Is bisacodyl absorbed at all from suppositories in man?

A HPLC procedure was developed to determine free BHPM in human plasma and urine after prior deconjugation of its glucuronides with glucuronidase. A single dose administration of a 10 mg bisacodyl suppository from Glaxo Wellcome, Poznań (Poland) to 16 volunteers each resulted in its low active metabolite (BHPM) plasma levels (10-55 microgram l(-1)) according to general assumptions. Its prompt laxative effect appeared within 56.6+/-10.8 min. The calculated serum half-life time of BHPM glucuronide excretion in urine was approximately 7.32+/-0.99 h. BHPM was excreted in urine in only 3. 36+/-0.52% if compared with the above bisacodyl rectal dose administered. Any relationship between BHPM plasma and/or urine levels and its laxative action does not occur. These results confirm the thesis that the laxative action of bisacodyl suppositories is initiated through a direct interaction of the drug in the rectum.     

Is preclinical data sharing the new norm?

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Branched peptides for the modulation of protein-protein interactions: more arms are better than one?

Combinatorial peptide libraries from synthetic or biological sources have been largely used in the last two-decades with the aim of identifying bioactive peptides that specifically bind proteins and modulate their interactions with other protein partners. Differently from biological libraries, synthetic methods allow the development of different kinds of libraries based on two main characteristics: i) the use of building blocks and chemical bonds different from those naturally occurring and ii) the possibility of designing scaffolds with non-linear shapes, as cyclic and branched structures. These two features, alone or in combination, have increased the chemical and structural diversity of peptide libraries expanding the offer of collections for the screenings. Here we describe our and other experiences with branched peptides and the results obtained in the last fifteen years. These clearly indicate how the use of short multimerized peptides can represent a successful approach for different applications ranging from affinity chromatography to the modulation of protein-protein interactions in different biological contexts.     

The benefits of bilateral versus unilateral amplification for the elderly: are two always better than one?

The use of bilateral hearing aids is based on the assumption that the human auditory system functions best when both ears receive incoming acoustic information. There is evidence, however, that some elderly individuals perform better while using unilateral as opposed to bilateral amplification. The main objective of the present study was to compare speech recognition in noise in elderly hearing-impaired patients initially fitted with bilateral hearing aids while they used unilateral versus bilateral amplification. A secondary goal was to investigate the association between performance with one versus two hearing aids and central auditory function as measured by a dichotic test, and to evaluate the effect of increasing age on these two measures. Twenty-eight patients (mean age 72.8 years, range: 62-86) with bilateral symmetrical mild-to-severe sensorineural hearing loss fitted with digital hearing aids, participated in the study. Speech recognition in noise was assessed in three conditions: (1) aided right ear, (2) aided left ear, (3) aided bilaterally, using the AB open-set monosyllabic word test at a signal-to-noise ratio of +10 dB. Speech stimuli were presented at 70 dB SPL via a loudspeaker located at 0 degree azimuth and the noise was presented via a second loudspeaker located at 180 degrees azimuth. In addition, dichotic listening abilities were evaluated using the threshold-of-interference test. The results of the present study indicated comparable mean group performance while using unilateral versus bilateral amplification. For the most of the patients (71%), however, speech recognition in noise was better while using unilateral amplification to the 'better' ear compared to bilateral amplification. While the performance in the dichotic test was not correlated with speech recognition in noise with bilateral versus unilateral amplification, the performance in these two tests deteriorated significantly with increasing age. Our results suggest that for elderly patients, bilateral amplification may not always be advantageous for speech recognition in noise. As most patients continue to use bilateral amplification, it is clear that there are listening situations in which bilateral amplification provides benefit. Sensitive performance measures that will tap critical aspects of daily binaural listening situations are therefore required. Finally, the deterioration in performance of the aging auditory system underscores the need to 'tailor' auditory habilitation to individual needs.     

Is Cerazette the minipill of choice?

Around 5% of women aged 16-49 years in Great Britain use a progestogen-only pill (POP; 'minipill') as contraception. These pills are used as alternatives to combined oral contraceptives (COCs), compared to which they are less reliable at preventing pregnancy: the estimated contraceptive failure rate of POPs is 0.5 pregnancies per 100 woman-years when used consistently and correctly, compared with 0.1 per 100 woman-years for COCs. Cerazette (Organon), a new POP, is being promoted by the company as "the first oestrogen free pill to consistently inhibit ovulation", as having "the efficacy of a combined pill, with the reassurance of an oestrogen free pill" and offering "reliable contraception for women of any reproductive age". Here, we consider whether Cerazette offers advantages over established POPs.     

Are two drugs better than one? A review of combination therapies for hypertension

Introduction: Current guidelines for pharmacotherapy briefly describe a role for combination antihypertensive therapy. However, guidance on whether combination therapy should be used at the time of initiating therapy or as add on, and the choice of combination therapy is scarce.

Areas covered: Current literature suggests that intensive blood pressure control is the key to managing cardiovascular risk. Along with lifestyle management, pharmacotherapy is an central component in the treatment of hypertension. Here, we aim to review the pathophysiology of hypertension, rationale for using combination therapy, and the different combinations of antihypertensive drug classes that are available in the market. Papers from 1967 through 2016 listed on PubMed on this topic were reviewed.

Expert opinion: Based on the review of the literature, combination antihypertensive therapies are more effective than monotherapy and are also well tolerated, safe and cost effective for treatment of hypertension. Further research is needed to help guide the choice of combination antihypertensive therapy in different patient populations based on age, gender, race and comorbidities.     

How meaningful are the results of nanotoxicity studies in the absence of adequate material characterization?

For the very few people who may not have an understanding ofnanotechnology, here is a quick overview. Nanotechnology isan emerging multidisciplinary technology that involves the synthesisof molecules in the nanoscale (i.e., 10^–9 m) size range.The origin of the term "nanotechnology" is derived from theGreek word "nano," meaning "dwarf." From a chemistry and materialscience perspective, the development of new products using nanomaterialsis exciting because, for a given particle-type, as one movesdown the nanoscale (i.e., as the particle size is decreasedwithin the nanoscale range), fundamental physical and chemicalproperties appear to change—often yielding completelynew and different physical/chemical properties. For example, titanium dioxide particle-types, lose their whitecolor and become colorless at decreasing size ranges < 50nm. Other particle-types, known for electrical insulating properties,may become conductive at the nanoscale; or insoluble substancescan become more