Duration of bone protection by a single osteoprotegerin injection in rats with adjuvant-induced arthritis

Daily osteoprotegerin (OPG) injection for 7 or more days prevents bone loss for 3 weeks in rats with adjuvant-induced arthritis (AdA). The present experiments defined the duration of bone protection in AdA provided by a single OPG bolus. Male Lewis rats received OPG at the onset or peak of clinical disease, after which bone mineral density (BMD), erosions, and osteoclasts were evaluated. An OPG bolus (4 mg/kg subcutaneously) at onset eliminated osteoclasts, preserved BMD for 7 days, and prevented bone erosions for 4 days. In contrast, an OPG bolus (1, 3, 10, or 30 mg/kg intravenously) given at the peak of disease eradicated osteoclasts in a dose-dependent manner but had no impact on bone integrity due to extensive pre-existing bone loss. These data indicate that one OPG injection will inhibit joint erosions for several days, and confirm that bone-sparing therapy must be initiated early in disease to protect joint integrity.     

Sleep and monoamines: differential radioautography of central neurons after systematic injection of tritiated 5-hydroxytryptophane (5 HTP 3H) or of dihydroxyphenylalanine (DOPA 3H)]

In normal cats 90 min. after the intravenous injection of 5 mg/kg of 5 HTP and 3H 5 HTP or DOPA and 3H DOPA a few reactive nerve cell bodies were identified by radioautography. On the contrary, 48 hrs. after p-chlorophenylalanin or subtotal lesion of raphe nuclei, these tracers showed numerous reactive neurons inside or outside the central monoaminergic systems.     

Disparition de la 5-hydroxytryptamine dans les granulations des glandes de la peau deDiscoglossus pictus et deRana temporaria après injection de réserpine

Summary 30 min after an intraperitoneal injection of reserpine (5 or 10 mg/kg) in the frog (Rana temporaria) and in the toad (Discoglossus pictus), a substance which has the properties of 5-hydroxytryptamine (argentaffine reaction, azoreaction, indoreaction and fluorescence in U.V. after formaldehyde) disappears from the skin glands; the histochemical reactions are more positive again 1 1/2 to 2 h after the injection of reserpine.     

Demonstration of exocytosis in the sinus gland of Astacus Leptodactylus (Nordmann) under the influence of serotonin injections]

Following a serotonin injection, a rise of exocytosis in the sinus gland of the crayfish Astacus leptodactylus is observed together with an increase of the glucose level in the hemolymph. The phenomenon of exocytosis reaches a peak between 2 and 4 h after injection, wheras the highest glucose level in the hemolymph appears between 4 and 6 h after the same injection.     

The timing of cyclophosphamide therapy in tumor-bearing rats affects the resistance to tumor challenge in survivors

Summary Cyclophosphamide given to rats 2 or 5 days after an injection of Yoshida ascites sarcoma cured approximately the same proportion of animals, but the resistance to a subsequent tumor challenge was found only in rats treated with the drug 5 days after tumor injection.     

Isoprenaline, modifications of the turnover of ATP in the perfused rat heart]

5 hrs after a single sub-cutaneous injection of the drug in a dose of 5 mg/kg, the ATP concentration was reduced by 15%, the incorporation of 14C adenine was augmented by 20% and the turnover of ATP was accelerated: the reduction of specific radioactivity attained 16%, 75 mn after the period of marquage, instead of 7% in the control hearts. When the drug was added to the perfusion fluid, there was no supplementary reduction of the ATP concentration and the action on the nucleotide turnover only existed if the ATP level was reduced by a pretreatment: the reduction of specific radioactivity then attained 24% after 75 min. of perfusion.     

The biotransformation of tritiated 3-dehydroecdysone by crayfish,Procambarus clarkii

The injection of 3-dehydroecdysone (3dhE, 5 /g), the major ecdysteroid secreted by the Y-organ of crayfishProcambarus clarkii, resulted in apolysis within about 5 days. The hormonal response at the molecular level was investigated by injection of the radio-labeled compound; within 3 h of injection of [³H]3dhE, most radio-isotope was found in the extracted epidermal tissues and identified as ecdysone, 20-hydroxyecdysone (20E), and their 3-hydroxy epimers. The biotransformation was undoubtedly performed in the peripheral area of the Y-organ. Cleavage of the polar conjugates, using an enzyme fromHelix pomatia, gave all of the above ecdysteroids including 3dhE. It was also found that the biosynthetic site of 3dhE was different from that of ecdysone at the subcellular level of the Y-organ.     

Neuromodulation by serotonin and octopamine in the honeybee: behaviour,neuroanatomy and electrophysiology

The biogenic amines serotonin (5HT) and octopamine (OA) exist in the bee and can modulate neuronal activity and behaviour. 5HT-like and OA-like immunoreactivities can be found in most neuropils of the brain. Binding sites for the two amines are also present in most brain neuropils. The highest density of binding sites for [³H]serotonin and [³H]octopamine was found in the mushroom bodies. In some brain areas, especially the mushroom bodies, mismatches exist between binding sites and immunoreactivities, suggesting that the two amines also bind to neuropils which are not directly innervated by 5HT-like or OA-like immunoreactive neurons. The action of the two amines on behaviour in the bee is antagonistic. In the antennal pathway, proboscis and antennal responses to olfactory and gustatory stimuli are enhanced by OA and reduced by 5HT. In olfactory conditioning experiments, storage and retrieval of the learned signal can be enhanced by OA and reduced by 5HT. The specificity of these effects depends on the site of amine application in the neuropil. In the visual system the direction specificity of the visual antennal response is enhanced by OA and reduced by 5HT after topical application or injection into the lobula, the third optic ganglion. Correlates for the behavioural modulation can be found in higher-order visual interneurons. While OA application can mimic the stimulation of the bee with sugar water, the behavioural conditions leading to the release of 5HT are not yet known.     

Endocannabinoids and β-amyloid-induced neurotoxicity in vivo: effect of pharmacological elevation of endocannabinoid levels

We investigated the involvement of endocannabinoids in the control of neuronal damage and memory retention loss in rodents treated with the β-amyloid peptide (1–42) (BAP). Twelve days after stereotaxic injection of BAP into the rat cortex, and concomitant with the appearance in the hippocampus of markers of neuronal damage, 2-arachidonoyl glycerol, but not anandamide, levels were enhanced in the hippocampus. VDM-11 (5 mg/kg, i.p.), an inhibitor of endocannabinoid cellular reuptake, significantly enhanced rat hippocampal and mouse brain endocannabinoid levels when administered sub-chronically starting either 3 or 7 days after BAP injection and until the 12–14th day. VDM-11 concomitantly reversed hippocampal damage in rats, and loss of memory retention in the passive avoidance test in mice, but only when administered from the 3rd day after BAP injection. We suggest that early, as opposed to late, pharmacological enhancement of brain endocannabinoid levels might protect against β-amyloid neurotoxicity and its consequences. Received 26 January 2006; received after revision 24 March 2006; accepted 12 April 2006     

Effect of glucagon administration on serum calcium and inorganic phosphorus in the freshwater mud eel,Amphipnous cuchia

Summary Glucagon injection inAmphipnous cuchia evokes a decreased level of serum calcium on day 1 which progresses till day 3. This response declines after day 5. The serum inorganic phosphorus level does not show any significant change.     

Desensitization by human chorionic gonadotropin (hCG): demonstration of a negative control of gonadotropin receptors by hCG at the level of testicular Leydig cells]

A single injection of hCG (500 IU) to intact and hypophysectomized prepubertal rat increases plasma testosterone levels and decreases hCG receptors in the testicular Leydig cells for 4 to 5 days. In intact animals testosterone exhibit a rapid increase within hours and a delayed paradoxical increase between 60 and 96 hours. In hypophysectomized animals the first peak is not present. In both intact and hypophysectomized rats hCG receptors are almost undetectable between 10 and 96 hours following hCG injection. Since receptor occupancy cannot account for this phenomenon it is concluded that hCG is exerting a negative control on its own receptors.     

Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines

In the context of developing a safe genetic vaccination strategy we tested and studied globin-stabilized mRNA-based vaccination in mice. This vaccination strategy has the advantages of genetic vaccination (easy production, adaptability to any disease and inexpensive storage when lyophilized), but not the drawbacks of DNA vaccination (long-term uncontrolled expression of a transgene, possibility of integration into the host genome and possible induction of anti-DNA antibodies). We report here that injection of naked -globin untranslated region (UTR)-stabilized mRNA coding for -galactosidase is followed by detectable translation in vivo. In addition, we show that such a vaccination strategy primes a T helper 2 (Th2) type of response which can be enhanced and shifted to a Th1-type immune response by application of recombinant granulocyte/macrophage colony-stimulating factor 1 day after mRNA injection. Our data demonstrate that the administration of globin UTR-stabilized mRNA is a versatile vaccination strategy that can be manipulated to fit the requirement of antiviral, antibacterial or antitumor immunity.Received 14 June 2004; received after revision 19 July 2004; accepted 9 August 2004     

Insect photoperiodism: the linden bug,Pyrrhocoris apterus,a species that measures daylength rather than nightlength

Summary Independent variation of the dark and light components of the daily photocycle has shown that the linden bug,Pyrrhocoris apterus, unlike other species, measures daylength rather than nightlength. Greatly extended dark periods coupled with a short photophase (a Nanda-Hamner protocol) shows peaks and troughs of diapause at about 16-h intervals, an extremely short period for a circadian clock. If circadian oscillations are involved in photoperiodic time measurement in this species, a photoinducible phase might lie in the early rather than the late subjective night.27 October 1986     

Changes in ecdysone levels in the spiderPisaura mirabilis nymphs (Araneae,Pisauridae)

Summary RIA of ecdysones are made on nymphal extracts ofPisaura mirabilis during the intermoulting cycle. The hormone level is low during exuviation and the greatest part of the intermoulting period but increases notably before and after ecdysis. The main hormonal peak or pre-ecdysial peak is due to -ecdysone, characterized by combined TLC/RIA.Acknowledgment. We wish to thank Dr M. Hirn for his help during the manipulations and J. Britton who has translated the text into English.     

脂多糖致感染性脑水肿大鼠星形胶质细胞的活化和凋亡

目的通过观察脂多糖（Lipopolysaccharide,LPS）致大鼠感染性脑水肿后星形胶质细胞的凋亡、活化及iNOS表达情况,探讨在LPS致脑水肿中星形胶质细胞的作用。方法84只雄性SD大鼠,随机分为3组：空白对照纽（C组,n=12）;生理盐水对照纽（S组,n=12）;感染性水肿组（L组,n=60）。感染性脑水肿组又按颈内动脉注射脂多糖后6h、12h、24h、48h、72h分为5个亚组（n=12）。向颈内动脉注射脂多糖LPS150μg（0．15ml）建立大鼠感染性脑水肿模型。采用HE染色、流式细胞检测和免疫纽化染色分别观察脑组织病理改变、星形胶质细胞凋亡、胶质纤维酸性蛋白（GFAP）和iNOS表达情况。结果与C组和S组比较,L组大鼠星形胶质细胞胞体变大、突起增多;细胞内GFAP和iNOS表达增强,12h达高峰,除72h组,其余亚组均有统计学差异（P〈0．05）;各亚组星形胶质细胞凋亡增多（P〈0．05）,24h凋亡最显著。C组和S纽比较无统计学意义（P〉0．05）。结论感染性脑水肿后星形胶质细胞凋亡增加,异常活化,分泌iNOS,参与感染性脑水肿的形成,在脑水肿的发生发展中发挥重要作用。     

Forecasting and analyzing economic activity with coincident and leading indexes: The case of Connecticut

We develop coincident and leading employment indexes for the Connecticut economy. Four employment-related variables enter the coincident index while five employment-related variables enter the leading index. The peaks and troughs in the leading index lead the peaks and troughs in the coincident index by an average of 3 and 9 months. Finally, we use the leading index in vector-autoregressive (VAR) and Bayesian vector-autoregressive (BVAR) models to forecast the coincident index, non-farm employment, and the unemployment rate.     

Action duCorynebacterium parvum sur les taux de lysozyme (muramidase) sérique

Summary An i.v. injection of 548 g of killedCorynebacterium parvum into C57B1 mice leads to significant changes in serum lysozyme (muramidase) levels. After an initial fall at 24 h, the activity of the enzyme increased progressively, reached a peak on the 9th day and returned to control range after the 15th day.     

Potentiation of immunologic memory by Corynebacterium parvum and its mechanism]

Immune response to bovine serum albumin (BSA) at dose of 2,50 mg/kg which is rather a weak immunogen in Rabbits, when given intravenous was highly potentiated when the animals received a previous single intravenous infection of 2 mg/kg of C. parvum, followed by subsequent BSA anamnestic challenges for several months. Thus, the antibody amounts synthesized following the 1st anamnestic injection (3 weeks) were 0,260 mg/ml in the control versus, 0,800 mg/ml in the C. parvum pretreated groups; following the 2nd anamnestic challenge (12 weeks afterwards) 1 mg/ml in the control versus, 2,50 mg/ml in the treated groups following the 3rd anamnestic challenge (28 weeks afterwards) 1,3 mg/ml in the control versus 5 mg/ml in the C. parvum pretreated groups; following the 4th anamnestic challenge (52 weeks afterwards) 0,300 mg/ml in the control versus 0,800 mg/ml in the C. parvum treated groups. On the whole for the four first anamnestic challenges the differences at peak levels between the control and C. parvum treated groups were about to 4. Furthermore, the antibody molecules synthesized by the C. parvum treated animals were found to belong to IgG class. The results suggest that the immunological mechanisms mobilized are peculiar to C. parvum since they could not be reproduced either by BCG or by Freun'd adjuvant under similar conditions.     

Insomnia induced by P-chlorophenylalanine in cats. Its reversibility by intraventricular injections of indolamines

Intraventricular injection of 250 microgram of 5 HTP induces both slow wave and paradoxical sleep, after 20-60 min. latencies, in insomniac Cats pretreated with P-chlorophenylalanine. Direct injections of 5 HTP in several brain stem structures do not induce sleep. The long latency or paradoxical sleep induction and its suppression with chloramphenicol suggest that indolamines are not directly responsible for paradoxical sleep, but that they act by controlling the synthesis and/or the liberation in the periventricular system of some specific paradoxical sleep inducing factor.