Membrane of Candida albicans as a target of berberine.

BACKGROUND: We investigated the mechanisms of anti-Candida action of isoquinoline alkaloid berberine, active constituent of medically important plants of Barberry species. METHODS: The effects on membrane, morphological transition, synthesis of ergosterol and the consequent changes in membrane permeability have been studied. Polarization and lipid peroxidation level of the membrane following berberine treatment have been addressed. RESULTS: Minimal inhibitory concentration (MIC) of berberine against C. albicans was 17.75 µg/mL. Cytotoxic effect of berberine was concentration dependent, and in sub-MIC concentrations inhibit morphological transition of C. albicans cells to its filamentous form. Results showed that berberine affects synthesis of membrane ergosterol dose-dependently and induces increased membrane permeability causing loss of intracellular material to the outer space (DNA/protein leakage). Berberine also caused membrane depolarization and lipid peroxidation of membrane constituents indicating its direct effect on the membrane. Moreover, ROS levels were also increased following berberine treatment indicating further the possibility of membrane damage. CONCLUSION: Based on the obtained results it seems that berberine achieves its anti-Candida activity by affecting the cell membrane.

Probiotics as an Adjuvant Therapy in Major Depressive Disorder.

BACKGROUND: Major depressive disorder is a common, debilitating psychiatric disorder, which originates from the interaction of susceptibility genes and noxious environmental events, in particular stressful events. It has been shown that dysregulation of hypothalamus-pituitary-adrenal (HPA) axis, imbalance between anti- and pro-inflammatory cytokines, depletion of neurotransmitters (serotonin, norepinephrine and/or dopamine) in the central nervous system, altered glutamatergic and GABAergic transmission have an important role in the pathogenesis of depression. Due to numerous diverse biological events included in the pathophysiology of depression a large number of antidepressant drugs exerting distinct pharmacological effects have been developed. Nevertheless, clinical needs are still not solved. RESULTS: Relatively new research strategies advanced the understanding of psychiatric illness and their connections with disturbances in gastrointestinal tract. The existence of bidirectional communication between the brain and the gut has been proven, and an increasing body of evidence supports the hypothesis that cognitive and emotional processes are influenced through the brain-gut axis. On the other hand, microbiome may influence brain function and even behavior giving to the specific microorganisms a psychobiotic potential. CONCLUSIONS: In this review we discuss the possibilities of classical antidepressant drug treatment being supported with the psychobiotics/probiotic bacteria in patients suffering from major depressive disorder.

Antituberculosis consortium founded in Rijeka (Croatia): implementation of public health measures between 1924-1945.

Between two World Wars the city of Rijeka was a port and industrial town whose infrastructure failed to provide adequate living conditions for numerous workers and their families. Insufficient organization of the health care system, poor living conditions-especially among the poor, low hygienic standards combined with a large number of transitory citizens made city and its citizens vulnerable to tuberculosis. Between 1924-1945 Rijeka was a part of the Kingdom of Italy. Therefore, the fight against tuberculosis was organised according to Italian public health plan and laws. In 1925, Antituberculosis consortium was founded in order to organise and coordinate antituberculosis activities in the city region. Despite its ambitious administrative measures it was unsuccessful in the field: Rijeka had a high mortality and morbidity rate due to tuberculosis. This article is based on unpublished archival material.

Differential effects of short- and long-term zolpidem treatment on recombinant α1ß2γ2s subtype of GABA(A) receptors in vitro.

AIM: Zolpidem is a non-benzodiazepine agonist at benzodiazepine binding site in GABA(A) receptors, which is increasingly prescribed. Recent studies suggest that prolonged zolpidem treatment induces tolerance. The aim of this study was to explore the adaptive changes in GABA(A) receptors following short and long-term exposure to zolpidem in vitro. METHODS: Human embryonic kidney (HEK) 293 cells stably expressing recombinant α1ß2γ2s GABA(A) receptors were exposed to zolpidem (1 and 10 µmol/L) for short-term (2 h daily for 1, 2, or 3 consecutive days) or long-term (continuously for 48 h). Radioligand binding studies were used to determine the parameters of [(3)H]flunitrazepam binding sites. RESULTS: A single (2 h) or repeated (2 h daily for 2 or 3 d) short-term exposure to zolpidem affected neither the maximum number of [(3)H]flunitrazepam binding sites nor the affinity. In both control and short-term zolpidem treated groups, addition of GABA (1 nmol/L-1 mmol/L) enhanced [(3)H]flunitrazepam binding in a concentration-dependent manner. The maximum enhancement of [(3)H]flunitrazepam binding in short-term zolpidem treated group was not significantly different from that in the control group. In contrast, long-term exposure to zolpidem resulted in significantly increase in the maximum number of [(3)H]flunitrazepam binding sites without changing the affinity. Furthermore, long-term exposure to zolpidem significantly decreased the ability of GABA to stimulate [(3)H]flunitrazepam binding. CONCLUSION: The results suggest that continuous, but not intermittent and short-term, zolpidem-exposure is able to induce adaptive changes in GABA(A) receptors that could be related to the development of tolerance and dependence.

The effects of zolpidem treatment on GABA(A) receptors in cultured cerebellar granule cells: changes in functional coupling.

AIMS: Hypnotic zolpidem is a positive allosteric modulator of γ-aminobutyric acid (GABA) action, with preferential although not exclusive binding for α1 subunit-containing GABA(A) receptors. The pharmacological profile of this drug is different from that of classical benzodiazepines, although it acts through benzodiazepine binding sites at GABA(A) receptors. The aim of this study was to further explore the molecular mechanisms of GABA(A) receptor induction by zolpidem. MAIN METHODS: In the present study, we explored the effects of two-day zolpidem (10 µM) treatment on GABA(A) receptors on the membranes of rat cerebellar granule cells (CGCs) using [(3)H]flunitrazepam binding and semi-quantitative PCR analysis. KEY FINDINGS: Two-day zolpidem treatment of CGCs did not significantly affect the maximum number (B(max)) of [(3)H]flunitrazepam binding sites or the expression of α1 subunit mRNA. However, as shown by decreased GABA [(3)H]flunitrazepam binding, two-day exposure of CGCs to zolpidem caused functional uncoupling of GABA and benzodiazepine binding sites at GABA(A) receptor complexes. SIGNIFICANCE: If functional uncoupling of GABA and benzodiazepine binding sites at GABA(A) receptors is the mechanism responsible for the development of tolerance following long-term administration of classical benzodiazepines, chronic zolpidem treatment may induce tolerance.