Effects of age and age-related hearing loss on the neural representation of speech cues.

OBJECTIVE: To examine the effects of aging and age-related hearing loss on the perception and neural representation of a time-varying speech cue. METHODS: P1, N1 and P2 cortical responses were recorded from younger and older normal-hearing adults, as well as older adults with age-related hearing loss. Synthetic speech tokens representing 10 ms increments along a /ba/-/pa/ voice-onset-time (VOT) continuum were used to evoke the responses. Each participant's ability to discriminate the speech tokens was also assessed. RESULTS: Compared with younger participants, older adults with and without hearing loss had more difficulty discriminating 10 ms VOT contrasts. In addition, both older groups elicited abnormal neural response patterns. There were no significant age-related findings for P1 latency; however, N1 latencies were prolonged for both older groups in response to stimuli with increased VOT durations. Also, P2 latencies were delayed for both older groups. The presence of age-related hearing loss resulted in a significant increase in N1 amplitude in response to voiceless stimuli. CONCLUSIONS: Aging and age-related hearing loss alter temporal response properties in the central auditory system. Because both older groups had difficulty discriminating these same speech stimuli, we conclude that some of the perceptual difficulties described by older adults might be due to age-related changes regulating excitatory and inhibitory processes. SIGNIFICANCE: Some of the speech understanding difficulties expressed by elderly adults may be related to impaired temporal precision in the aging auditory system. This might explain why older adults frequently complain that wearing a hearing aid makes speech louder, but does not necessarily improve their ability to understand speech.     

Upregulation of interleukin-1 receptors in mouse AtT-20 pituitary tumor cells following treatment with corticotropin-releasing factor.

Treatment of AtT-20 cell cultures with increasing concentrations of rat/human corticotropin-releasing factor (r/hCRF) for 24 h resulted in a dose-dependent 2-3 fold increase in specific 125I-labelled recombinant human IL-1 alpha (125I-IL-1 alpha) binding that was paralleled by a 70-80% decrease in 125I-Tyro-ovine CRF binding. Saturation analysis of 125I-IL-1 alpha binding in control and CRF-treated cultures indicated that CRF produced an increase in the density (Bmax) of IL-1 receptors without altering their affinity (KD). The CRF-induced upregulation of IL-1 receptors appears to be mediated through specific membrane receptors for CRF since the CRF receptor antagonist, alpha-helical oCRF (9-41), blocked the CRF-induced upregulation of IL-1 receptors without producing any effect on 125I-IL-1 alpha binding by itself. In summary, these data demonstrate complex interactions between CRF and IL-1 at the pituitary level and identify potential novel mechanisms for cytokines to alter neuroendocrine function.     

Modulation of beta-adrenergic receptors in the pituitary gland following adrenalectomy in rats

The effects of adrenalectomy on beta-adrenergic receptors in the rat pituitary were examined using quantitative in vitro autoradiography with 125I-iodocyanopindolol (125ICYP). 125ICYP binding in the anterior, intermediate and posterior lobes of the pituitary gland was significantly increased in chronically adrenalectomized rats. The increase in 125ICYP binding sites in the rat pituitary following adrenalectomy was not reversed by glucocorticoid replacement with dexamethasone. These data indicate that catecholamines of adrenomedullary origin are capable of modulating beta-adrenergic receptors in the pituitary gland and suggest that peripheral epinephrine may be important in regulating pituitary hormone secretion.     

The prevalence of peripheral arterial disease and medial arterial calcification in patients with chronic renal failure: requirements for diagnostics

BACKGROUND: Knowledge of the prevalence of peripheral arterial disease (PAD) in patients with chronic renal failure (CRF) is limited because of a lack of uniformity in disease definition and recognition. Furthermore, little is known of the prevalence of medial arterial calcification (MAC) in patients with CRF. Our goal is to study the prevalence of PAD and MAC defined by ankle brachial index (ABI) or toe brachial index (TBI) measurements in a Finnish population of patients with CRF consisting of predialysis and dialysis patients, as well as renal transplant recipients. METHODS: We examined 136 patients with CRF and 59 control subjects. Fifty-nine of the patients with CRF had moderate to severe predialysis CRF, 36 patients were on dialysis treatment, and 41 were renal transplant recipients. Mean age of patients was 51.9 +/- 11.5 years, and 39 patients (29%) had diabetes. ABI and TBI were measured by means of photoplethysmography. The definition of PAD required an ABI value of 0.90 or less, a TBI value of 0.60 or less, or a previous positive lower-extremity angiogram result. ABI values of 1.3 or greater or incompressible arteries at ankle level indicated MAC. The presence of claudication was determined by an interview. RESULTS: Prevalences of PAD on this study were 22.0% in patients with predialysis CRF, 30.6% in patients on dialysis treatment, 14.6% in renal transplant recipients, and 1.7% in the control group (P = 0.001). Prevalences of MAC were 23.7%, 41.7%, 23.1%, and 3.4% (P < 0.001), respectively. Only 9 patients had claudication, and 6 of those patients had PAD. CONCLUSION: Both asymptomatic PAD and MAC are common in patients with CRF. Therefore, we recommend the use of both ABI and TBI measurements in the evaluation of PAD in patients with CRF.     

Endocytosis of gold-labeled proteins and LDL byTrypanosoma cruzi

Endocytosis was studied at the ultrastructural level in different developmental forms ofTrypanosoma cruzi after incubation of the parasites in the presence of gold-labeled proteins (albumin-Au, peroxidase-Au and transferrin-Au) and low-density lipoprotein (LDL-Au). Epimastigote (culture) forms actively ingested LDL and proteins. Initially, gold particles were seen adhering only to the cytostome and inside the flagellar pocket. In parasites incubated at 4°C with transferrin-Au or peroxidase-Au, labeling was found only at these two sites, showing that receptor-mediated endocytosis occurs in both regions. In the cytoplasm, gold particles were seen only inside two different compartments: membrane-bound vesicles and reservosomes. Incubation of epimastigotes with acridine orange followed by fluorescence microscopy revealed intense orange staining, indicating that the reservosomes have an acidic pH. This staining was abolished after incubation of the parasites in the presence of ammonium chloride. These data confirm that this compartment is the site of accumulation of ingested lipids and proteins. Little intracellular labeling with transferrin-Au was found in in vitro — derived amastigotes and trypomastigotes (both lack reservosomes). However, although in amastigotes very few gold particles were seen bound to the cells, in trypomastigotes they were observed bound to the membrane that encloses the cell body, the flagellar pocket, and the flagellum, suggesting that the receptors are more abundant in this form.