Sedative load among community-dwelling people aged 75 years and older: a population-based study.

Background: Drugs with sedative properties are among the most widely used drugs in community-dwelling older people. Use of sedative drugs has been associated with falls and fractures, cognitive and memory impairment and impaired physical function among older people. The sedative load model has been developed to quantify the cumulative effect of taking multiple drugs with sedative properties.

Muscle strength and sedative load in community-dwelling people aged 75 years and older: a population-based study.

Background: Use of psychotropic and sedative drugs has been associated with impaired muscle strength. Muscle weakness predicts important outcomes for older people including functional disability and mortality. The objective of this study was to investigate if the use of drugs with sedative properties is associated with poorer muscle strength.

Concomitant use of SSRIs, NSAIDs/aspirin and gastroprotective drugs among residents of long-term care facilities: a medical record review.

Background And Objectives: Concomitant use of selective serotonin reuptake inhibitors (SSRIs) and nonsteroidal anti-inflammatory drugs (NSAIDs) [including aspirin (acetylsalicylic acid)] may potentiate the likelihood of upper gastrointestinal haemorrhage (UGIH). The objectives of this study were to determine the prevalence and factors associated with concomitant SSRI/NSAID use among residents of long-term care facilities, and to investigate the use of gastroprotective drugs among concomitant SSRI/NSAID users.

Methods: The study sample comprised 1087 out of 1444 residents of all 53 long-term care wards in Helsinki, Finland, in September 2003.

A comparison of four methods to quantify the cumulative effect of taking multiple drugs with sedative properties.

Background: Older people (ie, those aged >65 years) often use multiple drugs with sedative properties. These include drugs for intentional sedation and drugs that have sedation as an adverse reaction. Recent pharmacoepidemiologic studies have investigated the risks of multiple or combined sedative drug use.

Sedative load among long-term care facility residents with and without dementia: a cross-sectional study.

Background And Objective: People with cognitive impairment are particularly susceptible to adverse drug events linked to sedative and psychotropic drugs. A model to calculate sedative load has been developed to quantify the cumulative effect of taking multiple drugs with sedative properties. The objective of this study was to describe the sedative load and use of sedative and psychotropic drugs among long-term care facility residents with and without dementia.

Sedative load and mortality among residents of long-term care facilities: a prospective cohort study.

Background: Older people are often prescribed multiple drugs with sedative properties. Most research has focused on specific classes of sedative and psychotropic drugs. The cumulative effect of taking multiple drugs with sedative properties has been termed 'sedative load'.

A 100-kDa urinary protein is associated with insulin resistance in offspring of type 2 diabetic patients.

Aims/hypothesis: One-third of normoalbuminuric type 1 diabetic patients show immunoreactive nephrin in urine. Offspring of type 2 diabetic patients are insulin-resistant and susceptible to the development of diabetes. We investigated whether the offspring of type 2 diabetic patients show nephrin in urine and whether possible nephrinuria is associated with insulin resistance.

Nephrinuria in diabetic nephropathy of type 1 diabetes.

Diabetic nephropathy is the leading cause of end-stage renal disease. Because early diagnosis and treatment may prevent the complication, new tools for an early detection are needed. One of the key components of the glomerular filtration slit spanning between neighboring podocytes is nephrin.

Anandamide prodrugs. 1. Water-soluble phosphate esters of arachidonylethanolamide and R-methanandamide.

Phosphate esters of arachidonylethanolamide (AEA) and R-methanandamide were synthesized and evaluated as water-soluble prodrugs. Various physicochemical properties (pK(a), partition coefficient, aqueous solubility) were determined for the synthesized phosphate esters. The chemical stability of phosphate esters was determined at pH 7.

Design and synthesis of a novel L-dopa-entacapone codrug.

A novel codrug, in which L-Dopa and entacapone are linked via a biodegradable carbamate spacer to form a single chemical entity, was synthesized and studied kinetically. This carbamate codrug provides adequate stability [t(1/2) = 12.1 h (pH 1.

Synthesis and in-vitro/in-vivo evaluation of orally administered entacapone prodrugs.

Entacapone is a new inhibitor of catechol-O-methyltransferase (COMT) that is used as an adjunct to L-dopa therapy in the treatment of Parkinson's disease. The bioavailability of orally administered entacapone is, however, relatively low (29-46%). In this study we have prepared more lipophilic acyl and acyloxyacyl esters, an acyloxy alkyl ether and an alkyloxycarbonyl ester of entacapone, and we have evaluated them as potential prodrugs to enhance the oral bioavailability of entacapone.

Synthesis of a water-soluble prodrug of entacapone.

Entacapone was reacted with phosphorous oxychloride in dry pyridine to yield a phosphate ester. The phosphate promoiety increased aqueous solubility of the parent drug by more than 1700- and 20-fold at pH 1.2 and 7.

Bisphosphonate prodrugs: synthesis and in vitro evaluation of alkyl and acyloxymethyl esters of etidronic acid as bioreversible prodrugs of etidronate.

The synthesis and preliminary evaluation of novel alkyl and acyloxymethyl esters of etidronic acid as etidronate prodrugs is reported. Tetramethyl ester of etidronic acid was found be isomerized at pH 7.4 and P-C-P bridge was rearranged to P-C-O-P.

Piperazinylalkyl prodrugs of naproxen improve in vitro skin permeation.

Novel morpholinyl (4a) and piperazinylalkyl (4b-e) esters were synthesized and evaluated in vitro for their properties as bioreversible topically administered dermal prodrugs of naproxen. These ionizable prodrugs exhibited various aqueous solubilities and lipophilicities, depending on the pH of medium. As indicated by octanol-buffer partition coefficients (logP(app)) at pH 7.

Synthesis and in vitro/in vivo evaluation of novel oral N-alkyl- and N,N-dialkyl-carbamate esters of entacapone.

Entacapone has a relatively low oral bioavailability which may, in part, be due to its low aqueous solubility at low pH and/or its hydrophilic character at neutral pH. Various novel N-alkyl and N,N-dialkyl carbamate esters of entacapone were synthesized as possible prodrugs of entacapone in order to increase its aqueous solubility at an acidic pH and to increase its lipophilicity at neutral pH. Oral bioavailability of entacapone and selected carbamate esters were investigated in rats.

Synthesis and in vitro evaluation of novel morpholinyl- and methylpiperazinylacyloxyalkyl prodrugs of 2-(6-methoxy-2-naphthyl)propionic acid (Naproxen) for topical drug delivery.

Various novel morpholinyl- (3a,b) and methylpiperazinylacyloxyalkyl (3c-f) esters of 2-(6-methoxy-2-naphthyl)propionic acid were synthesized and evaluated in vitro for topical drug delivery as potential prodrugs of naproxen (1). Compounds 3a-f were prepared by coupling the corresponding naproxen hydroxyalkyl ester with the morpholinyl- or (4-methyl-1-piperazinyl)acyl acid in the presence of dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP) and quantitatively hydrolyzed (t(1/2) = 1-26 min) to naproxen in human serum. Compounds 3c-f showed higher aqueous solubility and similar lipophilicity, determined by their octanol-buffer partition coefficients (log P(app)), at pH 5.

Synthesis and in vitro evaluation of aminoacyloxyalkyl esters of 2-(6-methoxy-2-naphthyl)propionic acid as novel naproxen prodrugs for dermal drug delivery.

Purpose: To synthesize and evaluate various novel aminoacyloxyalkyl esters of naproxen (3a-i) and naproxenoxyalkyl diesters of glutamic and aspartic acids (3j-m) as potential dermal prodrugs of naproxen.

Methods: The prodrugs 3a-m were synthesized, and their aqueous solubilities, lipophilicities and hydrolysis rates were determined in a buffered solution and in human serum. The permeation of selected prodrugs across excised postmortem human skin was studied in vitro.

Bisphosphonate prodrugs: synthesis and in vitro evaluation of novel clodronic acid dianhydrides as bioreversible prodrugs of clodronate.

P,P'-Diacetyl, P,P'-dibutyroyl, P,P'-dipivaloyl, and P,P'-dibenzoyl (dichloromethylene)bisphosphonic acid dianhydride disodium salts (2a-d) were synthesized and evaluated as novel bioreversible prodrugs of clodronate. The anhydrides were prepared by reacting anhydrous tetrasodium clodronate with a large excess of the corresponding acid anhydride. The dianhydrides 2a-d alone were more lipophilic than the parent clodronate, as determined by drug partitioning between 1-octanol and phosphate buffer at pH 7.

In vitro evaluation of acyloxyalkyl esters as dermal prodrugs of ketoprofen and naproxen.

A series of acyloxyalkyl esters of ketoprofen and naproxen were synthesized and investigated as topical prodrugs with the aim of improving the dermal delivery of the drugs. In addition, some hydroxyalkyl esters of ketoprofen and naproxen were synthesized as possible intermediates of acyloxyalkyl prodrugs. All of the prodrugs were more lipophilic than their parent molecules, as evaluated by drug partitioning between 1-octanol and phosphate buffer at pH 7.

Co-administration of a water-soluble polymer increases the usefulness of cyclodextrins in solid oral dosage forms.

Purpose: The aim of this study was to investigate the effect of cyclodextrins (beta-CD, HP-beta-CD and (SBE)7m-beta-CD), and co-administration of a water-soluble polymer (HPMC) and cyclodextrins, on the oral bioavailability of glibenclamide in dogs.

Methods: Effects of cyclodextrins on the aqueous solubility of glibenclamide, with and without hydroxypropylmethylcellulose (HPMC), were determined by a phase-solubility method. Solid inclusion complexes were prepared by freeze-drying.

Simultaneous determination of clodronate and its partial ester derivatives by ion-pair reversed-phase high-performance liquid chromatography coupled with evaporative light-scattering detection.

A new ion-pair HPLC method coupled with evaporative light-scattering detection (ELSD) for the simultaneous determination of clodronate and its partial esters has been developed. The simultaneous chromatographic separation was achieved on a reversed-phase C8 column with a gradient system and butylamine as an ion-pair reagent. This method provides good enough reproducibility and sensitivity for in vitro determinations of clodronate and its ester derivatives.

An electron microscope study of resin production and secretion by the glands of seedlings of Betula pendula Roth.

Transmission and scanning electron microscopy were used to study the ultrastructure and secretory processes of resin glands on shoot stems of Betula pendula seedlings during seasonal growth. The multicellular peltate glands possess a cortex of columnar cells surrounding a parenchymal medulla differing from the stem parenchyma below. Myelin-like deposits comprising concentric layers of membranes and osmiophilic substances accumulate mainly in the cortical cells, while only the medullar cells have chloroplasts.

Directly acting geno- and cytotoxic agents from a wild mushroom Dermocybe sanguinea.

The wild mushroom, Dermocybe sanguinea, contains several anthraquinone pigments, of which emodin (1,3,8-trihydroxy-6-methylanthraquinone) is quantitatively the most important. In our preliminary tests, Dermocybe sanguinea extracts were genotoxic without metabolic activation. The ethanol extract of Dermocybe sanguinea was fractionated by flash chromatography, and the emodin contents of the fractions were determined by HPLC.

Polyene antibiotics increase the ionic permeability of synaptosomal plasma membranes.

The effects of antifungal heptaene antibiotics candicidin and amphotericin B were investigated in isolated cerebral cortical nerve terminals (synaptosomes). The synaptosomes were incubated with candicidin or amphotericin B in the presence or absence of external Ca2+. Candicidin (0.