Association of inflammaging (inflammation + aging) with higher prevalence of OAB in elderly population

Introduction

Although epidemiology studies consistently report increased prevalence of overactive bladder (OAB) with age, an accurate deciphering of causative links between the two entities remains elusive. Studies on aged rodent bladder have so far yielded contradictory results on age-associated changes in muscarinic receptors, which highlight the challenge posed by species differences in understanding OAB pathology. We hypothesized that age-related biochemical changes in bladder leading to altered bladder function will be reflected in altered urinary proteome of elderly OAB patients.

Methods

Single time point urine specimens were obtained from 140 OAB patients in the age range of 25–90 years of either sex coming routinely to the urology clinics. Eight chemokines in urine were measured by MILLIPLEX MAP human cytokine/chemokine multiplex immunoassay and ELISA. Multivariate and univariate statistical analyses were done to determine association of age with urinary chemokines in OAB patients.

Results

In agreement with age-dependent higher prevalence of OAB, the logistic regression of the data also revealed the significant association of OAB symptoms with age [odds ratio (OR) 1.12; 95 % CI, (1.072, 1.187), p = 0.0001]. Univariate analysis of 8 urinary proteins revealed an age-associated elevation of NGF (nerve growth factor) in 137 out of 140 OAB patients [Pearson r = 0.274; 95 %CI (0.112–0.422); p = 0.001]. Modest correlation with age was also noted for MCP-1 (monocyte chemoattractant protein-1), which was detected in 115 OAB patients, and the remaining chemokines were undetectable in nearly two-third of OAB patients included in our cohort.

Conclusions

Based on our findings, we postulate that age-associated biochemical changes may accentuate the inflammation associated with OAB. Urinary NGF elevation in elderly OAB patients may be a homeostatic response to counter the senescence of bladder nerves and arrest the progression of OAB into detrusor hyperactivity with impaired contractility. Likewise, elevation of MCP-1 may be related to decreased muscle mass and increased content of adipose tissue in bladder of elderly OAB patients. Urinary NGF and MCP-1 can serve as surrogate markers for monitoring age-associated biochemical changes and the effect of therapeutic interventions in OAB patients.     

Leptin effects on food and water intake in lines of chickens selected for high or low body weight

There is an association between autonomic nervous system output and obesity. The sympathetic nervous system stimulates lipid metabolism and regulates food intake and, hence, body weight. Leptin, produced by adipocytes in proportion to their size, has been shown to directly stimulate the satiety center. In the experiment reported here, food and water intake were compared after intracerebroventricular administration of human recombinant leptin to lines of chickens that had undergone divergent selection for over 45 generations from a common White Rock base population for high (HWS) or low (LWS) body weight at 8 weeks-of-age. Leptin caused a linear decrease in food intake in chickens from the LWS line whereas no effect was observed in those from the HWS line. The HWS chickens tended to have reduced water intake post leptin administration. Others reported that leptin decreased food intake in both broiler and Leghorn chickens. Leptin concentration in the central nervous system may not contribute directly to the difference of body weight between HWS and LWS chickens.     

Effects of 16, 16-dimethyl prostaglandin E2 on alkaline secretion in isolated canine gastric mucosa

An isolated fundic mucosal preparation of dog stomach which is capable of exhibiting an alkaline secretion is described. A stable secretion was established 40 min to 1 hr after the mucosa was pretreated with the H₂-antagonist cimetidine to block spontaneous acid output. Alkaline secretion decreased when Ca²⁺ was removed from the nutrient solution. This secretion was stimulated by dibutyryl cyclic GMP, but was not altered by acetylcholine, carbachol, or 16,16-dimethyl PGE₂. Alkaline secretion from a similar antral mucosal preparation was stimulated by 16,16-dimethyl PGE₂. We conclude that the 16,16-dimethyl PGE₂-stimulated bicarbonate secretion previously demonstrated inin vivo canine fundic mucosa is not the result of a direct effect of PG on gastric mucosal cells and that an intact blood circulation or cholinergic innervation is required for this action to occur.     

Aerosol delivery to non-ventilated infants by metered dose inhaler: Should a valved spacer be used?

In a randomized double-blind cross-over study on 20 spontaneously breathing, oxygen-dependent preterm infants who had received positive pressure ventilation for respiratory distress syndrome, we tested the hypothesis that the one-way non-rebreathing valves of aerosol spacer devices might impair rather than enhance the delivery of aerosols to small infants by metered dose inhalers (MDI). Ten infants were given 2 doses (200 μg/dose) of MDI albuterol through a neonatal Aerochamber® 4 h apart. At random sequence, one dose was delivered with the non-rebreathing valve of the Aerochamber® in place; for the other dose, the valve had been removed. The experiment was repeated on another ten infants using a different spacer device (Babyhaler®) with or without its one-way inspiratory valve removed. During the first hour following aerosol administration, use of the non-valved spacers was associated with a significantly greater degree of tachycardia in both groups, and also lower transcutaneous carbon dioxide tension in the Aerochamber® group. All infants showed a reduction in respiratory system resistance and an improvement in functional residual capacity following albuterol treatment. In both groups, maximum reduction in respiratory system resistance, recorded 30 min after aerosol delivery, was significantly greater following the use of the non-valved spacers (Aerochamber®: 51.2 ± 3.1% vs. 35.0 ± 2.8%, P < 0.0001; Babyhaler®: 38.8 ± 2.3% vs. 19.2 ± 1.4%, P < 0.0001) than following the use of the spacers with a valve. The findings provide indirect evidence supporting our hypothesis and suggest that when the MDI is used to deliver therapeutic aerosols to non-ventilated newborns or small infants, a spacer device without a non-rebreathing valve should be used. Pediatr. Pulmonol. 1997; 24:204–212. © 1997 Wiley-Liss, Inc.     

Binding of heme by glutathione S-transferase: a possible role of the erythrocyte enzyme

Human erythrocyte glutathione S-transferase activity is inhibited, probably competitively, by hemin with a Ki of 10(-7) M. It is postulated that glutathione S-transferase functions physiologically as a hemin-binding and/or transport protein in developing erythroid cells.     

Polymorphisms at the LDLR locus may be associated with ischemic cerebrovascular disease independent of lipid profile

The low-density lipoprotein receptor (LDLR) gene has been reported to be associated with cerebral infarction. This study aimed to explore 2 genetic LDLR variants, rs688 and rs5925, for their potential roles in cerebral infarction. This genetic association study was conducted within an isolated Taiwanese population; 815 ischemic stroke patients (431 with atherothrombotic stroke and 384 with lacunar infarction) and 430 normal controls were enrolled. There was no significant difference in the genetic frequency of rs688 and rs5925 between the control group and overall ischemic stroke, atherothrombotic stroke, or lacunar infarct groups. However, when analyzing the association between the haplotypes related to rs688 and rs5925 and cerebral ischemic stroke, the most common haplotype allele CT was used as the reference allele, and the haplotype TC associated with a 65% increased risk of overall ischemic stroke, 72% increased risk of atherothrombotic stroke, and 70% increased risk of lacunar infarction; this indicated a synergistic effect between these 2 single-nucleotide polymorphisms. The LDLR analysis based on the haplotypes rs688 and rs5925 was conducted in a Taiwanese population and provided preliminary evidence suggesting that genetic polymorphisms of LDLR are associated with cerebral infarction.     

5‐aminolevulinic acid induce apoptosis via NF‐κB/JNK pathway in human oral cancer Ca9–22 cells

J Oral Pathol Med (2010) 40 : 483–489 Background: 5‐aminolevulinic acid‐based photodynamic therapy (5‐ALA‐PDT) is being used to treat oral pre‐cancerous and cancerous lesions with some encouraging clinical outcomes. However, the exact mechanisms behind the photodynamic treatment are still not fully elucidated. Method: Flow cytometry, TdT‐mediated dUTP nick end labeling assay and Western blot analysis were used to investigate the effects of 5‐ALA‐PDT on human oral cancer Ca9–22 cells. Results: We found that 5‐ALA‐PDT induces apoptosis in Ca9–22 cells. Western blotting showed that 5‐ALA‐PDT activates both the caspase‐8 and caspase‐9 pathways, which differed from previous studies conducted in other cell types. Activation of JNK was evident as early as 30 min. The caspases activation was inhibited by JNK inhibitor SP600125. Treatment with NF‐κB inhibitor Bay 11‐7082 (Bay) completely abrogated ALA‐PDT‐induced JNK activation. In addition, Bay and SP600125 almost completely abolished ALA‐PDT‐induced apoptosis. Conclusion: These results demonstrate significant involvement of caspase‐8 and ‐9 and their upstream NF‐κB‐JNK pathways in ALA‐PDT‐induced apoptosis. Future studies on how NF‐κB and JNK activity regulate ALA‐PDT response should provide a better strategy for the treatment of oral cancer.