End Products Of Metabolism Research Articles

5595849 THE GUT MICROBIOME AND HYDROXYUREA EFFECT ON SICKLE CELL DISEASE CHILDREN FROM ANGOLA

Background: Sickle cell disease (SCD) is an inherited hematological disorder and a serious global health problem, affecting between 20 and 25 million people worldwide [1]. In the Sub-Saharan Africa, where it is more prevalent, it contributes up to 90% of under-5 mortality [2]. Although hydroxyurea (HU) is the leading treatment for these patients, its effects on the gut microbiome have not yet been explored. Some studies reported that gastroenteritis events were less frequent in SCA children taking HU and it also significantly improved the survival from pneumococcal infections [3,4]. HU may have a protective effect, not only by improving several hematological parameters but also by lowering the risk of some bacterial infections. Aims: In this context, the aim of this study was to investigate this association by characterizing the gut microbiome of an Angolan SCA pediatric population before and after 6 months of HU treatment and comparing with a control group of healthy siblings. Results: A total of 113 fecal samples were obtained and sequenced by NGS for the 16S rRNA gene (V3-V4 regions), which corresponded to 40 children in the control and before HU groups and 33 after HU, aged between 4-12 years old. Our findings revealed that these three groups exhibit some notable differences, especially within Lachnospiraceae and Ruminococcaceae family. After HU treatment there was an increase of several beneficial bacteria, such as: Blautia coccoides (p=0.009), Blautia luti (p<0.001), Blautia faecis (p=0.008), Bifidobacterium longum (p=0.011), Dorea formicigenerans (p<0.001), Dorea massiliensis (p=0.003), Eubacterium halii (p=0.004), Elusimicrobium spp (p=0.032), Ruminococcus callidus (p=0.037), Ruminococcus faecis (p=0.012), Roseburia spp (p=0.050) and Subdoligranulum variabile (p=0.009). Most of those OTUs are SCFAs producing species, having butyrate or propionate as end-products of bacterial metabolism, both exhibiting anti-inflammatory properties. Moreover, children before HU had higher abundance of bacteria considered pathogenic, like E. coli (p=0.001), Clostridiun_g24 (p=0.039) and H. influenzae (p=0.050). Conclusion: Overall, this study provides the first evidence of the HU effect on the gut microbiome and provides a rationale for further research for developing treatments to reduce gut microbiota-driven inflammation, which may attenuate the dysbiosis and chronic symptoms experienced by these patients. This work was supported by FCT/Aga Khan (project nº330842553) and FCT/MCTES (UIDB/05608/2020 and UIDP/05608/2020) –H&TRC.

BUTYRATE-INDUCED MITOCHONDRIAL FUNCTION IMPROVES BARRIER FUNCTION IN INFLAMMATORY BOWEL DISEASE (IBD)

Short-chain fatty acids (SCFAs), end-product of gut microbial metabolism, play an important role in colonic homeostasis. Butyrate is a prime SCFA that fuels intestinal epithelial cells (IECs). However, this energy source is deficient in inflammatory bowel disease (IBD) due to dysbiotic microbiota. In this study, we posit that butyrate supplementation drives mitochondrial respiration induced barrier function in IBD.

Physiological significance of elevated levels of lactate by exercise training in the brain and body.

For the past 200 years, lactate has been regarded as a metabolic waste end product that causes fatigue during exercise. However, lactate production is closely correlated with energy metabolism. The lactate dehydrogenase-catalyzed reaction uses protons to produce lactate, which delays ongoing metabolic acidosis. Of note, lactate production differs depending on exercise intensity and is not limited to muscles. Importantly, controlling physiological effect of lactate may be a solution to alleviating some chronic diseases. Released through exercise, lactate is an important biomarker for fat oxidation in skeletal muscles. During recovery after sustained strenuous exercise, most of the lactate accumulated during exercise is removed by direct oxidation. However, as the muscle respiration rate decreases, lactate becomes a desirable substrate for hepatic glucose synthesis. Furthermore, improvement in brain function by lactate, particularly, through the expression of vascular endothelial growth factor and brain-derived neurotrophic factor, is being increasingly studied. In addition, it is possible to improve stress-related symptoms, such as depression, by regulating the function of hippocampal mitochondria, and with an increasingly aging society, lactate is being investigated as a preventive agent for brain diseases such as Alzheimer's disease. Therefore, the perception that lactate is equivalent to fatigue should no longer exist. This review focuses on the new perception of lactate and how lactate acts extensively in the skeletal muscles, heart, brain, kidney, and liver. Additionally, lactate is now used to confirm exercise performance and should be further studied to assess its impact on exercise training.

Reduced-particle size wheat bran and endoxylanase supplementation in broiler feed affect arabinoxylan hydrolysis and fermentation with broiler age differently.

Since the caecal microbiota of young broilers are not yet able to ferment the dietary fibre (DF) fraction of the feed to a large extent, increasing the accessibility of DF substrates along the gastrointestinal tract is crucial to benefit from the health stimulating metabolic end-products (e.g. butyric acid) generated upon microbial DF fermentation. Therefore, the present study aimed to evaluate the potential of reduced-particle size wheat bran (RPS-WB) and endoxylanases as feed additives to stimulate arabinoxylan (AX) hydrolysis and fermentation along the hindgut of young broilers. To this end, RPS-WB and endoxylanase supplementation were evaluated in a 2×2 factorial design using a total of 256 male 1-d-old chicks (Ross 308). Broilers were assigned to 4 dietary treatments: a basal wheat-based diet with (1) no feed additives (control, CTRL), (2) an endoxylanase (XYL; Econase XT 25at 0.10g/kg diet), (3) 1% wheat bran with an average reduced particle size of 297μm (RPS-WB) and (4) an endoxylanase and 1% RPS-WB (RPS-WB+XYL). Each dietary treatment was replicated 8 times and on d 10 and 28, respectively, 24 and 16 broilers per treatment group were euthanised to analyse AX degradation, short-chain fatty acid production and digesta viscosity in the ileum and caecum. Broilers receiving XYL in their diet showed increased AX solubilisation and fermentation at both d 10 and 28 compared to the CTRL group (P<0.05). Adding RPS-WB to the diet stimulated wheat AX utilisation by the primary AX degraders in the caecum at 10d of age compared to the CTRL group, as observed by the high AX digestibility coefficient for the RPS-WB supplemented group at this young age (P<0.05). At 28d, RPS-WB supplementation lowered body-weight gains but increased butyric acid concentrations compared to the XYL and CTRL group (P<0.05). Although no synergistic effect for RPS-WB+XYL broilers was observed for AX hydrolysis and fermentation, these findings suggest that both additives can raise a dual benefit to the broiler as a butyrogenic effect and improved AX fermentation along the ileum and caecum were observed throughout the broiler's life.

Impact of inorganic iron and haem on the human gut microbiota; An in vitro batch-culture approach.

Although iron is an essential nutrient for humans, as well as for almost all other organisms, it is poorly absorbed (~15%) from the diet such that most passes through the upper gut into the large intestine. The colonic microbiota is thus exposed to, and potentially influenced by, such residual iron which could have an impact on human health. The aim of the research described here is to determine how the major forms of dietary iron (inorganic iron and haem) influence metabolic activity and composition of the human gut microbiota by utilizing an in vitro parallel, pH-controlled anaerobic batch culture approach. Controlled iron provision was enabled by the design of a 'modified' low-iron gut-model medium whereby background iron content was reduced from 28 to 5 μM. Thus, the impact of both low and high levels of inorganic and haem iron (18-180 μM and 7.7-77 μM, respectively) could be explored. Gut-microbiota composition was determined using next generation sequencing (NGS) based community profiling (16S rRNA gene sequencing) and flow-fluorescent in situ hybridization (FISH). Metabolic-end products (organic acids) were quantified using gas chromatography (GC) and iron incorporation was estimated by inductively coupled plasma optical emission spectroscopy (ICP-OES). Results showed that differences in iron regime induced significant changes in microbiota composition when low (0.1% w/v) fecal inoculation levels were employed. An increase in haem levels from 7.7 to 77 μM (standard levels employed in gut culture studies) resulted in reduced microbial diversity, a significant increase in Enterobacteriaceae and lower short chain fatty acid (SCFA) production. These effects were countered when 18 μM inorganic iron was also included into the growth medium. The results therefore suggest that high-dietary haem may have a detrimental effect on health since the resulting changes in microbiota composition and SCFA production are indicators of an unhealthy gut. The results also demonstrate that employing a low inoculum together with a low-iron gut-model medium facilitated in vitro investigation of the relationship between iron and the gut microbiota.

Development and validation of a predictive nomogram for sarcopenia among older people in China.

Development and validation of a predictive nomogram for sarcopenia among older people in China.

Bacterial composition along the digestive tract of the Horned Screamer (Anhima cornuta), a tropical herbivorous bird.

The Horned Screamer (Anhima cornuta) is an herbivorous bird that inhabits wetlands of the South American tropical region. We hypothesize that due to its herbivorous niche, its digestive tract compartments may have bacteria specialized in fermenting complex plant carbohydrates. To test this hypothesis, we compared the bacterial communities along the gastrointestinal tract (GIT) of a Horned Screamer captured in Venezuela. Samples were taken from tissues and content of the proventriculus and the small intestine (considered for this study as upper GIT), and the large intestine and cecum (lower GIT). The bacterial community was characterized by sequencing the V4 region of the 16S rRNA gene. Bioinformatic analysis was performed using QIIME, QIITA and Microbiome Analyst. The association between microbial taxonomy and function was analyzed using their Greengenes OTU IDs and a custom KEGG BRITE hierarchical tree and visualized with BURRITO. The Screamer's gastrointestinal microbiota was composed by seven phyla being Firmicutes and Bacteroidetes the most predominant. The dominant taxa in the upper GIT were Helicobacter, Vibrio, Enterobacter, Acinetobacter and Staphylococcus. The dominant taxa in the lower GIT were Oribacterium, Blautia, Roseburia, Ruminococcus, Desulfovibrio, Intestinimonas, Marvinbryantia and Parabacteroides. Complete degradation of cellulose to the end-products acetate, propanoate, butanoate and acetoacetate was found in the upper and lower GIT without significant differences. Our study confirmed changes in bacterial community composition throughout the GIT of the Horned Screamer primarily associated with the production of metabolic end-products of carbohydrate digestion essential for the fermentation of the herbivorous diet.

Butyrate: More Than a Short Chain Fatty Acid.

The mechanistic understanding of the importance and the potential benefits of the gut microbiome has exploded in potential roles in human health and disease. Short chain fatty acids (SCFAs), including butyrate, are one of the key metabolic end products that has been a major focus of microbiome understanding. This brief review aims to describe butyrate's relation to certain biological concepts and their clinical application. Butyrate has reportedly been described as a potent pro-resolution molecule that has a significant role in maintaining gut immunity, supporting gut barrier function, regulation of histone deacetylase (HDAC), and numerous systemic roles. Further research is needed to explore potential benefits of adding SCFAs for patients receiving total parenteral nutrition. Butyrate plays several biological roles in intestinal epithelium anti-inflammatory pathways with clear benefits in numerous acute and chronic disease states and overall human health helping to maintain homeostasis.

Vitamin C transporter SVCT1 serves a physiological role as a urate importer: functional analyses and in vivo investigations

Uric acid, the end product of purine metabolism in humans, is crucial because of its anti-oxidant activity and a causal relationship with hyperuricemia and gout. Several physiologically important urate transporters regulate this water-soluble metabolite in the human body; however, the existence of latent transporters has been suggested in the literature. We focused on the Escherichia coli urate transporter YgfU, a nucleobase-ascorbate transporter (NAT) family member, to address this issue. Only SLC23A proteins are members of the NAT family in humans. Based on the amino acid sequence similarity to YgfU, we hypothesized that SLC23A1, also known as sodium-dependent vitamin C transporter 1 (SVCT1), might be a urate transporter. First, we identified human SVCT1 and mouse Svct1 as sodium-dependent low-affinity/high-capacity urate transporters using mammalian cell-based transport assays. Next, using the CRISPR-Cas9 system followed by the crossing of mice, we generated Svct1 knockout mice lacking both urate transporter 1 and uricase. In the hyperuricemic mice model, serum urate levels were lower than controls, suggesting that Svct1 disruption could reduce serum urate. Given that Svct1 physiologically functions as a renal vitamin C re-absorber, it could also be involved in urate re-uptake from urine, though additional studies are required to obtain deeper insights into the underlying mechanisms. Our findings regarding the dual-substrate specificity of SVCT1 expand the understanding of urate handling systems and functional evolutionary changes in NAT family proteins.

A study of the relationship between serum uric acid levels and pain in patients with migraine.

Serum uric acid (SUA), the end product of purine metabolism acts as an antioxidant and is related to oxidative stress. It has been reported that SUA may be involved in the pathogenesis of neurodegenerative diseases including Alzheimer disease, Huntington disease, Parkinson disease, and multiple sclerosis. However, studies evaluating SUA levels in migraine are scarce. This study aimed to explore the relationship between pain characteristics and SUA levels in patients with migraine and compare SUA levels in migraine patients during a headache attack and headache-free period with those control groups. This prospective, cross-sectional study included 78 patients with migraine and 78 healthy subjects who were randomly selected from hospital personnel as the control group. Headache characteristics (duration of attack, pain intensity, and headache frequency) and sociodemographic features were recorded. The SUA level was measured once in the control group and twice in the migraine patients, during the migraine attack and headache-free periods. Although the SUA levels of the migraine group in the headache-free period were higher than those of the control group, the difference was not statistically significant. Gender was not significantly related to the change in SUA levels between the attack and headache-free period. When the correlation between age, duration of migraine, frequency, duration, and intensity of pain was evaluated; the difference between SUA levels in female migraine patients was weakly correlated with headache intensity, whereas male patients had a moderate correlation. ( P < .05; R > 0.250, and R > 0.516, respectively). The difference in SUA level in the migraine attack period compared to the headache-free period showing a positive correlation with pain intensity suggested that SUA may have a role in migraine due to its antioxidant role.

The in-silico evaluation of important GLUT9 residue for uric acid transport based on renal hypouricemia type 2

Uric acid is the end product of purine metabolism. Uric acid transporters in the renal proximal tubule plays a key role in uric acid transport. Functional abnormalities in these transporters could lead to high or low levels of uric acid in the blood plasma, known as hyperuricemia and hypouricemia, respectively. GLUT9 has been reported as a key transporter for uric acid reuptake in renal proximal tubule. GLUT9 mutation is known as causal gene for renal hypouricemia due to defective uric acid uptake, with more severe cases resulting in urolithiasis and exercise induced acute kidney injury (EIAKI). However, the effect of mutation is not fully investigated and hard to predict the change of binding affinity. We comprehensively described the effect of GLUT9 mutation for uric acid transport using molecular dynamics and investigated the specific site for uric acid binding differences. R171C and R380W showed the significant disruption of the structure not affecting transport dynamics whereas L75R, G216R, N333S, and P412R showed the reduced affinity of the extracellular vestibular area towards urate. Interestingly, T125 M showed a significant increase in intracellular binding energy, associated with distorted geometries. We can use this classification to consider the effect mutations by comparing the transport profiles of mutants against those of chemical candidates for transport and providing new perspectives to urate lowering drug discovery using GLUT9.

The Efficacy of Cyranose in Detecting In Vitro Volatile Organic Compounds

Background and Hypothesis: Electronic-noses are a subtype of electronic-sensing technology designed to reproduce human smell via sensor arrays and pattern recognition algorithms. Specifically, they can detectheadspace volatile organic compounds (VOCs) , which are end products of human metabolism (normal and disease-specific) mainly excreted in the breath, urine, and feces. VOCs are often emitted before the onset of clinical symptoms of many diseases, making them useful screening biomarkers. Additionally, the portable, inexpensive, and non-invasive nature of e-noses allows for easy clinical implementation for point-of-care (POC) disease screening/diagnosis. We hypothesize that Cyranose, one e-nose model, can differentiate headspace VOCs between healthy cells and cells stressed with an in vitro inflammatory state.&#x0D; Project Methods: Human Intestinal Epithelial Cells (HIEC-6s) and Umbilical Stem Cells (USCs) were cultured in their respective 50 mL complete media at 37o C in 5% CO2. Upon reaching appropriate confluence, cells were washed using PBS and passaged with TrypLE Express. Cells werecounted with a hemocytometer and Trypan blue exclusion, then added to a 12 well plate and exposed to either TNF-α (50 ng/mL), LPS (200 ng/mL), or hypoxia (5% O2) for 24 hours.Supernatant (1.5 mL) was added to Eppendorf tubes, sealed with parafilm, and heated to 40o C for 30 minutes. Headspace VOC profiles were analyzed with Cyranose and compared to controls.&#x0D; Results: Using the “identify” function on Cyranose, it was unreliable in correctly distinguishing VOCs between HIEC-6s and USCs from their controls under all treatment conditions. While Cyranosesensors did generate smellprint profiles that showed differences between HIEC-6s and USCsagainst controls with LPS treatment, small sample sizes limit these results. &#x0D; Conclusion and Future Directions: This study demonstrates that new method designs are necessary when identifying in vitro VOC profiles using Cyranose. Future considerations should include the concentration of treatments/cells, cell types, treatment duration, supernatant volume, number of samples prepared, heatblock temperature, and/or a different e-nose model.

BUTYRATE-INDUCED MITOCHONDRIAL FUNCTION IMPROVES BARRIER FUNCTION IN INFLAMMATORY BOWEL DISEASE (IBD)

Abstract BACKGROUND Short-chain fatty acids (SCFAs), end-product of gut microbial metabolism, play an important role in colonic homeostasis. Butyrate is a prime SCFA that fuels intestinal epithelial cells (IECs). However, this energy source is deficient in inflammatory bowel disease (IBD) due to dysbiotic microbiota. In this study, we posit that butyrate supplementation drives mitochondrial respiration induced barrier function in IBD. METHODS Normal human Colon mucosal (NCM460) epithelial cells were treated overnight with different concentration of sodium butyrate (SB; 0.5-5.0mM) with or without TNF (1ng/ml). To model mitochondrial deficiency, TFAM (mitochondrial transcriptional factor A), was silenced (shTFAM) in NCM460 cells. For mitochondrial respiration assessment, NCM cells were maintained and treated with SB (-/+TNF) under glucose-free medium and Oxygen consumption rate (OCR) was measured using high-throughput Seahorse XFe24 Extracellular Flux Analyzer (Agilent Technologies). Gene expression analysis was determined by RT-qPCR from total RNA isolated from untreated and treated NCM cells as well as in mitochondria-deficient shTFAM NCMs compared to shControl cells. All assays were performed in triplicate and fold changes were calculated using the ΔΔCT method. RESULT Seahorse analysis showed significant increase in Maximal respiratory capacity, spare respiratory capacity and ATP production at sub-optimal (2mM) and optimal (5mM) SB concentrations, suggesting a SB induced mitochondrial respiration and capacity to overcome oxidative stress. At molecular level, SB significantly increased the expression of genes associated with mitochondrial biogenesis (TFAM), complex I (Ndufa1, Ndufa4, Ndufa6), complex IV (Cox6A1) and complex V (ATP5E, ATP8), at optimal 5mM concentration. The effect of SB was more pronounced under inflammatory condition when NCM cells were treated in the presence of low dose TNF. Further transcriptomic analysis of TFAM-deficient NCMs demonstrated significant decrease in mRNA of major butyrate transporters (MCT1, MCT4, ABCG2) compared to TFAM-proficient shControl cells, irrespective of any treatment. Similar decreased expression pattern was observed for tight junction genes (ZO1 and Occludin) in shTFAM compared to shControl cells. However, butyrate transporters and ZO1 mRNA increased significantly in both shTFAM and shControl cells after SB treatment at sub-optimal concentration (2mM) in the presence of TNF. Interestingly, only shTFAM cells showed increase in transcript level of Occludin after SB+TNF treatment, with no effect in shControl. CONCLUSION These data suggest that butyrate metabolism is a critical player in promoting oxidative health of mitochondria, which further drives transporter-mediated butyrate utilization and promotes barrier integrity under inflammatory conditions as in IBD.

Microbial Treatment of di (2-ethyl hexyl) Phthalate by Lysinibacillus xylanilyticus Isolated from Landfill Soil

The bacterial strains were isolated from landfill soil contaminated with phthalate, collected from dump yard near Byepass, Patna. Thestrain named T23 was chosen among the isolated strains due to its high efficacy towards the degradation. We observed the effects ofvarious environmental and chemical factors for optimising the conditions for degradation. The strain T23 was identified as Lysinibacillusxylanilyticus based on its phenotypic as well as phylogenetic characteristics by performing 16S rRNA gene sequencing and for thedetermination of the metabolic end products after degradation. Gas chromatography and mass spectrometry (GC-MS) analysis was doneand the degradable intermediates obtained were 7, 10, 13-Hexadecatrienoic acid, Cyclotrisiloxane, n-Hexadecanoic acid, Oleic Acid andErucic acid. The strain T23 showed maximum degradation at pH 8.5 and temperature was 10.5 and it could tolerate up to 0-15% NaCl.Maximum degradation was exhibited at the carbon source, dextrose, and nitrogen source, casein. The 23 strain was having maximumpotential for degradation which can be used for various remediation purposes.

Butyrate Differentiates Permissiveness to Clostridioides difficile Infection and Influences Growth of Diverse C. difficile Isolates.

A disrupted "dysbiotic" gut microbiome engenders susceptibility to the diarrheal pathogen Clostridioides difficile by impacting the metabolic milieu of the gut. Diet, in particular the microbiota-accessible carbohydrates (MACs) found in dietary fiber, is one of the most powerful ways to affect the composition and metabolic output of the gut microbiome. As such, diet is a powerful tool for understanding the biology of C. difficile and for developing alternative approaches for coping with this pathogen. One prominent class of metabolites produced by the gut microbiome is short-chain fatty acids (SCFAs), the major metabolic end products of MAC metabolism. SCFAs are known to decrease the fitness of C. difficile in vitro, and high intestinal SCFA concentrations are associated with reduced fitness of C. difficile in animal models of C. difficile infection (CDI). Here, we use controlled dietary conditions (8 diets that differ only by MAC composition) to show that C. difficile fitness is most consistently impacted by butyrate, rather than the other two prominent SCFAs (acetate and propionate), during murine model CDI. We similarly show that butyrate concentrations are lower in fecal samples from humans with CDI than in those from healthy controls. Finally, we demonstrate that butyrate impacts growth in diverse C. difficile isolates. These findings provide a foundation for future work which will dissect how butyrate directly impacts C. difficile fitness and will lead to the development of diverse approaches distinct from antibiotics or fecal transplant, such as dietary interventions, for mitigating CDI in at-risk human populations. IMPORTANCE Clostridioides difficile is a leading cause of infectious diarrhea in humans, and it imposes a tremendous burden on the health care system. Current treatments for C. difficile infection (CDI) include antibiotics and fecal microbiota transplant, which contribute to recurrent CDIs and face major regulatory hurdles, respectively. Therefore, there is an ongoing need to develop new ways to cope with CDI. Notably, a disrupted "dysbiotic" gut microbiota is the primary risk factor for CDI, but we incompletely understand how a healthy microbiota resists CDI. Here, we show that a specific molecule produced by the gut microbiota, butyrate, is negatively associated with C. difficile burdens in humans and in a mouse model of CDI and that butyrate impedes the growth of diverse C. difficile strains in pure culture. These findings help to build a foundation for designing alternative, possibly diet-based, strategies for mitigating CDI in humans.

Gilbert’s syndrome as a model for studying the effects of bilirubin

Numerous scientific studies conducted over the past years expand our understanding of the physiological and pathophysiological effects of bilirubin. In this review of the literature, the authors, using the example of Gilbert’s syndrome, as a classic condition occurring with hyperbilirubinemia, discuss the results of clinical and experimental studies demonstrating the protective mechanisms and the protective role of elevated bilirubin concentration in relation to diseases accompanied by metabolic inflammation, oncological diseases, and a number of others. The authors focus on the hormonal function of bilirubin and its potential therapeutic effect discussed in recent scientific works. The purpose of this review of the literature is to expand the understanding of bilirubin from the clinician’s usual in the context of the end product of heme and antioxidant metabolism to a signaling molecule involved in the pathophysiology of many diseases.

Role of Serum Uric Acid in Metabolic Syndrome: A Cross-sectional Study in Central Karnataka

Abstract Background: Elevated levels of uric acid are the end product of purine metabolism. Uric acid levels are regulated by xanthine oxidase enzyme. Increased xanthine oxidase activity results in the generation of free radicals. Hence, elevated uric acid levels are the manifestations of oxidative stress. Meanwhile, raised uric acid can trigger release of inflammatory mediatory and create the inflammatory state. Thus, inflammation and oxidative stress are the important events in the pathogenesis of metabolic syndrome. This study aimed to find the association of uric acid levels with metabolic syndrome and the individual components of metabolic syndrome. Methodology: A comparative, descriptive, cross-sectional study was conducted among 50 metabolic syndrome cases and 50 controls. Clinical examination followed by laboratory investigations for the estimation of serum uric acid, fasting blood sugar, postprandial blood sugar, glycated hemoglobin, high sensitivity C-reactive protein (Hs-CRP), fasting insulin, and lipid profile. Insulin resistance (IR) was calculated by homeostatic model assessment-IR (HOMA-IR). Results: In the metabolic syndrome patients’ group, serum uric acid was found to have strong positive correlation with body mass index, blood pressure, glycemic indices, IR, lipid profile, and Hs-CRP. It was found that there was 2.5 times higher risk of development of metabolic syndrome with every unit increase in serum uric acid levels and this association was found to be statistically significant. Conclusion: Uric acid can be used as the marker for the early identification of metabolic syndrome or as a prognostic marker in the diagnosed cases of metabolic syndrome.

The relationship between hyperuricemia and atrial fibrillation in patients with heart failure

Objective Uric acid is the end product of purine metabolism. Overproduction and insufficient excretion cause an increase in serum uric acid(SUA) levels. In some studies, it has been shown that hyperuricemia is an independent predictor of cardiovascular mortality and poor prognosis of heart failure(HF). It has been found that the level of SUA may also be a biomarker to be used in demonstrating inflammation and oxidative stress. Recent studies have shown that inflammation and oxidative stress play a role in the pathogenesis of both HF and atrial fibrillation(AF). In this study, we aimed to investigate whether the level of SUA is associated with the development of AF in patients with HF. Methods A total of 1342 patients with HF who applied to outpatient clinic between 2018 and 2022 were scanned. Patients with one of the exclusion criteria were not included in the study. As a result, 538 HF patients were included. These patients were divided into 2 groups as new-diagnosed AF patients and patients without AF. Results SUA level was 9.29±2.93 mg/dL in patients with AF and 7.67±2.5 mg/dL in patients who did not develop AF, which was statistically significant(p&lt;0.001) Also furosemide use was 92.5% and 72.6% in patients with and without AF, respectively(p&lt;0.001). Other results of the study are described in the main text. In our multivariate analysis, SUA level and furosemide use were found to be associated with the development of AF[1.21 (1.09-1.35) p &lt;0.001 for SUA; 5.33 (1.87-15.18)(p=0.002) for furosemide]. Conclusion Hyperuricemia may increase the development of AF in patients with HF. According to this, correction of hyperuricemia can contribute positively to mortality and morbidity in HF patients.

Effects of antimicrobials on the gastrointestinal microbiota of dogs and cats.

Among several environmental factors, exposure to antimicrobials has been in the spotlight as a cause of profound and long-term disturbance of the intestinal microbiota. Antimicrobial-induced dysbiosis is a general term and includes decreases in microbial richness and diversity, loss of beneficial bacterial groups, blooms of intestinal pathogens and alterations in the metabolic functions and end-products of the microbiota. Mounting evidence from human and experimental animal studies suggest an association between antimicrobial-induced dysbiosis and susceptibility to gastrointestinal, metabolic, endocrine, immune and neuropsychiatric diseases. These associations are commonly stronger after early life exposure to antimicrobials, a period during which maturation of the microbiota and immune system take place in parallel. In addition, these associations commonly become stronger as the number of antimicrobial courses increases. The repeatability of these findings among different studies as well as the presence of a dose-dependent relationship between antimicrobial exposure and disease development collectively require careful consideration of the need for antimicrobial use. There are limited studies are available in dogs and cats regarding the long-term effects of antimicrobials on the microbiota and subsequent susceptibility to diseases. This review discusses the effects of antimicrobials on the gastrointestinal microbiota and the most important associations between antimicrobial-induced dysbiosis and diseases in humans, dogs, and cats.

HYPERURICEMIA AS AN INTERDISCIPLINARY PROBLEM

Introduction Uric acid is the end product of purine nucleotide metabolism in the human body. Elevation of uric acid in the blood is known as hyperuricemia. Its participation in the development of gout is well known. According to the latest reports, it plays a role in developing cardiovascular and central nervous diseases. Aim This review article discusses the mechanisms and risk factors of hyperuricemia, its complications, and treatments that highlight hyperuricemia as a multi-faceted disorder requiring optimal treatment and rehabilitation. Materials and methods Pubmed and ClinicalKeys databases were used for searching for relevant research results. We focused on studies published in less than 5 years, but older references were also analyzed, if they brought valuable reports to our work. Results The analysis of the presented articles can indicate the role of hyperuricemia not only in the formation of gout, but also in hypertension, cardiovascular and kidney diseases and neurological disorders. Conclusions Due to the increase in the incidence of hyperuricemia worldwide and its consequences, maintaining an adequate level of uric acid is an essential aspect of patient management for clinicians. In addition to pharmacological treatment of hyperuricemia, patients should be considered for diet modification and increased physical activity. Further studies are needed to improve guidelines and recommendations for treating hyperuricemia and patient education.