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The present paper deals with the effect of deformation delayed creep and shrinkage of the concrete on the seismic response of shear walls reinforced concrete strengthened with composite materials having a sinusoidal distribution of fibers. The lateral stiffness of shear walls RC, adhesives and composite material taking into account the phenomenon of creep and shrinkage of concrete described by the Eurocode 2, and widthwise varying fiber volume fraction of the composite plate has been determined by a finite element model. Large earthquakes recorded in Algeria (El-Asnam and Boumerdes) have been tested to demonstrate the accuracy of the proposed method. Numerical results obtained are discussed and the factors influencing the seismic response of reinforced concrete shear walls strengthened taking account the effects of the delay mechanism creep and shrinkage of concrete are highlighted. Prospects are being studied

In the present study, an experimental study is presented for a flow around an isolated wing equipped by a winglet and profiled with Naca 0012. Several cases of winglets were tested according to the angle ß: 0°, 55°, 65°and 75°. For all these cases at a velocity of 20, 30 and 40 meters per second, wind tunnel tests are performed and compared for different angles of incidence. It is observed that the aerodynamic performance of the winglet with β= 55° differ favorably for positive angle of incidence compared for other cases.

Nasal delivery of an oligomeric tau antibody loaded into micelles reduces pathology and ameliorates cognition in a mouse model of tauopathy.

Synapse loss is currently the best biological correlate of cognitive decline in Alzheimer's disease and other tauopathies. Synapses seem to be highly vulnerable to tau-mediated disruption in neurodegenerative tauopathies. However, it is unclear how and when this leads to alterations in function related to the progression of tauopathy and neurodegeneration. We used the well-characterized rTg4510 mouse model of tauopathy at 5-6 months and 7-8 months of age, respectively, to study the functional impact of cortical synapse loss. The earlier age was used as a model of prodromal tauopathy, with the later age corresponding to more advanced tau pathology and presumed progression of neurodegeneration. Analysis of synaptic protein expression in the somatosensory cortex showed significant reductions in synaptic proteins and NMDA and AMPA receptor subunit expression in rTg4510 mice. Surprisingly, in vitro whole-cell patch clamp electrophysiology from putative pyramidal neurons in layer 2/3 of the somatosensory cortex suggested no functional alterations in layer 4 to layer 2/3 synaptic transmission at 5-6 months. From these same neurons, however, there were alterations in dendritic structure, with increased branching proximal to the soma in rTg4510 neurons. Therefore, in vivo whole-cell patch clamp recordings were utilized to investigate synaptic function and integration in putative pyramidal neurons in layer 2/3 of the somatosensory cortex. These recordings revealed a significant increase in the peak response to synaptically driven sensory stimulation-evoked activity and a loss of temporal fidelity of the evoked signal to the input stimulus in rTg4510 neurons. Together, these data suggest that loss of synapses, changes in receptor expression and dendritic restructuring may lead to alterations in synaptic integration at a network level. Understanding these compensatory processes could identify targets to help delay symptomatic onset of dementia., Competing Interests: AC, LJ, TKM, SB were all employees of Eli Lilly & Company at the time of this work. There are no other competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Synapse loss correlates with cognitive decline in Alzheimer's disease, and soluble oligomeric amyloid beta (Aβ) is implicated in synaptic dysfunction and loss. An important knowledge gap is the lack of understanding of how Aβ leads to synapse degeneration. In particular, there has been difficulty in determining whether there is a synaptic receptor that binds Aβ and mediates toxicity. While many candidates have been observed in model systems, their relevance to human AD brain remains unknown. This is in part due to methodological limitations preventing visualization of Aβ binding at individual synapses. To overcome this limitation, we combined two high resolution microscopy techniques: array tomography and Förster resonance energy transfer (FRET) to image over 1 million individual synaptic terminals in temporal cortex from AD (n = 11) and control cases (n = 9). Within presynapses and post-synaptic densities, oligomeric Aβ generates a FRET signal with transmembrane protein 97. Further, Aβ generates a FRET signal with cellular prion protein, and post-synaptic density 95 within post synapses. Transmembrane protein 97 is also present in a higher proportion of post synapses in Alzheimer's brain compared to controls. We inhibited Aβ/transmembrane protein 97 interaction in a mouse model of amyloidopathy by treating with the allosteric modulator CT1812. CT1812 drug concentration correlated negatively with synaptic FRET signal between transmembrane protein 97 and Aβ. In human-induced pluripotent stem cell derived neurons, transmembrane protein 97 is present in synapses and colocalizes with Aβ when neurons are challenged with human Alzheimer's brain homogenate. Transcriptional changes are induced by Aβ including changes in genes involved in neurodegeneration and neuroinflammation. CT1812 treatment of these neurons caused changes in gene sets involved in synaptic function. These data support a role for transmembrane protein 97 in the synaptic binding of Aβ in human Alzheimer's disease brain where it may mediate synaptotoxicity., (© 2024. The Author(s).)

Tau hyperphosphorylation and aggregation is a common feature of many dementia-causing neurodegenerative diseases. Tau can be phosphorylated at up to 85 different sites, and there is increasing interest in whether tau phosphorylation at specific epitopes, by specific kinases, plays an important role in disease progression. The AMP-activated protein kinase (AMPK)-related enzyme NUAK1 has been identified as a potential mediator of tau pathology, whereby NUAK1-mediated phosphorylation of tau at Ser356 prevents the degradation of tau by the proteasome, further exacerbating tau hyperphosphorylation and accumulation. This study provides a detailed characterisation of the association of p-tau Ser356 with progression of Alzheimer's disease pathology, identifying a Braak stage-dependent increase in p-tau Ser356 protein levels and an almost ubiquitous presence in neurofibrillary tangles. We also demonstrate, using sub-diffraction-limit resolution array tomography imaging, that p-tau Ser356 co-localises with synapses in AD postmortem brain tissue, increasing evidence that this form of tau may play important roles in AD progression. To assess the potential impacts of pharmacological NUAK inhibition in an ex vivo system that retains multiple cell types and brain-relevant neuronal architecture, we treated postnatal mouse organotypic brain slice cultures from wildtype or APP/PS1 littermates with the commercially available NUAK1/2 inhibitor WZ4003. Whilst there were no genotype-specific effects, we found that WZ4003 results in a culture-phase-dependent loss of total tau and p-tau Ser356, which corresponds with a reduction in neuronal and synaptic proteins. By contrast, application of WZ4003 to live human brain slice cultures results in a specific lowering of p-tau Ser356, alongside increased neuronal tubulin protein. This work identifies differential responses of postnatal mouse organotypic brain slice cultures and adult human brain slice cultures to NUAK1 inhibition that will be important to consider in future work developing tau-targeting therapeutics for human disease., (© 2024. The Author(s).)

The synapse has consistently been considered a vulnerable and critical target within Alzheimer's disease, and synapse loss is, to date, one of the main biological correlates of cognitive decline within Alzheimer's disease. This occurs prior to neuronal loss with ample evidence that synaptic dysfunction precedes this, in support of the idea that synaptic failure is a crucial stage within disease pathogenesis. The two main pathological hallmarks of Alzheimer's disease, abnormal aggregates of amyloid or tau proteins, have had demonstrable effects on synaptic physiology in animal and cellular models of Alzheimer's disease. There is also growing evidence that these two proteins may have a synergistic effect on neurophysiological dysfunction. Here, we review some of the main findings of synaptic alterations in Alzheimer's disease, and what we know from Alzheimer's disease animal and cellular models. First, we briefly summarize some of the human evidence to suggest that synapses are altered, including how this relates to network activity. Subsequently, animal and cellular models of Alzheimer's disease are considered, highlighting mouse models of amyloid and tau pathology and the role these proteins may play in synaptic dysfunction, either in isolation or examining how the two pathologies may interact in dysfunction. This specifically focuses on neurophysiological function and dysfunction observed within these animal models, typically measured using electrophysiology or calcium imaging. Following synaptic dysfunction and loss, it would be impossible to imagine that this would not alter oscillatory activity within the brain. Therefore, this review also discusses how this may underpin some of the aberrant oscillatory patterns seen in animal models of Alzheimer's disease and human patients. Finally, an overview of some key directions and considerations in the field of synaptic dysfunction in Alzheimer's disease is covered. This includes current therapeutics that are targeted specifically at synaptic dysfunction, but also methods that modulate activity to rescue aberrant oscillatory patterns. Other important future avenues of note in this field include the role of non-neuronal cell types such as astrocytes and microglia, and mechanisms of dysfunction independent of amyloid and tau in Alzheimer's disease. The synapse will certainly continue to be an important target within Alzheimer's disease for the foreseeable future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Meftah and Gan.)

A new generation of a green polymeric matrix, chitosan/alginate-polyethyleniminemethylene phosphonic acid (CHIT/ALG-PEIMPA) was examined in comparative study of adsorption and preconcentration of non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac and ibuprofen. The influences of experimental parameters like pH, time reaction, initial concentration, ionic strength were investigated. The scanning electron microscopy (SEM) images showed heterogeneous morphology with different particle sizes of agglomerates from few micrometers to a hundred micrometers and irregular particles shape, before pharmaceuticals products adsorption. However, after adsorption, SEM micrograph reveals a smooth surface structure of agglomerate, and even in this smaller magnification, it was possible to observe the formation of homogenous and regular surface of CHIT/ALG-PEIMPA. Elementary analysis (EDX) reveals that the phosphonic acid (PEIMPA) was successfully cross-linked onto chitosan/alginate. The maximal adsorption capacity was found to be 222 mg.g -1 , and 122 mg.g -1 under optimum conditions for diclofenac and ibuprofen respectively. The kinetic modeling followed the pseudo-second-order rate expression for both pharmaceutical drugs. Thermodynamics data leads to an exothermic and spontaneous adsorption processes (∆H = -34.32 KJ mol -1 ; ∆H =-21.59 KJ mol -1 ), respectively for diclofenac and ibuprofen., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

When planning treatment for Graves' disease with 131 I, the effective half-life (T eff ) should be estimated individually as it depends on biological characteristics such as iodine uptake and excretion, which differ from an individual to another (Berg et al. 1996). All the methods to quantify T eff described in the literature are quite complex and are difficult to be used in clinical routine. With the aim of optimizing this process, a simplified method is proposed here to evaluate T eff of 131 I during treatment of Graves' disease. The present study suggests improving the method of determining T eff based on thermoluminescence dosimetry. This involves implementing a new method and includes reduction of TLD (Thermoluminescent Dosimeter) measurements. The proposed method was validated on patients with Graves' disease. The radiation dose delivered to the patients was determined using the MIRD (Medical Internal Radiation Dosimetry) formalism. The relative difference between T eff obtained based on seven measurement intervals at [0-24 h, 24-48 h, 48-72 h, 72-96 h, 96-120 h, 120-144 h, 144-168 h] and based on three measurement intervals at [0-24 h, 72-96 h, 144-168 h] and [0-24 h, 120-144 h, 144-168 h] was 1.9% and 3.81%, respectively. Comparison of doses obtained based on a general T eff and on a personalized T eff gave a statistically significant difference with a correlation coefficient R 2 of 0.44. The T eff obtained from just three measurements was found to be sufficiently accurate and easily applicable. The results obtained demonstrate the need to determine and use personalized T eff values instead of using a fixed value of 7 days.

An Al/ p -Si/poly[2-methoxy-5-(2-ethylhexoxy)- p -phenylenevinylene] (MEH-PPV)/Ag organic heterojunction has been prepared using homemade ultrasonic spray pyrolysis (USP) equipment for deposition of the organic thin film and physical vapor deposition (PVD) for the metallic contacts. The organic layer produced on glass was analyzed by optical and morphological methods. The bandgap of the organic thin film was found to be ~ 2.03 eV with a thickness of around 140 nm, using ultraviolet-visible (UV-Vis) and scanning electron microscopy (SEM) characterization, respectively. The amorphous nature of the MEH-PPV polymer was confirmed by its x-ray diffraction pattern. To determine the electrical parameters, the heterojunction based on MEH-PPV was characterized by current-voltage ( I - V ) and capacitance-voltage ( C - V ) measurements in the dark at room temperature. The ideality factor and barrier height of the organic heterojunction were found to be 3.6 eV and 0.56 eV to 0.59 eV, respectively, with an average series resistance of 94.39 Ω, based on the I - V characteristics. The barrier height was also calculated based on the capacitance-voltage measurements, yielding slightly different results due to the applied frequencies of 10 kHz ( ϕ B = 0.50 ) and 1 MHz ( ϕ B = 0.74 ) , respectively., Competing Interests: Conflict of InterestThe authors declare that they have no conflicts of interest., (© The Minerals, Metals & Materials Society 2021.)

The glymphatic system, that is aquaporin 4 (AQP4) facilitated exchange of CSF with interstitial fluid (ISF), may provide a clearance pathway for protein species such as amyloid-β and tau, which accumulate in the brain in Alzheimer's disease. Further, tau protein transference via the extracellular space, the compartment that is cleared by the glymphatic pathway, allows for its neuron-to-neuron propagation, and the regional progression of tauopathy in the disorder. The glymphatic system therefore represents an exciting new target for Alzheimer's disease. Here we aim to understand the involvement of glymphatic CSF-ISF exchange in tau pathology. First, we demonstrate impaired CSF-ISF exchange and AQP4 polarization in a mouse model of tauopathy, suggesting that this clearance pathway may have the potential to exacerbate or even induce pathogenic accumulation of tau. Subsequently, we establish the central role of AQP4 in the glymphatic clearance of tau from the brain; showing marked impaired glymphatic CSF-ISF exchange and tau protein clearance using the novel AQP4 inhibitor, TGN-020. As such, we show that this system presents as a novel druggable target for the treatment of Alzheimer's disease, and possibly other neurodegenerative diseases alike., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Narcolepsy type 1 is a disabling disorder with four primary symptoms: excessive-daytime-sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. The later three symptoms together with a short rapid eye movement (REM) sleep latency have suggested impairment in REM sleep homeostatic regulation with an enhanced propensity for (i.e. tendency to enter) REM sleep. To test this hypothesis, we challenged REM sleep homeostatic regulation in a recognized model of narcolepsy, the orexin knock-out (Orex-KO) mice and their wild-type (WT) littermates. We first performed 48 hr of REM sleep deprivation using the classic small-platforms-over-water method. We found that narcoleptic mice are similarly REM sleep deprived to WT mice. Although they had shorter sleep latency, Orex-KO mice recovered similarly to WT during the following 10 hr of recovery. Interestingly, Orex-KO mice also had cataplexy episodes immediately after REM sleep deprivation, anticipating REM sleep rebound, at a time of day when cataplexy does not occur in baseline condition. We then evaluated REM sleep propensity using our new automated method of deprivation that performs a specific and efficient REM sleep deprivation. We showed that REM sleep propensity is similar during light phase in Orex-KO and WT mice. However, during the dark phase, REM sleep propensity was not suppressed in Orex-KO mice when hypocretin/orexin neuropeptides are normally released. Altogether our data suggest that in addition to the well-known wake-promoting role of hypocretin/orexin, these neuropeptides would also suppress REM sleep. Therefore, hypocretin/orexin deficiency would facilitate the occurrence of REM sleep at any time of day in an opportunistic manner as seen in human narcolepsy.

Alzheimer's disease is connected to a number of other neurodegenerative conditions, known collectively as 'tauopathies', by the presence of aggregated tau protein in the brain. Neuroinflammation and oxidative stress in AD are associated with tau pathology and both the breakdown of axonal sheaths in white matter tracts and excess iron accumulation grey matter brain regions. Despite the identification of myelin and iron concentration as major sources of contrast in quantitative susceptibility maps of the brain, the sensitivity of this technique to tau pathology has yet to be explored. In this study, we perform Quantitative Susceptibility Mapping (QSM) and T2* mapping in the rTg4510, a mouse model of tauopathy, both in vivo and ex vivo. Significant correlations were observed between histological measures of myelin content and both mean regional magnetic susceptibility and T2* values. These results suggest that magnetic susceptibility is sensitive to tissue myelin concentrations across different regions of the brain. Differences in magnetic susceptibility were detected in the corpus callosum, striatum, hippocampus and thalamus of the rTg4510 mice relative to wild type controls. The concentration of neurofibrillary tangles was found to be low to intermediate in these brain regions indicating that QSM may be a useful biomarker for early stage detection of tau pathology in neurodegenerative diseases., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The choice and appropriate use of animal models in drug discovery for Alzheimer's disease (AD) is pivotal to successful clinical translation of novel therapeutics, yet true alignment of research is challenging. Current models do not fully recapitulate the human disease, and even exhibit various degrees of regional pathological burden and diverse functional alterations. Given this, relevant pathological and functional endpoints must be determined on a model-by-model basis. The present work explores the rTg4510 mouse model of tauopathy as a case study to define best practices for the selection and validation of cognitive and functional endpoints for the purposes of pre-clinical AD drug discovery., Methods: Male rTg4510 mice were first tested at an advanced age, 12 months, in multiple behavioural assays (step 1). Severe tau pathology and neurodegeneration was associated with profound locomotor hyperactivity and spatial memory deficits. Four of these assays were then selected for longitudinal assessment, from 4 to 12 months, to investigate whether behavioural performance changes as a function of accumulation of tau pathology (step 2). Experimental suppression of tau pathology-via doxycycline administration-was also investigated for its effect on functional performance., Results: Progressive behavioural changes were detected where locomotor activity and rewarded alternation were found to most closely correlate with tau burden and neurodegeneration. Doxycycline initiated at 4 months led to a 50% suppression of transgene expression, which was sufficient to prevent subsequent increases in tau pathology and arrest related functional decline., Conclusions: This two-step approach demonstrates the importance of selecting assays most sensitive to the phenotype of the model. A robust relationship was observed between pathological progression, development of phenotype, and their experimental manipulation-three crucial factors for assessing the translational relevance of future pre-clinical findings.

Increased levels of reactive oxygen species (ROS) play a vital role in the pathogenesis of various diseases. Thus, antioxidants would play pivotal roles in the therapy of ROS-induced diseases. Regarding this fact, in the present study, we compared the relative scavenging potency and cytoprotective effects of 15 Mn-salen complexes (EUKs: eukarion antioxidant compounds), having different substituted groups, against induced free radicals (O(2)(˙-), H(2)O(2), (˙)OH, and ABTS(˙+)) and protein carbonylation (PCO) in vitro as well as H(2)O(2)-induced damages and lipofuscin production in cellular systems. The results revealed that all Mn-salen complexes had considerable effects on O(2)(˙-), H(2)O(2), and (˙)OH scavenging, relative to common antioxidants, in a concentration-dependent manner. Further, our data demonstrated that the nature and position of different substitutions on the salen ring had significant effects on scavenging activity, PCO formation, as well as suppression of cytotoxicity and apoptosis induced in cells by H(2)O(2). Among studied complexes, EUK-15 and -123 showed the most catalase and superoxide dismutase activities, whereas their (˙)OH-scavenging activities were very weak. The cytoprotective effects of the salens, mainly EUK-15 and -123, were also associated with a significant reduction in the extent of intracellular lipofuscin pigments. Evaluation of the 15 salen derivatives clearly indicated these compounds possess ROS-scavenging activity and this activity is potentiated by the presence of para and ortho alkoxy groups.

A systematic computational study is carried out to investigate hydrogen bond (HB) interactions in the real crystalline structures of L-cysteine at 30 and 298 K by density functional theory (DFT) calculations of electric field gradient (EFG) tensors at the sites of O-17, N-14, and H-2 nuclei. One-molecule (monomer) and nine-molecule (cluster) models of L-cysteine are created by available crystal coordinates at both temperatures and the EFG tensors are calculated for both models to indicate the effect of HB interactions on the tensors. The calculated EFG tensors at the level of B3LYP and B3PW91 DFT methods and 6-311++G** and cc-pVTZ basis sets are converted to those experimentally measurable nuclear quadrupole resonance (NQR) parameters i.e. quadrupole coupling constants (qcc) and asymmetry parameters (eta(Q)). The evaluated NQR parameters reveal that the EFG tensors of (17)O, (14)N, and (2)H are influenced and show particular trends from monomer to the target molecule in the cluster due to the contribution of target molecule to classic N-H...O, and non-classic S-H...O and S-H...S types of HB interactions. On the other hand, atoms in molecules (AIM) analyses confirm the presence of HB interactions and rationalize the observed EFG trends. The results indicate different contribution of various nuclei to HB interactions in the cluster where O2 and N1 have major contributions. The EFG tensors as well as AIM analysis at the H6 site show that the N1-H6...O2 HB undergoes a significant change from 30 to 298 K where changes in other N-H...O interactions are almost negligible. There is a good agreement between the calculated (14)N NQR parameters and reported experimental data.

A systematic computational study was carried out to characterize the hydrogen bond, HB, interactions of sulfabenzamide crystal structure by DFT calculations of electric field gradient, EFG, tensors at the sites of 14N, 17O, and 2H nuclei. The computations were performed with the B3LYP and B3PW91 DFT methods and 6-311+G and 6-311++G* standard basis sets using the Gaussian 98 package. To perform the calculations, a hydrogen-bonded heptameric cluster of sulfabenzamide was created by X-ray coordinates where the hydrogen atom positions were optimized and the EFG tensors were calculated for the target molecule. Additional optimization and EFG calculations were also performed for crystalline monomer and an isolated gas-phase sulfabenzamide. The calculated EFG tensors were converted to the experimentally measurable nuclear quadrupole resonance, NQR, parameters: quadrupole coupling constant, C(Q), and asymmetry parameter, eta(Q). The results reveal that the geometrical and NQR parameters of the optimized isolated gas-phase and crystalline phase are different. In addition, the difference between the calculated NQR parameters of the monomer and the target molecule shows how much H-bonding interactions affect the EFG tensors of each nucleus. The evaluated NQR parameters reveal that due to the contribution of the target molecule to N-H...O and C-H...O hydrogen bond interactions, the EFG tensors at the sites of N1, O3 and H1 undergo significant changes from monomer to the target molecule in cluster. These features reveal the major role of N-H...O type intermolecular HBs in cluster model of sulfabenzamide which the presence of these interactions can lead to polymorphism directly related to the drug activity and related properties.

Ecto 5' nucleotidase (5'NT) is an integral plasma membrane enzyme located on most mammalian cells, and it is zinc dependent. We assayed 5'NT activity in the lymphocytes of two groups of subjects. The first group of six subjects had a mild state of zinc deficiency, as measured on the basis of zinc levels in lymphocytes, granulocytes, and platelets, but were otherwise healthy. They received 50 mg zinc as acetate orally for 12 weeks. The second six subjects were normal human volunteers in whom a mild state of zinc deficiency was induced experimentally by dietary techniques (4.2 to 5.6 mg daily zinc intake). For the assay of 5'NT, intact lymphocytes were incubated with 8-14C-labeled inosine monophosphate as substrate. Product and substrate were separated by thin-layer chromatography. Zinc level in cells was measured by flameless atomic absorption technique. In the first group of subjects with zinc deficiency, the decreased activity of 5'NT was corrected and the cellular zinc levels were normalized by oral zinc supplementation (p less than 0.01). In the second group of subjects, the baseline data were compared with those in early zinc depletion (4 to 8 weeks) and late depletion periods (greater than 20 weeks). A decrease in the activity of 5'NT was observed during the early zinc depletion phase. Zinc levels in lymphocytes, granulocytes, and platelets decreased significantly only during the late zinc depletion phase (p less than 0.01). Plasma zinc level did not change even during the late zinc depletion phase. Our studies show that 5'NT activity may be a sensitive and useful indicator of mild deficiency of zinc in human subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell-mediated immunity in human subjects is affected adversely as a result of zinc deficiency. The mechanism by which a deficiency of zinc may affect lymphocyte proliferation and functions, is not well understood at present. Nucleoside phosphorylase (NPase), a purine catabolic pathway enzyme, is zinc dependent, and a congenital deficiency of this enzyme is known to affect adversely cell-mediated immunity. This effect has been related to an accumulation of toxic nucleotides in lymphocytes as a result of NPase deficiency. Inasmuch as the effect of zinc deficiency on the activity of NPase and the levels of nucleotides in human lymphocytes has not been previously reported, we assayed these parameters in human subjects with zinc deficiency before and after zinc supplementation. A mild deficiency of zinc was diagnosed in those having decreased zinc in two out of three cell lineages (less than 42 micrograms in granulocytes, less than 48 micrograms in lymphocytes, and less than 1.70 microgram in platelets, per 10(10) cells). In comparison with five subjects with sufficient zinc, six subjects with zinc deficiency showed a decrease in the activity of NPase (p = 0.01), an increase in adenosine diphosphate (ADP) level (p = 0.008), a decreased adenosine triphosphate (ATP)-to-ADP ratio (p = 0.0001), and an increase in both guanosine triphosphate (GTP) (p = 0.02) and deoxyadenosine triphosphate (dGTP) (p = 0.04 in the lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)