Fluoxetine effect on kidney water reabsorption

Background. The pathogenesis of hyponatraemia caused by fluoxetine (Fx) use in the treatment of depression is not well understood. It has been attributed to a SIADH, although ADH-enhanced plasma level has not yet been demonstrated in all the cases reported in humans. This experiment aimed at investigating the effect of fluoxetine on the kidney and more specifically in the inner medullary collecting duct (IMCD). Methods. ( 1) In vivo study: ( a) 10 rats were injected daily i. p. with 10 mg/kg fluoxetine doses. After 10 days, rats were sacrificed and blood and kidneys were collected. (b) Immunoblotting studies for AQP2 protein expression in the IMCD from injected rats and in IMCD tubules suspension from 10 normal rats incubated with 10(-7) M fluoxetine. ( 2) In vitro microperfusion study: The osmotic water permeability (P-f, mu m/s) was determined in normal rats IMCD (n = 6), isolated and perfused by the standard methods. Results. In vivo study: ( a) Injected rats with fluoxetine lost about 12% body weight; Na+ plasma level decreased from 139.3 +/- 0.78 mEq/1 to 134.9 +/- 0.5 mEq/1 ( p < 0.01) and K+ and ADH plasma levels remained unchanged. ( b) Immunoblotting densitometric analysis of the assays showed an increase in AQP2 protein abundance of about 40%, both in IMCDs from injected rats [ control period (cont) 99.6 +/- 5.2 versus Fx 145.6 +/- 16.9, p < 0.05] and in tubule suspension incubated with fluoxetine ( cont 100.0 +/- 3.5 versus 143.0 +/- 2.0, p < 0.01). In vitro microperfusion study fluoxetine increased Pf in the IMCD in the absence of ADH from the cont 7.24 +/- 2.07 to Fx 15.77 +/- 3.25 ( p < 0.01). Conclusion. After fluoxetine use, the weight and plasma Na+ level decreased, and the K+ and ADH plasma levels remained unchanged, whereas the AQP2 protein abundance and water absorption in the IMCD increased, leading us to conclude that the direct effect of fluoxetine in the IMCD could explain at least in part, the hyponatraemia found sometime after this drug use in humans.

The effects of moderate and low levels of acoustic overstimulation on stereocilia and their tip links in the guinea pig

Guinea pigs were exposed to pure tones of 10 kHz at intensities between 98 and 115 dB SPL for 5-30 min, to produce varying degrees of acoustic trauma. Changes in auditory thresholds were measured electrophysiologically, and the animals were immediately fixed for scanning electron microscopy. Correlation between morphological changes to the hair bundle and losses in threshold, showed that with the smallest degrees of trauma (98 dB SPL for 15 min, mean maximum threshold loss of 22 dB), damage was confined to a small stretch of inner hair cells (IHC), with only subtle changes to the stereocilia of the outer hair cells (OHC). At exposure intensities greater than 102 dB SPL (duration: 15 min) the IHC stereocilia in the centre of the lesion were always substantially disarrayed. Substantial damage to the OHC bundles was seen only with exposures above 110 dB SPL(duration: greater than or equal to 5 min), producing threshold losses of 50 dB or more. Tip links were lost only where the stereocilia were disarrayed. It is concluded that the tip links are not the most vulnerable components of the cochlear hair cell, but that relatively low levels of acoustic stimulation can cause significant damage to the stereociliary bundle of the IHCs.

The Qu-Prolog unification algorithm: Formalisation and correctness

Qu-Prolog is an extension of Prolog which performs meta-level computations over object languages, such as predicate calculi and lambda-calculi, which have object-level variables, and quantifier or binding symbols creating local scopes for those variables. As in Prolog, the instantiable (meta-level) variables of Qu-Prolog range over object-level terms, and in addition other Qu-Prolog syntax denotes the various components of the object-level syntax, including object-level variables. Further, the meta-level operation of substitution into object-level terms is directly represented by appropriate Qu-Prolog syntax. Again as in Prolog, the driving mechanism in Qu-Prolog computation is a form of unification, but this is substantially more complex than for Prolog because of Qu-Prolog's greater generality, and especially because substitution operations are evaluated during unification. In this paper, the Qu-Prolog unification algorithm is specified, formalised and proved correct. Further, the analysis of the algorithm is carried out in a frame-work which straightforwardly allows the 'completeness' of the algorithm to be proved: though fully explicit answers to unification problems are not always provided, no information is lost in the unification process.

Mechanism of ribonuclease inhibition by ribonuclease inhibitor protein based on the crystal structure of its complex with ribonuclease A

We describe the mechanism of ribonuclease inhibition by ribonuclease inhibitor, a protein built of leucine-rich repeats, based on the crystal structure of the complex between the inhibitor and ribonuclease A. The structure was determined by molecular replacement and refined to an R(cryst) of 19.4% at 2.5 Angstrom resolution. Ribonuclease A binds to the concave region of the inhibitor protein comprising its parallel beta-sheet and loops. The inhibitor covers the ribonuclease active site and directly contacts several active-site residues. The inhibitor only partially mimics the RNase-nucleotide interaction and does not utilize the pi phosphate-binding pocket of ribonuclease A, where a sulfate ion remains bound. The 2550 Angstrom(2) of accessible surface area buried upon complex formation may be one of the major contributors to the extremely tight association (K-i = 5.9 x 10(-14) M). The interaction is predominantly electrostatic; there is a high chemical complementarity with 18 putative hydrogen bonds and salt links, but the shape complementarity is lower than in most other protein-protein complexes. Ribonuclease inhibitor changes its conformation upon complex formation; the conformational change is unusual in that it is a plastic reorganization of the entire structure without any obvious hinge and reflects the conformational flexibility of the structure of the inhibitor. There is a good agreement between the crystal structure and other biochemical studies of the interaction. The structure suggests that the conformational flexibility of RI and an unusually large contact area that compensates for a lower degree of complementarity may be the principal reasons for the ability of RI to potently inhibit diverse ribonucleases. However, the inhibition is lost with amphibian ribonucleases that have substituted most residues corresponding to inhibitor-binding residues in RNase A, and with bovine seminal ribonuclease that prevents inhibitor binding by forming a dimer. (C) 1996 Academic Press Limited

Role for postoperative cortisol response to desmopressin in predicting the risk for recurrent Cushing`s disease

In the early postoperative period of Cushing`s disease patients, desmopressin may stimulate ACTH secretion in the remnant corticotrophic tumour, but not in nontumour suppressed cells. Objective The aim of this study is to evaluate the serum cortisol responses to desmopressin after pituitary surgery, establishing an optimal cut-off for absolute increment (Delta) of serum cortisol (F) suitable to predict recurrence risk. Design Retrospective case record study. Patients Fifty-seven Cushing`s disease patients submitted to pituitary surgery and desmopressin stimulation in the early postoperative with a long-term follow-up (20-161 months) were studied. Methods and measurements Serum cortisol levels after desmopressin test (10 mu g IV) 15-30 days after adenomectomy were used to determine Delta F (absolute increment of F: F peak - F baseline). Sensitivity and specificity of Delta F were calculated and a ROC curve was performed to establish an optimal cut-off for Delta F to predict recurrence risk. Results Fifteen patients had immediate postoperative failure (basal F > 165 nmol/l; 6 mu g/dl) and one patient was lost during the follow-up. Forty-one patients achieved initial remission and were followed-up. Five of 11 patients who recurred had Delta F > 193 nmol/l (7 mu g/dl), but none of 30 patients who remained in prolonged remission showed Delta F > 193 nmol/l after postoperative desmopressin stimulation. Conclusions Persistence of cortisol response (Delta F > 193 nmol/l) to desmopressin in the early postoperative period can help to identify Cushing`s disease patients with initial remission who present risk for later recurrence.

FGF-23 as a Predictor of Renal Outcome in Diabetic Nephropathy

Background and objectives Fibroblast growth factor 23 (FGF-23) has emerged as a new factor in mineral metabolism in chronic kidney disease (CKD). An important regulator of phosphorus homeostasis, FGF-23 has been shown to independently predict CKD progression in nondiabetic renal disease. We analyzed the relation between FGF-23 and renal outcome in diabetic nephropathy (DN). Design, setting, participants, & measurements DN patients participating in a clinical trial (enalapril+placebo versus enalapril+losartan) had baseline data collected and were followed until June 2009 or until the primary outcome was reached. Four patients were lost to follow-up. The composite primary outcome was defined as death, doubling of serum creatinine, and/or dialysis need. Results At baseline, serum FGF-23 showed a significant association with serum creatinine, intact parathyroid hormone, proteirturia, urinary fractional excretion of phosphate, male sex, and race. Interestingly, FGF-23 was not related to calcium, phosphorus, 25OH-vitamin D, or 24-hour urinary phosphorus. Mean follow-up time was 30.7 +/- 10 months. Cox regression showed that FGF-23 was an independent predictor of the primary outcome, even after adjustment for creatinine clearance and intact parathyroid hormone (10 pg/ml FGF-23 increase = hazard ratio, 1.09; 95% CI, 1.01 to 1.16, P = 0.02). Finally, Kaplan-Meier analysis showed a significantly higher risk of the primary outcome in patients with FGF-23 values of >70 pg/ml. Conclusions FGF-23 is a significant independent predictor of renal outcome in patients with macroalbuminuric DN. Further studies should clarify whether this relation is causal and whether FGF-23 should be a new therapeutic target for CKD prevention. Clin J Am Soc Nephrol 6: 241-247, 2011. doi: 10.2215/CJN.04250510

Bone marrow cell therapy prevents infarct expansion and improves border zone remodeling after coronary occlusion in rats

Background: Since the cell therapy benefits for myocardial infarction are mainly related to infarct reduction by regenerating lost myocardium or increasing survival of tissues at risk, we evaluated the effects of bone marrow-derived mononuclear cells (MNC), implanted after the completion of necrosis, on infarct progression and cardiac remodeling. Methods: After 48 h of induction of myocardial infarction (MI), Lewis-inbred rats were injected with 6 x 10(6) cells (MI + MNC) or saline (MI). After six weeks, scar dimension, ventricular morphology and function were analyzed by echocardiography followed by histomorphology of the infarcted and border zones. Results: After therapy, the relative size of the infarct was smaller in MI + MNC (37 +/- 1% of the left ventricle) than in MI (43 +/- 1%). While the MI group exhibited parallel elongation of the infarcted (31.6 +/- 3.8% increase) and reminiscent ventricular portions (33.5 +/- 3.7%), MNC therapy preserved the initial infarct length. Infarcted walls were thicker (979 +/- 31 mm) in the MNC group than in the untreated group (709 +/- 41 mm), also demonstrating an absence of infarct expansion. In the border zones, MNC led to increased capillary densities and capillary/myocyte ratios. The cardiac systolic function remained depressed in MI, but improved by 19 +/- 5% in MI + MNC which reduced the incidence of pulmonary arterial hypertension (37.5% in MI and 6.25% in MI + MNC). Conclusion: MNC therapy prevented the infarct expansion and thinning related to cardiac remodeling and was associated with an improvement of border zone microcirculation: as a result, MNC therapy reduced typical MI dysfunctional repercussions. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Subclavian Vein an Unusual Access for the Removal of Intravascular Foreign Bodies

Catheter migration or catheter fracture and consequent migration of a fragment is a rare complication that occurs in 1% of the patients. Despite the low incidence, embolization may cause severe and potentially fatal complications, with the mortality rates varying between 24 and 60%. The gold standard treatment for this condition is the extraction of the fragmented catheter by the intravascular percutaneous route, through the common femoral vein. If it is not available, the extraction procedure must be performed through an alternative access. This article describes a fully successful removal of a fragmented catheter by percutaneous intravascular access obtained through the right subclavian vein.

Clinical and immunopathological evaluation of epidermolysis bullosa acquisita

P>Background. Epidermolysis bullosa acquisita (EBA) is a subepidermal blistering disease with IgG antibodies against collagen VII. The disease is heterogeneous and can lead to significant morbidity. Aim. To characterize the clinical and laboratory profile of patients with EBA from Sao Paulo, Brazil. Methods. In total, 12 patients (mean age 24 years) were analysed for cutaneous and mucosal involvement, laboratory data and response to treatment. Results. Mucosal involvement occurred in 11 of the 12 patients (eyes in 4/12, nose in 4/9, pharynx-larynx in 5/9 and oesophagus in 4/10; 3 patients did not undergo nasopharyngeal examination and 2 paediatric patients did not undergo endoscopy). Using direct immunofluorescence, different patterns of deposits were found at the basement membrane zone: IgG (12/12), IgA (6/12), IgM (4/12), C3 (11/12). Indirect immunofluorescence (IIF) was positive in 6 of 12 patients, and IIF on salt-split skin detected dermal deposition in 10 of 12 patients. Antinuclear antibodies were found in 3 of 12 patients, but none of them fulfilled the criteria for systemic lupus erythematosus. After treatment, total remission was achieved in three patients and partial remission in five (three were maintained on minimal treatment, one on the full treatment and one was able to come off treatment). Two patients were lost to follow-up and the remaining two had disease flares. Complications were mainly mucosal (oesophageal stenosis, laryngeal synechia, symblephara and trichiasis). Conclusions. Mucosal involvement in EBA is a determining factor for disease morbidity. Complete evaluation of the patient, focusing on both cutaneous and extracutaneous sites is essential, as EBA may evolve to refractory disease, severely compromising its outcome.

Non-equilibrium energy and momentum accommodation coefficients of Ar atoms scattered from Ni(001) in the thermal regime: A molecular dynamics study

Molecular dynamics simulations are used to study energy and momentum transfer of low-energy Ar atoms scattered from the Ni(001) surface. The investigation concentrates on the dependence of these processes on incident energy, angles of incidence and surface temperature. Energy transfer exhibits a strong dependence on the surface temperature, at incident energies below 500 meV, and incident angles close to specular incidence. Above 500 meV, the surface temperature dependence vanishes, and a limiting value in the amount of energy transferred to the surface is attained. Momentum exchange is investigated in terms of tangential and normal components. Both components exhibit a weak surface temperature dependence, but they have opposite behaviours at all incidence angles. In each component, momentum can be lost or gained following the interaction with the surface. (C) 1997 Elsevier Science B.V.

Entecavir Treatment for up to 5 Years in Patients with Hepatitis B e Antigen-Positive Chronic Hepatitis B

Sustained virologic suppression is a primary goal of therapy for chronic hepatitis B (CHB). In study entecavir (ETV)-022, 48 weeks of entecavir 0.5 mg was superior to lamivudine for virologic suppression for hepatitis B e antigen (HBeAg)-positive CHB. A total of 183 entecavir-treated patients from ETV-022 subsequently enrolled in study ETV-901. We present the results after up to 5 years (240 weeks) of continuous entecavir therapy. The entecavir long-term cohort consists of patients who received >= 1 year of entecavir 0.5 mg in ETV-022 and then entered ETV-901 with a treatment gap <= 35 days. In ETV-901 the entecavir dose was 1.0 mg daily. For patients with samples available at Year 5, proportions with hepatitis B virus (HBV) DNA <300 copies/mL, normal alanine aminotransferase (ALT) levels, HBeAg loss, and HBeAg seroconversion were determined. In all, 146 patients met criteria for inclusion in the entecavir long-term cohort. At Year 5, 94% (88/94) had HBV DNA <300 copies/mL and 80% (78/98) had normal ALT levels. In addition to patients who achieved serologic responses during study ETV-022, 23% (33/141) achieved HBeAg seroconversion and 1.4% (2/145) lost hepatitis B surface antigen (HBsAg) during study ETV-901. Through 5 years, entecavir resistance emerged in one patient. The safety profile of entecavir was consistent with previous reports. Conclusion: Extended therapy with entecavir through 5 years maintained or increased rates of HBV DNA suppression and ALT normalization. Additional patients also achieved HBeAg loss and seroconversion. Entecavir provides sustained viral suppression with minimal resistance during long-term treatment of HBeAg-positive CHB. (HEPATOLOGY 2010;51:422-430.)

Customized Topography-guided Photorefractive Keratectomy With the MEL-70 Platform and Mitomycin C to Correct Hyperopia After Radial Keratotomy

PURPOSE: To evaluate topography-guided photorefractive keratectomy (PRK) for correcting hyperopia and astigmatism after radial keratotomy (RK). METHODS., Prospective study of 12 consecutive patients (19 eyes) who were treated with topography-guided PRK with 0.02% mitomycin C using an Asclepion-Meditec MEL-70 excimer laser with a 9.5-mm ablation zone. All eyes were operated by the same surgeon and followed for 1 year. RESULTS: Thirteen eyes had complete epithelialization by day 7 and all eyes by day 10. At 1 year, uncorrected visual acuity was 20/25 or better in 42.1% of eyes and 20/40 or better in 68.4%. Preoperative mean spherical equivalent refraction was +3.80 +/- 2.47 diopters (D) and +0.24 +/- 2.36 D (P <.001) 1 year postoperative, with 47.4% of eyes being within +/- 1.00 D and 73.7% within +/- 2.00 D. Preoperative mean cylinder was -2.30 +/- 1.41 D and -0.62 +/- 0.73 D (P <.1001) 1 year postoperative. At 1 year, 68.4% of eyes gained at least 1 line of best-spectacle corrected visual acuity, 36.8% gained more than 1 line, and only 2 eyes lost 1 line (one due to corneal haze). Three eyes developed central haze. Mean regression from 6 to 12 months in these 3 eyes was +1.83 D and in the remaining 16 eyes was -0.50 D. CONCLUSIONS: Topography-guided PRK with mitomycin C was safe and reasonably effective for the treatment of hyperopia after RK [J Refract Surg. 2008;24:911-922.]

Photorefractive keratectomy and butterfly laser epithelial keratomileusis: A prospective, contralateral study

PURPOSE: To evaluate results of two surface excimer laser refractive surgery techniques-photorefractive keratectomy (PRK) and butterfly laser epithelial keratomileusis (butterfly LASEK). METHODS: A prospective, randomized, double-masked study of 51 patients (102 eyes) who underwent laser refractive surgery. One eye of each patient was randomized to be operated with PRK and the fellow eye with butterfly LASEK Patients were followed for 1 year. RESULTS: No significant difference between groups for distance uncorrected visual acuity (UCVA) (P=.559) was noted. At 1 year, 98% (50 eyes) in the PRK group and 96.1% (49 eyes) in the butterfly LASEK group reached UCVA of 20/20. Predictability, efficacy, safety, and stability were not statistically significant between groups. Safety index was 1.0 for PRK and 0.996 for butterfly LASEK, One eye in the butterfly LASEK group lost one line of best-spectacle corrected visual acuity. At 12 months, 94.1% (48 eyes) and 86.3% (44 eyes) in the PRK and butterfly LASEK groups (P=.188), respectively, had a spherical equivalent refraction of +/- 0.50 diopters. Slight haze was observed in both groups. A statistical difference in haze between the groups was observed only in the first postoperative month, with higher intensity in the butterfly LASEK group (0.18 +/- 0.39) compared to the PRK group (0.08 +/- 0.21) (P=.04). CONCLUSIONS: Butterfly LASEK had similar predictability, efficacy, safety, stability, and haze incidence to PRK for the treatment of low to moderate myopia. However, on the second postoperative day, PRK showed better UCVA than butterfly LASEK.

Disarrangement of Collagen Fibers in Reinke`s Edema

Objective/Hypothesis: To describe the arrangement of collagen fibers in the superficial layer of the lamina propria of the vocal folds with Reinke` edema. Study Design: Cross sectional analysis of the lamina propria of the vocal folds with Reinke`s edema (RE). Method: The picrosirius polarization method was used to study the arrangement of collagen fiber. Findings of collagen disarrangement were categorized semiquantitatively and correlated with RE severity, age, cigarette smoking and duration of dysphonia. Results: Analysis of 20 specimens of vocal folds with RE showed that the intertwined network of collagen fibers resembling a wicker-basket normally observed in vocal folds was disarranged in RE. The collagen fibers were loosely arranged, fragmented and intermixed with varying amounts of myxoid stroma. Moderate and large areas of disarrangement (90% of cases) predominated. Collagen fiber arrangement in the region underneath the epithelium was better preserved when compared with fibers in the deeper region of the superficial layer of the lamina propria. There was a statistical difference in collagen disarrangement between grade II and grade III severity (P = .007) that appeared to be due to the large areas of disarrangement observed in 73% of patients with grade III severity and in 44% of grade II severity. Age was the only variable correlated with collagen fiber disarrangement (r = 0.47, P = .037). Conclusion: Our findings suggest that the flexible framework which maintains the uniformity of the lamina propria was lost in RE caused by the disarrangement of the collagen fibers.

Elastic Fibers in Reinke`s Edema

Objectives: We describe the distribution of elastic system fibers in the superficial layer of the lamina propria of Reinke`s edema, as compared with normal vocal folds. Methods: Weigert`s resorcin-fuchsin stain after oxidation with 10% oxone was used to study the arrangement of elastic fibers. The findings were categorized and afterward compared with the severity of Reinke`s edema. Results: Analysis of 20 specimens of vocal folds with Reinke`s edema showed that the network of thin elastic fibers in Reinke`s space lost their undulated appearance and had a tangled aspect. In addition, these fibers were no longer parallel to the epithelial basement membrane, but had a random distribution scattered throughout Reinke`s space. The elastic fiber network immediately below the epithelial basement membrane also appeared more fragmented in Reinke`s edema because of some alteration in organization combined with the 5-mu m-thick histologic sectioning plane. No significant difference in the degree of elastic system fiber disarrangement was observed between severity grades II and III (p = 0.382). Large areas of disarrangement were predominant (80% of cases). Conclusions: The disarrangement of elastic fibers in Reinke`s edema may cause insufficient tissue resistance and resilience, contributing to the hypermobility observed in Reinke`s edema.