Comparison between epidermal growth factor, transforming growth factor-alpha and EGF receptor levels in regions of adult rat brain.

Examination of adult rat brain regions by specific radioimmunoassays revealed a widespread distribution of transforming growth factor-alpha (TGF-alpha), but not epidermal growth factor (EGF), the peptide that had previously been reported to be present in rodent brain. Polyadenylated RNA samples from the different regions of rat brain were analyzed by Northern blot to identify mRNA species encoding precursor proteins for EGF (preproEGF), TGF-alpha (preproTGF-alpha), and the EGF/TGF-alpha receptor. The results indicate that TGF-alpha is the most abundant ligand for the EGF/TGF-alpha receptor in most parts of the brain analyzed. Message for preproEGF was only detectable after prolonged autoradiographic exposure; levels of preproEGF mRNA were between two and three orders of magnitude lower in brain than those expressed in control tissue (kidney), and one to two orders of magnitude lower than preproTGF-alpha mRNA levels in all brain regions. These results were confirmed by analysis of mRNA by RT/PCR, and support the hypothesis that expression of preproEGF mRNA in the brain is limited to smaller discrete areas, whereas preproTGF-alpha gene expression is almost ubiquitous.     

Effect of body mass index on bone mineral density is age-specific

Background and aimsObesity and osteoporosis are two important and growing public health problems worldwide. Body mass index (BMI) has been found to be inversely related to the risk of osteoporotic fracture. We aimed to assess the association of BMI with thoracic vertebral bone mineral density (BMD) measured from a quantitative computed tomography (QCT).Methods and resultsWe retrospectively evaluated the data from 15,758 consecutive patients (5675 females and 10,083 males) between age 20–90 years, who underwent Coronary Artery Calcium (CAC) scoring. Quantitative data analyses of thoracic trabecular BMD (mg/cm³) was performed with a phantom system or phantomless using validated software. The gender-specific subgroup was divided based on age (<45, 45–55, 55–65, >65 yrs in females; <40,40–60,>60 yrs in Males) and weight by BMI (kg/m²) as < 25 (normal or low weight), >25 - <30 (overweight) and >30 (obesity). Analysis of variance (ANOVA) and Scheffe's post hoc procedure tested the association of body weight/BMI on BMD. A significant positive association between the body weight and BMD existed in obese population in elder groups in both genders (p < 0.05). There was no significant difference in BMD in 40–60 years in men and <55 years in women with normal or low weight compared to overweight or obese cohorts.ConclusionsWe concluded that the effect of weight on BMD is age-specific and the BMD should be monitored routinely with a cardiac CT scan in the senile population.     

Economic Burden of Opioid-Induced Constipation Among Long-Term Opioid Users with Noncancer Pain

Background

Opioid-induced constipation (OIC) can be a debilitating side effect of opioid therapy and may result in increased medical costs. The published data on the economic burden of OIC among long-term opioid users are limited.

Objective

To assess the economic burden of OIC in patients with noncancer pain in a managed care population in the United States.

Methods

This retrospective study used 2007–2011 data from the Truven Health MarketScan Commercial and Medicare databases. The study included adults with ≥12 months of insurance enrollment before and after starting long-term (≥90 days) use of opioids. Patients were excluded if they had cancer or a diagnosis of drug abuse or drug dependence during the study period, or if they had constipation or bowel obstruction within 90 days before starting opioid therapy during the study period. OIC was identified by International Classification of Diseases, Ninth Edition codes for constipation (564.0) or bowel obstruction (560.x) within 12 months of the initiation of an opioid. Patients with OIC were identified in the nonelderly, elderly (age ≥65 years), and long-term care populations. Differences in costs and healthcare resource utilization were calculated using propensity scoring.

Results

A total of 13,808 nonelderly (age, 48.6 ± 10.4 years; female, 50%) and 2958 elderly patients (age, 78.7 ± 8.1 years; female, 70%) met the study inclusion criteria. Of 401 nonelderly and 194 elderly patients with OIC, 85 patients initiated opioid therapy in a long-term care facility (age, 80.7 ± 11.6 years; female, 77%). After matching by key covariates, patients with OIC had significantly more hospital admissions than patients without OIC (nonelderly, 33% vs 22%, respectively; P <.001; elderly, 51% vs 31%, respectively; P <.001) and longer inpatient stays (nonelderly, 3.0 ± 8.4 days vs 1.0 ± 3.0 days, respectively; P <.001; elderly, 5.2 ± 12.2 days vs 2.1 ± 4.0 days, respectively; P <.001). The group with OIC had significantly higher total healthcare costs than the group without OIC in all 3 study cohorts (nonelderly, $23,631 ± $67,209 vs $12,652 ± $19,717, respectively; elderly, $16,923 ± $38,191 vs $11,117 ± $19,525, respectively; long-term care, $16,000 ± $22,897 vs $14,437 ± $25,690, respectively; all P <.05).

Conclusion

To the best of our knowledge, this is the first study to analyze the economic impact of long-term use of opioids among patients with OIC, using real-world data. The findings underscore the significant economic burden associated with long-term opioid use for noncancer pain in a managed care population. Effective therapies for OIC may reduce the associated economic burden and improve quality of life for long-term opioid users.     

Metabolomic analysis of patient plasma yields evidence of plant-like α-linolenic acid metabolism in Plasmodium falciparum

Metabolomics offers a powerful means to investigate human malaria parasite biology and host-parasite interactions at the biochemical level, and to discover novel therapeutic targets and biomarkers of infection. Here, we used an approach based on liquid chromatography and mass spectrometry to perform an untargeted metabolomic analysis of metabolite extracts from Plasmodium falciparum-infected and uninfected patient plasma samples, and from an enriched population of in vitro cultured P. falciparum-infected and uninfected erythrocytes. Statistical modeling robustly segregated infected and uninfected samples based on metabolite species with significantly different abundances. Metabolites of the α-linolenic acid (ALA) pathway, known to exist in plants but not known to exist in P. falciparum until now, were enriched in infected plasma and erythrocyte samples. In vitro labeling with (13)C-ALA showed evidence of plant-like ALA pathway intermediates in P. falciparum. Ortholog searches using ALA pathway enzyme sequences from 8 available plant genomes identified several genes in the P. falciparum genome that were predicted to potentially encode the corresponding enzymes in the hitherto unannotated P. falciparum pathway. These data suggest that our approach can be used to discover novel facets of host/malaria parasite biology in a high-throughput manner.