Pancreatic cancer (PC) frequency and incidence have grown rapidly in recent years. One of the most serious problems with PC is the existence of asymptotic manifestations, which frequently delays early detection, and until the diagnosis is established, tumor cells progress to the metastatic stage. Another significant concern with PC is the scarcity of well-defined pharmacotherapeutic drugs. The aim of this study was to develop an efficient nanocarrier system to augment the efficacy of raloxifene (RLX) against PC cells. As a result, the current investigation was carried out in order to give an effective treatment method, in which an optimum RLX loaded phospholipid-based vesicles with melittin (PL-MEL) was chosen using experimental design software, with particle size, zeta potential and entrapment efficiency % as dependent variables. Furthermore, anticancer activity against PANC1 cells was assessed. The optimized nanovesicle parameters were 172.5 nm for the measured size, zeta potential of -0.69 mV, and entrapment efficiency of 76.91% that were in good agreement with the expected ones. RLX-raw, plain formula, and optimized RLX-PL-MEL showed IC concentrations of 26.07 ± 0.98, 9.166 ± 0.34, and 1.24 ± 0.05 µg/mL, respectively. Furthermore, cell cycle analysis revealed that the nanovesicle was most effective in the G2-M phase, whereas Bax, and Bcl-2 estimates revealed that optimized RLX formula had the highest apoptotic activity among treatments investigated. However, as compared to RLX alone or plain formula alone, the optimized formula demonstrated higher expression of TNFα and Bax while a significant reduction of Bcl-2 and NF-κB expression was observed. mitochondrial membrane potential (MMP) analysis confirmed the apoptosis as well as the anticancer effect of the optimized formula. Thus, the present study results showed an improvement in the anti-PC effects of the RLX with phospholipid conjugated melittin, making it a novel treatment approach against PC.

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Interest in decimal arithmetic increased considerably in recent years. This paper presents new designs for decimal floating point (DFP) addition, multiplication, fused multiply-add, division, and square root. It stresses the importance of energy savings achieved by hardware implementations of the IEEE standard for decimal floating point. To the best of the authors knowledge, this is the first work to discuss energy savings in DFP and the first to present a hardware implementation of a fused multiply-add. Our Newton-Raphson based divider is over three times faster than the similar design previously reported.

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Haloperidol (Hal) is a well-known typical antipsychotic. Hepatic first pass metabolism leads to its limited oral bioavailability. This study aimed at enhancing transdermal delivery of Hal via spanlastic formulae. Hal-loaded spanlastics of Span®60 and an edge activator (EA) were successfully prepared by ethanol injection method according to a 3.4 full factorial design. In this design, independent variables were X, EA type, and X, Span®60 to EA ratio. Y, percentage entrapment efficiency (EE%); Y, particle size (PS); Y, deformability index (DI); and Y, percentage drug released after 4h (Q4h), were chosen as dependent variables. The Fourier-transform infrared spectral analysis showed no considerable chemical interaction between Hal and the used excipients. Both factors affected significantly all the responses except DI. Desirability of each prepared formula was calculated based on maximizing EE% and Q4h and minimizing PS. Formula F6, with X, Tween®80, and X, 8:2, had the highest desirability value followed by F7, with X, Tween®80, and X, 6:4, and both were chosen as selected formulae (SF) for further investigation. F6 (having more entrapped Hal), F7 (of smaller PS), and Hal solution in propylene glycol were subjected to ex vivo permeation test through newborn rat skin. Both formulae showed marked enhancement in drug permeation compared with drug solution. The significantly higher Q and J of F7 from F6 may indicate that the smaller particle size aided more than higher entrapment in achieving a higher permeation for Hal of 3.5±0.2μg/cm.h. These results are promising for further investigation of this formula.

BACKGROUND: Hyperhomocysteinemia, vitamin B12 and folate deficiency have been linked to cognitive dysfunction in multiple sclerosis (MS) patients.

OBJECTIVE: This study aimed to investigate the relation of serum homocysteine (Hcy), vitamin B12 and folate to cognitive functions in MS patients.

SUBJECTS AND METHODS: Forty-five MS patients and twenty matched healthy controls were included. Subjects were submitted to cognitive assessment using a selected psychometric battery and measurement of serum levels of homocysteine, B12 and folic acid.

RESULTS: MS patients showed significant worse performance in cognitive scales compared to controls (P  ≤ 0.05). Serum homocysteine, vitamin B12 and folate showed no significant difference between patients and controls (P  > 0.05). Serum homocysteine was negatively correlated with total score of Addenbrooke's Cognitive Examination (ACE), paced auditory serial addition test and controlled oral word association test scores. Serum vitamin B12 was positively correlated with ACE language, visuospatial and total scores and negatively correlated with trail making B score. Serum folate was significantly positively correlated with ACE language and total scores. Homocysteine was the only significant predictor for cognitive impairment in MS patients.

CONCLUSION: Serum homocysteine may play a role in cognitive dysfunction in MS patients.