κ-Opioid Signaling in the Lateral Hypothalamic Area Modulates Nicotine-Induced Negative Energy Balance

Several studies have reported that nicotine, the main bioactive component of tobacco, exerts a marked negative energy balance. Apart from its anorectic action, nicotine also modulates energy expenditure, by regulating brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. These effects are mainly controlled at the central level by modulation of hypothalamic neuropeptide systems and energy sensors, such as AMP-activated protein kinase (AMPK). In this study, we aimed to investigate the kappa opioid receptor (κOR)/dynorphin signaling in the modulation of nicotine’s effects on energy balance. We found that body weight loss after nicotine treatment is associated with a down-regulation of the κOR endogenous ligand dynorphin precursor and with a marked reduction in κOR signaling and the p70 S6 kinase/ribosomal protein S6 (S6K/rpS6) pathway in the lateral hypothalamic area (LHA). The inhibition of these pathways by nicotine was completely blunted in κOR deficient mice, after central pharmacological blockade of κOR, and in rodents where κOR was genetically knocked down specifically in the LHA. Moreover, κOR-mediated nicotine effects on body weight do not depend on orexin. These data unravel a new central regulatory pathway modulating nicotine’s effects on energy balance.     

Tailored-Made Polydopamine Nanoparticles to Induce Ferroptosis in Breast Cancer Cells in Combination with Chemotherapy

Ferroptosis is gaining followers as mechanism of selective killing cancer cells in a non-apoptotic manner, and novel nanosystems capable of inducing this iron-dependent death are being increasingly developed. Among them, polydopamine nanoparticles (PDA NPs) are arousing interest, since they have great capability of chelating iron. In this work, PDA NPs were loaded with Fe³⁺ at different pH values to assess the importance that the pH may have in determining their therapeutic activity and selectivity. In addition, doxorubicin was also loaded to the nanoparticles to achieve a synergist effect. The in vitro assays that were performed with the BT474 and HS5 cell lines showed that, when Fe³⁺ was adsorbed in PDA NPs at pH values close to which Fe(OH)₃ begins to be formed, these nanoparticles had greater antitumor activity and selectivity despite having chelated a smaller amount of Fe³⁺. Otherwise, it was demonstrated that Fe³⁺ could be released in the late endo/lysosomes thanks to their acidic pH and their Ca²⁺ content, and that when Fe³⁺ was co-transported with doxorubicin, the therapeutic activity of PDA NPs was enhanced. Thus, reported PDA NPs loaded with both Fe³⁺ and doxorubicin may constitute a good approach to target breast tumors.     

Influence of Different Additives on the Interaction of Quinolone Antibiotic Drug with Surfactant: Conductivity and Cloud Point Measurement Study

Conductometric and cloud point (CP) measurement studies have been performed to investigate the interaction of tetradecyltrimethylammonium bromide (TTAB) and Triton® X-100 (TX-100) with ciprofloxacin hydrochloride (CFH) in different solvents over the temperature range of 295.15–315.15 K. CFH is used for the treatment of various bacterial infections. The observed critical micelle concentration (CMC) values of TTAB were found to be reduced in the presence of electrolytes (Na₂SO₄/Na₃PO₄), and this reduction proceeds with the elevation of salt concentration. The order of the CMC of TTAB follows the trend: > >. The observed CMC values of TTAB were found to increase with increasing temperature and decrease with increasing concentration of CFH in aqueous medium. The values of Gibbs free energy of micellization () for the TTAB/TTAB + CFH mixture were found to be negative, implying spontaneous micellization. The estimated CP of TX-100 decreases with increasing concentration of TX-100 in aqueous medium. The CP values first decrease with increasing concentration of CFH and then increase at higher concentration of CFH almost in all cases investigated. The values of free energy of clouding were found to be positive in all cases studied implying that phase separation of TX-100 was nonspontaneous. The other thermodynamic parameters associated with the micellization of TTAB and the phase separation of TX-100 were estimated and explained.     

Control strategies for reactive batch distillation

A batch reactor may be combined directly with a distillation column by distilling off the light component product in order to increase the reactor temperature or to improve the product yield of an equilibrium reaction. The same amount of the light product should be removed as the amount being formed by the reaction at any time. A linearized model has been developed which describes the process behaviour satisfactorily for control analysis purposes. The controllability of a combined batch reactor/batch distillation column is found to depend strongly on the operating conditions and on the time during the run. In general, controlling only the reactor temperature (one-point bottom control) is difficult since the set-point has to be specified below a maximum value in order to avoid break-through of an intermediate component in the ditillate. This maximum value may be difficult to know a priori. For the example considered in this study, control of both reactor temperature and distillate composition (two-point control) is also found to be difficult due to large interactions in the column. As with one-point bottom control, the reactor temperature has to be specified below a maximum value. However, energy can be saved since the heat duty can be decreased with time. Controlling the temperature on a tray in the column (one-point column control) is found to give good performance for the given process with no loss of reactant and a high reactor temperature, although no direct control of the reactor temperature is obtained.     

A new method for manufacturing nanostructured electrodes on glass substrates

The present paper describes a new method for manufacturing a nanostructured porous layer of TiO₂ on a conducting glass substrate for use in a dye-sensitized photoelectrochemical cell. The method involves deposition of a layer of semiconductor particles onto a conducting substrate and compression of the particle layer to form a mechanically stable, electrically conducting, and porous nanostructured film at room temperature. Photoelectrochemical characteristics and morphology of the resulting nanostructured films are presented. The potential use of the new manufacturing method in the future applications of nanostructured systems is discussed.     

Long-term effect of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy

The aim of our study was to evaluate whether inhibition of ACE (lisinopril 10-20 mg/day) can reduce the rate of decline in kidney function more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg/day), usually in combination with a diuretic. We performed a prospective, randomized, parallel study for 42 months, double blind for the first 12 months and single blind thereafter. Forty-three (21 lisinopril and 22 atenolol) hypertensive NIDDM patients with diabetic nephropathy were enrolled. Data from 36 patients (17 lisinopril and 19 atenolol, 60 +/- 7 years of age, 27 men) who completed at least 12 months of the study period are presented. At baseline, the two groups were comparable: glomerular filtration rate (51Cr-EDTA plasma clearance) was 75 +/- 6 and 74 +/- 8 ml x min(-1) x 1.73 m(-2), mean 24-h ambulatory blood pressure (A&D TM2420) was 110 +/- 3 and 114 +/- 2 mmHg, and 24-h urinary albumin excretion rate was 961 (range 331-5,727) and 1,578 (476-5,806) mg/24 h in the lisinopril and atenolol groups, respectively. The mean follow-up time was similar, 37 and 35 months in the lisinopril and atenolol groups, respectively. Mean ambulatory blood pressure was equally reduced in the two groups, 12 +/- 2 and 10 +/- 2 mmHg in the lisinopril and atenolol groups, respectively. Glomerular filtration rate declined in a biphasic manner with a faster initial (0 to 6 months) change of 1.25 +/- 0.49 and 0.81 +/- 0.29 ml x min(-1) x month(-1) followed by a slower sustained decline (6 to 42 months) of 0.59 +/- 0.10 and 0.54 +/- 0.13 ml x min(-1) x month(-1) in the lisinopril and atenolol groups, respectively. No significant differences were observed in either initial or sustained decline in glomerular filtration rate between the two groups. Urinary albumin excretion was reduced (% reduction of baseline) more in the lisinopril than in the atenolol group, at 55 (95% CI 29-72) and 15% (-13 to 34), respectively (P = 0.01). In conclusion, the relentless decline in kidney function characteristically found in hypertensive NIDDM patients with diabetic nephropathy can be reduced equally effectively by two antihypertensive treatments, the beta-blocker atenolol and the ACE inhibitor lisinopril.