Biological Treatment Approaches Research Articles

Microbial mats as a biological treatment approach for saline wastewaters: the case of produced water from hydraulic fracturing.

Treatment of produced water, i.e. wastewater from hydraulic fracturing, for reuse or final disposal is challenged by both high salinity and the presence of organic compounds. Organic compounds in produced water may foul physical-chemical treatment processes or support microbial corrosion, fouling, and sulfide release. Biological approaches have potential applications in produced water treatment, including reducing fouling of physical-chemical treatment processes and decreasing biological activity during produced water holding; however, conventional activated sludge treatments are intolerant of high salinity. In this study, a biofilm treatment approach using constructed microbial mats was evaluated for biodegradation performance, microbial community structure, and metabolic potential in both simulated and real produced water. Results demonstrated that engineered microbial mats are active at total dissolved solids (TDS) concentrations up to at least 100,000 mg/L, and experiments in real produced water showed a biodegradation capacity of 1.45 mg COD/gramwet-day at a TDS concentration of 91,351 mg/L. Additionally, microbial community and metagenomic analyses revealed an adaptive microbial community that shifted based upon the sample being treated and has the metabolic potential to degrade a wide array of contaminants, suggesting the potential of this approach to treat produced waters with varying composition.

Effect of Low-Density Static Magnetic Field on the Oxidation of Ammonium by Nitrosomonas europaea and by Activated Sludge in Municipal Wastewater.

Ammonium removal is a key step in biological wastewater treatment and novel approaches that improve this process are in great demand. The aim of this study is to test the hypothesis that ammonium removal from wastewater can be stimulated by static magnetic fields. This was achieved by analysis of the effects of static magnetic field (SMF) on the growth and activity of Nitrosomonas europaea, a key ammonia-oxidising bacterium, where increased growth and increased ammonia oxidation rate were detected when bacteria were exposed to SMF at 17 mT. Additionally, the effect of SMF on mixed cultures of ammonia oxidisers in activated sludge, incubated in sequencing batch bioreactors simulating wastewater treatment process, was assessed. SMFs of 30 and 50 mT, but not of 10 mT, increased ammonium oxidation rate in municipal wastewater by up to 77% and stimulated ammonia oxidiser growth. The results demonstrate the potential for use of static magnetic fields in increasing ammonium removal rates in biological wastewater treatment plants.

Imbalanced protein expression patterns of anabolic, catabolic, anti-catabolic and inflammatory cytokines in degenerative cervical disc cells: new indications for gene therapeutic treatments of cervical disc diseases.

Degenerative disc disease (DDD) of the cervical spine is common after middle age and can cause loss of disc height with painful nerve impingement, bone and joint inflammation. Despite the clinical importance of these problems, in current publications the pathology of cervical disc degeneration has been studied merely from a morphologic view point using magnetic resonance imaging (MRI), without addressing the issue of biological treatment approaches. So far a wide range of endogenously expressed bioactive factors in degenerative cervical disc cells has not yet been investigated, despite its importance for gene therapeutic approaches. Although degenerative lumbar disc cells have been targeted by different biological treatment approaches, the quantities of disc cells and the concentrations of gene therapeutic factors used in animal models differ extremely. These indicate lack of experimentally acquired data regarding disc cell proliferation and levels of target proteins. Therefore, we analysed proliferation and endogenous expression levels of anabolic, catabolic, ant-catabolic, inflammatory cytokines and matrix proteins of degenerative cervical disc cells in three-dimensional cultures. Preoperative MRI grading of cervical discs was used, then grade III and IV nucleus pulposus (NP) tissues were isolated from 15 patients, operated due to cervical disc herniation. NP cells were cultured for four weeks with low-glucose in collagen I scaffold. Their proliferation rates were analysed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide. Their protein expression levels of 28 therapeutic targets were analysed using enzyme-linked immunosorbent assay. During progressive grades of degeneration NP cell proliferation rates were similar. Significantly decreased aggrecan and collagen II expressions (P<0.0001) were accompanied by accumulations of selective catabolic and inflammatory cytokines (disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix metalloproteinase 3, interleukin-1β, interleukin-1 receptor) combined with low expression of anti-catabolic factor (metalloproteinase inhibitor 3) (P<0.0001). This study might contribute to inhibit inflammatory catabolism of cervical discs.

Endogenous Bioactive Proteins in Three-Dimensional Cultured Nucleus Pulposus Cells of Herniated Intervertebral Discs: Identification of Potential Target Proteins for Gene Therapeutic Approaches

Introduction Painful degenerative disc diseases have been targeted by different biological treatment approaches. Nucleus pulposus (NP) cells play a central role in intervertebral disc (IVD) maintenance by orchestrating catabolic, anabolic, and inflammatory factors that affect the extracellular matrix. IVD degeneration is associated with imbalances of these factors, resulting in a catabolic inflammatory metabolism. Therefore, accurate knowledge about their quantity and quality with regard to matrix synthesis is vital for a rational gene therapeutic approach. Materials and Methods NP cells were isolated from 63 patients operated due to lumbar disc herniation (mean age 56/range 29-84 years). Then, three-dimensional culture with low-glucose was completed in a collagen type I scaffold for 4 weeks. Subsequently, cell proliferation evaluation was performed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and intracellular concentration of 28 endogenously expressed anabolic, catabolic, inflammatory factors and relevant matrix proteins was determined by enzyme-linked immunosorbent assay. Specimen-related grades of degeneration were confirmed by preoperative magnetic resonance imaging. Results Independent from gender, age, and grade of degeneration proliferation rates remained similar in all groups of NP cells. Progressive grades of degeneration, however, showed a significant influence on accumulation of selective groups of factors such as disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix metalloproteinase 3, metalloproteinase inhibitor 1 and 2, interleukin-1β, and interleukin-1 receptor. Along with these changes, the key NP matrix proteins aggrecan and collagen II decreased significantly. The concentration of anabolic factors bone morphogenetic proteins 2, 4, 6, and 7; insulin-like growth factor 1; and transforming growth factor β1 and 3, however, remained below the minimal detectable quantities. Conclusion The advantage of the relative mass value evaluation method is the ability to perform precise quantifications of protein concentrations. To our knowledge, this method has not been applied to analyze a broad array of endogenously expressed bioactive factors in NP cells from a larger number of human specimens. The findings indicate that progressive degenerative changes in NP may be problematic with regard to biologic treatment strategies. Hence, gene therapeutic interventions regulating relevant bioactive factors identified in this work might contribute to the development of regenerative treatment approaches for degenerative disc diseases. Disclosure of Interest None declared

Fungal and enzymatic treatment of mature municipal landfill leachate

The aim of our study was to evaluate biotreatability of mature municipal landfill leachate by using white rot fungus and its extracellular enzymes. Leachates were collected in one active and one closed regional municipal landfill. Both chosen landfills were operating for many years and the leachates generated there were polluted by organic and inorganic compounds. The white rot fungus Dichomitus squalens was able to grow in the mature leachate from the closed landfill and as it utilizes present organic matter as a source of carbon, the results were showing 60% of DOC and COD removal and decreased toxicity to the bacterium Aliivibrio fischeri. On the other hand, growth of the fungus was inhibited in the presence of the leachate from the active landfill. However, when the leachate was introduced to a crude enzyme filtrate containing extracellular ligninolytic enzymes, removal levels of COD and DOC reached 61% and 44%, respectively. Furthermore, the treatment led to detoxification of the leachate to the bacterium Aliivibrio fischeri and to reduction of toxicity (42%) to the plant Sinapis alba. Fungal and enzymatic treatment seems to be a promising biological approach for treatment of mature landfill leachates and their application should be further investigated.

Limited Arthroplasty for Osteoarthritis of the Knee: A Critical Analysis Review.

Cartilage lesions are among the most commonly reported knee injuries1 and can progress to osteoarthritis2-4. These lesions have been reported to cause limitations in quality of life similar to severe osteoarthritis4. A number of biological treatment approaches have been proposed, and these approaches can be classified into one of five categories: palliative, reparative, restorative, reconstructive, and corrective. Debridement is a palliative measure aimed at stabilizing the lesion and eliminating mechanical symptoms. Marrow stimulation, such as microfracture or chondroplasty, is an example of a reparative technique. In contrast, chondral and osteochondral transplantation aim to restore injured tissue. Allografts and prosthetic devices are used to reconstruct defects, and osteotomy is used to address the underlying anatomy of the disease. With the exception of palliative treatment and reconstruction involving the use of a prosthetic device, all of these approaches require prolonged rehabilitation to ensure adequate biological response, remodeling, and healing. While excellent long-term results have been reported …

Platelet-rich plasma: why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration

PurposeThe aim of this review was to analyze the available evidence on the clinical application of this biological approach for the injective treatment of cartilage lesions and joint degeneration, together with preclinical studies to support the rationale for the use of platelet concentrates, to shed some light and give indications on what to treat and what to expect from intra-articular injections of platelet-rich plasma (PRP).MethodsAll in vitro, in vivo preclinical and clinical studies on PRP injective treatment in the English language concerning the effect of PRP on cartilage, synovial tissue, menisci, and mesenchymal stem cells were considered. A systematic review on the PubMed database was performed using the following words: (platelet-rich plasma or PRP or platelet concentrate or platelet lysate or platelet supernatant) and (cartilage or chondrocytes or synoviocytes or menisci or mesenchymal stem cells).ResultsFifty-nine articles met the inclusion criteria: 26 were in vitro, 9 were in vivo, 2 were both in vivo and in vitro, and 22 were clinical studies. The analysis showed an increasing number of published studies over time. Preclinical evidence supports the use of PRP injections that might promote a favourable environment for joint tissues healing. Only a few high-quality clinical trials have been published, which showed a clinical improvement limited over time and mainly documented in younger patients not affected by advanced knee degeneration.ConclusionsBesides the limits and sometimes controversial findings, the preclinical literature shows an overall support toward this PRP application. An intra-articular injection does not just target cartilage; instead, PRP might influence the entire joint environment, leading to a short-term clinical improvement. Many biological variables might influence the clinical outcome and have to be studied to optimize PRP injective treatment of cartilage degeneration and osteoarthritis.Level of evidenceIV.

A combinatorial relative mass value evaluation of endogenous bioactive proteins in three-dimensional cultured nucleus pulposus cells of herniated intervertebral discs: identification of potential target proteins for gene therapeutic approaches.

Painful degenerative disc diseases have been targeted by different biological treatment approaches. Nucleus pulposus (NP) cells play a central role in intervertebral disc (IVD) maintenance by orchestrating catabolic, anabolic and inflammatory factors that affect the extracellular matrix. IVD degeneration is associated with imbalances of these factors, resulting in a catabolic inflammatory metabolism. Therefore, accurate knowledge about their quantity and quality with regard to matrix synthesis is vital for a rational gene therapeutic approach. NP cells were isolated from 63 patients operated due to lumbar disc herniation (mean age 56 / range 29 - 84 years). Then, three-dimensional culture with low-glucose was completed in a collagen type I scaffold for four weeks. Subsequently cell proliferation evaluation was performed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and intracellular concentration of 28 endogenously expressed anabolic, catabolic, inflammatory factors and relevant matrix proteins was determined by enzyme-linked immunosorbent assay. Specimen-related grades of degeneration were confirmed by preoperative magnetic resonance imaging. Independent from gender, age and grade of degeneration proliferation rates remained similar in all groups of NP cells. Progressive grades of degeneration, however, showed a significant influence on accumulation of selective groups of factors such as disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix metalloproteinase 3, metalloproteinase inhibitor 1 and 2, interleukin-1β and interleukin-1 receptor. Along with these changes, the key NP matrix proteins aggrecan and collagen II decreased significantly. The concentration of anabolic factors bone morphogenetic proteins 2, 4, 6 and 7, insulin-like growth factor 1, transforming growth factor beta 1 and 3, however, remained below the minimal detectable quantities. These findings indicate that progressive degenerative changes in NP may be problematic with regard to biologic treatment strategies. Hence, gene therapeutic interventions regulating relevant bioactive factors identified in this work might contribute to the development of regenerative treatment approaches for degenerative disc diseases.

Prediction of landfarming period using degradation kinetics of petroleum hydrocarbons: test with artificially contaminated and field-aged soils and commercially available bacterial cultures

This study predicts the optimal landfarming period for the total petroleum hydrocarbons (TPHs)-contaminated field soils that are subject to the combined landfarming and Fenton oxidation treatment. The TPHs degradation in the artificially contaminated model soils and the field-aged contaminated soils were compared in a laboratory scale. The soils were bioaugmented with the 16 petroleum hydrocarbon-degrading microbial cultures that are commercially available in Korea. The TPHs degradation by bioaugmentation in the model soils was 81 ± 2% after 56 days, while it was only 27 ± 2% after 74 days in the field-aged soils. The lower degradation in the field-aged soils can be attributed to the removal of a large part of the biodegradable and volatile TPHs fractions during the weathering process. The two-compartment model that can depict a fast-degradation phase followed by a slow-degradation phase predicted that the remedial goal of 475 mg kg−1 of TPHs could be achieved in the model soils within the conventional landfarming period of 60–120 days in Korea; however, the predicted period for the field-aged soils (710–4,086 days) was not practical requiring a combined biological and chemical treatment approach. Based on the kinetics study, the optimal landfarming period for the field-aged soils was 3 weeks and pre-Fenton oxidation can be used to meet the remedial goal. The two-compartment model can be useful for predicting landfarming period for the combined landfarming and Fenton oxidation treatment of field-aged TPHs contaminated soils. The prediction of the optimal landfarming period could lead to the reduction in both the treatment cost and period.

Non-pharmacological biological treatment approaches to difficult-to-treat depression.

There has been substantial recent interest in novel brain stimulation treatments for difficult-to-treat depression. Electroconvulsive therapy (ECT) is a well established, effective treatment for severe depression. ECT's problematic side-effect profile and questions regarding optimal administration methods continue to be investigated. Magnetic seizure therapy, although very early in development, shows promise, with potentially similar efficacy to ECT but fewer side effects. Vagus nerve stimulation (VNS) and repetitive transcranial magnetic stimulation (rTMS) are clinically available in some countries. Limited research suggests VNS has potentially long-lasting antidepressant effects in a small group of patients. Considerable research supports the efficacy of rTMS. Both techniques require further study of optimal treatment parameters. Transcranial direct current stimulation may provide a low-cost antidepressant option if its efficacy is substantiated in larger samples. Deep brain stimulation is likely to remain reserved for patients with the most severe and difficult-to-treat depression, requiring further exploration of administration methods and its role in depression therapy. New and innovative forms of brain stimulation, including low-intensity ultrasound, low-field magnetic stimulation and epidural stimulation of the cortical surface, are in early stages of exploration and are yet to move into the clinical domain. Ongoing work is required to define which brain stimulation treatments are likely to be most useful, and in which patient groups. Clinical service development of brain stimulation treatments will likely be inconsistent and variable.

Innovative biological water treatment for the removal of elevated ammonia

The objective of this work was to demonstrate the effectiveness of an innovative and simple biological water treatment approach for removing 3.3 mg nitrogen (N) per litre ammonia and iron from water using a pilot study conducted at a utility in Iowa. Biological water treatment can be an effective approach to addressing low ammonia levels; however, providing adequate oxygen to address source water ammonia levels greater than 1.5 mg/L N is challenging. The treatment consisted of a biological “contactor” combined with aeration, followed in series with a dual granular media filter. Orthophosphate was necessary to satisfy biological nutrient requirements, and maintaining near‐saturated dissolved oxygen levels throughout the contactor was important. The pilot project demonstrated that a contactor and filter operated at loading rates of 2.2 gpm/sq ft and 2.0 gpm/sq ft, respectively, met desired finished water quality objectives. The contactor alone was able to completely biologically oxidize all of the ammonia to nitrate. Contactor maintenance was minimal.

Mesenchymal stem cells and cartilage lesions

In this issue of the journal, Filardo et al. [1] give an overview of the available clinical evidence to support the use of mesenchymal stem cells in the treatment of cartilage injuries. They found that there is an increasing body of evidence—from both clinical and mostly preclinical studies—that mesenchymal stem cells might be the future when it comes to treating cartilage lesions. There is obviously growing interest in various biological treatment alternatives today, and several treatment alternatives are commercially available. But, in spite of increased interest in biological treatment, we still have a long way to go. The above-mentioned study is a systemetic review, but most of the studies included were preclinical, and only 18 clinical studies on patients were found. Of these 18 studies, none were randomised and only 5 were comparative. Almost half of the studies were case reports. In other words, for the best possible clinical evidence we need randomised studies, either comparing the biological treatment alternatives with other well-known treatments, such as autologous cartilage implantation (ACI) or microfracture. Of course, we are facing problems in terms of good study design, in most cases due to the heterogeneous patient cohorts (age, gender, concomitnat injuries, etc.), making comparisons difficult or in some cases even impossible. There are still several unanswered questions, like the optimal cell source and the best way of delivery. Today, we base a lot of our knowledge on low-quailty studies and we—the researchers—must shape the future in a secure mode. Many of the studies are based on weak methodology, small cohorts, short follow-up time and only limited reports of complications. We must walk on steady bones in the future in order to take care of our patients in the best possible manner. What is important, however, is the growing interest in biological treatment approaches, and an increasing number of studies have been published during the last years. The growing interest is directed towards focal cartilage damage to frank osteoarthritis, with minimally invasive surgical approaches, either augmented or as growth factors or scaffolds. Several technical improvements have been developed during the last few years, and many of them are promising, at least in the short-term. Mesenchymal stem cells can be considered to be at least a promising approach, and the early clinical results are of interest in both the treatment of focal cartilage injuries and possibly osteoarthritis. With regards to osteoarthritis, we still have a long way to go. Also, we need to consider the risks; we know some of the risks but not all. For instance, the differentation of the mesenchymal stem cells into unwanted tissue is something that needs to be considered. In other words, instead of cartilage we might end up with bone. There are also some concerns about what can happen during the culture process of the mesenchymal stem cells. What lies in the future? Today it is more or less obvious that the treatment of cartilage and other sportsrelated injuries with biological alternatives is still in its infancy and that more and better studies are needed; especially, we need to take the promising preclinical results from the laboratory to the patients. This can only be achieved with well-designed randomised controlled trials. We also need to gain increased knowledge about the natural history, but this is something that takes a long, long time, and we might not be prepared to wait. We need to understand many more details about the nature J. Karlsson (&) Department of Orthopaedics, Sahlgrenska University Hospital, 431 80 Molndal, Sweden e-mail: jon.karlsson@telia.com

Quality and value in cancer care

Quality and value in cancer care

Research Advances in Geriatric Depression

Technical advances have facilitated the exploration of factors related to geriatric depression and have helped generate novel biological and psychosocial treatment approaches. This review summarizes the main advancements in epidemiology, clinical presentation and course, genetics, and other areas of biological research. Treatment interventions outlined in this paper include electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy, vagus nerve stimulation, deep brain stimulation, depression prophylaxis, multidisciplinary approaches to depression treatment, and psychotherapy. Forms of psychotherapy for geriatric depression summarized include interpersonal psychotherapy, supportive psychotherapy, cognitive-behavioral therapy, problem-solving therapy, and ecosystem-focused therapy. Neuroimaging techniques based on magnetic resonance imaging are discussed briefly, including volumetric brain studies, diffusion tensor imaging, fractional anisotropy, fiber tractography, ma...

Non-pharmacological biological treatment approaches to difficult-to-treat depression

Non-pharmacological biological treatment approaches to difficult-to-treat depression

Enhancing human nucleus pulposus cells for biological treatment approaches of degenerative intervertebral disc diseases: a systematic review

Intervertebral disc (IVD) degeneration has been described as an aberrant, cell-mediated, age- and genetics-dependent molecular degeneration process, which can be accelerated by nutritional, mechanical and toxic factors. Collective involvement of these factors can result in structural failures, which are often associated with pain. Current treatment approaches are restricted to symptomatic therapies, not addressing options of restoring structural or biological deterioration of the IVD as the underlying problem. Therapeutic potentials of IVD cell transplantation, biomaterials, inhibiting or activating bioactive factors, including gene-therapeutic approaches, have been shown in vitro or in small animal models. Since human degenerative IVD cells display distinctive features with regard to cell biology and regenerative potential, we attempted a systematic review, investigating the in vitro response of human nucleus pulposus cells to different stimuli. Therefore, we conducted an electronic database search on Medline through July 2011 to identify, compare and discuss publications concerning the effects of cell-cell stimulation, bioactive factors, biomaterials and combinations thereof in terms of cell isolation, proliferation, differentiation and matrix protein synthesis. This survey and discussion might serve as a source for designing future biological treatment strategies for the human IVD.

Distillery wastewater: bioremediation approaches

The alcohol distilleries are growing extensively worldwide due to widespread industrial applications of alcohol such as in chemicals, pharmaceuticals, cosmetics, beverages, food and perfumery industry, etc. The industrial production of ethanol by fermentation results in the discharge of large quantities of high-strength liquid wastes. Distillery wastewater is one of the most polluted waste products to dispose because of the low pH, high temperature, dark brown colour, high ash content and high percentage of dissolved organic and inorganic matter with high biochemical oxygen demand (BOD) and chemical oxygen demand (COD) values. Its characteristics are depending on the feed stock and various aspects of ethanol production process. Spent wash polluted the water bodies into ways; first, the highly coloured nature which can block out sunlight, thus reducing oxygenation of the water by photosynthesis and hence becomes detrimental to aquatic life. Second, it has a high pollution load which would result in eutrophication of contaminated water sources. Distillery wastewater, without any treatment can result in depletion of dissolved oxygen in the receiving water streams and poses serious threat to the aquatic flora and fauna. This review presents an account of the problems associated with distillery wastewater and a detailed study of existing biological treatment approaches. The role of various microorganisms and their enzymes in the wastewater treatment has been discussed to develop a better understanding of the phenomenon.

Reply to the letter by Dhillon and colleagues

We would like to thank Prof. Dhillon and colleagues for the opportunity to revisit and explore some interesting and very controversial aspects of this innovative biological treatment approach. In a previous study [5] and in the subsequent analysis ‘‘platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis’’ [3] cited by Dhillon et al., we aimed to analyze our preliminary results with the use of intra-articular knee injections of platelet-rich plasma (PRP) as minimally invasive treatment for knee degenerative pathology. Our findings suggested the potential to reduce pain and improve both knee function and quality of life with short-term efficacy, especially in younger patients with chondral degenerative lesions or early osteoarthritis (OA). First of all, we would like to answer the observations made about the PRP preparation method. Our procedure involved a 150-ml venous blood sample, which was centrifuged twice to produce a 20-ml unit of PRP. The PRP was then divided into 4 small units of 5 ml each. All of the open procedures were performed in an A-class sterile hood. As correctly underlined, once prepared, the first PRP sample was injected within 4–6 h. The remaining samples were immediately stored at -30 C, in order to avoid the risks of bacterial proliferation and accumulation of pyrogenic cytokines, and towed after 3 and 6 weeks for the other cycle injections. We disagree with the doubts about the storing procedure. Freezing them gives us the time to proceed with the quality analysis. This has to be considered as an advantage, not a disadvantage, with respect to the open procedures for fresh PRP application. In fact, now in our clinical practice, we are also freezing the first sample; this delays the first injection but increases the safety procedure, ensuring a controlled not contaminated intraarticular delivery of the product. The alteration of the morphology and decrease in platelet functional properties, which includes degranulation of alpha-granules, after storing platelets in freezing conditions, is well known. On the contrary, there are no data on the effect of freezing on the clinical results of platelet injections and freeze-thawing is even one of the methods used for releasing intracellular GFs [2, 9]. Some studies, as well as some of our preliminary unpublished data, show a not significant influence of freezing on GF release, and frozen platelets have also been used by other authors [2, 8]. Regarding methods that increase the storage life of platelets in freezing conditions, such as the mentioned dimethylsulfoxide (DMSO), they involve further platelet manipulation and carry some risks, too (not excluding severe adverse events such as neurological toxicity), and removing it before patient administration also means losing cells and bioactive molecules [4]. Having freshly harvested PRP might preserve all the platelet functions better, but currently the data are still controversial and we cannot say that freeze-thawing adversely affects their properties to the point of impairing their clinical efficacy. Cellularity is another debated aspect of not secondary importance when evaluating PRP properties and the results obtained with its application. In fact, not only platelets but also leukocytes, monocytes, macrophages, and mast cells are contained in many platelet concentrates. Some authors define PRP as only platelets and attribute better results to leukocyte depletion, because of the deleterious effects of proteases and reactive oxygen released from white cells; G. Filardo E. Kon (&) M. Marcacci Biomechanics Laboratory–III Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy e-mail: e.kon@biomec.ior.it

Psychopharmakologie und andere biologische Verfahren zur Therapie der Depression

Biological treatment procedures are based on evidence-based guidelines. According to all of them, a correct diagnosis of depression is required before starting therapy. Within recent years many different types of antidepressants have been introduced to the pharmacotherapeutic armamentarium. The "newer" antidepressants were developed with a view to reduced side effects. However, the classes of antidepressants currently available differ little in their antidepressant efficacy, thus, all producing treatment responses of 50 - 75 %. Therefore, the selection of a particular antidepressant for the individual patient depends on various factors: patient's prior experience with medication, concurrent medical conditions that may be worsened by selected antidepressants, concomitant use of non-psychiatric medications that may lead to negative drug-drug interactions, a drug's short and long-term side effects, physician's experience with the medication and patient's history of adherence to medication. Importantly, if the patient does not show any improvement after two to four weeks of treatment with an antidepressant dose at the upper level of the standard dose, it becomes less likely that he will respond to this particular medication later. When a partial or non-response is present, several therapeutic options are available: (1) combining two antidepressants from different classes, (2) switch to new antidepressant from a different or the same pharmacological class and (3) augmentation strategies. For patients who are reluctant to take traditional antidepressants, herbal remedies such as hypericum perforatum (St. John's Wort) provide an alternative for treatment of mild to moderate depression. Besides pharmacological treatment options non pharmacological biological interventions are available. Electroconvulsive therapy and partial sleep deprivation are very effective in the treatment of acute depression. Especially for seasonal affective disorders light therapy is a well established treatment alternative. Further new biological treatment approaches such as rapid transcranial magnetic stimulation (rTMS) showed inconsistent results.

Leptomeningeal carcinomatosis from renal cell cancer: treatment attempt with radiation and sunitinib (case report)

A case of leptomeningeal carcinomatosis in a patient with known brain and lung metastases from renal cell cancer without previous systemic therapy is presented. Neoplastic meningitis (NM) developed 31 months after first diagnosis of simultaneous extra- and intracranial recurrence of kidney cancer and surgical resection of a cerebellar metastasis. In spite of local radiotherapy to the macroscopic NM lesions in the cervical and lumbar spine followed by initiation of sunitinib, the patient succumbed to his disease 4 months after the diagnosis of NM. The untreated lung metastases progressed very slowly during almost 3 years of observation. This case illustrates important issues around both biological behaviour and treatment approaches in metastatic renal cell cancer.