bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic delay of oral squamous cell carcinoma in two diagnosis centers in Córdoba Argentina
Authors: Morelatto R. A. , Herrera M. C. , Fernández E. N. , Corball A. G. , López de Blanc S. A.
Published: August 2010

Abstract:  The aim of the present study was to investigate diagnostic delay in oral cancer (OC) in two diagnosis centers in Córdoba, Argentina. Special attention was paid to the role of the patient and the professional in the diagnostic delay.

Methods:  Seventy clinical records of patients with newly diagnosed oral squamous cell carcinoma were included.

Results:  Both patients and professionals were responsible for the delay in diagnosis. This delay was longer for tumors in early stages. Multiple logistic regression analysis indicated that the professional delay was the most associated variable to the stage of tumor (P = 0.03).

Conclusions:  Continuing education in OC and pre‐cancerous lesions is important to reduce the professional delay. The findings of the present study also indicate that 58% of the patients are partially responsible for delay in the diagnosis of OC. Intensive public promotion and educational campaigns against OC are also needed to increase patient awareness.
An orthotopic floor‐of‐mouth model for locoregional growth and spread of human squamous cell carcinoma
Authors: Henson B. , Li F. , Coatney D. D. , Carey T. E. , Mitra R. S. , Kirkwood K. L. , D’Silva N. J.
Published: August 2010

The molecular investigation of head and neck cancer targets requires the utilization and optimization of established animal models to characterize the effects of gene transcription and protein expression on invasion and metastasis. Floor‐of‐the‐mouth murine models have been developed to study tumor growth, invasion, and metastasis of murine squamous cell carcinoma (SCC) cells in immunocompetent mice and invasion and metastasis of human SCC cells in nude mice. However, there are tumor cell lines that do not produce tumors in mice, using standard techniques, thus reducing the utility of the model to study specific genetic or treatment conditions. Furthermore, these techniques require large tumor volumes raising the possibility of airway compromise. In this report, we detail significant modifications to the orthotopic floor‐of‐mouth murine model for human SCC to facilitate predictable growth of a large panel of University of Michigan SCC cell lines. Furthermore, we describe the use of bioluminescence and micro‐computed tomography to monitor tumor growth and bony invasion.
Presence of ghost cells and the Wnt signaling pathway in odontomas
Authors: Tanaka Akio , Okamoto Motoyoshi , Yoshizawa Dai , Ito Shigeru , Alva Patricia González , Ide Fumio , Kusama Kaoru
Published: August 2010

Background:  Although it has been reported that ghost cells are present in odontomas, the generation mechanism of these cells is unclear. To evaluate the presence of ghost cells and involvement of the Wnt signaling pathway, we examined the expression of hard keratins, β‐catenin and Lef‐1 in odontomas.

Methods:  Sixty‐nine cases of odontoma were examined immunohistochemically with the use of antibodies against human hair proteins, β‐catenin and Lef‐1.

Results:  Expression of hard keratins was found only in the cytoplasm of ghost cells in 46 (66.7%) of the 69 odontomas. Compound odontomas (78.8%) showed a higher incidence of ghost cells than complex odontomas (29.4%). Histopathologically, ghost cells were found within odontogenic epithelium adjacent to immature enamel and in the centre of Liesegang‐ring‐like calcified materials. Expression of β‐catenin and Lef‐1 was observed in the cytoplasm and nucleus of odontogenic epithelial cells adjacent to the ghost cells in immature odontomas.

Conclusion:  These findings suggest that odontoma is a hard keratin‐expressing tumor‐like lesion, and that the Wnt signaling pathway may be involved in the formation of ghost cells in odontomas.
Functional −1562 C‐to‐T polymorphism in matrix metalloproteinase‐9 (MMP‐9) promoter is associated with the risk for oral squamous cell carcinoma in younger male areca users
Authors: Tu Hsi‐Feng , Wu Cheng‐Hsien , Kao Shou‐Yen , Liu Chung‐Ji , Liu Tsung‐Yun , Lui Man‐Tin
Published: August 2010

Background:  Circulating matrix metalloproteinase‐9 (MMP‐9) is a prognostic factor for gastric cancer and vascular diseases, and has been associated with head and neck cancers. The −1562 C‐to‐T polymorphism in MMP‐9 promoter (abbreviated MMP‐9−1562 C>T polymorphism) leads to differential transcription, and is associated with increased susceptibility to neoplastic and vascular diseases. Thus, our aim was to determine whether a functional MMP‐9 polymorphism might also influence the risk or affect the progression of areca‐associated oral cancers.

Methods:  Genomic DNAs were obtained from peripheral blood cells of male subjects with areca‐associated oral squamous cell carcinoma (OSCC) (n = 192), oral submucosal fibrosis (OSF) (n = 73), and non‐diseased areca users (n = 191). The PCR‐based restriction fragment length polymorphism analysis was performed for MMP‐9 genotyping.

Results:  MMP‐9
−1562 C>T polymorphism was not associated with the risk of OSCC or OSF. However, when subjects were stratified by the median age, an association with the risk of OSCC was found in younger patients (P = 0.029). The T allele frequency was significantly higher in the subset of older patients with buccal mucosa OSCC than older patients with OSCC in counterpart locations. The joint MMP‐9−1562 C>T and MMP‐3−1171 5A>6A functional polymorphisms were not associated with OSCC risk or patient survival.

Conclusion:  Aberrant MMP‐9 expression is closely related to tumor invasiveness and the prognosis of head and neck cancers. However, functional MMP‐9−1562 C>T polymorphism is associated with OSCC risk only in younger areca chewers. The impact of aging or areca‐related effect on this functional polymorphism should be elucidated.
Immunohistochemical detection of uPA, uPAR, PAI‐1, and maspin in ameloblastic tumors
Authors: Kumamoto H. , Ooya K.
Published: August 2010

Background:  To evaluate the roles of extracellular matrix (ECM)‐degrading serine proteinase in progression of odontogenic tumors, expression of urokinase‐type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor‐1 (PAI‐1), and maspin was analyzed in ameloblastic tumors as well as in tooth germs.

Methods:  Tissue specimens of 10 tooth germs, 45 ameloblastomas, and 5 malignant ameloblastic tumors were examined immunohistochemically with the use of antibodies against uPA, uPAR, PAI‐1, and maspin.

Results:  Immunohistochemical reactivity for uPA, uPAR, PAI‐1, and maspin was detected in normal and neoplastic odontogenic tissues: uPA was recognized predominantly in mesenchymal cells, uPAR was evident in epithelial cells, PAI‐1 was found in both epithelial and mesenchymal cells, and maspin was expressed only in epithelial cells. The levels of uPA and uPAR immunoreactivity in ameloblastic tumors were slightly higher than the levels in tooth germs, while PAI‐1 reactivity in ameloblastomas tended to be lower than that in tooth germs. The level of maspin immunoreactivity in ameloblastomas was significantly higher than that in tooth germs, and ameloblastic carcinoma showed decreased maspin reactivity.

Conclusion:  Expression of uPA, uPAR, PAI‐1, and maspin in tooth germs and ameloblastic tumors suggests that interactions among these molecules contribute to ECM degradation and cell migration during tooth development and tumor progression. Altered expression of the serine proteinase and its associated molecules in ameloblastic tumors may be involved in oncogenesis of odontogenic epithelium.
Immunohistochemical detection of phosphorylated JNK, p38 MAPK, and ERK5 in ameloblastic tumors
Authors: Kumamoto H. , Ooya K.
Published: August 2010

Background:  To evaluate roles of mitogen‐activated protein kinases (MAPKs) in oncogenesis and cytodifferentiation of odontogenic tumors, expression of phosphorylated JNK (p‐JNK), p38 MAPK (p‐p38 MAPK), and ERK5 (p‐ERK5) was analyzed in ameloblastic tumors as well as in tooth germs.

Methods:  Ten tooth germs, 47 ameloblastomas, and 5 malignant ameloblastic tumors were examined immunohistochemically with the antibodies against p‐JNK, p‐p38 MAPK, and p‐ERK5.

Results:  Immunoreactivity for p‐JNK was detected in epithelial or neoplastic cells detached from the basement membrane in 7 tooth germs and 7 ameloblastomas, and the expression levels of p‐JNK in ameloblastic tumors were significantly lower than that in tooth germs. Expression of p‐p38 MAPK was found in epithelial or neoplastic cells in tooth germs and ameloblastic tumors except for two ameloblastomas, and increased expression was found in keratinizing cells of acanthomatous ameloblastomas. The expression level of p‐p38 MAPK in ameloblastomas was significantly higher than the levels in tooth germs and malignant ameloblastic tumors. Immunoreactivity for p‐ERK5 was found predominantly in epithelial or neoplastic cells near the basement membrane in tooth germs and ameloblastic tumors. The expression levels of p‐ERK5 in ameloblastic tumors were slightly higher than that in tooth germs, and plexiform ameloblastomas showed significantly higher p‐ERK5 expression than follicular ameloblastomas.

Conclusion:  Expression of p‐JNK, p‐p38 MAPK, and p‐ERK5 in tooth germs and ameloblastic tumors suggests that these MAPK signaling pathways contribute to cell proliferation, differentiation, or apoptosis in both normal and neoplastic odontogenic tissues. Altered expression of these phosphorylated MAPKs in ameloblastic tumors may be involved in oncogenesis and tumor cell differentiation.
Detection and genotyping of human papillomavirus DNA in samples from healthy Sardinian patients: a preliminary study
Authors: Montaldo Caterina , Mastinu Andrea , Quartuccio Marta , Piras Vincenzo , Denotti Gloria , Pisano Elisabetta , Orrù Germano
Published: August 2010

The human papillomavirus (HPV) is involved in the development of different benign and malignant lesions that include in particular squamous tumours of the cervix, skin and the respiratory tracts. In particular, the ‘high risk’ HPV type 16 (HPV 16) causes genito‐rectal epithelial cancers and is suspected of causing epithelial cancers of the head and neck. To determine the presence and genotypes of HPV was determined in saliva samples from 164 subjects recruited from the Department of Surgery and Odontostomatological Sciences (University of Cagliari). For this study a sensitive seminested polymerase chain reaction (PCR) method was used to detect HPV‐DNA; moreover in all positive samples, HPV genotyping was based on sequencing of the HPV genome L1 region. The results obtained with these patients (who were ethnically homogeneous), showed an interesting percentage of positive samples for HPV‐DNA (30 samples out of 164–18.3%). Only two HPV genotypes have been identified in these patients, HPV 16 and HPV 31 with 76.7% and 23.3% of the positive specimens, respectively, both correlating with high carcinogenic risk. This preliminary result leads us to reflect on the presence of HPV in saliva, in particular in young asymptomatic subjects (15.38%), and its prognostic value for the possible incidence in Sardinia of oral carcinoma.
Investigation of functional gene polymorphisms: IL‐1B, IL‐6 and TNFA in benign migratory glossitis in Brazilian individuals
Authors: Guimarães André Luiz Sena , Correia‐Silva Jeane de Fátima , Diniz Marina Gonçalves , Xavier Guilherme Machado , Horta Martinho Campolina Rebello , Gomez Ricardo Santiago
Published: August 2010

Background:  Benign migratory glossitis (BMG) is a very common immunological oral disease of unknown aetiology.

Methods and subjects:  Fifty‐three consecutive subjects affected by BMG and 53 age‐ and sex‐matched control subjects were genotyped for IL‐1B, IL‐6 and TNFA polymorphisms. Binary logistic regression models were fitted and values of P < 0.05 were considered significant.

Results:  A significant difference in the distribution of IL‐1B genotypes was observed in the group with BMG in univariate analyses (P = 0.01). The multivariate analyses showed that the CT genotype of the IL1‐B gene was significantly associated with a high risk to develop BMG (P = 0.02, OR 2.76). The combined presence of IL‐1β high and intermediate producers genotypes was also associated with BMG in multivariate analyses (P = 0.01, OR 3.05). IL‐6 and TNFA polymorphisms were not associated with BMG in the univariate and multivariate analyses.

Conclusion:  Our findings demonstrate that the polymorphism +3954 IL‐1B is associated with an increased risk of BMG development and suggest a genetic basis for disease development.
Investigation of functional gene polymorphisms interleukin‐1β, interleukin‐6, interleukin‐10 and tumor necrosis factor in individuals with oral lichen planus
Authors: Xavier Guilherme Machado , Sá Alessandra Rosa de , Guimarães André Luiz Sena , Silva Tarcília Aparecida da , Gomez Ricardo Santiago
Published: August 2010

Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. There are some studies in the literature demonstrating association between cytokines genes polymorphisms and susceptibility to develop some immune‐mediate conditions. The purpose of this study was to investigate cytokine gene polymorphisms in a sample of Brazilian patients with OLP. Fifty‐three patients with OLP (mean age = 43.1 years; range 20–68 years) and 53 healthy volunteers (mean age = 42.9 years; range 21–67) were genotyped for IL‐1β +3954 (C/T), IL‐6−174 (G/C), IL‐10−1082 (G/A) and TNFA−308 (G/A) gene polymorphisms. Statistical analysis was based on the use of logistic regression (P‐values below 0.05 were considered as significant). IL‐6 and TNFA homozygous genotypes were significantly more often detected in OLP patients. These genotypes were associated with an increased risk of OLP development (OR 6.89 and 13.04, respectively). IL‐1β and IL‐10 gene polymorphisms were not related to OLP development. Our findings clearly demonstrate an association between inheritance of IL‐6 and TNFA gene polymorphisms and OLP occurrence, thus giving additional support for genetic basis of this disease.
In vitro candidacidal activity of a synthetic killer decapeptide (KP) against Candida albicans cells adhered to resin acrylic discs
Authors: Manfredi M. , Merigo E. , Salati A. , Conti S. , Savi A. , Polonelli L. , Bonanini M. , Vescovi P.
Published: August 2010

Background:  Oral Candida spp., and C. albicans in particular, are considered as important aetiological agents in the pathogenesis of denture‐induced stomatitis. Several studies have reported that C. albicans is able to easily adhere to different medical devices, such as vascular and urinary catheters or acrylic denture surfaces, and that adhesion is a fundamental step in the initial pathogenic process of colonization and further possible infection. Recently, a synthetic decapeptide (KP) derived from the sequence of a single‐chain recombinant anti‐idiotypic antibody, acting as a functional internal image of a microbicidal, broad spectrum yeast killer toxin, has been reported to kill in vitro C. albicans cells and to exert a therapeutic activity against experimental mucosal and systemic candidiasis.

Methods:  The aim of this study was to evaluate, through a CFU assay, the candidacidal activity of KP on sanded acrylic resin discs, previously colonized by C. albicans cells.

Results and conclusions: At 100 μg/ml KP showed over 90% of killing activity on C. albicans cells adhered to resin discs, when compared with a scramble peptide used as control. The results of this study suggest a potential effect of KP on C. albicans cells adhered on the surface of resin materials, such as prosthetic dentures.
Analysis of the neoplastic nature and biological potential of sporadic and nevoid basal cell carcinoma syndrome‐associated keratocystic odontogenic tumor
Authors: Katase Naoki , Nagatsuka Hitoshi , Tsujigiwa Hidetsugu , Gunduz Mehmet , Tamamura Ryo , Pwint Han Phuu , Rivera Rosario Santos , Nakajima Motowo , Naomoto Yoshio , Nagai Noriyuki
Published: August 2010

Background:  Keratocystic odontogenic tumor (KCOT), also known as odontogenic keratocyst, is a benign cystic neoplasm, which may be associated with nevoid basal cell carcinoma syndrome (NBCCS) and if it does, will occur as multiple cystic lesions. KCOT is locally destructive despite its bland histological features. However, the neoplastic nature of KCOT is not well established.

Heparanase is an endo‐d‐glucuronidase enzyme that specifically cleaves heparan sulfate (HS) and the increase of its level in tumors promotes invasion, angiogenesis, and metastasis.

Methods:  To investigate the neoplastic character of KCOT, we studied the localization patterns of heparanase in KCOT, focusing on the differences between sporadic and NBCCS‐associated KCOTs, by immunohistochemistry and in situ hybridization. To compare the expression pattern of these cysts with non‐tumorous odontogenic developmental cyst, dentigerous cyst was included.

Results:  All the odontogenic cysts showed positive immunoreaction for heparanase protein in various intensities. The expression pattern of heparanase gene corresponded to that of protein expression. Interestingly, intense gene and protein expressions were observed in KCOT associated with NBCCS compared with sporadic ones and dentigerous cyst.

Conclusions:  The results implied that heparanase expression may be correlated with the neoplastic properties of KCOT, particularly in NBCCS‐associated cases.
Oral lichen planus in relation to transaminase levels and hepatitis C virus
Authors: Ali A A. , Suresh C. S.
Published: August 2010

Background:  Elevation of transaminase levels was reported earlier in patients with oral lichen planus. The association between hepatitis C virus (HCV) and lichen planus had given positive and negative results. The controversies and uncertainties regarding the association of HCV and the liver function status (transaminase levels) in oral lichen planus inspired us to conduct this study.

Patients and Methods:  This study was performed on 40 patients with different types of oral lichen planus as a study group and 40 healthy cases as control group. All patients were subjected to routine blood test and urine analysis and the estimation of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels. The values of SGOT and SGPT levels ≤40 IU / l were considered within normal limits. Anti‐HCV titer was estimated in all cases.

Results:  Fourteen patients (35%) with oral lichen planus had diabetes mellitus, while six (15%) cases of the control group had diabetes mellitus (P = 0.04). Regarding SGOT and SGPT levels, it was elevated in 19 cases (47.5%) and in 4 cases (10%) of the study group and control group, respectively (P = 0.0002). In relation to the type of oral lichen planus, out of 15 erosive cases, 80% (12 cases) showed elevated SGOT/SGPT levels. Out of 25 non‐erosive cases, 7 (28%) patients showed elevated SGOT/SGPT levels (P < 0.01). Anti‐HCV titer was negative in all cases.

Conclusion:  We can conclude that diabetes mellitus and elevated transaminase levels might be related to the development of oral lichen planus lesions. There is a strong association between elevated SGOT/SGPT levels and detection of erosive type of such lesions. However, no correlation between oral lichen planus and HCV infection could be assessed in the present study.
Nomenclature and classification of potentially malignant disorders of the oral mucosa
Authors: Warnakulasuriya S. , Johnson Newell. W. , Van Der Waal I.
Published: August 2010

At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the UK issues related to terminology, definitions and classification of oral precancer were discussed by an expert group. The consensus views of the Working Group are presented here. The term, ‘potentially malignant disorders’, was recommended to refer to precancer as it conveys that not all disorders described under this term may transform into cancer. Critically evaluating all definitions proposed so far for oral leukoplakia, the Working Group agreed that the term leukoplakia should be used to recognize ‘white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer’. An outline was proposed for diagnosing oral leukoplakia that will prevent other oral white disorders being misclassified as leukoplakia. The Working Group discussed the caveats involved in the current use of terminology and classification of oral potentially malignant disorders, deficiencies of these complex systems, and how they have evolved over the past several decades. The terminology presented in this report reflects our best understanding of multi‐step carcinogenesis in the oral mucosa, and aspires to engender consistency in use.
Prevalence of oral cancer and pre‐cancer and associated risk factors among tea estate workers in the central Sri Lanka
Authors: Ariyawardana A. , Sitheeque M. A. M. , Ranasinghe A. W. , Perera I. , Tilakaratne W. M. , Amaratunga E. A. P. D. , Yang Yi‐Hsin , Warnakulasuriya S.
Published: August 2010

Background: To screen for oral cancer or not is being debated, but for high‐risk populations with minimal access to regular dental care systematic oral examinations could provide some benefit.

Methods: We undertook oral mucosal examinations of labourers employed in tea estate plantations in Sri Lanka. In a two‐stage screening procedure, first by estate medical officers and then by visiting specialists, we examined 12 716 persons at their workplaces achieving a coverage of one‐sixth of the total workforce.

Results: Fourteen oral cancers and 848 subjects with oral pre‐cancer (6.7%) were detected giving population prevalences of 46.1 per 1000 for leukoplakia and 16.4 per 1000 for oral submucous fibrosis. Among subjects with any oral mucosal disorder (n = 1159) proportions of current users of betel quid, smokers and alcohol use was recorded at 92%, 31% and 61% respectively. The synergistic effect of these three risk habits on the development of oral leukoplakia was evident in mixed habit groups.

Conclusions: The prevalence of oral pre‐cancer in tea estate labourers was higher than estimates reported in previous studies. In the absence of state‐sponsored preventive activities, it is necessary to improve the capacity of individual health practitioners and small medical centres to participate in oral health promotion and oral cancer/pre‐cancer screening.
ORIGINAL ARTICLE: Antibody to the Chlamydia trachomatis 60 kDa Heat Shock Protein in Follicular Fluid and In Vitro Fertilization Outcome
Authors: Jakus Sharon , Neuer Andreas , Dieterle Stefan , Bongiovanni Ann Marie , Witkin Steven S.
Published: August 2010

Problem

The association between 60 kDa Chlamydia trachomatis heat shock protein (CHSP60) antibodies and the etiology and outcomes of in vitro fertilization (IVF) outcomes is not well known.

Method of study

A retrospective study with a double‐blind analysis of follicular fluid from 253 IVF patients for IgG antibodies to CHSP60.

Results

The CHSP60 antibodies were detected in 74.1% of women without embryo implantation and in 47.9% of women with 1–3 implantations per IVF cycle (P = 0.0004). CHSP60 antibodies were detected in 69.5% of women with tubal occlusion and 49.7% of women with other causes of infertility (P = 0.01). CHSP60 antibody detection was unrelated to maternal age, number of oocytes collected, or percentage of oocytes fertilized.

Conclusion

Detection of IgG antibody to CHSP60 may indicate persistence of C. trachomatis in the upper genital tract with low implantation rates resulting from a chronic inflammatory reaction. Alternatively, as human hsp60 is expressed in early stage embryogenesis, a cross‐reacting antibody may induce destruction of the embryo.
ORIGINAL ARTICLE: Gender Dichotomy in Antibody Response in a T‐Cell Lymphoma: Involvement of IL‐13 and Gonadal Hormones
Authors: Deepak Praveen , Kumar Sanjay , Acharya Arbind
Published: August 2010

Problem  Dalton’s lymphoma (DL) shows very high interleukin (IL)‐13 level in the serum and ascitic fluid. Therefore, in the present study, we investigated if any sexual dichotomy in the level of IL‐13, and resulting B‐cell activation and Ig subclass switching also exist in the tumor‐bearing host.

Method of study  Serum and ascitic fluid of different groups of DL‐bearing mice were isolated and IL‐13 level and various Ig levels in serum were quantified by double‐sandwich enzyme‐linked immunosorbent assay. Further, the B cells were isolated from DL‐bearing mice and effects of various concentrations of IL‐13 and sex steroids were measured.

Results  Uncastrated and hormone replaced DL‐bearing mice showed sexual dichotomy in IL‐13 level, and subsequent difference in Ig‐level and this was found to be more pronounced in females. Similarly, in vitro study suggested that estrogen treatment, in combination with IL‐13, strongly modulates B‐cell Ig switching in comparison to testosterone treatment in association with IL‐13.

Conclusion  It can be concluded that IL‐13, in concert with gonadal hormones, differentially modulates the B‐cell function in a tumor‐bearing host.
ORIGINAL ARTICLE: Endometrial Explant Culture for Characterizing Equine Endometritis
Authors: Nash Deborah , Lane Elizabeth , Herath Shan , Martin Sheldon I.
Published: August 2010

Problem Endometritis after insemination is ubiquitous in the horse and is associated with semen and/or bacteria in the uterus. In up to 40% of horses, inflammation persists causing infertility. An endometrial explant culture was developed to study uterine secretion of prostaglandin F2α(PGF2α) in response to physiological and pathological challenge.

Method of study Uteri were collected from mares, the endometrium dissected and explants from the uterine body or horn cultured in William’s or RPMI medium. The response of explants to oxytocin, semen or bacteria compared to untreated tissue was tested by collecting medium after 24 and 72 hr and measuring PGF2αby radioimmunoassay.

Results Explants from the uterine horn and cultured in William’s medium secreted the most PGF2αafter challenge with oxytocin. Explants treated with semen produced a PGF2αresponse after 72 hr. Explants collected from mares in the transition season treated with killedS. zooepidemicusorE. colilipopolysaccharide (LPS) secreted increased concentrations of PGF2αafter 24 and 72 hr. The response to LPS was inhibited by polymyxin B. Follicular and luteal phase explants did not respond to treatments.

Conclusions An endometrial explant culture was developed that measured PGF2αand may be used to study endometritis.
ORIGINAL ARTICLE: MBL2 Genetic Screening in Patients with Recurrent Vaginal Infections
Authors: Milanese Michele , Segat Ludovica , De Seta Francesco , Pirulli Doroti , Fabris Annalisa , Morgutti Marcello , Crovella Sergio
Published: August 2010

Problem  Mannose‐binding lectin (MBL) is an important component of the innate immunity, present at the mucosal level in vagina: a common pathogen’s entry point.

Method of study  We used a rapid genotyping method based on melting temperature assay to search for three single nucleotide polymorphisms (SNPs) located in the first exon of the MBL2 gene and we also measured MBL serum levels in patients with recurrent bacterial vaginosis (rBV) and recurrent vulvovaginal candidiasis (rVVC).

Results  Detected frequencies of MBL2 SNPs were comparable to the ones already reported for the Italian population and no significant differences were found between rVVC, rBV and controls. MBL serum levels did not show significant differences between the studied groups.

Conclusion  No correlation for the screened mutations has been found neither in protecting nor in favoring the infection in rVVC and rBV patients. Our data demonstrate a lack of association between functional polymorphisms in the first exon of MBL2 gene, MBL deficiency,VVC and rBV.
ORIGINAL ARTICLE: Systemic Changes in Haemostatic Balance are not Associated with Increased Levels of Circulating Microparticles in Women with Recurrent Spontaneous Abortion
Authors: Toth Bettina , Nieuwland Rienk , Kern Meike , Rogenhofer Nina , Berkmans René , Rank Andreas , Lohse Peter , Friese Klaus , Thaler Christian J.
Published: August 2010

Problem  Placental fibrin deposits in patients wih recurrent spontaneous abortion (RSA) indicate an exaggerated haemostatic response. This ‘hypercoagulability’ may involve pro‐coagulant factors such as circulating microparticles (MPs). We investigated the relationship between circulating pro‐coagulant MPs and systemic coagulation in RSA patients.

Method of study  Platelet‐ and endothelial cell‐derived microparticles (PMPs, EMPs) were evaluated by flow cytometry in RSA patients (n = 51) and compared to controls (n = 24) using annexin V (total numbers of MP), and antibodies against CD61, CD63 and CD62P (PMP), as well as CD144 and CD62E (EMP). Prothrombin fragment 1 + 2 (F1+2) and thrombin generation were determined to assess the pro‐coagulant potential of MP.

Results  Numbers of annexin V‐binding MP were nearly similar in RSA patients and controls. However, a subgroup of ten RSA patients (10/51; 20%) presented with MP concentrations >10,000 × 106/L, compared to only one women out of the control group (1/24; 4%; P = 0.038). Neither PMP and EMP nor F1+2 and thrombin generation differed significantly within the study population.

Conclusion  The present study shows that circulating MPs are not directly associated with the extent of systemic coagulation activation in RSA patients. We hypothesize that increased numbers of circulating MPs either are only indirectly associated with coagulation during pregnancy of RSA patients, or affect abortion via mechanisms independently from hypercoagulation.
REVIEW ARTICLE: Clinical Relevance of Oxidative Stress in Male Factor Infertility: An Update
Authors: Agarwal Ashok , Makker Kartikeya , Sharma Rakesh
Published: August 2010

Male factor has been considered a major contributory factor to infertility. Along with the conventional causes for male infertility such as varicocele, cryptorchidism, infections, obstructive lesions, cystic fibrosis, trauma, and tumors, a new, yet important cause has been identified: oxidative stress. Oxidative stress (OS) is a result of the imbalance between reactive oxygen species (ROS) and antioxidants in the body, which can lead to sperm damage, deformity and eventually male infertility. This involves peroxidative damage to sperm membrane and DNA fragmentation at both nuclear and mitochondrial levels. OS has been implicated as the major etiological factor leading to sperm DNA damage. OS‐induced DNA damage can lead to abnormalities in the offspring including childhood cancer and achondroplasia. In this article, we discuss the need of ROS in normal sperm physiology, the mechanism of production of ROS and its pathophysiology in relation to male reproductive system. The benefits of incorporating antioxidants in clinical and experimental settings have been enumerated. We also highlight the emerging concept of utilizing OS as a method of contraception and the potential problems associated with it.
REVIEW ARTICLE: Antimicrobial Polypeptides are Key Anti‐HIV‐1 Effector Molecules of Cervicovaginal Host Defense
Authors: Cole Alexander M. , Cole Amy Liese
Published: August 2010

Mucosal surfaces of the cervix and vagina are portals for heterosexual transmission of human immunodeficiency virus type 1 (HIV‐1) and, therefore, play a fundamental role in the pathogenesis of primary infection. Cationic antimicrobial polypeptides including defensins are the principal effector molecules of mucosal innate immunity against microbes and viruses such as HIV. In cervicovaginal secretions, antimicrobial polypeptides constitute the majority of the intrinsic anti‐HIV‐1 activity, synergism between cationic polypeptides is complex, and full anti‐HIV‐1 activity involves the complete complement of cationic polypeptides. Periods in which cationic antimicrobial polypeptide expression is reduced are likely associated with increased susceptibility to HIV‐1 infection. This review provides an overview of the role of cationic antimicrobial polypeptides in innate cervicovaginal anti‐HIV‐1 host defense, and discusses how hormones and bacterial infections can regulate their expression. Emphasis is placed on the θ‐defensin (retrocyclin) class of anti‐HIV‐1 peptides and their potential for development as topical microbicides to prevent HIV‐1 transmission.
REVIEW ARTICLE: Immune Physiology of the Mammalian Ovary – A Review
Authors: Bukovsky Antonin , Caudle Michael R.
Published: August 2010

The immune system, besides orchestrating the immune response, plays an important role in the regulation of tissue homeostasis. We refer to this later activity as ‘immune physiology.’ In human ovaries, immune system‐related cells and molecules accompany corpus luteum development and regression and cancer progression. They also accompany the origination of new rat and human germ cells by asymmetric division of ovarian surface epithelium cells, symmetric division and migration of germ cells, and follicular growth. Currently prevailing dogma on the preservation of human oocytes from the fetal period until menopause (‘storage’ doctrine) vs. oocyte renewal in invertebrates and lower vertebrates (‘continued formation’ doctrine) raises question as to the disadvantage from an evolutionary point of view of prolonged oocyte storage in humans. We attempted to reconcile these two opposing views by proposing the prime reproductive period (PRP) doctrine as follows: The ‘storage’ doctrine fits two periods of the life in human females, that between the termination of fetal oogenesis and puberty or pre‐menarcheal period (about 10–12 years), and also that period from the end of PRP (at about 38 years of age) until menopause. On the contrary, the ‘continued formation’ doctrine accounts for oocyte and follicular renewal during the PRP, and insures the availability of fresh oocytes for the development of healthy progeny. Further study on ‘immune physiology’ may help us better understand ovarian physiology and pathology in general, including infertility caused by premature ovarian failure, the pathophysiology of degenerative diseases and mechanisms of malignancy and metastasis.
ORIGINAL ARTICLE: Effect of Sulfasalazine on Basal and Bacteria‐Stimulated Interleukin‐8 Production by Endocervical Epithelial Cells
Authors: Peltier Morgan R. , Tee Siew C. , Kinzler Wendy L. , Smulian John C.
Published: August 2010

Problem  Sulfasalazine (SASP) inhibits lipopolysaccharide‐induced nuclear‐factor kappa B activation and interleukin‐8 (IL‐8) production by cultured explants of placenta, amnion and choriodecidua. Bacteria‐induced IL‐8 production in the cervix is a potential mechanism for premature cervical ripening that may lead to preterm birth. Our objective was to determine if SASP inhibits IL‐8 production by endocervical cells stimulated with bacterial pathogens associated with preterm birth.

Method of study  Human endocervical cells were incubated with 0–1.6 mm SASP and then stimulated with Ureaplasma parvum, Escherichia coli, or Gardnerella vaginalis. Conditioned medium was then harvested and production of IL‐8 was quantified by ELISA. Viability of the cells was ascertained at the end of the experiment with the MTT‐assay.

Results  At the highest concentration tested (1.6 mm), SASP significantly inhibited IL‐8 production by cultures stimulated with E. coli (P < 0.001), U. parvum (P < 0.001), and G. vaginalis (P < 0.001). Viability of the cells, however, was significantly reduced by SASP at 0.8 and 1.6 mm in both the presence and absence of bacteria for all experiments.

Conclusion  Although high concentrations of SASP inhibit IL‐8 production by cultures of endocervical cells stimulated with pathogens associated with preterm birth, this effect may be because of toxicity of the antibiotic on the cells.
ORIGINAL ARTICLE: Effect of Progesterone on HLA‐E Gene Expression in JEG‐3 Choriocarcinoma Cell Line
Authors: Huang Zhongying , Hyodo Hironobu , Fujii Tomoyuki , Nagamatsu Takeshi , Matsumoto Junko , Kawana Kei , Yamashita Takahiro , Yasugi Toshiharu , Kozuma Shiro , Taketani Yuji
Published: August 2010

Problem  Among class Ib human leukocyte antigen (HLA) molecules, HLA‐E is known to be a major ligand of CD94/NKG2 receptor on natural killer (NK) cells, and to play a pivotal role in recognition of extravillous trophoblasts (EVTs) by maternal immune cells. However, it is scarcely known how HLA‐E expression is regulated in EVTs.

Method of study  In this study, we investigated whether progesterone, an essential hormone in maintaining pregnancy, regulated HLA‐E expression in EVT‐like cell line, JEG‐3. HLA‐E mRNA amount in cultured JEG‐3 cells was assessed by real‐time PCR and cell‐surface HLA‐E protein was analyzed by flowcytometry.

Results  Real‐time PCR showed 3.5‐fold increase 1 hour after the addition of 1000 ng/ml progesterone. This response was dimished by the addition of RU486, an antagonist for progesterone receptor. Flowcytometry indicated that 1000 ng/ml progesterone slightly enhanced HLA‐E expression on the surface of JEG‐3.

Conclusion  These results suggest that progesterone up‐regulates HLA‐E expression in JEG‐3 cells through the pathway mediated by progesterone receptor. Our findings might give a new insight into immunomodulatory function of progesterone at fetomaternal interface.
ORIGINAL ARTICLE: In Vitro and In Vivo Studies Evaluating Recombinant Plasmid pCXN2‐mIzumo as a Potential Immunocontraceptive Antigen
Authors: An Gang , Huang Tian‐Hua , Wang De‐Gang , Xie Qing‐Dong , Ma Lian , Chen De‐Yu
Published: August 2010

Problems  Study on feasibility of pCXN2‐mIzumo as a potential immunocontraceptive antigen.

Method of study  Two groups of mice received 100 μg/mouse plasmids of pCXN2‐mIzumo and pCXN2 respectively. RT‐PCR Immunofluorescence assay and ELISA were performed to observe pCXN2‐mIzumo expression and antibody response in the inoculated mice. Sperm penetration assay and animal mating were employed to detect differences of in vitro fertilization (IVF) rate and mean litter size between the experimental and control groups.

Results  Izumo cDNA positive bands were detected in sample from mice immunized with pCXN2‐mIzumo. IgG response started to rise at 2 weeks after first boost and reached the highest antibody titers at 2 weeks after third boost of immunization with pCXN2‐mIzumo in the experimental mice. In vitro fertilization rate in the experimental group (11.57%) was significantly lower than that in control (36.60%). Significant difference of mean litter size between female experimental and control groups was observed, and there was significant negative correlation between individual anti‐serum titers and litter size (r = −0.308, P < 0.05).

Conclusion  pCXN2‐mIzumo plasmid possesses appreciable anti‐fertility potential.
ORIGINAL ARTICLE: Sperm Antibodies, Intra‐Acrosomal Sperm Proteins, and Cytokines in Semen in Men from Infertile Couples
Authors: Ulcova‐Gallova Zdenka , Gruberova Jitka , Vrzalova Jindra , Bibkova Katarina , Peknicova Jana , Micanova Zdenka , Topolcan Ondrej
Published: August 2010

Problem  The aim of this study was to investigate seminal sperm‐agglutinating antibodies, intra‐acrosomal proteins, sperm head abnormalities, and cytokines (IL‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p70 TNF‐α, and IFN‐γ) in men from infertile couples.

Method of study  The direct mixed anti‐immunoglobulin reaction test for IgG, IgA, and IgE in semen, and immunocytochemical method using monoclonal antibodies and indirect immunofluorescence for the examination of intra‐acrosomal proteins in the spermatozoa were used. Cytokines in seminal plasma were determined by multiplex immunoanalytic xMAP (LUMINEX) technology.

Results  Sperm‐agglutinating antibodies, IgG and IgA, in seminal plasma were found to be more in asthenospermatic and oligoasthenospermatic men than in normospermatic men. Sperm head pathology and very low amounts of acrosomal proteins were frequently detected in pathologic semen samples. Cytokine levels defined as ‘high’ (based on the 75 percentile for each cytokine in all groups) were obtained especially for IL‐8, IL‐5, IL‐6, and IL‐10. The high cellularity in semen was correlated with higher IL‐5.

Conclusion  Immunologic cause of male infertility is a very important risk factor in the pathogenesis of sperm cells. Sperm autoantibodies and the presence of intra‐acrosomal factors must be studied together, cytokines according to accessory cellularity in the semen.
Children's fluid intake during diarrhoea: a comparison of questionnaire responses with data from observations
Authors: Zaman K , Sack DA , Chakraborty J , Yunus M , Baqui AH , Black RE
Published: August 2010

Many of the individual questions used by the World Health Organization for household surveys on diarrhoea management have not been systematically assessed. This study assessed the use of simple questions to caretakers of children to estimate the proportion of young children who received increased quantities of fluids during diarrhoeal episodes by comparing caretakers' responses with data obtained by direct observations. Children aged 4–35 mo (n= 215) with diarrhoea starting within the last 24 h were observed for 12 h. These children were observed for 12 h again 2 wk later, when healthy. On the following day the questionnaire was administered to the caretakers. The observation focused on the frequency of feeding episodes, including breastfeeding and the type and quantity of fluids consumed by the child. The same questionnaire was administered to the caretakers of another group of children (n= 421) with diarrhoea in the past 2wk. The mean number of feedings (6.0 ± 3.8 vs 5.0 ± 3.5), breastfeeding episodes (11.2 ± 3.6 vs 8.4 ± 3.3), breastfeeding duration (85.8 ± 36.3 min vs 49.1 ± 22.8 min), other fluid intake (345.8 ± 309.6 ml vs 120.9 ± 136.4 ml) and total fluid consumption (653.9 ± 240.4 ml vs 399.5 ± 133.6 ml) were significantly higher (p < 0.0001) during diarrhoea compared with healthy periods. At the population level, the simple questionnaire administered to caretakers was found to have high agreement between the reported increase in fluid consumption and the actual increase in fluid intake (defined as ≥100ml). At the individual level, caretakers' questionnaire responses for detecting increased fluid intake were highly sensitive (84.3%), but specificity (36.4%) and agreement (0.22) were low.

Conclusion: This study documents that children had higher fluid intake, which included both breast milk and other fluid, during acute episodes of diarrhoea. Further research is warranted to improve the specificity and agreement of caretakers' responses to simple questions regarding change in fluid intake during diarrhoeal episodes.
Effectiveness and tolerability of ibuprofen‐arginine versus paracetamol in children with fever of likely infectious origin
Authors: Nadal C Figueras , Garía de Miguel Ma J , Campderá A Gómez , Fernández J Pou , Calatayud G Alvarez , Bayle M Sánchez ,   the Paediatric Fever Co‐operative Group from the Spanish Paediatric Association
Published: August 2010

The aim of this multicentre, double‐blind, randomized study was to assess the paediatric antipyretic efficacy of a new ibuprofen formulation containing L‐arginine for gastric protection, compared with the efficacy of paracetamol. For this purpose 100 patients were given ibuprofen‐arginine (1 drop/kg: 6.67mg/kg) and 99 paracetamol (4 drops/kg: 10.65 mg/kg). The main efficacy endpoint was the mean change in tympanic temperature 4 h after drug intake. Twelve patients were excluded because of early vomiting or spitting out the medication. The resulting efficacy analysis population included a total of 88 patients treated with ibuprofen‐arginine and 87 with paracetamol. Mean change in tympanic temperature (°C) showed no difference between groups (p= 0.527) but more patients in the ibuprofen‐arginine group attained a temperature reduction greater than 2°C (p= 0.043). A total of 107 patients required antipyretic rescue medication, with a smaller proportion in the ibuprofen‐arginine group. Although this was not statistically significant, a trend towards improved activity was observed (p= 0.100). Overall efficacy was judged from the recovery or improvement in 68.8% of patients in the ibuprofen‐arginine group compared with 65.5% in the paracetamol group. Nineteen patients reported adverse events, with vomiting being the most common complaint, but no differences were detected between treatments.

Conclusion: Based on the present results, ibuprofen‐arginine oral drops have shown to be a safe, well‐tolerated and potent paediatric antipyretic agent. Hence, ibuprofen‐arginine should be considered as an adequate choice for the control of paediatric fever of likely infectious aetiology.
Central airways stenosis in school‐aged children: differential diagnosis from asthma
Authors: Linna O , Hyrynkangas K , Lanning P , Nieminen P
Published: August 2010

This study assessed the value of spirometry and chest X‐rays in the diagnosis of airways stenosis in the tracheal or laryngeal regions at school age. A series of 14 patients was studied. Six of them had vascular ring anomalies, four subglottic stenosis, two aberrant innominate artery, one tracheal stenosis and one a laryngeal web. Four patients were suffering from chronic cough and ten from dyspnoea, noisy breathing and cough upon physical exercise. Two had had their symptoms since infancy and five since 3–6 y of age, whereas seven had had their first symptoms at school age. Nine patients had previously been suspected of having asthma, and five of them had been using inhaled corticosteroids, one inhaled sodium cromoglycate and one peroral terbutaline without any effect. The ratio of forced expiratory volume in 1 s (FEV1) to peak expiratory flow (PEF) was abnormally high in most of the patients. All six children with vascular ring anomalies also had an abnormal aortic configuration on a chest X‐ray, and narrowing of the trachea was seen in two of the four with subglottic stenosis. Two children had both chest X‐rays and spirometry values within the normal limits.

Conclusion: The results show that children with stenosis in the laryngeal or tracheal region may not have their first symptoms until school age. Many patients are falsely suspected of having asthma. Simple spirometry and chest X‐rays will help the physician to make the correct diagnosis in these patients.
Score of neonatal acute physiology as a measure of illness severity in mechanically ventilated term babies
Authors: Sutton L , Bajuk B , Berry G , Sayer GP , Richardson V , Henderson‐Smart DJ
Published: August 2010

The objectives of this population‐based, case‐control cohort study were to describe the use of the score of neonatal acute physiology (SNAP) as a measure of illness severity in mechanically ventilated term infants, to compare the SNAP scores of the different diagnostic groups, to assess the contribution of the individual SNAP items to the overall SNAP severity category, and to assess SNAP as a predictor of mortality and neonatal intensive care unit (NICU) resource utilization (length of stay (LOS) and duration of ventilation (LOV)). The study was carried out in Sydney and four large rural/urban health areas in New South Wales, Australia. The subjects—182 singleton term infants with no major congenital anomalies—were admitted to a tertiary NICU for mechanical ventilation. Highest mean (SD) SNAP scores occurred in infants ventilated for meconium aspiration (18 (9)), and perinatal asphyxia (17 (9)), compared with pulmonary hypertension (14 (6)) and respiratory distress syndrome (13 (5)). The individual SNAP items that contributed most to SNAP moderate and severe categories were blood gas items, creatinine, urine output, blood glucose, and seizures. Predictors of death included total SNAP score, individual SNAP items (urine output, pH, Oxygenation Index (OI)), 5‐min Apgar, gestational age >40 wk, growth restriction, and ventilation for asphyxia/apnoea. SNAP alone was not a good predictor of NICU resource utilization (LOS, LOV) in term infants. The best predictors were LOV for LOS, and a combination of SNAP and the reason for ventilation for LOV.

Conclusion: SNAP is a useful measure of severity of illness in sick term neonates admitted to a tertiary NICU. This measure can be used to predict neonatal morbidity and mortality, and to some extent NICU resource utililization.