Gradual Decrement Research Articles

The Comparison of Experimental and Analytical Study of the Gaussian IntensityDistribution for Light Emitting Diodes Beam

Problem statement: Wireless communication using white Light Emitting Diodes (LEDs) is the latest research field for next-generation commu nication. This study studies the comparison of Gaussian intensity distribution of the white LED us ing experimental and analytical method. The white LEDs are conducted to transmit an audio signal to t he receiver. The receiver circuit consist of solar cell connected to the speaker to recover the audio signa l. From the comparison of experimental and analytical data, the Gaussian plot of experimental data is steeper than the analytical data, meaning t hat the LED has small-divergence beam. Conclusion/Recommendations: The output voltage of experimental works decrease exponentially with the distance whiles the Full Width Half Maximum (FWHM) value increase exponentially with the distance. The gradual increment and decrement of the analytical signal can be applicable to visible ligh t communication implementation as such light source can cover wide area for signal transmission.

A 15-Year Prospective Epidemiological Account of Acute Traumatic Injuries During Official Professional Soccer League Matches in Japan

Background: Few prospective epidemiological studies on soccer match injuries have collected continuous data using subjects from the same group. Purpose: To investigate long-term injury-induced changes during official matches in the professional Japanese soccer league. Study Design: Descriptive epidemiological study. Methods: Acute injuries during official matches among top-division Japanese professional soccer leaguers were prospectively collected from 1993 to 2007. Injuries preventing player participation for 7 days or more were defined as a reportable injury. Interseasonal variations of injury rate (IR: injuries/1000/player hours) and injury pattern (type, location, circumstances, severity, injury time, positional role, and relationship to weather) were analyzed. Results: Throughout the study period, 2947 injuries from 3984 matches occurred. Mean annual IR was 21.77/1000 player hours, and annual variance showed gradual decrement throughout the study period. The proportion of injury type and location were not significantly changed. Sprain and contusion as injury type and thigh and ankle joint as location were the most common in every season. Contact-related injuries comprised 73.3% on average and were observed to occur more frequently during the last 15 minutes and extra time of match play. The proportion of foul play–related injuries showed a clear declining trend. The proportion of severe injury showed a sporadic increase from 2001 to 2004. The second, fifth, and sixth 15-minute match segments showed a higher IR. Goalkeepers had a lower IR versus other field players. Matches on rainy days resulted in a lower IR than did those held under other weather conditions. Conclusion: Long-term surveillance and statistical feedback of injury characteristics to organization members were considered effective in improving safer play awareness among players and for referees to reduce injury incidence, particularly foul play–related injuries.

Non‐surgical management of post‐cesarean uterine infection with marked myometrial gas formation

Gas in an infected organ generally indicates a severe infection, often requiring surgery; however, data are lacking as to post-cesarean gas-forming uterine infection. A 27-year-old Japanese primigravida underwent a difficult cesarean section, after which a high fever continued. Computed tomography (CT) revealed marked gas in the uterine anterior myometrium. Diagnosing this condition as post-cesarean uterine scar infection, we recommended surgical intervention, that is, hysterectomy or at least drainage; however, the patient refused it. Considering the patient's desire and lack of organ-failure signs, we employed intensive antibiotic treatment for 6 weeks. Serial CT indicated a gradual decrement in the gas amount and she recovered completely after 8 weeks. This case suggests that surgical procedure may not always be necessary for post-cesarean gas-forming uterine infection and CT may be useful to detect/follow this condition.

Short-term habituation of auditory evoked potential and neuromagnetic field components in dependence of the interstimulus interval

Repeated auditory stimulation results usually in a response decrement of event-related potential components. In the current study, we investigated the impact of the interstimulus interval (ISI) on the response decrement. Healthy subjects were stimulated with trains of five tones, with an ISI of 600, 1,200, or 1,800 ms within the trains. Auditory evoked potentials (AEP) were recorded from the vertex, as well as neuromagnetic auditory evoked fields (AEF) from the left temporal region. Stimulus repetition led to a response decrement for the studied AEP components (N100 and P200) and AEF components (N100m and P200m). However, for all used ISIs, there was no further response decrement after the 2nd stimulus. The ISI affected only the magnitude but not the kind of the response decrement. No evidence for a gradual response decrement was revealed at any used ISI. This finding indicates that the response decrement is probably due to the refractoriness of cell assemblies involved in the generation of AEP and AEF components, rather than the result of a genuine habituation process. The finding questions habituation as the mechanism behind short-term decrements of AEP/AEF components.

Similarity and difference in the processing of same- and other-race faces as revealed by eye tracking in 4- to 9-month-olds

Fixation duration for same-race (i.e., Asian) and other-race (i.e., Caucasian) female faces by Asian infant participants between 4 and 9 months of age was investigated with an eye-tracking procedure. The age range tested corresponded with prior reports of processing differences between same- and other-race faces observed in behavioral looking time studies, with preference for same-race faces apparent at 3 months of age and recognition memory differences in favor of same-race faces emerging between 3 and 9 months of age. The eye-tracking results revealed both similarity and difference in infants’ processing of own- and other-race faces. There was no overall fixation time difference between same race and other race for the whole face stimuli. In addition, although fixation time was greater for the upper half of the face than for the lower half of the face and trended higher on the right side of the face than on the left side of the face, face race did not impact these effects. However, over the age range tested, there was a gradual decrement in fixation time on the internal features of other-race faces and a maintenance of fixation time on the internal features of same-race faces. Moreover, the decrement in fixation time for the internal features of other-race faces was most prominent on the nose. The findings suggest that (a) same-race preferences may be more readily evidenced in paired comparison testing formats, (b) the behavioral decline in recognition memory for other-race faces corresponds in timing with a decline in fixation on the internal features of other-race faces, and (c) the center of the face (i.e., the nose) is a differential region for processing same- versus other-race faces by Asian infants.

The Effect of Reducing the Number of Electrodes on Spatial Hearing Tasks for Bilateral Cochlear Implant Recipients

Many studies have documented the effect of reducing spectral information for speech perception in listeners with normal hearing and hearing impairment. While it is understood that more spectral bands are needed for unilateral cochlear implant listeners to perform well on more challenging listening tasks such as speech perception in noise, it is unclear how reducing the number of spectral bands or electrodes in cochlear implants influences the ability to localize sound or understand speech with spatially separate noise sources. The purpose of this study was to measure the effect of reducing the number of electrodes for patients with bilateral cochlear implants on spatial hearing tasks. Performance on spatial hearing tasks was examined as the number of bilateral electrodes in the speech processor was deactivated equally across ears and the full frequency spectrum was reallocated to a reduced number of active electrodes. Program parameters (i.e., pulse width, stimulation rate) were held constant among the programs and set identically between the right and left cochlear implants so that only the number of electrodes varied. Nine subjects had used bilateral Nucleus or Advanced Bionics cochlear implants for at least 12 mo prior to beginning the study. Only those subjects with full insertion of the electrode arrays with all electrodes active in both ears were eligible to participate. Two test measures were utilized to evaluate the effect of reducing the number of electrodes, including a speech-perception-in-noise test with spatially separated sources and a sound source localization test. Reducing the number of electrodes had different effects across individuals. Three patterns emerged: (1) no effect on localization (two of nine subjects), (2) at least two to four bilateral electrodes were required for maximal performance (five of nine subjects), and (3) performance gradually decreased across conditions as electrode number was reduced (two of nine subjects). For the test of speech perception in spatially separated noise, performance was affected as the number of electrodes was reduced for all subjects. Two categories of performance were found: (1) at least three or four bilateral electrodes were needed for maximum performance (five of seven subjects) and (2) as the number of electrodes were reduced, performance gradually decreased across conditions (two of seven subjects). Large individual differences exist in determining maximum performance using bilateral electrodes for localization and speech perception in noise. For some bilateral cochlear implant users, as few as three to four electrodes can be used to obtain maximal performance on localization and speech-in-noise tests. However, other listeners show a gradual decrement in performance on both tasks when the number of electrodes is reduced.

Imperatoxin Induces a Biphasic Response in Ca2+ Sparks

Imperatoxin induces a biphasic response in Ca2+ sparksImperatoxin A (IpTxa), isolated from the venom of the African scorpion Pandinus imperator, has been shown to specifically activate ryanodine receptors (RyR) and to be capable of translocating across cell membranes. IpTxa enhances [3H]ryanodine binding to sarcoplasmic reticulum (SR) and stabilizes subconducting states in single channels. We previously demonstrated that IpTxa alters the amplitude of calcium transients in intact field-stimulated cells, causing a rapid increase in transient amplitude. This is followed by a gradual decrement in amplitude to a new steady state at lower amplitude than in control. The current study seeks to clarify how IpTxa acts on RyRs to perturb Ca2+ handling in cardiomyocytes. We employed visualization of IpTxa-modified Ca2+ sparks in saponin-permeabilized cells to facilitate direct titration of RyRs with known concentrations of IpTxa, ranging from 500pM to 50nM. In addition, we modified our sparks protocol to enable a comparison of the caffeine-releasable SR Ca2+ load before and after treatment with the toxin. Our results demonstrate that IpTxa induces a biphasic RyR response, typified by a transient increase in spark frequency, amplitude, FWHM, and FDHM, which is rapidly followed by a sharp decrease in the same parameters. Comparison of pre- and post-toxin caffeine-releasable SR Ca2+ consistently reveals that SR content has been reduced as a result of IpTxa perfusion to approximately 75% of control. These results are consistent with the biphasic response observed in Ca2+ transient experiments. We believe that IpTxa sensitizes RyR to luminal Ca2+, leading to increased Ca2+ release and subsequent depletion of Ca2+ from the SR. Our findings have exciting implications for translational research into cardiac diseases such as catecholaminergic polymorphic ventricular tachycardia, in which acute RyR hyperactivity is hypothesized to trigger arrhythmias leading to sudden cardiac death.

Study of biocomplexity in an aquatic ecosystem through ascendency

The ascendancy concept aims at quantitatively describing the growth and development of an ecosystem as whole. Growth is an increase in the total system throughflow, while development is taken to be a rise in the average mutual information inherent in the network flow structure. As an ecosystem matures and goes through a series of successional stages, its ascendancy exhibits a propensity to increase. In any ecosystem the equilibrium condition may gradually turn into a chaotic situation for different reasons. In this paper a model is proposed of an aquatic ecosystem comprising of three groups, viz., phytoplankton, zooplankton and fish. Rate parameters are changed according to the change of the size of the organisms. The model is run in different conditions with gradual decrement of the body sizes of zooplankton. Allometric principle of the relationship of body size of zooplankton and two rate parameters (growth rate and half saturation constant) are incorporated in this model. According to allometric principle gradual decrement of body sizes of zooplankton consequently increases the grazing rate and decreases the half-saturation constant of this organisms. The system exhibits different states (equilibrium point – stable limit cycle – doubling and ultimately chaos) by gradual increase of zooplankton grazing rate and decrease of half-saturation constant. This paper tests the high level of ascendancy of the systems at the edge of oscillation before starting of the chaos. This high level of throughflow and mutual information, i.e. Ascendency supports the hypothesis that the system can coordinate the most complex behavior and shows maximum biocomplexity in this situation.

Long-term follow-up of postmenopausal breast cancer patients following discontinuation of tamoxifen therapy

BackgroundThere is a need to evaluate the extent of endometrial pathologies that might develop in postmenopausal breast cancer patients following discontinuation of tamoxifen (TAM) therapy. MethodsThe medical records of 153 postmenopausal breast cancer patients who remained untreated following discontinuation of tamoxifen therapy were evaluated for various clinical features, for endometrial thickness measurements, as detected by transvaginal ultrasonography, and for various endometrial pathologies detected. The last endometrial thickness measurement performed before discontinuation of tamoxifen was compared with endometrial thickness measured following discontinuation of tamoxifen. ResultsPatients were followed for 37.5±31.3 months. There was a gradual and significant decrement of endometrial thickness measured at the last ultrasonographic study performed before cessation of tamoxifen, compared to that observed in all four ultrasonographic studies performed following discontinuation of tamoxifen (P=0.001). Endometrial thickness gradually and significantly decreased in correlation with the time intervals of the four ultrasonographic studies performed following discontinuation of tamoxifen (P=0.001). Overall, 40 hysteroscopies were performed in 38 (24.8%) patients. No tissue was obtained in 18 (11.8%) patients. Overall endometrial pathologies were diagnosed in 22 (14.4%) patients. Benign endometrial polyps were the most frequent endometrial pathology recovered: 17 (11.1%) patients. No endometrial malignancy was diagnosed. The rate of endometrial pathologies considerably decreased with the extension of time following discontinuation of tamoxifen therapy. ConclusionsLong-term follow-up of postmenopausal breast cancer patients who remained untreated following discontinuation of TAM therapy did not reveal any malignant endometrial pathology. Only few benign endometrial pathologies were diagnosed, which became fewer in time.

The effects of transient attention on spatial resolution and the size of the attentional cue

It has been shown that transient attention enhances spatial resolution, but is the effect of transient attention on spatial resolution modulated by the size of the attentional cue? Would a gradual increase in the size of the cue lead to a gradual decrement in spatial resolution? To test these hypotheses, we used a texture segmentation task in which performance depends on spatial resolution, and systematically manipulated the size of the attentional cue: A bar of different lengths (Experiment 1) or a frame of different sizes (Experiments 2-3) indicated the target region in a texture segmentation display. Observers indicated whether a target patch region (oriented line elements in a background of an orthogonal orientation), appearing at a range of eccentricities, was present in the first or the second interval. We replicated the attentional enhancement of spatial resolution found with small cues; attention improved performance at peripheral locations but impaired performance at central locations. However, there was no evidence of gradual resolution decrement with large cues. Transient attention enhanced spatial resolution at the attended location when it was attracted to that location by a small cue but did not affect resolution when it was attracted by a large cue. These results indicate that transient attention cannot adapt its operation on spatial resolution on the basis of the size of the attentional cue.

GABAergic modulation of developing pedunculopontine nucleus

Rapid eye movement sleep decreases dramatically during development. We tested the hypothesis that some of this decrease may be due to GABAergic inhibition of reticular activating system neurons. Recordings of pedunculopontine neurons in vitro showed that the gamma-amino-butyric acid, receptor agonist muscimol depolarized noncholinergic cells early in the developmental decrease in rapid eye movement sleep, and hyperpolarized them later. Most cholinergic cells were hyperpolarized throughout the period tested. The gamma-amino-butyric acid b receptor agonist baclofen hyperpolarized both cholinergic and noncholinergic cells, although the degree of polarization decreased with age. Part of the gradual decrement in rapid eye movement sleep during development may be due in part to the increasing inhibition mediated by gamma-amino-butyric acid, a receptor on pedunculopontine neurons. This influence, however, appears to be mainly on noncholinergic cells.

Exposure to Varying Concentration of Fungal Spores in Grain Storage Godowns and its Effect on the Respiratory Function Status among the Workers

Grain storage depot workers suffer from different respiratory problems after getting the exposure to storage grain dust. Which is a mixture of pesticides, fungi, silica, bacteria, spores, storage mites, animal hairs, pollens etc. The present study was undertaken to evaluate the fungal spore concentration in summer and winter season as well as the pulmonary function status of the workers; studies are limited in our country. In summer and winter seasons, air sampling was done to measure the airborne fungal spore concentration inside the godowns by Rotorod sampler, UK. Aspergilla, Alternaria, Drechslera, Epicoccum, Nigrospora, Periconia were very much common and found higher in winter compared to summer. The respiratory functional status was assessed in two groups of workers of the same storage grain depot (total n=316) in summer (n=136) and in winter (n=180). List of the workers was collected from the authority and randomly selected every alternate worker and divide them for the studies in summer and winter seasons. Slow Vital Capacity (SVC), Forced Vital Capacity (FVC), and Peak Expiratory Flow Rate (PEFR) were recorded and Forced Expiratory Volume in one second (FEV1), FEV1% and different flow rates were calculated. The Immunoglobulin- E (IgE) level in the blood serum was assessed on post shift pulmonary function tests (PFT) decreased workers. The age, height and weight of the same categories of workers of both studies are highly comparable. Mean PFT values in summer found higher than winter. A gradual decrement of values were found as age was increased but not with duration of exposure. Post-shift PFT was carried in 21.8% (69) workers of which 46.4% (32) workers showed the decrement of values. The serum IgE level of the post-shift PFT decreased subjects was found more than 250 IU/ml in 53.1% (17) workers. Restrictive, obstructive and combined types of respiratory impairments were noticed among the workers. Presence of different spores in varying concentration in the working atmosphere may be responsible for the post shift decrement of PFT, allergic symptoms, high IgE level and respiratory impairments among the workers.

Standardized assessment of cognitive functioning during development and aging using an automated touchscreen battery

This study examined the effects of age, gender and education on subjects spanning nine decades on a new cognitive battery of 12 tests. One thousand and seven participants between 6 and 82 completed the battery under standardized conditions using an automated, computerized touchscreen. Sensitive indicators of change were obtained on measures of attention and working memory, learning and memory retrieval, and language, visuospatial function, sensori-motor and executive function. Improvement tended to occur through to the third and fourth decade of life, followed by gradual decrement and/or stabilized performance thereafter. Gender differences were obtained on measures of sustained attention, verbal learning and memory, visuospatial processing and dexterity. Years of education in adults was reflected in performance on measures of verbal function. Overall, the test battery provided sensitive indicators on a range of cognitive functions suitable for the assessment of abnormal cognition, the evaluation of treatment effects and for longitudinal case management.

Contrast sensitivity tests in predicting visual function

Testing contrast sensitivity function is one of the most important tests available for evaluating functional visual impairment. The contrast level determines visual function more precisely than the visual acuity measurement. There are numerous contrast sensitivity function tests, but the two that are clinically practical are Pelli-Robson and MARS. Both tests use uniform letter size with a gradual decrement of contrast from nearly 100% to less than 5%. The decrease in contrast between each letter is 0.15 log units for the Pelli, and 0.04 log units for the MARS. The sensitivity of the MARS test makes it ideal to document small losses of CSF over time. Scoring the test will be described as well as two case studies and conclusions from a study of 122 patients.

Cell-induced copper ion-mediated low density lipoprotein oxidation increases during in vivo monocyte-to-macrophage differentiation

Macrophage activation is associated with the production and release of reactive oxygen species (ROS), which are capable of mediating oxidative modification of low-density lipoprotein (LDL). In the present study we questioned whether cellular capacity to oxidize LDL increases during in vivo monocyte /macrophage maturation. We developed a novel model for macrophage maturation in vivo using mouse peritoneal macrophages (MPMs) harvested at increasing intervals after intraperitoneal thioglycollate injection. Macrophage maturation was evidenced by a progressive increase in cellular size, density, granulation, and expression of cell surface markers CD11b and CD36, and by a gradual decrement in myeloperoxidase activity. Cellular capacity to stimulate copper ion-mediated oxidation of LDL increased gradually by up to 2-fold during in vivo macrophage maturation in Balb/C mice, similar to the pattern observed during 1,25-dihydroxyvitamin D 3-induced in vitro differentiation of the PLB-985 cell line. These effects were attributed to a gradual increase in production of ROS by up to 9-fold. The mechanism for the increase in cellular oxidative stress during macrophage maturation could be related, at least in part, to NADPH oxidase activation, as demonstrated by a gradual increase over time in p47 phox expression (mRNA and protein) and in its translocation to the plasma membrane. In conclusion, in vivo monocyte-to-macrophage differentiation is associated with increased cell capacity to oxidize LDL, which may represent a protective mechanism for rapid removal of atherogenic LDL from extracellular spaces in the arterial wall.

Cell-induced copper ion-mediated low density lipoprotein oxidation increases during in vivo monocyte-to-macrophage differentiation

Macrophage activation is associated with the production and release of reactive oxygen species (ROS), which are capable of mediating oxidative modification of low-density lipoprotein (LDL). In the present study we questioned whether cellular capacity to oxidize LDL increases during in vivo monocyte/macrophage maturation. We developed a novel model for macrophage maturation in vivo using mouse peritoneal macrophages (MPMs) harvested at increasing intervals after intraperitoneal thioglycollate injection. Macrophage maturation was evidenced by a progressive increase in cellular size, density, granulation, and expression of cell surface markers CD11b and CD36, and by a gradual decrement in myeloperoxidase activity. Cellular capacity to stimulate copper ion-mediated oxidation of LDL increased gradually by up to 2-fold during in vivo macrophage maturation in Balb/C mice, similar to the pattern observed during 1,25-dihydroxyvitamin D3-induced in vitro differentiation of the PLB-985 cell line. These effects were attributed to a gradual increase in production of ROS by up to 9-fold. The mechanism for the increase in cellular oxidative stress during macrophage maturation could be related, at least in part, to NADPH oxidase activation, as demonstrated by a gradual increase over time in p47phox expression (mRNA and protein) and in its translocation to the plasma membrane. In conclusion, in vivo monocyte-to-macrophage differentiation is associated with increased cell capacity to oxidize LDL, which may represent a protective mechanism for rapid removal of atherogenic LDL from extracellular spaces in the arterial wall.

Pulmonary function abnormalities associated with exposure to automobile exhaust in a diesel bus garage and roads.

In Kolkata city the road transports are maintained by private and Government organization. A major work force belonged to the State Transport Corporation (KSTC), Government of West-Bengal. The pollution caused by these vehicles affects the workers health and caused different types of respiratory problems. This study was undertaken to assess the pulmonary function status of these workers. City KSTC garage workers were investigated and categorically divided into two group: garage mechanics and the (2) those transporting the passengers (drivers and conductors). Vital capacity (VC), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) were recorded by Spirovit-SP-10 (Schiller Ltd, Switzerland) and Wright's Peak Flow Meter (UK) on 236 workers. The different flow volumes, FEV(1), FEV(1%), and flow rates, FEF(02-121), FEF(25-75%), etc. were calculated. The administrative people had higher PFT than the other categories. Drivers and conductors have almost equal mean PFT values but mechanical workers had slightly higher. PFT values according to different age ranges and duration of exposure showed gradual decrement as age and duration of exposure increased. Non-smokers had higher lung volumes compared to smokers and ex-smokers. Restrictive, obstructive and combined types of impairments were noticed in 28.4%, 1.7% and 2.9%, respectively, workers. The restrictive impairment was found to be 30.4% in conductors; 28.9% in drivers, 27.9% in mechanics and 21.7% in administration people. Obstructive type of impairment was found to be 2.9% in both drivers and conductors. The effect of pollution by dust and fumes may be responsible for these pulmonary function impairments, restrictive impairments being greater.

Patterns of change: information change and congressional budget deliberations revisited

How did the Planning Programming Budgeting System (PPBS), and the Congressional Budget and Impoundment Control Act (CBA) of 1974 change the nature of budget hearing deliberations in Congress? This study focuses upon the inquiry search patterns from 1949 through 1984 for the three House Appropriations subcommittees that reviewed the Forest, Parks, Prison, Internal Revenue, and Immigration and Naturalization Services' budget requests. After PPBS was implemented, all three subcommittees emphasized programmatic questioning more and object-of-expenditure questioning less. The more prevalent pattern of change was an abrupt change after implementing the budget reform followed by a gradual cumulative effect in subsequent years. A less prevalent pattern was an abrupt change followed by a gradual decrement over time.

Negative feedback functions in chronically stressed rats: role of the posterior paraventricular thalamus

A gradual decrement in hypothalamic–pituitary–adrenal (HPA) activity is observed following repeated exposure to the same stressor, such as repeated restraint. This decrement, termed habituation, may be partly due to alterations in corticosterone-mediated negative feedback inhibition of the HPA axis. We have previously found that the posterior division of the paraventricular thalamus (pPVTh) regulates habituated HPA activity without altering HPA responses to acute stress. Therefore, in the present study, we examined the role of the pPVTh in delayed feedback inhibition of plasma corticosterone responses to repeated restraint. Dexamethasone was administered subcutaneously 2 h prior to 30 min restraint to induce delayed negative feedback inhibition of the HPA axis. In the first experiment, we determined that a 0.05-mg/kg dose of dexamethasone produced submaximal suppression of corticosterone responses to acute restraint and used this dose in the remainder of the experiments. In Experiment 2, we examined dexamethasone-induced feedback inhibition to corticosterone responses to a single or eighth restraint exposure since negative feedback functions in chronically stressed rats are not well studied. We found that corticosterone levels following dexamethasone treatment were similar in repeatedly restrained compared to acutely restrained rats. In Experiment 3, we lesioned the pPVTh and examined dexamethasone-induced feedback inhibition of corticosterone responses to a single or eighth exposure to restraint. pPVTh lesions attenuated dexamethasone-induced inhibition of corticosterone at 30 min in chronically stressed rats but had no effect in acutely stressed rats. These data suggest that negative feedback functions are maintained in rats exposed to repeated restraint and implicate the pPVTh as a site that contributes to these negative feedback functions specifically under chronic stress conditions.

Molecular target structures in alloxan-induced diabetes in mice

Type 1 diabetes results from irreversible damage of insulin-producing β-cells. In laboratory animals, diabetes can be induced with alloxan (ALX), a 2,4,5,6-tetraoxopyrimidine. ALX is a potent generator of reactive oxygen species (ROS), which can mediate β-cell toxicity. However, the initial lesions on essential β-cell structures are not known. In this study, we report that the glucose transporter 2 (GLUT2) and glucokinase (GK) are target molecules for ALX. Ex vivo, a gradual decrement of both GLUT2 and GK mRNA expression was found in islets isolated from ALX-treated C57BL/6 mice. This reduction was more pronounced for GLUT2 than for GK. The mRNA expression of β-actin was also slightly affected with time after ALX exposure, the proinsulin mRNA, however, remained unaffected as well as the pancreatic total insulin content. Pretreatment with D-glucose (D-G) protected the mRNA expression of GLUT2 and GK against ALX toxicity and prevented diabetes. Yet, in these euglycemic mice, an impaired oral glucose tolerance persisted. Pretreatment with 5-thio-D-glucose (5-T-G) failed to prevent ALX diabetes, administration of zinc sulfate (Zn 2+)-enriched drinking water, however, reduced ALX-induced hyperglycemia. In conclusion, ALX exerted differential toxicity on β-cell structures similar to in vitro results reported from this laboratory. Furthermore, the present results differ from those reported for the diabetogen streptozotocin (STZ). Injections of multiple low doses (MLD) of STZ reduced GLUT2 expression only, but failed to affect expression of GK and proinsulin as well as β-actin as internal control. MLD-STZ diabetes was prevented by pretreatment with both D-G and 5-T-G and administration of Zn 2+-enriched drinking water. Apparently, ALX and MLD-STZ exert diabetogenicity by different pathways requiring different interventional schedules for prevention.