Pathophysiology and treatment of osteoporosis: challenges for clinical practice in older people.

Osteoporosis, a common chronic metabolic bone disease is associated with considerable morbidity and mortality. As the prevalence of osteoporosis increases with age, a paralleled elevation in the rate of incident fragility fractures will be observed. This narrative review explores the origins of bone and considers physiological mechanisms involved in bone homeostasis relevant to management and treatment. Secondary causes of osteoporosis, as well as osteosarcopenia are discussed followed by an overview of the commonly used pharmacological treatments for osteoporosis in older people.

Effect of Ni content in PdNi/C anode catalysts on power and methanol co-generation in alkaline direct methane fuel cell type.

PdNi electrocatalysts supported on carbon were used as anode materials for methane oxidation in alkaline direct methane fuel cells (ADMEFCs). The electrocatalysts were successfully synthesized by the NaBH4 reduction method. X-ray diffraction measurements showed the formation of non-alloyed Pd in the face- centered cubic (FCC) structure for all materials and formation of NiO and Ni(OH)2 species. TEM images showed that the metal particles are well dispersed on the support with small agglomeration regions. Information about the surface structure of the catalyst were obtained by Raman spectra, mainly confirming the presence of Ni(OH)2. The species observed by DEMS, that is, methanol (m/z = 32), CO2 (m/z = 44) and potassium formate (m/z = 84) were confirmed by FTIR, which also showed the presence of a high amount of carbonate in the methane oxidation products of the ADMEFC with Pd50Ni50/C as the anode catalyst. Tests in ADMEFCs showed that the dependence of the maximum power density on nickel content in the catalysts goes through a maximum value of 13.5 µW cm-2 at 50 at% Ni. Moreover, the amount of produced methanol decreases with increasing Ni content in the PdNi/C catalysts. Both these results can be explained by the enhanced methanol oxidation in the presence of nickel.

First record of Craspedacusta sowerbii Lankester, 1880 (Hydrozoa, Limnomedusae) in a natural freshwater lagoon of Uruguay, with notes on polyp stage in captivity.

The freshwater cnidarian Craspedacusta sowerbii Lankester 1880, has invaded lakes and ponds as well as artificial water bodies throughout the world. The first record in Uruguay corresponding to the jellyfish was made in 1961 in two artificial fountains, with no mention of the polyp form. Although local reports of other related polyp species have been made, information on the benthic form of C. sowerbii is lacking. Here we report the finding of live frustules, solitary individuals, medusae and colonies from a natural lagoon in August 2010, allowing us to observe the morphology and behavior of the polyp stage in captivity. In addition, molecular identification and remarks on the potencial path of introduction are presented. This is the first record in Uruguay of both polyp and medusa stages of C. sowerbii in a natural water body, Del Medio Lagoon (Dpto. de Florida), Uruguay.

Biomonitoring of environmental stress in Pollicipes pollicipes from the northern coast of Portugal: a non-destructive approach using haemolymph.

In the intertidal area, the interactions between anthropogenic contaminants and natural variations (biotic and abiotic factors) are poorly understood. Consequently, there is a great need for new assessment procedures to characterize the biological responses occurring in organisms from this extreme environment. Considering the intrinsic inter-individual variations among organisms from a single population, it is important to propose new methods that address this variability, by validating a sampling strategy in target groups of organisms, encompassing seasonal fluctuations. This strategy must however be less invasive than traditional methods, avoiding the mandatory sacrifice of the sampled organisms. By doing so, it is also possible to increase the ecological relevance of obtainable data, and contribute to minimize damage to endangered species. The main purpose of the present study was to assess the influence of seasonal variations in the responses elicited by anthropogenic compounds on a marine crustacean species, by using a biomarker-based approach. According to this purpose, the seasonal variations in key physiological responses (biomarkers) were investigated in the crustacean Pollicipes pollicipes from the Northern coast of Portugal. Biomarkers used for this purpose were the activity of the phase II biotransformation isoenzymes glutathione-S-transferases (GSTs), the activity of cholinesterases (ChEs), and the levels of lipid peroxidation (TBARS). All biomarkers were quantified in distinct tissues (such as cirri, and peduncle) and haemolymph (a non-destructive source of biological samples). The glycogen content in peduncle tissue, and the variation in haemocyte number in haemolymph were also analyzed. Samples were collected monthly, during a year, in Lavadores, located in the proximity of an estuarine area (Douro River). The results showed a seasonal pattern in all tested biomarkers. The results also showed a significant increase in GSTs activities, and in peroxidative damage, especially during warmer months. The lowest ChEs values were recorded during the rainy season. The results also showed a similar pattern among all tested tissues, validating the proposed use of the haemolymph as a source tissue for non-lethal sampling strategy for biomarker determinations. Glycogen content was apparently related to the reproductive cycle, with lower values being observed in spring and summer. Total haemocyte count (THC) increased during summer months. The results pointed to an influence of natural variations in the levels of biomarkers in P. pollicipes, highly dependent upon abiotic factors, a factor that must be considered when interpreting biological responses elicited by anthropogenic contaminants from the marine coastal environment. The validation of haemolymph as a non-lethal source tissue for the quantification of biomarkers was successfully attained, opening the possibility of less invasive and almost unlimited sampling in a small number of organisms.

Ecotoxicological effect of zinc pyrithione in the freshwater fish Gambusia holbrooki.

Currently diverse biocidal agents can be used for distinct applications, such as personal hygiene, disinfection, antiparasitic activity, and antifouling effects. Zinc pyrithione is an organometallic biocide, with bactericidal, algicidal and fungicidal activities. It has been recently incorporated in antifouling formulas, such as paints, which prevent the establishment of a biofilm on surfaces exposed to the aquatic environment. It has also been used in cosmetics, such as anti-dandruff shampoos and soaps. Previously reported data has shown the presence of this substance in the aquatic compartment, a factor contributing to the potential exertion of toxic effects, and there is also evidence that photodegradation products of zinc pyrithione were involved in neurotoxic effects, namely by inhibiting cholinesterases in fish species. Additional evidence points to the involvement of zinc pyrithione in alterations of metal homeostasis and oxidative stress, in both aquatic organisms and human cell models. The present work assesses the potential ecotoxicity elicited by zinc pyrithione in the freshwater fish Gambusia holbrooki after an acute (96 h) exposure. The oxidative stress was assessed by the quantification of the activities of specific enzymes from the antioxidant defense system, such as catalase, and glutathione-S-transferases; and the extent of peroxidative damage was quantified by measuring the thiobarbituric acid reactive substances levels. Neurotoxicity was assessed through measurement of acetylcholinesterase activity; and a standardized method for the description and assessment of histological changes in liver and gills of was also used. Zinc pyrithione caused non-specific and reversible tissue alterations, both in liver and gills of exposed organisms. However, histopathological indices were not significantly different from the control group. In terms of oxidative stress biomarkers, none of the tested biomarkers indicated the occurrence of pro-oxidative effects, suggesting that the oxidative pathway is not the major toxicological outcome of exposure to zinc pyrithione.

Risk factors, clinical features and outcomes of visceral leishmaniasis in solid-organ transplant recipients: a retrospective multicenter case-control study.

Visceral leishmaniasis (VL) is a rare disease in solid-organ transplant (SOT) recipients. Therefore, little is known about the risk factors and disease behavior in the transplant setting. This multicenter, matched case-control study (1:2 ratio) was designed to determine the risk factors, clinical features and outcomes of VL among this population. Control and case subjects were matched by center, transplant type and timing. Thirty-six VL cases were identified among 25 139 SOT recipients (0.1%). VL occurred 5.7-fold more frequently in Brazil than in Spain, presenting a median time of 11 months after transplantation. High-dose prednisone in the preceding 6 months was associated with VL. Patients were diagnosed over 1 month after symptom onset in 25% of cases. Thirty-one patients (86%) were febrile upon diagnosis, 81% exhibited visceromegaly and 47% showed pancytopenia. Concomitant infection was common. Parasites were identified in 89% of patients; the remaining patients were diagnosed by serology. The majority of the patients received amphotericin B. Relapses occurred in 25.7% of cases, and the crude mortality rate was 2.8%. VL after SOT is related to the VL prevalence in the general population. Delayed diagnosis frequently occurs. Liposomal amphotericin is the most commonly used therapy; mortality is low, although relapses are common.

Ecotoxicological effects of salicylic acid in the freshwater fish Salmo trutta fario: antioxidant mechanisms and histological alterations.

The presence of pharmaceutical drugs in aquatic ecosystems has been widely reported during the past years. Salicylic acid (SA) is mainly used in human medicine as an analgesic and antipyretic drug, being also active in preventing platelet aggregation. To study the ecotoxicological effects potentially elicited by SA in freshwater fish, brown trout individuals (Salmo trutta fario) were chronically exposed (28 days) to this drug, in order to evaluate the enzymatic and histological effects, in both gills and liver. A qualitative and semi-qualitative evaluation of the gills and liver was performed, and also a quantitative evaluation of various lamellar structures. Oxidative stress was quantified trough the determination of glutathione S-transferases (GSTs), glutathione reductase (GRed), total and selenium-dependent glutathione peroxidase (GPx) and Catalase (Cat) activities. Lipid peroxidative damage was also assessed by the quantification of thiobarbituric acid reactive substances (TBARS) in the liver. The here-obtained data showed the occurrence of oxidative stress, reflected by an increased activity of GPx and GRed in the liver; additionally, it was possible to observe non-specific histological changes in gills. The global significance of the entire set of results is discussed, giving emphasis to the ecological relevance of the responses.

Acute effects of tetracycline exposure in the freshwater fish Gambusia holbrooki: antioxidant effects, neurotoxicity and histological alterations.

A large body of evidence was compiled in the recent decades showing a noteworthy increase in the detection of pharmaceutical drugs in aquatic ecosystems. Due to its ubiquitous presence, chemical nature, and practical purpose, this type of contaminant can exert toxic effects in nontarget organisms. Exposure to pharmaceutical drugs can result in adaptive alterations, such as changes in tissues, or in key homeostatic mechanisms, such as antioxidant mechanisms, biochemical/physiological pathways, and cellular damage. These alterations can be monitored to determine the impact of these compounds on exposed aquatic organisms. Among pharmaceutical drugs in the environment, antibiotics are particularly important because they include a variety of substances widely used in medical and veterinary practice, livestock production, and aquaculture. This wide use constitutes a decisive factor contributing for their frequent detection in the aquatic environment. Tetracyclines are the individual antibiotic subclass with the second highest frequency of detection in environmental matrices. The characterization of the potential ecotoxicological effects of tetracycline is a much-required task; to attain this objective, the present study assessed the acute toxic effects of tetracycline in the freshwater fish species Gambusia holbrooki by the determination of histological changes in the gills and liver, changes in antioxidant defense [glutathione S-transferase (GST), catalase (CAT), and lipoperoxidative damage] as well as potential neurotoxicity (acetylcholinesterase activity). The obtained results suggest the existence of a cause-and-effect relationship between the exposure to tetracycline and histological alterations (more specifically in gills) and enzymatic activity (particularly the enzyme CAT in liver and GST in gills) indicating that this compound can exert a pro-oxidative activity.

Effect of acetaminophen exposure in Oncorhynchus mykiss gills and liver: detoxification mechanisms, oxidative defence system and peroxidative damage.

The increasing presence of pharmaceutical drugs in nature is cause of concern due to the occurrence of oxidative stress in non-target species. Acetaminophen is widely used in human medicine as an analgesic and antipyretic drug, and it is one of the most sold non-prescription drugs. The present study aimed to assess the toxic effects of acetaminophen (APAP) in Oncorhynchus mykiss following acute and chronic exposures in realistic levels. In order to evaluate the APAP effects in the rainbow trout, gills and liver were analyzed with biochemical biomarkers, such as catalase (CAT), total and selenium-dependent glutathione peroxidase (GPx), glutathione reductase (GRed) and glutathione-S-transferases (GSTs) activity and also lipid peroxidation levels (TBARS). The results obtained in all tests indicate that a significant response of oxidative stress was established, along with the increase of APAP concentrations. The establishment of an oxidative stress scenario occurred with the involvement of all tested biomarkers, sustaining a generalized set of pro-oxidative effects elicited by APAP. Additionally, the occurrence of oxidative damage strongly suggests the impairment of the antioxidant defense mechanism of O. mykiss. It is important to note that the occurrence of oxidative deleterious effects and peroxidative damages occurred for concentrations similar to those already reported for several freshwater ecosystems. The importance of these assumptions is further discussed under the scope of ecological relevance of the assessment of effects caused by pharmaceuticals in non-target organisms.

The Gooseneck Barnacle (Pollicipes pollicipes) as a candidate sentinel species for coastal contamination.

The assessment of toxic effects caused by complex mixtures of contaminants in the marine environment requires previous validation of toxicological criteria, which may include biomarker end points with distinct biological meanings. This is the case of oxidative stress/phase II detoxification (glutathione-S-transferases activity), oxidative damage (thiobarbituric acid reactive substances), and neurotransmission (cholinesterase activity), which are likely to be affected after toxic insults by common marine pollutants. The main purpose of the present study was to assess potential biological alterations in the mollusk species Pollicipes pollicipes (gooseneck barnacle) caused by human contamination and seasonality, during a period of 1 year, in three different areas of the North Atlantic shore of Portugal. Our results indicate that fluctuations of the mentioned biomarkers were strongly related to seasonality, but they may also suffer influence by the already documented patterns of chemical contamination. Organisms collected in contaminated sampling sites (urban areas and oil refinery) showed greater levels of metabolic enzymes and increased levels of lipid peroxidation. These alterations were more evident during the summer, and, in some cases, spring months, suggesting an association between the presence of chemical stressors and temperature-dependent seasonal physiological fluctuations, which contribute to the modulation of the toxic response. In general terms, P. pollicipes was shown to be a promising organism in coastal biomonitoring programs, with an adequate sensitivity toward contamination and/or seasonal fluctuations. However, it is of the utmost importance to consider seasonal fluctuations in physiological parameters that modulate the toxic response. These factors can ultimately compromise the development and interpretation of data from marine biomonitoring programs if a thorough characterization of biological responses is not previously performed.

An efficient strategy to detect latent fingermarks on metallic surfaces.

The aim of this work is to use metal sputtering for the development of latent fingermarks on metallic surfaces by taking advantage of the prints' topography. In order to promote the preferential deposition onto fingerprints' ridges the deposition parameters should be optimized. After a previous selection, copper and gold thin films were deposited by magnetron sputtering onto stainless steel substrates where fingermarks were intentionally placed. After optimizing the deposition parameters, the influence of the fingermarks' age was studied. The quality of the developed fingermarks was evaluated visually and through optical and scanning electron microscopy. The morphology of the copper and gold thin films was examined by high resolution scanning electron microscopy. The preferential magnetron sputtering deposition of copper and gold thin films, 20-30 nm thick, allows latent fingermarks to be successfully developed. The gold films are more promising, especially for detecting non-fresh fingermarks and for conserving the developed marks. It was possible to detect the contours of the ridges and localize minutiae features in a one-month aged impression developed by gold deposition. These films present discontinuous surface and columnar cross-sections, while copper thin films have a featureless morphology.

TEM characterization of As-deposited and annealed Ni/Al multilayer thin film.

Reactive multilayer thin films that undergo highly exothermic reactions are attractive choices for applications in ignition, propulsion, and joining systems. Ni/Al reactive multilayer thin films were deposited by dc magnetron sputtering with a period of 14 nm. The microstructure of the as-deposited and heat-treated Ni/Al multilayers was studied by transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM) in plan view and in cross section. The cross-section samples for TEM and STEM were prepared by focused ion beam lift-out technique. TEM analysis indicates that the as-deposited samples were composed of Ni and Al. High-resolution TEM images reveal the presence of NiAl in small localized regions. Microstructural characterization shows that heat treating at 450 and 700°C transforms the Ni/Al multilayered structure into equiaxed NiAl fine grains.

Ti/Al nanolayered thin films.

Ti/Al multilayer thin films with modulation periods up to 100 nm were characterised at the nanoscale level. The Ti/Al multilayers were deposited onto stainless steel substrates by magnetron sputtering from Ti and Al targets. Time on flight secondary ion mass spectroscopy analyses were carried out in order to verify the layered structure and check both the effect of contaminants such as oxygen and the intermixing at the interfaces. Structural analyses were performed by X-ray diffraction and transmission electron microscopy. The deposition procedure gives rise to a nanometric multilayer structure, where elemental Ti and Al can be identified, even for the lowest period multilayer (4 nm). The multilayer films consist of a-Ti plus Al with nanometric grain sizes. The grain size is determined by the multilayer modulation period, having both similar values. In the as-deposited state no intermetallic compounds were detected. During the deposition process some intermixing occurred at the interfaces, which should assume some importance in decreasing the heat of the exothermic reaction between Ti and Al, particularly as the modulation period decreases.

Specific aspects of erectile dysfunction in spinal cord injury.

According to preliminary studies, the overall incidence of spinal cord injury (SCI; traumatic and medical) in Spain is estimated to be between 12 and 20 per million inhabitants, and almost 80% of these injuries occur in young men. SCI causes organic changes in men leading to erectile dysfunction (ED), impaired ejaculation, and changes in genital orgasmic perception. A vast majority of men with both complete and incomplete SCI will require treatment for ED, and the therapeutic options should include sexual counseling so that the patient can be informed about his disorder and can adjust his sexual behavior accordingly. The first-line treatment of choice is oral drugs, such as phosphodiesterase inhibitors (sildenafil, tadalafil, and vardenafil). Sildenafil has been shown to be highly effective and well tolerated in men with ED of various etiologies, including SCI. Data are also presented on sublingual apomorphine, which has limited indications for the treatment of ED in SCI, and on constrictive rings and vacuum systems. Second-line treatments include intracavernous injections of prostaglandin E(1), papaverine, and phentolamine, alone or in combination, which have been shown to be highly effective in the treatment of ED in men with SCI. Finally, for third-line treatments, the indications for surgical methods are given, including penile prostheses and neuroprosthesis of anterior sacral roots. These devices should be reserved for the cases when the above-mentioned methods have repeatedly failed. Historically, the treatment of ED among patients with SCI has been managed by clinicians in physical medicine and rehabilitation. Thus, the criteria for referral and the competencies of these specialists are established, and they should be included as an integral part of the rehabilitation program.

Biological evaluation of recombinant human erythropoietin in pharmaceutical products

The potencies of mammalian cell-derived recombinant human erythropoietin pharmaceutical preparations, from a total of five manufacturers, were assessed by in vivo bioassay using standardized protocols. Eight-week-old normocythemic mice received a single subcutaneous injection followed by blood sampling 96 h later or multiple daily injections with blood sampling 24 h after the last injection. Reticulocyte counting by microscopic examination was employed as the end-point using the brilliant cresyl blue or selective hemolysis methods, together with automated flow cytometry. Different injection schedules were investigated and dose-response curves for the European Pharmacopoeia Biological Reference Preparation of erythropoietin were compared. Manual and automated methods of reticulocyte counting were correlated with respect to assay validity and precision. Using 8 mice per treatment group, intra-assay precision determined for all of the assays in the study showed coefficients of variation of 12.1-28.4 percent for the brilliant cresyl blue method, 14.1-30.8 percent for the selective hemolysis method and 8.5-19.7 percent for the flow cytometry method. Applying the single injection protocol, a combination of at least two independent assays was required to achieve the precision potency and confidence limits indicated by the manufacturers, while the multiple daily injection protocol yielded the same acceptable results within a single assay. Although the latter protocol using flow cytometry for reticulocyte counting gave more precise and reproducible results (intra-assay coefficients of variation: 5.9-14.2 percent), the well-characterized manual methods provide equally valid alternatives for the quality control of recombinant human erythropoietin therapeutic products.

Biological evaluation of recombinant human erythropoietin in pharmaceutical products.

The potencies of mammalian cell-derived recombinant human erythropoietin pharmaceutical preparations, from a total of five manufacturers, were assessed by in vivo bioassay using standardized protocols. Eight-week-old normocythemic mice received a single subcutaneous injection followed by blood sampling 96 h later or multiple daily injections with blood sampling 24 h after the last injection. Reticulocyte counting by microscopic examination was employed as the end-point using the brilliant cresyl blue or selective hemolysis methods, together with automated flow cytometry. Different injection schedules were investigated and dose-response curves for the European Pharmacopoeia Biological Reference Preparation of erythropoietin were compared. Manual and automated methods of reticulocyte counting were correlated with respect to assay validity and precision. Using 8 mice per treatment group, intra-assay precision determined for all of the assays in the study showed coefficients of variation of 12.1-28.4% for the brilliant cresyl blue method, 14.1-30.8% for the selective hemolysis method and 8.5-19.7% for the flow cytometry method. Applying the single injection protocol, a combination of at least two independent assays was required to achieve the precision potency and confidence limits indicated by the manufacturers, while the multiple daily injection protocol yielded the same acceptable results within a single assay. Although the latter protocol using flow cytometry for reticulocyte counting gave more precise and reproducible results (intra-assay coefficients of variation: 5.9-14.2%), the well-characterized manual methods provide equally valid alternatives for the quality control of recombinant human erythropoietin therapeutic products.

Sexually transmitted diseases in the elderly. Review of 28 cases.

Sir, People over the age of 65 represent an increasingly large proportion of the population. In fact, ageing brings about some decrease in sexual arousal and activity [1] related to physical illness or medication needed to control a health condition [2]. Nevertheless, it is encouraging to find out that many elderly continue to be sexually active until their sixties, seventies and even eighties [3]. Information concerning the incidence of sexually transmitted infections in old people is sparse. Six retrospective studies have been published before [4-9]. They confirmed that the incidence of sexually transmitted diseases in patients over 65 years was significant for both newly acquired disease and for residual complications. Beyond that, there are sporadic case reports of HIV infection in older persons [10, 11], emphasising the persistence of risk behaviour in this population.

Morphology of the testis of the one-humped camel in relation to reproductive activity.

Histological and morphometric studies on the camel testis have been carried out systematically at regular monthly intervals during a period of one year. The testicular weight was minimal during summer, while the maximum weight was attained during the coldest months from November until March. Diameters of the seminiferous tubules were multiphasic with a tendency to be wider during summer. The ratio of the area occupied by seminiferous tubules to that occupied by interstitial tissue revealed that the latter occupied a larger area than that of the seminiferous tubules during winter, while a reversed relationship occurred from March onwards and was especially marked after April, i.e. in summer. In addition, spermatogenesis was noted in all testes examined throughout the year; however, there was a difference in the quality and quantity of spermatogenic cells between the monthly groups evaluated. November, December and January were the months in which spermatogenic activity was most striking. A correlation was established between testicular weight, amount and quality of testicular interstitial tissue, spermatogenesis and epididymal sperm content and, hence, testicular function on the one hand and season of the year on the other hand. The cyclic structural changes in the testis appeared to be in parallel with the rutting activity of the camel. It was suggested also that the camel is not a typical seasonal breeder as it does not go through sexual quiescence. The reproductive activity of the camel builds up during September and October, and the animal is in actual rut during November, December, January and February, with a drop in March and thereafter.