N-Acetylcysteine is an effective analog of glutathione in reactions with reactive oxygen species.

The kinetic characteristics of the interaction of N-acetylcysteine (ASH) with reactive oxygen species (ROS), peroxyl radicals and hydrogen peroxide were determined. It was found that in terms of activity ASH in these reactions is similar to glutathione GSH, the main endogenous bioantioxidant. The kinetics of heat release in the interaction of GSH and ASH with H2O2 was studied for the first time by isothermal calorimetry. It is shown that the kinetic curves of heat release and changes in specific heat release rates practically coincide for both thiols taken in the stoichiometric ratio in the known reaction 2 TSH + H2O2 → TSST + 2 H2O. This indicates the relative autonomy of the S-H and S-S bonds in thiols and disulfides, which are not affected by other groups in the molecule. At pH<7, ASH, like GSH, interacts with H2O2 to form thiyl radicals, which initiate thiol-ene reactions with unsaturated phenol resveratrol. Under the same conditions, ASH ensures nearly the same radical initiation rates as GSH, and thiyl radicals from ASH are close in activity to GS• in chain propagation reactions.

Parenting, mental health and economic pathways to prevention of violence against children in South Africa.

BACKGROUND: Parenting programs based on social learning theory have increasing empirical evidence for reducing violence against children. Trials are primarily from high-income countries and with young children. Globally, we know little about how parenting programs work to reduce violence, with no known studies in low or middle-income countries (LMICs). This study examines mechanisms of change of a non-commercialized parenting program, Parenting for Lifelong Health for Teens, designed with the World Health Organization and UNICEF. A cluster randomized trial showed main effects on parenting and other secondary outcomes. We conducted secondary analysis of trial data to investigate five potential mediators of reduced violence against children: improved parenting, adolescent behaviour, caregiver mental health, alcohol/drug avoidance, and family economic strengthening. METHODS: The trial was implemented in rural South Africa with 40 sites, n = 552 family dyads (including adolescents aged 10-18 and primary caregivers). Intervention sites (n = 20) received the 14-session parenting program delivered by local community members, including modules on family budgeting and savings. Control sites (n = 20) received a brief informational workshop. Emotional and physical violence against children/adolescents and each potential mediator were reported by adolescents and caregivers at baseline and 9-13 months post-randomisation. Structural equation modelling was used to test simultaneous hypothesized pathways to violence reduction. RESULTS: Improvements in four pathways mediated reduced violence against children: 1) improved parenting practices, 2) improved caregiver mental health (reduced depression), 3) increased caregiver alcohol/drug avoidance and 4) improved family economic welfare. Improved child behaviour was not a mediator, although it was associated with less violence. CONCLUSIONS: Simultaneously bolstering a set of family processes can reduce violence. Supporting self-care and positive coping for caregivers may be essential in challenging contexts. In countries with minimal or no economic safety nets, linking social learning parenting programs with economic strengthening skills may bring us closer to ending violence against children.

Design, modeling, and experimental validation of an acoustofluidic platform for nanoscale molecular synthesis and detection.

Microfluidic technologies are increasingly implemented to replace manual methods in biological and biochemical sample processing. We explore the feasibility of an acoustofluidic trap for confinement of microparticle reaction substrates against continuously flowing reagents in chemical synthesis and detection applications. Computational models are used to predict the flow and ultrasonic standing wave fields within two longitudinal standing bulk acoustic wave (LSBAW) microchannels operated in the 0.5-2.0 MHz range. Glass (gLSBAW) and silicon (siLSBAW) pillar arrays comprise trapping structures that augment the local acoustic field, while openings between pillars evenly distribute the flow for uniform exposure of substrates to reagents. Frequency spectra (acoustic energy density E ac vs frequency) and model-predicted pressure fields are used to identify longitudinal resonances with pressure minima in bands oriented perpendicular to the inflow direction. Polymeric and glass particles (10- and 20-µm diameter polystyrene beads, 6 µm hollow glass spheres, and 5 µm porous silica microparticles) are confined within acoustic traps operated at longitudinal first and second half-wavelength resonant frequencies (f 1,E = 575 kHz, gLSBAW; f 1,E = 666 kHz; and f 2,E = 1.278 MHz, siLSBAW) as reagents are introduced at 5-10 µl min-1. Anisotropic silicon etched traps are found to improve augmentation of the acoustic pressure field without reducing the volumetric throughput. Finally, in-channel synthesis of a double-labeled antibody conjugate on ultrasound-confined porous silica microparticles demonstrates the feasibility of the LSBAW platform for synthesis and detection. The results provide a computational and experimental framework for continued advancement of the LSBAW platform for other synthetic processes and molecular detection applications.

Augmented longitudinal acoustic trap for scalable microparticle enrichment.

We introduce an acoustic microfluidic device architecture that locally augments the pressure field for separation and enrichment of targeted microparticles in a longitudinal acoustic trap. Pairs of pillar arrays comprise "pseudo walls" that are oriented perpendicular to the inflow direction. Though sample flow is unimpeded, pillar arrays support half-wave resonances that correspond to the array gap width. Positive acoustic contrast particles of supracritical diameter focus to nodal locations of the acoustic field and are held against drag from the bulk fluid motion. Thus, the longitudinal standing bulk acoustic wave (LSBAW) device achieves size-selective and material-specific separation and enrichment of microparticles from a continuous sample flow. A finite element analysis model is used to predict eigenfrequencies of LSBAW architectures with two pillar geometries, slanted and lamellar. Corresponding pressure fields are used to identify longitudinal resonances that are suitable for microparticle enrichment. Optimal operating conditions exhibit maxima in the ratio of acoustic energy density in the LSBAW trap to that in inlet and outlet regions of the microchannel. Model results guide fabrication and experimental evaluation of realized LSBAW assemblies regarding enrichment capability. We demonstrate separation and isolation of 20 µm polystyrene and ∼10 µm antibody-decorated glass beads within both pillar geometries. The results also establish several practical attributes of our approach. The LSBAW device is inherently scalable and enables continuous enrichment at a prescribed location. These features benefit separations applications while also allowing concurrent observation and analysis of trap contents.

Quantum dots protected from oxidative attack using alumina shells synthesized by atomic layer deposition.

Applications of luminescent quantum dots require the materials to be stable under a wide range of temperatures, photon fluxes and chemical environments. In this work, we demonstrate that Al2O3 shells synthesized by atomic layer deposition on films of CdTe quantum dots are effective to prevent chemical degradation for up to 17 hours under continuous illumination at 90 °C in ambient air. Control samples with no Al2O3 coating experienced extensive oxidation and severe quenching of the photoluminescence intensity under these conditions.

ACANTHOCEPHALANS PROSTHENORCHIS CF. ELEGANS (ARCHIACANTHOCEPHALA: OLIGACANTHORHYNCHIDAE), PARASITES OF PRIMATES IN THE MOSCOW ZOO.

Acanthocephalans Prosthenorchis cf. elegans were found in primates in the Moscow Zoo. The larvae of these parasites (cistacanths) were found in cockroaches Blattella germanica that had been captured near aviaries of infected animals. Descriptions and drawings of adult parasites and their larvae are given. Analysis of Prosthenorchis cf. elegans genes ITS 1 rDNA and CO 1 mtDNA shows phylogenetic relations of these parasites with several representatives of the class Archiacanthocephala. The obtained molecular data, however, do not support the monophyly of the family Oligacanthorhynchidae and the order Oligacanthorhynchida.

Topological properties of microwave magnetoelectric fields.

Collective excitations of electron spins in a ferromagnetic sample dominated by the magnetic dipole-dipole interaction strongly influence the field structure of microwave radiation. A small quasi-two-dimensional ferrite disk with magnetic-dipolar-mode (MDM) oscillation spectra can behave as a source of specific fields in vacuum, termed magnetoelectric (ME) fields. A coupling between the time-varying electric and magnetic fields in the ME-field structures is different from such a coupling in regular electromagnetic fields. The ME fields are characterized by strong energy confinement at a subwavelength region of microwave radiation, topologically distinctive power-flow vortices, and helicity parameters [E. O. Kamenetskii, R. Joffe, and R. Shavit, Phys. Rev. E 87, 023201 (2013)]. We study topological properties of microwave ME fields by loading a MDM ferrite particle with different dielectric samples. We establish a close connection between the permittivity parameters of dielectric environment and the topology of ME fields. We show that the topology of ME fields is strongly correlated with the Fano-resonance spectra observed at terminals of a microwave structure. We reveal specific thresholds in the Fano-resonance spectra appearing at certain permittivity parameters of dielectric samples. We show that ME fields originated from MDM ferrite disks can be distinguished by topological portraits of the helicity parameters and can have a torsion degree of freedom. Importantly, the ME-field phenomena can be viewed as implementations of space-time coordinate transformations on waves.

The computational and experimental investigations of photophysical and spectroscopic properties of BF2 dipyrromethene complexes.

The electronic excited states of BF2 dipyrromethene (2BrDPM, DPMI, DPMII, PM567 and 4PhDPM) complexes were investigated using the extended multi-configuration quasi-degenerate at the second order of perturbation theory (XMCQDPT2) and the second-order approximate coupled-cluster (CC2) methods. The excitation energies calculated by CC2 are significantly overestimated by 0.42-0.59 eV because of the substantial contributions of double excitation levels to excited states (>10%). However, the calculated XMCQDPT2 excitation energies agree well with experimental ones within the accuracy 0.11-0.20eV. The very low lasing efficiency (7.8-8.4%) of 4PhDPM compound was explained by the T1→T4 and T1→T5 reabsorptions at XMCQDPT2 level of theory. The molecular photonics of pyrromethenes are studied using a combination of the first-principle and semi-empirical calculations. The main mechanism for the deactivation of the energy of the first singlet excited electronic state is the radiative electronic transition for DPMI, DPMII, PM567 and 4PhDPM compounds. Also, the main mechanism for the quenching of fluorescence in considered complexes (except DPMII compound) is the internal conversion. The processes of the internal conversion and intersystem crossing compete with each other in DPMII compound. The measured and calculated fluorescence quantum yields agree well for all considered molecules.

[Possibilities of correction of rheological properties of the blood and free radical processess in patients with acute myocardial infarction combined with type 2 diabetes mellitus].

Aim of the study was assessment of rheological parameters of the blood and processes of free radical oxidation as well as rate of arrhythmia development in patients with acute myocardial infarction (AMI) and type 2 diabetes mellitus (DM) whose otherwise standard therapy was supplemented with 90% omega-3 polyunsaturated fatty acid (PFA). We examined 63 patients with AMI and concomitant diabetes. 90% omega-3 PFA was given to 16 of these patients. Control group consisted of 22 practically healthy patients. Investigation of blood rheological parameters included measurement of viscosity of whole blood, determination of aggregation and morphofunctional structure of erythrocytes. Free radical processes were assessed by total amount of nitrates and nitrites in blood plasma, concentration of citrulline and malone dialdehyde. In patients with AMI taking its course at the background of type 2 DM compared with control group we observed changes of rheological properties of blood and processes of free radical oxidation which led to lowering of tissue oxygen supply. Standard therapy of AMI in more than 50% of patients did not result in adequate correction of impaired rheological parameters of blood. Addition of 90% omega-3 PFA to standard treatment of AMI was associated with improvement of aggregation and cytoarchitectonics of erythrocytes, lowering of activity of free radical oxidation, and by the end of 2nd week of treatment--with lessening of number of ventricular disturbances of cardiac rhythm. Thus supplementation of standard therapy with preparation 90% omega-3 PFA in patients with AMI and type 2 DM facilitates improvement of rheological properties of blood and processes of free radical oxidation, and prevention of arrhythmia.

[Peculiarities of electrostatic interactions between amino acids and salicylic acid in aqueous solution].

Based on calorimetric data, the enthalpy of the transfer of salicylic acid to aqueous buffer solutions with the addition of different amino acids at the constant acidity of medium pH 7.35 was determined. It was shown that the exothermicity of transfer and negative enthalpic coefficients for these pairwise interactions of salicylic acid with amino acids considerably increase with increasing charge of amino acid existing in the ionic form under these conditions. Weak interactions of salicylic acid with the anionic form of aspartic and glutamic acids are related to the repulsion between anion carboxyl groups. More intensive interactions are observed for zwitter-ions of glycine and alanine. The most intensive specific interactions with salicylic acid are observed for lysine and arginine, which exist in the solution as cations.

[Cytoarchitectonics and parameters of aggregation of erythrocytes in patients with acute myocardial infarction].

AIM: To assess cytoarchitectonics and parameters of aggregation of erythrocytes in patients with acute myocardial infarction, to elucidate their relationships with risk factors of ischemic heart disease. MATERIAL AND METHODS: We examined 80 patients with acute myocardial infarction, 20 patients with stable angina pectoris comprised control group. Patients were divided into subgroups according to depth of damage of the myocardium and presence of statins in the treatment scheme. Examination included assessment of cytoarchitectonics and parameters of aggregation of erythrocytes, determination of blood plasma lipid spectrum and concentration of fibrinogen. RESULTS AND CONCLUSIONS: Pronounced pathological changes of cytoarchitectonics of erythrocytes and parameters of their aggregation develop in acute myocardial infarction. These changes increase with increase of depth of myocardial damage. Inclusion of statins in the scheme of treatment leads to significant improvement of the parameters studied. This improvement is more pronounced in patients with non-Q-wave myocardial infarction. Presence of significant interrelationships between cytoarchitectonics of erythrocytes and their aggregation and levels of low density lipoprotein cholesterol, concentration of fibrinogen.

Management of pituitary apoplexy: clinical experience with 40 patients.

BACKGROUND: Pituitary apoplexy is a rare major clinical event with neurological, neuro-ophthalmological, cardiovascular and hormonal consequences, resulting from an acute infarction of pituitary adenoma. We report our experience with a series of 40 patients presenting with pituitary apoplexy. PATIENTS: Forty patients (27 males, 13 females; mean age, 51.2 yr) were admitted to our medical center between years 1985-2002 with acute presentation of pituitary apoplexy. Visual field defects occurred in 61% and ocular paresis in 40% of subjects. Sixty-three percent of adenomas were nonfunctional, and prolactinomas comprised 31%. RESULTS: Thirty-four patients underwent transsphenoidal pituitary decompression. Visual fields and ophthalmoplegia improved in 81% and 71%, respectively. During follow-up (4.5+/-5.4 yr), 79% of patients developed hypogonadotrophic hypogonadism, central hypothyroidism appeared in 54% and hypocortisolism--in 40% of patients. Permanent diabetes insipidus was diagnosed in 8%. Serial sellar MRI showed disappearance of pituitary tumor in 63% of operated subjects. Six patients (3 with PRL-secreting and 3 nonfunctional adenomas) were treated medically (corticosteroids, dopamine agonists), two patients (out of three) with visual deficits improved, and tumor shrinkage was noted in four. CONCLUSIONS: We present a large series of patients with pituitary apoplexy. Most subjects were operated, but six were treated conservatively. Almost all patients improved clinically, including those who were not operated, but hormonal deficiencies are very common.

Mutation analysis of the MEN1 gene in Israeli patients with MEN1 and familial isolated hyperprolactinemia.

Multiple endocrine neoplasia type 1 (MEN-1) is characterized by hyperfunction and tumor formation of the parathyroids, anterior pituitary and endocrine pancreas. We carried out exon-specific, PCR-based DNA sequencing of the coding exons of the MEN1 gene in 8 Israeli MEN1 patients: 4 familial and 4 sporadic. We similarly analyzed Israeli families with a unique phenotype of isolated hyperprolactinemia (HPRL). Four mutations were detected in 4 MEN1 patients: C to T alteration at nucleotide 2608 resulting in R108X, and three intronic insertions/deletions (a 13 basepair (bp) deletion and a 1 bp insertion both in intron 1, and a 2 bp insertion in intron 3) leading to exonic frame shifts as they encompass the splice junctions. An additional patient exhibited a compound mutation: a G to T change at position 7614 resulting in E463X, and insertion/deletion of 9 bp at position 7622-7630 resulting in EAE466-468X. Haplotype analysis showed no segregation of phenotype with 11q13 markers in 4 familial HPRL, and no men 1 germline mutations were detected in three representative individuals, from 3 families. Our results confirm that men 1 gene germline mutations occur in the majority of patients with clinically diagnosed MEN1, and that familial HPRL is a genetically distinct disorder.

Increase in PDX-1 levels suppresses insulin gene expression in RIN 1046-38 cells.

RIN1046-38 cells (RIN-38) exhibit a passage-dependent reduction in both basal and glucose-regulated insulin secretion, accompanied by decreased insulin content. In an attempt to explain the mechanism of the gradual decrease in insulin production in cultured cells, we analyzed the insulin promoter activity and the levels of an important trans-activator of the insulin gene, PDX-1, as a function of aging in culture. We demonstrate that the decrease in insulin content and secretion is reflected in decreased promoter activity and is associated with a decrease in E47 and BETA2 nuclear factors, but with a paradoxical 3-fold increase in PDX-1 protein levels. To dissect the effect of increased PDX-1 from the decrease in the additional transcription factors on insulin promoter activity, we overexpressed PDX-1 protein in low passage RIN-38 cells by recombinant adenovirus technology. PDX-1 overexpression did not reduce E47 and BETA2 levels, but was sufficient to suppress rat insulin promoter activity in a dose-dependent manner. The fact that PDX-1 levels participate in trans-activation of insulin promoter activity was demonstrated in HIT-T15 cells. Treating HIT-T15 cells with 1-2 multiplicity of infection of AdCMV-PDX-1 increased rat insulin promoter activity, whereas higher doses repressed insulin promoter activity in these cells as in RIN-38 cells. Our data demonstrate that PDX-1 regulates transcription of the insulin gene in a dose-dependent manner. Depending on its nuclear dosage and the levels of additional cooperating transcription factors, PDX-1 may act as an activator or a repressor of insulin gene expression, such that low as well as high doses may be deleterious to insulin production.

Enhanced Na+/H+ exchange in Cushing's syndrome reflects functional hypermineralocorticoidism.

BACKGROUND: Patients with Cushing's syndrome exhibit a bimodal distribution of maximal rates of the erythrocyte amiloride-sensitive Na+/H+ exchange (NHE). Enhanced erythrocyte NHE has recently been found in patients with primary aldosteronism. OBJECTIVE: To test the hypothesis that occult hypermineralocorticoidism in a subset of patients with Cushing's syndrome is responsible for the greater than normal NHE. METHODS: NHE was measured as maximal initial rate (Vmax) of amiloride-inhibited efflux of H+ into an alkaline Na+-containing medium, for 47 patients with hypercortisolism (20 with pituitary adenomas, 18 with adrenal adenomas, and nine with ectopic production of adrenocorticotropin). Clinical appearance, blood pressure levels, plasma aldosterone and deoxycorticosterone levels, serum electrolytes, and urine (tetrahydrocortisol plus 5-alpha-tetrahydrocortisol) : tetrahydrocortisone ratios were assessed for all patients. Twenty patients (10 with greater than normal NHE and 10 with low-to-normal NHE) were randomly selected from 47 patients with hypercortisolism, and treated with 200 mg/day spironolactone for 7 days. NHE in these patients was assessed before starting the treatment and 2 days after its cessation. RESULTS: Greater than normal NHE (Vmax) was associated with peripheral edema, high diastolic blood pressure, hypokalemia, and high urine (tetrahydrocortisol plus 5-alpha-tetrahydrocortisol) : tetrahydrocortisone ratios. The enhanced NHE was rapidly normalized by treatment with spironolactone. CONCLUSION: Erythrocyte NHE in patients with hypercortisolism and functional hypermineralocorticoidism is greater than normal due to incomplete peripheral conversion of cortisol (which binds to mineralocorticoid receptors) into metabolically inactive cortisone.

Enhanced erythrocyte Na+/H+ exchange predicts diabetic nephropathy in patients with IDDM.

Diabetic nephropathy develops in a subset of patients with an apparently hereditary predisposition. Microalbuminuria and elevated arterial pressure have been proposed as predictors of nephropathy but both appear when renal damage is impending. Enhanced sodium-hydrogen exchange in the cell membranes of diabetic patients is an early marker of diabetic nephropathy but its predictive value has not been assessed. In this study, sodium-hydrogen exchange was measured in erythrocytes as an initial velocity of amiloride-inhibited H+ efflux (pH 6.35-6.45) into a Na+ - containing medium (pH 7.95-8.05) in 156 non-microalbuminuric insulin-treated diabetic patients (98 women, 58 men, age 33+/-8 years, diabetes duration prior to enrollment 15+/-4 years) during 8 years of follow-up. Enhanced erythrocyte sodium-hydrogen exchange predicted diabetic nephropathy alone and in association with a familial tendency to hypertension/nephropathy with 86 and 96% sensitivity, and 80% specificity. Thus, sodium-hydrogen exchange appears to detect a subset of diabetic patients prone to develop renal damage, in whom a more intensive treatment modality might be considered.

[Red cell Na+/H+ exchange and role of protein kinase C in its stimulation in diabetes mellitus, essential hypertension and nephropathy].

Na+/H+ exchange (NHE) was measured as maximal initial velocity of pH-dependent H+ efflux from red cells into an alkaline medium containing Na+ in patients with insulin-dependent or noninsulin-dependent diabetes, with and without hypertension and in normoglycemic, essential hypertensives and normal controls (50 subjects in each subgroup). Maximal velocities of NHE were found in microalbuminuric patients in all subgroups, and NHE correlated with the rate of micro-albuminuria (r = 0.61, p = 0.02). Daily insulin requirements were greater in those with elevated NHE (84 +/- 8 vs 42 +/- 4 U/day). There was no correlation between NHE and levels of plasma glucose, HbA1 and plasma aldosterone and lipid profile and PRA. NHE was correlated with plasma prolactin (r = 0.51, p = 0.02) and PTH r = 0.24, p = 0.05). In uremic patients, NHE was inversely correlated with creatinine clearance (r = -0.48, p = 0.03). Since calphostin C, a selective inhibitor of protein kinase C, lowered increased NHE in vitro, the protein kinase C-dependent pathway of the exchanger regulation was concluded to be responsible for NHE activation in diabetes mellitus and essential hypertension.

Gynecomastia following spinal cord disorder.

Gynecomastia, an excessive development of the mammary glands in men, is a known phenomenon among patients with spinal cord disorder, yet in the last 50 years it has not been fully described in relation to spinal cord disorder. Over a period of 2 years, six patients with spinal cord disorder (4 secondary to a traumatic injury, 1 to decompression sickness, and 1 to transverse myelitis) manifested gynecomastia. The onset of gynecomastia occurred between 1 to 6 months after injury. These patients are presented along with a review of the possible causes for gynecomastia and a suggested workup routine. A clinical examination for the presence of gynecomastia should be performed for every patient with spinal cord disorder and a thorough endocrinological workup should follow to rule out malignancy and reassure the anxious patient undergoing a disruption of his body image.

Hyperprolactinemia in postmenopausal women.

OBJECTIVE: To study the clinical cause and course of hyperprolactinemia in postmenopausal women. DESIGN: Retrospective case-note study. SETTING: Tertiary care hospital. PATIENT(S): Six postmenopausal women with hyperprolactinemia. MAIN OUTCOME MEASURE(S): Clinical history and physical examination, serum levels of PRL, LH, FSH, computed tomography (CT) of the pituitary gland before and after treatment with bromocriptine. RESULT(S): At presentation, the mean age was 57.5 +/- 7.5 SD years. The mean level of PRL was 1,427 +/- 1,599 ng/mL (1,427 +/- 1,599 micrograms/L). All women suffered from secondary amenorrhea for a mean duration of 31.8 +/- 5.6 years. Five of six had galactorrhea at some time in the past. Pituitary imaging revealed a pituitary macroadenoma in four women, an enlarged sella suggestive of a pituitary macroadenoma in one woman, and a microadenoma in one. After treatment with bromocriptine, the PRL level decreased in all women to within normal limits. Five of six women developed hot flushes after the PRL level returned to normal. CONCLUSION(S): Most cases of hyperprolactinemia in postmenopausal women are due to macroadenoma rather than microadenoma, the common finding in younger women. The clinical course is suggestive of a prolonged disease that was not detected earlier, although clinical signs were present. These findings are suggestive of an enlargement of microadenomas to macroadenomas as time passes.

Amiloride-sensitive Na+/H+ exchange in erythrocytes of patients with NIDDM: a prospective study.

Intensive treatment of non-insulin-dependent diabetes mellitus (NIDDM) decreases the rate of microvascular complications, but is associated with increased incidence of cardiovascular morbidity. Enhanced permeability of plasma membranes for sodium (e.g. sodium-hydrogen exchange, NHE) may predict the subset of diabetic patients for whom intensive modalities of treatment are indicated despite their potential risk. However, the accuracy of NHE as a marker of microangiopathy has not been assessed. In this study NHE as initial velocity of amiloride-inhibited H+ efflux from erythrocytes (pHi 6.35-6.45) into an Na(+)-containing medium (pHo 7.95-8.05), was estimated during 8 years of follow-up in 138 non-microalbuminuric diabetic patients (74 women, 64 men, age 52 +/- 4 years) treated with antihyperglycaemic drugs for 14 +/- 2 years. Appearance of microalbuminuria, overt proteinuria, azotaemia and retinopathy was assessed annually. Enhanced erythrocyte NHE predicted diabetic nephropathy alone and in association with a family history of hypertension and/or nephropathy with a sensitivity of 86 and 93%, respectively. No association was found between NHE and retinopathy in NIDDM. It is concluded that assessment of erythrocyte NHE can identify a subset of patients likely to develop renal damage, for whom an aggressive treatment approach might be considered.