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Biomedical subjects

M Drozdz

Publications and source records attributed to M Drozdz.

At least 19 recordsLinked to original sources

Composition of the editing complex of Trypanosoma brucei.

The RNA editing that produces most functional mRNAs in trypanosomes is catalysed by a multiprotein complex. This complex catalyses the endoribonucleolytic cleavage, uridylate addition and removal, and RNA ligation steps of the editing process. Enzymatic and in vitro editing analyses reveal that each catalytic step contributes to the specificity of the editing and, together with the interaction between gRNA and the mRNA, results in precisely edited mRNAs. Tandem mass spectrometric analysis was used to identify the genes for several components of biochemically purified editing complexes. Their identity and presence in the editing complex were confirmed using immunochemical analyses utilizing mAbs specific to the editing complex components. The genes for two RNA ligases were identified. Genetic studies show that some, but not all, of the components of the complex are essential for editing. The TbMP52 RNA ligase is essential for editing while the TbMP48 RNA ligase is not. Editing was found to be essential in bloodstream form trypanosomes. This is surprising because mutants devoid of genes encoding RNAs that become edited survive as bloodstream forms but encouraging since editing complex components may be targets for chemotherapy.

Amino Acid Sequence↗

[Renal osteodystrophy in dialysis patients as estimated by three-point bone densitometry].

The aim of a study was to estimate the renal osteodystrophy status using bone densitometry in relation to selected biochemical parameters of calcium-phosphate metabolism. The study population consisted of 123 patients with end-stage renal disease, including 24 patients treated with continuous ambulatory peritoneal dialysis (CAPD), aged between 22 and 73 years (mean 49.9 years), on dialysis program for mean period of 14.9 months and 99 patients on maintenance hemodialysis for mean period of 58.8 months, aged between 19 and 72 years (mean 46.6 years). Densitometric measurements using DEXA technique were performed in three different skeletal points: distal ends of both radial bones, lumbar spinal region and femoral neck. Concomitantly, serum concentrations of total and ionized calcium, phosphates and parathormone as well as alkaline phosphatase serum activity were measured. Among male patients treated with CAPD significantly higher BMD values in right forearm were found as compared to women treated with this method (0.769 vs. 0.616; p < 0.001). Higher values of BMD were also found in both forearms in whole CAPD population as compared to those on hemodialysis. However, there was no difference in densitometry results between CAPD and HD patients as well as between men and women within these groups, when measured in femoral neck and lumbar spinal region. Among hemodialysis patients higher levels of phosphates and PTH were found as compared to CAPD, doses of drugs used for treatment of osteodystrophy--calcium carbonate, aluminum hydroxide and active vitamin D were also higher in individuals on HD. In addition, in CAPD patients statistically significant, positive correlations were found between BMD value in lumbar spinal area as well as in femoral neck and amount of ingested calcium carbonate, between BMD in lumbar spinal area and aluminum hydroxide dose taken by patients and between BMD in both forearms and dose of active vitamin D. We failed to demonstrate any relationship between obtained densitometric results as well as biochemical markers of calcium-phosphate metabolism and quantitative parameters of dialysis adequacy in both treatment modes. Obtained results let us to conclude that renal osteodystrophy is less advanced in patients treated with peritoneal dialysis, however this may be related only to markedly shorter renal replacement therapy period in this group. Lack of significant abnormalities in densitometry measurements taken in lumbar spinal area and femoral neck, while they are present in forearms, may suggest that the latter point of skeleton may be most useful for identification of bone mass deficiency in dialyzed patients.

Absorptiometry, Photon↗

[Use of modern microscopic techniques for examining dialysis membrane properties].

The aim of the study was the microscopic evaluation of internal structure of cuprophane and polysulfone membrane and their surface analysis before and after reprocessing. The investigations were performed using an optical measurement system (Digital Instruments), a scanning electron microscope (SEM) and an atomic force microscope (AFM). We confirmed by SEM that reprocessing completely removed biofilm from both membranes surface. The analysis based on AFM visualized channels in the examined membrane. The diameter of the channels varied from 150 nm for cuprophane to 380 nm for polysulfone. The roughness expressed as root mean square (RMS) was higher for cuprophane than for polysulfone membrane. The physical differences between nanostrucure of the examined membranes might be responsible for lower biocompatibility of cuprophane.

Biocompatible Materials↗

Structure of a regulatory 3' untranslated region from Trypanosoma brucei.

The African trypanosome Trypanosoma brucei multiplies in mammalian extracellular fluids (bloodstream forms) and in the midgut of Tsetse flies (procyclic forms). The control of gene expression that is necessary to survive in these two environments operates almost exclusively at the posttranscriptional level, and the sequences responsible are located in the 3' untranslated regions of the mRNAs. The major surface proteins of procyclic trypanosomes, EP1, EP2, EP3, and GPEET, are not expressed in bloodstream forms. The 3' untranslated regions of these four mRNAs are not very similar, but all contain a conserved 26mer sequence that is required for developmental regulation. We have analyzed the conformation of the EP1 3' UTR in vitro by enzymatic digestion and lead hydrolysis, and in vivo by modification with DMS and with CMCT (introduced by electroporation). Results indicate that the 3' UTR can be divided into three domains. Domains I and III, at the 5' and 3' ends, form stable structures, but the central domain (domain II), which includes the 26mer, has no stable interactions either within itself, or with other parts of the 3' UTR. Domain I contains three leadzymes that do not conform to the previously reported consensus.

3' Untranslated Regions↗

Is CAPD a renal replacement therapy method of choice for women?

The aim of this study was to evaluate if there were any differences in clinical outcome as well as in values of quantitative adequacy/nutritional parameters in ESRD patients treated with continuous ambulatory peritoneal dialysis, depending on their sex. Nutritional and adequacy parameters: NPCR, Kt/V, weekly creatinine clearance (wClCr), dialysis index (DI), serum albumin concentration, as well as clinical parameters such as hospitalization rate, admission rate, peritonitis rate, exit-site infection rate and co-morbidity score were evaluated in 31 CAPD patients (12 F and 19 M). Lower comorbidity score (0.583 vs. 1.58 points; p < 0.05) and higher Kt/V total and residual (2.25 vs. 1.57; p < 0.01 and 1.7 vs. 1.42; p < 0.01, respectively) were found in women as compared to men. The value of the quantitative nutritional parameter--NPCR--was also higher in women (0.842 vs. 0.73 g/kg b.w./24 hours; p < 0.05). Despite these differences, only a small difference was found in the clinical outcome and survival between men and women. The obtained data may suggest that women can achieve better treatment results with the CAPD method as compared to men.

Adult↗

Progression to end-stage renal disease in children with posterior urethral valves.

Diagnostic and therapeutic strategies in boys with congenital posterior urethral valves (PUV) have much improved in past decades, but the impact of these changes on the progression to end-stage renal disease (ESRD) has rarely been investigated. We followed renal function in 20 boys with PUV from diagnosis to ESRD. From the first observation period (1969-1978) to the second period (1979-1992) we found a marked drop in age at diagnosis, at valve resection, at first increase of serum creatinine (SCr), and at onset of ESRD. The progression was analyzed by calculating the slope of 1/SCr and the probability of renal survival. In all patients combined, renal survival at the age of 10 years was 35%. In children undergoing valve resection in the 1st year of life, renal survival was worse than in those undergoing later surgery (15% vs. 65% after 10 years, P=0.006). Patients with a SCr>1.2 mg/dl before the age of 12 months progressed more rapidly to ESRD than those attaining this level later. The lower the minimum level of SCr observed after initial surgery, the older the patient at the onset of ESRD. The presence of renal dysplasia or hypoplasia, but not of vesicoureteric reflux, was associated with a more rapid progression. Mean body height at ESRD was -2.3+/-1.3 standard deviation score compared with controls, and was lower if PUV was diagnosed before the age of 6 months.

Adolescent↗

Circadian variations of androstenedione, dehydroepiandrosterone sulfate and free testosterone in obese women with menstrual disturbances.

OBJECTIVE: To assess the 24 h profile of androgenemia related to the androgens of both the ovarian and adrenal origin in obese women with menstrual disturbances. METHODS: The association of body mass and body fat distribution with circadian variations of selected androgens of ovarian and adrenal origin was examined in 16 obese women with menstrual disturbances (BMI between 38 and 51 kg/m2; WHR between 0.80 and 0.99) and in 16 healthy volunteers with normal body weight (BMI between 21 and 24.6 kg/m2; WHR between 0.73 and 0.76). The age range of all subjects was 29 to 40 (mean: 36.9+/-3.2 years). RESULTS: lts. Both the patients and control subjects showed a significant 24 h rhythm of androstenedione (A) and free testosterone (FT), while the circadian oscillations of dehydroepiandrosterone sulphate (DHEAS) did not differ significantly. In all obese women mean 24 h A, DHEAS and FT levels were significantly higher than those in controls. Moreover, the disturbances of DHEAS and FT secretion in the form of acrophase shift (for DHEAS from 7.37 to 3.45 h and for FT from 6.04 to 3.31 h) and the elevation of their 24 h amplitude values were observed. All obese women showed higher values of FT/A and FT/DHEAS indexes in selected clock time of day/night cycle (except those at 8.00 h for FT/A and at 5.00 h for FT/DHEAS) when compared to control group. A positive correlation was noted in all women studied between the values of BMI index, WHR ratio and mean 24 h level of androgens studied as well as FT/A and FT/ DHEAS indexes. A weaker correlation was found between body mass and body fat distribution on the one hand and fasting level of hormones studied on the other. Higher correlation between the values of WHR ratio and mean 24 h FT levels as well as FT/DHEAS indexes were obtained in obese women when compared to those of healthy subjects. CONCLUSIONS: Our findings suggest that, when assessing the androgen disturbances in obese patients, it is more useful to determine their circadian pattern than the basal level. The most reliable indicators of hyperandrogenism in obese women are: the 24 h concentration profile of FT and the value of FT/DHEAS index, not only during fasting but also after a meal at various time intervals. Circadian FT concentration and FT/DHEAS index values are essential indicators for visceral distribution of adipose tissue.

Journal Article↗

Assessment of bone metabolism in obese women.

OBJECTIVE: To evaluate the bone metabolism in obese women by the estimation of selected markers of bone formation. METHODS: The concentration of plasma parathyroid hormone (PTH) and selected markers of bone formation [osteocalcin (BGP) in plasma, carboxyterminal propeptide of type I procollagen (PICP) and alkaline phosphatase (AP) activity in blood serum] and bone resorption [cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in blood serum and urinary excretion of calcium (Ca)] in 18 extremely obese women (BMI>40 kg/m2) with android phenotype (WHR>0.8) and in 20 healthy women with normal body weight. The age range of all subjects was 25 to 42 years (mean: 36.82 + 3.95). RESULTS: All obese women showed significantly increased concentration of plasma PTH, BGP and serum PICP, ICTP and elevated urinary excretion of Ca. CONCLUSIONS: The obtained results show that in extremely obese women with android phenotype bone metabolism disturbances may occur pointing at increased bone formation and resorption.

Journal Article↗

[The usefulness of normalized protein catabolic rate (NPCR) and serum albumin concentration measurement for evaluation of clinical status in patients treated with continuous ambulatory peritoneal dialysis].

Malnutrition is a serious and common problem among patients dialyzed with peritoneal dialysis. Simple and reproducible methods of nutritional status assessment are needed for early problem identification to prevent and treat this complication. The aim of the present study was to evaluate the usefulness of albumin serum concentration and normalized protein catabolic rate (NPCR) derived from urea kinetic modeling session to assess the clinical status of ESRD patients treated with Continuous Ambulatory Peritoneal Dialysis (CAPD). Statistically significant, negative correlations between NPCR and hospitalization rate (r = -0.307; p < 0.05) and co-morbidity score (r = -0.429; p < 0.001) as well as statistically higher NPCR in the group of patients who survived the whole study period (0.82 vs. 0.74 in Non-Survivors; p < 0.01) support the value of this marker as an indicator of clinical status of peritoneal dialysis patients. Significant, negative correlations between serum albumin level and co-morbidity score (r = -0.379; p < 0.05), peritonitis rate (r = -0.359; p < 0.05) and hospitalization rate (r = -0.601; p < 0.005) were also found. Low absolute values of NPCR for the whole population as well as significant, positive correlations of this marker with dialysis adequacy parameters with concomitant lack of such correlations for albumin indicate, that NPCR as a nutritional marker should be interpreted with caution, and always regarded to the calculation method.

Adult↗

Assessment of the relationship between collagen metabolism and selected hormonal factors in extremely obese women before and after jejunoileostomy.

The majority of obese persons have hyperinsulinemia and disturbances in the secretion of melatonin, catecholamines and pituitary, thyroid, adrenal and gonadal hormones. These hormones play an important role in the regulation of collagen metabolism either by acting directly or by influencing IGF-I production. This study aimed at ascertaining whether, and to what degree, the changes in the concentration of hormones listed above as well as in the concentration of sex hormone-binding globulin (SHBG) and insulin-like growth factor-I (IGF-I) affect the metabolism of collagen as evaluated indirectly from the measurement of propeptides of type I (PICP) and type III procollagen (PIIINP) in blood serum and hydroxyproline in urine. The study compared 30 women with extreme obesity before and three to five years after jejunoileostomy with 20 healthy women of reproductive age. All non-operated obese women showed significantly increased concentration of serum insulin, IGF-I, melatonin, norepinephrine, free triiodothyronine, estradiol, total and free testosterone, PICP, PIIINP and urinary excretion of hydroxyproline, while the levels of epinephrine, progesterone and SHBG were significantly decreased. Changes in the level of the examined markers of collagen metabolism correlated positively with the concentration of insulin, IGF-I and sex hormones, while the correlation with epinephrine, cortisol and thyroid hormones was negative. All women who were treated previously by jejunoileostomy showed a decreased of body mass to regular values, normalization of hormonal disturbances and normal collagen metabolism. The obtained results show that the increased collagen metabolism observed in extremely obese women is caused indirectly by altered endocrine activity.

Journal Article↗

Association of body mass and body fat distribution with serum melatonin levels in obese women either non-operated or after jejunoileostomy.

The association of body mass index (BMI) and body fat distribution (as measured by waist-to-hip circumference ratio; WHR) with serum melatonin (MEL) levels determined at 02 and 14 h were examined in 22 non-operated obese women and 21 obese women who underwent jejunoileostomy for morbid obesity 2 to 6 years earlier as well as in 20 gender and age-matched healthy controls with normal body weight. All non-operated obese women either with moderate or morbid obesity had significantly higher MEL concentration at 14 h compared with controls, whereas the amount of MEL secreted at 02 h was elevated only in morbidly obese women. The mean differences between serum MEL levels at 14 h and 02 h (delta MEL) was reduced in morbidly obese women - it may be due to desynchronisation of its circadian rhythmicity. Among women who underwent jejunoileostomy for morbid obesity the values of MEL were normalized only in those with a noted body mass reduction and with BMI and WHR indexes less than 28 kg/m² and 0.83, respectively. MEL correlated positively with BMI and WHR indexes at 14 h in all subjects studied. Negative correlation was noted between the relative values of delta MEL and BMI in both non-operated and operated obese women with BMI indexes >31 kg/m².

Journal Article↗

Assessment of relationship between hypothalamo-pituitary dysfunction and peripheral endocrine function in normotensive and hypertensive obese men.

The relationship between hypothalamo-pituitary function and various hormonal factors (insulin, cortisol, thyroid hormones, sex steroid hormones, SHBG, IGF-I) was investigated in 34 obese men (16 normotensive and 18 hypertensive) and 15 healthy male volunteers aged 35 to 50 years. Hyperinsulinaemia in obese men was associated with altered hypothalamo-pituitary function as indicated by impaired GH, PRL and cortisol secretion in response to insulin induced hypoglycaemia. On the other hand, hyperinsulinaemia and disorders in GH, PRL and cortisol release were associated with lower levels of reverse triiodothyronine, gonadotropins, testosterone, 17-corticoids and SHBG and higher levels of triiodothyronine, estradiol, 17-hydroxycorticoids and IGF-I. Various disorders of hypothalamo-pituitary axis and adrenal, thyroid and testicular function occur more frequently in hypertensive obese men with android distribution of adipose tissue.

Journal Article↗

[Use of urea kinetic modeling for evaluating the efficacy of reusing capillary dialyzers].

The aim of the study was to evaluate the influence of follow fiber dialyzers reprocessing procedure on urea kinetic modeling parameters, dialysis effectiveness for small molecules and effective clearance/predicted clearance ratio. Fifty patients (27 F, 23 M) aged 18-61 years (mean 47) being on maintenance hemodialysis due to end stage renal failure for 4-136 months were included into the study. Patients were treated 3 times a week with blood flow 160-290 ml/min and dialysate flow 500 ml/min. The dialysis time was calculated individually based on urea kinetic modeling parameters. Reprocessing of dialyzers was performed using Renatron RS 8300 and Renalin as sterilized agent. Dialysers with ppr below 80% were excluded from the use. Mean values of dialysis index Kt/V, TAC and dialysis effectiveness (Ct/C0) for urea, creatinine, uric acid and kalium as well as values of effective/predicted clearance ratio for consecutive reprocessing procedures were compared with the results obtained for the new dialyzers. There was no significant influence of reprocessing procedure on Kt/V, TAC and Ct/C0 for tested substances and studied clearances. The obtained results indicates that dialysers reprocessing procedure performed according to the described protocol was safe and didn't decrease dialysis effectiveness.

Adolescent↗

Effect operative weight reduction on Hypothalamo-Pituitary, -adrenal and -ovarian axes function in obese women with menstrual disturbances.

The aim of the study was to evaluate insulin (Ins), pituitary hormones (GH, PRL, LH, FSH), sex hormone-binding globulin (SHBG) and insulin-like growth factor-I (IGF-I) under basal conditions as well as the changes in GH, PRL and F levels after insulin-induced hypoglycemia in 21 obese women before and one year after jejunoileostomy as well as in 20 healthy female volunteers with normal body weight (aged 27 to 36 years). Before surgery all obese women had irregular menstrual cycles. In 14/21 non-operated morbidly obese women and after operative weight reduction (jejunoileostomy), the GH, PRL and F response to insulin-induced hypoglycemia was lower than that in non-obese healthy controls. No difference, however, was observed in GH, PRL and F secretion in non-operated obese women as compared with obese women after jejunoileostomy. Hypothalamic disturbances in the release of GH, PRL and F corresponded to higher levels of sex steroid hormones, IGF-I, and also to lower values of LH/FSH index and SHBG capacity in serum. After jejunoileostomy the pituitary-ovarian axis function as well as SHBG and IGF-I concentrations were normalized only in patients with a noted body mass reduction and with normal preoperative GH, PRL and F secretion dynamics. In these women the menstruation became regular.

Journal Article↗

[Preliminary results of treating patients with chronic renal failure with the help of CAPD].

This study is the preliminary review of the above 2 year period of treatment of patients with chronic renal failure being on CAPD in our center. The study was performed in 14 patients during the cumulative period of 192 patient-months. The analysis of infectious and non-infectious complications was conducted, and patients were also monitored in terms of quantitive measurements of dialysis adequacy and nutritional status using such parameters like total Kt/V (urea), total Weekly Creatinine Clearance (tWCC), normalized protein catabolic rate (npcr) and serum albumin level. We also analysed the influence of residual renal function (RRF) on these parameters and relationships between them. During the study period we observed 7 episodes of peritonitis with the medium rate of 1 episode per 24.7 patient-months. Six of them were treated succesfully conservatively, but in one case catheter removal was necessary because of uneffective farmacological therapy. We also observed two episodes of exist site infection (ESI), one treated finally by catheter replacement. Two technical problems also occurred: leakage into abdominal wall and through the catheter tunnel. During the observation period all patients remained alive, although one was transfered to HD after 14 months of CAPD (earlier 4 months on manual IPD) because of lack of adequacy and severe peritonitis. Obtained results of nutritional status indicate, that 50% of patients were malnourished in terms of npcr and 35.7% in terms of serum albumin level. Seven of 14 patients were adequately dialysed acording to Kt/V, 9 according to tWCC.

Adult↗

[Use of urea kinetic modeling in patients on maintenance hemodialysis].

The effect of urea kinetic modeling (u.k.m.) application on dialysis efficiency and metabolic status was evaluated in 50 maintenance dialyzed patients. U.k.m. sessions were performed once a month based on the self-developed computer program to control dialysis. The dialysis index (Kt/V), the time averaged concentration (TAC), protein catabolic rate (pcr) and dialysis effectiveness (Ct/Co) were evaluated and the results obtained at the beginning and after 2, 4, and 8 months of the study were compared. Kt/V had risen significantly in the modeled patients from 1.04 to 1.24 and was accompanied by 12% Ct/Co increase of urea removal after 8 months. The tendency of the moderate (non significant) decrease of TAC from 54.57 to 52.48 mg% BUN was observed during the study. According to the NCDS criteria the percentage of adequately dialyzed patients increased from 42% at the beginning to 64% after 80 months; underdialyzed patients decreased from 16% to 6% and malnourished also from 16% to 6%, respectively, after u.k.m. application. Dialysis effectiveness for creatinine and uric acid described by Ct/Co for the above after 4 and 8 months was significantly increased when compared with the results obtained at the beginning of the study. These results indicate that u.k.m. application allowed to take control over uremic toxemia and improved dialysis adequacy in patients on maintenance dialysis. Protein catabolic rate in studied patients increased from 1.18 to 1.24 g/kg/per day during the study and it was accompanied by a total blood protein and serum albumin increase. This could indicate improvement of the nutritional status of dialyzed subjects.

Adolescent↗

[Results of the treatment of acute renal failure in 3 selected dialysis units in southern Poland 1981-1990].

The results of the treatment of patients with acute renal failure (ARF) in dialysis units of Kraków, Nowy Sacz and Tarnów were estimated on the basis of prepared questionnaire. The increased number of patients treated because of ARF was demonstrated in the successive years of the study. The mortality rate in the tested group of patients remained about 27%. It depended on the cause of ARF and equalled to 26.7% in medical, 36.7% in surgical, 8% in obstetrical and 6.7 in urological patients, respectively.

Acute Kidney Injury↗