Responses of brain and behavior to changing day-length in the diurnal grass rat (Arvicanthis niloticus).

Seasonal affective disorder (SAD) is a major depressive disorder that recurs in the fall and winter when day-length gets short. It is well accepted that day-length is encoded by the principal circadian clock located in the suprachiasmatic nucleus (SCN), but very little is known about day-length encoding in diurnal mammals. The present study utilized the grass rat, Arvicanthis niloticus, to investigate how the circadian system responds to photoperiodic changes in a diurnal mammal that shows day-length-dependent mood changes. The animals were initially housed in equatorial day-length (12h, EP) followed by either long (16h, LP) or short (8h, SP) photoperiods. The LP animals showed an expansion of the peak phase of the PER1 and PER2 rhythm in the SCN as well as an extended behavioral active phase. In contrast, the SP animals did not show any compression of their active phase nor a change in the peak duration of PER1 or PER2 expression, compared to those in EP. The results suggest that the circadian system in the diurnal grass rats is less responsive when day-length gets short compared to when it gets longer. The depression-like behaviors were assessed using sweet solution preference (SSP) and forced swimming test (FST). Animals in the SP group showed decreased SSP and increased immobility time in FST as compared to the EP group, suggesting a depressive phenotype. The present study serves as the first step toward exploring the role that the circadian system plays in SAD using a diurnal rodent model.

Fibrinogen breakdown, long-lasting systemic fibrinolysis, and procoagulant activation during alteplase double-bolus regimen in acute myocardial infarction.

Recent clinical studies comparing accelerated versus bolus administration of alteplase tissue plasminogen activator (t-PA) suggest similar thrombolytic efficacy, but reveal higher bleeding complications among older patients during the double-bolus regimen. The objective of the present study was to characterize the hemostatic profile of t-PA administered as double-bolus doses of 50 mg, at intervals of 30 minutes. Among 50 patients with acute myocardial infarction treated by double-bolus t-PA thrombolysis, coagulation and fibrinolysis parameters, as well as t-PA levels, were monitored. Monitored t-PA levels peaked at 5 and 35 minutes and were detectable within the therapeutic range even after 90 minutes. Marked systemic fibrinolytic activation was indicated by 75% depletion of both plasminogen and fibrinogen, as well as by 19-fold and 300-fold increases of fibrin degradation and fibrinogen degradation products. Plasminogen-activator inhibitor activity was completely suppressed. Pronounced procoagulant activation was reflected by a 3.4-fold increase of both factor XIIa and prothrombin fragment 1+2, and by a threefold increase of thrombin-antithrombin complex. Independent of t-PA weight dosage, fibrinolytic activation was more pronounced among older patients (> or = 63 years). We conclude that t-PA after bolus administration has a long half-life. Double-bolus regimen leads to a long-lasting systemic fibrinolytic state, which is even more remarkable among older patients--a fact that may explain the higher bleeding complications reported for this age group.

Q fever vaccines for animals.

The results of different workgroups and those obtained in own investigations with Q fever vaccines for cattle and sheep are reviewed and discussed. In field trials Coxiella (C.) burnetii vaccines of inactivated whole cells (WC) in phase (ph) I as well as WC ph II vaccines prevented infections of cows exposed to naturally infected environments, provided they were vaccinated as noninfected calves. To monitor calves for this purpose the sensitive ELISA has superseded the complement fixation test (CF). WC ph I vaccines failed to prevent shedding by uninfected cattle and sheep which were vaccinated and subsequently challenged by parenteral inoculation with viable organisms, but reduced shedding, and prevented pathological lesions and clinical symptoms. The results obtained in field trials with a commercially available vaccine consisting of killed WC ph II of C. burnetii and inactivated WC of Chlamydia psittaci indicated that vaccination had significantly improved fertility in vaccinated herds. However, the mechanism of protection is unclear because the function of the chlamydial component in this vaccine is not yet defined. Cattle given this vaccine can be distinguished from naturally infected cattle because the former produce predominantly non-complement-binding IgG2, detectable by ELISA. This vaccine frequently causes undesirable local reactions. Antigens of C. burnetii (strain "Frankfurt", ph II) prepared by propagation in cell cultures and successive purification by guanidinium hydrochloride- and chloroform/methanol-extraction (CMR), as well as a major protein extracted from these CMR preparations represent potential vaccine candidates without such side effects.