Serum arginase activity in postsurgical monitoring of patients with colorectal carcinoma

BACKGROUND: Colorectal carcinoma (CRC) is one of the most common malignancies. In the current work, the role of arginase as a diagnostic marker in patients with recurrent CRC and colorectal liver metastases (CRCLM) was studied. METHODS: Arginase activity was monitored in serum from 40 patients with primary CRC and from 100 patients with CRCLM. Blood was taken before and after patients underwent tumor resection. Studies were conducted for 3 years. RESULTS: Preoperative arginase activity in serum from patients with CRC and CRCLM was much greater compared with the arginase activity in serum from healthy control blood donors. One and two cut-off levels of increased arginase activity were observed in patients with CRC and CRCLM, respectively. After patients underwent tumor resection, the arginase activity decreased to normal values in both patients with CRC and patients with CRCLM. Activity levels remained low in patients who did not develop recurrent CRC or CRCLM (first or second). In patients who developed subsequent recurrences or metastases that appeared after surgery, during 3 years of surveillance, a significant rise in serum arginase activity was observed. The clinical prognosis for patients was worst when the postoperative serum arginase activity was very high, because those patients more often developed second liver metastases or died. CONCLUSIONS: The authors conclude that the determination of serum arginase activity may be a complementary test to confirm the occurrence of CRC and may be useful for the early diagnosis of patients who develop recurrent CRC and/or CRCLM.     

Radiocirculography in congenital heart disease in children with intracardiac shunts

A modification of radiocirculography suitable for the investigation of children suffering from congenital heart disease was developed and tested in 55 children with intracardiac shunts. Comparison of data derived from radiocirculography with the data obtained by conventional cardiac catheterisation showed radiocirculography has a high degree of accuracy when it is used to assess shunt size. Pulmonary arterial and capillary pressures and pulmonary resistance values were derived from radiocirculography findings and compared with those obtained from catheterisation studies: only in children of school age could the two be closely correlated. In cyanotic heart disease morphological analysis of the radiocirculographic curves proved an especially helpful diagnostic aid. The close agreement between the assessment of aortic override when using angiography and radiocirculography was demonstrated.     

From manual to artificial intelligence fitting: Two cochlear implant case studies

Objective: To assess whether CI programming by means of a software application using artificial intelligence (AI), FOX®, may improve cochlear implant (CI) performance.

Patients: Two adult CI recipients who had mixed auditory results with their manual fitting were selected for an AI-assisted fitting. Even after 17 months CI experience and 19 manual fitting sessions, the first subject hadn’t developed open set word recognition. The second subject, after 9 months of manual fitting, had developed good open set word recognition, but his scores remained poor at soft and loud presentation levels.

Main outcome measure(s): Cochlear implant fitting parameters, pure tone thresholds, bisyllabic word recognition, phonemic discrimination scores and loudness scaling curves.

Results: For subject 1, a first approach trying to optimize the home maps by means of AI-proposed adaptations was not successful whereas a second approach based on the use of Automaps (an AI approach based on universal, i.e. population based group statistics) during 3 months allowed the development of open set word recognition. For subject 2, the word recognition scores improved at soft and loud intensities with the AI suggestions. The AI-suggested modifications seem to be atypical.

Conclusions: The two case studies illustrate that adults implanted with manual CI fitting may experience an improvement in their auditory results with AI-assisted fitting.     

Phosphatidylinositol-dependent phospholipases C Plc2 and Plc3 of Candida albicans are dispensable for morphogenesis and host-pathogen interaction

Phospholipases play an important role as virulence factors in human pathogens. Candida albicans, the major fungal pathogen of humans, encodes phospholipases of type A, B, C and D. Type B Plb2 and type D Pld1 phospholipases have been shown to contribute to virulence in this organism. We analyzed, in C. albicans, PLC2 and PLC3, two highly conserved genes coding for phosphatidylinositol-dependent phospholipases C with homology to the known virulence factor PlcA in the human pathogen Listeria monocytogenes. We show that expression of PLC2 and PLC3 is upregulated under different filament-inducing conditions and in the constitutive filamentous mutant tup1Delta. In order to analyze PLC2 and PLC3 function in C. albicans, we constructed strains that carry PLC2 or PLC3 under a constitutive promoter and strains that lack all four PLC2/3 alleles. These strains were not affected in their ability to produce filaments under non-inducing conditions, nor was filamentation modified under inducing conditions, suggesting that PLC2/3 are not critical determinants of the yeast-to-hypha switch. In a cell culture model for macrophage interaction, phagocytosis of C. albicans and subsequent killing were not influenced by PLC2/3. These results demonstrate that C. albicans PLC2 and PLC3 are dispensable for virulence; moreover, they underline the sharp contrast with the function of plcA in L. monocytogenes.     

Reactivity of alveolar macrophages during granulomatous inflammation of the lungs under conditions of acute massive blood loss

Reactivity of mouse alveolar macrophages by their ability to phagocytize killedSt. aureus bacteria and production of reactive oxygen metabolites (nitro blue tetrazolium test) in response to zymosan administration was studied under normal conditions and after acute massive blood loss. Zymosan-induced granulomatous inflammation of the lungs during acute massive blood loss 2-fold inhibited the increase in oxidative metabolism of alveolar macrophages. Suppressed production of toxic oxygen radicals in alveolar macrophages was accompanied by accelerated recovery of cells on the surface of the respiratory tract. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 9, pp. 257–260, September, 2004     

Auswirkung der Hochfrequenzapplikation auf den Zungengrund

BACKGROUND AND OBJECTIVE: A newly developed radio-frequency monopolar needle electrode was evaluated in vitro on porcine tongues. PATIENTS AND METHODS: Porcine tongues with different tissue temperatures (20+/-1) degrees C and (32+/-2) degrees C were coagulated for 90 s. In a second step, 23 coagulations at 7 W were applied (34+/-2) degrees C. RESULTS: The volume of the lesion correlated well with increasing temperature. In step two, the mean energy was 238 J and the mean volume of the lesion was 507 mm(3) (100+/-15)%. Prolonged energy application did not correlate with a larger volume of the lesion. CONCLUSION: The new radio-frequency needle electrode can reduce tongue volume in a precise and controlled manner (SD+/-15%).     

Impact of holmium:YAG and neodymium:YAG lasers on the efficacy of DNA delivery in transitional cell carcinoma

New approaches in the treatment of transitional cell carcinoma (TCC) are using gene therapy to influence the disease at the genetic level. Technical advances in genomics, the availability of tissue-specific gene promoters and other developments have made this approach more realistic. Transporting the gene into the target cell is still the major problem. Several transfection techniques have been introduced. Transfection of naked DNA is one of the simplest to perform but transfection rates have been very poor. We investigated the influence of laser energy on transfection efficacy in urothelial cancer cells in vitro with two types of medical lasers. A suspension of human transitional cancer cells (UM-UC3; 3.5 million cells/ml) was mixed with 200 g of plasmid DNA (pEGFP-N1). Two types of laser energy, neodymium:YAG (Nd:YAG) and holmium:YAG (Ho:YAG), were applied to the cell suspension in different energy settings. Twenty four hours after treatment, transfection rates were measured with FACS analysis. Energy setting parameters that determine the efficacy of laser were investigated. The significance of different transfection rates was estimated with the students t-test. We demonstrated that the Nd:YAG laser was not suitable for achieving significant transfection of the reporter gene to the cells. In contrast, the Ho:YAG laser produced satisfactory transfection rates. There was an increase in transfection with increasing frequency of laser pulses, from 16% with 2 Hz up to 40% with 10 Hz (p<0.0005). Pulse frequency was therefore stabilised at 10 Hz. Pulse energy (mJ) showed the same dependency: a transfection rate of 18.3% was achieved with 1,000 mJ and 53.8% with 2,000 mJ (p>0.0005). Additionally, we investigated the impact of total pulse number (imp) with different pulse energies. At 1,000 mJ, a transfection rate of 18.3% was estimated with 200 imp and 48.56% with 750 imp, (p<0.0005). At 2,000 mJ, a transfection rate of 53.8% was achieved with 200 imp and 58.26% with 500 imp. The optimal laser setting observed in this experiment was 10 Hz, 2,000 mJ and 500 imp. This study indicates that the efficacy of naked DNA delivery into TCC in vitro is improvable by application of Ho:YAG laser energy. The Nd:YAG laser did not increase transfection rates in our model. Our results with the Ho:YAG laser are encouraging for further studies to optimise DNA delivery. As TCC tissue is relatively easy to access, this method could become an effective and minimally invasive procedure in urothelial cancer treatment.     

The influence of oxalate on renal epithelial and interstitial cells

Most renal stones in humans are composed of calcium oxalate. An increase in urinary oxalate levels has been shown to result in renal epithelial cell injury and crystal retention. However, the underlying mechanisms are unclear. Although the localization of primary stone formation and the associated cells playing the pivotal role in stone formation are still unknown, renal epithelial cells and interstitial cells seem to be involved in this process. The aim of this study was to evaluate the effects of oxalate on distinct renal epithelial and endothelial cells as well as fibroblasts. The first part focused on the toxicity of oxalate on the cells and a potential time- and dose-dependency. In the second part, renal epithelial cells were cultured in a two-compartment model to examine the vulnerability of the tubular or basolateral side to oxalate. LLCPK1, MDCK, renal fibroblast and endothelial cell lines were cultured under standard conditions. In part 1, cells were grown in standard culture flasks until confluent layers were achieved. Sodium oxalate was delivered at final concentrations of 1, 2 and 4 mM to either the apical or basolateral side (plain medium was delivered to the contralateral side). Cell survival was assessed microscopically by trypan blue staining after 1, 2 and 4 h. The influence of oxalate on proliferation and apoptosis induction was also investigated. In the second part, MDCK and LLCPK1 cells were grown in 6-well plates until confluent layers were achieved. Sodium oxalate at the above concentrations was applied, to either the apical or basolateral side and plain medium was delivered to the opposite side. The same protocol was then followed as in part 1. Part 1: sodium oxalate led to a time- and concentration-dependent decline in cell survival that was comparable in LLCPK1 and MDCK. Non-tubular cell lines like fibroblasts and endothelial cells were significantly more vulnerable to oxalate. These observations were reflected by significant impairment to cell proliferation. We could not demonstrate an induction of apoptosis in any cell line. Part 2: both cell lines were more vulnerable to oxalate on the basolateral side. This effect was more pronounced in MDCK cells at high oxalate concentrations (4 mM). Cells are apparently more resistant on the apical (tubular) side. Our results show that sodium oxalate has a negative effect on the growth and survival of renal epithelial cells and, to a greater extent, also fibroblasts and endothelial cells. We could not demonstrate any induction of apoptotic processes which implies a direct induction of cell necrosis. The finding of interstitial calcification and the proximity of tubules, vessels and interstitial cells make involvement of non-tubular renal cells in tissue calcification processes possible. Renal epithelial cells are apparently more vulnerable to oxalate on their basolateral side. Therefore, calcification processes within the interstitium may exert pronounced toxic effects to these cells, leading to inflammation and necrosis. These observations further support the idea of the interstitium as a site of primary stone formation.