berghei-infected mice [43], and in Ghanaian children cerebral malaria mortality was not associated with IL-17 [15]. While IL-17F levels were similar in NEG, MM and SM infants, the cytokine IL-31, which has comparable effects to IL-17 [44], was highest in SM patients. IL-17 and IL-31 both have

additive effects on secretion of cytokines and chemokines [44,45], and Selleck PI3K Inhibitor Library IL-31, a member of the gp130/IL-6 cytokine family [45], may recruit polymorphonuclear cells, monocytes and T cells to an inflammatory site in vivo[46]. IL-31 will induce the genes of inflammatory chemokines MIP-1β, MIP-3α, MIP-3β[47,48] and proinflammatory cytokines IL-6, IL-8, IL-16 and IL-32 [44,45]. IL-31-receptor-deficiency in mice injected with Schistosoma mansoni eggs resulted in severe

Hydroxychloroquine order pulmonary inflammation, enlarged granuloma and significantly more IL-4, IL-5 and IL-13 than in wild-type mice [48]. In allergic asthma patients, serum levels of IL-31 were elevated above controls [49], a further suggestion that the IL-31/IL-31R signalling pathway will regulate type 2 inflammations [48]. Another key player promoting Th2 type responses, the cytokine IL-33, is considered a mediator of pathology with allergies and septic shock [50–52]; IL-33 was suggested to function as an alarmin [53], to alert after endothelial or epithelial cell damage during trauma, stress or infection [53]. IL-33 levels were enhanced in infants with MM and SM, clearly above NEG, selleck chemical correlated positively with parasite densities, and diminished strongly following parasite clearance. Sequestration of P. falciparum-infected erythrocytes or the release of merozoites may have amplified IL-33 production by endothelial cells, and additional cytokines augmented by IL-33 are IL-5, IL-13, TNF and IL-3 [54]. Furthermore, IL-33 will promote splenomegaly, blood eosinophilia and epithelial hyperplasia, massive mucus production in lungs

and pulmonary inflammation [55]. To what extent the enhanced production of IL-31 and IL-33 may contribute to pathogenesis of acute P. falciparum infection to cerebral inflammation and vascular obstructions should be investigated further. For the development of cerebral malaria, an important role has been attributed to cytokines and chemokines [56,57]. With severe P. falciparum infection an increased production of MCP-1/CCL2, MIP-1α and MIP-1β, and also IL-8/CXCL8, has been observed [9,13], and the mortality risk with cerebral malaria (CM) was associated independently with the serum concentration of IP-10/CXCL10 [15]. The chemokines IP-10/CXCL10 and MIG/CXCL9, together with their common receptor CXCR3, are required for the development of murine CM [58]. MIG/CXCL9 and its receptor are expressed predominantly in Th1 cells, and MIG/CXCL9 is considered to be a predictive marker for antigen-specific IFN-γ-secreting peripheral blood mononuclear cells (PBMCs) in volunteers immunized with irradiated P. falciparum sporozoites [59].

interdigitale (four cases) and Trichophyton mentagrophytes var. mentagrophytes (one case). Concomitant dermatophytosis at other locations was confirmed in seven cases (25%). Toenail onychomycosis was associated with tinea pedis in five cases. Distal and lateral subungual onychomycosis was the most common clinical pattern. The superficial white type was found in two cases of toenail onychomycosis caused NVP-AUY922 chemical structure by T. rubrum and T. tonsurans.

During the period of study, only 5.1% of all investigated people were children up to 16 years. The prevalence of onychomycosis tended to increase over the years and represented 15.5% of all nail dystrophies in children. Therefore, dermatologists must consider onychomycosis in the differential diagnosis of nail alterations in children and always perform a mycological study to confirm the diagnosis. “
“An 83-year-old man presented with an approximately 1-year history of an extensive inflammatory purulent crusted lesion in the bald area of the scalp diagnosed as tinea caused by Trichophyton rubrum. The scalp biopsy specimen showed

suppurative folliculitis with perifollicular abscesses in upper dermis, and periodic acid-Schiff-positive fungal elements within the hair follicles and MLN0128 nmr in the hyperkeratotic horny layer. The infection probably spread from diseased fingernails. A cure of the scalp lesion was achieved 2 months after starting daily oral treatment with 250 mg terbinafine. To our knowledge, the case presented is the first in which a suppurative abscess-forming T. rubrum infection of the bald area of the scalp in an immunocompetent man has been described. “
“The authors describe two cases of successful and safe posaconazole use in patients of a surgical intensive care unit of a university hospital. “
“Post-sternotomy infectious complications, including superficial and deep wound infections, sternal osteomyelitis and mediastinitis, are rarely caused by fungi. Trichosporon asahii is the main Trichosporon species that causes systemic infection in humans. Most cases involved neutropenic patients with hematologic

Adenosine malignancies. We report a unique case of a non-cancer, non-neutropenic but severely ill patient who developed an ultimately lethal T. asahii infection after sternotomy. We speculate that our patient had been colonized with the fungus and his surgical site infection may have been related to his emergency revascularization surgery. Therapy with liposomal amphotericin failed to sterilize the bloodstream despite in vitro susceptibility results. The addition of voriconazole helped sterilizing the bloodstream without changing the outcome. Physicians must be aware of the continuously expanding spectrum of infections with this emerging difficult-to-treat fungal pathogen. “
“We present a case of infection due to Cladophialophora carrionii, an agent of Chromoblastomycosis in a 37-year-old Indian male.

64 Subsequent studies demonstrated that renal injury was prevented in fH knockout mice that were also C5-deficient or when given an inhibitory anti-C5 antibody, suggesting that terminal complement activation contributes to the pathology.59 Interestingly,

when fI KO mice were generated they also showed low plasma C3 levels, indicating complement consumption, but unlike fH knockout mice they did not develop MPGN.81 Furthermore, fH/fI double deficient mice also failed to develop MPGN.81 Because fI converts C3b into iC3b and C3d, these data suggest that the development of MPGN may depend more on the forms of activated C3 generated by the AP. Thrombotic microangiopathies are a group of diseases characterized by thrombocytopenia, microangiopathic haemolytic anaemia, and either impaired renal or neurologic Opaganib function.82 Thrombotic this website thrombocytopenic pupura has varying degrees of renal impairment, but many other organs can be affected, particularly the nervous system. Contrastingly, haemolytic uraemic syndrome (HUS) is another disease in this category, but symptoms are largely restricted

to the kidney. There are two types of HUS, distinguished by the presence or absence of diarrhoea caused by Shiga toxin-producing bacteria.82 Diarrhoea-positive, or D+ HUS, is the most common form of HUS and can usually be cured with antibiotics and symptomatic treatment.82 On the other hand, diarrhoea-negative HUS, often referred to as atypical HUS (aHUS), only makes up 5–10% of HUS cases but has a much poorer prognosis.83 Approximately 50% of aHUS patients progress to end-stage renal failure and at least 25% of cases are fatal.84 It is still unclear what triggers aHUS episodes although it is believed to be initiated by endothelial Thymidylate synthase cell injury caused by

infection or other exogenous injury.35 While mutations in procoagulant proteins such as thrombomodulin have been found in some aHUS cases,85 the majority of mutations found in aHUS patients have been with AP complement proteins. A multitude of clinical studies over the last decade have demonstrated that at least half of the familial cases of aHUS are caused by mutations in the complement system that lead to uncontrolled AP activation.25,35,86 While a few cases have reported mutations in C3 or fB that tend to produce aberrant C3bBb convertases more resistant to inactivation,87–89 most mutations affect the function of regulatory proteins fH, fI and MCP.35,90,91 In fact, the genes for these proteins are all located on the same region of chromosome 1 (1q32), called the regulators of complement activation gene cluster,92,93 making the latter a ‘hot’ chromosomal spot for aHUS-related mutations. A few cases of dysfunctional C4bp have also been reported,94 but interestingly DAF, another regulators of complement activation gene, has not been linked to any aHUS patients to date.

By real-time polymerase chain reaction (RT-PCR), the PTEN gene expression in the tumor was lower than in the five non-neoplastic brain tissues used as control.

Mutation analysis did not show any variation in INI-1 and PTEN sequence while P53 analysis showed the presence of homozygote P72R variation. Fluorescent in situ hybridization analysis showed polysomy of chromosome 2 while amplification of N-MYC was not detected. Owing to the rarity of embryonal tumor with abundant neuropil and true rosettes, each new case should be recorded to produce a better clinical, pathological and molecular BMS-354825 characterization of this lesion. “
“Neurofibromatosis type 2 (NF2) is a hereditary tumor syndrome. The hallmark of NF2 is bilateral vestibular schwannoma. In addition, glioma is one of the diagnostic criteria of NF2. In this retrospective study the clinical presentation and histopathological features of 12 spinal gliomas from NF2 patients were assessed. Ten tumors were previously diagnosed as ependymomas and two as astrocytomas. However, upon re-evaluation selleckchem both astrocytomas expressed epithelial membrane antigen in a dot-like fashion and in one case it was possible to perform electron microscopy revealing junctional complexes and cilia typical for ependymoma. The findings suggest that NF2-associated spinal gliomas are ependymomas. Based on the fact that NF2-associated gliomas are

almost Dapagliflozin exclusively spinal and that no NF2 mutations have been found in sporadic cerebral gliomas, we suggest that “glioma” in the current diagnostic criteria for NF2 should be specified as “spinal ependymoma”. “
“Rhabdoid meningioma is an uncommon meningioma variant categorized as WHO grade III. The majority of cases occur in adulthood. Herein, we describe a right fronto-temporal rhabdoid meningioma affecting a 3-year-old boy. The lesion measured approximately

4 cm in diameter and incorporated the ipsilateral middle cerebral artery. Sub-total surgical excision of the mass was performed. Histologically, the tumor was mainly composed of globoid plump cells with inclusion-like eosinophilic cytoplasm, peripheral nuclei, prominent nucleoli and occasional intra-nuclear cytoplasmic pseudo-inclusion. The cells appeared in many areas loosely arranged and focally disclosed a papillary architecture. At immunohistochemistry, the tumor cells were EMA, vimentin, HHF35, PgR, INI-1 and p53 positive. The proliferative index (Mib-1) was 15% in the most positive areas. Ultrastructurally, tumoral cells showed an abundant cytoplasm, which was filled with numerous intermediate filaments. Desmosomal junctions were seen. RT-PCR revealed the presence of NF2 gene expression. Molecular study did not indicate alterations of the INI-1 gene, whereas it showed the presence of Pro72Arg in exon 4 at heterozygous state in the TP53 gene.

This newly developed animal model now includes three major hallmarks Selleck BMS 907351 of AD: genetically related age-dependent β-amyloidosis and tau hyperphosphorylation, complemented with experimentally induced cholinergic cell loss. Prospectively, such an attempt using 3xTg mice with modifiable cholinergic dysfunction appears promising for studies addressing different aspects of this devastating disease. Currently, acetylcholinesterase

inhibitors are still, despite their limitations, the most widely used drugs for symptomatic AD therapy [81]. Selective α7 nicotinic acetylcholine receptor partial agonists are now in clinical trials and have been demonstrated to be beneficial in preclinical studies by potentiating the acetylcholine response of α7 nicotinic acetylcholine receptors [82]. The presented data support the view that drugs targeting the cholinergic neurotransmission remain justified as a potential treatment strategy of AD (for review see [47]). The authors thank Drs Reinhard Schliebs and Thomas Arendt for critical reading of an earlier version from this article. We are

thankful to Dr Peter Davies (Pathology, Albert Afatinib molecular weight Einstein College of Medicine, New York, USA), Dr Sascha Weggen (Neuropathology, University of Düsseldorf, Germany) and Dr Christian Czech (Hoffmann-La-Roche, Basel, Switzerland) for the donation of antibodies and Drs Frank M. LaFerla and Salvatore Oddo (University of California, Irvine, CA, USA) for pairs of triple-transgenic and WT mice. The technical assistance of Dr Anke Hoffmann, Ute Bauer and Marita Heindl is gratefully acknowledged. The biochemical part of the study was supported by the Alzheimer Forschung Initiative e.V. (to O.W.). The study was designed by Wolfgang Härtig who also performed the histological work together with Simone Goldhammer (SG) as part of her MD thesis. Immunolesions were made by Johannes Kacza. All biochemical data were generated by Annika Saul and Oliver Wirths. Histological Adenosine figures were produced by Jens Grosche, Simone Goldhammer and Dominik Michalski. The manuscript was written

by Wolfgang Härtig and considerably improved by Oliver Wirths and Dominik Michalski. “
“Upon denervation, skeletal muscle fibres initiate complex changes in gene expression. Many of these genes are involved in muscle fibre remodelling and atrophy. Amyotrophic Lateral Sclerosis (ALS) leads to progressive neurodegeneration and neurogenic muscular atrophy. Disturbed calcium homeostasis and misfolded protein aggregation both in motor neurons and muscle fibres are key elements of ALS pathogenesis that are mutually interdependent. Therefore, we hypothesized that the calcium sensor STIM 1 might be abnormally modified and involved in muscle fibre degeneration in ALS and other types of NMA. We examined ALS and NMA patient biopsy and autopsy tissue and tissue from G93A SOD1 mice by immunohistochemistry and immunoblotting.

The present work presents evidence that a progressively growing, endogenous tumor indeed fails to activate NK-cell effector functions. Escape from NK-cell surveillance seems

to be more complex than the hypothesis of failing priming or failing triggering might suggest. Possibly, NK cells are exhausted as a consequence of prolonged activation, as it was described for T cells 44. Alternately, developing tumors might actively paralyze NK cells. These observations should be considered when establishing, e.g. approaches JAK inhibitor of adoptive NK-cell transfer. All cell lines were cultured in RPMI 1640 (Invitrogen, Karlsruhe, Germany) medium supplemented with 5% heat-inactivated FBS, 2 mM L-Glutamine, 100 U/mL penicillin and streptomycin, non essential aa, and 50 μM 2-ME. Cells were kept

at 37°C in a humidified 5% CO2 atmosphere. A20 and MPC11 are BALB/c-derived B-cell lymphoma cell lines 45, 46. The variant A20low expressing reduced levels of MHC class I was generated by transfection of A20 with an mCMV-derived gene 6. The murine lymphoma cell line YAC-1 served as a target for NK-cell killing in cytotoxicity assays 47. DC were generated exactly as previously described 22. λ-myc cell lines myc-B, myc-E and 291S were generated by seeding primary lymphoma cells from λ-myc mice on irradiated MRC-5 fibroblasts as a feeding layer. After about 2 wk of culture, cells were able Sorafenib to grow independently. All animals were kept under specific pathogen-free conditions in our animal facility. C57BL/6 and BALB/c WT mice were purchased from Bommice (Ry, Denmark). λ-myc mice 29 are of C57BL/6 origin and were bred in our own facility. All animal experiments were in accordance with relevant regulations and had been approved by the Regierung von Oberbayern. Groups of at least six age-matched mice were used for experiments. Animals were treated with 10 nMol

CpG-ODN 1668 (Metabion, Martinsried, Germany) that was injected i.p. in 1- to 2-wk intervals 6 or received 5×105 DC subcutaneously as described earlier 22. NK-cell depletion was done by using anti-asialo GM1 Ab (Wako, Neuβ, Germany). 100–300 μL were administered i.v. and i.p. 1 day before each CpG-ODN injection Thiamine-diphosphate kinase in λ-myc mice; 300 μL were given i.p. 1 day before as well as 2 and 9 days after challenge with myc-B tumor cells in WT mice. NKT cells were not affected by treatment with anti-asialo GM1. In total, 104 to 105 myc-B, myc-E, 291S or MPC11 cells or 106 A20 or A20low cells were injected i.v. Phenotyping of NK cells was done by labeling with the following mAb: CD49b (DX5, BD Pharmingen, Heidelberg, Germany), CD45R (RA3-6B2, BD Pharmingen), NKG2D (CX5, eBioscience, San Diego, USA), Ly49D (4E5, BD Pharmingen), Ly49I (YLI-90, BD Pharmingen), CD69 (H1.

3B) and recovered a population of F4/80+ macrophages. Interestingly, Itgb2−/− Enzalutamide solubility dmso macrophages showed a broader range of F4/80 expression than WT macrophages (Supporting Information Fig. 3B). We assessed inflammatory cytokine production in these thioglycollate-elicited macrophages by intracellular

cytokine staining. F4/80high Itgb2−/− peritoneal macrophages exhibited increased TLR4 responses over WT cells (Fig. 2A and B). The percentage of IL-12 p40- and IL-6-producing Itgb2−/− peritoneal macrophages was significantly elevated over WT cells following LPS stimulation, whereas TNF production remained unaffected by β2 integrin deletion, mirroring the phenotype of BM-derived macrophages (Fig. 2B). Thus, these data demonstrate that, in addition to BM-derived macrophages, β2 integrins also negatively regulate TLR-induced IL-12 p40 and IL-6 production in inflammatory macrophage populations. To identify the contribution of β2 integrins to inhibiting TLR responses in vivo, we injected WT and Itgb2−/− mice with LPS i.p. and measured inflammatory cytokine levels in serum up click here to 4 h after injection. The kinetics for TNF,

IL-12 p40, and IL-6 induction were similar between WT and Itgb2−/− mice, with the peak serum concentration of each cytokine occurring at the same time in both (Fig. 2C). However, differences in the magnitude of cytokine production were observed. Serum IL-12 p40 levels were dramatically increased in Itgb2−/− mice such that by 4 h post-injection, Itgb2−/− animals displayed approximately three times the concentrations observed in WT controls. Itgb2−/− mice also presented with significantly

elevated serum IL-6 and TNF in response to LPS injection (Fig. 2C). While Itgb2−/− mice have changes in leukocyte populations, including increased Tolmetin circulating neutrophils, that make interpreting in vivo findings challenging, these data did support our in vitro findings that β2 integrins inhibited TLR responses in two distinct macrophage populations, BM-derived macrophages and thioglycollate-elicited macrophages. TLR stimulation in macrophages results in secretion of the anti-inflammatory cytokine IL-10 that acts in an autocrine or paracrine manner to dampen TLR activation [25]. Interestingly, culture of human macrophages on fibrinogen-coated plates induces IL-10 expression, as well as the expression of proteins such as A20, Hes-1, and ABIN-3, which are known to inhibit TLR signaling [20]. Fibrinogen is a β2 integrin ligand and plating of human macrophages onto fibrinogen-coated plates presumably induces a β2 integrin signal, though other receptors may also be engaged [26-29].

2d). Higher concentrations of rapamycin (up to 100 ng/ml) did not further Everolimus cost enhance T cell proliferation after TLR-7 ligation of PDC. T cells stimulated by PDC secreted proinflammatory (IFN-γ, IL-17) and anti-inflammatory (IL-10) cytokines (Fig. 2e), but no T helper type 2 (Th2) cytokines (data

not shown). Treatment of PDC with rapamycin suppressed the capacity of PDC to stimulate IFN-γ and IL-10 secretion by T cells irrespective of the mode of PDC-activation. Because rapamycin enhances the capacity of TLR-7 activated PDC to stimulate CD4+ T cells, we determined whether these CD4+ cells acquired a different cytokine production profile. CFSE-stained naive and memory T cells were stimulated by TLR-7 activated PDC that were treated or not treated with rapamycin. After 7 days these T cells were restimulated with PMA/ionomycin and intracellular IFN-γ, EPZ015666 IL-17 and IL-10 accumulation was determined. Figure 2f shows that rapamycin

treatment of PDC reduced the generation of IFN-γ-producing and IL-10-producing naive Th cells, while leaving IFN-γ and IL-10 production in the memory Th cell compartment unaffected. IL-17 was not induced in naive Th cells by TLR-7 PDC (< 1%), but rapamycin treatment of PDC slightly reduced the numbers of IL-17-producing memory Th cells. To find an explanation for the observed increase in T cell proliferation induced by rapamycin-treated TLR7-activated PDC, we determined the effects

of rapamycin on the expression of major histocompatibility complex (MHC) and co-stimulatory molecules on PDC. Rapamycin did not affect expression of MHC class I and II molecules on PDC under any of the stimulation conditions (data not shown). CD40 expression on PDC was suppressed by rapamcyin in both stimulation conditions, while CD86 expression was not affected. Interestingly, rapamycin enhanced up-regulation of CD80 significantly on from TLR-7-ligated PDC, but not on TLR-9-activated PDC (Fig. 3a). In the absence of rapamycin a subpopulation of TLR-7-stimulated PDC did not express CD80, while in the presence of rapamycin all PDC up-regulated CD80 expression. To determine whether the increased CD80 expression might be responsible for the increased ability of rapamycin-treated TLR-7-activated PDC to stimulate T cell proliferation, a neutralizing antibody against CD80 was added to co-cultures of TLR-7-stimulated PDC and allogeneic T cells. As rapamycin inhibits IFN-α production by TLR-7-activated PDC and IFN-α has an inhibitory effect on T cell proliferation [26, 27], we also determined the effect of a neutralizing IFN-α-R2 antibody on the T cell stimulatory capacity of TLR-7-activated PDC.

In addition, patients with fibrosis had lower FCRN mRNA levels compared to patients without fibrosis (P = 0·041). No relationship between FCRN mRNA levels and other phenotypical features of CVID (presence of chronic diarrhoea, splenomegaly, granulomas, lymphadenopathy or autoimmune phenomena) Copanlisib was documented. No correlation was found between FCRN mRNA level and pre-infusion IgG and also serum albumin levels

in CVID patients. However, a correlation was demonstrated between FCRN mRNA level and the decline in serum IgG concentration during the second week after IVIg infusion (D14/D7 ratio) (P = 0·045 Spearman’s correlation coefficient). The higher the FCRN mRNA expression, the less pronounced the decrease in IgG concentration in the tracked period after IVIg infusion was observed [6].

We also showed a significant positive correlation between FCRN mRNA expression and the ‘efficiency index’ defined as: [IgG trough level – IgG residual level (g/l)]/IgG dose (g/kg/week [7]; P = 0·05). selleck compound We did not document any correlation between FCRN mRNA expression and serum albumin levels in our CVID patients (P = 0·258). Our findings show that FcRn may play a role in the development of lung structural abnormalities, which are the principal life-threatening complications in patients with CVID, as well as in the catabolism of therapeutically administered IVIg. However, our results were obtained in a limited number of patients and show borderline statistical significance, and

need to be interpreted carefully. This study was supported by grant NT 111414-5/2010 of the Czech Ministry of Health. J. L. has received consultation fees from Baxter and LFB Biotechnologies; research 17-DMAG (Alvespimycin) HCl support from Shire and Baxter; honoraria for lectures from Biotest and Baxter; and support for clinical studies from Octapharma and CSL Behring. “
“Our and others’ previous studies have shown that Schistosoma japonicum (SJ) infection can inhibit allergic reactions. We recently reported that DCs played an important role in SJ infection-mediated inhibition of allergy, which was associated with enhanced IL-10 and T regulatory cell responses. Here, we further compared the role of CD8α+ DC and CD8α− DC subsets for the inhibitory effect. We sorted CD8α+ DC (SJCD8α+ DC) and CD8α− DC (SJCD8α− DC) from SJ-infected mice and tested their ability to modulate allergic responses in vivo. The data showed that the adoptive transfer of SJCD8α− DC was much more efficient than SJCD8α+ DC for the suppression of allergic airway eosinophilia, mucus overproduction, antigen-specific IgE responses, and Th2 cytokines (IL-4 and IL-5).

Functional data are summarized in Table 2. contraction [25, 28, 8, 27] graded effect [54]; contraction [52] No resistance to U46619, ET-1, and 5HT [55] ATP-induced in resistance attenuated [55] No change (PGI2 induced tone) [55] U46619-induced contraction [70] No basal tone [9, 10] No sensitivity to SNP [70] Relaxation in pressurized vessels [68] Dilatation of large placental arteries [16] No contraction to U46619 [70] sensitivity to SNP [70] Contraction in pressurized vessels

[68] 4AP mimics contraction effect of hypoxia [25] 4AP perfusion pressure [4] 4AP basal tone in control only [69] 4AP basal tone and ET-1-induced contraction [58] ScTX-1; MgTX; COR no basal tone effect [36] ScTX-1; MgTX U46619-induced contraction [36] 4AP basal tone in control only [69] ScTX-1; MgTX; COR no basal tone effect https://www.selleckchem.com/products/PLX-4032.html [36] COR U46619-induced

contraction [36] 4AP sig. IK [25]; hypoxia did NOT IK further in presence of 4AP [25] 4AP sig. IK in CPA VSMC [5] PIN basal tone (low/control) and relaxes U46619-induced contraction (high/low; not control) [69, 72] GLIB U46619-, MG-132 concentration AVP- and ET-1-induced contraction [72] GLIB no effect on SNAP –induced relaxation [58] KRN2391 basal tone; U46619-induced contraction [33] CROM no basal tone effect; desensitized U46619-induced contraction [33] KRN4884 no basal tone effect; desensitized U46619-induced contraction [33] PIN basal tone and U46619 contraction (high/low; not control) [69] KRN2391 basal tone (control) and U46619-induced contraction [33] CROM

no basal tone effect; U46619-induced contraction [33] KRN4884 no basal tone effect; U46619-induced contraction [33] No whole-cell KATP currents observed [25] GLIB-sensitive alteration in VSMC but not EC Vm [20] IbTX no effect on basal tone [69] IbTX max U46619 contraction in control only; no effect high/low [69] CTX SNAP-induced relaxation [58] IbTX slightly IK in small and large arteries [25] TEA; IbTX; CTX; 1-EBIO; TRAM-34 modify IK in CPA VSMC [5] In support of the Sulfite dehydrogenase placental perfusion data, the presence of KATP channels was demonstrated by inhibition of agonist-induced contraction with glibenclamide [72]. Subsequent studies found reduced basal tone of chorionic plate arteries and veins with pinacidil and KRN2391; in addition, precontracted vessels were demonstrated to significantly relax upon exposure to pinacidil, KRN2391, and cromakalim [69, 33]. The observation that calcitonin gene-related peptide-induced alterations in isolated placental artery and venous reactivity are also partially mediated by KATP channel activation [13] lends further weight to the notion that KATP channel activation modifies blood vessel tone in both arms of the fetoplacental circulation.