Tetrahydroaminoacridine improves passive avoidance retention defects induced by aging and medial septal lesion but not by fimbria-fornix lesion.

The present study examines whether tetrahydroaminoacridine (THA) can improve the deterioration in passive avoidance (PA) retention performance induced by medial septal (MS) and fimbria-fornix (FF) lesions in young rats or by aging. Retention of young MS-lesioned rats was improved by pretraining injection of THA at 3 mg/kg, but not by THA at 1 mg/kg or by either of the posttraining doses of THA (1 and 3 mg/kg). Pretraining injections of THA at 1 or 3 mg/kg had no effect on the PA retention performance of FF-lesioned rats. Age-induced PA failure was alleviated by pretraining administration of THA at 1 and 3 mg/kg. Posttraining injections of THA (1 or 3 mg/kg) had no effect on PA retention performance of aged rats. These results demonstrate that 1) THA may improve hippocampal cholinergic denervation-induced functional deficits and 2) some of the age-related PA deficits may be due to a cholinergic deficit and can be reversed with THA.     

Spatial Learning and Noradrenaline Content in the Brain and Periphery of Young and Aged Rats

The present experiment studied whether a dysfunction of the noradrenergic neurons is related to spatial learning impairment by investigating the levels of noradrenaline in the brain and periphery as well as the acquisition of water maze task in saline-pretreated young rats, in noradrenergic neurotoxin (DSP-4)-pretreated young rats and in saline-pretreated aged rats. Aged rats, which had an increased escape latency onto the hidden platform, revealed a decreased noradrenaline content in the heart, but not in the hippocampus, striatum, or hypothalamus, whereas DSP-4-pretreated rats had decreased noradrenaline content in the brain; the acquisition of water maze task was not impaired. These results suggest that the peripheral noradrenergic system can show age-related changes different from those in the central noradrenergic system, and they failed to provide support for the hypothesis that decreased activity of the central noradrenergic nerves is related to impairment in the acquisition of the water maze task.     

Age-dependent stimulation by atrium explants or nerve growth factor of nerve fibre outgrowth from cocultured embryonic rat sympathetic ganglia

Whole sympathetic superior cervical ganglia of 14- and 15-day-old rat embryos were cultured in a collagen gel medium for 24 h with or without explants of heart atrium from the same animals or from newborn rats. The extent of nerve fibre outgrowth was estimated by counting the number of nerve fibres crossing each arc of a sector drawn in the microscope ocular. Only few nerve fibres extended from the ganglia of the 14-day-old embryos cultured in the pure control medium. Addition of exogenous nerve growth factor did not stimulate the poor growth. While the growth of nerve fibres in the presence of atrium explants of newborn rats did not significantly differ from that in cultures without any target tissue, the presence of atrium explants of the same, 14-day-old, embryo resulted in clearly enhanced fibre outgrowth from the ganglia, which was inhibited by antiserum to the nerve growth factor. The ganglia of 15-day-old embryos cultured without target tissue in the control medium produced only sparse fibre outgrowth which was excessively increased by exogenous nerve growth factor. Coculture with atrium explants of 15-day-old embryos or newborn rats produced an increased overall nerve fibre growth, as well as predominance of those fibres growing toward the target tissue. The growth-promoting effect of the atrium of 15-day-old embryos was only partially prevented by antiserum to the nerve growth factor, while that elicited by newborn rat atrium was totally inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)     

Persisting axonal degeneration in the hippocampus after transection of the fimbria-fornix

Degeneration within the hippocampus was examined at the light microscopic level using the Gallyas silver stain two, four or nine months after bilateral transection of the fimbria-fornix and commissural connections. At two or four months after the lesion the strata oriens and radiatum of the subicular end of the CA1 subfields were strongly argyrophilic as was the inner third of the molecular layer of the dentate gyrus. At nine months post-lesion argyrophilia diminished but clearly persisted in the same layers. Electron microscopic examination revealed a large number of electron-dense axon terminals in the argyrophilic areas, most of them making asymmetric synaptic contacts with dendritic spines. These findings suggest that at least a portion of the Schaffer collaterals of the CA3 pyramidal cells and associational collaterals of hilar neurons were in a process of acute degeneration at all time points after the initial surgical trauma. This persistent synaptic reorganization of intrahippocampal circuits may be related to abnormal electrical activity observed several months after fimbria-fornix transection.     

Acute Kidney Injury Following Aortic Valve Replacement in Patients Without Chronic Kidney Disease

BackgroundThe data on acute kidney injury (AKI) in patients without chronic kidney disease (CKD) after transcatheter aortic valve replacement (TAVR) are limited. The study sought to compare the incidence of AKI and its impact on 5-year mortality after TAVR and surgical aortic valve replacement (SAVR) in patients without CKD.MethodsThis registry included data from 6463 consecutive patients who underwent TAVR or SAVR. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m². AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. For sensitivity analysis, propensity-score matching between TAVR and SAVR was performed.ResultsThe study included 4555 consecutive patients (TAVR, n = 1215 and SAVR, n = 3340) without CKD. Propensity-score matching identified 542 pairs. Patients who underwent TAVR had a significantly lower incidence of AKI in comparison to those who underwent SAVR (unmatched 4.7% vs 16.4%, P < 0.001, multivariable analysis: odds ratio, 0.29, 95% confidence interval [CI], 0.20-0.41; matched 5.9% vs 19.0%, P < 0.001). Patients with AKI had significantly increased 5-year mortality compared with those without AKI (unmatched 36.0% vs 19.1%, log-rank P < 0.001; matched 36.3% vs 24.0%, log-rank P < 0.001). The adjusted hazard ratios for 5-year mortality were 1.58 (95% CI, 1.20-2.08) for AKI grade 1, 3.27 (95% CI, 2.09-5.06) for grade 2, and 4.82 (95% CI, 2.93-8.04) for grade 3.ConclusionsTAVR in patients without CKD was associated with a significantly less frequent incidence of AKI compared with SAVR. AKI significantly increased the risk of 5-year mortality after either TAVR or SAVR, and increasing severity of AKI was incrementally associated with 5-year mortality.     

Molecular characterization of chromosome 7 long arm deletions in myeloid disorders

Partial deletion of the long arm of chromosome 7 is a common abnormality in the bone marrow cells of patients with myelodysplastic syndrome (MDS) or acute nonlymphocytic leukemia (ANLL). This study was undertaken to characterize the chromosome breakpoints in molecular terms and to determine if hemizygosity or submicroscopic deletions occur in patients without any cytogenetically detectable abnormality of chromosome 7. We studied restriction fragment length polymorphisms with 10 chromosome 7-specific DNA probes in separated WBC fractions. No molecular abnormalities occurred in lymphocyte-derived DNA. Several probes located in band 7q22 or distally thereof detected deletion of one allele in granulocyte-derived DNA from all four patients with chromosome 7 long arm deletion. In the granulocytes of one patient heterozygosity for the T cell receptor beta chain gene (in band 7q35) indicated that the deletion was interstitial. NJ-3, a proalpha2(I)collagen gene probe (in band 7q21-22) detected heterozygosity in the granulocytes of one patient. No hemizygosity or deletions were found in four patients with two normal chromosomes 7. These results confirm that mature granulocytes but not lymphocytes are derived from the abnormal clone. Interstitial deletions exist, and the extent of deleted genomic material varies among patients.