Expression of CD133 as a cancer stem cell marker in invasive gastric carcinoma.

INTRODUCTION: Gastric cancer is considered to be the fourth most common malignancy worldwide and the second cause of cancer deaths. Regarding the cancer stem cells (CSCs) theory, they are a small group of tumor cells with unrestricted self-renewal and differentiation abilities that help tumor formation. There is an interest in the utility of CD133 as a promising marker to detect the tumor stem cell population for a variety of solid malignancies including gastric cancer. Tumors that express stem cell markers such as CD133 are found to be more aggressive tumors with poor prognosis and high liability for recurrence. This study aimed to evaluate the immunohistochemical expression of CD133 in invasive gastric carcinoma and study the relation between CD133 immunohistochemical expression and different clinicopathological parameters. MATERIAL AND METHODS: 77 cases of gastric carcinoma were collected from the surgical pathology unit at the Gastroenterology Center, Mansoura University, Egypt. CD133 expression in tumor tissue was evaluated by immunohistochemistry. RESULTS: CD133 expression positively correlated with tumor metastasis and recurrence. Multivariate analysis revealed CD133 positivity to be an independent prognostic factor for tumor recurrence (P = 0.03). CONCLUSION: CD133 is a good marker that can predict tumor recurrence and metastasis in gastric carcinoma. Even though, studies regarding CSCs are still in their initial stages especially those related to CD133 in gastric cancer.

Investigation of belinostat-induced genomic instability by molecular cytogenetic analysis and pathway-focused gene expression profiling.

Histone deacetylases (HDACs), which regulate transcription and specific functions such as tumor suppression by p53, are frequently altered in tumors and have a contentious role in carcinogenesis. HDAC inhibitors, which have a long history of use in psychiatry and neurology, have recently been tested as possible treatments for tumors. Belinostat received regulatory approval in the USA on July 3, 2014, for use against peripheral T-cell lymphoma. However, the unavailability of information on belinostat genotoxicity in normal cells and the molecular mechanisms involved in the genetic instability after exposure to belinostat encouraged us to conduct this study. Our data showed that the exposure of mice to belinostat at the recommended human doses induced chromosome breakage, whole-chromosome lagging, and oxidative DNA damage in bone marrow cells in a dose-dependent manner. The expression levels of 84 genes involved in the DNA damage signaling pathway were evaluated by using an RT2 Profiler PCR array. Belinostat exposure altered the expression of 25 genes, with statistically significant changes observed in 17 genes. The array results were supported by RT-PCR and western blotting experiments. Collectively, our results showed that belinostat exposure caused oxidative DNA damage and downregulated the expression of genes involved in DNA damage repair, which may be responsible for belinostat-induced genomic instability. Thus, the clinical usage of this drug should be weighed against the hazards of carcinogenesis, and the observed genotoxicity profile of belinostat may support further development of efficient HDAC inhibitors with weaker genotoxicity.

The Effect of Sperm Morphology and Sire Fertility on Calving Rate of Finnish Ayrshire AI Bulls.

Good-quality semen is a prerequisite for successful and profitable artificial insemination (AI) of modern dairy cattle. Fertility of the bulls is evaluated with andrological examinations and semen analyses, such as morphology. However, little attention has been paid to the inheritance of bull fertility. In this study, we correlated sperm morphology, birth year and station of 695 AI bulls with calving rate (CR). Sperm morphology was clearly associated with CR underlining the usefulness of morphological examination in the assessment of fertility. The correlation between the proportion of normal spermatozoa and CR was significant (p < 0.001). No significant differences were detected between stations or birth years. We also compared the CR of 695 AI bulls with the CR of their 27 sires to study the inheritance of fertility. Sire's CR did not correlate with the CR of the sons (p = 0.218). This result indicates that at least when sires of acceptable CR are used to produce sons for use in AI the inheritance of CR is not significantly correlated.

Genotoxic evaluation of chloroacetonitrile in murine marrow cells and effects on DNA damage repair gene expressions.

Although chloroacetonitrile (CAN), a disinfection by-product of chlorination of drinking water, is considered a rodent carcinogen that induces lung adenomas in mice, previous studies on its genotoxicity have yielded inconclusive results. Thus, its cancer mode of action has not been clearly defined. We evaluated CAN-induced genotoxicity in mice using mouse bone marrow micronucleus test, comet assays and expression of genes associated with DNA damage repair. Mice exposed to CAN at 8.75, 17.5, 35 and 52.5mg/kg for 7 days did not exhibit any significant increases in the incidence of micronuclei formation at 24 and 48h after last exposure. However, CAN caused significant suppressions of erythroblast proliferation at the highest dose. In the alkaline comet assay, there was a significant increase in the incidence of DNA strand breaks in mice killed after 3h of last treatment with 35 and 52.5mg/kg/day CAN, while no significant difference in the DNA strand breaks was found in mice killed after 24h of the last treatment. However, slight (but significant) CAN-induced oxidative DNA damage was detected following Fpg digestion at 3-h sampling time, digestion with EndoIII resulted in considerable increases in oxidative DNA damage at 3 and 24h after the last exposure to 35 and 52.5mg/kg/day CAN as detected by oxidative comet assays. The expression of DNA repair genes OGG1 , Apex1, PARP1 and p53 were up-regulated in mice given 35mg/kg/day CAN at 3h but not in 24h after the last treatment except OGG1 . However, the significant up-regulation of OGG1 at 24h after the last treatment further indicates the occurrence of oxidative DNA damage. Overall, CAN exposure is associated with up-regulation of DNA repair gene expression and the induction of oxidative DNA damage, which may be at least partially responsible for CAN-induced genotoxicity and eventually cause carcinogenicity.

Utilizing combusted PET plastic waste and biogenic oils as efficient pour point depressants for crude oil.

The deposition of paraffin on pipelines during crude oil transit and low-temperature restart processes poses a significant challenge for the oil industry. Addressing this issue necessitates the exploration of innovative materials and methods. Pour point depressants (PPDs) emerge as crucial processing aids to modify paraffin crystallization and enhance crude oil flow. This study focuses on the combustion of polyethylene terephthalate (PET) waste, a prevalent plastic, in two distinct oils (castor and jatropha). The resulting black waxy substances (PET/Castor and PET/Jatropha) were introduced in varying weights (1000, 2000, and 3000 ppm) to crude oil. The PET/castor oil combination demonstrated a remarkable reduction in pour point from 18 to -21 °C at 3000 ppm concentration, significantly more effective than PET/jatropha blends. Substantial decreases in viscosity (up to 75%) and shear stress (up to 72%) were also observed for both blends, most prominently at lower temperatures near the pour point. The synergistic effect of PET and oils as nucleating agents that alter crystallization patterns and restrict crystal growth contributes to this enhanced low-temperature flow. This highlights the potential of PET plastic waste as an economical, abundant, and eco-friendly additive to develop high-performance PPDs for crude oil.

The small molecule Erk1/2 signaling pathway inhibitor PD98059 improves DNA repair in an experimental autoimmune encephalomyelitis SJL/J mouse model of multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disorder in which the myelin sheath covering the central nervous system axons is damaged or lost, disrupting action potential conduction and leading to various neurological complications. The pathogenesis of MS remains unclear, and no effective therapies are currently available. MS is triggered by environmental factors in genetically susceptible individuals. DNA damage and DNA repair failure have been proposed as MS genetic risk factors; however, inconsistent evidence has been found in multiple studies. Therefore, more investigations are needed to ascertain whether DNA damage/repair is altered in this disorder. In this context, therapies that prevent DNA damage or enhance DNA repair could be effective strategies for MS treatment. The overactivation of the extracellular-signal-related kinase 1 and 2 (Erk1/2) pathway can lead to DNA damage and has been linked to MS pathogenesis. In our study, we observed substantially elevated oxidative DNA damage and slower DNA repair rates in an experimentally autoimmune encephalomyelitis animal model of MS (EAE). Moreover, statistical decreases in oxidative DNA strand breaks and faster repair rates were observed in EAE animals injected with the Erk1/2 inhibitor PD98059 (PD). Moreover, the expression of several genes associated with DNA strand breaks and repair changed in EAE mice at both the mRNA and protein levels, as revealed by the RT2 Profiler PCR array and verified by RT-PCR and protein analyses. The treatment with PD mitigated these changes and improved DNA repair gene expression. Our results demonstrate clear associations between Erk1/2 activation, DNA damage/repair, and MS pathology, and further suggest that PD therapy may be a promising adjuvant therapeutic strategy.

A potential role of mesenchymal stem cells derived from human umbilical cord blood in ameliorating psoriasis-like skin lesion in the rats.

BACKGROUND: Psoriasis is a common autoimmune inflammatory skin disease, with no clear cause, treated with topical agents and phototherapy, conventional immunosuppressant drugs and biologic agents. Stem cell therapy has generated significant interest in regenerative medicine. The aim of this study was to use mesenchymal stem cell (MSC) therapy compared to the topical application of the standard conventional corticosteroid cream. MATERIALS AND METHODS: Forty male adult albino rats were used, divided into four groups, 10 rats each: group I (control), group II (psoriasis-like lesions induced by usage of Aldara cream), group III (treated with betamethasone) and group IV (treated with MSCs). Specimens were stained with haematoxylin and eosin, Masson's trichrome, immune-histochemical technique for CD4, CD8 and CD31. Ultra-sections were prepared for transmission electron microscope (TEM) examination. RESULTS: Mesenchymal stem cells demonstrated efficacy in reduction of disease severity in the form of uniform epidermal thickness covered by a very thin keratin layer. Normally arranged layers of epidermal layers, with a clear border demarcation, were seen between the epidermis and the dermis with apparently intact basement membrane. TEM showed absence of gaps between the tightly connected cells of the basal layer and the resting basement membrane. CONCLUSIONS: Application of MSCs raises hope for developing a new, safe and effective therapy for psoriatic patients, avoiding the side effects of betamethasone.

Salubrious effects of dexrazoxane against teniposide-induced DNA damage and programmed cell death in murine marrow cells.

The intention of the present study was to answer the question whether the catalytic topoisomerase-II inhibitor, dexrazoxane, can be used as a modulator of teniposide-induced DNA damage and programmed cell death (apoptosis) in the bone marrow cells in vivo. The alkaline single cell gel electrophoresis, scoring of chromosomal aberrations, micronuclei and mitotic activity were undertaken in the current study as markers of DNA damage. Apoptosis was analysed by the occurrence of a hypodiploid DNA peak and caspase-3 activity. Oxidative stress marker such as intracellular reactive oxygen species production, lipid peroxidation, reduced and oxidised glutathione were assessed in bone marrow as a possible mechanism underlying this amelioration. Dexrazoxane was neither genotoxic nor apoptogenic in mice at the tested dose. Moreover, for the first time, it has been shown that dexrazoxane affords significant protection against teniposide-induced DNA damage and apoptosis in the bone marrow cells in vivo and effectively suppresses the apoptotic signalling triggered by teniposide. Teniposide induced marked biochemical alterations characteristic of oxidative stress including accumulation of intracellular reactive oxygen species, enhanced lipid peroxidation, accumulation of oxidised glutathione and reduction in the reduced glutathione level. Prior administration of dexrazoxane ahead of teniposide challenge ameliorated these biochemical alterations. It is thus concluded that pretreatment with dexrazoxane attenuates teniposide-induced oxidative stress and subsequent DNA damage and apoptosis in bone marrow cells. Based on our data presented, strategies can be developed to decrease the teniposide-induced DNA damage in normal cells using dexrazoxane. Therefore, dexrazoxane can be a good candidate to decrease the deleterious effects of teniposide in the bone marrow cells of cancer patients treated with teniposide.

Chemical composition and acaricidal properties of Deverra scoparia essential oil (Araliales: Apiaceae) and blends of its major constituents against Tetranychus urticae (Acari: Tetranychidae).

The essential oil of Deverra scoparia Coss. & Durieu was investigated for its acaricidal activity against the worldwide pest twospotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae). The essential oil was analyzed by fast gas chromatography (GC) and GC-mass spectrometry. The activities of its individual and blended constituents were determined. Our study showed that female mortality increased with increasing D. scoparia oil concentrations, with LD50 and LD90 values at 1.79 and 3.2 mg liter(-1), respectively. A reduction in fecundity had already been observed for concentrations of 0.064, 0.08, and 0.26 mg liter(-1) D. scoparia essential oil. Ten major components, comprising 98.52% of the total weight, were identified; a-pinene was the most abundant constituent (31.95%) followed by sabinene (17.24%) and delta3-carene (16.85%). The 10 major constituents of D. scoparia oil were individually tested against T. urticae females. The most potent toxicity was found with alpha-pinene, delta3-carene, and terpinen-4-ol. The presence of all constituents together in the artificial mixture caused a significant decrease in the number of eggs laid by females, at 0.26 mg liter(-1) (11 eggs), compared with the control (50 eggs). The toxicity of blends of selected constituents indicated that the presence of all constituents was necessary to reproduce the toxicity level of the natural oil.

Proliferation, DNA repair and apoptosis in androgenetic alopecia.

BACKGROUND: Androgenetic alopecia is a common hair disorder, resulting from interplay of genetic, endocrine and ageing factors. Meanwhile, it is unclear if an altered degree of proliferation or increased apoptosis could contribute to its pathogenesis. OBJECTIVE: To evaluate the role of proliferation, DNA damage and apoptosis in the pathogenesis of androgenetic alopecia. METHODS: Thirty biopsies were taken from the frontal (bald) area and occipital (hairy) area of 15 male patients with androgenetic alopecia, as well as five specimens from frontal area of five age-matched controls. These specimens were used for immunohistochemical staining of cell proliferation [proliferating cell nuclear antigen (PCNA)] and DNA repair markers (XRCC1, APE1, PARP-1) as well as apoptosis regulatory protein p53. RESULTS: The frontal bald area of patients showed significantly higher levels of X-ray Cross Complementing-1 (XRCC1; P<0.001) and p53 (P<0.001) expression when compared with occipital hairy area of patients and frontal area of controls (P=0.003 and 0.04, respectively). On the other hand, there were significantly lower expression of PCNA (P<0.001) and apurinic/apyridinic endonuclease 1 (APE1; P=0.001 and 0.02) when compared with the frontal area of controls and occipital area of patients, respectively. Meanwhile, APE1 showed significant inverse correlation with p53 overexpression (P=0.03). CONCLUSION: The frontal bald area of patients with androgenetic alopecia has lower proliferation rate that result in follicular miniaturization. There is increased DNA damage that would be beyond the capacity of cells to repair in advanced cases. An alternative pathway would take place in order to eliminate the damaged cells through apoptosis.

[Eye and Behçet's disease]. / Œil et maladie de Behçet.

Behçet's disease is a chronic multisystem disorder characterized by relapsing inflammation for which the underlying histopathology is an occlusive vasculitis. The disease has a high prevalence in the Mediterranean region, Far and Middle Eastern countries. It is clinically characterized by oral and genital ulcerations, ocular inflammatory involvement, skin lesions, vascular involvement and numerous other systemic manifestations. Uveitis is by far the most common ocular manifestation of Behçet's disease. It typically presents in the form of relapsing-remitting panuveitis with retinal vasculitis that may result in severe visual loss. Management of Behçet's uveitis relies on corticosteroid therapy, conventional immunosuppressive drugs and biological agents and requires a close collaboration between ophthalmologist and internist. A better understanding of the auto-inflammatory process and of the role of cytokines implicated in the pathogenesis of Behçet's disease will enable researchers to develop more specific and effective therapy.

Eye and Behçet's disease.

Behçet's disease is a chronic multisystem disorder characterized by relapsing inflammation for which the underlying histopathology is an occlusive vasculitis. The disease has a high prevalence in the Mediterranean region, Far and Middle Eastern countries. It is clinically characterized by oral and genital ulcerations, ocular inflammatory involvement, skin lesions, vascular involvement and numerous other systemic manifestations. Uveitis is by far the most common ocular manifestation of Behçet's disease. It typically presents in the form of relapsing-remitting panuveitis with retinal vasculitis that may result in severe visual loss. Management of Behçet's uveitis relies on corticosteroid therapy, conventional immunosuppressive drugs and biological agents and requires a close collaboration between ophthalmologist and internist. A better understanding of auto-inflammatory process and of the role of cytokines implicated in the pathogenesis of Behçet's disease will enable researchers to develop more specific and effective therapy.

Novel ambulatory glucose-sensing technology improves hypoglycemia detection and patient monitoring adherence in children and adolescents with type 1 diabetes.

PURPOSE: Glucose monitoring [GM] is a mainstay of diabetes control and management. Improving glycemic control is essential to prevent microvascular complications. However, adherence to GM can be a challenge in children and adolescents. Detecting hypoglycemia is essential for its prevention and treatment. We aim to study the impact of the flash ambulatory glucose monitoring in detecting hypoglycemia and enhancing adherence in children and adolescents with type 1 diabetes. METHODS: The study is prospective involving 3 hospital visits. Children and adolescents with diabetes were enrolled in the study which involved a period on conventional glucose self-monitoring [glucometers] followed by a similar period of monitoring using the flash glucose monitoring device (FreeStyle Libre). Frequency of GM, duration and frequency of hypoglycemia were compared on conventional and the flash monitoring. RESULTS: 75 subjects were studied. Age mean (range) was 11.9 years (2-19). Significant difference was seen in hypoglycemia detection between both testing devices. 68 (94%) and 65 (90%) patients detected nocturnal and diurnal hypoglycemia respectively on Flash monitoring compared to 12 (16.6%) and 30 (41%) on glucometer testing (p < 0.00). Mean (range) duration of hypoglycemia was 95 min (15-330). Statistically-significant difference was found between the frequency of GM on glucometer testing compared with Flash monitoring (2.87 and 11.6/day) (p < 0.001). CONCLUSIONS: Flash monitoring is a useful tool to improve adherence to GM and detecting hypoglycemia [diurnal and nocturnal] in children and adolescents with type 1 diabetes.

Assessment of DNA repair efficiency in the inbred BTBR T+tf/J autism spectrum disorder mouse model exposed to gamma rays and treated with JNJ7777120.

Information regarding DNA repair in autism is limited to a few studies, which have reported inconsistent results. Therefore, we designed a study to determine whether DNA repair efficiency is altered in autism and to investigate whether the H4 ligand JNJ7777120 can enhance DNA repair efficiency in BTBR T+tf/J (BTBR) mice; we also attempted to elucidate the mechanism(s) underlying this amelioration. Evaluation of DNA damage using the comet assay on bone marrow cells showed increased levels of DNA damage in BTBR mice compared with age-matched control C57BL/6J mice. Conversely, BTBR animals pretreated with 20 mg/kg JNJ7777120 for five days exhibited significant decreases in DNA damage compared with that of control BTBR mice. Our results also indicated higher sensitivity of BTBR mice exposed to gamma rays to DNA damage generation. A marked difference was observed between BTBR and C57BL/6J mice at different sampling times after irradiation, with BTBR mice showing a higher percentage of DNA damage and slower repair rate than that of C57BL/6J mice. JNJ7777120 led to enhanced repair of the DNA damage induced by radiation when administered to BTBR mice five days prior to radiation. Additionally, oxidative stress in BTBR mice was significantly elevated with a reduced GSH/GSSG ratio; significant amelioration was subsequently observed in JNJ7777120-pretreated BTBR mice. Furthermore, repetitive behaviors were also attenuated in BTBR mice by JNJ7777120 treatment without altering locomotor activity. Our results suggest that JNJ7777120 can be developed for use as a therapeutic agent to enhance DNA repair efficiency in autism spectrum disorder.

Evaluation of aneugenic effects of bisphenol A in somatic and germ cells of the mouse.

Bisphenol A (BPA) is a synthetic monomer widely used to polymerize polycarbonate plastics and resins. It is shown in vitro to interfere with microtubules, producing aberations in mitotic and meiotic spindles. An increase of meiotic abnormalities in untreated female mice from an experimental colony was temporally correlated with the accidental release of BPA from polycarbonate cages and bottles damaged by inadvertent treatment with harsh alkaline detergents [P.A. Hunt, K.E. Koehler, M. Susiarjo, C.A. Hodges, A. Ilagan, R.C. Voigt, S. Thomas, B.F. Thomas, T.J. Hassold, Bisphenol A exposure causes meiotic aneuploidy in the female mouse, Curr. Biol. 13 (2003) 546-553]. In the present study, potential aneugenic effects of BPA on mouse male and female germ cells and bone marrow cells have been evaluated after acute, sub-chronic or chronic in vivo exposure. Female mice were orally treated with a single BPA dose, with 7 daily administrations or exposed for 7 weeks to BPA in drinking water. No significant induction of hyperploidy or polyploidy was observed in oocytes and zygotes at any treatment condition. The only detectable effect was a significant increase of metaphase II oocytes with prematurely separated chromatids after chronic exposure; this effect, however, had no irreversible consequence upon the fidelity of chromosome segregation during the second meiotic division, as demonstrated by the normal chromosome constitution of zygotes under the same exposure condition. With male mice, no delay of meiotic divisions was found after six daily oral doses of BPA with the BrdU assay. Similarly, no induction of hyperploidy and polyploidy was shown in epydidimal sperm hybrized with probes for chromosomes 8, X and Y, 22 days after six daily oral BPA doses. Finally, two daily oral BPA doses did not induce any increase of micronucleus frequencies in polychromatic erythrocytes of mouse bone marrow. In conclusion, our results do not add evidence to the suspected aneugenic activity of BPA and suggest that other factors or co-factors should be considered to explain the unexpected burst of meiotic abnormalities previously attributed to accidental BPA exposure.

[Hydatid disease of the first rib treated surgically by the Roos approach]. / Hydatidose de la première côte opérée par voie de Roos.

Hydatid disease is a parasitic infection due to Echinococcus granulosus. Since involvement of the ribs and in particular the first rib is rare, diagnosis and treatment in these locations can pose special problems. The purpose of this report is to describe the case of a 27-year-old man in whom an apical left opacity was discovered by chance. Clinical examination was normal. Thoracic ultrasound demonstrated multilocular cyst in the left apical region of the thorax. Thoracic computed tomography (CT) demonstrated a hydatid cyst originating from the first rib. The patient was operated using the technique known as the Roos approach. The procedure consisted of cystectomy with resection of the first rib. The multiloculated appearance of the lesion and erosion at the first rib was consistent with hydatid cyst. The Roos approach is the technique of choice for the treatment of the first rib.

Synthesis and spectroscopic studies on chromium(III) complex containing mixed-valence chrysenesemiquinone-chrysenecatecholate ligands and 2,2'-bipyridine coligand.

The synthesis and spectroscopic properties of Cr(bpy)(chrySQ)(chryCat), a complex containing chromium(III) metal ion and chrysenequinone ligand in its partially reduced (chrySQ) and fully reduced (chryCat) forms, are described. The complex has been prepared by two different routes from Cr(CO)6 and Cr(chrySQ)3. Variable temperature magnetic susceptibility measurements indicated a strong antiferromagnetic coupling between Cr(III) (S=3/2) and chrysenesemiquinone radical (S=1/2), giving a magnetic coupling constant J=-342 cm(-1). Ligand-based redox couples were observed in the electrochemical studies that consist of quasi-reversible chrySQ/chryCat and bpy/bpy*- reductions and chryCat/chrySQ oxidation at negative potentials and irreversible chrySQ/chryBQ oxidation at positive potential. However, the metal was inert in the studied potential range. The electronic spectra of the complex revealed interesting properties. In addition to interaligand pi-pi* and n-pi* transitions, other bands corresponding to Cr(t(2g))-->chrySQ(pi*) and Cr(t(2g))-->bpy(pi*) metal-to-ligand charge-transfer MLCT transitions were observed. The infrared spectral analysis was informative in assigning the vibrations due to SQ and Cat ligands. Also, it was a useful tool in confirming the coordination of bpy ligand to chromium metal ion.

[Broncholithiasis]. / Broncholithiase.

INTRODUCTION: Broncholithiasis is defined as the presence of calcified material in the bronchial lumen. The aim of our work was to study the clinical, radiological and therapeutic aspects of broncholithiasis. OBSERVATIONS: We report the histories of 6 patients identified over 14 years (1990-2004). They included 4 men and 2 women with an average age of 50 years. A past history of pulmonary tuberculosis was found in 2 cases. The presenting symptom was haemoptysis in 4 patients. Fibreoptic bronchoscopy was performed in all patients and broncholiths were found in two. Thoracic CT scan was performed in 5 patients and in 3 showed hilar and parenchymal calcification, suggesting the diagnosis of broncholithiasis. The diagnosis was confirmed in 2 patients by bronchoscopy, in 2 others by surgical biopsy and in the remaining 2 by the CT appearances. Three patients were operated on: 2 for diagnosis and the third for haemostasis. Pulmonary tuberculosis was discovered in 2 patients, one by culture and the other by surgical biopsy. The outcome was satisfactory in all cases. CONCLUSIONS: Broncholithiasis presents a problem of differential diagnosis from other pulmonary pathologies on account of misleading clinical, endoscopic and radiological features.

Impact of dexrazoxane on doxorubicin-induced aneuploidy in somatic and germinal cells of male mice.

PURPOSE: Despite dexrazoxane's increasing use in mitigating doxorubicin-induced cardiotoxicity, no data are available in the literature on the potential aneugenicity of drug combination. Therefore, detailed evaluation of aneugenic potential of this combination is essential to provide more insights into aneuploidy induction that may play a role in the development of secondary malignancies and reproductive toxicity after treatment with doxorubicin. Thus, our aim was to determine whether dexrazoxane has influence on the aneuploidy induced by doxorubicin in germinal and somatic cells of male mice. METHODS: Sperm BrdU-incorporation assay, sperm FISH assay and the bone marrow micronucleus test complemented by FISH assay were used to determine aneuoploidy. Moreover, the formation of 8-OHdG, one of the oxidative DNA damage by-products, has been evaluated. RESULTS: Dexrazoxane was not aneugenic at the doses tested. Pre-treatment of mice with dexrazoxane significantly reduced doxorubicin-induced aneuploidy in a dose-dependent manner. Doxorubicin induced marked biochemical alterations characteristic of oxidative DNA damage, and prior administration of dexrazoxane before doxorubicin challenge ameliorated this biochemical marker. CONCLUSION: This study provides evidence that dexrazoxane has a protective role in the abatement of doxorubicin-induced aneuploidy. This activity resides, at least in part, in its radical scavenger activity. Thus, dexrazoxane can avert secondary malignancies and abnormal reproductive outcomes in cured cancer patients exposed to doxorubicin.