SGLT2 inhibition potentiates the cardiovascular, renal, and metabolic effects of sGC stimulation in hypertensive rats with prolonged exposure to high-fat diet.

Prolonged high-fat diet (HFD) accelerates the cardiovascular, renal, and metabolic dysfunction in hypertensive rats with altered renal development (ARDev). Soluble guanylate cyclase (sGC) stimulation or sodium-glucose cotransporter 2 (SGLT2) inhibition may improve cardiovascular, renal, and metabolic function in settings of hypertension and obesity. This study examined whether 6 wk treatment with an SGLT2 inhibitor (empagliflozin, 7 mg/kg/day) enhances the cardiovascular, renal, and metabolic effects of a sGC stimulator (praliciguat, 10 mg/kg/day) in hypertensive rats with ARDev and prolonged exposure to HFD. Arterial pressure (AP), renal vascular resistance (RVR), fat abdominal volume (FAV), insulin resistance, leptin and triglycerides levels, and intrarenal infiltration of inflammatory cells were higher, but cardiac output and creatinine clearance were lower in hypertensive rats (n = 15) than in normotensive rats (n = 7). Praliciguat administration (n = 10) to hypertensive rats reduced (P < 0.05) AP, FAV, plasma concentrations of leptin and triglycerides, and increased (P < 0.05) cardiac output and creatinine clearance. Empagliflozin administration (n = 8) only increased (P < 0.05) glucosuria and creatinine clearance and decreased (P < 0.05) plasma leptin and triglycerides concentrations in hypertensive rats. Simultaneous administration of praliciguat and empagliflozin (n = 10) accelerated the decrease in AP, improved glucose tolerance, reduced (P < 0.05) incremental body weight gain, and decreased (P < 0.05) insulin resistance index, RVR, and the infiltration of T-CD3 lymphocytes in renal cortex and renal medulla. In summary, the combined administration of praliciguat and empagliflozin leads to a greater improvement of the cardiovascular, renal, and metabolic dysfunction secondary to prolonged exposure to HFD in hypertensive rats with ARDev than the treatment with either praliciguat or empagliflozin alone.NEW & NOTEWORTHY This is the first study, to our knowledge, showing that SGLT2 inhibition potentiates the beneficial cardiovascular, renal, and metabolic effects elicited by sGC stimulation in hypertensive rats with prolonged high-fat diet. The effects of the simultaneous administration of praliciguat and empagliflozin are greater than those elicited by either one alone. The effects of the simultaneous treatment may be related to a greater reduction in the inflammatory status.

Expression of spindle assembly checkpoint proteins BubR1 and Mad2 expression as potential biomarkers of malignant transformation of oral leukoplakia: an observational cohort study.

BACKGROUND: The Spindle Assembly Checkpoint (SAC) is a surveillance mechanism essential to ensure the accuracy of chromosome segregation during mitosis. Our aim was to evaluate the expression of SAC proteins in oral carcinogenesis, and to assess their potential in predicting malignant transformation of oral leukoplakia. MATERIAL AND METHODS: We analysed the immunoexpression of BubR1, Mad2, Bub3, and Spindly proteins in 64 oral biopsies from 52 oral leukoplakias and 12 normal tissues. Univariate and multivariate analysis were performed to evaluate predictive factors for malignant transformation (MT). RESULTS: We observed that BubR1 and Mad2 were more highly expressed in high dysplasia grade lesions than in low grade or normal tissues (P<0.05). High expression of Spindly was significantly correlated with a high Ki-67 score (P=0.004). Six (11.5%) oral leukoplakias underwent malignant transformation. In univariate analysis, the binary dysplasia grade (high grade) (P<0.001) was associated with a higher risk of malignant transformation as well as high BubR1 (P<0.001) and high Mad2 (P=0.013) expression. In multivariate analysis, high expression of BubR1 and Mad2 when combined showed an increased risk for malignant transformation (P=0.013; HR of 4.6, 95% CI of 1.4-15.1). CONCLUSIONS: Our findings reveal that BubR1 and Mad2 were associated with an increased risk for malignant transformation independently of histological grade and could be potential and useful predictive risk markers of malignant transformation in oral leukoplakias.

Fate of Mycobacterium avium subsp. paratuberculosis and changes in bacterial diversity populations in dairy slurry after chemical treatments.

AIMS: A major drawback of using dairy slurry as fertilizer is that it may contains pathogens such as Mycobacterium avium subsp. paratuberculosis (MAP), and it could represent a risk to animal and public health. Thus, the aim of this study was to evaluate the fate of MAP and bacterial communities in dairy slurry after chemical treatments. METHODS AND RESULTS: Cattle slurry, naturally contaminated with MAP, was collected from a dairy herd and divided into 32 glass bottles which were assigned to eight different treatments (control, 3·0% CaO, 0·5% NaOH; 0·087%, 0·11% and 0·14% H2 SO4 ; and 1·0 and 2·5% KMnO4 ). Treated dairy slurry samples were evaluated at 0, 1, 3, 7, 15, 30 and 60-days following treatment application for viable MAP and dairy slurry pH, and in addition temperature in this material was monitored continuously. Bacterial counts were estimated at each sampling time. A Bayesian zero-inflated Poisson mixed model was fitted to assess the effect of each treatment on the count of MAP cells. Model results indicated that only the 3·0% CaO treatment had a statistically important negative effect on MAP counts during the study period. For most treatments, MAP was undetectable immediately after chemical treatment but re-appeared over time, in some replicates at low concentrations. However, in those cases MAP counts were not statistically different than the control treatment. Regarding the fate of the other bacterial populations, the Firmicutes phylum was the dominant population in the un-treated slurry while Clostridia class members were among the most prevalent bacteria after the application of most chemical treatments. CONCLUSION: Only 3% CaO treatment had a statistically important negative effect on MAP viability in cattle slurry. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides evidence of MAP partial control in dairy slurry. This information should be considered as a best management practice to reduce MAP and other pathogens for slurry management on dairy farms.

A histological evaluation of the surgical margins from human oral fibrous-epithelial lesions excised with CO2 laser, Diode laser, Er:YAG laser, Nd:YAG laser, electrosurgical scalpel and cold scalpel.

BACKGROUND: We aim to evaluate the presence of histological artefacts in the surgical margins of human oral fibro-epithelial hyperplasias excised with lasers of different wavelengths, and also electrosurgical scalpel and cold scalpel. Moreover, we aim to determine if some of these instruments could impair the normal histological diagnosis of these lesions. MATERIAL AND METHODS: We included 130 consecutive surgical samples of 80 females and 50 males (mean age of 53.82±16.55) with a histological diagnosis of an oral benign fibrous-epithelial hyperplasias. The samples were categorized into 6 groups according to the type of instrument used: CO2 laser group, diode laser group, Er:YAG laser group, Nd:YAG laser group, electrosurgical scalpel group and cold scalpel group. Histological instrument-induced changes were microscopic evaluated and related with clinical and pathological variables. RESULTS: The instrument with highest tissue damage extension (TDE) was the electrosurgical scalpel (1002.2µm±434.92), followed by diode laser (913.73 µm±322.45), Nd:YAG (899.83µm±327.75), CO2 laser (538.37µm±170.50), Er:YAG laser (166.47µm±123.85), and at last with fewer alterations the cold scalpel group (2.36µm±7.27) (P < 0.001). The most regular incision was observed in CO2 laser group, followed by Er:YAG laser, Nd:YAG laser, electrosurgical scalpel and diode laser group with the less regular incision using cold scalpel as comparison (P < 0.001). A correlation was found between the incision score and TDE (P < 0.001). Regarding histological diagnosis, no case showed any limitation of diagnosis related with the use of any instrument evaluated. CONCLUSIONS: Our results suggest that lasers can be used for the excision of oral benign fibrous-epithelial hyperplasias, without hispathological diagnosis limitations, as long as the physical properties of each laser are known and respected. Er:YAG laser have shown to be a laser with few tissue damage extension and with good incision regularity, been a possible instrument of choice for the surgical removal of these lesions.

Carbon monoxide sensing properties of B-, Al- and Ga-doped Si nanowires.

Silicon nanowires (SiNWs) are considered as potential chemical sensors due to their large surface-to-volume ratio and their possible integration into arrays for nanotechnological applications. Detection of harmful gases like CO has been experimentally demonstrated, however, the influence of doping on the sensing capacity of SiNWs has not yet been reported. For this work, we theoretically studied the surface adsorption of a CO molecule on hydrogen-passivated SiNWs grown along the [111] crystallographic direction and compared it with the adsorption of other molecules such as NO, and O2. Three nanowire diameters and three dopant elements (B, Al and Ga) were considered, and calculations were done within the density functional theory framework. The results indicate that CO molecules are more strongly adsorbed on the doped SiNW than on the pristine SiNW. The following trend was observed for the CO adsorption energies: E A[B-doped] > E A[Al-doped] > E A[Ga-doped] > E A[undoped], for all diameters. The electronic charge transfers between the SiNWs and the adsorbed CO were estimated by using a Voronoi population analysis. The CO adsorbed onto the undoped SiNWs has an electron-acceptor character, while the CO adsorbed onto the B-, Al-, and Ga-doped SiNWs exhibits an electron-donor character. Comparing these results with the ones obtained for the NO and O2 adsorption, the larger CO adsorption energy on B-doped SiNWs indicates their good selectivity towards CO. These results suggest that SiNW-based sensors of toxic gases could represent a clear and advantageous application of nanotechnology in the improvement of human quality of life.

Lithium effects on the mechanical and electronic properties of germanium nanowires.

Semiconductor nanowire arrays promise rapid development of a new generation of lithium (Li) batteries because they can store more Li atoms than conventional crystals due to their large surface areas. During the charge-discharge process, the electrodes experience internal stresses that fatigue the material and limit the useful life of the battery. The theoretical study of electronic and mechanical properties of lithiated nanowire arrays allows the designing of electrode materials that could improve battery performance. In this work, we present a density functional theory study of the electronic band structure, formation energy, binding energy, and Young's modulus (Y) of hydrogen passivated germanium nanowires (H-GeNWs) grown along the [111] and [001] crystallographic directions with surface and interstitial Li atoms. The results show that the germanium nanowires (GeNWs) with surface Li atoms maintain their semiconducting behavior but their energy gap size decreases when the Li concentration grows. In contrast, the GeNWs can have semiconductor or metallic behavior depending on the concentration of the interstitial Li atoms. On the other hand, Y is an indicator of the structural changes that GeNWs suffer due to the concentration of Li atoms. For surface Li atoms, Y stays almost constant, whereas for interstitial Li atoms, the Y values indicate important structural changes in the GeNWs.

The antioxidant capacity of erythrocyte concentrates is increased during the first week of storage and correlated with the uric acid level.

BACKGROUND AND OBJECTIVES: Red blood cells (RBCs) suffer from lesions during cold storage, depending in part on their ability to counterbalance oxidative stress by activating their antioxidant defence. The aim of this study was to monitor the antioxidant power (AOP) in erythrocyte concentrates (ECs) during cold storage. MATERIALS AND METHODS: Six ECs were prepared in saline-adenine-glucose-mannitol (SAGM) additive solution and followed during 43 days. The AOP was quantified electrochemically using disposable electrode strips and compared with results obtained from a colorimetric assay. Haematological data, data on haemolysis and the extracellular concentration of uric acid were also recorded. Additionally, a kinetic model was developed to extract quantitative kinetic data on the AOP behaviour. RESULTS: The AOP of total ECs and their extracellular samples attained a maximum after 1 week of storage prior to decaying and reaching a plateau, as shown by the electrochemical measurements. The observed trend was confirmed with a colorimetric assay. Uric acid had a major contribution to the extracellular AOP. Interestingly, the AOP and uric acid levels were linked to the sex of the donors. CONCLUSION: The marked increase in AOP during the first week of storage suggests that RBCs are impacted early by the modification of their environment. The AOP behaviour reflects the changes in metabolism activity following the adjustment of the extracellular uric acid level. Knowing the origin, interdonor variability and the effects of the AOP on the RBCs could be beneficial for the storage quality, which will have to be further studied.

Attitudes of the first cohort of student groups trained together at the University of Portsmouth Dental Academy towards dental interprofessional education.

OBJECTIVE: This study explored, and compared, the attitudes of student groups trained at the University of Portsmouth Dental Academy (UPDA) in 2010/2011 towards dental interprofessional education (IPE). METHODS: The study population consisted of fifth-year student dentists (n = 80) from King's College London Dental Institute, second- and third-year dental hygiene and therapy (n = 38) and first-year dental nursing (n = 14) students from UPDA. A 19-item, validated and dentally modified questionnaire, 'Readiness for Inter-Professional Learning Scale (RIPLS)', was administered. RIPLS contains three subscales: teamwork and collaboration, professional identity and roles and responsibilities. Mean (x¯) and standard deviation (SD) of the scores were calculated, following reversal of negative items. All the analyses were carried out using SPSS version 20 and STATA version 11. RESULTS: An overall response rate of 71% (n = 94) was achieved. In reference to teamwork and collaboration, all groups strongly indicated that IPE can contribute to learning teamwork skills (x¯ = 24.98, SD = 3.5) and improving relationships with team members (x¯ = 12.93, SD = 1.63); however, the scores did not differ between the groups (P = 0.09 and P = 0.16, respectively). Concerning professional identity, student dentists had significantly higher preference for a discipline-based approach (P = 0.002); were more likely to agree that 'it is not necessary for undergraduate dental and dental care professional students to learn together' (P = 0.01); and perceived that 'clinical problem-solving skills can only be learnt effectively with other students from their own discipline' (P = 0.02) than dental hygiene and therapy students. In relation to roles and responsibilities, participants demonstrated a strong sense of their own professional role. Student dentists reported that they had 'to gain more knowledge and skills' than dental hygiene and therapy (P = 0.01) and dental nursing (P = 0.01) students. Dental hygiene and therapy students were less likely than student dentists to agree that 'the role of dental nurses and hygienists was to mainly provide support for dentists' (P = 0.001). CONCLUSION: The findings suggest that IPE was perceived as beneficial in relation to teamwork; however, the study raises issues regarding professional identity and roles. Educators should consider differing perceptions of professional roles and identities when planning and delivering interprofessional programmes.

Type of surgical treatment and recurrence of oral leukoplakia: A retrospective clinical study.

BACKGROUND: Oral leukoplakia (OL) is the most typical potentially malignant disorder of the oral mucosa. We aimed to evaluate the clinical outcome of oral leukoplakia treated with several types of lasers and with the use of quantic molecular resonance (QMR) lancet, in terms of recurrence rate. MATERIAL AND METHODS: Eighty-seven previously untreated OL (52 occurring in females and 35 in males, mean age of 59.4 ± 13.9 years) were consecutively submitted to surgical treatment at University Hospital of Parma, Italy, and Hospital de Valongo, Portugal, (1999 to 2012). Interventions were subclassified into 5 groups according to the instrument used for the surgical removal of OL (cold blade - 17; Nd:YAG 1064nm laser - 14; Er:YAG 2940nm laser - 33; CO2 10600nm laser - 15; and QMR scalpel - 8). The mean follow-up period after treatment was 21.6 months (range 1-151 months). The outcome of treatment was scored through the same clinical protocol in the two participating units. Statistical analysis were carried by univariate analysis using chi-square test (or Pearson's test when appropriate). RESULTS: Recurrences were observed in 24 cases of OL (27.6%). Malignant transformation occurred in one patient (1.1%) after a period of 35 months. Statistical comparison of the 5 surgical treatment modalities showed no differences in clinical outcomes nor in the recurrence rate of OL. However, when Er:YAG laser group was compared with traditional scalpel, a significantly better outcome in cases treated with Er:YAG laser (P = 0.015) was highlighted. CONCLUSIONS: Our results suggests that Er:YAG laser could be a promising option for the treatment of OL.

Aluminium foil as a single-use substrate for MALDI-MS fingerprinting of different melanoma cell lines.

Herein, we present the intact cell matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) for the fingerprinting of human melanoma cancer cell lines grown on aluminium foil. To perform the MALDI-MS assay, melanoma cells were cultured on a flat and thin foil, which was directly transferred to the target plate of MALDI-MS for analysis. The influence of a wide range of cell fixation protocols (i.e. formalin-based and alcohol-based methods) and MALDI matrices on the obtained characteristic spectra was investigated. For the optimization of the MALDI-MS protocol, the MS fingerprints of the melanoma WM-239 cell line with and without an overexpressed enhanced green fluorescent protein were employed. The fingerprints obtained from WM-239 cells grown on aluminium foil were compared with the intact cell MALDI-MS of the cell pellet and presented higher sensitivity in a high m/z range. The optimized protocol was subsequently applied to characterise melanoma cell lines derived from different cancer stages and allowed identification of unique MS signals that could be used for differentiation between the studied cell lines (i.e. molecular weight equal to 10.0 kDa and 26.1 kDa).

Detection of latent tuberculosis infection among migrant farmworkers along the US-Mexico border.

BACKGROUND: Migrant farmworkers are among the highest-risk populations for latent TB infection (LTBI) in the United States with numerous barriers to healthcare access and increased vulnerability to infectious diseases. LTBI is usually diagnosed on the border using the tuberculin skin test (TST). QuantiFERON-TB Gold In-Tube (QFT-GIT) also measures immune response against specific Mycobacterium tuberculosis antigens. The objective of this study is to assess the comparability of TST and QFT-GIT to detect LTBI among migrant farmworkers on the border, as well as to examine the effects of various demographic and clinical factors on test positivity. METHODS: Participants were recruited using mobile clinics on the San Luis US-Mexico border and tested with QFT-GIT and TST. Demographic profiles and clinical histories were collected. Kappa coefficients assessed agreement between TST and QFT-GIT using various assay cutoffs. Logistic regression examined factors associated with positive TST or QFT-GIT results. RESULTS: Of 109 participants, 59 of 108 (55 %) were either TST (24/71, 34 %) or QFT-GIT (52/106, 50 %) positive. Concordance between TST and QFT-GIT was fair (71 % agreement, ĸ = 0.38, 95 % CI: 0.15, 0.61). Factors associated with LTBI positivity included smoking (OR = 1.26, 95 % CI-1.01-1.58) and diabetes/high blood sugar (OR = 0.70, 95 % CI = 0.51-0.98). DISCUSSION: Test concordance between the two tests was fair, with numerous discordant results observed. Greater proportion of positives detected using QFT-GIT may help avoid LTBI under-diagnosis. Assessment of LTBI status on the border provides evidence whether QFT-GIT should replace the TST in routine practice, as well as identifies risk factors for LTBI among migrant populations.

Prognostic significance of CD44v6, p63, podoplanin and MMP-9 in oral squamous cell carcinomas.

OBJECTIVES: To analyse the expression of the CD44v6, p63, podoplanin and MMP-9, and their prognostic significance in patients with oral squamous cell carcinomas (OSCC). MATERIAL AND METHODS: Immunohistochemistry technique was performed on 60 OSCC for detection of CD44v6, p63, podoplanin and MMP-9 proteins. Extent and intensity of staining were evaluated in tumour cells and were compared with patients' clinical-pathological characteristics and survival. RESULTS: CD44v6 expression was detected at the membrane of tumour cells of 94% cases. Nuclear expression of p63 protein was present in 96.5%. Podoplanin was observed at the membrane of tumour cells of 94% cases. MMP-9 was found in the cytoplasm of tumour cells in 83.7% cases. A high level of expression (67%-89%) in all four proteins was noted. Podoplanin was associated with the expression of MMP-9 (P = 0.010) and both were associated with lymph node metastasis (P = 0.011 and P = 0.018, respectively). Co-expression of podoplanin/MMP-9 was an adverse independent prognostic factor for cancer-specific survival (P = 0.008) and recurrence-free survival (P = 0.042). CONCLUSION: Podoplanin and MMP-9 together could contribute to tumour progression and dissemination of OSCC. Their combined overexpression showed an adverse effect on survival, suggesting that they could be regarded as important prognostic biomarkers in OSCC.

Favourable impact of regular swimming in young people with haemophilia: experience derived from 'Desafio del Caribe' project.

Swimming is beneficial for persons with haemophilia (PWH) providing good maintenance of the cardiovascular and musculoskeletal system and improving many psychological characteristics. In the Desafío del Caribe Project, young PWH from Venezuela and Mexico took part in an open water competition in the Gulf of Mexico under a multidisciplinary team supervision. Eight severe haemophilia A, two moderate haemophilia A, one severe haemophilia B and two moderate haemophilia B subjects were included. Haematological, musculoskeletal and psychological evaluations were carried out before and during training for the competition. Training program included physical exercise routines and swimming practices that alternated between pools and open water. Swimmers had coverage with factor concentrates before pool and open water trainings. In physiatric evaluations, the Hemophilia Joint Health Score (HJHS) was used. The objective of the psychology area was to analyse self-esteem, precompetition anxiety, coping mechanisms and relaxation levels. The need of factor prophylaxis before intense trainings was confirmed. In the musculoskeletal system a decrease of elbow pain as well as an increase of muscle strength in the ankles were observed. In the psychological area significant differences between the first and second test in self-esteem levels, cognitive anxiety and group cohesion were found. PWH must be provided with orientation and encouragement to practice swimming regularly. High competition exercise must be supervised by a multidisciplinary team which must evaluate the pros and cons of the activity to make relevant recommendations.

Renal Effects of Cyclooxygenase Inhibition When Nitric Oxide Synthesis Is Reduced and Angiotensin II Levels Are Enhanced.

The involvement of both cyclooxygenase (COX) isoforms in regulating renal function is well known but their interactions with other regulatory mechanisms, such as angiotensin II (Ang II) and nitric oxide (NO), are not well defined. This study has evaluated the relative contribution of both COX isoforms in regulating renal function when NO synthesis is reduced with and without a simultaneous increment in Ang II levels. The renal responses to a nonselective (meclofenamate) or a selective COX2 (nimesulide) inhibitor were examined in dogs pretreated with L-NAME with or without an intrarenal Ang II infusion. Meclofenamate induced a greater (P < 0.05) renal vasoconstriction than nimesulide in dogs pretreated with L-NAME. This vasoconstriction seems to be Ang II-dependent because it was reduced (P < 0.05) by captopril administration. Meclofenamate also induced a greater (P < 0.05) renal vasoconstriction than that elicited by nimesulide in dogs with reduced NO synthesis and elevated Ang II levels. The renal vasoconstriction induced by nimesulide but not that elicited by meclofenamate in dogs pretreated with L-NAME and Ang II, decreased (P < 0.05) during an extracellular volume expansion. These results demonstrate that the nonselective COX inhibition induces a greater renal vasoconstriction than that elicited by the selective COX2 inhibition when NO synthesis is reduced, and when NO synthesis is reduced and Ang II levels are elevated.

COX2 inhibition during nephrogenic period induces ANG II hypertension and sex-dependent changes in renal function during aging.

This study was performed to test the hypothesis that ANG II contributes to the hypertension and renal functional alterations induced by a decrease of COX2 activity during the nephrogenic period. It was also examined whether renal functional reserve and renal response to volume overload and high sodium intake are reduced in 3-4- and 9-11-mo-old male and female rats treated with vehicle or a COX2 inhibitor during nephrogenic period (COX2np). Our data show that this COX2 inhibition induces an ANG II-dependent hypertension that is similar in male and female rats. Renal functional reserve is reduced in COX2np-treated rats since their renal response to an increase in plasma amino acids levels is abolished, and their renal ability to eliminate a sodium load is impaired (P < 0.05). This reduction in renal excretory ability is similar in both sexes during aging but does not induce the development of a sodium-sensitive hypertension. However, the prolonged high-sodium intake at 9-11 mo of age leads to a greater proteinuria in male than in female (114 ± 12 µg/min vs. 72 ± 8 µg/min; P < 0.05) COX2np-treated rats. Renal hemodynamic sensitivity to acute increments in ANG II is unaltered in both sexes and at both ages in COX2np-treated rats. In summary, these results indicate that the reduction of COX2 activity during nephrogenic period programs for the development of an ANG II-dependent hypertension, reduces renal functional reserve to a similar extent in both sexes, and increases proteinuria in males but not in females when there is a prolonged increment in sodium intake.

Sex-dependent hypertension and renal changes in aged rats with altered renal development.

Numerous studies have evaluated blood pressure (BP) and renal changes in several models of developmental programming of hypertension. The present study examined to what extent BP, renal hemodynamic, and renal structure are affected at an old age in male and female animals with altered renal development. It also evaluated whether renal damage is associated with changes in cyclooxygenase (COX)-2 and neuronal nitric oxide synthase (NOS1) expression and immunoreactivity. Experiments were carried out in rats at 10-11 and 16-17 mo of age treated with vehicle or an ANG II type 1 receptor antagonist during the nephrogenic period (ARAnp). A progressive increment in BP and a deterioration of renal hemodynamics were found in both sexes of ARAnp-treated rats, with these changes being greater (P < 0.05) in male rats. The decrease in glomerular filtration rate at the oldest age was greater (P < 0.05) in male (74%) than female (32%) ARAnp-treated rats. Sex-dependent deterioration of renal structure was demonstrated in optical and electron microscopic experiments. COX-2 and NOS1 immunoreactivity were enhanced in the macula densa of male but not female ARAnp-treated rats. The present study reports novel findings suggesting that stimuli that induce a decrease of ANG II effects during renal development lead to a progressive increment in BP and renal damage at an old age in both sexes, but these BP and renal changes are greater in males than in females. The renal damage is associated with an increase of COX-2 and NOS1 in the macula densa of males but not females with altered renal development.

Renal effects induced by prolonged mPGES1 inhibition.

The importance of membrane-bound PGE synthase 1 (mPGES1) in the regulation of renal function has been examined in mPGES1-deficient mice or by evaluating changes in its expression. However, it is unknown whether prolonged mPGES1 inhibition induces significant changes of renal function when Na(+) intake is normal or low. This study examined the renal effects elicited by a selective mPGES1 inhibitor (PF-458) during 7 days in conscious chronically instrumented dogs with normal Na(+) intake (NSI) or low Na(+) intake (LSI). Results obtained in both in vitro and in vivo studies have strongly suggested that PF-458 is a selective mPGES1 inhibitor. The administration of 2.4 mg·kg(-1)·day(-1) PF-458 to dogs with LSI did not induce significant changes in renal blood flow (RBF) and glomerular filtration rate (GFR). A larger dose of PF-458 (9.6 mg·kg(-1)·day(-1)) reduced RBF (P < 0.05) but not GFR in dogs with LSI and did not induce changes of renal hemodynamic in dogs with NSI. Both doses of PF-458 elicited a decrease (P < 0.05) in PGE2 and an increase (P < 0.05) in 6-keto-PGF1α. The administration of PF-458 did not induce significant changes in renal excretory function, plasma renin activity, and plasma aldosterone and thromboxane B2 concentrations in dogs with LSI or NSI. The results obtained suggest that mPGES1 is involved in the regulation of RBF when Na(+) intake is low and that the renal effects elicited by mPGES1 inhibition are modulated by a compensatory increment in PGI2. These results may have some therapeutical implications since it has been shown that prolonged mPGES1 inhibition has lower renal effects than those elicited by nonsteroidal anti-inflammatory drugs or selective cyclooxygenase-2 inhibitors.

Should all patients be optimized to the same preoperative hemoglobin level to avoid transfusion in primary knee arthroplasty?

BACKGROUND AND OBJECTIVE: Optimization of the preoperative hemoglobin (Hb) level is an effective way to reduce allogeneic transfusion in total knee arthroplasty (TKA) though the procedure is expensive, requires close monitoring and is often inconvenient for patients with reduced mobility. Our aim was to investigate the value of preoperative Hb levels to predict transfusion and thereby tailoring Hb optimization to patient characteristics. MATERIALS AND METHODS: All consecutive patients who undergone primary TKA in our center over 2 years, and received tranexamic acid intraoperatively, were reviewed. The adjusted association between preoperative Hb levels and transfusion was assessed by multivariate logistic regression, and the estimated probability of transfusion for individual patients was derived from the logistic model. RESULTS: Out of the 784 patients who meet the inclusion criteria, risk of transfusion was associated with poorer performance status, as measured by the America Association of Anestesiology (ASA) score III/IV (OR: 3·3, P < 0·001) and lower preoperative Hb level (OR 3·8 for each g/dl below 13 g/dl; P < 0·001). According to the Hb level, the estimated probability of transfusion was 0·03 (range: 0·03-0·64) for ASA I/II patients and 0·10 (range: 0·10-0·84) for ASA III/IV. CONCLUSION: Not all the patients undergoing TKA who receive tranexamic acid need the same preoperative Hb optimization target. Two easily available factors, such as the ASA score and the Hb level, can help individualize the Hb optimization target.

Helicobacter pylori identification: a diagnostic/confirmatory method for evaluation.

The Helicobacter pylori extra gastric reservoir is probably the oral cavity. In order to evaluate the presence of this bacterium in patients with periodontitis and suspicious microbial cultures, saliva was collected from these and non-periodontitis subjects. PCRs targeting 16S rRNA gene and a 860 bp specific region were performed, and digested with the restriction enzyme DdeI. We observed that the PCR-RFLP approach augments the accuracy from 26.2 % (16/61), found in the PCR-based results, to 42.6 % (26/61), which is an excellent indicator for the establishment of this low-cost procedure as a diagnostic/confirmatory method for H. pylori evaluation.