Motivation for physical activity in the Jordanian military: Possible determinants of physical activity in male and female recruits.

Given the obligatory nature of physical fitness training in the military and in order to guide intervention development, our study assessed possible motivational determinants as suggested by self-determination theory in addition to other possible determinants. A cross-sectional study was conducted among 218 military recruits during their basic training in Jordan. Physical activity and lifestyle behaviors were measured using the Arab Teens Lifestyle Study (ATLS). Psychosocial variables were assessed using the Exercise Self-Efficacy Scale (ESE), Behavioral Regulation Exercise Scale (BREQ-2) and Exercise Benefits/Barriers Scale (EBBS). Bivariate correlation analysis revealed that identified self-regulation, introjected regulation and exercise self-efficacy scores were positively associated with higher Metabolic Equivalent of Task (METs) and minutes per week of physical activity among male recruits and the overall sample respectively. Among females, only external regulation was positively associated with the total METs/week. Being a male was significantly associated with higher minutes of physical activity among the overall sample. Multivariate regression analyses showed that identified regulation was significantly and positively associated with higher minutes of physical activity among the overall sample and male recruits in addition to higher METs per week among the male recruits. Also, the amotivation score was significantly and positively associated with higher minutes of physical activity among the overall sample and male recruits. A multivariate regression analysis for female recruits showed no significant associations. Intervention developers are advised to increase autonomous forms of motivation through structured enjoyable physical fitness programs in order to enhance intrinsic motivation in the long term.

Correlates of Dietary Behaviors Among Young Emirati Males Completing Compulsory Military Service.

INTRODUCTION: It is important to understand the correlates of different dietary behaviors in a military context in the United Arab Emirates (UAE) to guide intervention development to prevent and treat obesity as it has a significant impact at the country and regional level. This study aimed to assess different dietary behaviors and their association with potential correlates including age, marital status, educational level, smoking status, screen time, dietary knowledge, eating self-efficacy, and general self-efficacy. MATERIALS AND METHODS: The study used a cross-sectional design and included 153 (M = 25.9 years, SD = ± 3.2) military recruits completing their basic training at a single military camp in the UAE. Dietary behaviors of these recruits were measured using the Arab Teens Lifestyle Study. Other potential correlates included dietary knowledge, general self-efficacy, and eating efficacy. The ethical approval was obtained from the research ethics committee in the UAE university. RESULTS: Daily intake of fruits, vegetables, and breakfast was reported by 14.4%, 25.5%, and 22.9% of the military recruits, respectively. Almost half of the recruits (46.4%) consumed sugar-sweetened drinks more than 3 times a week, 39.2% consumed fast food more than 3 times a week, and 37.3% consumed sweets/chocolates more than 3 times a week. Bivariate regression analyses revealed that eating self-efficacy was positively associated with breakfast and dairy food consumption, although it was inversely associated with sugar, fast-food, and French fries intake. Age was significantly and inversely associated with sugar, fast-food, and energy drink intake. Moreover, nutrition knowledge was significantly and positively correlated with vegetable intake and negatively correlated with energy drink consumption. Multiple regressions showed that lower age and lower eating self-efficacy were found to be the main predictors for sugar-sweetened drinks (adjusted R2 = 0.112) and fast-food intake (adjusted R2 = 0.084). Also, a higher dietary knowledge score was a predictor of vegetable intake (adjusted R2 = 0.093), although age and smoking predict energy drink intake (adjusted R2 = 0.225). CONCLUSIONS: The results show that unhealthy eating patterns are common among new recruits in the UAE military. The study suggests that age, eating self-efficacy, and nutrition knowledge are the main correlates of selected dietary behaviors. Interventions are advised to target these correlates to achieve healthier dietary habits inside the military.

Modelling and Optimization for Mortar Compressive Strength Incorporating Heat-Treated Fly Oil Shale Ash as an Effective Supplementary Cementitious Material Using Response Surface Methodology.

Fly oil shale ash (FOSA) is a waste material known for its pozzolanic activity. This study intends to investigate the optimum thermal treatment conditions to use FOSA efficiently as a cement replacement material. FOSA samples were burned in an electric oven for 2, 4, and 6 h at temperatures ranging from 550 °C to 1000 °C with 150 °C intervals. A total of 333 specimens out of 37 different mixes were prepared and tested with cement replacement ratios between 10% and 30%. The investigated properties included the mineralogical characteristics, chemical elemental analysis, compressive strength, and strength activity index for mortar samples. The findings show that the content of SiO2 + Al2O3 + Fe2O3 was less than 70% in all samples. The strength activity index of the raw FOSA at 56 days exceeded 75%. Among all specimens, the calcined samples for 2 h demonstrated the highest pozzolanic activity and compressive strength with a 75% strength activity index. The model developed by RSM is suitable for the interpretation of FOSA in the cementitious matrix with high degrees of correlation above 85%. The optimal compressive strength was achieved at a 30% replacement level, a temperature of 700 °C for 2 h, and after 56 days of curing.

Development of Self-Emulsifying Drug Delivery Systems (SEDDSs) Displaying Enhanced Permeation of the Intestinal Mucus Following Sustained Release of Prototype Thiol-Based Mucolytic Agent Load.

In this study, mucoactive self-emulsifying drug delivery systems (SEDDSs) based on sustained release of N-acetylcysteine (NAC) were developed for providing effective intestinal mucopermeation. Polymeric ionic complexes of NAC were formed with polyethyleneimine (PEI), Eudragit E 100, and Eudragit RS 100 and loaded into a novel SEDDS. The SEDDSs exhibited a stable average size of 75 ± 12 nm (polydispersity index (PDI) < 0.3) and showed a rise in the zeta potential from −17.31 mV to −7.72 mV. On Caco-2 cells, SEDDSs at 1−3% were non-cytotoxic. An average of 91.8 ± 5.4% NAC was released from SEDDSs containing Eudragit E 100 (p ≤ 0.05) and Eudragit RS 100 (p ≤ 0.001) complexes at a significantly slower rate within 80 min, whereas the SEDDS containing PEI released NAC in a matter of seconds. Similarly, the SEDDS complexes revealed a time-dependent reduction in mucus dynamic viscosity of 52.6 ± 19.9%. Consequently, as compared with a blank SEDDS, mucodiffusion revealed about 2- and 1.8-fold significantly greater mucopermeation of SEDDSs anchoring Eudragit E 100−NAC and RS 100−NAC complexes (p ≤ 0.05), respectively. The mucoactive SEDDSs, which steadily released NAC while permeating the mucus, were linked to a significantly increased mucopermeation in vitro as a result of optimal mucolytic targeting.

Development of Fluorescently Labeled Self-Emulsifying Drug Delivery Systems (SEDDS) for Prolonged Stability, In Vitro Sustained Release, and Cellular Uptake.

AIMS: In this study, four fluorescein hydrophobic ionic complexes were formed with the cationic polymers Eudragit RS, Eudragit RL, Eudragit E, and polyethyleneimine (PEI) to provide fluorescein sustained release, sustained cellular uptake, and stability. METHODS: Complexes were loaded in a self-emulsifying drug delivery system (SEDDS) composed of 40% Tween 80, 20% Kolliphor EL, 15% 2-n-Octyl-1-dodecanol, and 25% dipropylene glycol. SEDDS were investigated regarding their size, polydispersity index (PDI), zeta potential, and cytotoxicity. Fluorescein release from SEDDS was performed in phosphate buffer (pH 6.8 and pH 8), and the released fluorescein was evaluated for cellular uptake. Moreover, fluorescein from all of the SEDDS pre-concentrates was released at different time points to check its long-term stability over six months. RESULTS: The average fluorescein load in SEDDS was 0.045%. SEDDS showed an average droplet size of 24.9 ± 1.6 nm with PDI ≤ 0.3. SEDDS complexes diluted 1:100 increased the zeta potential from -7.3 mV to +3.7 mV and provided > 85% cell viability. A 92.27 ± 3.18% fluorescein exhibited a few seconds of immediate release when used as control or PEI complex in SEDDS. On the contrary, Eudragit-fluorescein complexes in SEDDS showed sustained release of 87.01 ± 5.22% fluorescein in ≤ 70 min with 22.19 ± 14.56% and 59.27 ± 16.57% released at 10 min in pH 6.8 and pH 8 release media, respectively. Comparatively, the medium at pH 6.8 maintained a significantly improved sustained fluorescein release (p ≤ 0.001). Furthermore, Eudragit RS/RL compared to Eudragit E, significantly exhibited a slower fluorescein release rate from SEDDS (p ≤ 0.01). The cellular uptake of the released fluorescein was 72.4 ± 8.2% for all SEDDS complexes after 3 h. Eudragit complexes compared to PEI complex in SEDDS significantly showed m ore sustained fluorescein cellular uptake at 1 h and 2 h (p ≤ 0.001). However, SEDDS complexes showed the longest fluorescein stability with PEI after six months, whereas fluorescein stability for SEDDS containing fluorescein as Eudragit complex and control showed 39.1% and 82.5% fluorescence decrease, respectively, after three months. CONCLUSION: In the developed SEDDS, the presence of hydrophobic ionic complexes can significantly promote longer stability and sustained cellular uptake of fluorescein while releasing in a sustained manner.

Dual-Acting Zeta-Potential-Changing Micelles for Optimal Mucus Diffusion and Enhanced Cellular Uptake after Oral Delivery.

CONTEXT: Overcoming the intestinal mucosal barrier can be a challenge in drug delivery. Nanoemulsions with negative zeta potentials can effectively permeate the mucus layer, but those with positive zeta potentials are better taken up by cells; a nanoemulsion with capricious zeta potential from negative to positive can achieve both good permeation and high uptake. OBJECTIVE: This study aimed to develop dual-acting zeta-potential-amphoteric micelles enabling optimal muco-permeation and enhancement of cellular uptake. METHODS: A micellar pre-concentrate was prepared from 15% Labrasol, 15% Kolliphor EL, 30% Kolliphor RH 40, and 40% dimethylsulfoxide. The micellar pre-concentrate was loaded with anionic stearic acid (SA), forming ionic complexes with cationic polymers at a ratio of 25:1 with Eudragit RS 100 and Eudragit RL 100. Blank micelles and those containing complexes were separately diluted in physiological buffers and examined for their droplet sizes, polydispersity indices (PDIs), zeta potentials, and cytotoxicity. The SA release from the micellar complexes was evaluated in 0.1 mM phosphate buffer (pH 6.8) containing 0.001% fluorescein, thereby enabling an instant decrease in fluorescence. Finally, the micelles were loaded with the model drug fluorescein diacetate (FDA) and evaluated for their muco-permeation behavior and cellular uptake. RESULTS: The micellar dilutions formed micelles at the critical micelle concentration (CMC) of 312 µg/mL and showed a uniform average droplet size of 14.2 nm, with a PDI < 0.1. Micellar dilutions were non-cytotoxic when used at 1:100 in a physiological medium. Micelles loaded with ionic complexes achieved a sustained release of 95.5 ± 3.7% of the SA in 180 min. Moreover, the zeta potential of the complex-loaded micelles shifted from -5.4 to +1.8 mV, whereas the blank micelles showed a stabilized zeta potential of -10 mV. Furthermore, the negatively charged blank and complex-loaded micelles exhibited comparable muco-permeation, with an overall average of 58.2 ± 3.7% diffusion of FDA. The complex-loaded micellar droplets, however, provided a significantly higher cellular uptake of the model drug FDA (2.2-fold, p ≤ 0.01) Conclusion: Due to undergoing a shift in zeta potential, the modified micelles significantly enhanced cellular uptake while preserving mucus-permeating properties.

Occupational burnout and job satisfaction among physicians in times of COVID-19 crisis: a convergent parallel mixed-method study.

BACKGROUND: Healthcare professionals including physicians were subjected to an increased workload during the COVID-19 crisis, leaving them exposed to significant physical and psychological distress. Therefore, our present study aimed to (i) assess the prevalence of burnout and levels of job satisfaction among physicians in Jordan, and (ii) explore physicians' opinions, experiences, and perceptions during the pandemic crisis. METHODS: This was a mixed-method study that utilized a structured web-based questionnaire and semi-structured individual interviews. The 10-Item Burnout Measure-Short version (BMS), and the 5-Item Short Index of Job Satisfaction (SIJS) were adopted to assess occupational burnout and job satisfaction, respectively. Semi-structured interviews were conducted, based on a conceptual framework that was developed from Herzberg's Two-Factor Theory of Motivation and Job Demands-Resources Model. Descriptive statistics and regression models, as well as inductive thematic analysis, were used to analyze quantitative and qualitative data, respectively. RESULTS: A total of 973 survey responses and 11 interviews were included in our analysis. The prevalence of burnout among physicians was (57.7%). Several significant factors were positively associated with burnout, including female gender, working at highly loaded hospitals, working for long hours, doing night shifts, lack of sufficient access to personal protective equipment, and being positively tested for SARS-CoV-2. Regarding job satisfaction, regression analysis revealed that age was positively associated with higher levels of job satisfaction. On contrary, being a general practitioner or specialist, working at highly loaded hospitals, low salaries, and suffering from burnout have predicted lower levels of job satisfaction. Besides, four themes have emerged from the thematic analysis: (i) Work-induced psychological distress during the pandemic, (ii) Decision-driven satisfactory and dissatisfactory experiences, (iii) Impact of the pandemic on doctor-patient communication and professional skills, and (iv) Economic impacts of the pandemic crisis and lockdown. CONCLUSION: A significant physical and psychological burden was associated with the COVID-19 pandemic. Reliable efforts should be implemented aiming at protecting physicians' physical and mental wellbeing, enhancing their working conditions, and raising awareness about burnout. Evidence-based decisions and proper utilization of financial and human resources at institutional and national levels are believed to be crucial for the sustainability of the health workforce, especially in crises.

The Impact of the COVID-19 Pandemic and Emergency Distance Teaching on the Psychological Status of University Teachers: A Cross-Sectional Study in Jordan.

The COVID-19 pandemic has struck many countries globally. Jordan has implemented strict nationwide control measures to halt the viral spread, one of which was the closure of universities and shifting to remote teaching. The impact of this pandemic could extend beyond the risk of physical harm to substantial psychological consequences. Our study aimed at assessing 1) psychological status, 2) challenges of distance teaching, and 3) coping activities and pandemic-related concerns among university teachers in Jordan in the midst of COVID-19-related quarantine and control measures. We conducted a cross-sectional study using an anonymous online survey. The measure of psychological distress was obtained using a validated Arabic version of the Kessler Distress Scale (K10). Other information collected included sociodemographic profile, methods used to handle distress, motivation to participate in distance teaching, and challenges of distance teaching as well as the most worrisome issues during this pandemic. Three hundred eighty-two university teachers returned completed surveys. Results of K10 showed that 31.4% of respondents had severe distress and 38.2% had mild to moderate distress. Whereas gender was not associated with distress severity, age had a weak negative correlation (Rho = -0.19, P < 0.0001). Interestingly, most teachers had moderate to high motivation for distance teaching. Engagement with family was the most reported self-coping activity. More than half of the participants were most concerned and fearful about SARS-CoV-2 infection. In conclusion, university teachers have shown to exhibit various levels of psychological distress and challenges during the implementation of precautionary national measures in the battle against COVID-19 in Jordan.

Self-Emulsifying Drug Delivery Systems: Hydrophobic Drug Polymer Complexes Provide a Sustained Release in Vitro.

The aim of this study was to develop hydrophobic ionic drug polymer complexes in order to provide sustained drug release from self-emulsifying drug delivery systems (SEDDS). Captopril (CTL) was used as an anionic model drug to form ionic complexes with the cationic polymers Eudragit RS, RL, and E. Complexes of polymer to CTL charge ratio 1:1, 2:1, and 4:1 were incorporated in two SEDDS, namely FA which was 40% Kolliphor RH 40, 20% Kolliphor EL, and 40% castor oil and FB, which was 40% Kolliphor RH 40, 30% glycerol, 15% Kolliphor EL, and 15% castor oil. Blank and complex loaded SEDDS were characterized regarding their droplet size, polydispersity index (PDI), and zeta potential. Resazurin assay was performed on Caco-2 cells to evaluate the biocompatibility of SEDDS. Release of CTL from SEDDS was determined in release medium containing 0.2 mg/mL of 5,5'-dithiobis(2-nitrobenzoic acid) (DNTB) allowing quantification of free drug released into solution via a thiol/disulfide exchange reaction between CTL and DNTB forming a yellow dye. The droplet size of SEDDS FA and SEDDS FB were in the range of 100 ± 20 nm and 40 ± 10 nm, respectively, with a PDI < 0.5. The zeta potential of SEDDS FA and SEDDS FB increased after the incorporation of complexes. Cell viability remained above 80% after incubation with SEDDS FA and SEDDS FB in a concentration of 1% and 3% for 4 h. Without any polymer, CTL was entirely released from both SEDDS within seconds. In contrast, the higher the cationic lipophilic polymer to CTL ratio in SEDDS, the more sustained was the release of CTL. Among the polymers which were evaluated, Eudragit RL provided the most sustained release. SEDDS FA containing Eudragit RL and CTL in a ratio of 1:1 released 64.78 ± 8.28% of CTL, whereas SEDDS FB containing the same complex showed a release of 91.85 ± 1.17% within 1 h. Due to the formation of lipophilic ionic polymer complexes a sustained drug release from oily droplets formed by SEDDS can be achieved. Taking into account that drugs are otherwise instantly released from SEDDS, results of this study might open the door for numerous additional applications of SEDDS for which a sustained drug release is essential.

Dietary, physical activity, and weight management interventions among active-duty military personnel: a systematic review.

BACKGROUND: Research has been conducted to assess the effectiveness of weight management, dietary and physical activity interventions in military settings. However, a recent and comprehensive overview is lacking. The aim of this systematic review is to examine the evidence and describe key components of effective interventions in terms of improving body composition, dietary behaviors, and physical activity among active-duty military personnel. METHODS: PubMed, PsycInfo, and CINAHL were searched on the 17th of November 2017 to identify interventions that promoted diet and/or physical activity among active-duty military personnel. Studies were included if they assessed outcomes related to anthropometric measurements, dietary behaviors, or fitness/physical activity levels. There were no restrictions regarding publication date, follow-up duration, and sex. After screening, a total of 136 studies were eligible. Of these studies, 38 included an educational and/or behavioral change component, and 98 had only physical or fitness training as part of basic military training. Only studies that included an educational and/or behavioral change component were assessed for quality using the Effective Public Health Practice Project tool and included in the qualitative synthesis of the results. RESULTS: Based on consistent evidence from studies that were rated as moderate or strong, there is good evidence that military weight management interventions are effective in improving body composition for durations of up to 12 months. Effective interventions are more likely to be high intensity (have a greater number of sessions), are more often delivered by specialists, and use theoretical base/behavioral change techniques and a standardized guideline. Dietary interventions can potentially reduce total fat and saturated fat intake. Dietary interventions that target the kitchen staff and/or increase the availability of healthy food are more likely to be effective in the short term. The results regarding military physical fitness interventions were inconclusive. CONCLUSION: Despite limitations such as the diversity and heterogeneity of the included interventions, outcome measurements, and follow-up duration, this systematic review found good evidence that weight management interventions are effective, especially in terms of weight loss. More studies are needed to acquire solid evidence for effectiveness for durations longer than 12 months and to identify key components of the effective dietary and physical activity educational and/or behavioral change interventions, especially in countries outside Europe and the US.

Intranasal drug delivery of olanzapine-loaded chitosan nanoparticles.

The aim of this study was to investigate olanzapine (OZ) systemic absolute bioavailability after intranasal (i.n.) administration in vivo to conscious rabbits. Furthermore, the study investigated the potential use of chitosan nanoparticles as a delivery system to enhance the systemic bioavailability of olanzapine following intranasal administration. Olanzapine-loaded chitosan nanoparticles were prepared through ionotropic gelation of chitosan with tripolyphosphate anions and studied in terms of their size, drug loading, and in vitro release. The OZ nanoparticles were administered i.n. to rabbits, and OZ plasma concentration at predetermined time points was compared to i.n. administration of OZ in solution. The concentrations of OZ in plasma were analyzed by ultra performance liquid chromatography mass spectroscopy (UPLC/MS). OZ-loaded chitosan nanoparticles significantly (p < 0.05) enhanced systemic absorption with 51 ± 11.2% absolute bioavailability as compared to 28 ± 6.7% after i.n. administration of OZ solution. The results of the present study suggest that intranasal administration of OZ-loaded chitosan nanoparticles formulation could be an attractive modality for delivery of OZ systemically.

Prevalence and risk factors of muscle complications secondary to statins.

INTRODUCTION: The aim of the study was to investigate the prevalence and risk factors of muscle complications among patients using statins. METHODS: We conducted a prospective comparative study on 345 patients receiving statins and compared the findings with an age- and gender-matched control group of 85 subjects. Univariate and multivariate analyses with logistic regression models were used to study the association of different patient and disease characteristics with muscle complications. RESULTS: Adverse reactions were reported by 21% of patients and 5.9% of controls (P = 0.0013). Objective weakness was found in 15% of the patients who reported muscle symptoms (3.2% of the total cohort), but not in controls. Older age, longer duration of statin use, diabetes, stroke, and lower body mass index were associated with increased risk of developing these symptoms. CONCLUSIONS: Adverse reactions to statins may be more common than previously reported, and they may be affected by specific patient and disease characteristics.

Bioavailability of Δ9-tetrahydrocannabinol following intranasal administration of a mucoadhesive gel spray delivery system in conscious rabbits.

BACKGROUND: The purpose of this study was to investigate the potential of the intranasal route for systemic delivery of solubilized Δ9-tetrahydrocannabinol (THC). A further aim was to investigate the effect of nasally administered chitosan-based nasal bioadhesive gel on THC bioavailability as a formulation strategy to decrease normal mucociliary drug clearance. METHOD: The THC formulations were administered intranasally and compared to intravenous administration utilizing conscious rabbits. RESULTS: After nasal administration, the THC nasal solution afforded a C(max) value of 20 ± 3 ng/mL at 20 minutes. Interestingly, the THC loaded in chitosan gel formulation followed almost the same profile at early time points and subsequently afforded a higher C(max) value of 31 ± 4 ng/mL (T(max) = 45 minutes). The absolute bioavailability of THC after nasal delivery was studied to compare plasma THC concentrations after nasal administration with those after intravenous injection. Absolute bioavailability values were 13.3 ± 7.8% and 15.4 ± 6.5% for the THC nasal solution and gel formulations, respectively. CONCLUSION: The results of the present study suggest that intranasal administration of THC in solution or in a chitosan-based nasal gel formulation could be an attractive modality for delivery of THC systemically.

Intranasal drug delivery of didanosine-loaded chitosan nanoparticles for brain targeting; an attractive route against infections caused by AIDS viruses.

The primary aim of this study was to investigate intranasal (i.n.) administration as a potential route to enhance systemic and brain delivery of didanosine (ddI). A further aim was to investigate the potential use of chitosan nanoparticles as a delivery system to enhance the systemic and brain targeting efficiency of ddI following i.n. administration. Didanosine-loaded chitosan nanoparticles, were prepared through ionotropic gelation of chitosan with tripolyphosphonate anions, and characterized in terms of their size, drug loading, and in vitro release. The nanoparticles were administered i.n. to rats, compared to i.n. and intravenous (i.v.) administration of ddI in solution. The concentrations of ddI in blood, CSF, and brain tissues were analyzed by ultra performance liquid chromatography mass spectroscopy (UPLC/MS). The brain/plasma, olfactory bulb/plasma and CSF/plasma concentration ratios were significantly higher (P < 0.05) after i.n. administration of ddI nanoparticles or solution than those after i.v. administration of didanosine aqueous solution. The ratio of ddI concentration values of the nanoparticles to the solution at 180 min post-i.n. dosing was 2.1 and 1.9 in CSF and brain, respectively. Thus, both the i.n. route of administration and formulation of ddI in chitosan nanoparticles increased delivery of ddI to CSF and brain.

Intratumoral delivery of Paclitaxel in solid tumor from biodegradable hyaluronan nanoparticle formulations.

In the current study, novel paclitaxel-loaded cross-linked hyaluronan nanoparticles were engineered for the local delivery of paclitaxel as a prototype drug for cancer therapy. The nanoparticles were prepared using a desolvation method with polymer cross-linking. In vitro cytotoxicity studies demonstrated that less than 75% of the MDA-MB-231 and ZR-75-1 breast cancer cells were viable after 2-day exposure to paclitaxel-loaded hyaluronan nanoparticles or free paclitaxel, regardless of the dose. These results suggest that hyaluronan nanoparticles maintain the pharmacological activity of paclitaxel and efficiently deliver it to the cells. Furthermore, in vivo administration of the drug-loaded nanoparticles via direct intratumoral injection to 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor in female rats was studied. The paclitaxel-loaded nanoparticles treated group showed effective inhibition of tumor growth in all treated rats. Interestingly, there was one case of complete remission of tumor nodule and two cases of persistent reduction of tumor size that was observed on subsequent days. In the case of free paclitaxel-treated group, the mean tumor volume increased almost linearly (R(2) = 0.93) with time to a size that was 4.9-fold larger than the baseline volume at 57 days post-drug administration. Intratumoral administration of paclitaxel-loaded hyaluronan nanoparticles could be a promising treatment modality for solid mammary tumors.

Nicotine exposure can be detected in cerebrospinal fluid of active and passive smokers.

A simple, rapid and sensitive liquid chromatography/mass spectrometry (LC/MS) method has been utilized for the quantitative determination of nicotine and its major metabolite cotinine (COT) in human cerebrospinal fluid (CSF) of active and passive smokers. CSF samples from 18 smokers, 15 non-smokers, 15 children, 15 infants, and 9 neonatal were analyzed for nicotine (NIC) and cotinine content. Cotinine levels in the CSF of smokers ranged from 27.3 to 457.1 ng/ml, whereas nicotine levels were considerably lower (6.0-215.1 ng/ml). Cotinine could be detected in 4 of the 15 CSF samples from non-smokers (3.5-30.4 ng/ml), and a few other passive smokers, including neonates from smoking mothers (15.6-81.1 ng/ml). The concentrations of cotinine in CSF samples suggests that nicotine easily passes into the CSF, which makes it an excellent CSF marker for tobacco-smoke exposure.

An HPLC method for the simultaneous determination of neurotoxic dipyridyl isomers in human plasma.

Several studies on dipyridyl isomers have suggested that they are neurotoxic and that chronic exposure to these compounds could be a potential human health hazard. A reversed phase HPLC method was developed for the simultaneous quantitation of 2,2'-dipyridyl and its four positional isomers, 2,3'-, 2,4'-, 3,4'- and 4,4'-dipyridyl in human plasma. Plasma samples were basified, extracted with 1-chlorobutane, evaporated, the residue reconstituted in mobile phase, and an aliquot part was analyzed by HPLC. Chromatographic separations were performed on a C(18) reversed phase Sunfire column eluted with a mobile phase composed of potassium phosphate (pH 3.5; 25 mM)-acetonitrile (80:20, v/v). Isomers were separated with good resolution, and quantification was determined utilizing an internal standard of quinoxaline. The method has been validated over a range from 30 to 2000 ng/ml with correlation coefficients higher than 0.995. Extraction recoveries for the dipyridyl isomers averaged from 65 to 92%. Limit of detection and limit of quantitation for the dipyridyl isomers ranged from 15 to 70 ng/ml and 30 to 90 ng/ml, respectively. The inter- and intra-day variation did not exceed 7% with an accuracy range of 96-102%. The described analytical method was successfully utilized for the determination of dipyridyl isomers in human plasma and suggested the need for more routine monitoring of tobacco smokers and other individuals who are involuntarily exposed to environmental source of dipyridyl isomers.

Scopolamine sublingual spray: an alternative route of delivery for the treatment of motion sickness.

The purpose of this study was to develop a sublingual drug delivery spray formulation of scopolamine hydrobromide (L-(-)-hyoscine hydrobromide) and to determine the absolute bioavailability of scopolamine hydrobromide following sublingual delivery and to investigate the effect of a bioadhesive on the pharmacokinetic parameters of this drug in a rabbit model. Rabbits received a single scopolamine free base equivalent sublingual dose of 100 microg/kg and this was compared to intravenous administration of the drug. Blood samples were collected at different time points, and plasma scopolamine concentrations were determined using a new sensitive and specific LC/MS analytical method which utilized electrospray ionization detection. The bioavailability of sublingual scopolamine was determined by comparing plasma concentrations after sublingual spray delivery with equivalent intravenous doses. Following delivery of the sublingual spray dose, the average Cmax was 1024.4+/-177 ng/mL, and the AUC value was found to be 61067.6+/-9605 ng.min/mL. Relative to the intravenous dose (100% bioavailability), the bioavailability was 79.8% after sublingual spray administration. The addition of 2% chitosan, a bio-adhesive material and an absorption enhancer, showed a significant improvement in scopolamine sublingual absorption (p<0.05) was observed. Considering the limitations of delivering scopolamine orally or transdermally to patients who experience motion sickness, the sublingual route of administration using a spray delivery dosage form, is a potential alternative modality for the prevention of nausea and vomiting associated with motion sickness.