Fluoxetine induces direct inhibitory effects on mesenchymal stem cell­derived osteoprogenitor cells independent of serotonin concentration.

Selective serotonin reuptake inhibitors are the most commonly prescribed antidepressants worldwide, which have been reported to exert potential detrimental effects on bone mineral density and increase the risk of developing fractures. The present study aimed to investigate the pathways underlying the negative effects of fluoxetine on bone using mesenchymal stem cells (MSCs) derived from rat adipose tissue as a source of osteoprogenitor cells. MSCs were harvested from adipose tissue using a collagenase enzyme digestion method and were allowed to differentiate into osteoprogenitor cells. Various concentrations of fluoxetine were added to the cells, which were harvested and analyzed by flow cytometry to detect apoptotic markers Annexin V and caspase­3, in order to assess the levels of apoptosis. The levels of endogenous serotonin released in the extracellular matrix were measured using a serotonin ELISA kit. The underlying molecular pathways associated with the effects of fluoxetine on bone were investigated with reverse transcription­quantitative polymerase chain reaction. The results of the present study revealed a significant dose­dependent increase in apoptosis in response to increasing doses of fluoxetine, which was independent of serotonin levels in the culture supernatant. These findings indicated that fluoxetine exerted a direct inhibitory effect on bone cells via an apoptosis­dependent pathway. Furthermore, the expression levels of serotonergic genes, including serotonin 1B receptor, serotonin 2A receptor (HTR2A), serotonin 2B receptor and serotonin transporter, were down regulated; of these genes, HTR2A exhibited the highest expression levels. Further in vitro and in vivo studies are required to verify this association and to determine the molecular pathways involved in fluoxetine­induced bone loss. Fluoxetine­induced apoptosis of osteoprogenitor cells may be the mechanism underlying the increased incidence of bone loss observed in patients treated with fluoxetine.

Enhancing quantum phase transitions in the critical point of Extended TC-Dicke model via Stark effect.

A system of N two-level atoms, Tavis-Cummings Dicke (TC-Dicke) model, interacting with a one-mode electromagnetic radiation field in the presence of the Stark shifts is studied, which is expected to predict new phenomena that are not explored in the original TC-Dicke model. We obtained the potential energy surface of the system using a trial state the direct product of coherent states in each subspace. In the frame of mean-field approaches, the variational energy is evaluated as the expectation value of the Hamiltonian for this state. The order of the quantum phase transitions is determined explicitly and numerically. We estimate the ground-state energy and the macroscopic excitations in the superradiant phase. Moreover, we investigated the critical properties of the TC-Dicke model in the classical spin limit and coherent state. We observed that in the thermodynamic limit, the energy surface takes a simple form a direct description of the phase transition. Moreover, it is found that when the microwave amplitude changes the new phase transition occurs with the Stark shift. The analytical solutions and numerical results, which appear in this paper are agreement with our paper which published recently in Int. J. Mod. Phys. B when we studied the same model using a different coherent state.

Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation.

BACKGROUND AND PURPOSE: Microglial cells are important mediators of the immune response in the CNS. The phytocannabinoid, cannabidiol (CBD), has been shown to have central anti-inflammatory properties, and the purpose of the present study was to investigate the effects of CBD and other phytocannabinoids on microglial phagocytosis. EXPERIMENTAL APPROACH: Phagocytosis was assessed by measuring ingestion of fluorescently labelled latex beads by cultured microglial cells. Drug effects were probed using single-cell Ca²âº imaging and expression of mediator proteins by immunoblotting and immunocytochemistry. KEY RESULTS: CBD (10 µM) enhanced bead phagocytosis to 175 ± 7% control. Other phytocannabinoids, synthetic and endogenous cannabinoids were without effect. The enhancement was dependent upon Ca²âº influx and was abolished in the presence of EGTA, the Ca²âº channel inhibitor SKF96365, the transient receptor potential (TRP) channel blocker ruthenium red, and the TRPV1 antagonists capsazepine and AMG9810. CBD produced a sustained increase in intracellular Ca²âº concentration in BV-2 microglia and this was abolished by ruthenium red. CBD rapidly increased the expression of TRPV2 and TRPV1 proteins and caused a translocation of TRPV2 to the cell membrane. Wortmannin blocked CBD enhancement of BV-2 cell phagocytosis, suggesting that it is mediated by PI3K signalling downstream of the Ca²âº influx. CONCLUSIONS AND IMPLICATIONS: The TRPV-dependent phagocytosis-enhancing effect of CBD suggests that pharmacological modification of TRPV channel activity could be a rational approach to treating neuroinflammatory disorders involving changes in microglial function and that CBD is a potential starting point for future development of novel therapeutics acting on the TRPV receptor family.

Oxidative stress in systemic lupus erythematosus and rheumatoid arthritis patients: relationship to disease manifestations and activity.

AIM: The present work was undertaken to study the status and contribution of oxidative stress in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients. Relationship of the markers of oxidative stress to clinical manifestations, disease activity, damage and medications used were well considered. METHODS: Thirty SLE and 30 RA female patients were included in the study and clinical examination and investigations were performed and disease activity was assessed. Markers of oxidative stress, including malondialdehyde (MDA) and antioxidant scavengers with glutathione (GSH) and glutathione peroxidase (GSH Px) were assessed. RESULTS: Level of MDA, GSH and GSH Px were remarkably altered in RA and SLE patients compared to controls. Markers of increased oxidative stress and impaired antioxidant capacity were profound in RA and significantly reflected disease activity in RA and SLE, with special attention to alopecia and lupus nephritis. RA patients receiving methotrexate had significantly altered parameters and the steroid dose in SLE patients correlated with these markers. CONCLUSION: Oxidative stress was increased and more profound in RA than SLE and could well reflect disease activity, with special attention to SLE patients with alopecia and nephritis. Medications used are closely related to the oxidant/antioxidant imbalance. Considering antioxidants in novel therapeutic strategies is important in SLE and RA patients.

Integrated Management of Childhood Illnesses strategy: compliance with referral and follow-up recommendations in Gezira State, Sudan.

OBJECTIVES: To determine the extent to which families follow referral and follow-up recommendations given in accordance with the Integrated Management of Childhood Illnesses (IMCI) strategy and the factors that influence families' responses to such recommendations. METHODS: Children aged 2 months-5 years who presented to an IMCI-trained health worker in Massalamia Health Area, Sudan, were recruited. Children with an IMCI classification that indicated the need for referral or follow-up were traced to determine whether the family complied with the referral or follow-up recommendation. Caretakers were interviewed to find out why they had or had not complied. Focus group discussions were held with health workers, caretakers, and community members. FINDINGS: Overall, 5745 children were enrolled. Of these, 162 (3%) were considered to be in need of urgent referral: 53 (33%) attended a hospital on the day of the referral, with a further 37 (23%) visiting the hospital later than the day of referral. About half of families cited cost as the reason for not visiting a hospital. A total of 1197 (21%) children were classified as needing follow-up. Compliance with a follow-up recommendation was 44% (529 children). Almost 165 (90%) of caretakers who were aware of and did not comply with follow-up, said they had not done so because the child was better. Compliance increased with the caretaker's level of education, if drugs were provided during the first visit, and if the follow-up period was short (2 or 5 days). CONCLUSION: In Massalamia--a resource-constrained environment in which IMCI implementation was well received by the community--only about half of children judged to be in need of urgent referral were taken for that care within 24 hours. Most children in need of follow-up received their first treatment dose in the health facility. This aspect of IMCI was commented upon favourably by caretakers, and it may encourage them to return for follow-up. Rates of return might also improve if return visits for children currently asked to return after 14 or 30 days were scheduled earlier.