T-type calcium channels are inhibited by fluoxetine and its metabolite norfluoxetine

Fluoxetine, a widely used antidepressant that primarily acts as a selective serotonin reuptake inhibitor, also inhibits various neuronal ion channels. Using the whole-cell patch-clamp technique, we have examined the effects of fluoxetine and norfluoxetine, its major active metabolite, on cloned low-voltage-activated T-type calcium channels (T channels) expressed in tsA 201 cells. Fluoxetine inhibited the three T channels Ca(V)3.1, Ca(V)3.2, and Ca(V)3.3 in a concentration-dependent manner (IC(50) = 14, 16, and 30 microM, respectively). Norfluoxetine was a more potent inhibitor than fluoxetine, especially on the Ca(V)3.3 T current (IC(50) = 5 microM). The fluoxetine block of T channels was voltage-dependent because it was significantly enhanced for T channels in the inactivated state. Fluoxetine caused a hyperpolarizing shift in steady-state inactivation, with a slower rate of recovery from the inactivated state. These results indicated a tighter binding of fluoxetine to the inactivated state than to the resting state of T channels, suggesting a more potent inhibition of T channels at physiological resting membrane potential. Indeed, fluoxetine and norfluoxetine at 1 microM strongly inhibited cloned T currents (approximately 50 and approximately 75%, respectively) in action potential clamp experiments performed with firing activities of thalamocortical relay neurons. Altogether, these data demonstrate that clinically relevant concentrations of fluoxetine exert a voltage-dependent block of T channels that may contribute to this antidepressant's pharmacological effects.     

Response surface methodology for optimization of methylene blue adsorption onto carboxymethyl cellulose-based hydrogel beads: adsorption kinetics,isotherm, thermodynamics and reusability studies

Environment-friendly composite hydrogel beads based on carboxymethyl cellulose (CMC), alginate (Alg) and graphene oxide (GO) were synthesized by an ionotropic gelation technique and studied as an efficient adsorbent for methylene blue (MB). The chemical structure and surface morphology of the prepared hydrogel beads were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential thermal analysis (DTA) and point of zero charge (pH_pzc). A hybrid response surface methodology integrated Box–Behnken design (RSM-BBD) was successfully developed to model, simulate, and optimize the biosorption process. The synergistic effects between three critical independent variables including adsorbent dose (0.3–0.7 g), pH of the MB solution (6.5–9.5) and initial MB concentration (15–45 mg L⁻¹) on the MB adsorption capacity (mg g⁻¹) and removal efficiency (%) were statistically studied and optimized. The performance of the RSM-BBD method was found to be very impressive and efficient. Results proved that the adsorption process follows a polynomial quadratic model since high regression parameters were obtained (R²-value = 99.8% and adjusted R²-value = 99.3%). Analysis of variance (ANOVA) further confirms the validity of the suggested model. The optimal conditions for 96.22 ± 2.96% MB removal were predicted to be 0.6 g of CMC-Alg/GO hydrogel beads, MB concentration of 15 mg L⁻¹ and pH of 9.5 within 120 min. The adsorption equilibrium is better described by the Freundlich isotherm, indicating that physisorption is the rate controlling mechanism. The MB adsorption process was thermodynamically spontaneous and endothermic. A reusability study revealed that the prepared adsorbent is readily reusable. The adsorbent still maintains its ability to adsorb MB for up to four cycles. Results reported in this study demonstrated that CMC-Alg/GO hydrogel beads are an effective, promising and recyclable adsorbent for the removal of MB from aqueous solutions.

Environment-friendly composite hydrogel beads based on carboxymethyl cellulose (CMC), alginate (Alg) and graphene oxide (GO) were synthesized by an ionotropic gelation technique and studied as an efficient adsorbent for methylene blue (MB).     

Utilization of in vitro maturation in cases with a FSH receptor mutation

Journal of Assisted Reproduction and Genetics - To identify the FSH receptor (FSHR) variant and efficacy of in vitro maturation (IVM) in a 28-year-old woman with secondary amenorrhea, primary...     

Effects of fentanyl administration on general and cerebral haemodynamics in sick newborn infants

Despite the wide use of fentanyl for analgesia in newborns, concerns have been raised about potential haemodynamic side-effects. Since sick newborns may lose their cerebral blood flow autoregulation, a drug-induced haemodynamic instability could lead to brain injury. We assessed the effects of a 15-min infusion of fentanyl (3μg/kg) on the general and cerebral haemodynamics in I5 newborns (median gestational age 29 weeks, 25th–75th percentile, range 28–31 weeks; birthweight 1170 g. range 955–1790 g). The heart rate and mean arterial blood pressure were continuously recorded. Mean cerebral blood flow velocity and pulsatility index were measured using pulsed Doppler ultrasound before, during and up to 60 min after the onset of fentanyl administration. No significant modification of general or cerebral haemodynamics was observed. In conclusion, the infusion or 3μg/kg of fentanyl did not lead to any deleterious effect on the general or cerebral haemodynamics in sick normovolaemic newborns.     

Real‐time high‐resolution magnetic resonance tracking of macrophage subpopulations in a murine inflammation model: a pilot study with a commercially available cryogenic probe

Macrophages present different polarization states exhibiting distinct functions in response to environmental stimuli. However, the dynamic of their migration to sites of inflammation is not fully elucidated. Here we propose a real‐time in vivo cell tracking approach, using high‐resolution (HR)‐MRI obtained with a commercially available cryogenic probe (Cryoprobe?), to monitor trafficking of differently polarized macrophages after systemic injection into mice. Murine bone marrow‐derived mononuclear cells were differentiated ex vivo into nonpolarized M0, pro‐inflammatory M1 and immunomodulator M2 macrophage subsets and labeled with citrate‐coated anionic iron oxide nanoparticles (AMNP). These cells were subsequently intravenously injected to mice bearing calf muscle inflammation. Whole body migration dynamics of macrophage subsets was monitored by MRI at 4.7 T with a volume transmission/reception radiofrequency coil and macrophage infiltration to the inflamed paw was monitored with the cryogenic probe, allowing 3D spatial resolution of 50 µm with a scan time of only 10 min. Capture of AMNP was rapid and efficient regardless of macrophage polarization, with the highest uptake in M2 macrophages. Flow cytometry confirmed that macrophages preserved their polarization hallmarks after labeling. Migration kinetics of labeled cells differed from that of free AMNP. A preferential homing of M2‐polarized macrophages to inflammation sites was observed. Our in vivo HR‐MRI protocol highlights the extent of macrophage infiltration to the inflammation site. Coupled to whole body imaging, HR‐MRI provides quantitative information on the time course of migration of ex vivo‐polarized intravenously injected macrophages. Copyright © 2012 John Wiley & Sons, Ltd.     

Nodular hidradenoma in a 19-year-old woman

Hidradenomas are rare adnexal tumors. Recently, two groups have been individualized: those with eccrine differentiation called poroid hidradenoma and those with apocrine differentiation called clear-cell hidradenoma or nodular hidradenoma. Herein we report a case of 19-year old woman with a nodular hidradenoma of the scapular region. Our report highlights the clinic-pathological characteristics of these tumors and emphasizes the benefit of complete local excision to prevent risk of recurrence and possible malignant potential.     

IFNGR2 genetic polymorphism associated with sex-specific paranoid schizophrenia risk

Background: Considering current scientific evidence about the significant role of chronic low grade inflammation in the physiopathology of schizophrenia, it has been hypothesized that changes in pro-inflammatory cytokines such as interferon gamma may have a significant role in the predisposition to schizophrenia.

Aim: This study focuses on identifying whether the functional polymorphism of interferon gamma receptor 2 (IFNGR2) is a risk factor for the development of schizophrenia.

Methods: This study was conducted by the RFLP-PCR on a Tunisian population composed of 225 patients with different sub-types of schizophrenia and 166 controls.

Results: The IFNGR2 (Q64R) polymorphism analysis showed higher frequencies of minor homozygous genotype (RR) and allele (R) in all patients compared to controls (21.8% vs 10.2%; p?=?.006, OR?=?2.54) and (44% vs 34.9%; p?=?.01; OR?=?1.46), respectively. This correlation was confirmed only for males. This study also noted a significant increase of the mutated homozygous (RR) genotype and (R) allele frequencies of IFNGR2 in paranoid schizophrenics compared to controls (31.4% vs 10.2%; p?=?.001; OR?=?3.34 and 47.2% vs 34.9%; p?=?.009; OR?=?1.66, respectively). This increase remains significant after using binary logistic regression to eliminate confounding factors such as age and sex. Additionally, carriers of RR genotype have significant lower scores on the Scale of Assessment of Positive (SAPS) and negative (SANS) symptoms comparatively to the carrier of the QQ?+?QR genotypes, suggesting that the R recessive allele carriers could have milder symptoms.

Conclusion: The IFNGR2Q64R polymorphism is correlated with male sex and paranoid schizophrenia. It is suggested that a chronic neuroinflammation may predispose to the paranoid schizophrenia development in men.