Low bone mineral density and associated factors in patients with haemophilia in Colombia.

INTRODUCTION: Patients with haemophilia may have lower levels of bone mineral density (BMD) compared with the general population. Moreover, haemophilic patients have increased risk factors for low bone mineral density (LBMD) such as arthropathy and resulting immobility, increasing their risk for osteoporosis and fractures. AIM: To assess the prevalence of LBMD and associated risk factors among a group of Colombian haemophilic patients. METHODS: In this case-control study, 90 patients with haemophilia A and B, over the age of five, were recruited. Controls were healthy participants matched by age, gender, body mass index (BMI), socioeconomic status, and race. All participants underwent dual energy X-ray absorptiometry (DXA) and the Global Physical Activity Questionnaire. Blood tests were collected to evaluate LBMD determinants in cases. RESULTS: BMD was lower in cases than in the control group. BMD of femoral necks was 0.907 g/cm2 in cases vs. 1.020 g/cm2 in controls (P = .019), and BMD of hips 0.930 g/cm2 in cases vs. 1030 g/cm2 in controls (P = .019). The greater the severity of haemophilia, the lower BMD in spine, femoral neck, and hips. Elevated C-protein levels were found in 44.1% of patients with LBMD and 14.8% with normal BMD (P = .003). The study found an adjusted prevalence ratio of 2.11, indicating that haemophilic patients are two times more likely to have LBMD (CI95% = 1.43-3.11 P < .001). CONCLUSION: Results from the present study showed that haemophilia was associated with a higher frequency of LBMD. Severity of haemophilia, haemophilic arthropathy, and elevated C-reactive protein levels was directly associated with LBMD.

The skin-depigmenting potential of Paeonia lactiflora root extract and paeoniflorin: in vitro evaluation using reconstructed pigmented human epidermis.

OBJECTIVE: The roots of the herb Paeonia lactiflora ('White Peony') are used in association with other herbs in traditional clinical cosmetic practice in China as oral treatment for skin pigmentary disorders, such as brown or dark pigmentary spots. However, the skin-depigmenting potential of Paeonia lactiflora root extract and its main ingredient paeoniflorin has been scarcely investigated by topical application. The purpose of this study was to evaluate the efficacy of Paeonia lactiflora root extract and paeoniflorin as skin whitening agent in cosmetic application. METHODS: Paeonia lactiflora root extract (containing 53.25% of paeoniflorin) and paeoniflorin (97% purity) were applied topically on reconstructed pigmented human epidermis model, a three-dimensional (3D) human skin equivalent, showing morphological and functional characteristics similar to those of in vivo human skin. Two specific methods were used for quantifying melanin inside the reconstructed pigmented epidermis: Fontana-Masson staining (2D quantification) and multiphoton microscopy (3D quantification). RESULTS: Compared to vehicle (dimethyl sulfoxide DMSO), a significant decrease in 2D and 3D melanin content was observed after topical application on reconstructed pigmented epidermis of Paeonia lactiflora extract at 300 µg mL(-1) (-28% and -27%, respectively) and paeoniflorin at 120 µg mL(-1) /250 µM (-30% and -23%, respectively), which is in the same order of magnitude as the positive reference 4-n-butylresorcinol at 83 µg mL(-1) /500 µM (-26% and -40%, respectively). CONCLUSION: These results demonstrate, for the first time, the depigmenting potential of paeoniflorin and thus the potential interest of using Paeonia lactiflora root extracts containing paeoniflorin in cosmetic or dermatological applications for reducing the severity of some hyperpigmented skin disorders.

Non-invasive short-term assessment of retinoids effects on human skin in vivo using multiphoton microscopy.

BACKGROUND: The occlusive patch test developed for assessing topical retinoids activity in human skin has been extended as a short-term screening protocol for anti-ageing agents. In this model, biopsies are performed at the end of the occlusion period for morphological and immuno-histochemistry analysis. Multiphoton microscopy is a recent non-invasive imaging technique that combined with image processing tools allows the in vivo quantification of human skin modifications. OBJECTIVE: To validate with gold standards of anti-ageing that are retinoids, the relevance of multiphoton microscopy for kinetic and quantitative assessment in this model. METHODS: Twenty women, aged 50-65 years, were enrolled. Retinol 0.3% (RO) and Retinoic acid 0.025% (RA) were applied to the dorsal photo-damaged side of their forearm under occlusive patches for 12 days. A patch alone was applied to a third area as control. Evaluation was performed at day D0, D12 (end of treatment), D18 and D32 using multiphoton microscopy. Epidermal thickness, normalized area of the dermal-epidermal junction (DEJ) and melanin density were estimated using 3D image processing tools. RESULTS: Main significant results are: Epidermal thickening at D12, D18 and D32 with RO and at D12, D18 with RA vs. baseline and vs. CONTROL: Increased DEJ undulation at D32 with RO and at D12 with RA vs. baseline and vs. CONTROL: Decreased melanin content with RO (at D12 and D18 vs. baseline and at D32 vs. baseline and vs. control) and with RA (at D12 vs. baseline). CONCLUSIONS: This study shows that multiphoton microscopy associated to specific 3D image processing tools allows cutaneous effects induced by topical retinoids in this in vivo model to be non-invasively detected, quantified and followed over time. This innovative approach could be applied to the evaluation of other active compounds.

Adenosine 5'-monophosphate in asthma: gas exchange and sputum cellular responses.

Adenosine 5'-monophosphate (AMP) bronchoprovocation reproduces the lung function abnormalities that occur spontaneously during acute asthma and detects peripheral airway inflammation better than direct bronchoconstrictive agents. Pulmonary gas exchange disturbances may reflect changes in small airways related to airway inflammation rather than bronchoconstriction alone. The present authors investigated whether AMP induced a greater imbalance in the ventilation/perfusion ratio than methacholine (MCh), at an equivalent degree of bronchoconstriction, with and without salbutamol pre-medication. In total, 36 asthmatics were studied in three randomised, double-blind, crossover studies: 1) before and after AMP or MCh; 2) before and 30 min after salbutamol or placebo, followed by AMP; or 3) MCh challenge. Sputum was collected before and 4 h post-challenge. Compared with MCh, AMP provoked similar pulmonary gas exchange abnormalities at an equivalent degree of intense bronchoconstriction (forced expiratory volume in one second decrease of 28-44%). While salbutamol blocked AMP- or MCh-induced bronchoconstriction, arterial oxygen tension (P(a,O(2))) and alveolar-arterial oxygen tension difference (P(A-a,O(2))) disturbances induced by AMP and MCh were only partially blocked (P(a,O(2)) by 46 and 42%, respectively; P(A-a,O(2)) by 58 and 57%, respectively). Compared with MCh, AMP increased the percentage of neutrophils (mean+/-se increased from 28+/-4% to 38+/-4%), but this increase did not occur after salbutamol pre-treatment. Both adenosine 5'-monophosphate and methacholine induced similar peripheral airway dysfunction. The fully inhibited adenosine 5'-monophosphate-induced neutrophilia with residual hypoxaemia observed after salbutamol treatment is probably related to beta(2)-agonists acting on both bronchial and pulmonary circulation.

Second harmonic imaging and scoring of collagen in fibrotic tissues.

We compare second harmonic generation (SHG) to histological and immunohistochemical techniques for the visualization and scoring of collagen in biological tissues. We show that SHG microscopy is highly specific for fibrillar collagens and that combined SHG and two-photon excited fluorescence (2PEF) imaging can provide simultaneous three-dimensional visualization of collagen synthesis and assembly sites in transgenic animal models expressing GFP constructs. Finally, we propose several scores for characterizing collagen accumulation based on SHG images and appropriate for different types of collagen distributions. We illustrate the sensitivity of these scores in a murine model of renal fibrosis using a morphological segmentation of the tissue based on endogenous 2PEF signals.

Downstaging of bilobar hepatocellular carcinoma after radioembolization with 90Y microspheres as a bridge to liver transplantation. / Downstaging de carcinoma hepatocelular bilobar tras radioembolización con microesferas de 90Y como puente al trasplante hepático.

Hepatic radioembolization with 90Y is an increasingly widely used locoregional therapy in the treatment of hepatocellular carcinoma. Its potential benefit has recently been described as a downstaging treatment, achieving a decreased tumour burden and allowing patients to be rescued for more radical treatments, such as liver transplantation. The case is presented of a patient diagnosed with multifocal bilobar hepatocellular carcinoma, Barcelona Clinic Liver Cancer (BCLC) intermediate stage, in whom treatment with 90Y achieved a satisfactory radiological response with a very significant reduction of tumour burden, allowing rescue with liver transplantation.

Simultaneous fluorimetric determination of acetylsalicylic acid metabolites in urine by partial least squares multivariate calibration.

A method is described for the simultaneous determination of the main urinary acetylsalicylic acid (aspirin) metabolites, salicyclic, salicyluric and gentisic acids, based on their native fluorescence. The urine was extracted into diethyl ether in acid medium, and back-extracted with glycine/sodium hydroxide buffer solution at pH 9.4. A comparative study of the results found using the excitation, the emission and the combination of the excitation plus the emission spectral data, as analytical signals, was performed. The data set, composed of the excitation plus the emission spectra, was selected as the analytical signal. The optimum wavelengths to record the excitation (lambda(em)=444 nm) and the emission spectra (lambda(ex)=323 nm) were selected to maximize the contribution from gentisic acid, which is the minor urinary metabolite. Partial least squares (PLS-1) multivariate calibration was then applied for the determination. Recovery values from urine samples spiked with salicyclic, salicyluric and gentisic acids varied from 90.1 to 97.6% (mean 93.6%), from 90.0 to 110% (mean 97.9%) and from 89.9 to 104.7% (mean 98.5%), respectively.

Phototautomerism in the lowest excited singlet state of 1-hydroxy-2-carboxyanthraquinone.

The dependence of the absorption and fluorescence spectra of 1-hydroxy-2-carboxy-anthraquinone on pH and Hammett acidity have been studied. This compound exhibits phototautomerism in its uncharged and its singly-charged anionic species in aqueous media. Its ground state (pK(a)) and lowest excited singlet-state (pK(a)( *)) dissociation constants have been determined by absorptiometric and fluorimetric titrations and the assignment of the pK(a) and pK( *)(a) values to the equilibria concerned has been carefully considered.

Host-guest stabilized room temperature phosphorescence in beta-cyclodextrin/ bromoalcohol solutions from 2-naphthyl-oxy-acetic acid and 1-naphthyl-acetic acid.

Room temperature phosphorescence (RTP) from 2-naphthyl-oxy-acetic acid (NOA) and 1-naphthyl-acetic acid (NAA), with stabilization by use of beta-cyclodextrin (beta-CD) as a host system, has been examined. 2-Bromoethanol and 2,3-dibromopropanol have been evaluated as external heavy atom perturbers to enhance the rate of intersystem crossing and, consequently, populating the triplet state for phosphorescence emission. The deoxygenation of the solutions was achieved chemically by use of sodium sulphite. The spectral characteristics of the phosphorescence emission from these relatively polar compounds and the optimization of the chemical variables involved are reported. The role of the bulkiness of the bromoalcohol employed, in comparison with the unoccupied space of the interior of the cyclodextrin cavity by the guest, is an important factor in the attainment of an effective RTP emission, and should be taken into account in the selection of the appropriate external heavy atom for the observation of RTP from other organic molecules of interest by this approach. 2,3-Dibromopropanol seems a more adequate bromoalcohol than 2-bromoethanol for the observation of RTP emission in the systems investigated.

Cardiac conduction disturbances in mixed connective tissue disease.

BACKGROUND: Myocardial involvement occurs in about 20% of patients with mixed connective tissue disease. The purpose of this study was to determine the prevalence of conduction disturbances, their association with other manifestations of the disease. OBJECTIVE: Determine the prevalence of cardiac conduction disturbances in patients with mixed connective tissue disease attended in an institute in Mexico City and their relation with other manifestations of the disease. METHODS: One hundred thirteen patients admitted to the Institute with a diagnosis of mixed connective tissue disease were divided into those with conduction disturbances (n = 23) and those without (n = 90). Over a mean follow-up of 10.2 +/- 7.8 years, clinical course, treatment, duration of the disease, types of conduction disturbances and systemic alterations were examined. RESULTS: There was an overwhelming predominance of women in both groups. Conduction disturbances occurred in about 20% of the patients with mixed connective tissue disease and that was not possible to find significant differences in the outcome of them. As could be expected a significant difference between the two groups was QRS axis, related to anterior hemiblock, the most common conduction alteration observed. During the follow-up one patient death in-group A, but none in group B. CONCLUSION: Conduction disturbances were present in 20%; in agree with other authors in the literature. However, did not participate in the outcome of the disease.

Single-shot diffractive imaging with a table-top femtosecond soft x-ray laser-harmonics source.

Coherent x-ray diffractive imaging is a powerful method for studies on nonperiodic structures on the nanoscale. Access to femtosecond dynamics in major physical, chemical, and biological processes requires single-shot diffraction data. Up to now, this has been limited to intense coherent pulses from a free electron laser. Here we show that laser-driven ultrashort x-ray sources offer a comparatively inexpensive alternative. We present measurements of single-shot diffraction patterns from isolated nano-objects with a single 20 fs pulse from a table-top high-harmonic x-ray laser. Images were reconstructed with a resolution of 119 nm from the single shot and 62 nm from multiple shots.

Micrometer scale ex vivo multiphoton imaging of unstained arterial wall structure.

BACKGROUND: We characterize the application of multiphoton microscopy to the observation of the extracellular matrix of fresh unstained vessels. METHOD: Combined two-photon-excited fluorescence (2PEF) and second harmonic generation (SHG) imaging of large arteries reveals the architecture of elastin and collagen fibers in the vessel wall with remarkable specificity. RESULTS: We present elastin/collagen imaging in unstained rat vessels at both micrometer and whole vessel scales, and we characterize the optical properties of rat carotid artery and aorta walls. We apply this method to evidence deleterious effects of residual doses of a pesticide on the vessel wall. CONCLUSION: This study illustrates the potential of 2PEF/SHG microscopy for pharmacological studies in unlabeled arteries.

Dandy-Walker syndrome without hydrocephalus in an adult.

It is commonly believed that Dandy-Walker malformation is due to increased intracranial pressure resulting from atresia of the foramina of the fourth ventricle, but this is not true in all cases. An adult with asymptomatic Dandy-Walker malformation without hydrocephalus was studied. Increased intracranial pressure could not have caused the malformation in the posterior fossa in this case since no hydrocephalus was present. The findings in this case support the view that Dandy-Walker malformation is due to congenital abnormalities that are not necessarily related to obstruction of CSF flow from the fourth ventricular foramina.

Radiological investigation of sellar region masses in children.

The treatment and prognosis of sellar region masses in children differ according to the type of tumor, and thus accurate determination of the extent and characteristics of the lesion is important. Evaluation by conventional skull radiography, complex-motion tomography, radionuclide imaging, computed tomography, cerebral air studies, and cerebral angiography has demonstrated definable characteristics of the various types of tumors and often allows distinction from benign processes.

Psychometric differentiation of psychogenic and organic erectile disorders.

A study was conducted to assess the discriminant validity of patient responses to a questionnaire in distinguishing between organic and psychogenic erectile dysfunction. A total of 56 urologist-referred veterans slept for 3 nights in a sleep laboratory for nocturnal penile tumescence recording. Based on nocturnal penile tumescence results 48 patients were assigned to an organic group and the remaining 8 were assigned to a psychogenic group. A discriminant function analysis of questionnaire responses yielded a highly significant discriminant function [chi-square (19) equals 63.88, p less than 10(-6)], and all 56 patients were classified correctly into the nocturnal penile tumescence-defined organic and psychogenic groups. It was concluded that verbally reported data contain diagnostically meaningful information and that such information can compare favorably with information collected through standard laboratory-based nocturnal penile tumescence techniques.