An opposite pattern was observed for progression of nephropathy. The authors note that the findings of the study are consistent with CVD studies and the role that SFAs may play in insulin sensitivity and other factors affecting diabetes control. Nonetheless, the authors consider that control of BP and blood glucose and cessation of smoking should remain the therapeutic objectives for modifiable risk factors. When these objectives are obtained, other measures such as encouraging PUFA and MIFA over SFA EPZ015666 manufacturer may help prevent micro and macroalbuminuria.118 Table A5 presents a summary of the relevant studies found by the search strategy

in relation to dietary fat. With the exception of the study by Cardenas et al.118 discussed above, the studies are either of short duration and thus provide little useful evidence for the role of dietary fat in the progression of CKD. Relevant details of the studies are provided in Table A12. In summary, there are insufficient reliable studies to support a recommendation in relation to the prevention and management of CKD in people with type 2 diabetes. Intake

of protein in the usual range does not appear to be associated buy Pexidartinib with the development of CKD. However, long-term effects of consuming >20% of energy as protein on development of CKD has not been determined. Although diets high in protein and low in carbohydrate may produce short-term weight loss and improved glycaemic control, it has not been established that weight loss is maintained in the long term. There have been few prospective controlled studies of low protein diets in people with type 2 diabetes and kidney disease. The studies that have been performed have generally been deficient in experimental design, in methods for measuring kidney function and/or in duration of follow-up. Furthermore, the level of compliance with a low protein diet has not always been assessed objectively by urinary urea

nitrogen excretion. A particular criticism is that changes in the creatinine pool Dichloromethane dehalogenase and creatinine intake seen in low protein diet studies render measurements of creatinine clearance or the reciprocal of serum creatinine unreliable for the assessment of GFR.119 The objective of the systematic review was to assess the effects of dietary protein restriction on the progression of diabetic nephropathy in people with diabetes (type 1 and type 2 diabetes).120 The review identified 11 studies (9 RCTs and 2 before and after trials) where diet modifications were followed for at least 4 months. Before and after trials were included as it was considered that people could act as their own controls. Of these studies 8 were of people with type 1 diabetes, one type 2 diabetes and two included both type 1 and type 2 diabetes.

The patients were grouped into the following categories: International Federation of Gynecology and Obstetrics (FIGO) stage IB (n = 16) and stage IIA–IIIB (n = 24). All tissues were subjected to immunohistochemical staining for IL-32 as described previously27

and clinically correlated with FIGO stage and survival, and the following results were obtained. In the serial section, immunohistochemical staining for COX-2 was also conducted to determine whether IL-32 and COX-2 are co-localized in cervical cancer cells. This study was approved by the Chungnam National University Hospital. The IL-32γ and COX-2 were amplified from the genomic DNA of human CaSki cells via PCR, using the following primers, respectively: IL-32γ: 5′-CTGGAATTCATGTGCTTCCCGAAG-3′ (forward), 5′-GAAGGTCCTCTCTGATGACA-3′ (reverse); COX-2: 5′-CCCAAGCTTGGGCTCAGACAGCAAAGC CTA-3′ (forward), 5′-CTAGTCTAGACTAGCTACAGTTCAGTCGAACGTTCTTT-3′ (reverse). Interleukin-32γ find more www.selleckchem.com/products/BKM-120.html was cloned into the EcoRI and XhoI sites of pCDNA3.1 using EcoRI and SalI, and COX-2 was ligated with pCDNA3.1 vector using the HindIII and XbaI sites. The promoters of IL-32 and COX-2 were amplified via PCR from human genomic DNA. The IL-32 promoter (−746/+25) was constructed as previously reported.21 The COX-2 promoter (−880/+9) used the following primers: 5′-CGGGATCCAAATTCTGGCCATCGCCGCTT-3′ (forward), 5′-CCAAGCTTTGACAATTGGTCGCTAA

CCGAG-3′

(reverse) cloned into the MluI and HindIII sites of the pGL3-basic vector, and the inserted sequences were confirmed via DNA sequencing. Both pTarget/E7 and pTarget/E7 antisense (E7AS) were described in a previous report.25,28 C33A/pOPI3, C33A/E7, SiHa and CaSki cells were seeded on six-well plates at a density of 3 × 105 cells per well, then grown to confluence, reaching approximately 80% at the time of transfection. For each well, plasmid DNA (1 μg) was introduced into the cells using an identical volume of Lipofectamine 2000 reagent (Invitrogen, Carlsbad, CA) in accordance with the manufacturer’s instructions. The pTarget Gemcitabine and pTarget/E7AS plasmid were transfected into C33A/E7, SiHa and CaSki cells to confirm the E7 oncogene-specific effect on IL-32 and COX-2 expression in HPV-expressing cervical cancer cells. The pGL3 basic, pGL3b/IL-32 promoter, and pGL3b/COX-2 promoter were respectively co-transfected with pTarget, pTarget/E7 and pTarget/E7AS into C33A/pOPI3, C33A/E7, SiHa and CaSki cells to determine the specific effects of E7 on the transcriptional activities of IL-32 and COX-2. Additionally, pCDNA3.1, pCDNA3.1/COX-2, pCDNA3.1/IL-32γ, siCONTROL and siIL-32 (Dharmacon, Lafayette, CO) were respectively transfected into SiHa and CaSki cells to evaluate expression between COX-2 and IL-32 by the HPV E7 oncogene. Interleukin-32γ is the most active form of IL-32 isoforms.

4%) (P = 0.011) and MUI occurred in four (36.4%) (P = 0.011). Conclusion: Significant risk factors for the development of SUI and MUI after transvaginal simple diverticulectomy include a UD measuring over 3 cm and a UD located in the proximal urethra. “
“In the urine storage

phase, mechanical stretch stimulates bladder afferents. These urinary bladder afferent sensory nerves consist of small diameter Aδ- and C-fibers running in the hypogastic and pelvic nerves. Neuroanatomical studies have revealed a complex neuronal network within the bladder wall. The exact mechanisms that underline mechano-sensory transduction in bladder afferent terminals remain ambiguous; however, a wide range of ion channels (e.g. TTX-resistant Na+ channels, Kv channels and hyperpolarization-activated cyclic nucleotidegated

cation channels, degenerin/epithelial Na+ channel), and receptors (e.g. TRPV1, TRPM8, TRPA1, P2X2/3, etc.) have been identified selleck screening library at bladder afferent terminals and have implicated in the generation and modulation of afferent signals, which are elcited by a wide range of bladder stimulations including physiological bladder filling, noxious distension, cold, chemical irritation and inflammation. The mammalian transient receptor potential (TRP) family consists of 28 channels that can be subdivided into six different classes: TRPV (Vanilloid), TRPC (Canonical), TRPM (Melastatin), TRPP (Polycystin), TRPML (Mucolipin), and TRPA (Ankyrin). TRP

channels are activated by a diversity of physical (voltage, heat, cold, mechanical stress) or chemical (pH, osmolality) stimuli and by binding of specific ligands, Talazoparib nmr enabling them to act as multifunctional sensors at the cellular level. TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1 have been described in different parts of the urogenital tract. Although only TRPV1 among TRPs has been extensively studied so far, more evidence is slowly accumulating about the role of other TRP channels, ion channels, and receptors in the pathophysiology of the urogenital tract, and may provide a new strategy for the treatment of bladder dysfunction. “
“To evaluate relation between red cell distribution width (RDW) and benign prostatic hyperplasia (BPH). The overall study population consisted of 942 men with lower urinary tract symptoms (LUTS), ranging triclocarban in age from 60 to 85 years old. Patients with disorder or medication that can influence lower urinary tract or erythrocytes were excluded from the study. The relationship between RDW, white blood cell (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and prostate volume, International Prostate Symptom Score (IPSS) were assessed with multivariate linear regression model. Patients were analyzed in four groups stratified according to the quartiles of prostate volume. The one-way analysis of variance (anova) was used to compare RDW, WBC CRP, and ESR between different quartiles of prostate volume.

All patients or their guardians gave informed consent and assent before the blood collection. Leukocyte isolation and serum samples.  Whole blood was collected into tubes containing ethylene diamine tetraacetic acid and kept for 1 h at room temperature. The tubes from five subjects were standardized to the number of WBC in 3000/μl. The cellular and cell-free serum fractions were separated, and cells were washed twice in 2 ml of phosphate buffer saline (PBS), followed

by centrifugation at 300 g for 5 min. The leukocyte pellets were resuspended in 100 μl of PBS and were incubated with 10 μl of 2% rabbit serum (Dako) for 30 min selleck chemicals at 4 °C to block Fc receptors. The supernatant was removed, and the remaining pellets were resuspended in 2 ml of PBS. The leukocyte preparation was hemolysed in erythrocyte lysing solution at room temperature for 10 min, followed

by centrifugation at 300 g for 5 min. The leukocyte pellets were washed twice and finally resuspended in 2 ml of PBS. To avoid variability in the flow cytometric analysis, the serum and the leukocytes prepared from the same controls were used throughout this study. Laboratory findings of the neutropenic patient with KS are shown in Table 2. Serum samples were separated by centrifugation at 700 g for 15 min at room temperature and were stored at −40 °C until time of assay. Flow learn more cytometry.  Flow cytometric analysis of cell specimens was performed on a FACSCalibur (Becton Dickinson Biosciences, San Jose, CA, USA). Neutrophils were initially gated by their characteristic forward scatter (FSC) and side scatter (SSC) profiles, which represent size and granularity, respectively. Cells in these gates were then analysed for fluorescence intensity. Within the neutrophil cluster, a minimum of 10,000 cells were analysed. Flow cytometric analysis of GIFT.  Anti-neutrophil antibodies on the surface SB-3CT of neutrophils were tested by the direct granulocyte immunofluorescence test (D-GIFT). Anti-neutrophil antibodies in serum were tested by the indirect granulocyte immunofluorescence test (I-GIFT). D-GIFT was performed on the leukocytes described in Table 1 (case A through

E) in PBS, incubated with FITC-conjugated goat F(ab’)2 anti-human IgG (Biosource) and PE-conjugated mouse anti-human CD13 (BD Biosciences) for 30 min at 4 °C. After washing, neutrophils were analysed on a FACSCalibur (Becton Dickinson Biosciences). I-GIFT was performed by the addition of 10 μl of serum from the patient, disease control or normal controls to treated leukocytes, incubation for 30 min at 4 °C, followed by centrifugation at 300 g for 5 min. After washing once with 2 ml of PBS containing 0.2% bovine serum albumin, the following monoclonal antibodies were used for staining: 2.5 μl of FITC-conjugated goat F(ab’)2 anti-human IgG (Biosource) and 2.5 μl of PE-conjugated mouse anti-human CD13 (BD Biosciences) for 30 min at 4 °C.

Similar to the Helicobacter model, IL-23 was responsible for inducing IL-17 production and colon-specific selleck chemicals tissue inflammation, and depletion of the Sca-1+ ILCs prevented development of colitis [3]. The idea that IL-17 production by ILCs can contribute to autoimmune disease has also been explored in humans. IL-17-producing cells are increased in the intestine of patients with ulcerative colitis and Crohn’s disease [8]. CD3− cells contributed significantly to the production of IL-17, both IL-17a and IL-17f mRNA

transcripts were increased in CD3− cells isolated from the intestines of patients with IBD as compared with transcripts in healthy controls [8]. In addition, there is an increased frequency of ILCs in the colon and ileum of patients CTLA-4 antibody inhibitor with Crohn’s disease but not ulcerative

colitis [8]. However, since the absolute numbers of IL-17-producing ILCs in the inflamed intestine are very small, it is still unclear whether these cells play a direct role in driving IBD. Therefore, further studies are needed to determine their exact role. There have been a small number of reports showing that NK cells produce IL-17. Since human NKR-LTi cells have been shown to secrete IL-17 [82], careful analysis and interpretation of the results are essential to avoid confusion between IL-17 production by NKR-LTi cells and that by classical NK cells. In the steady state, NK cells in the spleen do not express RORγt [5]; however, upon infection with Toxoplasma gondii, splenic NK cells have enhanced

RORγt expression and secrete IL-17 [4]. A recent report has also shown that CD56+CCR4+ human peripheral blood NK cells produce both IL-17 and IFN-γ and express the transcription factors RORγt and Tbet [98]. These cells are not NKR-LTi cells, since the NK cells in this study did not express IL-7R (CD127), nor IL-23R, and since NKR-LTi cells are not thought to exist in human peripheral blood [82, 89]. iNKT cells are a subset of T cells that express a semi-invariant TCR that recognizes glycolipids presented by CD1d molecules expressed on APCs. There have been a number of recent reports demonstrating that iNKT O-methylated flavonoid cells play a role in host protection against infection via the production of IL-17. Expression of RORγt in developing iNKT precursor cells is associated with the development of a preprogrammed IL-17-producing subset that does not express NK1.1 [99]. The signals that induce RORγt expression in iNKT precursors and lineage commitment have not yet been defined. These NK1.1− iNKT cells are capable of secreting IL-17 not only in response to stimulation with the synthetic ligand α-galactosylceramide or its analogue PBS-57, but also following stimulation with natural ligands, including LPS or glycolipids derived from Sphingomonas wittichii and Borrelia burgdorferi [100]. This IL-17-producing NK1.1− subset is present at high frequency in the lung, comprising up to 40% of pulmonary iNKT cells in naïve mice.

We also observed an increase in the microbicidal activity of alveolar macrophages of Lr1505- and Lc431-treated mice; this activity was significantly greater in the latter group (Table 1). Furthermore, the microbicidal activity of alveolar macrophages from the Lr1506-treated group was similar to that of the control mice. We next evaluated cytokine production by macrophages challenged in vitro with the pathogenic strain C. albicans EX 527 in vitro AV4. All treatments increased production of TNF-α and IL-1β in peritoneal

macrophages; we observed no significant differences between treatments (Fig. 3a). Administration of Lr1505 and Lc431 increased the capacity of alveolar macrophages to produce TNF-α and IL-1β in response to C. albicans challenge, whereas administration of Lr1506 did not induce changes in the concentrations selleck chemicals llc of these

cytokines (Fig. 3b). To evaluate the effect of lactobacilli treatments on peritoneal macrophages in vivo, we challenged the various groups of mice intraperitoneally with 108 cells of pathogenic C. albicans AV4 and took samples from liver, spleen and blood 48 hours later to analyze the presence of yeasts. Untreated control animals had positive counts of the pathogen in all the studied tissues (Table 2). Lc431, Lr1505 and Lr1506 treatments significantly reduced C. albicans counts in the liver during the studied period. In addition, animals treated with the different lactobacilli strains were able to eliminate the pathogenic yeast from blood and spleen (Table 2). In addition, in order to evaluate the influence

ID-8 of Lc431, Lr1505 and Lr1506 on the activity of alveolar macrophages in vivo, we challenged the various groups of mice intranasally with 107 cells of pathogenic C. albicans AV4 and 48 hours later, took samples of lung and blood to determine the presence of yeast. The control animals had positive pathogen counts in both lung and blood (Table 2). Mice treated with Lc431 or Lr1505 had significantly lower C. albicans counts in the lungs than did the control group; Lr1506 did not induce changes in this variable. Moreover, all treatments were able to induce clearance of the pathogenic yeast from blood (Table 2). We next studied the immune response in the peritoneal cavity after challenge with C. albicans AV4. The number of leukocytes, macrophages and neutrophils in the peritoneal cavity increased in all experimental groups after challenge with the pathogen (Fig. 4a, b). However, mice treated prophylactically with Lc431, Lr1505 or Lr1506 had significantly greater macrophage and neutrophil counts than did those in the control group (Fig. 4a, b). We also observed increased concentrations of TNF-α and IFN-γ in peritoneal fluid after challenge with the pathogen in all experimental groups (Fig. 4c, d). However, groups receiving lactobacilli had greater cytokine concentrations than did controls. Nasal challenge with pathogenic C.

RNA analysis indicated that mhuA and mhuB are each transcribed from individual Fur-regulated promoters. Pexidartinib chemical structure Moreover, RNA analysis of an mhuB deletion mutant and a promoter reporter assay coupled with β-galactosidase suggested that MhuB could function as an activator for mhuA transcription. Finally, the role of MhuA as the heme/hemoglobin receptor was confirmed by construction of an mhuA deletion mutant and its complemented strain followed by growth assay. Iron is an element integral to the growth of almost all bacteria.

However, the availability of iron for bacteria is limited because it is usually present as insoluble ferric hydroxide polymers in an aerobic environment or bound to iron-binding proteins such as transferrin and lactoferrin in mammalian hosts (1). Therefore, most bacteria have

evolved the ability to acquire iron under iron-restricted conditions. Numerous bacteria produce and secrete siderophores (low-molecular weight iron-binding chelators) which can remove ferric iron from iron-binding proteins. In Gram-negative bacteria, ferric ion complexed with siderophore (ferrisiderophore) is transported into cells via a TonB-dependent specific uptake system, consisting of an outer membrane receptor protein and an ABC transporter (2). In addition, certain bacteria acquire heme as a nutritional iron source by a TonB-dependent system, similar selleck kinase inhibitor to those for ferrisiderophores, which includes the binding of heme or heme-containing proteins such as hemoglobin to the cell surface receptor, followed by transport of the intact heme moiety into the cell (3). Siderophores are unable to remove the iron from heme. Moreover, when intracellular iron concentrations are high, expression of those systems studied to CHIR-99021 nmr date is negatively regulated at the transcriptional level by a global iron-binding repressor protein called Fur (ferric uptake regulation) with ferrous ion as a corepressor, (4, 5). V. mimicus was first described as a group of biochemically atypical strains of V. cholerae

(6) but they share some pathogenic factors such as enterotoxins and hemolysins (7). V. mimicus, like other pathogenic Vibrio species, inhabits environmental water, including river, brackish, and sea water, and causes diarrhea through eating fish and shellfish contaminated with the bacterium (8). The present authors have previously reported that V. mimicus secretes the siderophore aerobactin in response to iron restriction (9), and that the iucABCD genes engage in aerobactin biosynthesis. They have also reported that the ferriaerobactin complex is incorporated into the cytosol via the 77-kDa IROMP, IutA, and the ABC transporter, MatCDB (10). V. mimicus also expresses 80-kDa IROMP under iron-restricted conditions (9). Hence, V. mimicus is expected to use at least one other iron source besides ferriaerobactin. Although many Vibrio species, including V.

These effectors could arise naturally as the tumours develop, such as the T cells seen in many melanoma patients,2,63,64 or from intentional

immunization with tumour-associated antigens,2–4 or could even be T cells that have been expanded and even genetically modified in vitro and adoptively transferred.65,66 Hence, although we have shown effects of the fusion protein as a single agent, probably enhancing innate responses and the endogenous T-cell response, we hypothesize that the fusion protein mTOR inhibitor would be even more effective in conjunction with immunization schemes. In this context there are a wide variety of innovative approaches for initiating anti-tumour cellular immune responses that show substantial promise (reviewed in refs 1 and 67) as well as recent clinical successes in patients with prostate cancer.68,69 The data presented here represent the first ‘proof of principle’ of the protease-activated cytokine approach using specific

inhibition. Importantly, the tethered cytokine strategy using specific inhibition is a platform technology that could be employed selleck compound with different immunomodulatory agents to either promote (e.g. IL-12) or inhibit (IFN-β or IL-10) cellular immune responses. This would be particularly useful for cytokines that have potent anti-tumour effects like IL-12 but systemic side-effects limit their usefulness when given systemically.11,70 The scFv format is particularly flexible in this regard. An scFv could be developed against almost any target molecule given the extremely large antibody repertoire in the scFv library and could be made against immunomodulators such as chemokines where the receptor approach is not easily implemented. It is also important to consider that the cytokine environment in the tumour would probably be affected in a cascade fashion as the infiltrating cells change. As a result, it may be possible to alter the balance of cytokines from the generally suppressive environment of the tumour, rich in a variety of immunosuppressive factors, enzymes and cells,1,71–74 to one that is conducive to an ongoing immune response leading to the eradication of

tumours. CYTH4 The authors would like to thank Drs Edward Messing and Baek Kim for encouragement and helpful suggestions, Dr Robert Rose and Christopher Lane for helpful advice on insect cell expression of proteins, and Drs Barth, Leddy, Courtney, Simon, Valentino and Cohen for comments on the manuscript. This work was made possible by generous gifts from Steven and Alison Krausz and F.C. Blodgett. John Puskas, Denise Skrombolas and Abigail Sedlacek were supported by 5T32AI00728 from the National Institutes of Health. None of the authors involved with this work has any financial interests or any other conflict of interest to disclose. “
“The effects of the soluble forms of the endotoxin receptor molecules sMD-2 and sCD14 on bacterial growth were studied.

Although further research is still needed, cell and gene therapy based on stem cells, particularly using neurons and glia derived from iPSCs, ESCs or NSCs, will become a routine treatment for patients suffering from neurodegenerative diseases and also stroke and spinal cord injury. Cell replacement therapy and gene transfer to the diseased or injured brain have provided the basis for the development

of potentially powerful new therapeutic strategies for human neurological diseases. However, the paucity of suitable cell types for cell therapy in patients suffering from neurological disorders has hampered the development of this promising therapeutic Selleckchem RG7420 approach. In recent years, neurons and glial cells have successfully been generated from stem cells such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs) and neural stem cells (NSCs), and extensive efforts by investigators to develop stem cell-based brain transplantation therapies have been carried out. Stem cells are defined as cells that have the ability to renew themselves continuously and possess pluripotent ability to differentiate into many cell types. Two types of mammalian pluripotent stem cells, ESCs derived from the inner cell mass of blastocysts and embryonic germ cells (EGCs) obtained from post-implantation embryos, have been identified and these stem cells give rise to various organs and tissues.[1, Selleckchem BI2536 2]

Recently there has been an exciting development in generation of a new class of pluripotent stem cells, iPSCs, from adult somatic cells such as skin fibroblasts by introduction of embryogenesis-related genes.[3, 4] A recent study has indicated that patients’ own fibroblasts could directly be converted into neurons by combinatorial expression of three neural lineage-specific transcription factors, Ascl1, Brn2 and Myt1l. These induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials, and form functional synapses.[5] In another study, a combination of five transcriptional factors Mash1, Ngn2, Sox2, Nurr1 and Ptx3,

can directly and effectively reprogram human fibroblasts into dopaminergic (DA) neurons. The reprogrammed cells stained positive for cell type-specific markers for DA neurons.[6] In addition to ESCs and iPSCs, tissue-specific Megestrol Acetate stem cells could be isolated from various tissues of more advanced developmental stages such as hematopoietic stem cells (HSCs), amniotic fluid stem cells, bone marrow MSCs, adipose tissue-derived stem cells, and NSCs. Among these, existence of multipotent NSCs has been known in developing or adult rodent brain with properties of indefinite growth and potential to differentiate into three major cell types of CNS, neurons, astrocytes and oligodendrocytes.[7-11] In humans, existence of NSCs with multipotent differentiation capability has also been reported in embryonic and adult human brain.

Addition of 4AP, a relatively nonspecific KV channel blocker, significantly increased isolated arterial and venous basal tone and agonist-induced vasoconstriction [58, 69]. Chorionic plate arterial contraction has also been noted to be increased with more isoform-specific blockers margatoxin and stromatoxin-1, but only correolide increased contraction of chorionic plate veins [36]; basal

tone was unaffected. These data selleck chemicals suggest KV1.2 and/or KV2.1 and KV1.5 in the control of agonist-induced contraction of human placental arteries and veins, respectively. Expression of other 4AP-insensitive KV7 channels has also been suggested; Mistry et al. noted low-level expression of KV7 channels in villus vascular tissues [47], and we have preliminary functional data demonstrating 4AP-insensitive KV7 channel activity in isolated chorionic plate arteries [45]. Endothelin-1 precontracted placental arterial relaxation to SNAP has been shown to be reduced in the presence of charybdotoxin, suggestive of functional BKCa and IKCa channels [58]. Agonist (U46619)-induced

contraction (but not basal tone) is increased by iberiotoxin in chorionic plate Ipilimumab in vitro arteries but not veins; however, this finding was inconsistent with altered bath oxygenation [69]. Currently, the only functional evidence for twin-pore K+ channel O-methylated flavonoid activity has come from Wareing et al.; TASK-1 expression was noted (RT-PCR; Western blotting) and anandamide increased basal tone and agonist-induced contraction in isolated chorionic plate arteries [69]. These data do not represent a definitive proof of a role for TASK-1 channels in the control of fetoplacental vascular reactivity as anandamide has also been suggested to inhibit KV1.2 and KV1.5 channels (whose presence has also been suggested

using more specific blockers [36]). Taken together, these data suggest that a range of K+ channels are present in the fetoplacental vasculature and that they significantly contribute to normal vascular function (Table 2). However, these data are far from complete. The role of KCa channel subtypes requires further elucidation including an assessment of endothelial vs. smooth muscle cell reactivity using primary isolates or cultured cells. Future experiments with isolated smooth muscle and endothelial cells will also be key in determining if placental vascular K+ channels are the primary sensors of altered tissue oxygenation status. Altered K+ channel function has been suggested to induce increased vascular smooth muscle contractility in chronic hypertension [61]. Whether this occurs in FGR, where clinical umbilical arterial Doppler ultrasound waveform measurements suggest increased resistance to blood flow [59], remains unclear.