Does midazolam inhibit the development of acute tolerance to the analgesic effect of alfentanil?

Alfentanil-midazolam analgesic interactions were studied in rats with continuous infusions or bolus injections of the drugs. Analgesia was determined by measuring the threshold of motor response to noxious pressure. The continous constant-rate infusion of alfentanil demonstrated that after an initial peak, the analgesia profoundly declined due to the development of acute tolerance. When alfentanil (250 μg·kg⁻¹·h⁻¹) was given together with midazolam (3 mg·kg⁻¹·h⁻¹), the decline in the analgesic effect of alfentanil was attenuated. Following the 4 h period of the constant-rate (250 μg·kg⁻¹·h⁻¹) infusion of alfentanil, when acute tolerance was already developed, midazolam (3 mg·kg⁻¹) given as a bolus injection enhanced the alfentanil-induced anesthesia. At the same time, when alfentanil was given as a bolus injection (30 μg·kg⁻¹) with or without midazolam (3 mg·kg⁻¹) also by bolus injection, no changes were seen to indicate an enhancement of the analgesic effect of alfentanil by midazolam. The results suggest that midazolam attenuates the development of acute tolerance to the analgesic effect of alfentanil.     

Primary production of the kelp Lessonia corrugata varies with season and water motion: Implications for coastal carbon cycling

Kelp forests provide vital ecosystem services such as carbon storage and cycling, and understanding primary production dynamics regarding seasonal and spatial variations is essential. We conducted surveys at three sites in southeast Tasmania, Australia, that had different levels of water motion, across four seasons to determine seasonal primary production and carbon storage as living biomass for kelp beds of Lessonia corrugata (Order Laminariales). We quantified blade growth, erosion rates, and the variation in population density and estimated both the net biomass accumulation (NBA) per square meter and the carbon standing stock. We observed a significant difference in blade growth and erosion rates between seasons and sites. Spring had the highest growth rate (0.02 g C · blade⁻¹ · d⁻¹) and NBA (1.62 g C · m⁻² · d⁻¹), while summer had the highest blade erosion (0.01 g C · blade⁻¹ · d⁻¹), with a negative NBA (−1.18 g C · m⁻² · d⁻¹). Sites exhibiting lower blade erosion rates demonstrated notably greater NBA than sites with elevated erosion rates. The sites with the highest water motion had the slowest erosion rates. Moreover, the most wave-exposed site had the densest populations, resulting in the highest NBA and a greater standing stock. Our results reveal a strong seasonal and water motion influence on carbon dynamics in L. corrugata populations. This knowledge is important for understanding the dynamics of the carbon cycle in coastal regions.     

Curcumin has immunomodulatory effects on RANKL‐stimulated osteoclastogenesis in vitro and titanium nanoparticle‐induced bone loss in vivo

Wear particle‐stimulated inflammatory bone destruction and the consequent aseptic loosening remain the primary causes of artificial prosthesis failure and revision. Previous studies have demonstrated that curcumin has a protective effect on bone disorders and inflammatory diseases and can ameliorate polymethylmethacrylate‐induced osteolysis in vivo. However, the effect on immunomodulation and the definitive mechanism by which curcumin reduces the receptor activators of nuclear factor‐kappa B ligand (RANKL)‐stimulated osteoclast formation and prevents the activation of osteoclastic signalling pathways are unclear. In this work, the immunomodulation effect and anti‐osteoclastogenesis capacities exerted by curcumin on titanium nanoparticle‐stimulated macrophage polarization and on RANKL‐mediated osteoclast activation and differentiation in osteoclastic precursor cells in vitro were investigated. As expected, curcumin inhibited RANKL‐stimulated osteoclast maturation and formation and had an immunomodulatory effect on macrophage polarization in vitro. Furthermore, studies aimed to identify the potential molecular and cellular mechanisms revealed that this protective effect of curcumin on osteoclastogenesis occurred through the amelioration of the activation of Akt/NF‐κB/NFATc1 pathways. Additionally, an in vivo mouse calvarial bone destruction model further confirmed that curcumin ameliorated the severity of titanium nanoparticle‐stimulated bone loss and destruction. Our results conclusively indicated that curcumin, a major biologic component of Curcuma longa with anti‐inflammatory and immunomodulatory properties, may serve as a potential therapeutic agent for osteoclastic diseases.     

Montelukast abrogates prednisolone‐induced hepatic injury in rats: Modulation of mitochondrial dysfunction,oxidative/nitrosative stress,and apoptosis

The aim of this study was to investigate the protective effect of montelukast (MTK) against prednisolone‐induced hepatic injury in rats. Twenty‐eight male albino rats were categorized into four equal groups. Group I served as the control group; group II: rats orally received prednisolone (5 mg·kg^?1·d^?1) for 30 days; groups III and IV: rats orally received MTK at 10 and 20 mg·kg^?1·d^?1, respectively, simultaneously with prednisolone for 30 days. Serum liver enzymes, hepatic mitochondrial function, oxidative/nitrosative stress, and inflammatory and apoptotic markers were evaluated, and the results were confirmed by histopathological examination. MTK showed significant hepatic protection evidenced by alleviated histological lesion and improvement of mitochondrial function, oxidative/nitrosative stress, and inflammatory and apoptotic changes induced by prednisolone, with more profound protection in higher MTK dose (20 mg·kg^?1). In view of these findings, we can conclude that MTK may have hepatoprotective potential, beyond its therapeutic value for asthmatic patients during their course of corticosteroid therapy.     

Hesperetin suppresses RANKL-induced osteoclastogenesis and ameliorates lipopolysaccharide-induced bone loss

Destructive bone diseases caused by osteolysis are increasing in incidence. They are characterized by an excessive imbalance of osteoclast formation and activation. During osteolysis, the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways are triggered by receptor activator of NF-κB ligand (RANKL), inflammatory factors, and oxidative stress. Previous studies have indicated that the common flavanone glycoside compound hesperetin exhibits anti-inflammatory and antioxidant activity by inhibition of NF-κB and MAPK signaling pathways. However, the direct relationship between hesperetin and osteolysis remain unclear. In the present study, we investigated the effects of hesperetin on lipopolysaccharide (LPS)-induced osteoporosis and elucidated the related mechanisms. Hesperetin effectively suppressed RANKL-induced osteoclastogenesis, osteoclastic bone resorption, and F-actin ring formation in a dose-dependent manner. It also significantly suppressed the expression of osteoclast-specific markers including tartrate-resistant acid phosphatase, matrix metalloproteinase-9, cathepsin K, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1. Furthermore, it inhibited osteoclastogenesis by inhibiting activation of NF-κB and MAPK signaling, scavenging reactive oxygen species, and activating the nuclear factor E2 p45-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling pathway. Consistent with in vitro results, hesperetin effectively ameliorated LPS-induced bone loss, reduced osteoclast numbers, and decreased the RANKL/OPG ratio in vivo. As such, our results suggest that hesperetin may be a great candidate for developing a novel drug for destructive bone diseases such as periodontal disease, tumor bone metastasis, rheumatoid arthritis, and osteoporosis.     

Caffeine antagonizes several central effects of diazepam

In spinal cats, caffeine (3–30 mg·kg^?1 i.v.) reduced the increase of dorsal root potentials (DRPs) caused by diazepam (0.1–1 mg·kg^?1 i.v.) without affecting the prolongation of DRPs evoked by phenobarbitone (10–20 mg·kg^?1 i.v.). Caffeine antagonized the depression by diazepam, but not that by phenobarbitone, of the ventral root-evoked Renshaw cell discharge. In unrestrained cats, 50 mg·kg^?1 caffeine i.p. abolished the elevation induced by 1 mg·kg^?1 diazepam i.p. of the threshold for eliciting a rage reaction by stimulation of the lateral hypothalamus, but was ineffective against the threshold increase caused by 20 mg·kg^?1 phenobarbitine i.p. In the horizontal wire test in mice, caffeine was more potent in reversing the depression of performance induced by diazepam that that by phenobarbitone (ED50 1.8 mg·kg^?1 and 139 mg·kg^?1 p.o., respectively). The reduction of skeletal muscle tone in mice produced by diazepam was antagonized by low doses of caffeine (ED50 0.53 mg·kg^?1 p.o.). While caffeine at low doses (0.3-3 mg·kg^?1 p.o.) abolished the anticonflict effect of diazepam in rats, high doses (ED50 160 mg·kg^?1 p.o.) were necessary to antagonize the anticonvulsant effect of diazepam on pentylene-tetrazole-induced seizures in mice. The interaction between caffeine and diazepam is not due to a competition at the benzodiazepine receptors but may involve purinergic mechanisms.     

Prevention of wear particle-induced osteolysis by a novel V-ATPase inhibitor saliphenylhalamide through inhibition of osteoclast bone resorption

Wear particle-induced peri-implant loosening (Aseptic prosthetic loosening) is one of the most common causes of total joint arthroplasty. It is well established that extensive bone destruction (osteolysis) by osteoclasts is responsible for wear particle-induced peri-implant loosening. Thus, inhibition of osteoclastic bone resorption should prevent wear particle induced osteolysis and may serve as a potential therapeutic avenue for prosthetic loosening. Here, we demonstrate for the first time that saliphenylhalamide, a new V-ATPase inhibitor attenuates wear particle-induced osteolysis in a mouse calvarial model. In vitro biochemical and morphological assays revealed that the inhibition of osteolysis is partially attributed to a disruption in osteoclast acidification and polarization, both a prerequisite for osteoclast bone resorption. Interestingly, the V-ATPase inhibitor also impaired osteoclast differentiation via the inhibition of RANKL-induced NF-κB and ERK signaling pathways. In conclusion, we showed that saliphenylhalamide affected multiple physiological processes including osteoclast differentiation, acidification and polarization, leading to inhibition of osteoclast bone resorption in vitro and wear particle-induced osteolysis in vivo. The results of the study provide proof that the new generation V-ATPase inhibitors, such as saliphenylhalamide, are potential anti-resorptive agents for treatment of peri-implant osteolysis.     

Pyrroloquinoline Quinine Inhibits RANKL-Mediated Expression of NFATc1 in Part via Suppression of c-Fos in Mouse Bone Marrow Cells and Inhibits Wear Particle-Induced Osteolysis in Mice

The effects of pyrroloquinoline quinine (PQQ) on RANKL-induced osteoclast differentiation and on wear particle-induced osteolysis were examined in this study. PQQ inhibited RANKL-mediated osteoclast differentiation in bone marrow macrophages (BMMs) in a dose-dependent manner without any evidence of cytotoxicity. The mRNA expression of c-Fos, NFATc1, and TRAP in RANKL-treated BMMs was inhibited by PQQ treatment. Moreover, RANKL-induced c-Fos and NFATc1 protein expression was suppressed by PQQ. PQQ additionally inhibited the bone resorptive activity of differentiated osteoclasts. Further a UHMWPE-induced murine calvaria erosion model study was performed to assess the effects of PQQ on wear particle-induced osteolysis in vivo. Mice treated with PQQ demonstrated marked attenuation of bone erosion based on Micro-CT and histologic analysis of calvaria. These results collectively suggested that PQQ demonstrated inhibitory effects on osteoclast differentiation in vitro and may suppress wear particle-induced osteolysis in vivo, indicating that PQQ may therefore serve as a useful drug in the prevention of bone loss.     

Dehydrocostus lactone attenuates osteoclastogenesis and osteoclast‐induced bone loss by modulating NF‐κB signalling pathway

Osteolysis is characterized by overactivated osteoclast formation and potent bone resorption. It is enhanced in many osteoclast‐related diseases including osteoporosis and periprosthetic osteolysis. The shortage of effective treatments for these pathological processes emphasizes the importance of screening and identifying potential regimens that could attenuate the formation and function of osteoclasts. Dehydrocostus lactone (DHE) is a natural sesquiterpene lactone containing anti‐inflammatory properties. Here, we showed that DHE suppressed receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclast formation and osteoclast marker gene expression. It also inhibited F‐actin ring formation and bone resorption in a dose‐dependent manner in vitro. Moreover, DHE inhibited the RANKL‐induced phosphorylation of NF‐κB, mitigated bone erosion in vivo in lipopolysaccharide‐induced inflammatory bone loss model and particle‐induced calvarial osteolysis model. Together, these results suggest that DHE reduces osteoclast‐related bone loss via the modulation of NF‐κB activation during osteoclastogenesis indicating that it might be a useful treatment for osteoclast‐related skeletal disorders.     

Assessment of EDDS and vermicompost for the phytoextraction of Cd and Pb by sunflower (Helianthus annuus L.)

The effects of Ethylenediamine disuccinic acid (EDDS) (0 and 5?mmol·kg^?1) as a synthetic chemical amendment, vermicompost (0 and 5%w/w) as an organic amendment and their combined application were evaluated for the phytoextraction by sunflower (Helianthus annuus L.) of cadmium (Cd) and lead (Pb) at three artificial contamination levels in soils (0, 50, and 100?mg·kg^?1 for Cd and 0, 100, and 200?mg·kg^?1 for Pb). The results showed that the application of EDDS was the most effective method to increase Pb and Cd concentrations in both parts of the plant. The results also showed that the application of EDDS increased 9.27% shoot Pb content at 200?mg·kg^?1 but decreased 15.95% shoot Cd content at 100?mg·kg^?1 contamination level with respect to the respective controls. The bioavailable concentrations of Cd at 100?mg·kg^?1 and Pb at 200?mg·kg^?1 contamination level in the soil at the end of experiment increased 25% and 26%, respectively after the application of EDDS but vermicompost decreased 43.28% the bioavailable Pb concentration relative to their controls. Vermicompost increased the remediation factor index of Cd, thus making it the best treatment for the phytoextraction of Cd. The combined application of EDDS and vermicompost was the best amendment for Pb phytoextraction.     

Cover Image,Volume 120, Number 11, November 2019

Skeletal tissue homeostasis is maintained via the balance of osteoclastic bone resorption and osteoblastic bone formation. Autophagy and apoptosis are essential for the maintenance of homeostasis and normal development in cells and tissues. We found that Bax-interacting factor 1 (Bif-1/Endophillin B1/SH3GLB1), involving in autophagy and apoptosis, was upregulated during osteoclastogenesis. Furthermore, mature osteoclasts expressed Bif-1 in the cytosol, particularly the perinuclear regions and podosome, suggesting that Bif-1 regulates osteoclastic bone resorption. Bif-1-deficient (Bif-1 ^−/−) mice showed increased trabecular bone volume and trabecular number. Histological analyses indicated that the osteoclast numbers increased in Bif-1 ^−/− mice. Consistent with the in vivo results, osteoclastogenesis induced by receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) was accelerated in Bif-1 ^−/− mice without affecting RANKL-induced activation of RANK downstream signals, such as NF-κB and mitogen-activated protein kinases (MAPKs), CD115/RANK expression in osteoclast precursors, osteoclastic bone-resorbing activity and the survival rate. Unexpectedly, both the bone formation rate and osteoblast surface substantially increased in Bif-1 ^−/− mice. Treatment with β-glycerophosphate (β-GP) and ascorbic acid (A.A) enhanced osteoblastic differentiation and mineralization in Bif-1 ^−/− mice. Finally, bone marrow cells from Bif-1 ^−/− mice showed a significantly higher colony-forming efficacy by the treatment with or without β-GP and A.A than cells from wild-type (WT) mice, suggesting that cells from Bif-1 ^−/− mice had higher clonogenicity and self-renewal activity than those from WT mice. In summary, Bif-1 might regulate bone homeostasis by controlling the differentiation and function of both osteoclasts and osteoblasts (235 words).     

Nepetin inhibits osteoclastogenesis by inhibiting RANKL‐induced activation of NF‐κB and MAPK signalling pathway,and autophagy

Aseptic prosthetic loosening due to wear particle–induced inflammatory osteolysis is the main cause of failure for artificial joint replacement. The inflammatory response and the production of pro‐osteoclastic factors lead to elevation of osteoclast formation and excessive activity results in extensive bone destruction around the bone‐implant interface. Here we showed that Nepetin, a natural bioactive flavonoid with proven anti‐inflammatory and anti‐proliferative properties, potently inhibited RANKL‐induced osteoclast differentiation, formation and bone resorption in vitro, and protected mice against the deleterious effects of titanium particle–induced calvarial osteolysis in vivo. Mechanistically, Nepetin attenuated RANKL‐induced activation of NF‐κB and MAPK signalling pathways and TRAF6‐dependent ubiquitination of Beclin 1 which is necessary for the induction of autophagy. In brief, our study demonstrates the potential therapeutic application of Nepetin against osteoclast‐mediated osteolytic diseases.     

Helvolic acid attenuates osteoclast formation and function via suppressing RANKL-induced NFATc1 activation

Excessive osteoclast formation and function are considered as the main causes of bone lytic disorders such as osteoporosis and osteolysis. Therefore, the osteoclast is a potential therapeutic target for the treatment of osteoporosis or other osteoclast-related diseases. Helvolic acid (HA), a mycotoxin originally isolated from Aspergillus fumigatus , has been discovered as an effective broad-spectrum antibacterial agent and has a wide range of pharmacological properties. Herein, for the first time, HA was demonstrated to be capable of significantly inhibiting receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption in vitro by suppressing nuclear factor of activated T cells 1 (NFATc1) activation. This inhibition was followed by the dramatically decreased expression of NFATc1-targeted genes including Ctr (encoding calcitonin receptor), Acp5 (encoding tartrate-resistant acid phosphatase [TRAcP]), Ctsk (encoding cathepsin K), Atp6v0d2 (encoding the vacuolar H+ ATPase V0 subunit d2 [V-ATPase-d2]) and Mmp9 (encoding matrix metallopeptidase 9) which are osteoclastic-specific genes required for osteoclast formation and function. Mechanistically, HA was shown to greatly attenuate multiple upstream pathways including extracellular signal-regulated kinase (ERK) phosphorylation, c-Fos signaling, and intracellular Ca ²⁺ oscillation, but had little effect on nuclear factor-κB (NF-κB) activation. In addition, HA also diminished the RANKL-induced generation of intracellular reactive oxygen species. Taken together, our study indicated HA effectively suppressed RANKL-induced osteoclast formation and function. Thus, we propose that HA can be potentially used in the development of a novel drug for osteoclast-related bone diseases.     

Temporal-spatial distribution,environmental significance and release risks of phosphorus in the sediments of a tropical mountain’s deep drinking water reservoir in southeastern China

In this study, the fractionation and distribution of phosphorus (P) in the core sediments of the Shanmei reservoir were investigated by using the chemical extraction method in directions for the first time in order to understand its bio-availability, adsorption characteristics, potential release and environmental significance. The results of the study showed that P in the sediments mainly consisted of inorganic phosphorus (IP) and that IP mainly consisted of non-apatite phosphorus (NAIP). The horizontal and temporal distributions of the P fractions were different from each other, but the vertical distribution was similar, which indicated a trend of stabilization after falling. The content of total phosphorus (TP), IP, organic phosphorus (OP), NAIP, apatite phosphorus (AP), and bio-available phosphorus (BAP) in the sediments during the three seasons ranged from 193.85 to 1664.05 mg·kg^?1, 126.90 to 1127.70 mg·kg^?1, 43.74 to 669.29 mg·kg^?1, 57.62 to 937.07 mg·kg^?1, 32.58 to 250.71 mg·kg^?1, and 41.06 to 871.82 mg·kg^?1, respectively. NAIP contents in the sediments accounted for more than 50% of TP. Using an analysis from three aspects, the eutrophication risk index (ERI) could be used to assess the potential release of P in the sediments, and there was a high release risk of P in the sediments in the Shanmei reservoir.     

柠檬香蜂草对铜的耐性及其积累特征研究

以柠檬香蜂草(Melissa officinalis)幼苗为材料,设置不同浓度Cu~(2+)胁迫(CK、200、400、800和1 000mg·kg~(-1))盆栽实验,测定胁迫0、7、14、21、28d后植物生物量、叶绿素含量、抗氧化酶活性、可溶性蛋白含量、丙二醛(MDA)含量以及植物体内Cu含量等指标,探讨柠檬香蜂草对Cu~(2+)的耐受性及其积累特征。结果表明:(1)相同处理时间下,柠檬香蜂草除MDA含量外其他所有指标均随着Cu~(2+)胁迫处理浓度的增加呈低浓度促进、高浓度抑制的变化趋势,且高浓度组(800和1 000mg·kg~(-1))与低浓度组(200和400mg·kg~(-1))之间差异显著(P0.05);MDA含量在1 000mg·kg~(-1)浓度下持续增长至第14天后开始下降。(2)柠檬香蜂草体内Cu的积累量随Cu胁迫浓度的升高呈先增加后减少的趋势,并在浓度为400mg·kg~(-1)时达到最高值(0.71mg/盆)。(3)在整个胁迫过程中,柠檬香蜂草植株的铜富集系数及其耐性系数均随Cu浓度的增加而减小,各处理浓度对Cu的耐性系数均大于0.5,富集系数均大于1。研究发现,柠檬香蜂草对Cu胁迫具有一定耐受性和富集能力,具有成为铜污染土壤修复植物的潜力。     

Neonatal exposure to bisphenol A advances pubertal development in female rats

Neonatal exposure to bisphenol A (BPA) is hypothesized to advance pubertal development. However, the effects of neonatal BPA exposure on pubertal development has not been described. In this study, female Sprague‐Dawley rats were exposed to 0.05, 0.5, 5, or 10 mg·kg^?1·day^?1 BPA, or corn oil vehicle alone from postnatal day 1 (PND1) to PND10 via subcutaneous injection. We evaluated day of vaginal opening (DVO), ovarian morphology, serum hormone concentrations, and hypothalamic expression of Gnrh1 and Kiss1 in female rats at PND35. DVO was significantly advanced in rats exposed to 5 and 10 mg·kg^?1·day^?1 BPA. Serum hormone concentrations increased as BPA dose increased. Additionally, hypothalamic Gnrh1 and Kiss1 expression were increased with BPA exposure; rats exposed to 10 mg·kg^?1·day^?1 BPA had significantly upregulated hypothalamic Gnrh1 and Kiss1 expressions in terms of both messenger RNA and protein levels. Our results suggest that exposure to a 10 mg·kg^?1·day^?1 dose of BPA might advance pubertal development significantly. In addition, within the range of 0 to 10 mg·kg^?1·day^?1, neonatal exposure to BPA may affect pubertal development in a dose‐dependent manner.     

Scutellarein inhibits RANKL-induced osteoclast formation in vitro and prevents LPS-induced bone loss in vivo

Osteoporosis, arthritis, Peget's disease, bone tumor, periprosthetic joint infection, and periprosthetic loosening have a common characteristic of osteolysis, which is characterized by the enhanced osteoclastic bone resorptive function. At present, the treatment target of these diseases is to interfere with osteoclastic formation and function. Scutellarein (Scu), a flavonoids compound, can inhibit the progress of tumor and inflammation. However, the role of Scu in inflammatory osteolysis isn’t elucidated clearly. Our study showed that Scu inhibited bone destruction induced by LPS in vivo and OC morphology and function induced by RANKL in vitro. Mechanistic studies revealed that Scu suppressed osteoclastic marker gene expression by RANKL-induced, such as Ctsk9, Mmp9, Acp5, and Atp6v0d2. In addition, we found that the inhibition effects of osteoclastogenesis and bone resorption function of Scu were mediated via attenuating NF-κB and NFAT signaling pathways. In conclusion, the results showed that Scu may become a potential new drug for the treatment of inflammatory osteolysis.     

外源5-氨基乙酰丙酸对NaCl胁迫下酸枣光合特性的影响

以2年生酸枣幼苗为试验材料,探讨不同浓度NaCl(0、4、8、12g·kg-1)胁迫下喷施5-氨基乙酰丙酸(ALA,75、150mg·L~(-1))对酸枣光合特性的影响。结果显示:(1)不同浓度NaCl胁迫下,外源ALA对酸枣叶片的净光合速率(Pn)、胞间二氧化碳浓度(Ci)、气孔导度(Gs)、蒸腾速率(Tr)及叶绿素含量等具有明显促进作用。(2)在不同浓度NaCl胁迫下,喷施75mg·L~(-1)的ALA仅在NaCl浓度为4和8g·kg-1处理下对酸枣Tr值具有显著提高作用,而喷施150mg·L~(-1) ALA在各NaCl浓度胁迫下对其Pn、Ci和Tr均具有显著促进作用。(3)在重度NaCl胁迫(12g·kg-1)下,喷施150mg·L~(-1) ALA对酸枣叶片叶绿素含量具有显著提高作用,而喷施75mg·L~(-1)浓度ALA却无明显提高。研究表明,在NaCl胁迫条件下,外源ALA能有效改善酸枣叶片光合气体交换参数,提高叶绿素含量,从而缓解NaCl胁迫的伤害,提高其光合能力,并以喷施150mg·L~(-1) ALA的缓解效果更好。     

In vivo pharmacokinetics and in vitro production of cocaethylene in pregnant guinea pigs

Simultaneous exposure to cocaine and ethanol results in the formation of cocaethylene, an active metabolite of cocaine. The concurrent abuse of both cocaine and ethanol is common during human pregnancy, but the kinetics of elimination and formation of this ethyl ester of cocaine have not been studied during pregnancy in any species. In the late gestation guinea pig (61 to 63 days), cocaethylene, at doses of 2 to 4 mg · kg⁻¹, is rapidly eliminated with a half-life of 29 min and a total body clearance of 77 ml · min⁻¹ · kg⁻¹. It is formed enzymatically by hepatic microsomal preparations from fetal, neonatal and maternal guinea pigs. The maximum rate of cocaethylene production (apparent V_max) when either ethanol or cocaine are varied while the other substrate is held constant, increases with age, from the late fetal period (65 days gestation, term 70 days) to adulthood. However, the Michaelis-Menten constant (apparent K_M) does not change with age. The rapid elimination of cocaethylene, coupled with the slow rate of formation (apparent V_max of 140 pmol · min⁻¹ · mg microsomal protein⁻¹) and the small amount of plasma analyzed most likely explains the inability to detect cocaethylene in vivo after concomitant cocaine and ethanol administration.     

Inhibition of osteoclast function by adenovirus expressing antisense protein-tyrosine kinase 2

Osteoclast activation is initiated by adhesion to bone, cytoskeletal rearrangement, formation of the sealing zone, and formation of the polarized ruffled membrane. Previous findings suggest that protein-tyrosine kinase 2 (PYK2), a cytoplasmic kinase related to focal adhesion kinase, participates in these events. This study examines the role of PYK2 in adhesion-mediated signaling and osteoclast function, using PYK2 antisense. We produced a recombinant adenovirus containing a 300-base pair reversed 5'-coding region of PYK2 and used full-length PYK2 as a control. Murine osteoclast-like cells or their mononuclear precursors were generated in a co-culture of bone marrow and osteoblasts. Infection with antisense adenovirus significantly reduced the expression of endogenous PYK2 protein relative to uninfected cells or to cells infected with sense PYK2 and caused: 1) a reduction in osteoclast formation in vitro; 2) inhibition of cell spreading and of actin ring formation in osteoclasts plated on glass or bone and of attachment and spreading of osteoclast precursors plated on vitronectin; 3) inhibition of bone resorption in vitro; 4) marked reduction in p130(Cas) tyrosine phosphorylation; and 5) no change in alpha(v)beta(3) integrin expression or c-Src tyrosine phosphorylation. Taken together, these findings support the hypothesis that PYK2 plays a central role in the adhesion-dependent cytoskeletal organization and sealing zone formation required for osteoclastic bone resorption.