Effects of preadipocytes derived from mice fed with high fat diet on the angiogenic potential of endothelial cells.

BACKGROUND AND AIMS: Obesity promotes a persistent inflammatory process in the adipose tissue, activating the endothelium and leading to vascular dysfunction. Preadipocytes can interact with endothelial cells in a paracrine way stimulating angiogenesis. However, the potential of preadipocytes from adipose tissue of high fat diet (HFD) fed animal to stimulate angiogenesis has not been evaluated yet. The aim of this study was to investigate the effects of such diet on the angiogenic potential of preadipocytes in a mice model. METHODS AND RESULTS: We have evaluated body weight gain, fasting glucose levels and insulin resistance, mRNA expression in preadipocytes and endothelial cells after co-culture with preadipocytes, in vivo vascular function and in vitro endothelial cell migration and tubulogenesis. High fat diet promoted an increase in body weight, glycemic index and insulin resistance in mice. Preadipocytes mRNA expression of factors involved in angiogenesis was higher in these animals. In endothelial tEnd cells mRNA expression of factors involved in vessel growth were higher after co-culture with preadipocytes derived from mice fed with HFD. Although no significant differences were observed in in vivo vasodilatation response between control and HFD groups, endothelial tEnd cells showed an increase in migration and tubulogenesis when cultivated with conditioned media from preadipocytes derived from mice fed with HFD. CONCLUSION: Hypoxic and growth factors produced by preadipocytes derived from mice fed with HFD have higher capacity than preadipocytes derived from mice fed with standard diet to stimulate the angiogenic potential of endothelial cells, contributing to vascular disorders in obesity.

Microcirculatory effects of zinc on fructose-fed hamsters.

BACKGROUND AND AIMS: Fructose is a major dietary component directly related to vascular dysfunction and diseases such as obesity, diabetes, and hypertension. Zinc is considered a non-pharmacological alternative for treating diabetes due to its antioxidant and hyperglycemia-lowering effects in diabetic animals. Therefore, the aim of this study was to evaluate the effects of dietary zinc supplementation on the microcirculatory parameters of fructose-fed hamsters. METHODS AND RESULTS: Male hamsters (Mesocricetus auratus) were fed drinking water substituted by 10% fructose solution for 60 days, whereas control animals were fed drinking water alone. Their microcirculatory function was evaluated using cheek pouch preparation, as well as their blood glucose and serum insulin levels. Their microcirculatory responses to acetylcholine (ACh, an endothelium-dependent vasodilator) and to sodium nitroprusside (SNP, an endothelium-independent vasodilator) as well as the increase in macromolecular permeability induced by 30 min of ischemia/reperfusion (I/R) were noted. Endothelium-dependent vasodilation was significantly increased in control animals with high zinc supplementation compared to the groups without zinc supplementation. Zinc was able to protect against plasma leakage induced by I/R in all control and fructose-fed groups, although the microvascular permeability was higher in animals fed drinking water substituted by 10% fructose solution compared to those fed filtered drinking water alone. CONCLUSION: Our results indicate that dietary zinc supplementation can improve microvascular dysfunction by increasing endothelial-dependent dilatation and reducing the increase in macromolecular permeability induced by I/R in fructose-fed animals.

Effect of levofloxacin treatment on semen hyperviscosity in chronic bacterial prostatitis patients.

Changes in seminal fluid viscosity (SFV), reactive oxygen species (ROS) production, cytokines and seminal leucocyte concentration related to microbiological outcome in patients with chronic bacterial prostatitis (CBP) were studied. One hundred and ten infertile patients with CBP (positive sperm culture ≥10(5) colony-forming units [CFU] ml(-1), pathogens or Chlamydia in expressed prostatic secretions) were treated with levofloxacin 500 mg daily for 14 consecutive days per month for 3 months. In case of bacterial prostatitis, two conditions were examined: responders, eradication of 0 to <10(3) CFU ml(-1) (n = 78) and poor responders, >10(3) to <10(5) CFU ml(-1) (n = 32). Compared with poor responders, responders showed a significant increase of sperm progressive motility and a significant decrease in seminal leucocyte count, SFV, liquefaction time, ROS production (in all fractions and conditions), seminal tumour necrosis factor-α and interleukin 6. None of these variables showed significant differences compared with a control group of 37 fertile men. On the other hand, the poor responders showed significant changes in these variables compared with matched pretreatment values. In patients with CBP, antibiotic therapy alone leads to eradication in ≈71%, with improvement of sperm progressive motility, SFV and the framework of prooxidative factors. However, in the remaining ≈29% with poor antibiotic responsiveness, a deterioration of all variables is observed.

Relationship of semen hyperviscosity with IL-6, TNF-α, IL-10 and ROS production in seminal plasma of infertile patients with prostatitis and prostato-vesiculitis.

Changes in levels of oxidative damage products in semen and their relationship to seminal fluid viscosity (SFV) have recently received increasing research interest. We analysed whether SFV was associated with ROS generation, levels of cytokines TNF-alpha (TNF-α), IL-6 and IL-10 and seminal leucocyte concentration, and whether ROS production was related to the extent of infections/inflammations at one (prostatitis) or two (prostato-vesiculitis) male accessory glands. We studied 169 infertile patients, with chronic bacterial prostatitis (PR, n = 74) and/or bilateral prostato-vesiculitis (PV, n = 95), as diagnosed by the ultrasound (US) criteria. Healthy fertile men (n = 42) served as controls. In the PV patient group, SFV, semen characteristics and ROS production had median values that were significantly higher than those found in PR patients and controls, although other sperm variables had values significantly lower than those found in PR patients or controls. In PV infertile patients, ROS generation and pro-inflammatory cytokines levels were higher than those found in PR infertile patients and controls, although seminal IL-10 levels in PV and PR patients were lower than those found in the controls. In PR patients, the levels of SFV were positively related to TNF-α (r = 0.67; P < 0.01), fMLP-stimulated ROS production in the 45% Percoll fraction (r = 0.687, P < 0.01) and the 90% Percoll fraction in basal condition (r = 0.695, P < 0.01), and after fMLP-stimulation (r = 0.688, P < 0.01). Thus, our data indicated that seminal hyperviscosity is associated with increased oxidative stress in infertile men and increased pro-inflammatory interleukins in patients with male accessory gland infection, more when the infection was extended to the seminal vesicles.

PARP-1 protein expression in glioblastoma multiforme.

One of the most common type of primary brain tumors in adults is the glioblastoma multiforme (GBM) (World Health Organization grade IV astrocytoma). It is the most common malignant and aggressive form of glioma and it is among the most lethal ones. Poly (ADP-ribose) polymerase 1 (PARP-1) gene, located to 1q42, plays an important role for the efficient maintenance of genome integrity. PARP-1 protein is required for the apoptosis-inducing factor (AIF) translocation from the mitochondria to the nucleus. PARP-1 is proteolytically cleaved at the onset of apoptosis by caspase-3. Microarray analysis of PARP-1 gene expression in more than 8,000 samples revealed that PARP-1 is more highly expressed in several types of cancer compared with the equivalent normal tissues. Overall, the most differences in PARP-1 gene expression have been observed in breast, ovarian, endometrial, lung, and skin cancers, and non-Hodgkin's lymphoma. We evaluated the expression of PARP-1 protein in normal brain tissues and primary GBM by immunohistochemistry. Positive nuclear PARP-1 staining was found in all samples with GBM, but not in normal neurons from controls (n=4) and GBM patients (n=27). No cytoplasmic staining was observed in any sample. In conclusion, PARP-1 gene is expressed in GBM. This finding may be envisioned as an attempt to trigger apoptosis in this tumor, as well as in many other malignancies. The presence of the protein exclusively at the nucleus further support the function played by this gene in genome integrity maintenance and apoptosis. Finally, PARP-1 staining may be used as GBM cell marker.

Single sublethal dose of microcystin-LR is responsible for different alterations in biochemical, histological and physiological renal parameters.

Microcystins (MCYSTs) are very stable cyclic peptidic toxins produced by cyanobacteria. Their effects on hepatic tissue have been studied extensively, and they are considered to be a potent hepatotoxin. However, several effects of MCYST on other organs have also been described, but generally in studies using higher doses of MCYST. In the present work, we investigated the effect of a single sublethal dose of MCYST-LR (55 µg/kg) in Wistar rats and analyzed different aspects that influenced renal physiology, including toxin accumulation, excretion, histological morphology, biochemical responses and oxidative damage in the kidney. After 24 h of exposure to MCYST-LR, it was possible to observe an increased glomerular filtration rate (6.28 ± 1.56 vs 2.16 ± 0.48 µl/min per cm(2)) compared with the control group. Increase of interstitial space and collagen deposition corresponded to a fibrotic response to the increased production of reactive oxygen species. The observed decrease of Na(+) reabsorption was due to inhibition of the activity of both Na(+) pumps in proximal tubules cells. We suggested that this modulation is mediated by the effect of MCYST as a phosphatase protein inhibitor that maintains the sustained kinase-mediated regulatory phosphorylation of the ATPases. The observed alteration of Na(+) active transporters lead to damage of renal function, since are involved in regulation of water and solute reabsorption in proximal tubules. The results of this report reinforce the importance of understanding the molecular effects of a single sublethal dose of MCYST-LR, which, in this study, was responsible for macro-alterations found in the renal parenchyma and renal physiology in rats.

Expression of STRBP mRNA in patients with cryptorchidism and Down's syndrome.

The most frequent defect of the male urogenital tract at birth is cryptorchidism. Cryptorchidism causes primitive testicular pathology responsible for infertility. Men with Down's syndrome (DS) have an increased risk of cryptorchidism. The spermatid perinuclear RNA-binding protein (STRBP) gene codifies a microtubule-associated RNA-binding protein and it is highly expressed in the testis as well as in the brain. At both levels, this gene seems to play a relevant role in the regular development of these organs. These observations prompted us to evaluate the expression of STRBP mRNA in 5 DS men with cryptorchidism and 5 normal healthy men (controls) by quantitative Real Time PCR in peripheral blood leukocytes. We found a decreased expression of the STRBP gene in men with DS and cryptorchidism compared with controls. This finding suggests that the impaired expression of this gene in DS may play a pathogenetic role in the altered brain and testicular development in subjects with DS and cryptorchidism.

Bone marrow-derived mononuclear cell therapy attenuates silica-induced lung fibrosis.

This study tests the hypothesis that bone marrow-derived mononuclear cell (BMDMC) therapy may reduce lung inflammation and fibrosis leading to an improvement in respiratory mechanics in a murine model of silicosis. 52 female C57BL/6 mice were randomly assigned into four groups. In the silica group (SIL), silica suspension (20 mg/50 µL in saline) was intratracheally instilled. In the control animals, 50 µL saline was administered intratracheally. At 1 h, the control and SIL groups were further randomised, receiving BMDMC (2×106 i.v. control-cell and SIL-cell) or saline (50 µL i.v. control and SIL). BMDMC were obtained from male donor mice. At day 15, lung mechanics, histology, and the presence of Y chromosome, interleukin (IL)-1ß, IL-1α, IL-1 receptor antagonist (IL-1RN), IL-1 receptor type 1, transforming growth factor (TGF)-ß and caspase-3 mRNA expressions in lung tissue were analysed. In the SIL-cell group, the fraction area of granuloma, the number of macrophages and the collagen fibre content were reduced, yielding improved lung mechanics. The presence of male donor cells in lung tissue was not confirmed using detection of Y chromosome DNA. Nevertheless, caspase-3, IL-1ß, IL-1α, IL-1RN and TGF-ß mRNA expression diminished after cell therapy. In conclusion, BMDMC acted on inflammatory and fibrogenic processes improving lung function through paracrine effects.

Expression of SPANX proteins in normal prostatic tissue and in prostate cancer.

The sperm protein associated with the nucleus in the X chromosome (SPANX) gene family encode for proteins that are not only expressed in germ cells, but also in a number of tumors. In addition, SPANX genes map in an interval of the X chromosome (namely, Xq27), which has been found to be associated with familial prostate cancer by linkage analysis. The aim of this study was therefore to evaluate SPANX protein expression in normal prostate tissues and in prostate carcinoma. For this purpose, formalin-fixed and paraffin-embedded sections obtained from 15 normal (at autopsy) donors and 12 men with prostate cancer were analyzed by immunohistochemistry. About 40% of both normal and tumor prostate samples resulted SPANX positive. Signals were exclusively with the nucleus in normal prostate cells, whereas both nuclear and cytoplasmic positivity was observed in tumor cells. In conclusion, these findings showed that SPANX genes are expressed in both normal and tumor prostate gland, but the latter showed a peculiar cytoplasmic staining positivity. This suggests a possible association between SPANX over expression and prostate cancer development. Additional studies are needed to corroborate this hypothesis.

IL-6, TNFalfa, IL-10 in the seminal plasma of patients with bacterial male accessory gland infections after sequential therapy.

AIM: In previous studies the authors have demonstrated a worse spermatic outcome associated to overproduction of ROS in infertile patients with urogenital infections extended to more glands (prostato-vesciculitis, PV) compared to what observed in patients with prostatitis (P) (cat II according to the National Institutes of Health [NIH]). Among the reasons of an inadequate post-therapeutical response, the duration of each therapeutical phase could be the only bias of empirism entrusted only to the monitoring of obvious ''traditional'' end-points, resulting underrated for various reasons (costs, lacking methodological standardization, choice of the cytokines to be monitored). The evaluation of other therapeutical endpoints (cytokine dosage in the seminal plasma; analysis of ROS) is therefore all important. METHODS: In order to evaluate how to optimize the therapeutic response in infertile patients with P o PV chronic-bacterial, the authors wanted to monitor the pattern of the pro-oxidants cytokines TNFalfa, IL-6 in the seminal plasma (met. sandwich ELISA high sensitivity <0.039 pg/mL, R&D System Europe Ltd, UK) and of IL-10 (chosen as antioxidant cytokine) after sequential therapy (antibiotic - non-steroidal anti-inflammatory drugs antioxidant). RESULTS AND CONCLUSIONS: The modifications of the levels of TNFalfa, IL-6 ed IL-10 recorded in the present study during the sequential therapy for P or PV microbic offer some issues for reflection for interesting clinical-diagnostical implications: 1) possible revision of sequences and/or duration of the therapeutical phases in course of PV; and 2) the role to assign to the IL-10 (assumed as anti-inflammatory cytokine).

Sperm parameter abnormalities, low seminal fructose and reactive oxygen species overproduction do not discriminate patients with unilateral or bilateral post-infectious inflammatory prostato-vesiculo-epididymitis.

We have shown that patients with prostato-vesiculo-epididymitis (PVE) have the worst sperm output compared to patients with prostato-vesiculitis or prostatitis alone. The present study was undertaken to closely examine whether unilateral or bilateral PVE had a different impact on sperm parameters, seminal fructose levels and reactive oxygen species (ROS) overproduction. To accomplish this, 78 patients with persistent post-infectious inflammatory PVE, clearly identified by scrotal and transrectal ultrasonography, and 30 patients with asymptomatic post-infectious inflammatory prostatitis (control group) underwent semen analysis (including seminal leukocyte concentration and number of spermiophagies), seminal fructose measurement and sperm ROS production from 45 and 90% Percoll fractions. Fifty patients turned out to have PVE bilaterally, whereas the remaining 28 had unilateral PVE. Patients with bilateral PVE had sperm concentration and total sperm number significantly lower than those found in patients with unilateral PVE. The other sperm parameters, the physicochemical properties (hyperviscosity, the presence of nonspecific agglutination, delayed liquefaction), seminal fructose levels and ROS production in both 45 and 90% Percoll fractions turned out similar between the two groups. Patients with bilateral or unilateral PVE had sperm parameters, seminal fructose levels and ROS production significantly worst than those found in patients with prostatitis alone. In conclusion, although patients with bilateral PVE had a decreased number of spermatozoa, the other sperm parameters and seminal fructose levels did not reflect the extension of PVE. Therefore, the diagnosis of unilateral or bilateral involvement of this complicated form of male accessory gland infection relies on scrotal and transrectal ultrasonography.

[Unilateral testicular cancer: incidence and effects of a contralateral testiculopathy on the sperm output]. / Neoplasia testicolare monolaterale: frequenza ed effetti di una coincidentale testiculopatia controlaterale sul quadro spermatico.

AIM: The aim of this paper was to evaluate the incidence of a non-tumoral, contralateral primitive testiculopathy and its relative influence on sperm quality of patients with unilateral testicular cancer. METHODS: Twenty-four patients (mean age 26 years, range 19-38) with testicular germ cell cancer (seminomas, SEM, in 10 cases; nonseminomas, NSEM, in the remaining 14 patients) after orchiectomy and before radiotherapy or chemotherapy underwent semen analysis, physical examination and scrotal ultrasound of their survivor testis. RESULTS: Patients with SEM had sperm concentration, total sperm count and forward motility significantly higher than those found in patients with NSEM. Altogether, 5 out of 24 patients (2 SEM; 3 NSEM) (20.8%) showed azoospermia; 10 patients (41.7%) (3 SEM; 7 NSEM) had oligo-, astheno- and/or terato-zoospermia (OAT). The remaining 9 patients (37.5%) (5 SEM; 4 NSEM) showed normal sperm parameters. The testicular volume of the left over testis was reduced (<12 ml) in 4 out of 5 (80%) azoospermic patients, in 7 out of 10 patients (70%) of OAT patients, but in no patient (0%) with normozoospermia. A testicular biopsy performed on the survivor testis of 5 patients with azoospermia (4 of them had a reduced testicular volume) confirmed the primitive testiculopathy, showing a histological pattern of Sertoli cell syndrome only in 4 of them (80%) and maturation arrest in the other case (20%). CONCLUSIONS: Less (OAT) or more severe (azoospermia) sperm output impairment in patients with unilateral testicular cancer is associated with a coincidental, contralateral to unilateral testicular cancer, primitive testiculopathy expressed as reduced testicular volume and impairment spermatogenesis at the testicular biopsy.

Synthesis and anti-aggregatory activity of linear retro-inverso RGD peptides.

Six retro-inverso tri- and tetrapeptide analogues of RGD were prepared and their anti-aggregatory activity was determined by platelet aggregation tests in comparison with the corresponding parent peptides. An efficient method for the introduction of a malonyl-aspartic residue into a peptide chain is described for the first time. A 2-3-fold decrease in potency or total loss of bioactivity was observed with the new peptides; structure-activity relationships are discussed.

Chemical and enzymatic treatment of endothelin.

Endothelin-1 (ET), the most potent vasoconstrictor yet discovered, is a peptide containing 21 amino acids with two intrachain disulfide bridges. With the aim of obtaining two-chain derivatives, Et was submitted to chemical and enzymatic treatments. Reaction of ET with CNBr in 70% HCOOH gave, in addition to the expected [Hse7 lactone]-7,8-seco-ET and unreacted material, a by-product whose molecular weight was 25 m.u. greater than that of ET. When the reaction mixture, after lyophilisation, was immediately quenched with NH3-saturated dry MeOH, two products could be recovered in a 5:1 ratio, both obtained by nucleophilic attack of the homoserine lactone: the expected [Hse7-NH2]-7,8-seco-ET and [Hse7]ET, resulting from competitive intramolecular reaction of the deprotonated alpha-amino group of the Asp8 residue. The Lys9-Glu10 bond turned out to be very resistant to enzymatic attack both by Lys-C-endopeptidase and trypsin. The 9,10-seco-ET derivative could be obtained by treatment with Lys-C-endopeptidase only by using a high enzyme/ET ratio and after a prolonged incubation time. Cleavage of the Lys9-Glu10 bond could not be achieved by treatment with trypsin, even with a high enzyme/substrate ratio. The main product was 13,14-seco-ET, deriving from the action of chymotripsin (present as an impurity in the trypsin preparation) on Tyr13. The structure of these peptides was confirmed by amino-acid sequence analysis and fast atom bombardment mass spectrometry (FAB-MS). Nicking of the ET structure at different positions had different impact on the biological properties of the resulting derivatives.

Role of positions 9 and 10 in the endothelin molecule for biological activity and discrimination of receptor subtypes.

The importance of residues 9 and 10 in endothelin-1 was assessed by studying the responses of the guinea-pig ileum to [Ala9]endothelin-1 and [Ala10]endothelin-1. Both analogues induced relaxation followed by contraction. [Ala9]Endothelin-1 showed similar ED50 values and maximum response to those of endothelin-1, whereas [Ala10]endothelin-1 showed a larger ED50 value and was a partial agonist. Endothelin-1 and [Ala10]endothelin-1 induced similar degrees of tachyphylaxis, whereas [Ala9]endothelin-1 induced very little tachyphylaxis, indicating that Lys9 is important for inducing tachyphylaxis. Apamin inhibited the relaxation induced by endothelin-1 and [Ala9]endothelin-1 but not that induced by [Ala10]endothelin-1. BQ-123 (cyclo[D-Trp-D-Asp-Pro-D-Val-Leu), a specific endothelin ETA receptor antagonist, inhibited [Ala9]endothelin-1-, but not [Ala10]endothelin-1-induced contraction. Cross-tachyphylaxis and additivity studies indicated that [Ala9]endothelin-1, like endothelin-1, acts at the endothelin ETA receptor, whereas [Ala10]endothelin-1 behaved as an endothelin ETB receptor agonist, like sarafotoxin S6c. Thus, the residue at position 10 plays a significant role in receptor activation and is a candidate for further exploration of receptor antagonism.

D-amino acid scan of endothelin: importance of amino acids adjacent to cysteinyl residues in isomeric selectivity.

A systematic approach to map the functionally important determinants of endothelin-1 (ET-1) by a D-amino acid scan is described. Correct orientation of the amino acid side chains was generally of paramount importance both for binding at the ETA receptor and for contracting activity. This was particularly valid for positions 2, 8, 14, 16-21 (the four Cys residues were kept unaltered). Nevertheless, increment of binding affinity was observed by inversion of configuration at positions 6, 7, 9 and 10. In addition, [D-Lys9]ET was an agonist about four times more potent than the natural compound. Usually both 1,4- and 1,3-isomers (corresponding, respectively, to the correct and misfolded disulfide bridges of ET) were obtained, and usually the isomer formed in larger amount had the higher HPLC retention time and the higher biological activity. However, four out of seventeen single-point D-amino acid analogues could be isolated only in one isomeric form. In three cases (D-Ser2, D-Ser4, D-Val12), the inverted amino acid was adjacent to a Cys residue, and in one case (D-Lys9) it was one amino acid apart, thus suggesting a possible effect of the bridged cysteinyl residues in isomeric selectivity.

Evaluation of a well-type ionization chamber for calibration of HDL and LDR brachytherapy sources.

The Atomlab 44D well-type ionization chamber is being evaluated for calibration of high dose rate (HDR) Ir-192 and low dose rate (LDR) Cs-137 sources. The chamber has a flat response (sweet spot) of +/- 0.5% along approximately 3.5 cm for an Ir-192 HDR linear source and 3 cm for a Cs-137 LDR spherical source. The short-term stability of the chamber was determined using a cylindrical Cs-137 source positioned in the sweet spot region. The chamber response over a range of 17.4 mCi (644 MBq, Cs-137) and 8.82 Ci (326 GBq, Ir-192) is evaluated. The chamber may be used for calibrating the activities of both HDR Ir-192 and LDR brachytherapy sources.

Structure-activity relationships of endothelin-1 analogues.

The importance of residues 9 and 10 for endothelin-1 (ET-1) biologic activity was assessed by studying the responses of the guinea pig ileum to [Ala9]-ET-1 and [Ala10]-ET-1. Both analogues induced relaxation followed by contraction. [Ala9]-ET-1 showed similar ED50 value and maximal response to those of ET-1, whereas [Ala10]-ET-1 had a larger ED50 value and was a partial agonist, as was IRL1620. ET-1 and [Ala10]-ET-1 induced similar degrees of tachyphylaxis, whereas [Ala9]-ET-1 induced very little tachyphylaxis, indicating that Lys9 is important for inducing tachyphylaxis. BQ-123, an ETA antagonist, did not inhibit the relaxation. It did inhibit [Ala9]-ET-1- and ET-1-induced contractions but not [Ala10]-ET-1- and IRL1620-induced contractions. Cross-tachyphylaxis and additivity studies indicated that [Ala9]-ET-1, like ET-1, acts at the ETA receptor, whereas [Ala10]-ET-1 behaved as an ETB receptor agonist, like sarafotoxin S6c. Therefore, the residue at position 10 plays a significant role in receptor activation and is a candidate for further exploration of receptor antagonism. FCE27037 (cyclo [D-Cys11-Cys15]-ET-1[8-21]) inhibited the contractile but not the relaxant component of the response induced by IRL1620. These results indicate that FCE27037 is a new ETB antagonist and a useful tool that can discriminate pharmacologically the functionally distinct ETB receptors present in the guinea pig ileum.

Uncertainty in delivered dose resulting from the distribution of source activities in a Selectron LDR afterloader.

The uncertainty in the delivered dose resulting from the distribution of 137Cs source activity in a clinical Selectron LDR unit has been studied. A comparison is made of the dose delivered to a point 'A' in an implant with sources of equal activity to the actual dose delivered in the same implant with source activities randomly chosen from the population in the afterloader.