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The design, synthesis, and evaluation of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are big challenges today. In this work, two 5-acetamido-2-hydroxy benzoic acid derivatives were proposed, increasing the alkyl position (methyl) in an acetamide moiety, and synthesized, and their structural elucidation was performed using 1H NMR and 13C NMR. The changes in methyl in larger groups such as phenyl and benzyl aim to increase their selectivity over cyclooxygenase 2 (COX-2). These 5-acetamido-2-hydroxy benzoic acid derivatives were prepared using classic methods of acylation reactions with anhydride or acyl chloride. Pharmacokinetics and toxicological properties were predicted using computational tools, and their binding affinity (kcal/mol) with COX-2 receptors (Mus musculus and Homo sapiens) was analyzed using docking studies (PDB ID 4PH9, 5KIR, 1PXX and 5F1A). An in-silico study showed that 5-acetamido-2-hydroxy benzoic acid derivates have a better bioavailability and binding affinity with the COX-2 receptor, and in-vivo anti-nociceptive activity was investigated by means of a writhing test induced by acetic acid and a hot plate. PS3, at doses of 20 and 50 mg/kg, reduced painful activity by 74% and 75%, respectively, when compared to the control group (20 mg/kg). Regarding the anti-nociceptive activity, the benzyl showed reductions in painful activity when compared to acetaminophen and 5-acetamido-2-hydroxy benzoic acid. However, the proposed derivatives are potentially more active than 5-acetamido-2-hydroxy benzoic acid and they support the design of novel and safer derivative candidates. Consequently, more studies need to be conducted to evaluate the different pharmacological actions, the toxicity of possible metabolites that can be generated, and their potential use in inflammation and pain therapy.

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BACKGROUND: Loss of anterior permanent teeth can have a detrimental effect on children's quality of life and the therapeutic approaches are always a challenge. From a physiologic and psychological standpoint, the use of dental implants has several advantages in replacing missing teeth. However, several studies have shown that conventional implants are not indicated in patients that are still growing, since they interfere with the sagittal and transversal growth of the maxilla. Recent literature has suggested that Mini Dental Implants (MDIs) can be successfully applied in growing patients, without interfering with the normal craniofacial growth process. CASE REPORT: This report describes the replacement of missing teeth in a 10-year-old patient by a mini implant of 1.8 mm diameter. After a six-year follow-up period, the mini implant did not follow the regular growth process of the maxilla, resulting in functional and aesthetic complications. Removal of the mini implant entailed some difficulties.

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A minimum insertion torque has been suggested for immediate function of regular diameter implants. Even when there is a growing tendency to use Mini Dental Implants (MDIs) for immediate function of dentures, there is no clinical data concerning MDIs insertion torque, nor its influence on implant failure. The aim of this prospective study was to assess the insertion torque of immediate loaded MDIs in edentulous patients and its association with risk failure. Ninety MDIs were placed in the anterior mandible of 45 edentulous patients, two per patient. The insertion torque was recorded with an electronic device and failures were documented during two years follow-up. All implants were immediately loaded with overdentures, using ball (44/90) or bar (46/90) attachments. A Kaplan­Meier survival probability estimator and a fitted multiple Cox regression model were performed to establish the influence of insertion torque and other clinical parameters on implant risk failure. The average insertion torque of 90 MDIs was 12.5±7.8 Ncm. A cumulative survival rate of 94.2% (5/90) was found by means of the Kaplan-Meier estimation. The Cox proportional-hazards regression model showed no association between insertion torque and MDIs failure. MDIs have much lower insertion torque than average conventional implants. The insertion torque of MDIs immediately loaded with mandibular dentures, seems not to be a risk factor associated to failure, at two years follow-up.

Un mínimo torque de inserción ha sido sugerido para realizar carga inmediata de implantes de diámetro regular. Aún cuando existe una tendencia creciente a utilizar Mini Implantes Dentales (MID) para la función inmediata de las prótesis totales, no hay datos clínicos relativos a los valores de torque de inserción de estos, ni tampoco de su influencia en el fracaso del implante. El objetivo de este estudio prospectivo fue evaluar el torque de inserción de mini implantes dentales con carga inmediata en pacientes desdentados y su asociación con el riesgo de fracaso. Noventa MIDs fueron colocados en la mandíbula anterior de 45 pacientes desdentados, dos por paciente. El torque de inserción fue obtenido con un dispositivo electrónico y los fracasos fueron documentadas a dos años de seguimiento. Todos los implantes fueron cargados inmediatamente con sobredentaduras, usando un sistema de retención de bola (44/90) o barra (46/90). Se utilizó el estimador de probabilidad de sobrevida de Kaplan-Meier y el modelo riesgos proporcionales de Cox ajustado para establecer la influencia de torque de inserción y otros parámetros clínicos sobre el riesgo de fracaso del implante. El promedio de torque de inserción de 90 MIDs fue 12,5±7,8 Ncm . Los MIDs mostraron a través de la estimación de Kaplan-Meier, una tasa de supervivencia acumulada de 94,2% (5/90). El modelo de riesgos proporcionales de Cox reveló que no existe asociación entre el valor de torque de inserción y el fracaso MIDs. MIDs tienen un valor de torque de inserción mucho más bajo que los implantes convencionales. El torque de inserción de MIDs cargados inmediatamente con prótesis mandibulares, no parece ser un factor de riesgo asociado al fracaso, a dos años de seguimiento.

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OBJECTIVES: To evaluate the effect of maximum bite force (mBF) on marginal bone loss (MBL) around mini-implants in edentulous patients wearing mandibular overdentures with two retention systems: ball and bar. MATERIAL AND METHODS: Forty-five totally edentulous patients were selected from a public health center. All of them received two mini-implants (1.8 x 15 mm; Sendax) in the anterior mandible using a minimally invasive technique. A single randomization was performed to allocate the patients in two groups. Group I (n=22) received two single ball-type mini-implants and Group II (n=23) received two mini-implants splinted with a prefabricated bar. The mBF was recorded using a press-sensitive sheet Dental Prescale (Fuji) and MBL using standardized radiographs of each mini-implant at the baseline and 5, 7, 10, and 15 months after surgery; the values were compared between groups. RESULTS: Two members of Group I failed to complete the study, decreasing the number of participants to 20. There was no relationship between the mBF and the MBL of the mini-implants (Spearman's rhor(s)=0.147; P=0.378). At the 15-month follow-up, the average mBF for Group I (ball) was 247.53 +/- 132.91 N and that of Group II (bar) only 203.23 +/- 76.85 N (Mann-Whitney test; P=0.586). The MBL values were also higher for Group I (1.40 +/- 1.02 mm) than Group II (0.84 +/- 0.66 mm) during the entire 15-month follow-up period (Mann-Whitney test; P=0.077). CONCLUSIONS: No relationship was found between mBF and MBL for patients wearing overdentures retained on mini-implants using bar or ball attachment systems.

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AIMS: The aim of this research was to determine the suitability of coliphages (bacteriophages) for assessing the microbial quality of groundwater. METHODS AND RESULTS: The number of several bacterial indicators (faecal coliforms, Escherichia coli, enterococci and spores of sulfite-reducing clostridia) and bacteriophages (somatic coliphages, F-specific RNA bacteriophages and bacteriophages infecting Bacteroides fragilis) were determined in groundwater of aquifers in various geographical areas. Results show that the relative abundance, determined as percentages of positive detections, of the bacterial indicators and bacteriophages varies depending on the aquifer. CONCLUSIONS: A single bacterial indicator may not be enough to assess microbiological quality in certain aquifers. One bacterial indicator and a bacteriophage parameter provide more information than two bacterial indicators. SIGNIFICANCE AND IMPACT OF THE STUDY: Coliphages (CPH) provide different information from that provided by bacterial indicators on the microbial quality of groundwater in different geographical areas. Easy, fast and inexpensive methods for the detection of CPH are feasible in both industrialized and developing countries.

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AIMS: To evaluate the feasibility of bacteriophages as a complementary tool for water quality assessment in surface waters from different parts of the globe. METHODS AND RESULTS: Faecal coliform bacteria, enterococci, spores of sulphite-reducing clostridia, somatic coliphages, F-specific RNA bacteriophages and bacteriophages infecting Bacteroides fragilis were determined by standardized methods in raw sewage and in 392 samples of river water from 22 sampling sites in 10 rivers in Argentina, Colombia, France and Spain, which represent very different climatic and socio-economic conditions. The results showed that the indicators studied maintained the same relative densities in the raw sewage from the different areas. Classifying the river water samples according to the content of faecal coliform bacteria, it can be observed that the relative densities of the different bacterial indicators and bacteriophages changed according to the concentration of faecal coliform bacteria. There was a relative increase in the densities of all groups of bacteriophages and sulphite-reducing clostridia with respect to faecal coliforms and enterococci in the samples with low counts of faecal coliform bacteria. CONCLUSIONS: The numbers of bacterial indicators and bacteriophages were similar in the different geographical areas studied. Once released in rivers, the persistence of the different micro-organisms differed significantly. Bacteriophages and spores of sulphite-reducing clostridia persisted longer than faecal coliforms and enterococci. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacteriophages in river water samples provide additional information to that provided by bacteria about the fate of faecal micro-organisms in river water. The easy, fast and cheap methods for phage determination are feasible both in industrialized and developing countries.

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Nuclear, mitochondrial, and plasma membrane events associated with apoptosis were investigated in rat neutrophils cultivated for 3, 24, and 48 h in the absence or presence of glutamine (0.5, 1.0, and 2.0 mM). Condensation of chromatin was reduced after 24 or 48 h of culture in the presence of glutamine compared with its absence as assessed by Hoechst 33342 staining. The level of Escherichia coli phagocytosis in the presence of glutamine was markedly increased compared with the level achieved by cells cultured in the absence of glutamine. Annexin V binding to externalized phosphatidylserine was reduced in the presence of glutamine. Sensitive fluorochrome rhodamine 123, as determined by fluorescence-activated cell sorting and confocal microscopy, was used to monitor loss of the mitochondrial transmembrane potential. In the absence of glutamine, neutrophils exhibited a marked reduction in the uptake of rhodamine 123. In the presence of 1.0 or 2.0 mM glutamine, the uptake of rhodamine was 20 or 38% higher, respectively. Similar effect was found in human neutrophils by measuring DNA fragmentation and mitochondrial transmembrane potential. Therefore, glutamine protects from events associated with triggering and executing apoptosis in both rat and human neutrophils.

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It has been widely recognized that the hippocampus and striatum are clearly more susceptible to oxidative stress than the remaining brain regions. However, the mechanism involved is not known. The activities of the antioxidant enzymes CuZn-superoxide dismutase (SOD), Mn-SOD and catalase were measured in the hippocampus and striatum and the results were compared to cortex and cerebellum (less susceptible to oxidative stress) after 3 h of a global transient ischemia/reperfusion. CuZn-SOD activities were reduced in all brain regions, but mainly in the hippocampus and striatum. Mn-SOD activity was lowered in the striatum, whereas catalase activity was reduced in the hippocampus and striatum. Our findings indicate that in the earlier phase of ischemia/reperfusion the decay in activities of catalase and SOD may be related with the high susceptibility of the hippocampus and striatum to oxidative damage.

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Objetivos: En este estudio prospectivo de determinaron las modificaciones en la expresión y el valor predictivo de p53, p21 wafi/sdII/cipi, PCNA, hMLH1, hMSH2, Bcl2 y TUNEL en pacientes con cáncer de cervix localmente avanzado tratadas con quimioterapia de inducción y radioterapia. Pacientes y métodos: Se obtuvieron muestras de 24 pacientes (IBbulky/IIIB, 95 por ciento carcinomas escamosos) antes de la quimioterapia y a los 30 días del tratamiento. Trece pacientes recibieron un esquema de drogas basado en cisplatino y como la respuesta a esta terapia no fue buena, a las otras 11 pacientes se les administró vinorelbine e ifosfamida. Luego de la quimioterapia todas las pacientes recibieron radioterapia. La expresión de los marcadores moleculares en las biopsias pre- y post quimioterapia se estudió por inmunohistoquímica y la apoptosis fue evaluada por la técnica del TUNEL mejorada recientemente. Para comparar los cambios en la expresión de los marcadores moleculares y para correlacionarlos con la evaluación clínica (media de seguimiento: 31 meses para las pacientes que recibieron cisplatino y 19 para las que recibieron vinorelbine e ifosfamida) se realizaron análisis estadísticos. Resultados y conclusiones: La quimioterapia de inducción no aumentó la sobrevida de las pacientes, el 50 por ciento tuvo enfermedad progresiva (EP) o falleció (F). La expresión de p21waf1/sdII/cip1, hMLF1, hMSH2, y Bcl-2 no mostró cambios significativos después de la quimioterapia y no correlacionó con la evaluación clínica. La expresión de p53 no se modificó luego de la quimioterapia, las pacientes con tumores p53 positivos mostraron una tendencia a tener una sobrevida menor. Las pacientes con EP o que fallecieron mostraron niveles altos de PCNA, a diferencia de aquellas que estuvieron libres de enfermedad (LE) o con enfermedad estable (EE) (50 por ciento versus 17 por ciento, respectivamente, p<0.004). La sobrevida de las pacientes con bajos índices de TUNEL (igual o menor al valor medio entre las biopsias pre y post-quimioterapia de 1.5) fue significativamente más corta que las pacientes que presentaron índices de TUNEL altos (p<0.009). Nuestros resultados muestran que la quimioterapia de inducción (los dos tratamientos aplicados en este estudio) no mejoró la sobrevida de pacientes con cáncer de cervix... (AU)

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Objetivos: En este estudio prospectivo de determinaron las modificaciones en la expresión y el valor predictivo de p53, p21 wafi/sdII/cipi, PCNA, hMLH1, hMSH2, Bcl'2 y TUNEL en pacientes con cáncer de cervix localmente avanzado tratadas con quimioterapia de inducción y radioterapia. Pacientes y métodos: Se obtuvieron muestras de 24 pacientes (IB'bulky/IIIB, 95 por ciento carcinomas escamosos) antes de la quimioterapia y a los 30 días del tratamiento. Trece pacientes recibieron un esquema de drogas basado en cisplatino y como la respuesta a esta terapia no fue buena, a las otras 11 pacientes se les administró vinorelbine e ifosfamida. Luego de la quimioterapia todas las pacientes recibieron radioterapia. La expresión de los marcadores moleculares en las biopsias pre- y post quimioterapia se estudió por inmunohistoquímica y la apoptosis fue evaluada por la técnica del TUNEL mejorada recientemente. Para comparar los cambios en la expresión de los marcadores moleculares y para correlacionarlos con la evaluación clínica (media de seguimiento: 31 meses para las pacientes que recibieron cisplatino y 19 para las que recibieron vinorelbine e ifosfamida) se realizaron análisis estadísticos. Resultados y conclusiones: La quimioterapia de inducción no aumentó la sobrevida de las pacientes, el 50 por ciento tuvo enfermedad progresiva (EP) o falleció (F). La expresión de p21waf1/sdII/cip1, hMLF1, hMSH2, y Bcl-2 no mostró cambios significativos después de la quimioterapia y no correlacionó con la evaluación clínica. La expresión de p53 no se modificó luego de la quimioterapia, las pacientes con tumores p53 positivos mostraron una tendencia a tener una sobrevida menor. Las pacientes con EP o que fallecieron mostraron niveles altos de PCNA, a diferencia de aquellas que estuvieron libres de enfermedad (LE) o con enfermedad estable (EE) (50 por ciento versus 17 por ciento, respectivamente, p<0.004). La sobrevida de las pacientes con bajos índices de TUNEL (igual o menor al valor medio entre las biopsias pre y post-quimioterapia de 1.5) fue significativamente más corta que las pacientes que presentaron índices de TUNEL altos (p<0.009). Nuestros resultados muestran que la quimioterapia de inducción (los dos tratamientos aplicados en este estudio) no mejoró la sobrevida de pacientes con cáncer de cervix...

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We report a 50-year-old woman with a recent myocardial infarction in whom a myocardial perfusion single photon emission computed tomography (SPECT) with Thallium201 was done simultaneously with a F18-fluorodeoxyglucose (FDG) SPECT to study glucose metabolism. Myocardial infarction was located in the anteroseptal and apical regions and an echocardiography, done at the second day of evolution, showed a septo-apical hypokinesia. On the tenth day, a coronary angiography showed a critical lesion of the anterior descending coronary artery and an angioplasty with stent placement was performed on the next day. On the twelfth day, a resting, redistribution 201Tl SPECT to study viability and a FDG-SPECT with a dual head high-energy collimator camera were done. Images, acquired 45 min after injection, were analyzed visually. In anterior and medial apical sectors, discordance between flux and metabolism, considered a classical mismatch, was observed. Echocardiographic hypokinesia disappeared three month after revascularization.

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PURPOSE: Double-phase scintigraphy with Tc-99m sestamibi is a good method to detect hyperfunctioning parathyroid glands. This study tried to determine the best time for delayed images: 2 or 4 hours. METHODS: Fifty-six patients were studied, and 35 of them had primary hyperparathyroidism (mean age, 53 +/- 13 years; 54% were women). Cervical ultrasonography was performed on 29 of 56 (52%) patients and surgery in 16 of 56 (29%) patients. The dose was 740 MBq (20 mCi) given intravenously, and the acquisition was performed at 10 minutes, 2 h, and 4 h using anterior views, including the mediastinum. Studies that had positive results were analyzed blindly by two independent observers, who selected the best definition for abnormal activity. RESULTS: Nineteen of 56 (34%) studies were negative and 37 of 56 (66%) were positive, 25 of them with one focus and 12 with two or more parathyroid foci. Analysis revealed 76% agreement between the observers (the rest was classified by consensus). In 70% of the cases, the best delayed image was obtained at 2 hours, in 16% at 4 hours (P < 0.00001), and in 14% both images were similar. In those cases with better images at 4 hours, the 2-hour images also showed the lesions. In two patients, lesions were seen only at 2 hours. These results could be explained by tracer decay, washout of parathyroid activity, or both. CONCLUSIONS: The best protocol should include the early 10-minute image and the 2-hour delayed view. Further controls do not appear necessary. This may be important for patient throughput.

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BACKGROUND: Exercise EKG is used as the test of choice in the diagnosis of coronary artery disease. Classical parameters are angor and ST depression representing myocardial ischemia. AIM: To correlate exercise EKG parameters with SPECT 201Thallium to know their likelihood ratios for ischemia. PATIENTS AND METHODS: Two hundred seventy four patients (171 men), aged 58 years old as a mean, were studied. Of these, 23% had a prior myocardial infarction. The likelihood ratios for the presence of ischemia of ST depression, failure to increase blood systolic pressure, the presence of angor and its duration during stress testing were calculated according to the results of SPECT 201Thallium. Seventy one patients were also subjected to a coronary angiography. RESULTS: Among men, likelihood ratios for the presence of angor, failure to increase systolic pressure, ST alterations and duration of angor were 6.9, 6.15, 1.77 and 1.27 respectively. Among women, the figures were 5.45, 1.77, 0.58 and 1.4 respectively. The diagnostic accuracy of SPECT 201Thallium, when correlated with the results of coronary angiography, was 85%. CONCLUSIONS: Among men, the best exercise EKG predictors for myocardial ischemia were the failure to increase systolic blood pressure and the presence of angor. Among women the only significant predictor was the presence of angor.

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Incidence of unsuccessful anesthesia with the Gow-Gates mandibular block may be greater than that for the inferior alveolar nerve block until the administrator gains experience with this technique. The aim of this study was to develop a support instrument for the Gow-Gates mandibular block in an attempt to make the described procedure easier and more precise, especially for beginners. In a preliminary clinical experiment 40 patients were anesthetized with this new device; a control group of 40 patients was anesthetized without the instrument. The operators were 80 dental students without previous clinical experience in the Gow-Gates technique. In the experimental group 39 (97.5%) of the 40 patients were provided with complete anesthesia. In the control group 31 (77.5%) of the 40 patients were completely anesthetized. It appears that the new device allows a great level of success with the Gow-Gates mandibular block, irrespective of the clinical experience of the operator.

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The case of a 49 yr old alcoholic women with clinical and laboratory findings that suggested a Cushing syndrome is presented. The functional tests showed cortisol suppression greater than 50% of the basal value with 8 mg of dexamethasone and no response in the combined dexamethasone/desmopressin test. Pituitary Nuclear Magnetic Resonance (NMR) was negative, Abdominal Computed Axial Tomography suggested hyperplastic adrenal glands; adrenal nodules were not found in the NMR. Pituitary or hipothalamic Cushing with secondary autonomous micronodular adrenal hyperplasia was suspected. Norcholesterol-I131 SPECT scintigraphy under dexamethasone suppression demonstrated a functional adrenal hyperplasia which was hystologically confirmed.

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En la experiencia de los autores, sobre 3 hemihepatectomias derechas y 5 segmentectomias, 2 resecciones mayores, 1 por hepatocarcinoma y 1 por traumatismo, fueron ejecutadas por digitoclasia por via cisural con "clampeo" vascular aferente, vena porta y arteria hepatica por periodos prolongados a 55 y 35 minutos, sin deteccion de anormalidades intra o postoperatorias.Esta y la experiencia de otros autores, contribuyen a afirmar que la isquemia normotermica del higado (maniobra de Pringle) puede extenderse mas alla de los 15 minutos, hecho que generalmente se lo acepta como dogma

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En la experiencia de los autores, sobre 3 hemihepatectomias derechas y 5 segmentectomias, 2 resecciones mayores, 1 por hepatocarcinoma y 1 por traumatismo, fueron ejecutadas por digitoclasia por via cisural con "clampeo" vascular aferente, vena porta y arteria hepatica por periodos prolongados a 55 y 35 minutos, sin deteccion de anormalidades intra o postoperatorias.Esta y la experiencia de otros autores, contribuyen a afirmar que la isquemia normotermica del higado (maniobra de Pringle) puede extenderse mas alla de los 15 minutos, hecho que generalmente se lo acepta como dogma

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