A first report of Pseudosuccinea columella (Say, 1817), an alien intermediate host for liver fluke, in Malawi.

Starting in October 2021, quarterly malacological surveys have been undertaken in Malawi, with the sampling of 12 specified freshwater habitats throughout a calendar year. Each survey monitors the presence of aquatic intermediate snail hosts of medical and veterinary importance. In March 2023, the alien lymnaeid species Pseudosuccinea columella was encountered for the first time in the surveys, in Nsanje District. This species identity was later confirmed upon DNA analysis of mitochondrial ribosomal 16S sequences. In July 2023, P. columella was also noted at single sites within Mangochi and Chikwawa Districts, and again in Nsanje District, with an additional location observed. Of particular importance, our sampled location in Mangochi District was directly connected to Lake Malawi, which expands the species list of invasive molluscs in this lake. While P. columella is a well-known intermediate snail host for human and animal fascioliasis, screening collected snails for trematode cercariae, alongside molecular xenomonitoring, did not yield equivocal evidence of active fluke infection. However, the newly recognized presence of this alien intermediate snail host within Lake Malawi, and along the Shire River Valley, flags a new concern in altered local transmission potential for human and animal fascioliasis.

An alien intermediate snail host in Malawi - Orientogalba viridis (Quoy and Gaimard, 1832) - A new concern for schistosomiasis transmission in Africa?

The freshwater amphibious snail Orientogalba viridis commonly occurs in eastern Asia, on certain Pacific islands and more importantly has recently dispersed into Europe. Since this snail is now considered an invasive species, its distribution is of growing parasitological interest as an alien intermediate host for various trematodes, particularly liver flukes. As part of ongoing surveillance for snail-borne diseases in Malawi, a population of O. viridis was first observed in May 2023, alongside an alarming presence of a human schistosome cercaria. This snail population later underwent detailed morphological characterisation with both snail and parasite identities confirmed upon DNA barcoding. This seminal observation triggered more extensive local snail surveys, finding 3 further populations in separated rice paddies, with further field-caught snails (n = 465) screened for infection and a selection used for repeated experimental challenges with miracidia from Schistosoma haematobium and Schistosoma mattheei. Although no field-caught (and experimentally exposed) snail was seen to shed schistosome cercariae, molecular xenomonitoring for schistosomiasis provided tangible evidence of putative transmission potential. Our first report of O. viridis here in Malawi, and more broadly in Africa, flags a need for increased vigilance for this invasive species alongside local clarification(s) of its transmission potential for trematodiases of either medical and/or veterinary importance.

A report of Bilharziella polonica cercariae in Knowsley Safari, Prescot, United Kingdom, with notes on other trematodes implicated in human cercarial dermatitis.

As part of surveillance of snail-borne trematodiasis in Knowsley Safari (KS), Prescot, United Kingdom, a collection was made in July 2021 of various planorbid (n = 173) and lymnaeid (n = 218) snails. These were taken from 15 purposely selected freshwater habitats. In the laboratory emergent trematode cercariae, often from single snails, were identified by morphology with a sub-set, of those most accessible, later characterized by cytochrome oxidase subunit 1 (cox1) DNA barcoding. Two schistosomatid cercariae were of special note in the context of human cercarial dermatitis (HCD), Bilharziella polonica emergent from Planorbarius corneus and Trichobilharzia spp. emergent from Ampullacaena balthica. The former schistosomatid was last reported in the United Kingdom over 50 years ago. From cox1 analyses, the latter likely consisted of two taxa, Trichobilharzia anseri, a first report in the United Kingdom, and a hitherto unnamed genetic lineage having some affiliation with Trichobilharzia longicauda. The chronobiology of emergent cercariae from P. corneus was assessed, with the vertical swimming rate of B. polonica measured. We provide a brief risk appraisal of HCD for public activities typically undertaken within KS educational and recreational programmes.

Methodological factors influencing inhalation bioaccessibility of metal(loid)s in PM2.5 using simulated lung fluid.

In this study, methodological factors influencing the dissolution of metal(loid)s in simulated lung fluid (SLF) was assessed in order to develop a standardised method for the assessment of inhalation bioaccessibility in PM2.5. To achieve this aim, the effects of solid to liquid (S/L) ratio (1:100 to 1:5000), agitation (magnetic agitation, occasional shaking, orbital and end-over-end rotation), composition of SLF (artificial lysosomal fluid: ALF; phagolysosomal simulant fluid: PSF) and extraction time (1-120 h) on metal(loid) bioaccessibility were investigated using PM2.5 from three Australian mining/smelting impacted soils and a certified reference material. The results highlighted that SLF composition significantly (p < 0.001) influenced metal(loid) bioaccessibility and that when a S/L ratio of 1:5000 and end-over-end rotation was used, metal(loid) solubility plateaued after approximately 24 h. Additionally, in order to assess the exposure of metal(loid)s via incidental ingestion of surface dust, PM2.5 was subjected to simulated gastro-intestinal tract (GIT) solutions and the results were compared to extraction using SLF. Although As bioaccessibility in SLF (24 h) was significantly lower than in simulated GIT solutions (p < 0.05), Pb bioaccessibility was equal to or significantly higher than that extracted using simulated GIT solutions (p < 0.05).

An inhalation-ingestion bioaccessibility assay (IIBA) for the assessment of exposure to metal(loid)s in PM10.

Although metal(loid) bioaccessibility of ambient particulate matter, with an aerodynamic diameter of <10µm (PM10), has recently received increasing attention, limited research exists into standardising in-vitro methodologies using simulated lung fluid (SLF). Contradictions exist regarding which assay parameters should be adopted. Additionally, potential continuation of metal(loid) dissolution once PM10 is cleared from the lungs and passed through the gastro-intestinal tract (GIT) has rarely been addressed. The objective of this study was to assess parameters that influence inhalation bioaccessibility in order to develop a conservative assay that is relevant to a human inhalation scenario. To achieve this aim, the effect of solid to liquid (S/L) ratio, extraction time, agitation and five major SLF compositions on the bioaccessibilities of arsenic (As) and lead (Pb) was investigated using PM10 from three Australian mining/smelting impacted regions. Using the biologically relevant parameters that resulted in the most conservative outcomes, bioaccessibility of metal(loid)s in PM10 was assessed in SLF, followed by simulated GIT solutions. Results from this study revealed that fluid composition and S/L ratio significantly affected metal(loid) dissolution (p<0.05). The highest Pb bioaccessibility resulted using simulated lung-gastric solution, while that of As resulted using simulated lung-gastric-small intestinal tract solutions. Compared to SLF alone, metal(loid) dissolution using the inhalation-ingestion bioaccessibility assay (IIBA) was significantly higher (p<0.05) for all PM10 samples.

Adipokines as atherothrombotic risk factors in obese subjects: Associations with haemostatic markers and common carotid wall thickness.

BACKGROUND AND AIMS: Some crucial associations between obesity-related altered adipokine levels and the main factors of atherosclerotic, atherothrombotic processes are not fully known. We analysed the relationships of classic adipokines, namely leptin, resistin, adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) with the markers of platelet activation, including mean platelet volume (MPV), platelet surface/soluble P-selectin, platelet-derived microparticles (PMPs), the parameters of coagulation abnormalities and common carotid intima-media thickness (IMT) in obese patients with or without atherosclerotic comorbidities in comparison to age- and sex-matched controls. METHODS AND RESULTS: We enrolled 154 obese individuals, including 98 suffering from atherosclerotic concomitant conditions, 56 free of atherosclerotic comorbidities and 62 healthy controls. Plasma levels of leptin, resistin, adiponectin, TNF-α, IL-6, soluble P-selectin, and plasminogen activator inhibitor-1 antigen (PAI-1 ag) were analysed by ELISA. Platelet surface P-selectin and PMPs were measured by flow cytometry. IMT was detected by ultrasonography. Adipokines were closely associated with markers of platelet hyperactivity, hypercoagulability, hypofibrinolysis and IMT. Significant independent associations were found between leptin and platelet count (p < 0.0001), MPV (p = 0.019), PMPs (p < 0.0001), fibrinogen (p = 0.001), factor VIII (FVIII) activity (p = 0.035); adiponectin and PAI-1 ag (p = 0.035); resistin and soluble P-selectin (p = 0.002); TNF-α and PAI-1 ag (p < 0.0001); and IL-6 and fibrinogen (p = 0.011). Finally, leptin (p = 0.0005), adiponectin (p = 0.019), IL-6 (p = 0.001), MPV (p = 0.0003), PMP (p = 0.008), and FVIII activity (p = 0.043) were independent predictors of IMT. CONCLUSION: Overall, we suggest that in obese subjects altered adipokine levels play a key role in common carotid atherosclerosis both directly and through haemostatic parameters.

The winds from HL Tau.

Outflowing motions, whether a wind launched from the disc, a jet launched from the protostar, or the entrained molecular outflow, appear to be a ubiquitous feature of star formation. These outwards motions have a number of root causes, and how they manifest is intricately linked to their environment as well as the process of star formation itself. Using the Atacama Large Millimeter/submillimeter Array (ALMA) Science Verification data of HL Tau, we investigate the high-velocity molecular gas being removed from the system as a result of the star formation process. We aim to place these motions in context with the optically detected jet, and the disc. With these high-resolution (∼1 arcsec) ALMA observations of CO (J=1-0), we quantify the outwards motions of the molecular gas. We find evidence for a bipolar outwards flow, with an opening angle, as measured in the redshifted lobe, starting off at 90°, and narrowing to 60° further from the disc, likely because of magnetic collimation. Its outwards velocity, corrected for inclination angle is of the order of 2.4 km s-1.

MutL protein homologue 1(MLH1) in colon adenocarcinomas of the dog: minireview.

The mismatch repair gene MLH1 is a gene encoding the mismatch repair protein MutL homolog 1 (MLH1), important for repairing mutations generated during DNA replication. MLH1 absence has been observed in human gastrointestinal tumours as well as tumours of the female reproductive tract. We describe the functions of MLH 1 in cell cycle regulation and DNA mismatch repair. In this sense we discuss foriegn knowledges, in which the canine colon adencarcinoma is less frequently diagnosed in Czech and Slovak regions. We briefly described a molecular mechanism of evolution of MSI+ and MSI- colorectal carcinomas in human, and this was confronted with the current opinion of canine colon adenocarcinomas. We suppose that canine colon adenocarcinomas may occur in higher frequency, but they are underdiagnosed in the clinical veterinary practice. At the end, we describe two cases of dogs diagnosed with colorectal adenocarcinoma. The authors propose the centralized collection of colon adenocarcinoma samples from dogs, in one reference veterinary histopathological laboratory, which would analyse mismatch repair proteins.

Determination of binding capacity and adsorption enthalpy between Human Glutamate Receptor (GluR1) peptide fragments and kynurenic acid by surface plasmon resonance experiments. Part 2: Interaction of GluR1270-300 with KYNA.

In the course of our previous work, the interactions of two peptide fragments (GluR1201-230 and GluR1231-259) of human glutamate receptor (GluR1201-300) polypeptide with kynurenic acid (KYNA) were investigated by surface plasmon resonance (SPR) spectroscopy. Besides quantitation of the interactions, the enthalpies of binding of KYNA on certain peptide fragment-modified gold surfaces were also reported. In the present work, a third peptide fragment (GluR1270-300) of the glutamate receptor was synthesized and its interaction with KYNA was investigated by an SPR technique. This 31-membered peptide was chemically bonded onto a gold-coated SPR chip via a cysteine residue. The peptide-functionalized biosensor chip was analyzed by atomic force microscopy (AFM) and theoretical calculations were performed on the structure and dimensions of the peptide on the gold surface. In order to determine the isosteric heat of adsorption of the binding of KYNA on the peptide-functionalized gold thin film, SPR experiments were carried out between +10°C and +40°C. The results on the GluR1270-300-KYNA system were compared with the previously published binding parameters of the interactions of GluR1201-230 and GluR1231-259 with KYNA. The binding abilities of KYNA with all three peptide fragments immobilized on the gold surface were estimated by a molecular docking procedure and the binding free energies of these AMPA receptor subunits with KYNA were determined.

Bovine serum albumin-sodium alkyl sulfates bioconjugates as drug delivery systems.

Precipitation of bovine serum albumin (BSA) by anionic surfactants with alkyl chains of increasing lengths (octyl, decyl, dodecyl sulfates) was studied at room temperature, at pH 3.0, in isotonic sodium chloride solution. The particle size of albumin, the zeta potential, the surface charge and fluorescent properties of BSA-surfactant composites were investigated concerning addition of increasing amount of surfactant. The thermal stability of the systems was monitored by calorimetric analysis (DSC). The formation of the well-ordered structure in the self-assembly process in liquid phase was studied by XRD measurement. The structure of the precipitated BSA-surfactant nanocomposites was characterized by small-angle X-ray scattering (SAXS). Finally, ibuprofen (IBU) molecules were enclosed in BSA-surfactant bioconjugate systems and the release properties of the drug were investigated. It has been found out that, as a consequence to the increasing number of carbon atoms in the alkyl chains of the surfactant, the structure and the fluorescent properties of the aggregates formed can be controlled due to the increase in the hydrophobicity of BSA-surfactant composites. The bioconjugates are well applicable as carrier to realize controlled release of drug molecules.

Determination of binding capacity and adsorption enthalpy between Human Glutamate Receptor (GluR1) peptide fragments and kynurenic acid by surface plasmon resonance experiments.

The interaction between kynurenic acid (KYNA) and two peptide fragments (ca. 30 residues) of Human Glutamate Receptor 201-300 (GluR1) using surface plasmon resonance (SPR) spectroscopy was investigated. Because of the medical interest in the neuroscience, GluR1 is one of the important subunits of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR). AMPARs are ionotoropic glutamate receptors, which are mediating fast synaptic transmission and are crucial for plasticity in the brain. On the other hand, KYNA has been suggested to have neuroprotective activity and it has been considered for apply in therapy in certain neurobiological disorders. In this article the adsorption of the GluR1201-230 and GluR1231-259 peptides were studied on gold biosensor chip. The peptides were chemically bonded onto the gold surface via thiol group of L-cysteine resulted in the formation of peptide monolayer on the SPR chip surface. Because the GluR1231-259 peptide does not contain L-cysteine the Val256 was replaced by Cys256. The cross sectional area and the surface orientation of the studied peptides were determined by SPR and theoretical calculations (LOMETS) as well. The binding capability of KYNA on the peptide monolayer was studied in the concentration range of 0.1-5.0 mM using 150 mM NaCl ionic strength at pH 7.4 (±0.02) in phosphate buffer solutions. In order to determine the binding enthalpy the experiments were carried out between +10°C and +40°C. The heat of adsorption was calculated by using adsorption isotherms at different surface loading of KYNA on the SPR chip.

Development of the nano-dust analyzer (NDA) for detection and compositional analysis of nanometer-size dust particles originating in the inner heliosphere.

A linear time-of-flight mass spectrometer is developed for the detection and chemical analysis of nanometer-sized particles originating near the Sun. Nano-dust particles are thought to be produced by mutual collisions between interplanetary dust particles slowly spiraling toward the Sun and are accelerated outward to high velocities by interaction with the solar wind plasma. The WAVES instruments on the two STEREO spacecraft reported the detection, strong temporal variation, and potentially high flux of these particles. Here we report on the optimization and the results from the detailed characterization of the instrument's performance using submicrometer sized dust particles accelerated to 8-60 km/s. The Nano Dust Analyzer (NDA) concept is derived from previously developed detectors. It has a 200 cm(2) effective target area and a mass resolution of approximately m/Δm = 50. The NDA instrument is designed to reliably detect and analyze nanometer-sized dust particles while being pointed close to the Sun's direction, from where they are expected to arrive. Measurements by such an instrument will determine the size-dependent flux of the nano-dust particles and its variations, it will characterize the composition of the nano-dust and, ultimately, it may determine their source. The flight version of the NDA instrument is estimated to be <5 kg and requires <10 W for operation.

Brachypodium distachyon as a model for defining the allergen potential of non-prolamin proteins.

Epitope databases and the protein sequences of published plant genomes are suitable to identify some of the proteins causing food allergies and sensitivities. Brachypodium distachyon, a diploid wild grass with a sequenced genome and low prolamin content, is the closest relative of the allergen cereals, such as wheat or barley. Using the Brachypodium genome sequence, a workflow has been developed to identify potentially harmful proteins which may cause either celiac disease or wheat allergy-related symptoms. Seed tissue-specific expression of the potential allergens has been determined, and intact epitopes following an in silico digestion with several endopeptidases have been identified. Molecular function of allergen proteins has been evaluated using Gene Ontology terms. Biologically overrepresented proteins and potentially allergen protein families have been identified.

In vivo direct interaction of the antibiotic primycin on a Candida albicans clinical isolate and its ergosterol-less mutant.

Interaction of primycin antibiotic with plasma membrane, and its indirect biological effects were investigated in this study. The antifungal activity of primycin against 13 human pathogenic Candida ATCC and CBS reference species and 74 other Candida albicans clinical isolates was investigated with a microdilution technique. No primycin-resistant strain was detected. Direct interaction of primycin with the plasma membrane was demonstrated for the first time by using an ergosterol-producing strain 33erg+ and its ergosterol-less mutant erg-2. In growth inhibition tests, the 33erg+ strain proved to be more sensitive to primycin than its erg-2 mutant, indicating the importance of the plasma membrane composition in primycin-induced processes. The 64 µg ml-1 (56.8 nM) primycin treatment induced an enhanced membrane fluidity and altered plasma membrane dynamics, as measured by steady-state fluorescence anisotropy applying a trimethylammonium-diphenylhexatriene (TMA-DPH) fluorescence polarization probe. The following consequences were detected. The plasma membrane of the cells lost its barrier function, and the efflux of 260-nm-absorbing materials from treated cells of both strains was 1.5-1.8 times more than that for the control. Depending on the primycin concentration, the cells exhibited unipolar budding, pseudohyphae formation, and a rough cell surface visualized by scanning electron microscopy.

Behavioral and endocrine effects of chronic exposure to low doses of chlorobenzenes in Wistar rats.

Chlorobenzenes have often been applied to study persistent organic pollutants with endocrine disruptor effects (POP/EDCs), but with the focus mainly on physiological aspects. Few data exist on the effects of chlorobenzenes and most POP/EDCs on anxiety or other arginine-vasopressin (AVP)- and oxytocin (OXT)-mediated behavior, albeit exposure to POP/EDCs or their ambient mixtures, even in low doses, may pose health risks for subjects living in contaminated areas and/or consuming polluted food. Our primary aim was therefore to demonstrate behavioral effects of longterm exposure to a discrete dose of a chlorobenzene mixture, and to draw attention to the results of subtoxic oral exposure on anxiety-related elements and the possible underlying endocrine processes. Adult male Wistar rats were treated daily with a mixture (ClB) of 1 µg/kg each of hexachlorobenzene and 1,2,4-trichlorobenzene via a gastric tube for 30, 60 or 90 days. After exposure, anxiety-related behavioral elements were determined in open-field and elevated plus maze tests. At euthanasia, the plasma levels of AVP, OXT and adrenocorticotrophic hormone (ACTH) were measured. Simultaneously, pituicytes from subjects were cultured to study the levels of basal and serotonin- or norepinephrinestimulated AVP and OXT secretion. Various anxiety-related behavioral elements were observed to be increased in both tests. The plasma AVP, OXT and ACTH concentrations were increased, to extents depending on the duration of exposure. The basal and monoamine-stimulated levels of AVP and OXT secretion of pituicytes prepared from the ClB-exposed rats were also elevated. Thus, certain anxietyrelated behavioral and endocrine elements were modulated by long-term exposure to ClB. As adult subjects were involved, which are generally less susceptible to toxic agents, it may be concluded that discrete doses of POP/EDC chlorobenzenes that are low enough to fall below the range of legal regulation may exert anxiogenic effects, which suggests that certain anxiogenic disorders may be induced environmentally in exposed human populations.

From farm to fork follow-up of thermotolerant campylobacters throughout the broiler production chain and in human cases in a Hungarian county during a ten-months period.

A study tracking thermotolerant campylobacters from the setting of the broilers throughout the whole rearing period, slaughter and sale of chicken products in five consecutive broiler rotations of the same henhouse as well as in two different other farms was conducted in a well-defined geographic area (Hajdú-Bihar county, Hungary) between March 2006 and Feb 2007. All notified cases of human campylobacteriosis in this area during the study period were also included. One hundred and one, 44, 23 and 282 Campylobacter jejuni and 13, 15, 20 and 60C. coli were isolated from broiler houses, slaughterhouses, retail shops and human samples, respectively. Sixty-two isolates collected from broilers or their environment selected from different flocks (57C. jejuni, 5C. coli), 92 isolates collected from abattoirs and retail shops (72C. jejuni, 20C. coli), as well as 85 randomly selected human isolates (74C. jejuni, 11C. coli) were subjected to PFGE analysis using restriction enzymes KpnI and SmaI. Sixty-six of the isolates produced unique Sma-Kpn profiles; the majority (46) of these were of human origin. The remaining isolates formed PFGE clusters of between 2-25 isolates with 14 (12C. jejuni and 2C. coli) main clusters comprised of five or more isolates with identical KpnI-SmaI patterns. Two genetic clones of C. jejuni (clone A, n=25; clone B, n=20) included 18% of isolates from different sources. Generally, isolates from one cluster were found in 1-3 different flocks, notably, clone B was present in three rotations including those from the two independent farms. Six of the seven investigated flocks had one or two characteristic prevalent clones. Transmission of clones between consecutive flocks was frequently seen. Spread of both C. jejuni and C. coli was traced multiple times along the food chain; eight C. jejuni, but no C. coli clones were detected both in broilers and humans. These data suggest that broilers were the major source for C. jejuni but not for C. coli in the studied area and period. For C. jejuni the carryover of strains between consecutive flocks may be a common event, but the strain is eventually replaced by another and consecutive carryover events seem to be infrequent. The majority of the human disease was due to nonepidemic strains; some clones were transmitted from more than one broiler flocks (including epidemiologically unrelated flocks) to humans multiple times.

Further analysis of behavioral and endocrine consequences of chronic exposure of male Wistar rats to subtoxic doses of endocrine disruptor chlorobenzenes.

Many chemicals utilized by humans are present as environmental pollutants and may influence homeostasis from neurological, immunological, endocrinological and/or behavioral aspects. Such agents, acting alone or in ambient mixtures, may be biologically active even at extremely low doses, and it may be postulated that stable, bioaccumulative, reactive endocrine disruptors may affect central and/or peripheral secretion of arginine-vasopressin (AVP) and oxytocin (OXT) and thereby related physiological and behavioral functions, potentially leading to disorders in exposed subjects. The primary aim of this study was to demonstrate effects of chronic exposure to a low dose of an orally administered chlorobenzene mixture on anxiety-related and aggressive behavior mediated largely by AVP and OXT. Chlorobenzenes were applied to model ambient mixtures of endocrine disruptors. Adult, male Wistar rats were exposed daily to 0.1 µg/kg of 1,2,4-trichlorobenzene and hexachlorobenzene via a stomach tube for 30, 60 or 90 days, after which anxiety-related and aggressive behavioral elements were examined in open-field, elevated plus maze and resident-intruder tests. The plasma levels of AVP, OXT and adrenocorticotrophic hormone at the endpoints were measured by radioimmunoassay or immunochemiluminescence assay. The levels of basal and serotonin- or norepinephrine-stimulated AVP and OXT secretion in pituicyte cultures prepared from the posterior lobe of the pituitaries were also measured. The hormone levels proved to be increased to extents depending on the duration of exposure to the chlorobenzenes. Several anxiety-related and aggressive behavioral elements were also enhanced following chlorobenzene exposure, while certain explorative and locomotive elements of the animals were decreased. As both physiological and behavioral elements were modulated by chronic, subtoxic doses of chlorobenzenes, it is concluded that doses of such environmental pollutants low enough to fall outside the range of legal regulation may pose potential risks of anxiogenic and/or aggressive consequences in exposed subjects, including humans.

Relationship of adipokines and non-esterified fatty acid to the insulin resistance in non-diabetic individuals.

BACKGROUND: Altered secretion of adipokines and non-esterified fatty acid (NEFA) seems to play a pivotal role in the abdominal obesity-related insulin resistance (IR). AIM: To determine semi-quantitatively the impact of serum NEFA, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin, and resistin levels on IR measured by homeostasis model assessment (HOMA-IR). MATERIAL/SUBJECTS: Seventy-four Caucasian subjects forming 3 age-, and sex-matched groups were included into the study [Group 1 and 2: non-diabetic obese patients, no.= 25, body mass index (BMI): 28-39.9 kg/m(2), no.=25, BMI≥40 kg/m(2), respectively, and Group 3: 24 healthy, normal weight control subjects]. METHODS: Serum levels of NEFA and adipokines as well as other metabolic variables including HOMA-IR were measured. RESULTS: HOMA-IR was associated positively with BMI, waist circumference, serum NEFA, leptin, IL-6, and TNF-α levels, negatively with adiponectin, with no significant relation to resistin. In multiple regression analyses, of these factors leptin was a strong, IL-6 and adiponectin were weak independent predictors of HOMA-IR, while the others were not significant determinants of HOMA-IR. However, even together, they explained only 35-36% of variance of HOMAIR. CONCLUSIONS: Although IR has associations with many of the investigated parameters, of these, only serum level of leptin, and in lesser degree IL-6 and adiponectin are independent determinants of the severity of IR. Moreover, even together they explain only a minority of variance IR.