Paracoccidioides brasifiensis killing by IFN-gamma, TNF-alpha and GM-CSF activated human neutrophils: role for oxygen metabolites

Paracoccidioidomycosis, a deep mycosis endemic in Latin America, is a chronic granulomatous disease caused by the fungus Paracoccidioides brasiliensis. Phagocytic cells play a critical role against the fungus and several papers show the effects of activator and suppressive cytokines on macrophage and monocyte functions. However, the studies focusing on polymorphonuclear neutrophils (PMNs) antifungal functions are scarcer. Thus, the objective of the present paper was to assess the capacity of human PMNs to kill virulent P brasiliensis strain in vitro, before and after priming with different cytokines. Moreover, the involvement of oxygen metabolites in this activity was evaluated. Nonactivated cells failed to exhibit antifungal activity. However, when these cells were IFN-gamma, TNF-alpha or GM-CSF activated, a significative fungicidal activity was detected. This process was significantly inhibited when P brasiliensis challenge occurred in presence of catalase (CAT - a scavenger of H2O2) and superoxide dismutase (SOD - a scavenger of superoxide anion). From these results it is concluded that cytokines activation is required for P brasiliensis killing by human PMNs, and that H2O2 and Superoxide anion participate as effectors molecules in this process.

A linearly tunable low-voltage CMOS transconductor with improved common-mode stability and its application to (gm)-C filters

A linearly tunable low-voltage CMOS transconductor featuring a new adaptative-bias mechanism that considerably improves the stability of the processed-signal common,mode voltage over the tuning range, critical for very-low voltage applications, is introduced. It embeds a feedback loop that holds input devices on triode region while boosting the output resistance. Analysis of the integrator frequency response gives an insight into the location of secondary poles and zeros as function of design parameters. A third-order low-pass Cauer filter employing the proposed transconductor was designed and integrated on a 0.8-mum n-well CMOS standard process. For a 1.8-V supply, filter characterization revealed f(p) = 0.93 MHz, f(s) = 1.82 MHz, A(min) = 44.08, dB, and A(max) = 0.64 dB at nominal tuning. Mined by a de voltage V-TUNE, the filter bandwidth was linearly adjusted at a rate of 11.48 kHz/mV over nearly one frequency decade. A maximum 13-mV deviation on the common-mode voltage at the filter output was measured over the interval 25 mV less than or equal to V-TUNE less than or equal to 200 mV. For V-out = 300 mV(pp) and V-TUNE = 100 mV, THD was -55.4 dB. Noise spectral density was 0.84 muV/Hz(1/2) @1 kHz and S/N = 41 dB @ V-out = 300 mV(pp) and 1-MHz bandwidth. Idle power consumption was 1.73 mW @V-TUNE = 100 mV. A tradeoff between dynamic range, bandwidth, power consumption, and chip area has then been achieved.

On designing linearly-tunable ultra-low voltage CMOS gm-C filters

A linearly-tunable ULV transconductor featuring excellent stability of the processed signal common-mode voltage upon tuning, critical for very-low voltage applications, is presented. Its employment to the synthesis of CMOS gm-C high-frequency and voiceband filters is discussed. SPICE data describe the filter characteristics. For a 1.3 V-supply, their nominal passband frequencies are 1.0 MHz and 3.78 KHz, respectively, with tuning rates of 12.52 KHz/mV and 0.16 KHz/m V, input-referred noise spectral density of 1.3 μV/Hz1/2 and 5.0μV/Hz1/2 and standby consumption of 0.87 mW and 11.8 μW. Large-signal distortion given by THD = 1% corresponds to a differential output-swing of 360 mVpp and 480 mVpp, respectively. Common-mode voltage deviation is less than 4 mV over tuning interval.

A Gm-C bump equalizer for low-voltage low-power applications

A low-voltage low-power 2nd-order CMOS pseudo-differential bump-equalizer is presented. Its topology comprises a bandpass section with adjustable center frequency and quality factor, together with a programmable current amplifier. The basic building blocks are triode-operating transconductors, tunable by means of either a DC voltage or a digitally controlled current divider. The bump-equalizer as part of a battery-operated hearing aid device is designed for a 1.4V-supply and a 0.35μm CMOS fabrication process. The circuit performance is supported by a set of simulation results, which indicates a center frequency from 600Hz to 2.4kHz, 1≤Q≤5, and an adjustable gain within ±6dB at center frequency. The filter dynamic range lies around 40dB. Quiescent consumption is kept below 12μW for any configuration of the filter.

Ativação e diferenciação de monócitos humanos com GM-CSF in vitro para aquisição de atividade fungicida contra o Paracoccidioides brasiliensis: papel dos metabólitos do oxigênio e nitrogênio

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)