Other techniques such as cyanoacrylates, fibrin glues, the Medtronic™ U-Clip®, and laser bonding have low levels of evidence supporting their use. Further research is required to establish any role for these techniques. © 2011 Wiley Periodicals, Inc. Microsurgery, 2012. “
“There is an increasing demand for successful free tissue transfer, with postoperative CHIR-99021 monitoring of flaps a key to early salvage. Monitoring methods have ranged from clinical techniques to invasive options, of which two are particularly applicable to buried flaps (Cook-Swartz Doppler probe and microdialysis). The evidence for these options has been represented largely in separate cohort studies,

with no single study comparing these three techniques. We aim to perform this comparison in a single cohort of patients. A prospective, consecutive cohort study comparing clinical monitoring, microdialysis and the implantable Doppler probe was undertaken. In 20 patients receiving 22 flaps, 21 flaps were monitored with microdialysis, 18 flaps with clinical observation, and 21 flaps with the Cook-Swartz Implantable Doppler probe. Exclusion was based on applicability and availability intra-operatively. Efficacy was assessed through Proteases inhibitor sensitivity, specificity, positive, and negative predictive values. Nineteen of 22 flaps had no suspected anastomotic problems; 3 of 22 flaps were explored for anastomotic

problems, with two salvaged and one lost. The implantable Doppler and microdialysis were found to detect flap statistically earlier than clinical assessment, with microdialysis better at detecting flap compromise: 100% specificity (confidence acetylcholine interval 31–100%) when compared to the implantable probe and clinical assessment

(67%: 13–98% and 33%: 2–87%, respectively). Each of the Cook-Swartz Doppler probe, microdialysis and clinical assessment was found suitable for monitoring in free tissue transfer. The implantable Doppler and microdialysis offer the potential for earlier detection of flap compromise. © 2014 Wiley Periodicals, Inc. Microsurgery, 2014. “
“Local or distant metastatic recurrence after therapy is observed in 20–30% of cases of head-and-neck cancer. An unfavorable course may occur after cervical lymph node dissection due to loss of immunoprotective lymph nodes in the head-and-neck region. To overcome this problem, we performed autologous lymph node transplantation from the groin after head-and-neck cancer resection and cervical lymph node dissection. The patient was a 63-year-old man with squamous cell carcinoma in the mesopharyngeal lateral wall. After tumor resection and right cervical lymph node dissection, a lymph node-containing superficial circumflex iliac artery perforator flap was transplanted from the left groin. Pathological examination showed that cancer had invaded the primary tumor tissue stump. Thus, radiotherapy (66 Gy) was performed for the residual tumor from days 28 to 84 after surgery.

5). We explain the lack of tumor rejection and DC migration by OX86 treatment in CD40−/− as a consequence of insufficient CD40L upregulation by Tem cells and therefore insufficient DC reactivation in the tumor microenvironment. To demonstrate that OX40 stimulation promoted in vivo the direct adjuvanticity of Tem cells toward DCs via CD40/CD40L,

Tem cells were sorted from tumors 24 h after treatment with OX86 or rat IgG and were co-cultured with WT or CD40−/− BMDCs. After 24 h, BMDC maturation was estimated by the expression of CD80 and CD86 (Fig. 5A). We found that WT BMDCs received a stronger stimulation by Tem cells pre-treated in vivo with OX86, Tanespimycin price than with isotype matched control Ab. However, CD40-deficient BMDCs could not increase the expression of maturation markers after co-culture with Tem cells obtained from either OX86 or mock-treated tumors (Fig. 5B and C). We cannot exclude that a reverse CD4/CD40L-mediated interplay may occur between Tem cells and DCs, thus explaining the superior capacity of OX40-triggered Tem cells to costimulate WT DCs. Indeed, OX40-stimulated Tem cells, expressing higher CD40L levels, could be more receptive to CD40-mediated signals provided by WT but not CD40-null DCs, thus in turn boosting WT DCs via signals

other than the CD40/CD40L axis, for instance through enhanced cytokine secretion. However, we failed to 17-DMAG (Alvespimycin) HCl detect an increased production of IFN-γ, TNF-α, IL-17 or IL-6 ex vivo by tumor-infiltrating lymphocytes (TILs) upon OX86 intratumoral Dasatinib chemical structure administration (Supporting Information Fig. 6). These data demonstrate that tumor-infiltrating

Tem cells, stimulated in vivo with OX86, directly provided the adequate stimuli for DC ex vivo reactivation in a CD40/CD40L-dependent manner. The effects of OX40 triggering on Treg and Teff cells in tumor rejection were separately investigated. In different contexts, Treg cells may adopt preferential suppression mechanisms among a variety of possibilities 2. IL-10 is one of the best-known cytokines endowed with immune-suppressive functions. Il10 gene expression characterizes Treg-cell signature 30, even though a significant IL-10 expression at the protein level can be detected in naïve mice only in the intestine 15, 31. Treg-cell-derived IL-10 is redundant for the control of systemic autoimmunity but becomes crucial for the control of inflammation at the mucosal interfaces with the external environment, such as in lungs and colon 32. In chronic inflammation-related tumorigenesis, Treg cells may turn from anti- to pro-inflammatory and pro-tumorigenic. Indeed, along the development of colon polyposis, Treg cells lose the ability to secrete the anti-inflammatory IL-10 and switch to the pro-inflammatory and pro-tumorigenic IL-17 33.

Several data suggest that the inflammasome in infiltrating macrophages and renal dendritic cells promotes renal inflammation. However, the role of each inflammasome component (NLRP3, learn more ASC, and Caspase-1) in renal tubular cells remains unclear. We demonstrated that renal collecting duct (CD) epithelial cell was the major site of

ASC expression in mouse unilateral ureteral obstruction (UUO) model. The role of ASC in renal inflammation and fibrosis was investigated in vivo and in vitro. Methods: C57BL/6J-background wild-type (WT) and ASC-knockout (ASC-KO) mice underwent UUO. Primary mouse CD epithelial cells were used in in vitro study. Results: Expression of mRNA for inflammasome components, NLRP3, ASC, and Caspase-1 as well as IL-1β was time-dependently increased in the ligated kidney after UUO. ASC-KO showed significant amelioration in tubulointerstitial injury and fibrosis histologically. Flow cytometric analysis showed that increase in CD45+ leukocytes

was remarkably suppressed in ASC-KO, indicating that inflammatory response was ameliorated in ASC deficiency. Inositol monophosphatase 1 Immunohistochemistry showed ASC was upregulated in a portion ABT-888 clinical trial of renal tubules after UUO. Double immunofluorescence analysis showed that most ASC positive tubules were co-stained with aquaporin-2 (AQP2), collecting duct marker. In in vitro study, we identified the constitutive expression of NLRP3, ASC and Caspase-1 in primary mouse CD epithelial cells using western blotting. After extracellular ATP stimulation, active Caspase-1 and mature

form of IL-1β secretion were observed. CD epithelial cells from ASC-KO mice did not show the response to ATP. ATP-induced IL-1β release was inhibited significantly by P2X7R antagonist, blocking K+ efflux, or antioxidant N-acetyl cysteine (NAC). Conclusion: ASC was upregulated in CD epithelial cells after UUO and contributed to inflammation and fibrosis. Extracellular ATP stimulated IL-1β release in CD epithelial cells ASC-dependently. This inflammasome activation was mediated through P2X7R-potassium efflux and ROS-dependent pathways. These findings suggest that potential immunological role of CD by inflammasome activation.

v.) rabbit IgG administration (IVIgG) on allergic airway inflammation and lung antigen-presenting cells (APCs) in a murine model of ovalbumin (OVA) sensitization and challenge. In OVA-challenged mice, IVIgG attenuated airway eosinophilia, airway hyperresponsiveness and goblet cell hyperplasia and also inhibited the local T helper type (Th) 2 cytokine levels. Additionally, IVIgG attenuated the proliferation of OVA-specific CD4+ T cells transplanted into OVA-challenged mice. Ex selleck chemicals vivo co-culture with OVA-specific CD4+ cells and lung CD11c+ APCs from mice with IVIgG revealed the attenuated transcription level of Th2 cytokines,

suggesting an inhibitory effect of IVIgG on CD11c+ APCs to induce Th2 response. Next, to analyse the effects on Fcγ receptor IIb and dendritic cells (DCs), asthmatic features

in Fcγ receptor IIb-deficient mice were analysed. IVIgG failed to attenuate airway eosinophilia, airway inflammation and goblet cell hyperplasia. However, the lacking effects of IVIgG on airway eosinophilia in Fcγ receptor IIb deficiency were restored by i.v. transplantation of wild-type bone marrow-derived CD11c+ DCs. These results demonstrate that IVIgG attenuates asthmatic features and the function of lung CD11c+ DCs via Fcγ receptor IIb in RG-7388 supplier allergic airway inflammation. Targeting Fc portions of IgG and Fcγ receptor IIb on CD11c+ DCs in allergic asthma is a promising therapeutic strategy. Bronchial asthma is a disorder of the conducting airways characterized by variable airflow obstruction, but is also a chronic inflammatory disease of the airway associated with an immune response to inhaled antigens, which

leads to airway infiltration of eosinophils and mast cells, goblet cell hyperplasia and airway hyperresponsiveness (AHR). These pathophysiological Dynein features are induced by T helper type (Th)2 proliferation and production of Th2 cytokines, such as interleukin (IL)-4, IL-5 and IL-13 [1]. Anti-inflammatory drugs, primarily corticosteroids, comprise the conventional treatment for chronic Th2 airway inflammation. The current anti-inflammation strategies to manage bronchial asthma have limited clinical efficacy for some patients. Immunoglobulins (Igs) and Fc receptors (FcRs) play important roles in bronchial asthma pathogenesis. FcRs are expressed on many kinds of immune cells and control the cellular functions. Among Igs, IgE plays a crucial role in the pathogenesis of asthma by binding airborne inhalant allergen to activate various cellular inflammatory reactions of immune cells through FcεRI. Anti-IgE therapy, one of the controllers to manage bronchial asthma, reduces the free IgE available to activate effector cells [2]. In contrast, IgG reportedly has immunomodulatory effects on the immune response to common inhalant allergens. Immunotherapy by allergen vaccination is accompanied by an increase in allergen-specific IgG titres [3].

7 log10 copies/mL in men with gonorrhea44 and 1.0 log10 copies/mL during semen CMV reactivation.45 Both genital infections

and bacterial vaginosis (BV), an imbalance in the normal vaginal flora, have a similar effect in the female genital tract.22 HSV-2 merits individual mention, because suppressive therapy in HIV/HSV-2 co-infected individuals with acyclovir-based medications Selleckchem Cetuximab has been consistently associated with a reduction in both the blood and genital tract HIV viral load,31 although a recent clinical trial of HSV-2 suppression in HIV co-infected individuals did not reduce HIV transmission to their sex partners.46 Furthermore, genital infections do not only increase HIV transmission RG7422 supplier from a co-infected individual, but they have been consistently linked with increased HIV susceptibility in an HIV-uninfected person,47 likely due to immune alterations outlined in the next section. HSV-2 infection, even if asymptomatic (as most cases are) increases HIV susceptibility approximately threefold in both men and women,48 and BV increases a

woman’s susceptibility by 60%.49 Genital co-infections may play a key role in HIV transmission, but for them to play a role in racial and geographical imbalances in HIV prevalence, a similar imbalance must exist in their own prevalence. Studies have

shown that this is the case. For instance, while the HSV-2 seroprevalence Methocarbamol is around 15–20% in white women from the USA, it is over 50% in black women from the USA50 and African/Caribbean women from Canada,51 and it may exceed 80% in adult women from sub-Saharan Africa.52 Rates of BV in women from sub-Saharan Africa are approximately double those in the rest of the world,53 and within North America BV preferentially affects African-American women for reasons that are poorly understood.54,55 Given that both HSV-2 and BV each predispose to the other and to the acquisition of a range of other STIs,56 it is clear that genital co-infections may be an important mechanism driving the association of black race and HIV prevalence. As stated above, a critical determinant of HIV susceptibility is the number and density of HIV-susceptible target cells to which the virus can gain access at the site of exposure. Perhaps the clearest demonstration of this is the fact that male circumcision reduces HIV acquisition by approximately 60%.57,58 This is presumably because of the direct removal of the HIV target cells that are present in the foreskin,59,60 although the pathophysiology and immune correlates of HIV acquisition in the foreskin remain poorly defined.

Meanwhile, the results of the competition analyses suggested that loxP insertion, not only at 191 nt but also at 143 nt, possibly affected the efficiency of virus packaging. Among the six pairs of loxP-containing viruses, we chose 15L and 19L for the competition assay because the difference in the ratio of the viral titers for these viruses was the smallest (Table 2); thus, this difference probably had a minimal effect on the competition analysis. Furthermore, the differences

in the viral growth between 15L, 19L or ΔL and the competitor may reflect a difference in packaging efficiency. Although the titer of the competitor after the seventh passage was higher than not only that of 19L, but also that of 15L, this difference was not observed in the competition analysis. For the competitor virus, the ratio of the titer in the seventh stock versus selleckchem that

in the conventional stock (6.7 in Table 1) was slightly higher than that for 15L, 19L and ΔL, thereby suggesting that the replication efficiency of the competitor virus might be effective. However, while the titer of 15L alone was identical to that of ΔL (both 3.2 in Table 1) and the ratio of ΔL + competitor did not change during the seventh passage, the decrease in the ratio of the 15L + competitor in the competition analysis was remarkable (Figs. 3a,b). R788 mw Therefore, because these decreases did not depend on the replication efficiency, these results suggested that the insertion of loxP upstream

of the cis-acting packaging domain influenced the packaging step. One Tyrosine-protein kinase BLK report has claimed that a virus lacking the region from 53 nt to 322 nt at the left-end of the virus genome showed a packaging efficiency that was nearly comparable to that of the wild type (19), suggesting that these insertions may not influence the packaging efficiency. Although we examined the effect of loxP insertion only at 143 nt or 191 nt, because the loxP sequence is a palindrome structure, the insertion of such a sequence might actively hamper the binding of some factor, thereby disturbing the packaging to the same extent. This negative effect of loxP insertion is probably a useful characteristic for a helper virus in HD-AdV construction. During the construction of HD-AdV, the incomplete excision of the packaging domain of a helper virus in Cre-expressing 293 cells remains a very important problem: approximately 5% of helper virus persists in crude HD-AdV stocks (33, 34). Such incomplete excision might result from the toxicity of highly expressed Cre in 293 cells (35–38) or from a shut-off mechanism for Cre expression during vector replication (33). FLP and FLPe, which is a thermo-stabilized FLP, have also been applied for this purpose, and their excision efficiencies were reportedly similar to or a little more than that of Cre (16, 17).

TLR4, the classical receptor for lipopolysaccharide on Gram-negative bacteria, has also been implicated as a sensor for an unidentified, heat-sensitive mycobacterial ligand (Quesniaux et al., 2004; Lahiri et al., 2008). Other important innate immune receptors are the cytosolic nucleotide-binding and oligomerization domain-like receptors or NOD-like receptors (NLRs), which are TLR-related proteins responsible for recognition of intracellular pathogens, including mycobacteria. NOD1 and NOD2 specifically bind diaminopimelic acid and the peptidoglycan breakdown

product muramyl dipeptide, triggering the production of proinflammatory cytokines. This suggests a synergistic effect between NLRs and TLR2 in tuberculosis (Korbel et al., 2008). As mentioned earlier, both TLR and NLR ligands promote inflammation by triggering the release of chemokines and proinflammatory cytokines, expression of adhesion molecules and recruitment of macrophages, DCs this website and polymorphonuclear neutrophils (Korbel et al., 2008). After antigen processing and expression of epitopes in an MHC-restricted manner, mature DCs can stimulate naive T cells to differentiate into effector cells. Depending on the ligand, the immune response may thus be skewed toward CTL responses or toward a particular Th response (Boog, 2008). Based on increasing evidence for the contribution of CD1-restricted immune responses to protection against tuberculosis, CD1-restricted,

nonproteinaceous ligands, such as glycolipids, are also being considered as potential candidates for new tuberculosis vaccines (Hamasur et al., 2003). In conclusion, mycobacterial ligands have great potential as adjuvants due to their ability to activate the innate immune Selleckchem Cabozantinib response, ultimately leading to cellular and humoral responses against coadministered antigens (Mills, 2009). In this context, synthetic ligands capable of targeting TLRs more precisely and safely than pathogen-derived ligands are being designed (Guy, 2007). However, a great deal of work is still required, because the success

of vaccination is related to the route of administration, the delivery method used and the APC population stimulated by the adjuvant. On the other hand, TLR overstimulation can also generate unwanted toxic effects, and so adjuvant dose and mechanism of action must be carefully considered and potential toxicities should be investigated and enough characterized (Boog, 2008). Despite the limited number of adjuvant systems approved for clinical applications, several vaccine delivery and adjuvant combinations have been evaluated, resulting in promising preliminary formulations. Currently, four leading adjuvants for tuberculosis subunit vaccines are being investigated: CAF01 (LipoVac), developed by the Statens Serum Institute, is a novel tuberculosis vaccine adjuvant utilizing N,N′-dimethyl-N,N′-dioctadecylammonium (DDA) liposomes with the synthetic mycobacterial immunomodulator α, α′-trehalose 6,6′-dibehenate (TDB) inserted into the lipid bilayer.

18 A STAT-5 phosphorylation assay was used to gauge IL-7 responsiveness in CD4+ and CD8+ cells. The increase of the percentage of P-STAT-5 cells, and an example of constitutive P-STAT-5 and IL-7-induced P-STAT-5, in HD and NHP are shown in Fig. 5(a,b). In NHPs, (n = 15) 84·4 ± 10·8% and 60·6 ± 12% of CD4+ and CD8+ cells showed an increase of P-STAT-5 cells in response to IL-7 stimulation. Similar numbers were obtained in PBMCs from HDs (n = 10): 87·6 ± 7·6% and 62·3 ± 15·4% in CD4+ and click here CD8+

cells, respectively. CD4+ and CD8+ subsets showed comparable responses to IL-7 stimulation as measured by STAT-5 phosphorylation in NHPs and HDs. In HDs and NHPs more CD4+ cells than CD8+ cells showed STAT-5 phosphorylation (consistent with higher levels of IL-7Rα expression on CD4+ T cells) but the amplitude (measured by MFI) was not statistically different between CD4+ and CD8+ cells. The presence of regulatory cells was assessed by expression analysis of CD25 and FoxP3 in the CD4+, CD8+ and CD4+ CD8+ T-cell compartments (gating strategy see Supplementary Fig. S2). In NHPs, the

CD4+ T-cell compartment showed the following frequencies: 16·5% (median values) were CD25intermediate (CD25interm.) and 0·5% stained for CD25bright; in CD4+ CD8+ T cells: 19·6% cells were CD25interm. and 1·4% were CD25bright; in CD8+ T cells: 1% were CD25interm. and 0·07% CD25bright (Table 2). Compared with HDs, higher frequencies of CD4+ CD25interm. T cells and CD4+ CD8+ CD25interm./bright,

and CD8+ CD25bright T cells (21%) were detected in PBMCs from NHPs. Analysis buy Pifithrin-�� of FoxP3 expression in the different CD25+/− T-cell compartments showed that the majority of CD25bright T cells in NHPs were FoxP3+ (87·5% of CD4+ and 76% of CD4+ CD8+ and CD8+ T cells), whereas Clomifene only 10–20% of CD25interm. T cells showed FoxP3 expression (Fig. 6a). In contrast, almost no FoxP3 expression could be observed in human CD4+ CD8+ CD8+ T cells that exhibited the CD25interm. phenotype. Analysis of PBMCs from four of eight HDs showed that CD4+ CD8+ and CD8+ T cells, which displayed a CD25bright phenotype, stained also positive for FoxP3. In summary, statistically higher frequencies (P ≤ 0·05) of CD4+/− CD25interm.FoxP3+/−, CD4± CD8± CD25interm./high FoxP3+/− and CD8± CD25interm./high FoxP3+/− were detected in NHPs than in HDs. Expression of the IL-7Rα on NHP CD25bright T cells was inversely correlated with expression of FoxP3, which is similar to the situation described in humans.25 More than 90% of NHP CD4+ CD8+ CD25interm./bright FoxP3+ T-cell subsets did not express the IL-7Rα, whereas the majority of CD4+ CD8+ CD25+/− FoxP3− (33–67%) were positive for IL-7Rα (% of IL-7Rα expression is shown for CD4+ T cells in Fig. 6b). The same trend was observed in HDs. However, 9% of human CD4+ CD25bright FoxP3+ T cells expressed the IL-7Rα (Fig. 6b), this was not true for the same T-cell subset in NHPs (3·8%).

Co-transfection experiments designed to validate the miR-155 binding site present in the 3′UTR of SOCS-1 were also performed using FA-associated liposomes. Two hundred microlitres of FA-lipoplexes, containing pmiR-155 and a plasmid encoding the reporter gene luciferase and the 3′UTR of SOCS-1 (pSOCS-1 3′UTR) were delivered to N9 cells to obtain a final plasmid concentration 3-deazaneplanocin A supplier of 1 μg/well for each plasmid. In parallel experiments, plasmid (p) GFP was used in addition to pSOCS-1

3′UTR to serve as a control. In all transfection protocols, after 4 hr of incubation, the medium was replaced by new RPMI-1640 medium and N9 microglia cells were incubated for different periods of time, before further analysis. Luciferase expression following

co-transfection of pSOCS-1 3′UTR and pmiR-155 or pGFP was evaluated by assessing luciferase activity. Briefly, 48 hr after transfection, cells were washed twice with PBS and 100 μl lysis buffer (1 mm dithiothreitol, 1 mm EDTA, 25 mm Tris–phosphate, 8 mm MgCl2, 15% glycerol, 1% [volume/volume (v/v)] Triton X-100, pH 7·8) were added to each well. After cell lysis at Cetuximab order −80°, 50 μl of each lysate were incubated with luciferin and ATP and light production was determined in a luminometer (Lmax II384; Molecular Devices, San Jose, CA). The protein content of the lysates was evaluated through the DC Protein Assay reagent (Bio-Rad, Hercules, CA), using BSA as the standard.

Data were expressed as relative light units of luciferase per mg of total cell protein and presented as fold change with respect to control (untransfected cells). Total RNA, including small RNA species, was extracted from N9 microglia cells or primary microglia cultures using the miRCURY™ Isolation Kit – Cells (Exiqon), according to the manufacturer’s recommendations for cultured cells. Briefly, after cell lysis, the total RNA was adsorbed to a silica matrix, washed with the recommended buffers and eluted with 35 μl RNase-free water by centrifugation. After RNA quantification, cDNA conversion for miRNA quantification was performed ioxilan using the Universal cDNA Synthesis Kit (Exiqon). For each sample, cDNA for miRNA detection was produced from 20 ng total RNA according to the following protocol: 60 min at 42° followed by heat-inactivation of the reverse transcriptase for 5 min at 95°. The cDNA was diluted 80 × with RNase-free water before quantification by qRT-PCR. Synthesis of cDNA for mRNA quantification was performed using the iScript cDNA Synthesis Kit (Bio-Rad) and employing 1 μg total RNA for each reaction, by applying the following protocol: 5 min at 25°, 30 min at 42° and 5 min at 85°. Finally, the cDNA was diluted 1 : 4 with RNase free water. Quantitative PCR was performed in an iQ5 thermocycler (Bio-Rad) using 96-well microtitre plates.

11 Flash pulmonary oedema (FPE) is probably the most widely accepted indication for renal revascularization. Cardiac dysfunction and ARVD go hand in hand, which, coupled with other factors, predisposes to FPE. Renal artery constriction can cause hypertension mediated predominantly by the renin-angiotensin-aldosterone system (RAAS).41 A normally functioning contralateral kidney can INCB024360 mw respond to increased RAAS activity on the affected side by suppression of its own renin secretion to help prevent

volume overload. Should both kidneys be affected by RAS then this homeostatic safety valve will not function leading to higher risk of volume overload. Neurohormonal mediated endothelial dysfunction brought about by CH5424802 excess stimulation of the RAAS causes increased pulmonary capillary permeability and further contributes towards FPE.42 Additionally, CKD is associated with increased arterial stiffness,43 concentric left ventricular hypertrophy,44 and increased left ventricular stiffness.45 This triad makes the circulatory system exquisitely sensitive to alterations in volume state, with little physiological reserve to deal with volume expansion. In the setting of FPE, ARVD is, predictably, often bilateral or present in a solitary functioning kidney. Although there are no

randomized or observational studies, revascularization has been shown to be of benefit in small series and case reports,46,47 with a suggestion that those with bilateral disease are most likely to benefit.48 Resistant hypertension (RH), defined as uncontrolled blood pressure (>160/90 mmHg) despite use of three or more

antihypertensive medications, is an area of ongoing debate. Therapeutic measures to treat hypertension have evolved rapidly over the years, and many drug therapies are applicable in patients with ARVD. Given the relationship between untreated hypertension and deterioration of renal function, effective treatment is paramount. While previously nephrectomies of ischaemic kidneys were undertaken to treat ‘malignant’ hypertension,49 with the Thalidomide advent of antihypertensives targeted to block the RAAS, and percutaneous revascularization techniques, this approach is now no longer applicable. Despite these pharmacological advances, there is often reticence to use angiotensin converting enzyme inhibitors (ACEi) and receptor blockers (ARB). These are very effective treatments for renovascular driven hypertension but there are widely held beliefs that bilateral RAS is a contra-indication for their use. Although it is beyond dispute that ACEi or ARB use can reduce GFR in certain individuals, patients with unilateral disease and a normally functioning contralateral kidney do not usually suffer this fate.50 Indeed, our experience is that many patients with significant bilateral RAS can tolerate RAAS blockade without detriment to function.