Circulating levels of B-cell activating factor in paediatric patients with malignancy with or without cancer-related cachexia.

BACKGROUND: Cancer-related cachexia is a multifactorial syndrome characterised by progressive loss of body weight and it affects a large proportion of patients with advanced cancer. Cachexia is associated with reduced treatment tolerance, response to therapy, quality of life and duration of survival, whereas some of its mechanisms are shared across the whole continuum of diseases in the population, either cancer-related or non-cancer related e.g. systemic inflammation, increased lipolysis, insulin resistance and reduced physical performance. However, so far there has been only little effort to utilise the integrative physiology of adipose tissue to achieve therapeutic gain. B cell-activating factor (BAFF) is a novel member of the TNF ligand superfamily, is mainly produced by myeloid cells and has recently been shown to participate in B-cell survival and B- and T-cell maturation, but also in adipogenesis. Therefore, it represents an elegant candidate molecule linking the immune system and adipose tissue metabolism, both being involved deeply in the pathogenesis of cachexia. Moreover, it has been described very recently that BAFF directly influences secretion of IL-6 and IL-10. MATERIAL AND METHODS: In this study, pre-treatment circulating levels of BAFF were investigated in a cohort of 83 paediatric patients with malignancy (0-18 y) with or without cancer-related cachexia using ELISA-based methodology. RESULTS: Apart from logical significant associations of BAFF circulating levels with disease severity in B-lineage malignancies (ALL or B-cell lymphomas), we observed significant elevation of BAFF in adolescent patients with Ewing sarcoma and rhabdomyosarcoma, compared to the circulating levels appropriate for given age. CONCLUSION: To the best of our knowledge, this is so far the first study focusing on BAFF in paediatric malignancies with or without cancer-related cachexia. More research into whether BAFF can represent a useful circulating biomarker for detection and monitoring of the cancer-related cachexia is imperative.

Occurrence of metabolic osteopathy in patients with chronic pancreatitis.

INTRODUCTION: Chronic pancreatitis is an inflammatory disease manifested by maldigestion and, in an advanced stage, by malabsorption. The aim of our research was to monitor the occurrence of metabolic osteopathies (osteopenia, osteoporosis and osteomalacia) in patients with chronic pancreatitis. PATIENTS AND METHODS: The group consisted of 73 patients (17 women and 56 men) in different stages of chronic pancreatitis. In all patients we determined serum concentrations of Ca, P, 25-OH vitamin D, 1,25-(OH)(2) vitamin D, alkaline phosphatase and its bone isoenzyme. Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA) in the lumbar spine (L(1)-L(4)) and in the proximal femur. When bone pathology was identified by DXA, we determined the other to exclude other causes of secondary osteopathy and the 24-hour loss of calcium and phosphorus in the urine. RESULTS: Osteopathy was found in 39% of patients, i.e. osteopenia in 26%, osteoporosis in 5% and osteomalacia in 8% of cases. CONCLUSION: The occurrence of relatively high percentages of metabolic osteopathies in patients with chronic pancreatitis may correlate, namely in advanced stages of the disease, with the malabsorption of vitamin D to the enterohepatic circulation. In initial forms of pancreatitis, it is not possible to exclude progression of osteopathy due to changes of the intestinal flora, with disturbance of vitamin D absorption to the intestinal mucosa.

Genetics of humoral and cytokine activation in heart failure and its importance for risk stratification of patients.

The study objective is to prove an association among plasma concentration of big endothelin and endothelin-1, other clinical parameters and two frequent polymorphisms - G8002A and -3A/-4A - in the endothelin-1 (EDN-1) coding gene (6p21-23), and among plasma concentration of TNF alpha and gene polymorphisms TNF alpha -308 A/G, -238 A/G, TNF beta Ncol and 3'TACE (tumour necrosis factor alpha converting enzyme) in patients with chronic heart failure (CHF). The second objective is to find an association between polymorphisms G8002A and -3A/4A EDN-1 with diabetes mellitus (DM), peripheral artery disease (PAD) and myocardial infarction (MI) in patients with chronic heart failure (CHF). The study population included 266 patients with symptomatic CHF and proven dysfunction of the left ventricle (LV). Genotyping and plasma concentrations of humoral substances were examined in 224 patients with ejection fraction (EF) below 40%. No associations between plasma concentrations of endothelin-1 and big endothelin and polymorphisms G8002A (p=0.87, p=0.81) and -3A/-4A (p=0.871, p=0.749) in the gene coding endothelin-1 were found. No associations were observed between plasma concentration of TNF alpha and genotypes in four polymorphisms in TNF alpha, beta and TACE genes. A significant correlation was seen between plasma concentration of big endothelin and pulmonary congestion. Patients with ischemic heart disease (IHD) and previous MI showed a difference in the distribution of genotype G8002A for endothelin-1: allele G 0.718 and A 0.282 vs those without MI: allele G 0.882 and A 0.118, (p<0.05). Patients with IHD and DM had allele G in 0.67 and A 0.33, while those without DM had allele G in 0.790 and A in 0.209 (p<0.03). Patients with IHD and concomitant PAD had allele G in 0.718 and A in 0.282 vs those without PAD allele G in 0.882 and A in 0.118 (p<0.0004). Patients with dilative cardiomyopathy (DCMP) showed no differences in genotype G8002A and presence of DM or PAD. It might be speculated that in the case of endothelin-1 and TNF alpha in CHF the genetic determination is not important, and plasma concentrations are influenced more by the disease severity. Ischemics with previous MI, concomitant DM or PAD showed more frequently allele A and less often allele G than those without these diseases. A genotype with allele A is associated with higher risk of concomitant diseases.

Increased activity of superoxide dismutase in advanced stages of head and neck squamous cell carcinoma with locoregional metastases.

The aim of the study was to investigate relationship between activity of superoxide dismutase (SOD), malondialdehyde (MDA) and tumor necrosis factor alpha (TNFalpha) and between Ala-9Val polymorphism in the gene encoding MnSOD (SOD2) and the initial stage and prognosis of the head and neck squamous cell carcinoma (HNSCC). Prospective study cohort comprised 88 patients who underwent surgical treatment for the diagnosis of HNSCC (53 patients were diagnosed with locoregional metastatic spread (N+) at the time of diagnosis). After the initial surgery subjects were followed for the subsequent period of 26 months during which 14 manifested relapse. Genotypes were detected by the PCR-based methodology. Activity of p-SOD, ery-SOD and TNFalpha were determined by ELISA, and the concentration of MDA by high performance liquid chromatography. Genotype and allele frequencies of the Ala-9Val differed neither between groups defined according to the stage of primary disease (TNM), nor between relapse vs. remission groups after the follow-up (p>0.05). Activity of p-SOD was significantly higher in T3/4 stage compared to T1/2 (p=0.01) and was also higher in N+ compared to N0 patients (p=0.002). Carriers of the Ala/Ala genotype had higher p-SOD activity (p=0.04). There was no significant difference in DFI between SOD2 genotype groups (p>0.05), however, the Ala/Ala group exhibited the shortest median DFI. In conclusion, our results suggest that increased p-SOD at the time of the initial treatment for HNSCC is connected with greater extent and nodal metastatic spread of the initial disease and with an earlier relapse of the disease. Progression of the disease might be further modified by the presence of Ala/Ala genotype of the SOD2. Activity of p-SOD could thus offer diagnostic as well as prognostic value.

Time course of urinary neopterin in a non-Hodgkin's lymphoma patient during chemotherapy and radiotherapy.

The objective of this study was to follow urinary neopterin in a patient affected by non-Hodgkin's lymphoma during the three months treatment from the onset of the disease. In the study a patient affected by non-Hodgkin's lymphoma in Stage IV (centrocyto-centroblastic type) was enrolled. He was treated with combined chemotherapy and local radiotherapy. Neopterin was measured by high performance liquid chromatography in the first morning urine specimens. The time course of urinary neopterin levels ranged from 110 to 524 micromol x mol(-1) creatinine (mean 261, SD 67.5 micromol x mol(-1) creatinine). Over 70 % of the received values were higher than the upper limit of normal excretion of healthy subjects. Longitudinal analysis showed a relatively big variance of urinary neopterin with a tendency of decrease during the treatment. The significant decrease of urinary neopterin was observed till after the radiotherapy period which followed the chemotherapy period. In conclusions, the response to the therapy was accompanied by a reversal tendency of neopterin excretion to physiological values. This study confirms neopterin as a suitable additional parameter for the control of non-Hodgkin's lymphoma therapy.

Homocysteine during the menstrual cycle in depressive women.

BACKGROUND: Two possible factors that may have a causal relation with both depressive disorder and cardiovascular disease are elevated homocysteine and steroid hormones. Our previous study found significant changes in the plasma homocysteine concentration during the menstrual cycle in healthy women. The purpose of this study therefore was to test homocysteine in depressive women treated with fluoxetine during the menstrual cycle. MATERIALS AND METHODS: Thirteen premenopausal women suffering from mixed anxiety-depressive disorder and a control group of 15 healthy women were enrolled in this study. The homocysteine concentration was determined by high-performance liquid chromatography with fluorescence detection, and estradiol, progesterone and cortisol by RIA methods. RESULTS: We found significantly higher plasma homocysteine concentrations in the follicular phase than in the luteal phase of the menstrual cycle in both the depressive group (P < 0.003) and the controls (P < 0.0009). Moreover, the patient values of total homocysteine were significantly higher in the follicular phase (P < 0.03) and also in the luteal phase (P < 0.007) than the values of the controls. Estradiol and cortisol were significantly higher in the follicular phase of the patients compared with the control group. CONCLUSION: According to our results, women suffering from mixed anxiety-depressive disorder have not only significantly different concentrations of homocysteine in the follicular and luteal phase of the menstrual cycle but also higher plasma homocysteine compared with healthy women. More elevated homocysteine in the depressive than in the healthy premenopausal women points to the notion that psychological factors might be important when considering the homocysteine concentration.

Effect of treatment of hypothyroidism on the plasma concentrations of neuroactive steroids and homocysteine.

Autoimmune thyroiditis with hypothyroidism is frequently accompanied by symptoms of psychiatric disorders and atherogenic changes in lipid metabolism. Recent studies suggest that some neuroactive steroids and homocysteine are involved in the pathophysiology of both disorders. Homocysteine metabolism may be affected by some steroids. We were interested if the treatment of hypothyroidism would affect the above factors. We studied plasma concentrations of allopregnanolone, pregnenolone sulfate, dehydroepiandosterone and its sulfate, progesterone, estradiol and homocysteine in 14 patients (12 women, 2 men) during the 3-month treatment with levothyroxine. Steroids and thyroid function were monitored by measuring thyrotropin, free triiodothyronine, free thyroxine and levels of thyroid antimicrosomal antibodies and antibodies to thyroglobulin. We have found that with the restoration of the thyrotropin level, free triiodothyronine, free thyroxine and homocysteine levels decreased, but the levels of steroids were not significantly altered. Steroid concentrations correlated negatively with the level of thyroid antimicrosomal antibodies.

Homocysteine in breast cyst fluid.

BACKGROUND: Elevated plasma homocysteine concentrations have been reported in a variety of carcinoma, including those of the breast. The risk of breast cancer is higher in patients suffering from gross cystic disease. The breast cyst fluid contains unusual amounts of low- and high- molecular substances, including steroid hormones and their conjugates. The present study was undertaken to find out the presence of homocysteine in the fluid filling the cysts and have its concentration compared with other thiols, levels of Na+/K+ ratio and steroid hormones. Materials and methods Fourteen women suffering from gross cystic disease were enrolled in this study. Cystic concentrations of homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cys-Gly) and glutathione (GSH) were determined by high performance liquid chromatography, with fluorescence detection; estradiol (E2), progesterone, allopregnanolone and pregnenolone sulfate (PregS) by RIA methods. RESULTS: Mean levels of Hcy, Cys, Cys-Gly, Na+/K+, E2 and PregS in the fluid filling the breast cysts were significantly higher than the corresponding plasma concentrations. In addition, a negative correlation was found between cystic Hcy and the Na+/K+ ratio (Rs = -0.72, P = 0.003) and positive correlations between cyst Hcy and estradiol (Rs = 0.64, P = 0.018) and Hcy and PregS (Rs = 0.60, P = 0.025). Conclusion The study provides the first evidence of thiol concentrations in the breast cyst fluid. The finding of a negative correlation between homocysteine and the Na+/K+ ratio support the idea that the homocysteine concentration in breast cysts might be used clinically as a marker for the development of breast cancer disease.

Changes of plasma total homocysteine levels during the menstrual cycle.

BACKGROUND: It is known that plasma total homocysteine (tHcy) levels are lower in premenopausal and pregnant women compared with postmenopausal women. To confirm the suggestion that sex steroid hormones are nongenetic factors affecting homocysteine metabolism, we investigated the effect of natural steroid hormone levels on the fasting plasma tHcy in healthy women during the menstrual cycle. MATERIALS AND METHODS: Fifteen premenopausal women were enrolled in this study. Plasma tHcy, estradiol, progesterone and cortisol concentrations were measured in the luteal and follicular phase. The plasma tHcy concentration was determined by high performance liquid chromatography with fluorescence detection, and the steroid hormones by RIA methods. RESULTS: Mean homocysteine values increased from 7.8 micromol L-1 in the luteal phase to 8.9 micromol L-1 in the follicular phase (P < 0.000005, Student's paired t-test). We also found slight negative but insignificant correlations of homocysteine levels with estradiol in both phases of the menstrual cycle. In the case of cortisol and progesterone, no significant correlations with plasma homocysteine were found. CONCLUSION: The study provides the first evidence of significant differences in plasma homocysteine concentration during the menstrual cycle. From our observed findings it is necessary to account for the phase of the menstrual cycle when determining homocysteine in premenopausal women.

[Oncopterin in clinical diagnosis]. / Onkopterin v klinické diagnostice.

In the submitted review the author presents hitherto published data on the new tumour marker oncopterin which was assessed in urine of patients with different types of tumours. Oncopterin is a derivative of endogenous pterins and trimethylene amine needed for the synthesis of polyamines which are synthetized specially in proliferating cells. Urinary oncopterin excretion can be assessed by high resolution liquid chromatography (HPLC). As test for the presence of malignant growth it seems to have a relatively high specificity.