呼吸前反馈调节、情景想象和过度通气

通过大量的科学证据 ,我们论述了代谢的负反馈调节不是呼吸调节的唯一机制。醒觉时呼吸的前反馈调节起了主导作用 ,前反馈调节可以在血气异常引起的负反馈调节之前 ,对将要发生的异常进行纠正 ,预见性地改变通气 ,而代谢的变化随后发生 ,避免了负反馈调节所具有的波动和滞后的缺点 ,使呼吸调节系统具有更大的灵活性和适应能力。在前反馈调节的形成过程中 ,经典的巴甫洛夫条件反射学说可能起了重要作用 .尤其重要的是表象作为条件刺激形成的条件反射 ,研究表象作为条件刺激如何形成呼吸的前反馈调节对揭示高通气综合征的发病机制具有重要意义…     

Thrombopoietin stimulates megakaryocytopoiesis, myelopoiesis, and expansion of CD34+ progenitor cells from single CD34+Thy-1+Lin- primitive progenitor cells

Thrombopoietin (TPO) or MpI ligand is known to stimulate megakaryocyte (MK) proliferation and differentiation. To identify the earliest human hematopoietic cells on which TPO acts, we cultured single CD34+Thy- 1+Lin- adult bone marrow cells in the presence of TPO alone, with TPO and interleukin-3 (IL-3), or with TPO and c-kit ligand (KL) in the presence of a murine stromal cell line (Sys1). Two distinct growth morphologies were observed: expansion of up to 200 blast cells with subsequent differentiation to large refractile CD41b+ MKs within 3 weeks or expansion to 200-10,000 blast cells, up to 25% of which expressed CD34. The latter blast cell expansions occurred over a 3- to 6-week period without obvious MK differentiation. Morphological staining, analysis of surface marker expression, and colony formation analysis revealed that these populations consisted predominantly of cells committed to the myelomonocytic lineage. The addition of IL-3 to TPO-containing cultures increased the extent of proliferation of single cells, whereas addition of KL increased the percentage of CD34+ cells among the expanding cell populations. Production of multiple colony- forming unit-MK from single CD34+Thy-1+Lin- cells in the presence of TPO was also demonstrated. In limiting dilution assays of CD34+Lin- cells, TPO was found to increase the size and frequency of cobblestone areas at 4 weeks in stromal cultures in the presence of leukemia inhibitory factor and IL-6. In stroma-free cultures, TPO activated a quiescent CD34+Lin-Rhodamine 123lo subset of primitive hematopoietic progenitor cells into cycle, without loss of CD34 expression. These data demonstrate that TPO acts directly on and supports division of cells more primitive than those committed to the MK lineage.     

Wound healing effect of methanolic leaf extract of Napoleona vogelii(Family:Lecythidaceae) in rats

Objective:To investigate the wound healing properly of Napoleona vogelii leaf extract in folkloric medicine.Methods:Roth sexes of adult albino rats(n=25) were used in this study and another group(n=30) were subjected to acute toxicity test(LD_(50)) of the plant extract.For the LD_(50),three randomized groups of 5 rats were first treated with 10,100,1 000 mg/kg body weight(bw),orally.This w as followed by a second treatment of 1500,3000,and 5 000 mg/kg bw of the leaf extract with continual monitoring of the animals for mortality or non-mortality.Incision wounds(1.3cm) were created on the skin of five groups of 5 rals using surgical blade under anesthesia.The first group was topically treated with petroleum jelly alone,group 2 was topically applied 400 mg/mL w/v of the reference drug,Neobaein,while group 3-5 were topically treated with 5-50 mg/mL w/v of the plant extract,respectively.Results:The percentage yield of the extract was 49.80%w/w dry matter.The phytochemical analysis revealed several bioactive constituents including glycosides,tannins,alkaloids,perpenoids.saponins,steroids,proteins,and carbohydrates.The LD_(50) was beyond our experimental limit and was not determined.Increased concentrations(5,20,and 50mg/mL w/v) of the extract had significant(ANOVA,P0.05) healing effect on the incision wounds giving rise to 125%-140% while treatmentawith Neobacin resulted in 150% healing effect on the third treatment regimen compared to the control(100%).Conclusions:These data indicate that Napoleona vogelii leaf extract contains potent bioactive compounds containing wound healing activity,substantiating its use as a wound healer in folkloric medicine.     

Electron tomography on γ‐aminobutyric acid‐ergic synapses reveals a discontinuous postsynaptic network of filaments

The regulation of synaptic strength at γ‐aminobutyric acid (GABA)‐ergic synapses is dependent on the dynamic capture, retention, and modulation of GABA A‐type receptors by cytoplasmic proteins at GABAergic postsynaptic sites. How these proteins are oriented and organized in the postsynaptic cytoplasm is not yet established. To better understand these structures and gain further insight into the mechanisms by which they regulate receptor populations at postsynaptic sites, we utilized electron tomography to examine GABAergic synapses in dissociated rat hippocampal cultures. GABAergic synapses were identified and selected for tomography by using a set of criteria derived from the structure of immunogold‐labeled GABAergic synapses. Tomography revealed a complex postsynaptic network composed of filaments that extend ～100 nm into the cytoplasm from the postsynaptic membrane. The distribution of these postsynaptic filaments was strikingly similar to that of the immunogold label for gephyrin. Filaments were interconnected through uniform patterns of contact, forming complexes composed of 2–12 filaments each. Complexes did not link to form an integrated, continuous scaffold, suggesting that GABAergic postsynaptic specializations are less rigidly organized than glutamatergic postsynaptic densities. J. Comp. Neurol. 522:921–936, 2014. © 2013 Wiley Periodicals, Inc.     

Cannabinoid receptor 1-expressing neurons in the nucleus accumbens

Endocannabinoid signaling critically regulates emotional and motivational states via activation of cannabinoid receptor 1 (CB1) in the brain. The nucleus accumbens (NAc) functions to gate emotional and motivational responses. Although expression of CB1 in the NAc is low, manipulation of CB1 signaling within the NAc triggers robust emotional/motivational alterations related to drug addiction and other psychiatric disorders, and these effects cannot be exclusively attributed to CB1 located at afferents to the NAc. Rather, CB1-expressing neurons in the NAc, although sparse, appear to be critical for emotional and motivational responses. However, the cellular properties of these neurons remain largely unknown. Here, we generated a knock-in mouse line in which CB1-expressing neurons expressed the fluorescent protein td-Tomato (tdT). Using these mice, we demonstrated that tdT-positive neurons within the NAc were exclusively fast-spiking interneurons (FSIs). These FSIs were electrically coupled with each other, and thus may help synchronize populations/ensembles of NAc neurons. CB1-expressing FSIs also form GABAergic synapses on adjacent medium spiny neurons (MSNs), providing feed-forward inhibition of NAc output. Furthermore, the membrane excitability of tdT-positive FSIs in the NAc was up-regulated after withdrawal from cocaine exposure, an effect that might increase FSI-to-MSN inhibition. Taken together with our previous findings that the membrane excitability of NAc MSNs is decreased during cocaine withdrawal, the present findings suggest that the basal functional output of the NAc is inhibited during cocaine withdrawal by multiple mechanisms. As such, CB1-expressing FSIs are targeted by cocaine exposure to influence the overall functional output of the NAc.Cannabinoid receptor type 1 (CB1) has been extensively implicated in a variety of psychological and psychiatric disorders, including drug addiction (1, 2). Recent studies suggest that CB1 within the nucleus accumbens (NAc), a key component of the brain reward circuit, plays a particularly important role in the development and maintenance of cocaine-induced behavioral alterations (3). Compared with the extensive expression of CB1 in the striatum, the mRNA and protein levels of CB1 within the NAc are sparse, leading to the notion that CB1 at afferent terminals projecting to the NAc are largely responsible for intra-NAc, CB1-dependent, cocaine-induced behaviors (4–6). However, a recent study primarily targeting CB1-expressing neurons demonstrates that inhibiting the expression of CB1 within the NAc antagonizes cocaine-induced reward responses (7). This and other results (8) suggest that CB1-expressing neurons in the NAc, although sparse, are critical for cellular and behavioral alterations induced by cocaine and other drugs of abuse.To examine these putative CB1-expressing neurons within the NAc, we generated a knock-in mouse line in which CB1-expressing neurons expressed the fluorescent protein td-Tomato (tdT). Our results show that tdT-positive neurons within the NAc were exclusively fast-spiking interneurons (FSIs). These FSIs were not only electrically connected with each other but exerted extensive inhibitory control on nearby medium spiny neurons (MSNs), the principal neurons in the NAc, via monosynaptic connections. Furthermore, the membrane excitability of these neurons became significantly up-regulated throughout short- and long-term withdrawal from repeated exposure to cocaine. These results suggest that CB1-expressing FSIs within the NAc are neural substrates targeted by cocaine exposure and influence the overall functional output of the NAc.