Ventrolateral hypothalamic lesions in obese-hyperglycemic mice (obob)

Summary Bilateral electrolytic lesions were induced on the ventrolateral nucleus (VLN) of obese-hyperglycemic mice (obob) and lean littermates, with or without previous body weight reduction. All lean animals with VLN damage died within the first four post-operative days. In contrast, all obese mice (obob) with no prior body weight reduction recovered following an initial period of aphagia and rapid body weight loss. Three out of five reducedobob mice died following VLN lesions. - Two months after the operation the body weight of all lesionedobob mice stabilized at a level significantly lower than that of the sham operated obese; their serum immunoreactive insulin and blood glucose levels were also lower. - These data indicate thatobob mice respond normally to bilateral lesions of VLN and that their excess adiposity, by protecting them during the early post-operative period, facilitates their recovery. The final stabilization of the body weight of lesionedobob at a level lower than that of control mice is compatible with the view that the VLN acts as the low set point controller in the regulation of body weight.

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Ventrolaterale hypothalamische Läsionen bei obes- hyperglykämischen Mäusen (obob)

Zusammenfassung Bilaterale electrolytische Läsionen wurden in den ventrolateralen Kernen (VLN) von obeshyperglykämischen Mäusen (obob) und normalen Wurfgeschwistern mit oder ohne vorherige Gewichtsreduktion vorgenommen. Alle normalen Mäuse mit VLN-Läsionen starben innerhalb von vier Tagen nach der hypothalamischen Operation. Im Gegensatz dazu erholten sich alle fetten Mäuse (obob), deren Gewicht vor der hypothalamischen Operation nicht reduziert worden war, nach einer Periode von Aphagie und rapidem Gewichtsverlust. Drei von fünf gewichtsreduziertenobob-Mäusen starben nach der VLN-Operation. - Zwei Monate nach der Operation stabilisierten sich die Gewichte aller operiertenobob-Tiere auf einem statistisch signifikant niedrigeren Niveau, als dem der scheinoperierten fetten Mäuse entsprach. Immunoreaktives Insulin und Blutglucose waren bei diesen Tieren ebenfalls erniedrigt. - Die Ergebnisse deuten darauf hin, daßobob-Mäuse eine normale Reaktion auf die bilaterale Zerstörung der VLN zeigen und daß die überschüssige Fettmasse zu ihrer Erholung beitrug, indem sie ihnen in der Zeit unmittelbar nach der Operation Schutz gewährte. Die spätere Gewichtsstabilisation derobob auf einem subnormalen Niveau ist mit der gegenwärtigen Ansicht zu vereinbaren, daß die ventrolateralen hypothalamischen Kerne als die Regulatoren der unteren Körpergewichtsgrenze dienen.

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Lésions ventrolatérales de l'hypothalamus chez des souris obèses hyperglycémiques (obob)

Résumé Des lésions électrolytiques bilatérales du noyau ventrolateral (VLN) ont été pratiquées chez des souris obèses-hyperglycémiques (obob) et chez des souris de même portée non-obèses, avec ou sans réduction pondérale préalable. Tous les animaux maigres porteurs de lésions VLN décédèrent dans les quatre premiers jours post opératoires. Au contraire, toutes les souris obèses (obob) sans réduction pondérale préalable récupérèrent après une courte période d'aphagie et de perte de poids. Trois des cinq sourisobob préalablement soumises à un régime amaigrissant succombèrent après lésion du VLN. Deux mois après l'opération, le poids de tous lesobob porteurs de lésions du VLN atteignit un niveau stable mais significativement inférieur à celui des animaux soumis à une opération simulée. Il en fut de même du taux d'insuline immunoréactive et du glucose sanguin. -Ces résultats indiquent que la réponse desobob aux lésions bilatérales du VLN est normale et que leur excès de tissu adipeux les protège dans la période post opératoire et facilite leur récupération. La stabilisation du poids desobob à un niveau inférieur à la normale est compatible avec l'hypothèse que le VLN contrôle la limite inférieure du poids.

     

Altered reactivity of the rat adrenal medulla

Previous studies have suggested that experimental alterations in adrenomedullary reactivity, i.e., changes in catecholamine release in response to a standard dose of acetylcholine, may be partially accounted for by changes occurring at the level of the adrenal medulla itself, independent of both the central nervous system and the innervation of the adrenal gland. The present study was designed to investigate the morphology of adrenal chromaffin cells in rats subjected to chronic hypoglycemia induced by long acting insulin, and to assess this morphology in terms of associated changes in catecholamine content and release. Surgically isolated, perfused adrenal gland preparations were utilized to characterize the functional release of catecholamines from the adrenal medulla. Pretreatment with long acting insulin resulted in a selective depletion of epinephrine stores and acetylcholine-mediated epinephrine release, but did not appear to significantly affect either the levels or the release of norepinephrine. The biochemical effects of long acting insulin persisted for several days after termination of the treatment, exhibiting a gradual recovery over a period of approximately 5 days. Electron microscopic examination of the adrenal chromaffin cells revealed a progressive degranulation and vacuolization of numerous chromaffin cells followed by a compensatory biosynthetic response and a gradual recovery toward the morphology of control cells. The functional release of catecholamines from adrenal chromaffin cells was further examined in preparations of perfused adrenal slices. Acetylcholine-mediated catecholamine release was significantly decreased in slices of adrenal glands prepared from insulin treated rats when compared with that of control animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

尿液中水孔蛋白-2的检测及其与肾组织中表达的相关性

目的 研究尿液ＡＱＰ２水孔蛋白检测的方法及其与肾脏ＡＱＰ２水孔蛋白表达量之间的相关性,为应用尿液ＡＱＰ２蛋白监测机体的水重吸收状况提供理论依据。方法 用Ｗｅｓｔｅｒｎ印迹分析法测定自由进水和禁水２４ｈ大鼠肾脏ＡＱＰ２的表达量及尿液ＡＱＰ２的含量,并分析两者之间的相关性。结果 ＡＱＰ２蛋白可在尿液中检测到。尿液ＡＱＰ２与肾脏ＡＱＰ２吴正相关（ｒ＝０．７９９）。结论：尿液ＡＱＰ２水平可以反映肾脏集合管     

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: ROLE OF AT1 RECEPTORS IN THE CENTRAL CONTROL OF SYMPATHETIC VASOMOTOR FUNCTION

• 1 In a number of species, high concentrations of angiotensin II (AngII) receptors have been found in the rostral ventrolateral medulla (RVLM) in the hindbrain, which is an important region involved in the modulation of sympathetic vasomotor tone. The present review describes studies in which the contribution of angiotensin receptors in the brainstem to cardiovascular regulation, in particular sympathetic vasomotor reflexes, has been examined in conscious and anaesthetized rabbits.
• 2 In conscious rabbits, fourth ventricular infusions of AngII produced dose-dependent pressor responses as doses 400 times less than equipressor intravenous doses. Chronic baroreceptor denervation increased the sensitivity to AngII by 1000-fold. Administration of prazosin i.v. blocked the pressor response, suggesting that the mechanism involved sympathetic vasoconstriction.
• 3 The pattern of haemodynamic changes in response to AngII injected into the fourth ventricle (4V) involved decreased total peripheral conductance and mesenteric conductance, but a rise in hindlimb conductance. Sinoaortic denervation changed the hindlimb fall in conductance to an increase, suggesting that muscle vasomotor pathways were particularly inhibited by baroreceptor feedback mechanisms.
• 4 In anaesthetized rabbits, infusion of AngII into the RVLM increased blood pressure and transiently increased resting renal sympathetic nerve activity. The renal sympathetic baroreflex curves were shifted to the right and the upper plateau of the sympathetic reflex increase was markedly increased.
• 5 The pressor actions of 4V AngII were blocked by administration of a peptide antagonist injected into the RVLM or by the angiotensin AT₁ antagonist losartan injected into the 4V. These results suggest that mainly AT₁ receptors are involved and that the RVLM is a likely candidate site for the modulation of the renal sympathetic baroreflex.
• 6 Losartan administration into the 4V in conscious rabbits increased resting renal sympathetic tone and enhanced renal sympathetic baroreflex and chemoreflexes.
• 7 Our studies suggest that there are sympathoexcitatory AT₁ receptors in the RVLM accessible to AngII from the cerebrospinal fluid. In addition, an AT₁ receptor pathway normally inhibits the sympathoexcitation produced by baroreceptor unloading or chemoreceptor activation. The effect of losartan suggests that there is greater tonic activity within the sympathoinhibitory pathways. These two actions suggest that angiotensin receptors in the brainstem modulate sympathetic responses to specific afferent inputs, thus forming part of a potentially important mechanism for the integration of characteristic autonomic response patterns.

     

Aromatic L-amino acid decarboxylase-immunohistochemistry in the cat lower brainstem and midbrain

By indirect immunohistochemistry, the present study examined the distribution of neuronal structures in the cat medulla oblongata, pons, and midbrain, showing immunoreactivity to aromatic L-amino acid decarboxylase (AADC), which catalyzes the conversion of L-3, 4-dihydroxyphenylalanine (L-DOPA) to dopamine, and 5-hydroxytryptophan to serotonin (5HT). With simultaneous and serial double immunostaining techniques, immunoreactivity to this enzyme was demonstrated in most of the catecholaminergic and serotonergic neurons. We could also demonstrate AADC-IR cell bodies that do not contain tyrosine hydroxylase (TH-) or 5HT-immunoreactivity (called "D-type cells") outside such monoaminergic cell systems. At the medullo-spinal junction, very small D-type cells were found within and beneath the ependymal layer of the 10th area of Rexed surrounding the central canal. D-type cells were localized in the caudal reticular formation, nucleus of the solitary tract, a dorsal aspect of the lateral parabrachial nucleus, and pretectal areas as have been reported in the rat. Furthermore, the present study describes, in the cat brainstem, new additional D-type cell groups that have not been reported in the rat. Dense or loose clusters of D-type cells were localized in the external edge of the laminar trigeminal nucleus, dorsal motor nucleus of the vagus, external cuneate nucleus, nucleus praepositus hypoglossi, central, pontine, and periaqueductal gray, superficial layer of the superior colliculus, and area medial to the retroflexus. D-type cells were loosely clustered in the lateral part of the central tegmental field dorsal to the substantia nigra, extending dorsally in the medial division of the posterior complex of the thalamus and medial side of the brachium of the inferior colliculus. They extended farther rostrodorsally along the medial side of the nucleus limitans and joined with the pretectal cell group. Almost all these cells were very small and ovoid to round with 1-2 short processes with the exception of dorsal motor vagal cells. AADC-IR axons were clearly identified in the vagal efferent nerves, longitudinal medullary pathway, dorsal tegmental bundle rostral to the locus coeruleus. Serotonergic axons were identified not only in the central tegmentum field and lateral side of the central superior nucleus, but also in the ventral surface of the medulla oblongata. We describe principal densely stained fiber plexuses in the cat brainstem. The findings of the present study provide a morphological basis for neurons that decarboxylate endogenous and exogenous L-DOPA, 5HTP, and other aromatic L-amino acids.     

Synaptic inhibition in the isolated respiratory network of neonatal rats

Gramicidin-perforated patch-clamp recording revealed phasic Cl^–-mediated hyperpolarizations in respiratory neurons of the brainstem–spinal cord preparation from newborn rats. The in vitro respiratory rhythm persisted after block of γ-aminobutyric acid (GABA), i.e. GABA_A, receptor-mediated inhibitory postsynaptic potentials (IPSPs) with bicuculline and/or glycinergic IPSPs with strychnine. In one class of expiratory neurons, bicuculline unmasked inspiration-related excitatory postsynaptic potentials (EPSPs), leading to spike discharge. Bicuculline also blocked hyperpolarizations and respiratory arrest due to bath-applied muscimol, whereas strychnine antagonized similar responses to glycine. The reversal potential of respiration-related IPSPs and responses to GABA, muscimol or glycine was not affected by CO₂/HCO₃^–-free solutions, but shifted from about ?65 mV to values more positive than ?20 mV upon dialysis of the cells with 144 instead of 4 mm Cl^–. Impairment of GABA uptake with nipecotic acid or glycine uptake with sarcosine evoked a bicuculline- or strychnine-sensitive decrease of respiratory frequency which could lead to respiratory arrest. Also, the GABA_B receptor agonist baclofen led to reversible suppression of respiratory rhythm. This in vitro apnoea was accompanied by a K⁺ channel-mediated hyperpolarization (reversal potential ?88 mV) of tonic cells, whereas membrane potential of neighbouring respiratory neurons remained almost unaffected. Both baclofen-induced hyperpolarization and respiratory depression were antagonised by 2-OH-saclofen, which did not affect respiration-related IPSPs per se. The results show that synaptic inhibition is not essential for rhythmogenesis in the isolated neonatal respiratory network, although (endogenous) GABA and glycine have a strong modulatory action. Hyperpolarizing IPSPs mediated by GABA_A and glycine receptors provide a characteristic pattern of membrane potential oscillations in respiratory neurons, whereas GABA_B receptors rather appear to be a feature of non-respiratory neurons, possibly providing excitatory drive to the network.     

The ventrolateral medulla of the cat mediates vestibulosympathetic reflexes

Extracellular recordings were made from 94 neurons located in the ventrolateral medulla (VLM) whose firing rate was affected by vestibular nerve (VN) stimulation; 50 of these units were in the subretrofacial (SRF) nucleus, which contains cells that make direct excitatory connections with sympathetic preganglionic neurons. The sample included 12 SRF cells which were antidromically driven from the upper thoracic spinal cord and had conduction velocities of 10 m/s or less; the effect of VN stimulation on all but one of these units was inhibition. The onset latency of the response to VN stimulation was long [20.3 +/- 3.7 (S.E.M.) ms, n = 9, for the antidromically activated neurons and 12.1 +/- 1.2 ms, n = 73, for the others], suggesting that the effects were predominantly polysynaptic. In addition, most of the spontaneously active units tested (33/36) received convergent inputs from the carotid sinus nerve (CSN), as would be expected for neurons which influence sympathetic outflow. Vestibular-elicited inhibition of SRF neurons with projections to the intermediolateral cell column could account for late, long duration inhibition of sympathetic discharges produced by labyrinth stimulation.     

尾部退化综合征产前超声表现

目的 观察胎儿尾部退化综合征(CRS)产前超声表现。方法 回顾性分析32胎CRS产前超声资料,观察其超声表现及伴发异常。结果 32胎中,7胎于妊娠早期(<孕14周)、25胎于妊娠中晚期(14～40周)检出;均表现为脊柱尾部发育不良伴不同程度椎体缺如,其中27胎(27/32,84.38%)骶尾椎受累,31胎(31/32,96.88%)合并其他系统异常。7胎于妊娠早期检出的CRS胎儿均合并其他系统异常,其中5胎肢体异常、4胎颈部透明层增厚。25胎于妊娠中晚期检出的CRS中,14胎(14/25,56.00%)合并肛门闭锁,12胎(12/25,48.00%)合并肾脏异常,8胎(8/25,32.00%)肢体受累;其中13胎可见脊髓末端,8胎脊髓拴系。随访中30例妊娠终止,1胎失访,1胎活产。结论 CRS产前超声表现具有特异性,且多合并其他系统畸形。     

Fluoroscopic Anatomy of Right-Sided Heart Structures for Transcatheter Interventions

Performing transcatheter tricuspid valve interventions requires a thorough knowledge of right-heart imaging. Integration of chamber views across the spectrum of imaging modalities (i.e., multislice computed tomography, fluoroscopy, and echocardiography) can facilitate transcatheter interventions on the right heart. Optimal fluoroscopic viewing angles for guiding interventional procedures can be obtained using pre-procedural multislice computed tomography scans. The present paper describes fluoroscopic viewing angles necessary to appreciate right-heart chamber anatomy and their relationship to echocardiography using multislice computed tomography.