a partial grain substitute in cattle feed rations. Dietary supplementation of glycerol is associated with increased propionate, butyrate, valerate, and isovalerate concentrations in the rumen. Glycerol can be used at up to 10%–15% of the dietary dry matter (DM) and is well-established as a treatment for ketosis in cows. Glycerol increases plasma glucose and may reduce non-esterified fatty acids and β-hydroxybutyrate levels. The use of glycerol does not have a clear effect on DM intake, milk yield, or milk composition. However, some authors have reported an increase in milk yield after glycerol supplementation associated with decreased milk fat concentration. It is also possible that the concentration in the milk of odd-chain fatty acids and cis-9, trans-11 conjugated linoleic acid may increase after glycerol application.

Efficacy of propylene glycol on prevention and treatment of ketosis for dairy cows in lactation stage

The objective of this study was to evaluate the efficacy of propylene glycol (PG) on prevention and treatment of ketosis in dairy cows from 09/2018 to 03/2019. The study consisted of 2 experiments using a total of 126 multiparous dairy cows in a HF crossbred herd. Cows in both experiments were randomly assigned to treatments in a randomized complete block design. In Exp. 1, 96 cows without ketosis disease (BHBA &lt; 1.4 mmol/L) were assigned to 2 groups (48 cows/group), including (1) untreated control group (no PG) and (2) treatment group (oral PG for 3 consecutive days after parturition). In Exp. 2, 30 ketotic cows (BHBA ≥ 1.4 mmol/L) were divided into 3 groups (10 cows/group), including (1) cows provided with glucose + vitamin B12 + dexamethasone (TT1), (2) cows treated with PG for 3 days (TT2), and (3) combination of TT1 and TT2 (TT3). The results of the Exp. 1 showed that the proportion of ketotic cows was lower (P &lt; 0.01) in the PG-treated group (18.75%) than in the control group (47.92%). The PG treatment also reduced (P &lt; 0.01) the blood ketone concentration of cows as compared with the control without PG use (0.89 vs. 1.22 mmol/L). In the Exp. 2, after treatment the reduction of blood ketone concentration was much greater (P &lt; 0.01) in TT3 cows (1.97 mmol/L) than in TT2 cows (1.30 mmol/L) and TT1 cows (1.23 mmol/L). The percentage of cows recovered from ketosis was greatest in TT3 (90%), followed by TT2 (60%), and then TT1 (50%) (P &gt; 0.05).

Rational treatments for ketosis in fresh cows

Hyperketonemia affects over 40% of dairy cows in early lactation. The prevalence of hyperketonemia (determined by spot checks within herds) is about 20%. Negative impacts of hyperketonemia most notably include decreased milk yield, increased risk for displaced abomasum, and increased risk for early lactation herd removal. Cowside blood betahydroxybutyrate tests are now available for rapid and accurate diagnosis of hyperketonemia. Urine and milk tests can also be used, but have substantial disadvantages. Accurate and early diagnosis of hyperketonemia after calving allows early and effective treatment. This mitigates about half of the negative impacts of hyperketonemia such as decreased milk yield, increased risk for displaced abomasum, and increased risk for herd removal. Mild to moderate cases of hyperketonemia in individual cows are best treated with an oral glucose precursor such as propylene glycol. Intravenous glucose should be reserved for severe cases and followed with oral glucose precursors.