Therapeutic Treatments for Osteoporosis—Which Combination of Pills Is the Best among the Bad?

Osteoporosis is a chronical, systemic skeletal disorder characterized by an increase in bone resorption, which leads to reduced bone density. The reduction in bone mineral density and therefore low bone mass results in an increased risk of fractures. Osteoporosis is caused by an imbalance in the normally strictly regulated bone homeostasis. This imbalance is caused by overactive bone-resorbing osteoclasts, while bone-synthesizing osteoblasts do not compensate for this. In this review, the mechanism is presented, underlined by in vitro and animal models to investigate this imbalance as well as the current status of clinical trials. Furthermore, new therapeutic strategies for osteoporosis are presented, such as anabolic treatments and catabolic treatments and treatments using biomaterials and biomolecules. Another focus is on new combination therapies with multiple drugs which are currently considered more beneficial for the treatment of osteoporosis than monotherapies. Taken together, this review starts with an overview and ends with the newest approaches for osteoporosis therapies and a future perspective not presented so far.     

Functional significance of the cell volume for detecting sperm membrane changes and predicting freezability in dog semen

Due to the similarity of plasma membrane changes induced by capacitation and cryopreservation, the parameters describing sperm response to capacitating conditions can be used for evaluating the cryopreservation response in many animal systems. In dog sperm, the response of the total sperm population to ionophore treatment has been shown to be an indication of the freezability of semen samples. Another sperm functional characteristic decisive for cryopreservability is cell volume regulation, due to the generation of essential osmotic gradients across the plasma membrane during the freeze-thaw cycles. In the present study, cryopreservation-induced changes in the membrane functional integrity were examined by monitoring the osmotically induced response of cell volume and the response to an ionophore in live cell populations. Cell volume measurements were performed on Percoll-washed suspensions of freshly diluted and frozen-thawed dog spermatozoa. The proportion of live acrosome-reacted cells was evaluated by flow cytometry after incubation under capacitating conditions in the presence of the calcium ionophore, A23187. During freezing-thawing, significant membrane changes occurred related to the disturbance of volume control ability and the loss of a proportion of live acrosome-reacted cells (P < 0.05). There were significant differences between individuals with respect to the degree of functional and structural membrane changes after thawing. Significant correlations were found between acrosomal integrity and functional membrane integrity. When assessed in freshly diluted semen, these parameters correlated with those of frozen-thawed semen samples, pointing to the similarities between mechanisms of cryopreservation-related changes and those mechanisms that mediate changes in membrane permeabilities and in cell volume regulation. The detection of changes in the sperm plasma membrane by monitoring the sperm cell volume represents a simple, rapid and sensitive method to estimate sperm quality after the cryopreservation procedure. The individual variability in response to osmotic stress or to calcium ionophore treatment appears to reflect the subtle differences in the sperm membrane functionality which are crucial for the prediction of cryopreservability.     

Arteriovenous Malformations—Current Understanding of the Pathogenesis with Implications for Treatment

Arteriovenous malformations are a vascular anomaly typically present at birth, characterized by an abnormal connection between an artery and a vein (bypassing the capillaries). These high flow lesions can vary in size and location. Therapeutic approaches are limited, and AVMs can cause significant morbidity and mortality. Here, we describe our current understanding of the pathogenesis of arteriovenous malformations based on preclinical and clinical findings. We discuss past and present accomplishments and challenges in the field and identify research gaps that need to be filled for the successful development of therapeutic strategies in the future.     

Economical and ecological comparison of granular activated carbon (GAC) adsorber refill strategies

Technical constraints can leave a considerable freedom in the design of a technology, production or service strategy. Choosing between economical or ecological decision criteria then characteristically leads to controversial solutions of ideal systems. For the adaptation of granular-activated carbon (GAC) fixed beds, various technical factors determine the adsorber volume required to achieve a desired service life. In considering carbon replacement and recycling, a variety of refill strategies are available that differ in terms of refill interval, respective adsorber volume, and time-dependent use of virgin, as well as recycled GAC. Focusing on the treatment of contaminant groundwater, we compare cost-optimal reactor configurations and refill strategies to the ecologically best alternatives. Costs and consumption of GAC are quantified within a technical-economical framework. The emissions from GAC production out of hard coal, transport and recycling are equally derived through a life cycle impact assessment. It is shown how high discount rates lead to a preference of small fixed-bed volumes, and accordingly, a high number of refills. For fixed discount rates, the investigation reveals that both the economical as well as ecological assessment of refill strategies are especially sensitive to the relative valuation of virgin and recycled GAC. Since recycling results in economic and ecological benefits, optimized systems thus may differ only slightly.     

Ultrastructural characteristics of ovine bone marrow‐derived mesenchymal stromal cells cultured with a silicon stabilized tricalcium phosphate bioceramic

Bioceramics are being used in experimental bone engineering application in association with bone marrow derived mesenchymal stem cells (BM‐MSCs) as a new therapeutic tool, but their effects on the ultrastructure of BM‐MSCs are yet unknown. In this study we report the morphological features of ovine (o)BM‐MSCs cultured with Skelite, a resorbable bioceramic based on silicon stabilized tricalcium phosphate (SiTCP), able to promote the repair of induced bone defect in sheep model. oBM‐MSCs were isolated from the iliac crest, cultured until they reached near‐confluence and incubated with SiTCP. After 48 hr the monolayers were highly damaged and only few cells adhered to the plastic. Thus, SiTCP was removed, and after washing the cells were cultured until they became confluent. Then, they were trypsinizated and processed for transmission electron microscopy (TEM) and RT‐PCR analysis. RT‐PCR displayed that oBM‐MSCs express typical surface marker for MSCs. TEM revealed the presence of electron‐lucent cells and electron‐dense cells, both expressing the CD90 surface antigen. The prominent feature of electron‐lucent cells was the concentration of cytoplasmic organelles around the nucleus as well as large surface blebs containing glycogen or profiles of endoplasmic reticulum. The dark cells had a multilocular appearance by the presence of peripheral vacuoles. Some dark cells contained endocytic vesicles, lysosomes, and glycogen aggregates. oBM‐MSCs showed different types of specialized interconnections. The comparison with ultrastructural features of untreated oBM‐MSCs suggests the light and dark cells are two distinct cell types which were differently affected by SiTCP bioceramic. Skelite cultured ovine BM‐MSCs display electron‐dense and electron‐lucent cells which are differently affected by this bioceramic. This suggests that they could play a different role in bioceramic based therapy.     

Total Urban Water Cycle Models in Semiarid Environments��Quantitative Scenario Analysis at the Area of San Luis Potosi, Mexico

Systems view thinking and holistic urban water cycle concepts are increasingly called upon for integrated analysis of urban water systems to mitigate water stress in large urban agglomerations. However, integrated analysis is frequently not applied due to the inherent complexity, limitations in data availability and especially the lack of guidelines and suitable software tools. The paper presents the application of the total urban water balance model UVQ to the City of San Luis Potosi (1.2 Mio inhabitants) under the arid conditions of Northern Mexico. UVQ is a lumped parameter model which describes water and contaminant flows from source to sink in urban areas and includes all water types such as rainwater, imported water, surface runoff, wastewater and groundwater. The results were especially useful for spatially explicit groundwater recharge calculation in urban areas. A range of urban water scenarios, including different supply strategies and the effect of externalities such as demand change, were simulated and compared to a calibrated baseline scenario. The analysis demonstrated that shallow urban groundwater resources can substantially mitigate problems of water scarcity and overexploitation of deep aquifers if appropriate water quality protection or fit-for-use paradigms are put into place. The modelling exercise delivers relevant information for the decision making process and identifies the most relevant shortcomings in current monitoring systems. This represents a key step on the path to water sensitive and sustainable urban development, including the urban aquifers which have been neglected in the management policy of most cities of the Mexican arid zone.     

Effect of Glucans from Caripia montagnei Mushroom on TNBS-Induced Colitis

In this study, we evaluated the effect of different doses of polysaccharides extracted from Caripia montagnei mushroom at different intervals of treatment on colonic injury in the model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The FT-IR analysis and NMR showed that the polysaccharides from this species of mushroom are composed of α- and β-glucans. The colonic damage was evaluated by macroscopic, histological, biochemical and immunologic analyses. The results showed the reduction of colonic lesions in all groups treated with the glucans. Such glucans significantly reduced the levels of IL-6 (50 and 75 mg/kg, p < 0.05), a major inflammatory cytokine. Biochemical analyses showed that the glucans from C. montagnei acted on reducing levels of alkaline phosphatase (75 mg/kg, p < 0.01) and myeloperoxidase (p < 0.001), a result confirmed by the reduction of cellular infiltration observed microscopically. The increase of catalase activity possibly indicates a protective effect of these glucans on colonic tissue, confirming their anti-inflammatory potential.     

Freshwater Plants Synthesize Sulfated Polysaccharides: Heterogalactans from Water Hyacinth (Eicchornia crassipes)

Sulfated polysaccharides (SP) are found mainly in seaweeds and animals. To date, they have only been found in six plants and all inhabit saline environments. Furthermore, there are no reports of SP in freshwater or terrestrial plants. As such, this study investigated the presence of SP in freshwaters Eichhornia crassipes, Egeria densa, Egeria naja, Cabomba caroliniana, Hydrocotyle bonariensis and Nymphaea ampla. Chemical analysis identified sulfate in N. ampla, H. bonariensis and, more specifically, E. crassipes. In addition, chemical analysis, FT-IR spectroscopy, histological analysis, scanning electron microscopy (SEM) and energy-dispersive X-ray analysis (EDXA), as well as agarose gel electrophoresis detected SP in all parts of E. crassipes, primarily in the root (epidermis and vascular bundle). Galactose, glucose and arabinose are the main monosaccharides found in the sulfated polysaccharides from E. crassipes. In activated partial thromboplastin time (APTT) test, to evaluate the intrinsic coagulation pathway, SP from the root and rhizome prolonged the coagulation time to double the baseline value, with 0.1 mg/mL and 0.15 mg/mL, respectively. However, SP from the leaf and petiole showed no anticoagulant activity. Eichornia SP demonstrated promising anticoagulant potential and have been selected for further studies on bioguided fractionation; isolation and characterization of pure polysaccharides from this species. Additionally in vivo experiments are needed and are already underway.