Transcellular transport of isosmotic volumes by the rabbit gall-bladder in vitro

1. Fluid transport rate and oxygen consumption (Q(O2)) were studied in rabbit gall-bladder preparations in vitro exposed on both sides to identical Ringer solutions with NaCl concentrations (and osmolarities) varying from 70 to 140 m-equiv Na(+)/l.).2. The time sequence of acute effects on transport rate resulting from sudden changes in the NaCl concentration of the bathing solutions indicated that, (a) as a primary effect, fluid volume transfer rate remained unaffected whereas Na transport rate changed abruptly in direct proportion to the Na concentration of the bathing media; (b) a secondary, delayed and partly reversible depression of fluid transfer rate following elevation of the NaCl concentration was observed only when the rate of transport was relatively high initially.3. A fixed, and highly significant, linear relationship between changes in transport-linked oxygen consumption (DeltaQ(O2)) and measured net fluid volume transport (DeltaT(vol)) was found independent of the NaCl concentration of the bathing media, dQ(O2)/dT(vol) being 0.22 +/- 11% and 0.25 +/- 8% in bladders incubated in solutions containing 140 and 70 m-equiv Na(+)/l. respectively.4. Oxygen consumption per equiv of Na(+) (calculated) transported varied in inverse proportion to the Na concentration of the bathing media, dQ(O2)/dT(Na) being 0.0016 +/- 11% and 0.0036 +/- 8% in ;140 R' and ;70 R' solutions, respectively.5. Removal of K from the bathing solutions was followed by a gradual and partly reversible depression of fluid transport rate to a minimum level (about 100 x 10(-4) mul H(2)O. min(-1).mg(-1)) independent of the initial transport rate.6. It is concluded that the range of absorption rates of isosmotic fluid from the gall-bladder lumen represents a range of energy requiring capacities for transfer of fluid volume units; the data suggest that the intracellular (cytoplasmic) ion composition, depending on the presence of external K, as well as hormonal action may influence the capacity of the transcellular fluid transport mechanism.7. A model (a ;mechanical volume pump') for transcellular transfer of fluid volume units, allowing for flexible specificity with regard to the actively transported solutes, and requiring the presence of Na(+) and Cl(-), is proposed.     

Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a systematic review and meta-analysis

Background  

Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis.     

The effect of hypertensive disorders in pregnancy on small for gestational age and stillbirth: a population based study

Background  

Hypertensive disorders in pregnancy are leading causes of maternal, fetal and neonatal morbidity and mortality worldwide. However, studies attempting to quantify the effect of hypertension on adverse perinatal outcomes have been mostly conducted in tertiary centres. This population-based study explored the frequency of hypertensive disorders in pregnancy and the associated increase in small for gestational age (SGA) and stillbirth.     

Apo E in multiple sclerosis and optic neuritis: the apo E-epsilon4 allele is associated with progression of multiple sclerosis

OBJECTIVE: To investigate the association between apolipoprotein E (Apo E) genotype in multiple sclerosis (MS) and acute monosymptomatic optic neuritis (ON) in a genetically homogeneous population with a high frequency of the Apo epsilon4 allele. BACKGROUND: The association between heterozygosity of Apo epsilon4 and the development of MS is thoroughly investigated, while the association between homozygosity of Apo epsilon4 and the development of MS is insufficiently studied. The association between Apo E genotype and disease progression remains controversial. METHODS: 475 patients were included, 385 with MS and 90 with ON, consecutively seen in the MS clinic in the County of Copenhagen. Clinical data were obtained from medical records and degree of disability was determined prospectively using the Kurtzke expanded disability status scale (EDSS). Blood samples were used for Apo E genotyping. Disease progression was evaluated by the progression index (PI = EDSS/disease duration). Apo E genotype distribution was compared with 361 healthy controls. RESULTS: The Apo epsilon genotype distribution in the MS and ON groups was similar to the controls. The rate of disease progression in the group of MS patients with a disease duration of 10 years or less was significantly faster in the Apo epsilon4 positive group (heterozygosity and homozygosity for Apo epsilon4) (PI = 1.41) compared to the Apo epsilon4 negative group (PI =0.92) (P =0.009). Observing the MS subgroups, we found that the group of patients with RRMS had a faster rate of disease progression in the Apo epsilon4 positive group (PI =1.12) compared to the Apo epsilon4 negative group (P =0.77) (P =0.024). CONCLUSIONS: Apo E genotypes do not influence the development of MS and ON. The Apo epsilon4 allele seems to predispose carriers with MS to a faster progression of disease.     

Nitric oxide synthase expression and enzymatic activity in multiple sclerosis

We used post-mortem magnetic resonance imaging (MRI) guidance to obtain paired biopsies from the brains of four patients with clinical definite multiple sclerosis (MS). Samples were analyzed for the immunoreactivity (IR) of the three nitric oxide (NO) synthase isoforms [inducible, neuronal and endothelial nitric oxide synthase (NOS)], and enzymatic NO synthase activity. MRI guided biopsies documented more active plaques than macroscopic examination, and histological examination revealed further lesions. Inducible NOS (iNOS) was the dominant IR isoform, while reactive astrocytes were the dominant iNOS expressing cells in active lesions. NOS IR expressing cells were widely distributed in plaques, in white and gray matter that appeared normal macroscopically, and on MR. Endothelial NOS (eNOS) was highly expressed in intraparenchymal vascular endothelial cells of MS patients. A control group matched for age and sex showed no such changes. Our data support the hypothesis that NO is a pathogenic factor in MS, and that NOS IR is strongly expressed in brain regions appearing normal by MRI.     

Genetic and environmental influences on self-reported reduced hearing in the old and oldest old

OBJECTIVES: The aim of the present twin study was to estimate the relative importance of genetic and environmental factors in variation in self-reported reduced hearing among the old and the oldest old. DESIGN: Self-reported hearing abilities of older twins assessed at intake interview in a population-based longitudinal survey. SETTING: Denmark. PARTICIPANTS: Twins age 75 and older identified in the population-based Danish Twin Registry in 1995. An interview was conducted with 77% of 3,099 individuals in the study population. In 1997 and 1999, a follow-up contact to the survivors was made and an additional 2,778 twins, age 70-76, were included in the study. MEASUREMENTS: Reduced hearing was assessed by the same question in all interview waves. Heritability (proportion of the population variance attributable to genetic variation) was estimated using structural-equation analyses. RESULTS: The prevalence of self-reported reduced hearing corresponded to previous studies and showed the expected age and sex dependence. Concordance rates, odds ratios, and correlations were consistently higher for monozygotic twin pairs than for dizygotic twin pairs in all age and sex categories, indicating heritable effects. Structural-equation analyses revealed a substantial heritability for self-reported reduced hearing of 40% (95% CI = 19-53%). The remaining variation could be attributed to individuals' nonfamilial environments. CONCLUSION: We found that genetic factors play an important role in self-reported reduced hearing in both men and women age 70 and older. Because self-reports of reduced hearing involve misclassification, this estimate of the genetic influence on hearing disabilities is probably conservative. Hence, genetic and environmental factors play a substantial role in reduced hearing among the old and oldest old. This suggests that clinical epidemiological studies of age-related hearing loss should include not only information on environmental exposures but also on family history of hearing loss and, if possible, biological samples for future studies of candidate genes for hearing loss.     

Celecoxib reduces microvessel density in patients treated with nasopharyngeal carcinoma and induces changes in gene expression. Ann Oncol 2006; 17: 1625-1630

The publisher wishes to apologise to the authors of this articlefor the incorrect reproduction of one of the author names andfor deleting two sections of text from the discussion sectionof the article. The author W. L. Soon should have been printed as