Concentrations In Body Fluids Research Articles

225 Kidney function and nitrogen excretion in Brown Swiss and Holstein dairy cows

Abstract The agricultural sector contributes to nitrogen (N) emissions since farm animals excrete considerable N amounts via feces and urine. To reduce N emissions by dairy cattle, methods predicting accurately individual N emissions are of great interest. Recent data showed that Brown Swiss (BS) cows have greater urea concentrations in milk and blood than Holstein (HO) cows. However, it is still unknown if greater BUN concentrations in a particular breed are congruently reflected by concomitantly increased contents of nitrogenous compounds in other media (e.g., urine and saliva). Thus, the present study simultaneously assessed biomarkers for kidney function like urea, and creatinine and symmetric dimethylarginine (SDMA) concentrations in several body fluids (i.e., blood, urine, milk, and saliva) as well as nitrogen excretion in feces in BS and HO cows under identical feeding conditions. Blood, saliva, urine, and feces were sampled in 31 multiparous BS and 46 HO cows kept under identical feeding and management conditions. Samples were collected at different lactational stages after the monthly DHIA control test-day. Concentrations of urea and creatinine were measured in serum, urine, and saliva. Symmetric dimethylarginine was determined in serum, which is an established indicator for glomerular filtration rate (GFR). Feces were analyzed for dry matter content and nitrogen concentrations. Data on milk urea and protein concentrations, and daily milk yield were obtained from the monthly DHIA test-day records. The effects of breed, time, and parity number on blood, saliva, urine, feces, and milk parameters were evaluated with the GLM procedure with breed, time, and parity number as fixed effects. Differences between BS and HO were assessed by the Tukey-corrected t-test at P < 0.05. Dry matter intake and body weight were similar in BS and HO cows (P > 0.05). No differences between BS and HO were observed for milk yield, fecal DM and nitrogen content. BS cows showed greater urea concentration (25.8 ± 0.7 vs 21.8 ± 0.7 mg/dL), and protein content in milk (3.70 ± 0.08 vs 3.45 ± 0.07%) than HO cows (P < 0.01). Concentrations of urea, creatinine, and SDMA in serum, were greater in BS than in HO cows (P < 0.01) with 5.46 ± 0.19 vs 4.72 ± 0.13 mmol/L for urea, 105.96 ± 2.23 vs 93.07 ± 1.50 mmol/l creatinine, and 16.78 ± 0.69 vs 13.39 ± 0.44 µg/dL SDMA, respectively. Urea and creatinine concentrations in urine and saliva did not differ among breeds. Despite greater urea and creatinine concentrations in blood, and milk urea content in BS compared with HO, excretion of these parameters did not differ between breeds in urine. Our results suggest a reduced renal glomerular filtration rate in BS compared with HO. The underlying mechanisms require further investigations.

Prestin in Human Perilymph, Cerebrospinal Fluid, and Blood as a Biomarker for Hearing Loss.

Determining the concentration of prestin in human blood, cerebrospinal fluid (CSF), and perilymph (PL), and evaluating its suitability as a clinical biomarker for sensori-neural hearing loss (SNHL). Human blood, CSF, and PL samples were intraoperatively collected from 42 patients with tumors of the internal auditory canal or with intracochlear tumors undergoing translabyrinthine or middle fossa tumor removal. Prestin concentration was measured using enzyme-linked immunosorbent assay and linear regression analyses were performed to investigate its associations with audiological as well as vestibular test results. Tertiary referral center. The median prestin concentration in blood samples of the 42 study participants (26 women, mean ± standard deviation age, 52.7 ± 12.5 years) was 1.32 (interquartile range, IQR, 0.71-1.99) ng/mL. CSF prestin levels were significantly higher with 4.73 (IQR, 2.45-14.03) ng/mL (P = .005). With 84.74 (IQR, 38.95-122.00) ng/mL, PL prestin concentration was significantly higher compared to blood (P = .01) and CSF (P = .03) levels. Linear regression analyses showed significant associations of CSF prestin concentration with preoperative hearing levels (pure-tone average and word recognition; P = .008, R2 = 0.1894; P = .03, R2 = 0.1857), but no correlations with blood or PL levels. This study's findings highlight the volatile nature of prestin levels and provide the first insights into this potential biomarker's concentrations in body fluids apart from blood. Future investigations should comprehensively assess human prestin levels with different etiologies of SNHL, prestin's natural homeostasis and systemic circulation, and its temporal dynamics after cochlear trauma. Finally, clinically approved detection kits for prestin are urgently required prior to considering a potential translational implementation of this diagnostic technique.

Measurements of cadmium levels in relation to tobacco dependence and as a function of cytisine administration

Cigarette smoking delivers a number of heavy metals, including cadmium (Cd), into the body. Bioaccumulation may result in an increase in pathological consequences over time. The assessment of changes in serum Cd concentrations during the treatment of cigarette dependence with cytisine was performed for the first time. Parameters assessing smoking habits, strength of addiction, and effectiveness of therapy were analyzed. Cd was determined before, during, and after the end of treatment. The serum Cd levels were significantly higher in the smokers than in the nonsmokers. Significant differences in Cd concentrations between sampling times in smokers were observed. Individuals who stopped smoking had significantly lower Cd concentrations compared to baseline. A significant positive correlation between the serum Cd before treatment and smoking urges was also obtained. Additionally, salivary Cd determinations were performed before treatment to evaluate the use of this method to assess cigarette addiction. Our findings indicate that Cd can be used as a biomarker of smoking addiction, and provide an alternative assessment of tobacco smoke exposure to other methods. The results provide new knowledge related to Cd concentrations in human body fluids and may play a role in monitoring and assessing the efficacy of cytisine for smoking cessation.

Cancer diagnosis using label-free SERS-based exosome analysis.

Exosomes, carrying distinctive biomolecules reflective of their parent cell's status and origin, show promise as liquid biopsy biomarkers for cancer diagnosis. However, their clinical translation remains challenging due to their relatively low concentration in body fluids. Surface-Enhanced Raman spectroscopy (SERS) has recently gained significant attention as a label-free and sensitive technique for exosome analysis. This review explores label-free SERS for exosome detection, covering exosome isolation and characterization methods, advancements in SERS substrates, and fingerprint analysis techniques using machine learning. Furthermore, we emphasize the challenges and offer insights into the future prospects of SERS-based exosome analysis to enhance cancer diagnosis.

Optical blood glucose non-invasive detection and its research progress.

Blood glucose concentration is an important index for the diagnosis of diabetes, its self-monitoring technology is the method for scientific diabetes management. Currently, the typical household blood glucose meters have achieved great success in diabetes management, but they are discrete detection methods, and involve invasive blood sampling procedures. Optical detection technologies, which use the physical properties of light to detect the glucose concentration in body fluids non-invasively, have shown great potential in non-invasive blood glucose detection. This article summarized and analyzed the basic principles, research status, existing problems, and application prospects of different optical glucose detection technologies. In addition, this article also discusses the problems of optical detection technology in wearable sensors and perspectives on the future of non-invasive blood glucose detection technology to improve blood glucose monitoring in diabetic patients.

Graves hastalığında serum neopterin düzeylerinin değerlendirilmesi

Aim: Graves' disease is a disease with an autoimmune basis in which the synthesis and release of thyroid hormone from the thyroid gland increases. Interferon-gamma (IFN-γ) released from activated T lymphocytes causes macrophages to produce neopterin (NPT), increasing its concentration in serum and other body fluids. There is a relationship between NPT and the production of free oxygen radicals by these cells. In this study, it was aimed to measure serum NPT levels in individuals with Graves' disease.
 Material and Method: The study included 13 newly diagnosed Graves' patients (neopterin levels were measured at the time of first diagnosis and at the 3rd month of treatment) and 16 Graves' patients who were followed up in endocrinology outpatient clinics for at least one year. NPT levels of 23 healthy individuals without any disease were taken as the control group. Free triiodothyronine (T3), free thyroxine (T4), thyroglobulin, and thyroid stimulating hormone (TSH) levels were measured in the blood samples of the participants.
 Results: Serum NPT levels were found to be higher in Graves' patients compared to the control group (6.66 nmol/L in newly diagnosed patients, 9.24 nmol/L in patients at the 3rd month of treatment, 10.68 nmol/L in patients followed for one year or more, 1.44 nmol/L in the control group, respectively, p

Effect of Nonsurgical Periodontal Treatment on Salivary and Plasma Superoxide Dismutase Levels of Patients Suffering from Periodontitis.

Antioxidant capacity is frequently measured by evaluating superoxide dismutase (SOD) concentration in body fluids. The aim of this study was to compare SOD concentrations in the saliva and plasma of patients with periodontitis to those measured in a group of patients with healthy periodontium, as well as to evaluate the influence of nonsurgical periodontal therapy on salivary and plasma SOD in periodontitis patients. For this purpose, 40 systemically healthy patients aged 30-70 years who had at least 20 teeth were recruited, 20 of whom had periodontitis, and 20 served as healthy periodontitis-free controls. In all participants, periodontal status was assessed via the plaque index (PI), gingival index (GI), papilla bleeding index (PIB), probing depth (PD), and clinical attachment level (CAL), and the SOD concentration in both saliva and plasma was determined by conducting a commercial immunoenzymatic ELISA test. In periodontitis patients, periodontal indices and saliva and blood samples were taken at the beginning of the study, as well as 3 months after periodontal therapy, while in the control group, these data were gathered at the beginning of the study only. SOD values in the saliva of patients with periodontitis (0.244 U/µL) were statistically significantly higher compared with patients with healthy periodontium (0.017 U/µL). Moreover, periodontal therapy led to a statistically significant decrease in this marker in the saliva of patients with periodontitis (p = 0.023), which was comparable with that measured in the control group. On the other hand, no statistically significant differences were noted in plasma SOD values either between the two groups or at follow-up compared with baseline in the group with periodontitis. These findings suggest that the elevated salivary SOD in patients with periodontal disease may represent a mechanism of tissue protection against oxidative stress that occurs in response to periodontal disease.

Potential release of trace metal ions from metallic orthodontic appliances and dental metal implants: A Review of in vitro and in vivo experimental studies

Metallic wear nanoparticles, corrosion products and trace metal ions release from metallic materials, e.g. metallic alloys and pure metals, implanted into the human and animal's body in orthodontic surgery is becoming a major cause for concern. Additionally, metallic wear nanoparticles can themselves undergo a corrosion process contributing to the total level of dissolved metal ions. This review briefly provides an overview of both metallic alloys and pure metals used in implant materials in dental surgery. A short section is dedicated to important biomaterials and their corrosive behavior in both real solutions and various types of media that model human and animal's biological fluids and tissues. The present review gives an overview of analytical methods, techniques and different approaches applied to the measurement of in vivo and in vitro trace metals released into body fluids and tissues from patients and animals carrying metal dental implants and metallic orthodontic appliances. Reference levels of ion concentrations in body fluids and tissues that have been determined by a host of studies are compiled, reviewed and presented in this paper. This review summarizes data, describing the potential toxicity of metal wear debris, free metallic ions and corrosion products release from metallic orthodontic appliances (metal surgical implants) in vivo and in vitro. Finally, a collection of published clinical data on in vivo and in vitro released trace metals from metal dental implants is included.

Simultaneous Comparison of Aqueous Humor and Serum Metabolic Profiles of Diabetic and Nondiabetic Patients Undergoing Cataract Surgery-A Targeted and Quantitative Metabolomics Study.

The aim of this study was to compare the aqueous humor (AH) and serum concentrations of metabolites in diabetic (n = 36) and nondiabetic (n = 36) senior adults undergoing cataract surgery. Blood samples were collected before surgery and AH during surgery. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted metabolomic and lipidomic analyses of samples were performed using the AbsoluteIDQ® p180 kit. Out of 188 metabolites targeted by the kit, 41 and 133 were detected in >80% of AH and serum samples, respectively. Statistical analysis performed to indicate metabolites differentiating diabetic and nondiabetic patients showed 8 and 20 significant metabolites in AH and serum, respectively. Pathway analysis performed for significant metabolites revealed that galactose metabolism is mostly affected in the AH, while arginine biosynthesis is mostly affected in the serum. Among metabolites that differentiate diabetic and nondiabetic patients, arginine was the only metabolite common to both serum and AH samples, as well as the only one with a decreased concentration in both body fluids of diabetic patients. Concentrations of the rest were elevated in AH and lowered in serum. This may suggest different mechanisms of diabetes-related dysregulation of the local metabolism in the eye in comparison to systemic changes observed in the blood.

Systematic review and meta-analysis investigating nicotine, cotinine and carbon monoxide exposures in people who both smoke and use nicotine replacement therapy.

To determine effects of concurrent smoking and nicotine replacement therapy (NRT) use on reported heaviness of smoking, nicotine (cotinine) body fluid and exhaled air carbon monoxide (CO) concentrations. Systematic review and meta-analysis of RCTs, which test interventions permitting concurrent NRT use and smoking and comparing, within participants, outcomes when smoking with those when smoking and using NRT concurrently. Measurements included reported number of cigarettes smoked per day (CPD), body fluid cotinine and expired air CO concentrations. Twenty-nine studies were included in the review. Meta-analysis of nine showed that, compared with when solely smoking, fewer cigarettes were smoked daily when NRT was used (mean difference during concurrent smoking and NRT use, -2.06 CPD [95% CI = -3.06 to -1.07, P < 0.0001]). Meta-analysis of seven studies revealed a non-significant reduction in exhaled CO during concurrent smoking and NRT use (mean difference, -0.58 ppm [95% CI = -2.18 to 1.03, P = 0.48]), but in the three studies that tested NRT used in the lead-up to quitting (i.e. as preloading), a similar reduction in exhaled CO was statistically significant (mean difference, -2.54 ppm CO [95% CI = -4.14 to -0.95, P = 0.002]). Eleven studies reported cotinine concentrations, but meta-analysis was not possible because of data reporting heterogeneity; of these, seven reported lower cotinine concentrations with concurrent NRT use and smoking, four reported no differences, and none reported higher concentrations. People who smoke and also use nicotine replacement therapy report smoking less heavily than people who solely smoke. When nicotine replacement therapy is used in the lead-up to quitting (preloading), this reported smoking reduction has been biochemically confirmed. There is no evidence that concurrent smoking and nicotine replacement therapy use result in greater nicotine exposure than solely smoking.

The Impact of Copper Ions on the Activity of Antibiotic Drugs.

Copper (Cu) is an essential trace metal and its concentration in body plasma is tightly regulated. An increase in Cu concentration in body fluids is observed in numerous pathological conditions, including infections caused by microorganisms. Evidence shows that Cu ions can impact the activity of antibiotics by increasing efficiency or diminishing/neutralizing antibiotic activity, forming complexes which may lead to antibiotic structure degradation. Herein, we represent the evidence available on Cu-antibiotic interactions and their possible impact on antimicrobial therapy efficiency. So far, in vitro studies described interactions between Cu ions and the majority of antibiotics in clinical use: penicillins, cephalosporins, carbapenems, macrolides, aminoglycosides, tetracyclines, fluoroquinolones, isoniazid, metronidazole. In vitro-described degradation or lower antimicrobial activity of amoxicillin, ampicillin, cefaclor, ceftriaxone, and meropenem in the presence of Cu ions suggest caution when using prescribed antibiotics in patients with altered Cu levels. On the other hand, several Cu-dependent compounds with antibacterial activity including the drug-resistant bacteria were discovered, such as thiosemicarbazones, disulfiram, dithiocarbamates, 8-hydroxiquinoline, phenanthrolines, pyrithione. Having in mind that the development of new antibiotics is already marked as inadequate and does not meet global needs, the potential of Cu-antibiotic interactions to change the efficiency of antimicrobial therapy requires further investigation.

Fabrication of osteogenesis induced WE43 Mg-Hydroxyapatite composites with low biodegradability and increased biocompatibility for orthopedic implant applications

Good biocompatibility, low biodegradation rate and excellent mechanical properties are essential for desirable performance of metallic biomaterials during osseointegration process. In the present study, bioabsorbable WE43 Mg alloy was used for fabrication of bio-composites with addition of nanosized hydroxyapatite (HA) particles by means of multi pass friction stir processing (FSP) for orthopedic implant applications. Microstructure, in vitro biodegradation and biocompatibility, wettability, and microhardness of resultant bio-composites were characterized. Results showed that applying severe plastic deformation through FSP caused significant grain refinement of Mg matrix and homogenous dispersion of fragmented secondary phase particles. Moreover, applying higher number of FSP passes increased uniformity of distribution of HA nanoparticles throughout Mg matrix. Compared to coarse grain samples, grain refined samples showed lower Mg2+ concentration and H2 evolution in simulated body fluid (SBF). Moreover, addition of HA into Mg matrix, reduced Mg2+ release and H2 evolution. The bio-composites illustrated uniformly and flatly corroded surface compared to samples without HA nanoparticles. During immersion of the bio-composites in SBF solution, a cauliflower structure of Ca–P compounds deposited on the surface of bio-composites which confirmed acceptable biomineralization. Contact angle measurement demonstrated that wettability of fabricated bio-composites increased by increasing number of FSP passes. Mouse osteoblast MC3T3 cell culture indicated that the fabricated bio-composites with uniform distribution of HA nanoparticles showed excellent in vitro biocompatibility, cell viability, and cell proliferation. Eventually, it was found that applying further FSP and presence of HA nanoparticles resulted in increased microhardness which is an indication of higher load-bearing capability of the fabricated bone implants.

Physiological activation of human and mouse bitter taste receptors by bile acids

Beside the oral cavity, bitter taste receptors are expressed in several non-gustatory tissues. Whether extra-oral bitter taste receptors function as sensors for endogenous agonists is unknown. To address this question, we devised functional experiments combined with molecular modeling approaches to investigate human and mouse receptors using a variety of bile acids as candidate agonists. We show that five human and six mouse receptors are responsive to an array of bile acids. Moreover, their activation threshold concentrations match published data of bile acid concentrations in human body fluids, suggesting a putative physiological activation of non-gustatory bitter receptors. We conclude that these receptors could serve as sensors for endogenous bile acid levels. These results also indicate that bitter receptor evolution may not be driven solely by foodstuff or xenobiotic stimuli, but also depend on endogenous ligands. The determined bitter receptor activation profiles of bile acids now enable detailed physiological model studies.

Enasidenib treatment in two individuals with D-2-hydroxyglutaric aciduria carrying a germline IDH2 mutation.

D-2-hydroxyglutaric aciduria type II (D2HGA2) is a severe inborn disorder of metabolism caused by heterozygous R140 mutations in the IDH2 (isocitrate dehydrogenase 2) gene. Here we report the results of treatment of two children with D2HGA2, one of whom exhibited severe dilated cardiomyopathy, with the selective mutant IDH2 enzyme inhibitor enasidenib. In both children, enasidenib treatment led to normalization of D-2-hydroxyglutarate (D-2-HG) concentrations in body fluids. At doses of 50 mg and 60 mg per day, no side effects were observed, except for asymptomatic hyperbilirubinemia. For the child with cardiomyopathy, chronic D-2-HG inhibition was associated with improved cardiac function, and for both children, therapy was associated with improved daily functioning, global motility and social interactions. Treatment of the child with cardiomyopathy led to therapy-coordinated changes in serum phospholipid levels, which were partly recapitulated in cultured fibroblasts, associated with complex effects on lipid and redox-related gene pathways. These findings indicate that targeted inhibition of a mutant enzyme can partly reverse the pathology of a chronic neurometabolic genetic disorder.

Cheap and Mass-Producible Electrochemical Sensor of Hydrogen Peroxide

Abstract Hydrogen peroxide is present naturally in any living cell. Although hydrogen peroxide concentration in cell is strictly regulated during normal metabolism, several human diseases lead to increased hydrogen peroxide concentration in body fluids. It is beneficial to monitor hydrogen peroxide levels in human body for early disease diagnostics. This can be done by creation of electronic device, which will use electrochemical sensor in order to perform automated hydrogen peroxide concentration measurement in a sample. The aim of the research is to use printed circuit board (PCB) technology in order to create a replaceable electrochemical hydrogen peroxide sensor that could be cheaply mass-produced to enable further development of automated health diagnostics device.

Metal concentrations in cerebrospinal fluid, blood, serum, plasma, hair, and nails in amyotrophic lateral sclerosis: A systematic review and meta-analysis

BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive muscle wasting, paralysis, and respiratory failure. Whereas approximately 10–15 % of ALS cases are familial, the etiology of the remaining, sporadic ALS cases remains largely unknown. Environmental exposures have been suggested as causative factors for decades, and previous studies have found elevated concentrations of metals in ALS patients. PurposeThis meta-analysis aims to assess metal concentrations in body fluids and tissues of ALS patients. MethodsWe searched the MEDLINE and EMBASE databases on December 7th, 2022 for cross-sectional, case-control, and cohort studies which measure metal concentrations in whole blood, blood plasma, blood serum, cerebrospinal fluid (CSF), urine, erythrocytes, nail, and hair samples of ALS patients. Meta-analysis was then performed when three or more articles existed for a comparison. FindingsTwenty-nine studies measuring 23 metals were included and 13 meta-analyses were performed from 4234 screened entries. The meta-analysis results showed elevated concentrations of lead and selenium. Lead, measured in whole blood in 6 studies, was significantly elevated by 2.88 µg/L (95 % CI: 0.83–4.93, p = 0.006) and lead, measured in CSF in 4 studies, was significantly elevated by 0.21 µg/L (95 % CI: 0.01 – 0.41, p = 0.04) in ALS patients when compared to controls. Selenium, measured in serum/plasma in 4 studies, was significantly elevated by 4.26 µg/L (95% CI: 0.73 – 7.79, p = 0.02) when compared to controls.Analyses of other metal concentrations showed no statistically significant difference between the groups. ConclusionLead has been discussed as a possible causative agent in ALS since 1850. Lead has been found in the spinal cord of ALS patients, and occupational exposure to lead is more common in ALS patients than in controls. Selenium in the form of neurotoxic selenite has been shown to geochemically correlate to ALS occurrence in Italy. Although no causal relationship can be established from the results of this meta-analysis, the findings suggest an involvement of lead and selenium in the pathophysiology of ALS. After a thorough meta-analysis of published studies on metal concentrations in ALS it can only be concluded that lead and selenium are elevated in ALS.

A Simple, sensitive, and selective electrochemical aptasensor for cortisol based on rGO‐AuNPs

AbstractCortisol is a steroid hormone naturally produced by the adrenal glands. It participates in and controls several processes in the body and is considered an important physiological biomarker. Due to its very low concentrations in body fluids, its detection requires high sensitivity and specificity. Here, we present a simple electrochemical biosensor based on reduced graphene oxide (rGO) modified with gold nanoparticles (AuNPs) for the immobilization of the cortisol‐specific aptamer (Ap) (MCH‐Ap‐AurGO/GCE). Important analytical parameters for identifying the target analyte were optimized, such as conditions and amount of immobilized Ap, the influence of the concentration and nature of the supporting electrolyte, pH of the medium, and incubation time. The optimized conditions for the aptasensor were: concentration of Ap 1.0 × 10−6 mol L−1, support electrolyte Tris/HCl 50 mmol L−1, MgCl2 10 mmol L−1, and NaCl 10 mmol L−1, at pH 5.0 and incubation time of 15 min. A linear response range was obtained from 1 × 10−18 up to 1 × 10−11 mol L−1 of cortisol with a detection limit (LOD) of 1.0 × 10−18 mol L−1. A curve adjusted for operational purposes in the saliva sample was fitted for the concentration range between 0.5 × 10−14 and 1 × 10−11 mol L−1, with a linear regression equation ΔRtc/Rtc1 = 2.70 + 0.17 × log([Cortisol]). The aptasensor demonstrated a great potential for detecting cortisol in a simple, fast, and highly sensitive way, opening its path for application in real samples, which present levels below the concentration in which cortisol is commonly found in body fluids.

Liver-directed gene therapy for ornithine aminotransferase deficiency.

Gyrate atrophy of choroid and retina (GACR) is a chorioretinal degeneration caused by pathogenic variants in the gene encoding ornithine aminotransferase (OAT), an enzyme mainly expressed in liver. Affected patients have increased ornithine concentrations in blood and other body fluids and develop progressive constriction of vision fields leading to blindness. Current therapies are unsatisfactory and better treatments are highly needed. In two mouse models of OAT deficiency that recapitulates biochemical and retinal changes of GACR, we investigated the efficacy of an intravenously injected serotype 8 adeno-associated (AAV8) vector expressing OAT under the control of a hepatocyte-specific promoter. Following injections, OAT-deficient mice showed reductions of ornithine concentrations in blood and eye cups compared with control mice injected with a vector expressing green fluorescent protein. AAV-injected mice showed improved electroretinogram response and partial restoration of retinal structure up to one-year post-injection. In summary, hepatic OAT expression by AAV8 vector was effective at correction of hyperornithinemia and improved function and structure of the retina. In conclusion, this study provides proof-of-concept of efficacy of liver-directed AAV-mediated gene therapy of GACR.

Effects of replacing inorganic salts of trace minerals with organic trace minerals in the pre- and postpartum diets on mineral status, antioxidant biomarkers, and health of dairy cows.

Our objectives were to evaluate the effects of complete replacement of supplementary inorganic salts of trace minerals (ITM; cobalt (Co), copper (Cu), manganese (Mn), zinc (Zn) sulfates and sodium (Na) selenite) by organic trace minerals (OTM; Co, Cu, Mn, Zn proteinates, and selenized yeast) in both pre- and postpartum diets on trace minerals (TM) concentrations in body fluids and liver, antioxidant and inflammation biomarkers in blood, and postpartum health of dairy cows. Pregnant cows were blocked by parity and body condition score and randomly assigned to ITM (n = 136) or OTM (n = 137) 45 d before expected calving. Both groups received the same pre- and postpartum diets except for the source of supplementary TM. The day of calving was considered study d 0 and blood was collected on d -45, -21, -14, -10, -7, -3, 0, 3, 7, 10, 14, 23, 65, and 105 for analyses of TM and biomarkers. Concentrations of TM were also investigated in the liver (d 105), milk (d 7, 23, 65, 105), urine (d -21, 21, 65, 105), ruminal fluid and feces (d -21, 21, 65). Incidence of clinical and subclinical health conditions were evaluated. Complete replacement of ITM by OTM resulted in greater concentration of selenium (Se) in serum (0.084 vs. 0.086 µg/mL; P < 0.01), milk (0.24 vs. 0.31 µg/g; P < 0.01), and ruminal fluid (0.54 vs. 0.58 µg/g; P = 0.06), and reduced concentration of Se in urine (1.54 vs. 1.23 µg/g; P<0.01). For concentration of Co in serum, an interaction between treatment and time was detected (P < 0.01). Cows supplemented with OTM had greater concentrations of Co on d -7 and 0 (0.30 vs. 0.33 ng/mL; P < 0.01) but lower concentrations of Co on d 23, 65, and 105 (0.34 vs. 0.31 ng/mL; P < 0.05), in addition to reduced concentration of Co in feces (1.08 vs. 0.99 µg/g; P = 0.04) and, for multiparous only, in urine (0.019 vs. 0.014 µg/g; P < 0.01). Cows supplemented with OTM had lower postpartum concentrations of glutamate dehydrogenase (20.8 vs. 17.8 U/L; P < 0.05) and higher albumin on d -10 (36.0 vs. 36.7 g/L; P = 0.04) and 23 (36.9 vs. 37.6 g/L; P = 0.03) relative to calving. Primiparous cows fed OTM had lower concentration of ceruloplasmin in plasma (55 vs. 51 mg/L; P ≤ 0.05). Cows supplemented with OTM had less incidence of lameness (14% vs. 7%; P = 0.05), elevated nonesterified fatty acids (NEFA) (61% vs. 44%; P < 0.01), and multiple metabolic problems (35% vs. 20%; P < 0.01). Despite the lack of differences in Cu, Mn, and Zn concentrations and antioxidant capacity, complete replacement of ITM by OTM altered concentrations of Se and Co, supported liver and hoof health, and reduced the risk of postpartum elevated NEFA.

Pathological conditions associated with hyperhomocysteinemia

The effect of excessive homocysteine concentration in human blood, on the cells and tissues of the body is very complex. The effect associated with the induction of oxidative stress and disruption of the biochemical balance of the intracellular space has a negative impact on the physiology of cells and the regularity of their functioning by changing their metabolism. This may result in the formation and development of atherosclerotic lesions, disorders in the coagulation system leading to thrombosis and, consequently, embolism, pathological changes in the central nervous system, which may translate into the formation of mental disorders, neurodegenerative diseases, depression and dementia. In addition, hyperhomocysteinemia affects the possible pathologies and complications of pregnancy associated with them, as well as the implications for fetal development if its aforementioned condition. The work presented here outlines the mechanisms that determine the formation of the aforementioned disease entities as a result of too much homocysteine and the clinical significance of these relationships. With the development of science and the increasing number of publications related to the impact of hyperhomocysteinemia on diverse disease entities, there are voices suggesting the inclusion of studies on homocysteine concentrations in body fluids in screening as risk factors for the development of these diseases or using them for their control and treatment.