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PubMed1996

Recovery of human skin collagen synthesis after short-term topical corticosteroid treatment and comparison between young and old subjects.

In the present study, the recovery of the collagen synthesis rate after topical potent glucocorticoid treatment in the human skin in vivo was investigated. In the first experiment, two age groups were compared: young subjects with an age range of 21-26 years (mean 23), and old subjects, aged 55-70 years (mean 64). Twenty healthy male volunteers applied betamethasone-17-valerate to their abdominal skin for 3 days twice a day. Suction blisters were induced on the treated areas, and on the opposite side (healthy non-treated skin), of the abdominal skin on the day following the discontinuation of the treatment, and on the second and seventh day. In another experiment, suction blisters were induced after the treatment and 2 weeks later on the treated area and on healthy skin, in eight male volunteers. In both experiments, the aminoterminal propeptides of type I and III collagens (PINP and PIIINP, respectively) were measured radioimmunologically from the suction blister fluid. Corticosteroid treatment decreased the collagen synthesis in both age groups after a 3-day treatment period, and essentially no recovery in the collagen synthesis could be seen during a 1-week corticoid-free period. The inhibition and downregulation of collagen synthesis in the corticoid-treated skin was similar in both young and old subjects, up to 7 days after the treatment. During the 2-week corticoid-free period, collagen synthesis was recovered to about 50% of the level seen in the non-treated skin, indicating that collagen synthesis is not completely normalized in the human skin even during a 2-week corticoid-free period.

Administration, Topical↗
PubMed1997

Effect of topical tretinoin on non-sun-exposed human skin connective tissue: induction of tenascin but no major effect on collagen metabolism.

The effects of topical tretinoin on collagen synthesis and degradation were studied in 29 volunteers. The subjects applied 0.1% tretinoin cream on their non-sun-exposed abdominal skin once a day for 1 week (n = 10) (experiment 1) or twice a day for 2 weeks (n = 8) (experiment 2) or once a day for 2 months (n = 11) (experiment 3). After the treatments, suction blisters were induced and amino-terminal propeptides of type I and III procollagens (PINP, PIIINP, respectively) (experiments 1 and 3) and carboxy-terminal propeptide of type I procollagen (PICP) (experiment 2) were assayed as an index of de novo collagen synthesis by radioimmunoassays. Matrix metalloproteases 2 (MMP-2) and 9 (MMP-9) were assayed by the zymography method in experiment 2. In experiment 3, histology, immunohistochemistry of type I and III procollagens, tenascin, mRNA levels of type I collagen alpha 1-chain [alpha 1 (I)], interstitial collagenase (MMP-1), MMP-2, MMP-9 by slot-blot analysis and the levels of alpha 1 (I) collagen mRNA by a quantitative polymerase chain reaction method were studied. The proportional area of elastic fibres visualized in Verhoeff-stained sections was analysed by computerized digital image analysis. The results indicated that treatment with topical tretinoin does not markedly induce de novo synthesis of collagen in vivo or affect matrix metalloproteases. In the immunohistochemical staining, tenascin was increased in the papillary dermis. As it has been suggested that tretinoin could counteract the atrophogenic effect of corticoids on the dermis, the effect of a combination of betamethasone-17-valerate (once a day) and tretinoin (once a day) on the propeptide levels was also studied. Betamethasone alone caused a 60% decrease in the concentrations of PINP and PIIINP, and a similar decrease was found after the combination treatment, indicating that topical tretinoin administered during short treatment periods does not counteract the inhibitory effect of a potent corticoid on collagen propeptides.

Abdomen↗
PubMed1976

Induction of glycosuria and hyperglycemia by topical corticosteroid therapy.

A patient with psoriasis is described who had an abnormal response to the glucose tolerance test without other evidence of diabetes and then developed postprandial hyperglycemia and glycosuria during a period of topical administration of a corticosteroid cream, halcinonide cream 0.1%, under occlusion. A second patient with a similar glucose tolerance test result showed postprandial hyperglycemia when treated similarly with betamethasone valerate cream 0.1%. Two additional patients with midly abnormal responses to glucose tolerance tests showed no evidence of altered glucose metabolism when treated with halcinonide cream in a similar manner.

Administration, Topical↗
PubMed2006

1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone in the treatment of intertriginous psoriasis: a double-blind, randomized controlled study.

OBJECTIVE: During the last decades, management of intertriginous psoriasis (IP) has been unsatisfactory because of the adverse effects associated with long-term corticosteroid application and the lack of alternatives. Recently, both pimecrolimus and tacrolimus have been investigated for this indication and shown to be safe and effective. So far, to our knowledge, a comparison of one of these drugs with standard regimens for IP has not been performed. DESIGN: A single-center, 4-week, double-blind, randomized, vehicle-controlled comparison study to assess the safety and efficacy of 1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone valerate in the treatment of IP. SETTING: Dermatologic hospital at Ruhr University of Bochum. PATIENTS: Eighty adults with IP. INTERVENTIONS: Treatment of IP with 1% pimecrolimus, 0.005% calcipotriol, 0.1% betamethasone, or the vehicle once daily for 28 days. MAIN OUTCOME MEASURES: Mean reduction of the Modified Psoriasis Area and Severity Index (M-PASI) score after 28 days of treatment was considered the primary outcome measure, which was analyzed on an intention-to-treat basis. The secondary outcome was a visual analog scale score for itching. RESULTS: After 4 weeks of treatment, the 3 active compounds and the vehicle resulted in a significant decrease in mean M-PASI score (86.4% for 0.1% betamethasone, 62.4% for 0.005% calcipotriol, 39.7% for 1% pimecrolimus, and 21.1% for vehicle). The 0.1% betamethasone was significantly more effective than 1% pimecrolimus during the study period (P<.05). No significant difference was found between 0.005% calcipotriol and 0.1% betamethasone and between 0.005% calcipotriol and 1% pimecrolimus. The visual analog scale score for pruritus decreased by 78% for 0.1% betamethasone, 57% for 0.005% calcipotriol, 35% for 1% pimecrolimus, and 43% for the vehicle, again demonstrating a clear advantage for the corticosteroid (P<.05). CONCLUSIONS: The 1% pimecrolimus was shown to be less potent than 0.1% betamethasone in the treatment of IP. Considering the adverse-effect profile of long-term application of corticosteroids, occasional or intermittent rescue therapy with short-term topical corticosteroids and maintenance with a less potent agent, such as 1% pimecrolimus or 0.005% calcipotriol, might be appropriate for patients with IP in general practice.

Administration, Cutaneous↗
PubMed1999

Characterization of partially transesterified poly(beta-hydroxyalkanoate)s using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) was used for the characterization of a partially transesterified poly(beta-hydroxyalkanoate), PHA, polymer produced by the bacterial strain Alcaligenes eutrophus using saponified vegetable oils as the sole carbon sources. The transesterification was carried out separately under acidic and basic conditions to obtain PHA oligomers weighing less than 10 kDa. The intact oligomers were detected in their cationized [M + Na](+) and [M + K](+) forms by MALDI-TOFMS. A composition analysis, using the MALDI-TOF spectra, indicate that the oligomers obtained via acid catalysis were terminated with a methyl 3-hydroxybutyrate end group, and those obtained by base catalysis had a methyl crotonate (olefinic) termination. In addition to HB (hydroxy butyrate), the oligomers were found to contain a small percentage of HV (hydroxy valerate). This was independently confirmed using gas chromatography/mass spectrometry (GC/MS). In comparison, the analysis of a commercial PHA polymer, transesterified under identical conditions, only showed the presence of HB, i.e. a pure PHB homopolymer. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗
PubMed1996

Omega amino acids in peptide design: incorporation into helices.

Incorporation of easily available achiral omega-amino acid residues into an oligopeptide results in substitution of amide bonds by polymethylene units of an aliphatic chain, thereby providing a convenient strategy for constructing a peptidomimetic. The central Gly-Gly segment of the helical octapeptide Boc-Leu-Aib-Val-Gly-Gly-Leu-Aib-Val-OMe(1) has been replaced by delta-amino-valeric acid (delta-Ava) residue in the newly designed peptide Boc-Leu-Aib-Val-delta-Ava-Leu-Aib-Val-OMe(2). 1H-nmr results clearly suggest that in the apolar solvent CDCl3, the delta-Ava residue is accommodated into a folded helical conformation, stabilized by successive hydrogen bonds involving the NH groups of Val(3), delta-Ava(4), and Leu(5). The delta-Ava residue must adopt a gauche-gauche-trans-gauche-gauche conformation along the central polymethylene unit of the aliphatic segment, a feature seen in an energy-minimized model conformation based on nmr parameters. The absence of hydrogen bonding functionalities, however, limits the elongation of the helix. In fact, in CDCl3, the folded conformation consists of an N-terminal helix spanning residues 1-4, followed by a Type II beta-turn at residues 5 and 6, whereas in strongly solvating media like (CD3)2SO, the unfolding of the N-terminal helix results in beta-turn conformations at Leu(1)-Aib(2). The Type II beta-turn at the Leu(5)-Aib(6) segment remains intact even in (CD3)2SO.CD comparisons of peptides 1 and 2 reveal a "nonhelical" spectrum for 2 in 2,2,2-trifluoroethanol.

Amino Acids↗
PubMed1998

Calcium phosphate induction by sol-gel-derived titania coatings on titanium substrates in vitro.

Titanium and its alloys are used widely in the manufacture of orthopedic and dental implants. Sol-gel-prepared titania is able to stimulate bone-like apatite formation in in vitro and in vivo cultures. These materials can be used, for example, as coatings on dental and orthopedic implants. However, the processes that lead to apatite formation are not fully understood. In this study different kinds of titania coatings on commercially pure titanium (c.p. Ti) were tested for apatite-forming ability. The rate of apatite formation is considered to be descriptive of a material's bioactive (bone-bonding) potential. Apatite-forming tests were done in simulated body fluid (SBF). Apatite-forming ability was highest with the addition of valeric acid to sol (600 degrees C) or with sintering sol-gel coatings at 450 degrees-550 degrees C. At that temperature range calcium phosphate forms on the coatings in 1 week. Calcium phosphate forming is observed in 1 day on standard coatings sintered at 500 degrees C.

Biocompatible Materials↗
PubMed1999

1H-NMR analysis of microbial-derived organic acids in primary root carious lesions and saliva.

In addition to lowered pH values, the molecular profile and concentrations of microbial-derived organic acids in carious dentin are important demineralization parameters involved in the induction, development and progression of dental caries. High-resolution proton ((1)H) NMR spectroscopy was employed to examine the organic acid status of primary root carious lesions. (1)H-NMR analysis of post-neutralized perchloric acid extracts of active carious lesions revealed that at an operating frequency of 600 MHz, the (1)H-NMR-detectable organic acid composition of carious dentin samples (mean molecular percentage content +/- standard error; the mean molecular percentage content is defined here as the mean of the concentration of each (1)H-NMR-visible organic acid/anion expressed as a percentage of total (1)H-NMR-detectable organic acid/anion level in each sample) was acetate 51 +/- 2%, formate 37 +/- 2%, lactate 5 +/- 1%, propionate 3 +/- 0.8%, pyruvate 2.4 +/- 0.3%, n-butyrate 1.2 +/- 0.2%; succinate 0.1 +/- 0.1%; iso-butyrate, n- and iso-valerate, and n- and iso-caproate (total) <0.2%. Further components detectable included alanine, glycine, choline, phosphorylcholine, trimethylamine oxide, methanol, glycolate and assorted saccharides. In view of their high dissociation constants (K(a)), our results demonstrate that formic and pyruvic acids (K(a) = 1.77 x 10(-4) and 3.20 x 10(-3) mol/dm(3), respectively) contribute substantially to the decreased pH values associated with active caries lesions (cf. lactate K(a) = 1.40 x 10(-4) mol/dm(3)), and hence the pathogenesis of primary root caries.

Aged↗
PubMed2000

Improving the performance of an acid-labile 4-hydroxymethyl phenoxyacetic acid (HMP) linker on resin and SynPhase grafted solid-supports.

A replacement of the acetic acid moiety by valeric acid within the 4-hydroxymethylphenoxyacetic acid (HMP) linker (Sheppard RC, Williams BJ. Acid-labile resin linkage agents for use in solid phase peptide synthesis. Int. J. Peptide Protein Res. 1982; 20: 451-454) significantly improved its performance in terms of loading capacity, yield and purity of the final products. The results indicated the spacer-linker combination and type of solid supports are important factors for solid-phase synthesis.

Biochemistry↗
PubMed2005

Combination injectable contraceptives for contraception.

BACKGROUND: Combination injectable contraceptives provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes. OBJECTIVES: To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of combination injectable contraceptives. SEARCH STRATEGY: We searched computerized databases for randomized controlled trials of combination injectable contraceptives. SELECTION CRITERIA: Randomized controlled trials reported in any language were eligible if they compared a combination injectable with any other contraceptive method (e.g., a second combination injectable contraceptive, progestin-only injectable contraceptive, other hormonal contraceptive or barrier method) or placebo. We limited the review to currently marketed combination injectable contraceptives. DATA COLLECTION AND ANALYSIS: The primary reviewer evaluated all titles and abstracts from the literature searches to determine their eligibility. Two reviewers independently extracted data from the eligible trials. Data on contraceptive efficacy, bleeding patterns, continuation, and side effects were entered and analyzed with RevMan 4.2. MAIN RESULTS: Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA) 25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5 mg. These combination injectable contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems, but had higher rates of discontinuation due to other reasons than the progestin-only comparison contraceptives. Studies comparing two combination injectable contraceptives found that NET-EN 50 mg plus E(2)V 5 mg resulted in less overall early discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials making this comparison. The NET-EN plus E(2)V group also had more cyclical (regular) bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates. AUTHORS' CONCLUSIONS: While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation rates are dependent on many other factors. Future research should be directed toward interventions to improve the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinical sites, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.

Algestone↗
PubMed2006

Nicobrevin for smoking cessation.

BACKGROUND: Nicobrevin is a proprietary product marketed as an aid to smoking cessation. It contains quinine, menthyl valerate, camphor and eucalyptus oil. OBJECTIVES: The objective of this review was to assess the effects of Nicobrevin on long term smoking cessation SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register. SELECTION CRITERIA: Randomized trials comparing Nicobrevin to placebo or an alternative therapeutic control, which reported smoking cessation with at least six months follow up. DATA COLLECTION AND ANALYSIS: Data were sought on the outcome, method of randomization, and completeness of follow up. MAIN RESULTS: We identified no trials meeting the full inclusion criteria including long-term follow up. AUTHORS' CONCLUSIONS: There is no evidence available from long-term trials that Nicobrevin can aid smoking cessation.

Humans↗
PubMed1975

Cytopathological effects of estradiol on the arcuate nucleus of the female rat. A possible mechanism for pituitary tumorigenesis.

Large subcutaneous doses (2 mg/21 days) of estradiol valerate (EV) given over several months will induce a prolactin and growth hormone-secreting pituitary tumor in female rats. The medial basal hypothalami (MBHs) of such EV-treated animals were examined at different time intervals with light and electron microscopes to determine whether EV affects the MBH and to relate any observed effects to the process of tumorigenesis. The MBHs of extensively treated rats exhibited profound glial and neuronal changes. The filament content of astrocytes was greatly increased and large dense pleomorphic inclusions filled both astrocytic perikarya and processes. Degenerating neuronal elements have been observed in the neuropil of extensively treated animals. Dark cells identified as M cells were seen to engage in phagocytosis and were loaded with dense inclusions. Some neurons in MBH contained large quantities of lipofuscin that was different in appearance from that of normal females of the same age. The glial reaction developed gradually. At earlier stages of EV treatment there were fewer reactive glia and these contained fewer inclusions. Myelin figures often occurred in these early inclusions. Reactive glia in EV-treated rats did not appear in the preoptic area, dorsomedial nucleus or lateral hypothalamus but were found in ventromedial nucleus. Retired breeders and starvation-stressed rats resembled normal controls. These pathological changes in MBH may result from a direct effect of EV on the hypothalamus. It is possible that, in addition to its effects on the hypophysis, EV suppresses or injures hypophysiotropic cells in MBH, thus releasing pituitary chromophobes from inhibitory hypothalamic influences. This could result in hypersecretion and neoplasia.

Animals↗
PubMed1989

Development and maintenance of a polycystic condition in ovaries autotransplanted under the kidney capsule.

A single injection of estradiol valerate (EV) produces a polycystic ovarian (PCO) condition in the rat. The development of the PCO condition coincides with alterations in the endogenous plasma gonadotropin patterns, suggesting that PCO may be a response to abnormal gonadotropin stimulation. Other factors, however, such as direct autonomic innervation, also contribute significantly to the regulation of the ovary and could be important in generating and/or maintaining PCO. We have, therefore, removed and autotransplanted one ovary in each of eight rats under the capsule of the ipsilateral kidney, thus totally disrupting its innervation. The animals were injected with EV and both ovaries of each animal were examined 8 weeks later. In a second group of animals, we induced the PCO condition, autotransplanted one polycystic ovary in each animal under the kidney capsule, and examined the ovaries 2 weeks later. In both groups the autotransplanted ovaries exhibited the full range of polycystic morphology, as did the intact ovary in each animal. We conclude that since a major perturbation in innervation affects neither the development nor the maintenance of PCO, autonomic innervation does not play a crucial role in this disorder.

Animals↗
PubMed1990

Remission of the polycystic ovarian condition (PCO) in the rat following hemiovariectomy.

The estradiol valerate-induced polycystic ovarian condition in the rat represents a normal ovarian response to aberrant endocrine stimuli. Although we have shown that removal of one polycystic ovary (hemiovariectomy) results in restoration of cyclicity and normal morphology in the remaining ovary by 1 week, nothing is known about the process of recovery or about the role of the hypothalamo-pituitary unit in initiating recovery. We have therefore examined ovaries at 3, 12, 24, 48, and 120 hours following removal of the contralateral polycystic ovaries. The ovarian content and size distribution of healthy and atretic follicles was determined, as well as the occurrence of follicular cysts, type III large follicular structures, and corpora lutea. The plasma LH pattern was also examined at a short postoperative interval. At 3 hours, there was a significant increase in mean ovarian weight that coincided with the emergence of healthy large secondary follicles. By 12 hours, there was a significant sustained diminution in the number of atretic follicles of all sizes, but the total number of healthy follicles did not increase significantly until 120 hours. The cystic follicles had all but disappeared by 120 hours because of mechanical compression by newly developing ovarian tissue. Ovarian recovery is, therefore, biphasic, consisting of a very early diminution in atresia coincident with, and perhaps caused by, a major alteration in the plasma LH pattern. The second phase is characterized by a wave of follicular recruitment and development.

Animals↗
PubMed1990

Induction of Stein-Leventhal-like polycystic ovaries (PCO) in the rat: a new model for cystic ovarian disease.

An injection of estradiol valerate (EV) in the rat produces an anovulatory polycystic ovarian (PCO) condition. Chronic estrogen exposure, produced by subcutaneously implanted, estradiol (E2)-containing chronic release capsules, results in acyclicity and in hypothalamic changes similar to those seen in the EV-injected rat. We, therefore, examined the ovarian histology and plasma gonadotropin patterns in the E2-implanted rat and found that this model exhibits a polycystic ovarian condition and a plasma gonadotropin pattern very different from those in the EV-treated model. The plasma patterns of LH and FSH are bimodal consisting of small frequent pulses as well as less frequent large episodes of long duration. The ovaries contain multiple small cysts, characterized by an extensively hypertrophied theca interna, and vast chords of hypertrophied secondary interstitial cells. In contrast, cystic follicles in EV-treated rats are fewer in number, but much larger than those in the E2-implanted animals. The cystic theca and the secondary interstitial cell clusters are also far less extensive in the EV-induced polycystic ovary. These and other differences between the two types of PCO indicate that they are produced by fundamentally different morphogenic mechanisms. The cystic ovary produced by the E2 implants is similar in appearance to that seen in the human Stein-Leventhal condition, and thus provides a new model for the study of cystic ovarian disease.

Animals↗
PubMed1991

Thecal and interstitial cells in polycystic ovaries (PCO) in the rat.

Two different types of experimentally-induced polycystic ovaries (PCO) have been examined. A macrocystic ovarian condition is induced by estradiol valerate (EV) injection, whereas a microcystic ovarian condition is engendered with subcutaneous estradiol implants. In both of these models thecal and secondary interstitial cells were characterized using three functionally significant indices. Expression of alkaline phosphatase was evaluated immunohistochemically, hCG/LH-binding capacity was assessed by means of EM radioautography, and the size and percent cytoplasmic area of intracytoplasmic lipid were determined, in the same cells, by morphometry. In both types of ovary, thecal cells of healthy and atretic follicles stained heavily for alkaline phosphatase whereas cystic theca exhibited little or no staining. Intermittent faintly stained patches of secondary interstitial cells, as well as intensely stained spheroidal cell clusters, were most numerous in the microcystic ovary and occurred less frequently in the macrocystic ovary. Cystic thecal cells in both conditions exhibited large lipid droplets and minimal hCG binding. Lipid droplet area was minimal and hCG binding maximal in secondary interstitial cells of both types of ovary. It is concluded that specific clusters of secondary interstitial cells are important steroidogenic elements in PCO, whereas cystic theca is relatively inert.

Alkaline Phosphatase↗
PubMed1979

Effects of estrogen on cartilage and experimentally induced osteoarthritis.

Estradiol valerate did not ameliorate experimentally induced osteoarthritis in the rabbit. Both normal and osteoarthritic cartilage were susceptible to estradiol suppression of proteoglycan synthesis. Protoeglycan concentration was not diminished with estradiol, suggesting estradiol suppression of proteoglycan catabolism. The severity of osteoarthritis was unchanged despite markedly decreased proteoglycan catabolism. The severity of osteoarthritis was unchanged despite markedly decreased protoeglycan synthesis in the estrogen treated animals. Osteophyte proteoglycan metabolism differed from other osteoarthritic lesions. Differences in the metabolism of femoral and tibial articular cartilage were observed.

Animals↗
PubMed2001

Metabolic engineering of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) composition in recombinant Salmonella enterica serovar typhimurium.

A recombinant strain of Salmonella enterica serovar Typhimurium (mutant in propionate-activation activity) was metabolically engineered to control the composition of poly(3-hydroxybutyrate-co-3-hydroxy- valerate) (PHBV), a polyhydroxyalkanoate copolymer with commercially desirable properties. A gene (prpE) encoding propionyl-CoA synthetase was placed under the control of the IPTG-inducible taclacUV5 promoter (P(taclacUV5)) while the polyhydroxyalkanoate synthesis operon (phaBCA) from Acinetobacter sp. RA3849 was coexpressed under the control of the arabinose-inducible araBAD promoter (P(BAD)). S. enterica, harboring both constructs, was grown in medium containing a fixed substrate concentration and the composition of the copolymer was varied between 2 mol% and 25 mol% 3-hydroxyvalerate by controlling the IPTG level in the medium. This "dial-a-composition" system should find application in cases where the substrate concentration of a feedstream for PHBV bioplastic production is not adjustable.

Acinetobacter↗