Investigation of the effects of concomitant caffeine administration on the metabolic disposition of pyrazinamide in rats

The utility of pyrazinamide (PZA) in the short-course antituberculous treatment is well established. All available data support the idea that the PZA metabolite pyrazinoic acid (PA) is the active compound against M. tuberculosis. This situation warranted a deeper investigation of possible interactions with respect to its metabolic disposition. Caffeine, which is widely used as a drug and is a common constituent of most diets, shares with PZA the same metabolic enzyme, xanthine oxidase (XO). This study investigated if, and in what manner, concomitant administration of caffeine affects PZA metabolism. PZA and caffeine, in various doses (PZA=50 or 100 mg kg(-1) and caffeine= 0, 50, 100, and 150 mg kg(-1)), were administered to female Sprague-Dawley rats. PZA and its three main metabolites were quantified in 24 h urine samples by reversed phase-HPLC Concomitant administration of 100 mg kg(-1) caffeine and 50 mg kg(-1) PZA increased from the excretion (p<0.05) of the most water-soluble and the least toxic PZA metabolite 5-hydroxypyrazinoic acid (5-OH-PA) from 66.18+/-10.87 to 94.56+/-8.65 micromol/24 h. This effect was more pronounced when 100 mg kg(-1) of PZA was administered increasing excretion of 5-OH-PA from 113.28+/-70 to 173.23+/-17.82 micromol/24 h. These results show that the metabolic disposition of PZA is affected by concomitant caffeine intake.     

Social cohesion,cultural identity,and drug use in Mexican rural communities

The objective of this study was to explore drug use in Mexican rural communities and its relationship to social cohesion, cultural identity, migration, and transculturation. Community models typification was used, considering cohesion as the central point of analysis. The research was conducted during 15-day periods in each of nine communities during 1991. Both documentary and ethnographic techniques were used to gather information. Results indicated that rural communities where there was little or no drug use among its members show more social cohesion, cultural identity, and community links consolidation, and more capacity for integrating change. This pattern is most apparent among young community members who have had more contact with the outer world (drug trafficking, North American culture, and Mexican urban culture).     

Neoclerodane and labdane diterpenoids from Plectranthus ornatus

Three new diterpenoids, a neoclerodane and two labdane derivatives, have been isolated from an acetone extract of Plectranthus ornatus. The structures of these compounds (plectrornatins A-C, 1-3, respectively) were established mainly by spectroscopic means, particularly by 1D and 2D NMR studies and, in the case of the neoclerodane 1, by an X-ray diffraction analysis. Compounds 1 and 3 showed moderate antimicrobial activity against five Candida species and selected Gram negative and Gram positive bacteria strains.     

Characterization of an O-glycosylated plaque-associated protein from Alzheimer disease brain

In this work we characterized a 90-kDa glycoprotein from Alzheimer disease (9OAzgp) brain extracts that is recognized by the GalNAc-specific lectin from Amaranthus leucocarpus (ALL), as determined through Western blot. The 90Azgp was purified by electro-elution, and its amino acid sequence determined from peptides obtained after trypsin digestion through MALDI-TOF (Matrix-assisted laser desorption ionization-time of flight), and compared with the relative values obtained from the NCBInr (Swiss-Prot 10/01/2001) database. The 90Azgp showed 32% and 42% homology with the KIAA0310 protein from human brain and the human gastric mucin, respectively. Presence of O-glycosidically linked glycans in the proteins recognized by ALL was confirmed by inhibition of the lectin-glycoprotein interaction through hapten-inhibition assays and also by elimination of the O-glycosidically linked glycans after treatment with O-glycanase from Diplococcus pneumoniae. Electron transmission microscopy confirmed that the receptor recognized by the lectin is processed in the Golgi apparatus of AD neurons. Although the specific role of this glycoprotein has not been identified, considering that the presence of this lectin receptor co-localized with neuritic plaques and in AD sprouting neurons, it could suggest that the O-glycosyl-protein identified by the A. leucocarpus lectin participates in the pathogenesis of neurodegenerative diseases.     

PDGF(BB) increases myocardial production of VEGF: shift in VEGF mRNA splice variants after direct injection of bFGF, PDGF(BB), and PDGF(AB)

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis. We hypothesized that a combination of recombinant angiogenic proteins might induce myocardial VEGF production and cause a shift in the mRNA signal produced. MATERIALS AND METHODS: The left ventricles of New Zealand white rabbits were injected with 500 microL of saline, basic fibroblast growth factor (bFGF), platelet-derived growth factor-AB (PDGF(AB)), platelet-derived growth factor-BB (PDGF(BB)), bFGF + PDGF(AB), or bFGF + PDGF(BB). Myocardial VEGF production was analyzed by ELISA while mRNA splice variants were analyzed by RT-PCR 3 and 7 days after injection. RESULTS: PDGF(BB) alone caused the most pronounced induction of VEGF. Three days after injection the induction of VEGF by PDGF(BB) was significant compared to all treatment groups, except the bFGF + PDGF(BB) group. Induction of VEGF by PDGF(BB) was associated with a decrease in mRNA production of VEGF(121) within the myocardium. CONCLUSIONS: Injection of PDGF(BB) induces significant production of VEGF within the myocardium. This induction of VEGF production is associated with a shift toward other, less soluble forms of VEGF. These findings may allow more precise regulation of the myocardial response to therapeutic angiogenesis.     

Pacemaker infections

Infectious complications following pacemaker implantation are not common but can be particularly severe. The reported incidence varies from 0.5 to 5% in the literature. The duration of the procedure and repeat procedures are considered to be predisposing factors. The main cause of these infections is thought to be local contamination during the implantation. The commonest causal organism is staphylococcus. Because the presentation may be atypical, the diagnosis is often confirmed by transesophageal echocardiography which is the investigation of choice for imaging a vegetation on an endocavitary pacing lead in cases of infectious endocarditis. The seriousness of this infection requires early diagnosis and adapted treatment including double bactericidal antibiotherapy and complete ablation of the material. Systematic preoperative prophylactic antibiotic therapy is recommended.     

An extremely rare case of adenoma malignum with large cystic tumor which resulted in urinary obstruction.

BACKGROUND: Adenoma malignum is a rare variant of uterine cervical adenocarcinoma. In this report, we present an extremely rare case of adenoma malignum with large cystic lesions (diameter of more than 10 cm) which elicited urinary obstruction. CASE: A 46-year-old Japanese woman, gravida 2, para 2, visited her local doctor for urinary obstruction, and 950 ml of urine was catheterized. Since abdominal ultrasonography suggested ovarian cystic tumor, she was referred to our hospital. Vaginal examination and ultrasonography revealed a child-head-sized multilocular cystic tumor in the Douglas pouch. Abnormal massive discharge was not observed at the time of admission. During preoperative examination, massive mucinous discharge suddenly occurred without pain. The cystic tumor size shrank from x10 cm to x4.0 cm in maximum diameter. Emergent abdominal hysterectomy was performed. The operative findings revealed collapsed cystic lesions in the posterior wall of the uterine cervix. Microscopically, the multiple cysts in the cervix were composed of high columnar and slightly atypical monolayer cells similar to endocervical mucinous cells. Vaginal invasion was also partly observed. Most of the tumor cells were positive for carcinoembryonic antigen and HIK1083 in their cytoplasm, and scattered chromogranin A-positive endocrine cells were also found in tumor glands, corresponding to minimal deviation adenocarcinoma (adenoma malignum). These lesions were diagnosed as FIGO stage IIa. The patient is disease-free 2 years after primary surgery. CONCLUSION: In the present report, we describe an extremely rare case of adenoma malignum with large cystic lesions reaching a diameter of 12 cm which resulted in urinary obstruction.     

PRLTS Gene Alterations in Human Prostate Cancer

Since loss of heterozygosity on 8p22-p21,3 has been found frequently in prostate cancer, the status of a candidate tumor suppressor gene named PRLTS gene, recently cloned from the same region in some human malignancies, was examined in the present study. DNAs were isolated from 69 Japanese prostate cancer patients (37 localized and 32 cancer-death cases). Loss of heterozygosity at this gene locus was observed in 15 of 36 (42%) localized prostate cancer patients and 22 of 32 (69%) cancer-death patients. One cancer-death patient had a missense mutation, ACG→ATG (Thr→Met) at codon 64 in metastatic tumor tissues of pelvic lymph node and liver, and these tissues showed loss of the homologous allele, indicating that "two-hit" mutation of the PRLTS gene had occurred in this case. The others did not show any mutation, regardless of the presence or absence of loss of heterozygosity. Although loss of heterozygosity at the PRLTS gene locus is a relatively common abnormality, mutation of this gene is rare in prostate cancer.     

MRI findings of dysplasia epiphysealis hemimelica

We report a boy with dysplasia epiphysealis hemimelica of the knee, particularly emphasizing MRI findings. When he was 14 months of age, plain radiography exhibiting juxta-articular soft tissue mass with small, punctate, calcified foci did not warrant the definitive diagnosis, while MRI clearly demonstrated osteocartilaginous overgrowth of the femoral epiphysis. The epiphyseal mass mostly showed the same signal intensity as normal cartilage but contained low signal spots corresponding to calcified foci. The cartilaginous cap was depicted as a mottled area of high intensity on a T2-weighted image. When the patient was 4 years of age, this ossified mass was resected surgically and pathologically identified as osteochondroma incorporated into the epiphysis.     

Embryonal rhabdomyosarcoma of the uterine corpus in a 76-year-old patient

BACKGROUND: Primary embryonal rhabdomyosarcoma of the uterine corpus is an extremely rare tumor. A case of rhabdomyosarcoma originating in the uterine myoma is presented with a review of the literature. CASE: A 76-year-old female presented with a half-year history of abdominal swelling and fever of unknown origin. A 15 x 15 x 17 cm myoma-like tumor was noted on the anterior wall of the uterine myometrium. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. The histology and immunohistochemistry aided in the final diagnosis of a pure embryonal rhabdomyosarcoma of the uterine corpus. This patient received three courses of CYVADIC chemotherapy consisting of cyclophosphamide, vincristine, doxorubicin, and dacarbazine after the surgery and is now alive with no evidence of disease 10 months from her surgery. CONCLUSION: This case is extremely rare with respect to the uterine corpus origin, especially the myoma nodule and the age of the patient.