The effect of lamotrigine on platelet monoamine oxidase type B activity in patients with bipolar depression

Lamotrigine is an anticonvulsant drug effective in the treatment of epilepsy and bipolar depression. Preclinical data showed that lamotrigine inhibited monoamine oxidase (MAO) activity in vitro. The aim of the study was to determine the effects of 6-weeks lamotrigine treatment on platelet MAO type B (MAO-B) activity in patient with bipolar depression. The study included 26 female patients with bipolar I disorder in depressive episode (DSM-IV criteria, Hamilton Depression Rating Scale (HAMD) and Young Mania Rating Scale). Platelet MAO-B activity was determined spectrofluorimetrically before and after 6 weeks of the treatment with a relatively low dose of lamotrigine (100 mg/day). Six weeks of treatment with lamotrigine significantly decreased platelet MAO-B activity in bipolar depressed patients. This inhibitory effect was not related to smoking status and was independent of the treatment combinations (lamotrigine alone or in combination with either lithium or antipsychotics). Lamotrigine treatment induced a decrease in total HAMD scores in bipolar depressed patients, which was not significantly correlated with reduction of platelet MAO-B activity. These findings provide in vivo insight of lamotrigine effect on platelet MAO-B activity in patients with bipolar depression. Its in vivo MAO-B inhibiting effect might have contributed in part to its antidepressant activity.     

A Case Report of Porphyria Variegata Management in the Emergency Department

Background: Porphyria variegata (VP) is one of the hepatic porphyrias that results from the deficiency of protoporphyrinogen oxidase, an enzyme in the heme synthesis pathway. The name porphyria variegata refers to its many presentations, which include various neuropsychiatric and cutaneous manifestations. Emergency department (ED) presentations due to VP are most commonly neuropathic abdominal pain. Case Report: We present the case of a 57-year-old woman presenting to an ED with abdominal pain consistent with prior VP attacks. In addition to analgesics and supportive care, infusion of intravenous dextrose resulted in improvement in her symptoms. Conclusion: Intravenous dextrose and heme administration remain the first-line treatment for abdominal pain attributable to known acute hepatic porphyria attacks. Recently, the mechanism of action of carbohydrates in treating porphyria has been elucidated. Current information on this illness and ED management are discussed.     

The anti-Candida activity of Thymbra capitata essential oil: effect upon pre-formed biofilm

Ethopharmacological relevance

Thymbra capitata essential oil is traditionally considered to exhibit powerful antiseptic properties, thus being used to treat cutaneous infections. The aim of the present study was to evaluate the effect of Thymbra capitata essential oil upon pre-formed biofilm of different Candida strains while comparing it with the activity against planktonic cells.

Materials and methods

Fifteen Candida isolates were included, corresponding to clinical and collection type strains. Essential oil was obtained by hydrodistillation and its composition analysed by GC/MS. Activity upon planktonic cells was evaluated according to M27-A3 macromethod. Its effect upon 24 h preformed biofilm biomass was determined using the crystal violet procedure and the metabolic activity was studied applying the XTT/menadione technique.

Results

Biofilm biomass and metabolic activity of all tested species were reduced up to 50% at MIC values. The effect was more pronounced at double MIC values, achieving >80% reduction, except for Candida albicans that presented a more resistant profile (62%).

Conclusion

Thymbra capitata essential oil presented an important effect upon Candida biofilms. It is proposed as a valuable antifungal product to be used in an appropriate pharmaceutical formulation for the management of resistant mucocutaneous candidosis.     

A novel method for long term bone marrow culture and genetic modification of murine neutrophils via retroviral transduction

Neutrophils are a critical component of the innate immune response to invading microbial pathogens. However, an excessive and/or prolonged neutrophil response can result in tissue injury that is thought to underlie the pathogenesis of various inflammatory diseases. The development of novel therapeutic strategies for inflammatory diseases depends on an improved understanding of regulation of neutrophil function. However, investigations into neutrophil function have been constrained in part by the difficulty of genetically modifying neutrophils using current techniques. To overcome this, we have developed a novel method for the genetic modification of murine bone marrow derived progenitor cells using retroviral transduction followed by long term bone marrow culture to generate mature neutrophils. These neutrophils are functionally mature as determined by morphology, surface marker (Gr1, CD11b, CD62L and CXCR2) expression, and functional attributes including the ability to generate superoxide, exocytose granule contents, chemotax, and phagocytose and kill bacteria. Further, the in vitro matured neutrophils are capable of migrating to an inflammatory site in vivo. We utilized this system to express the Bcl-2 transgene in mature neutrophils using the retroviral vectors pMIG and pMIT. Bcl-2 overexpression conferred a substantial delay in spontaneous apoptosis of neutrophils as assessed by annexin V and 7-amino-actinomycin D (7AAD) staining. Moreover, Bcl-2 overexpression did not alter granulopoiesis, as assessed by morphology and surface marker expression. This system enables the genetic manipulation of progenitor cells that can be differentiated in vitro to mature neutrophils that are functional in vitro and in vivo.     

The neutrophil serine protease PR3 induces shape change of platelets via the Rho/Rho kinase and Ca signaling pathways

Introduction

Proteinase 3 (PR3) is released from neutrophil azurophilic granules and exerts complex effects on the inflammatory process. PR3 catalyzes the degradation of a number of macromolecules, but the consequences on blood cells are less well defined. In the present study, the effect of PR3 on human platelets was thoroughly investigated.

Methods

The experiments were performed on washed platelets freshly isolated from blood donated by healthy human volunteers. Platelets shape change and aggregation was measured on a Chrono-Log aggregometer. The phosphorylated form of MYPT1 was visualized by immunostaining. Platelet activation was further evaluated by flow cytometry.

Results

PR3 induced platelet shape change but not aggregation. Flow cytometry analysis showed that PR3 induced no P-selectin expression or binding of fibrinogen to the platelets, and it did not change the activation in response to PAR1- or PAR4-activating peptides or to thrombin. Furthermore, Fura-2 measurement and immuno-blotting analysis, respectively, revealed that PR3 stimulated small intracellular Ca^2 + mobilization and Thr696-specific phosphorylation of the myosin phosphatase target subunit 1 (MYPT1). Separate treatment of platelets with the Rho/Rho kinase inhibitor Y-27632 and the intracellular Ca^2 + chelator BAPTA/AM reduced the shape change induced by PR3 whereas concurrent treatment completely inhibited it.

Conclusion

The data shows that the neutrophil protease PR3 is a direct modulator of human platelets and causes shape change through activation of the Rho/Rho kinase and Ca^2 + signaling pathways. This finding highlights an additional mechanism in the complex interplay between neutrophils and platelets.     

Effect of Zataria multiflora Boiss. essential oil on growth and aflatoxin formation by Aspergillus flavus in culture media and cheese

The effect of Zataria multiflora Boiss. essential oil (EO) against growth, spore production and aflatoxin formation by Aspergillus flavus ATCC 15546 was investigated in synthetic media as well as Iranian ultra-filtered white cheese in brine. EO effectively inhibited radial growth and spore production on potato dextrose agar (PDA) in a dose-dependent manner. At 200 ppm, the radial growth and sporulation reduced by 79.4% and 92.5%, respectively. The growth was completely prevented at EO ? 400 ppm on PDA, and minimum fungicidal concentration (MFC) of the oil was estimated at 1000 ppm. The oil also significantly suppressed mycelial growth and aflatoxin synthesis in broth medium at all concentrations tested (P < 0.05). At 150 ppm of EO, the mycelial growth and aflatoxin accumulation reduced by 90% and 99.4%, respectively. The EO at all concentrations tested, had an inhibitory effect against radial fungal growth and aflatoxin production by A. flavus in cheese. However, no concentration of EO examined was able to completely inhibit the growth and aflatoxin production in cheese. The results suggested the potential substitution of the antifungal chemicals by this EO as a natural inhibitor to control the growth of molds in foods such as cheese.