Fluoxetine and 8-OH-DPAT in the lateral septum enhances and impairs retention of an inhibitory avoidance response in rats.

The present study investigated the role of lateral septal serotonin (5HT) in memory consolidation and the subtype of 5HT receptors involved in this process. Rats with cannulae implanted bilaterally into the lateral septum were trained in an inhibitory avoidance task. Immediately after training, the septal serotonergic function was manipulated by pharmacological agents selectively blocking 5HT reuptake (fluoxetine and zimelidine), antagonizing 5HT2 receptors (ketanserin and ritanserin), or activating 5HT1A receptors, respectively. Results indicated that direct fluoxetine infusions into the lateral septum at a dose of 6 micrograms/0.5 microliter and zimelidine at a dose of 5 micrograms/0.5 microliter both markedly enhanced memory. Intralateral septal injections of ketanserin (0.3 microgram/0.5 microliter and 0.5 microgram/0.5 microliter) and ritanserin (0.3 microgram/0.5 microliter and 0.6 microgram/0.5 microliter) did not have a significant effect by themselves on memory, and neither did they attenuate the memory-facilitating effect of fluoxetine in the same area. Intralateral septal infusions of 8-hydroxy-2-(di-n-propylamino)tetralin at 5 micrograms/0.5 microliter significantly impaired memory retention. These findings altogether support the notion that the lateral septal nuclei of rats are involved in the memory processes of inhibitory avoidance learning. Furthermore, postsynaptic 5HT receptor activation (not the 5HT2 receptor subtype) probably exerts a facilitatory effect while presynaptic 5HT1A receptor activation exerts an impairing effect on the memory consolidation process, probably due to autoreceptor inhibition of 5HT release.     

E(f)-current contributes to whole-cell calcium current in low calcium in frog sympathetic neurons

Because Ca(2+) plays diverse roles in intracellular signaling in neurons, several types of calcium channels are employed to control Ca(2+) influx in these cells. Our experiments focus on resolving the paradox of why whole-cell current has not been observed under typical recording conditions for one type of calcium channel that is highly expressed in frog sympathetic neurons. These channels, referred to as E(f)-channels, are present in the membrane at a density greater than the channels that carry approximately 90% of whole-cell current in low Ba(2+); but, E(f)-current has not been detected in low Ba(2+). Using Ca(2+) instead of Ba(2+) as the charge carrier, we recorded a possible E-type current in frog sympathetic neurons. The current was resistant to specific blockers of N-, L-, and P/Q-type calcium channels but was more sensitive to Ni(2+) block than was N- or L-current. Current amplitude in Ca(2+) is slightly greater than that in Ba(2+). In 3 mM Ca(2+), the current contributed approximately 12% of total current at peak voltage and increased at voltages more hyperpolarized to the peak, reaching approximately 40% at -30 mV, where whole-cell current starts to activate. The presence of E(f)-current in 3 mM Ca(2+) suggests a potential role for E(f)-channels in regulating calcium influx into sympathetic neurons.     

Detection and deletion of motion artifacts in electrogastrogram using feature analysis and neural networks

Electrogastrogram is a surface measurement of gastric myoelectrical activity, and electrogastrography has been an attractive method for physiological and pathophysiological studies of the stomach due to its nonivasive nature. Motion artifacts, however, ruin the electrogastrogram (EGG), and make the analysis very difficult and sometimes even impossible. They must be eliminated from EGG signals before analysis. Up to now, this can only be done by visual inspection, which is not only time-consuming but also subjective. In this study, a method using feature analysis and neural networks has been developed to realize automatic detection and elimination of the motion artifacts in EGG recordings by computer. Experiments were conducted to investigate the characteristics of different motion artifacts. Useful features were extracted, and different combinations of the features used as the input of the neural network were compared to obtain the optimal performance for the detection of motion artifacts using the artificial neural network.     

Changes in HIV-1 incidence in heroin users in Guangxi Province, China

Guangxi Province, China recently experienced an outbreak of HIV-1 infection among heroin users. We studied HIV-1 incidence rates and associated risk factors for HIV-1 infection among heroin users residing in Pingxiang City. A total of 318 heroin users were followed from February 1998 through January 1999 (median follow-up: 8.1 months). Of these, 130 were prospectively followed from January through September 1999 (median follow-up: 8.3 months). HIV-1 and hepatitis C virus (HCV) incidence rates for each period were calculated. A generalized estimating equation approach was implemented to identify independent risk factors associated with HIV-1 infection across both periods. Among 318 study participants, 97.2% were men. The median age was 22 years. Approximately 60% reported sharing needles. HIV-1 prevalence at baseline was 15.4%. During the first follow-up period, HIV-1 incidence was 2.38 per 100 person years (py), and HCV incidence was 26.8 per 100 py. During the second follow-up period, HIV-1 incidence was 6.86 per 100 py, and HCV incidence was 28.9 per 100 py. After controlling for age and other factors, HCV seropositivity, history of sexually transmitted diseases, and sharing needles were independently associated with HIV-1 infection. These data suggest that HIV-1 incidence was rising over time in Pingxiang City, Guangxi Province. The high incidence of HCV heightens the importance of enhanced prevention programs to reduce injection and needle sharing among heroin users.     

Molecular and biochemical mechanisms ofPasteurella haemolyticaleukotoxin-induced cell death

Pasteurella haemolyticaleukotoxin (LKT) is a member of the RTX family of pore-forming toxins that kill bovine immune cells. Several studies have suggested that RTX toxins kill target cells by the induction of apoptosis. In the present study, BL3 bovine leukaemia cells were exposed to LKT and assessed by molecular and flow cytometric techniques that measure different aspects of apoptotic cell death. The intoxicated cells demonstrated morphological, light scatter and Hoechst 33258 staining characteristics consistent with cells undergoing apoptosis. The cells also exhibited internucleosomal DNA fragmentation and poly (ADP-ribose) polymerase (PARP) cleavage, both indicators of apoptosis. LKT-treated cells bound annexin-V-FITC indicating that phosphatidylserine groups were translocated from the inner to the outer leaflet of the cell membrane. The effect of LKT on cells was dose dependent and inhibitable by incubation with anti-LKT monoclonal antibody. Finally, an early step for induction of apoptosis appears to be the binding of LKT to a β2 integrin since pre-incubating cells with anti-β2 integrin antibodies inhibited LKT-induced apoptosis. This study provides new insights into understanding the pathogenesis of bovine pasteurellosis and could lead to the development of both preventative and therapeutic strategies for disease management.     

Identification of testis development and spermatogenesis-related genes in human and mouse testes using cDNA arrays

We have constructed cDNA microarrays from the human testis large insert cDNA library, containing 9216 genes, together with several housekeeping genes. The cDNA microarrays were used to identify gene expression differences between human fetal and adult testes. Of >8700 hybridized clones, 731 exhibited significant differential expression characteristics. About 7500 genes were identified when the same cDNA microarrays were used for hybridization with cDNA probes from mouse testis, with 256 genes having significant differential expression between the age of 1-4 weeks. Among these genes, 101 were identified as critically related to testis development and possibly to spermatogenesis since they were found in both human and mouse testes, and expressed differentially at different stages of testis development. Of the 101 development-related genes, 59 full-length cDNAs have been sequenced previously, while the full-length cDNAs of the other 42 genes have not been published. We have obtained 11 full-length sequences of the 42 genes and deposited them in the GenBank. The conserved testis development-related genes found in both human and mouse testes may include genes that are likely to be involved in testicular functions, especially spermatogenesis, thus providing a basis for further functional characterization of the genes in mouse models.