Serine proteases belonging to the kallikrein group may play a central role in desquamation. We have identified human kallikreins 5, 7, and 14 (hK5, hK7, hK14) in catalytically active form in stratum corneum. All three enzymes are produced as inactive precursors. In this work, we prepared recombinant enzymes and enzyme precursors and characterized the catalytic properties of hK5 and hK14. With peptide substrates hK5 and hK14 both showed trypsin-like specificity and alkaline pH-optima. For the substrates tested, hK14 was superior to hK5 as regards maximum catalytic rate as well as catalytic efficiency. hK5, but not hK14, could activate pro-hK7 in a reaction which was optimal at pH 5-7. hK5 could activate its own precursor as well as pro-hK14. This was in contrast to hK14, which could activate pro-hK5 but not its own precursor. The activation of pro-hK5 either by auto-activation or by hK14 occurred at maximum rate at neutral or weakly alkaline pH, whereas activation of pro-hK14 by hK5 was optimal at pH 6-7. We conclude that the enzymes studied may be part of a protease cascade in the stratum corneum, and that the observed pH effects may have physiological relevance.

OBJECTIVES:To assess and quantify the risk of druginduced dry mouth as a side effect in older people. DESIGN: Systematic review and metaanalysis. SETTING: A search of the literature was undertaken using Medline, Embase, Cochrane, Web of Science, and PubMed from 1990 to 2016. PARTICIPANTS: Older people (aged ≥60) who participated in intervention or observational studies investigating drug use as an exposure and xerostomia or salivary gland hypofunction as adverse drug outcomes. MEASUREMENTS: Two pairs of authors screened titles and abstracts of studies for relevance. Two authors independently extracted data, including study characteristics, definitions of exposure and outcome, and methodological quality. For the metaanalyses, random-effects models were used for pooling the data and I 2 statistics for exploring heterogeneity. RESULTS: Of 1,544 potentially relevant studies, 52 were deemed eligible for inclusion in the final review and 26 in metaanalyses. The majority of studies were of moderate methodological quality. In the intervention studies, urological medications (odds ratio (OR) = 5.91, 95% confidence interval (CI) = 4.04-8.63; I 2 = 62%), antidepressants (OR = 4.74, 95% CI = 2.69-8.32, I 2 = 21%), and psycholeptics (OR = 2.59, 95% CI = 1.79-3.95, I 2 = 0%) were significantly associated with dry mouth. In the observational studies, numbers of medications and several medication classes were significantly associated with xerostomia and salivary gland hypofunction. CONCLUSION:Medication use was significantly associated with xerostomia and salivary gland hypofunction in older adults. The risk of dry mouth was greatest for drugs used for urinary incontinence. Future research should develop a risk score for medication-induced dry mouth to assist with prescribing and medication management. J Am Geriatr Soc 66:76-84, 2018.

Persons with dementia had a higher probability of use of paracetamol and were about as likely as persons without dementia to use any analgesic, opioids and NSAIDs, after adjustment for confounders. This may reflect a recent increased awareness of pain and pain management in persons with dementia, compared with previous studies that have reported an underuse of analgesics in persons with dementia. However, further research is needed to analyse if persons with dementia are appropriately treated for pain with regard to type of analgesic drug, pain intensity, indication, dosage and regimen.