ABSTRACT
This study aimed to investigate the absorption mechanism of three curcumin constituents in rat small intestines. Self-emulsification was used to solubilize the three curcumin constituents, and the rat in situ intestinal perfusion method was used to study factors on drug absorption, including drug mass concentration, absorption site, and the different types and concentrations of absorption inhibitors. Within the scope of experimental concentrations, three curcumin constituents were absorbed in rat small intestines through the active transport mechanism.
Subject(s)
Adjuvants, Pharmaceutic/pharmacology , Curcumin/analogs & derivatives , Curcumin/pharmacokinetics , Enzyme Inhibitors/pharmacokinetics , Intestinal Absorption , Intestine, Small/metabolism , 2,4-Dinitrophenol/pharmacokinetics , ATP-Binding Cassette Transporters/antagonists & inhibitors , Animals , Chromatography, High Pressure Liquid/methods , Curcumin/chemistry , Diarylheptanoids , Emulsions , Female , Intestinal Absorption/drug effects , Intestine, Small/drug effects , Male , Multidrug Resistance-Associated Protein 2 , Multidrug Resistance-Associated Proteins/analysis , Multidrug Resistance-Associated Proteins/antagonists & inhibitors , Perfusion Imaging/methods , Probenecid/pharmacology , Rats, Sprague-Dawley , Reference Values , Reproducibility of Results , Time Factors , Uncoupling Agents/pharmacology , Verapamil/pharmacologyABSTRACT
CONCLUSIONS: Significant difference in the incidence of mitochondrial DNA (mtDNA) mutations was found between the Chinese and USA populations. The identification of the mtDNA A1555G mutation in a large proportion of Chinese probands with nonsyndromic sensorineural hearing loss (NSHL) provides a molecular explanation for the high prevalence of aminoglycoside-induced deafness in China. OBJECTIVE: The aim was to characterize the audiological and genetic features of NSHL due to mutations in mtDNA. SUBJECTS AND METHODS: The mtDNA and audiogram analyses were performed in 498 NSHL patients (290 from China and 208 from the USA) with and without history of aminoglycoside exposure. A PCR and restriction enzyme digestion protocol was used for mutational screening and the European Workshop on Genetic Hearing Loss criteria were applied for audiological classification. RESULTS: All Chinese probands (15.5%) with mtDNA mutation were found to carry the homoplasmic mtDNA A1555G mutation, whereas four probands (1.9%) from the USA were found to carry the mtDNA A1555G and two (1%) had mtDNA G7444A. Approximately 63% of the probands with mtDNA mutations had post-lingual hearing loss and 56.8% of them had a medical history of exposure to aminoglycosides. Hearing losses are bilateral, sensorineural, and symmetric. The main audiogram shapes found were sloping.
Subject(s)
DNA, Mitochondrial/genetics , Hearing Loss, Sensorineural/physiopathology , Hearing/physiology , Mutation , Adolescent , Adult , Aged , Aged, 80 and over , Aminoglycosides/adverse effects , Asian People , Audiometry, Pure-Tone , Child , China/epidemiology , Deafness/chemically induced , Deafness/genetics , Deafness/physiopathology , Gene Frequency , Hearing Loss, Sensorineural/epidemiology , Hearing Loss, Sensorineural/genetics , Humans , Middle Aged , Polymerase Chain Reaction , United States/epidemiology , White PeopleABSTRACT
OBJECTIVE: To analysis whether there is any mtDNA 1555A-->G homoplasmic point mutation among familial nonsyndromic deafness. METHOD: Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to screen the mutation 1555A-->G among four nonsyndromic deafness families. RESULT: The same mutations were checked out in 4 of 5 individuals in 1 of 4 families. CONCLUSION: The 1555A-->G change on mtDNA might be one of the multiple genetic defects and pathogenetic of familial nonsyndromic deafness.
Subject(s)
DNA, Mitochondrial/genetics , Deafness/genetics , Point Mutation , Adolescent , Adult , DNA Mutational Analysis , Female , Humans , Male , PedigreeABSTRACT
OBJECTIVE: To study the diagnostic significance of otoacoustic emission in patients with genetic progressive sensorineural hearing loss. METHOD: To analyse the cochlear function pure tone audiometry Transient Evoked Otoacoustic Emission (TEOAE) and distortion Products Otoacoustic Emission (DPOAE) were measured in 54 members of a six-generation family with genetic progressive sensorineural hearing loss (108 cases) and 50 normal people. RESULT: The family was autosomal dominant heritage. In the group with pure tone thresholds more than 20 dB HL, the amplitudes of TEOAE descended or disappeared in 84% cases and the amplitudes of DPOAE declined or vanished in 82% cases. In the group with normal pure tone thresholds, the amplitudes of TEOAE descended in 75% cases and the amplitudes at one of the frequencies of DPOAE dropped or disappeared in 64% cases. But the incidence of TEOAE and DPOAE in normal people was 100%. CONCLUSION: OAE had important significance in the diagnosis of genetic hearing loss at early stage.
Subject(s)
Cochlea/physiopathology , Hearing Loss, Sensorineural/genetics , Otoacoustic Emissions, Spontaneous , Adolescent , Adult , Audiometry, Pure-Tone , Child , Female , Hearing Loss, Sensorineural/diagnosis , Humans , Male , Middle Aged , PedigreeABSTRACT
OBJECTIVE: To study the Mitochondrial DNA 7445A-->G mutation in nonsyndromic deafness patients in Chinese population. METHOD: Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to screen the mitochondrial DNA 7445A-->G mutation among 128 nonsyndromic deafness individuals from 32 pedigrees, 135 sporadic nonsyndromic deafness patients and 100 normal subjects. RESULT: The 7445A-->G mutation did not appear in the experiment. CONCLUSION: Incidence of the mitochondrial 7445A-->G mutation was lower than that of mtDNA 1555A-->G mutation in nonsyndromic deafness patients in China.
Subject(s)
DNA, Mitochondrial/genetics , Deafness/epidemiology , Deafness/genetics , China/epidemiology , DNA Mutational Analysis , Female , Humans , MaleSubject(s)
Deafness/genetics , Mutation , Myosins/genetics , Retinitis Pigmentosa/genetics , Adolescent , Adult , Child , Female , Humans , Male , Pedigree , Phenotype , SyndromeABSTRACT
Evoked otoacoustic emissions (EOAE) and auditory brainstem evoked response (ABR) were tested in patients with high frequency cochlear hearing loss and subjects with normal hearing. Results showed that: 1. In the normal group, the main component of EOAE varied between 0.5-5kHz. 2. There was a close correlation between the pure-tone audiogram figure and EOAE spectrum. 3. The I/O function curves of EOAE displayed non-linear characteristics and a trend of saturation with higher stimulus levels in the normal group. In the patient group the growth rates of EOAE and ABR were remarkably higher than those in the normal group with high stimulus levels. It suggests that the abnormal EOAE are probably relevant to the recruitment phenomenon in cochlear hearing loss.