New Insights in Staging and Chemotherapy of African Trypanosomiasis and Possible Contribution of Medicinal Plants

Human African trypanosomiasis (HAT) is a fatal if untreated fly-borne neuroinflammatory disease caused by protozoa of the species Trypanosoma brucei (T.b.). The increasing trend of HAT cases has been reversed, but according to WHO experts, new epidemics of this disease could appear. In addition, HAT is still a considerable burden for life quality and economy in 36 sub-Saharan Africa countries with 15–20 million persons at risk. Following joined initiatives of WHO and private partners, the fight against HAT was re-engaged, resulting in considerable breakthrough. We present here what is known at this day about HAT etiology and pathogenesis and the new insights in the development of accurate tools and tests for disease staging and severity monitoring in the field. Also, we elaborate herein the promising progresses made in the development of less toxic and more efficient trypanocidal drugs including the potential of medicinal plants and related alternative drug therapies

Generalized Fokker-Planck equation, Brownian motion, and ergodicity

Microscopic theory of Brownian motion of a particle of mass $M$ in a bath of molecules of mass $m\ll M$ is considered beyond lowest order in the mass ratio $m/M$. The corresponding Langevin equation contains nonlinear corrections to the dissipative force, and the generalized Fokker-Planck equation involves derivatives of order higher than two. These equations are derived from first principles with coefficients expressed in terms of correlation functions of microscopic force on the particle. The coefficients are evaluated explicitly for a generalized Rayleigh model with a finite time of molecule-particle collisions. In the limit of a low-density bath, we recover the results obtained previously for a model with instantaneous binary collisions. In general case, the equations contain additional corrections, quadratic in bath density, originating from a finite collision time. These corrections survive to order $(m/M)^2$ and are found to make the stationary distribution non-Maxwellian. Some relevant numerical simulations are also presented

Several small Josephson junctions in a Resonant Cavity: Deviation from the Dicke Model

We have studied quantum-mechanically a system of several small identical Josephson junctions in a lossless single-mode cavity for different initial states, under conditions such that the system is at resonance. This system is analogous to a collection of identical atoms in a cavity, which is described under appropriate conditions by the Dicke model. We find that our system can be well approximated by a reduced Hamiltonian consisting of two levels per junction. The reduced Hamiltonian is similar to the Dicke Hamiltonian, but contains an additional term resembling a dipole-dipole interaction between the junctions. This extra term arises when states outside the degenerate group are included via degenerate second-order (L\"{o}wdin) perturbation theory. As in the Dicke model, we find that, when N junctions are present in the cavity, the oscillation frequency due to the junction-cavity interaction is enhanced by $\sqrt{N}$. The corresponding decrease in the Rabi oscillation period may cause it to be smaller than the decoherence time due to dissipation, making these oscillations observable. Finally, we find that the frequency enhancement survives even if the junctions differ slightly from one another, as expected in a realistic system.Comment: 11 pages. To be published in Phys. Rev.

Fullerenol nanoparticles as a new delivery system for doxorubicin

Doxorubicin is a very potent chemotherapeutic drug, however its side effects limit its clinical use. The aim of this research was to investigate the properties of a fullerenol/doxorubicin nanocomposite, its potentially cytotoxic and genotoxic effects on malignant cell lines, as well as its toxicity towards zebra fish embryos. Chromatographic, NMR and mass spectral analysis of the nanocomposite imply that interactions between doxorubicin and fullerenol are non-covalent bonds. The stability of the nanocomposite was confirmed by the use of atomic force microscopy, dynamic light scattering and transmission electron microscopy. The nanocomposite, compared to the free doxorubicin at equivalent concentrations, significantly decreased the viability of MCF-7 and MDA-MB-231 cells. The flow cytometry results indicated that doxorubicin-loaded fullerenol could remarkably increase the uptake of doxorubicin suggesting that fullerenol might be a promising intracellular targeting carrier for the efficient delivery of antitumor drugs into tumor cells. The nanocomposite also affected cell cycle distribution. A genotoxicity test showed that the nanocomposite at all examined concentrations on MCF-7 and at lower concentrations on MDA-MB-231 cells caused DNA damage. Consequently, cell proliferation was notably reduced when compared with controls. Results of the zebrafish embryotoxicity assay showed a decreased overall toxicity, particularly cardiotoxicity and increased safety of the nanocomposite in comparison to doxorubicin alone, as manifested by a higher survival of embryos and less pericardial edema

Spontaneous emission and lifetime modification caused by an intense electromagnetic field

We study the temporal evolution of a three-level system (such as an atom or a molecule), initially prepared in an excited state, bathed in a laser field tuned at the transition frequency of the other level. The features of the spontaneous emission are investigated and the lifetime of the initial state is evaluated: a Fermi "golden rule" still applies, but the on-shell matrix elements depend on the intensity of the laser field. In general, the lifetime is a decreasing function of the laser intensity. The phenomenon we discuss can be viewed as an "inverse" quantum Zeno effect and can be analyzed in terms of dressed states.Comment: 25 pages, 6 figure

A new perturbative expansion of the time evolution operator associated with a quantum system

A novel expansion of the evolution operator associated with a -- in general, time-dependent -- perturbed quantum Hamiltonian is presented. It is shown that it has a wide range of possible realizations that can be fitted according to computational convenience or to satisfy specific requirements. As a remarkable example, the quantum Hamiltonian describing a laser-driven trapped ion is studied in detail.Comment: 32 pages; modified version with examples of my previous paper quant-ph/0404056; to appear on the J. of Optics B: Quantum and Semiclassical Optics, Special Issue on 'Optics and Squeeze Transformations after Einstein

Resonance fluorescence spectrum in a weak squeezed field with an arbitrary bandwidth

We analyze the linewidth narrowing in the fluorescence spectrum of a two-level atom driven by a squeezed vacuum field of a finite bandwidth. It is found that the fluorescence spectrum in a low-intensity squeezed field can exhibit a (omega - omega(0))(-6) frequency dependence in the wings. We show that this fast fall-off behavior is intimately related to the properties of a narrow-bandwidth squeezed field and does not extend into the region of broadband excitation. We apply the Linear response model and find that the narrowing results from a convolution of the atom response with the spectrum of the incident field. On the experimental side, we emphasize that the linewidth narrowing is not sensitive to the solid angle of the squeezed modes coupled to the atom. We also compare the fluorescence spectrum with the quadrature-noise spectrum and find that the fluorescence spectrum for an off-resonance excitation does not reveal the noise spectrum. We show that this difference arises from the competing three-photon scattering processes. [S1050-2947(98)04308-X]

Actigraphy in Human African Trypanosomiasis as a Tool for Objective Clinical Evaluation and Monitoring: A Pilot Study

The clinical picture of the parasitic disease human African trypanosomiasis (HAT, also called sleeping sickness) is dominated by sleep alterations. We here used actigraphy to evaluate patients affected by the Gambiense form of HAT. Actigraphy is based on the use of battery-run, wrist-worn devices similar to watches, widely used in middle-high income countries for ambulatory monitoring of sleep disturbances. This pilot study was motivated by the fact that the use of polysomnography, which is the gold standard technology for the evaluation of sleep disorders and has greatly contributed to the objective identification of signs of disease in HAT, faces tangible challenges in resource-limited countries where the disease is endemic. We here show that actigraphy provides objective data on the severity of sleep-wake disturbances that characterize HAT. This technique, which does not disturb the patient's routine activities and can be applied at home, could therefore represent an interesting, non-invasive tool for objective HAT clinical assessment and long-term monitoring under field conditions. The use of this method could provide an adjunct marker of HAT severity and for treatment follow-up, or be evaluated in combination with other disease biomarkers in body fluids that are currently under investigation in many laboratories