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PubMed2003

Alteration in the glutathione, glutathione peroxidase, superoxide dismutase and lipid peroxidation by ascorbic acid in the skin of mice exposed to fractionated gamma radiation.

BACKGROUND: In spite of the immense therapeutic gains produced by the fractionated irradiation (IR) regimen, radiation burden on the skin increases significantly. Protection of skin might enable use of higher radiation doses for better therapeutic gains. Ascorbic acid (AA), an essential ingredient of the human diet, is known to be a free radical scavenger and radioprotective agent. This study was undertaken to evaluate the effect of ascorbic acid on the radiation-induced changes in the status of glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and lipid peroxidation (LPx) in the skin of mice exposed to 10, 16 and 20 Gy of fractionated gamma radiation. METHODS: One group of the animals was administered daily with double distilled water (DDW), while the other group received 250 mg/kg b. wt. of ascorbic acid once daily, consecutively for 5, 8 or 10 days, before hemibody (below rib cage) exposure to 2 Gy/day of gamma-rays. Skin biopsies from both the groups were collected for the biochemical estimations. RESULTS: The irradiation of animals resulted in a dose-dependent decline in the activities of superoxide dismutase, glutathione peroxidase and glutathione contents. Ascorbic acid pretreatment resulted in a significant increase in the activities of both the enzymes and glutathione in the irradiated mouse skin. Normal concentrations of glutathione could not be restored even by day 6 post-irradiation. Conversely, lipid peroxidation increased in a dose-dependent manner in both the groups reaching a peak concentration by 3 h post-irradiation, while the ascorbic acid pretreatment inhibited the radiation-induced increase in lipid peroxidation. CONCLUSIONS: The ascorbic acid treatment arrested the decline in the activities of superoxide dismutase and glutathione peroxidase, glutathione contents and inhibited the radiation-induced lipid peroxidation in the skin of mice exposed to different doses of fractionated gamma radiation.

Animals↗
PubMed2000

Development and repair of cataract induced by ultraviolet radiation.

BACKGROUND: Several epidemiological investigations show a correlation between cataract development and the dose of ultraviolet radiation (UVR) received. It is experimentally well established that exposure of animal eyes to UVR induces cataract. Most cataracts develop as a gradual increase in lens opacity. Despite this, current estimations of toxicity for cataract are based on the concept that cataract is a binary event. Moreover, current exposure limits for UVR are based on subjective inspections with slit lamp microscopy. PURPOSE: The first purpose of the present study was to determine a statistically defined maximum acceptable dose for ultraviolet radiation-induced cataract based on quantitative data of forward light scattering in lenses. The second purpose was to find possible explanations for light scattering by investigating the morphology and the refractive index distribution in the lens. The third purpose was to describe the development of cataract after UVR on the cellular level. METHODS: Six-week-old, female Sprague-Dawley rats received UVR unilaterally in vivo. The radiation from a high pressure mercury lamp was collimated, passed through a water filter and an interference filter or a monochromator (lambdaMAX = 300 nm), and projected onto the cornea. The exposure time was 15 min. The exposure dose ranged between 0.1 and 20 kJ/m2 and the animals were kept between 6 hours and 32 weeks after exposure. The extracted lenses were photographed and forward light scattering was measured. Other methods included light microscopy, fluorescence microscopy, transmission and scanning electron microscopy, freeze-fracture and microradiography. RESULTS AND CONCLUSIONS: From a long-term experiment, it was concluded that UVR-exposed lenses scatter light more than their contralaterals and that a higher dose induces more light scattering. After exposure to 5 kJ/m2, the mean forward light scattering remains unchanged between 1 and 32 weeks. Earlier observations, taken together with the current findings, indicate that the optimal time to detect low dose UVR-induced cataract is one week after exposure in rats. The intensity of forward light scattering increases exponentially with increased UVR dose between 0.1 and 14 kJ/m2. Based on this continuous dose-response, a method to determine a maximum acceptable dose to avoid UVR-induced cataract was developed. The statistically defined lower limit of pathologic light scattering is projected on the dose-response function. The dose corresponding to that point can be estimated and was suggested to be called the Maximum Acceptable Dose (MAD). Two low dose UVR exposures with 0 or 6 h intervals between the exposures produce the same degree of lens opacification. When the second exposure follows 24 or 48 h after the termination of the first, lenticular damage increases. Repair processes between 24 and 48 h after exposure appear to be sensitive to UVR, and an additional exposure during this time may aggravate cataract development. Lenses exposed to UVR grow more slowly than their non-exposed contralaterals. This decrease in lens growth was more pronounced with increasing dose. Low doses led to decreased water content in the lens whereas high doses led to swelling. At 6 months after low dose UVR exposure, no global change of the refractive index was found. However, local variations of the refractive index induce a subtle cortical light scattering. In vivo low dose UVR induces programmed cell death which peaks 24 h post-exposure and involves the entire lens epithelium. Dead cells are removed from the epithelium by phagocytosis. This leads to disintegration of the lens epithelium, associated with flake-like opacities at the lens surface. After one week, the epithelium and the equatorial parts of superficial lens fibers contain extracellular spaces. The extracellular spaces together with locally disarranged fibers produce a corrugated opaque lens surface and equatorial opacities. Within several weeks after ex

Animals↗
PubMedDate not supplied

Inhibition of Raf-1 protein kinase by antisense phosphorothioate oligodeoxyribonucleotide is associated with sensitization of human laryngeal squamous carcinoma cells to gamma radiation.

BACKGROUND: Previous studies suggest a central role for Raf-1 protein kinase in mitogenic and radiation damage responsive signaling pathways. PURPOSE: Here we report that the expression and enzymatic activity of Raf-1 protein are inhibited in SQ-20B cells exposed to raf antisense oligodeoxyribonucleotide (As-ODNs) directed against the translation initiation site of human c-raf-1 cDNA. In contrast, treatment of SQ-20B cells with an equimolar concentration of raf sense oligodeoxy-ribonucleotide (S-ODNs) had no effect on the expression and activity of Raf-1. RESULTS: We have observed radiosensitization of raf As-ODNs-treated SQ-20B cells. The dose modifying factor of As-ODNs treatment was approximately 1.4. CONCLUSIONS: These studies demonstrate that raf As-ODNs is a DNA sequence-specific radiosensitizer that may have potential for use in the radiation therapy of cancers.

Base Sequence↗
PubMed1995

Prostate specific antigen-monitored combination radiotherapy for patients with prostate cancer. I-125 implant followed by external-beam radiation.

BACKGROUND: Because results of retropubic I-125 implantation for prostate cancer have been poor, external beam radiation was added postimplant. Serum prostate specific antigen (PSA) was used to assess this approach of combined irradiation. METHODS: Two hundred and thirty-nine patients with clinical Stage T1 or T2 but surgically node-negative prostate cancer were treated. Results were monitored by serial serum PSA evaluation. Positive clinical findings or a rising PSA level defined recurrent disease. RESULTS: With a median follow-up of 45 months (range, 24-120 months), the Kaplan-Meier projected disease free survival rate was 74% at 5 years and 66% at 10 years. Overall at a 60-month minimum follow-up, 77% of patients had a PSA of 0.5 ng/ml or less. This nadir level is highly predictive of a long term disease free survival, significantly better than pretreatment PSA, grade, or clinical Stage T1 or T2. CONCLUSIONS: The PSA-monitored disease free survival rate after combination irradiation appears comparable with that after radical prostatectomy and perhaps superior to that after external-beam radiation. This effect was achieved even though lower-than-usual doses of radiation from both sources were administered. The combination of an I-125 implant followed by external-beam radiation produces high doses within the prostate and, to a lesser extent, in the periprostatic tissue. Additive and synergistic effects from simultaneous irradiation may be responsible for these results.

Aged↗
PubMed2004

Nitric oxide inhibitable isoforms of adenylate cyclase mediate epithelial secretory dysfunction following exposure to ionising radiation.

BACKGROUND: Hyporesponsiveness of the intestinal epithelium to secretagogues occurs in different models of intestinal injury, including radiation enteropathy, and in human disease. While this impairment of barrier function has been linked to increased inducible nitric oxide synthase (iNOS) activity, the cellular target of NO in this phenomenon is not known, although recent studies suggest that some isoforms of adenylate cyclase are inhibited by NO. AIMS: To determine adenylate cyclase isoform distribution in colonic epithelial cells and, in particular, the physiological significance of NO inhibitable adenylate cyclase isoforms 5 and 6 in radiation induced epithelial secretory dysfunction. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR), immunocytochemistry, and immunohistochemistry were used to examine adenylate cyclase expression. The responsiveness of mouse colon to secretagogues 72 hours post-15 Gy gamma radiation or following in vitro exposure to NO donors was measured in Ussing chambers. Also, cAMP, cGMP, and ATP levels were measured. RESULTS: RT-PCR, immunocytochemistry, and immunohistochemistry showed that adenylate cyclase 5 was expressed in mouse colon, and isoforms 5 and 6 were expressed in human biopsies and intestinal epithelium. Pharmacological studies showed that these isoforms are functionally important in chloride secretion. NO mediated hyporesponsiveness to secretagogues is primarily a result of decreased adenylate cyclase activity, and not G(i) activation or decreased cellular ATP levels. CONCLUSIONS: NO inhibitable isoforms of adenylate cyclase are expressed in mouse and human secretory colonic epithelia, and appear to be the target of radiation induced NO to reduce the responsiveness to cAMP dependent secretagogues.

Adenosine Triphosphate↗
PubMed2005

Bystander effects in UV-induced genomic instability: antioxidants inhibit delayed mutagenesis induced by ultraviolet A and B radiation.

BACKGROUND: Genomic instability is characteristic of many types of human cancer. Recently, we reported that ultraviolet radiation induced elevated mutation rates and chromosomal instability for many cell generations after ultraviolet irradiation. The increased mutation rates of unstable cells may allow them to accumulate aberrations that subsequently lead to cancer. Ultraviolet A radiation, which primarily acts by oxidative stress, and ultraviolet B radiation, which initially acts by absorption in DNA and direct damage to DNA, both produced genomically unstable cell clones. In this study, we have determined the effect of antioxidants on induction of delayed mutations by ultraviolet radiation. Delayed mutations are indicative of genomic instability. METHODS: Delayed mutations in the hypoxanthine phosphoribosyl transferase (hprt) gene were detected by incubating the cells in medium selectively killing hprt mutants for 8 days after irradiation, followed by a 5 day period in normal medium before determining mutation frequencies. RESULTS: The UVB-induced delayed hprt mutations were strongly inhibited by the antioxidants catalase, reduced glutathione and superoxide dismutase, while only reduced glutathione had a significant effect on UVA-induced delayed mutations. Treatment with antioxidants had only minor effects on early mutation frequencies, except that reduced glutathione decreased the UVB-induced early mutation frequency by 24%. Incubation with reduced glutathione was shown to significantly increase the intracellular amount of reduced glutathione. CONCLUSION: The strong effects of these antioxidants indicate that genomic instability, which is induced by the fundamentally different ultraviolet A and ultraviolet B radiation, is mediated by reactive oxygen species, including hydrogen peroxide and downstream products. However, cells take up neither catalase nor SOD, while incubation with glutathione resulted in increased intracellular levels of glutathione. Previously, we have shown that ultraviolet induced delayed mutations may be induced via a bystander effect and that this effect is 5-fold higher for UVB radiation than for UVA radiation. Therefore, we propose that the antioxidants inhibit an ultraviolet radiation-induced bystander effect and that the effect is transmitted via the medium and via an internal transfer between cells, like gap junctional intercellular communication, for UVB radiation and only by the latter mechanism for UVA radiation.

Journal Article↗
PubMedDate not supplied

The influence of ionizing radiation on spore germination and emergent hyphal growth response reactions of microfungi.

The accident at the Chernobyl Atomic Energy Station resulted in radiation contamination of large tracts of land and particularly the reactor building itself. Sustained exposure of microfungi to radiation appears to have resulted in formerly unknown adaptive features, such as directed growth of fungi to sources of ionizing radiation. We evaluate here spore germination and subsequent emergent hyphal growth of microfungi in the presence of pure gamma or mixed beta and gamma radiation of fungi isolated from a range of long term background radiation levels. Conidiospore suspensions were exposed to collimated beams of radiation and percent spore germination and length of emergent hyphae were measured. All fungal species isolated from background radiation showed inhibition or no response in germination when irradiated. Isolates from sites with elevated radiation showed a stimulation in spore germination (69% mixed radiation and 46% for gamma irradiation). Most isolates from low background radiation sites showed a significant reduced or no response to exposure to either source of radiation, whereas the stimulatory effect of experimental exposure to radiation appeared to increase in magnitude as prior exposure to radiation increased. We propose that the enhanced spore germination and hyphal growth seen in the exposure trials is induced by prior long term exposure to radiation and these factors could be important in controlling the decomposition of radionuclide-bearing resources in the environment.

Beta Particles↗
PubMedDate not supplied

[Keratosis lichenoides chronica and prolonged exposure to infrared radiation].

BACKGROUND: We report a case of keratosis lichenoides chronica and prolonged exposure to a source of heat (infrared radiation). CASE REPORT: A 35 year-old man was examined for a symmetric and reticulate dermatosis on the abdomen, the interior of arms and lower extremities. The lesions had progressed over several months. They were characterized by hyperpigmentation, erythematous, bullous and squamous papules. These lesions were associated with those of the scalp, evoking seborrheic dermatitis. The patient was exposed to a source of heat with an electric radiator on his bare chest everyday. The skin biopsy showed a lichenoid reaction. All these elements allowed to put the diagnosis of keratosis lichenoides chronica, probably actived by the infrared light. DISCUSSION: Keratosis lichenoides chronica is a rare acquired dermatosis of the young adult. Its physiopathology remains elusive. This dermatosis is characterized by keratosic violaceous lichenoid papules distributed symmetrically. The eruption is usually asymptomatic. The histological examination indicates a lichenoid reaction. The progression is chronic and the disease is very resistant to therapy. Keratosis lichenoides chronica has never been described as being able to be induced by Koebner's phenomenon. In the literature, two cases of erythema ab igne were associated with lichen planus. For some authors, keratosis lichenoides chronica is an entity itself, for others it would be related to lichen planus. These arguments enabled us to diagnose keratosis lichenoides chronica probably activated by the infrared light.

Adult↗
PubMed1998

Modelling the enhancement of fractionated radiotherapy by gene transfer to sensitize tumour cells to radiation.

BACKGROUND AND PURPOSE: Several strategies now exist for the use of gene transfer methodologies to sensitize tumour cells to radiation. These include the transfection of genes synthesizing cytokines, p53 gene replacement and methods based on the use of HSV-tk and gancyclovir. Very recently, the sequencing of radioprotector or repair genes, such as ATM, Ku80 and XRCC2, has made it possible to consider the design of gene transfer strategies resulting in protector gene knock-out. Selectivity of transfected gene expression might be achieved by use of tissue-specific promoters or by the trophism of viral vectors. The purpose of this study was to evaluate the probable efficacy of such strategies. METHODS: We have modelled gene transfer-mediated radiosensitization of tumour cells during radiotherapy, focusing on anti-protector gene strategies, to explore the role of transfection frequency, sensitizing efficacy, transfection stability, untransfectable subpopulations, the timing of gene therapy and the treatment schedule structure. RESULTS: We predict a substantial therapeutic benefit of gene transfer treatment (with at least weekly transfection) which modifies cellular radiosensitivity by a factor of 1.5 or more, despite modest efficiency of cellular transfection (e.g. 50%), transient retention of the transfected gene (e.g. 2-day half-life) and the existence of a small minority (e.g. 1%) of untransfectable cells. CONCLUSIONS: The analysis shows repeated administration of gene transfer treatment to be obligatory and implies that the existence of untransfectable minority subpopulations (i.e. cells inaccessible to the vector) will be the major limiting factor in therapy. Experimental work is needed to confirm these predictions before clinical studies begin.

Gene Expression Regulation↗
PubMed2006

Sensitivity of rice to ultraviolet-B radiation.

BACKGROUND: Depletion of the stratospheric ozone layer leads to an increase in ultraviolet-B (UVB: 280-320 nm) radiation reaching the earth's surface, and the enhanced solar UVB radiation predicted by atmospheric models will result in reduction of growth and yield of crops in the future. Over the last two decades, extensive studies of the physiological, biochemical and morphological effects of UVB in plants, as well as the mechanisms of UVB resistance, have been carried out. SCOPE: In this review, we describe recent research into the mechanisms of UVB resistance in higher plants, with an emphasis on rice (Oryza sativa), one of the world's most important staple food crops. Recent studies have brought to light the following remarkable findings. UV-absorbing compounds accumulating in the epidermal cell layers have traditionally been considered to function as UV filters, and to play an important role in countering the damaging effects of UVB radiation. Although these compounds are effective in reducing cyclobutane pyrimidine dimer (CPD) induction in plants exposed to a challenge exposure to UVB, certain levels of CPD are maintained constitutively in light conditions containing UVB, regardless of the quantity or presence of visible light. These findings imply that the systems for repairing DNA damage and scavenging reactive oxygen species (ROS) are essential for plants to grow in light conditions containing UVB. CONCLUSION: CPD photolyase activity is a crucial factor determining the differences in UVB sensitivity between rice cultivars. The substitution of one or two bases in the CPD photolyase gene can alter the activity of the enzyme, and the associated resistance of the plant to UVB radiation. These findings open up the possibility, in the near future, of increasing the resistance of rice to UVB radiation, by selective breeding or bioengineering of the genes encoding CPD photolyase.

DNA, Plant↗
PubMed1999

Functional assessment of cutaneous microvasculature after radiation.

BACKGROUND AND PURPOSE: To determine if laser Doppler flowmetry could be used to non-invasively evaluate microvasculature function after radiation therapy (RT), we assessed blood flow response to heating in women following RT after breast conservation. MATERIALS AND METHODS: Forty women with unilateral stage I/II breast cancer treated with conservative surgery and RT were evaluated at varying intervals post RT. Ten patients were retested after an interval of 55 to 57 months to assess reproducibility of the control data. A laser Doppler probe fitted into a heat source was used to non-invasively measure blood flow in a small area of skin on the treated breast and a matched area on the untreated side. The heating element increased skin surface temperature to 40 degrees C, permitting assessment of heat stress induced changes in blood flow. RESULTS: Blood flow increased in response to heating in the untreated and treated breast skin, however the magnitude of the increase was significantly greater in the non-irradiated skin. The difference in relative blood flow to the heat stress was found to be greatest in patients < or =6 months post RT. In the patients who were >36 months post RT, there was no significant difference seen in relative blood flow between the irradiated and non-irradiated sides. Cutaneous blood flow response to the heat stress was very reproducible when women were reassessed 55 to 57 months after initial testing. CONCLUSIONS: Laser Doppler flowmetry can quantify the reduced response of irradiated microvasculature to a heat stress. The difference in relative blood flow to a heat stress is greatest in patients < or =6 months post RT, and normalized in patients >36 months post RT.

Adult↗
PubMed2003

[Relationship between ataxia telangiectasia mutant(ATM) expression of HL-60 and SiHA cell lines and their cell cycle arrest after 60Co radiation].

BACKGROUND & OBJECTIVE: Ataxia telangiectasia is caused by ataxia telangiectasia mutant(ATM) gene and it is characterized by hypersensitivity to the radiation. So the ATM expression should be related to the radiation sensitivity. This study was designed to investigate the relationship between ATM expression in two kinds of tumor cell lines and their cell cycle arrest after irradiation of ionization radiation to explore their self-protection function. METHODS: ATM mRNA and protein expression of HL-60 and SiHA cell lines were measured by semi-quantitive reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. The cells were irradiated at the dose of 6, 10, and 15 Gy by (60)Co and the change of apoptosis and cell cycle arrest phenomenon at the time of 6, 12, 24, 48, and 60 hours after the radiation were observed. RESULTS: The ATM mean protein fluorescent intensity of HL-60 and SiHA cells were 14.11+/-2.38 and 27.74+/-1.16,respectively. The ATM protein abundance in SiHA was two times more than that in HL-60,and consistent with this, the ATM RNA relative expression of HL-60 and SiHA cells were 0.09 and 0.80, respectively. The ATM transcript levels in SiHA are 9 times more than that in HL-60. The G(2)/M phase arrest after the radiation was observed in both cell lines, whereas SiHA exhibits a much strong cell cycle arrest than HL-60. CONCLUSION: The cell cycle arrest of HL-60 and SiHA cell lines to the irradiation corresponds to their ATM expression levels. The lower ATM expression, the weaker response for cell cycle arrest induced by radiation.

Apoptosis↗
PubMed2004

MR imaging of the temporal stem: anatomic dissection tractography of the uncinate fasciculus, inferior occipitofrontal fasciculus, and Meyer's loop of the optic radiation.

BACKGROUND AND PURPOSE: The MR anatomy of the uncinate fasciculus, inferior occipitofrontal fasciculus, and Meyer's loop of the optic radiation, which traverse the temporal stem, is not well known. The purpose of this investigation was to study these structures in the anterior temporal lobe and the external and extreme capsules and to correlate the dissected anatomy with the cross-sectional MR anatomy. METHODS: Progressive dissection was guided by three-dimensional MR renderings and cross-sectional images. Dissected segments of the tracts and the temporal stem were traced and projected onto reformatted images. The method of dissection tractography is detailed in a companion article. RESULTS: The temporal stem extends posteriorly from the level of the amygdala to the level of the lateral geniculate body. The uncinate and inferior occipitofrontal fasciculi pass from the temporal lobe into the extreme and external capsules via the temporal stem. Meyer's loop extends to the level of the amygdala, adjacent to the uncinate fasciculus and anterior commissure. These anatomic features were demonstrated on correlative cross-sectional MR images and compared with clinical examples. CONCLUSION: This study clarified the MR anatomy of the uncinate and inferior occipitofrontal fasciculi and Meyer's loop in the temporal stem and in the external and extreme capsules, helping to explain patterns of tumor spread. The inferior occipitofrontal fasciculus is an important yet previously neglected tract. These results provide a solid anatomic foundation for diffusion tractography of the normal temporal stem and its tracts, as well as their abnormalities in brain disorders such as epilepsy, postoperative complications, trauma, schizophrenia, and Alzheimer disease.

Cadaver↗
PubMed1992

Tinea corporis confined to irradiated skin. Radiation port dermatophytosis.

BACKGROUND: Radiation port dermatophytosis (RPD) is an uncommon condition in which patients receiving radiation therapy concurrently have tinea corporis that is confined primarily to the irradiated skin. METHODS: The case of a 33-year-old man is reported who was receiving cobalt-60 radiation therapy for a nasopharyngeal carcinoma. During therapy, a dermatophyte infection developed in the treated field. RESULTS: Including this patient, there have been only three cases of RPD reported in the world literature. The clinical characteristics of patients with RPD are reviewed. The diagnosis, management, and pathogenesis of this condition are discussed. CONCLUSIONS: Because the cutaneous manifestations of RPD may be misinterpreted clinically as acute radiation-induced dermatitis, this condition may be more prevalent than the paucity of published reports suggests.

Adult↗
PubMed1999

Argon beam coagulation for treatment of symptomatic radiation-induced proctitis.

BACKGROUND: Radiation proctitis is a complication of radiotherapy for malignant pelvic disease. Argon beam coagulation is a new and rapidly evolving technology that permits a "no-touch" electrocoagulation of diseased tissue. METHODS: We analyzed retrospectively the records of 7 patients with prostatic and endometrial cancers treated with irrradiation (median radiation dose was 6840 cGy, range 2400 to 7200 cGy). The median time to onset of symptoms after the conclusion of radiotherapy was 20 months (range 16 to 48 months); symptoms consisted of rectal bleeding and tenesmus in all patients. The patients underwent argon beam coagulation after colonoscopic evaluation. The usual treatment interval was 3 weeks (range 1 to 3 weeks). RESULTS: A median of 2 treatment sessions (range 2 to 4) was necessary for complete symptom relief. All interventions were well tolerated without complications. During follow-up (median 24 months, range 18 to 24 months), there was no recurrence of symptoms (bleeding, tenesmus). CONCLUSIONS: Argon beam coagulation is a safe, well tolerated, and effective treatment option in symptomatic radiation proctitis.

Aged↗
PubMed2005

Different responses by cultured aortic and venous smooth muscle cells to gamma radiation.

BACKGROUND: Stenosis of hemodialysis arteriovenous grafts is usually focal and caused by the proliferation of vascular smooth muscle cells (SMCs). External radiation of the graft is a potential strategy to prevent stenosis; however, the relative responsiveness of arterial and venous SMCs to radiation is unknown. METHODS: Human aortic and saphenous vein SMCs were cultured in a medium containing growth factors and serum and treated with 0 to 50 Gy in a gamma irradiator. At 2 to 20 days post-irradiation, cell counting, methylthiazoletetrazolium dye reduction, [(3)H]-thymidine uptake, and bromodeoxyuridine (BrdU) incorporation assays were performed. RESULTS: All assays showed that 1 to 50 Gy inhibited the proliferation of both aortic and venous SMCs in a dose-dependent manner. Importantly, venous cells were less susceptible to radiation in all assays, compared to aortic cells. At day 10, 1 to 50 Gy of radiation inhibited the increase in the number of aortic cells by 24% to 66% and venous cells by 8% to 25% (P < 0.01) (aortic vs. venous). The differences between aortic and venous cells varied among different assays and were most pronounced in the BrdU assay. CONCLUSION: Inasmuch as myointimal hyperplasia occurs at both arterial and venous anastomoses, future strategies using radiation to prevent hemodialysis vascular access stenosis should take these differences into consideration.

Antimetabolites↗
PubMed2002

An investigation into the use of pilocarpine as a sialagogue in patients with radiation induced xerostomia.

BACKGROUND: Radiation therapy to the head and neck region can be an effective form of treatment for malignancies. Unfortunately damage to salivary glands may occur. Treatment of resultant dry mouth is at present very poor. The purpose of this pilot study was to investigate whether pilocarpine dissolved in artificial saliva and administered in a mouth spray would be effective in relieving such symptoms. METHODS: Twenty-three patients with radiation induced hyposalivation were recruited for this randomized, double-blind investigation. Subjects were randomly allocated to placebo or control medicaments used for eight weeks. All subjects were evaluated for the severity of their xerostomia associated symptoms prior to administration of the spray and again eight weeks later. RESULTS: The questionnaire and the visual analogue scale did not reveal any improvements in the dry mouth symptoms between cases and controls. Side-effects were reported among cases, mostly mild and tolerable. All patients taking pilocarpine (with base salivary flow rates > 0ml/min) demonstrated improvement in stimulated and unstimulated salivary flow rates. Candida counts decreased among the cases and controls although decrease among the cases was much greater. CONCLUSIONS: The results obtained indicate that provided residual functioning salivary tissue exists, pilocarpine used as formulated is effective and warrants further investigation.

Aerosols↗
PubMed2001

Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation.

BACKGROUND: Radiotherapy prevents local recurrence of breast cancer after breast-conserving surgery. We evaluated the effect of a supplementary dose of radiation to the tumor bed on the rates of local recurrence among patients who received radiotherapy after breast-conserving surgery for early breast cancer. METHODS: After lumpectomy and axillary dissection, patients with stage I or II breast cancer received 50 Gy of radiation to the whole breast in 2-Gy fractions over a five-week period. Patients with a microscopically complete excision were randomly assigned to receive either no further local treatment (2657 patients) or an additional localized dose of 16 Gy, usually given in eight fractions by means of an external electron beam (2661 patients). RESULTS: During a median follow-up period of 5.1 years, local recurrences were observed in 182 of the 2657 patients in the standard-treatment group and 109 of the 2661 patients in the additional-radiation group. The five-year actuarial rates of local recurrence were 7.3 percent (95 percent confidence interval, 6.8 to 7.6 percent) and 4.3 percent (95 percent confidence interval, 3.8 to 4.7 percent), respectively (P<0.001), yielding a hazard ratio for local recurrence of 0.59 (99 percent confidence interval, 0.43 to 0.81) associated with an additional dose. Patients 40 years old or younger benefited most; at five years, their rate of local recurrence was 19.5 percent with standard treatment and 10.2 percent with additional radiation (hazard ratio, 0.46 [99 percent confidence interval, 0.23 to 0.89]; P=0.002). At five years in the age group 41 to 50 years old, no differences were found in rates of metastasis or overall survival (which were 87 and 91 percent, respectively). CONCLUSIONS: In patients with early breast cancer who undergo breast-conserving surgery and receive 50 Gy of radiation to the whole breast, an additional dose of 16 Gy of radiation to the tumor bed reduces the risk of local recurrence, especially in patients younger than 50 years of age.

Adult↗