Localization of Idd11 using NOD congenic mouse strains: elimination of Slc9a1 as a candidate gene

 Type 1 diabetes is a multigenic autoimmune disease, the genetic basis for which is perhaps best characterized in the nonobese diabetic (NOD) mouse model. We previously located a NOD diabetes susceptibility locus, designated Idd11, on mouse Chromosome (Chr) 4 by analyzing diabetic backcross mice produced after crossing NOD/Lt with the nondiabetic resistant strain C57BL/6 (B6) strain. In order to confirm Idd11 and further refine its location, three NOD congenic mouse strains with different B6 derived intervals within Chr 4 were generated. Two of the congenic strains had a significant decrease in the cumulative incidence of diabetes compared with NOD/Lt control mice. The third NOD congenic strain, containing a B6 interval surrounding the Slc9a1 locus, was not protected against diabetes. These results define a new distal boundary for Idd11 and eliminate the Slc9a1 gene as a candidate. The Idd11 locus has now been definitively mapped to a 13cM interval on mouse Chr 4. Received: 15 May 1999 / Revised: 25 September 1999     

Dynamic Changes of CD4<Superscript>+</Superscript>CD25<Superscript>+</Superscript> Regulatory T Cells in NOD.H-2<Superscript>h4</Superscript> Mice with Iodine-Induced Autoimmune Thyroiditis

Iodine is an essential trace element for thyroid hormone synthesis and metabolism, either low or high intake may lead to thyroid disease, but the pathogenetic mechanisms by which iodine interacts with the thyroid autoimmune are poorly understood. We investigated the dynamic changes of CD4⁺CD25⁺ regulatory T cells in NOD.H-2^h4 mice with iodine-induced autoimmune thyroiditis (AIT), and explore potential immune mechanism of AIT induced by iodine. NOD.H-2^h4 mice were randomly divided into two groups, and received plain water or water containing 0.005% sodium iodide. Eight weeks after iodine provision, the incidences of thyroiditis, relative weights of thyroids, and serum thyroglobulin antibody titers in the iodine-supplied groups were significantly increased compared to the control groups (p < 0.05). The AIT mice had fewer CD4⁺CD25⁺Foxp3⁺ T cells and reduced Foxp3 mRNA expression in splenocytes compared with the controls (p < 0.01), and maintained relatively low levels during the development of thyroiditis. The changes described above aggravated gradually with the extension of iodine treatment. These data suggest that CD4⁺CD25⁺ regulatory T cells may be involved in the pathogenesis and development of AIT induced by iodine.     

The root–soil system of Norway spruce subjected to turning moment: resistance as a function of rotation

The reactions of trees to wind, rockfall, and snow and debris flow depend largely on how strong and deformable their anchorage in the soil is. Here, the resistive turning moment M of the root–soil system as a function of the rotation ϕ at the stem base plays the major role. M(ϕ) describes the behavior of the root–soil system when subject to rotational moment, with the maximum M(ϕ) indicating the anchorage strength M _a of the tree. We assessed M(ϕ) of 66 Norway spruce (Picea abies L. Karst) by pulling them over with a winch. These 45- to 170-year-old trees grew at sites of low and high elevation, with a diameter at breast height DBH = 14–69 cm and a height H = 9–42 m. M(ϕ) displayed a strong nonlinear behavior. M _a was reached at a lower ϕ for large trees than for small trees. Thus overhanging tree weight contributed less to M _a for the large trees. Overturning also occurred at a lower ϕ for the large trees. These observations show that the rotational ductility of the root–soil system is higher for small trees. M _a could be described by four monovariate linear regression equations of tree weight, stem weight, stem volume and DBH ² ·H (0.80 < R ² < 0.95), and ϕ at M _a, ϕ _a, by a power law of DBH²·H (R ² = 0.85). We found significantly higher M _a for the low-elevation spruces than for the high-elevation spruces, which were more shallowly anchored, but no significant difference in ϕ _a. The 66 curves of M(ϕ), normalized (_n) by M _a in M-direction and by ϕ _a in ϕ-direction, yielded one characteristic average curve: . Using and the predictions of M _a and ϕ _a, it is shown that M(ϕ) and the curves associated with M(ϕ) can be predicted with a relative standard error ≤25%. The parameterization of M(ϕ) by tree size and weight is novel and provides useful information for predicting with finite-element computer models how trees will react to natural hazards.     

Effect of clenbuterol on apoptosis,adipogenesis, and lipolysis in adipocytes

Clenbuterol, a beta₂-adrenergic receptor (β₂-AR) selective agonist, has been shown to decrease body fat in animals and can induce apoptosis in adipose tissue in mice. We hypothesized that direct actions of a β-adrenergic receptor agonist on adipocytes could trigger the observed apoptotic effect. The hypothesis was inspected by investigating the direct effect of clenbuterol on apoptosis, adipogenesis, and lipolysis in vitro using the 3T3-L1 cell line and rat primary adipocytes. Cells were treated with 10⁻⁹ to 10⁻⁵ M clenbuterol depending on the experiments. There was no apoptotic effect of clenbuterol both in 3T3-L1 cells and rat primary adipocytes. Adipogenesis monitored by Oil Red O staining and AdipoRed™ assay was modestly decreased by clenbuterol treatment (p < 0.05). In fully differentiated primary adipocytes, clenbuterol increased basal lipolysis compared with the control (p < 0.01). In summary, direct stimulation of β₂-AR by clenbuterol does not cause apoptosis in adipocytes, despite a direct lipolytic stimulation and attenuation of adipogenesis.     

Effect of intense interval workouts on running economy using three recovery durations

The purposes of this study were to determine whether running economy (RE) is adversely affected following intense interval bouts of 10 × 400-m running, and whether there is an interaction effect between RE and recovery duration during the workouts. Twelve highly trained male endurance athletes [maximal oxygen consumption; V˙O_{2 max} =72.5 (4.3) ml·kg⁻¹·min⁻¹; mean (SD)] performed three interval running workouts of 10 × 400 m with a minimum of 4 days between runs. Recovery duration between the repetitions was randomly assigned at 60, 120 or 180 s. The velocity for each 400-m run was determined from a treadmill V˙O_{2 max} test. The average running velocity was 357.9 (9.0) m · min⁻¹. Following the workout, the rating of perceived exertion (RPE) increased significantly (P < 0.01) as recovery duration between the 400-m repetitions decreased (14.4, 16.1, and 17.7 at 180s, 120s, and 60 s recovery, respectively). Prior to and following each workout, RE was measured at speeds of 200 and 268 m · min⁻¹. Changes in RE from pre- to post-workout, as well as heart rate (HR) and respiratory exchange ratio (R) were similar for the three recovery conditions. When averaged across conditions, oxygen consumption (V˙O₂) increased significantly (P < 0.01) from pre- to post-test (from 38.5 to 40.5 ml · kg⁻¹ · min⁻¹ at 200 m · min⁻¹, and from 53.1 to 54.5 ml · kg⁻¹ · min⁻¹ at 268 m · min⁻¹, respectively). HR increased (from 124 to 138, and from 151 to 157 beats · min⁻¹ respectively) and R decreased (from 0.90 to 0.78, and from 0.93 to 0.89, respectively) at 200 and 268 m · min⁻¹, respectively (P < 0.01). This study showed that RE can be perturbed after a high-intensity interval workout and that the changes in V˙O₂, HR and R were independent of the recovery duration between the repetitions. Accepted: 23 June 1997     

Changes in Serum Zinc Levels Associated with Giardiasis and Dietary Zinc Intake in Mice

The association of giardiasis with the malabsorption of zinc remains controversial. This study investigated changes in serum zinc levels in Giardia-infected mice subjected to different dietary zinc regimens. Thirty-five mice (strain C₃H/H_eJ) were randomly categorized into two groups. The first group was inoculated with 5 × 10⁶ Giardia trophozoites (n = 18), and the second group remained Giardia free (n = 17). Each group (Giardia infected and Giardia free) was randomly classified into three subgroups and given low (9 mg Zn/kg), normal (33 mg Zn/kg), and high levels (288 mg Zn/kg) of dietary zinc over a 2-week period for acclimation. Fourteen days post-Giardia infection, all of the mice were euthanized and blood samples were collected. The number of trophozoites was quantified (hematocytometer), and serum zinc levels were determined via atomic absorption spectrophotometry. Significant increases in the median weights were only found in the Giardia-free mice (p < 0.05). A higher final median weight was found in the Giardia-free group when compared with that of the Giardia-infected group given low dietary zinc (p = 0.013). In the Giardia-infected group with low dietary zinc, the geometric mean of trophozoites was 3,498 ± 101 (SE) per milliliter. The Giardia-infected group had lower serum zinc levels than did the Giardia-free group with the high dietary zinc regimens (p < 0.05). Our results are consistent with studies among human populations, but further studies are required to elucidate the actual mechanism governing the zinc–giardiasis interaction.     

Enhanced activation of dendritic cells by autologous apoptotic microvesicles in MRL/lpr mice

IntroductionSystemic lupus erythematosus is associated with a persistent circulation of modified autoantigen-containing apoptotic debris that might be capable of breaking tolerance. We aimed to evaluate apoptotic microvesicles obtained from lupus or control mice for the presence of apoptosis-associated chromatin modifications and for their capacity to stimulate dendritic cells (DC) from lupus and control mice.MethodApoptotic microvesicles were in vitro generated from splenocytes, and ex vivo isolated from plasma of both MRL/lpr lupus mice and normal BALB/c mice. Microvesicles were analyzed using flow cytometry. Bone marrow-derived (BM)-DC cultured from MRL/lpr or BALB/c mice were incubated with microvesicles and CD40 expression and cytokine production were determined as measure of activation.ResultsMicrovesicles derived from apoptotic splenocytes or plasma of MRL/lpr mice contained more modified chromatin compared to microvesicles of BALB/c mice, and showed enhanced activation of DC, either from MRL/lpr or BALB/c mice, and consecutively an enhanced DC-mediated activation of splenocytes. The content of apoptosis-modified chromatin in microvesicles of apoptotic splenocytes correlated with their potency to induce interleukin-6 (IL-6) production by DC. Microvesicle-activated MRL/lpr DC showed a significant higher production of IL-6 and tumor growth factor-β (TGF-β) compared to BALB/c DC, and were more potent in the activation of splenocytes.ConclusionApoptotic microvesicles from MRL/lpr mice are more potent activators of DC, and DC from MRL/lpr mice appear relatively more sensitive to activation by apoptotic microvesicles. Our findings indicate that aberrations at the level of apoptotic microvesicles and possibly DC contribute to the autoimmune response against chromatin in MRL/lpr mice.     

Effect of Alcoholic Intoxication on the Risk of Inflammatory Bowel Disease: A Nationwide Retrospective Cohort Study

PurposeThis study investigated whether alcoholic intoxication (AI) increases the risk of inflammatory bowel disease (IBD) by using a population-based database in Taiwan.MethodsThis retrospective matched-cohort study included 57 611 inpatients with new-onset AI (AI cohort) and 230 444 randomly selected controls (non-AI cohort). Each patient was monitored for 10 years to individually identify those who were subsequently diagnosed with Crohn disease (CD) and ulcerative colitis (UC) during the follow-up period. Cox proportional hazard regression analysis was conducted to determine the risk of IBD in patients with AI compared with controls without AI.ResultsThe incidence rate of IBD during the 10-year follow-up period was 2.69 per 1 000 person-years and 0.49 per 1 000 person-years in the AI and non-AI cohorts, respectively. After adjustment for age, sex, and comorbidity, the AI cohort exhibited a 3.17-fold increased risk of IBD compared with the non-AI cohort (hazard ratio [HR] = 3.17, 95% confidence interval [CI] = 2.19–4.58). Compared with the non-AI cohort, the HRs of CD and UC were 4.40 and 2.33 for the AI cohort, respectively. After stratification for the severity of AI according to the duration of hospital stay, the adjusted HRs exhibited a significant correlation with the severity; the HRs of IBD were 1.76, 6.83, and 19.9 for patients with mild, moderate, and severe AI, respectively (p for the trend < .0001).ConclusionThe risk of IBD was higher in patients with AI and increased with the length of hospital stay.     

Osmotic water permeability of isolated vacuoles

We measured the osmotic water permeability (P _os) of vacuoles isolated from onion (Allium cepa L.), rape (Brassica napus L.), petunia (Petunia hybrida Hook.) and red beet (Beta vulgaris L.). For all the vacuolar types investigated, P _os values were in the range 200–1000 μm s⁻¹. The change in membrane surface area induced by an osmotic gradient was smaller than 2–6%. The vacuolar P _os values for red beet and onion were reduced by 1 mM HgCl₂, to 14% and 30% of the control values, respectively, but were partially restored to 51% and 76% by 5 mM β-mercaptoethanol. These results suggest that aquaporins were present in all the vacuoles tested. In HgCl₂-treated onion vacuoles, the reduced P _os (56 μm s⁻¹) had a low activation energy (approx. 6 kJ mol⁻¹), indicating that water permeation was still occurring mainly via aquaporins, and that the water permeability of the lipid part of the vacuolar membrane is probably very low. Received: 18 February 1999 / Accepted: 21 June 1999     

Phenotypic variation in seasonal adjustments of testis size, body weight, and food intake in deer mice: role of pineal function and ambient temperature

We investigated pineal function as well as reproductive and energetic characteristics in male deer mice (Peromyscus maniculatus) that differentially respond to short photoperiod with full, partial or no gonadal regression. In mice at both high (23 °C) and low temperature (1 °C), these phenotypic differences in reproductive responses to short days were not reflected by differences in urinary excretion of 6-sulphatoxy-melatonin, the main metabolite of pineal melatonin. Neither duration nor amplitude or phase-angle of nocturnal peaks in 6-sulphatoxymelatonin significantly differed between reproductive phenotypes at either temperature. Differences in testis size were, however, associated with different energy requirements. In gonadally regressed males only, food intake and body weight were significantly (P < 0.01) reduced by up to 29% and 13% respectively. Chronic cold exposure (5 °C) had no effect on the proportion of males undergoing testicular regression under short days, but caused a general elevation in body weights among all mice (P < 0.05). Phenotypic differences in body weight and food intake were maintained in the cold. Together, these results suggest that within-population variation of reproductive responses in male deer mice is based on post-pineal differences in the regulation of gonadal function, and that phenotypic characteristics in reproductive and energetic responses to short days are largely unaffected by ambient temperature. Accepted: 2 October 1995     

Topographic analysis of dimension estimates of EEG and filtered rhythms in epileptic patients with complex partial seizures

Nonlinear dynamic properties were analyzed on the EEG and filtered rhythms recorded from healthy subjects and epileptic patients with complex partial seizures. Estimates of correlation dimensions of control EEG, interictal EEG and ictal EEG were calculated. The values were demonstrated on topograms. The delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (13–30 Hz) and gamma (30–40 Hz) components were obtained and considered as signals from the cortex. Corresponding surrogate data was produced. Firstly, the influence of sampling parameters on the calculation was tested. The dimension estimates of the signals from the frontal, temporal, parietal and occipital regions were computed and compared with the results of surrogate data. In the control subjects, the estimates between the EEG and surrogate data did not differ (P > 0.05). The interictal EEG from the frontal region and occipital region, as well as its theta component from the frontal region, and temporal region, showed obviously low dimensions (P < 0.01). The ictal EEG exhibited significantly low-dimension estimates across the scalp. All filtered rhythms from the temporal region yielded lower results than those of the surrogate data (P < 0.01). The dimension estimates of the EEG and filtered components markedly changed when the neurological state varied. For each neurological state, the dimension estimates were not uniform among the EEG and frequency components. The signal with a different frequency range and in a different neurological state showed a different dimension estimate. Furthermore, the theta and alpha components demonstrated the same estimates not only within each neurological state, but also among the different states. These results indicate that the theta and alpha components may be caused by similar dynamic processes. We conclude that the brain function underlying the ictal EEG has a simple mechanism. Several heterogeneous dynamic systems play important roles in the generation of EEG. Received: 10 December 1999 / Accepted in revised form: 8 May 2000     

Achilles tendon loading during walking: application of a novel optic fiber technique

An optic fiber (? 0.5 mm) was utilized for the study of Achilles tendon forces (ATF) in eight volunteers who walked over a 10 m force platform at three speeds (1.1 ± 0.1 m × s⁻¹, 1.5 ± 0.1 m × s⁻¹ and 1.8 ± 0.2 m × s⁻¹). The presented ATF-time curves showed great intersubject variation in magnitudes of the sudden release of force after initial contact and in the peak ATF's (1430 ± 500 N). This intersubject variation in the peak force decreased only by 4% when cross-sectional area of the tendon was considered. Measured ground reaction forces and plantar pressures confirmed that the subjects walked quite normally during recordings. The peak ATF was found to be rather insensitive to speed in contrast to the rate of ATF development which increased 32% ( p < 0.5) from slow to fast walking speed. It is concluded that the optic fiber technique can be applied to study loading of the musculo-tendinous complex during normal locomotion such as walking. Accepted: 13 October 1997     

Serum Mercury Level and Multiple Sclerosis

Exposure to heavy metals has been associated to a higher incidence of multiple sclerosis. In this work, we present a possible relationship between serum mercury levels and development of multiple sclerosis in Isfahan, the third largest city in Iran. Seventy-four patients affected by multiple sclerosis were retrieved from multiple sclerosis (MS) clinic in Isfahan, Iran. By matching sex and age, 74 healthy volunteers were chosen as control group. Blood samples were collected and serum mercury content was determined. Serum mercury level in MS patients was significantly higher than controls (9.6 ± 10.17 vs. 5.7 ± 8.6, P = 0.037). Concerning all MS patients, serum mercury value was significantly higher than the mercury concentration founded in control subjects {odd ratio: 2.39 (CI, 1.96–2.94), P = 0.00}. Serum mercury level is higher in MS patients with odd ratio equal to 2.39 compared with healthy individuals. It may reveal that high mercury levels in serum might help MS development in susceptible individuals. More studies with larger sample size are needed to confirm this hypothesis.     

High-dose green tea polyphenols induce nephrotoxicity in dextran sulfate sodium-induced colitis mice by down-regulation of antioxidant enzymes and heat-shock protein expressions

Previously, we reported that oral feeding of 1% green tea polyphenols (GTPs) aggravated the dextran sulfate sodium (DSS)-induced colitis in mice. In the present study, we assessed the toxicity of 1% GTPs in several organs from normal and DSS-exposed mice. Sixty-two male ICR mice were initially divided into four groups. Non-treated group (group 1, n = 15) was given standard diet and water, GTPs (group 2, n = 15) received 1% GTPs in diet and water, DSS (group 3, n = 15) received diet and 5% DSS in water, and GTPs + DSS group (group 4, n = 17) received 1% GTPs in diet and 5% DSS in water. We found that group 4 significantly increased (P < 0.05) kidney weight, the levels of serum creatinine and thiobarbituric acid-reactive substances in both kidney and liver, as compared with those in group 3. The mRNA expression levels of antioxidant enzymes and heat-shock proteins (HSPs) in group 4 were lower than those of group 3. For instance, heme oxygenase-1 (HO-1), HSP27, and 90 mRNA in the kidney of group 4 were dramatically down-regulated as compared with those of group 3. Furthermore, 1% GTPs diet decreased the expression of HO-1, NAD(P)H:quinone oxidoreductase 1 (NQO1) and HSP90 in kidney and liver of non-treated mice. Taken together, our results indicate that high-dose GTPs diet disrupts kidney functions through the reduction of antioxidant enzymes and heat-shock protein expressions in not only colitis but also non-treated ICR mice.     

Studies on water transport through the sweet cherry fruit surface: characterizing conductance of the cuticular membrane using pericarp segments

Water conductance of the cuticular membrane (CM) of mature sweet cherry fruit (Prunus avium L. cv. Sam) was investigated by monitoring water loss from segments of the outer pericarp excised from the cheek of the fruit. Segments consisted of epidermis, hypodermis and several cell layers of the mesocarp. Segments were mounted in stainless-steel diffusion cells with the mesocarp surface in contact with water, while the outer cuticular surface was exposed to dry silica (22 ± 1 °C). Conductance was calculated by dividing the amount of water transpired per unit area and time by the difference in water vapour concentration across the segment. Conductance values had a log normal distribution with a median of 1.15 × 10⁻⁴ m s⁻¹ (n=357). Transpiration increased linearly with time. Conductance remained constant and was not affected by metabolic inhibitors (1 mM NaN₃ or 0.1 mM carbonylcyanide m-chlorophenylhydrazone) or thickness of segments (range 0.8–2.8 mm). Storing fruit (up to 42 d, 1 °C) used as a source of segments had no consistent effect on conductance. Conductance of the CM increased from cheek (1.16 ± 0.10 × 10⁻⁴ m s⁻¹) to ventral suture (1.32 ± 0.07 × 10⁻⁴ m s⁻¹) and to stylar end (2.53 ± 0.17 × 10⁻⁴ m s⁻¹). There was a positive relationship (r²=0.066**; n=108) between conductance and stomatal density. From this relationship the cuticular conductance of a hypothetical astomatous CM was estimated to be 0.97 ± 0.09 × 10⁻⁴ m s⁻¹. Removal of epicuticular wax by stripping with cellulose acetate or extracting epicuticular plus cuticular wax by dipping in CHCl₃/methanol increased conductance 3.6- and 48.6-fold, respectively. Water fluxes increased with increasing temperature (range 10–39 °C) and energies of activation, calculated for the temperature range from 10 to 30 °C, were 64.8 ± 5.8 and 22.2 ± 5.0 kJ mol⁻¹ for flux and vapour-concentration-based conductance, respectively. Received: 23 March 2000 / Accepted: 28 July 2000     

Effects of artificially-induced anaemia on sudomotor and cutaneous blood flow responses to heat stress

The influence of artificially induced anaemia on thermal strain was evaluated in trained males. Heat stress trials (38.6°C, water vapour pressure 2.74 kPa) performed at the same absolute work rates [20 min of seated rest, 20 min of cycling at 30% peak aerobic power (V˙O_2peak), and 20 min cycling at 45% V˙O_2peak] were completed before (HST1) and 3–5 days after 3 units of whole blood were withdrawn (HST2). Mild anaemia did not elevate thermal strain between trials, with auditory canal temperatures terminating at 38.5°C [(0.16), HST1] and 38.6°C [(0.13), HST2; P > 0.05]. Given that blood withdrawal reduced aerobic power by 16%, this observation deviates from the close association often observed between core temperature and relative exercise intensity. During HST2, the absolute and integrated forearm sweat rate (m˙ _sw) exceeded control levels during exercise (P < 0.05), while a suppression of forehead m˙ _sw occurred (P < 0.05). These observations are consistent with a possible peripheral redistribution of sweat secretion. It was concluded that this level of artificially induced anaemia did not impact upon heat strain during a 60-min heat stress test. Accepted: 17 April 1997     

Relationship Between Serum Calcium and Magnesium Concentrations and Metabolic Syndrome Diagnostic Components in Middle-Aged Korean Men

It is thought that calcium and magnesium may be related to metabolic disorders such as obesity and metabolic syndrome; however, to date, there have been few studies investigating the association between serum calcium and magnesium levels and metabolic syndrome in middle-aged male adults. We aimed to investigate the association between serum calcium and magnesium levels and metabolic syndrome in Korean middle-aged male adults. Study subjects included 213 men aged 30∼60 years. MetS risk score is determined by adding the number of risk factors, waist circumference, triacylglyceride (TG), HDL cholesterol, glucose, and blood pressure (BP). The study population was divided into three groups according to the MetS risk score: group I (MetS risk score ≤1; n = 106), group II (MetS risk score = 2; n = 51), and group III (MetS risk score ≥3; n = 56). The serum Ca, according to increase of MetS risk score, was significantly higher (p < 0.001), and there was no significant difference in serum Mg concentration among the three groups. Subjects with high TG and high BP had higher serum calcium levels than those without such abnormalities. Subjects with higher glucose had lower serum magnesium levels than those without such abnormality. The correlation analysis indicated that the serum Ca had positive correlations with the MetS risk score (r = 0.1769, p < 0.01), serum TG (r = 0.2516, p < 0.001), and DBP (r = 0.2246, p < 0.01). The correlation analysis indicated that the serum Mg had an inverse relationship with serum glucose (r = −0.2404, p < 0.001). In conclusion, serum Ca had positive association with TG and BP, while serum Mg had negative association with serum glucose after adjusting age and BMI among the middle-aged Korean male adults.     

Aged mice have increased inflammatory monocyte concentration and altered expression of cell-surface functional receptors

The expression of monocyte cell-surface receptors represents one index of immune dysfunction, which is common with aging. Although mouse models of aging are prevalent, monocyte subset assessment is rare. Our purpose was to compare cell receptor expression on classic (CD115⁺/Gr-1^high) and non-classic (CD115⁺/Gr-1^low) monocytes from 80- or 20-week-old CD-1 mice. Three-colour flow cytometry was used to determine the concentration of monocyte subsets and their respective cell-surface expression of TLR2, TLR4, CD80, CD86, MHC II and CD54. These receptors were selected because they have been previously associated with altered monocyte function. Data were analysed with independent t-tests; significance was set at P < 0.05. Old mice had a greater concentration of both classic (258%, P = 0.003) and non-classic (70%, P = 0.026) monocytes. The classic : non-classic monocyte ratio doubled in old as compared with that in young mice (P = 0.006), indicating a pro-inflammatory shift. TLR4 (↓27%, P = 0.001) and CD80 (↓37%, P = 0.004) were decreased on classic monocytes from old as compared with those from young mice. TLR2 (↑24%, P = 0.002) and MHCII (↓21%, P = 0.026) were altered on non-classic monocytes from old as compared with those from young mice. The increased classic : non-classic monocyte ratio combined with changes in the cell-surface receptor expression on both monocyte subsets is indicative of immune dysfunction, which may increase age-associated disease risk.     

Blood flow in the carotid artery during breath-holding in relation to diving bradycardia

The present study investigated the mechanism of diving bradycardia. A group of 14 healthy untrained male subjects were examined during breath-holding either out of the water (30–33°C), in head-out immersion, or in whole-body submersion (27–29°C) in a diving pool. Blood velocity, blood volume flow in the carotid artery, diastolic blood pressure and electrocardiogram were measured and recorded during the experiments. The peak blood velocity increased by 13.6% (P < 0.01) and R-wave amplitude increased by 57.1% (P < 0.005) when the subjects entered water from air. End-diastolic blood velocity in the carotid artery increased significantly during breath-holding, e.g. increased from 0.20 (SD 0.02) m · s⁻¹ at rest to 0.33 (SD 0.04) m · s⁻¹ (P < 0.001) at 50.0 s in breath-hold submersion to a 2.0-m depth. Blood volume flow in the carotid artery increased by 26.6% (P < 0.05) at 30 s and 36.6% (P < 0.001) at 40 s in breath-hold submersion to a 2.0-m depth. Diastolic blood pressure increased by 15.4% (P < 0.01) at 60 s during breath-holding in head-out immersion. Blood volume flow, and diastolic blood pressure increased significantly more and faster during breath-holding in submersion than out of the water. There was a good negative correlation with the heart rate: the root mean square correlation coefficient r was 0.73 (P < 0.001). It was concluded that an increased accumulation of blood in the aorta and arteries at end-diastole and decreased venous return, caused by an increase in systemic peripheral resistance during breath-holding, underlies diving bradycardia. Accepted: 22 November 1996     

Comparison of Anti-Hyperglycemic Effect of Inorganic Constituents and Organic in Traditional Chinese Medicine,Jinqi Compound Recipe

An attempt has been made to compare the hypoglycemic effect of the organic constituents and the inorganic constituents in traditional Chinese medicine, Jinqi compound recipe. Alloxan-induced hyperglycemic mice were used in the study. The body weights, blood glucose, HbA1c, insulin secretion, and glycogen synthesis of the mice were analyzed respectively. After the mice were administered (oral) with organic constituents, the blood glucose and the HbA1c of alloxan-induced hyperglycemic mice decreased (p < 0.05, p < 0.01) and the glycogen synthesis of alloxan-induced hyperglycemic mice elevated (p < 0.05). Also, the body weight of the alloxan-induced hyperglycemic mice was increased gradually. However, the same result did not occur in the inorganic constituent-treated groups. It is noted that neither organic constituents nor inorganic constituents could elevate the level of serum insulin in the alloxan-induced hyperglycemic mice significantly. It is implied that the hypoglycemic effect for type 2 diabetes was caused by the organic constituents of Jinqi recipe. The results can be used to set new standards to control the quality of the Jinqi recipe.