The metabolic clearance of progesterone in the pregnant rat: absence of a physiological role for the lung

The metabolic clearance rate (MCR) of progesterone is among the highest for all steroid hormones studied, yet it is difficult to apportion this high MCR to specific organ contributions. The isolated lung has been shown to metabolize progesterone, and since this tissue receives the entire cardiac output, potentially it could make a major contribution to the overall MCR. This possibility was examined in the present study by measuring lung extraction of [3H]progesterone under steady-state conditions in the intact pregnant rat. Anesthetized rats (n = 6) were infused with [3H]progesterone via a femoral vein for 100 min on Day 16 of pregnancy. After the onset of steady state (40 min), four blood samples were obtained at 20-min intervals from the right ventricle and from the aorta, and the concentrations of [3H]progesterone and its metabolites were determined. Throughout the sampling period, mean arterial pressure and heart rate remained stable (two-way analysis of variance), as did the production rate (3.76 +/- 0.35 mg/day; mean +/- SEM) and the MCR (34.8 +/- 3.5 ml/min) of progesterone. Despite this high rate of clearance, there was no difference between the concentration of [3H]progesterone in arterial and right ventricular blood, indicating no net extraction of progesterone during passage through the lung. Furthermore, there was no change in the concentration of either lipid-soluble or aqueous-soluble [3H]progesterone metabolites during trans-lung passage. These observations demonstrate that the lung does not contribute to the MCR of progesterone when measured under physiological and steady-state conditions. Therefore, the relationship, MCR (ml/min) = whole-body extraction (%) x cardiac output (ml/min), is upheld for progesterone in the rat.     

Localization of the circadian pacemakers of Hemideina thoracica (Orthoptera; Stenopelmatidae)

The location of the circadian pacemakers of the orthopteran Hemideina thoracica (White) has been investigated through observation of the effects of surgical removal of brain tissues (principally optic lobes and tracts) on free-running and entrained locomotor rhythms. Bilobectomy and severance of optic tracts invariably resulted in arrhythmicity, whereas rhythmicity was sustained following unilateral lobectomy, generally with increases in the free-running period (FRP) and decreases in both the active-phase lengths and activity-to-rest ratios of the rhythm. Bilobectomized subjects could be entrained by temperature cycles, but exhibited no transients or residual rhythmicity, indicating that temperature brought about a direct response or masking effect. These results support the hypothesis that the circadian locomotor pacemakers of Hemideina are located within each optic lobe, and that there are no extraoptic centers for the control of the timing of locomotor activity. Although confirmation of the pacemaker role of the optic lobes requires transplantation of the tissues, the conclusion may be drawn by inference from other studies (e.g., Leucophaea maderae--Page, 1983; Gryllus bimaculatus--Tomioka and Chiba, 1986). Light entrainment continued after surgical binding and blackening of the compound eyes and ocelli, supporting the view that direct illumination of neural tissue through the cuticle may be one possible pathway for light entrainment.     

Frostbite and the significance of a temperature-sensation scale in field and laboratory conditions

The literature indicates that rapid thawing in water between 42 and 45C provides the best prognosis for frostbitten limbs.A temperature:sensation scale for the normal hand was derived and tested in laboratory and field conditions. The scale permitted the preparation of water suitable for frostbite treatment by the majority of subjects without access to a thermometer. The maximum observed inaccuracy was 1.2C outside the preferred range but was well withing the safe range for treatment.

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Zusammenfassung Die beste Prognose zur Behandlung von Erfrierungen bietet nach den Erfahrungen in der Literatur das schnelle Auftauen von erfrorenen Gliedern bei Wassertemperaturen von 42–45C. Für die gesunde Hand wurde eine Temperatur-Wahrnehmungsskala aufgestellt und unter verschiedenen Bedingungen im Laboratorium und im Freien geprüft. Ohne Zugang zu einem Thermometer gestattete die Skala in der Mehrzahl der FÄlle die ErwÄrmung von Wasser auf Temperaturen, die für die Behandlung von Erfrierungen geeignet sind. Die grösste Ungenauigkeit zwischen SchÄtzwert und Thermometerwert war 1.2C ausserhalb des gewünschten aber noch innerhalb des für die Behandlung zulÄssigen Bereiches.

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Résumé D'après les indications de plusieurs auteurs, le meilleur traitement de membres gelés consiste à les dégeler dans de l'eau à une temperature entre 42 et 45C. Une échelle température-sensation pour la main normale a été mise au point et vérifiée au laboratoire ainsi qu'en plain air.Cette méthode a permis la préparation d'eau en vue d'un traitement de gelures sans faire usage d'un thermomètre dans la plupart des cas. L'erreur maximum observée était de 1,2 C sans que les limites de l'intervalle propice à un traitement ne soient jamais dépassées.

     

Evidence of biotic resistance to exotic plant invasion in degraded Bornean forests

Intact tropical forests are generally considered to be resistant to invasions by exotic species, although the shrub Clidemia hirta (Melastomataceae) is highly invasive in tropical forests outside its native range. Release from natural enemies (e.g., herbivores and pathogens) contributes to C. hirta invasion success where native melastomes are absent, and here we examine the role of enemies when C. hirta co-occurs with native Melastomataceae species and associated herbivores and pathogens. We study 21 forest sites within agricultural landscapes in Sabah, Malaysian Borneo, recording herbivory rates in C. hirta and related native Melastoma spp. plants along two 100-m transects per site that varied in canopy cover. Overall, we found evidence of enemy release; C. hirta had significantly lower herbivory (median occurrence of herbivory per plant = 79% of leaves per plant; median intensity of herbivory per leaf = 6% of leaf area) than native melastomes (93% and 20%, respectively). Herbivory on C. hirta increased when closer to native Melastoma plants with high herbivory damage, and in more shaded locations, and was associated with fewer reproductive organs on C. hirta. This suggests host-sharing by specialist Melastomataceae herbivores is occurring and may explain why invasion success of C. hirta is lower on Borneo than at locations without related native species present. Thus, natural enemy populations may provide a “biological control service” to suppress invasions of exotic species (i.e., biotic resistance). However, lower herbivory pressures in more open canopy locations may make highly degraded forests within these landscapes more susceptible to invasion.     

In vivo micro-CT scanning of a rabbit distal femur: repeatability and reproducibility

Before in vivo micro-CT scanning can be used to investigate femoral trabecular microarchitecture over time in rabbits, its repeatability and reproducibility must be demonstrated. To accomplish this, both distal femurs of two 6-month-old New Zealand white rabbits were scanned five times each in 1 day under different conditions (repeatability). Scanning was done at 28 microm isotropic voxel size to produce five image stacks of each femur. Three operators then followed a standard image processing protocol (reproducibility) to isolate two separate cubes from each anterior femoral condyle [total n = (8 cube sites)(5 scans)(3 operators) = 120]. Bone volume fraction (BV/TV) of the eight different cube sites (sample) ranged from 0.408 to 0.501 (mean: 0.453); trabecular thickness (Tb.Th) ranged from 158.1 to 185.5 microm (mean: 168.6 microm); and trabecular separation (Tb.Sp) ranged from 179.4 to 233.1 microm (mean: 204.7 microm). Using ANOVA and the variance component method, the total process variation was +/- 14.1% of the mean BV/TV of 0.453. The sample variation was +/- 13.9% (p < 0.001), the repeatability was +/- 2.1% (p < 0.001), and the reproducibility was +/- 0.1% (p > 0.05). Results were similar for Tb.Th and Tb.Sp. Though the contribution due to repeatability was statistically significant for each of the three indices, the natural sample differences were far greater than differences caused by repeated scanning under different conditions or by different operators processing the images. These findings suggest that in vivo micro-CT scanning of rabbit distal femurs was repeatable and reproducible and can be used with confidence to measure differences in trabecular bone microarchitecture at a single location in a longitudinal study design.     

Mesenchymal stromal cells augment CD4+ and CD8+ T-cell proliferation through a CCL2 pathway

Background aimsMesenchymal stromal cells (MSC) derived from bone marrow are immunosuppressive in vitro and in vivo. Recent evidence, however, has shown that in certain settings, MSC can also be immunostimulatory. The mechanisms involved in this process are largely unknown.MethodsMouse spleen T cells were stimulated with allogeneic mixed lymphocyte reaction (MLR) or anti-CD3/CD28 beads and treated with autologous bone marrow MSC or MSC-conditioned medium. CD4+ and CD8+ T-cell proliferation was analyzed after treatment.ResultsWe show that MSC have both suppressive and stimulatory functions toward T cells after stimulation with anti-CD3/CD28 beads or in an MLR. This depended on the ratio of MSC to responder T cells, with low numbers of MSC increasing and higher numbers inhibiting T-cell proliferation. Immunostimulatory function was mediated, in part, by soluble factors. MSC immunosuppression of the MLR was indirect and related to inhibition of antigen-presenting cell maturation. Direct effects of MSC-conditioned medium during anti-CD3/CD28 stimulated proliferation were entirely stimulatory and required the presence of the T-cell receptor. MSC supernatant contained both CCL2 and CCL5 at high levels, but only CCL2 level correlated with the ability to augment proliferation. An anti-CCL2 antibody blocked this proliferative activity.ConclusionsCCL2 plays an important role in the immunostimulatory function of MSC, and we further hypothesize that the immunomodulatory role of MSC is determined by a balance between inhibitory and stimulatory factors, suggesting the need for caution when these cells are investigated in clinical protocols.     

Repeated oral administration of capsaicin increases anxiety-like behaviours with prolonged stress-response in rats

This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02% capsaicin into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of capsaicin. Stereotypy counts and rostral grooming were significantly increased, and caudal grooming decreased, in capsaicin-treated rats during the ambulatory activity test. In elevated plus maze test, not only the time spent in open arms but also the percent arm entry into open arms was reduced in capsaicin-treated rats compared with control rats. In forced swim test, although swimming duration was decreased, struggling increased in the capsaicin group, immobility duration did not differ between the groups. Repeated oral capsaicin did not affect the basal levels of plasma corticosterone; however, the stress-induced elevation of plasma corticosterone was prolonged in capsaicin treated rats. Oral capsaicin exposure significantly increased c-Fos expression not only in the nucleus tractus of solitarius but also in the paraventricular nucleus. Results suggest that repeated oral exposure to capsaicin increases anxiety-like behaviours in rats, and dysfunction of the hypothalamic-pituitary-adrenal axis may play a role in its pathophysiology.     

Evaluation of selective inhibitors of 11β-HSD1 for the treatment of hypertension

In an effort to understand the origin of blood-pressure lowering effects observed in recent clinical trials with 11β-HSD1 inhibitors, we examined a set of 11β-HSD1 inhibitors in a series of relevant in vitro and in vivo assays. Select 11β-HSD1 inhibitors reduced blood pressure in our preclinical models but most or all of the blood pressure lowering may be mediated by a 11β-HSD1 independent pathway.