Biomedical subjects

D Ding

Publications and source records attributed to D Ding.

At least 37 records · Page 2Linked to original sources

PubMed2000

Acidosis induces necrosis and apoptosis of cultured hippocampal neurons.

Acidosis, hypoxia, and hypoglycemia rapidly and transiently appear after reduction of cerebral blood flow. Acidosis also accompanies head trauma and subarachnoid hemorrhage. These insults result in necrotic and apoptotic loss of neurons. We previously demonstrated that transient acidification of intracellular pH from 7.3 to 6.5 induces delayed neuronal loss in cultured hippocampal slices (49). We now report that acidosis induced both necrotic and apoptotic loss of neurons. Necrosis and apoptosis were distinguished temporally and pharmacologically. Necrosis appeared rapidly and was dose dependent with the duration of the acidosis treatment. Apoptosis was delayed with maximal number of apoptotic cells seen with a 30-min acidosis treatment. Apoptotic neuronal loss was accompanied by DNA fragmentation and was blocked by inhibitors of protein and RNA synthesis, ectopic expression of the anti-apoptotic gene bcl-2, or an inhibitor of caspases, proteases known to be activated during apoptosis. Necrotic neuronal loss was unaffected by these treatments. Hypothermia, a treatment known to attenuate neuronal loss following a variety of insults, blocked both acidosis-induced necrosis and apoptosis. These results indicate that acidosis is neurotoxic in vitro and suggest that acidosis contributes to both necrotic and apoptotic neuronal loss in vivo.

Acidosis↗

PubMed2000

Hearing loss following exposure during development to polychlorinated biphenyls: a cochlear site of action.

Maternal exposure to polyhalogenated hydrocarbons results in early postnatal hypothyroxenemia and a low-frequency hearing loss in adult offspring (Goldey et al., 1995a. Toxicol. Appl. Pharmacol. 135, 67-76; Herr et al., 1996. Fundam. Appl. Toxicol. 33, 120-128). The purpose of the present work was to determine whether the site-of-action of this auditory impairment was within the cochlea. Primiparous Long-Evans rats were given daily oral doses of corn oil (control) or 8 mg/kg of the commercial PCB mixture Aroclor 1254 (A1254) from gestation day (GD) 6 through postnatal day (PND) 21. Auditory thresholds for 1-, 4-, 16-, and 40-kHz tones were assessed using reflex modification audiometry in young adult offspring on postnatal days (PND) 92-110. Approximately 6 weeks after auditory assessments, a subset of animals (n=4 per group) were killed for histological assessment of the cochlea. Surface preparations of the organ of Corti were prepared from one cochlea per animal and modiolar sections were prepared from the opposite cochlea. Consistent with previous findings, auditory thresholds for 1-kHz tones were elevated by approximately 25 dB in the A1254-exposed animals. Thresholds for all higher frequencies were not different compared to controls. Surface preparations of the organ of Corti revealed a mild to moderate loss of outer hair cells in the upper-middle and apical turns. Inner hair cells were not affected. Modiolar sections failed to reveal alterations in any other cochlear structures. There was also no apparent loss of ganglion cells. These data clearly link the loss of low-frequency hearing caused by exposure during development to A1254 to a loss of outer hair cells in the organ of Corti. The mechanism that underlies this developmental ototoxicity remains to be determined. These data provide the first evidence of a structural deficit in the nervous system of adult animals exposed to PCBs during development.

Animals↗

PubMed2000

Auditory plasticity and hyperactivity following cochlear damage.

This paper will review some of the functional changes that occur in the central auditory pathway after the cochlea is damaged by acoustic overstimulation or by carboplatin, an ototoxic drug that selectively destroys inner hair cells (IHCs) in the chinchilla. Acoustic trauma typically impairs the sensitivity and tuning of auditory nerve fibers and reduces the neural output of the cochlea. Surprisingly, our results show that restricted cochlear damage enhances neural activity in the central auditory pathway. Despite a reduction in the auditory-nerve compound action potential (CAP), the local field potential from the inferior colliculus (IC) increases at a faster than normal rate and its maximum amplitude is enhanced at frequencies below the region of hearing loss. To determine if this enhancement was due to loss of sideband inhibition, we recorded from single neurons in the IC and dorsal cochlear nucleus before and after presenting a traumatizing above the unit's characteristic frequency (CF). Following the exposure, some neurons showed substantial broadening of tuning below CF, less inhibition, and a significant increase in discharge rate, consistent with a model involving loss of sideband inhibition. The central auditory system of the chinchilla can be deprived of some of its cochlear inputs by selectively destroying IHCs with carboplatin. Selective IHC loss reduces the amplitude of the CAP without affecting the threshold and tuning of the remaining auditory nerve fibers. Although the output of the cochlea is reduced in proportion to the amount of IHC loss, the IC response shows only a modest amplitude reduction, and remarkably, the response of the auditory cortex is enhanced. These results suggest that the gain of the central auditory pathway can be up- or down regulated to compensate for the amount of neural activity from the cochlea.

Animals↗

PubMed2000

Effects of AC and DC stimulation on chinchilla SOAE amplitude and frequency.

The effects of AC and DC current on spontaneous otoacoustic emissions (SOAEs) were studied in normal chinchillas and chinchillas with selective inner hair cell (IHC) loss. Electrical stimulation was delivered through an electrode on the round window or through an electrode in scala media. SOAE frequencies ranged from 4 to 11 kHz and amplitudes ranged from 13 to 51 dB SPL. AC simulation suppressed SOAE amplitude. The suppression contours had a narrowly tuned, low-threshold tip located above the frequency of the SOAE. AC suppression contours were similar to acoustic suppression contours except that the AC suppression contours lacked a high-threshold, low frequency tail. The lowest threshold of the AC suppression contour was 3.9 microA rms whereas the lowest acoustic suppression threshold was 19 dB SPL. AC stimulation, which induced an electrically evoked otoacoustic emission, interacted with the SOAE to generate distortion product otoacoustic emissions (DPOAEs) of up to 26 dB SPL at 2f(S)-f(AC) (f(S)=SOAE). DPOAE amplitude increased with AC current, but saturated at high levels. DC current steps affected both SOAE frequency and amplitude. Positive current at the round window decreased SOAE amplitude and frequency whereas negative current increased SOAE frequency, but had little effect on amplitude. The effects of AC and DC current on SOAEs in animals with IHC loss were similar to those in normal chinchillas.

Animals↗

PubMed2000

Induction of spontaneous otoacoustic emissions in chinchillas from carboplatin-induced inner hair cell loss.

Fifteen chinchillas were evaluated for spontaneous otoacoustic emissions (SOAEs) before and after administering carboplatin (126-200 mg/kg), an anti-neoplastic drug that selectively destroys inner hair cells (IHCs) in this species. SOAEs were absent from all animals prior to carboplatin treatment, but at 1 week post-treatment, 47% of the animals and 30% of the ears had developed SOAEs. SOAE frequencies were clustered between 5 and 10 kHz and SOAE intensity ranged from 10 to 32 dB SPL. All of the ears with SOAEs had IHC lesions exceeding 60% throughout most of the cochlea and two ears had outer hair cell lesions of 25-60% at a cochlear place associated with the frequency of the SOAE. Thus, high doses of carboplatin that cause IHC loss can be used to create an animal model with SOAEs.

Animals↗

PubMed2000

Inner hair cell loss leads to enhanced response amplitudes in auditory cortex of unanesthetized chinchillas: evidence for increased system gain.

Carboplatin preferentially destroys inner hair cells (IHCs) in the chinchilla inner ear, while retaining a near-normal outer hair cell (OHC) population. The present study investigated the functional consequences of IHC loss on the compound action potential (CAP), inferior colliculus potential (ICP) and auditory cortex potential (ACP) recorded from chronically implanted electrodes. IHC loss led to a reduction in CAP amplitude that was roughly proportional to IHC loss. The ICP amplitude was typically reduced by IHC loss, but the magnitude of this reduction was generally less than that observed for the CAP. In contrast to the CAP and ICP, ACP amplitudes were generally not reduced following IHC loss. In some animals, the ACP amplitude remained at pre-carboplatin values despite substantial IHC loss. However, in other animals, IHC loss led to an increase ('enhancement') of ACP amplitude. ACP enhancement was greatest at 1-2 weeks post-carboplatin, returning towards baseline amplitudes at 5 weeks post-carboplatin. In other animals, the ACP remained enhanced up to 5 weeks post-carboplatin. We interpret the transient and sustained enhancement of ACP amplitude following partial IHC loss as evidence of functional reorganization occurring at or below the level of the auditory cortex. These results suggest that the gain of the central auditory pathway increases following IHC loss to compensate for the reduced input from the cochlea.

Action Potentials↗

PubMed2000

Preparation and evaluation of a sustained-release formulation of nifedipine HPMC tablets.

A nifedipine (NF) polyethylene glycol (PEG) solid dispersion was prepared. Using this solid dispersion, NF hydroxypropylmethylcellulose (HPMC) matrix tablets were prepared. Both the high-viscosity grade HPMC (Methocel K15M) and low-viscosity grade HPMC (Methocel K100) were applied in the tablets to form the matrix. The dissolution and absorption of NF from the tablet were evaluated as a formulation that had a sustained release over 24 hr. The Hixson-Crowell equation and Higuchi equation were used to investigate the dissolution mechanism, and the erosion and diffusion codependent mechanism was established. Adalat GITS 30 was used as a reference dosage form. Each beagle dog was also administered an intravenous injection to obtain the pharmacokinetics parameters. The Loo-Riegelman method was applied to study the in vitro/in vivo correlation of the tested tablets and Adalat GITS 30, and significant correlation was proved. Absolute bioavailability and comparative bioavailability of the tested tablet were studied. The results indicated that the NF HPMC tablet could be an ideal 24-hr sustained-release formulation.

Absorption↗

PubMed2000

Second-harmonic generation of the nth-order Bessel beam.

We investigate the second-harmonic generation of the nth-order Bessel beam in the nonlinear medium. The analysis is based on the Khokhlov-Zabolotskaya-Kuznetsov wave equation under the second-order approximation in nonlinear acoustics. The theory indicates that for an nth-order Bessel beam, the second-harmonic beam is nearly diffraction-free in the radial direction and behaves as a Bessel beam of the order 2n, and that the axial pressure amplitude is proportional to the square root of propagation distance. A variety of applications in many fields of nonlinear acoustics and nonlinear optics is expected.

Acoustics↗

PubMed2000

Higher-order harmonics of limited diffraction Bessel beams

We investigate theoretically the nonlinear propagation of the limited diffraction Bessel beam in nonlinear media, under the successive approximation of the KZK equation. The result shows that the nth-order harmonic of the Bessel beam, like its fundamental component, is radially limited diffracting, and that the main beamwidth of the nth-order harmonic is exactly 1/n times that of the fundamental.

Journal Article↗

PubMed2000

A genetic study of the depressive respiratory responses to hypoxia in chronic obstructive pulmonary disease patients with type II respiratory failure.

OBJECTIVE: The depression of the ventilatory and P(0.1 )responses to hypoxia and hypercapnia may play an important role in the development of CO(2) retention in the patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate if there is any linkage relationship between the depressed ventilatory and P(0.1) response phenotypes and the microsatellite markers on chromosome 6q21.1-21.2 among Chinese people. METHODS: P(0.1) and ventilatory responses to hypoxia were measured in six COPD patients with type II respiratory failure, as well as in their 21 normal adult offsprings. Polymerase chain reaction (PCR), denaturing polyacrylamide gel electrophoresis and silver staining techniques were used to study the amplified fragment length polymorphism. Linkage analysis was done with the LINKAGE program. RESULTS: Hypoxia response was low in 10 offsprings, and normal in the other 11 offsprings. Linkage analysis showed the maximum Lod score was 1.74(D6S276, theta = 0.10). CONCLUSION: The depressed hypoxia response might have been influenced by genetic factors. The model was in accord with autosomal dominant inheritance. The disease-related gene was linked to D6S276 locus.

Adult↗

PubMed2000

[Genetical analysis on cross incubation of Beauveria bassiana].

Heterokaryon of Beauveria bassiana was formed during the cross incubation of two vegetative compatible strains with genetic markers of actidione resistance and 34 degrees C tolerance. The chromosome(s) or its fragment successive losses, recombination and segreation led to haploidization during the conidia formation period. After at least 4 generations of parasexual cycle, the genetic character of heterokayon could get to relative stable. Genetic marker and RAPD analysis indicated that the combinants showed the phenomenon of preferential selection of one parental type by unrandom chromosome lossing and the gene of the other parental strain was suppressed or lost completely. Different culture medium, in vivo or in vitro, and different mixture ratio of original strain spores could affect parasexual process and then the preferential selection. The results also demonstrated the heterosis effect of cross culture.

Chromosome Deletion↗

PubMed1999

Cu/Zn SOD deficiency potentiates hearing loss and cochlear pathology in aged 129,CD-1 mice.

Copper/zinc superoxide dismutase (Cu/Zn SOD) is a first-line defense against free radical damage in the cochlea and other tissues. To determine whether deficiencies in Cu/Zn SOD increase age-related hearing loss and cochlear pathology, we collected auditory brainstem responses (ABRs) and determined cochlear hair cell loss in 13-month-old 129/CD-1 mice with (a) no measurable Cu/Zn SOD activity (homozygous knockout mice), (b) 50% reduction of Cu/Zn SOD (heterozygous knockout mice), and (c) normal levels of Cu/Zn SOD (wild-type mice). ABRs were obtained by using 4-, 8-, 16-, and 32-kHz tone bursts. Cochleas were harvested immediately after testing, and separate counts were made of inner and outer hair cells. Compared with wild-type mice, homozygous and heterozygous knockout mice exhibited significant threshold elevations and greater hair cell loss. Phenotypic variability was higher among heterozygous knockout mice than among wild-type or homozygous knockout mice. Separate groups of wild-type and homozygous knockout mice were examined for loss of spiral ganglion cells and eighth nerve fibers. At 13 months of age, both wild-type and knockout mice had significantly fewer nerve fibers than did 2-month-old wild-type mice, with significantly greater loss in aged knockout mice than in aged wild-type mice. Thirteen-month-old knockout mice also had a significant loss of spiral ganglion cells compared with 2-month-old wild-type mice. The results indicate that Cu/Zn SOD deficiencies increase the vulnerability of the cochlea to damage associated with normal aging, presumably through metabolic pathways involving the superoxide radical.

Aging↗

PubMed1999

[Study on the correlation of silicosis with antioxidant and antioxidase].

Plasma vitamin C(P-VC), vitamin E(P-VE) and beta-carotene(P-beta-CAR) contents and the activities of superoxide dismutase(E-SOD), catalase(E-CAT) and glutathione peroxidase (E-GSH-Px) in erythrocyte in 73 silicosis patients and 60 healthy control subjects were measured. The average levels of P-VC, P-VE, P-beta-CAR, E-SOD, E-CAT and E-GSH-Px of patients were significantly lower than those of the controls (P < 0.001). All indexes were correlated to the course, condition and pulmonary function of silicosis patients. The results analyzed by stepwise regression showed that the correlation between course, condition and pulmonary function of patients and P-VE and E-SOD was close. The balance between oxidation and the antioxidation in silicosis patients may be disturbed, and oxygen free radical reaction may be pathologically exacerbated.

Adult↗

PubMed1999

Leupeptin protects sensory hair cells from acoustic trauma.

Calpains, a family of calcium activated proteases, promote the breakdown of cellular proteins, kinases, phosphatases and transcription factors. Calpain inhibitors attenuate some neurodegenerative processes in certain cell types. Here we show that leupeptin, a potent calpain inhibitor, protects the sensory hair cells in the inner ear from acoustic overstimulation (48 h, 100 or 105 dB SPL, octave band noise at 4 kHz). Acoustic overstimulation caused a significant increase in calpain immunolabeling in the sensory epithelium suggesting a possible role in noise-induced cochlear degeneration. Infusion of leupeptin into the inner ear significantly reduced the amount of sensory cell loss from acoustic overstimulation. However, leupeptin did not protect against hair cell loss from the ototoxic drug, carboplatin.

Animals↗

PubMed1999

Different 3' untranslated regions target alternatively processed hu-li tai shao (hts) transcripts to distinct cytoplasmic locations during Drosophila oogenesis.

Cytoplasmic mRNA localization is one method by which protein production is restricted to a particular intracellular site. We report here a novel mechanism for localization of transcripts encoding distinct protein isoforms to different destinations. Alternative processing of transcripts produced in the Drosophila ovary by the hu-li tai shao (hts) locus introduces distinct 3' untranslated regions (3'UTRs) that differentially localize the mRNAs. Three classes of hts mRNA (R2, N32 and N4) are synthesized in the germ line nurse cells and encode proteins with adducin-homologous amino-terminal regions but divergent carboxy-terminal domains. The R2 and N32 classes of mRNA remain in the nurse cells and are not transported into the oocyte. In contrast, the N4 class of transcripts is transported from the nurse cells into the oocyte starting at stage 1, is subsequently localized to the oocyte cortex at stage 8 and then to the anterior pole from stage 9 on. All aspects of N4 transcript transport and localization are directed by the 345-nucleotide(nt)-long 3' untranslated region (3'UTR). The organization of localization elements in the N4 3'UTR is modular: a 150 nt core is sufficient to direct transport and localization throughout oogenesis. Additional 3'UTR elements function additively together with this core region at later stages of oogenesis to maintain or enhance anterior transcript anchoring. The swallow locus is required to maintain hts transcripts at the anterior pole of the oocyte and functions through the N4 3'UTR. In addition to the three classes of germ line-expressed hts transcripts, a fourth class (R1) is expressed in the somatic follicle cells that surround the germ line cells. This transcript class encodes the Drosophila orthologue of mammalian adducin.

3' Untranslated Regions↗

PubMed1999

[Cost-effectiveness analysis of treatment of chronic hepatitis B with interferon in Chinese city].

OBJECTIVE: In this article, we evaluated the economic significance of treating HBeAg-positive chronic hepatitis B with interferon in Chinese population. METHODS: Cohort of 1,000 hypothetical HBeAg-positive chronic hepatitis B patients treated with interferon was compared to patients with routine treatment in respect of cost and effectiveness. The costs of routine treatment were estimated by surveys in four Chinese cities (Beijing, Shanghai, Nanning and Shijiazhuang). Natural history of HBeAg-positive chronic hepatitis B and the efficacy of interferon were determined by meta-analysis. Outcome of the disease and medical cost of the two cohorts were predicted over a period of 30 years using survival analysis. Thus, cost per life year and cost per QALY(Quality adjusted life year) with the interferon treatment were calculated. Sensitivity analysis was performed to test the firmness of the conclusion. RESULTS: Costs per life year and per QALY saved were no more than 2,359 Yuan(RMB) and 1,775 Yuan (RMB) respectively. In Shanghai and Beijing, medical costs could be saved due to the use of interferon. CONCLUSIONS: Treatment of chronic hepatitis B with interferon was cost-effective and should be considered in the allocation of health resource in Chinese cities.

Antiviral Agents↗

PubMed1999

Auditory deprivation of the central auditory system resulting from selective inner hair cell loss: animal model of auditory neuropathy.

Auditory neuropathy is often characterized by normal thresholds, present otoacoustic emissions, poor speech discrimination, absent acoustic reflexes, absent or abnormal auditory brainstem response waveform, but normal late cortical potential. This paper describes an animal model that has many characteristics of auditory neuropathy. Chinchillas can be deprived of a significant portion of the neural inputs to the central auditory system by administering carboplatin, an antineoplastic agent that selectively destroys inner hair cells (IHCs) and type I auditory nerve fibers. Selective IHC loss has no effect on distortion product otoacoustic emissions or the cochlear microphonic potential, implying normal outer hair cell function. However, selective IHC loss causes the amplitude of the compound action potential to decrease in proportion to the degree of IHC loss. However, the threshold of the CAP shows little increase with mild to moderate IHC loss. Acoustically responsive auditory nerve fibers in ears with mild to moderate IHC loss have normal thresholds and tuning curves with narrowly tuned tips. Although the central auditory pathway is deprived of much of its sensory inputs, the amplitude of the local field potential in the auditory cortex was normal or enhanced, while those from the inferior colliculus were slightly reduced. The results are related to those of a patient with auditory neuropathy.

Animals↗

PubMed1999

[The role of breathing control disorder in the development of carbon dioxide retention in patients with obesity hypoventilation syndrome].

OBJECTIVE: To define the role of breathing control in the pathogenesis of carbon dioxide (CO(2)) retention in patients with obesity hypoventilation syndrome. METHODS: 10 obese obstructive sleep apnea syndrome (OSAS) patients were studied. They were separated according to their waking arterial partial pressure of CO(2) (PaCO(2)), 5 being eucapnic and 5 hypercapnic. Both groups had similar body mass index, apnea hypopnea index and normal lung function. The hypoxic (Delta P(0.1)/Delta SaO(2), Delta V(E)/Delta SaO(2)) and the hypercapnic response (Delta P(0.1)/Delta PaCO(2), Delta V(E)/Delta PaCO(2)) were tested before and during continuous positive airway pressure (CPAP) treatment (at 2, 4, 6 weeks). RESULTS: Compared with the eucapnic patients, all the hypercapnic patients had lower Delta P(0.1)/Delta SaO(2) [(-0.04 +/- 0.02) cmH(2)O% vs (-0.14 +/- 0.03) cmH(2)O%], Delta V(E)/Delta SaO(2) [(-0.17 +/- 0.04) L x min(-1)% vs (-0.34 +/- 0.04) L x min(-1)%], Delta P(0.1)/Delta PaCO(2) [(0.23 +/- 0.1) cmH(2)O/mm Hg vs (0.49 +/- 0.1) cmH(2)O/mm Hg], Delta V(E)/Delta PaCO(2) [(1.32 +/- 0.7) L x min(-1) x mm Hg(-1) vs (2.18 +/- 0.81) L x min(-1) x mm Hg(-1)] and the Delta P(0.1)/Delta SaO(2), Delta V(E)/Delta SaO(2) were also lower than the normal value. After treatment with CPAP, the hypercapnic and the hypoxic response of the hypercapnic patients increased gradually, at about 4 approximately 6 week, both of them increased to the normal range, PaCO(2) showed a complete return to eucapnia, their weight were unchanged. CONCLUSION: The depressed breathing control play an important role in the development of CO(2) retention in OSAS patients, and the disorder in breathing control may be secondary to hypoxia, hypercapnia and sleep disorder related to the OSAS.

Adult↗