Is glucocorticoid-induced osteonecrosis after kidney transplantation related to osteoporosis?

Sir, Osteopenia and osteonecrosis (ON) cause important long-termmorbidity in renal transplant (Tx) recipients with increasingincidences because of longer graft survival and related drugexposure. A 38-year-old woman who started on haemodialysis in November2001 had a renal Tx from a live relative in March 2003 due tochronic pyelonephritis with vesicoureteral reflux related end-stagerenal disease. She had persistent secondary amenorrhoea 2 monthsbefore dialysis treatment. Throughout this period she had calcitrioland phosphorus binders for controlling secondary hyperparathyroidism.Her pre-Tx serum     

Kikuchi ultrafast nanodiffraction in four-dimensional electron microscopy

Coherent atomic motions in materials can be revealed using time-resolved X-ray and electron Bragg diffraction. Because of the size of the beam used, typically on the micron scale, the detection of nanoscale propagating waves in extended structures hitherto has not been reported. For elastic waves of complex motions, Bragg intensities contain all polarizations and they are not straightforward to disentangle. Here, we introduce Kikuchi diffraction dynamics, using convergent-beam geometry in an ultrafast electron microscope, to selectively probe propagating transverse elastic waves with nanoscale resolution. It is shown that Kikuchi band shifts, which are sensitive only to the tilting of atomic planes, reveal the resonance oscillations, unit cell angular amplitudes, and the polarization directions. For silicon, the observed wave packet temporal envelope (resonance frequency of 33 GHz), the out-of-phase temporal behavior of Kikuchi's edges, and the magnitude of angular amplitude (0.3 mrad) and polarization elucidate the nature of the motion: one that preserves the mass density (i.e., no compression or expansion) but leads to sliding of planes in the antisymmetric shear eigenmode of the elastic waveguide. As such, the method of Kikuchi diffraction dynamics, which is unique to electron imaging, can be used to characterize the atomic motions of propagating waves and their interactions with interfaces, defects, and grain boundaries at the nanoscale.     

Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients

Background:

Our aim was to investigate the prognostic and predictive value of the oncogenic MAPKK-like protein T-cell-originated protein kinase (TOPK) stratified by KRAS and BRAF mutations in patients with sporadic, hereditary and metastatic colorectal cancer (CRC) treated with anti-EGFR therapy.

Methods:

Immunohistochemistry (IHC) for TOPK was performed on four study groups. Group 1 included two subgroups of 543 and 501 sporadic CRC patients used to test the reliability of TOPK expression by IHC. In Group 2, representing an additional 222 sporadic CRCs, the prognostic effect of TOPK stratified by KRAS and BRAF was assessed. The prognostic effect of TOPK was further analysed in Group 3, representing 71 hereditary Lynch syndrome-associated CRC patients. In Group 4, the predictive and prognostic value of TOPK was analysed on 45 metastatic patients treated with cetuximab or panitumumab stratified by KRAS and BRAF gene status.

Results:

In both sporadic CRC subgroups (Group 1), associations of diffuse TOPK expression with clinicopathological features were reproducible. Molecular analysis of sporadic CRCs in Group 2 showed that diffuse TOPK expression was associated with KRAS and BRAF mutations (p<0.001) and with poor outcome in patients with either mutation in univariate and multivariate analysis (P=0.017). In hereditary patients (Group 3), diffuse TOPK was linked to advanced pT stage. In metastatic patients treated with anti-EGFR therapy (Group 4), diffuse TOPK expression was linked to dismal outcome despite objective response to treatment (P=0.01).

Conclusions:

TOPK expression is an unfavourable prognostic indicator in sporadic patients with KRAS or BRAF mutations and also in patients with metastatic disease experiencing a response to anti-EGFR therapies. The inhibition of TOPK, which could benefit 30–40% of CRC patients, may represent a new avenue of investigation for targeted therapy.     

Our experience with fulminant hepatic failure in Turkish children: etiology and outcome

Fulminant hepatic failure is a rare and devastating event during childhood. The etiology of liver failure is reported to change according to age and geographical location. We aimed to investigate, retrospectively, causes and outcome of fulminant hepatic failure in Turkish children. Thirty-four children with fulminant hepatic failure were analysed by means of etiology and outcome. Etiological factor, clinical presentation, encephalopathy stage and biochemical parameters were correlated with outcome. Acute viral hepatitis was detected in 12 cases (35.2 per cent) and hepatitis A was the most commonly detected cause among cases with fulminant hepatic failure (n = 9, 26.4 per cent). Hepatitis B and non A-E infection were diagnosed in two (5.8 per cent) and one (2.9 per cent) cases, respectively. Wilson's disease was defined in four patients (12.5 per cent). Budd-Chiari syndrome (2.9 per cent), autoimmune hepatitis (2.9 per cent) and mushroom poisoning (2.9 per cent) were other detected causes of fulminant hepatic failure in this group. No viral, metabolic, toxic or anatomic reason could be detected in the remaining 15 (44.1 per cent) patients and they were evaluated as cryptogenic. Mortality was 67.6 per cent (23 cases). Encephalopathy grade, total and indirect bilirubin levels were found to be significantly higher in patients who died (p = 0.004, p = 0.03, p = 0.04). Seven patients could have been transplanted (two cadavaric, five living related) and the mortality of this group was 28.5 per cent (n = 2). It was concluded that fulminant hepatitis A virus (HAV) infection is the most common detectable cause of fulminant hepatic failure in Turkish children.     

The in vivo effect of a Brassica oleracea var. capitata extract on Ehrlich ascites tumors of MUS musculus BALB/C mice

An extract of Brassica oleracea var. capitata juice was prepared using petroleum ether, ether, ethanol and an Al2O3 column. The healing and tumor protecting effects of this extract were tested on Ehrlich ascites (EA) solid tumors of Mus musculus BALB/C mice. Complete disappearance of the tumors was observed in 54.5% of the animals in the experimental group (n = 22) which received 20 mg/day of the extract i.p. for 28 days. Regression of the tumors (27%), fixation of tumor size (4%) and an increase in tumor size (18%) were also recorded. Neither tumor size fixation nor regression was recorded in the control group which received physiological serum (0.5 ml/day). The healing effect was found to be related to the starting tumor size. The healed animals in the experimental group were followed for 6-7 months and no tumor recurrence was recorded. The protective effect of this extract on tumor formation was also tested. Experimental animals (n = 35) received 20 mg/day of the extract i.p. for 20 days. Physiological serum was administered to a control group (n = 30). Transplantation of solid tumors was performed on the 20th day and extract administration was discontinued. Transplantation success was recorded 20 days after transplantation. In the experimental group, only three out of 35 mice showed tumor development, whereas in the control group the number was 23 out of 35 mice. It was also observed that the extract prevented the development of liquid EA tumors. This extract was also found to be nontoxic. Brassica oleracea var. capitata had a healing effect as well as a protective effect on EA solid tumors of mice. These results are in agreement with our previous results obtained from a liquid Brassica oleracea var. acephala juice extract.     

Effect of tenoxicam on biochemical serum parameters of rats

Tenoxicam is a nonsteroidal analgesic of the oxicam group, which possesses both antipyretic and anti-inflammatory characteristics. The use of tenoxicam has recently increased and it is reported in the literature that treatments lasting between a few weeks to three months caused increases in serum alanine transferase (ALT), aspartate transferase (AST), gamma glutamyl transferase (GGT) and bilirubin in humans. Toxic dose treatments to rats caused alterations in renal parameters. To verify these observations, various biochemical parameters were examined following administration of nontoxic doses of tenoxicam to rats. Rats were divided into three groups. One group received tenoxicam 0.6 mg/kg/day; the second group received 1.2 mg/kg/day i.p. The control group received normal saline i.p. At the end of 15 days, blood samples from the animals' hearts were taken for routine biochemical tests. No statistically significant changes were observed in serum urea, uric acid, creatinine, electrolytes, ALT, AST, total protein, bilirubin or glucose levels between the treatment groups and control groups. Increases in GGT levels were found to be statistically significant in both of the treatment groups compared with the control group.     

A case of Acremonium strictum peritonitis

During the past two decades opportunistic fungal infections have emerged as important causes of morbidity and mortality in patients with severe underlying illnesses. A few cases of Acremonium spp. infections have been described in immunocompromised patients, but they have on occasion been reported as the cause invasive disease in immunocompetent individuals. Peritonitis is a common clinical problem that occurs in patients with end-stage renal disease treated by continuous ambulatory peritoneal dialysis (CAPD). Yeasts, or rarely molds, may also cause peritonitis in patients on CAPD and we present here a case caused by Acremonium strictum.     

The effect of sulfasalazine in pentylenetetrazole-induced seizures in rats

We aimed to reveal the anti-convulsant effects sulfasalazine and its mechanism in pentylenetetrazole (PTZ)-induced seizures in rats. Forty-eight male Wistar albino rats (200-250 g) were randomly divided into two groups: 24 for electroencephalography (EEG) recording (group A) and 24 for behavioral studies (group B). About 70 mg/kg PTZ was used for behavioral studies after sulfasalazine administration and 35 mg/kg PTZ was used for EEG recording after sulfasalazine administration. Electrodes were implanted on the dura mater over the left frontal cortex and the reference electrode was implanted over the cerebellum for EEG recording. Racine’s convulsion scale, first myoclonic jerk onset time, spike percentages, brain malondialdehyde (MDA), superoxide dismutase (SOD), and prostaglandin F2α (PGF2α) levels were evaluated between the groups. First myoclonic jerk onset time was significantly shorter in the saline group than both 250 and 500 mg/kg sulfasalazine groups (P<0.05). Racine''s convulsion scores were significantly lower in the 250 and 500 mg/kg sulfasalazine groups than the saline group (P<0.05, P<0.001). The two sulfasalazine groups had lower spike percentages than the saline group (P<0.05). Significantly lower MDA and PGF2α levels were observed in the 250 and 500 mg/kg sulfasalazine groups compared with the saline group (P<0.05, P<0.001, respectively). SOD increased significantly in both sulfasalazine groups compared with the PTZ+saline group (P<0.05). Our study demonstrated that sulfasalazine had protective effects on PTZ-induced convulsions by protecting against oxidative and inflammatory damage associated with PTZ.