Full-Length Infectious Clones of Two New Isolates of Tomato Mosaic Virus Induce Distinct Symptoms Associated with Two Differential Amino Acid Residues in 128-kDa Protein.

In 2017, two new tomato mosaic virus (ToMV) isolates were collected from greenhouses in Buyeo, Chungcheongnam-do, South Korea. Full-length cDNAs of the new ToMV isolates were cloned into dual cauliflower mosaic virus 35S and T7 promoter-driven vectors, sequenced and their pathogenicities investigated. The nucleotide sequences of isolates GW1 (MH507165) and GW2 (MH507166) were 99% identical, resulting in only two amino acid differences in nonconserved region II and the helicase domain, Ile668Thr and Val834Ile. The two isolates were most closely related to a ToMV isolate from Taiwan (KJ207374). Isolate GW1 (Ile668, Val834) induced a systemic hypersensitive response in Nicotiana benthamiana compared with the isolate GW2, which a single residue substitution showed was due to Val834.

Allopurinol Protects against Ischemia/Reperfusion-Induced Injury in Rat Urinary Bladders.

Bladder ischemia-reperfusion (I/R) injury results in the generation of reactive oxygen species (ROS) and markedly elevates the risk of lower urinary tract symptoms (LUTS). Allopurinol is an inhibitor of xanthine oxidase (XO) and thus can serve as an antioxidant that reduces oxidative stress. Here, a rat model was used to assess the ability of allopurinol treatment to ameliorate the deleterious effects of urinary bladder I/R injury. I/R injury reduced the in vitro contractile responses of longitudinal bladder strips, elevated XO activity in the plasma and bladder tissue, increased the bladder levels of tumor necrosis factor-α (TNF-α), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase, reduced the bladder levels of extracellular regulated kinase (ERK), and decreased and increased the bladder levels of Bcl-2 and Bax, respectively. I/R injury also elevated lipid peroxidation in the bladder. Allopurinol treatment in the I/R injury was generated significantly ameliorating all I/R-induced changes. Moreover, an in situ fluorohistological approach also showed that allopurinol reduces the generation of intracellular superoxides enlarged by I/R injury. Together, the beneficial effects of allopurinol reducing ROS production may be mediated by normalizing the activity of the ERK, JNK, and Bax/Bcl-2 pathways and by controlling TNF-α expression.

Protective effect of N-acetylcysteine against ischemia/reperfusion injury in rat urinary bladders.

Ischemia/reperfusion (I/R) injury represents an important cause of bladder contractile dysfunction. One of the major causes leading to this dysfunction is thought to be reactive oxygen species formation. In this study, we investigated the potential benefit of N-acetylcysteine (NAC), a potent antioxidant that neutralizes free radicals, in a rat model of urinary bladder injury. NAC treatment rescues the reduction of contractile response to I/R injury in a dose-dependent manner. In addition, all levels of reactive oxygen species, lipid peroxidation, and NADPH-stimulated superoxide production in the I/R operation+NAC (I/R+NAC) group also decreased compared with a marked increase in the I/R operation+saline (I/R+S) group. Moreover, an in situ fluorohistological approach also showed that NAC reduces the generation of intracellular superoxides enlarged by I/R injury. Together, our findings suggest that NAC has a protective effect against the I/R-induced bladder contractile dysfunction via radical scavenging property.

Neuregulin 1 up-regulates the expression of nicotinic acetylcholine receptors through the ErbB2/ErbB3-PI3K-MAPK signaling cascade in adult autonomic ganglion neurons.

We investigated effects of Neuregulin 1 (NRG1) on the expression of nicotinic acetylcholine receptor (nAChR) in major pelvic ganglion (MPG) from adult rat. MPG neurons were found to express transcripts for type I and III NRG1s as well as α and ß-type epidermal growth factor (EGF)-like domains. Of the four ErbB receptor isoforms, ErbB1, ErbB2, and ErbB3 were expressed in MPG neurons. Treating MPG with NRG1ß significantly increased the transcript and protein level of the nAChR α3 and ß4 subunits. Consistent with these molecular data, nicotinic currents (I(ACh) ) were significantly up-regulated in NRG1ß-treated sympathetic and parasympathetic MPG neurons. In contrast, the type III NRG1 and the α form of the NRG1 failed to alter the I(ACh) . Inhibition of the ErbB2 tyrosine kinase completely abolished the effects of NRG1ß on the I(ACh) . Stimulation of the ErbB receptors by NRG1ß activated the phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK). Immunoblot analysis revealed that PI3K-mediated activation of Akt preceded Erk1/2 activation in NRG1ß-treated MPG neurons. Furthermore, specific PI3K inhibitors abrogated the phosphorylation of Erk1/2, while inhibition of MEK did not prevent the phosphorylation of Akt. Taken together, these findings suggest that NRG1 up-regulates nAChR expression via the ErbB2/ErbB3-PI3K-MAPK signaling cascade and may be involved in maintaining the ACh-mediated synaptic transmission in adult autonomic ganglia.

Changes in Urinary Symptoms and Tolerance due to Long-term Ureteral Double-J Stenting.

PURPOSE: Most studies have reported the effects of short-term double-J ureteral stenting on patient symptoms. We reviewed the changes in symptoms and the factors associated with tolerance due to long-term stenting. MATERIALS AND METHODS: We investigated 20 patients (mean age±SD, 58.3±11.8 years). The patients consisted of those with cervical cancer (n=12), retroperitoneal fibrosis (n=5), colon cancer (n=1), rectal cancer (n=1), and endometrial cancer (n=1). A questionnaire that included domains for urinary symptoms and quality of life (QoL) scores for evaluation of urinary symptoms (International Prostate Symptom Score, or IPSS), a 10-cm linear visual analogue scale (VAS) score rated from 0 (no pain) to 10 (unendurable pain) for tolerance, and uroflowmetry were performed at every replacement. RESULTS: Frequency and urgency on the storage symptom score, residual urine sensations, and intermittency on the voiding symptom score were significantly aggravated at the initial stenting (p<0.05), but the sum of the storage symptom score and urgency improved with time (p<0.05). The quality of life score and total IPSS score also changed significantly (p<0.05). However, although the QoL score and the total IPSS score after stenting were not decreased to less than before stenting, the QoL score was significantly decreased at 9 months (p<0.05), and the total IPSS score was significantly decreased at 12 months (p<0.05). CONCLUSIONS: The symptoms were acutely aggravated at first, but the results showed increased tolerance with time. Adaptation of the bladder and desensitization of the patients may be important factors in the increased tolerance.

Detrusor and blood pressure responses to dorsal penile nerve stimulation during hyperreflexic contraction of the bladder in patients with cervical cord injury.

OBJECTIVE: To investigate the immediate effect of dorsal penile nerve (DPN) stimulation on detrusor pressure (P(det)) and blood pressure during hyperreflexic contractions of the bladder in patients with cervical spinal cord injury (SCI). DESIGN: Blood pressure and P(det) monitoring during cystometry with and without DPN stimulation. SETTING: Urodynamic laboratory in a university hospital in Korea. PARTICIPANTS: Eight men (age range, 20-55y) with cervical SCI that was incurred from 4 months to 10 years before this study. INTERVENTION: During water cystometry, blood pressure was monitored with an intra-arterial catheter introduced percutaneously into the radial artery and was recorded simultaneously with the P(det). Blood pressure was also measured manually with an electronic blood pressure cuff. Electric stimulation was applied to the DPN by using surface electrodes each time a bladder contraction was detected. Stimulation intensity was twice the threshold of the pudendal-anal reflex. MAIN OUTCOME MEASURES: P(det), systolic blood pressure, and diastolic blood pressure. RESULTS: As P(det) increased, the blood pressure increased in all cases. All the reflex contractions of the bladder were effectively suppressed by DPN stimulation, and as the P(det) decreased during stimulation, radial arterial pressure also decreased immediately and significantly. CONCLUSIONS: DPN stimulation can decrease P(det) and the increased blood pressure associated with it.