An autoradiographic study of subcortical forebrain projections from mediodorsal and adjacent midline thalamic nuclei in the rabbit

Conclusions from lesion studies on the subcortical efferent connections of the thalamic mediodorsal nucleus have been varied and conflicting. In this autoradiographic study, tritiated proline was injected into the mediodorsal nucleus and adjacent midline nuclear areas (intermediodorsal nucleus and paraventricular nucleus of the thalamus) of 18 rabbits. Terminal labeling from injections that included parts of the paraventricular nucleus was seen in the following ipsilateral areas: central amygdaloid nucleus, lateral septum, a restricted portion of the nucleus of the stria terminalis, entorhinal cortex and the entire extent of the medial (periventricular) hypothalamus. Injections that encroached into the intermediodorsal nucleus produced ipsilateral labeling in most of the nucleus accumbens, layers II and III of the olfactory tubercle, the magnocellular portion of the posterolateral basal amygdaloid nucleus and the caudate nucleus. Injections restricted to the mediodorsal nucleus produced labeling only in the ipsilateral caudate nucleus.It is concluded that medial portions of the mediodorsal nucleus only project to the caudate nucleus; whereas the midline nuclei project to the other eight subcortical areas in addition to the caudate nucleus. By attributing to the midline nuclei many of the projections previously associated with the mediodorsal nucleus, many discrepancies from earlier reports can be explained by lesion of fibers of passage. Efferent functional relationships of the mediodorsal nucleus with subcortical centers may be established through the caudate projections or projections to other thalamic structures, such as the adjacent midline nuclei.     

AmpliSensor—聚合酶链反应定量检测肺结核患者外周血结 …

目的 探讨ＡｍｐｌｉＳｅｎｓｏｒ－聚合酶链反应定量检测外周血中结核分支杆菌ＤＮＡ在肺结核的应用价值。方法 采用ＱｌＡａｍｐ和ＡｃｕＰｕｒｅ法提取，制备全血中模板ＴＢ－ＤＮＡ，应用ＡｍｐｌｉＳｅｎｓｏｒ－ＰＣＲ定量检测，并与ＩＳ６１１０－单管巢式聚合酶链反应（ＳＮ－ＰＣＲ）作比较。结果２００例肺结核患者的血液标本中，两种方法测得结核分支杆菌ＤＮＡ的阳性率分别为６０．５％、６３．５％。８５例非结核肺病     

ON THE ROLE OF RECURRENT INHIBITORY FEEDBACK IN MOTOR CONTROL

This article reviews presumed roles of recurrent inhibition in motor control, that have been proposed over the past five decades. The discussion is structured in an order of increasing complexity. It starts out with the simplest and earliest circuit, that is recurrent self-inhibition of skeleto-motoneurons, and related functions. It soon becomes clear that in order to understand recurrent inhibition, we must look beyond the simple self-inhibitory CNS circuit. First, recurrent inhibition must be seen in the context of other neural circuits. Second, some quantitative features appear to be correlated with features of the neuromusculo-skeletal periphery. Third, the aspect of lateral inhibition between different members of a motoneuron pool as well as between different motoneuron pools points to the essential multiple input-multiple output structure of recurrent inhibition that again can be understood only by correlating it with features of the neuromusculo-skeletal periphery. Another extension results from the discovery that recurrent inhibition affects not only skeleto-motoneurons, but also γ-motoneurons, Ia inhibitory interneurons mediating reciprocal inhibition between antagonist motoneurons, other Renshaw cells and cells of origin of the ventral spinocerebellar tract (VSCT). Then the view broadens again, investigating the potential role that recurrent inhibition plays in two far-ranging theories of motor control, the inverse-dynamics approach and the equilibrium-point hypothesis. Finally, the present author tries to formulate, in broad strokes, a personal functional interpretation of recurrent inhibition. All the functional considerations, right or wrong, should yield ideas for new experiments, and this then is the last objective of this review. Copyright © 1996 Elsevier Science Ltd.     

Biological definition of multiple chemical sensitivity from redox state and cytokine profiling and not from polymorphisms of xenobiotic-metabolizing enzymes

Background

Multiple chemical sensitivity (MCS) is a poorly clinically and biologically defined environment-associated syndrome. Although dysfunctions of phase I/phase II metabolizing enzymes and redox imbalance have been hypothesized, corresponding genetic and metabolic parameters in MCS have not been systematically examined.

Objectives

We sought for genetic, immunological, and metabolic markers in MCS.

Methods

We genotyped patients with diagnosis of MCS, suspected MCS and Italian healthy controls for allelic variants of cytochrome P450 isoforms (CYP2C9, CYP2C19, CYP2D6, and CYP3A5), UDP-glucuronosyl transferase (UGT1A1), and glutathione S-transferases (GSTP1, GSTM1, and GSTT1). Erythrocyte membrane fatty acids, antioxidant (catalase, superoxide dismutase (SOD)) and glutathione metabolizing (GST, glutathione peroxidase (Gpx)) enzymes, whole blood chemiluminescence, total antioxidant capacity, levels of nitrites/nitrates, glutathione, HNE-protein adducts, and a wide spectrum of cytokines in the plasma were determined.

Results

Allele and genotype frequencies of CYPs, UGT, GSTM, GSTT, and GSTP were similar in the Italian MCS patients and in the control populations. The activities of erythrocyte catalase and GST were lower, whereas Gpx was higher than normal. Both reduced and oxidised glutathione were decreased, whereas nitrites/nitrates were increased in the MCS groups. The MCS fatty acid profile was shifted to saturated compartment and IFNgamma, IL-8, IL-10, MCP-1, PDGFbb, and VEGF were increased.

Conclusions

Altered redox and cytokine patterns suggest inhibition of expression/activity of metabolizing and antioxidant enzymes in MCS. Metabolic parameters indicating accelerated lipid oxidation, increased nitric oxide production and glutathione depletion in combination with increased plasma inflammatory cytokines should be considered in biological definition and diagnosis of MCS.     

Effects of Li(+) transport and Li(+) immobilization on Li(+)/Mg(2+) competition in cells: implications for bipolar disorder

Li(+)/Mg(2+) competition has been implicated in the therapeutic action of Li(+) treatment in bipolar illness. We hypothesized that this competition depended on cell-specific properties. To test this hypothesis, we determined the degree of Li(+) transport, immobilization, and Li(+)/Mg(2+) competition in lymphoblastomas, neuroblastomas, and erythrocytes. During a 50 mM/L Li(+)-loading incubation, Li(+) accumulation at 30 min (mmoles Li(+)/L cells) was the greatest in lymphoblastomas (11.1+/-0.3), followed by neuroblastomas (9.3+/-0.5), and then erythrocytes (4.0+/-0.5). Li(+) binding affinities to the plasma membrane in all three cell types were of the same order of magnitude; however, Li(+) immobilization in intact cells was greatest in neuroblastomas and least in erythrocytes. When cells were loaded for 30 min in a 50 mM/L Li(+)-containing medium, the percentage increase in free intracellular [Mg(2+)] in neuroblastoma and lymphoblastoma cells ( approximately 55 and approximately 52%, respectively) was similar, but erythrocytes did not exhibit any substantial increase ( approximately 6%). With the intracellular [Li(+)] at 15 mM/L, the free intracellular [Mg(2+)] increased by the greatest amount in neuroblastomas ( approximately 158%), followed by lymphoblastomas ( approximately 75%), and then erythrocytes ( approximately 50%). We conclude that Li(+) immobilization and transport are related to free intracellular [Mg(2+)] and to the extent of Li(+)/Mg(2+) competition in a cell-specific manner.     

Melatonin differentially modulates the expression and function of the hMT1 and hMT2 melatonin receptors upon prolonged withdrawal

Melatonin is synthesized and released following a circadian rhythm and reaches its highest blood levels during the night. It relays signals of darkness to target tissues involved in regulating circadian and seasonal rhythms. Here, we report the expression of human melatonin receptors type 1 and 2 (hMT(1) and hMT(2), respectively) in Chinese hamster ovary (CHO) cells following exposure to melatonin treatments mimicking the amplitude (400 pM) and duration (8 hr) of the nightly melatonin peak and upon withdrawal. Exposure of CHO-MT(1) cells to melatonin (400 pM) for 0.5, 1, 2, 4, and 8 hr significantly increased specific 2-[125I]iodomelatonin (500 pM) binding to hMT(1) melatonin receptors upon 16-hr withdrawal. However, the same treatment did not affect the expression of hMT(2) melatonin receptors. The increase in specific 2-[125I]iodomelatonin (500 pM) binding (162+/-29%, N=3, P<0.05) 16 hr after melatonin withdrawal was parallel to increases in hMT(1) melatonin receptor mRNA (231+/-33%, N=4, P<0.05). This effect was due to an increase in the total number of hMT(1) receptors [B(max) 833+/-97 fmol/mg protein (N=3), control; 1449+/-41 fmol/mg protein (N=3), treated], with no change in binding affinity. The melatonin-mediated increase in MT(1) melatonin receptor expression upon withdrawal was not mediated through either a direct effect of the hormone in the promoter's vector or in the rate of mRNA degradation. In conclusion, melatonin differentially regulates the expression of its own receptors, which may have important implications in the transduction of dark signals in vivo.     

New insights into doxorubicin-induced cardiotoxicity: the critical role of cellular energetics

Cardiotoxic side-effects represent a serious complication of anticancer therapy with anthracyclines, in particular with doxorubicin (DXR) being the leading drug of the group. Different hypotheses, accentuating various mechanisms and/or targets, have been proposed to explain DXR-induced cardiotoxicity. This review focuses on the myocardial energetic network as a target of DXR toxic action in heart and highlights the recent advances in understanding its role in development of the DXR related cardiac dysfunction. We present a survey of DXR-induced defects in different steps of cardiac energy metabolism, including reduction of oxidative capacity of mitochondria, changes in the profile of energy substrate utilization, disturbance of energy transfer between sites of energy production and consumption, as well as defects in energy signaling. Considering the wide spectrum and diversity of the changes reported, we attempt to integrate these facts into a common framework and to discuss important functional and temporal relationships between DXR-induced events and the possible underlying molecular mechanisms.     

Anti-hyperuricemic and nephroprotective effects of Modified Simiao Decoction in hyperuricemic mice

Ethnopharmacological relevance

Modified Simiao Decoction (MSD), based on clinical experience, has been used for decades and famous for its efficiency in treating hyperuricemic and gouty diseases.

Aim of the study

To investigate the effects of MSD on anti-hyperuricemic and nephroprotective effects are involved in potassium oxonate-induced hyperuricemic mice.

Materials and methods

The effects of MSD were investigated in hyperuricemic mice induced by potassium oxonate. MSD were fed to hyperuricemic mice daily at a dose of 0.45, 0.90, 1.80 g/kg for 10 days, and allopurinol (5 mg/kg) was given as a positive control. Serum and urine levels of uric acid and creatinine, and fractional excretion of uric acid (FEUA) were determined by colorimetric method. Its nephroprotective effects were evaluated by determining a panel of oxidative stress markers after the intervention in hyperuricemic mice. Simultaneously, protein levels of urate transporter 1 (URAT1) and organic anion transporter 1 (OAT1) in the kidney were analyzed by Western blotting.

Results

MSD could inhibit XOD activities in serum and liver, decrease levels of serum uric acid, serum creatinine and BUN, and increased levels of urine uric acid, urine creatinine, FEUA dose-dependently through down-regulation of URAT1 and up-regulation of OAT1 protein expressions in the renal tissue of hyperuricemic mice. It also effectively reversed oxonate-induced alterations on renal MDA levels and SOD activities in this model.

Conclusion

MSD processes uricosuric and nephroprotective actions by regulating renal urate transporters and enhancing antioxidant enzymes activities to improve renal dysfunction in hyperuricemic mice.     

Changes of intracellular sodium and potassium ion concentrations in frog spinal motoneurons induced by repetitive synaptic stimulation

A post-tetanic membrane hyperpolarization following repetitive neuronal activity is a commonly observed phenomenon in the isolated frog spinal cord as well as in neurons of other nervous tissues. We have now used double-barrelled Na⁺- and K⁺-ion-sensitive microelectrodes to measure the intracellular Na⁺- and K⁺-concentrations and also the extracellular K⁺-concentration of lumbar spinal motoneurons during and after repetitive stimulation of a dorsal root. The results show that the posttetanic membrane hyperpolarization occurred at a time when the intracellular [Na⁺] reached its maximal value, intracellular [K⁺] had its lowest level and extracellular [K⁺] was still elevated. The hyperpolarization was blocked by ouabain and reduced by Li⁺.These data support the previous suggestion that an electrogenic Na^+/K⁺ pump mode may be the mechanism underlying the post-tetanic membrane hyperpolarization.