We found an increased percentage of IL-2-positive cells in all pa

We found an increased percentage of IL-2-positive cells in all patients, without differences between patients with isolated HT or associated HDAC inhibition with NEAD. IFN-γ+ cells were also increased in both groups, but the median percentage of those with isolated HT was lower than in patients with HT+NEAD (19·0 versus 29·9%; P = 0·0082). An increased number of IL-4-positive cells was observed in three of 33 (9·1%) patients

with isolated HT and in 25 of 35 patients with NEAD [71%; P < 0·0001; relative risk (RR) = 3·18]. The median values of IL-4+ cells (HT = 5·0% versus HT + NEAD = 16·8%) confirmed this large difference (P < 0·0001). A clear-cut increase of IL-4+ lymphocytes characterizes patients with autoimmune thyroiditis who have associated non-endocrine autoimmune disorders. These findings may represent an initial tool to detect patients with autoimmune thyroiditis in which additional non-endocrine autoimmune disorders may be awaited. Chronic autoimmune thyroiditis may occur as a single disease or associated with further endocrine autoimmune diseases [1–3]. These polyglandular autoimmune syndromes (PAS) are classified as juvenile form (PAS I) or adult form (PAS II) [1,2]. The association of autoimmune thyroiditis with non-endocrine autoimmune disorders has also been recognized [4] (identified throughout as NEAD), sometimes included

in PA DAPT chemical structure III syndrome [5]. The association of NEAD with autoimmune thyroiditis includes atrophic gastritis/pernicious anaemia [6,7], coeliac disease (CD) [8], vitiligo [9], anti-phospholipid syndrome [10] and many other autoimmune diseases (see [5] for a review). Such an association may reflect common genetic [11] and environmental factors [12], but shared immunological features also seem to be involved [13]. The immunological characterization of these associations was often based on the presence of co-existing organ-specific autoantibodies in serum [4], but their pathogenesis is, as yet, incompletely Reverse transcriptase understood. In recent years, the role of cellular immune

responses has been characterized in some of these diseases when in isolated form [13–16]. Multi-parameter flow cytometry permits simultaneous detection of two or more cytokines, allowing direct T helper type 1 (Th1) versus Th2 determination, and has emerged as the premier technique for studying cytokine production at the single-cell level [17,18]. By using this technique, a prevalent Th1-driven autoimmune response has been clearly recognized in Hashimoto’s thyroiditis (HT) [19] and this assumption has been validated in studies where the Th1-distinctive cytokines [interferon (IFN)-γ, interleukin (IL)-2] have been measured in serum [20] and in intrathyroidal lymphocytes [21]. Recently, a mild increase in the synthesis of Th-17 cytokines in patients with HT has also been reported [22]. A Th1 lymphocyte polarization even characterizes some related autoimmune disorders (CD, atrophic gastritis, type 1 diabetes) when occurring in isolated form [14–16].

11 FGF-23 is a 251 amino acid protein that is predominantly synth

11 FGF-23 is a 251 amino acid protein that is predominantly synthesized and secreted by cells from an osteoblast lineage,12,13 and has an estimated half-life in the circulation

of 58 min.14 FGF-23 can be detected with an enzyme-linked immunosorbent assay, in which antibodies detect N-terminal and C-terminal portions. An alternative C-terminal assay recognizes only the C-terminal fragments Sirolimus supplier of active and inactive FGF-23.15 Early debate focused on whether the circulating FGF-23 is biologically active or whether the available assays also detect inactive compounds. A recent study compared the immune-based and intact FGF-23 assays with an assessment of FGF-23 bioactivity and western blot characterization of circulating FGF-23.16 The assays strongly correlated with each other and with FGF-23 bioactivity. The western blot detected only intact FGF-23 suggesting that virtually all circulating FGF-23 is biologically active. About 80% of total body phosphate is present in bone, 9% in skeletal muscle and only 0.1% in extracellular fluid.17 The distal duodenum is responsible for most phosphate absorption, a process actively mediated by calcitriol.18,19 In the kidneys about 95% of filtered phosphate is reabsorbed in the proximal tubular cells, a process driven by a high extracellular sodium gradient that is actively maintained

by a Na+-K+-ATPase.18 This is further facilitated by Na-P co-transporters on the luminal side of the tubular cells, which are modulated by parathyroid hormone (PTH) and calcitriol.20 FGF-23 induces phosphaturia by reducing the number selleck products of co-transporters on the renal tubular cells, as well as mitigating the effects of calcitriol on intestinal absorption.21 Montelukast Sodium PTH can stimulate phosphaturia in a similar manner; however, studies from transgenic mice suggest that FGF-23 induced phosphaturia is not PTH dependent.22 The biological effects of FGF-23 are exerted through activation of FGF receptors (FGF-R). Klotho is a trans-membrane

protein originally described in mice with a phenotype of accelerated ageing and atherosclerosis.23 Klotho directly interacts with FGF-R, allowing it to bind FGF-23 with a higher affinity and increased specificity.13,24 The activation of FGF-R therefore occurs in a Klotho-dependent manner.24 Klotho-deficient mice manifest a similar phenotype to FGF-23 deficient mice despite high circulating levels of the FGF-23.8 The tissue selectivity of FGF-23 may be conferred by Klotho expression in the renal tubule and parathyroid glands.25 The expression of FGF-R and Klotho in the parathyroid glands also supports a regulatory effect of FGF-23 on PTH secretion.26 The main known physiological role of FGF-23 is to regulate urinary phosphate excretion and maintain a stable serum phosphate (Fig. 1).27 An important secondary role is the counter-regulation (against PTH) of vitamin D biosynthesis.

2d,h) To study the effect of Leishmania virulence on DC differen

2d,h). To study the effect of Leishmania virulence on DC differentiation, we tested the ability of the four Lm clones to interfere with the expression of CD1a, HLA-DR, CD80 and CD86 during DC differentiation. We observed that all tested Lm clones were able to down-modulate CD1a expression significantly when compared with DCs differentiated without parasites (P = 0·002) (Fig. 3). click here No significant

differences were observed between HV and LV Lm clones. We also showed a slight decrease in HLA-DR and CD80 expression as well as a slight increase in CD86 expression in the presence of Lm promastigotes when compared to uninfected DCs, but these results were not significant (Fig. 3). To evaluate the impact of virulence on cytokine production by DCs, the

four Lm clones were incubated with immature DCs for 48 h and IL-12p70, IL-10 and TNF-α production was analysed. We did not observe significant differences in IL-12p70, IL-10 or TNF-α production between Lm-infected DCs and uninfected cells for all tested clones. The effect of virulence of Lm parasites was also analysed on cytokine production Decitabine cost during IFN-γ-, LPS- or IFN-γ/LPS-induced maturation of DCs. As shown in Fig. 4, highly significant levels of IL-12p70, IL-10 and TNF-α were detected in infected and uninfected LPS or IFN-γ/LPS matured DCs when compared with immature cells. Interestingly, we observed that infected and LPS-matured DCs produced lower levels of IL-12p70 than uninfected LPS-matured DCs, whereas the presence of parasites did not affect IL-12p70 production in IFN-γ/LPS-matured DCs. No IL-12p70 production was detected in infected and IFN-γ-stimulated DCs. These results were observed regardless of Lm clones virulence. We also showed a slight increase of IL-10 production in the presence of all clones except LV and of

TNF-α production in the presence of HVΔlmpdi and LVΔlmpdi clones during LPS-induced maturation of DCs (Fig. 4). In this study, we evaluated correlations between human ADAMTS5 DC response and Lm clones that were differentially pathogenic in BALB/c mice. The contrasting pathogenicity of these clones was more pronounced than it was for the isolates from which they were derived. Indeed, unlike the LV isolate that induced mild disease, the LV clone was not able to induce lesions in mice (unpublished data). We showed that infection rate and parasite burden were significantly higher in DCs infected with HV than with LV. Previously, using the wild Lm isolates LmHV and LmlV, we showed a significantly higher parasite burden in LmHV-infected human monocytes, suggesting that the high virulent isolate was able to replicate more rapidly inside the phagolysosome [23]. Here, we extend these observations to human DCs. We showed significant differences in uptake and intracellular growth of Lm clones having different levels of virulence. We also observed a significant decrease in infection rate and parasite burden in HVΔlmpdi-infected DCs compared with HV-infected DCs.

The tail vein is usually used, although other veins (e g penile

The tail vein is usually used, although other veins (e.g. penile vein,14 femoral vein15 and retro-orbital plexus16) have been used. A great deal of technical expertise is required to perform this, particularly in mice (due to the small size of their veins and their predisposition not to lie still despite restraint, particularly in the case of the C57BL/6 strain). The main complication of tail vein injection is skin necrosis in the event of tissue extravazation. Selleck LEE011 Due to the narrow therapeutic index of Adriamycin, a small difference

in dose administered can potentially lead to a large variation in disease severity. Another route of administration is the substernal intra-cardiac (∼7 mg/kg in male Wistar rats) approach,17 which requires general PFT�� anaesthesia. The intra-renal route, whereby Adriamycin is injected directly into the kidney (pre- and post-contralateral nephrectomy) is associated with induction of renal injury within 4 weeks. Direct injection

of the renal artery has not been used except in pharmacodynamic studies in dogs.18 Despite their reported safety, the invasiveness of the intra-cardiac and intra-renal routes of administration has precluded widespread application. Intraperitoneal administration has been favoured for its ease of use, particularly in mice19 but due to variable absorption through the peritoneal membrane, inconsistency in induction of renal injury compared with the intravenous route has made this method less favoured. A variety of conditions can affect the delivery of Adriamycin to the target organ. Temporary clipping of one renal artery during the intravenous administration of Adriamycin partially protects the clipped kidney from proteinuric renal injury.14,20 In addition, inhibition of renal blood flow by nitric

oxide inhibition protects against glomerulosclerosis. These studies provide substantial proof that Adriamycin acts directly on the kidney to induce tissue injury.21 Male rats are more Masitinib (AB1010) susceptible than female rats to Adriamycin-induced nephropathy. Castration renders male rats less susceptible compared with sham-operated rats, indicating that sex hormones may contribute to the pathogenesis of Adriamycin-induced renal injury.22 Because of the difference in severity of renal injury, choice of sex is a major factor in designing an experiment using AN as a model of renal injury. In this animal model, the histological changes resemble those of human focal glomerulosclerosis, with podocyte fusion, focal segmental and global glomerular sclerosis and tubulointerstitial inflammation and fibrosis (Fig. 1).23 Adriamycin induces thinning of the glomerular endothelium and podocyte effacement associated with loss of size- and charge-specific barrier to filtration of plasma proteins.11 These changes are seen as early as 1–2 weeks after Adriamycin injection, and are severe by 4 weeks (Fig. 2).

3% incidence of preoperative anemia No significant differences w

3% incidence of preoperative anemia. No significant differences were noted in outcomes of these patients relative to their anemic state, although a higher percent did receive a blood transfusion (18% of anemic patients vs. 6% of nonanemic patients, P < 0.0001). There was a significant incidence of postoperative anemia (93.4%). A subgroup analysis demonstrated that worsening postoperative anemia was significantly

related to preoperative HgB (P < 0.0001), bilateral cases (P < 0.0001), immediate reconstructions (P < 0.0001), increased estimated blood loss (P = 0.0001), and higher rates of intraoperative fluid administration (P = 0.025). A higher incidence of medical complications was observed GSK1120212 in cohorts with HgB < 10 (P = 0.018). Conclusions: Anemia affects a significant portion of breast reconstruction patients. While preoperative anemia is not associated with increased risk of flap related complications, postoperative anemia may be associated with an increased risk of medical complications. © 2013 Wiley Periodicals, Inc. Microsurgery 34:261–270, 2014. "
“Massive bony defects of the lower extremity are usually the result of high-energy trauma, tumor resection, or severe sepsis. Vascularized fibular grafts are useful in the reconstruction

of large skeletal defects, especially in cases of scarred and avascular recipient sites, or in patients with combined bone and soft-tissue defects. Microvascular free fibula transfer is considered the most suitable autograft FGFR inhibitor for

reconstruction of the middle tibia because of its long cylindrical straight shape, mechanical strength, predictable vascular pedicle, and hypertrophy potential. The ability to fold the free fibula into two segments or to combine it with massive allografts is a useful technique for reconstruction of massive bone defects of the femur or proximal tibia. It can also be transferred with skin, fascia, or muscle as a composite flap. Uroporphyrinogen III synthase Proximal epiphyseal fibula transfer has the potential for longitudinal growth and can be used in the hip joint remodeling procedures. Complications can be minimized by careful preoperative planning of the procedure, meticulous intraoperative microsurgical techniques, and strict postoperative rehabilitation protocols. This literature review highlights the different surgical techniques, indications, results, factors influencing the outcome, and major complications of free vascularized fibular graft for management of skeletal or composite defects of the lower limb. © 2011 Wiley-Liss, Inc. Microsurgery, 2011. “
“The purpose of this report of a small series was to describe the technique of total sacrectomy reconstruction using a pedicled vertical rectus abdominis musculocutaneous (VRAM) flow-through flap anastomosed to a free fibula flap. We reviewed all consecutive total sacrectomy reconstructions performed from 2009 to 2011. Surgical technique and patient outcomes were assessed.

We measured participants’ own QOL and that of two hypothetical co

We measured participants’ own QOL and that of two hypothetical colorectal cancer health states using a rating scale, and a utility-based QOL measure, the time trade-off, with extremes of 0 (death) and 1 (full health). Results:  Recipients of kidney transplants (n = 79) had the highest mean QOL weights of 0.79 (standard deviation (SD) = 0.34) compared with participants with CKD 3–5 (n = 53) with mean QOL weights of 0.70 (SD = 0.39), and those on dialysis (n = 89), who had the lowest mean QOL weights of 0.62 (SD = 0.41) (P = 0.02). Having early and advanced stage colorectal cancers were valued at mean QOL weights of 0.44 (SD = 0.41) AZD5363 in vivo and 0.12 (SD = 0.25) among people with moderate stage

CKD; 0.45 (SD = 0.39) and 0.11 (SD = 0.24) among dialysis patients; 0.62 (SD = 0.36) and 0.18 (SD = 0.29) among kidney transplant recipients. Conclusions:  People with CKD have poor

QOL. Having coexistent illnesses such as cancer further reduces the overall well-being of individuals with kidney disease. In addition to the development of effective screening and treatment programs to improve cancer outcomes in people with CKD, our study also highlights the need for effective interventions to improve the QOL in people with selleck products CKD, particularly those with major comorbidities like cancer. “
“Background:  Haemodialysis (HD) circuits are known to produce microemboli. Patent foramen ovale (PFO) may be important in HD patients by allowing right to left intracardiac shunting of microemboli (blood clots or microbubbles), which may pass into the cerebral circulation. Methods:  We undertook bubble contrast transthoracic echocardiography to identify PFO in HD patients and in a control population of peritoneal dialysis patients. We interrogated draining arteriovenous fistulae to confirm that microemboli are created during HD. We then

undertook transcranial Doppler scanning of the middle cerebral artery before Sitaxentan and during dialysis, with and without Valsalva augmentation, to detect cerebral microemboli in HD patients and in the control group. Results:  Eighty patients (age 60.4 ± 15.0 years) were recruited to the study. In 12 of 51 HD patients and five of 29 peritoneal dialysis patients a PFO was found (21.3%). Ultrasound scanning of draining arteriovenous fistulae showed a significant difference in the number of microemboli before (1.63 ± 3.47 hits per 5 min) and during (31.6 ± 28.9 hits per 5 min) HD (P = 0.012). However, there was no evidence of microembolization to the middle cerebral artery before or during HD in the study or control groups. Conclusions:  Although microemboli are detectable in the draining arteriovenous fistulae of patients undergoing HD, there was no evidence of cerebral microembolization in the middle cerebral artery during HD in those with or without a PFO. The results contrast with previous reports demonstrating microemboli in the carotid circulation during HD.

These studies provide evidence that the strength of the TCR signa

These studies provide evidence that the strength of the TCR signal can play a direct role in directing the extent of

both thymocyte deletion and Treg-cell differentiation, and suggest that distinct TCR signaling thresholds and/or pathways can promote CD4SP thymocyte deletion versus Treg-cell formation. “
“In June this year, it was 30 years since the identification of the first AIDS patient (see the review in this issue 1). Despite rapid responses PCI-32765 solubility dmso by scientists and doctors to understand this disease in both clinical and experimental systems 2, 3, human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS (Fig. 1), continues to feature among world’s three major killers destroying millions of lives, families and communities. More than 30 drugs have been developed just for HIV-1 and there have been three successful trials showing their impressive preventive potential. However, because of the drug unavailability, particularly in resource selleck compound poor settings, side effects and potential development of resistance, the best hope for a profound fall in the incidence of HIV-1 infection remains the development of an effective prophylactic HIV-1 vaccine. Here, we discuss

T-cell vaccine designs mainly, briefly mentioning antibody vaccines. Even if a vaccine that actively stimulates broadly neutralizing antibodies (bNAbs) can be made 4, it will be hard to stop some HIV-1 infection occurring (e.g. through cell–cell transmission) and T-cell-mediated

immune responses to control infection will be required. T cells function by killing HIV-1-infected cells and producing soluble factors that can directly and indirectly control HIV-1 spread. While T cells cannot prevent the transmitted virus from infecting host cells, potent vaccine-induced HIV-1-specific T-cell responses could increase the dose of incoming virus necessary to establish infection (i.e. decrease acquisition) IMP dehydrogenase 5, limit the extent of viral replication during primary viremia (i.e. reduce tissue damage), lower the virus load at set point (i.e. reduce further virus transmission) and slow the rate of CD4+ T-cell decline (i.e. delay the development of AIDS). The simian immunodeficiency virus/macaque challenge model strongly supports this view, showing that potent T-cell responses alone can lower virus load and delay the development of AIDS 6–8. Thus, ideally, a successful HIV-1 vaccine will induce both T-cell and antibody responses; however, an effective T- or B-cell vaccine alone is nonetheless likely to impact the epidemic 9. Scientists developing HIV-1 vaccines face a long list of challenges. Although these differ for the induction of effective T-cell responses in comparison with induction of the desired bNAb specificity by active immunization, one major hurdle is common, namely the extreme HIV-1 variability.

It may appear complex and driven by technical

language A

It may appear complex and driven by technical

language. At its heart, however, it asks a simple question: in the circumstance of this patient what is the right thing to do? An approach based on the key ethical principles provides a structure in the decision-making process around the appropriateness of dialysis; in this way ethics can lead to better and more nuanced decision-making. Several guidelines on the initiation of and withdrawal from dialysis provide assistance in these deliberations, including the (USA) RPA guidelines and to a lesser extent the CARI guidelines. Each of the bioethical principles is important. Autonomy does not override the other principles. All clinicians, including Nephrologists, have a responsibility to carefully balance the benefits and burdens

of treatment, including dialysis, and communicate that recommendation to the patient and family. The wishes and values of a patient should NVP-LDE225 mw be considered but they should not, taken alone, be determinative. This issue arises when a patient or family wants treatment that is not felt Roxadustat molecular weight to be appropriate by the nephrologist. In difficult cases Nephrologists should seek the advice and formal opinion of colleagues and, where available, a Bioethicist. This is particularly useful when conflict arises within families about which treatment pathway should be adopted. Advance care planning is a process of patient-centred discussion, ideally involving family/significant others, to assist the patient to understand how their illness might affect them, identify their goals and establish how medical treatment might help them to achieve these. An individual must be competent to make decisions about their healthcare in order to participate in Advance Care Planning. Advance Care Planning discussions may result in the formulation ZD1839 nmr of an Advance Care Plan which articulates the individual’s wishes, preferences, values and goals relevant to their current and future health care.

An Advance Care Plan is only one useful outcome from the Advance Care Planning process, the education of patient and family around prognosis and treatment options is likely to be beneficial whether or not a plan is written or the individual loses decision-making capacity at the end of life. Advance care planning should be available to all patients with CKD, including ESKD on renal replacement therapy. Such plans need to be reviewed regularly as patients’ circumstances may change. Advance care planning provides benefits to patients as their end of life wishes are more likely to be known and followed when individuals have been through the Advance Care Planning process; feelings of isolation and lack of hope may be experienced when individuals are not able to honestly and openly discuss their hopes and fears for the future with loved ones. Having Advance care discussions does not result in loss of hope for patients.

0104 is needed to induce significant PAR-4 expression As it is u

0104 is needed to induce significant PAR-4 expression. As it is unlikely to accumulate such a high concentration of the allergens in the body, upregulated PAR-1 and PAR-4 expression should not play an important role in cockroach allergy. In contrast, Per a 1.0101-induced upregulation of expression of PAR-2 may be involved in cockroach allergy as only 100 ng/ml

of Per a 1.0101 is required to induce significant increase in PAR-2 expression. Activation of PAR-2 has been recognized to play an important role in allergic diseases. Patients with asthma express an increased amount of PAR-2 on respiratory epithelial cells [20], and PAR-2 activation in human airways is associated with contraction selleck chemicals llc learn more of human airways and contributes to the hyperplasia and hyper-responsiveness evident in the asthmatic airway [21]. Furthermore, our results indicate that Per a 1.0101 and Per a 1.0104 are not proteases. Therefore, their actions on PARs should not depend on enzymatic activity. Once again like rPer a 7, we observed the expression of certain mRNAs of PARs, but not corresponding proteins in P815 cells upon rPer a 1.0101 and rPer a 1.0104 challenge. This dissociation

between gene and protein expression has been reported previously [22] and there are many complicated and varied post-transcriptional mechanisms involved in turning mRNA into protein [23], which may help to explain our earlier observations. Like Per a 7, both rPer a 1.0101 and rPer a 1.0104 can induce secretion of Th2 cytokines IL-4 and IL-13 from P815 cells. As overexpression of IL-4 is predominantly found in the airways of asthmatics [24] and IL-4 is the key cytokine in development of Th2 cell responses [25], IL-13, which shares a receptor component with IL-4, is a critical cytokine for allergen-induced asthma [26], and the findings that rPer a 1.0101 and rPer a 1.0104 can induce IL-4

and during IL-13 release from mast cells may be of importance for cockroach allergy. As much lower concentrations of rPer a 1.0101 and rPer a1.0104 are required to induce IL-4 and IL-13 release than to upregulate expression of PARs, cytokine release may be an earlier event than altered expression of PAR expression when mast cells are challenged by Per a 1.01 allergens. In conclusion, we have demonstrated for the first time that American cockroach allergens Per a 1.0101 and Per a1.0104 have no enzymatic activity, but can modulate the expression of PARs in P815 cells. They can also provoke Th2 cytokines IL-4 and IL-13 secretion from the mast cells. Our results suggest that Per a 1.0101 and Per a1.0104 are likely to contribute to the development of cockroach-related allergic disease through modulation of mast cell behaviour. This project was sponsored by the grants from the Li Ka Shing Foundation, Hong Kong, China (No. C0200001); the Major State Basic Research Program of China (973 Program) (No.

The same group also identified a homologue of the C  elegans mult

The same group also identified a homologue of the C. elegans multi-membrane spanning, RNA importing protein SID-1. The gene encoding this protein contains 21 exons and spans over 50 kb to potentially https://www.selleckchem.com/products/pci-32765.html encode a 115 556 Mr protein (SmSID-1) (38). These findings indicate that an intact RNAi

pathway has evolved in schistosomes. It has now also been shown that RNAi can be experimentally applied in schistosomes and appropriate transformation protocols have been adapted and developed (Table 2). The first report of successful RNAi in schistosomes was published in 2003 (40) showing that soaking of S. mansoni cercariae in dsRNA resulted in silencing of the major gut-associated proteinase, cathepsin B (SmCB1 or Sm31). In the same year, Boyle and colleagues (41) reported the successful silencing of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and of a glucose transporter (SGTP1) gene in sporocysts of S. mansoni. Here for the first time a functional phenotype was detectable as the exposure of the parasite to SGTP1

dsRNA reduced the ability of sporocysts to take up glucose by 40%. These two publications R428 concentration clearly confirmed that RNAi can be utilized in schistosomes and that the silencing effect in larval stages of the parasite was potent and specific. In short succession, RNAi studies in schistosomes were published by a number of groups. The proteins attracting the most interest were proteolytic enzymes (metallo-, cysteine, and serine proteases), genes belonging to signalling pathways implicated in adult worm pairing and/or egg deposition, or genes playing a role in reproduction. These groups of proteins are essential in the life cycle of schistosomes and therefore are potential targets for

novel anti-parasite chemotherapy and immunotherapy. A number of studies have been undertaken to understand the role of signal transduction pathways in schistosomes and their role in the interaction of the parasite with its host environment and amongst themselves. One such example is the TGF-β signalling pathway that seems to be essential for schistosome embryogenesis. Schistosomes are exceptional amongst trematodes in the way that they have evolved separate sexes, and Cell press the sexual development of the female requires constant contact with the male. Blocking components of the parasite TGF-β signalling pathway by RNAi would likely abolish worm pairing and egg production, and as a consequence, egg-associated pathology will not develop. This makes this pathway a potential target for novel intervention strategies for transmission and disease control (42–45). Indeed, Freitas et al. (42) described that RNAi-mediated knock-down of SmInAct (a member of the TGF-beta superfamily) expression in eggs led to a developmental arrest indicating a role of this protein during embryogenesis of schistosomes. Another signal transduction pathway was investigated by Beckmann et al. (46). The authors silenced a Syk kinase, which is expressed in the gonads of adult schistosomes.