Accumulation In Body Fluids Research Articles

Effects of microplastics on the kidneys: a narrative review

Micro- and nanoplastics (MPs) are small synthetic organic polymer particles (<5 mm and <1 μm, respectively) that originate directly from plastic compounds or result from the degradation of plastic. These particles are a global concern since they are widely distributed in water, air, food and soil, and recent scientific evidence has linked MPs to negative biological effects. Although these particles are difficult to detect in humans, MPs have been identified in different biological fluids and tissues, such as the placenta, lung, intestines, liver, blood, urine, and kidneys. Human exposure to MPs can occur by ingestion, inhalation, or dermal contact, potentially causing metabolic alterations. Data from experimental and clinical studies have revealed that the ability of MPs to promote inflammation, oxidative stress, and organ dysfunction and negatively affect clinical outcomes is associated with their accumulation in body fluids and tissues. Although evidence of the putative action of MPs in the human kidney is still scarce, there is growing interest in studying MPs in this organ. In addition, chronic kidney disease (CKD) requires investigation because this condition is potentially prone to MP accumulation. The purpose of the present article is (i) to review the general aspects of MP generation, available analytic methods for identification and the main known biological toxic effects and (ii) to describe and critically analyze key experimental and clinical studies that support a role of MPs in kidney disease.

Alkaptonuria.

Alkaptonuria is a rare inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase activity. The consequent homogentisic acid (HGA) accumulation in body fluids and tissues leads to a multisystemic and highly debilitating disease whose main features are dark urine, ochronosis (HGA-derived pigment in collagen-rich connective tissues), and a painful and severe form of osteoarthropathy. Other clinical manifestations are extremely variable and include kidney and prostate stones, aortic stenosis, bone fractures, and tendon, ligament and/or muscle ruptures. As an autosomal recessive disorder, alkaptonuria affects men and women equally. Debilitating symptoms appear around the third decade of life, but a proper and timely diagnosis is often delayed due to their non-specific nature and a lack of knowledge among physicians. In later stages, patients' quality of life might be seriously compromised and further complicated by comorbidities. Thus, appropriate management of alkaptonuria requires a multidisciplinary approach, and periodic clinical evaluation is advised to monitor disease progression, complications and/or comorbidities, and to enable prompt intervention. Treatment options are patient-tailored and include a combination of medications, physical therapy and surgery. Current basic and clinical research focuses on improving patient management and developing innovative therapies and implementing precision medicine strategies.

Dietary pyrroloquinoline quinone hinders aging progression in male mice and D-galactose-induced cells.

Background: Understanding and promoting healthy aging has become a necessity in the modern world, where life expectancy is rising. The prospective benefits of the antioxidant pyrroloquinoline quinone (PQQ) in healthy aging are promising. However, its role in aging remains unclear. Thus, this study aimed to investigate the effect of PQQ on preventing the progression of aging and to explore its underlying molecular mechanisms. Methods: Naturally aged C57BL/6J male mice were fed a normal diet with or without PQQ (20mg/kg/day) for 10 weeks. Body composition was measured by bioimpedance at weeks 0 and 8. The integument conditions were evaluated at weeks 0, 4, and 8. Muscle strength and function were examined at week 8. At the ninth week, computed tomography images of the mice were captured, and blood and tissue samples were collected. The levels of inflammatory cytokines in the gastrocnemius muscle were measured, and the muscle fiber cross-sectional area in the soleus muscle was examined. Additionally, a D-galactose (D-gal)-induced cell aging model was used to study the effects of PQQ intervention on cell proliferation, senescence, differentiation, ROS levels, and mitochondrial function in myoblasts (C2C12). Cell proliferation and monolayer permeability of D-gal-induced intestinal epithelial cells (IEC6) were also examined. Results: Aged mice suffered from malnutrition; however, PQQ supplementation ameliorated this effect, possibly by improving metabolic dysfunction and small intestinal performance. PQQ prevented rapid loss of body fat and body fluid accumulation, attenuated muscle atrophy and weakening, reduced chronic inflammation in skeletal muscles, and improved skin and coating conditions in aged mice. Furthermore, PQQ intervention in D-gal-treated C2C12 cells improved mitochondrial function, reduced cellular reactive oxygen species (ROS) levels and senescence, and enhanced cell differentiation, consequently preventing age-related muscle atrophy. In addition, PQQ increased cell proliferation in D-gal-treated IEC6 cells and consequently improved intestinal barrier function. Conclusion: PQQ could hinder the aging process and particularly attenuate muscle atrophy, and muscle weakness by improving mitochondrial function, leading to reduced age-related oxidative stress and inflammation in muscles. PQQ may also ameliorate malnutrition caused by intestinal barrier dysfunction by enhancing IEC proliferation. This study provides evidence for the role of PQQ in aging and suggests that PQQ may be a potential nutritional supplementation that can be included in healthy aging strategies.

Assessment of the Concentration of 51 Elements in the Liver and in Various Parts of the Human Brain-Profiling of the Mineral Status.

The anthropogenic environment and diet introduce many metals into the human body, both essential and toxic. Absorption leads to systemic exposure and accumulation in body fluids and tissues. Both excess and deficiency of trace elements are health hazards. The primary aim of the present study was to evaluate the concentration of 51 elements in liver samples and 11 selected brain regions obtained at post-mortem examination from a population of adults living in south-eastern Poland (n = 15). A total of 180 analyses were performed by inductively coupled plasma mass spectrometry in two independent replicates. The collected data show very high individual variability in the content of the investigated elements. Macroelements such as sodium, magnesium, phosphorus, potassium, calcium, iron, and zinc occurred in the highest concentrations and with the greatest statistically significant variations. Although the elemental content of the brain and liver differed significantly, the strongest positive correlation between liver and polus frontalis was observed for the essential element selenium (0.9338) and the strongest negative one for manganese (-0.4316) and lanthanum (-0.5110). The brain areas studied have different requirements for phosphorus, manganese, iron, and molybdenum. In addition, males had a significantly (p < 0.05) higher brain content of lanthanides and actinides than females. The results of this study show that the inhabitants of south-eastern Poland are exposed to a fairly uniform accumulation of aluminum and vanadium in the brain, which have the highest affinity to the thalamus dorsalis. This result proves that there is environmental exposure to these elements.

Myocardial tissue characterization and mortality in transcatheter aortic valve replacement

Abstract Background Cardiac decompensation in severe aortic stenosis involves accumulation of myocardial extracellular matrix and congestion, which can be objectively quantified by cardiac magnetic resonance (CMR) and bioelectrical impedance spectroscopy (BIS). The aim of this study was to determine whether the extent of extracellular matrix pre-intervention correlates with congestion and is associated with adverse outcomes. Methods Consecutive patients scheduled for transcatheter aortic valve replacement (TAVR) underwent assessment of volume status using BIS, and CMR, and were prospectively followed. CMR included T1 mapping and extracellular volume (ECV) quantification for the assessement of diffuse myocardial tissue alterations and T2 mapping (n=100) for the assessment of myocardial edema. The combination of all-cause death and heart failure (HF) hospitalization was selected as primary study endpoint. Results 180 patients (80.6±7.2 y/o, 48.9% female) with valid BIS and CMR data were included. ECV levels≥median was linked to worse ventricular function, more severe pulmonary hypertension and mitral/tricuspid regurgitation (p for all&amp;lt;0.05). Fluid levels significantly correlated with ECV (r=0.403, p&amp;lt;0.001) and T2 (r=0.378, p=0.015), but not T1 relaxation times (p&amp;gt;0.05). Moreover, fluid levels were independently associated with CMR-ECV by multivariate linear regression analysis (p&amp;lt;0.001), alongside with body mass index, left ventricular ejection fraction and hematocrit (p for all&amp;lt;0.05). In total, 22.9% (39/170) had experienced an event (22 deaths, 17 heart failure) 13.4±7.5 months following TAVR. ECV levels≥median of 27.0% were significantly associated with the combined endpoint by Kaplan Meier estimates (log rank, p&amp;lt;0.001, Figure 1), but also with HF hospitalization (p&amp;lt;0.001) and death (p=0.020), when analyzed separately. Quantitively, every 1% increase in ECV increased event hazard by 11% [hazard ratio 1.111, 95% confidence interval 1.030–1.198, p=0.007]. After multivariate adjustment for important clinical, laboratory and CMR parameters, ECV≥median remained independently associated with outcome (p=0.045), alongside with serum albumin (p&amp;lt;0.001) and body fluid levels (p=0.015) by Cox regression analysis. Conclusions Cardiac decompensation in AS involves myocardial ECV expansion and body fluid accumulation. Fluid accumulation seems to impact the amount of ECV, and both parameters are independently associated with adverse outcomes following TAVR. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Österreichische Kardiologische Gesellschaft

Application of two-dimensional fractional-order convolution and bounding box pixel analysis for rapid screening of pleural effusion.

Pleural effusion is a pathologic symptom in which there is accumulation of body fluids around the lungs. A chest radiograph is a rapid examination technique and does not require complex setup for making a preliminary diagnosis of lung and heart diseases. In radiographic visualization, the symptom patterns appear as light or dark areas in the lung cavity. Computer-aided diagnosis is an automatic manner that can rapidly highlight the object region by preanalyzing medical images. It can improve the problems of manual inspection and allow diagnosis in remote medical facilities. Based on the ratios of lung anatomy, the automatic screening manner based on pattern recognition can be viewed as pixel value detection in the bilateral lung cavities. In this study, a fractional-order convolution (FOC) process is used to enhance the original image for an accurate extrapolation of the desired object in an image. The specific object image feature can be improved, and an accurate quantification of the pleural effusion region can be obtained using the suitable ranges of fractional-order parameters. Based on the boundaries of homogeneous regions, the pixel ratios of the lung anatomy between normal and abnormal conditions can be computed. The pleural effusion sizes and volumes can be rapidly estimated through the number of pixel changes. The experimental results reveal that the feature maps are similar and stable on image enhancement and segmentation with two fractional-order enhancement masks, as fractional-order v = 0.05 to 0.20 for mask 1# and v = 0.80 to 0.95 for mask 2#, respectively. The results also demonstrate the feasibility of the study on combining two-dimensional image FOC-process and bounding box pixel analysis to estimate the moderate and large effusion sizes from 500-2,000 mL.

Smart Pleural Effusion Drainage Monitoring System Establishment for Rapid Effusion Volume Estimation and Safety Confirmation

Pleural effusion is the pathologic accumulation of body fluids around the unilateral or bilateral lungs that is primarily caused by heart disease. A chest radiograph is a rapid examination technique used to provide a preliminary diagnosis of lung and heart diseases. Computer-aided diagnosis with the digitalized image is an automated approach that addresses the drawbacks of manual inspection. In this study, two corner detectors along with a two-dimensional convolution process are used to enhance the chest X-ray image for an accurate extrapolation of the bilateral lung cavities. Based on bounding box pixel analysis, the pixel ratios of the lung anatomy between normal and abnormal conditions can be estimated to identify the pleural effusion size. Next, a smart drainage monitoring system is developed to improve the current functions of the traditional drainage tool and confirm the drainage safety, including (a) drainage volume and required time detection, (b) unplanned removal warning, and (c) physiological status monitoring. The experimental result will be used to determine the feasibility of the proposed effusion volume estimation algorithm and the efficiency of the smart drainage monitoring prototyping tool. The proposed smart drainage monitoring system and the computer-aided method with digitalized images can be further applied in real clinical practice in the intensive care unit.

Myeloid cells pave the way for lymphatic system development and maintenance.

The maintenance of tissue homeostasis is indispensable for health. In particular, removal of toxic compounds from cells and organs is a vital process for the organism. The lymphatic vasculature works in order to ensure the efficient removal of tissue waste. Forbidden over the last decade when more attention was paid to the blood vasculature, studies on the lymphatic vasculature have gained momentum during the last couple of years. The lymphatic vasculature naturally runs parallel to the blood vasculature and their synergistic work is critical for maintaining tissue homeostasis. Diminished lymphatic function results in accumulation of body fluids in tissues and gives rise to edema. Recently, it became obvious that immune cells including myeloid cells and lymphocytes are able to interact with and control the development and function of the lymphatic vasculature. In this review, we will focus on the interaction between myeloid cells, including macrophages, monocytes, and dendritic cells, with lymphatic vessels.

The Influence of Surface Roughness on Biocompatibility and Fatigue Life of Titanium Based Alloys

This article deals with the effect of treatment on the mechanical properties ofbiocompatible alloys. In the case of implants, it is desirable to ensure good biocompatibility. Generally, the environment in the body is very aggressive and implants can quickly degrade due the corrosion. The process of corrosion leads to the release of harmful particles into the body. Other reasons for rejection of the implants, is their coverage bacterial plaque. Another reason for the rejection of the implant may be a smooth surface. In some cases, the tissue does not adhere to the smooth surface of the implant, in this regionsoccurs an accumulation of body fluids. This problem can be solved with a rough surface. From the viewpoint of fatigue resistance, the rough surface containing grooves and holes has a negative influence on the fatigue resistance against mechanical loading. The rough surface can be produced by machining or asymmetric deposition of particles of oxides, nitrides or other particles on surface. In this work the formation and propagation of fatigue cracks in the material with granular surface is analysed. The formation and growth of fatigue crack originated from granular surface is simulated. Also, experimental studies were carried out.

Nebulized Epinephrine Limits Pulmonary Vascular Hyperpermeability to Water and Protein in Ovine With Burn and Smoke Inhalation Injury.

To test the hypothesis that nebulized epinephrine ameliorates pulmonary dysfunction by dual action-bronchodilation (β2-adrenergic receptor agonism) and attenuation of airway hyperemia (α1-adrenergic receptor agonism) with minimal systemic effects. Randomized, controlled, prospective, and large animal translational studies. University large animal ICU. Twelve chronically instrumented sheep. The animals were exposed to 40% total body surface area third degree skin flame burn and 48 breaths of cooled cotton smoke inhalation under deep anesthesia and analgesia. The animals were then placed on a mechanical ventilator, fluid resuscitated, and monitored for 48 hours in a conscious state. After the injury, sheep were randomized into two groups: 1) epinephrine, nebulized with 4 mg of epinephrine every 4 hours starting 1 hour post injury, n = 6; or 2) saline, nebulized with saline in the same manner, n = 6. Treatment with epinephrine had a significant reduction of the pulmonary transvascular fluid flux to water (p < 0.001) and protein (p < 0.05) when compared with saline treatment from 12 to 48 hours and 36 to 48 hours, respectively. Treatment with epinephrine also reduced the systemic accumulation of body fluids (p < 0.001) with a mean of 1,410 ± 560 mL at 48 hours compared with 3,284 ± 422 mL of the saline group. Hemoglobin levels were comparable between the groups. Changes in respiratory system dynamic compliance, mean airway pressure, PaO2/FiO2 ratio, and oxygenation index were also attenuated with epinephrine treatment. No considerable systemic effects were observed with epinephrine treatment. Nebulized epinephrine should be considered for use in future clinical studies of patients with burns and smoke inhalation injury.

Establishment of proprotein convertase, furinA knocked-out lines in medaka, Oryzias latipes, and unique form of medaka furin-like prorprotein convertase (mflPC)

Furin is a member of the subtilisin-like proprotein convertase family. Medaka furin-like proprotein convertase (mflPC), a unique form of medaka FurinA (mFurinA) (GenBank accession no. AB092685.1) was cloned from the ovary cDNA library. Compared to human furin (GenBank accession no. NM_002569.3) and mFurinA in the structural motif of mflPC, only the catalytic domain and the N-terminal region of the P domain are highly conserved, but more C-terminal domains are truncated. Based on our research, there three forms of furin, mFurinA, mflPC and mFurinB that exist in medaka. These three genes are expressed in the developing embryos and ubiquitously in adult tissues.To investigate the function of mFurinA and mflPC, as a first step, mFurinA KO lines were established. The mFurinA KO larvae with abnormal phenotypes exhibit edema, abnormal body fluid accumulation in the pericardial and yolk sacs, enlarged hearts, clogged blood vessels, structurally weak eyes, and a very short life. The data suggests that abnormal processing of TGF-β may be one of the causes of these disorders. FurinA KO medaka is a good model for the study of human diseases such as Fraser Syndrome and Marfan syndrome. The creation of human genomic disorder models using recently advanced genome editing procedures informs us of the function of key molecules and their role in causing equivalent human disorders and will be useful as a tool to identify the mechanisms involved.

Development and testing of a scale to assess fluid overload symptoms

AimThis study aimed to develop and test the reliability and validity of a scale about fluid overload symptoms in patients with heart failure. BackgroundFluid overload symptoms are a common cause of admission of patients with heart failure. An instrument that is quick to complete and easy to use for the measurement of fluid overload symptoms would be beneficial for early intervention and avoidance of hospital admission. MethodsFifty-six participants were recruited from cardiology wards. Internal consistency reliability was assessed using Cronbach's alpha coefficient. Validity was assessed using Pearson's correlation coefficient and exploratory factor analysis. ResultsThis new instrument had a Cronbach's alpha of .81. Exploratory factor analysis revealed two factors (breathing symptoms and body fluid accumulation symptoms) with acceptable criterion validity. ConclusionsThe fluid overload symptoms scale exhibits reliability with construct and criterion validity. It would be more beneficial if further testing is done.

Chronic administration of methylmalonate on young rats alters neuroinflammatory markers and spatial memory

The methylmalonic acidemia is an inborn error of metabolism (IEM) characterized by methylmalonic acid (MMA) accumulation in body fluids and tissues, causing neurological dysfunction, mitochondrial failure and oxidative stress. Although neurological evidence demonstrate that infection and/or inflammation mediators facilitate metabolic crises in patients, the involvement of neuroinflammatory processes in the neuropathology of this organic acidemia is not yet established. In this experimental study, we used newborn Wistar rats to induce a model of chronic acidemia via subcutaneous injections of methylmalonate (MMA, from 5th to 28th day of life, twice a day, ranged from 0.72 to 1.67μmol/g as a function of animal age). In the following days (29th–31st) animal behavior was assessed in the object exploration test and elevated plus maze. It was performed differential cell and the number of neutrophils counting and interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels in the blood, as well as levels of IL-1β, TNF-α, inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT) in the cerebral cortex were measured. Behavioral tests showed that animals injected chronically with MMA have a reduction in the recognition index (R.I.) when the objects were arranged in a new configuration space, but do not exhibit anxiety-like behaviors. The blood of MMA-treated animals showed a decrease in the number of polymorphonuclear and neutrophils, and an increase in mononuclear and other cell types, as well as an increase of IL-1β and TNF-α levels. Concomitantly, MMA increased levels of IL-1β, TNF-α, and expression of iNOS and 3-NT in the cerebral cortex of rats. The overall results indicate that chronic administration of MMA increased pro-inflammatory markers in the cerebral cortex, reduced immune system defenses in blood, and coincide with the behavioral changes found in young rats. This leads to speculate that, through mechanisms not yet elucidated, the neuroinflammatory processes during critical periods of development may contribute to the progression of cognitive impairment in patients with methylmalonic acidemia.

Integrating climate-related stressor effects on marine organisms: unifying principles linking molecule to ecosystem-level changes

MEPS Marine Ecology Progress Series Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsTheme Sections MEPS 470:273-290 (2012) - DOI: https://doi.org/10.3354/meps10123 Integrating climate-related stressor effects on marine organisms: unifying principles linking molecule to ecosystem-level changes Hans-O. Pörtner* Integrative Ecophysiology, Alfred-Wegener-Institute, Am Handelshafen 12, 27570 Bremerhaven, Germany *Email: hans.poertner@awi.de ABSTRACT: Climate change effects on marine ecosystems involve various stressors, predominantly temperature, hypoxia and CO2, all of which may combine with further anthropogenic stressors such as pollutants. All life forms respond to these drivers, following potentially common principles, which are insufficiently understood. Specific understanding may be most advanced in animals where the concept of ‘oxygen and capacity dependent thermal tolerance’ (OCLTT) is an integrator of various effects, linking molecular to ecosystem levels of biological organisation. Recent studies confirm OCLTT involvement in the field, causing changes in species abundance, biogeographical ranges, phenology and species predominance. At the whole-animal level, performance capacity set by aerobic scope and energy budget, building on baseline energy turnover, links fitness (within a thermal window) and functioning at the ecosystem level. In variable environments like the intertidal zone, animals also exploit their capacity for passive tolerance. While presently the temperature signal appears predominant in the field, effects may well involve other stressors, acting synergistically by narrowing the aerobic OCLTT window. Recent findings support the OCLTT concept as a common physiological basis linking apparently disjunct effects of ocean warming, acidification and hypoxia in a so-called climate syndrome. In brief, warming-induced CO2 accumulation in body fluids links to the effects of ocean acidification mediated by the weak acid distribution of CO2. Temperature-induced hypoxemia links to the hypoxia sensitivity of thermal tolerance. Future work will need to develop proxies for the temperature-dependent effects of climate-related stressors and also identify the principles operative in organisms other than animals and their underlying mechanisms. Mechanism-based modelling efforts are then needed to develop reliable organism to ecosystem projections of future change. KEY WORDS: Ocean warming · Hypoxia · Acidification · Climate change · Ecosystem change · Aerobic scope · Energy budget · Mechanism-based projections Full text in pdf format PreviousCite this article as: Pörtner HO (2012) Integrating climate-related stressor effects on marine organisms: unifying principles linking molecule to ecosystem-level changes. Mar Ecol Prog Ser 470:273-290. https://doi.org/10.3354/meps10123 Export citation RSS - Facebook - Tweet - linkedIn Cited by Published in MEPS Vol. 470. Online publication date: December 06, 2012 Print ISSN: 0171-8630; Online ISSN: 1616-1599 Copyright © 2012 Inter-Research.

Isolated Neonatal Seizures: Adenylosuccinase Deficiency is Another Cause!

I read with great interest the very useful review “Isolated Neonatal Seizures: When to Suspect Inborn Errors of Metabolism” by Ficicioglu and Bearden [ [1] Ficicioglu C. Bearden D. Isolated neonatal seizures: When to suspect inborn errors of metabolism. Pediatr Neurol. 2011; 45: 283-291 Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar ]. I would like to add adenylosuccinase deficiency to their causes for suspicion. This genetic, mainly neurologic disorder of the de novo purine synthesis was first reported in 1984 [ [2] Jaeken J. van den Berghe G. An infantile autistic syndrome characterized by the presence of succinylpurines in body fluids. Lancet. 1984; 2: 1058-1061 PubMed Google Scholar ]. Most of the approximately 60 reported patients demonstrate variable associations of moderate to severe psychomotor retardation, epilepsy after their first years, autistic features, and growth retardation [ [3] van den Berghe G. Vincent M.-F. Marie S. Disorders of purine and pyrimidine metabolism. in: Saudubray J.-M. van den Berghe G. Walter J.H. Inborn metabolic diseases: Diagnosis and treatment. 5th ed. Springer-Verlag, Berlin2012: 499-518 Crossref Scopus (11) Google Scholar ]. However, a subgroup of patients presents with intractable seizures beginning within the first days or weeks of age [ [4] Mouchegh K. Zikánová M. Hoffmann G.F. et al. Lethal fetal and early neonatal presentation of adenylosuccinate lyase deficiency: Observation of 6 patients in 4 families. J Pediatr. 2007; 150: 57-61 Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar ]. Often severe hypotonia is associated such as seen, e.g., in nonketotic hyperglycinemia and γ-aminobutyric acid transaminase deficiency, as mentioned by Ficicioglu and Bearden [ [1] Ficicioglu C. Bearden D. Isolated neonatal seizures: When to suspect inborn errors of metabolism. Pediatr Neurol. 2011; 45: 283-291 Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar ]. These seizures can lead to death or severe mental retardation. In some patients, intrauterine growth retardation, microcephaly, fetal hypokinesia, and a lack of fetal heart rate variability have also been observed. Adenylosuccinase catalyzes two steps in purine synthesis: the conversion of succinyl aminoimidazole carboxamide ribotide to aminoimidazole carboxamide ribotide (in the de novo pathway), and the conversion of adenylosuccinate to adenosine monophosphate. Its deficiency results in the accumulation in body fluids of succinyl purines, i.e., succinyl aminoimidazole carboxamide riboside and succinyl adenosine (the dephosphorylated substrates of the enzyme). A modified Bratton-Marshall (colorimetric) test performed on urine can be used as a screening test, but some medications such as sulfonamides cause a false-positive result. A final diagnosis requires high-pressure liquid chromatography with ultraviolet light detection, or high-pressure liquid chromatography with electrospray ionization tandem mass spectroscopy. Isolated Neonatal Seizures: When to Suspect Inborn Errors of MetabolismPediatric NeurologyVol. 45Issue 5PreviewNeonatal seizures are common, and often comprise the first clinical indicator of central nervous system dysfunction. Although most neonatal seizures are secondary to processes such as hypoxic-ischemic injury, infection, or cortical malformations (which are readily identifiable through routine testing and imaging), seizures secondary to inborn errors of metabolism can be much more difficult to diagnose, and thus a high index of suspicion is required. The early diagnosis of inborn errors of metabolism is crucial, considering that many can receive effective treatment (e.g., dietary supplementation or restriction) with favorable long-term outcomes. Full-Text PDF ResponsePediatric NeurologyVol. 47Issue 3PreviewWe thank Dr. Jaaken for his insightful discussion of adenylosuccinase deficiency as a cause of neonatal seizures. Our review was intended to offer an overview of metabolic disorders presenting with isolated neonatal seizures, i.e., neonatal seizures not associated with other characteristic abnormalities. Dr. Jaaken is correct in observing that neonatal seizures may constitute an atypical presentation of this rare disease, with six cases reported in the literature [1]. However, the severe form of adenylosuccinase deficiency that presents with neonatal seizures is often accompanied by severe hypotonia, intrauterine growth retardation, and magnetic resonance imaging abnormalities that are variable but that generally include dysmyelination [2]. Full-Text PDF

A quantitative assessment of alkaptonuria

Alkaptonuria (AKU) is due to excessive homogentisic acid accumulation in body fluids due to lack of enzyme homogentisate dioxygenase leading in turn to varied clinical manifestations mainly by a process of conversion of HGA to a polymeric melanin-like pigment known as ochronosis. A potential treatment, a drug called nitisinone, to decrease formation of HGA is available. However, successful demonstration of its efficacy in modifying the natural history of AKU requires an effective quantitative assessment tool. We have described two potential tools that could be used to quantitate disease burden in AKU. One tool describes scoring the clinical features that includes clinical assessments, investigations and questionnaires in 15 patients with AKU. The second tool describes a scoring system that only includes items obtained from questionnaires used in 44 people with AKU. Statistical analyses were carried out on the two patient datasets to assess the AKU tools; these included the calculation of Chronbach's alpha, multidimensional scaling and simple linear regression analysis. The conclusion was that there was good evidence that the tools could be adopted as AKU assessment tools, but perhaps with further refinement before being used in the practical setting of a clinical trial.

Absorption and metabolism of benzoic acid in growing pigs1

Dietary benzoic acid (BA) supplementation causes a pronounced reduction in urinary pH but only small changes in blood pH. The present study aimed to investigate the portal absorption profile, hepatic metabolism of BA, and renal excretion of hippuric acid (HA) underlying the relatively small impact of BA on systemic acid-base status. Eight growing pigs (BW = 63 +/- 1 kg at sampling) fitted with permanent indwelling catheters in the abdominal aorta, hepatic portal vein, hepatic vein, and mesenteric vein were allocated to 4 sampling blocks and randomly assigned to control (CON; nonsupplemented diet) or BA supplementation (B; control diet + 1% BA top-dressed). Feed intake was restricted to 3.6% of BW and the ration divided into 3 equally sized meals offered at 8-h intervals. Blood pH (7.465 and 7.486 +/- 0.004) and urinary pH (4.99 and 7.01 +/- 0.09) were less (P = 0.03 and P < 0.01) in B compared with CON. The arterial concentration, net portal flux, and net hepatic uptake of BA increased (P < 0.01) in B compared with CON. The net portal flux of BA increased (P < 0.01) after feeding with B, but remained positive (P < 0.01) at all sampling times (n = 8). Recovery of dietary BA as increased net portal flux and hepatic uptake of BA was 87 +/- 5% and 89 +/- 15%, respectively. The recovery of dietary BA as urinary excretion of BA and HA was 0.08 +/- 0.02% and 85 +/- 7%, respectively. It is concluded that the small impact of BA supplementation on systemic acid-base status was caused by a protracted BA absorption and efficient hepatic extraction and glycine conjugation in combination with efficient renal clearance of HA. Together, these physiological mechanisms prevented major BA and HA accumulation in body fluids.

Is there any novelty on the horizon of heart failure management in internal medicine? The evaluation of body fluid accumulation

Is there any novelty on the horizon of heart failure management in internal medicine? The evaluation of body fluid accumulation

Dissociation of antihyperglycaemic and adverse effects of partial perioxisome proliferator-activated receptor (PPAR-γ) agonist balaglitazone

Balaglitazone is a novel thiazolidinedione in clinical development for the treatment of type 2 diabetes. Common side effects associated with PPARγ receptor agonists are weight gain, oedema and adipogenesis. Balaglitazone is a selective partial PPARγ agonist and it has been speculated that such compounds have a more favourable safety margin than full agonists. We have compared impact of equi-efficacious antihyperglycaemic doses of balaglitazone with full PPARγ agonist rosiglitazone on body fluid accumulation, cardiac enlargement, and adipogenesis. Equi-efficacious antihyperglycaemic doses (ED 90) of balaglitazone (3 mg/kg/day) and rosiglitazone (6 mg/kg/day) were determined in male diabetic db/db mice. In adult male rats treated for up to 42 days, feeding, drinking, anthropometry, and plasma volumes were measured. Total plasma volume was measured with dye dilution technique. Compared to vehicle, rosiglitazone consistently increased food intake throughout the 42 day treatment period. In contrast, balaglitazone increased food intake in the last week of the experiment. However, both rosiglitazone and balaglitazone increased water intake. After 42 days, rosiglitazone treated rats displayed significantly elevated adiposity. Rosiglitazone increased total blood and plasma volumes throughout the treatment. Twenty-one days of balaglitazone treatment had no significant impact on blood or plasma volumes, whilst 42 days of balaglitazone increased plasma volume but to a significantly lesser extent than seen for rosiglitazone (vehicle: 46.1 ± 1.5; balaglitazone: 50.8 ± 1.21; rosiglitazone: 54.6 ± 1.6 ml/kg). Heart weight was significantly elevated only in rosiglitazone treated animals. At doses inducing comparable antihyperglycaemic control, the full PPARγ agonist, rosiglitazone, induces more pronounced body fluid retention and heart enlargement than seen for the partial PPARγ agonist, balaglitazone. Thus, partial agonists may pose safer alternative to current anti-diabetic therapy with full PPARγ agonist.

Management of extreme azotemia from urinary tract obstruction without dialysis. Clinical correlates and kinetic modeling of the recovery of renal function

The recovery of renal function following release of urinary tract obstruction with advanced azotemia determines both the need for emergency dialysis in the early post-obstructive period and the long-term planning for chronic kidney disease management. A man with prostatic cancer who presented with 16 days of anuria and a serum creatinine (Scr) of 42.7 mg/dl but had evidence suggesting residual renal function was managed conservatively and reached a steady-state Scr of 1.6 mg/dl within 84 h of urinary bladder catheterization. Modeling of the decrease in Scr taking into account the decline in the body creatinine pool that existed prior to the release of the obstruction and the accumulation in body fluids of creatinine produced after the release of the obstruction suggested that recovery of the value of glomerular filtration rate corresponding to the steady-state Scr occurred at the release of the urinary obstruction. The case illustrates both the clinical factors that may lead to the decision to postpone dialysis in a patient presenting with extreme obstructive azotemia and a novel method of modeling the recovery of renal function after release of the obstruction.