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Many studies have indicated that the risk of cognitive impairment is higher in patients with rheumatoid arthritis (RA). Additionally, patients with RA may have a lower incidence of cognitive impairment with long-term use of ibuprofen. This study was aimed at investigating the impacts of RA on memory function and the mechanisms that ibuprofen may exhibit to improve memory function in rats with collagen-induced arthritis (CIA). Ibuprofen (30 mg/kg) was given twice daily to CIA rats for two weeks starting from Day 18 following the first immunization. Memory function was measured by the Morris water maze (MWM) test and long-term potentiation (LTP). The proinflammatory cytokine levels and downstream signaling pathways, including mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB), were examined. Furthermore, the glutamatergic system, including glutamate transporters/receptors and brain extracellular levels of glutamate, was investigated. The results showed that the impaired learning memory in CIA rats, examined by the MWM test and LTP, can be ameliorated by ibuprofen treatment. Along with the improvement in memory deficits, ibuprofen attenuated both neuroinflammation and the associated elevated levels of phosphorylated p38, JNK, and p65 in the hippocampus of CIA rats. In addition, the decreased excitatory amino acid transporter 2 level, the increased extracellular glutamate, and the upregulated hippocampal NMDA receptor 2B of CIA rats were all normalized by ibuprofen treatment. These findings suggest that the effect of ibuprofen on the memory improvement in CIA rats is associated with the normalization of the activated MAPK and NF-κB pathways and the aberrant glutamatergic system., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The objective of this study was to evaluate the effects of prior-infection and repeated vaccination on post-vaccination antibody titers., Methods: A(H1N1)pdm09 strain was included in 2009 pandemic monovalent, 2010-2011, and 2011-2012 trivalent influenza vaccines (MIVpdm09, TIV10/11, TIV11/12) in Taiwan. During the 2011-2012 influenza season, we conducted a prospective sero-epidemiological cohort study among schoolchildren from grades 1 - 6 in the two elementary schools in Taipei with documented A(H1N1)pdm09 vaccination records since 2009. Serum samples were collected at pre-vaccination, 1-month, and 4-months post-vaccination (T1, T2, T3). Anti-A(H1N1)pdm09 hemagglutination inhibition titers (HI-Ab-titers) were examined. We also investigated the impact of four vaccination histories [(1) no previous vaccination (None), (2) vaccinated in 2009-2010 season (09v), (3) vaccinated in 2010-2011 season (10v), and (4) vaccinated consecutively in 2009-2010 and 2010-2011 seasons (09v + 10v)] and pre-vaccination HI-Ab levels on post-vaccination HI-Ab responses as well as adjusted vaccine effectiveness (aVE) against serologically-defined infection from T2 to T3., Results: TIV11/12 had zero serious adverse events reported. A(H1N1)pdm09 strain in TIV11/12 elicited seroprotective Ab-titers in 98% of children and showed promising protection (aVE: 70.3% [95% confidence interval (CI): 51.0-82.1%]). Previously unvaccinated but infected children had a 3.96 times higher T2 geometric mean titer (T2-GMT) of HI-Ab than those naïve to A(H1N1)pdm09 (GMT [95% CI]: 1039.7[585.3-1845.9] vs. 262.5[65.9-1045], p = 0.046). Previously vaccinated children with seroprotective T1-Ab-titers had a higher T2-GMT and a greater aVE than those with non-seroprotective T1-Ab-titers. Repeatedly vaccinated children had lower T2-GMT than those receiving primary doses of TIV11/12. However, after controlling prior infection and T1-Ab-titers, differences in T2-GMT among the four vaccination histories became insignificant (p = 0.16)., Conclusion: This study supports the implementation of annual mass-vaccination with A(H1N1)pdm09 in schoolchildren for three consecutive influenza seasons when vaccine and circulating strains were well matched, and found that prior infection and pre-vaccination HI-Ab levels positively impacted post-vaccination HI-Ab responses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Mood disorders are a severe health burden but molecular mechanisms underlying mood dysfunction remain poorly understood. Here, we show that wild-type p53-induced phosphatase 1 (Wip1) negatively responds to the stress-induced negative mood-related behaviors. Specifically, we show that Wip1 protein but not its mRNA level was downregulated in the hippocampus but not in the neocortex after 4 weeks of chronic unpredictable mild stress (CUMS) in mice. Moreover, the CUMS-responsive WIP1 downregulation in the hippocampus was restored by chronic treatment of fluoxetine (i.p. 20 mg/kg) along with the CUMS procedure. In addition, Wip1 knockout mice displayed decreased exploratory behaviors as well as increased anxiety-like and depression-like behaviors in mice without impaired motor activities under the non-CUMS condition. Furthermore, the Wip1 deficiency-responsive anxiety-like but not depression-like behaviors were further elevated in mice under CUMS. Although limitations like male-alone sampling and multiply behavioral testing exist, the present study suggests a potential protective function of Wip1 in mood stabilization., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

Recent findings from our lab indicate that metabotropic glutamate receptor (mGluR) activation elicits eating, and the goal of the current study was to specify whether the lateral hypothalamus (LH) is the actual brain site mediating this effect. To examine this issue we injected the selective mGluR group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) unilaterally into the LH and surrounding regions (n=5-8 subjects/brain site) of satiated adult male Sprague-Dawley rats and measured elicited feeding. We determined that 1.0 nmol elicited food intake only within the LH. Increasing the dose to 10 or 25 nmol produced a more sustained effect in the LH, and also elicited eating in several other brain sites. These results, demonstrating that the LH mediates the eating elicited by low doses of DHPG, suggest that the LH may contain mGluR whose activation can produce eating behavior., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A 74-year-old woman presented with a 3-day history of fever and left flank pain. The imaging study revealed a huge complicated cyst in the left kidney. The cyst had a mass effect to the abdomen. We performed laparoscopic renal cyst unroofing. The histopathologic examination disclosed renal tuberculosis of the cyst wall and cystic fluid. Renal tuberculosis is not uncommon; however, renal tuberculosis presenting as a renal cyst is very rare., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Denbinobin (5-hydroxy-3,7-dimethoxy- 1,4-phenanthraquinone), a biologically active chemical isolated from Ephemerantha lonchophylla, has been demonstrated to display anti-cancer activity. Breast cancer is the leading cause of female mortality, and the high mortality is mainly attributable to metastasis. Src kinase activity is elevated in many human cancers, including breast cancer, and is often associated with aggressive disease. In the present study, we examined the anti-metastatic effects of denbinobin through decreasing Src kinase activity in human and mouse breast cancer cells. Denbinobin caused significant block of Src kinase activity in both human and mouse breast cancer cells. Moreover, phosphorylation of the signaling molecules focal adhesion kinase, Crk-associated substrate and paxillin downstream of Src was also inhibited by denbinobin. Furthermore, denbinobin inhibited the in vitro migration, invasion and in vivo metastasis of breast cancers in a mouse metastatic model. The denbinobin-treated group showed a significant reduction in tumor metastasis, orthrotopic tumor volume, and spleen enlargement compared to the control group. In addition, transfection of breast cancer cells with a plasmid coding for a constitutively active Src prevented the denbinobin-mediated phosphorylation of Src and downstream molecules and cell migration. Our findings provide evidences that denbinobin inhibits Src-mediated signaling pathways involved in controlling breast cancer migration and metastasis, suggesting that it has therapeutic potential in breast cancer treatment., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Transurethral resection of bladder tumors is performed for the treatment of bladder cancer. We describe our surgical technique for transurethral resection of bladder tumors. It is easy to control the tissue depth of resection using the lateral resecting portion of the conventional right-angle loop electrode., Technical Considerations: Since April 2006, we have performed this technique on 57 consecutive lesions in 37 patients. The surgeon rotates the resectoscope and uses the lateral resecting portion of the right-angle loop electrode to control the tissue depth during transurethral resection. The tissue depth of resection can be precisely controlled by the surgeon using this technique. No bladder perforation or uncontrollable bleeding was observed., Conclusions: The described surgical tip is a safe technique to prevent bladder perforation during transurethral resection of bladder tumors.

Studies on chemoprevention of cancer are generating increasing interest. The anti-neoplastic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) involves cyclooxygenase (COX)-dependent and COX-independent mechanisms. Evidence suggests that mitogen-activated protein kinases (MAPKs) may mediate apoptotic signaling induced by anti-neoplastic agents. While many reports have revealed the existence of MAPK activation in apoptosis induced by various stimuli, the signaling transduction pathways used by NSAIDs to trigger apoptosis in human renal cell carcinoma (RCC) remain largely unknown. Treatment of RCC 786-O cells with indomethacin resulted in growth regression and apoptosis. Caspase-dependent apoptosis was evidenced by the detection of enzymatic activities of caspase-3, caspase-6, and caspase-9 and suppression of toxicity using a caspase inhibitor. Indomethacin treatment was associated with increased expression of glucose-regulated protein 78 (GRP78) and C/EBP homologus protein (CHOP) and activation of ATF-6, characteristics of endoplasmic reticulum stress. In addition, the concomitant induction of peroxisome proliferator-activated receptor (PPAR), especially PPAR-beta, was apparent in treated cells. Western blotting revealed the activation of extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun N-terminal kinase (JNK) with indomethacin treatment. Selective inhibitors of ERK, p38 MAPK, and JNK suppressed the induction of GRP78, CHOP, and PPAR-beta, attenuated indomethacin-induced cytotoxicity and reduced increased caspase activity. LY294002, a phosphoinositide-3 kinase (PI3K)/AKT inhibitor, and Trolox, an antioxidant, suppressed indomethacin-induced cytotoxicity and caspase activation. Furthermore, Trolox attenuated indomethacin-induced increased phosphorylation in ERK, p38 MAPK, JNK, and AKT. In conclusion, our findings establish a mechanistic link between the oxidative stress, PI3K/AKT pathway, MAPK pathway and indomethacin-induced cellular alterations and apoptosis in 786-O cells.

Objectives: To determine the risk factors for postprostatectomy inguinal hernia development., Methods: From January 1998 to June 2004, we investigated the medical records of 201 consecutive patients who had undergone radical retropubic prostatectomy. Postoperatively, 25 (12.4%) of 201 patients developed an inguinal hernia. The preoperative factors, including age, presence of diabetes mellitus, smoking, and previous unilateral hernioplasty, of this group were compared with those of the 176 patients who did not develop an inguinal hernia. The postoperative parameters, including pathologic stage, specimen weight, adjuvant radiotherapy, and postoperative wound-related problems, were compared between the two groups., Results: The patients who had undergone previous unilateral hernioplasty developed a groin hernia after prostatectomy more frequently than those who did not (P = 0.001, Fisher's exact test). Additionally, once a postoperative wound-related problem occurred, the incidence of postprostatectomy groin hernia increased substantially (P = 0.025, logistic regression analysis)., Conclusions: We suggest routine repair of the contralateral groin for patients who have undergone previous unilateral hernioplasty. Prevention of wound-related problems appears to decrease the incidence of postprostatectomy groin hernias.

A 12F Foley catheter is introduced retrogradely through the urethral stump and situated with the balloon partially inflated in the bulbous urethra after radical retropubic prostatectomy. This maneuver provides clear visualization of the urethral stump through gentle traction of the Foley catheter.

Whole-cell patch-clamp recordings obtained from 36 hypothalamic supraoptic nucleus neurons in explant preparations evaluated a role for GABA(B) receptors in modulating postsynaptic inhibitory and excitatory currents evoked by electrical stimulation in the organum vasculosum of the lamina terminalis. At a holding current of -65 mV, application of baclofen (1-10 microM) induced a dose-dependent reduction in the amplitude of pharmacologically isolated inhibitory and excitatory postsynaptic currents, converted paired-pulse depression in inhibitory postsynaptic currents to paired-pulse facilitation, and enhanced paired-pulse ratios for excitatory postsynaptic currents. In media containing 2-hydroxysaclofen (200-400 microM), baclofen-associated events were blocked and paired-pulse depression in evoked inhibitory postsynaptic currents was abolished. In addition, a progressive increase in the amplitude of inhibitory postsynaptic currents implied that GABA was endogenously active at presynaptic GABA(B) receptors. In contrast, no paired-pulse depression was observed for inhibitory postsynaptic currents evoked in six non-magnocellular neurons. Neither baclofen nor 2-hydroxysaclofen altered holding currents or input resistances in supraoptic neurons, or altered the kinetics of the evoked responses.These observations imply that the terminals of both inhibitory (GABAergic) and excitatory (glutamatergic) afferents to supraoptic nucleus neurons from organum vasculosum lamina terminalis neurons are subject to modulation by presynaptic GABA(B) receptors, and that this modulation is preferentially directed to the inhibitory inputs.

This study investigated the origin of a dopaminergic innervation of the hypothalamic supraoptic nucleus. In pentobarbital-anaesthetized male Long-Evans rats, a transpharyngeal approach was used to inject a retrograde tracer, rhodamine latex microspheres, into the supraoptic nucleus. After 13-26 h survival under anaesthesia, animals were perfused transcardially, the brain sectioned and processed for tyrosine hydroxylase immunofluorescence, a marker for hypothalamic dopaminergic neurons. In six cases with injections restricted to the supraoptic nucleus, rhodamine-labelled microspheres were observed in a population of tyrosine hydroxylase-positive neurons located in the A15 cells below the anterior commissure (A15 dorsal) and above the optic chiasm (A15 ventral), and the dorsal and lateral periventricular A14 cell group. Occasional double-labelled cells were seen in the medial and lateral hypothalamus and bed nucleus of the stria terminalis, but rarely in other known dopaminergic cell groups, notably the ventral tegmental area (A10), zona incerta (A13) and substantia nigra. In support of a role for dopamine in neurohypophysial regulation, these observations indicate that the major dopaminergic input to magnocellular neurons in the hypothalamic supraoptic nucleus is derived from a relatively sparse population of neurons located in the A14 and A15 cell groups.

Corticostriatal neurons linking the prefrontal cortex and the nucleus accumbens connect the terminal fields of the ascending mesotelencephalic dopamine neurons and may potentially mediate cortical dopaminergic modulation of subcortical dopamine transmission. In our attempt to develop a brain slice preparation that maximally preserves this prefrontal accumbens pathway for in vitro electrophysiological studies, knowledge of the complete course of its projection is critical. Microinjection of biotin-dextran amine as an anterograde tracer into the prefrontal cortex revealed the following in the coronal, sagittal and oblique planes of rat brain. (1) Axonal fibers from the rostral prelimbic cortex projected at an angle of approximately 60 degrees to the horizontal plane through the infralimbic region and mainly entered the rostromedial accumbens. Some also chose a ventral route to enter the "core" of the accumbens. (2) From the central ventral prelimbic regions, axons spread out diffusely and descended to the dorsal accumbens. They then entered throughout the rostral-caudal "shell" of the nucleus accumbens. (3) From the caudal prelimbic region of the prefrontal cortex, axonal fibers descended approximately 10 degrees to the coronal plane and entered the dorsal nucleus accumbens and the caudate nucleus. The denser caudate-projecting fibers gave rise to collaterals that entered the accumbens "core". These results suggest that brain slices that preserve the rostral prelimbic-medial accumbens pathway can be obtained by an oblique (approximately 60 degrees) cut, whereas preservation of the caudal prefrontal-accumbens neurons necessitates a 10 degrees cut. Finally, in whole-cell patch-clamp recordings of accumbens neurons in such slices, orthodromically evoked excitatory postsynaptic potentials to deep layer prefrontal cortical stimulation were observed, thus confirming the functional preservation of portions of this prefrontal cortex nucleus accumbens pathway.

1. Dehydrozingeronolol (DZPN; 0.1, 0.5, 1.0 mg/kg, i.v.) produced a dose-dependent bradycardia response and a sustained pressor action in urethane-anesthetized normotensive rats. DZPN inhibited the tachycardia effects by (-)isoproterenol, but had no blocking effect on the arterial pressor responses induced by phenylephrine. 2. In in vitro study, DZPN antagonized (-)isoproterenol-induced positive chronotropic effects in guinea-pig isolated right atria and relaxation responses in rat isolated uterus horns. 3. DZPN causes mild direct cardiac depression at high concentrations without intrinsic sympathomimetic activity (ISA). 4. The order of potency of beta-adrenoceptor antagonists in competing for the [3H]dihydroalprenolol binding sites was (-)propranolol >> DZPN > or = atenolol.

We have performed penile vein ligation on 35 patients with venogenic impotence from July 1989 to December 1991. The criteria for surgery were (1) age less than 60 years; (2) negative vasoactive agent intracavernous injection but normal penile arterial function, and (3) abnormal venous leakage documented by dynamic infusion cavernosometry and cavernosography. The procedure in venous ligation is excision of the deep dorsal vein from coronary sulcus to pubic arch, and ligation of cavernous veins after identification. The average follow-up was 27.5 months (range 12-37 months) for 30 patients. The 2 patients who revealed no erection at all immediately after operation had dense adhesion of penile hilar region caused in one case by severe pelvic trauma and in the other by pubic bone fracture. Twenty-eight (93.3%) patients were found to sustain excellent erection within 3 months postoperatively. However, only 12 (40.0%) patients sustained spontaneous erection at long-term follow-up, while another 7 (23.3%) responded to intracavernous injection. It is worth mentioning that tortuous and marked dilation of the deep dorsal vein and/or cavernous veins were found intraoperatively in 6 patients who were observed to have excellent erections postoperatively. Inadequate elimination of the leakage veins, especially crural veins, is the most likely factor in those who had a recurrence of erectile dysfunction. However, the corpus cavernosum, particularly a myopathic condition or inadequate neurotransmitters, also plays an important role. Complications included shortness of penis (3 patients), penile deviation (3), numbness of glans penis (4) and wound infection (1).(ABSTRACT TRUNCATED AT 250 WORDS)

Repeated intracavernous injections in healthy monkeys with 2 kinds of vasoactive agents [papaverine and prostaglandin E1 (PGE1) 3 monkeys each] and normal saline (2 monkeys) were conducted in this study. The purpose was to observe the effect of long-term injection on histopathological changes of the cavernous tissue, as well as the change in drug sensitivity (dosage dependence). Different dosages of the same volume (double, single and half dose) of these 3 agents were injected, twice weekly, 10 times alternatively, with rigidity and maintenance of erection recorded. After long-term injection (papaverine group: 37, 60, 60 times; PGE1 group: 26, 60, 60 times; normal saline group: 60, 60 times), all monkeys were sacrificed and the penises were collected for light-microscopic (LM) and electron-microscopic (EM) examinations. Dose-dependent response with reversed drug sensitivity was found in the papaverine group, but only elongation to tumescence was found in the PGE1 group, even with double dosage (probably because of scarce PGE1 receptors in monkey's penile tissue). Histopathologically, mild to moderate fibrotic changes and distortion of normal architecture were predominant findings in LM while aggregation of mitochondria, irregular shape or atrophy of cells were obvious in EM observation in the papaverine group. On the other hand, limited fibrosis with preservation of corpora cavernosa and hypertrophy of smooth muscle were noted in the PGE1 group. This study indicated that less histopathological change occurred in the PGE1 group after long-term intracavernous injection.

The integrative role of the nucleus accumbens and subpallidal area in relaying hippocampal signals to the mesencephalic locomotor region in the brainstem was investigated electrophysiologically in urethan-anaesthetized rats. A behavioural study of the functional connections was also performed in freely moving rats. In the electrophysiological experiments, subpallidal output neurons to the pedunculopontine nucleus and the adjacent ventral gray were first identified by their antidromic responses to electrical stimulation of the pedunculopontine nucleus. Hippocampal stimulation was then shown to inhibit orthodromically some of these subpallidal neurons. The inhibitory response was attenuated following microinjection of a dopamine D2 agonist (LY 171555), but not a D1 agonist (SKF 38393), into the accumbens. This suggests that signal transmission from the hippocampus to the subpallidal output neurons to the pedunculopontine nucleus is modulated by a D2 receptor-mediated mechanism in the nucleus accumbens. Injections of N-methyl-D-aspartate into the ventral subiculum of the hippocampus resulted in a threefold increase in locomotor responses. Injection of a D2 agonist into the accumbens reduced the hyperkinetic response dose-dependently and suggests that D2 receptors regulate locomotor responses initiated by the hippocampal-accumbens pathway. Injection of nipecotic acid, a GABA uptake inhibitor, into the subpallidal area or of procaine, a neural transmission blocker, into the region of the pedunculopontine nucleus, also reduced significantly the hippocampal-induced hyperkinetic response. These results provide evidence of limbic (e.g. hippocampus) influences on locomotor activity by way of nucleus accumbens-subpallidal-pedunculopontine nucleus connections which may contribute to adaptive behaviour. Signal transmission from the hippocampus may be regulated by a dopamine D2 receptor mechanism in the accumbens, presumably mediated by the converging mesolimbic dopaminergic input from the ventral tegmental area.

The integrative role of the ventral striatum in transmitting signals from the hippocampus to the ventral pallidal and subpallidal areas was investigated in urethane-anaesthetized rats using an extracellular single-unit recording technique. Neurones of the nucleus accumbens were first activated by single-pulse stimulation of the ventral subiculum of the hippocampus. Further tests were made to investigate whether these accumbens neurones could be activated antidromically by stimulation of either the ventral pallidal or subpallidal areas. More than 4 times as many accumbens neurones, activated by hippocampal stimulation, responded antidromically to stimulation of subcommissural ventral pallidum than to stimulation of the sublenticular subpallidal area. This observation suggests that the hippocampus has preferential inputs to accumbens efferent neurones which project monosynaptically to the ventral pallidum. Spontaneously active neurones in the ventral pallidum and subpallidal area were inhibited by stimulation of the ventral subiculum of the hippocampus. These inhibitory responses were reduced when glutamic acid diethyl ester, a glutamate antagonist, was microinjected into the medial accumbens, apparently blocking the hippocampal-accumbens glutamatergic synapses to both the ventral pallidal-directed and the subpallidal-directed accumbens efferents. This evidence suggests that signals from the hippocampus reach ventral pallidal and subpallidal regions by way of the nucleus accumbens. The presence of a projection from ventral pallidal and subpallidal regions to the brainstem mesencephalic locomotor region further supports the hypothesis that limbic (e.g. hippocampus) can influence somatomotor activities by way of the nucleus accumbens and its efferent projection to ventral pallidal and subpallidal regions.