Resiniferatoxin and Tetrodotoxin Induced NPY and TH Immunoreactivity Changes Within the Paracervical Ganglion Neurons Supplying the Urinary Bladder

Both resiniferatoxin (RTX) and tetrodotoxin (TTX) have been reported to be effective in several urinary bladder dysfunction clinical trials. The aim of this study was to establish the effect of intravesical administration of RTX and TTX on neuropeptides Y (NPY) and tyrosine hydroxylase (TH) relationship in the paracervical ganglion (PCG) neurons supplying the urinary bladder in the pig. TH is an enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine (DOPA) and is used as a marker of catecholaminergic neurons. NPY augments the vasoconstrictor effects of noradrenergic neurons, and is involved in pathophysiological processes as a neuromodulator. To identify the PCG neurons supplying urinary bladder Fast Blue (FB) was injected into the bladder wall prior to intravesical RTX or TTX administration. Consequent application of immunocytochemical methods revealed that in control group 64.08 % of FB-positive PCG neurons contain NPY and 4.25 % TH. Intravesical infusion of RTX resulted upregulation of the NPY-IR neurons to 82.97 % and TH-IR to 43.78 %. Also administration of TTX induced further increase number of TH-IR neurons to 77.49 % but induced decrease number of NPY-IR neurons to 57.45 %. Both neurotoxins affect chemical coding of the PCG neural somata supplying urinary bladder, but the effects of their action are different. This results shed light on possible involvement of RTX and TTX on curing tissue, and potentially could help us to broaden our neurourological armamentarium.     

Enhanced Expression of Plasminogen Activators and Inhibitor in the Healing of Tympanic Membrane Perforation in Rats

The significance of plasminogen activation during the tympanic membrane (TM) healing is known mainly from studies performed on knock-out mice. In the previous study, we reported activation of genes coding proteins of plasminogen activation and inhibition system in rat’s TM perforation healing. The aim of the present study was the evaluation of protein products expressed by these genes and their tissue distribution using Western blotting and immunofluorescent method, respectively, during 10-day observation period after injury. Otomicroscopical and histological evaluation were employed to assess the healing process. The expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) were significantly upregulated in the proliferation phase, with subsequent gradual attenuation during remodeling phase of healing process, when keratinocyte migration was weakening. The expression of plasminogen activator inhibitor type 1 (PAI-1) also showed the highest levels during the proliferation phase. The increase of tissue plasminogen activator (tPA) expression was observed during the whole observation period, with the highest activity during the remodeling phase. Immunofluorescence of these proteins was present mainly in migrating epithelium. Our study found that plasminogen activation (uPA, uPAR, tPA) and inhibitory (PAI-1) molecules form a well-structured regulatory system of the epithelial migration that is critical to the healing of TM after its perforation.

     

Depression during the COVID-19 pandemic among people living with HIV: Are low HIV/AIDS stigma and high perceived emotional support protective resources?

This study has two objectives: first, to examine changes in depressive symptoms among people living with HIV (PLWH) during the COVID-19 pandemic and, second, to verify the role of HIV/AIDS stigma and perceived emotional support (PES) in the heterogeneity of these changes. The participants were 392 people with a medical diagnosis of HIV who have undergone antiretroviral therapy. Depression was measured at three time points with 6-month intervals using the Centre for Epidemiological Studies Depression Scale (CES-D). PES was evaluated with the Berlin Social Support Scales, and HIV/AIDS-related stigma was assessed with the Berger HIV Stigma Scale. Latent growth class modelling identified four trajectories of depression over the study period: three stable (very high, high, and very low) and one increasing. Both the very high and high stable trajectories had baseline values above the CES-D cut-off point for depression, suggesting that 57.6% of the sample was likely to be diagnosed with depression. After controlling for sociodemographic and clinical variables, stigma and PES were found to be significant covariates of the obtained trajectories; however, they did not protect against an increase in depression symptoms. There was no overall increase in depression symptoms among the PLWH participants during the pandemic, but this change in depression symptoms was heterogeneous. We observed the potential development of depression in initially well-functioning individuals despite their personal resources differing only slightly from those who remained resilient.