The diagnosis of cystic fibrosis (CF) is based on characteristic clinical and laboratory findings. However, a subgroup of patients present with an atypical phenotype that comprises partial CF phenotype, borderline sweat tests and one or even no common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. The aim of this study was to evaluate the role of nasal potential difference (PD) measurements in the diagnosis of CF patients with an atypical presentation and in a population of patients suspected to have CF.Nasal PD was measured in 162 patients from four different groups: patients with classical CF (n=31), atypical phenotype (n=11), controls (n=50), and patients with questionable CF (n=70). The parameter, or combination of nasal PD parameters was calculated in order to best discriminate all CF patients (including atypical CF) from the non-CF group.The patients with atypical CF disease had intermediate values of PD measurements between the CF and non-CF groups. The best discriminate model that assigned all atypical CF patients as CF used: e(response to chloride-free and isoproterenol/response to amiloride)with a cut-off >0.70 to predict a CF diagnosis. When this model was applied to the group of 70 patients with questionable CF, 24 patients had abnormal PD similar to the atypical CF group. These patients had higher levels of sweat chloride concentration and increased rate of CFTR mutations.Nasal potential difference is useful in diagnosis of patients with atypical cystic fibrosis. Taking into account both the sodium and chloride transport elements of the potential difference allows for better differentiation between atypical cystic fibrosis and noncystic fibrosis patients. This calculation may assist in the diagnostic work-up of patients whose diagnosis is questionable.

Bipolar disorder (BD) is a severe and common chronic mental illness characterized by recurrent mood swings between depression and mania. The biological basis of the disease is poorly understood and its treatment is unsatisfactory. Although in past decades the “monoamine hypothesis” has dominated our understanding of both the pathophysiology of depressive disorders and the action of pharmacological treatments, recent studies focus on the involvement of additional neurotransmitters/neuromodulators systems and cellular processes in BD. Here, evidence for the participation of Na+, K+-ATPase and its endogenous regulators, the endogenous cardiac steroids (ECS), in the etiology of BD is reviewed. Proof for the involvement of brain Na+, K+-ATPase and ECS in behavior is summarized and it is hypothesized that ECS-Na+, K+-ATPase-induced activation of intracellular signaling participates in the mechanisms underlying BD. We propose that the activation of ERK, AKT, and NFκB, resulting from ECS-Na+, K+-ATPase interaction, modifies neuronal activity and neurotransmission which, in turn, participate in the regulation of behavior and BD. These observations suggest Na+, K+-ATPase-mediated signaling is a potential target for drug development for the treatment of BD.

Lipid bilayers containing chlorophyll (Chl) or magnesium octaethylporphyrin (MgOEP) and separating solutions containing varying amounts of differing acceptors are illuminated by a dye laser pulse (FWHM 0.3 microseconds) at 590 mm. Interfacial charge transfer is measured at the first current peak in a voltage clamp circuit. The constants describing the hyperbolic saturations of the charge transferred by differing acceptors are only weakly related to the redox potential of the acceptors. An assymetric molecule, anthraquinone-2-sulfonate, is over 20 times as effective in accepting the electron as is the symmetrical anthraquinone-2,6-disulfonate. In contrast to this variable effectiveness, the maximum amount of charge transferred as a function of acceptor redox potential is constant up to a cut-off value: -0.6 V (vs. standard hydrogen electrode) for MgOEP and -0.5 V for Chl. The reversible redox potential of MgOEP in the bilayer was determined by following both the decrease in photoactivity and the transmembrane potential as a function of aqueous redox potential. It is +0.77 V for MgOEP and approximately 0.7 V for Chl (limited by stability). Thus, a total of 1.4 V of reversible redox potential (free energy) is obtained from 1.8 eV (internal energy) of the triplet excited state of MgOEP.

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The mediation of redox reactions through bilayer lipid membranes was studied. With an appropriate choice of electron acceptors the redox process can be limited either by the chemical reaction rate between the mediator and the reactants or by the shuttle frequency of the mediator through the membrane. Both modes were demonstrated for redox reactions mediated by 2,6 dichlorobenzoquinone (DCBQ) and by alpha-tocopherol with ascorbate entrapped inside vesicles using ferricyanide (a mild oxidant) or hexachloroiridate (a strong oxidant) in the external solution. The redox processes were reaction rate-limited and diffusion-limited for ferricyanide and hexachloroiridate, respectively. The kinetics of the redox processes in the diffusion- and the reaction rate-limited modes allows the determination of the shuttle frequencies and of the interfacial reaction rates of the mediators, respectively. The shuttle frequencies of DCBQ and alpha-tocopherol were approximately 8 and 0.08 s-1, respectively, in L-alpha-dipalmitoyl phosphatidylcholine (DPPC) cholesterol vesicles at 25 degrees C. Interfacial reaction rates between the mediators and ferricyanide were about two- and tenfold lower compared with bulk reaction rates for DCBQ (water) and tocopherol (50% ethanol solution), respectively, i.e., tocopherol is relatively less accessible to aqueous oxidants at the membrane interface. Tocopherol and oxidized tocopherol are reversible hydrophobic redox couples that interact very rapidly with strong oxidants. In both modes of mediation DCBQ was more effective than alpha-tocopherol.