O6-Methylguanine and O6-methylguanine-dna methyltransferase activity in tissues of BDF-1 mice treated with antiparasitic drugs

Levels of the DNA promutagenic methylation damage, O⁶-methylguanuine (O⁶-MeG) and the activity of the O⁶-methylguanuine-DNA methyltransferase (MGMT), the enzyme responsible for repairing O⁶-MeG, were measured at various time intervals in tissues of BDF-1 mice administered a single therapeutic dose of the antischistosomal agents hycanthone, oxaminiquine and metrifonate. Hycanthone increased O⁶-MeG in the liver-DNA after 6 h, then decreased by 3-fold after 48 h. Lower levels of the adduct and a slower rate of formation were found in the intestine and bladder. MGMT activities were significantly lower in the liver (74%) and bladder (25%) compared to control animals after 6 h, then restored by 48 h. Oxaminiquine increased O⁶-MeG in all tissues, but spleen, after 6 h and persisted only in the bladder after 48 h. Liver and bladder tissues of these animals exhibited a pattern of alteration in the MGMT activity similar to that observed for hycanthone. Metrifonate induced a profile of O⁶-MeG comparable to that of oxaminiquine but the levels of the adduct were about 2-fold lower. Hepatic MGMT in these animals was significantly lower (∼38%) than the control values after 6 h, then restored by 48 h. A significant negative correlation was obtained between O⁶-MeG and MGMT activity in the liver (r=−0.85), intestine (r=−0.62) and bladder (r=−0.59). These results demonstrate that treatment with antischistosomal agents may lead to the formation of promutagenic alkylation damage in the tissue DNA and alterations in the DNA repair capacity.     

Effects of an ergonomic program on the quality of life and work performance of university staff with physical disabilities: A clinical trial with three-month follow-up

Background

Problems related to physical disability may have an extremely negative impact in the work environment, reducing productivity and contributing to health problems and a worsening quality of life.

Comparative effectiveness study of single high-dose cisplatin with fractionated doses cisplatin in first-line therapy for treatment-naive Chinese patients with advanced non–small-cell lung cancer

BackgroundCisplatin is one of the most effective chemotherapeutic drugs for patients with advanced non–small-cell lung cancer (NSCLC). Single high-dose cisplatin is a commonly used chemotherapy regimen in the world. At present, fractionated doses cisplatin is used in most hospitals in China. Although many doctors have begun to try a single dose of cisplatin, there are still few studies on the comparison of the 2 regimens. This study describes the efficacy and side effects of cisplatin single-dose administration and fractionated doses regimen in the treatment of advanced NSCLC.MethodsA retrospective study was conducted on 219 patients with advanced NSCLC who received chemotherapy with DDP were divided into 2 groups according to the single dose of cisplatin from January 2014 to December 2017. For experimental group, 108 patients were enrolled and received DDP at a dose of 75 mg/m² on day 1. A total of 111 patients were enrolled in the control group, and DDP was administrated at 25 mg/m² on days 1-3. The efficacy, toxicity, and progression-free survival of the 2 groups were observed and analyzed.ResultsIn the experimental group, the numbers of patients who received PR, SD, and PD were 66, 34, and 8 respectively. In the control group, the numbers of patients who received PR, SD, and PD were 18, 77, and 16 respectively. The percentages of patients with a objective response rate response in the experimental group were significantly higher than that in the control group (61.11% vs 16.22%, P < 0.0001). The incidence of III-IV vomiting in the experimental group was lower than that in the control group (11.11% vs 26.13%). The incidence of I-II hiccups in the experimental group was higher than that in the control group (15.74% vs 10.81%). None of the patients had III-IV degree nephrotoxicity. Myelosuppression mainly manifested as leukopenia. In the experimental group, the incidence of I-II degree of leukopenia was 71.30%, and the III-IV degree was 7.41%, which was 74.77% and 11.71 respectively in the control group. A small number of patients have a decrease in mild platelets and hemoglobin.ConclusionFor patients with advanced NSCLC who require chemotherapy with DDP regimen, the short-term effect of single-dose administration of DDP is better than that of fractional small-dose administration. Toxicity can be tolerated and it is worth promoting clinically.     

Hypofractionated intensity-modulated radiotherapy in locally advanced unresectable pancreatic cancer: A pilot study

PurposeTo test feasibility and safety of hypofractionated intensity modulated radiotherapy (H-IMRT) in pancreatic adenocarcinoma (PAC) treatment.MethodsPatients with unresectable nonmetastatic PAC were prospectively enrolled on a pilot study. Patients received H-IMRT to gross tumor volume to a total dose of 52 Gy (4 Gy/fraction). Toxicity rates, duodenal dosimetric parameters, and clinical outcomes were evaluated.ResultsTen patients received H-IMRT regimen. Objective tumor response was recorded in all patients but one. Gastrointestinal toxicity was the most common acute side effect and its severity moderately correlated with duodenal maximum dose (ρ = 0.46) and percentage of duodenal volume exposed to 5 Gy (ρ = 0.46). The 1-year overall and disease-free survival were 83.3% and 68.6%, respectively.ConclusionH-IMRT seems to guarantee a high local control rate without severe toxicity. Its use in unresectable nonmetastatic PAC needs to be further investigated.     

Cranial giant cell arteritis mimickers: A masquerade to unveil

Giant cell arteritis (GCA) is a large-vessel vasculitis that affects cranial and extra-cranial arteries. Extra-cranial GCA presents mainly with non-specific symptoms and the differential diagnosis is very broad, while the cranial form has more typical clinical picture and physicians have a lower threshold for diagnosis and treatment. Although temporal artery biopsy (TAB) has an established role, ultrasound (US) is being increasingly used as the first-line imaging modality in suspected GCA. Vasculitides (especially ANCA-associated), hematological disorders (mainly amyloidosis), neoplasms, infections, atherosclerosis and local disorders can affect the temporal arteries or might mimic the symptoms of cranial GCA and produce US and TAB findings that resemble those of temporal vasculitis. Given that prompt diagnosis is essential and proper treatment varies significantly among these diseases, in this review we aimed to collectively present disorders that can masquerade cranial GCA.