Pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH) is suppressed by alpha-adrenergic antagonists in ovariectomized (OVX) rabbits, thus suggesting that initiation of GnRH pulses requires the presence of norepinephrine (NE) stimulation. Terminals of NE neurons are located in proximity with GnRH cells in the hypothalamus, including the arcuate nucleus-median eminence (AME) region. Synaptic NE molecules may be catabolized or transported back to NE terminals (i.e. reuptake) via specific NE transporter proteins (NET). Thus, the amount of synaptic NE acting on GnRH cells is a function of the rate of NE release, metabolism and reuptake. Hypothetically, the rise and fall of a GnRH pulse may be associated with the similar fluctuations of synaptic NE release and/or NET activity. To test this hypothesis, we examined the effects of AME administration of desipramine (DMI, a specific NET blocking drug) on GnRH release. First, we delivered 0.2-10 mM doses of DMI continuously for 1 h via an AME microdialysis (microD) system into intact male rabbits. We found that each AME-DMI infusion, between dosages of 1 mM and 10 mM, stimulated a GnRH pulse, and that the size of these GnRH pulses were proportional to the dosage of DMI. To confirm the specificity of DMI on NET, we measured catecholamine content in microD samples by HPLC. The temporal (60 min) DMI induced a pattern of NE release that included a rising limb within the first 20-30 min; although NE returned to baseline values within the period of DMI treatment. Neither epinephrine nor dopamine levels were changed by DMI. Second, a median dose of DMI (5 mM) was given by microD for 60 min in four separate rabbit models: gonadal intact females (F-INT), intact males (M-INT), gonadectomized females (F-GDX) and castrated males (M-GDX). Individual microD samples were measured for NE and GnRH. Regardless of gender or gonadal status, 5 mM of DMI concomitantly induced a pulse-like release of NE and GnRH. Furthermore, the response of GnRH to DMI was greater in GDX rabbits than in INT animals of both genders. Third, we administered DMI (5 mM) for 30 min via a push-pull perfusion (PPP) system during four repeated 90 min intervals, in either F-INT or ovariectomized (F-GDX) females, and measured GnRH in PPP samples. In both F-INT and F-GDX, each DMI challenge induced a GnRH pulse. In F-INT, all sequential DMI-induced GnRH pulses were nearly equal in size. In contrast, in F-GDX, the first DMI-induced GnRH pulse was greater than subsequent ones. Collectively, these observations are consistent with the concept of noradrenergic regulation of pulsatile GnRH release, and we conclude that the temporal activity of NET may be an integral part of the mechanism by which GnRH pulses operate.

Adrenergic Uptake Inhibitors↗

PubMed1998

The role of Müller's muscle reconsidered.

It is a traditional teaching that the levator aponeurosis is the main transmitter of the levator palpebrae muscle. However, there are several points that raise doubts in this fundamental concept of the levator aponeurosis as being the primary interconnecting mechanism in upper lid elevation. Despite the structural integrity of the levator complex, drooping of the upper eyelids is seen to develop in situations such as Horner's syndrome and in times of excessive fatigue and sleepiness. Amid the controversy in the literature regarding the specific role of the levator aponeurosis in the lid-elevating mechanism, we have observed that the levator aponeurosis fails to make constant attachment to the tarsal plate. This has led us to speculate on the possible role of the posterior lamella - Müller's muscle - as the primary transmitter of the levator muscle action to the tarsal plate.

Blepharoptosis↗

PubMed1997

ATP P2X receptors mediate fast synaptic transmission in the dorsal horn of the rat spinal cord.

ATP has been proposed to mediate synaptic transmission in the spinal cord dorsal horn, particularly in the pathway carrying nociceptive information. Using transverse spinal cord slices from postnatal rats, we show that EPSCs mediated by P2X receptors, and presumably activated by synaptically released ATP, are evoked in a subpopulation of spinal cord lamina II neurons, a region known to receive strong input from nociceptive primary afferents. The P2X receptors on acutely dissociated dorsal horn neurons are nondesensitizing, insensitive to alphabeta methylene ATP, and show strong but variable sensitivity to the antagonists suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). These characteristics are consistent with a heterogeneous population of P2X receptors, the composition of which includes P2X2, P2X4, and P2X6 receptor subtypes. Our results suggest that ATP-activated P2X receptors in lamina II of the rat spinal cord may play a role in transmitting or modulating nociceptive information.

Adenosine Triphosphate↗

PubMed1997

Comparative biodistribution of meta-Tetra(Hydroxyphenyl) chlorin in multiple species: clinical implications for photodynamic therapy.

BACKGROUND AND OBJECTIVE: To optimize photodynamic therapy, it is necessary to know the distribution of photosensitizer in normal tissue as well as tumors and to know how well animal models match human. This study measured the biodistribution of meta-Tetra(Hydroxyphenyl) Chlorin (mTHPC) in three species of animals and in humans. STUDY DESIGN/MATERIALS AND METHODS: mTHPC was injected intravenously into dogs, rabbits, and humans, and drug levels in various tissues were determined 6 days later. One dog was perfused with 3 L of saline to remove blood trapped within organs. RESULTS: Absolute and relative concentrations of drug in specific tissues varied between species and between individuals. There was a general pattern of distribution. Highly vascularized tissues had the highest levels of mTHPC, not simply due to trapping of blood. mTHPC did not localize in bone and did not cross the blood-brain barrier. Humans had much higher levels of drug in their plasma and tissues than did animals. CONCLUSIONS: First, drug retention varies from one tissue to another. Second, there is significant variability from one individual to another, whether animal or human. Third, current models cannot accurately predict from animal studies the optimum dose for humans. Measurement of photosensitizer level in plasma at time of treatment would allow optimal photodynamic dosing.

Animals↗

PubMed1997

The Bellagio Task Force report on transplantation, bodily integrity, and the International Traffic in Organs.

Explore the source record for details and available documents.

Animals↗

PubMed1997

Performance characteristics of combined haemodialysis/haemoperfusion system for removal of blood toxins.

The application of high clearance haemodialysis (HD) for removal of small molecules of waste metabolites, has been practised for many years. Haemoperfusion (HP) is capable of effective removal of middle and protein-bound molecules. The combined HD/HP system is thought to give a more effective treatment for patients of renal failure or drug intoxication. This paper discusses the performance characteristics of removal of toxic substances (e.g. paraquat and creatinine), using the combined HD/HP recycled system in two different arrangements (HD-HP and HP-HD). The results demonstrate that for most favourable adsorbing solutes, the HD-HP arrangement gives higher performance whereas, HP-HD arrangement is more suitable and gives more effective detoxication characteristics for unfavourable adsorbing solutes.

Adsorption↗

PubMed1997

Characterization of hemin binding activity of Streptococcus pneumoniae.

Streptococcus pneumoniae is a causative agent of bacterial pneumonia, otitis media, meningitis, and bacteremia. It causes considerable morbidity and mortality throughout the world, especially among children, the elderly, and immunocompromised individuals. We have demonstrated previously that the growth of S. pneumoniae is limited under iron-depleted conditions and can be restored by the addition of either hemin or hemoglobin. In the present study, we showed that S. pneumoniae had the ability to bind hemin and that the level of hemin binding activity was not affected by supplementation of the growth medium with iron. Approximately 70 to 80% of the hemin binding activity was mediated by proteinase-resistant components, and the remainder was mediated by proteins. Hemin binding proteins were located in both soluble extract and envelope fractions of pneumococcal cells. By batch affinity chromatography, a major hemin binding polypeptide with an apparent molecular mass of 43 kDa was identified in the cell lysate of S. pneumoniae. Polyclonal antibodies against this polypeptide were raised. By immunoblot analysis, this hemin binding polypeptide was localized in the envelope and did not exhibit any variation in molecular weight among all serotypes tested. The subcellular distribution of hemin binding activity may have functional implications.

Carrier Proteins↗

PubMed1997

Airway goblet cell mucin: its structure and regulation of secretion.

Mucociliary clearance is a major function of the airway epithelium. This important function depends both on the physicochemical properties of the airway mucus and on the activity of the cilia. The former, in turn, is dependent mainly on the quality and quantity of mucous glycoproteins or mucins, which are produced by two different cell types, namely, goblet cells of the epithelium and mucous cells of the submucosal gland. Neither the structural nor the functional differences of mucins produced by these two cell types are yet known. The availability of primary airway epithelial cell culture systems, however, has made it possible to study the structure and regulation of airway goblet cells to some extent. The epithelial mucins are extremely hydrophobic and are associated with various macromolecules, the quality and quantity of which may also affect the physicochemical properties of the mucus. Secretion of epithelial mucins is stimulated by various factors, including a number of inflammatory agents. The recent progress in mucin molecular biological research will allow us to identify different mucin core proteins produced by those different cell types, and, hopefully, the differential functions of these mucins in health and disease.

Animals↗

PubMed1997

Immunologic epitope, gene, and immunity involved in pneumococcal glycoconjugate.

Pneumococcal infection persists as a major cause of pneumonia, otitis media, and meningitis in infants. Children less than 2 years of age show the highest incidence of pneumococcal diseases. Production of monoclonal antibody (MAb) to polysaccharide (PS) and binding characteristics to PS epitopes were studied. Removal of the O-acetyl group from 9V PS by alkali hydrolysis resulted in a decreased binding with rabbit 9V antiserum (AS). However, the binding reaction with 9V MAb was less affected by the loss of O-acetyl content. Type 9V IgG MAb provided passive protection and enhanced the opsonophagocytic activity of polymorphonuclear (PMN) leukocytes to kill type 9V pneumococci. The pathogenecity of pneumococci is attributed to various virulence factors distributed on the cell surface, including capsular polysaccharide and protein antigens, for example, pneumolysin, autolysin, pneumococcal surface protein A (PspA), pneumococcal surface adhesion (PsaA), and hemin binding protein. Some of these protein antigens may be used as a component to combine with pneumococcal PS vaccine or as a carrier of conjugate vaccine. Clinical trials of pneumococcal conjugate vaccines showed that covalent linkage of capsular PS to protein carriers improved the immunogenicity of the PS. Development of glycoconjugate vaccine for selected pneumococcal types will help solve the problem of poor immunogenecity of PS vaccine in young children used for prevention of pneumococcal infection.

Amino Acid Sequence↗

PubMed1997

Anesthetic management in parturients with uterine rupture preoperatively--report of two cases.

Uterine rupture is a rare obstetric emergency, and the diagnosis of rupture is not always obvious. High surgical delivery rate today which tends to increase the incidence of the disaster urged us to present this report. Two cases of spontaneous rupture of uterus are described. Case 1 concerns spontaneous rupture of a previously intact uterus; case 2 is a rupture due to placenta percreta. A review relevant to its incidence, risk factors, clinical characteristics, and anesthetic managements is given.

Adult↗

PubMed1997

The preliminary study and tentative animal study on the sintered PDLLA/TCP composites as bone fracture internal fixation.

Polyesters based on the lactic acid have been reported safety and biodegradation in the human beings for two decades. The greatest advantage of the material is its degradation only conducted by the hydrolysis, where the ester backbones are supposed to be unchained in the aqueous condition. The final degradable products are carbon dioxide and water which can be metabolized and digested in the physiological environment. The goal of this study was aimed to develop a composite sintered with poly-DL-lactide (PDLLA) and tricalcium phosphate (TCP) ceramic particles as orthopedic application. The TCP particles in a range of 30-60 wt% (with 5 wt% increment) were doped into the PDLLA matrix for the reinforcement, which were prepared by the melting and hot pressing techniques. The basic mechanical strength, biodegradable behavior, and biological response of the composites will be investigated in the study. Various techniques, such as pH meter, UV, FTIR, XRD ect., were used to examine and record the degradable process of the composites soaked in the saline for 1-16 weeks. The rabbit femur condyle fracture fixation test was used to evaluate the tissue compatibility and the effects of bone fracture fixation of the composites. The histological observation and x-ray photography were applied for investigating assistance. In the histological evaluation of rabbit femur condyle fracture fixation test, the surface of the composite with 50 wt% TCP addition was attached by the new generated bone without fibrous tissue around after 8 weeks implantation. The fracture bone was gradually healing and the composite always firmly and properly fixed on the fracture area during the implanted period, which provided a breeding environment for normal bone remodeling. The developed composite was thought to be an alternative material for orthopedic application in the future, especially in bone screw and bone plate.

Animals↗

PubMed1996

Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons.

Nitric oxide (NO) has been proposed to act as a retrograde messenger during long-term potentiation (LTP) in the CA1 region of hippocampus, but the inaccessibility of the presynaptic terminal has prevented a definitive test of this hypothesis. Because both sides of the synapse are accessible in cultured hippocampal neurons, we have used this preparation to investigate the role of NO. We examined LTP following intra- or extracellular application of an NO scavenger, an inhibitor of NO synthase, and a membrane-impermeant NO donor that releases NO only upon photolysis with UV light. Our results indicate that NO is produced in the postsynaptic neuron, travels through the extracellular space, and acts directly in the presynaptic neuron to produce long-term potentiation, supporting the hypothesis that NO acts as a retrograde messenger during LTP.

Animals↗

PubMed1996

Synaptic strengthening through activation of Ca2+-permeable AMPA receptors.

Postsynaptic Ca2+ elevation during synaptic transmission is an important trigger for short- and long-term changes in synaptic strength in the vertebrate central nervous system. The AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate) receptors, a subfamily of glutamate receptors, mediate much of the excitatory synaptic transmission in the brain and spinal cord. It has been shown that a subtype of the AMPA receptor is Ca2+-permeable and is present in the subpopulations of neurons. When synaptically localized, these receptors should mediate postsynaptic Ca2+ influx, providing a trigger for changes in synaptic strength. Here we show that Ca2+-permeable AMPA receptors are synaptically localized on a subpopulation of dorsal horn neurons, and that they provide a synaptically gated route of Ca2+ entry, and that activation of these receptors strengthens synaptic transmission mediated by AMPA receptors. This pathway for postsynaptic Ca2+ influx may provide a new form of activity-dependent modulation of synaptic strength.

Action Potentials↗