Improvement of cognitive dysfunction by a novel phosphodiesterase type 5 inhibitor, Tadalafil.

There is substantial evidence for the modulatory role of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterases (PDEs) in memory and synaptic plasticity, and an increase in intracellular cGMP facilitates these processes. The present study was aimed at the neuropharmacological investigations of tadalafil (TAD 5, 10, and 20 mg/kg, p.o.) and further involvement of nitric oxide (NO)-cGMP in its effects. The effects of tadalafil and its combination with NG -nitro-L-arginine methyl ester (L-NAME) were investigated in scopolamine- and diabetes-induced cognitive dysfunction using elevated plus maze (EPM) and object recognition (ORT) tests. The results of EPM revealed that the scopolamine- and diabetes-induced learning and memory deficit was dose dependently attenuated after administration of TAD (TAD 10 and 20 mg/kg, p.o.) in both paradigms studied. Administration of L-NAME (20 mg/kg) aggravated scopolamine- and diabetes-induced learning and memory deficit. Co-administration of L-NAME (20 mg/kg) after TAD (20 mg/kg) produced significant increase in cognitive performance as compared to scopolamine- and diabetic- control group. This showed that L-NAME (20 mg/kg) aggravated scopolamine- and diabetes-induced learning and memory deficit was significantly reversed by TAD (20 mg/kg). The results of the present study revealed that tadalafil by inhibiting PDE5 possibly elevated the cGMP level that through a diversity of its substrates produced neuropharmacological effects in cognitive dysfunction.

Sensitivity of streamflow patterns to river regulation and climate change and its implications for ecological and environmental management.

Streamflow patterns support complex ecosystem functions and services. However, the direct impacts of flow regulation and climate change on patterns of streamflow are less studied. This study aims to analyse the sensitivity of streamflow patterns to the effects of flow regulation and climate change in the Goulburn-Broken catchment in Victoria, Australia. Daily streamflow was classified into low, medium, high, and overbank flow metrics using a statistical quantile-based approach. Trends and percent changes in streamflow metrics during the 1977-2018 period were analysed, and effects of change in rainfall, regulation, and flow diversion on streamflow patterns were predicted using a generalized additive model and path analysis. Low flows and medium flows increased by 26%, and high flows and overbank flows decreased by 31% during the period between 1977 and 2018. While current river regulation and flow diversion practices would dominate future change in magnitude, duration, and frequency of the streamflow, the timing of flow metrics would be dominated by variation in rainfall. These could bring a new ecological and environmental risk to the riverine ecosystem. It is recommended to increase the duration of high flows (90-120 days) and overbank flows (10-30 days) and the frequency of overbank flows to at least once every 1-2 years during wet periods to mitigate ecological and environmental risks of climate change and flow regulation in the Goulburn-Broken catchment.

Effects of change in streamflow patterns on water quality.

Streamflow patterns are closely linked with the quality of stream water, but they are often dealt separately. Due to this, the effects of change in streamflow patterns resulting from river regulation and flow diversion on stream water quality remain under-investigated. This study models change in water quality indicators including pollutants (total suspended solids and turbidity), nutrients (total nitrogen and phosphorus), dissolved oxygen, nitrogen (kjeldahl), pH, and salinity caused by the change in streamflow patterns under different scenarios of river regulation, flow diversion, and rainfall. The generalized additive model was used and the Goulburn-Broken catchment, Australia was chosen as the case study. It was found that concentrations of pollutants and nutrients increased by 38% while dissolved oxygen and nitrogen (kjeldahl) decreased by 35% during the period 1990-2018. These changes were associated with an average increase of 20% in low and medium flows, an average decline of 22% in high and overbank flows and a 15% decline in rainfall. Under the scenario of climate change, river regulation and flow diversion, the overbank flow patterns would mimic the effects of low and medium flows on the water quality indicators that would raise the concentration of pollutants, nutrients, and salinity by 19%. Restoration of high flows would decrease these concentrations by 28% relative to current concentrations, however, it would also reduce dissolved oxygen, nitrogen (kjeldahl), and pH. Effects of streamflow patterns on water quality have implications for environmental flow management, thus, this study recommends critical adjustments in low, medium, and high flows for improving water quality.