Biomedical subjects

C Y Chiang

Publications and source records attributed to C Y Chiang.

At least 19 recordsLinked to original sources

PubMed2006

Involvement of glia in central sensitization in trigeminal subnucleus caudalis (medullary dorsal horn).

Central sensitization is a crucial mechanism underlying the increased excitability of nociceptive pathways following peripheral tissue injury and inflammation. We have previously demonstrated that the small-fiber excitant and inflammatory irritant mustard oil (MO) applied to the tooth pulp produces glutamatergic- and purinergic-dependent central sensitization in brainstem nociceptive neurons of trigeminal subnucleus caudalis (Vc). Recent studies have implicated both astrocytes and microglia in spinal nociceptive mechanisms, showing, for example, that inhibition of spinal astroglial metabolism or spinal microglial p38MAPK activation can attenuate hyperalgesia in inflammatory pain models but have not tested effects of glial inhibitors on central sensitization in functionally identified spinal nociceptive neurons. The aim of the present study was to determine whether glial cells are involved in the MO-induced central sensitization in Vc nociceptive neurons, by examining the effects of intrathecally applied SB203580 (SB), an inhibitor of p38MAPK, and fluoroacetate (FA), an inhibitor of the astroglial metabolic enzyme aconitase. During continuous superfusion of phosphate-buffered saline over Vc, MO application to the pulp-induced central sensitization in Vc nociceptive neurons reflected in significant increases in cutaneous mechanoreceptive field (RF) size and responses to noxious mechanical stimuli and a decrease in mechanical activation threshold. The i.t. application of SB or FA markedly attenuated the MO-induced increases in pinch RF size and responses to noxious stimuli and the decrease in activation threshold. Neither SB nor FA application significantly affected the baseline (i.e., pre-MO application) RF and response properties. These results suggest that glial metabolic processes are important in the development of Vc central sensitization.

Aconitate Hydratase↗

PubMed2006

Central sensitization in thalamic nociceptive neurons induced by mustard oil application to rat molar tooth pulp.

We have recently demonstrated that application of mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces central sensitization that is reflected in changes in spontaneous activity, mechanoreceptive field (RF) size, mechanical activation threshold, and responses to graded mechanical stimuli applied to the neuronal RF in trigeminal brainstem subnucleus caudalis and subnucleus oralis. The aim of this study was to test whether central sensitization can be induced in nociceptive neurons of the posterior thalamus by MO application to the pulp. Single unit neuronal activity was recorded in the ventroposterior medial nucleus (VPM) or posterior nuclear group (PO) of the thalamus in anesthetized rats, and nociceptive neurons were classified as wide dynamic range (WDR) or nociceptive-specific (NS). MO application to the pulp was studied in 47 thalamic nociceptive neurons and found to excite over 50% of the 35 VPM neurons tested and to produce significant long-lasting (over 40 min) increases in spontaneous activity, cutaneous pinch RF size and responses to graded mechanical stimuli, and a decrease in threshold in the 29 NS neurons tested; a smaller but statistically significant increase in mean spontaneous firing rate and decrease in activation threshold occurred following MO in the six WDR neurons tested. Vehicle application to the pulp did not produce any significant changes in six VPM NS neurons tested. MO application to the pulp produced pronounced increases in spontaneous activity, pinch RF size, and responses to mechanical stimuli, and a decrease in threshold in three of the six PO neurons. In conclusion, application of the inflammatory irritant MO to the tooth pulp results in central sensitization of thalamic nociceptive neurons and this neuronal hyperexcitability likely contributes to the behavioral consequences of peripheral inflammation manifesting as pain referral, hyperalgesia and allodynia.

Action Potentials↗

PubMed2005

Endogenous ATP involvement in mustard-oil-induced central sensitization in trigeminal subnucleus caudalis (medullary dorsal horn).

Central sensitization represents a sustained hypersensitive state of dorsal horn nociceptive neurons that can be evoked by peripheral inflammation or injury to nerves and tissues. It reflects neuroplastic changes such as increases in neuronal spontaneous activity, receptive field size, and responses to suprathreshold stimuli and a decrease in activation threshold. We recently demonstrated that purinergic receptor mechanisms in trigeminal subnucleus caudalis (Vc; medullary dorsal horn) are also involved in the initiation and maintenance of central sensitization in brain stem nociceptive neurons of trigeminal subnucleus oralis. The aim of the present study was to investigate whether endogenous ATP is involved in the development of central sensitization in Vc itself. The experiments were carried out on urethan/alpha-chloralose anesthetized and immobilized rats. Single neurons were recorded and identified as nociceptive-specific (NS) in the deep laminae of Vc. During continuous saline superfusion (0.6 ml/h it) over the caudal medulla, Vc neuronal central sensitization was readily induced by mustard oil application to the tooth pulp. However, this mustard-oil-induced central sensitization could be completely blocked by continuous intrathecal superfusion of the wide-spectrum P2X receptor antagonist pyridoxal-phosphate-6-azophenyl-2, 4-disulphonic acid tetra-sodium (33-100 microM) and by apyrase (an ectonucleotidase enzyme, 30 units/ml). Superfusion of the selective P2X1, P2X3 and P2X(2/3) receptor antagonist 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate (6-638 microM) partially blocked the Vc central sensitization. The two P2X receptor antagonists did not significantly affect the baseline nociceptive properties of the Vc neurons. These findings implicate endogenous ATP as an important mediator contributing to the development of central sensitization in nociceptive neurons of the deep laminae of the dorsal horn.

Action Potentials↗

PubMed2005

A method to determine the utility of the third diagnostic and the second follow-up sputum smear examinations to diagnose tuberculosis cases and failures.

SETTING: Forty-two laboratories in four countries. OBJECTIVE: To determine the number of sputum smear examinations required to identify one additional case of tuberculosis from a third serial diagnostic smear or one additional treatment failure from a second serial follow-up smear. MATERIAL AND METHODS: Country-specific prevalence of new cases and failures among 59 665 examinees were determined, as well as the incremental yield from serial smears. The reciprocal value of the product of the prevalence of cases or failures and the respective incremental yield from the last serial smear provided the number of slides that have to be examined to identify one additional case or failure. RESULTS: The expected prevalence of cases among suspects ranged from 5.4% to 32.8%; the incremental yield from a third serial smear ranged from 0.7% to 7.2%. Between 122.7 and 796.3 smears were required to identify one additional case with the third serial smear. The prevalence of failures among follow-up examinees ranged from 1.0% to 2.5%; the incremental yield from the second follow-up serial smear ranged from 4.5% to 26.9%. Between 164.8 and 2133.4 slides were required to identify one additional failure with the second serial smear. CONCLUSION: The utility of serial smears can be rationally determined by careful review of program data.

Follow-Up Studies↗

PubMed2005

Patient and health system delays in the diagnosis and treatment of tuberculosis in Southern Taiwan.

SETTING: Tainan city, Tainan county and 13 townships of Kaohsiung county, Southern Taiwan. OBJECTIVE: To measure delays in the diagnosis and treatment of sputum-positive tuberculosis (TB) and to determine factors associated with delays in seeking health care (patient delay) and in starting anti-tuberculosis treatment (health system delay). DESIGN: A population-based patient interview study. RESULTS: Median patient delay was 7 days (range 0-730). Median health system delay was 23 days (range 0-489), 13 for smear-positive patients and 37 for smear-negative patients (P < 0.005). Median total delay was 44 days (range 0-730). Age <65 years was associated with longer patient delay. Negative smear, absence of haemoptysis, not having a chest radiograph at the first medical consultation and visiting clinics for first consultation were associated with a longer health system delay. Age <65 years, negative smear and cough as the only presenting symptom were associated with longer total delay. CONCLUSION: Patient delay was substantially shorter than health system delay. To reduce health system delay, clinics need to be involved and the referral mechanism must be strengthened. Physicians should maintain high alert for TB and perform prompt sputum smear examinations.

Adolescent↗

PubMed2002

The impact of national health insurance on the notification of tuberculosis in Taiwan.

SETTING: General notification of tuberculosis in Taiwan. OBJECTIVES: To ensure the completeness of notification of tuberculosis (TB) in Taiwan, the Bureau of National Health Insurance (NHI) introduced two policies in 1997: 1) the no-notification-no-reimbursement (NNNR) policy, and 2) the notification-fee (NF) policy. The goals of this study were to investigate the impact of the NNNR and NF policies on notification of TB. DESIGN: Review of all cases notified to the National TB Register from 1995 to 1999 to determine calendar trend, type of case and source of notification. RESULTS: There were 11,453 and 13,612 reported cases in 1995 and 1996, respectively. Following the implementation of the NHI policies, there was a 47% increase in 1997, with 20 021 reported cases. Quarterly reporting of cases reached a historic peak in the third quarter of 1997. The increase in reported cases was mainly from general hospitals/clinics. Since 1998, the number of reported cases has declined steadily, at a rate of 7% and 3% in 1998 and 1999, respectively. CONCLUSIONS: The NNNR and NF policies had a significant impact on notification of TB in Taiwan. These policies substantially improved completeness of reporting, an observation with implications for surveillance of other reported diseases.

Disease Notification↗

PubMed2001

Phytoremediation of MTBE from a groundwater plume.

The feasibility of phytoremediation to both remediate and hydraulically contain a methyl tert-butyl ether (MTBE)-contaminated groundwater plume was investigated in a three-phase study that included the following elements: (i) a laboratory bioreactor study that examined the fate and transport of 14C-radiolabeled MTBE in hybrid poplar trees, (ii) a novel approach for a mathematical modeling study that investigated the influence of deep-rooted trees on unsaturated and saturated groundwater flow, and (iii) a field study at a Houston site with MTBE-contaminated groundwater where hybrid poplar trees were planted. In the laboratory study, the predominant fate pathway was uptake and evapotranspiration of [14C]-MTBE from leaves and stems of poplar cuttings rooted in hydroponic solution. The modeling study demonstrates that phytohydraulic containment of MTBE in groundwater by deep-rooted trees can be achieved. The field study demonstrated significant groundwater uptake of groundwater by deep-rooted trees via direct measurement in the first three seasons. The use of vegetation may provide a cost-effective in-situ alternative for containment and remediation of MTBE-contaminated groundwater plumes.

Biodegradation, Environmental↗

PubMed2001

Complete atrio-ventricular block as a major clinical presentation of the primary cardiac lymphoma: a case report.

It is uncommon for malignant lymphomas to present primarily with cardiac invasion as the main clinical feature. What we are interested in is not only where the disease is, but also those symptoms that it may induce. Sudden onset of complete atrio-ventricular block is one of the most common clinical presentations. Cardiac tamponade is another common disease entity which, if it locates over outlets of great vessels, may also exert symptoms of obstructive vessels. Diagnosis can be made by needle aspiration under the guidance of transcutaneous or transesophageal echocardiography. Both CT scan and MRI play positive roles in the diagnosis of cardiac lymphomas, and the latter can even provide much more image information than the former. We report a 70-year-old male with primary cardiac lymphoma with initial clinical pictures of sudden onset of complete atrio-ventricular block. Chemotherapy was utilized with cyclophosphamide, vincristine and prednisolone (COP) initially for four courses and followed by adding doxorubicin (CHOP) for another three courses. The patient was still in remission status after treatment for 2 years.

Aged↗

PubMed2001

Neuroplasticity induced by tooth pulp stimulation in trigeminal subnucleus oralis involves NMDA receptor mechanisms.

We have recently demonstrated that application of the mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces significant increases in jaw muscle electromyographic (EMG) activity and neuroplastic changes in trigeminal (V) subnucleus caudalis. Since subnucleus oralis (Vo) as well as caudalis receives projections from molar pulp afferents and is also an integral brain stem relay of afferent input from orofacial structures, we tested whether MO application to the exposed pulp induces neuroplastic changes in oralis neurons and whether microinjection of MK-801, a noncompetitive NMDA antagonist, into the Vo influences the pulp/MO-induced neuroplastic changes in chloralose/urethan-anesthetized rats. Single neuronal activity was recorded in Vo, and neurons classified as low-threshold mechanoreceptive (LTM), wide dynamic range (WDR), nociceptive-specific (NS), deep (D), or skin/mucosa and deep (S + D). The spontaneous activity, mechanoreceptive field (RF) size, mechanical threshold, and response to suprathreshold mechanical stimuli applied to the neuronal RF were assessed prior to and throughout a 40- to 60-min period after MO application to the maxillary molar pulp. In animals pretreated with saline microinjection (0.3 microl) into the Vo, MO application to the pulp produced a significant increase in spontaneous activity, expansion of the pinch or deep RF, decrease in the mechanical threshold, and increase in response to suprathreshold mechanical stimuli of the nociceptive (WDR, NS, and S + D) neurons except for those nociceptive neurons having their RF only in the intraoral region. The pulpal application of MO did not produce any significant neuroplastic changes in LTM neurons. Furthermore, in animals pretreated with MK-801 microinjection (3 microg/0.3 microl) into the Vo, MO application to the pulp did not produce any significant changes in the RF and response properties of nociceptive neurons. In other animals pretreated with saline (0.3 microl) or MK-801 (3 microg/0.3 microl) microinjected into the Vo, mineral oil application to the pulp did not produce any significant changes in RF and response properties of nociceptive neurons. These findings indicate that the application of MO to the tooth pulp can induce significant neuroplastic changes in oralis nociceptive neurons and that central NMDA receptor mechanisms may be involved in these neuroplastic changes.

Animals↗

PubMed2001

On the direct products of measurement structures.

This paper considers the direct products of relational systems of the same type and scales defined thereon, as well as the invariance properties of functions on such product structures. The results will be applied to a theory of multidimensional scale types.

Analysis of Variance↗

PubMed2001

Does nifedipine aggravate cyclosporin--induced gingival overgrowth? An experiment in rats.

BACKGROUND: Nifedipine (NIF) may aggravate cyclosporin A (CsA)-induced gingival overgrowth because the potentiated gingival overgrowth has been observed in the patients treated with CsA and NIF. The purpose of this study was to evaluate whether NIF could aggravate the CsA-induced gingival overgrowth in a rat model. METHODS: Ninety male Sprague-Dawley rats were divided into 6 groups: the first group received 8 mg/kg of CsA daily by gastric feeding for 6 weeks; the second and third groups received NIF daily at a dosage of 10 or 50 mg/kg; the fourth and fifth groups received CsA (8 mg/kg) and NIF (10 or 50 mg/kg); and the sixth group received solvents as a negative control. Gingival dimensions (including bucco-lingual depth, mesio-distal width, and vertical height) were assessed bi-weekly from impressed stone models of the mandibular incisal region. At the end of the experiment, the animals were sacrificed. Following histopathological procedures, serial horizontal sections were obtained at the base of the central incisal papilla. Two tissue levels were selected for histometric analysis. Level 1 was defined as the point where the lingual gingiva embraced the bucco-lingual midpoint of the roots and the level 2 as the point where the lingual gingiva at the enamel-dentinal junction approximated the bucco-proximal angle of the roots. The bucco-lingual depth and the mesio-distal width of the papilla were recorded on 5 consecutive sections at the 2 levels, respectively. RESULTS: At the 6-week observations, the gingival dimensions (including the depth, width, and height) significantly increased after CsA therapy and the increasing treatment duration; however, only the mesio-distal width increased after NIF therapy. For NIF therapy alone, a positive linear relation was noted by increased NIF treatment dosages in all gingival dimensions at week 6. But, this relationship was not found in the combined therapies. By histometry, tissue dimensions increased following single drug therapy, either CsA or NIF, at both levels. In animals with the combined therapies, the tissue dimensions decreased if the animals received 10 mg NIF, while they rebounded to control levels with the 50 mg dosage. A dose-dependent positive pattern by NIF was noted in tissue dimensions, but the pattern did not occur in animals that received combined therapy. CONCLUSIONS: The gingival dimensions increased after CsA or NIF therapy, although they were more prevalent with CsA. But the augmenting pattern in gingival morphology observed with CsA therapy decreased when the animals received additional NIF. Therefore, we question whether NIF is a critical factor in aggravating the CsA-induced gingival overgrowth.

Animals↗

PubMed2001

Cyclosporin-induced gingival overgrowth at the newly formed edentulous ridge in rats: a morphological and histometric evaluation.

BACKGROUND: Since cyclosporin A (CsA)-induced overgrowth seldom occurs at sites distant from teeth, the periodontal ligament has been considered significant. The aim of this study was to examine overgrowth occurrence at the edentulous ridge--the sites without the ligament--after CsA therapy in rats. METHODS: After extracting all right maxillary molars, 16 Sprague-Dawley rats underwent a 2-week healing period. The animals were separated into CsA and control groups. CsA rats received 15 mg/kg of CsA by gastric feeding for 4 weeks, while the control group received only mineral oil. At the end of study, all animals were sacrificed and stone models were immediately obtained by rubber-based impressions. The edentulous ridge morphology, including the bucco-lingual width and the vertical height, was measured on the models. For histometry, 10 sections were selected from the edentulous ridge of each animal after undecalcified tissue preparation. The soft tissue areas of the edentulous ridge and the trabecular bone morphology of the dental alveolus were measured. RESULTS: CsA therapy produced a significant increase of the ridge width and height, measured from the stone models, when compared to the control group. Under histometry, CsA resulted in a significant increase of the epithelium, connective tissue, and total soft tissue areas. The measured trabecular bone volume was affected by both examining factors: the drug therapy and the location of the dental alveolus. CsA therapy produced a significant loss of bone volume but a significant increase of the bone-specific surface area. Although the mean osteoid volume was similar between CsA and control groups, a significant decrease of the fractional formation surface in the CsA group was revealed. CONCLUSIONS: An enlarged edentulous ridge and an altered dental alveolar bone morphology were observed in CsA-treated animals at the end of the study; therefore, we suggest that CsA may induce not only a soft tissue overgrowth but also an alveolar bone alteration at the edentulous ridge. The hypothesis that tooth or periodontal ligament is an essential component for the overgrowth development is questioned.

Alveolar Process↗

PubMed2001

Pulmonary resection in the treatment of patients with pulmonary multidrug-resistant tuberculosis in Taiwan.

SETTING: Chronic Disease Control Bureau, Department of Health, Taiwan. OBJECTIVE: To evaluate the role of pulmonary resection in the treatment of pulmonary tuberculosis resistant to isoniazid and rifampin (MDR-TB). DESIGN: In a retrospective cohort study, 27 MDR-TB patients who underwent pulmonary resection between December 1990 and March 1999 were reviewed. Individually-tailored treatment regimens were selected at a once-weekly staff conference following review of the patient's case history and drug susceptibility results. Surgery was performed for selected patients, essentially those: 1) whose medical treatment had failed, or for whom treatment failure seemed highly likely, or for whom post-treatment relapse seemed likely, 2) with predominantly localised disease, 3) with adequate cardiopulmonary reserve, and 4) whose treatment regimen had been composed of at least two effective drugs to diminish the mycobacterial burden. RESULTS: There was no surgical mortality apart from one peri-operative death (4%). Three patients (11%) developed complications, and 24 (92%) patients demonstrated sputum conversion and/or remained negative after surgery. Twenty-three patients have already completed treatment, and during a mean of 42 +/- 18 follow-up months (range 15-80 months), one patient relapsed. This patient was disease-free after another course of treatment. CONCLUSION: For selected patients, pulmonary resection may improve the outcome of pulmonary MDR-TB.

Adult↗

PubMed2001

Inflammatory pseudotumor of the lung in a coal miner with pneumoconiosis.

Inflammatory pseudotumors of the lung are uncommon and etiologically diverse lesions that often present as solitary masses in the lung. It may be difficult to distinguish these lesions from more commonly encountered lung neoplasms. Inflammatory pseudotumors can also occur in other organs, but the lung is most commonly involved. We describe a 63-year-old male coal miner with a 40-year history of dust exposure, who had a large right middle lobe mass on chest roentgenograms, with slow growth over the 7 years prior to admission. Repeated transthoracic echo-guided biopsies of the mass were indicative of an inflammatory and reactive process. The radiographic, histologic, and clinical findings indicated a diagnosis of inflammatory pseudotumor. The patient refused surgical intervention and was regularly followed at our outpatient clinic. Follow-up chest roentgenograms for 1 year revealed that the tumor size was stable. This case suggested that inflammatory pseudotumor, although uncommon, should be included in the differential diagnosis in a patient with pneumoconiosis and a solitary mass in the lung.

Biopsy, Needle↗

PubMed2000

Heterobimetallics of nickel-iron dinitrosyl: electronic control by chelate and diatomic ligands.

Reaction of [PPN][Fe(NO)2(SePh)2] (1) with dimeric [Ni(mu-SCH2CH2SCH2CH2S)]2 in the presence of additional NO2- produced the neutral heterobimetallic [(ON)Ni[(mu-SCH2CH2)2S]Fe(NO)2] complex (2). The X-ray crystal structures of 1 and 2 show distorted tetrahedral iron dinitrosyl groups, assigned according to the Feltham-Enemark notation as [Fe(NO)2]9 The Fe-NO bonds are off linearity by an average of approximately equals 10 degrees for compounds 1 and 2, while a more linear Ni-NO coordination with a Ni-NO distance of 1.644(2) A was found in 2. The v(NO) value of complex 2 is consistent with an assignment for [Ni(NO)]9 of Ni0(NO)+ as is known for analogous phosphine derivatives, P3Ni0(NO)+. EPR signals of g values = 2.02-2.03 confirmed the existence of the odd electron in the chalcogenated [Fe(NO)2]9 compounds. Two [Fe(NO)2]10 complexes coordinated by the nickel(II) dithiolate, (bismercaptoethanediazacyclooctane)nickel(II), (Ni-1), (Ni-1)Fe(CO)(NO)2 and (Ni-1)Fe(NO)2, were prepared for comparison to the Ni0(NO)+ derivative and other monomeric and homodimetallic derivatives of the Fe(NO)2 fragment. While the oxidation level of Fe(NO)2 is the primary determinant of v(NO) values, they are also highly sensitive to ancillary ligands and, thereby, the distal metal influence through the bridging thiolate donor.

Binding Sites↗

PubMed1999

Involvement of trigeminal subnucleus caudalis (medullary dorsal horn) in craniofacial nociceptive reflex activity.

We have previously shown that an increase in electromyographic (EMG) activity of digastric (DIG) and masseter (MASS) muscles can be reflexly evoked by injection into the rat's temporomandibular joint (TMJ) region of the small-fibre excitant and inflammatory irritant mustard oil (MO). Since the trigeminal (V) subnucleus caudalis (Vc, i.e. medullary dorsal horn) has traditionally been viewed as an essential brainstem relay site of nociceptive information from craniofacial tissues, an EMG study was carried out in 45 anaesthetized rats to determine if Vc is involved in the MO-evoked increases in jaw muscle EMG activity. The effects of histologically confirmed surgical or chemical lesions of Vc on this evoked EMG activity were tested in different groups of rats. MO injection into the left TMJ region of intact rats evoked bilateral increases in EMG activity of DIG and MASS which could be significantly reduced by surgical transection of the left caudal brainstem at the obex level; MO injection into the right TMJ region in these same rats still readily evoked increases in EMG activity. A sagittal section medial to Vc or transection at the level of the second cervical spinal segment did not produce any significant reduction in the reflexly evoked EMG activity. Neurones in Vc, as opposed to fibres of passage, appear to be important for the MO-evoked EMG activity, since injection into Vc of the neurotoxic chemical ibotenic acid significantly reduced the mustard oil-evoked EMG activity. The Vc also appears to play a role in the activation of contralateral V motoneurons, as evidenced by the activation of the contralateral DIG and MASS muscles by the injection of MO into the left TMJ region of intact rats and by the reduction of this evoked EMG activity in the contralateral DIG and MASS of rats with a surgical transection or ibotenic acid lesion of the left Vc. These findings suggest that Vc may be a critical element in the neural pathways underlying the reflex responses evoked bilaterally in DIG and MASS muscles by noxious stimulation of the TMJ region.

Animals↗

PubMed1999

Interleukin-1 and tumor necrosis factor activities partially account for calvarial bone resorption induced by local injection of lipopolysaccharide.

The present study was undertaken to test the hypothesis that tumor necrosis factor (TNF) and/or interleukin-1 (IL-1) activity mediates lipopolysaccharide (LPS)-induced bone resorption in vivo. To test this hypothesis, Escherichia coli LPS or Porphyromonas gingivalis LPS was injected into the subcutaneous tissues overlying mouse calvariae. Histological sections, prepared from the center of the lesion, were stained for tartrate-resistant acid phosphatase, and histomorphometric analysis was performed to quantify the osteoclast number and the area of bone resorption. In time course experiments using normal mice, a peak of bone resorption occurred 5 days after endotoxin stimulation. In dose-response experiments, IL-1 receptor type 1 deletion (IL-1R(-/-)), TNF double-receptor p55/p75 deletion (TNF p55(-/-)/p75(-/-)), combined TNF p55 and IL-1 receptor type 1 deletion (TNF p55(-/-)/IL-1R(-/-)), and IL-1beta-converting enzyme-deficient (ICE(-/-)) mice and the respective wild-type mice were injected with 500, 100, or 20 micrograms of P. gingivalis LPS and sacrificed 5 days after LPS injection. At the highest dose (500 micrograms), significant decreases in osteoclast number occurred in mutant mice compared to wild-type mice: (i) a 64% reduction for the TNF p55(-/-)/IL-1R(-/-) mice, (ii) a 57% reduction for the IL-1R(-/-) mice, (iii) a 41% reduction for the TNF p55(-/-)/p75(-/-) mice, and (iv) a 38% reduction for the ICE(-/-) mice. At the two lower doses, bone resorption was apparent but no significant differences between mutant and wild-type animals were observed. The present data indicate that at higher doses, LPS-induced bone resorption is substantially mediated by IL-1 and TNF receptor signaling. Furthermore, IL-1 receptor signaling appears to be slightly more important than TNF receptor signaling. At lower LPS doses, other pathways leading to osteoclast activity that are independent of TNF and IL-1 are involved.

Animals↗

PubMed1999

Effects of GABA receptor antagonist on trigeminal caudalis nociceptive neurons in normal and neonatally capsaicin-treated rats.

We have recently demonstrated that significant increases in cutaneous mechanoreceptive field (RF) size and spontaneous activity occur in nociceptive neurons of trigeminal subnucleus caudalis (Vc, the medullary dorsal horn) of adult rats depleted of C-fiber afferents by neonatal treatment with capsaicin. These neuronal changes in capsaicin-treated (CAP) rats are suggestive of central neuroplasticity and involve N-methyl-D-aspartic acid (NMDA) receptor mechanisms. The present study examined whether the GABA(A) receptor antagonist bicuculline (BIC) or the GABA(B) receptor antagonist 2-hydroxysaclofen (SAC) can influence the RF properties and activity of Vc nociceptive neurons classified as either nociceptive-specific or wide-dynamic range in CAP adult rats or in neonatally vehicle-treated (CON) rats. C-fiber depletion was confirmed in the CAP rats by a significant decrease in plasma extravasation of Evans blue dye in a skin area receiving topical application of mustard oil, a small-fiber excitant and inflammatory irritant. As previously reported, marked increases in cutaneous RF size and spontaneous activity occurred in Vc nociceptive neurons of adult CAP rats, compared with CON rats. GABA(A) receptor blockade by BIC (i.t.) in CON rats produced a significant increase in spontaneous activity and in pinch RF size and tactile RF size (or appearance of a tactile area in the RF of nociceptive-specific neurons), as well as a significant lowering of the mechanical threshold and a significant enhancement of responses to pinch stimuli applied to the RF. In CAP rats, GABA(A) receptor blockade also produced significant changes similar to those documented in CON rats, except for a paradoxical and significant decrease in pinch RF size and no noticeable changes in responses to pinch stimuli. GABA(B) receptor blockade by SAC (i.t. ) did not produce any significant changes in Vc nociceptive neurons in either CON or CAP rats. These results suggest that GABA(A) receptor-mediated inhibition may be involved in maintaining the functional expression of Vc nociceptive neuronal properties in normal conditions, and that in animals depleted of their C-fiber afferents, some features of this GABA(A) receptor-mediated modulation may be disrupted such that a GABA(A) receptor-mediated excitation is manifested.

Animals↗