Comprehensive <Superscript>1</Superscript>H NMR metabolic profiling of body fluids for differentiation of meningitis in adults

Introduction

Meningitis, a morbidly infectious central nervous system pathology is accompanied by acute inflammation of the meninges, causing raised intracranial pressure linked with serious neurological sequelae.

Objective

To observe the variation in the metabolic profile, that may occur in serum and urine along with CSF in adults using ¹H NMR spectroscopy, with an attempt of appropriate and timely treatment regimen.

Methods

The ¹H NMR-based metabolomics has been performed in 115 adult subjects for differentiating bacterial meningitis (BM) and tubercular meningitis (TBM).

Results

The discriminant function analysis (DFA) of the three bio-fluids collectively identified 3-hydroxyisovalerate, lactate, glucose, formate, valine, alanine, ketonic bodies, malonate and choline containing compounds (choline and GPC) as significant metabolites among cases versus control group. The differentiation of bacterial meningitis and tuberculous meningitis (BM vs. TBM) can be done on the basis of identification of 3-hydroxyisovalerate, isobutyrate and formate in case of CSF (with a correct classification of 78 %), alanine in serum (correct classification 60 %), valine and acetone in case of urine (correct classification 89.1 %). The NMR spectral bins based orthogonal signal correction principal component analysis score plots of significant metabolites obtained from DFA also provided group classification among cases versus control group in CSF, serum and urine samples. The variable importance in projection scores also identified similar significant metabolites as obtained from DFA, collectively in CSF, serum and urine samples, responsible for differentiation of meningitis.

Conclusion

The CSF contained metabolites which are formed during infection and inflammation, and these were also found in significant quantity in serum and urine samples.

     

Strain improvement of <Emphasis Type="Italic">Trichoderma viride</Emphasis> for increased cellulase production by irradiation of electron and <Superscript>12</Superscript>C<Superscript>6+</Superscript>-ion beams

Objectives

To improve cellulase production and activity, Trichoderma viride GSICC 62010 was subjected to mutation involving irradiation with an electron beam and subsequently with a ¹²C⁶⁺-ion beam.

Results

Mutant CIT 626 was the most promising cellulase producer after preliminary and secondary screening. Soluble protein production and cellulase activities were increased mutifold. The optimum temperature, pH and culture time for the maximum cellulase production of the selected mutant were 35 °C, pH 5 and 6 days. The highest cellulase production was obtained using wheat bran. The prepared cellulases from T. viride CIT 626 had twice the hydrolytic performance with sawdust (83 %) than that from the parent strain (42.5 %). Furthermore, molecular studies demonstrated that there were some key mutation sites suggesting that some amino acid changes in the protein caused by base mutations had led to the enhanced cellulase production and activity.

Conclusions

Mutagenesis with electron and ¹²C⁶⁺-ion beams could be developed as an effective tool for improvement of cellulase producing strains.

     

Miniaturized <Superscript>1</Superscript>H-NMR method for analyzing limited-quantity samples applied to a mouse model of Leigh disease

Introduction

The analysis of limited-quantity samples remains a challenge associated with mouse models, especially for multi-platform metabolomics studies. Although inherently insensitive, the highly specific characteristics of nuclear magnetic resonance (NMR) spectroscopy make it an advantageous platform for global metabolite profiling, particularly in mitochondrial disease research.

Objectives

Show method equivalency between a well-established standard operating protocol (SOP) and our novel miniaturized ¹H-NMR method.

Method

The miniaturized method was performed in a 2 mm NMR tube on a standard 500 MHz NMR spectrometer with a 5 mm triple-resonance inverse TXI probe at room temperature.

Results

Firstly, using synthetic urine spiked with low (50 µM), medium (250 µM) and high (500 µM) levels (n?=?10) of nine standards, both the SOP and miniaturized method were shown to have acceptable precision (CV?<?15%), relative accuracy (80–120%), and linearity (R²?>?0.95), except for taurine. Furthermore, statistical equivalence was shown using the two one-sided test. Secondly, pooled mouse quadriceps muscle extract was used to further confirm method equivalence (n?=?3), as well as explore the analytical dynamics of this novel approach by analyzing more-concentrated versions of samples (up to 10× concentration) to expand identification of metabolites qualitatively, with quantitative linearity. Lastly, we demonstrate the new technique’s application in a pilot metabolomics study using minute soleus muscle tissue from a mouse model of Leigh syndrome using Ndufs4 KO mice.

Conclusion

We demonstrate method equivalency, supporting our novel miniaturized ¹H-NMR method as a financially feasible alternative to cryoprobe technology—for limited-quantity biological samples in metabolomics studies that requires a volume one-tenth of the SOP.

     

Automated metabolite identification from biological fluid <Superscript>1</Superscript>H NMR spectra

Introduction

Metabolite identification in biological samples using Nuclear Magnetic Resonance (NMR) spectra is a challenging task due to the complexity of the biological matrices.

Objectives

This paper introduces a new, automated computational scheme for the identification of metabolites in 1D ¹H NMR spectra based on the Human Metabolome Database.

Methods

The methodological scheme comprises of the sequential application of preprocessing, data reduction, metabolite screening and combination selection.

Results

The proposed scheme has been tested on the 1D ¹H NMR spectra of: (a) an amino acid mixture, (b) a serum sample spiked with the amino acid mixture, (c) 20 blood serum, (d) 20 human amniotic fluid samples, (e) 160 serum samples from publicly available database. The methodological scheme was compared against widely used software tools, exhibiting good performance in terms of correct assignment of the metabolites.

Conclusions

This new robust scheme accomplishes to automatically identify peak resonances in ¹H-NMR spectra with high accuracy and less human intervention with a wide range of applications in metabolic profiling.

     

Automation of chemical assignment for identifying molecular formula of S-containing metabolites by combining metabolomics and chemoinformatics with <Superscript>34</Superscript>S labeling

Introduction

Sulfur-containing metabolites (S-metabolites) in organisms including plants have unique benefits to humans. So far, few analytical methods have explored such metabolites.

Objectives

We aimed to develop an automatic chemically assigning platform by metabolomics and chemoinformatics with ³⁴S labeling to identify the molecular formula of S-metabolites.

Methods

Direct infusion analysis using Fourier transform ion cyclotron resonance-mass spectrometry provided ultra-high-resolution data including clearly separated isotopic ions—¹⁵N, ³⁴S, ¹⁸O, and ¹³C₂—in the flower, silique, leaf, stem, and root of non-labeled and ³⁴S-labeled Arabidopsis thaliana. Chemoinformatic analysis assigned several elemental compositions of S-metabolites to the acquired S-containing monoisotopic ions using mass accuracy and peak resolution in the non-labeled metabolome data. Possible elemental compositions were characterized on the basis of diagnostic scores of the exact mass and isotopic ion pattern, and a database search. By comparing elemental compositions assigned to the ³⁴S-labeled data with those assigned to the non-labeled data, the elemental composition of S-metabolites were determined. The determined elemental compositions were surveyed using the in-house database, which stores molecular formulae downloaded from metabolome databases.

Results

We identified 35 molecular formulae for known S-metabolites and characterized 72 for unknown. Chemoinformatics required around 1.5 min to analyze a pair of the non-labeled and ³⁴S-labeled data of the organ.

Conclusion

In this study, we developed an automation platform for automatically identifying the presence of S-metabolites. We identified the molecular formula of known S-metabolites, which are accessible in free databases, together with that of unknown. This analytical method did not focus on identifying the structure of S-metabolites, but on the automatic identification of their molecular formula.

     

Accumulation of Fascin<Superscript>+</Superscript> cells during experimental autoimmune neuritis

Background

Experimental autoimmune neuritis (EAN) is a well-known animal model of human demyelinating polyneuropathies and is characterized by inflammation and demyelination in the peripheral nervous system. Fascin is an evolutionarily highly conserved cytoskeletal protein of 55 kDa containing two actin binding domains that cross-link filamentous actin to hexagonal bundles.

Methods

Here we have studied by immunohistochemistry the spatiotemporal accumulation of Fascin?+?cells in sciatic nerves of EAN rats.

Results

A robust accumulation of Fascin?+?cell was observed in the peripheral nervous system of EAN which was correlated with the severity of neurological signs in EAN.

Conclusion

Our results suggest a pathological role of Fascin in EAN.

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticphatology.diagnomx.eu/vs/6734593451114811

     

Characterization of ankylosing spondylitis and rheumatoid arthritis using <Superscript>1</Superscript>H NMR-based metabolomics of human fecal extracts

Introduction

The differences in fecal metabolome between ankylosing spondylitis (AS)/rheumatoid arthritis (RA) patients and healthy individuals could be the reason for an autoimmune disorder.

Objectives

The study explored the fecal metabolome difference between AS/RA patients and healthy controls to clarify human immune disturbance.

Methods

Fecal samples from 109 individuals (healthy controls 34, AS 40, and RA 35) were analyzed by ¹H NMR spectroscopy. Data were analyzed with principal component analysis (PCA) and orthogonal projection to latent structure discriminant (OPLS-DA) analysis.

Results

Significant differences in the fecal metabolic profiles could distinguish AS/RA patients from healthy controls but could not distinguish between AS and RA patients. The significantly decreased metabolites in AS/RA patients were butyrate, propionate, methionine, and hypoxanthine. Significantly increased metabolites in AS/RA patients were taurine, methanol, fumarate, and tryptophan.

Conclusion

The metabolome variations in feces indicated AS and RA were two homologous diseases that could not be distinguished by ¹H NMR metabolomics.

     

Enhanced succinic acid production in <Emphasis Type="Italic">Corynebacterium glutamicum</Emphasis> with increasing the available NADH supply and glucose consumption rate by decreasing H<Superscript>+</Superscript>-ATPase activity

Objectives

To enhance succinic acid production in Corynebacterium glutamicum by increasing the supply of NADH and the rate of glucose consumption by decreasing H⁺-ATPase activity.

Results

A mutant of C. glutamicum NC-3-1 with decreased H⁺-ATPase activity was constructed. This increased the rate of glycolysis and the supply of NADH. Fermentation of C. glutamicum NC-3-1 gave 39 % higher succinic acid production (113 and 81 g/l), a 29 % higher succinic acid yield (0.94 and 0.73 g succinic acid/g glucose) and decreased by-products formation compared to that of C. glutamicum NC-3 in 5 l bioreactor.

Conclusion

The point mutation in C. glutamicum NC-3-1 increased the rate of glycolysis and resulted in higher succinic acid production, higher succinic acid yield and significantly decreased formation of by-products.

     

Early dysregulation of the memory CD8<Superscript>+</Superscript> T cell repertoire leads to compromised immune responses to secondary viral infection in the aged

Background

Virus-specific memory CD8⁺ T cells persist long after infection is resolved and are important for mediating recall responses to secondary infection. Although the number of memory T cells remains relatively constant over time, little is known about the overall stability of the memory T cell pool, particularly with respect to T cell clonal diversity. In this study we developed a novel assay to measure the composition of the memory T cell pool in large cohorts of mice over time following respiratory virus infection.

Results

We find that the clonal composition of the virus-specific memory CD8⁺ T cell pool begins to change within months of the initial infection. These early clonal perturbations eventually result in large clonal expansions that have been associated with ageing.

Conclusions

Maintenance of clonal diversity is important for effective long-term memory responses and dysregulation of the memory response begins early after infection.

     

FISH<Superscript>+</Superscript>CD34<Superscript>+</Superscript>CD38<Superscript>-</Superscript> cells detected in newly diagnosed acute myeloid leukemia patients can predict the clinical outcome

Background

In acute myeloid leukemia (AML), the leukemia initiating cells (LICs) or leukemia stem cells (LSCs) is found within the CD34⁺CD38^- cell compartment. The LICs subpopulation survives chemotherapy and is most probable the cause of minimal residual disease (MRD), which in turn is thought to cause relapse. The aim of this study was to determine the prognostic value of the percentage of LICs in blasts at diagnosis.

Design and methods

The percentage of LICs in the blast population was determined at diagnosis using a unique Flow-FISH analysis, which applies fluorescent in situ hybridization (FISH) analysis on flow cytometry sorted cells to distinguish LICs within the CD34⁺CD38^- cell compartment. Fourty-five AML patients with FISH-detectable cytogenetic abnormalities treated with standardized treatment program were retrospectively included in the study. Correlations with overall survival (OS), events-free survival (EFS) and cumulative incidence of relapse (CIR) were evaluated with univariate and multivariate analysis.

Results

The percentage of LICs is highly variable in patients with acute myeloid leukemia, ranged from 0.01% to 52.8% (median, 2.1%). High LIC load (≥1%) negatively affected overall survival (2-year OS: 72.57% vs. 16.75%; P?=?0.0037) and events-free survival (2-year EFS: 67.23% vs. 16.33%; P?=?0.0018), which was due to an increased cumulative incidence of relapse (2-year CIR: 56.7% vs. 18.0%; P?=?0.021). By multivariate analysis, high LIC load retained prognostic significance for OS and EFS.

Conclusions

In the present study, we established the Flow-FISH protocol as a useful method to distinguish normal and leukemic cells within the CD34⁺CD38^- cell subpopulation. The high percentage of LICs at diagnosis was significantly correlated with increased risk of poor clinical outcome.

     

Selective oxidation of UDP-glucose to UDP-glucuronic acid using permeabilized <Emphasis Type="Italic">Schizosaccharomyces pombe</Emphasis> expressing human UDP-glucose 6-dehydrogenase

Objectives

To use permeabilized cells of the fission yeast, Schizosaccharomyces pombe, that expresses human UDP-glucose 6-dehydrogenase (UGDH, EC 1.1.1.22), for the production of UDP-glucuronic acid from UDP-glucose.

Results

In cell extracts no activity was detected. Therefore, cells were permeabilized with 0.3 % (v/v) Triton X-100. After washing away all low molecular weight metabolites, the permeabilized cells were directly used as whole cell biocatalyst. Substrates were 5 mM UDP-glucose and 10 mM NAD⁺. Divalent cations were not added to the reaction medium as they promoted UDP-glucose hydrolysis. With this reaction system 5 mM UDP-glucose were converted into 5 mM UDP-glucuronic acid within 3 h.

Conclusions

Recombinant permeabilized cells of S. pombe can be used to synthesize UDP-glucuronic acid with 100 % yield and selectivity.

     

Response of Degarelix treatment in human prostate cancer monitored by HR-MAS <Superscript>1</Superscript>H NMR spectroscopy

Introduction

The androgen receptor (AR) is the master regulator of prostate cancer cell metabolism. Degarelix is a novel gonadotrophin-releasing hormone blocker, used to decrease serum androgen levels in order to treat advanced human prostate cancer. Little is known of the rapid metabolic response of the human prostate cancer tissue samples to the decreased androgen levels.

Objectives

To investigate the metabolic responses in benign and cancerous tissue samples from patients after treatment with Degarelix by using HRMAS ¹H NMR spectroscopy.

Methods

Using non-destructive HR-MAS ¹H NMR spectroscopy we analysed the metabolic changes induced by decreased AR signalling in human prostate cancer tissue samples. Absolute concentrations of the metabolites alanine, lactate, glutamine, glutamate, citrate, choline compounds [t-choline = choline + phosphocholine (PC) + glycerophosphocholine (GPC)], creatine compounds [t-creatine = creatine (Cr) + phosphocreatine (PCr)], taurine, myo-inositol and polyamines were measured in benign prostate tissue samples (n = 10), in prostate cancer specimens from untreated patients (n = 7) and prostate cancer specimens from patients treated with Degarelix (n = 6).

Results

Lactate, alanine and t-choline concentrations were significantly elevated in high-grade prostate cancer samples when compared to benign samples in untreated patients. Decreased androgen levels resulted in significant decreases of lactate and t-choline concentrations in human prostate cancer biopsies.

Conclusions

The reduced concentrations of lactate and t-choline metabolites due to Degarelix could in principle be monitored by in vivo ¹H MRS, which suggests that it would be possible to monitor the effects of physical or chemical castration in patients by that non-invasive method.

     

Contribution of direct electron transfer mechanisms to overall electron transfer in microbial fuel cells utilising <Emphasis Type="Italic">Shewanella oneidensis</Emphasis> as biocatalyst

Objectives

To investigate the contribution of direct electron transfer mechanisms to electricity production in microbial fuel cells by physically retaining Shewanella oneidensis cells close to or away from the anode electrode.

Results

A maximum power output of 114 ± 6 mWm^?2 was obtained when cells were retained close to the anode using a dialysis membrane. This was 3.5 times more than when the cells were separated away from the anode. Without the membrane the maximum power output was 129 ± 6 mWm^?2. The direct mechanisms of electron transfer contributed significantly to overall electron transfer from S. oneidensis to electrodes, a result that was corroborated by another experiment where S. oneidensis cells were entrapped in alginate gels.

Conclusion

S. oneidensis transfers electrons primarily by direct electron transfer as opposed to mediated electron transfer.

     

Maize rhizosphere priming: field estimates using <Superscript>13</Superscript>C natural abundance

Introduction

Root-mediated changes in soil organic matter (SOM) decomposition, termed rhizosphere priming effects (RPE), play crucial roles in the global carbon (C) cycle, but their mechanisms and field relevance remain ambiguous. We hypothesize that nitrogen (N) shortages may intensify SOM decomposition in the rhizosphere because of increase of fine roots and rhizodeposition.

Methods

RPE and their dependence on N-fertilization were studied using a C₃-to-C₄ vegetation change. N-fertilized and unfertilized soil cores, with and without maize, were incubated in the field for 50 days. Soil CO₂ efflux was measured, partitioned for SOM- and root-derived CO₂, and RPE was calculated. Plant biomass, microbial biomass C (MBC) and N (MBN), and enzyme activities (β-1,4-glucosidase; N-acetylglucosaminidase; L-leucine aminopeptidase) were analyzed.

Results

Roots enhanced SOM mineralization by 35 % and 126 % with and without N, respectively. This was accompanied by higher specific root-derived CO₂ in unfertilized soils. MBC, MBN and enzyme activities increased in planted soils, indicating microbial activation, causing positive RPE. N-fertilization had minor effects on MBC and MBN, but it reduced β-1,4-glucosidase and L-leucine aminopeptidase activities under maize through lower root-exudation. In contrast, N-acetylglucosaminidase activity increased with N-fertilization in planted and unplanted soils.

Conclusions

This study showed the field relevance of RPE and confirmed that, despite higher root biomass, N availability reduces RPE by lowering root and microbial activity.

     

rDolphin: a GUI R package for proficient automatic profiling of 1D <Superscript>1</Superscript>H-NMR spectra of study datasets

Introduction

Adoption of automatic profiling tools for ¹H-NMR-based metabolomic studies still lags behind other approaches in the absence of the flexibility and interactivity necessary to adapt to the properties of study data sets of complex matrices.

Objectives

To provide an open source tool that fully integrates these needs and enables the reproducibility of the profiling process.

Methods

rDolphin incorporates novel techniques to optimize exploratory analysis, metabolite identification, and validation of profiling output quality.

Results

The information and quality achieved in two public datasets of complex matrices are maximized.

Conclusion

rDolphin is an open-source R package (http://github.com/danielcanueto/rDolphin) able to provide the best balance between accuracy, reproducibility and ease of use.

     

<Superscript>1</Superscript>H NMR metabolic profiling of gastric cancer patients with lymph node metastasis

Introduction

Gastric cancer (GC) is a malignant tumor worldwide. As primary pathway for metastasis, the lymphatic system is an important prognostic factor for GC patients. Although the metabolic changes of gastric cancer have been investigated in extensive studies, little effort focused on the metabolic profiling of lymph node metastasis (LNM)-positive or negative GC patients.

Objectives

We performed ¹H NMR spectrum of GC tissue samples with and without LNM to identify novel potential metabolic biomarkers in the process of LNM of GC.

Methods

¹H NMR-based untargeted metabolomics approach combined with multivariate statistical analyses were used to study the metabolic profiling of tissue samples from LNM-positive GC patients (n?=?40), LNM-negative GC patients (n?=?40) and normal controls (n?=?40).

Results

There was a clear separation between GC patients and normal controls, and 33 differential metabolites were identified in the study. Moreover, GC patients were also well-classified according to LNM-positive or negative. Totally eight distinguishing metabolites were selected in the metabolic profiling of GC patients with LNM-positive or negative, suggesting the metabolic dysfunction in the process of LNM. According to further validation and analysis, especially BCAAs metabolism (leucine, isoleucine, valine), GSH and betaine may be as potential factors of diagnose and prognosis of GC patients with or without LNM.

Conclusion

To our knowledge, this is the first metabolomics study focusing on LNM of GC. The identified distinguishing metabolites showed a promising application on clinical diagnose and therapy prediction, and understanding the mechanism underlying the carcinogenesis, invasion and metastasis of GC.

     

Diel plant water use and competitive soil cation exchange interact to enhance NH<Subscript>4</Subscript><Superscript>+</Superscript> and K<Superscript>+</Superscript> availability in the rhizosphere

Aims

Hydro-biogeochemical processes in the rhizosphere regulate nutrient and water availability, and thus ecosystem productivity. We hypothesized that two such processes often neglected in rhizosphere models — diel plant water use and competitive cation exchange — could interact to enhance availability of K⁺ and NH₄ ⁺, both high-demand nutrients.

Methods

A rhizosphere model with competitive cation exchange was used to investigate how diel plant water use (i.e., daytime transpiration coupled with no nighttime water use, with nighttime root water release, and with nighttime transpiration) affects competitive ion interactions and availability of K⁺ and NH₄ ⁺.

Results

Competitive cation exchange enabled low-demand cations that accumulate against roots (Ca²⁺, Mg²⁺, Na⁺) to desorb NH₄ ⁺ and K⁺ from soil, generating non-monotonic dissolved concentration profiles (i.e. ‘hotspots’ 0.1–1 cm from the root). Cation accumulation and competitive desorption increased with net root water uptake. Daytime transpiration rate controlled diel variation in NH₄ ⁺ and K⁺ aqueous mass, nighttime water use controlled spatial locations of ‘hotspots’, and day-to-night differences in water use controlled diel differences in ‘hotspot’ concentrations.

Conclusions

Diel plant water use and competitive cation exchange enhanced NH₄ ⁺ and K⁺ availability and influenced rhizosphere concentration dynamics. Demonstrated responses have implications for understanding rhizosphere nutrient cycling and plant nutrient uptake.

     

G-CSF/anti-G-CSF antibody complexes drive the potent recovery and expansion of CD11b<Superscript>+</Superscript>Gr-1<Superscript>+</Superscript> myeloid cells without compromising CD8<Superscript>+</Superscript> T cell immune responses

Background

Administration of recombinant G-CSF following cytoreductive therapy enhances the recovery of myeloid cells, minimizing the risk of opportunistic infection. Free G-CSF, however, is expensive, exhibits a short half-life, and has poor biological activity in vivo.

Methods

We evaluated whether the biological activity of G-CSF could be improved by pre-association with anti-G-CSF mAb prior to injection into mice.

Results

We find that the efficacy of G-CSF therapy can be enhanced more than 100-fold by pre-association of G-CSF with an anti-G-CSF monoclonal antibody (mAb). Compared with G-CSF alone, administration of G-CSF/anti-G-CSF mAb complexes induced the potent expansion of CD11b⁺Gr-1⁺ myeloid cells in mice with or without concomitant cytoreductive treatment including radiation or chemotherapy. Despite driving the dramatic expansion of myeloid cells, in vivo antigen-specific CD8⁺ T cell immune responses were not compromised. Furthermore, injection of G-CSF/anti-G-CSF mAb complexes heightened protective immunity to bacterial infection. As a measure of clinical value, we also found that antibody complexes improved G-CSF biological activity much more significantly than pegylation.

Conclusions

Our findings provide the first evidence that antibody cytokine complexes can effectively expand myeloid cells, and furthermore, that G-CSF/anti-G-CSF mAb complexes may provide an improved method for the administration of recombinant G-CSF.

     

Metabolic profiling by <Superscript>1</Superscript>H NMR spectroscopy of saliva shows clear distinction between control and diseased case of periodontitis

Introduction

Periodontitis is a chronic, non-reversible inflammatory disease of the oral cavity leading to destruction of periodontal tissues. Thus, the estimation of bacterial metabolite, tissue damage and secretory metabolites of the triggered inflammatory cells likely to yield results. It may be of value for understanding the pathophysiology of the disease by metabolic profiling of saliva samples using high-resolution NMR spectroscopy.

Objective

The study will evaluate the difference in salivary metabolites in healthy and periodontal condition along with fetching of possible biomarkers in case of chronic periodontitis.

Methods

¹H- NMR spectroscopy has been employed in 114 saliva samples in search of distinctive differences and spectral data were further subjected to multivariate analysis.

Result

One-hundred metabolites were characterised and assigned in the ¹H NMR spectra of saliva. The statistical analysis of control (Healthy subjects) and diseased (Periodontal subjects) using PLS-DA model resulted in R² of 0.84 and Q² of 0.79. There was an elevation in the concentration of statistically discriminant metabolites. The twenty newly identified metabolites in saliva indicates bacterial population shift along with change in homeostasis. These disturbs the biofilm, a real protector against any possible bio-damage on tooth surface. These newly identified metabolites could define better geographically diversified periodontal condition.

Conclusion

Analysis clearly differentiates healthy subjects from the diseased ones. Few newly identified metabolites along with the pool of metabolites may serve as biomarkers for distinguishing the severity and complexity of periodontitis.

     

<Superscript>123</Superscript>I-ADAM SPET imaging of serotonin transporter in patients with epilepsy and comorbid depression

Background

Purpose of the study was to investigate alterations in midbrain serotonin transporter (SERT) binding in patients with epilepsy and symptoms of depression compared to patients with epilepsy with no symptoms of depression.

Methods

We studied 12 patients with epilepsy (7 patients had focal and 5 had generalized epilepsy syndromes). The presence of self-reported symptoms of depression was assessed using Beck Depression Inventory (BDI) and the Emotional State Questionnaire (EST-Q). The binding potential of the SERT was assessed by performing brain single photon emission tomography (SPET) using the SERT radioligand 2-((2-((dimethylamino)methyl)phenyl)thio)-5-(123)iodophenylamine (¹²³I-ADAM).

Results

Seven patients had BDI and EST-Q subscale scores greater than 11 points, which was interpreted as the presence of symptoms of depression. We found that ¹²³I-ADAM binding was not significantly different between patients with epilepsy with and without symptoms of depression. In addition, ¹²³I-ADAM binding did not show a significant correlation to either BDI or EST-Q depression subscale scores and did not differ between patients with focal vs. generalized epilepsy.

Conclusion

The results of our study failed to demonstrate alterations of SERT binding properties in patients with epilepsy with or without symptoms of depression.