Stress, allostatic load and mental health in Indigenous Australians.

The aim of this narrative review was to demonstrate how the notion of allostatic load (AL) relates directly to the mental health disparities observed between Indigenous and non-Indigenous Australians. We also endeavored to synthesize the results of the limited number of studies examining stress and AL in Indigenous Australians in order to explore the potential public health benefits of the AL concept. A range of literature examining health inequalities, psychosocial determinants of mental illness and AL was explored to demonstrate the applicability of stress biology to the significant mental health burden faced by Indigenous Australians. Furthermore, all original studies indexed in MEDLINE that provided quantitative data on primary stress biomarkers in Indigenous Australians were selected for review. Evidence of hypothalamic-pituitary-adrenal axis dysregulation and increased AL is apparent even in the handful of studies examining stress biomarkers in Indigenous Australians. Urinary, salivary, hair and fingernail cortisol, hair cortisone, urinary epinephrine, heart rate variability and the cortisol awakening response are all AL parameters which have been shown to be dysregulated in Indigenous Australian cohorts. Furthermore, associations between some of these biomarkers, self-perceived discrimination, exposure to stressful life events and symptoms of psychiatric disorders in Indigenous Australians have also been demonstrated. The continued assessment of AL biomarkers and their relationship with past traumas, lifetime stressors and socio-economic factors amongst Indigenous Australians is important to addressing the mental health this population. Measurement of AL biomarkers in a culturally appropriate manner may lead to more targeted preventative measures, interventions and policies, which mitigate the effects of stress at both the individual and societal level.

Monocytes of patients with amyotrophic lateral sclerosis linked to gene mutations display altered TDP-43 subcellular distribution.

AIMS: Cytoplasmic accumulation of the nuclear protein transactive response DNA-binding protein 43 (TDP-43) is an early determinant of motor neuron degeneration in most amyotrophic lateral sclerosis (ALS) cases. We previously disclosed this accumulation in circulating lymphomonocytes (CLM) of ALS patients with mutant TARDBP, the TDP-43-coding gene, as well as of a healthy individual carrying the parental TARDBP mutation. Here, we investigate TDP-43 subcellular localization in CLM and in the constituent cells, lymphocytes and monocytes, of patients with various ALS-linked mutant genes. METHODS: TDP-43 subcellular localization was analysed with western immunoblotting and immunocytofluorescence in CLM of healthy controls (n = 10), patients with mutant TARDBP (n = 4, 1 homozygous), valosin-containing protein (VCP; n = 2), fused in sarcoma/translocated in liposarcoma (FUS; n = 2), Cu/Zn superoxide dismutase 1 (SOD1; n = 6), chromosome 9 open reading frame 72 (C9ORF72; n = 4), without mutations (n = 5) and neurologically unaffected subjects with mutant TARDBP (n = 2). RESULTS: TDP-43 cytoplasmic accumulation was found (P < 0.05 vs. controls) in CLM of patients with mutant TARDBP or VCP, but not FUS, in line with TDP-43 subcellular localization described for motor neurons of corresponding groups. Accumulation also characterized CLM of the healthy individuals with mutant TARDBP and of some patients with mutant SOD1 or C9ORF72. In 5 patients, belonging to categories described to carry TDP-43 mislocalization in motor neurons (3 C9ORF72, 1 TARDBP and 1 without mutations), TDP-43 cytoplasmic accumulation was not detected in CLM or in lymphocytes but was in monocytes. CONCLUSIONS: In ALS forms characterized by TDP-43 mislocalization in motor neurons, monocytes display this alteration, even when not manifest in CLM. Monocytes may be used to support diagnosis, as well as to identify subjects at risk, of ALS and to develop/monitor targeted treatments.

Impact of Candida spp. isolation in the respiratory tract in patients with intensive care unit-acquired pneumonia.

In immunocompetent patients with nosocomial pneumonia, the relationship between Candida spp. isolation in respiratory samples and outcomes or association with other pathogens is controversial. We therefore compared the characteristics and outcomes of patients with intensive care unit-acquired pneumonia (ICUAP), with or without Candida spp. isolation in the respiratory tract. In this prospective non-interventional study, we assessed 385 consecutive immunocompetent patients with ICUAP, according to the presence or absence of Candida spp. in lower respiratory tract samples. Candida spp. was isolated in at least one sample in 82 (21%) patients. Patients with Candida spp. had higher severity scores and organ dysfunction at admission and at onset of pneumonia. In multivariate analysis, previous surgery, diabetes mellitus and higher Simplified Acute Physiology Score II at ICU admission independently predicted isolation of Candida spp. There were no significant differences in the rate of specific aetiological pathogens, the systemic inflammatory response, and length of stay between patients with and without Candida spp. Mortality was also similar, even adjusted for potential confounders in propensity-adjusted multivariate analyses (adjusted hazard ratio 1.08, 95% CI 0.57-2.05, p 0.80 for 28-day mortality and adjusted hazard ratio 1.38, 95% CI 0.81-2.35, p 0.24 for 90-day mortality). Antifungal therapy was more frequently prescribed in patients with Candida spp. in respiratory samples but did not influence outcomes. Candida spp. airway isolation in patients with ICUAP is associated with more initial disease severity but does not influence outcomes in these patients, regardless of the use or not of antifungal therapy.

Tracheal tube biofilm removal through a novel closed-suctioning system: an experimental study.

BACKGROUND: Tracheal tube biofilm develops during mechanical ventilation. We compared a novel closed-suctioning system vs standard closed-suctioning system in the prevention of tracheal tube biofilm. METHODS: Eighteen pigs, on mechanical ventilation for 76 h, with P. aeruginosa pneumonia were randomized to be tracheally suctioned via the KIMVENT* closed-suctioning system (control group) or a novel closed-suctioning system (treatment group), designed to remove tracheal tube biofilm through saline jets and an inflatable balloon. Upon autopsy, two tracheal tube hemi-sections were dissected for confocal and scanning electron microscopy. Biofilm area, maximal and minimal thickness were computed. Biofilm stage was assessed. RESULTS: Sixteen animals were included in the final analysis. In the treatment and control group, the mean (sd) pulmonary burden was 3.34 (1.28) and 4.17 (1.09) log cfu gr(-1), respectively (P=0.18). Tracheal tube P. aeruginosa colonization was 5.6 (4.9-6.3) and 6.2 (5.6-6.9) cfu ml(-1) (median and interquartile range) in the treatment and control group, respectively (P=0.23). In the treatment group, median biofilm area was 3.65 (3.22-4.21) log10 µm2 compared with 4.49 (4.27-4.52) log10 µm2 in the control group (P=0.031). In the treatment and control groups, the maximal biofilm thickness was 48.3 (26.7-71.2) µm (median and interquartile range) and 88.8 (43.8-125.7) µm, respectively. The minimal thickness in the treatment and control group was 0.6 (0-4.0) µm and 23.7 (5.3-27.8) µm (P=0.040) (P=0.017). Earlier stages of biofilm development were found in the treatment group (P<0.001). CONCLUSIONS: The novel CSS reduces biofilm accumulation within the tracheal tube. A clinical trial is required to confirm these findings and the impact on major outcomes.

Development of an algorithm incorporating pharmacokinetics of adalimumab in inflammatory bowel diseases.

OBJECTIVES: Several decision algorithms based on the measurement of infliximab (IFX) trough levels and antibodies to IFX have been proposed. Whether such algorithms can be extrapolated to the pharmacokinetics of adalimumab (ADA) has yet to be determined. METHODS: A prospective study included all consecutive patients with inflammatory bowel disease (IBD) having a disease flare while being on ADA 40 mg every 2 weeks were included. All patients were primary responders to ADA therapy and were anti-tumor necrosis factor (TNF) naive. ADA trough levels and antibodies against ADA (AAA) were measured blinded to clinical data (Elisa LISA-Tracker, Theradiag). All patients were optimized with ADA 40 mg weekly. Four months later, in the absence of clinical remission (CR; Crohn's disease activity index <150 for Crohn's disease (CD), and Mayo score <2 for ulcerative colitis), patients were treated with IFX therapy. Patients were divided into three groups based on ADA trough levels and based on previous studies: group A, ADA>4.9 µg/ml; group B, ADA<4.9 µg/ml and undetectable levels of AAA (<10 ng/ml); and group C, ADA<4.9 µg/ml and AAA >10 ng/ml. RESULTS: A total of 82 patients were included (55% CD; mean age=43 years, disease duration=7.4 years, duration of ADA therapy=17 months). After optimization of ADA treatment, 29.2% of patients achieved CR in group A (N=41), 67% in group B (N=24), and 12% in group C (N=17; P<0.01 between groups A/B and B/C). C-reactive protein level at the time of relapse, disease duration, duration of ADA therapy, and IBD type was not predictive of CR after ADA optimization by univariate analysis. The response to ADA optimization was significantly more durable in group B (15 months) than in groups A and C (4 and 5 months, respectively). Fifty-two patients who failed following ADA optimization (63%) were treated with IFX, and 30.6% of them achieved CR. CR rates following IFX initiation were 6.9%, 25%, and 80% in groups A, B, and C, respectively (P<0.01 between groups C/A and between groups C/B). Duration of response to IFX was significantly higher in group C than in groups A and B (14 vs. 3 and 5 months, respectively, P<0.01). CONCLUSIONS: The presence of low ADA trough levels without AAA is strongly predictive of clinical response in 67% of cases after ADA optimization. Conversely, low ADA levels with detectable AAA are associated with ADA failure, and switching to IFX should be considered. ADA trough levels >4.9 µg/ml are associated with failure of two anti-TNF agents (ADA and IFX) in 90% of cases, and switching to another drug class should be considered.

Silica nanoparticles as tracers of the gelation dynamics of a natural biopolymer physical gel.

The gelation of methylcellulose in water has been studied by X-ray photon correlation spectroscopy, electrophoresis and rheological measurements by looking into the dynamics of silica nanoparticles as tracers in the polymer matrix. The temperature and scattering vector dependence of the structural relaxation time is investigated at the nanometric length scale during the formation of the strong gel state. We find a stress-dominated dynamics on approaching the gel state, characterized by a hyper-diffusive motion of the silica particles. These results support the idea of a unifying scenario for the dynamics of complex out of equilibrium soft materials.

Acquisition of resistant microorganisms and infections in HIV-infected patients admitted to the ICU.

Whether critically ill human immunodeficiency virus (HIV)-infected patients are at risk of acquiring nosocomial infections and resistant or potentially resistant microorganisms (RPRMs) remains to be clarified. The aim was to compare the acquisition of RPRMs, infections and mortality in critically ill HIV-infected and non-infected patients. An observational, prospective cohort study of patients admitted to a medical intensive care unit (ICU) was undertaken. Swabbing of nares, pharynx and rectum, and culture of respiratory secretions were obtained within 48 h of admission and thrice weekly thereafter. Clinical samples were obtained as deemed necessary by the attending physician. Clinical variables, severity scores on admission and exposures during ICU stay were collected. Logistic regression was used to evaluate ICU mortality. Out of the 969 included patients, 64 (6.6%) were HIV-infected. These patients had a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score on admission (19.5 ± 6.6 vs. 21.1 ± 5.4, p = 0.02), stayed longer in the care unit and were more exposed to several invasive devices and antibiotics. There were no differences in the rate of acquisition of RPRMs and the only difference in ICU-acquired infections was a significantly higher incidence of catheter-related bacteraemia (3% vs. 9%, p = 0.03). The ICU-related mortality was similar in both groups (14% vs. 16%, p = 0.70) and in HIV-infected patients, it tended to be associated with a lower CD4 cell count (p = 0.06). Despite a longer ICU stay, critically ill HIV-infected patients did not show a higher rate of RPRMs acquisition. The rate of ICU-acquired infection was similar between HIV-infected and non-infected patients, except for catheter-related bacteraemia, which was higher in the HIV-infected population. Mortality was similar in both groups.

Comparison of acquisition of resistant microorganisms and infections in critically-ill patients with and without malignancies.

BACKGROUND: Patients with malignancies are often considered at risk of acquiring infections by resistant or potentially resistant microorganisms (RPRMs). However, data supporting this contention is scarce. We have compared critically ill patients with haematological malignancies (HM), solid tumours (ST) and without cancer (NC) in terms of acquisition of RPRMs, infections and mortality. METHODS: Observational, prospective cohort study of patients admitted to a medical intensive care unit (ICU). Swabbing of nares, pharynx and rectum, and culture of respiratory secretions were obtained within 48 h of admission and thrice weekly thereafter. Clinical samples were obtained as deemed necessary by the attending physician. Clinical variables, severity scores on admission and exposures during ICU stay were also collected. Multivariable logistic regression analysis was used to evaluate ICU mortality. RESULTS: Out of 969 included patients 127 (13.1%) had HM and 93 (9.6%) had ST. Patients with malignancies were more frequently exposed to central venous catheterization, methylprednisolone, and any antipseudomonal antibiotic whereas they were less commonly exposed to invasive mechanical ventilation. Patients with HM were more often admitted with an infection. There were no differences among groups in terms of RPRMs acquisition during ICU stay or prevalence of ICU-acquired infections due to any microorganism, including RPRMs. Having a HM was an independent predictor of mortality regardless of APACHE II score. CONCLUSION: Critically ill cancer patients did not show a higher rate of RPRMs acquisition nor ICU-acquired infections. Mortality was higher in the HM group and it was not accurately predicted on admission by APACHE II score.

Pregnancy induces molecular alterations reflecting impaired insulin control over glucose oxidative pathways that only in women with a family history of Type 2 diabetes last beyond pregnancy.

In circulating lymphomonocytes (CLM) of patients with Type 2 diabetes (DM2) pyruvate dehydrogenase (PDH), the major determinant of glucose oxidative breakdown, is affected by a cohort of alterations reflecting impaired insulin stimulated glucose utilization. The cohort is also expressed, although incompletely, in 40% of healthy young subjects with a DM2-family history (FH). Pregnancy restrains glucose utilization in maternal peripheral tissues to satisfy fetal requirements. Here we explore whether pregnant women develop the PDH alterations and, if so, whether there are differences between women with and without FH (FH+, FH-). Ten FH+ and 10 FH- were evaluated during pregnancy (12-14, 24-26, and 37-39 weeks) and 1 yr after (follow-up) for fasting plasma glucose and insulin as well as body mass index (BMI), and for the PDH alterations. Twenty FH- and 20 FH+ non-pregnant women served as controls. All FH+ and FH- controls exhibited normal clinical parameters and 8 FH+ had an incomplete cohort of PDH alterations. In FH- and FH+ pregnant women at 12-14 weeks clinical parameters were normal; from 24-26 weeks, with unvaried glucose, insulin and BMI rose more in FH- and only in the latter recovered the 12-14 weeks values at follow-up. In all FH-, the cohort of PDH alterations was incomplete at 24-26 weeks, complete at 37-39 weeks, and absent at follow-up but complete from 12-14 weeks including follow-up in all FH+. In FH-, the cohort is an acquired trait restricted to pregnancy signaling transiently reduced insulin-stimulated glucose utilization; in FH+, instead, it unveils the existence of an inherited DM2-related background these women all have, that is awakened by pregnancy and as such lastingly impairs insulin-stimulated glucose utilization.

Synthesis and evaluation of the mucoadhesivity of a CD-chitosan derivative.

Combining mucoadhesive characteristics of a biodegradable polymer such as chitosan with the potential to enhance drug release by increasing the solubility of poorly water-soluble drugs has great potential for pharmaceutical technology and drug delivery design. Polymeric delivery systems have been extensively researched in an attempt to achieve modified drug release. Cyclodextrins (CD) offer an alternative approach. These cyclic oligosaccharides have the ability to form non-covalent complexes with a number of drugs altering their physicochemical properties. In the continuing challenge to improve the properties of delivery systems, this paper focuses on the modification of chitosan by introducing beta-cyclodextrin and to test the mucoadhesive strength and inclusion properties of this synthesised cyclodextrin-polymer. beta-Cyclodextrin was successfully grafted onto a chitosan chain polymer with a cyclodextrin grafting yield of 7% and a CD-chitosan yield of 85%. Although the complexation of (+)-catechin by the grafted beta-CD was found to be about five times weaker than that by the beta-CD monoaldehyde and natural beta-CD, the inclusion properties of the chitosan-CD remain promising. The mucoadhesive properties of chitosan-CD were compared to that of pectin (reference) and the parent chitosan with the use of a tensile separation test. The chitosan-CD showed mucoadhesive strengths of 12% stronger than pectin, but 13.5% weaker than the parent chitosan. The synthesised chitosan-CD-polymer exhibits characteristics of a possible mucoadhesive drug delivery system with some inclusion properties from beta-cyclodextrin.

Specific interactions in modified chitosan systems.

This paper concerns the bulk and interfacial properties of a series of alkylated chitosans having different alkyl chain lengths grafted randomly along the main chitosan chain. Chitosan has a low degree of acetylation (5%); on chitosan derivatives, the role of the degree of grafting and of length of the alkyl chains are examined. The optimum alkyl chain length is C12 and the degree of grafting 5% to get physical gelation based on the formation of hydrophobic domains. The cross-linking is essentially controlled by the salt concentration: it is shown that 0.025 M AcONa is needed to screen electrostatic interchain repulsions. Hydrophobic interactions produce highly non-Newtonian behavior with large thinning behavior; this behavior is suppressed in the presence of cyclodextrins able to cap the hydrophobic alkyl chains. The interfacial properties of the chitosan derivatives were tested for the air/aqueous solution interfaces. Specifically, the role of their structure on the kinetic of film formation was examined showing that excess of external salt favors the stabilization of the interfacial film. The derivatives with a higher degree of substitution and longer alkyl chains are more efficient and give a higher elastic modulus compared to the model surfactant as a result of the chain properties.

Role of substituents on the properties of some polysaccharides.

This paper concerns the influence of the chemical structure on the physical properties of some polysaccharides. Especially, we proposed to discuss the role of the substituents on these properties. In some cases, non-carbohydrate substituents play a minor role on rheological properties in the presence of a salt excess as shown on xanthan and succinoglycan. The rheology of aqueous solution of these stereoregular polysaccharides is controlled by the conformation (helical conformation) whose stability is not largely influenced by these substituents. On the other hand, the interaction between galactomannan and xanthan depends on the presence of acetyl substituents on xanthan but also on the xanthan conformation. However, for polymers such as gellan, XM-6 or BEC 1615, complete deacetylation induces the ability to form physical gels in given thermodynamic conditions. The presence of carbohydrate substituents or short side chains was also examined. Especially in the gellan family, the role of position of substitution (position 3 on the glucose unit C or position 6 on the A glucose) was presented. It is concluded that the substituents giving the higher stability for the helical conformation (higher DeltaH and Tm values) also cause a lower salt sensitivity for the helical stability. The role of the substituents on the properties is also described for natural polymers and their chemically or enzymatically modified derivatives.

Structure and properties of a bacterial polysaccharide named Fucogel.

The chemical structure of a polysaccharide named Fucogel was characterized and the position of acetylation was identified by NMR. A conformational analysis was performed on this 3-sugar repeating unit. From this, the persistence length, characterizing the stiffness of the polysaccharide, was determined and the role of the presence of acetyl group, reducing the stiffness, was pointed out. The helical conformations were also predicted, one of these being in agreement with X-ray data obtained on a similar polysaccharide. Experimental characterization of the native and deacetylated polysaccharides was developed. SEC experiments allowed us to determine the molar mass and the persistence length on the deacetylated polysaccharide. The value is in good agreement with that predicted from the molecular modeling. Microcalorimetry, rheology, and fluorescence spectroscopy demonstrated respectively that no helical conformation exists in solution but that loose interchain interactions due to the acetyl substituents exist in dilute solutions.

Structure and properties of a bacterial polysaccharide from a Klebsiella strain (ATCC 12657).

The chemical structure and the rheological behavior of the Klebsiella polysaccharide ATCC 12657 was studied and compared with data described in the literature and obtained for similar polysaccharides. The acetylated polysaccharide presents in solution a normal viscoelastic behavior with no evidence of an ordered conformation whatever the experimental conditions are. The deacetylated form can induce the formation of physical gels, in the presence of salt excess or ethanol. Microcalorimetry, optical rotation, and rheology experiments demonstrate that a thermally reversible and highly cooperative conformational transition occurs at the same temperature than a sol-gel transition. The melting of the gel and the conformational transition temperatures are dependent on the nature of cations and ionic concentration, whereas the gel strength is only influenced by polymer concentration.

Hydration of hyaluronan polysaccharide observed by IR spectrometry. II. Definition and quantitative analysis of elementary hydration spectra and water uptake.

We recorded a series of spectra of sodium hyaluronan (HA) films that were in equilibrium with their surrounding humid atmosphere. The hygrometry of this atmosphere extended from 0 to 0.97% relative humidity. We performed a quantitative analysis of the corresponding series of hydration spectra that are the difference spectra of the film at a defined hygrometry minus the spectrum of the dried film (hygrometry = 0). The principle of this analysis is to use this series of hydration spectra to define a limited number (four) of "elementary hydration spectra" over which we can decompose all hydration spectra with good accuracy. This decomposition, combined with the measurements of the numbers of H(2)O molecules at the origin in these elementary hydration spectra of the three characteristic vibrational bands of H(2)O, allowed us to calculate the hydration number under different relative humidity conditions. This number compares well with that determined by thermogravimetry. Furthermore, the decomposition defines for each hygrometry value which chemical mechanisms represented by elementary hydration spectra are active. This analysis is pursued by determining for the elementary hydration spectra the number of hydrogen bonds established by each of the four alcohol groups found in each disaccharide repeat unit before performing the same analysis for amide and carboxylate groups. These results are later utilized to discuss the structure of HA at various stages of hydration.

Hydration of hyaluronan polysaccharide observed by IR spectrometry. III. Structure and mechanism of hydration.

The results of the analysis of hydration spectra of Na(+) hyaluronan (HA) performed in a companion study are translated in terms of chemical mechanisms. We find that dried HA is characterized by chains having ordered parts of at least 6 disaccharide repeat units that extend over 60 A. The order is mainly due to C3O3H...O5 and C4O4H...O5 hydrogen bonds that hinder rotations around beta(1-4) and beta(1-3) glycoside bonds. Along one chain there are two-thirds of the N-H amide groups and carboxyl groups that are directly hydrogen bonded, with no water intermediate, to form N-H...(-)O-C=O hydrogen bonds, which are collateral to C3O3H...O5 hydrogen bonds. The existence of these N-H...(-)O-C=O bonds is somewhat in opposition to literature descriptions. In this dry state a "water wire" of 4-5 H(2)O molecules, which are anchored on C=O carboxyl groups and hydrating the Na(+) CO(-) ionic group, establishes hydrogen bonds on other hydrophilic groups of the same chain or other chains and remains embedded in HA, even at 104 degrees C. Hydration occurs at low hygrometry around the remaining one-third of the N-H...(-)O-C=O pairs that are not hydrogen bonded. Each of these N-H and (-)O-C=O groups is hydrated by a nanodroplet of some 25 H(2)O molecules that finds other sites for binding and hydrates 2 disaccharide repeat units. At higher hygrometry bigger nanodroplets hydrate all hydrophilic sites.

Hydration of polysaccharide hyaluronan observed by IR spectrometry. I. Preliminary experiments and band assignments.

This article is the first one in a series dedicated to the study of hyaluronan as observed by IR spectrometry. The goal is to determine its hydration mechanism and the structural changes this mechanism implies. Hyaluronan is a natural polysaccharide that is widely used in biomedical applications and cosmetics. Its macroscopic properties are significantly dependent on its degree of hydration. In this article we record the IR spectrum of a several micron thick dried film and deduce that four or five residual H(2)O molecules remain around each disaccharide repeat unit in the dried film. We then compare the spectra of sodium hyaluronan and its acid form to assign vibrational bands linked to the carboxylate group. We proceed with a qualitative analysis of the spectral changes induced by changes of temperature and hygroscopicity, two independent parameters that act by modifying the hydrogen bond network of the sample. This enables us to assign most of the vibrational bands of the hydrophilic groups and to distinguish the bands that are due to these hydrophilic groups when they are or are not hydrogen bonded. It constitutes a prerequisite for the quantitative analysis of hydration spectra that will be described in the following articles of this series.

Enhanced blood insulin overcomes pyruvate dehydrogenase derangements that reflect systemic insulin resistance in obese adolescents.

Pyruvate dehydrogenase (PDH) has low activity in the circulating lymphocytes (CL) of obese adolescents and adults. In vitro, it is unresponsive to insulin at 5 micro-units/ml and is activated at 50 micro-units/ml, in contrast with activation and inhibition respectively at these concentrations in CL from controls. These changes are seen as being indicative of a molecular disorder underlying insulin resistance. The aims of the present study were to determine whether a substantial enhancement of blood insulin levels restores the PDH activity in CL from obese adolescents and abolishes the in vitro alterations, and whether PDH activity and indices of insulin resistance are correlated. Six obese adolescents and six normal-weight controls underwent a 4 h frequently sampled intravenous glucose test with minimal model analysis, to bring about a sharp rise in blood insulin and provide a reliable index of insulin sensitivity (S(I)). PDH activity was evaluated in CL obtained from blood samples at set times before and after their exposure to insulin in vitro. Insulin levels rose in all subjects in the first 10 min, although to a much greater extent in the obese group, and then decreased until the end of the test (240 min; t(240)). PDH activity in CL paralleled the insulin pattern in the control subjects, whereas in the obese subjects it was below normal 3 min before the start of the test (t(-3)), but rose significantly throughout the test. PDH responses in vitro to insulin in CL taken from the control subjects at t(-3) and t(240) and in CL taken from the obese subjects at t(-3) were as reported above, but were normal (i.e. the same as in control CL) in CL taken from the obese subjects at t(240). Baseline PDH activity was inversely correlated with body mass index and with fasting insulin, and directly correlated with S(I). These results show that a brief and sharp enhancement of blood insulin overcomes derangements in PDH that reflect systemic insulin resistance in obese adolescents.

Two types of hydrophobic aggregates in aqueous solutions of chitosan and its hydrophobic derivative.

The aggregation phenomena in aqueous solutions of hydrophobically modified (HM) chitosan, containing 4 mol % of n-dodecyl side chains, were studied by viscometry and fluorescence spectroscopy with pyrene as a probe. The results are compared with those for unmodified chitosan. Surprisingly, fluorescence data reveal the appearance of intermolecular hydrophobic aggregates both in chitosan and in HM chitosan. Nevertheless, these polymers exhibit quite different rheological properties: upon the formation of aggregates the viscosity of HM chitosan sharply increases, while that of unmodified chitosan raises only slightly. The aggregation models for both chitosan and its hydrophobic derivative were proposed. It was shown that in solutions of HM chitosan two types of hydrophobic domains exist: hydrophobic domains typical for different associating polymers with hydrophobic side chains and hydrophobic domains inherent to chitosan itself.