Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN.

STUDY QUESTION: Could seminal plasma clusterin play a role in the uptake of stress-damaged proteins by dendritic cells? SUMMARY ANSWER: Seminal plasma clusterin, but not serum clusterin, promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN. WHAT IS KNOWN ALREADY: Clusterin is one of the major extracellular chaperones. It interacts with a variety of stressed proteins to prevent their aggregation, guiding them for receptor-mediated endocytosis and intracellular degradation. The concentration of clusterin in semen is almost 20-fold higher than that found in serum, raising the question about the role of seminal plasma clusterin in reproduction. No previous studies have analyzed whether seminal plasma clusterin has chaperone activity. We have previously shown that seminal plasma clusterin, but not serum clusterin, expresses an extreme abundance of fucosylated glycans. These motifs enable seminal plasma clusterin to bind DC-SIGN with very high affinity. STUDY DESIGN, SIZE, DURATION: In vitro experiments were performed to evaluate the ability of seminal plasma clusterin to inhibit the precipitation of stressed proteins, promoting their uptake by dendritic cells via DC-SIGN (a C-type lectin receptor selectively expressed on dendritic cells (DC)). Moreover, the ability of seminal plasma clusterin to modulate the phenotype and function of DCs was also assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Clusterin was purified from human semen and human serum. Catalase, bovine serum albumin, glutathione S-transferase, and normal human serum were stressed and the ability of seminal plasma clusterin to prevent the precipitation of these proteins, guiding them to DC-SIGN expressed by DCs, was evaluated using a fluorescence-activated cell sorter (FACS). Endocytosis of stressed proteins was analyzed by confocal microscopy and the ability of seminal plasma clusterin-treated DCs to stimulate the proliferation of CD25+FOXP3+CD4+ T cells was also evaluated by FACS. MAIN RESULTS AND THE ROLE OF CHANCE: Seminal plasma clusterin interacts with stressed proteins, inhibits their aggregation (P < 0.01) and efficiently targets them to dendritic cells via DC-SIGN (P < 0.01). DCs efficiently endocytosed clusterin-client complexes and sorted them to degradative compartments involved in antigen processing and presentation. Moreover, we also found that the interaction of seminal plasma clusterin with DC-SIGN did not change the phenotype of DCs, but stimulates their ability to induce the expansion of CD25+FOXP3+CD4+ T lymphocytes (P < 0.05 versus control). LIMITATIONS, REASONS FOR CAUTION: All the experiments were performed in vitro; hence the relevance of our observations should be validated in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that by inducing the endocytosis of stress-damaged proteins by DCs via DC-SIGN, seminal plasma clusterin might promote a tolerogenic response to male antigens, thereby contributing to female tolerance to seminal antigens. STUDY FUNDING/COMPETING INTERESTS: The present research was supported by the Consejo Nacional de Investigaciones Científicas y Técnicas, the Buenos Aires University School of Medicine, and the Agencia Nacional de Promoción Científica y Tecnológica (Argentina). The authors have no conflicts of interest to declare.

[Open surgery, laparoscopic Palomo varicocelectomy and embolization in children with varicocele]. / Cirugía abierta, Palomo laparoscópico y embolización en niños con varicocele.

OBJECTIVES: Our aim was to prove the outcomes in varicocele treatment during last 10 years in our institution regarding to the recurrence rate and reactive hydrocele in children and adolescents treated with open technique, laparoscopic approach or embolization. PATIENTS AND METHODS: Medical charts of patients with varicocele younger than 17 years old were reviewed. Age, weight, surgery indications, treatment (open surgery, laparoscopic Palomo varicocelectomy or embolization), location, varicocele grade, hospital stays, recurrence, postoperative hydrocele, genitofemoral nerve damage, infection, bleeding, postoperative incisional hernia and re-do varicocelectomy were collected. RESULTS: From 2000 to 2010, 98 boys with varicocele diagnosis were treated in our institution. Mean age of patients was 12 years. The varicocele location in all cases was on the left side. Grade III varicocele was found in 94 boys and grade II in 4 patients. Indications for surgery were high grade in 81, chronic pain in 16 and testicular hypotrophy in 1. Treatment approach was as follows: 12 patients underwent open surgery (Palomo or Ivanissevich technique), 32 underwent embolization and laparoscopic Palomo varicocelectomy was performed in 54. We found a global recurrence rate of 14.3% and an overall postoperative hydrocele of 24.5% Recurrence rate was higher in the embolization group than the open surgery and laparoscopic group. Three patients presented intraoperative bleeding in the laparoscopic group and there was one conversion to open surgery. CONCLUSIONS: Our retrospective review proves that laparoscopic Palomo varicocelectomy is a safe and efficient approach to treat varicocele in pediatric population, because of its low recurrence rate without any major adverse outcome. Due to our high secondary hydrocele formation, lymphatic sparing laparoscopic procedure should be taken into account in order to decrease this complication.

[Structural alterations of the smooth muscle and of the EGFR expression and C-kit in congenital pyeloureteral stenosis. Relationship with its pathogenesis]. / Alteraciones estructurales del músculo liso y de la expresión de EGFR y C-kit en la estenosis pieloureteral congénita. Relación con su patogénesis.

PURPOSE: To assess the role that the muscular dysplasia, epidermal growth factor (EGFR) and interstitial cells of Cajal (ICC) C-kit +, may have in the pathophysiology of pyeloureteral stenosis (EPU). MATERIALS AND METHODS: 30 samples were studied UPJ (ureteropelvic junction), with 25 UPJ obstruction and 5 controls. Performed with Masson's trichrome staining and immunohistochemical techniques for smooth muscle actin, EGFR (epidermal growth factor) and CD117 (C-kit) (Dako). We compared the results statistically. RESULTS: The control group was diffuse positivity of EGFR in the muscle layer in samples of EPU was positive in 4%, weak in 16% and negative in 80%. The controls are C-kit + ICC between the muscle cells showed a decreased density in the samples of obstruction. Masson's trichrome highlighted the increase of inter-and intramuscular collagen and attenuated muscle fibers, thinner and individualized, in the inner muscular layer of the cases of EPU also evident with the actin. Differences between groups were statistically significant (p < 0.001). CONCLUSIONS: Our results suggest that dysplastic changes in the muscle layer, the low expression of EGFR and the decrease or absence of C-kit + ICC, may participate in the pathophysiology of UPJ obstruction.

Low prevalence of complications of delayed herniotomy in the extremely premature infant.

AIM: To study the relationship between the delay of herniotomy in the extremely premature infant and the rate of complications in comparison with full-term children. METHODS: A follow-up study of three groups of neonates operated on for inguinal hernia was performed. The groups were defined as: a) the short-waiting group (SWG): prematures (mean gestational age: 32.56 +/- 0.62; n = 9) operated on within 2 wk of diagnosis (median: 5 d); b) the long-waiting group (LWG): prematures (mean gestational age: 28.38 +/- 1; n = 21) operated on after more than 2 wk (median: 39 d); and c) control group of full-term children (FTG); (mean gestational age: 38.18 +/- 0.29; median of timing: 3 d; n = 11). Several variables (gestational age, weight at birth and at surgery, side of the inguinal herrnia, timing, duration of surgery, type of anaesthesia, length of hospitalization), as well as the occurrence of apnoea, incarceration and testicular atrophy were compared between groups. RESULTS: Timing was the only variable that was different between the LWG and the other two groups (p < 0.001, ANOVA). Seven preoperative episodes of incarceration occurred: one in the SWG, two in the LWG and four in the FTG (p = 0.138, chi2). In the follow-up study two testicular atrophies, related to previous episodes of incarceration, were found: one in the FTG and the other in the SWG (p = 0.221, chi2). CONCLUSION: The deferral of herniotomy in the extremely premature infant, until the child is ready to be discharged from the neonatal unit, does not seem to increase the risk of incarceration episodes or testicular atrophy.

Streptococcus pneumoniae: evolución de la resistencia a los antimicrobianos en un hospital de niños de Córdoba, Argentina / Streptococcus pneumoniae: evolution of antibiotic resistance in a pediatric hospital in Córdoba, Argentina

The wide variety of prevalence of antimicrobial resistant Streptococcus pneumoniae in different countries confirms the importance of determining local patterns of resistance. From 1992 to 2000, we studied the pattern of antimicrobial resistance in S. pneumoniae and its evolution along the years, using 468 strains isolated in the Hospital de Niños de Córdoba. A total of 177 isolates (37.8) were not susceptible to penicillin, with 19 intermediate and 18.8 resistant strains. High and intermediate resistance levels to cefotaxime were 4.9 and 10.9, respectively. Decreased susceptibility to trimethoprim/sulfamethoxazole (TMS), erythromycin, chloramphenicol, and rifampin was found in 194 isolates (41.5), 32 (6.8), 13 (2.8) and 3 (0.6), respectively. No isolates resistant to vancomycin were detected. The most commonly combined resistance patterns were: penicillin/TMS (35.6) and penicillin/TMS/cefotaxime (11.8). This study highlights the increased rate of drug resistant S. pneumoniae during the last years, and the importance of antimicrobial resistance surveillance of adequate empirical therapy involving local and regional susceptibility patterns.

Evaluación de la inmunofluorescencia indirecta como prueba suplementaria para el diagnóstico de la infección por HIV-1 / Evaluation of indirect inmunofluorescence as a confirmatory test for the diagnosis of HIV-1 infection

Se comparó la eficiencia diagnóstica de la inmunofluorescencia indirecta (IFI) como método confirmatorio de la infección por HIV-1 en muestras de suero de 362 personas con conductas de alto y bajo riesgo. El panel compuesto por 220 positivos, 122 negativos y 20 indeterminados por Western blot (WB) fue ensayado por una técnica de IFI desarrollada en nuestro laboratorio. La sensibilidad calculada fue 98,63 por ciento y la espicificidad 98,36 por ciento, indicando que la IFI es un método alternativo para la confirmación de la presencia de anticuerpos contra el HIV-1. Dado que su costo es menor que el 10 por ciento comparado con el del WB, se justifica su introducción en el algoritmo de diagnóstico serológico de HIV-1. Se observó también una relación directa entre la reactividad de las proteínas del WB y los resultados de IFI. En 15 muestras con resultado indeterminado por WB e inespecífico por IFI, las bandas más observadas fueron la p24 seguida de la gp160; por otro lado los anticuerpos contra las glicoproteínas virales son los que presentan mayor frecuencia en las muestras positivas débiles, demostrando su alto valor predictivo

CO2 laser surgery in osteomyelitis.

OBJECTIVE: To prove that the thermal energy of CO2 lasers, when applied on the fistula, pyogenic sac, and septic bone in cases of osteomyelitis, creates an aseptic area, diminishes relapses, and promotes healing in those patients treated. SUMMARY BACKGROUND DATA: CO2 laser surgery, whether used in a focused or unfocused manner, has been incorporated into surgical procedures because of its incisive, coagulating, and antiseptic properties. These forms and characteristics are especially useful in the treatment of chronic osteomyelitis. METHODS: The authors recorded their experiences with 80 patients (10-75 years) with different types of chronic osteomyelitis. Classical surgical procedures were performed incorporating the CO2 laser beam. RESULTS: Of the 80 patients, 45 healed with a single application combined with sequestrectomy implant removal, etc. Twenty-two patients needed up to three sessions to heal. Twelve patients did not heal, 1 asked for an amputation, and 3 were unavailable for follow-up procedures. We did not evaluate antibiotics prescribed, or cultures taken, due to the multiplicity of drugs used by chronic osteomyelitis patients with disease progression, and the various permutations and combinations of germs involved. CONCLUSIONS: Although CO2 laser beam surgery cannot replace classic surgical procedures in osteomyelitis, it is an important adjunctive tool that helps enhance surgical effects and assists in the healing process.

Different integrated and unintegrated HIV-1 DNA after superinfection and cell to cell transmission

Efficient superinfection of H9HTLVIIIB cell line (persistently infected with HIVHXB2 strain) with HIVMN strain is reported. The superinfecting viral DNA was found in the chromosomic and extrachromosomic fractions at early stages, but at 48 hours post superinfection, it remained mainly unintegrated. Interestingly, superinfected cells only produced HIVHXB2 in the supernatant and no increase of viral yield of this persistent virus was observed. Remarkably, virions of both strains, HIVHXB2 and HIVMN, were recovered after cocultivating superinfected cells with MT2 cell line. In the extrachromosomic fractions of seven different superinfected subclons of H9HTLVIIIB, viral DNA of the superinfecting HIVMN strain predominated while in the chromosomic fraction, the proportion of superinfecting viral DNA differed. The study of the presence of different integrated and unintegrated genomes in a single cell could be crucial in the understanding of HIV biology.

Mortalidad perinatal en la provincia de Chubut / Perinatalmortality in the province of Chubut

Se analizarona través de un método clasificatorio sencillo las muertes perinatales (n:115) ocurridas en los hospitales de Comodoro Rivadavia, Trelew, Puerto Madryn y Esquelen 1994. El método empleado puede agrupar rápidamente las causas evitables con el objetivo de desarrollar futuras acciones preventivas o curativas del sistema de salud. En la mortalidad fetal predominaron los fetos macerados con peso menora 2500 grs. En la mortalidad neonatal las causas más comunes fueron: bajo peso y prematurez (66 por ciento) y muy bajo peso (45 por ciento). Casi la mitad de la mortalidad neonatal ocurrió en el primer día de vida. Se comprobó una muy elevada frecuencia (43 por ciento) de falta de control del embarazo en la- mortalidad fetal y neonatal. Los resultados obtenidos con el método clasificatorio propuesto permiten inferir la necesidad de mejorar los niveles de atención primaria dela embarazada y los estándares de atención del neonato de bajo peso para disminuir la mortalidad perinatal

[Wegener's granulomatosis of the nasal fossa]. / Granulomatosis de Wegener localizada en fosas nasales.

A 62-year-old female patient consulted for a suppurative-hemorrhagic nasal condition 18 months evolution. Exploration found granulomatous rhinitis which was producing septal perforation and histology compatible with necrotizing granulomatous vasculitis, fulfilling the diagnostic criteria for focal Wegener's granulomatosis, in view of the absence of lung and renal damage. Treatment with trimethoprim-sulfamethoxazole alone described in the medical literature as an option for this process, yielded excellent results with remission of symptoms and normalization of the exploration.

Detection of HPV DNA by in situ hybridization in benign, premalignant and malignant lesions of the oral mucosa.

Evidence has accumulated in recent years that relates certain types of human papillomaviruses (HPV) to the development of some tumors. We use in situ hybridization to study DNA from HPV 6/11, 16/18 and 31/33/35 in 6 squamous papillomas, 18 hyperkeratotic/acanthosis lesions with and without dysplasia (5 and 13 cases respectively) and 27 squamous cell carcinomas of the oral mucosa. HPV DNA was found in 66% of squamous papillomas, 38.4% of hyperkeratotic/acanthosis lesions without dysplasia, 60% of epithelial dysplasia and 37% of squamous cell carcinomas. HPV DNA 6/11 was the most common type found, and in squamous cell carcinomas HPV DNA appear more frequently in well differentiated tumors.

Detection of anti-HIV antibodies in saliva.

It is sometimes difficult in clinical practice to identify carriers of the AIDS virus. Such identification is of unquestionable value in oral pathology, both for determining the pathogenesis of certain lesions and for assessing their significance to the patient. We evaluated several commercially available diagnostic techniques for the detection of anti-HIV antibodies in serum, and examined the feasibility of adapting such techniques to tests on saliva. The technique chosen for experimental adaptation required only slight modifications for use with this medium. We compared the results obtained in serum from intravenous drug users with a western blot assay designed to detect p24 viral protein, against the findings with a test designed to detect salivary antibodies. The likelihood of cross-reactions in saliva containing high concentrations of other antiviral antibodies was also studied. The specificity and sensitivity of the modified saliva test were 100% and 96% respectively, and no cross-reactions were observed.

[Oral lesions in a group of heroin addicts]. / Lesiones bucales en una población heroinómana.

Lesions of the oral mucous membrane are studied in 100 heroin dependent people compared with 100 control, other habits like smoking, alcohol ingesting and sexual oral practices are also taking in consideration. Salival flux and other salival characteristics are also analyzed. The heroin dependent people show significative increase in salival filament but this difference that's not exit of we also analyze in the lesions of lips, tongue, palate and vestibule in relation to controls. Nevertheless in the take into account only smokers and drinkers of both groups the only lesions significantly more frequent are those on the lips.

Intermediate filament and carcinoembryonic antigen expression in salivary gland pleomorphic adenoma.

In recent years immunohistochemical studies have become of relevance in the discovery of significant antigenic structures in human cells. Filamentous protein structures with a diameter between that of microtubules and microfilaments have recently been described with the name of intermediate filaments. These structures play an important role in certain cellular functions such as cytokinesis and chromosome movements during cell division. The immunohistochemical expression of these filaments in tumoral disease is identical to that seen in normal cells of the type the tumor arises in. We describe the expression of some of these filaments and of carcinoembryonic antigen in an attempt to clarify the complex origin of pleomorphic adenoma of the salivary glands.

Enfoque epidemiológico del programa de diagnóstico precoz del cáncer cérvico uterino

Se realiza un análisis de los principales resultados del programa de detención precoz del cáncer cérvico uterino en la provincia de Cienfuegos, precisándose algunos elementos que inciden negativamente en el programa como son:El porcentaje de menores de 30 años, la limitada incorporación de mujeres con el primer examen y la existencia de recursos;se establecen relaciones entre aspectos y se reflexiona sobre la impoprtancia de incrementar la cobertura en los grupos de mayor riesgo,así como de aumentar, acorde a los recursos existentes, el riesgo entre el primer exameny los siguientes

Analysis of immune response in oral tumors.

Currently, there is widespread disagreement over the role of the immune system in controlling, via the major histocompatibility complex, the organism's response to cells in the process of tumoral degeneration. One possible mechanism by which tumoral cells escape detection by the antitumoral surveillance system is the lack of expression of HLA class I molecules. The APAAP technique was used to study the levels of expression of these molecules and other cell markers on 27 oral cavity tumors. Heterogenous class I expression was recorded, some tumors completely lacking class I antigens. Similar patterns of expression were found for beta-2 microglobulin and ABC molecules (different class I chains encoded in different chromosomes). The number of DR/DP positive cells was similar to the number of immune cells infiltrating the tumors. Statistical analyses failed to show any significant relationship between class I antigen expression and the anatomoclinical parameters of tumoral aggressivity considered.

[Denture stomatitis. Its relation to candida albicans]. / Estomatitis por prótesis. Su relación con la cándida albicans.

One of the most usual complications of the patients that carry a prosthesis is one called stomatitis denture. Its etiology is not clear enough. In this work we study ninety people, sixty of them wear prosthesis. We take samples of different places in the mouth to plate and class C. Albicans. We look for the relationship of results with the clinical parameters of the patient.