Inhibition of high affinity uptake of GABA by branched fatty acids

Several branched fatty acids including an antiepileptic agent nDPA were tested as potential inhibitors of high affinity uptake of GABA by brain slices and synaptosomes. Only three compounds (2-butyl-3-propylhexanoic acid, 5-propyloctanoic acid, 2-propylpenten-2-oic acid) were found to be relatively weak inhibitors of the uptake system. There was no correlation between anticonvulsant properties of the branched fatty acids and their potencies as inhibitors of high affinity uptake of GABA.     

HIV and other sexually transmitted diseases at a rural hospital in Zimbabwe

OBJECTIVE: To define the epidemiological characteristics of STD patients attending an outpatient clinic in rural Zimbabwe, to examine the aetiologic agents causing infection and to determine their relationship with HIV infection. SUBJECTS: 319 men and 146 women, making a sample of about 7% all patients attending an STD clinic during the 3 month study period. Microbiological data were collected from 104 men and 72 women selected randomly from these. Pregnant women were excluded and patients who had received antibiotics within the previous 14 days were excluded from the microbiology sub-sample. SETTING: An outpatient STD clinic at a District Hospital on a major truck route about 300 km north of the capital, Harare. METHODS: All new patients attending the clinic during a 3 month period were enrolled for clinical and epidemiological investigations using a standard procedure. Specimens for microbiological investigation were taken from every second patient seen on the first three days of each week. RESULTS: The typical patient was male (m:f ratio 2.2) aged 20-29 years (68% patients), not married (56% men) and in paid employment (66% men vs. 27% for the district). In men the most common presenting feature was genital ulceration, while in women, discharges were more common. Genital warts were noted frequently in both sexes. In the sub-sample examined microbiologically, H ducreyi was isolated from 46% ulcers clinically diagnosed as chancroid, and motile spirochaetes were detected in 25% painless ulcers. Neither of these were detected in ulcers in women, but HSV antigen was found as frequently in ulcers from men (19%) as from women (17%). In patients with genital discharges, gonococcal infection occurred in 64% men and 17% women, while T vaginalis was isolated from 39% women and only 8% men. Over 60% gonococcal isolates were PPNG, and 18% showed in vitro resistance to tetracycline. Yeasts, mainly C albicans were isolated from 42% women with a discharge and 25% women with ulcers. In men the presence of yeasts was associated with superficial ulceration and itchiness of the glans. Positive HIV-1 serology was found in 64% patients. There was no statistical association with current genital ulcers, though there was an association with previous STD episodes and particularly with serological evidence of syphilis. Apart from yeasts, there was no association between positive HIV-1 serology and the presence of pathogens in the genital tract. CONCLUSIONS: The high prevalence of HIV-1 antibodies in STD patients in Karoi suggests integration of STD and AIDS control programmes to be a necessity. Since paid employment was a common feature of both STD clinic attendance and HIV-1 seropositivity, these programmes may be effectively directed through the work place.     

Inhibition of tolbutamide 4-methylhydroxylation by a series of non-steroidal anti-inflammatory drugs in V79-NH cells expressing human cytochrome P4502C10

1. To study the role of cytochrome P4502C10 in the metabolism of the non-steroidal antiinflammatory drugs (NSAIDs) diclofenac, phenylbutazone, fenoprofen, ibuprofen, flurbiprofen, ketoprofen and naproxen, a cell line was developed stably expressing CYP2C10 cDNA. A retroviral vector construct, containing a human CYP2C10 cDNA, was transfected in V79-NH Chinese hamster lung cells by calcium phosphate co-precipitation. Sublines stably expressing human cytochrome P450 cDNA were established by selection with the neomycin analogue G418. 2. Enzymatic activity of CYP2C10 was detected by 4-methylhydroxylation of tolbutamide. This activity was inhibited to background levels by preincubation with the CYP2C9/10 inhibitor sulphaphenazole. 3. Preincubations with the NSAIDs ketoprofen, phenylbutazone, flurbiprofen and diclofenac (all 250 microM) caused a decrease in 4-methylhydroxylation of tolbutamide (500 microM), significantly different from control values (p < 0.05). Inhibition of this activity was not seen in preincubations with the NSAIDs fenoprofen, ibuprofen and naproxen (250 microM). 4. The V79-NH CYP2C10 cell line we have developed has been shown to be a useful tool to predict drug-drug interactions.     

The growth of Malawian preschool children from different socioeconomic groups

Productive infection with HIV-1, the virus responsible for AIDS, requires the involvement of host cell factors for completion of the replicative cycle, but the identification of these factors and elucidation of their specific functions has been difficult. A human cDNA, TRBP, was recently cloned and characterized as a positive regulator of gene expression that binds to the TAR region of the HIV-1 genome. Here we demonstrate that this factor is encoded by a gene, TARBP2, that maps to human chromosome 12 and mouse chromosome 15, and we also identify and map one human pseudogene (TARBP2P) and two mouse TRBP-related sequences (Tarbp2-rs1, Tarbp2-rs2). The map location of the expressed gene identifies it as a candidate for the previously identified factor encoded on human chromosome 12 that has been shown to be important for expression of HIV-1 genes. Western blotting indicates that despite high sequence conservation in human and mouse, the TARBP2 protein differs in apparent size in primate and rodent cells.     

Gynecologic effects of tamoxifen and the association with endometrial carcinoma

Tamoxifen has been used as an adjuvant therapy for breast cancer for nearly two decades. The benefits of adjuvant tamoxifen therapy in prolonging disease-free and overall survival have been shown in randomized clinical trials. Despite this, some developing evidence suggests that tamoxifen causes a 2- to 3-fold increase in endometrial cancer. This paper reviews the reports of endometrial carcinoma in tamoxifen-treated patients. Two hundred fifty cases of endometrial carcinoma are reported, but only one case is identified in a premenopausal woman. When documented, 77% (n=127) of the cases are good-grade (grade 1 or 2) and 80% (n=125) are stage-I disease. Since the distribution of good grade (79%) and stage I (74%) from the Surveillance, Epidemiology and End Results (SEER) data are comparable, concerns about more aggressive or late-stage disease appear to be unwarranted. The modest increase in the incidence of early-stage, good-grade endometrial carcinoma described during tamoxifen therapy suggests that it would be unreasonable to institute an aggressive detection strategy of endometrial biopsies. This approach would only lead to further detection bias and would not be cost-effective. Physicians should ensure that patients do not have pre-existing endometrial cancer prior to adjuvant tamoxifen therapy for breast cancer and, furthermore, they should educate patients about signs and symptoms of early endometrial carcinoma and when reported these should be followed up with a gynecologic examination.     

Assessment of sensorimotor neglect after occlusion of the middle cerebral artery in the rat

Evaluating the efficacy of neuroprotective drugs in rat models of focal cerebral ischemia has involved histological and behavioral batteries to examine treatment outcome. However, the behavioral tests used to date provide little insight into the nature of the neurological impairments. To provide an analysis of a possible "neglect" syndrome after occlusion of the middle cerebral artery, M. I. Posner's (1980) visual attentional paradigm was adapted for use in the rat. A paw-reaching task and a test of somatosensory "neglect" also were used to assess forelimb sensorimotor function. The lesion group displayed unilateral deficits; however, there was no evidence of attentional dysfunction. Results are consistent with the conclusion that the behavioral deficits identified arise from a somatosensory deficit rather than hemineglect due to dysfunctional spatial attention.     

Focal adhesion kinase-dependent apoptosis of melanoma induced by tyrosine and phenylalanine deficiency

We found previously that restriction of tyrosine (Tyr) and phenylalanine (Phe) inhibited growth and metastasis of B16BL6 murine melanoma and arrested these cells in the G0-G1 phase of the cell cycle. Here, we report that deprivation of these two amino acids in vitro induces apoptosis in B16BL6 and in human A375 melanoma cells but not in nontransformed, neonatal murine epidermal cells or human infant foreskin fibroblasts. Four days after deprivation of Tyr and Phe in vitro, 37% of B16BL6 and 51% of A375 melanoma cells were undergoing apoptosis. Apoptosis was not associated with elevation in intracellular calcium or alteration in p53 or c-myc protein expression. Expression and Tyr phosphorylation of focal adhesion kinase (FAK) were inhibited in both melanoma cell lines by deprivation of Tyr and Phe but not by deprivation of glutamine or serum. Tyr phosphorylation of FAK in Tyr- and Phe-deprived melanoma cells was enhanced within 30 min of refeeding with complete DMEM. FAK protein expression recovered within 60 min, and cell viability recovered within 24 h. Genistein, a tyrosine kinase inhibitor that specifically inhibits Tyr phosphorylation of FAK, did not induce apoptosis in A375 melanoma cells at a concentration of 50 microM. Genistein prevented the recovery of cell viability upon refeeding with Tyr and Phe to previously deprived A375 melanoma cells. These data collectively indicate that apoptosis induced by Tyr and Phe deprivation is FAK-dependent.     

Effect of dietary patterns on the blood/urine concentration of the selected toxic metals (Cd,Hg, Pb) in Korean children

Food Science and Biotechnology - This study was aimed to examine the association the blood/urinary concentration of toxic metal (Hg, Pb, and Cd) with children’s dietary patterns. This...     

Isolation of lactic acid bacteria starters from <Emphasis Type="Italic">Jeung</Emphasis>-<Emphasis Type="Italic">pyun</Emphasis> for sourdough fermentation

Lactic acid bacteria (LAB) are key for the fermentation of sourdoughs to improve the quality and nutritive value of bread. The aim of this study was to isolate the LAB starter for sourdough fermentation from Jeung-pyun, a Korean traditional rice cake. Among the twenty two LAB screened, five isolates were selected based on exo-polysaccharide production. Among them, three isolates showed cell growth greater than 8.5 Log CFU/g, maximum increase in the volume of dough, and dextran concentration up to 0.16%. During the sourdough fermentation, pH and total titratable acidity (TTA) were changed, as the three isolates synthesized lactic acid and acetic acid with fermentation quotients less than 2.0. They were identified as Leuconostoc lactis EFEL005, Lactobacillus brevis EFEL004, and Le. citreum EFEL006. They displayed good fermentation properties (growth, dextran production, pH, and TTA) in dough and they are regarded as potential starters to be used in sourdough fermentation.