Promoting absorption of drugs in humans using medium-chain fatty acid-based solid dosage forms: GIPET™

One of the most important and challenging goals in drug delivery is overcoming the poor oral absorption of high-value therapeutics that include peptides. Gastrointestinal Permeation Enhancement Technology (GIPET?) attempts to address this question by safely delivering drugs across the small intestine in therapeutically relevant concentrations. GIPET is based primarily on promoting drug absorption through the use of medium-chain fatty acids, medium-chain fatty acid derivatives and microemulsion systems based on medium-chain fatty acid glycerides formulated in enteric-coated tablets or capsules. Importantly, these excipients are generally regarded as safe and the systems are formulated in such a way that there is no change in chemical composition of the active ingredient. More than 300 volunteers have been administered GIPET formulations in 16 Phase I studies of 6 separate drugs comprising both single- and repeat-dosing regimes. Oral bioavailability of alendronate, desmopressin and low-molecular-weight heparin in humans was increased using GIPET formulations compared with unformulated controls. GIPET was well tolerated by human subjects. Using fluxes of markers of epithelial permeability, the effects of GIPET on the human intestine were shown to be rapid, short-lived and reversible in vivo. These data suggest that GIPET formulations have genuine potential as a platform technology for safe and effective oral drug delivery of a wide range of poorly permeable drugs.     

MALDI-TOF mass spectrometry analysis of small molecular weight compounds (under 10 KDa) as biomarkers of rat hearts undergoing arecoline challenge

Context: Statistical and clinical reports indicate that betel nut chewing is strongly associated with progression of oral cancer because some ingredients in betel nuts are potential cancer promoters, especially arecoline. Early diagnosis for cancer biomarkers is the best strategy for prevention of cancer progression. Several methods are suggested for investigating cancer biomarkers. Among these methods, gel-based proteomics approach is the most powerful and recommended tool for investigating biomarkers due to its high-throughput. However, this proteomics approach is not suitable for screening biomarkers with molecular weight under 10 KDa because of the characteristics of gel electrophoresis.

Objective: This study investigated biomarkers with molecular weight under 10 KDa in rats with arecoline challenge.

Materials and methods: The centrifuging vials with membrane (10 KDa molecular weight cut-off) played a crucial role in this study. After centrifuging, the filtrate (containing compounds with molecular weight under 10 KDa) was collected and spotted on a sample plate for MALDI-TOF mass spectrometry analysis.

Results: Compared to control, three extra peaks (m/z values were 1553.1611, 1668.2097 and 1740.1832, respectively) were found in sera and two extra peaks were found in heart tissue samples (408.9719 and 524.9961, respectively). These small compounds should play important roles and may be potential biomarker candidates in rats with arecoline.

Discussion and conclusions: This study successfully reports a mass-based method for investigating biomarker candidates with small molecular weight in different types of sample (including serum and tissue). In addition, this reported method is more time-efficient (1 working day) than gel-based proteomics approach (5~7 working days).     

Employment Hardships and Single Mothers’ Self-Rated Health: Evidence from the Panel Study of Income Dynamics

Using a national sample of single mothers from the 2007 and 2009 waves of the Panel Study of Income Dynamics, this study examined the effects of multiple employment statuses on the selfrated health of single mothers during the recent economic recession. Unlike other studies, the current study minimized selection bias by controlling for prior self-rated health, in addition to other predisposing factors, enabling factors, and need factors. We found that underemployment, but not unemployment, is associated with lower levels of self-rated health of single mothers. Results further indicate that the 25–39 age range (compared to the 18–24 age range), lower family income, prior lower self-rated health, more chronic diseases, and binge drinking place single mothers at an increased risk of lower levels of self-rated health. In contrast, strength-building physical activity is significantly associated with higher levels of self-rated health. Implications for health care policy and social work practice are drawn from the results.     

Role of viral RNA and lipid in the adverse events associated with the 2010 Southern Hemisphere trivalent influenza vaccine

In Australia, during the 2010 Southern Hemisphere (SH) influenza season, there was an unexpected increase in post-marketing adverse event reports of febrile seizures (FS) in children under 5 years of age shortly after vaccination with the CSL 2010 SH trivalent influenza vaccine (CSL 2010 SH TIV) compared to previous CSL TIVs and other licensed 2010 SH TIVs. In an accompanying study, we described the contribution to these adverse events of the 2010 SH influenza strains as expressed in the CSL 2010 SH TIV using in vitro cytokine/chemokine secretion from whole blood cells and induction of NF-κB activation in HEK293 reporter cells. The aim of the present study was to identify the root cause components that elicited the elevated cytokine/chemokine and NF-κB signature. Our studies demonstrated that the pyrogenic signal was associated with a heat-labile, viral-derived component(s) in the CSL 2010 SH TIV. Further, it was found that viral lipid-mediated delivery of short, fragmented viral RNA was the key trigger for the increased cytokine/chemokine secretion and NF-κB activation. It is likely that the FS reported in children <5 years were due to a combination of the new influenza strains included in the 2010 SH TIV and the CSL standard method of manufacture preserving strain-specific viral components of the new influenza strains (particularly B/Brisbane/60/2008 and to a lesser extent H1N1 A/California/07/2009). These combined to heighten immune activation of innate immune cells, which in a small proportion of children <5 years of age is associated with the occurrence of FS. The data also demonstrates that CSL TIVs formulated with increased levels of splitting agent (TDOC) for the B/Brisbane/60/2008 strain can attenuate the pro-inflammatory signals in vitro, identifying a potential path forward for generating a CSL TIV indicated for use in children <5 years.     

Arzneimittelversorgung bei psychischen Erkrankungen

The use of psychotropic drugs has substantially changed during the last two decades. Whereas 1992 the largest amount dispensed with was benzodiazepine-tranquilizing drugs the antidepressants became the most prescribed drug group in 2012, especially due to the increase of selective-serotonine-reuptake-inhibitors (SSRI). The evidence for the treatment of mild depressions compared to placebo is poor. In the treatment of bipolar disorders mainly used are SSRI and lithium.     

Human papillomavirus (HPV) infection and genotype frequency in the oral mucosa of newborns in Milan,Italy

Human papillomavirus (HPV) causes cutaneous and mucosal infections in both adults and children. In order to evaluate HPV prevalence and the spectrum of genotypes in the oral cavity of paediatric subjects, a retrospective study was carried out on oral-pharyngeal swabs collected from 177 newborns aged 0–6 months. HPV-DNA was detected by a nested-PCR; the viral typing was made through DNA sequencing. HPV infection was identified in 25 subjects (14.1%) and the sequence analysis showed eight distinct genotypes. These data confirm HPV detection in newborn oral mucosa. Further investigations are needed to clarify the methods of HPV acquisition.     

Editorial: The integration of pharmacological and nonpharmacological treatments in drug/alcohol addiction

No abstract available for this article.     

Operative outcomes of single-port-access laparoscopy-assisted vaginal hysterectomy compared with single-port-access total laparoscopic hysterectomy

ObjectiveThis study aims to compare between operative outcomes of single-port-access laparoscopy-assisted vaginal hysterectomy (SPA-LAVH) and single-port-access total laparoscopic hysterectomy (SPA-TLH), further subdivided by vaginal cuff closure via laparoscopic suture (VCC-L) or via the vaginal route (VCC-V).Materials and methodsA custom-made port was used for single-port laparoscopy in 111 patients who underwent SPA-LAVH (n = 33), SPA-TLH with VCC-L (n = 35), and SPA-TLH with VCC-V (n = 43) during October 2009–October 2010. Records were reviewed retrospectively.ResultsA significant difference in the operating time was observed among the groups (p = 0.009). SPA-TLH with VCC-L took a significantly longer time to be performed (118.6 ± 41.8 minutes) than SPA-TLH with VCC-V (98.6 ± 21.3 minutes) or SPA-LAVH (102.0 ± 20.3 minutes). The decrease in hemoglobin level on the 1^st day postsurgery was significantly smaller in case of SPA-LAVH (1.56 ± 0.97 g/dL, p = 0.005) compared with that in case of SPA-TLH with VCC-L (2.19 ± 0.95 g/dL) and SPA-TLH with VCC-V (2.24 ± 0.95 g/dL). No significant differences in other surgical outcomes were found.ConclusionSPA-TLH with laparoscopic vaginal suture required the longest operating time, and hemoglobin changes were smaller in the SPA-LAVH group than in the other groups. In patients undergoing SPA laparoscopy, we recommend the SPA-LAVH procedure.