Cauda equina movement during the Valsalva maneuver in two patients with Lumbar spinal canal stenosis

Lumbar spinal canal stenosis (LSS) is a common spinal disorder among older people. Some LSS patients say that their pain worsens when they lift heavy objects. The Valsalva maneuver is the optimal breathing pattern for producing maximal force. Herein, we present two cases of LSS where the movement of the cauda equina was observed during the Valsalva maneuver.Case Summary: Case 1: A 74-year-old female with a history of LSS presented to our Department of Urology with frequent urination. The patient was diagnosed as having uterine and bladder prolapse. Pelvic cine MRI scan was conducted for detailed evaluation. While the Valsalva maneuver was performed to diagnose pelvic organ prolapses, we observed movement of the cauda equina. Spine MRI and CT, performed one year before presentation, showed severe LSS due to degenerative spondylolisthesis. Case 2: A 73-year-old male underwent radical prostatectomy for prostate cancer. A follow-up cine MRI to confirm urethrorrhea showed the cauda equina moving during the Valsalva maneuver. Moderate LSS due to degenerative spondylolisthesis was retrospectively found on abdominal CT performed before prostatectomy. Conclusion: The findings of our report suggest that movement of the cauda equina during the Valsalva maneuver may be implicated in LSS.     

Stimulation of nonspecific resistance to infection induced by muramyl dipeptide analogs substituted in the gamma-carboxyl group and evaluation of N alpha-muramyl dipeptide-N epsilon-stearoyllysine.

Stimulation of resistance to infection induced by the analogs of muramyl dipeptide (MDP) having substituted functions in the gamma-carboxyl group of D-isoglutamyl residue was examined in experimental Escherichia coli infections in mice. An MDP analog which is an efficient strengthener of resistance to infection, N alpha-MDP-N epsilon-stearoyllysine [MDP-Lys(L18)], was selected through the comparative assessment of a number of compounds in three categories: (i) gamma-alkylamides, (ii) gamma-esters, and (iii) N alpha-MDP-N epsilon-acyllysine derivatives. Furthermore, the antiinfectious activity of MDP-Lys(L18) was evaluated bacteriologically in comparison with that of MDP. The effect of MDP-Lys(L18) on the susceptibility of mice to infections with various species of microorganisms was studied. Protective activity was greatest against E. coli and staphylococcal infections, considerable against Pseudomonas and Candida infections, and least against Klebsiella infection. The effects of bacterial inoculum size and MDP treatment timing, dose, and route of administration on protective activity were studied. The efficacy of MDP-Lys(L18) in protection tests was demonstrated for all administration routes, even the oral. Its high potency was confirmed by the smaller influence of inoculum size and particularly small value of the minimum dosage required for inducing protective activity. A decrease in bacterial survival was observed in the blood and organs of mice treated with the analog and infected with E. coli. The following two useful effects were obtained: the synergistic effect of glycopeptide and chemotherapeutic agents and the stimulation of resistance to infection in animals immunocompromised by cyclophosphamide treatment.     

Assessment of Effects of Air Pollution on Daily Outpatient Visits using the Air Quality Index

Background

The air quality index (AQI) is widely used to characterize the quality of ambient air. Chinese cities officially report the AQI on a daily basis. To assess the possible effects of air pollution on daily outpatient visits, we examined the association between AQI and the daily outpatient count.

Methods

Daily data on outpatient visits to each clinical department were collected from the Z county hospital of Datong City, China. The collection period was between 5 April and 30 June, 2012. Daily AQI data and meteorological information were simultaneously recorded. We compared outpatient counts between the index days and comparison days, and calculated Pearson’s product moment correlation coefficient between outpatient counts and AQI levels.

Results

The average AQI level for index days was significantly higher than that for comparison days. No significant difference was observed in temperature or relative humidity between index days and comparison days. The outpatient counts for pediatrics were significantly higher on index days than on comparison days, and no significant difference was noted in other clinical departments. The outpatient counts for pediatrics positively correlated with the AQI level, and no correlation was noted in other clinical departments.

Conclusion

The present study assessed the association between daily outpatient visits and air pollution using AQI. The results obtained suggest that air pollution could increase the outpatient count for pediatrics.     

Expression of cytoplasmic TFF2 is a marker of tumor metastasis and negative prognostic factor in gastric cancer

Trefoil factor family 2 (TFF2) is a small peptide constitutively expressed in the gastric mucosa, where it plays a protective role in restitution of gastric mucosa. TFF2 has also been shown to be expressed in some gastric cancers, but its role in tumor metastasis and patient prognosis has not been examined. In this study, we examined TFF2 expression at both the mRNA and protein levels and correlated these results with the clinicopathologic characteristics and prognosis of gastric cancer patients. Among the 144 curatively resected samples, 43 (30%) were positive for TFF2. TFF2 expression was preferentially observed in the infiltrating tumor cells sparing the superficial cells. Significantly increased expression of TFF2 was noted in large tumors of the diffuse type. An increased prevalence of TFF2 expression was also found in tumors with advanced T and N stage and in patients with lymphatic and venous invasion. Accordingly, patients with TFF2-expressing tumors had a significantly worse disease-free survival, and in multivariate analysis, this finding remained significant as an independent prognostic factor. Taken together, our results suggest that TFF2 expression may play a role in gastric cancer invasion and as such could be a useful target for therapeutic intervention.     

Metal ions induce bone-resorbing cytokine production through the redox pathway in synoviocytes and bone marrow macrophages

To evaluate the biological reactions to metal ions potentially released from prosthetic implants, we examined the ability of metal ions to produce bone-resorbing cytokines and the underlying mechanism using synoviocytes and bone marrow (BM) macrophages. The cells were incubated with NiCl(2), CoCl(2), CrCl(3) or Fe(2)(SO(4))(3) at optimal concentrations, which are detectable in joint fluid following total joint arthroplasty. The production of interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha were enhanced by all metal ions tested as determined by enzyme-linked immunosorbent assay. From the results of electrophoresis mobility shift assay, all metal ions enhanced the DNA-binding activity of nuclear factor kappaB (NF-kappaB), and p50-p65 heterodimers and p50 homodimers were the major subunits. These effects of the metal ions were considerably blocked by pyrrolidine dithiocarbamate (PDTC) known as a radical scavenger. An electron spin resonance study clearly demonstrated the ability of metal ions to generate activated oxygen species (AOS), especially hydroxyl radicals (*OH), which accounts for PDTC-blockade of metal ion-induced NF-kappaB activation and subsequent cytokine production. Taken together, our data raised the possibility that small amounts of metal ions released from prosthetic implants activate synoviocytes and BM macrophages through the AOS-mediated process (i.e. the redox pathway), and contribute to the initiation of osteolysis at the bone-implant interface.     

Colocalization of a carnosine-splitting enzyme,tissue carnosinase (CN2)/cytosolic non-specific dipeptidase 2 (CNDP2), with histidine decarboxylase in the tuberomammillary nucleus of the hypothalamus

Carnosine is a naturally occurring dipeptide (β-alanyl-l-histidine) present in mammalian tissues such as the brain and skeletal muscles. Carnosine is not only a radical scavenger but also a possible neurotransmitter-like molecule that regulates neuronal functions such as hypothalamic control of the autonomic nervous system. CN2 (CNDP2) is a cytosolic enzyme that can hydrolyze carnosine to yield l-histidine and β-alanine. In order to understand the functions of carnosine and CN2 in the brain, we have investigated the immunohistochemical localization of CN2 in the hypothalamus. CN2-immunoreactivity was highly concentrated in neuronal cells in the dorsal part of the tuberomammillary nucleus of the posterior hypothalamus. Since the tuberomammillary nucleus is the exclusive origin of histaminergic neurons, we further investigated whether CN2 is present in the histaminergic neurons. We found that CN2-immunoreactivity was colocalized with that of histidine decarboxylase, which is the key enzyme for histamine biosynthesis specifically expressed in the histaminergic neurons of the tuberomammillary nucleus. These results suggest that CN2 is highly expressed in the histaminergic neurons in the tuberomammillary nucleus, implying that it may supply histidine to histaminergic neurons for histamine synthesis.     

Alpha 1-adrenoceptor-mediated phosphoinositide breakdown and inotropic response in rat left ventricular papillary muscles

alpha 1-Adrenoceptor stimulation of rat left ventricular papillary muscles by phenylephrine in the presence of propranolol resulted in rapid breakdown of phosphatidylinositol 4,5-bisphosphate (PI-4,5-P2) and a triphasic inotropic response in a concentration-dependent manner. The release of inositol trisphosphate (IP3) was maximum within 30 seconds and remained high for at least 30 minutes. The IP3 formation was associated with a rapid, but small, increase in contractile force followed by a transient decline in the contractility prior to the development of a sustained and more pronounced positive inotropic response. Inhibition of PI-4,5-P2 hydrolysis by the alpha 1-adrenergic antagonist prazosin or the PI-4,5-P2 phosphodiesterase inhibitor neomycin blocked all components of the inotropic responses. Combined addition of 2,3-diphosphoglyceric acid, a competitive inhibitor of IP3 phosphatase, with phenylephrine doubled the IP3 formation and potentiated the initial phases of inotropic responses but had no effect on the sustained positive inotropic response. Nifedipine and Mn2+ did not block the transient inotropic responses but inhibited the sustained positive inotropic response. alpha 1-Adrenoceptor stimulation resulted in restoration of slow responses in the high K+-depolarized muscles in the time course similar to that of the development in the sustained positive inotropic response. Addition of phorbol-12,13-dibutyrate alone or in combination with caffeine or A23187 failed to produce a sustained positive inotropic effect, but pretreatment with this phorbol ester (1-100 nM) for 30 minutes resulted in dose-dependent potentiation of alpha 1-adrenoceptor-mediated sustained positive inotropic effect associated with enhanced slow responses. These results suggest that the inotropic effects mediated by cardiac alpha 1-adrenoceptor stimulation occur through the phosphodiesteratic cleavage of PI-4,5-P2, such that IP3 may produce transient inotropic effects by mobilizing intracellular Ca2+, while diacylglycerol, along with cofactors that are also generated on alpha 1-adrenoceptor stimulation, may provoke a sustained positive inotropic effect by potentiating slow Ca2+ channels through activation of protein kinase C.     

K201 modulates excitation-contraction coupling and spontaneous Ca2+ release in normal adult rabbit ventricular cardiomyocytes

OBJECTIVES: The drug K201 (JTV-519) increases inotropy and suppresses arrhythmias in failing hearts, but the effects of K201 on normal hearts is unknown. METHODS: The effect of K201 on excitation-contraction (E-C) coupling in normal myocardium was studied by using voltage-clamp and intracellular Ca(2+) measurements in intact cells. Sarcoplasmic reticulum (SR) function was assessed using permeabilised cardiomyocytes. RESULTS: Acute application of <1 micromol/L K201 had no significant effect on E-C coupling. K201 at 1 micromol/L decreased Ca(2+) transient amplitude (to 83+/-7%) without affecting I(Ca,L) or the SR Ca(2+) content. At 3 micromol/L K201 caused a larger reduction of Ca(2+) transient amplitude (to 60+/-7%) with accompanying reductions in I(Ca,L) amplitude (to 66+/-8%) and SR Ca(2+) content (74+/-9%). Spontaneous SR Ca(2+) release during diastole was induced by increasing intracellular [Ca(2+)]. At 1 micromol/L K201 reduced the frequency of spontaneous Ca(2+) release. The effect of K201 on SR-mediated Ca(2+) waves and Ca(2+) sparks was examined in beta-escin-permeabilised cardiomyocytes by confocal microscopy. K201 (1 micromol/L) reduced the frequency and velocity of SR Ca(2+) waves despite no change in SR Ca(2+) content. At 3 micromol/L K201 completely abolished Ca(2+) waves and reduced the SR Ca(2+) content (to approximately 73%). K201 at 1 micromol/L reduced Ca(2+) spark amplitude and frequency. Assays specific to SR Ca(2+)-ATPase and RyR2 activity indicated that K201 inhibited both SR Ca(2+) uptake and release. CONCLUSIONS: K201 modifies E-C coupling in normal cardiomyocytes. A dual inhibitory action on SERCA and RyR2 explains the ability of K201 to suppress spontaneous diastolic Ca(2+) release during Ca(2+) overload without significantly affecting Ca(2+) transient amplitude.