In vitro drug interaction between diflunisal and indomethacin via glucuronidation in humans

It was reported that the plasma concentration of indomethacin was increased with concomitant oral dosages of diflunisal in humans. Both indomethacin and diflunisal are glucuronidated in humans. The effects of diflunisal on the indomethacin glucuronidation were thus investigated in vitro using human liver microsomes (HLM) and human intestine microsomes (HIM) in order to assess the drug-drug interaction. The glucuronidation of indomethacin in HLM showed atypical kinetics with Km and Ksi values of 210 and 89.5 microM, respectively, while HIM exhibited Michaelis-Menten kinetics with a Km value of 17.4 microM. Diflunisal inhibited the indomethacin glucuronidation in HLM with IC50 values ranging from 100 to 231 microM. In HIM, inhibition of the indomethacin glucuronidation by diflunisal was more potent with IC50 values of 15.2-48.7 microM. When the clinical dose of diflunisal (250 mg b.i.d.) is taken into consideration, it is expected that the diflunisal concentration in the intestine would be higher than the IC50 values for indomethacin glucuronidation in the intestine. These findings suggest that the clinical drug-drug interaction between diflunisal and indomethacin may be at least partly attributable to the inhibition of indomethacin glucuronidation by diflunisal in the intestine.     

Humanized attention to parturition of adolescents: analysis of practices developed in an obstetric center

Quantitative study that aimed to analyze the practices developed in assisting the adolescent, from the account of health workers, in an Obstetric Center in a teaching hospital, based on the proposal of humanization of parturition of the Health Ministry. According to the workers, useful practices in assisting parturition, among them, orientations about relaxation techniques at parturition, improving the attachment between mother and child, are being carried out. However, the right to a companion has not been taken into account. The lithotomy position and standardization of trichotomy, episiotomy e amniotomy were registered. Medical records, among them partogram, anamnesis and physical and obstetric exam of the parturient, proved to the unsatisfactory. We conclude that, in the scenario investigated, are developed practices considered appropriate and inappropriate, showing the need to further encourage the use of procedures grounded in scientific evidence and inserted into the proposal to the humanization of birth.     

Subconjunctival administration of bucillamine suppresses choroidal neovascularization in rat

PURPOSE: Bucillamine is an antirheumatic drug with antiangiogenic properties that is currently used in clinical practice. Because bucillamine inhibits the production of VEGF, it is possible that this drug may inhibit choroidal neovascularization (CNV). Thus, the effect of bucillamine on the eyes of rats with experimental CNV was investigated in vivo by subconjunctival injection or oral intake. METHODS: CNV was induced in rat eyes by diode laser photocoagulation. The intensity of fluorescein leakage from the photocoagulated lesions was studied 7 and 14 days after photocoagulation. The areas of CNV lesions were measured histologically and studied immunohistochemically at days 4, 7, and 14. In addition, the concentration of the drug in ocular tissue and blood was measured by high-performance liquid chromatography-tandem mass spectrometry after the drug was delivered orally or subconjunctivally. RESULTS: After subconjunctival injection, fluorescein leakage from the CNV lesions decreased significantly compared with the control eyes throughout the study period. Histologic and immunohistochemical analyses 4, 7, and 14 days after photocoagulation demonstrated that the average size of the CNV lesions was reduced in the bucillamine-treated eyes compared with the control eyes. Subconjunctival injection maximized the ocular drug concentration while minimizing the blood concentration of the drug compared with oral intake. CONCLUSIONS: Subconjunctival injection of bucillamine significantly reduced the leakage and size of experimental CNV. These results suggest that bucillamine may be beneficial in treating CNV and that further studies can be considered to evaluate this possibility.     

p53 mutations in human aggressive and nonaggressive basal and squamous cell carcinomas.

PURPOSE: The purpose is to investigate whether aggressive basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) differ from nonaggressive BCC and SCC with respect to the p53 mutation spectrum and whether specific mutations can serve as prognostic indicators of tumor aggressiveness. EXPERIMENTAL DESIGN: We analyzed 342 tissues from patients with aggressive and nonaggressive BCCs and SCCs for p53 mutations by single-strand conformation polymorphism and nucleotide sequencing. RESULTS: p53 mutations were detected in 33 of 50 aggressive BCCs (66%), 37 of 98 nonaggressive BCCs (38%), 28 of 80 aggressive SCCs (35%), 28 of 56 nonaggressive SCCs (50%), and 3 of 29 samples of sun-exposed skin (10%). About 71% of the p53 mutations detected in aggressive and nonaggressive BCCs and SCCs were UV signature mutations. The frequency of CC to TT mutations in aggressive (36%) and nonaggressive SCCs (39%) was 2-fold higher than in aggressive (18%) and nonaggressive (14%) BCCs. In contrast, aggressive BCCs had a higher frequency (24%) of transversions than nonaggressive BCCs (8%) and aggressive (14%) and nonaggressive (11%) SCCs did. CONCLUSIONS: Our results indicate that UV radiation is responsible for the induction of p53 mutations and perhaps for the initiation of both aggressive and nonaggressive BCCs and SCCs. Although some differences in p53 mutation frequency, types of mutation, and hot spots were seen between aggressive and nonaggressive BCCs and SCCs, these factors do not constitute as clear-cut diagnostic or prognostic indicators of tumor aggressiveness. Tumor aggressiveness may be attributable to other genetic changes or events that occur during tumor progression.     

Incidence rate of satellite tumors in renal cell carcinoma

BACKGROUND: Nephron-sparing surgery for incidentally detected small renal tumors has been performed. The main objection to such surgery concerns the incidence rate of satellite renal tumors. In this study, the authors analyzed the rate of incidence and proliferative potential of satellite renal tumors. METHODS: The tumors of 124 renal cell carcinoma patients with a clinically identified unilateral and single tumor measuring 相似文献   

Chromosome rearrangement at 17q25 and xp11.2 in alveolar soft-part sarcoma: A case report and review of the literature.

BACKGROUND: Despite the characteristic histopathologic appearance of alveolar soft-part sarcoma (ASPS), its histogenesis remains unclear, and cytogenetic analysis of ASPS is limited to eight cases so far because of the extreme rarity of this disease. METHODS: The authors document a cytogenetic study of a primary case of ASPS in which a modern spectral karyotyping technique was used. RESULTS: A standard cytogenetic analysis of the primary tumor cells with G-banding revealed 46,XY, add(17)(q25) in 23 of 25 metaphases analyzed. This structural rearrangement of chromosome 17, involving band q25, was also present in 5 of 8 ASPS cases in the literature. Moreover, with the spectral karyotyping technique, the additional part of the long arm of chromosome 17 in the current case was found to originate from chromosome X, resulting in a final tumor karyotype of 46, XY, add(17)(q25).ish der(17)t(X;17) (p11.2;q25)(wcpX+). CONCLUSIONS: This case report documents a clonal chromosome abnormality of der(17)t(X;17)(p11.2;q25) in ASPS. The results of the current study indicate that further molecular analyses focused on 17q25 and Xp11.2 are of interest and could help to elucidate the pathogenesis of ASPS.     

Expression of human placenta alkaline phosphatase in placenta during pregnancy

To clarify the expression of PLAP during the course of pregnancy, the amount of PLAP mRNA and its activity in normal placental villi were measured. Both PLAP and its mRNA were found in placentae of as early as 7 weeks of gestation, and they continued to increase throughout pregnancy. But they showed different patterns of increase. The amount of PLAP mRNA began to increase dramatically around 13th week and probably continued to increase gradually until term. PLAP activity per gram of villi showed a gradual increase from around 13th week and a marked increase was observed after about 20th week. PLAP levels in sera from pregnant women were also measured, and they showed a pattern of increase imilar to that of PLAP activity per gram of villi. The continuous increase in the expression of PLAP throughout pregnancy suggests that PLAP may play a role in feto-maternal metabolism and placental differentiation.     

Amyotrophic lateral sclerosis and mercury--preliminary report

The mercury and selenium content in the hair of 13 ALS cases was studied by neutron activation analysis. The total mercury content of the hair was 3.70 +/- 2.73 ppm (mean +/- standard deviation) in the ALS patients as a whole, 4.46 +/- 3.16 ppm in the ALS patients from the middle of Kii Peninsula, and 2.49 +/- 1.38 ppm in the ALS patients from other region. As the comparison, mercury content was 2.43 +/- 0.79 ppm in the patients with Parkinsonism, and 2.10 +/- 1.13 ppm in the patients with multiple sclerosis (MS). The selenium content of the hair was 0.36 +/- 0.35 ppm for all ALS patients as a whole, 0.45 +/- 0.25 ppm in the ALS patients from the middle of the Kii Peninsula, and 0.21 +/- 0.47 ppm in the ALS from other region. There were no cases with higher values than mean values of control group, except one case from other regions. It is well known that the selenium decreases the toxicity of mercury in the human body. From these data mercury with low content of selenium might be one of the environmental factors which are thought to be involved in producing of ALS.     

Demyelinating changes in sural nerve biopsy of patients with HTLV-I-associated myelopathy

We describe the sural nerve pathology in 3 patients with HTLV-I-associated myelopathy (HAM). These patients showed remarkable symptoms of myelopathy and had high HTLV-I titers in the serum and CSF. The common pathologic findings in the sural nerves were as follows: slightly decreased density in myelinated fibers (6,567/mm2, 6,488/mm2, and 7,159/mm2; control 9,999 +/- 3,446/mm2), frequent occurrence of demyelinated and remyelinated fibers, and many degenerating fibers with globule-like myelin changes. Teased-fiber analysis indicated the globule-like changes (Dyck's G change) to be accompanied by the formation of adjacent demyelinated segments. The globules result from slowly repetitive degenerative changes of myelin and are considered to be a form of demyelination. However, they have seldom been found in other demyelinating neuropathies, indicating the demyelination process with globule formation in HAM to be rather specific for this disease.     

Complications of cervicofacial radiotherapy. Prevention, diagnosis and multidisciplinary treatment

This paper presents a review on the state of art about scientific knowledge on oral complications of head and neck radiotherapy, in an attempt to contribute for a better prevention, diagnosis and treatment. The authors also describe the protocols used on Instituto Português de Oncologia of Lisboa.