Porphyrin-based molecular clefts equipped with a strategically positioned carboxylic group have been synthesized. These ditopic porphyrins exhibit excellent binding affinity for many neutral substrates. X-ray structures of a porphyrin-water inclusion complex and a Zn(porphyrin)-methanol complex reveal how the carboxylic group interacts with substrates via H-bonding. Multipoint recognition is demonstrated in the differential binding of 1,2,3- versus 1,2,4-triazole, suggesting the possible use of such receptors to separate heterocyclic bases.

Crystallography, X-Ray↗

PubMedDate not supplied

Gender difference in ranolazine pharmacokinetics in rats.

Pharmacokinetics of ranolazine (RAN) in both female and male rats was studied. RAN concentrations in plasma were determined after oral administration of 12.5, 25 and 50 mg/kg RAN. Concentrations in tissues, recoveries of RAN in urine and bile were also analyzed following oral dose of 25 mg/kg. It was found that plasma concentrations of RAN in female rats were significantly higher than those in male rats. Drug exposures based on Cmax and AUC in female rats were roughly 2-to 3-fold of those in male rats. Terminate half-life T1/2 and MRT in male rats were shorter than those in female rats. The recoveries in urine and bile of female rats were also markedly higher than those in male rats'. Tissue concentrations of RAN in female rats were also markedly higher than those in male rats. These results demonstrated existence of marked gender difference in RAN pharmacokinetics in rats.

Acetanilides↗

PubMedDate not supplied

Gender differences in limonin pharmacokinetics in rats.

In the present study, the pharmacokinetics of limonin (LM) were investigated in male and female rats. LM concentrations in the plasma were determined after the oral administration of 36 mg/kg LM or after intravenous (i.v.) injection of LM 3.6 mg/kg respectively. Concentrations in the tissues, urine, feces and bile were also analyzed following the oral administration of 36 mg/kg of the test product. It was found that the plasma concentrations of LM in female rats were significantly higher (P < 0.01) than those in male rats. Assessment of the effects of limonin based on the C(max) and AUC in female rats showed that levels were about 50-fold higher than those in male rats after oral administration of 36 mg/kg LM. Furthermore, after i.v. administration of 3.6 mg/kg LM, the C(max) and AUC in female rats was found to be about 3-fold higher than those in male rats. The total excretion of LM in the urine and bile of female rats was also found to be significantly higher than in male rats, which displayed lower concentrations of LM in the tissues, amounting to around one-half to one-tenth of those in female rats, apart from levels in the rectum and duodenum. In conclusion, the present results demonstrate the existence of marked gender difference in LM pharmacokinetics in rats.

Administration, Oral↗

PubMedDate not supplied

Normal brain development in PS1 hypomorphic mice with markedly reduced gamma-secretase cleavage of betaAPP.

Presenilin 1-null mice die at birth from brain and skeletal developmental deformities due to disrupted Notch signaling. Presenilin 1-null mice also have severely reduced gamma-secretase cleavage of betaAPP. The assumption has been that facilitation of Notch signaling and betaAPP processing by presenilin 1 are analogous functions. Here we describe a presenilin 1-targetted mouse model that expresses extremely low levels ( approximately 1% of normal) of mutant PS1-M146L. Homozygous mice have significantly reduced viability due to a Notch-like phenotype. The animals that survive have severe axial skeletal deformities and markedly diminished gamma-secretase activity and accumulation of betaAPP-C100, but no obvious abnormalities in brain development. These results suggest that, in mice, a marked reduction of PS1-facilitated gamma-secretase activity is not detrimental to normal brain development.

Amyloid Precursor Protein Secretases↗

PubMedDate not supplied

Fatal occupational injuries in the construction industry of a new development area in east China, 1991 to 1997.

Two hundred thirty-five work-related deaths occurred in the construction industry in a new economic development area in eastern China between 1991 and 1997. These fatalities represented 55% of all occupational deaths. The average annual mortality rate was 51.5 per 100,000 construction workers. Falls were the leading cause of death (46.4%). Falls, collisions, struck by/against something, electrocutions, and excavation cave-ins were the main fatality antecedents, accounting for nearly 93.6% of all fatalities. The most common antecedents for incidents with multiple fatalities were falls, crane-related events, poisoning, and fire. These categories of antecedents were similar to those encountered in the construction industry in the United States. These data suggest that organizations need to focus on these event types when planning their prevention activities. Moreover, improved surveillance systems including computerized databases with narrative descriptions of injury events, antecedent factors, and person-time at-risk data are needed to target interventions more precisely.

Accidents, Occupational↗

PubMedDate not supplied

Femoral version and neck shaft angle.

We measured femoral anteversion by the Kingsley-Olmsted method in 24 unpaired, dry femurs. When the head and neck of the same femurs were measured by computed tomography (CT) scan, measurement was 5 degrees less than the Kingsley-Olmsted method, whereas ultrasound of the head and neck was 5 degrees higher. An anterior flat plane was also defined to help measure anteversion in patients with a high neck shaft angle. Physical and ultrasound measurement correlated well with the previous measurement by the Kingsley-Olmsted method and CT scan of anteversion. Although measurement by CT scan and ultrasound are different their results are both reproducible and measure the same parameters; however, ultrasound measurement yields a number approximately 10 degrees higher.

Anthropometry↗

PubMedDate not supplied

Evaluation of the PAPNET system for prescreening triage of cervicovaginal smears.

OBJECTIVE: To assess the PAPNET System for prescreening triage of cervical smears. STUDY DESIGN: We prospectively prescreened 5,170 consecutive cervicovaginal smears with the PAPNET System. The slides were then manually screened by cytotechnologists blinded to the PAPNET diagnoses. Cases identified as abnormal by either PAPNET or manual screening were reviewed by a cytopathologist. The PAPNET and manual diagnoses were correlated. RESULTS: Diagnostic concordance between PAPNET and manual screening was seen in 4,340 (84%) of the cases (3,167 negative, 1,038 abnormal and 135 unsatisfactory). Noncorrelation between PAPNET and manual diagnosis occurred in 794 cases (543 abnormal by PAPNET and negative manually, 228 negative by PAPNET and abnormal manually, 8 abnormal by PAPNET and unsatisfactory manually, 29 unsatisfactory by PAPNET and negative manually, 7 negative by PAPNET and unsatisfactory manually). The diagnostic sensitivity of the PAPNET System was 82%, diagnostic specificity 85%, predictive value of a positive test 66% and predictive value of a negative test 93.4%. The false negative fraction of PAPNET was 6.4% for low grade squamous intraepithelial lesion and above. CONCLUSION: PAPNET performed effectively for prescreening triage, increasing the accuracy of screening and reducing the screening time.

Evaluation Studies as Topic↗

PubMedDate not supplied

Risk factors for work-related low back pain in the People's Republic of China.

A critical review was conducted of studies of work-related low back pain in the People's Republic of China. The published literature in both the English and Chinese languages from 1983 to 1997 was reviewed for studies that permitted the calculation of prevalence ratios. Thirty-five papers were identified initially, and after quality inclusion/exclusion criteria were applied, 16 (14 in Chinese and two in English) were selected for more detailed review. Prevalence ratios were statistically elevated in all but two of the selected studies. Prevalence ratios for individual groups ranged from 2.0 to 8.5 for bending and twisting, 1.5 to 14.3 for static posture, 1.9 to 5.5 for whole-body vibration, and 2.6 to 9.4 for low-temperature exposure. The literature was limited by the absence of standardized and robust measures of low-back-pain outcomes and exposures and by the omission of fundamental details from research reports. Even with these limitations, the review findings suggest that three physical risk factors, all well known in the international literature, are associated with the prevalence of low back pain in the People's Republic of China.

China↗

PubMedDate not supplied

Study of the effects of aging on macromolecular synthesis in mouse steroid secreting cells using microscopic radioautography.

The effects of aging on DNA, RNA and protein synthesis in adrenal gland cortical cells and testicular Leydig cells of ddY mice at various ages (from prenatal day 19 to postnatal days 1, 3, 7, 14, months 1 and 6 and 1 and 2 years after birth) were examined using light and electron microscopic (EM) radioautography after labeling with [3H]-thymidine, [3H]-uridine and [3H]-leucine. The percentage of the labeled cells in the adrenal glands after [3H]-thymidine injection was greatest in the zona glomerulosa of the cortex and the medulla on embryonic day 19, in the zona fasciculata and zona reticularis of the cortex on postnatal day 1 and gradually decreased with aging. EM radioautography revealed that well developed cell organelles such as smooth surfaced endoplasmic reticulum, Golgi apparatus, mitochondria with tubular cristae and lipid droplets were more frequently observed in the cytoplasm of unlabeled cells as compared to cells labeled with [3H]-thymidine in the three zones of the cortex. The effects of aging on RNA synthesis in adrenal glands after [3H]-uridine injection revealed that all types of cells of the adrenal gland were labeled. In each cell, silver grains were localized over the nuclei and cytoplasm and were more dense in the nuclei than the cytoplasm. Grain counts were highest in the cortex and medulla on fetal day 19 and then gradually decreased with aging from postnatal day 14 to 1 year after birth. In the cortex, the number of silver grains was higher in the zona glomerulosa than in the other zones from fetal day 19 to 1 year and grain counts were higher in the medulla in the embryonic stage as compared to the postnatal stages. However, the number of labeled mitochondria and the mitochondrial labeling index increased with aging. The [3H]-thymidine labeling index in the Leydig cells of the testis was low at embryonic and early postnatal stages, increased slightly at 6 months and reached a peak at 9 months which was maintained at a relatively high level in senescence. The number of the silver grains over the nuclei and cytoplasm of Leydig cells due to [3H]-uridine labeling was observed from embryonic day 19 and increased from month 3 onwards. From adult to senescence, [3H]-uridine incorporation was maintained at high levels in the nuclei and was relatively low in the cytoplasm. The effects of aging on [3H]-leucine incorporation in Leydig cells were also examined. The labeling indices between embryonic and early postnatal stages showed no obvious differences although the number of the silver grains in both cytoplasm and nucleus increased from 6 months onwards and was maintained at high levels until senescence. From these results, it was concluded that the effects of aging on DNA, RNA and protein synthesis in steroid secreting cells such as adrenal gland cortical cells and testicular Leydig cells of mice correlated with the hormonal changes observed with aging.

Adrenal Cortex↗

PubMedDate not supplied

Two-deoxyglucose as an anti-metabolite in human carcinoma cell line RPMI-2650 and drug-resistant variants.

The accumulation of 2-deoxyglucose (2-DG), a glycolytic inhibitor, was investigated in a human nasal carcinoma cell line, RPMI-2650 and two of its drug-resistant variants (selected with taxol and melphalan) to assess manipulation of glycolytic potential as a selective means of reducing resistance. 2-DG uptake was increased 3-fold and 9.9-fold in taxol- and melphalan-resistant variants of RPMI-2650, respectively. Two of the principal factors associated with increased 2-DG uptake, namely glucose transporters and hexokinase activity, were increased in the resistant variants. Other changes in glucose metabolism that may affect 2-DG as an antimetabolite were observed, including increases in glucose-6-phosphate dehydrogenase of 10-fold and 100-fold for taxol- and melphalan-resistant variants, respectively, suggesting higher pentose phosphate activity; increased glutamine utilisation and greater sensitivity to iodoacetic acid-induced depletion of ATP levels in the parent relative to the resistant variants.

Antimetabolites, Antineoplastic↗

PubMedDate not supplied

In vitro cytotoxicity against human cancer cell lines during pulsed magnetic field exposure.

In an in vitro cell growth assay, carboplatin potency against A-431 cells increased after a 1 hour PMF (pulsed magnetic field) exposure (calculated peak field 5.2 mTesla, with an average field strength of 0.525 mTeslarms; pulses rose for 120 microseconds and then abruptly fell to neutral, and were repeated at a rate of 100 or 250 pulses per second). This potentiating effect was not observed with cisplatin or daunomycin. When cytotoxicity against HT-29 cells was measured, PMF exposure potentiated both carboplatin and daunomycin, but again, not cisplatin. Both cell types exhibited increased growth when exposed only to PMF. Exposure to PMF consistently increased the cell growth of these cancer cell lines, while only some in vitro antineoplastic agents were potentiated by PMFs.

Carboplatin↗

PubMedDate not supplied

Chemotherapy of human carcinoma xenografts during pulsed magnetic field exposure.

Immune deficient mice growing xenografts of HT-29 or A-431 cell lines were treated with cisplatin, carboplatin or doxorubicin in combination with one hour of wholebody pulsed magnetic field (PMF) exposure (calculated peak field 5.2 mTesla, with an average field strength of 0.525 mTeslarms; pulses rose for 120 microseconds and then abruptly fell to neutral, and were repeated at a rate of 250 pulses per second). At 24 days, the mice in each experiment were found to have significantly (p < 0.05, ANOVA) different tumor sizes among groups. The smallest mean tumor volume was consistently found in the drug+PMF group. With A-431 tumors, the cisplatin+PMF group (T) was significantly smaller, 52% [1-(100T/C)], than the cisplatin alone group (C). In HT-29 tumors, those treated with carboplatin+PMF had the smallest tumor volume at just 34% of the carboplatin-alone group. In HT-29 tumors, the doxorubicin+PMF group was 35% of the doxorubicin alone group.

Animals↗