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PubMed1993

Differential regulation of tyrosine hydroxylase protein and activity in rabbit sympathetic neurones after long-term cold exposure: altered responses in ageing.

The aim of this study was to investigate the response of sympathetic neurones to prolonged neural stimulation, using cold exposure as a non-invasive experimental paradigm. We examined the effects of prolonged (8 days and 4 wk) cold exposure on tyrosine hydroxylase (TH) protein and activity and neuropeptide Y (NPY) levels in sympathetic neurones of the superior cervical ganglion (SCG), together with NPY levels in the ear artery from young and aged rabbits. The main findings were as follows. In young rabbits, TH levels and TH activity were differentially regulated in response to prolonged cold exposure. TH levels rose whilst TH activity tended to decline. Decentralization of SCG from young animals before cold exposure abolished the rise in TH levels. TH activity in SCG from young rabbits was reduced by decentralization whilst cold exposure resulted in an increase in TH activity. Thus, TH activity was induced in the SCG in the absence of pre-ganglionic input, demonstrating a non-synaptic regulatory mechanism. In old rabbits, cold-induced changes were either delayed or failed to occur, indicating that the responses of sympathetic neurones to cold stress are impaired in old age.

Aging↗
PubMed1996

Developmental and activity-dependent changes in K+ currents in satellite glial cells in mouse superior cervical ganglion.

Voltage-gated K+ currents were recorded from freshly dissociated satellite glial cells wrapping around ganglion cells in mouse superior cervical ganglion (SCG) by whole-cell recordings of patch clamp techniques. Both inward and outward K+ currents during membrane hyperpolarization and depolarization were observed in these glial cells. The current-voltage relation of these K+ currents became almost linear in cells obtained more than 4 weeks after birth. The magnitude of the density of inward K+ currents, which were elicited during membrane hyperpolarization and were eliminated by external barium, progressively increased during the first month after birth. This developmental increase in the magnitude of inward K+ current density was not affected by decentralization of SCG done by transection of cervical sympathetic trunk (CST) 5 days after birth. In adult mice, the magnitude of the inward K+ current density decreased after chronic conduction blockade of CST by local application of tetrodotoxin. On the other hand, the magnitude of the inward K+ current density increased after daily intraperitoneal injection of reserpine and this increase was abolished by pre-treatment of decentralization of SCG. These results suggested that preganglionic innervation was not prerequisite for developmental increase in the inward K+ currents and preganglionic neuronal activity upregulates the inward K+ currents in adult mice. Neuronal regulation of glial K+ channel expression would assist in K+ clearance from periganglionic space to maintain neuronal activity.

4-Aminopyridine↗
PubMed1988

Surgical and pharmacological reductions in sympathetic nerve activity increase the neuropeptide Y-immunoreactivity content of the rat iris but not the vas deferens.

Decentralization of the superior cervical ganglion (S.C.G.) of the rat elevated the neuropeptide-Y immunoreactivity (NPY-ir) content of the ganglion on day 1 (+43%) but not on day 3 post-surgery. The content of NPY-ir in the iris was increased by decentralization (+40%) 3 days post-surgery, and treatment with clonidine (+43%), and pempidine (+82%). The levels of NPY-ir in the rat vas deferens were not affected by either surgical or pharmacological treatment. These results suggest NPY is released from sympathetic nerves in the iris but not vas deferens during normal sympathetic activity.

Animals↗
PubMed1988

The effect of pupil centration and diameter on ocular performance.

The variation in sphero-cylindrical refractive error with position in the human eye pupil is derived from the wavefront error of two subjects. The modulation transfer function is also calculated for 1, 2 and 3 mm pupils decentred 1 and 2 mm nasally and temporally. Whilst decentration causes relatively little difference in the M.T.F. at the smaller pupil size, it can produce marked degradation for the larger pupils which can be of significance in the experimental determination of contrast sensitivity or other visual functions.

Humans↗
PubMed1987

Investigations on urinary bladder reinnervation. Historical perspective and review.

Although nerve crossover surgery to bypass a spinal cord lesion and recentralize the decentralized bladder was first conceptualized in 1907, surprisingly few studies concerning this goal have been reported since. In addition to direct implantation of nerves into the detrusor, the studies reviewed have investigated the crossover of mixed roots (with and without nerve grafts), dorsal roots, ventral roots, pelvic, obturator and hypogastric nerves both in animal models, in human cadavers, and in human patients. Restoration of the micturition reflex through the use of nonsacral nerves has been achieved in cats. In addition, we have shown that the axons of a suprasacral mixed root (L7) when anastomosed to a sacral mixed root (S1) via a nerve graft can regenerate and recentralize the unilaterally decentralized bladder in the cat. The return of the micturition reflex after reconstruction of severed pelvic nerves has been documented, while the results of obstruction or hypogastric crossover have given diminished returns of bladder function. The direct implantation of nerves into the detrusor has not resulted in restoration of function. In addition, return of useful bladder function in humans after nerve crossover surgery has not been predictable. In part, present inability to achieve restoration of urinary bladder function may be a consequence of the complexity of micturition reflex organization and the inability to use techniques in humans that have given success in animals. Although, some of the technical aspects of nerve crossover surgery to bypass a spinal cord injury and restore functional micturition in those with neurogenic bladder dysfunction have been elucidated, further work is required to develop techniques that will enhance appropriate axonal regeneration to achieve reinnervation and return of useful function. Indeed, restoration of function may be limited by current microsurgical methodologies. Studies directed at understanding the neuropathophysiology of nerve injury and nerve surgery may be more fruitful in identifying factors than can be manipulated to achieve consistent return of useful function. In general, however, the results of the animal and human studies surveyed may be viewed with cautious optimism.

Animals↗
PubMed1986

Origins of the sympathetic projections to rat thyroid and parathyroid glands.

The present study aimed to characterize the localization and pathways of sympathetic neurons innervating the thyroid and parathyroid glands. In rats subjected to unilateral superior cervical ganglionectomy or unilateral decentralization of the superior cervical ganglion 7 days earlier, ipsilateral depression of thyroid norepinephrine (NE) and epinephrine content to 6-16% of the contralateral intact lobe was observed. In both groups of animals neuronal [3H]NE uptake by the ipsilateral thyroid lobe was suppressed. In unilaterally decentralized rats pineal catecholamine levels remained within normal values whereas in unilaterally ganglionectomized rats a 74% decrease of pineal NE and E content was found. Unilateral section of the external carotid nerve abolished, as did unilateral superior cervical ganglionectomy, neuronal [3H]NE uptake in the ipsilateral thyroid lobe. In contrast external carotid nerve section did not modify the neuronal uptake of [3H]NE in the pineal gland. Either unilateral superior cervical ganglionectomy or external carotid nerve section resulted in similar involution of ipsilateral thyroid lobes of hypophysectomized rats. These results indicate that postganglionic sympathetic perikarya innervating the thyroid-parathyroid territory are located in the middle and/or inferior cervical ganglia and send their axons through the SCG and the external carotid nerve to these glands.

Animals↗
PubMed1986

Ontogeny of adrenoceptor-mediated contractile responses of Müller's smooth muscle in the spontaneously hypertensive rat: role of impulse activity.

Contractile responses of Müller's smooth muscle to alpha-adrenoceptor stimulation were evaluated in anesthetized Spontaneously Hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats on postnatal days 1-80. Force of contraction elicited by methoxamine, tyramine and electrical stimulation of the preganglionic nerve in SHRs was significantly less than that of WKY rats throughout development. alpha-Adrenoceptor sensitivity, as evaluated by methoxamine ED50, was comparable at 10 and 20 days of age, but receptor sensitivity was decreased in SHRs at 40 and 80 days. Elimination of impulse activity by decentralization of the superior cervical ganglion on postnatal day 3 resulted in a decrease in force of contraction of about 25% in both strains, and responses in SHRs remained significantly below those of WKY rats. Decentralization increased adrenoceptor sensitivity in both groups, and differences between strains were eliminated. It is concluded that the smaller adrenoceptor-mediated contractions in SHRs are an intrinsic property of the muscle while adrenoceptor subsensitivity is a consequence of elevated sympathetic nerve activity in this strain.

Animals↗
PubMedDate not supplied

Peptidergic modulation of in situ canine intrinsic cardiac neurons.

In order to determine which peptides are involved in modulating intrinsic cardiac neurons, angiotensin II, atrial natriuretic peptide, bradykinin, calcitonin gene-related peptide, enkephalin, neuropeptide Y, oxytocin, substance P, and vasoactive intestinal peptide dissolved in saline were administered individually by microinjection adjacent to spontaneously active canine intrinsic cardiac neurons. No neuronal or cardiac responses were elicited when saline was administered into active loci or when peptides were administered into loci with no spontaneous activity. Each peptide elicited neuronal responses when administered into active loci in most animals, bradykinin eliciting neuronal responses in every active locus studied. Concomitant cardiovascular responses were elicited in many cases when every peptide except atriopeptin was studied. After cardiac decentralization, neuronal and cardiovascular responses to repeat doses of peptides occurred with less frequency than before decentralization, implying that connections with central and other intrathoracic neurons can influence the function of peptide-sensitive intrinsic cardiac neurons. After atropine and timolol administration, cardiovascular, but not neuronal, responses to peptides were eliminated, indicating that cardiovascular responses were dependent upon efferent parasympathetic and sympathetic neurons. It is concluded that a number of neuropeptides may be involved in regulation of cardiac function by intrinsic cardiac neurons.

Animals↗
PubMed1985

Whither the state in Yugoslav health care?

As part of their broader sociopolitical system of self-managing socialism, the Yugoslavs have attempted to create a health care system which is simultaneously destaticized, depoliticized, decentralized, democratized and economically and socially efficient. This paper provides a description and evaluation of the evolving self-managed health sector in post-World War II Yugoslavia. I argue that, despite repeated institution restructuring and innovation and some noteworthy accomplishments, the Yugoslavs have fallen short of their health objectives. After presenting alternative explanations for these shortcomings, I propose that they can best be understood in terms of the contradictions the Yugoslavs have encountered in their efforts to simultaneously pursue destatization, depoliticization, decentralization, democratization and social and economic efficiency. I conclude with an ideologically unpopular proposal that some form of continuous and legitimate central state coordination may be necessary to resolve current critical problems in Yugoslav health care (e.g. persistent deficits in health financing, shortages of basic medical supplies, duplication of expensive medical technology, unemployed health workers despite unmet health needs, persistent health inequalities).

Budgets↗
PubMed1985

Reforming health care in Hungary.

Over the past two decades Hungary has initiated a series of social and economic reforms which have emphasized decentralization of control and the reintroduction of market mechanisms into the socialized economy. These reforms both reflect and reinforce a changing social structure, in particular the growing influence of upper class special interest groups. Market reforms are an expression of concurrent ideological shifts in Hungarian society. We examined the political significance of three recent proposals to reform health services against the backdrop of broader social and economic changes taking place. The first proposes a bureaucratic reorganization, the second, patient co-payments, and the third, a voucher system. The problems each proposal identifies, as well as the constituency each represents, reveal a trend toward consolidation of class structure in Hungary. Only one of these proposals has any potential to democratize the control and management of the heath care system. Moreover, despite a governmental push toward decentralization, two of these proposals would actually increase centralized bureaucratic control. Two of the reforms incorporate market logic into their arguments, an indication that the philosophical premises of capitalism are re-emerging as an important component of the Hungarian world-view. In Hungary, as well as in other countries, social analysis of proposed health care reforms can effectively illuminate the social and political dynamics of the larger society.

Community Participation↗
PubMed1986

Social insurance and the delivery of social services in France.

An outline of the organization of the French social insurance and the social service delivery system is given. It is shown that the social insurance system, more so than in most other welfare states, strongly reflects various class and occupational interests. Therefore, it is also more prone to conflict along class lines, while other countries' social insurance systems tend to blurr class conflict. In addition, problems due to demographic shifts and economic changes are discussed and the populations affected, particularly the aged, identified. Some of the government's strategies to ameliorate the financial problems of the social insurance system are mentioned. The social service delivery system is found to suffer from bureaucratization and inefficiency. In order to correct this and to improve the quality of services, France has begun to decentralize the social service delivery system. There is little evidence, though, that decentralization, as presently practiced, is able to significantly improve the appropriateness of social services and increase the efficiency with which they are delivered. On the contrary, the political forces opposed to an elaborate welfare state tend to be strengthened. No doubt, the aged would also be affected by such political changes.

France↗
PubMed1989

Community health services and health care utilization in rural Bangladesh.

The study, which is based on data from two household level health surveys conducted in 1976 and 1987 in the Companiganj area of rural Bangladesh, examines the premise that the utilization of public health care services can be increased by increasing the availability and accessibility of effective medicines to the public and by improving the disease recognition and management by the health practitioners. The results of the study suggest that the availability and accessability of modern effective medicines through the provision of decentralized community-based rural health services, by a well-trained and well-managed field personnel structure, had an incremental impact on the utilization of modern health care from a rural health center and its subcenters. The study further reveals that, in 1976 as well as in 1987, the overwhelming majority of the rural Bangladesh population were using modern Western medical practitioners, although most of these practitioners were informally trained or self-trained without any formal medical degrees or training. It is concluded that the persons responsible for health program planning and health program implementation need to ensure that the access to basic public health care services be made broad enough to cover the majority of the rural population through a system of decentralized curative and preventive services, as well as through a system of adequate training and deployment of health professionals, including training programs to improve the quality of medical services offered by the informal and self-trained practitioners of modern medicines.

Adolescent↗
PubMed1988

Both synaptic and antidromic stimulation of neurons in the rat superior cervical ganglion acutely increase tyrosine hydroxylase activity.

Electrical stimulation of the preganglionic cervical sympathetic trunk produces an acute increase in the rate of DOPA synthesis in the rat superior cervical ganglion. The present study was designed to test the possibility that this acute transsynaptic stimulation of catechol biosynthesis could be, at least in part, a consequence of an increase in the firing rate of the postganglionic sympathetic neurons. For this purpose, the effect of stimulation in vitro of the preganglionic cervical sympathetic trunk was compared to that of stimulation of the predominantly postganglionic internal and external carotid nerves. Stimulation of the cervical sympathetic trunk at 10 Hz for 30 min produced a 4.6-fold increase in DOPA synthesis, while simultaneous stimulation of the two postganglionic trunks produced a 3.1-fold increase. The internal carotid nerve is known to contain a small population of preganglionic fibers that synapse on principal neurons in the ganglion before entering this nerve trunk. To eliminate the possibility that the effect of stimulation of the internal carotid nerve is mediated by synaptic stimulation via these preganglionic "through fibers", the effect of stimulation of previously decentralized ganglia was examined. While decentralization reduced the magnitude of the effect of stimulation of the internal and external carotid nerves, a 2.0-fold increase in DOPA synthesis was still seen. In addition, when these nerve trunks were stimulated in control ganglia that had been maintained in organ culture for 48 h to allow time for the degeneration of afferent nerve terminals, DOPA synthesis increased 4.1-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Evidence for a central site of action to explain the negative chronotropic effect of atropine: studies on the human transplanted heart.

The chronotropic response to atropine is biphasic; low doses cause slowing of the sinus rate and high doses cause acceleration. Although it is accepted that atropine functions as a competitive antagonist at high doses, the mechanism of the negative chronotropic response at low doses is controversial. Specifically, it is unclear whether the effect is mediated centrally or peripherally. Since at the time of cardiac replacement all central nervous system connections to the heart are severed, the transplanted heart is a unique model for separating these effects. Graded doses of atropine sulfate (0.5, 1.0, 2.0, 4.0, 8.0 and 40.0 micrograms/kg body weight) were administered to 12 human heart transplant recipients to test the hypothesis that the bradycardiac effect of low dose atropine is centrally mediated. The baseline sinus cycle lengths of the decentralized donor and innervated native sinus nodes were 694 +/- 20 and 733 +/- 27 ms, respectively. At the 0.5 and 1.0 microgram/kg doses, the cycle lengths of the native sinus node increased by 29.1 +/- 13.5 and 23.1 +/- 14.2 ms, respectively. At the 2.0 micrograms/kg dose the sinus cycle length again shortened to control. At the maximal dose of atropine the sinus cycle length shortened by 138.3 +/- 29.7 ms compared with control. In contrast, the decentralized donor sinus node exhibited a flat dose response to atropine. High dose atropine (40 micrograms/kg) caused no change in the donor heart's atrial effective refractory period, corrected sinus node recovery time, or sinoatrial conduction time measured by either the Strauss or the Narula method.(ABSTRACT TRUNCATED AT 250 WORDS)

Atropine↗
PubMed2005

Ocular higher-order wavefront aberration caused by major tilting of intraocular lens.

PURPOSE: To report a patient with a significant amount of ocular coma-like aberration that was caused by the tilting of an intraocular lens (IOL) who was treated successfully by IOL repositioning surgical procedure. DESIGN: Interventional case report. METHODS: At the Department of Ophthalmology, University of Tsukuba, a 52-year-old man complained of unclear and distorted vision in his left pseudophakic eye. The tilt and decentration of IOL were measured with the Scheimpflug videophotography system. Ocular and corneal wavefront aberrations were measured with the Hartmann-Schack aberrometer. RESULTS: The tilting angle was 28.87 degrees, and decentration was 1.78 mm. The ocular coma-like aberration was increased remarkably to 0.451 microm at 4.0 mm aperture diameter, and the simulated retinal image of a Landolt ring was blurred substantially. Ocular spheric-like, corneal coma-like, and corneal spheric-like aberrations were not increased. The IOL repositioning surgery significantly improved the IOL tilt, which resulted in the reduction of ocular coma-like aberration, recovery of simulated retinal image, and resolution of the patient's complaints. CONCLUSION: Major IOL tilting induces a large amount of ocular coma-like aberration, which deteriorates the patient's quality of vision.

Astigmatism↗
PubMed2005

Origin and pharmacological response of atrial tachyarrhythmias induced by activation of mediastinal nerves in canines.

We sought to determine the sites of origin of atrial tachyarrhythmias induced by activating mediastinal nerves, as well as the response of such arrhythmias to autonomic modulation. Under general anaesthesia, atrioventricular block was induced after thoracotomy in 19 canines. Brief trains of 5 electrical stimuli were delivered to right-sided mediastinal nerves during the atrial refractory period. Unipolar electrograms were recorded from 191 right and left atrial epicardial sites under several conditions, i.e. (i) with intact nervous systems and following (ii) acute decentralization of the intrathoracic nervous system or administration of (iii) atropine, (iv) timolol, (v) hexamethonium. Concomitant right atrial endocardial mapping was performed in 7 of these dogs. Mediastinal nerve stimulation consistently initiated bradycardia followed by atrial tachyarrhythmias. In the initial tachyarrhythmia beats, early epicardial breakthroughs were identified in the right atrial free wall (28/50 episodes) or Bachmann bundle region (22/50), which corresponded to endocardial sites of origin associated with the right atrial subsidiary pacemaker complex, i.e. the crista terminalis and dorsal locations including the right atrial aspect of the interatrial septum. Neuronally induced responses were eliminated by atropine, modified by timolol and unaffected by acute neuronal decentralization. After hexamethonium, responses to extra-pericardial but not intra-pericardial nerve stimulation were eliminated. It is concluded that concomitant activation of cholinergic and adrenergic efferent intrinsic cardiac neurons induced by right-sided efferent neuronal stimulation initiates atrial tachyarrhythmias that originate from foci anatomically related to the right atrial pacemaker complex and tissues underlying major atrial ganglionated plexuses.

Animals↗
PubMed2026

Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.

BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.

Humans↗
PubMed2006

Comprehensive management of the access to the electronic patient record: towards trans-institutional networks.

BACKGROUND: A system ensuring tight control access is used since 5 years at the University Geneva Hospitals (HUG) over a four campuses health care system with ambulatory care settings behaving like a small community care network. Access to identified clinical information is limited to care providers that have a therapeutic relationship with the patient and to those data needed for that relation. The same policy applies to administrative or scientific research accesses. This paper presents how the HUG met the challenging goal of protecting patient privacy within regulatory limits while keeping the system operational in terms of use and management. SOLUTION: The main characteristics of the system are: (a) an institution-wide policy for access rights to the computerized patient record; (b) an institutional management of the contracts of the collaborators; (c) access profiles based on application-independent, fine-grained access rights; (d) a decentralized attribution of profession-specific access profiles; (e) a complete, centralized log of all accesses to the clinical information system; and (f) a decentralized verification of the accesses. Many of these characteristics can be maintained when evolving towards a trans-institutional computerized patient record, but new constraints need to be taken into account.

Access to Information↗