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PubMed2005

Heterozygous indels as useful tools in the reconstruction of DNA sequences and in the assessment of ploidy level and genomic constitution of hybrid organisms.

In this paper we describe a simple approach using double peaks in chromatograms generated as artefacts in the vicinity of heterozygous indels, to identify the specific sequences present in individual strands of a given DNA fragment. This method is useful to assign bases in individuals that are heterozygous at multiple sites. In addition, the relative sizes of the double peaks help to determine the ploidy level and the relative contribution of the parental genomes in hybrids. Our interpretation was confirmed with the analysis of artificial mixtures of DNA of two different species. Results were robust with varying PCR and sequencing conditions. The applicability of this method was demonstrated in hybrids of the Squalius alburnoides complex and in heterozygotes of Chondrostoma oligolepis. Far from being limited to these fish models and the gene where it was tested (beta-actin), this sequence reconstruction methodology is expected to have a broader application.

Animals↗
PubMed1995

Bias in conditional inference: implications for mental models and mental logic.

Three experiments are reported in which subjects are given the opportunity to make any of the four inferences associated with conditional statements: modus ponens (MP), denial of the antecedent (DA), affirmation of the consequent (AC), and modus tollens (MT). The primary purpose of the research was to establish the generality and robustness of polarity biases that may be occasioned by systematic rotation of negative components in the conditional rules. In Experiments 1 & 2, three forms of conditionals were used: "if (not) p then (not) q", "(not) p only if (not) q" and "(not) q if (not) p". Experiment 1 used a conclusion evaluation task, whereas Experiment 2 used a conclusion production task. In Experiment 3, thematic conditionals were presented with and without a preceding scenario. The biases investigated were (a) affirmative premise bias--the tendency to draw more inferences with negative conclusions. The suggestive evidence for affirmative premise bias in the literature was not supported: very little evidence was found for it in the current experiments. Robust findings of negative conclusion bias were, however, found across the three experiments, although the bias was mostly restricted to DA and MT inferences. This suggests that the bias is best regarded as a difficulty with double negation. The results are discussed with respect to both the mental logic and mental model accounts of propositional reasoning. Neither theory as currently formulated can explain all of our findings, although a plausible revision of each is considered.

Adult↗
PubMed2003

Peptides that regulate food intake: appetite-inducing accumbens manipulation activates hypothalamic orexin neurons and inhibits POMC neurons.

Corticolimbic circuits involving the prefrontal cortex, amygdala, and ventral striatum determine the reward value of food and might play a role in environmentally induced obesity. Chemical manipulation of the nucleus accumbens shell (AcbSh) has been shown to elicit robust feeding and Fos expression in the hypothalamus and other brain areas of satiated rats. To determine the neurochemical phenotype of hypothalamic neurons receiving input from the AcbSh, we carried out c-Fos/peptide double-labeling immunohistochemistry in various hypothalamic areas known to contain feeding peptides, from rats that exhibited a significant feeding response after AcbSh microinjection of the GABA(A) agonist muscimol. In the perifornical area, a significantly higher percentage of orexin neurons expressed Fos after muscimol compared with saline injection. In contrast, Fos expression was not induced in melanin-concentrating hormone and cocaine-amphetamine-related transcript (CART) neurons. In the arcuate nucleus, Fos activation was significantly lower in neurons coexpressing CART and proopiomelanocortin, and there was a tendency for higher Fos expression in neuropeptide Y neurons. In the paraventricular nucleus, no significant activation of oxytocin and CART neurons was found. Thus AcbSh manipulation may elicit food intake through coordinated stimulation of hypothalamic neurons expressing orexigenic peptides and suppression of neurons expressing anorexigenic peptides. However, activation of many neurons not expressing these peptides suggests that additional peptides/transmitters in the lateral hypothalamus and accumbens projections to other brain areas might also be involved.

Animals↗
PubMed2002

Spinal cord injury elicits expression of keratan sulfate proteoglycans by macrophages, reactive microglia, and oligodendrocyte progenitors.

Keratan sulfate proteoglycans (KSPGs) are extracellular matrix molecules that appear to establish boundaries for axonal growth in the developing brain and spinal cord. In vitro studies confirm that KSPGs define inhibitory boundaries to extending neurites. The aim of the current study was to investigate whether KSPGs are expressed after spinal cord injury (SCI) and thereby might act as potential inhibitors of axonal growth. Adult Fischer 344 rats were subjected to spinal cord lesions, and the temporal and spatial expression of KSPGs was examined using the 5D4 monoclonal anti-KSPG antibody. In the intact spinal cord, a subpopulation of microglia expressed 5D4-KSPG throughout the white and gray matter. Within 24 hr of injury, 5D4-KSPG immunoreactivity substantially increased and appeared on cellular profiles in close proximity to the spinal cord lesion site, peaking 3 d after injury. Double immunolabeling revealed that 5D4-KSPG expression arose from multiple cell types at the lesion site, including reactive microglia, macrophages, and oligodendrocyte progenitors. Astrocytes were not identified as a source of 5D4-KSPG. The robust and extensive production of 5D4-KSPG at sites of SCI precedes the expression of other putatively inhibitory proteoglycan molecules such as chondroitin sulfate proteoglycans. This is the first demonstration that KSPGs are expressed after SCI in a temporal and spatial relationship that could exert an early and important role in modulating axonal growth after SCI.

Animals↗
PubMed2000

Garlic for treating hypercholesterolemia. A meta-analysis of randomized clinical trials.

PURPOSE: To investigate the effect of garlic on total cholesterol level in persons with elevated levels by conducting a meta-analysis of randomized, double-blind, placebo-controlled trials. DATA SOURCES: Systematic literature searches were conducted on the MEDLINE, EMBASE, BIOSIS, Cochrane Library, AMED, and CISCOM databases. Manufacturers of commercial garlic preparations and experts in the field were asked about published or unpublished trials. STUDY SELECTION: Selected trials were required to state that they were randomized, double-blind, and placebo-controlled; use garlic monopreparations; include persons with mean total cholesterol levels of at least 5.17 mmol/L (200 mg/dL); and report total cholesterol level as an end point. There were no language restrictions. DATA EXTRACTION: Two reviewers, blinded to key identifiers of each paper, independently extracted data in a standardized manner and assessed methodologic quality by using the Jadad scale. Discrepancies were settled through discussion. DATA SYNTHESIS: In the 13 trials included in the meta-analysis, garlic reduced total cholesterol level from baseline significantly more than placebo (P < 0.01); the weighted mean difference was -0.41 mmol/L (95% CI, -0.66 to -0.15 mmol/L) (-15.7 mg/dL [CI, -25.6 to -5. 7 mg/dL]). Six diet-controlled trials with the highest scores for methodologic quality revealed a nonsignificant difference between garlic and placebo groups; the weighted mean difference was -0.11 mmol/L (CI, -0.30 to 0.08 mmol/L) (-4.3 mg/dL [CI, -11.7 to 3.1 mg/dL]). CONCLUSIONS: The available data suggest that garlic is superior to placebo in reducing total cholesterol levels. However, the size of the effect is modest, and the robustness of the effect is debatable. The use of garlic for hypercholesterolemia is therefore of questionable value.

Chi-Square Distribution↗
PubMed1998

Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder.

OBJECTIVE: The authors assessed the experimental noradrenergic compound tomoxetine as an alternative treatment for adult attention deficit hyperactivity disorder (ADHD). METHOD: They conducted a double-blind, placebo-controlled, crossover study of tomoxetine in 22 adults with well-characterized ADHD. RESULTS: Treatment with tomoxetine at an average oral dose of 76 mg/day was well tolerated. Drug-specific improvement in ADHD symptom was highly significant overall and sufficiently robust to be detectable in a parallel-groups comparison restricted to the first 3 weeks of the protocol. Eleven of 21 patients showed improvement after receiving tomoxetine, compared with only two of 21 patients who improved after receiving placebo. Significant tomoxetine-associated improvement was noted on neuropsychological measures of inhibitory capacity from Stroop tests. CONCLUSIONS: This preliminary study showed that tomoxetine was effective in treating adult ADHD and was well tolerated. These promising results provide support for further studies of tomoxetine over an extended period of treatment.

Adult↗
PubMed2006

Renin angiotensin aldosterone system blockade and renal disease in patients with type 2 diabetes: a subanalysis of Japanese patients from the RENAAL study.

BACKGROUND: The Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study has previously shown losartan to confer significant benefits to patients with type 2 diabetes and nephropathy. The original study of 1513 patients included 96 Japanese patients; the present study is a post-hoc analysis of the effects of losartan in this Japanese subpopulation. METHODS: This double-blind, randomized study compared losartan (50 to 100 mg once daily) with placebo. The study medication was taken in addition to conventional antihypertensive treatment, and the mean follow-up period for the Japanese patients was 2.8 years. The primary endpoint was the composite of doubling of serum creatinine, endstage renal disease, or death. Secondary endpoints included changes in proteinuria levels. Safety was also evaluated. RESULTS: The primary composite endpoint was reached in fewer Japanese patients receiving losartan than placebo (50.0% versus 65.4%, respectively). The treatment effects of losartan were more robust when data were corrected for differences in proteinuria at baseline--a significant relative risk reduction of 45% with losartan (P=0.0397) was apparent. Treatment benefit exceeded that attributable to blood pressure changes alone. Levels of proteinuria were reduced with losartan compared with placebo, with an overall losartan treatment effect of 37.8% (P<0.001). Overall, losartan was similarly well tolerated in both the Japanese patients and the total population. CONCLUSIONS: In Japanese patients with type 2 diabetes and nephropathy, losartan offers renal protection and is generally well tolerated.

Adult↗
PubMed2004

[Chemoprevention of prostate cancer].

Despite advances in the detection and management of prostate cancer, this disease remains a major cause of morbidity and mortality in men. Increasing attention has focused on the role of chemoprevention for prostate cancer, i.e., the administration of agents that inhibit one or more steps in the natural course of prostate carcinogenesis. We review prostate cancer chemoprevention studies in Europe. Published studies were identified in a search of MEDLINE. Information about ongoing studies was provided by author access to protocols. A variety of chemoprevention studies have focused on the role of dietary factors, vitamins, and trace elements in prostate cancer. Some of these studies have been prospective, randomized, and double-blinded, while others have used retrospective or epidemiological approaches. Large-scale randomized studies are also evaluating the role of 5alpha-reductase inhibitors, which inhibit the conversion of testosterone to the more potent androgen dihydrotestosterone. Robust evidence is lacking for the value of chemopreventive agents in prostate cancer. Current evidence does suggest that vitamin E and selenium may have a role in prostate cancer chemoprevention. Data from two studies, one examining the type 1 5alpha-reductase selective inhibitor finasteride and the other using the dual 5a-reductase inhibitor dutasteride, will determine the benefits of androgen inhibition strategies for prostate cancer chemoprevention.

Anticarcinogenic Agents↗
PubMed2004

Chemotherapeutic prevention studies of prostate cancer.

PURPOSE: Despite advances in the detection and management of prostate cancer, this disease remains a major cause of morbidity and mortality in men. Increasing attention has focused on the role of chemoprevention for prostate cancer, ie the administration of agents that inhibit 1 or more steps in the natural history of prostate carcinogenesis. We review prostate cancer chemoprevention studies in Europe. MATERIALS AND METHODS: Published studies were identified in a search of MEDLINE. Information about ongoing studies was provided by author access to protocols. RESULTS: A variety of chemoprevention studies have focused on the role of dietary factors, vitamins and trace elements in prostate cancer. Some of these studies have been prospective, randomized and double-blinded, while others have used retrospective or epidemiological approaches. Large scale randomized studies are also evaluating the role of 5alpha-reductase inhibitors, which inhibit the conversion of testosterone to the more potent androgen dihydrotestosterone. CONCLUSIONS: Robust evidence is lacking for the value of chemopreventive agents in prostate cancer. Current evidence does suggest that vitamin E and selenium may have a role in prostate cancer chemoprevention. Data from 2 studies, 1 examining the type 1 5alpha-reductase selective inhibitor finasteride and the other using the dual 5alpha-reductase inhibitor dutasteride, will determine the benefits of androgen inhibition strategies for prostate cancer chemoprevention.

Anticarcinogenic Agents↗
PubMed2006

Cocaine-induced locomotor activity and Fos expression in nucleus accumbens are sensitized for 6 months after repeated cocaine administration outside the home cage.

Induction of the immediate early gene protein product Fos has been used extensively to assess neural activation in the striatum after repeated cocaine administration to rats in their home cages but rarely after repeated administration outside the home cage, which produces more robust locomotor sensitization. In the present study, we found cocaine-induced Fos expression in nucleus accumbens, but not caudate-putamen, was enhanced 1 and 6 months after repeated drug administration in locomotor activity chambers. Double-labelling of Fos protein and enkephalin mRNA indicated that Fos expression in nucleus accumbens was enhanced in enkephalin-positive, but not enkephalin-negative, medium spiny neurons. In contrast, cocaine-induced Fos expression was absent altogether in nucleus accumbens and unaltered in caudate-putamen 1 month after repeated cocaine administration in the home cage. As cocaine-induced locomotor activity was also enhanced 1 and 6 months after repeated cocaine administration in locomotor activity chambers, we wanted to confirm that neuronal activity in nucleus accumbens mediates cocaine-induced locomotor activity using our particular treatment regimen. Bilateral infusions of the GABA agonists baclofen and muscimol (1 microg/side) into nucleus accumbens of sensitized rats blocked cocaine-induced Fos expression and locomotor activity. Thus, while neuronal activity in both D1- and D2-type neurons in nucleus accumbens can mediate acute cocaine-induced locomotor activity, the enhanced activation of enkephalinergic D2-type neurons suggests that these latter neurons mediate the enhancement of cocaine-induced locomotor activity for up to 6 months after repeated drug administration outside the home cage.

Animals↗
PubMed1997

Topiramate: a new antiepileptic drug.

OBJECTIVE: To review proposed mechanisms of action, clinical pharmacology, efficacy, safety, and tolerability of the antiepileptic drug (AED) topiramate. METHODS: All available data from the clinical development program--published and unpublished data (provided by investigators or the RW Johnson Pharmaceutical Research Institute)--were analyzed, with emphasis on the results of double-blind, placebo-controlled trials. Data from open-label studies provided information about long-term efficacy and tolerability. FINDINGS: Topiramate is highly effective in the control of previously therapy-resistant partial seizures, with or without secondary generalization. In the refractory adult patient population enrolled in controlled clinical trials, seizures were reduced by 50% or more in 27-47% of patients compared with 0-18% in placebo-treated patients and by 75% or more in 9-36% of the patients compared with 0-9% of those receiving placebo. The most common adverse effects involve the central nervous system and are mild to moderate in nature. Adverse effects include somnolence, fatigue, psychomotor slowing, and concentration problems. The currently recommended dosing is lower and titration slower than schedules used in the clinical trials; this may improve the tolerability of topiramate. Topiramate has few interactions with currently available AEDs, but phenytoin concentrations increased in some patients. Topiramate can be used initially as adjunctive therapy. Plasma topiramate concentrations are reduced substantially when used with enzyme-inducing AEDs. Open-label data and a single double-blind trial suggest that topiramate monotherapy may be effective. Open-label data also indicate that topiramate may be effective in generalized seizures of nonfocal origin, including those associated with Lennox-Gastaut syndrome. CONCLUSIONS: The robust clinical effects of topiramate expand the therapeutic options for patients with epilepsy. Controlled clinical trials are needed to verify initial observations that topiramate may be effective against a broad spectrum of seizure types and to directly compare efficacy and tolerability with other new and standard AEDs.

Adult↗
PubMed2006

Making therapeutic decisions in adults with aplastic anemia.

The management of adults presenting with aplastic anemia (AA) requires careful exclusion of other causes of bone marrow failure. Late-onset inherited forms of AA may present in adulthood with subclinical disease. Recent long-term studies of HLA identical sibling donor BMT show excellent survival for patients under the age of 40 years, but chronic graft-versus-host disease (GVHD) is still a major problem, impacting on quality of life. Recent improvements in outcome after matched unrelated donor BMT may reflect better donor matching and use of reduced intensity conditioning regimens. For patients treated with immunosuppressive therapy (IST), antithymocyte globulin (ATG) and cyclosporin (CSA) remain the standard regimen with excellent overall survival but less impressive failure-free survival due to nonresponse, relapse and later clonal disorders. The benefit of adding granulocyte colony-stimulating factor (G-CSF) to ATG and CSA is unclear and being assessed in a further prospective European study. Patients who are refractory to conventional IST and currently ineligible for BMT represent difficult management problems. For these patients, new approaches to transplantation are being evaluated, such as fludarabine-based conditioning regimens and the potential use of double umbilical cord blood transplants, but there is a need for new immunosuppressive agents. Improved supportive care is likely to be a major factor in improved outcome of all AA patients whether treated with IST or BMT. Robust predictive factors for response to IST are needed to help in decision making at diagnosis and to help justify exploring novel approaches to therapy.

Adult↗
PubMed2006

Effects of single or repeated intravenous administration of kisspeptin upon dynamic LH secretion in conscious male rats.

The ability of kisspeptins, ligands of the G protein-coupled receptor 54, to potently elicit LH secretion is now undisputed. Yet, most of the pharmacological characterization of their gonadotropin-releasing effects has been conducted after intracerebral administration. In contrast, the effects of peripheral injection of kisspeptin remains less well defined. In this study, dynamic LH secretory responses to iv administration of kisspeptin-10 in different experimental settings are presented, and compared with those evoked by kisspeptin-52, using a protocol of serial blood sampling in conscious, freely moving male rats. LH responsiveness to peripheral administration of kisspeptin appeared extremely sensitive, as doses as low as 0.3 nmol/kg (0.1 microg/rat) evoked robust LH bursts, the magnitude of which was dose-dependent and apparently maximal in response to 3.0 and 30 nmol/kg kisspeptin-10. The ability of kisspeptin-10 to stimulate LH release was fully preserved, and even doubled in terms of relative increases, after short-term fasting despite suppression of prevailing LH levels. Repeated injections of kisspeptin-10 (four boluses, at 75-min intervals) evoked associated LH secretory pulses, the magnitude of which remained constant along the study period. Moreover, in this setting, in vivo LH responses to a terminal injection of GnRH were preserved, whereas basal and depolarization-induced GnRH release ex vivo was significantly enhanced. Finally, iv administration of kisspeptin-52 elicited dynamic LH responses analogous to that of kisspeptin-10; yet, their net magnitude and duration was slightly greater. In summary, we present in this study a series of experiments on the effects of systemic (iv) injection of single or repeated doses of kisspeptin upon dynamic LH secretion in conscious male rats. Aside from potential physiologic relevance, our present data might contribute to setting the basis for the rational therapeutic use of kisspeptin analogs in the pharmacological manipulation of the gonadotropic axis.

Animals↗
PubMed1995

Functional neuroanatomy of CCK4-induced anxiety in normal healthy volunteers.

OBJECTIVE: The authors tested the prediction of temporal cortex activation during experimentally induced anxiety by using positron emission tomography and the [15O]H2O bolus-subtraction method to determine regional cerebral blood flow (CBF) changes in normal volunteers challenged with a bolus injection of cholecystokinin tetrapeptide (CCK4). METHOD: Eight right-handed healthy subjects (five male, three female; mean age, 26.4 years) underwent four 60-second [15O]H2O scans separated by 15-minute intervals; each scan followed an intravenous bolus injection of either saline (placebo) or CCK4 (50 micrograms). Each subject received CCK4 once, as the first or second bolus, in a random-order, placebo-controlled, double-blind fashion. Two of the three placebo conditions were nominally identical, and the remaining placebo was used to control for anticipatory anxiety. Magnetic resonance imaging scans were obtained for subsequent anatomical correlation of blood flow changes. RESULTS: CCK4, but not placebo, elicited a marked anxiogenic response, reflected by robust increases in subjective anxiety ratings and heart rate. CCK4-induced anxiety was associated with 1) robust and bilateral increases in extracerebral blood flow in the vicinity of the superficial temporal artery territory and 2) CBF increases in the anterior cingulate gyrus, the claustrum-insular-amygdala region, and the cerebellar vermis. CONCLUSIONS: Some of the temporopolar cortex CBF activation peaks previously reported in humans in association with drug- and non-drug-induced anxiety, as well as the increase in regional CBF in the claustrum-insular-amygdala region, may be of vascular and/or muscular origin.

Adult↗
PubMed2005

Patterns of vascular and anatomical response after rotator cuff repair.

BACKGROUND: It has been assumed that a robust vascular response at the tendon to bone interface during rotator cuff repairs is an integral part to the healing process. There are few studies that have explored this in an in-vivo prospective fashion. PURPOSE: To prospectively characterize vascular and anatomical patterns in repaired rotator cuff tendons using Power Doppler sonography in a double-blinded fashion. STUDY DESIGN: Case control study; Level of evidence, 3. METHODS: Fifty patients undergoing rotator cuff repair were enrolled: 28 mini-open, 14 open, and 8 arthroscopic repairs; 20 patients were controls. Patients underwent Power Doppler sonography at 6 weeks, 3 months, and 6 months postoperatively. Power Doppler sonography analysis examined 6 areas of the rotator cuff repair: discretely marginated intrasubstance, partial-thickness defects, full-thickness defects, focal thinning of repair, presence of bursal or joint fluid, and location of anchors. A subjective scoring system assessed blood flow in each region. RESULTS: There was a predictable, significant decrease in vascular scores after rotator cuff repair over time. The mean vascular score was 11.6 at 6 weeks, 8.3 at 3 months, 7.0 at 6 months, and 2.4 for controls. There was a significant difference (P < .05) in vascular recruitment scores between each time period, with the most robust flow at the peritendinous region. The lowest vascular score was at the anchor site or cancellous trough. Forty-eight percent of the patients had a rotator cuff repair defect postoperatively. These findings did not correlate with functional assessment and outcome at 6 months. There was no significant difference in vascular scores between the defect and no-defect groups. Mean University of California, Los Angeles; L'Insalata; and American Shoulder and Elbow Surgeons scores at 6 months were 28.6, 86.3, and 81.5, respectively. Thirty-three percent of asymptomatic controls had a rotator cuff tear that averaged 7.6 x 7.1 mm. CONCLUSION: The robust vascular response dropped with time, which is not seen in asymptomatic shoulders. Nearly half of the patients demonstrated persistent rotator cuff defects after rotator cuff repair that did not correlate with functional outcome and physical findings at 6 months.

Adult↗
PubMed1999

Influence of a rapid change of left ventricular dimensions on the echocardiographic measurement of left ventricular mass by the Penn convention.

OBJECTIVE: The purpose of this study was to test the robustness of the measurement of left ventricle mass (LVM), using Devereux's formula, in the presence of a rapid change in left ventricular volume induced by nitroglycerin. DESIGN: Forty-eight healthy volunteers with excellent echocardiographic recordings were included. The intrapatient variability of LVM measurement was assessed by two consecutive echocardiograms. The intraobserver reproducibility was assessed by the rereading of 19 echocardiograms by the same observer. The effects of nitroglycerin were compared with those of a placebo in a double-blind random manner on, the left ventricular internal dimension in diastole (LVIDd), the interventricular septum thickness, the posterior wall thickness and the LVM. RESULTS: It was shown that both the intrapatient and the intraobserver reproducibility were high. Nitroglycerin induced a significant decrease in LVIDd compared with placebo (-0.21 +/- 0.24 versus 0.01 +/- 0.21 cm, respectively, P < 0.01) and a non-significant increase in wall thickness. These variations were negatively correlated with each other (r= -0.58, P< 0.01). Despite the change of ventricular dimensions, the variation of LVM induced by nitroglycerin was not significantly different from that induced by placebo (2.0 +/- 16.0 versus 4.7 +/- 17.0 g, respectively, not significant) and close to the intrapatient variability. CONCLUSION: This experiment failed to demonstrate any influence of a rapid variation of ventricle size on the calculation of LVM with the Penn convention and strongly supports the robustness of the method in vivo.

Adult↗
PubMedDate not supplied

Failure of tibolone to potentiate the pharmacological effect of fluoxetine in postmenopausal major depression.

BACKGROUND: Perimenopausal depression has been attributed to physiological progressive estrogen decline. Estrogen and derivatives have some mood-enhancing effects, although studies of using estrogen as an antidepressant have had mixed results. The gonadomimetic drug tibolone stimulates estrogen receptors in a tissue-selective fashion, increasing the gonadal activity without causing some of the usual side effects of other estrogen preparations. METHODS: A total of 31 postmenopausal outpatients with a major depressive disorder (MDD) participated in the study. Sixteen received the antidepressant fluoxetine (20 mg/day) plus tibolone (2.5 mg/day), and 15 received the same dose of fluoxetine plus placebo, assigned in a randomized fashion. RESULTS: After 8 weeks of treatment, the two groups had a similar level of improvement in their depressive symptoms. Both treatments were well tolerated, without significant side effects. Pretreatment and posttreatment serum hormonal levels did not predict the final response. CONCLUSIONS: Combining tibolone and fluoxetine did not represent a more robust antidepressant response than fluoxetine alone in postmenopausal women with MDD.

Aged↗
PubMed1999

In vivo nickel allergic contact dermatitis: human model for topical therapeutics.

Techniques to determine efficacy of topical agents on allergic contact dermatitis (ACD) may benefit from refinement. The aim of this study was to develop an in vivo human model system for the bioengineering and visual quantification of the effect of topical agents on nickel ACD, and to correlate ACD parameters. 14 nickel patch-test-positive subjects were included in a placebo-controlled, double-blind study after a pre-screening procedure with a standard diagnostic patch test with nickel sulfate in 54 healthy human volunteers. 5% nickel sulfate in petrolatum in a Finn Chamber was applied on forearm skin for 48 h to create a standardized dermatitis. Thereafter, the dermatitis was treated with a model topical agent and a placebo control while recording endpoint parameters daily for 10 days. Resolution was quantified with 4 parameters: visual scoring (VS), transepidermal water loss (TEWL) (Tewameter), skin blood flow volume (BFV) (laser Doppler flowmeter), and skin color (a* value) (Colorimeter). The model agent reduced cutaneous allergic reactions, especially on day 8 to 10, in comparison with the placebo control. A highly significant linear relationship exists among all parameters, except between a* and BFV. This model may provide robust biometrics for determining the efficacy of topical therapeutics on experimentally induced ACD.

Administration, Cutaneous↗