Selective Cathepsin S Inhibition with MIV-247 Attenuates Mechanical Allodynia and Enhances the Antiallodynic Effects of Gabapentin and Pregabalin in a Mouse Model of Neuropathic Pain.

Cathepsin S inhibitors attenuate mechanical allodynia in preclinical neuropathic pain models. The current study evaluated the effects when combining the selective cathepsin S inhibitor MIV-247 with gabapentin or pregabalin in a mouse model of neuropathic pain. Mice were rendered neuropathic by partial sciatic nerve ligation.

Airborne molds and bacteria, microbial volatile organic compounds (MVOC), plasticizers and formaldehyde in dwellings in three North European cities in relation to sick building syndrome (SBS).

There are few studies on associations between airborne microbial exposure, formaldehyde, plasticizers in dwellings and the symptoms compatible with the sick building syndrome (SBS). As a follow-up of the European Community Respiratory Health Survey (ECRHS II), indoor measurements were performed in homes in three North European cities. The aim was to examine whether volatile organic compounds of possible microbial origin (MVOCs), and airborne levels of bacteria, molds, formaldehyde, and two plasticizers in dwellings were associated with the prevalence of SBS, and to study associations between MVOCs and reports on dampness and mold.

Polycyclic aromatic hydrocarbons in electrocautery smoke during peritonectomy procedures.

Objective: This study identified and quantified polycyclic aromatic hydrocarbons (PAHs) in electrocautery smoke during 40 peritonectomy procedures and investigated any correlations and/or differences between levels of PAHs and perioperative variables.

Methods: PAHs were measured in personal and stationary sampling by 40 mm Millipore cassettes, for adsorption of both gaseous and particle-bound PAHs. Results.

Dampness and moulds in workplace buildings: associations with incidence and remission of sick building syndrome (SBS) and biomarkers of inflammation in a 10 year follow-up study.

There are few longitudinal studies on health effects of dampness and moulds in workplace buildings. We studied associations between dampness and indoor moulds in workplace buildings and selected biomarkers as well as incidence and remission of sick building syndrome (SBS). The study was based on a ten-year prospective study (1992-2002) in a random sample of adults (N=429) from the Uppsala part of the European Community Respiratory Health Survey (ECRHS).

Onset of mucosal, dermal, and general symptoms in relation to biomarkers and exposures in the dwelling: a cohort study from 1992 to 2002.

Unlabelled: We examined the associations between biomarkers of allergy and inflammation, indoor environment in dwellings, and incidence and remission of symptoms included in the sick building syndrome (SBS) and changes in the home environment of 452 adults who were followed from 1992 to 2002 within the Uppsala part of the European Community Respiratory Health Survey (ECRHS). The 10-year incidence (onset) of general, mucosal, and dermal symptoms was 8.5%, 12.

Sick building syndrome in relation to domestic exposure in Sweden--a cohort study from 1991 to 2001.

Background: Most studies on sick building syndrome (SBS) are cross-sectional and have dealt with symptoms among office workers. There are very few longitudinal cohort studies and few studies on SBS in relation to domestic exposures. The aim of this study was to investigate changes in SBS symptoms during the follow-up period and also to investigate changes in different types of indoor exposures at home and relate them to SBS symptoms in a population sample of adults from Sweden.

Indoor environment in dwellings, asthma, allergies, and sick building syndrome in the Swedish population: a longitudinal cohort study from 1989 to 1997.

Objectives: To investigate changes of sick building syndrome (SBS) and different types of indoor exposures at home over an 8-year follow-up period (1989-1997), and onset of SBS symptoms in relation to size of residence town and education level.

Methods: A random sample (0.1%) of the population in a 3-county region in Sweden, initially aged 20-65 years (n = 466).

Peritonectomy with high voltage electrocautery generates higher levels of ultrafine smoke particles.

Background: To adequately perform peritonectomy, the use of an electrocautery device at a high voltage is recommended. The aim of this study was to analyse the amount of airborne and ultrafine particles (UFP) generated during peritonectomy and to compare this with standard colon and rectal cancer surgery (CRC).

Method: UFP was measured approximately 2-3 cm from the breathing area of the surgeon (personal sampling) and 3 m from where the electrocautery smoke was generated (stationary sampling) from 14 consecutive peritonectomy procedures and 11 standard CRC resections.

Preclinical evaluation of 1H-benzylindole derivatives as novel human immunodeficiency virus integrase strand transfer inhibitors.

We have identified 1H-benzylindole analogues as a novel series of human immunodeficiency virus (HIV) integrase inhibitors with antiretroviral activities against different strains of HIV type 1 (HIV-1), HIV-2, and simian immunodeficiency virus strain MAC(251) [SIV(MAC(251))]. Molecular modeling and structure-activity relationship-based optimization resulted in the identification of CHI/1043 as the most potent congener. CHI/1043 inhibited the replication of HIV-1(III(B)) in MT-4 cells at a 50% effective concentration (EC(50)) of 0.

Acyclic nucleoside analogues as inhibitors of Plasmodium falciparum dUTPase.

We report the discovery of novel uracil-based acyclic compounds as inhibitors of deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase), an enzyme involved in nucleotide metabolism that has been identified as a promising target for the development of antimalarial drugs. Compounds were assayed against both P.falciparum dUTPase and intact parasites.

Urea-PETT compounds as a new class of HIV-1 reverse transcriptase inhibitors. 3. Synthesis and further structure-activity relationship studies of PETT analogues.

The further development of allosteric HIV-1 RT inhibitors in the urea analogue series of PETT (phenylethylthiazolylthiourea) derivatives is described here. The series includes derivatives with an ethyl linker (1-5) and racemic (6-16) and enantiomeric (17-20) cis-cyclopropane compounds. The antiviral activity was determined both at the RT level and in cell culture on both wild-type and mutant forms of HIV-1.

Metabolic profiles of endogenous and ethynyl steroids in plasma and urine from women during administration of oral contraceptives.

Conjugated ethynyl and endogenous steroids in plasma and urine from two women taking an oral contraceptive (Conlumin) containing 1 mg norethindrone and 50 micrograms mestranol have been analyzed by methods based on anion and ligand exchange chromatography and gas chromatography-mass spectrometry. Conjugated norethindrone and its reduced metabolites with 3 alpha,5 alpha, 3 alpha,5 beta, 3 beta,5 beta and 3 beta,5 alpha configurations were identified in the fluids. The quantitatively major metabolites in plasma were a disulphate of the 3 alpha,5 alpha isomer and a monosulphate of the 3 alpha,5 beta isomer.

The characterization of sulphated metabolites of norethindrone in human milk after oral administration of contraceptive steroids.

The excretion of ethynyl steroids in milk from a lactating woman taking a daily dose of an oral contraceptive (Conlumin) containing 1 mg of norethindrone and 50 micrograms of mestranol has been studied. Milk was diluted with aq. triethylamine sulphate and steroids were extracted on a Sep-Pak C18 cartridge at 60-64 degrees C.

Identification and quantitation of free and conjugated steroids in milk from lactating women.

A method for analysis of metabolic profiles of free and conjugated steroids in milk has been developed. Milk is diluted with aqueous triethylamine sulphate and liquid-solid extraction is achieved on a Sep-Pak C18 cartridge at 60-64 degrees C. Steroids are purified by chromatography on small columns of Lipidex 5000 and sulphohydroxypropyl Sephadex LH-20 [H+] prior to separation into neutral and phenolic compounds, glucuronide, mono- and disulphate conjugate groups on the lipophilic strong anion exchanger triethylaminohydroxypropyl Sephadex LH-20 (TEAP-LH-20).

Group separation and gas chromatography--mass spectrometry of conjugated steroids in plasma.

A method is described for analysis of metabolic profiles of conjugated steroids in plasma. Steroids are extracted by Amberlite XAD-2 or Sep-Pak C18 cartridges at 60 64 C in the presence of triethylamine sulphate and separated into unconjugated neutral and phenolic compounds, glucuronide, monosulphate and disulphate conjugate groups by chromatography on the lipophilic strong anion exchanger triethylaminohydroxypropyl Sephadex LH-20 (TEAP-LH-20). The conjugate moiety is hydrolyzed by brief enzymatic or solvolytic procedures and released steroids are separated into a neutral and a phenolic fraction on TEAP-LH-20.

Analysis of isomeric ethynylestradiol glucuronides in urine.

A method for separation and analysis of conjugates of ethynylestradiol in urine is described. Steroid conjugates are separated on a lipophilic strong anion exchanger (triethylaminohydroxypropyl Sephadex LH-230), and phenolic steroids released by enzyme hydrolysis or solvolysis ar isolated by chromatography on the same ion exchanger. Steroids carrying an ethynyl group are isolated by chromatography on SP-Sephadex (Ag+).