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[Fractional composition and methylation of liver cell nucleus histones during the early stages of radiation injury].

The radiation injury affects the quantitative ratio of histone fractions. The most pronounced changes in the percentage content towards a decrease are observed for the fractions F2a1 and F2a2 as well as for F2a 12 h and 24 h after irradiation, respectively. An increase by 41.8% is observed in the content of the fractions F2b+F3 12 h after irradiation. The methylation for all histones of the fractions increases considerably 2 h after irradiation, drops 12 h later in the fractions F2a1 and F3 and 24 h later in the fractions F3 and F1 as compared to the normal level.

Animals↗
PubMed1975

Potentiating effect of fetal thymus on fetal liver cells for the promotion of recovery from the radiation injury in murine allogenic radiation chimeras or a little bit of thymus goes a long, long way.

Lethally irradiated CBA (H-2k) mice were treated with small numbers of liver cells from strain-A (H-2a) fetal donors. Recovery from the radiation injury was dependent upon the dose of liver cells administered. Giving very small numbers of fetal thymus cells, in addition to liver cells, had a highly significant and salutary effect on survival. The results suggest that clinical transplantation of liver cells from a single fetus might succeed if thymus cells are added.

Animals↗
PubMed1977

Roentgen manifestations of radiation injury to the gastrointestinal tract.

Radiation injury of the gastrointestinal tract requires a minimum dose of 4200 to 4500 rads. The symptoms and signs of radiation injury usually appear within 6 to 24 months following therapy. The radiation induced changes include mucosal atrophy and ulceration associated with an obliterative endarteritis in the supportive vasculo-connective tissue. The roentgen manifestations are those of an ischemic process but may also mimic those of recurrent malignant disease. Obstruction, hemorrhage, and fistula formation are common complications. Surgery is frequently required. The morbidity and mortality is considerable.

Colon↗
PubMed1992

Therapies for radiation injuries: research perspectives.

Exposure to radiation damages the immune, hematopoietic, and gastrointestinal components of the host defense system. This may lead to serious endogenous or exogenous infections. When radiation injury is combined with other physical trauma, e.g., burn or wound, the resulting damage to these systems is synergistic, and treatment for infection requires multiple approaches. This paper reviews successful single and combined therapeutic modalities for infections in irradiated mice and irradiated mice inflicted with trauma that are currently conducted at the Armed Forces Radiobiology Research Institute. The models of endogenous and exogenous infection and combined injury are described. The management of wounds infected with bacteria, exogenous systemic infection due to gram-negative enteric bacteria, and the chemoprophylaxis of enteric-derived systemic infection with quinolones is described. Infections can be treated successfully with proper antimicrobial therapy. In gamma- and neutron-irradiated mice, the immunomodulator trehalose dimycolate (TDM) was effective in treating endogenous infection. TDM with the antimicrobial ceftriaxone was effective in treating exogenous infection due to Klebsiella pneumoniae. Improvement in managing infection in irradiated and injured hosts will require further research using these diagnostic and therapeutic modalities. Accurate biological dosimetry is critical in determining if victims are at risk of developing infection. We found that radiation induced changes in plasma diamine oxidase activity; monitoring these changes was a useful indicator of the severity of radiation injury.

Adjuvants, Immunologic↗
PubMed1991

Clinical value of PET with 18F-fluorodeoxyglucose and L-methyl-11C-methionine for diagnosis of recurrent brain tumor and radiation injury.

We studied 15 patients clinically suspected to have recurrent brain tumor or radiation injury, using positron emission tomography (PET) with 18F-fluorodeoxyglucose (18FDG) and L-methyl-11C-methionine (11C-Met). PET with 11C-Met (Met-PET) clearly delineated the extent of recurrent brain tumor as focal areas of increased accumulation of 11C-Met, and was useful for early detection of recurrent brain tumor. PET with 18FDG (FDG-PET) showed focal 18FDG-hypermetabolism in one patient with malignant transformation of low grade glioma, and demonstrated its usefulness for evaluation of malignant transformation. 18FDG-hypometabolism was observed in all patients with radiation injury, but was also found in one patient with recurrent malignant brain tumor. 11C-Met uptake in 3 patients with radiation injury was similar to that of the normal cortical tissue. FDG-PET can be used to initially exclude recurrent brain tumor which is seen as 18FDG-hypermetabolism. The combined use of Met-PET in addition to FDG-PET can improve the accuracy of differentiation of recurrent brain tumor with 18FDG-hypometabolism from radiation injury.

Adolescent↗
PubMed1991

[Preventive treatment of local radiation injuries in combined radiotherapy of rectal cancer].

Preventive therapy of local radiation injuries was conducted in 46 patients with inoperable rectal cancer during a course of combined radiotherapy after a radical program. Preventive therapy of local radiation injuries included a general action drug and a local use of ethonium. This course of radiotherapy after a radical program with the delivery of doses up to 90-95 Gy resulted in the reduction of the number of late local radiation injuries.

Adult↗
PubMed1989

[Late radiation injuries of the urinary tract].

A total of 400 patients with radiation injuries of the organs of the small pelvis were examined. Urinary dysfunction was found in 115 of them. Radionuclide renography with 131I-hippurane, excretory urography and ultrasound scanning were employed for their investigation. The principal cause of urinary dysfunction was the development of intrapelvic radiation fibrosis with ureteral compression and direct radiation injury of the ureter.

Dose-Response Relationship, Radiation↗
PubMed1977

Radiation injury in the neonatal canine kidney. I. Pathogenesis.

The effects of radiation on the developing canine kidney were investigated. Beagles were exposed to 330 R 60Co gamma-radiation on the 2nd postnatal day of life. The kidneys were examined at 2 days (6 hours after irradiation), 4, 8, 14, 22, 70, and 200 days of age with qualitative and quantitative light microscopy and scanning electron microscopy. The primary result of the radiation injury was a failure to form the normal number of nephrons. The kidneys of irradiated dogs had 42 per cent fewer nephrons (260,000) than the control dogs (445,000). In addition, extensive damage to forming nephrons produced dysplastic renal corpuscles and other corpuscles which were arrested in their development. Three mechanisms of radiation injury were identified. First, there was extensive mitosis-linked cell death in the nephrogenic zone. Second, mitotic delay resulted in only one-fifth of the normal mitotic activity in the nephrogenic zone through 2 days postirradiation. Third, there was an immediate and permanent cessation of nephron formation. The extensive injury in the outer renal cortex was compounded by the development of intercapillary glomerulosclerosis in some middle and inner cortical corpuscles by 200 days of age.

Animals↗
PubMed1991

Surgical management of intestinal radiation injury.

The management of 14 cases of radiation injury to the intestinal tract over a 4-year period is evaluated. The longest latent interval between radiation treatment and symptoms was 30 years. Eight patients were treated surgically; six were treated conservatively by laser therapy or application of formalin to the affected mucosa. The indications for surgery were rectovaginal fistula (four), rectal stricture (one), radiation proctitis (eight), and small bowel obstruction (one). Seven patients underwent large bowel resection. These consisted of four anastomoses with coloanal J-reservoirs, two low anterior resections, and one coloanal anastomosis without reservoir. There was no perioperative mortality. Morbidity occurred in one of the eight surgical cases. Radical resection of the radiation-damaged rectum has been shown to be a safe and reliable treatment for rectovaginal fistulas, rectal strictures, and proctitis unresponsive to medical measures. Coloanal J-reservoir is the procedure of choice to avoid urgency and frequency symptoms associated with coloanal sleeve anastomosis. Laser therapy for hemorrhagic proctitis can achieve an important place in the management of this problem without recourse to surgery.

Adult↗
PubMed1977

[Surgical management of left colon and rectal radiation injuries (author's transl)].

A. First of all, we can affirm after the analysis of 132 records: the predominance of gynecologic cancers and the frequent responsibility of medical associations in the determinism of advanced radiation injuries of colon and rectum; the typically variable appearence of these injuries with an usual delay going from 6 months to a year and limits from 2 months to 35 years; the difficulty of diagnosis between radiation injurie and recurrence of cancer especially in case of fistula and the severe forecost in case of cancer radiation injurie association. B. The surgical management exist only for non-indications and failures of medical treatment; the one stage resection with end to end anastomosis will be made exclusively on advanced, therefore non evolving and limited injuries; in most cases, the multiple stage resection must be preferred: first derivation in selected part (sigmoid or transverse colon) and secondary resection in healthy area; as regards the closure of colostomy, it must never occur before a 6 months delay and anastomosis radiologic check.

Abdominal Neoplasms↗
PubMed1989

[Preventive effect of TJ-48 on recovery from radiation injury].

Effects of Juzen-taiho-toh (TJ-48) on the recovery of haemopoietic systems from radiation injury are analyzed. Female C57BL/6 mice (6 to 8 week-old) were irradiated at doses of 0, 1, 2, 3, 5 or 7 Gy from a 60Co source. During the 7 days after irradiation, the mice were given TJ-48 solution (1.25g in 100ml distilled water). Seven days after irradiation, the mice were sacrificed, and cell counts of bone marrow (both femurs), thymus, spleen, and peripheral blood were made. The bone marrow cells were used for CFU-f, CFU-GM, BFU-E, and CFU-E assays. No difference were observed between the experimental and control groups. However, the CFU-S. d14 and CFU-S.d9 counts in the TJ-48-treated groups were greater than the respective values in the control groups, especially in the low-dose range of irradiation (1, 2, 3 Gy). In the assay for CFU-S.d14, the mice injected with TJ-48-treated bone marrow cells showed better general condition, heavier spleens with larger and more numerous colonies than the control mice. There was no difference in the number of CFU-f between TJ-48-treated and control groups. Since the CFU-S.d14 assay is thought to reflect the most primitive progenitor cells in the haemopoietic system, these results strongly suggest that TJ-48 acts on stem cells in the G0 phase to manifest recovery-enhancing effects from radiation injury.

Animals↗
PubMed1992

Adenosine triphosphate-magnesium chloride in radiation injury.

Although adenosine triphosphate-magnesium chloride (ATP-MgCl2) has demonstrated cytoprotective effects in a variety of adverse pathophysiologic conditions, its ability to alter radiation injury is unknown. The purpose of this study, therefore, was to assess the effects of ATP-MgCl2 on colorectal radiation injury after preoperative pelvic radiotherapy. Mixed-breed pigs (n = 36) received 4250 cGy preoperative external-beam pelvic radiotherapy (350 cGy fractions three times per week for 4 weeks). During radiotherapy, animals were randomly assigned to one of three treatment groups: (1) intravenous infusions of normal saline during radiotherapy, (2) intravenous ATP-MgCl2 (30 mumol/kg) during radiotherapy, or (3) intravenous ATP-MgCl2 (60 mumol/kg) during each radiotherapy session. After completion of radiotherapy and a 4-week rest period, animals underwent colorectal resection by either the two-layer hand-sewn (n = 18) or stapled end-to-end anastomosis technique (n = 18). Laser Doppler velocimetric readings were obtained to assess mural colonic blood flow after completion of anastomosis. A second laparotomy on postoperative day 5 or 11 was done to examine the following anastomotic parameters: (1) repeat laser Doppler velocimetry, (2) gross inflammatory scoring, (3) bursting pressure, (4) preoperative barium enema to identify leak or stenosis, (5) analysis of anastomotic hydroxyproline content, and (6) incidence of cutaneous injury in the radiation portals. ATP-MgCl2 administered intravenously at 60 mumol/kg led to (1) diminished colorectal seromuscular ischemia evidenced by laser Doppler velocimetric readings, (2) decreased skin and subcutaneous tissue injury in the treatment portals, (3) significantly decreased perianastomotic inflammatory reaction, and (4) increased early hydroxyproline content. There was no significant difference in the incidence of leakage or stenosis between the study groups, nor was the anastomotic bursting strength significantly different between the treatment groups. Therefore the administration of ATP-MgCl2 (60 mumol/kg) appears to offer significant cytoprotection from preoperative pelvic radiation therapy.

Adenosine Triphosphate↗
PubMed1992

Fractionation sensitivity and latency of late radiation injury to the mouse urinary bladder.

Transurethral bladder filling is a functional, non-invasive, in vivo assay of early and late radiation injury to the mouse bladder. Fractionated irradiations using single doses or 2, 3, 5, or 10 dose fractions in an overall time of 4 or 4.5 days, with a range of total doses, were given to the bladder of 12-14 week-old C3D2F1/Bom mice. In 372 mice, bladder volume at an intravesical pressure of 20 mmHg was measured before irradiation and at regular intervals thereafter. The endpoint for late bladder injury was a volume of less than 50% of the median pretreatment volume in all animals, occurring more than 30 days after irradiation. This endpoint was reached after a latent period ranging between 35 and 401 days. Fractionation and latency parameters were estimated using a mixture model. There was a highly statistically significant dose-dependency of the latent period (p < 10(-8)). The alpha/beta ratio was estimated at 5.8 Gy [95% confidence limits (3.6; 8.8) Gy] for 250 kVp X-rays. Thus late radiation injury in the mouse urinary bladder is one of the least sensitive late endpoints with respect to change in dose per fraction. Introducing early bladder injury as a variable in the model improved the fit significantly (p = 0.03), but the alpha/beta ratio remained unchanged. Thus the hypothesis that late bladder injury may be, at least in part, consequent upon early injury did not explain the relatively high alpha/beta ratio for this late endpoint.

Animals↗
PubMed1990

Polyamine accumulation and vasogenic oedema in the genesis of late delayed radiation injury of the central nervous system (CNS).

Polyamine (PA) accumulation has been associated with blood-brain barrier (BBB) disruption and vasogenic oedema after cold injury. PAs and water content were measured in a rat spinal cord model of late-delayed radiation injury and were found to be elevated at paralysis. The elevated PA levels could be significantly reduced by treatment with difluoromethylornithine (DFMO). In unirradiated rats DFMO reduced putrescine to undetectable levels after 10-12 weeks. These data suggest that blockade of PA synthesis may be useful in treating the vasogenic oedema of radiation injury and may improve CNS radiation tolerance.

Animals↗
PubMed1989

The effect of pentoxifylline on early and late radiation injury following fractionated irradiation in C3H mice.

An experiment was performed to test the effectiveness of pentoxifylline in reducing late radiation injury. One hundred and four C3H mice were randomized into eight groups of 13 mice each, and the right hind limbs were irradiated with 4000, 5000, 6000, or 7000 cGy in ten fractions. Each group was treated with once daily injections of either pentoxifylline or saline for 30+ weeks. An additional ten mice received daily injections of pentoxifylline or saline, but no irradiation. The pentoxifylline animals demonstrated significantly less late injury than the saline treated animals. The most obvious differences were observed in the 5000 and 6000 cGy groups. There were seven radiation related deaths in the saline treated control groups, but only one radiation related death in the pentoxifylline treated groups. Whereas 42% (20/48) of the saline treated animals had a late injury score of 3.0 or greater, only 8% (4/51) of the pentoxifylline treated animals had a late skin score as high as 3.0. Pentoxifylline had no effect on the acute radiation injury scores. The drug was well tolerated with no toxic effects noted. Pentoxifylline is a methyl xanthine derivative that is used to treat vascular occlusive disease in humans. It improves perfusion through small capillaries by improving the deformability of red blood cells, inhibiting platelet aggregation, and stimulating the release of prostacyclin. This study shows that the prophylactic administration of pentoxifylline can modify late radiation induced injury in the mouse extremity. It may have value in the prevention or treatment of late radiation induced injury in humans, and it could be a useful tool to help define the mechanisms of late radiation injury in specific organs.

Animals↗
PubMed1990

Evaluation of state of circulation in radiation injury using impedance plethysmography.

Seven patients with history of radiation burn were subjected to impedance plethysmographic investigation at Non-invasive Vascular Laboratory, K. E. M. Hospital. Impedance plethysmograms were recorded from various locations in both the upper extremities in supine and digits of both the hands in supine as well as on hyper-abduction in sitting position. Control values of blood flow index (BFI) and differential pulse arrival time (DPAT) were derived from similar data in 15 normal subjects. It was observed that digits having thinning of epidermis of skin recorded marked decrease in values of BFI and significant change in value of DPAT and these observations correlated well with thermography and vascular scintigraphy. Digits recording significant decrease in BFI, which were clinically normal, were found to have changes in the skin during follow up examination. Thus IPG provided a sensitive modality for detecting ischaemia in early stages in patients with history of radiation injury.

Adult↗