Dissociative electron attachment to 2,4,6-trichloroanisole and 2,4,6-tribromoanisole molecules.

2,4,6-trichloroanisole and 2,4,6-tribromoanisole were investigated by means of electron transmission spectroscopy and two different types of dissociative electron attachment spectrometers. The results obtained were interpreted with the support of density functional theory calculations. The dominant dissociative decay channels of the temporary molecular negative ions lead to the formation of Cl- and Br- in the low electron energy region. Formation of long-lived parent anions is observed at thermal electron energies. Their relative intensity depends on the experimental time window, ∼36 µs in the case of the static magnet mass analyzer and ∼200 µs for the quadrupole mass analyzer employed. The results obtained may be useful for rapid detection of these compounds in wine and pharmaceutical industries, as well as other branches connected to the food industry, e.g., packaging.

Delivery of Alginate Scaffold Releasing Two Trophic Factors for Spinal Cord Injury Repair.

Spinal cord injury (SCI) has been implicated in neural cell loss and consequently functional motor and sensory impairment. In this study, we propose an alginate-based neurobridge enriched with/without trophic growth factors (GFs) that can be utilized as a therapeutic approach for spinal cord repair. The bioavailability of key GFs, such as Epidermal Growth factor (EGF) and basic Fibroblast Growth Factor (bFGF) released from injected alginate biomaterial to the central lesion site significantly enhanced the sparing of spinal cord tissue and increased the number of surviving neurons (choline acetyltransferase positive motoneurons) and sensory fibres. In addition, we document enhanced outgrowth of corticospinal tract axons and presence of blood vessels at the central lesion. Tissue proteomics was performed at 3, 7 and 10 days after SCI in rats indicated the presence of anti-inflammatory factors in segments above the central lesion site, whereas in segments below, neurite outgrowth factors, inflammatory cytokines and chondroitin sulfate proteoglycan of the lectican protein family were overexpressed. Collectively, based on our data, we confirm that functional recovery was significantly improved in SCI groups receiving alginate scaffold with affinity-bound growth factors (ALG+GFs), compared to SCI animals without biomaterial treatment.

Immunohistochemical evidence for the presence of synaptic connections of nitrergic neurons in the rat rostral migratory stream.

The rostral migratory stream (RMS) is a migration route for neuroblasts originating in the richest neurogenic niche of the adult mammalian brain-the subventricular zone. Most studies are focused on cellular dynamics of migrating neuroblasts and interactions between neuroblasts and astrocytes which both represent the major cellular component of the RMS. Our previous experiments have brought evidence about the existence of a small population of mature neurons in the adult rat RMS with capacity to produce nitric oxide (NO). In order to further support functional significance of nitrergic cells, the aim of the present study was to determine whether NO producing neurons could form synapses. Sagittal sections from the adult rat brain were processed for simultaneous immunohistochemical detection of neuronal nitric oxide synthase (nNOS), the enzyme present in NO producing cells and synaptophysin, a glycoprotein found in synaptic vesicles. Synaptophysin positivity in the RMS was significantly lower in comparison with other brain areas, but its colocalization with nNOS-positive neurons was obvious. Our results suggest that nitrergic neurons in the RMS could be involved in a neuronal circuitry with potential impact on regulation of neurogenesis in the RMS.

Delayed maturation and altered proliferation within the rat rostral migratory stream following maternal deprivation.

The objective of this study was to investigate whether stressful experience during early postnatal period may influence morphological characteristics of the rat neurogenic pathway--the rostral migratory stream (RMS) and proliferation of neuronal precursors in three successive areas of the RMS: in the vertical arm, the elbow and the horizontal arm. To induce stress, the pups were subjected to repeated maternal deprivation during the first postnatal week after birth. Brains were analyzed at the seventh postnatal day. The controls matched the age of maternally deprived animals. Observation of hematoxylin-eosin stained sections showed that maternal deprivation did not affect the general morphological appearance of the RMS. The shape of the RMS of maternally deprived rats resembles the RMS of control animals. Maternal deprivation caused slight, not significant increase in the RMS thickness in comparison with control rats. Significant difference between the control and maternally deprived rats concerns the olfactory ventricle. While in seven days old control rats the olfactory ventricle is completely closed, in maternally deprived rats of the same age the olfactory ventricle was regularly visible as a narrow lumen at the axis of the RMS horizontal arm. This finding indicates delayed maturation of the migratory pathway as a consequence of stress. Proliferation activity has been assessed by immunoreactivity of the endogenous cell cycle protein Ki-67. The results of Ki-67 immunohistochemistry showed that seven days' maternal separation for 3 h daily induces significant quantitative changes in the number of proliferating cells within the RMS. The response of Ki-67-positive cells to stress differed in individual part of the RMS, with a marked decrease in the vertical arm and a significant increase in the elbow, suggesting heterogeneity of neural stem cells along the RMS; while in the RMS vertical arm the number of dividing cells significantly decreased, there was a marked increase of Ki-67-positive cells in the RMS elbow. This suggests heterogeneity of neural stem cells along the RMS.

Effects of 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitor pravastatin on membrane lipids and membrane associated functions of Methanothermobacter thermautotrophicus.

The role of archaeal membrane and its lipid constituents was investigated in bioenergetic functions of Methanothermobacter thermautotrophicus. The effects were determined of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, pravastatin, on lipid composition, and its impact on some bioenergetic functions of treated cells. Pravastatin remarkably inhibited the growth of M. thermautotrophicus. On membrane level, pravastatin treatment modulated the composition of the mixture of squalene and hydrosqualene derivatives as well as the activities of ATPase, A1Ao-ATP synthase and Na+/H+ antiporter. SDS-PAGE of chloroform-methanol extracts of membranes from control and pravastatin-treated cells revealed changes in the amount of AtpK proteolipids, which suggests that pravastatin modifies cell-membrane composition, hereby modulating the properties of some membrane-bound enzymes participating in energy transformation in methanoarchaea.

Membrane proteins and squalene-hydrosqualene profile in methanoarchaeon Methanothermobacter thermautotrophicus resistant to N,N'-dicyclohexylcarbodiimide.

The biochemical basis of a defective bioenergetic system was attempted to be determined in N,N'-dicyclohexylcarbodiimide (DCCD)-resistant mutant of Methanothermobacter thermautotrophicus. Components participating in the maintenance of methanoarchaeal membrane structure and function, such as the composition of the mixture of squalene and its hydrosqualene derivatives and also properties of membrane-associated proteins were compared in wild-type and mutant cells. The impairment of the bioenergetic system in DCCD-resistant mutant was detectable in the membrane-protein profile; it was also accompanied by changes in proportions of squalene-hydrosqualenes.

Pretreatment nomogram for predicting freedom from recurrence after permanent prostate brachytherapy in prostate cancer.

OBJECTIVES: To develop a prognostic nomogram to predict the freedom from recurrence for patients treated with permanent prostate brachytherapy for localized prostate cancer. METHODS: We performed a retrospective analysis of 920 patients treated with permanent prostate brachytherapy between 1992 and 2000. The clinical parameters included clinical stage, biopsy Gleason sum, pretreatment prostate-specific antigen (PSA) value, and administration of external beam radiation. Patients who received neoadjuvant androgen deprivation therapy were excluded. Failure was defined as any post-treatment administration of androgen deprivation, clinical relapse, or biochemical failure, defined as three PSA rises. Patients with fewer than three PSA rises were censored at the time of the first PSA rise. Data from two outside institutions served as validation. RESULTS: A nomogram that predicts the probability of remaining free from biochemical recurrence for 5 years after brachytherapy without adjuvant hormonal therapy was developed using Cox proportional hazards regression analysis. External validation revealed a concordance index of 0.61 to 0.64, and calibration of the nomogram suggested confidence limits of +5% to -30%. CONCLUSIONS: The pretreatment nomogram we developed may be useful to physicians and patients in estimating the probability of successful treatment 5 years after brachytherapy for clinically localized prostate cancer.

10-year biochemical (prostate-specific antigen) control of prostate cancer with (125)I brachytherapy.

PURPOSE: To report 10-year biochemical (prostate-specific antigen [PSA]) outcomes for patients treated with 125I brachytherapy as monotherapy for early-stage prostate cancer. METHODS AND MATERIALS: One hundred and twenty-five consecutively treated patients, with clinical Stage T1-T2b prostate cancer were treated with 125I brachytherapy as monotherapy, and followed with PSA determinations. Kaplan-Meier estimates of PSA progression-free survival (PFS), on the basis of a two consecutive elevations of PSA, were calculated. Aggregate PSA response by time interval was assessed. Comparisons were made to an earlier-treated cohort. RESULTS: The overall PSA PFS rate achieved at 10 years was 87% for low-risk patients (PSA < 10, Gleason Sum 2-6, T1-T2b). Of 59 patients (47%) followed beyond 7 years, 51 (86%) had serum PSAs less than 0.5 ng/mL; 48 (81%) had serum PSAs less than 0.2 ng/mL. Failures were local, 3.0%; distant, 3.0%. No patients have died of prostate carcinoma. The proportion of patients with a PSA < or =0.2 ng/mL continued to increase until at least 7-8 years posttherapy. A plot of PSA PFS against the proportion of patients achieving serum PSA of less than 0.2 ng/mL suggests a convergence of these two endpoints at 10 years. Patients treated in the era of this study (1988-1990) experienced a statistically improved PFS compared with an earlier era (1986-1987). This difference appears independent of patient selection, suggesting that the maturation of the technique resulted in improved biochemical control. CONCLUSION: With modern technique, monotherapy with 125I achieves a high rate (87%) of biochemical and clinical control in patients with low-risk disease at 10 years. The decline of PSA following brachytherapy with low-dose-rate isotopes can be protracted. Absolute PSA and PFS curves merge, and are comparable at 10 years.

Clinical staging of prostate cancer: reproducibility and clarification of issues.

The American Joint Committee on Cancer (AJCC) staging system for prostate cancer adopted in 1992 is based on tumor-node-metastasis (TNM) designations. It has been widely accepted for use in local and advanced disease. The purpose of this study was to assess reproducibility of staging among observers and to help clarify staging issues. Twelve prostate cancer cases were sent to 20 physicians with special expertise in prostate cancer including eight urologists, eight radiation oncologists, and four medical oncologists. Physicians were asked to assign a stage based on the 1992 AJCC clinical staging. The most frequently reported stage assigned to each case was taken to be the consensus. Agreement was the percentage of physicians who reported that particular stage. Seventy-five percent of the physicians responded. The overall agreement for assignment of T stage was 63.9%. Differences were found by specialty for inclusion of available information in designating a T stage. The overall agreement for N stage was 73.8%. The most common designation was Nx regardless of availability of a computed tomography scan. The overall agreement for M stage was 76.6%. Without a bone scan the most common designation was Mx regardless of Gleason grade or prostate-specific antigen (PSA). A frequent comment was that PSA was more indicative of disease extent than current clinical staging. The reproducibility of the 1992 clinical AJCC staging is poor even among experts in the field. This problem arises primarily from disagreement regarding which studies are included in assigning a stage. Some of these difficulties are addressed in the 1997 revision. However, the clinical staging does not address the true biological significance of disease in many instances.

The role of external beam radiotherapy with I-125/Pd-103 brachytherapy for prostate carcinoma.

BACKGROUND AND PURPOSE: To compare the biochemical outcomes of patients treated with Pd-103/I-125 brachytherapy alone vs. brachytherapy combined with external beam radiotherapy for early stage prostate carcinoma. METHODS: Brachytherapy monotherapy was used in 403 patients. Brachytherapy was combined with 45 Gy of external beam radiotherapy in 231 patients. Median follow-up was 58 months. To compare the biochemical outcomes of these two treatment approaches, patients were stratified into three relative risk groups: low risk, T(1)-T(2), Gleason 2-6/10, PSA< or =10.0; intermediate risk, T(3), Gleason 7-10/10, PSA>10.0 (one factor); high risk, T(3), Gleason 7-10/10, PSA>10.0 (two factors). RESULTS: The actuarial biochemical progression-free rate (bNED) for the entire 634 patients was 85% at 10 years. The bNED outcomes by risk group for monotherapy vs. combined therapy respectively were: low risk, 94 vs. 87%; intermediate risk, 84 vs. 85%; high risk, 54 vs. 62%. These differences did not reach statistical significance for any risk group. Rectal morbidity was slightly greater in the combined treatment patients. CONCLUSION: Although the addition of external beam irradiation to brachytherapy is conceptually appealing for patients with higher risk prostate carcinoma, we were unable to demonstrate a benefit. Whether this is because of patient selection biases within the risk groupings, an artefact of retrospective review, or because external radiotherapy does not offer additional benefit is uncertain.

Short-course androgen ablation combined with external-beam radiation therapy and low-dose-rate permanent brachytherapy in early-stage prostate cancer: a matched subset analysis.

BACKGROUND AND PURPOSE: In order to evaluate the effect of short-term androgen blockade on biochemical control rates for high-risk patients receiving a combination regimen of external-beam radiation therapy and low-dose-rate permanent seed implant brachytherapy, a retrospective matched subset analysis was performed. PATIENTS AND METHODS: Inclusion in the high-risk cohort required at least two of the following poor prognostic factors: serum prostate specific antigen (PSA) concentration > or = 10.0 ng/mL, Gleason score > or = 7, or clinical stage T(2c) or T(3a) disease. Twenty-one patients who underwent androgen ablation between June 1991 and December 1995 in addition to combined-modality radiation therapy qualified as high risk, as did 77 patients who underwent combined-radiation therapy only. There was no statistically significant difference between the two groups in terms of follow-up (mean 44.6 v 47.8 months, respectively), pretreatment PSA, clinical stage, biopsy Gleason score, or the presence of all three poor prognostic factors. RESULTS: The overall rates of freedom from biochemical failure at 5 years were 77% in the hormonally treated group and 58% in the nonhormonally treated group. The difference was not statistically significant by log rank test (P = 0.08). CONCLUSION: Longer follow-up with larger patient numbers is needed to define the role of adjuvant androgen ablation combined with radiation therapy.

Transperineal brachytherapy in patients with large prostate glands.

The purpose of this study is to help clarify the use of prostate size as a selection factor for prostate brachytherapy. From 1997 to 1998, 33 patients with a TRUS-based prostate volume greater than 50 cc were treated at the University of Washington by I-125 (144 Gy) or Pd-103 (115 Gy) implantation for prostatic carcinoma. These 33 patients comprised 7% of the total implants performed. Each patient underwent a preimplant TRUS study in the lithotomy position, taking serial axial images of the prostate at 0.5 cm intervals from the base of the gland to the apex. The contours on the preimplant TRUS images were used to calculate the prostate volumes reported here. Only one patient received supplemental external beam irradiation prior to implantation. Twelve patients were treated with neoadjuvant androgen ablation prior to implantation. The prostate volumes quoted here are those taken after hormonal downsizing. Postimplant axial CT images were digitized to calculate the CT-based target coverage. Preimplant urinary obstructive symptoms were quantified by the criteria of the American Urologic Association. Each patient was contacted at the time of this article preparation to update postimplant morbidity information. In all cases, at least 80% of the postimplant volume was covered, despite a median implant-related volume increase of 15%. Five of the 33 patients' postimplant CT scans showed some degree of incomplete target coverage of the anterior/lateral prostate margin. There was no clear association between inadequate anterior/lateral coverage and the degree of interference. Twelve of the 33 patients developed acute postimplant urinary retention, all occurring within 24 hr of implantation. Within this group of 33 patients with a large prostate volume, there was no relationship between the likelihood of acute or chronic urinary retention and preimplant prostate size or obstructive symptoms. Patients who developed postimplant retention lasting more than one week were generally managed by intermittent self-catheterization. By one month, 85% of patients were catheter-free. Based on the data reported here, we are more inclined to accept patients with a large prostate for implantation without insisting on preimplant size reduction. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 199-205 (2000).