bluuebunny/crossref_metadata_2025 huggingface dataset:
Heme-oxygenase-mediated iron accumulation in the liver
Authors: Khan Zia A , Barbin Yousef P , Cukiernik Mark , Adams Paul C , Chakrabarti Subrata
Published: September 2004

Heme oxygenase (HO) isozymes, HO-1 and HO-2, catalyze the conversion of heme to iron, carbon monoxide, and biliverdin. The present study was aimed at elucidating the role of the HO system in iron accumulation and oxidative stress in the liver. We have also studied the regulation of an iron exporter, ferroportin-1 (FPN-1), as an adaptive response mechanism to increased iron levels. Sprague-Dawley rats were treated with HO inducer hemin or HO inhibitor tin-protoporphyrin IX (SnPPIX) for 1 month. A portion of liver tissues was subjected to RT-PCR for HO-1, HO-2, and FPN-1 gene expression as well as an HO activity assay. Paraffin-embedded tissues were stained for iron with Prussian blue. Hepatic iron concentration was measured by High Resolution-Inductively Coupled Plasma-Mass Spectrometry. 8-hydroxy-2′-deoxyguanosine (8-OHdG) stain, a sensitive and specific marker of oxidative DNA damage, was performed to assess oxidative stress. Hemin treatment led to augmented HO expression and activity in association with increased iron accumulation and oxidative stress. FPN-1 expression was also found to be upregulated. SnPPIX treatment reduced HO activity, intracellular iron levels, and oxidative stress as compared to controls. Our data provides evidence of increased HO activity as an important pro-oxidant mechanism leading to iron accumulation in the liver.Key words: Kupffer cells, hepatocytes, iron overload, ferroportin-1, oxidative stress.
Barosensitive neurons in the rat tractus solitarius and paratrigeminal nucleus: a new model for medullary, cardiovascular reflex regulation
Authors: Junior Antonio Balan , Caous Cristofer André , Yu Yun-Guo , Lindsey Charles Julian
Published: September 2004

The nucleus of the solitary tract (NTS), a termination site for primary afferent fibers from baroreceptors and other peripheral cardiovascular receptors, contains blood pressure-sensitive neurons, some of which have rhythmic activity locked to the cardiac cycle, making them key components of the central pathway for cardiovascular regulation. The paratrigeminal nucleus (Pa5), a small collection of medullary neurons in the dorsal lateral spinal trigeminal tract, like the NTS, receives primary somatosensory inputs of glossopharyngeal, vagal, and other nerves. Recent studies show that the Pa5 has efferent connections to the rostroventrolateral reticular nucleus (RVL), NTS, and ambiguus nucleus, suggesting that its structure may play a role in the baroreceptor reflex modulation. In the present study, simultaneous recording from multiple single neurons in freely behaving rats challenged with i.v. phenylephrine administration, showed that 83% of NTS units and 72% of Pa5 units were baroreceptor sensitive. Whereas most of the baroreceptor-sensitive NTS and Pa5 neurons (86 and 61%, respectively) increased firing rate during the ascending phase of the pressor response, about 16% of Pa5 and NTS baroreceptor-sensitive neurons had a decreased firing rate. On one hand, the decrease in firing rate occurred during the ascending phase of the pressor response, indicating sensitivity to rapid changes in arterial pressure. On the other hand, the increases in neuron activity in the Pa5 or NTS occurred during the entire pressor response to phenylephrine. Cross-correlational analysis showed that 71% of Pa5 and 93% of NTS baroreceptor-activated neurons possessed phasic discharge patterns locked to the cardiac cycle. These findings suggest that the Pa5, like the NTS, acts as a terminal for primary afferents in the medullary-baroreflex or cardiorespiratory-reflex pathways.Key words: cardiovascular reflexes, baroreflex response, arterial blood pressure, multiple single unit recording.
Hydrogen peroxide induces heat shock protein and proto-oncogene mRNA accumulation in Xenopus laevis A6 kidney epithelial cells
Authors: Muller M , Gauley J , Heikkila John J
Published: September 2004

In this study, we examined the effect of hydrogen peroxide on the accumulation of various mRNAs encoding heat shock proteins (hsps) and proto-oncogenes in Xenopus A6 kidney epithelial cells. Hydrogen peroxide treatment enhanced the accumulation of hsp90, hsp70, hsp30, c-jun, c-fos, and actin mRNAs with distinct temporal patterns. Although hsp70, c-fos, and c-jun mRNA levels peaked at 1–2 h before declining, hsp30 and hsp90 mRNA levels were maximal at 4–6 h. Other mRNAs, including heat shock cognate hsc70, immunoglobulin binding protein, and ribosomal L8, were unaffected. Treatment of kidney cells with a combination of mild heat shock plus hydrogen peroxide resulted in a synergistic increase in the relative levels of both hsp70 and hsp30 mRNA, but not hsp90, c-fos, c-jun, or actin. This study suggests that analysis of hsp and proto-oncogene mRNA levels may be of value as molecular biomarkers of oxidative stress associated with various disease states and nephrotoxicity in kidney.Key words: Xenopus, kidney, mRNA, heat shock protein, hydrogen peroxide.
The effects of ketorolac and morphine on articular cartilage and synovium in the rabbit knee joint
Authors: Dogan Nazim , Erdem Ali Fuat , Gundogdu Cemal , Kursad Husnu , Kizilkaya Mehmet
Published: September 2004

Analgesics are commonly injected intra-articularly for analgesia after arthroscopic surgery, especially of knee joints. The aim of this study was to research the effects of ketorolac and morphine on articular cartilage and synovial membrane. This study used rabbit right and left hind knee joints. The treatments, saline, morphine, or ketorolac, were administered intra-articularly 24 h after injection, and 5 joints from animals in each drug group were chosen randomly to form Group I and subgroups of Group I. The same procedures were applied after 48 h and 10 days of injection to form Groups II and III, respectively, and subgroups of these groups. Knee joints were excised and a blinded observer evaluated the histopathology according to inflammation of the articular cartilage, inflammatory cell infiltration, hypertrophy, and hyperplasia of the synovial membrane. No histopathological changes were found in the control groups. In the ketorolac and morphine groups, there were varying degrees of synovial membrane inflammatory cell infiltration and minimal, mild, or moderate synovial membrane cell hyperplasia or hypertrophy. Except for the ketorolac group at 24 h, both ketorolac and morphine groups showed more histopathological changes than controls (p < 0.05). Morphine and ketorolac both cause mild histopathological changes in rabbit knee joints, morphine causing more than ketorolac, but both of the drugs can be used intra-articularly with safety.Key words: intra-articular analgesia, knee joint, histopathological changes, articular cartilage, synovial membrane.
Amino acid metabolism in the Zucker diabetic fatty rat: effects of insulin resistance and of type 2 diabetes
Authors: Wijekoon Enoka P , Skinner Craig , Brosnan Margaret E , Brosnan John T
Published: September 2004

We investigated amino acid metabolism in the Zucker diabetic fatty (ZDF Gmi fa/fa) rat during the prediabetic insulin-resistant stage and the frank type 2 diabetic stage. Amino acids were measured in plasma, liver, and skeletal muscle, and the ratios of plasma/liver and plasma/skeletal muscle were calculated. At the insulin-resistant stage, the plasma concentrations of the gluconeogenic amino acids aspartate, serine, glutamine, glycine, and histidine were decreased in the ZDF Gmi fa/fa rats, whereas taurine, α-aminoadipic acid, methionine, phenylalanine, tryptophan, and the 3 branched-chain amino acids were significantly increased. At the diabetic stage, a larger number of gluconeogenic amino acids had decreased plasma concentrations. The 3 branched-chain amino acids had elevated plasma concentrations. In the liver and the skeletal muscles, concentrations of many of the gluconeogenic amino acids were lower at both stages, whereas the levels of 1 or all of the branched-chain amino acids were elevated. These changes in amino acid concentrations are similar to changes seen in type 1 diabetes. It is evident that insulin resistance alone is capable of bringing about many of the changes in amino acid metabolism observed in type 2 diabetes.Key words: plasma amino acids, liver amino acids, muscle amino acids, gluconeogenesis.
β-adrenergic receptor blockade during exercise decreases intestinal lymphocyte apoptosis but not cell loss in mice
Authors: Marra S , Hoffman-Goetz L
Published: September 2004

Catecholamines induce apoptosis in various lymphoid populations. This process can occur with both α- and β-adrenoreceptors. Heavy exercise increases plasma catecholamine concentrations, and is also a cause of lymphocyte apoptosis, a possible explanation for postexercise lymphocytopenia. The purpose of this study was to examine the effects of adrenoreceptor antagonism on exercise-induced decreases and apoptosis of intestinal lymphocytes. Mice received an intraperitoneal injection of phentolamine (a nonselective α-blocker), nadolol (a nonselective β-blocker), or saline (vehicle) prior to an exhaustive bout of exercise. Total intestinal lymphocyte numbers, percent and number of CD3+ lymphocytes, and cell viability were assessed. Neither α- nor β-antagonism prevented exercise-induced cell loss in the intestine; however, pretreatment with nadolol significantly reduced the number of apoptotic and necrotic cells. Phentolamine administration appeared to increase the incidence of cell death among intestinal lymphocytes. Both drugs decreased the percentage of CD3+ intestinal lymphocytes. Our study suggests that catecholamines are not responsible for postexercise lymphocytopenia, but β-adrenoceptor blockade may confer protection against exercise-induced apoptosis of intestinal lymphocytes.Key words: catecholamines, exhaustive exercise, apoptosis, intestinal lymphocytes, rodents.
Heart rate variability following coronary artery bypass graft surgery as a function of recovery time, posture, and exercise
Authors: Brown C Ann , Wolfe Larry A , Hains Sylvia , Ropchan Glorianne , Parlow Joel
Published: September 2004

This study examined the claim made by Niemela et al. (1992) that the decline in heart rate variability after coronary artery bypass graft surgery is irreversible. We tested six women and 16 men six and 12 weeks postoperative in three postures: in the supine position, in the standing position, and during low-intensity steady-state exercise. Beat-by-beat arterial blood pressure and electrocardiographic R–R interval data were collected continuously for 10 min in each condition. R–R interval data were analyzed with spectral analysis; baroreflex data were analyzed using the sequence method. Our results show that the indices of parasympathetic modulation improved over time, as seen by an | increased spontaneous baroreflex sensitivity and parasympathetic indicator, that both indices were affected by posture, and that spontaneous baroreflex sensitivity was also affected by low-intensity exercise. The effects of posture are consistent with attenuated responses of healthy older subjects to orthostatic stress. Similarly, the effects of low-intensity exercise are consistent with findings in healthy subjects. We found that spontaneous baroreflex sensitivity declined during exercise, whereas, in healthy subjects, this is maintained during low-intensity steady-state exercise. Our results of significant functional recovery between six and 12 weeks postoperative suggest that at least some of the autonomic dysfunction following surgery is temporary. Previously, no such duration of study has lasted longer than four or six weeks following cardiac surgery, which may not have been long enough to show significant functional restoration in heart rate variability.Key words: heart rate variability, spontaneous baroreflex sensitivity, CABG surgery, posture, exercise.
Bradykinin microinjection in the paratrigeminal nucleus triggers neuronal discharge in the rat rostroventrolateral reticular nucleus
Authors: Caous Cristofer Andre , Balan Antonio , Lindsey Charles Julian
Published: September 2004

A small collection of neurons in the dorsal lateral medulla, the paratrigeminal nucleus (Pa5), projects directly to the rostroventrolateral reticular nucleus (RVL). Bradykinin (BK) microinjections in the Pa5 produce marked pressor responses. Also, the Pa5 is believed to be a component of the neuronal substrates of the somatosensory response and the baroreflex arc. Considering the developing interest in the functional physiology of the Pa5, the present study was designed to characterize RVL neuronal activity in response to BK microinjections in the Pa5 as well as to phenylephrine-induced blood pressure increases in freely behaving rats. Of the 46 discriminated RVL neurons, 82% responded with a 180% mean increase in firing rate after BK application to the paratrigeminal nucleus, before the onset of the blood pressure increase. Thirty (79%) of the RVL BK-excited neurons were baroreceptor-inhibited units that responded with a 30% decrease in firing rate in response to a phenylephrine-produced increase of blood pressure. Twenty-seven (71%) units of the latter population displayed cardiac-cycle-locked rhythmic activity. The findings demonstrate a BK-stimulated functional connection between the Pa5 and RVL that may represent the neural pathway in the BK-mediated pressor response. This pathway may be relevant to baroreflex mechanisms since it relates to cardiovascular pressure-sensitive neurons.Key words: bradykinin, arterial blood pressure, ensemble neuron recording, RVL, baroreflex.
Cell stiffness and receptors: evidence for cytoskeletal subnetworks
Authors: Huang Hayden , Sylvan Jeremy , Jonas Maxine , Barresi Rita , So Peter T. C. , Campbell Kevin P. , Lee Richard T.
Published: September 2004

Viscoelastic models of cells often treat cells as homogeneous objects. However, studies have demonstrated that cellular properties are local and can change dramatically on the basis of the location probed. Because membrane receptors are linked in various ways to the intracellular space, with some receptors linking to the cytoskeleton and others diffusing freely without apparent linkages, the cellular physical response to mechanical stresses is expected to depend on the receptor engaged. In this study, we tested the hypothesis that cellular mechanical stiffness as measured via cytoskeletally linked receptors is greater than stiffness measured via receptors that are not cytoskeletally linked. We used a magnetic micromanipulator to apply linear stresses to magnetic beads attached to living cells via selected receptors. One of the receptor classes probed, the dystroglycan receptors, is linked to the cytoskeleton, while the other, the transferrin receptors, is not. Fibronectin-coated beads were used to test cellular mechanical properties of the cytoskeleton without membrane dependence by allowing the beads to endocytose. For epithelial cells, transferrin-dependent stiffness and endocytosed bead-dependent stiffness were similar, while dystroglycan-dependent stiffness was significantly lower. For smooth muscle cells, dystroglycan-dependent stiffness was similar to the endocytosed bead-dependent stiffness, while the transferrin-dependent stiffness was lower. The conclusion of this study is that the measured cellular stiffness is critically influenced by specific receptor linkage and by cell type and raises the intriguing possibility of the existence of separate cytoskeletal networks with distinct mechanical properties that link different classes of receptors.
Laminin-α1 globular domains 3 and 4 induce heterotrimeric G protein binding to α-syntrophin's PDZ domain and alter intracellular Ca2+ in muscle
Authors: Zhou Yan Wen , Oak Shilpa A. , Senogles Susan E. , Jarrett Harry W.
Published: September 2004

α-Syntrophin is a component of the dystrophin glycoprotein complex (DGC). It is firmly attached to the dystrophin cytoskeleton via a unique COOH-terminal domain and is associated indirectly with α-dystroglycan, which binds to extracellular matrix laminin. Syntrophin contains two pleckstrin homology (PH) domains and one PDZ domain. Because PH domains of other proteins are known to bind the βγ-subunits of the heterotrimeric G proteins, whether this is also a property of syntrophin was investigated. Isolated syntrophin from rabbit skeletal muscle binds bovine brain Gβγ-subunits in gel blot overlay experiments. Laminin-1-Sepharose or specific antibodies against syntrophin, α- and β-dystroglycan, or dystrophin precipitate a complex with Gβγ from crude skeletal muscle microsomes. Bacterially expressed syntrophin fusion proteins and truncation mutants allowed mapping of Gβγ binding to syntrophin's PDZ domain; this is a novel function for PDZ domains. When laminin-1 is bound, maximal binding of Gsα and Gβγ occurs and active Gsα, measured as GTP-γ35S bound, decreases. Because intracellular Ca2+ is elevated in Duchenne muscular dystrophy and Gsα is known to activate the dihydropyridine receptor Ca2+ channel, whether laminin also altered intracellular Ca2+ was investigated. Laminin-1 decreases active (GTP-γS-bound) Gsα, and the Ca2+ channel is inhibited by laminin-1. The laminin α1-chain globular domains 4 and 5 region, the region bound by DGC α-dystroglycan, is sufficient to cause an effect, and an antibody that specifically blocks laminin binding to α-dystroglycan inhibits Gβ binding by syntrophin in C2C12 myotubes. These observations suggest that DGC is a matrix laminin, G protein-coupled receptor.
Preservation of folate transport activity with a low-pH optimum in rat IEC-6 intestinal epithelial cell lines that lack reduced folate carrier function
Authors: Wang Yanhua , Rajgopal Arun , Goldman I. David , Zhao Rongbao
Published: September 2004

Intestinal folate transport has been well characterized, and rat small intestinal epithelial (IEC-6) cells have been used as a model system for the study of this process on the cellular level. The major intestinal folate transport activity has a low-pH optimum, and the current paradigm is that this process is mediated by the reduced folate carrier (RFC), despite the fact that this carrier has a neutral pH optimum in leukemia cells. The current study addressed the question of whether constitutive low-pH folate transport activity in IEC-6 cells is mediated by RFC. Two independent IEC-6 sublines, IEC-6/A4 and IEC-6/PT1, were generated by chemical mutagenesis followed by selective pressure with antifolates. In IEC-6/A4 cells, a premature stop resulted in truncation of RFC at Gln420. A green fluorescent protein (GFP) fusion with the truncated protein was not stable. In IEC-6/PT1 cells, Ser135 was deleted, and this alteration resulted in the failure of localization of the GFP fusion protein in the plasma membrane. In both cell lines, methotrexate (MTX) influx at neutral pH was markedly decreased compared with wild-type IEC-6 cells, but MTX influx at pH 5.5 was not depressed. Transient transfection of the GFP-mutated RFC constructs into RFC-null HeLa cells confirmed their lack of transport function. These results indicate that in IEC-6 cells, folate transport at neutral pH is mediated predominantly by RFC; however, the folate transport activity at pH 5.5 is RFC independent. Hence, constitutive folate transport activity with a low-pH optimum in this intestinal cell model is mediated by a process entirely distinct from that of RFC.
Expression of granulocyte colony-stimulating factor is induced in injured rat carotid arteries and mediates vascular smooth muscle cell migration
Authors: Chen Xing , Kelemen Sheri E. , Autieri Michael V.
Published: September 2004

Granulocyte colony-stimulating factor (G-CSF) is a lineage-restricted hematopoietic growth factor that stimulates proliferation and maturation of hematopoietic progenitors and is a known powerful mobilizer of bone marrow-derived stem cells. Very little has been reported on G-CSF expression and modulation of vascular smooth muscle cell (VSMC) activation. The purpose of this study was to characterize the expression and effects of G-CSF on primary human VSMC and balloon angioplasty-injured rat carotid arteries. In cultured human VSMC, G-CSF mRNA and protein expression are induced by several cytokines, with the most potent being fetal calf serum and T-lymphocyte-conditioned media. G-CSF is not expressed in naive rat carotid arteries but is induced in neointimal SMC in carotid arteries subject to balloon angioplasty. G-CSF is chemotactic for human VSMC. There is a significant difference between unstimulated cells and those treated with G-CSF at 100 and 1,000 pg/ml ( P < 0.01 and 0.05 for 3 experiments). G-CSF also activates the GTPase Rac1, a regulator of cellular migration in VSMC. Inhibition of Rac1 inhibits G-CSF-driven VSMC migration. Important signal transduction protein kinases, including p44/42 MAPK, Akt, and S6 kinase, are also activated in response to G-CSF. This is the first report describing the expression of G-CSF in injured arteries and the multiple effects of G-CSF on VSMC activation. Together, our data suggest that G-CSF is an important mediator of inflammatory cell-VSMC communication and VSMC autocrine activation and may be an important mediator of the VSMC response to injury.
Acute effects of 17β-estradiol on myocardial pH, Na+, and Ca2+ and ischemia-reperfusion injury
Authors: Anderson Steven E. , Kirkland Dawn M. , Beyschau Andrea , Cala Peter M.
Published: September 2004

Evidence suggests that 1) ischemia-reperfusion injury is due largely to cytosolic Ca2+ accumulation resulting from functional coupling of Na+/Ca2+ exchange (NCE) with stimulated Na+/H+ exchange (NHE1) and 2) 17β-estradiol (E2) stimulates release of NO, which inhibits NHE1. Thus we tested the hypothesis that acute E2 limits myocardial Na+ and therefore Ca2+ accumulation, thereby limiting ischemia-reperfusion injury. NMR was used to measure cytosolic pH (pHi), Na+ (Na[Formula: see text]), and calcium concentration ([Ca2+]i) in Krebs-Henseleit (KH)-perfused hearts from ovariectomized rats (OVX). Left ventricular developed pressure (LVDP) and lactate dehydrogenase (LDH) release were also measured. Control ischemia-reperfusion was 20 min of baseline perfusion, 40 min of global ischemia, and 40 min of reperfusion. The E2 protocol was identical, except that 1 nM E2 was included in the perfusate before ischemia and during reperfusion. E2 significantly limited the changes in pHi, Na[Formula: see text] and [Ca2+]i during ischemia ( P < 0.05). In control OVX vs. OVX+E2, pHi fell from 6.93 ± 0.03 to 5.98 ± 0.04 vs. 6.96 ± 0.04 to 6.68 ± 0.07; Na[Formula: see text] rose from 25 ± 6 to 109 ± 14 meq/kg dry wt vs. 25 ± 1 to 76 ± 3; [Ca2+]i changed from 365 ± 69 to 1,248 ± 180 nM vs. 293 ± 66 to 202 ± 64 nM. E2 also improved recovery of LVDP and diminished release of LDH during reperfusion. Effects of E2 were diminished by 1 μM Nω-nitro-l-arginine methyl ester. Thus the data are consistent with the hypothesis. However, E2 limitation of increases in [Ca2+]i is greater than can be accounted for by the thermodynamic effect of reduced Na[Formula: see text] accumulation on NCE.
Nutrient-stimulated GLP-2 release and crypt cell proliferation in experimental short bowel syndrome
Authors: Martin G. R. , Wallace L. E. , Hartmann B. , Holst J. J. , Demchyshyn L. , Toney K. , Sigalet D. L.
Published: September 2004

Glucagon-like peptide-2 (GLP-2) is an enteroendocrine peptide that is released in response to luminal nutrients and has unique trophic actions in the gastrointestinal tract. These features suggest GLP-2 may be important in controlling intestinal adaptation. We examined the relationship over time of GLP-2 production and adaptation to intestinal resection, the effects of resection-induced malabsorption on GLP-2 production, and the correlation of endogenous serum GLP-2 levels with adaptation as measured by crypt-cell proliferation (CCP). We initially examined the effect of nutrient malabsorption, induced by a 90% resection of the proximal intestine studied on day 4, on the time course and levels of GLP-2 release. Secondly, the degree of malabsorption was varied by performing intestinal transection or 50, 75, or 90% resection of proximal small intestine. Finally, the relationship of GLP-2 levels over time with adaptation to a 90% resection was examined by determining GLP-2 levels on days 7, 14, and 28, and correlating this with intestinal adaptation, as assessed by morphology and CCP rate. A 90% resection significantly increased basal and postprandial GLP-2 levels, with a net increase in nutrient-stimulated exposure over 90 min; GLP-2 exposure (integrated levels vs. time) increased 12.7-fold in resected animals ( P < 0.001). Basal and postprandial GLP-2 levels significantly correlated with the magnitude of intestinal resection ( r2= 0.71; P < 0.001), CCP ( r2= 0.48; P < 0.005), and nutrient malabsorption (protein, P < 0.001; fat, P < 0.005). The increase in CCP was maintained to 28 days after small bowel resection and was associated with an ongoing elevation in GLP-2 release. These findings suggest that GLP-2 is important in initiating and maintaining the small intestinal adaptive response to resection.
Mechanism of salutary effects of androstenediol on hepatic function after trauma-hemorrhage: role of endothelial and inducible nitric oxide synthase
Authors: Shimizu Tomoharu , Szalay Laszlo , Choudhry Mashkoor A. , Schwacha Martin G. , Rue Loring W. , Bland Kirby I. , Chaudry Irshad H.
Published: September 2004

Recent studies have shown that administration of dehydroepiandrosterone (DHEA) after trauma-hemorrhage (T-H) improves cardiovascular and hepatic function in male animals. Although androstenediol, one of the DHEA metabolites, has been recently reported to produce salutary effects on cardiac function and splanchnic perfusion after T-H, it remains unknown whether androstenediol per se has any salutary effects on hepatic function under those conditions. To study this, male Sprague-Dawley rats underwent laparotomy and ∼90 min of hemorrhagic shock (35–40 mmHg), followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. Androstenediol (1 mg/kg body wt iv) was administered at the end of resuscitation, and the animals were killed 24 h later. T-H significantly reduced portal blood flow, bile production, and serum albumin levels. Portal pressure, serum alanine aminotransferase, hepatic nitrate/nitrite, inducible nitric oxide synthase (iNOS), and endothelin-1 markedly increased after T-H. The alterations in these parameters induced by T-H were significantly attenuated in rats treated with androstenediol. Endothelial NOS (eNOS) expression, which was not different between T-H and sham, was found to be significantly elevated in T-H androstenediol-treated rats. These data suggest that improvement in hepatic perfusion by androstenediol after T-H is likely due to a decrease in endothelin-1 and induction of eNOS. Moreover, the decrease in hepatic damage after androstenediol administration is likely related to liver iNOS downregulation. Thus androstenediol appears to be a novel and useful adjunct for restoring hepatic function in male animals after adverse circulatory conditions.
Alcohol ingestion before burn injury decreases splanchnic blood flow and oxygen delivery
Authors: Choudhry Mashkoor A. , Ba Zheng F. , Rana Shadab N. , Bland Kirby I. , Chaudry Irshad H.
Published: September 2004

Recent studies from our laboratory have shown that alcohol and burn injury impair intestinal barrier and immune functions. Although multiple factors can contribute to impaired intestinal barrier function, such an alteration could result from a decrease in intestinal blood flow (BF) and oxygen delivery (Do2). Therefore, in this study, we tested the hypothesis that alcohol ingestion before burn injury reduces splanchnic blood flow and oxygen delivery. Rats (250 g) were gavaged with alcohol to achieve a blood ethanol level in the range of 100 mg/dl before burn or sham injury (25% total body surface area). Day 1 after injury, animals were anesthetized with methoxyflurane. Blood pressure, cardiac output (CO), ±dP/d t, organ BF (in ml·min−1·100 g−1), and Do2 (in mg·ml−1·100 g−1) were determined. CO and organ BF were determined using a radioactive microsphere technique. Our results indicate that blood pressure, CO, and +dP/d t were decreased in rats receiving a combined insult of alcohol and burn injury compared with rats receiving either burn injury or alcohol alone. This is accompanied by a decrease in BF and Do2 to the liver and intestine. No significant change in BF to the coronary arteries (heart), brain, lung, skin, and muscles was observed after alcohol and burn injury. In conclusion, the results presented here suggest that alcohol ingestion before burn injury reduces splanchnic BF and Do2. Such decreases in BF and Do2 may cause hypoxic insult to the intestine and liver. Although a hypoxic insult to the liver would result in a release of proinflammatory mediators, a similar insult to the intestine will likely perturb both intestinal immune cell and barrier functions, as observed in our previous study.
Internal Models and Contextual Cues: Encoding Serial Order and Direction of Movement
Authors: Wainscott Stephanie K. , Donchin Opher , Shadmehr Reza
Published: September 2004

During reaching, the brain may rely on internal models to transform desired sensory outcomes into motor commands. This transformation depends on both the state of the limb and the cues that can identify the context of the movement. How are contextual cues and information about state of the limb combined in the computations of internal models? We considered a reaching task where forces on the hand depended on both the direction of movement (state of the limb) and order of that movement in a predefined sequence (contextual cue). When the cue was available, the motor system formed an internal model that used both serial order and target direction to program motor commands. Assuming that the internal model was formed by a population code through a combination of unknown basis elements, the sensitivity of the bases with respect to state of the limb and contextual cue should dictate how error in one type of movement affected all other movement types. Using a state-space theory, we estimated this generalization function and identified the adaptive system from trial-by-trial changes in performance. The results implied that the basis elements were tuned to direction of movement but output of each basis at its preferred direction was multiplicatively modulated by a weak tuning with respect to the contextual cue. Activity fields that multiplicatively encode diverse sources of information may serve as a general mechanism for a single network to produce context-dependent motor output.
Dominance of the Right Hemisphere and Role of Area 2 in Human Kinesthesia
Authors: Naito Eiichi , Roland Per E. , Grefkes Christian , Choi H. J. , Eickhoff Simon , Geyer Stefan , Zilles Karl , Ehrsson H. Henrik
Published: September 2004

We have previously shown that motor areas are engaged when subjects experience illusory limb movements elicited by tendon vibration. However, traditionally cytoarchitectonic area 2 is held responsible for kinesthesia. Here we use functional magnetic resonance imaging and cytoarchitectural mapping to examine whether area 2 is engaged in kinesthesia, whether it is engaged bilaterally because area 2 in non-human primates has strong callosal connections, which other areas are active members of the network for kinesthesia, and if there is a dominance for the right hemisphere in kinesthesia as has been suggested. Ten right-handed blindfolded healthy subjects participated. The tendon of the extensor carpi ulnaris muscles of the right or left hand was vibrated at 80 Hz, which elicited illusory palmar flexion in an immobile hand (illusion). As control we applied identical stimuli to the skin over the processus styloideus ulnae, which did not elicit any illusions (vibration). We found robust activations in cortical motor areas [areas 4a, 4p, 6; dorsal premotor cortex (PMD) and bilateral supplementary motor area (SMA)] and ipsilateral cerebellum during kinesthetic illusions (illusion-vibration). The illusions also activated contralateral area 2 and right area 2 was active in common irrespective of illusions of right or left hand. Right areas 44, 45, anterior part of intraparietal region (IP1) and caudo-lateral part of parietal opercular region (OP1), cortex rostral to PMD, anterior insula and superior temporal gyrus were also activated in common during illusions of right or left hand. These right-sided areas were significantly more activated than the corresponding areas in the left hemisphere. The present data, together with our previous results, suggest that human kinesthesia is associated with a network of active brain areas that consists of motor areas, cerebellum, and the right fronto-parietal areas including high-order somatosensory areas. Furthermore, our results provide evidence for a right hemisphere dominance for perception of limb movement.
Slow Adaptation in Fast-Spiking Neurons of Visual Cortex
Authors: Descalzo V. F. , Nowak L. G. , Brumberg J. C. , McCormick D. A. , Sanchez-Vives M. V.
Published: September 2004

Fast-spiking (FS) neurons are a class of inhibitory interneurons classically characterized as having short-duration action potentials (<0.5 ms at half height) and displaying little to no spike-frequency adaptation during short (<500 ms) depolarizing current pulses. As a consequence, the resulting injected current intensity versus firing frequency relationship is typically steep, and they can achieve firing frequencies of ≤1 kHz. Here we have investigated the properties of FS neurons discharges on a longer time scale. Twenty second discharges were induced in electrophysiologically identified FS neurons by means of current injection either with sinusoidal current or with square pulses. We found that virtually all FS neurons recorded in cortical slices do show spike-frequency adaptation but with a slow time course (τ = 2–19 s). This slow time course has precluded the observation of this property in previous studies that used shorter pulses. Contrary to the classical view of FS neurons functional properties, long-duration discharges were followed by a slow afterhyperpolarization lasting ≤23 s. During this postadaptation period, the excitability of the neurons was decreased on average for 16.7 ± 6.8 s, therefore rendering the cell less responsive to subsequent afferent inputs. Slow adaptation is also reported here for FS neurons recorded in vivo. This longer time scale of adaptation in FS neurons may be critical for balancing excitation and inhibition as well as for the understanding of cortical network computations.
Cannabinoid Agonist, CP 55,940, Prevents Capsaicin-Induced Sensitization of Spinal Cord Dorsal Horn Neurons
Authors: Johanek Lisa M. , Simone Donald A.
Published: September 2004

Low doses of cannabinoids applied intrathecally attenuate capsaicin-evoked heat and mechanical hyperalgesia via CB1 receptors. Although cannabinoids produce antinociception, in part, by attenuating responses of nociceptive neurons in the spinal cord, few studies have examined the effect of cannabinoids on sensitization of spinal neurons. We therefore investigated whether a cannabinoid receptor agonist, CP 55,940, attenuated excitation and sensitization of spinal nociceptive neurons produced by intraplantar injection of 0.1% capsaicin (10 μl). In rats, wide-dynamic-range (WDR) and high-threshold (HT) neurons were classified according to responses evoked by mechanical stimuli of varying intensity. CP 55,940 (10 μg in 50 μl) or vehicle was applied directly to the spinal cord and responses to mechanical (von Frey monofilament) and heat stimuli were recorded 10 min after drug treatment. CP 55,940 alone did not alter responses to mechanical stimuli; however the enhanced responses to mechanical stimuli after injection of capsaicin into the receptive field were dose dependently attenuated in both HT and WDR neurons. Vehicle-treated neurons increased their response to 300.6 ± 52.1% of baseline after capsaicin, whereas CP 55,940-treated neurons responded at 153.0 ± 27.1% of baseline. The effects of CP 55,940 on sensitization to heat were less pronounced; however, CP 55,940 attenuated the capsaicin-evoked decrease in heat threshold in HT neurons. The attenuation by CP 55,940 of sensitization to mechanical stimuli was blocked by pretreatment of the spinal cord with the CB1 receptor antagonist, SR141716A. These studies demonstrate that cannabinoid application to the spinal cord prevents central sensitization.
Movement-Related Discharge of Ventromedial Medullary Neurons
Authors: Foo H. , Mason Peggy
Published: September 2004

Studies in anesthetized animals implicate nonserotonergic cells in the ventromedial medulla (VMM) in opioid modulation of nociceptive transmission but do not reveal the conditions that engage VMM cells in unanesthetized rats. The few studies of VMM cells in unanesthetized rats show that VMM cells change their discharge across the sleep-wake cycle and during active movements. Since active movements are more likely to occur during waking than sleep, state-related discharge may in fact represent movement-related discharge. In this study, we recorded the discharge of VMM neurons in unanesthetized, drug-free, freely moving rats and examined whether neuronal activity was related to wake/sleep state, to motor activity, or to both factors. Most cells (45/67) were more active during waking states than sleeping states, 1 cell was more active during sleep states, and the remaining 21 cells did not fire preferentially across the sleep-wake cycle. Most wake-active cells (36/45) showed discharge bursts during movement bursts, and 9/11 wake-active cells were excited by noxious heat and innocuous air puff stimulation. In contrast, few state-independent cells (9/21) showed movement-related bursts in discharge. These results suggest that VMM neurons modulate spinal processes during phasic motor activity.
Functional Properties of Fast Spiking Interneurons and Their Synaptic Connections With Pyramidal Cells in Primate Dorsolateral Prefrontal Cortex
Authors: González-Burgos Guillermo , Krimer Leonid S. , Povysheva Nadya V. , Barrionuevo German , Lewis David A.
Published: September 2004

Recent studies suggest that fast-spiking (FS) interneurons of the monkey dorsolateral prefrontal cortex (DLPFC) exhibit task-related firing during working-memory tasks. To gain further understanding of the functional role of FS neurons in monkey DLPFC, we described the in vitro electrophysiological properties of FS interneurons and their synaptic connections with pyramidal cells in layers 2/3 of areas 9 and 46. Extracellular spike duration was found to distinguish FS cells from non-FS interneuron subtypes. However, a substantial overlap in extracellular spike duration between these populations would make classification of individual interneurons difficult. FS neurons could be divided into two main morphological groups, chandelier and basket neurons, with very similar electrophysiological properties but significantly different horizontal spread of the axonal arborization. In paired cell recordings, unitary inhibitory postsynaptic potentials (IPSPs) elicited by FS neurons in pyramidal cells had rapid time course, small amplitude at resting membrane potential, and were mediated by GABAAreceptors. Repetitive FS neuron stimulation, partially mimicking the sustained firing of interneurons in vivo, produced short-term depression of the unitary IPSPs, present at connections made by both basket and chandelier neurons and due at least in part to presynaptic mechanisms. These results suggest that FS neurons and their synaptic connections with pyramidal cells have homogeneous physiological properties. Thus different functional roles of basket and chandelier neurons in the DLPFC in vivo must arise from the distinct properties of the interneuronal axonal arborization or from a different functional pattern of excitatory and inhibitory connections with other components of the DLPFC neuronal network.
Alternate Leg Movement Amplifies Locomotor-Like Muscle Activity in Spinal Cord Injured Persons
Authors: Kawashima Noritaka , Nozaki Daichi , Abe Masaki O. , Akai Masami , Nakazawa Kimitaka
Published: September 2004

It is now well recognized that muscle activity can be induced even in the paralyzed lower limb muscles of persons with spinal cord injury (SCI) by imposing locomotion-like movements on both of their legs. Although the significant role of the afferent input related to hip joint movement and body load has been emphasized considerably in previous studies, the contribution of the “alternate” leg movement pattern has not been fully investigated. This study was designed to investigate to what extent the alternate leg movement influenced this “locomotor-like” muscle activity. The knee-locked leg swing movement was imposed on 10 complete SCI subjects using a gait training apparatus. The following three different experimental conditions were adopted: 1) bilateral alternate leg movement, 2) unilateral leg movement, and 3) bilateral synchronous (in-phase) leg movement. In all experimental conditions, the passive leg movement induced EMG activity in the soleus and medial head of the gastrocnemius muscles in all SCI subjects and in the biceps femoris muscle in 8 of 10 SCI subjects. On the other hand, the EMG activity was not observed in the tibialis anterior and rectus femoris muscles. The EMG level of these activated muscles, as quantified by integrating the rectified EMG activity recorded from the right leg, was significantly larger for bilateral alternate leg movement than for unilateral and bilateral synchronous movements, although the right hip and ankle joint movements were identical in all experimental conditions. In addition, the difference in the pattern of the load applied to the leg among conditions was unable to explain the enhancement of EMG activity in the bilateral alternate leg movement condition. These results suggest that the sensory information generated by alternate leg movements plays a substantial role in amplifying the induced locomotor-like muscle activity in the lower limbs.
Light-Directed Electrical Stimulation of Neurons Cultured on Silicon Wafers
Authors: Starovoytov Artem , Choi Jung , Seung H. Sebastian
Published: September 2004

Dissociated neurons cultured in vitro can serve as a model system for studying the dynamics of neural networks. Such studies depend on techniques for stimulating patterns of neural activity. We show a technique for extracellular stimulation of dissociated neurons cultured on silicon wafers. When the silicon surface is reverse biased, electrical current can be generated near any neuron by pulsing a laser. Complex spatiotemporal stimulation patterns can be produced by directing a single beam with an acousto-optic deflector. The technique can generate a stimulating current at any location in the culture. This contrasts with multielectrode arrays (MEAs), which can stimulate only at fixed electrode locations. To characterize reliability and spatial selectivity of stimulation, we used intracellular (patch-clamp) recordings to monitor the effect of targeted laser pulses on cultured hippocampal neurons. Action potentials could be stimulated with submillisecond precision and 100-micron spatial resolution at rates exceeding 100 Hz. Optimal control parameters for stimulation are discussed.
Spatial Representation of Hydrocarbon Odorants in the Ventrolateral Zones of the Rat Olfactory Bulb
Authors: Igarashi Kei M. , Mori Kensaku
Published: September 2004

The glomerular sheet of the olfactory bulb (OB) forms odorant receptor maps that are parceled into zones. We previously reported the molecular receptive range (MRR) property of individual glomeruli in the dorsal zone (zone 1) of the OB and showed that polar functional groups play a major role in activating glomeruli in this zone. However, the MRR property of glomeruli in zones 2–4 is not well understood yet. Using the method of intrinsic signal imaging, we recorded odorant-induced glomerular activity from the ventrolateral surface (zones 2–4) of rat OB. While hydrocarbon odorants that lack polar functional groups activate only a few glomeruli in zone 1, we found that a series of hydrocarbon odorants consistently activated many glomeruli in the ventrolateral surface. The hydrocarbon-responsive glomeruli were grouped into two clusters; glomeruli in one cluster (cluster H) responded to benzene-family hydrocarbons but not to cyclic terpene hydrocarbons. Glomeruli in the other cluster (cluster I) responded to both classes of hydrocarbons. Detailed analyses of MRR properties of individual glomeruli using hydrocarbon odorants and polar-functional-group-containing odorants showed that the common and characteristic molecular features effective in activating glomeruli in the clusters H and I are the hydrocarbon skeleton. These results suggest that ORs represented by glomeruli in these clusters recognize primarily the hydrocarbon skeleton of odorants, and thus imply a systematic difference in the manner of recognizing odorant molecular features between ORs in zone 1 and ORs in zones 2–4.
From Peasant Soldiering to Peasant Activism: Reflections on the Transition of a Martial Tradition in the Flaming Fields of Bihar
Authors: Hauser Walter
Published: September 2004

In his ethnohistory of the military labour market in eastern Hindustan, 1450-1850, Dirk Kolff is concerned as much with the qualities of the supply side of the market, that is the villages of the rural countryside, as by the demand side of what the state might need or when it might need it. He describes the towns and villages of the region as an armed society in the Mughal and early modern centuries, and implies that this martial ethos extends into the late nineteenth and the twentieth centuries. My suggestion is that the social, cultural, and political history of the twentieth century affirms this to be the case, generally in Gangetic north India, and speci fically so in Bhojpur and Bihar, the heart of Kolff's Hindustan. Dans son étude ethno-historique du marché du travail militaire en Hindoustan oriental entre 1450 et 1850, Dirk Kolff se concentre autant sur l'offre provenant des villages ruraux que sur la demande représentée par les besoins de l'Etat. Il décrit les villes et villages de la région pendant la période moghole et pre-modern comme une société guerrière, et sous-entend que leur idéologie militaire perdure aux XIXe et XXe siècles. L'histoire socio-culturelle et politique du vingtième siècle semble con firmer cette théorie dans la région nord de l'Inde, et plus précisément dans le Bhojpur et le Bihar, le centre de l'Hindoustan chez Kolff.