Ageratina adenophora damages the rumen epithelium via inducing the expression of inflammatory factors in goats.

The aim of this experiment was to investigate the effects of Ageratina adenophora on the expression of epithelium tight junction proteins and inflammatory factors in the rumen of goats. Twelve goats were randomly divided into three groups. The first group was the blank control group (n = 3, C) which was fed normal diet. The second group was fistulas control group (n = 3, RFC), which was fitted with rumen fistulas, and fed normal diet. The third group was the A. adenophora test group (n = 6, AA), which was fitted with rumen fistulas and fed a mixture of 60% of normal diet and 40% of A. adenophora grass powder. The feeding experiment lasted for 90 d, after which all goats were sacrificed and samples were collected from the rumen dorsal sac and ventral sac. The relative expression of mRNA of inflammatory factors in the rumen epithelium (tumor necrosis factor alpha [TNF-α], interferon gamma [IFN-γ], interleukin 1 beta [IL-1ß], IL-2, IL-4, IL-6, and IL-10) and tight junction protein genes (occludin, claudin-1, and ZO-1) was measured by quantitative real-time fluorescence PCR. Expression of tight junction proteins in the rumen epithelium was measured by Western blot. A correlation was established between the expression of inflammatory factors and tight junction protein genes using Graph Pad Prism. The results showed that A. adenophora caused a significant increase in the mRNA expression levels of TNF-α, IFN-γ, IL-1ß, IL-2, IL-6, and IL-10 in the rumen epithelial (P < 0.05 or P < 0.01). The expression of tight junction proteins at both gene and protein levels was significantly decreased (P < 0.05 or P < 0.01). Furthermore, the correlation analysis revealed that the changes in tight junction protein expression in the test group were closely related to the upregulation of the expression of inflammatory factors TNF-α and IFN-γ in rumen epithelial cells. In conclusion, the expression of inflammatory factors was increased and the expression of tight junction proteins was decreased in goats after feeding on A. adenophora, which caused some damage to the rumen epithelium.

The article aims to investigate the toxic effects of Ageratina adenophora, an invasive plant on the integrity of the rumen epithelium by measuring the changes in the expression of inflammatory factors and tight junction proteins after the consumption of A. adenophora in goats. The results showed that A. adenophora causes damage to the rumen epithelium by increasing the expression of pro-inflammatory markers like TNF-α and IFN-γ and reducing the expression of tight junction proteins such as occludin and claudin-1 in goats.

Endothelin type A receptor blockade increases renoprotection in congestive heart failure combined with chronic kidney disease: Studies in 5/6 nephrectomized rats with aorto-caval fistula.

BACKGROUND: Association of congestive heart failure (CHF) and chronic kidney disease (CKD) worsens the patient's prognosis and results in poor survival rate. The aim of this study was to examine if addition of endothelin type A (ETA) receptor antagonist to the angiotensin-converting enzyme inhibitor (ACEi) will bring additional beneficial effects in experimental rats. METHODS: CKD was induced by 5/6 renal mass reduction (5/6 NX) and CHF was elicited by volume overload achieved by creation of aorto-caval fistula (ACF). The follow-up was 24 weeks after the first intervention (5/6 NX). The treatment regimens were initiated 6 weeks after 5/6 NX and 2 weeks after ACF creation. RESULTS: The final survival in untreated group was 15%. The treatment with ETA receptor antagonist alone or ACEi alone and the combined treatment improved the survival rate to 64%, 71% and 75%, respectively, however, the difference between the combination and either single treatment regimen was not significant. The combined treatment exerted best renoprotection, causing additional reduction in albuminuria and reducing renal glomerular and tubulointerstitial injury as compared with ACE inhibition alone. CONCLUSIONS: Our results show that treatment with ETA receptor antagonist attenuates the CKD- and CHF-related mortality, and addition of ETA receptor antagonist to the standard blockade of RAS by ACEi exhibits additional renoprotective actions.

Mechanical and chemical cues synergistically promote human venous smooth muscle cell osteogenesis through integrin ß1-ERK1/2 signaling: A cell model of hemodialysis fistula calcification.

Arteriovenous fistula (AVF) is the vascular access of choice for renal replacement therapy. However, AVF is susceptible to calcification with a high prevalence of 40%-65% in chronic hemodialysis patients. Repeated needle puncture for hemodialysis cannulation results in intimal denudation of AVF. We hypothesized that exposure to blood shear stress in the medial layer promotes venous smooth muscle cell (SMC) osteogenesis. While previous studies of shear stress focused on arterial-type SMCs, SMCs isolated from the vein had not been investigated. This study established a venous cell model of AVF using the fluid shear device, combined with a high phosphate medium to mimic the uremic milieu. Osteogenic gene expression of venous SMCs upon mechanical and chemical cues was analyzed in addition to the activated cell signaling pathways. Our findings indicated that upon shear stress and high phosphate environment, mechanical stimulation (shear stress) had an additive effect in up-regulation of an early osteogenic marker, Runx2. We further identified that the integrin ß1-ERK1/2 signaling pathway was responsible for the molecular basis of venous SMC osteogenesis upon shear stress exposure. Mitochondrial biogenesis also took part in the early stage of this venopathy pathogenesis, evident by the up-regulated mitochondrial transcription factor A and mitochondrial DNA polymerase γ in venous SMCs. In conclusion, synergistic effects of fluid shear stress and high phosphate induce venous SMC osteogenesis via the ERK1/2 pathway through activating the mechanosensing integrin ß1 signaling. The present study identified a promising druggable target for reducing AVF calcification, which deserves further in vivo investigations.

Evaluation of surgical procedures of mouse urethra by visualization and the formation of fistula.

Visualization of the surgically operated tissues is vital to improve surgical model animals including mouse. Urological surgeries for urethra include series of fine manipulations to treat the increasing number of birth defects such as hypospadias. Hence visualization of the urethral status is vital. Inappropriate urethral surgical procedure often leads to the incomplete wound healing and subsequent formation of urethro-cutaneous fistula or urethral stricture. Application of indocyanine green mediated visualization of the urethra was first performed in the current study. Indocyanine green revealed the bladder but not the urethral status in mouse. Antegrade injection of contrast agent into the bladder enabled to detect the urethral status in vivo. The visualization of the leakage of contrast agent from the operated region was shown as the state of urethral fistula in the current hypospadias mouse model and urethral stricture was also revealed. A second trial for contrast agent was performed after the initial operation and a tendency of accelerated urethral stricture was observed. Thus, assessment of post-surgical conditions of urogenital tissues can be improved by the current analyses on the urethral status.

Bradykinin Receptor B1 and C-Reactive Protein as Prognostic Factors for Pharyngocutaneous Fistula Development After Laryngectomy.

Pharyngocutaneous fistulae (PCF) are one of the most common complications after laryngectomy. Predisposing risk factors have been studied, yet knowledge to determine which patients are prone to developing a fistula remains scarce. This study aims to establish prognostic parameters to identify individual patients at risk for PCF development. As PCF and inflammation seem to be interwoven, this work focuses on markers able to detect an inflammatory response. We retrospectively analyzed all patients who had undergone a laryngectomy at our clinic in the years 2007 to 2017 (n = 182). Immunohistochemical expression of bradykinin type 1 and 2 receptor and vascular endothelial growth factor receptor 2 was studied in all available tumor samples. Additionally, the clinical inflammation parameters 'body temperature', 'pain', 'c-reactive protein (CRP)', and 'leucocytes' were postoperatively tracked in all patients. The times between fistula diagnosis, therapeutic approach, and hospital discharge were recorded. We found a strong correlation between inflammation and the formation of a fistula. High bradykinin 1 receptor expression in the tumor samples correlated with postoperative PCF development. Persistently elevated CRP and leukocyte levels beyond the 6th postoperative day were also risk factors. A decreased time lapse between PCF diagnosis and surgical revision clearly correlated with a shorter hospital stay. In this study, we identified a bradykinin 1 receptor positive patient group at high risk for development of PCF. We recommend close monitoring for fistula formation in these patients to ensure timely intervention.

Hepatic Metabolomic and Transcriptomic Responses Induced by Cecal Infusion of Sodium Propionate in a Fistula Pig Model.

Short-chain fatty acids (SCFAs) are the major products of the microbial fermentation of indigestible carbohydrates. SCFAs are known to improve the host metabolism, but their underlying mechanism of action remains elusive. In this study, 16 growing pigs were infused with saline or sodium propionate solution (25 mL, 2 mol/L) through a cecal fistula twice a day during a 28 day experimental period. The results showed that the cecal infusion of the SCFA propionate decreased serum and liver triglyceride levels and increased serum PYY secretion in growing pigs. Hepatic metabolomics identified 12 metabolites that were significantly altered by propionate. These included decreased levels of lipid metabolism-related stearic acid and glycerol-2-phosphate; increased levels of TCA cycle components including malic acid, fructose-6-phosphate, and succinic acid; and decreased levels of the amino acid metabolism products aspartic acid and serine. Hepatic transcriptomics demonstrated that propionate inhibited fatty acid synthesis and promoted the lipid metabolic process. Pathway enrichment analysis showed that propionate accelerated gluconeogenesis and decreased glycolysis. Taken together, these data support a role of the SCFA propionate on host lipid and glucose metabolism.

Molecular evidence of tissue remodeling in an animal model of heart failure.

Heart failure (HF) is the final common pathway of many cardiovascular diseases. Metalloproteinases and their inhibitors, such as MMP9 and TIMP-1, assist in maintaining the extracellular matrix, leading to tissue remodeling observed after HF. Previous studies have shown that L-Arginine (LA) appears to have beneficial effects for the treatment of HF, contributing to vasodilation, the reestablishment of the endothelial function and an increase in muscle contractile force. This study analyzed heart tissue remodeling in an animal model of HF induced by aortocaval fistula (ACF) and submitted to LA treatment. After 4 weeks of ACF, animals were treated with LA for 4 weeks (SHAM-LA, HF-LA) or for 8-12 weeks with saline (SHAM, HF8, HF12). Rats were euthanized and the hearts removed for histological processing. The samples were stained with Hematoxylin-Eosin (HE), Masson's Thichome (MT), or submitted to immunohistochemistry (IHC) for MMP9 and TIMP-1. Light microscopy analysis showed cardiac striated muscle without fibrosis in all experimental groups. Immunostaining of MMP9 and TIMP-1 were positive for all experimental groups. LA administration significatively reduced MMP9 content after HF. These data indicate molecular changes in metalloproteinases expression prior to tissue remodeling and point out LA as an adjuvant therapy to pharmacological treatment of patients with HF.

Structural arrangement of vesicouterine fistula revisited: An immunohistochemical study documenting the presence of the endometrium.

Previous research has described a woman of reproductive age who presented with a vesicouterine fistula (VUF) of 20 months' duration. The VUF was lined with a metaplastic glandular epithelium containing both estrogen receptors (ER) and progesterone receptors (PR) in abundance. The aim of the present investigation was to evaluate the histology of the VUF canal when exposure to urine of the cellular elements within the fistula was of much shorter duration. A 41-year-old woman who developed a VUF during her third cesarean section was treated with transvesical fistula excision, electrocoagulation, and subsequent attempted hormonal treatment. Later, the patient underwent open surgery fistula repair. Postoperative specimens were subjected to anatomopathological examination together with immunohistochemical staining for ER and PR using monoclonal anti-human antibodies. Herein, we present for the first time detailed microscopic evidence that, at two separate timepoints, the fistulous tract was lined with the endometrium, which covered approximately 80% of the length of the VUF canal. In its intermediate segment, the urothelium formed an additional layer on the surface of the endometrium. At both timepoints, in the columnar epithelial and stromal endometrial cells lining the fistula, both ER and PR were present in abundance. In conclusion, VUF in subjects of reproductive age fulfill criteria for endometriosis. This study provides a rationale for the conservative treatment of VUF consistent with the hormonal treatment of endometriosis.

Transcatheter Closure of Congenital Coronary Artery Fistulas with a Giant Coronary Artery Aneurysm in Children: Experiences from a Single Center.

BACKGROUND: Transcatheter closure of congenital coronary artery fistulas (CCAFs) is an alternative therapy to surgery; however, data regarding transcatheter closure for CCAF with a giant coronary artery aneurysm (CAA) in pediatric patients are still limited due to the rarity of the disease. We aimed to evaluate the efficacy and safety of transcatheter closure for CCAF with a giant CAA in a pediatric population at a single center. METHODS: Medical records of pediatric patients (<18 years old) who underwent transcatheter closure of CCAF with a giant CAA between April 2007 and September 2016 at Guangdong Cardiovascular Institute (Guangdong, China) were reviewed. RESULTS: Twelve patients (median age, 6.1 years; range, 1.9-11.0 years) underwent successful transcatheter closure procedures. One patient underwent closure at both the entry and exit points of the CAA, three patients underwent closure at the exit point of the CAA, and eight patients underwent closure at the entry point of the CAA. After a mean follow-up of 7.2 years (range, 0.5-9.8 years), one patient (with closure at the exit point of the CAA) underwent transcatheter re-intervention because of a significant residual shunt. She eventually underwent a surgical procedure due to aneurysm dilation after the second intervention. One patient experienced thrombus formation within the CAA after the procedure. Among those with closure at the entry point of the CAA, a mild-to-moderate residual shunt was detected in three patients. CONCLUSIONS: Transcatheter closure appears to be a safe and effective alternative therapy for CCAF with a giant CAA in the pediatric population. Closure at the entry point of the CAA, and closure at both the entry and exit points when feasible, may reduce the risk of postinterventional complications.

Beneficial effects of mucous fistula refeeding in necrotizing enterocolitis neonates with enterostomies.

BACKGROUND: Necrotizing enterocolitis in premature neonates often results in bowel resection and stoma formation. One way to promote bowel adaptation before stoma closure is to introduce proximal loop effluents into the mucous fistula. In this study, we reviewed our experience with distal loop refeeding with respect to control group. METHODS: All patients with necrotizing enterocolitis between 2000 and 2014 necessitating initial diverting enterostomies and subsequent stoma closure in a tertiary referral center were included. Medical records were retrospectively reviewed. Demographic data, surgical procedures, and postoperative outcomes were analyzed. RESULTS: 92 patients were identified, with 77 patients receiving mucous fistula refeeding. The refeeding group showed less bowel ends size discrepancy (25 vs 53%, p=0.034) and less postoperative anastomotic leakage (3 vs 20%, p=0.029). Fewer refeeding group patients developed parenteral nutrition related cholestasis (42 vs 73%, p=0.045) and required shorter parenteral nutrition support (47 vs 135days, p=0.002). The mean peak bilirubin level was higher in the non-refeeding group (155 vs 275µmol/L, p<0.001). No major complication was associated with refeeding. CONCLUSIONS: Mucous fistula refeeding is safe and can decrease risk of anastomotic complication and parental nutrition related cholestasis. It provides both diagnostic and therapeutic value preoperatively and its use should be advocated. Level III Treatment Study in a Case Control Manner.

Sex-linked differences in the course of chronic kidney disease and congestive heart failure: a study in 5/6 nephrectomized Ren-2 transgenic hypertensive rats with volume overload induced using aorto-caval fistula.

The role of hypertension and the renin-angiotensin system (RAS) in sex-related differences in the course of chronic kidney disease (CKD) and congestive heart failure (CHF) remain unclear, especially when the two diseases are combined. In male and female Ren-2 transgenic rats (TGR), a model of hypertension with activation of endogenous RAS, CKD was induced by 5/6 renal mass reduction (5/6 NX) and CHF was elicited by volume overload achieved by creation of an aorto-caval fistula (ACF). The primary aim of the study was to examine long-term CKD- and CHF-related mortality, especially in animals with CKD and CHF combined, with particular interest in the potential sex-related differences. The follow-up period was 23 weeks after the first intervention (5/6 NX). We found, first, that TGR did not exhibit sexual dimorphism in the course of 5/6 NX-induced CKD. Second, in contrast, TGR exhibited important sex-related differences in the course of ACF-induced CHF-related mortality: intact female TGR showed higher survival rate than male TGR. This situation is reversed in the course of combined 5/6 NX-induced CKD and ACF-induced CHF-related mortality: intact female TGR exhibited poorer survival than male TGR. Third, the survival rate in animals with combined 5/6 NX-induced CKD and ACF-induced CHF was significantly worsened as compared with rat groups that were exposed to 'single organ disease'. Collectively, our present results clearly show that CKD aggravates long-term mortality of animals with CHF. In addition, TGR exhibit remarkable sexual dimorphism with respect to CKD- and CHF-related mortality, especially in animals with combined CKD and CHF.

Apolipoprotein A-V deficiency enhances chylomicron production in lymph fistula mice.

Apolipoprotein A-V (apoA-V), a liver-synthesized apolipoprotein discovered in 2001, strongly modulates fasting plasma triglycerides (TG). Little is reported on the effect of apoA-V on postprandial plasma TG, an independent predictor for atherosclerosis. Overexpressing apoA-V in mice suppresses postprandial TG, but mechanisms focus on increased lipolysis or clearance of remnant particles. Unknown is whether apoA-V suppresses the absorption of dietary lipids by the gut. This study examines how apoA-V deficiency affects the steady-state absorption and lymphatic transport of dietary lipids in chow-fed mice. Using apoA-V knockout (KO, n = 8) and wild-type (WT, n = 8) lymph fistula mice, we analyzed the uptake and lymphatic transport of lipids during a continuous infusion of an emulsion containing [(3)H]triolein and [(14)C]cholesterol. ApoA-V KO mice showed a twofold increase in (3)H (P < 0.001) and a threefold increase in (14)C (P < 0.001) transport into the lymph compared with WT. The increased lymphatic transport was accompanied by a twofold reduction (P < 0.05) in mucosal (3)H, suggesting that apoA-V KO mice more rapidly secreted [(3)H]TG out of the mucosa into the lymph. ApoA-V KO mice also produced chylomicrons more rapidly than WT (P < 0.05), as measured by the transit time of [(14)C]oleic acid from the intestinal lumen to lymph. Interestingly, apoA-V KO mice produced a steadily increasing number of chylomicron particles over time, as measured by lymphatic apoB output. The data suggest that apoA-V suppresses the production of chylomicrons, playing a previously unknown role in lipid metabolism that may contribute to the postprandial hypertriglyceridemia associated with apoA-V deficiency.

Eustachian tube duplication: a unique anomaly.

Very few eustachian tube anomalies have been published in the literature and have consisted of descriptions of diverticula, hypoplasia/aplasia, fistula, or aberrant associated musculature. We present a girl with a novel anomaly consisting of a eustachian tube duplication that originates in the nasopharynx and exits posterior to a microtic and atretic ear. We review the literature on eustachian tube anomalies and also consider the derivation of this anomaly.

The role for dickkopf-homolog-1 in the pathogenesis of Crohn's disease-associated fistulae.

BACKGROUND: One of the most challenging conditions in Crohn's disease (CD) patients is the treatment of perianal fistulae. We have recently shown that epithelial-to-mesenchymal transition (EMT) plays a crucial role during CD-fistulae development. Dickkopf-homolog 1 (DKK-1) is known to play a key role during EMT. Here, we investigated a role for DKK-1 in the pathogenesis of CD-associated fistulae. METHODS: Dkk-1 protein expression in CD-fistula specimens were investigated by immunohistochemistry. Colonic lamina propria fibroblasts (CLPF) were obtained from either non-IBD control patients or patients with fistulizing CD. HT-29 intestinal epithelial cells (IEC) were either grown as monolayers or spheroids. Cells were treated with either TNF-α, TGF-ß or IL-13. Knock-down of DKK-1 or ß-Catenin was induced in HT-29-IEC by siRNA technique. mRNA expression was determined by real-time-PCR. RESULTS: Dkk-1 protein was specifically expressed in transitional cells lining the fistula tracts. TGF-ß induced DKK-1 mRNA expression in HT-29-IEC, but decreased it in fistula CLPF. On a functional level, DKK-1 knock-down prevented TGF-ß-induced IL-13 mRNA expression in HT-29-IEC. Further, loss of ß-Catenin was accompanied by reduced levels of DKK-1 and, again, IL-13 in IEC in response to TGF-ß. In turn, treatment of HT-29-IEC as well as fistula CLPF with IL-13 resulted in decreased levels of DKK-1 mRNA. Treatment with TNF-α or the bacterial wall component, muramyl-dipeptide, decreased DKK-1 mRNA levels in HT-29-IEC, but enhanced it in fistula CLPF. DISCUSSION: We demonstrate that DKK-1 is strongly expressed in cells lining the CD-fistula tracts and regulates factors involved in EMT initiation. These data provide evidence for a role of DKK-1 in the pathogenesis of CD-associated perianal fistulae.

Persistent leak after glaucoma aqueous shunt implantation.

PURPOSE: To present 4 cases of persistent leak attributed to subconjunctival fistula formation after glaucoma aqueous shunt implantation. Our preferred method for management is also described. METHODS: Retrospective noncomparative case series. RESULTS: Four cases of persistent leak after glaucoma aqueous shunt surgery are described. Three patients had an underlying diagnosis of iridocorneal endothelial syndrome and 1 patient had a diagnosis of chronic panuveitis. Three patients had prior trabeculectomy with adjunctive periocular application of antiproliferative agents (mitomycin C and/or 5-fluorouracil). One patient had aqueous shunt implantation as a primary glaucoma procedure. Implantation of the Molteno (1 patient), Ahmed (2 patients), and Baerveldt (1 patient) aqueous shunts was uneventful in all cases. Early onset of the leak, between postoperative months 1 and 2, was typical. The use of aqueous suppressants, bandage contact lens, conjunctival photocoagulation, sutures, tissue adhesives, conjunctival autografts, and scleral patch grafts were unsuccessful in the described cases. Resolution of the leak occurred after removal of the aqueous shunt and elimination of the causative subconjunctival fistula. Histologic support for fistulization was obtained in 3 cases. Severe complications including endophthalmitis (1 patient), hypotony (4 patients), suprachoroidal hemorrhage (2 patients), and corneal decompensation (3 patients) occurred because of the persistent leaks. CONCLUSIONS: Persistent leak is a rare but important complication after glaucoma aqueous shunt implantation. Early consideration for the presence of a subconjunctival fistula, especially in patients with iridocorneal endothelial syndrome or chronic uveitis, can spare many ineffective efforts to repair the leak and prevent severe vision threatening complications.

Analysis of a single hemodialysis on phosphate removal of the internal fistula patients by mathematical and statistical methods.

Chronic kidney disease related mineral and bone disease (CKD-MBD) is a worldwide challenge in hemodialysis patients. In china, the number of dialysis patients is growing but few data are available about their bone disorders. In the current study, we aimed to evaluate the effect of clinical factors on the serum phosphorus clearance in the 80 maintenance hemodialysis (MHD) patients. Six clinical factors were identified for their association with the serum phosphorus clearance using the analysis of Spearman's single linear correlation, including predialysis serum phosphate level, CRR, membrane surface area of the dialyzer, effective blood flow rate, the blood chamber volume, and hematocrit. In an overall multivariate analysis, pre-P, CRR, membrane SA, and Qb were identified as independent risk factors associated with the serum phosphorus clearance. In conclusion, HD could effectively clear serum phosphorus. The analysis of CRR might help to estimate serum phosphorus reduction ratio.

Nicorandil: from ulcer to fistula into adjacent organs.

Nicorandil is an original vasodilatator used to control angina by decreasing cardiac preload and afterload. Since 1997, many reports of single or multiple nicorandil-induced ulcerations have been published. To date, eight cases of nicorandil-induced fistula into adjacent organs have been described. The pathogeneses of nicorandil-induced ulceration and fistula into adjacent organs are not yet elucidated. The two main hepatic biotransformation pathways of nicorandil are denitration and reduction of the alkyl chain leading to nicotinamide and niconitic acid which merge into the endogenous pool of nicotinamide adenine dinucleotide/phosphate. This merging which is known as saturable, may contribute to a slow and abnormal distribution of nicotinamide and nicotinic acid out of the endogenous pool. Under these special conditions, providing these two molecules in situ, nicotinic acid associated with nicotinamide may ulcerate rather recent or maintained trauma. Ulcers and fistulae induced by nicorandil heal after withdrawal. Surgical intervention is unnecessary and inappropriate as it is ineffective and exacerbates morbidity. All practitioners should be correctly informed about these serious but preventable nicorandil side effects, which mostly occur in the elderly and fragile population. In the absence of corrective measures, withdrawal of this original and active drug should be considered.

Iatrogenic inguinal chyle fistula: a rare case report.

Chyle fistula may be common in the neck and thorax region but it is a rare entity in the inguinal region. The rarity of the incidence of chyle fistula and the tremendous response to conservative management are the important aspects to be remembered. We hereby report a case of iatrogenic inguinal chyle fistula complicating a femoral vein cannulation.

CSF fistula through the left lumbar region in adult following a ventriculoperitoneal shunt surgery: a rare case report.

A cranial spinal fluid fistula through left lumbar region following a ventriculoperitoneal (VP) shunt is an extremely rare complication. We report a 25-year-old man who presented with the leakage of clear fluid from the left lumbar region, 3 years after a VP shunt surgery. Computerized tomography scan of abdomen revealed that the distal end of the catheter penetrated into the inner layer of the wall of left lumbar region. He was managed successfully with abdominal part of shunt catheter removal from primary cervical and abdominal incision, a new abdominal part of VP shunt catheter replacement and prophylactic antibiotic.

Bile acids regulate hepatic gluconeogenic genes and farnesoid X receptor via G(alpha)i-protein-coupled receptors and the AKT pathway.

Bile acids are important regulatory molecules that can activate specific nuclear receptors and cell signaling pathways in the liver and gastrointestinal tract. In the current study, the chronic bile fistula (CBF) rat model and primary rat hepatocytes (PRH) were used to study the regulation of gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) and the gene encoding short heterodimeric partner (SHP) by taurocholate (TCA). The intestinal infusion of TCA into the CBF rat rapidly (1h) activated the AKT (approximately 9-fold) and ERK1/2 (3- to 5-fold) signaling pathways, downregulated (approximately 50%, 30 min) the mRNA levels of PEPCK and G-6-Pase, and induced (14-fold in 3 h) SHP mRNA. TCA rapidly ( approximately 50%, 1-2 h) downregulated PEPCK and G-6-Pase mRNA levels in PRH. The downregulation of these genes by TCA was blocked by pretreatment of PRH with pertussis toxin (PTX). In PRH, TCA plus insulin showed a significantly stronger inhibition of glucose secretion/synthesis from lactate and pyruvate than either alone. The induction of SHP mRNA in PRH was strongly blocked by inhibition of PI3 kinase or PKCzeta by specific chemical inhibitors or knockdown of PKCzeta by siRNA encoded by a recombinant lentivirus. Activation of the insulin signaling pathway appears to be linked to the upregulation of farnesoid X receptor functional activity and SHP induction.