Findings on intraprocedural non-contrast computed tomographic imaging following hepatic artery embolization are associated with development of contrast-induced nephropathy

BACKGROUNDContrast-induced nephropathy (CIN) is a reversible form of acute kidney injury that occurs within 48-72 h of exposure to intravascular contrast material. CIN is the third leading cause of hospital-acquired acute kidney injury and accounts for 12% of such cases. Risk factors for CIN development can be divided into patient- and procedure-related. The former includes pre-existing chronic renal insufficiency and diabetes mellitus. The latter includes high contrast volume and repeated exposure over 72 h. The incidence of CIN is relatively low (up to 5%) in patients with intact renal function. However, in patients with known chronic renal insufficiency, the incidence can reach up to 27%.AIMTo examine the association between renal enhancement pattern on non-contrast enhanced computed tomographic (CT) images obtained immediately following hepatic artery embolization with development of CIN.METHODSRetrospective review of all patients who underwent hepatic artery embolization between 01/2010 and 01/2011 (n = 162) was performed. Patients without intraprocedural CT imaging (n = 51), combined embolization/ablation (n = 6) and those with chronic kidney disease (n = 21) were excluded. The study group comprised of 84 patients with 106 procedures. CIN was defined as 25% increase above baseline serum creatinine or absolute increase ≥ 0.5 mg/dL within 72 h post-embolization. Post-embolization CT was reviewed for renal enhancement patterns and presence of renal artery calcifications. The association between non-contrast CT findings and CIN development was examined by Fisher’s Exact Test.RESULTSCIN occurred in 11/106 (10.3%) procedures (Group A, n = 10). The renal enhancement pattern in patients who did not experience CIN (Group B, n = 74 with 95/106 procedures) was late excretory in 93/95 (98%) and early excretory (EE) in 2/95 (2%). However, in Group A, there was a significantly higher rate of EE pattern (6/11, 55%) compared to late excretory pattern (5/11) (P < 0.001). A significantly higher percentage of patients that developed CIN had renal artery calcifications (6/11 vs 20/95, 55% vs 21%, P = 0.02).CONCLUSIONA hyperdense renal parenchyma relative to surrounding skeletal muscle (EE pattern) and presence of renal artery calcifications on immediate post-HAE non-contrast CT images in patients with low risk for CIN are independently associated with CIN development.     

Ventromedial hypothalamus glucose‐inhibited neurones: A role in glucose and energy homeostasis?

The ventromedial hypothalamus (VMH) plays a complex role in glucose and energy homeostasis. The VMH is necessary for the counter‐regulatory response to hypoglycaemia (CRR) that increases hepatic gluconeogenesis to restore euglycaemia. On the other hand, the VMH also restrains hepatic glucose production during euglycaemia and stimulates peripheral glucose uptake. The VMH is also important for the ability of oestrogen to increase energy expenditure. This latter function is mediated by VMH modulation of the lateral/perifornical hypothalamic area (lateral/perifornical hypothalamus) orexin neurones. Activation of VMH AMP‐activated protein kinase (AMPK) is necessary for the CRR. By contrast, VMH AMPK inhibition favours decreased basal glucose levels and is required for oestrogen to increase energy expenditure. Specialised VMH glucose‐sensing neurones confer the ability to sense and respond to changes in blood glucose levels. Glucose‐excited (GE) neurones increase and glucose‐inhibited (GI) neurones decrease their activity as glucose levels rise. VMH GI neurones, in particular, appear to be important in the CRR, although a role for GE neurones cannot be discounted. AMPK mediates glucose sensing in VMH GI neurones suggesting that, although activation of these neurones is important for the CRR, it is necessary to silence them to lower basal glucose levels and enable oestrogen to increase energy expenditure. In support of this, we found that oestrogen reduces activation of VMH GI neurones in low glucose by inhibiting AMPK. In this review, we present the evidence underlying the role of the VMH in glucose and energy homeostasis. We then discuss the role of VMH glucose‐sensing neurones in mediating these effects, with a strong emphasis on oestrogenic regulation of glucose sensing and how this may affect glucose and energy homeostasis.     

Primary lumbosacral Wilms tumor associated with diastematomyelia and occult spinal dysraphism

Background The occurrence of an extrarenal Wilms tumor in the lumbosacral region is an extremely uncommon condition.Case report We report a case of Wilms tumor in the lumbosacral region that was associated with diastematomyelia and occult spina bifida. An 18-month-old girl presented with a swelling over the lower back with a tuft of hair on it, which she had had since birth. Imaging of the spine revealed spina bifida, bony diastematomyelia, and tethered cord. Excision of the bony spur and detethering of the cord was done. After a year, she had recurrence of swelling at the same site, weakness of both lower limbs, and incontinence of bladder and bowel. Excision of the mass and bony spur and detethering of the spinal cord were done. Histopathological examination showed features of a Wilms tumor.     

Graphene oxide based crosslinker for simultaneous enhancement of mechanical toughness and self-healing capability of conventional hydrogels

Extraordinary self-healing efficiency is rarely observed in mechanically strong hydrogels, which often limits the applications of hydrogels in biomedical engineering. We have presented an approach to utilize a special type of graphene oxide-based crosslinker (GOBC) for the simultaneous improvement of toughness and self-healing properties of conventional hydrogels. The GOBC has been prepared from graphene oxide (GO) by surface oxidation and further introduction of vinyl groups. It has been designed in such a way that the crosslinker is able to form both covalent bonds and noncovalent interactions with the polymer chains of hydrogels. To demonstrate the efficacy of GOBC, it was incorporated in a conventional polyacrylamide (PAM) and polyacrylic acid (PAA) hydrogel matrix, and the mechanical and self-healing properties of the prepared hydrogels were investigated. In PAM-GOBC hydrogels, it has been observed that the mechanical properties such as tensile strength, Young''s modulus, and toughness are significantly improved by the incorporation of GOBC without compromising the self-healing efficiency. The PAM-GOBC hydrogel with a modulus of about 0.446 MPa exhibited about 70% stress healing efficiency after 40 h. Whereas, under the same conditions a PAM hydrogel with commonly used crosslinker N,N′-methylene-bis(acrylamide) of approximately the same modulus demonstrated no self-healing at all. Similar improvement of self-healing properties and toughness in PAA-GOBC hydrogel has also been observed which demonstrated the universality of the crosslinker. This crosslinker-based approach to improve the self-healing properties is expected to offer the possibility of the application of commonly used hydrogels in many different sectors, particularly in developing artificial tissues.

Introduction of a two-dimensional graphene oxide-based crosslinker simultaneously improve the mechanical and self-healing properties of hydrogels by offering an interesting combination of covalent and reversible hydrogen bonds to polymer backbones.     

mda-9/Syntenin promotes metastasis in human melanoma cells by activating c-Src

The scaffold PDZ-domain containing protein mda-9/syntenin functions as a positive regulator of cancer cell progression in human melanoma and other tumors. mda-9/Syntenin regulates cell motility and invasion by altering defined biochemical and signaling pathways, including focal adhesion kinase (FAK), p38 mitogen-activated protein kinase (MAPK) and NF-κB, but precisely how mda-9/syntenin organizes these multiprotein signaling complexes is not well understood. Using a clinically relevant human melanoma model, we demonstrate that mda-9/syntenin physically interacts with c-Src and this communication correlates with an increase in FAK/c-Src complex formation and c-Src activation. Inhibiting mda-9/syntenin, using an adenovirus expressing antisense mda-9/syntenin or addition of c-Src siRNA, suppresses melanoma cell migration, anchorage-independent growth, and spontaneous tumor cell dissemination in vivo in a human melanoma animal metastasis model. These data are compatible with a model wherein interaction of MDA-9/syntenin with c-Src promotes the formation of an active FAK/c-Src signaling complex, leading to enhanced tumor cell invasion and metastatic spread. These provocative findings highlight mda-9/syntenin and its interacting partners as promising therapeutic targets for intervention of metastasis.     

Cerebral PET imaging and histological evidence of transglutaminase inhibitor cystamine induced neuroprotection in transgenic R6/2 mouse model of Huntington's disease

To investigate efficacy of cystamine induced neuroprotection, we conducted PET imaging studies of cerebral glucose metabolism with [(18)F]FDG (2-deoxy-2-[(18)F]fluoro-d-glucose) and striatal dopamine D2 receptor function with [(11)C]raclopride in R6/2 transgenic Huntington mice. In the control mice, exponentially decreasing glucose utilization was observed in the striatum N(str) [SUV]=(41.75+/-11.80)(58,str)*exp(-(0.041+/-0.007)*t [days]); cortex N(cort) [SUV]=24.14+/-3.66)(58,cort)*exp(-(0.043+/-0.007)*t [days]); and cerebellum N(cer) [SUV]=(34.97+/-10.58)(58,cer)*exp(-(0.037+/-0.008)*t [days]) as a function of age starting at 58 days. Given that the underlying degeneration rate in the cystamine treated mice is similar to that observed in control animals, the protection coefficient (beta) calculated from the equation N(t)=N(58)*exp(-(1-beta)*k*t) was 0.133+/-0.035 for the striatum; 0.122+/-0.028 for the cortex and 0.224+/-00.042 for the cerebellum with a dose of 100 mg/kg. The 50 mg/kg cystamine dose provided significant protection only for the striatum and only minor protection was obtained using lower doses. Striatal binding potential of [(11)C]raclopride was 1.059+/-0.030 in the control mice, and enhanced in the cystamine treated animals in a dose dependent manner up to 1.245+/-0.063 using the 100 mg/kg dose. Histological analysis confirmed cystamine induced neuroprotection of striatal and cortical neurons and Nissl staining revealed that formation of cellular inclusions was reversed in a dose dependent manner. Cerebral imaging and histological evidence support the use of cystamine as a neuroprotective agent for Huntington's disease (HD) pathology.     

Interaction of ascaridole,carvacrol, and caryophyllene oxide from essential oil of Chenopodium ambrosioides L. with mitochondria in Leishmania and other eukaryotes

The antileishmanial activity of the essential oil (EO) from Chenopodium ambrosioides L. has been demonstrated in vitro and in animal models, attributed to the major components of the EO. This study focused on the effects of the three major EO compounds carvacrol, caryophyllene oxide (Caryo), and the antileishmanial endoperoxide ascaridole (Asc) on mitochondrial functions in Leishmania tarentolae promastigotes (LtP). EO and Caryo were able to partially inhibit the leishmanial electron transport chain, whereas other components failed to demonstrate a direct immediate effect. Caryo demonstrated inhibition of complex III activity in LtP and in isolated complex III from other species. The formation of superoxide radicals was studied in Leishmania by electron spin resonance spectroscopy in the presence of iron chelators wherein selected compounds failed to trigger a significant immediate additional superoxide production in LtP. However, upon prolonged incubation of Leishmania with Asc and especially in the absence of iron chelators (allowing the activation of Asc), an increased superoxide radical production and significant impairment of mitochondrial coupling in Leishmania was observed. Prolonged incubation with all EO components resulted in thiol depletion. Taken together, the major components of EO mediate their leishmanicidal activity via different mitochondrial targets and time profiles. Further studies are required to elucidate possible synergistic effects of carvacrol and Asc and the influence of minor compounds.