Veratridine modifies the TTX-resistant Na channels in rat vagal afferent neurons

A number of neurotoxins from venoms of invertebrates and plants are ligands for voltage-gated Na⁺ channels and are useful tools for studying Na⁺ channel function and structure. Using whole-cell recordings from vagal afferent nodose neurons, we studied neurotoxins that target Na⁺ channels. We asked whether Ts3 (an α-scorpion toxin) and/or veratridine (a lipid-soluble toxin), could modify the TTX-resistant Na⁺ current generated by vagal afferent nodose neurons. Nodose TTX-resistant current was not affected by Ts3, whereas Ts3 slowed inactivation of the current generated by TTX-sensitive current component. We found that veratridine inhibited the TTX-resistant Na⁺ currents on rat nodose neurons. Interestingly, veratridine-modified Na⁺ channels developed a persistent current that accounted for the large tail current observed. We propose that veratridine modifies TTX-resistant Na⁺ channels through a mechanism distinct from its actions on other voltage-gated Na⁺ channels.     

Preoperative uracil, tegafur, and concomitant radiotherapy in operable rectal cancer: a phase II multicenter study with 3 years' follow-Up.

PURPOSE: To assess tolerance and efficacy of preoperative treatment with uracil/tegafur and radiotherapy (RT) followed by surgery and postoperative flurouracil (FU)/leucovorin (LV) in patients with rectal cancer. PATIENTS AND METHODS: Patients (n = 94) with potentially resectable tumors, ultrasound at stages T2N+ (n = 4), T3 (n = 77), T4 (n = 13) were treated with UFT (400 mg/m2/d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Patients underwent surgery 5 to 6 weeks later followed by four cycles of FU/LV. Primary end points included downstaging, pathologic responses, and sphincter-preserving surgery. Secondary end points were recurrence-free survival and overall survival. RESULTS: All patients received the full RT dose. Fifteen patients (16%) needed UFT dose reduction. Preoperative G3+ toxicities included diarrhea (14%), leukopenia (1%), thrombocytopenia (1%), and nausea (4%). The downstaging rate was 54%, pathologic complete response (pCR) was 9% and, in an additional 23%, there were only residual microscopic foci. When cellular viability criteria were taken into account, the pCR was 15%. From 43 patients with abdominoperineal resection indication, 11 (25%) had sphincter-preserving surgery performed. Postoperative scheduled chemotherapy dose was not administered to 24% of patients because of G3+ toxicity (diarrhea, 8%; mucositis, 9%; and leukopenia, 7%). Patients with downstaging had significantly higher survival and recurrence-free survival rates than those without. At 3 years, actuarial patterns of failure were pelvic, 5% and distant, 11%. OS was 75%. CONCLUSION: UFT combined with RT is safe and effective. In resectable rectal cancer, if preoperative treatment is considered, this approach can be an option.     

Camino intracranial pressure monitor: prospective study of accuracy and complications

OBJECTIVES: The fibreoptic device is a type of intracranial pressure monitor which seems to offer certain advantages over conventional monitoring systems. This study was undertaken to analyse the accuracy, drift characteristics, and complications of the Camino fibreoptic device. METHODS: One hundred and eight Camino intracranial pressure (ICP) devices, in their three modalities, were implanted during 1997. The most frequent indication for monitoring was severe head injury due to road traffic accidents. RESULTS: Sixty eight probe tips were cultured; 13.2% of the cases had a positive culture without clinical signs of infection, and 2.9% had a positive culture with clinical signs of ventriculitis. The most common isolated pathogen was Staphylococcus epidermidis. All patients were under cephalosporin prophylaxis during monitoring. Haemorrhage rate in patients without coagulation disorders was 2.1% and 15.3% in patients with coagulation abnormalities. Drift characteristics were studied in 56 cases; there was no drifting from the values expected according to the manufacturer's specifications in 34 probes. There was no relation between direction of the drift and duration of placement, nor between drift and time. CONCLUSIONS: Although the complication and drift rates were similar to those reported elsewhere, there was no correlation between the direction of the drift and long term monitoring despite the fact that some published papers refer to overestimation of values with time with this type of device.     

Intraabdominal abscess rate after laparoscopic appendectomy

BACKGROUND: Studies suggest increased intraabdominal abscess (IA) rates following laparoscopic appendectomy (LA), especially for perforated appendicitis. Consequently, an open approach has been advocated. The aim of our study is to compare IA rates following LA performed by a laparoscopic surgery and a general surgical service within the same institution. METHODS: Data of LA patients treated at Los Angeles County-University of Southern California (LAC-USC) Medical Center between March 1992 and June 1997 were reviewed. The main outcome measure was postoperative IA. RESULTS: In all, 645 LA were reviewed. A total of 413 LA (285 acute, 61 gangrenous, 67 perforated appendicitis) were performed by three general surgical services (10 attendings). Ten abscesses occurred postoperatively (2.4%), 6 with perforated appendicitis. After the laparoscopic service was introduced, 232 standardized LA (126 acute, 46 gangrenous, 60 perforated) were performed by two attendings. One IA occurred (gangrenous appendicitis). The IA rate for perforated appendicitis was significantly lower on the laparoscopic service (P = 0.025). There was no difference in IA rates for acute and gangrenous appendicitis. There was no mortality in either group. CONCLUSION: IA rate following LA for perforated appendicitis was significantly reduced on the laparoscopic service. Mastery of the learning curve and addition of specific surgical techniques explained this improved result. Therefore, laparoscopic appendectomy for complicated appendicitis may not be contraindicated, even for perforated appendicitis.     

Intraocular inflammation after Ultrasound Cyclo Plasty for the treatment of glaucoma

This is a prospective interventional clinical study evaluating intraocular inflammation developed after Ultrasound Cyclo Plasty (UCP) for the treatment of glaucoma. Eighteen eyes of 18 patients were treated with UCP second-generation probes (Eye OP1). After treatment, the mean intraocular pressure (IOP) significantly decreased from 26.8±7.2 to 18.8±6.1 mm Hg at day 1 and to 14.7±3.4 mm Hg at month 6 (all P<0.001). Mean laser flare-cell photometry value steeply increased after surgery from 12.1±7.5 to 64.1±53.9 ph/ms (P=0.001) at day 1, and then progressively decreased to respectively 60.6±49.7 at day 7, 43.5±38.5 at day 14 and 28.2±18.3 at month 1 (all P<0.05), returning at levels similar to baseline ones at month 3 and month 6 (respectively 16.7±6.2 and 12.8±10.2, both P>0.05). A significant negative correlation was found between postoperative increase of aqueous flare values and anterior chamber depth (R=-0.568, P=0.014). This timeframe may be considered reasonable for repeating UCP treatment, when required.     

Clinical Effects of the Immunization Protocol Using Loxosceles Venom in Naïve Horses

Bites of brown spiders (Loxosceles spp.) are responsible for dermonecrotic lesions and potentially systemic envenoming that can lead to death. The only effective therapy is the use of the antivenom, usually produced in horses. However, little is known about the consequences of the systematic use of the Loxosceles venom and adjuvants and of the bleedings on antivenom-producing horses. Thus, the aim of this study was to evaluate the clinical changes in horses in their first immunization protocol for Loxosceles antivenom production. Eleven healthy horses, never immunized, were evaluated in three different periods: T0 (before immunization); T1 (after their first venom immunization); and T2 (after their first bleeding). Horses were clinically evaluated, sampled for blood, and underwent electrocardiographic (ECG) recordings. Several suppurated subcutaneous abscesses occurred due to the use of Freund’s adjuvants and thrombophlebitis due to systematic venipunctures for the bleeding procedures. ECG showed arrhythmias in few horses in T2, such as an increase in T and R waves. In summary, the immunization protocol impacted on horses’ health, especially after bleeding for antivenom procurement.     

Potential therapeutic effect of Allium cepa L. and quercetin in a murine model of Blomia tropicalis induced asthma

Background

Asthma is an inflammatory condition characterized by airway hyperresponsiveness and chronic inflammation. The resolution of inflammation is an essential process to treat this condition. In this study we investigated the effect of Allium cepa L. extract (AcE) and quercetin (Qt) on cytokine and on smooth muscle contraction in vitro and its therapeutic potential in a murine model of asthma.

Methods

AcE was obtained by maceration of Allium cepa L. and it was standardized in terms of quercetin concentration using high performance liquid chromatography (HPLC). In vitro, using AcE 10, 100 or 1000 μg/ml or Qt 3.5, 7.5, 15 μg/ml, we measured the concentration of cytokines in spleen cell culture supernatants, and the ability to relax tracheal smooth muscle from A/J mice. In vivo, Blomia tropicalis (BT)-sensitized A/J mice were treated with AcE 100, 1000 mg/kg or 30 mg/kg Qt. We measured cell influx in bronchoalveolar lavage (BAL), eosinophil peroxidase (EPO) in lungs, serum levels of Bt-specific IgE, cytokines levels in BAL, and lung histology.

Results

We observed a reduction in the production of inflammatory cytokines, a relaxation of tracheal rings, and a reduction in total number of cells in BAL and EPO in lungs by treatment with AcE or Qt.

Conclusion

AcE and Qt have potential as antiasthmatic drugs, as they possess both immunomodulatory and bronchodilatory properties.     

Effect of oral CDP-choline on visual function in young amblyopic patients

Purpose The purpose of the study was to evaluate the effect on visual function of orally administered CDP-choline in addition to patching for the treatment of amblyopia in children. Methods This was an open label parallel group study comparing patching plus oral CDP-choline with patching alone. Sixty-one participants (aged between 5 and 10 years) suffering from anisometropic or strabismic amblyopia were divided at random into two groups: Group A, 800 or 1,200 mg (according to the body weight) of orally administered CDP-choline and 2-h patching a day; Group B, 2-h patching a day. Both groups were treated for 30 consecutive days. A follow-up visit was set 60 days after the treatment was discontinued. The main outcome measure was the change in visual acuity of amblyopic eyes as measured by Snellen’s E charts. The secondary outcome measures were changes in the visual acuity of amblyopic eye as measured by isolated letters (Snellen’s E) and changes in the contrast sensitivity of amblyopic eyes. Results The addition of CDP-choline to patching therapy was not found to be more effective than patching alone after 30-day treatment. The present results showed that adding CDP-choline to patching stabilised the effects obtained during the treatment period. In fact, whereas the participants treated only with patching showed a decrease in visual acuity at 90 days, these receiving CDP-choline and patching combined appeared to maintain the results obtained (two-way ANOVA: P = 0.0042). Similar results were obtained when measuring visual acuity by isolated Snellen’s E letters. Conclusions In amblyopic patients, CDP-choline combined with patching contributes to obtaining more stable effects than patching alone. Fabio De Gregorio works as an advisor for Tubilux Pharma S.p.A. The authors have full control of all primary data and they agree to allow Graefe’s Archives for Clinical and Experimental Ophthalmology to review their data if requested.     

2'-deoxyguanosine, 2'-deoxycytidine, and 2'-deoxyadenosine adducts resulting from the reaction of tetrahydrofuran with DNA bases

A recent study showed that tetrahydrofuran (THF), a widely used solvent, is carcinogenic in experimental animals. Despite its carcinogenic activity, there is a paucity of information regarding cellular toxicity, biomolecular damage, and genotoxicity induced by THF. We describe here the structural characterization of adducts produced by the reaction of oxidized THF with 2'-deoxyguanosine (dGuo-THF 1 and dGuo-THF 2), 2'-deoxyadenosine (dAdo-THF), and 2'-deoxycytidine (dCyd-THF). Adducts were isolated from in vitro reactions by reverse-phase HPLC and fully characterized on the basis of spectroscopic measurements. The stable derivatives obtained by the reduction of adducts with NaBH(4) (the case of dGuo-THF 1, dCyd-THF, and dAdo-THF) and the stable adduct dGuo-THF 2 were used as standards for optimization of chromatographic separations for adduct detection in DNA through HPLC/ESI/MS-MS. Using this methodology, we successfully detected the four adducts in calf thymus DNA reacted with oxidized THF. The present study also provides evidence that rat liver microsomal monooxigenases oxidize THF to the reactive electrophilic compounds that are able to damage the DNA molecule, as indicated by a significant increase in adduct dGuo-THF 1 level when NADPH was added to the THF/microsomes/dGuo incubation mixtures. Our data point to DNA-THF adducts as possible contributing factors to the toxicological effects of THF exposure.