Enhancement of Radiation Response by Paclitaxel in Mice According to Different Treatment Schedules

Purpose: The aim of our study was to determine if paclitaxel could be used as a radiosensitizer in vivo.

Materials and methods: Paclitaxel was tested as a single agent and combined with an X-ray treatment. Paclitaxel was administered i.p. in doses from 30 to 120 mg/kg b.w. to (C3D2F1) mice bearing spontaneous mammary carcinoma. Tumor growth delay (TGD) or tumor control dose (TCD₅₀, radiation dose needed to induce local tumor control in 50% of irradiated animals) and moist desquamation dose (MDD₅₀, radiation dose needed to induce serious moist desquamation in 50% of the non-tumor-bearing feet) were the endpoints. DNA flow cytometric analysis was performed.

Results: DNA analysis demonstrated a G2/M block of tumor cells and a depletion of cells in S phase, with a maximum at 24 h from paclitaxel administration. Administering paclitaxel, in graded doses, 15 min before a 10-Gy X-ray treatment resulted in a linear regression line, almost parallel to that with paclitaxel alone, with a growth delay of about 6 days. In contrast, varying the X-ray dose with a constant paclitaxel injection (45 mg/kg b.w.) treatment showed some degree of synergism as the linear regression curves diverged. Interval time and sequence between paclitaxel administration and a 10 Gy X-ray treatment did not influence TGD. Protocols with paclitaxel at 30, 45, or 60 mg/kg were combined with radiation treatments at various doses (from 10 to 65 Gy). Values of TCD50 varied from 50.8 Gy for X-ray alone to 31.8 Gy for paclitaxel 60 mg/kg + X-ray. No differences were observed among MDD of different protocols.

Conclusions: These results suggest that, under some conditions, paclitaxel combined with radiation can show superadditive effects and this result combined with the lack of severe normal tissue damage indicate that a favorable therapeutic gain can be obtained.     

Efficacy of the Sentinox Spray in Reducing Viral Load in Mild COVID-19 and Its Virucidal Activity against Other Respiratory Viruses: Results of a Randomized Controlled Trial and an In Vitro Study

Sentinox (STX) is an acid-oxidizing solution containing hypochlorous acid in spray whose virucidal activity against SARS-CoV-2 has been demonstrated. In this paper, results of a randomized controlled trial (RCT) on the efficacy of STX in reducing viral load in mild COVID-19 patients ({"type":"clinical-trial","attrs":{"text":"NCT04909996","term_id":"NCT04909996"}}NCT04909996) and a complementary in vitro study on its activity against different respiratory viruses are reported. In the RCT, 57 patients were randomized (1:1:1) to receive STX three (STX-3) or five (STX-5) times/day plus standard therapy or standard therapy only (controls). Compared with controls, the log₁₀ load reduction in groups STX-3 and STX-5 was 1.02 (p = 0.14) and 0.18 (p = 0.80), respectively. These results were likely driven by outliers with extreme baseline viral loads. When considering subjects with baseline cycle threshold values of 20–30, STX-3 showed a significant (p = 0.016) 2.01 log₁₀ reduction. The proportion of subjects that turned negative by the end of treatment (day 5) was significantly higher in the STX-3 group than in controls, suggesting a shorter virus clearance time. STX was safe and well-tolerated. In the in vitro study, ≥99.9% reduction in titers against common respiratory viruses was observed. STX is a safe device with large virucidal spectrum and may reduce viral loads in mild COVID-19 patients.     

ABO antibody titres: a multisite comparative study of equivalency and reproducibility for automated solid-phase and haemagglutination titration,and manual dilution with gel column agglutination technology

BackgroundABO antibody titres are important in many clinical decisions; however, much variability is observed in titre results. For reliable and reproducible titre results, automated ABO titration methods have been developed. In this 10-site study, we evaluated the equivalency of the automated ABO titration assays on the Galileo NEO, a fully automated blood bank analyzer (Immucor, Inc.) to manual titration with gel Column Agglutination Technology (CAT), as well as the reproducibility of both methods.Materials and methodsTen different locations participated in this study. The equivalency study included 70 random samples at each site. The reproducibility study tested the same blinded 30-sample panel at each study site. Anti-A and anti-B IgM and IgG antibody titres were tested with both the automated and manual methods; additionally, dithiothreitol (DTT) treatment was used to inactivate IgM antibodies in the manual CAT method.ResultsThe equivalency between CAT manual method and Galileo NEO automated titres at each site ranged from 38 to 88%; equivalency for each isotype was 66.2% for IgM, 60.6% for IgG, and 88.5% for DTT-treated IgG. The reproducibility study evaluated the titre variation of each sample obtained from the 10 sites. The average titre ranges (in doubling dilutions) for the automated and manual methods, respectively, were 2.15±1.0 and 4.03±1.8 for IgM, and 1.53±0.7 and 4.10±1.9 for IgG; for the manual DTT-treated IgG, the average titre range was 3.45±1.8 doubling dilutions.DiscussionThe results demonstrated that the Galileo NEO automated and manual CAT ABO titres are not equivalent. However, the study also demonstrated that titre reproducibility is enhanced with the Galileo NEO automated ABO titration assays relative to the manual CAT ABO titration method. Therefore, to improve management of patients receiving care across multiple institutions, our study supports the use of automated ABO titration.     

Lipid peroxidation induced by N-acetylcysteine in isolated rat hepatocytes

In isolated rat hepatocytes N-acetylcysteine induces an increase of lipid peroxidation, as evaluated by the malondialdehyde production and diene conjugation. Lipid peroxidation did not result in increased cell mortality. Antioxidants and free radicals scavengers completely protect toward lipid peroxidation induced by N-acetylcysteine.     

Laparoscopic Treatment of Gastric <Emphasis Type="SmallCaps">Gist</Emphasis>: Report of 21 Cases and Literature’s Review

Background Although the feasibility of laparoscopic resection of gastric gastrointestinal stromal tumors (GISTs) has been established, various aspects are debated. This paper describes the problems of minimally invasive resection of gastric GISTs and compares this experience with an extensive literature review. Study Design Between August 2001 and December 2006, 21 consecutive patients undergoing laparoscopic resection of gastric GISTs were enrolled in a prospective study. A literature review of laparoscopic treatment was performed on Pubmed using keywords GIST and surgery. A comparison with authors’ experience with open wedge-segmental resection of GISTs (25 cases from November 1995 to December 2000) was also carried out. Statistical analysis was based on chi-squared test and t Student evaluation. Results Twenty-one patients, mean age 50.1 years (range, 34–68 years), were submitted to laparoscopic wedge- segmental gastric resections. Mean tumor size was 4.5 cm (range, 2.0–8.5 cm). Mean operative time was 151 min (range, 52–310 min), the mean blood loss was 101 mL (range, 10–250 mL), and the mean hospital stay was 4.8 days (range 3–7 days). There were no major operative complications or mortalities. All lesions had negative resection margins. At a mean follow-up of 35 months, all patients were disease-free. Morbidity, mortality, length of stay, and oncologic outcomes were comparable to the open surgery retrospective evaluation (p = not significant). Conclusions As found also in the literature review, the laparoscopic resection is safe and effective in treating gastric GISTs. Given these findings as well as the advantages afforded by laparoscopic surgery, a minimally invasive approach should be the preferred surgical treatment in patients with small- and medium-sized gastric GISTs.     

Neurologic symptoms after great saphenous vein harvesting for coronary artery bypass grafting

AIM: Incidence evaluation of cutaneous neurologic symptoms in the lower limbs as a new event after great saphenous vein (GSV) harvesting for coronary artery bypass grafting (CABG). Each day we harvest the GSV for CABG. Some authors have reported the onset of saphenous neuralgia complex as a new event of which we would evaluate the incidence. METHODS: From January 2000, until June 2001, 2,091 patients underwent cardiac surgery; 1,326 underwent CABG, 1,227 of them using the GSV as a conduit for almost one graft. These patients were prospectively reviewed; all were preoperatively examined to determine the presence of normal sensation in the lower limbs and elude the presence of saphenous neuralgia. Then, we evaluated sensations in the lower limbs at 5 days, 8 weeks, and 5 months after operation to determine the new onset of saphenous neuralgia. The areas of sensory loss were recorded each time and reported in a diagram to obtain 3 areas. RESULTS: Hyperaesthesia and pain were noted in a few patients, especially at 5 days and 8 weeks control, but at 5 months none of them complained of real pain. CONCLUSION: This study demonstrates that saphenous neuralgia after harvesting the GSV for CABG is a rare consequence. The main symptom is anaesthesia but its duration is generally no longer than 2 months. Hyperaesthesia and pain, for the early onset and the early disappearance, are considered as a normal consequence of surgical procedure.