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1.
J Gastrointest Surg ; 28(3): 291-300, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38445924

ABSTRACT

BACKGROUND: Increased survival of patients undergoing total gastrectomy for gastric cancer has prompted several efforts to improve long-term postgastrectomy syndrome (PGS) outcomes. Whether a J-pouch (JP) reconstruction may be more beneficial than a standard Roux-en-Y (RY) is controversial. METHODS: A systematic review with meta-analysis was conducted, including studies reporting long-term outcomes of patients treated with total gastrectomy and JP vs RY esophagojejunostomy for gastric adenocarcinoma. A literature search was performed on PubMed, Scopus, and Google Scholar. Primary endpoints were symptom control, weight loss, eating capacity (EC), and quality of life (QoL) with at least 6 months of follow-up. Safety endpoints were explored. RESULTS: Overall, 892 patients were included from 15 studies (6 randomized controlled trials [RCTs] and 9 non-RCTs): 452 (50.7%) in the JP group and 440 (49.3%) in the RY group. Compared with RY, JP showed a significantly lower rate of dumping syndrome (13.8% vs 26.9%, odds ratio [OR], 0.29; 95% confidence interval [CI], 0.14-0.58; P < .001; I2 = 22%) and heartburn symptoms (20.4% vs 39.0%; OR, 0.29; 95% CI, 0.14-0.64; P = .002; I2 = 0%). Reflux (OR, 0.61; 95% CI, 0.28-1.32; P = .21; I2 = 42%) and epigastric fullness (OR, 0.60; 95% CI, 0.18-2.05; P = .41; I2 = 69%) were similar in both groups. Weight loss and EC were similar between the groups. QoL outcome seemed to be burdened by bias. There was no difference in morbidity, mortality, and anastomotic leak rate between groups. Operative time was significantly longer for JP than for RY (271.9 vs 251.6 minutes, respectively; mean difference, 21.55; 95% CI, 4.64-38.47; P = .01; I2 = 96%). CONCLUSION: JP reconstruction after total gastrectomy for gastric cancer is as safe as RY and may provide an advantage in postgastrectomy dumping syndrome and heartburn symptoms.


Subject(s)
Colonic Pouches , Postgastrectomy Syndromes , Stomach Neoplasms , Humans , Dumping Syndrome/etiology , Gastrectomy , Heartburn , Randomized Controlled Trials as Topic , Stomach Neoplasms/surgery , Weight Loss
2.
Minerva Surg ; 79(2): 147-154, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38252400

ABSTRACT

BACKGROUND: Open Abdomen (OA) is gaining popularity in damage control surgery (DCS) but there is not an absolute prognostic score to identify patients that may benefit from it. Our study investigates the correlation between the clinical frailty scale score (CFSS) and postoperative morbidity and mortality in patients undergoing OA. METHODS: Patients ≥65 yo undergoing OA in two referral centres between 2015 and 2020 were included and stratified according to CFSS in non-frail (NF), frail (F) and highly-frail (HF). The primary endpoint was 30-day mortality. Secondary endpoints were postoperative morbidity and 1- year survival. RESULTS: One hundred and thirty-six patients were included: 35 NF (25.7%), 56 F (41.2%), 45 HF (33.1%). Average age 76.8. The 73.5% of cases were non-traumatic diseases with no difference in preoperative characteristics. 95 (71.4%) had one complication, 26 NF (74.3%), 34 F (63.2%), 35 HF (77.8%) (P=0.301) and 59.4% had a complication with a CD≥3, 57.1% NF, 56.6% F and 64.4 HF. The 30-day mortality was 32.4%, higher in HF (46.7%) and F (30.4%) compared to NF (17.1%, P=0.018). The Overall 1-year survival was 41% (SE ±4) with statistically significant difference between HF vs. NF and HF vs. F (P=0.009 and P=0.029, respectively). In the univariate analysis, the only significant prognostic factor impacting mortality was CFSS, with HF having an HR of 1.948 (95% CI 1.097-3.460, P=0.023). CONCLUSIONS: When OA is a surgical option, frail patients should not be precluded, while HF should be carefully evaluated. The CFSS might be a good prognostic score for patients that may safely benefit from OA.


Subject(s)
Abdominal Cavity , Frailty , Humans , Aged , Frailty/diagnosis , Retrospective Studies , Frail Elderly , Abdomen/surgery
3.
Eur J Surg Oncol ; 49(11): 107069, 2023 11.
Article in English | MEDLINE | ID: mdl-37708660

ABSTRACT

BACKGROUND: Tumour-specific mesorectal excision (TSME) practice for rectal cancer only relies on small retrospective studies. This study aimed to perform a systematic review and meta-analysis to assess the oncological and functional outcomes of TSME practice. METHODS: A systematic review protocol was drawn to include all the studies that compared partial versus total mesorectal excision (PME vs TME) practised for rectal adenocarcinoma up to 16 cm from the anal verge. A systematic literature search was conducted on EMBASE-Medline, Pubmed and Cochrane Library. Reports were screened for the study's outcomes: oncological radicality, postoperative anastomotic leak risk and functional outcomes. Included studies were appraised for risk-of-bias and meta-analysed. Evidence was rated with the GRADE approach. RESULTS: Twenty-seven studies were included, consisting of 12325 patients (PME n = 4460, 36.2%; TME n = 7865, 63.8%). PME was performed for tumours higher than 10 cm from the anal verge in 54.5% of patients. There was no difference between PME and TME in circumferential resection margin positivity (OR 1.31, 95%CI 0.43-3.95, p = 0.64; I2 = 38%), and local recurrence risk (HR 1.05, 95%CI 0.52-2.10, p = 0.90; I2 = 40%). The postoperative leak risk (OR 0.42, 95%CI 0.27-0.67, p < 0.001; I2 = 60%) and the major low anterior resection syndrome risk (OR 0.34, 95%CI 0.28-0.40, p < 0.001; I2 = 0%) were lower after PME surgery. No difference was found in urinary incontinence (OR 0.68, 95%CI 0.13-3.67, p = 0.66) and urinary retention after early catheter removal (OR 2.00, 95%CI 0.24-16.51, p = 0.52). CONCLUSIONS: Evidence from this meta-analysis shows that TSME for rectal cancer has good oncological results and leads to the best-fitted functional results possible for the patient's condition.


Subject(s)
Laparoscopy , Rectal Neoplasms , Humans , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Postoperative Complications/epidemiology , Postoperative Complications/surgery , Retrospective Studies , Systematic Reviews as Topic , Anastomotic Leak/epidemiology , Anastomotic Leak/surgery , Treatment Outcome , Rectum/surgery , Rectum/pathology
4.
Updates Surg ; 74(2): 451-465, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35040077

ABSTRACT

BACKGROUND: There is no clear consensus about the best surgical strategy for patients with colorectal cancer (CRC) and synchronous liver metastases (SCRLM). METHODS: Between 2009 and 2019, patients with CRC and SCRLM considered for curative treatment were included. Perioperative and follow-up data were analysed to examine the safety and survival outcomes of primary first (PF), liver first (LF) and simultaneous resection (SR) strategies. RESULTS: 204 patients were identified, consisting of PF (n = 129), LF (n = 26) and SR (n = 49). Forty-five patients (22.1%) failed to have either the primary or the liver metastases resected following initial LF (n = 11, 42.3%) or PF (n = 34, 26.4%), respectively (p < 0.001). The postoperative morbidity rates were 31.0%, 38.4% and 40.8% in PF, LF and SR group, respectively (p = 0.409); the mortality rates were 2.3%, 0% and 4.1%, respectively (p = 0.547). The 1-, 3- and 5-year overall survival (OS) were 94%, 72%, 53% in the PF group, 74%, 54%, 36% in the LF group, and 91%, 74%, 63% in the SR group. LF group had the worst OS compared to PF and SR (p = 0.040, p = 0.052). The 1-, 3- and 5-year disease-free survival (DFS) were 31%, 15%, 10% in PF, 21%, 9% and 9% in LF and 45%, 28% and 28% in SR group, respectively. SR group had a better DFS compared to PF and LF (p = 0.005, p = 0.008). At the multivariate analysis, there was no difference between the three strategies in terms of OS (PF vs SR OS-HR 1.090, p = 0.808; LF vs SR OS-HR 1.582, p = 0.365) and the PF had a worse DFS compared to the SR approach (PF vs SR DFS-HR 1.803, p = 0.007; LF vs SR DFS-HR 1.252, p = 0.492). CONCLUSIONS: PF, LF and SR had comparable postoperative morbidity and mortality. The three surgical strategies had similar OS outcomes. The PF strategy was associated with a worse DFS than SR, while the LF approach was associated with a high failure rate to progress to the second stage (primary tumour resection).


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Colectomy , Hepatectomy , Humans , Liver Neoplasms/pathology , Retrospective Studies , Treatment Outcome
5.
Int J Med Robot ; 17(6): e2330, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34498805

ABSTRACT

BACKGROUND: The role of robotic surgery for colorectal cancer liver metastases (CRCLMs) has never been investigated in large series. METHODS: A systematic literature review was carried out on PubMed and Cochrane libraries. RESULTS: We selected nine studies between 2008 and 2021. Two hundred sixty-two patients were included. One hundred thirty-one patients underwent simultaneous resections. The mean blood loss was 309.4 ml (range, 200-450 ml), the mean operative time was 250.5 min (range, 198.5-449.0 min). The mean length of hospital stay was 7.98 days (range, 4.5 to 12 days). The overall postoperative mortality was 0.4%. The overall morbidity rate was 37.0%, Clavien-Dindo grade III-IV complications were 8.4%. The mean 3-year overall survival was 55.25% (range, 44.4-66.1%), the mean 3-year disease free survival was 37% (range, 33.3-41.9%) CONCLUSION: We can conclude that robotic-assisted surgery might be considered as a technical upgrade option for minimally invasive approach to CRCLM resections even for simultaneous operations and challenging cases.


Subject(s)
Colorectal Neoplasms , Laparoscopy , Liver Neoplasms , Robotic Surgical Procedures , Colorectal Neoplasms/surgery , Hepatectomy , Humans , Length of Stay , Liver Neoplasms/surgery , Postoperative Complications
6.
Cancers (Basel) ; 13(16)2021 Aug 10.
Article in English | MEDLINE | ID: mdl-34439171

ABSTRACT

Retroperitoneal sarcomas (RPS) are rare cancers whose management can be challenging due to various presentation patterns, multiple organ involvement, and a high local and distant recurrence rate. Histopathology and prognostic factors analysis are essential to predict the behaviour of the disease and plan the best therapeutic strategy. To date, surgery is still the main therapeutic option that guarantees a chance of cure from the primary disease. While chemotherapy and radiotherapy seem to be good options for controlling metastatic and recurrent irresectable disease, their role in the treatment of primary RPS remains unclear. This literature review aims to provide a comprehensive overview of the multidisciplinary aspects of RPS management in high-volume centres, summarising the diagnostic path, the prognostic factors, and the most suitable therapeutic options.

7.
Updates Surg ; 73(2): 495-502, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33725294

ABSTRACT

Despite advances in coloanal anastomosis techniques, satisfactory procedures completed without complications remain lacking. We investigated the effectiveness of our recently developed 'Short stump and High anastomosis Pull-through' (SHiP) procedure for delayed coloanal anastomosis without a stoma. In this retrospective study, we analysed functional outcomes, morbidity, and mortality rates and local recurrence of 37 patients treated using SHiP procedure, out of the 282 patients affected by rectal cancer treated in our institution between 2012 and 2020. The inclusion criterion was that the rectal cancer be located within 4 cm from the anal margin. One patient died of local and pulmonary recurrence after 6 years, one developed lung and liver metastases after 2 years, and one experienced local recurrence 2.5 years after surgery. No major leak, retraction, or ischaemia of the colonic stump occurred; the perioperative mortality rate was zero. Five patients (13.51%) had early complications. Stenosis of the anastomosis, which occurred in nine patients (24.3%), was the only long-term complication; only three (8.1%) were symptomatic and were treated with endoscopic dilation. The mean Wexner scores at 24 and 36 months were 8.3 and 8.1 points, respectively. At the 36-month check-up, six patients (24%) had major LARS, ten (40%) had minor LARS, and nine (36%) had no LARS. The functional results in terms of LARS were similar to those previously reported after immediate coloanal anastomosis with protective stoma. The SHiP procedure resulted in a drastic reduction in major complications, and none of the patients had a stoma.


Subject(s)
Postoperative Complications , Rectal Neoplasms , Anal Canal/surgery , Anastomosis, Surgical , Colon/surgery , Humans , Neoplasm Recurrence, Local , Rectal Neoplasms/surgery , Retrospective Studies
8.
Updates Surg ; 72(4): 1273-1277, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32856273

ABSTRACT

About 4% of patients with stomach cancer diagnosis have synchronous colorectal cancer and some of these patients may require a synchronous surgical resection. So far, only few minimally invasive series of synchronous resections have been described. We investigated the feasibility and safety of the synchronous robotic resection of the right colon and stomach malignancies, trying to identify a standardised and reproducible technique. It is essential to carefully plan the operation and the trocars positioning to minimise the number of robotic dockings and be able to operate comfortably. Herein, we describe our approach, which is safe and effective in terms of minimal invasiveness and oncological radicality. Robotic surgery could be used with even more advantage in complex multi-organ resections, providing the surgeon with a better vision, a more accurate dissection and longer instruments, to offer the patient all the benefits of a minimal invasive surgery.


Subject(s)
Adenocarcinoma/surgery , Colectomy/methods , Colon/surgery , Colorectal Neoplasms/surgery , Gastrectomy/methods , Minimally Invasive Surgical Procedures/methods , Robotic Surgical Procedures/methods , Stomach Neoplasms/surgery , Stomach/surgery , Feasibility Studies , Humans , Male , Middle Aged , Treatment Outcome
9.
Int J Surg Case Rep ; 72: 537-540, 2020.
Article in English | MEDLINE | ID: mdl-32698283

ABSTRACT

BACKGROUND: Polypoid endometriosis (PE) is a rare and uncommon variant of endometriosis that may present as a polypoid mass that simulates a malignant neoplasm. Typically, PE develops locally as a large benign pelvic mass. However, it may sometimes conceal a malignant disease in its context. CASE PRESENTATION: A 53 years old, nulliparous lady, had been treated over a 10-year period for recurrent and symptomatic polypoid endometriosis of the pelvis. During this time, she underwent four surgical resections, the final one being a total pelvic exenteration, with histology demonstrating the presence of a rare myxoid low grade Endometrial Stromal Sarcoma (ESS) that had arisen in PE. CONCLUSION: PE is a rare variant growth pattern of endometriosis which may involve different pelvic organs and can mimic a malignant mass in the pelvis. It mostly affects women in their peri- or post-menopausal age and it is not always related to hormonal therapy. Malignances, such as Endometrial Stromal Sarcoma in this case, can arise in the context of PE and their diagnosis can be challenging. Surgical excision may constitute radical multi-organ resection, particularly for recurrent and symptomatic cases. However, the recurrence rates after surgery can be significant.

10.
Tour Manag Perspect ; 35: 100698, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32509511

ABSTRACT

Quality in cultural heritage attractions is mainly approached from the visitors' satisfaction perspective, and the literature does not contain a clear definition of quality in the management of cultural heritage sites open to the public. The present study aims to reframe this trend. By way of theoretical contribution, we propose a definition of quality in cultural heritage attractions management based on dimensions such as the capacity of preserving the cultural assets, the ability to communicate effectively their significance, the quality of commodification for visitor use, and the ability to boost intercultural competence and promote intercultural dialogue. Based on the above, an empirical, qualitative study was conducted on the cultural heritage managers' current perceptions of quality. The results suggest that a profound asymmetry exists among practitioners' opinions and practices, and four types of cultural heritage managers were defined with regard to their perception of quality: Reactionary, Reticent, Pragmatic, Enthusiastic.

11.
J Nat Prod ; 75(7): 1294-8, 2012 Jul 27.
Article in English | MEDLINE | ID: mdl-22698255

ABSTRACT

The ability of the sodium salt of 3,4-secoisopimar-4(18),7,15-trien-3-oic acid (1), a diterpenoid obtained from Salvia cinnabarina, to inhibit the genotoxic effect of ethyl methanesulfonate (a clastogenic agent) and colcemid (an aneugenic agent), was studied using a micronucleus assay on cultured human lymphocytes. Cells were treated with 1 before (pretreatment), during (co-treatment), and after (post-treatment) treatment with the mutagens, in order to investigate the type of antimutagenic activity (desmutagenic or bioantimutagenic) manifested. In the range of concentrations tested (0.3-330 µM) 1 reduced significantly the frequency of micronuclei induced by ethyl methanesulfonate, in both pre- and co-treatment protocols (up to 74% and 70% of reduction, respectively), showing an anticlastogenic activity. Conversely, 1 did not inhibit the effect of colcemid in all treatments. The nuclear division index value of lymphocytes was not affected by treatment with 1, thus demonstrating that the anticlastogenic effect of 1 was not due to a cytotoxic effect. On the basis of the results obtained, it can be hypothesized that 1 exerts its anticlastogenic activity against ethyl methanesulfonate by a desmutagenic mechanism, possibly by chemical inactivation of the mutagen.


Subject(s)
Antimutagenic Agents/pharmacology , Diterpenes/pharmacology , Lymphocytes/drug effects , Mutagens/pharmacology , Salvia/chemistry , Antimutagenic Agents/chemistry , Antimutagenic Agents/isolation & purification , Diterpenes/chemistry , Diterpenes/isolation & purification , Ethyl Methanesulfonate/pharmacology , Humans , Lymphocytes/cytology , Micronucleus Tests , Molecular Structure , Sodium/pharmacology
12.
Environ Mol Mutagen ; 52(1): 69-71, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20839219

ABSTRACT

The potential genotoxicity of lavender essential oil and its major components, linalool, and linalyl acetate, was evaluated in vitro by the micronucleus test on peripheral human lymphocytes. In the range of non-toxic concentrations (0.5-100 µg/ml), linalyl acetate increased the frequency of micronuclei significantly and in concentration-dependent manner; lavender oil did so only at the highest concentration tested, whereas linalool was devoid of genotoxicity. None of the tested substances led to an increase in nucleoplasmic bridges or nuclear buds frequency. These findings suggest that the mutagenic activity of lavender oil can be related to the presence of linalyl acetate, which seems to have a profile of an aneugenic agent.


Subject(s)
Aneugens/toxicity , Lymphocytes/drug effects , Monoterpenes/toxicity , Oils, Volatile/toxicity , Plant Oils/toxicity , Acyclic Monoterpenes , Cells, Cultured , Humans , Lavandula , Lymphocytes/cytology , Micronucleus Tests
13.
Mutat Res ; 719(1-2): 7-13, 2011 Feb 03.
Article in English | MEDLINE | ID: mdl-20951227

ABSTRACT

An integrated approach based on environmental and biological monitoring, including the analysis of biomarkers of exposure [excretion of S-phenylmercapturic acid (S-PMA)], early biological effects [micronucleus (MN) frequency] and susceptibility (genetic polymorphisms), was applied to characterize benzene exposure in a group of 70 traffic policemen and 40 employees of the city of Bologna, Italy. Median personal benzene exposure was 6.55-fold higher for traffic policemen than for controls (P<0.0001). This higher exposure was confirmed by a significant, 2.53-fold higher S-PMA excretion in traffic policemen compared with that observed for indoor workers (P<0.0001). Median MN frequency was also significantly higher in policemen compared with indoor workers (P=0.001), emphasizing the genotoxic effect potentially associated with benzene exposure. With regard to biomarkers of susceptibility, the analysis revealed that high epoxide hydrolase (mEH) (predicted) enzyme activity was significantly correlated with a lower median MN frequency (P=0.003). A gene-gender interaction was observed for the glutathione-S-transferase M1 (GSTM1) genotype. The GSTM1-null genotype was associated with a significantly higher median MN frequency in men, not in women. Statistical analysis did not reveal any association between the presence of the protective allele, pushing the pathway towards benzene detoxification, and MN frequency or S-PMA excretion. Even though there are some limitations in the study, our results indicate that policemen are exposed to higher levels of benzene than individuals spending most of the time indoors. This higher exposure may contribute to DNA damage, suggesting an increase health risk from traffic benzene emission. Finally, a more comprehensive study is warranted in order to better elucidate the involvement of EPHX1 genotypes combination in benzene genotoxicity.


Subject(s)
Benzene/analysis , Environmental Pollutants/analysis , Occupational Exposure/analysis , Police , Acetylcysteine/analogs & derivatives , Acetylcysteine/urine , Adult , Benzene/poisoning , Environmental Pollutants/poisoning , Epoxide Hydrolases/genetics , Epoxide Hydrolases/metabolism , Female , Genotype , Glutathione Transferase/genetics , Humans , Italy , Linear Models , Male , Micronuclei, Chromosome-Defective/chemically induced , Micronucleus Tests/statistics & numerical data , Middle Aged , Occupational Exposure/adverse effects , Polymorphism, Genetic , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Risk Factors , Sex Factors , Young Adult
14.
Mutat Res ; 699(1-2): 23-8, 2010 Jun 17.
Article in English | MEDLINE | ID: mdl-20398787

ABSTRACT

beta-Caryophyllene is a bi-cyclic sesquiterpene that occurs in essential oils from several plants. A variety of biological activities have been ascribed to this compound. In particular, it seems to possess anti-carcinogenic properties, due to its capability to induce detoxifying enzymes or to enhance, in vitro and in vivo, the natural killer cell-induced cytotoxicity against tumours. Conversely, the knowledge on the DNA-damaging activity of the substance and its modulation is scanty. Therefore, in this study, we aimed at evaluating the capability of beta-caryophyllene to protect cultured human lymphocytes from the genotoxic damage induced by ethyl methanesulfonate (EMS) and colcemid (COL) in the micronucleus assay. To investigate the mechanisms of action of this sesquiterpene, the cultures were treated with the compound before (pre-treatment), during (co-treatment) and after (post-treatment) treatment with the mutagens. Up to 100 microg/ml, beta-caryophyllene by itself did not produce any cytotoxic and genotoxic effect, as shown by the value of the nuclear division index (NDI) and the frequency of micronuclei (MN). The test compound (0.1-100 microg/ml) significantly reduced the MN frequency induced by EMS in pre- and co-treatment protocols (up to 64.4% and 87% reduction, respectively). In the post-treatment protocol, beta-caryophyllene was not effective as an antimutagen. No significant reduction of COL-induced MN frequency was found. The antigenotoxic activity of beta-caryophyllene observed here suggests that this compound could act by chemical interaction with the mutagen in the growth medium (co-treatment) or in the cytoplasm of lymphocytes (pre-treatment), so acting as a desmutagen. These data encourage further studies to investigate the mode of action and the potential use of this compound as a chemopreventive agent.


Subject(s)
Antimutagenic Agents/pharmacology , Ethyl Methanesulfonate/antagonists & inhibitors , Ethyl Methanesulfonate/toxicity , Mutagens/toxicity , Sesquiterpenes/pharmacology , DNA Damage , Demecolcine/toxicity , Humans , Lymphocytes/drug effects , Micronucleus Tests , Polycyclic Sesquiterpenes
15.
Mutat Res ; 639(1-2): 20-6, 2008 Mar 01.
Article in English | MEDLINE | ID: mdl-18082847

ABSTRACT

Mutagen sensitivity assay, by measuring chromosome damage induced by an in vitro treatment of peripheral lymphocytes with bleomycin, has been proposed as a biomarker for assessing cancer susceptibility. Recently, a single nucleotide polymorphism (SNP A1450G) of the gene for bleomycin hydrolase (BLHX), a specific neutral cysteine protease able to metabolise bleomycin, was proposed as a plausible candidate to variation in mutagen sensitivity. To shed more light on the effect of BLHX genotype on the expression of chromosome damage induced in vitro by bleomycin, we determined mutagen sensitivity for 45 non-smoker healthy volunteers. The level of bleomycin-induced chromosome damage was assessed as frequencies of micronuclei (MN) in cytokinesis-blocked lymphocytes. The subjects were genotyped for the BLHX gene, to determine the possible effect of this polymorphism on mutagen sensitivity. No difference in the spontaneous value of MN was detected between the homozygotes wild-type (A/A) and the carriers of variant alleles A/G heterozygotes or G/G homozygotes (MN/1000 binucleated (BN) cells: 6.69+/-2.53 and 6.37+/-4.87, respectively). A substantial effect of BLHX polymorphism in predetermining individual mutagen sensitivity status was observed: subjects with the BLHX A/A genotype displayed significantly lower mean levels of bleomycin-induced MN frequency than the carriers of A/G or G/G variant alleles combined (12.00+/-3.76 MN/1000 BN vs. 16.37+/-8.86 MN/1000 BN, respectively; P=0.029). The multiple regression analysis, including BLHX genotype and age, confirmed the significant effect of BLHX variant alleles (A/G, G/G) on the chromosome damage induced by bleomycin (P=0.01), whereas age correlated only with the spontaneous MN frequency.


Subject(s)
Bleomycin/pharmacology , Cysteine Endopeptidases/genetics , Micronuclei, Chromosome-Defective/chemically induced , Polymorphism, Single Nucleotide , Adult , Alleles , Drug Resistance/genetics , Female , Gene Frequency , Genotype , Humans , Lymphocytes/drug effects , Lymphocytes/metabolism , Male , Mutagens/pharmacology
16.
Mutat Res ; 638(1-2): 90-7, 2008 Feb 01.
Article in English | MEDLINE | ID: mdl-17953974

ABSTRACT

Susceptibility to DNA damage varies among individuals and sensitivity to bleomycin (BLM) may reflect the inter-individual differences. BLM sensitivity in part may be explained by inherited differences in DNA repair genes. We investigated the association between genetic polymorphisms in the GSTT1, GSTM1, XPD, XRCC1 and XRCC3 genes and the levels of spontaneous and BLM-induced DNA damage in peripheral blood lymphocytes from 200 healthy, unexposed individuals. The investigation of BLM sensitivity on cancer- or disease-free subjects and not occupationally exposed to known mutagen represents the strengths of the present study, as the detection of genetic damage is not biased by any disease- and occupational-related factor. The micronucleus (MN) assay was used to detect the spontaneous and BLM-induced genetic damage whereas, genotype analysis was carried out using methods based on polymerase chain reaction. Poisson regression analysis showed that subject's age, gender and smoking status had no effect on the spontaneous and BLM-induced MN frequencies. Genotype analysis revealed a clear association between GSTT1-null and XPD polymorphisms and both spontaneous and BLM-induced MN frequencies, whereas the effect of the XRCC1 polymorphism was marginally significant only with regard to spontaneous MN frequency. Genotype analysis did not reveal a clear association between the other studied SNPs (GSTM1 and XRCC3) and MN frequencies. Poisson regression analysis revealed no association between the score of protective alleles and the frequency of spontaneous MN. However, an increased number of protective alleles was significantly associated with a lower frequency of BLM-induced MN (P=0.0003). This finding highlights the genetic basis for BLM sensitivity, which could be a valid and useful surrogate for identifying genotypes that might increase susceptibility in population exposed to carcinogens. Further investigations in a large sample size and including more SNPs, reflecting the complexity of DNA repair machinery, might lead to the identification of a genetic profile responsible for the susceptibility to genotoxicants, with a far-reaching long-term impact on primary prevention and early detection of disease associated genes.


Subject(s)
Bleomycin/toxicity , DNA-Binding Proteins/genetics , Glutathione Transferase/genetics , Micronuclei, Chromosome-Defective , Xeroderma Pigmentosum Group D Protein/genetics , Adult , Female , Genotype , Humans , Male , Micronucleus Tests , Middle Aged , Polymorphism, Single Nucleotide , X-ray Repair Cross Complementing Protein 1
17.
Br J Nutr ; 97(5): 921-7, 2007 May.
Article in English | MEDLINE | ID: mdl-17381982

ABSTRACT

In a single-dosing crossover study, we investigated the ability of apple fruit consumption to protect human lymphocytes against peroxide-induced damage to DNA. Six healthy, non-smoking male volunteers were placed for 2d on an antioxidant-poor (AP) diet. After 48h of AP diet, the volunteers were required to consume a homogenate obtained from 600g of red delicious unpeeled apples or water (500 ml); blood samples were collected 0, 3, 6 and 24 h post-consumption. To evaluate whether the apple intake was sufficient to restore resistance of DNA to oxidative damage, for each subject at any time point the plasma total antioxidant activity, reactive oxygen species (ROS) formation and induction of micronuclei (MN) in isolated lymphocytes following hydrogen peroxide (H2O2) treatment were measured. Results indicated a significant inhibition (58%, P <0.05) of H2O2-induced MN frequency in the plasma samples collected at 3 h after apple consumption, as compared with plasma samples collected at 0 h (4.17 (SD 1.83) v. 9.85 (SD 1.87) MN/1000 binucleated (BN) cells, respectively). A gradual return towards the value observed at 0 h was recorded starting from 6 to 24 h. MN frequency induced by H2O2 was significantly influenced by plasma total antioxidant activity (r = -0.95, P <0.05) and by the increase of intracellular ROS formation (r = 0.88, P <0.05). These findings suggest that the consumption of whole apple provides a useful dietary source of active scavengers to protect cells and tissue from oxidative stress and related DNA injury.


Subject(s)
DNA Damage/drug effects , Hydrogen Peroxide/pharmacology , Lymphocytes/physiology , Malus/physiology , Oxidants/pharmacology , Adult , Antioxidants/administration & dosage , Antioxidants/metabolism , Cells, Cultured , Cross-Over Studies , Diet , Eating/genetics , Eating/physiology , Humans , Lymphocytes/metabolism , Male , Micronuclei, Chromosome-Defective , Oxidation-Reduction , Oxidative Stress/drug effects , Oxidative Stress/genetics , Reactive Oxygen Species/metabolism
18.
Mutat Res ; 583(1): 1-11, 2005 May 02.
Article in English | MEDLINE | ID: mdl-15866461

ABSTRACT

Among the toxic chemicals present in the ambient air of urban centres, benzene raises particular concern due to its haematoxicity and leukaemogenic hazards, probably related to clastogenic factors. However, little is known about the health risks associated with environmental--rather than industrial--exposure to benzene. We analysed micronucleus (MN) frequencies in peripheral lymphocytes by use of the cytokinesis-block technique, and haematological parameters among 49 traffic police and 36 indoor workers (controls) in the city of Bologna. The analysis of urban air provided by a municipal air-quality monitoring station indicated that the levels of environmental benzene were often above the recommended threshold level (10 microg/m3) whereas other pollutants--nitrogen oxides, polycyclic aromatic hydrocarbon compounds, total suspended particulate matter, carbon monoxide, sulfur dioxide--did not exceed the maximum atmospheric concentration established for air-quality standards. Mean levels of individual airborne benzene exposure--as measured by personal devices worn during 4-h morning work-shifts--were six-fold higher in the traffic police than in controls (P=0.001). While no significant difference in haematological parameters was found between the two groups, MN frequency was significantly higher among the traffic police than in indoor workers (P=0.001). Among the study population, MN frequency was found to increase with age, but no influence was observed for gender or smoking. Although it cannot be excluded that the increase of MN frequency observed in traffic police could also depend, apart from benzene, on the complex mixture of pollutants encountered in urban air, our data indicate that elevated personal benzene exposure could represent a genetic risk. The analysis of biomarkers of genetic damage in subjects particularly exposed to environmental benzene deserves careful study.


Subject(s)
Air Pollutants/toxicity , Benzene/toxicity , DNA Damage , Occupational Exposure , Police , Adult , Case-Control Studies , Female , Hematologic Tests , Humans , Italy , Lymphocytes , Male , Micronucleus Tests , Molecular Epidemiology , Risk Assessment , Transportation , Urban Population , Vehicle Emissions
19.
Mutat Res ; 570(1): 105-17, 2005 Feb 15.
Article in English | MEDLINE | ID: mdl-15680408

ABSTRACT

Understanding the risks deriving from protracted exposure to low doses of ionizing radiation has remarkable societal importance in view of the large number of work settings in which sources of IR are encountered. To address this question, we studied the frequency of micronuclei (MN), which is an indicator of DNA damage, in a population exposed to low levels of ionizing radiation and in matched controls. In both exposed population and controls, the possible influence of single nucleotide polymorphisms in XRCC1, XRCC3 and XPD genes on the frequency of micronuclei was also evaluated. We also considered the effects of confounding factors, like smoking status, age and gender. The results indicated that MN frequency was significantly higher in the exposed workers than in the controls [8.62+/-2.80 versus 6.86+/-2.65; P=0.019]. Radiological workers with variant alleles for XRCC1 or XRCC3 polymorphisms or wild-type alleles for XPD exon 23 or 10 polymorphisms showed a significantly higher MN frequency than controls with the same genotypes. Smoking status did not affect micronuclei frequency either in exposed workers or controls, while age was associated with increased MN frequency in the exposed only. In the combined population, gender but not age exerted an influence on the yield of MN, being higher in females than in males. Even though there is a limitation in this study due to the small number of subjects, these results suggest that even exposures to low level of ionizing radiation could have genotoxic effects and that XRCC3, XRCC1 and XPD polymorphisms might contribute to the increased genetic damage in susceptible individuals occupationally exposed to chronic low levels of ionizing radiation. For a clear conclusion on the induction of DNA damage caused by protracted exposure to low doses of ionizing radiation and the possible influence of genetic polymorphism in DNA repair genes larger studies are needed.


Subject(s)
DNA Repair Enzymes/genetics , DNA Repair/radiation effects , Micronuclei, Chromosome-Defective/radiation effects , Polymorphism, Genetic , Biomarkers , DNA Repair Enzymes/metabolism , DNA Repair Enzymes/radiation effects , Genotype , Humans , Poisson Distribution
20.
Rev. AMRIGS ; 40(2): 100-5, abr.-jun. 1996.
Article in Portuguese | LILACS | ID: lil-181835

ABSTRACT

Revisäo bibliográfica sobre a Síndrome de Tristeza Pós-parto, buscando uma visäo atualizada sobre a epidemiologia, etiologia, diagnóstico, diagnóstico diferencial e tratamento da síndrome. Enfatiza-se o seu espaço dentro dos quadros psiquiátricos puerperais, como um entidade diagnóstica do puerpério imediato, situando-se à parte dos transtornos depressivos puerperais


Subject(s)
Humans , Female , Pregnancy , Depression, Postpartum , Puerperal Disorders
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