AIM:

To evaluate the anticancer effect of alpha-tomatine (i.p.) either alone or in combination with doxorubicin (i.v.) in a mouse tumour model.

METHODS:

We studied the effect of repeated alpha-tomatine (0.1 - 9 mg/kg) and/or doxorubicin (2 mg/kg) on the growth and mitotic activity of the solid Ehrlich tumour in vivo, as well as on the survival of the tumour-bearing mice.

RESULTS:

Monotherapy with alpha-tomatine had a significant dose-dependent anticancer effect which peaked at 1 mg/kg. This was shown by both slowed tumour growth and reduced tumour cell proliferation. We also provide the first evidence that the combination alpha-tomatine (1 mg/kg) and doxorubicin (2 mg/kg) had a synergistic effect and significantly prolonged the survival of the mice. Neither alpha-tomatine nor doxorubicin influenced the infiltration of tumours with CD3+ lymphocytes; nor were we able to find an in vivo modulation of the key molecules of two regulatory pathways reported in vitro as the principal anti-cancer mechanisms of alpha-tomatine, i.e. iNOS and phosphorylated ERK2. However, alpha-tomatine still led to intracellular DNA inhibition and protein synthesis in Ehrlich tumour cells in a short-term culture ex vivo with IC50 values of 8.7 and 6.6 µM.

CONCLUSIONS:

The results suggest that ΤΟΜ, especially in combination with doxorubicin, may be a promising agent for the treatment of malignant solid tumours. Despite growing knowledge of the mechanisms of ΤΟΜ action in cancer cells, most aspects remain unclear. Parallel organ toxicity, especially potential liver effects, requires careful attention when performing in vivo studies in the future.

INTRODUCTION:

Breast cancer is, now often diagnosed in patients older than 70 years due to longer life expectancy. The usual treatment is mastectomy to obviate radiotherapy or breast-conserving surgery followed by radiotherapy. The aim of this study was to investigate the need for adjuvant radiotherapy in older patients and the consequences of omitting radiotherapy following conservative surgery.

METHODS:

An extensive database search was made of patients who had been treated for breast cancer at the Department of Oncology, University Hospital Olomouc and the Atlas Hospital in Zlin (2004-2008). We identified 738 patients of whom 190 patients (25.7%) were older than 70 years of age. These were followed up for progression-free and overall survival. The cause of death was checked for breast cancer relapse.

RESULTS:

In total only 9 patients undergoing breast saving surgery were ultimately identified. No patient had confirmed local recurrence during the follow up period: Two patients have died due to distant metastasis without local relapse and one patient has died for reasons other than breast cancer.

CONCLUSION:

Omitting radiotherapy after breast saving surgery provides an opportunity for women to undergo breast saving surgery and avoid 7 weeks of radiotherapy. This could significantly improve patient quality of life. In our of many years experience and from published randomized data, this procedure is safe for a select group of patients 70 years of age and older.

AIMS:

Cancer patient's inherited genotype may influence his or her survival, but evidence for the role of these genetic differences in oral cancer survival has not yet been explored.

METHODS:

The authors evaluated polymorphisms in the GSTM1 and CYP1A1 genes for associations with overall survival in 100 oral squamous cell carcinoma (OSCC) treated patients and 100 controls who were followed up for survival within 2 years of the date of completion of their treatment. Overall survival was evaluated in Kaplan-Meier survival functions and Cox proportional hazards models.

RESULTS:

After adjustment for stage and histology, GSTM1null genotype was associated with shorter survival among OSCC patients, compared with GSTM1 present genotype. There was no association between CYP1A1 C genotype and survival in the overall study population.

CONCLUSION:

The study indicated a potential role for GSTM1 polymorphism in predicting the clinical outcomes of treated oral carcinoma patients.

BACKGROUND:

The aim of the present paper is to review the evolution of concepts regarding the use of Class I and III antiarrhythmic drugs (AADs) in myocardial infarction over the past four decades.

METHODS:

Results of animal experiments carried out by the authors and papers published between 1970 and 2012 in journals and the PubMed search system were used.

RESULTS:

Animal experiments carried out as early as the 1970s showed that Class IB and IC AADs lose their antiarrhythmic effect and electrically destabilize ventricles in the very early phase of myocardial ischemic focus formation. The cause of this is interaction between Class IB and IC AADs as well as Class III AADs with sympathetic neural activation (SNA) of the heart in the early phase of myocardial ischemia. Given the extremely high and uneven distribution of noradrenaline in tissue, SNA results in dispersion of the depolarization and repolarization processes in the ventricles. The clinical sequels of the interaction between the effects of AADs and SNA are as follows: the antiarrhythmic effect of AADs is restored in AMI once SNA has resolved; membrane-destabilization of the ventricles can be restored any time in the presence of randomly occurring SNA not only due to increasing myocardial ischemia but, also, as a result of psychological stress (emotions), and any pre-existing structural heart disease will enhance the pro-fibrillatory effect of a randomly occurring SNA.

CONCLUSIONS:

Despite the above risks, AADs continue to play an irreplaceable role in suppressing post-myocardial arrhythmias and in preventing sudden cardiac death following ICD placement. The risk of AADs' proarrhythmic effect in SNA can be reduced by combining them with beta-blockers. The last recourse when attempting to suppress malignant ventricular tachyarrhythmias is left sympathetic denervation of the heart.

INTRODUCTION:

Screening tests for gastrointestinal diseases acceptable for population with a high sensitivity and high specificity can now be offered by clinical laboratories. This paper summarizes major recent advances in this area of laboratory medicine.

METHODS:

Relevant articles published within the last 5 years in the NLM (National Library of Medicine) PubMed - Medline database covering the three gastrointestinal diseases - colorectal cancer, coeliac disease, and atrophic gastritis were included for this overview.

RESULTS:

In Europe, colorectal cancer (CRCA) is the second most frequent malignant disease. Quantitative immunochemical analysis of the stool for haemoglobin provides the best screening test to date, with both sensitivity and specificity approaching 95%. Even though coeliac disease (CD) affects approximately 1% of the general population, it remains largely unrecognised. Recommended methods for screening currently involve the detection of IgA and IgG antibodies against tissue transglutaminase and deamidated gliadin peptide. Evaluations of screening are now discussed for other diseases of the gastrointestinal tract - such as chronic atrophic gastritis (CAG), and inflammatory bowel disease (IBD). Detection of infection by Helicobacter pylori and stomach-specific plasmatic biomarkers, especially pepsinogen I/II ratio, could help with the prevention of gastric carcinomas. The use of faecal calprotectin as a screening test could substantially reduce the number of invasive methods necessary for the diagnostic work-up of patients with IBD.

CONCLUSIONS:

Screening tests for CRCA and CD have been used worldwide for many years. Screening strategies for gastrointestinal diseases are suggested in the text, based on recent basic science, clinical papers as well as our own experience.

AIMS:

Limited aeration has been demonstrated to cause slowdown in proliferation and delayed budding, resulting eventually in a unique unbudded G2-arrest in the obligate aerobic pathogenic yeast Cryptococcus neoformans. Also, the ability to adapt to decreased oxygen levels during pathogenesis has been identified as a virulence factor in C. neoformans. The aim of this study was to identify and characterize genes that are necessary for the proliferation slowdown and G2-arrest caused by limited aeration.

METHODS:

Random mutants were prepared and screened for lack of typical slowdown of proliferation under limited aeration. The CNAG_00156.2 gene coding for a zinc-finger transcription factor was identified in mutants showing most distinctive phenotype. Targeted deletion strain and reconstituted strain were prepared to characterize and confirm the gene functions. This gene was also identified in a parallel studies as homologous both to calcineurin responsive (Crz1) and PKC1-dependent (SP1-like) transcription factors.

RESULTS:

We have confirmed the role of the cryptococcal homologue of CRZ1/SP1-like transcription factor in cell integrity, and newly demonstrated its role in slowdown of proliferation and survival under reduced aeration, in biofilm formation and in susceptibility to fluconazole.

CONCLUSIONS:

Our data demonstrate a tight molecular link between slowdown of proliferation during hypoxic adaptation and maintenance of cell integrity in C. neoformans and present a new role for the CRZ1 family of transcription factors in fungi. The exact positioning of this protein in cryptococcal signalling cascades remains to be clarified.

INTRODUCTION:

ADAM33 is the candidate gene most commonly associated with asthma and airway hyperreactivity (AHR).

AIM:

The aim of this study was to determine whether level of AHR is associated with certain alleles or haplotypes of the ADAM33 gene in asthmatic children.

METHODS:

One hundred and nine asthmatic children and 46 controls from the general population were examined with spirometry before and after histamine and methacholine inhalation. All subjects were genotyped for single-nucleotide polymorphisms (SNPs) of the ADAM33 gene. Haplotypes were determined according to genotypes of the patient's parents.

RESULTS:

We found the three most frequent ADAM33 haplotypes (a1-3) were associated with the highest level of AHR to methacholine and histamine in 66% of asthmatic children. The paternally transmitted GGGCTTTCGCA haplotype was seen in 73.3% asthmatic children with serious AHR to methacholine challenge (paternal and maternal origin of haplotype 73.3% to 37.5, P=0.046) Significant differences in the relative frequency of paternal haplotypes with high levels of AHR to histamine were found (P=0.013).

CONCLUSION:

ADAM33 haplotypes (a1, a2, a3) are associated with severity of AHR and are significantly more often transmitted in the paternal line.

AIMS:

Recent studies report increased echogenicity of the substantia nigra (SN) in patients with Parkinson's disease (PD) using transcranial sonography (TCS). However, the main limitation to TCS is its dependence on the sonographer's experience. Experimental software for quantitative evaluation of the echogenic SN area was thus developed by us. The aim of this study was to test the reliability of the data using developed B-Mode Assist software in patients with parkinsonism and in healthy volunteers.

METHODS:

The SN was imaged from the right temporal bone window in mesencephalic plane using TCS. DICOM images of SN were saved, converted into JPEG format, encoded and processed. Two observers performed 3 automatic evaluations of the SN area (measurements of SN area in each gray scale intensity inside the region of interest) by counting the standard deviation of all 6 measurements using developed software. The average value of all 3 measurements of each observer was used for computing Cohen's kappa coefficient to determine inter-observer correlations. Cohen's kappa coefficients as an intra-observer correlation for observer 1 and observer 2 were counted from the first 2 measurements of both observers.

RESULTS:

In total, 92 images were evaluated using this software. The mean of the standard deviations was 3.87; Cohen's kappa for intra-observer agreement of two observers were 0.947, and 0.943, resp.; Cohen's kappa for inter-observers agreement was 0.880. The agreement between visual and automatic detection of SN pathology was in 97.8% images. The sensitivity, specificity, positive and negative predictive values of automatic measurement were 100, 96.2, 95.1, 100%, resp.

CONCLUSIONS:

The results show very reliable measurement of SN features using designed application with "almost perfect" inter-observer and intra-observer agreements.

BACKGROUND:

Arthrocentesis is a very gentle method for lavage of the joint space. The principle consists in the introduction of a pair of needles into the upper joint space and subsequent lavage using physiological saline or Ringer's solution. Arthrocentesis of the temporomandibular joint is used in both cases of acute closed lock and treatment of various temporomandibular disorders.

METHODS:

A literature search in Pubmed database, using key words: Temporomandibular joint (TMJ), Arthrocentesis, indications, technique, results.

CONCLUSION:

Arthrocentesis of the temporomandibular joint is a minimally invasive treatment method at the boundary between conservative and surgical therapy. It is usually performed on an out-patient basis under local anaesthesia. It is used both in cases of acute block caused by displacement of the articular disc and also to treat degenerative inflammatory diseases of the joints. The main objective of arthrocentesis is to wash out inflammatory mediators, release the disc, break adhesions, eliminate pain and improve joint mobility. It is a method with a minimum number of complications, it is simple and not demanding in terms of instruments, and it can be performed repeatedly. For this reason, it has become widespread and very popular in the treatment of internal disorders of the temporomandibular joint.

OBJECTIVE:

Abnormal haemodynamics is commonly agreed to be a major contributor to the development of distal anastomotic intimal hyperplasia. A new vascular graft design proposed by computational studies was used to demonstrate its surgical feasibility and to compare it with the conventional graft in a porcine model.

METHOD:

The device was used in 12 eight-month-old pigs, six received the new graft and six had a conventional graft. The proximal graft end was implanted into the aorta, the distal graft end was implanted into the iliac artery. The host artery was ligated in order to simulate occlusion. At 20 weeks after surgery the pigs were killed and the device was excised for histological and morphometric analysis.

RESULTS:

In five experimental grafts the reconstruction was occluded due to thrombosis; only one prosthesis was patent showing a minimum of neointimal hyperplasia. In the control group too only three of the six grafts were patent. A histological analysis revealed, as the cause of occlusion, fibrous tissue overgrowth corresponding in structure to neointimal hyperplasia. Differences in the number of obliterations and in occlusion rates between the profiles of the two groups were evaluated using the median test (P<0.05). The results were not statistically significant.

CONCLUSION:

Although mathematical modelling had shown significant haemodynamic benefits of a naturally bifurcated graft, our study did not confirm its superiority over conventionally used prostheses.