Treatment of ureteric lithiasis with retrograde ureteroscopy and holmium:YAG laser lithotripsy vs extracorporeal lithotripsy

OBJECTIVE

To analyse the efficiency of extracorporeal shockwave lithotripsy (ESWL) vs retrograde ureteroscopy and holmium:YAG laser lithotripsy, as ESWL is successful in 67–90% of cases but endoscopic lithotripsy with pneumatic lithotrites or lasers is successful in 90–96% of distal ureteric calculi, and holmium:YAG lithotripsy is effective in proximal ureteric calculi.

PATIENTS AND METHODS

From April 2006 to April 2008 we assessed 164 patients undergoing ureteric lithiasis in two homogeneous groups: group A included 83 treated with retrograde ureteroscopy and holmium:YAG endoscopic lithotripsy, and group B, 81 treated by ESWL. For laser lithotripsy we used 2071 mJ pulses at 3–6 Hz, with a mean of 1105 pulses and 2.5 kJ of total energy. ESWL was carried out using 37.5–87.5 mJ shock waves, a mean of 3650 shock waves and 187.6 J, with a radioscopy time of 1–4 min. The results were assessed after 3 weeks with plain films and ultrasonography, or urography. The efficiency of each procedure was assessed by calculating the relative risk, and results compared using the chi‐square or Student’s t‐test. The efficiency quotient (EQ) was determined for both procedures, and the focal applied energy quotient (FAEQ) used to assess ESWL.

RESULTS

The overall success rate for retrograde ureteroscopy and laser lithotripsy was 96.4% (80/83 patients), with an EQ of 0.52; a JJ catheter was placed in 67 patients. The success rate for the first ESWL session was 48%, and after repeat ESWL was 64% (52/81 patients), giving an EQ of 0.39. For successful treatments the FAEQ was 9.22, vs 6.47 for the failures (P < 0.005). There was a significant difference (P < 0.001) favouring laser lithotripsy, with an absolute benefit of 46% (95% confidence interval 33.8–57.9%), and number needed to treat of 2 (2–3), but no significant differences for lumbar ureteric calculi.

CONCLUSIONS

Endoscopic lithotripsy with the holmium laser is more effective than ESWL, but for lumbar ureteric calculi ESWL is therapeutically recommended as it is less invasive.     

CTGF Promotes Inflammatory Cell Infiltration of the Renal Interstitium by Activating NF-κB

Connective tissue growth factor (CTGF) is an important profibrotic factor in kidney diseases. Blockade of endogenous CTGF ameliorates experimental renal damage and inhibits synthesis of extracellular matrix in cultured renal cells. CTGF regulates several cellular responses, including adhesion, migration, proliferation, and synthesis of proinflammatory factors. Here, we investigated whether CTGF participates in the inflammatory process in the kidney by evaluating the nuclear factor-kappa B (NF-κB) pathway, a key signaling system that controls inflammation and immune responses. Systemic administration of CTGF to mice for 24 h induced marked infiltration of inflammatory cells in the renal interstitium (T lymphocytes and monocytes/macrophages) and led to elevated renal NF-κB activity. Administration of CTGF increased renal expression of chemokines (MCP-1 and RANTES) and cytokines (INF-γ, IL-6, and IL-4) that recruit immune cells and promote inflammation. Treatment with a NF-κB inhibitor, parthenolide, inhibited CTGF-induced renal inflammatory responses, including the up-regulation of chemokines and cytokines. In cultured murine tubuloepithelial cells, CTGF rapidly activated the NF-κB pathway and the cascade of mitogen-activated protein kinases, demonstrating crosstalk between these signaling pathways. CTGF, via mitogen-activated protein kinase and NF-κB activation, increased proinflammatory gene expression. These data show that in addition to its profibrotic properties, CTGF contributes to the recruitment of inflammatory cells in the kidney by activating the NF-κB pathway.Connective tissue growth factor (CTGF) is a member of the C-terminal cystein-rich proteins (CCN) family of early response genes. CTGF is a 38-kD cystein-rich secreted protein that is up-regulated in proliferative disorders or fibrotic lesions in several human diseases, including skin disorders, atherosclerosis, pulmonary fibrosis, and kidney diseases.^1,2 In human biopsies of different renal pathologies and in experimental models of kidney injury, renal CTGF overexpression was correlated with cellular proliferation and extracellular matrix (ECM) accumulation, both at glomerular and interstitial areas.^2–4 In the diabetic kidney, elevated CTGF expression co-localizes with sites of epithelial-to-mesenchymal transition (EMT) on the tubular epithelium.⁵ In cultured renal cells, recombinant CTGF significantly increases ECM production and induces transition of tubuloepithelial cells to myofibroblasts.^6–8 In experimental diabetic nephropathy in mice, the blockade on endogenous CTGF, by antisense oligonucleotides, has beneficial effects on renal damage progression.⁹ In cultured renal cells, CTGF blockade inhibits ECM accumulation and EMT caused by angiotensin II and transforming growth factor-β (TGF-β).^3,10 These data suggest that CTGF could be an important target for the treatment of renal fibrosis.CTGF also induces other cellular responses. Depending on the cell type, CTGF regulates cell growth, proliferation, and apoptosis. CTGF is a downstream mediator of TGF-β-induced apoptosis of mesothelial cells,¹¹ but contributes to the survival of hepatic stellate cells.¹² CTGF may play a role as a secreted tumor suppressor protein¹³ or contribute to promote tumor cell growth and invasion.¹⁴ Some studies suggested that CTGF could also be involved in the inflammatory response. CTGF is a chemotactic factor for monocytes¹⁵ and regulates cellular adhesion and migration in mesangial cells.¹⁶ Moreover, in cultured mesangial cells, CTGF enhances the production of proinflammatory factors, including chemotactic molecules, and activates nuclear factor-kappa B (NF-κB).¹⁷ However, there is no data about the in vivo effect of CTGF on the renal inflammatory process.The molecular mechanisms involved in CTGF signaling are far from being understood. CTGF interacts with tyrosine kinase receptors and integrins that activate multiple signaling systems including NF-κB and mitogen-activated protein kinase (MAPK) pathways.^12,17–19 Although the regulation of the inflammatory response in the kidney is a complex process, the activation of NF-κB plays a pivotal role. Experimental studies have shown that NF-κB blockade by different methods, including I-κB overexpression, NF-κB decoy oligonucleotides, NF-κB inhibitors (parthenolide among others), or indirectly by statins, glucocorticoids, and antioxidants, prevents renal damage.^20–23 Activation of renal NF-κB has been described in human kidney diseases, associated to proinflammatory factors overexpression.^24,25 We have now investigated whether CTGF could modulate the inflammatory response in the kidney and the mechanisms underlying this process, evaluating the involvement of the NF-κB signaling pathway.     

The chemokine receptor D6 has opposing effects on allergic inflammation and airway reactivity

RATIONALE: The D6 chemokine receptor can bind and scavenge several chemokines, including the T-helper 2 (Th2)-associated chemokines CCL17 and CCL22. Although D6 is constitutively expressed in the lung, its pulmonary function is unknown. OBJECTIVES: This study tested whether D6 regulates pulmonary chemokine levels, inflammation, or airway responsiveness during allergen-induced airway disease. METHODS: D6-deficient and genetically matched C57BL/6 mice were sensitized and challenged with ovalbumin. ELISA and flow cytometry were used to measure levels of cytokines and leukocytes, respectively. Mechanical ventilation was used to measure airway reactivity. RESULTS: The ability of D6 to diminish chemokine levels in the lung was chemokine concentration dependent. CCL17 and CCL22 were abundant in the airway, and their levels were attenuated by D6 when they were within a defined concentration range. By contrast, airway concentrations of CCL3, CCL5, and CCL11 were low and unaffected by D6. Allergen-challenged D6-deficient mice had more dendritic cells, T cells, and eosinophils in the lung parenchyma and more eosinophils in the airway than similarly challenged C57BL/6 mice. By contrast, D6-deficient mice had reduced airway responses to methacholine compared with C57BL/6 mice. Thus, D6 has opposing effects on inflammation and airway reactivity. CONCLUSIONS: The ability of D6 to scavenge chemokines in the lung is dependent on chemokine concentration. The absence of D6 increases inflammation, but reduces airway reactivity. These findings suggest that inhibiting D6 function might be a novel means to attenuate airway responses in individuals with allergic asthma.     

Hepatitis C virus: from oxygen free radicals to hepatocellular carcinoma

Epidemiological evidence clearly identifies chronic infection with hepatitis C virus (HCV) as a major risk factor for the development of hepatocellular carcinoma (HCC). Among the mechanisms that have been implicated in the pro-carcinogenic effect of HCV infection, an increased production of reactive oxygen species in the liver seems to have a major pathogenetic role in leading from chronic inflammation to cancer. Recent data have also demonstrated that HCV is capable of inducing this active production of free radicals per se, not just through inflammation, a feature peculiar to this virus and the specific activity of its core protein. This paper provides an overview of the inter-relationships between HCV, liver damage, free radical production and HCC, describing at least in part the complex network involving DNA oxidative damage, cytokine synthesis, proto-oncogene activation and oestrogen receptor expression, that may all be deeply involved in liver carcinogenesis.     

Diagnostic accuracy of a rapid fecal test to confirm Hpylori eradication after therapy： Prospective comparison with a laboratory stool test

AIM: To investigate the clinical performances of rapidstool test (ImmunoCard STAT HpSA, Meridian DiagnosticInc.) in the evaluation of eradication therapy of H pyloriand to compare it with a well-known and validatedlaboratory stool test (Amplified IDEA Hp StAR, Dako).METHODS: Stool samples of 122 patients wereevaluated after eradication therapy of H pylori. H pyloristatus was assessed by 13C-urea breath test (UBT).Stool specimens were tested using either the rapidimmunoassay kit or the laboratory immunoassay kit.RESULTS: Forty-three patients were infected and 79non-infected. Sensitivity and specificity of ImmunoCardSTAT and Hp StAR were 58.14% and 76.4%, and97.47% and 98.73%, respectively (P > 0.05). Overallagreement between the two tests was 92.6% (113 of122 cases).CONCLUSION: ImmunoCard STAT seems to haverather low performances, and it cannot be regarded as areliable tool in the post-treatment setting. Also Hp StARcannot be recommended to confirm H pylori eradicationafter treatment.     

An automated microdrop delivery system for neuronal network patterning on microelectrode arrays

The aim of this work is to present a new technique for defining interconnected sub-populations of cultured neurons on microelectrode arrays (MEAs). An automated microdrop delivery technique allows to design and realize spatially distributed neuronal ensembles by depositing sub-nanoliter volumes of adhesion molecules in which neurons grow and develop. Electrophysiological tests demonstrate that functionally interconnected clusters are obtained and experimental results (both spontaneous and stimulus evoked activity recordings) attesting the feasibility of the proposed approach are presented. By means of the automated system, different and specific architectures can be easily designed and functionally studied. In the presented system the speed of drop deposition is about 30 drops/min; the mean diameter is 147 microm; typical cell survival time is 4-5 weeks. By changing drop size and spacing, investigations about how the network dynamics is related to the network structure can be systematically carried out.