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1.
J Obstet Gynaecol Res ; 46(8): 1370-1377, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32500639

RESUMO

AIM: To quantify the impact of the number of prior cesarean deliveries (CD) on operative complications and preterm birth. Then to investigate the presence of a threshold, beyond which complications tend to be disproportionately dangerous. METHODS: This was a retrospective cohort observational study, where data corresponding to all CD done at our service, during an 8-year period, were collected and analyzed. In total, 1840 CD were performed. Patients were divided into five categories that corresponded to the number of CD. Primary outcome was the composite adverse maternal outcome, while preterm birth and individual complications were secondary outcomes. RESULTS: The composite adverse maternal outcome, preterm birth, as well as all individual complications related to CD, except for placental abruption, showed a significant rise in frequency that paralleled the increase in the number of CD. Furthermore, this increase tended to be continuous as the number of CD increased, with an evident surge after the fourth. CONCLUSION: In our population, increasing number of prior CD was a risk factor for a parallel increase in the rate of composite adverse maternal outcome, preterm birth and almost all intraoperative complications attributable to CD. Decreasing exposure to such surgeries by limiting family size to four offspring should be considered seriously in patient counseling.


Assuntos
Nascimento Prematuro , Cesárea/efeitos adversos , Feminino , Humanos , Recém-Nascido , Líbano/epidemiologia , Placenta , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos
2.
J Chem Phys ; 151(19): 194302, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31757131

RESUMO

Methoxyphenols (MPs) are a significant component of biomass burning emissions which mainly exists in our atmosphere in the gas phase where they contribute to the formation of secondary organic aerosols (SOAs). Rovibrational spectroscopy is a promising tool to monitor atmospheric MPs and infer their role in SOA formation. In this study, we bring a new perspective on the rovibrational analysis of MP isomers by taking advantage of two complementary devices combining jet-cooled environments and absorption spectroscopy: the Jet-AILES and the SPIRALES setups. Based on Q-branch frequency positions measured in the Jet-AILES Fourier-transform infrared (FTIR) spectra and guided by quantum chemistry calculations, we propose an extended vibrational and conformational analysis of the different MP isomers in their fingerprint region. Some modes such as far-IR out-of-plane -OH bending or mid-IR in-plane -CH bending allow us to assign individually all the stable conformers. Finally, using the SPIRALES setup with three different external cavity quantum cascade laser sources centered on the 930-990 cm-1 and the 1580-1690 cm-1 ranges, it was possible to proceed to the rovibrational analysis of the ν18 ring in-plane bending mode of the MP meta isomer providing a set of reliable excited state parameters, which confirms the correct assignment of two conformers. Interestingly, the observation of broad Q-branches without visible P- and R-branches in the region of the C-C ring stretching bands was interpreted as being probably due to a vibrational perturbation. These results highlight the complementarity of broadband FTIR and narrowband laser spectroscopic techniques to reveal the vibrational conformational signatures of atmospheric compounds over a large infrared spectral range.

3.
Opt Express ; 25(4): A191-A199, 2017 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-28241629

RESUMO

Field observations and theoretical studies have found that the volume scattering functions (VSFs) of oceanic particles exhibit minimum variability at angles near 120°. However, its physical interpretation is still unknown. We find this minimum variability angle represents the intersection of two backscattering-normalized VSFs, one representing particles of sizes smaller than the wavelength of light and the other larger than the wavelength of light. This also suggests that the VSFs of oceanic particles at angles between 90° and 180°, which play a critical role in ocean color study, can be modeled by linear mixing of these two end members. We further validate this mixing model using measured VSFs in coastal and oceanic waters around the US and develop a two-component model predicting the backward shapes of the VSFs.

4.
Encephale ; 43(1): 27-31, 2017 Feb.
Artigo em Francês | MEDLINE | ID: mdl-27216587

RESUMO

The paper describes an action research for indicative assessment of psychological problems of young children following the 2010 earthquake in Haiti, and the interest of using the Creole version of the questionnaire PSYCa 3-6. The survey took place in Port-au-Prince, and the evaluators were trained to a proper standardized administration of the questionnaire. BACKGROUND: The mental health needs of young children in natural disaster contexts often remain unaddressed. The lack of a rapid and simple tool for screening combined with few mental health professionals available to accurately diagnose and provide appropriate care mean that young children remain without care. Here, we present the results of psychological screening of young children aged 3 to 6 using the questionnaire PSYCa 3-6. METHODS: This study was conducted in Port-au-Prince, Haiti. The scale was translated into Haitian Creole using corroboration of independent translations and submitted twice to the parents at home, at the end of 2011 and again at the beginning of 2013. At the first stage 166 children 3 to 6 years old were included 49 of whom were included at the second stage. The results and diagnostic properties were assessed comparing the PSYCa 3-6 to the Clinical Global Impression Severity Scale as the gold standard. RESULTS: Boys were more prone to psychological disturbances than girls. The size and position among the siblings increased the score of psychological disturbance. The neighborhood and the perception of environmental violence had a significant impact on the score of psychological disturbance. The significant improvement in scores between the two examinations showed moderate resiliency whose main factors seemed to be the social support received by the family, the rapid return to school, faith and religious practice.


Assuntos
Desastres , Terremotos , Resiliência Psicológica , Estresse Psicológico/epidemiologia , Ordem de Nascimento/psicologia , Criança , Pré-Escolar , Feminino , Haiti/epidemiologia , Humanos , Masculino , Características de Residência , Transtornos de Estresse Pós-Traumáticos/epidemiologia
5.
J Phys Chem A ; 119(39): 10022-34, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26348119

RESUMO

Two setups based on CW cavity ring-down spectroscopy were used at Bruxelles and Rennes to record jet-cooled water dimer absorption between 7188 and 7285, and between 7357 and 7386 cm(-1). Some 19 absorption features are reported, significantly more than in the literature. Limited high-resolution information is available due to strong overlap between neighboring vibration-rotation-tunneling (VRT) structures and to spectral broadening induced by short upper state vibrational predissociation lifetimes, likely to range between 100 and 20 ps. Rotational band contours analyses are performed to assign the partly resolved VRT structures to the v1v2v3,vfvb = 000,11; 200,00; 000,20; and 101,00 zero-order vibrational states. Their wavenumbers are found to be 7192.34, 7225.86, 7240.57, and 7256.99 cm(-1), respectively. Both so-called acceptor-switching tunneling components are involved in the assignments whose tentative character is discussed.

6.
J Chem Phys ; 142(21): 214305, 2015 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-26049494

RESUMO

A new experimental setup coupling a High Enthalpy Source (HES) reaching 2000 K to a cw-cavity ring-down spectrometer has been developed to investigate rotationally cold hot bands of polyatomic molecules in the [1.5, 1.7] µm region. The rotational and vibrational molecular degrees of freedom are strongly decoupled in the hypersonic expansion produced by the HES and probed by cavity ring-down spectroscopy. Carbon monoxide has been used as a first test molecule to validate the experimental approach. Its expansion in argon led to rotational and vibrational temperatures of 6.7 ± 0.8 K and 2006 ± 476 K, respectively. The tetradecad polyad of methane (1.67 µm) was investigated under similar conditions leading to rotational and vibrational temperatures of 13 ± 5 K and 750 ± 100 K, respectively. The rotationally cold structure of the spectra reveals many hot bands involving highly excited vibrational states of methane.

7.
Phys Chem Chem Phys ; 16(10): 4797-806, 2014 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-24469411

RESUMO

The rovibrationally resolved Fourier transform (FT) far infrared (FIR) spectra of two intermolecular librations of (HF)3, namely the in-plane ν6 and out-of-plane ν4 bending fundamentals centered, respectively, at about 494 cm(-1) and 602 cm(-1), have been recorded for the first time under jet-cooled conditions using the supersonic jet of the Jet-AILES apparatus. The simultaneous rotational analysis of 245 infrared transitions belonging to both bands enabled us to determine the ground state (GS), ν6 and ν4 rotational and centrifugal distortion constants. These results provided definite experimental answers to the structure of such a weakly bound trimer: firstly the vibrationally averaged planarity of cyclic (HF)3, also supported by the very small value of the inertia defect obtained in the GS, secondly the slight weakening of the hydrogen bond in the intermolecular excited states evidenced from the center of mass separations of the HF constituents determined in the ground, ν6 = 1 and ν4 = 1 states of (HF)3 as well as the decrease of the fitted rotational constants upon excitation. Finally, lower bounds of about 2 ns on ν6 and ν4 state lifetimes could be derived from the deconvolution of experimental linewidths. Such long lifetimes highlight the interest in probing low frequency intermolecular motions of molecular complexes to get rid of constraints related to the vibrational dynamics of coupled anharmonic vibrations at higher energy, resulting in loss of rotational information.

8.
Phys Chem Chem Phys ; 15(25): 10141-50, 2013 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-23598884

RESUMO

Using synchrotron radiation, we performed the rotationally resolved Fourier transform infrared absorption spectroscopy of three bands of naphthalene C10H8, namely ν(46)-0 (centered at 782 cm(-1), 12.7 µm), ν(47)-0 (centered at 474 cm(-1), 21 µm), and ν(48)-0 (centered at 167 cm(-1), 60 µm). The intense CH bending out of plane ν(46)-0 band was recorded under supersonic jet-cooled conditions using a molecular beam (the Jet-AILES apparatus) and the low frequency ν(47)-0 and ν(48)-0 bands were measured at room temperature in a long absorption path cell. The simultaneous rotational analysis of these bands permitted us to refine the ground state (GS) and ν(46) rotational spectroscopic constants and to provide the first sets of constants for the ν(47) and ν(48) modes. The experimental rotational constants were then used as reference data to calibrate theoretical models in order to provide new insights into the accuracy of anharmonic calculations. The B97-1 functional associated with the cc-pVTZ and ANO-RCC basis sets gave a consistent set of results, for rotational constants and fundamental frequencies. The data presented here pave the way for the search of naphthalene through its far-infrared spectrum in different objects of the interstellar medium.

9.
Ann Med Surg (Lond) ; 85(9): 4289-4292, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37663699

RESUMO

Introduction: Perioperative management of female patients undergoing breast surgeries differs from other patients due to chronic pain and postoperative nausea and vomiting. The anesthesia could consist of opioid-free general anesthesia (OFA) or non-opioid-free general anesthesia (NOFA). OFA relies on multimodal analgesia preoperatively and postoperatively. However, it is not yet established whether OFA could replace NOFA as a standard regimen for the management of breast surgeries. The aim of this study is to evaluate the efficacy of OFA for breast surgeries in female patients. Materials and methods: Patients undergoing modified radical mastectomy were retrospectively recruited. Two groups were defined: group 1, consisting of treated patients using OFA and group 2, consisting of treated patients using NOFA. Mean time to extubate and mean dose of morphine after recovery were computed. Postoperative morphine and antiemetic use were assessed for up to 24 h. A comparison of the computed data was conducted between both groups. Results: A total of 116 patients were included with a mean age of 53±13 years. Group 1 consisted of 56 (mean age was 54±14 years). Group 2 consisted of 60 patients (mean age was 51±12 years). Demographic parameters and time to extubate did not yield significant differences. We noticed morphine sparing at T0 and T12 with statistically significant differences P=0.043 and P=0.006, respectively. Conclusion: OFA could be considered in modified radical mastectomy management in female patients; nerve block seemed to act as morphine sparing in operative and postoperative settings by providing significantly less time to extubate with less postoperative morphine requirement.

10.
Br J Cancer ; 105(2): 288-95, 2011 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-21712827

RESUMO

BACKGROUND: The transcription factor HOXC8 regulates many genes involved in tumour progression. This study was to investigate the role of HOXC8 in pancreatic ductal adenocarcinoma (PDAC) growth and metastasis. METHODS: The Hoxc8 expression was determined in 15 PDAC cell lines and human specimens by RT-polymerase chain reaction and/or immunohistochemistry. The effects of HOXC8 silencing by RNA interference were investigated by functional tests. RESULTS: The Hoxc8 mRNA expression in PDAC cell lines was negatively related to their growth in vivo. Except for Suit2-007 cells, only those with low Hoxc8 mRNA expression grew in nude rats. Successful down-regulation of HOXC8 expression caused increased proliferation, migration (P ≤ 0.05) and colony formation (P ≤ 0.05) in Suit2-007, Panc-1 and MIA PaCa-2 PDAC cells, respectively. The Hoxc8 mRNA levels in diseased human pancreas tissues were significantly increased over normal in PDAC and autoimmune chronic pancreatitis specimens (P<0.01, respectively), but negatively related to tumour stage (P=0.09). In primary and metastatic tumour samples, immunohistochemical staining for HOXC8 was stronger in surrounding than in neoplastic tissues. Furthermore, grading of primary carcinomas was negatively associated with HOXC8 staining (P=0.03). Liver metastases showed the lowest HOXC8 expression of all neoplastic lesions. CONCLUSION: These data indicate that HOXC8 expression is inversely related to PDAC progression and metastasis.


Assuntos
Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Proteínas de Homeodomínio/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Casos e Controles , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/fisiologia , Proteínas de Homeodomínio/antagonistas & inibidores , Proteínas de Homeodomínio/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , RNA Interferente Pequeno/farmacologia , Ratos , Ratos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
11.
J Phys Chem A ; 115(12): 2523-32, 2011 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-21381647

RESUMO

A series of hydrogen bonded complexes involving oxirane and water molecules have been studied. In this paper we report on the vibrational study of the oxirane-water complex (CH(2))(2)O-H(2)O. Neon matrix experiments and ab initio anharmonic vibrational calculations have been performed, providing a consistent set of vibrational frequencies and anharmonic coupling constants. The implementation of a new large flow supersonic jet coupled to the Bruker IFS 125 HR spectrometer at the infrared AILES beamline of the French synchrotron SOLEIL (Jet-AILES) enabled us to record first jet-cooled Fourier transform infrared spectra of oxirane-water complexes at different resolutions down to 0.2 cm(-1). Rovibrational parameters and a lower bound of the predissociation lifetime of 25 ps for the v(OH)(b) = 1 state have been derived from the rovibrational analysis of the ν(OH)(b) band contour recorded at respective rotational temperatures of 12 K (Jet-AILES) and 35 K (LADIR jet).

12.
Surg J (N Y) ; 7(3): e163-e167, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34295976

RESUMO

Hidradenitis suppurativa (HS) is a chronic inflammatory disease involving apocrine glands of the skin. It carries out an important burden on the daily life of the patient. Unfortunately, it presents a major concern for medical care management in the absence of clear guidelines for proper medical and surgical treatment. Hence, we report a case of concomitant axillary and perianal HS. We opted for surgical management using a novel technique, which proved efficacy for a year of follow-up recurrence free.

13.
ACS Omega ; 5(47): 30657-30670, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33283114

RESUMO

A sol/gel curing method is used in this work to synthesize hybrid partially bio-based polyhydroxyurethanes (PHUs) from dicarbonates derived from glycerol and various diamines. The method consists of end-capping the PHU prepolymers with moisture-sensitive groups, so sealants and adhesives can be produced from partially sustainable hybrid PHUs (HPHUs), similar to their preparation from end-capped conventional polyurethanes. Diglycerol dicarbonate (DGC) is synthesized and polymerized with different diamines of various chain lengths, and the resulting structural and thermal properties of the PHUs are qualitatively and quantitively characterized. This characterization led to two potential candidates: PHU 4, made of DGC and a poly(propylene glycol) diamine, and PHU 10, prepared from DGC and a poly(dimethylsiloxane) diamine. These polymers, with respective relative number-average molecular weights of 3200 and 7400 g/mol, are end-capped and left to cure under ambient lab conditions (22 °C and 40-50% humidity), and the curing processes are monitored rheologically. Notably, moisture curing does not require any catalyst. The chemical stability of the resulting hybrid PHUs (HPHUs) 4 and 10 in pure water is investigated to check the viability of applying them under outdoor conditions. Only HPHU 10 is found to be resistant to water and shows hydrophobicity with a contact angle of 109°. Tensile tests are conducted on HPHU 10 samples cured under lab conditions for a week and others cured for another week while being immersed in water. The mechanical properties, tensile strength and elongation at break, improve with the samples cured in water, indicating the high-water repellency of HPHU 10.

14.
Cureus ; 12(11): e11295, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33282572

RESUMO

Introduction Perioperative management of elderly patients differ from young patients due to physiologic and pharmacologic differences related to aging. Moreover, assessment for perioperative parameters and risks between age-matched elderly patients should be discerned while planning for the anaesthesia regimen. The latter could consist of opioid-free general anaesthesia (OFA) or non-opioid-free general anaesthesia (NOFA). Among the parameters for assessing the regimen's efficacy, time to extubate and pain control should be included. However, it is not yet established whether OFA could replace NOFA as a standard regimen for management of hip fracture. Therefore, the aim of this study is to evaluate the efficacy of OFA for hip surgeries in elderly patients. Methods This is a retrospective study consisting of patients undergoing hip surgeries under opioid-free or opioid-induced general anaesthesia. Two groups were defined: Group 1 consisting of treated patients using OFA and Group 2 consisting of treated patients using NOFA. Patient demographics (age, sex, and weight), mean time to extubate and mean dose of morphine after recovery were computed. Postoperative morphine use was assessed for up to 24 hours. Comparison of the computed data was conducted between both groups. Mean postoperative morphine use was compared using the Mann-Whitney U-test. The remainder of the means were compared using independent t-test. Qualitative data were compared using Fisher's exact test. Level of significance was set at p<0.05. Results A total of 73 patients were included. Group 1 consisted of 37 patients (12 were males with mean age 77±14 years) who underwent hip fracture procedure whereas Group 2 consisted of 36 patients (18 were males with mean age 73±17). There were significant differences when comparing sex, weight, and time to extubate (6.8±3 and 10±5 minutes in Groups 1 and 2, respectively; p<0.05). There were six patients in Group 1 and 17 patients in Group 2 that required postoperative morphine administration. Mann-Whitney U comparison of postoperative morphine use yielded significant differences (4.8±3 and 14.65±13 mg in Groups 1 and 2, respectively; p=0.001). Discussion This is the first study that assessed the efficacy of OFA compared to NOFA in the management of hip fractures. Non-significant differences in age might suggest that both groups are age matched. In addition, significant differences in time to extubate might help in reducing impact on ventilation, maintaining safe anaesthesia while minimizing intraoperative work overflow. Patients in Group 1 required less morphine in the postoperative setting than in Group 2. This might be explained by the sensation of paraesthesia which might have been confused with pain. Conclusions OFA could be considered in hip management in elderly patients; femoral and lateral cutaneous block seemed to act as morphine sparing in operative and postoperative settings by providing significantly less time to extubate with less postoperative morphine requirement.

15.
J Chem Phys ; 131(20): 204312, 2009 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-19947685

RESUMO

In this article, we report on a Fourier transform infrared study of absorption bands belonging to small-sized water clusters formed in a continuous slit nozzle expansion of water vapor seeded in argon carrier gas. Clear signatures of free and H-bonded OH vibrations in water aggregates from dimer to pentamer are seen in our spectra. Following an increase in argon backing pressure, the position of the cluster absorption bands varies from those characteristics of isolated water aggregates in the gas phase to those known for clusters trapped in a static argon matrix. These variations can be interpreted in terms of sequential solvation of the water clusters by an increasing number of argon atoms attached to water clusters. Our measured spectra are in good agreement with those obtained previously either for free or Ar coated small-sized water clusters using pulsed slit-jet expansions. Our results are equally in accord with those originating from a variety of tunable laser based techniques using molecular beams or free jets or from the study of water aggregates embedded in rare gas matrices. Distinctions are reported, however, and discussed. Ab initio calculations have made it possible to speculate on the average size of an argon solvation shell around individual clusters as well as on the development of the OH stretch vibrational shifts in mixed (H(2)O)(m)Ar(n) clusters having different compositions and architectures.

17.
Rev Sci Instrum ; 90(9): 093103, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31575252

RESUMO

The High Enthalpy Source (HES) is a novel high temperature source developed to measure infrared line-by-line integrated absorption cross sections of flowing gases up to 2000 K. The HES relies on a porous graphite furnace designed to uniformly heat a constant flow of gas. The flow compensates thermal dissociation by renewing continuously the gas sample and eliminating dissociation products. The flowing characteristics have been investigated using computational fluid dynamics simulation confirming good temperature uniformity. The HES has been coupled to a high-resolution Fourier transform spectrometer to record emission spectra of methane at temperatures ranging between 700 and 1400 K. A radiative model has been developed to extract absolute line intensities from the recorded spectra.

18.
J Neonatal Perinatal Med ; 12(4): 405-410, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31609705

RESUMO

BACKGROUND: Fetal well-being is assured during labor and delivery with the employment of electronic fetal heart monitoring (EFHM). In uncommon instances, maternal heart rate (MHR) instead of fetal heart rate (FHR) can be the source of signals on monitors (signal ambiguity) leading to erroneous interpretation and management. Information about MHR characteristics are comparatively inadequate. We aim to analyze and compare MHR and FHR characteristics during the first and second stages of labor. METHODS: A prospective cohort study was conducted in a single tertiary care center during a one year period. Fifty one healthy full term women with singleton pregnancies during labor were enrolled. Uterine contractions, MHR and FHR were recorded simultaneously during both stages of labor by monitors designed for twin gestation. RESULTS: When compared to FHR, MHR had significantly lower baseline rate during 1st and 2nd stages (p < 0.0001). It demonstrated also more marked beat-to-beat variability during both stages (p < 0.0001). MHR showed significantly more accelerations (p = 0.03 and p = 0.008) and less decelerations (p < 0.0001 and p = 0.021) during 1st and 2nd stages respectively. CONCLUSIONS: All characteristic parameters and patterns produced by FHR could be mimicked by MHR as well, though, at different frequencies. Understanding EFHM patterns suspected to be MHR artefacts and the employment of modern monitors that simultaneously obtain and display FHR and MHR can unmask ambiguity and avert related misinterpretation problems. Similar studies should be conducted in high-risk groups where the potential for fetal hypoxia/acidosis is increased.


Assuntos
Frequência Cardíaca Fetal , Frequência Cardíaca/fisiologia , Primeira Fase do Trabalho de Parto/fisiologia , Segunda Fase do Trabalho de Parto/fisiologia , Mães , Contração Uterina/fisiologia , Adulto , Cardiotocografia , Feminino , Frequência Cardíaca Fetal/fisiologia , Humanos , Trabalho de Parto , Gravidez , Estudos Prospectivos
19.
Mutat Res ; 640(1-2): 131-8, 2008 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-18249417

RESUMO

Estimates of genotoxic effects of mutagens at low and protracted doses are often based on linear extrapolation of data obtained at relatively high doses. To test the validity of such an approach, a comparison was made between the mutagenicity of N-methyl-N-nitrosourea (MNU) in T-lymphocytes of the rat following two treatment protocols, i.e. sub-chronic exposure to a low dose (15-45 repeated exposures to 1mg/kg of MNU) or acute exposure to a single high dose (15, 30 or 45 mg/kg of MNU). Mutation induction appeared dramatically lower following sub-chronic treatment compared to treatment with a single high exposure. Furthermore, DNA sequence analysis of the coding region of the hprt gene in MNU-induced mutants showed that acute high dose treatment causes mainly GC-->AT base pair changes, whereas sub-chronic treatment results in a significant contribution of AT base pair changes to mutation induction. We hypothesize that O(6)-methylguanine-DNA methyltransferase is saturated after acute treatments, while after sub-chronic treatment most O(6)-methylguanine is efficiently repaired. These data suggest (i) that risk estimations at low and protracted doses of MNU on the basis of linear extrapolation of effects measured at high dose are too high and (ii) that the protective effects of DNA repair processes are relatively strong at low sub-chronic exposure.


Assuntos
Metilnitrosoureia/toxicidade , Mutagênese , Baço/efeitos dos fármacos , Alquilantes , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Metilação , Metilnitrosoureia/administração & dosagem , Ratos , Ratos Wistar , Fatores de Tempo
20.
J Natl Cancer Inst ; 86(19): 1458-62, 1994 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-8089864

RESUMO

BACKGROUND: Mutations in the p53 tumor suppressor gene (also known as TP53) are common in human lung cancers. The wild-type form of p53 is dominant over the mutant; thus, restoration of wild-type p53 function in lung cancer cells may suppress their growth as tumors. PURPOSE: We investigated the therapeutic efficacy of direct administration of a retroviral wild-type p53 (wt-p53) expression vector (LNp53B) in an orthotopic human lung cancer model in nu/nu mice. METHODS: Proliferation of H226Br cells was determined by cell counting after infection with LNp53B in vitro. Irradiated (350 cGy) female BALB/c nu/nu mice were inoculated intratracheally with 2 x 10(6) H226Br cells (whose p53 gene has a homozygous mutation at codon 254) and treated beginning 3 days later with an intratracheal instillation of LNp53B retroviral supernatant for 3 days. RESULTS: Infection with LNp53B inhibited proliferation of H226Br cells in vitro. Thirty days after tumor cell inoculation, 62%-80% of the control mice showed macroscopic tumors of the right main stem bronchus. LNp53B suppressed H226Br tumor formation in 62%-100% of mice, and the effect was abrogated by dilution of the retroviral supernatant with inactive vector. CONCLUSIONS: Direct administration of a retroviral vector expressing wt-p53 may inhibit local growth in vivo of human lung cancer cells with abnormal p53 expression. IMPLICATIONS: Development of gene-replacement treatment strategies based on the type of mutations found in target cancers is warranted and may lead to the development of new adjunctive therapies and gene-specific prevention strategies for lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Genes p53 , Terapia Genética/métodos , Vetores Genéticos , Neoplasias Pulmonares/terapia , Retroviridae , Animais , Sequência de Bases , Southern Blotting , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Dados de Sequência Molecular , Transplante de Neoplasias , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , RNA Neoplásico/análise , Células Tumorais Cultivadas
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