Biomedical subjects

V R Narra

Publications and source records attributed to V R Narra.

At least 19 recordsLinked to original sources

PubMed2004

Magnetic resonance imaging with true fast imaging with steady-state precession and half-Fourier acquisition single-shot turbo spin-echo sequences in cases of suspected placenta accreta.

PURPOSE: To present the magnetic resonance imaging (MRI) findings of placenta accreta in suspected cases of placenta accreta with true fast imaging with steady-state precession (True FISP) and half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences. MATERIAL AND METHODS: Five patients underwent MRI with HASTE (n = 5) and/or True FISP (n = 4) sequences for suspected placenta accreta. Retrospective review of MRI was performed to define the location and extent of the implantation abnormality. RESULTS: The uteroplacental interface was visualized as three layers; inner low signal intensity layer, middle high signal intensity layer of myometrium, and outer low signal intensity layer of uterine serosa. Three cases were diagnosed with placenta accreta on MRI and focal non-visualization of the inner layer was demonstrated. CONCLUSION: The finding of focal non-visualization of the inner layer between the placenta and myometrium by MRI with True FISP and HASTE sequences was the diagnostic finding for placenta accreta.

Adult↗

PubMed1997

Radiotoxicity of gadolinium-148 and radium-223 in mouse testes: relative biological effectiveness of alpha-particle emitters in vivo.

The biological effects of radionuclides that emit alpha particles are of considerable interest in view of their potential for therapy and their presence in the environment. The present work is a continuation of our ongoing effort to study the radiotoxicity of alpha-particle emitters in vivo using the survival of murine testicular sperm heads as the biological end point. Specifically, the relative biological effectiveness (RBE) of very low-energy alpha particles (3.2 MeV) emitted by 148Gd is investigated and determined to be 7.4 +/- 2.4 when compared to the effects of acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210Po and 212Pb in equilibrium with its daughters, is used to revise and extend the range of validity of our previous RBE-energy relationship for alpha particles emitted by tissue-incorporated radionuclides. The new empirical relationship is given by RBE alpha = 9.14 - 0.510 E alpha where 3 < E alpha < 9 MeV. The validity of this empirical relationship is tested by determining the RBE of the prolific alpha-particle emitter 223Ra (in equilibrium with its daughters) experimentally in the same biological model and comparing the value obtained experimentally with the predicted value. The resulting RBE values are 5.4 +/- 0.9 and 5.6, respectively. This close agreement strongly supports the adequacy of the empirical RBE-E alpha relationship to predict the biological effects of alpha-particle emitters in vivo.

Alpha Particles↗

PubMed1996

Effects of a 1.5-Tesla static magnetic field on spermatogenesis and embryogenesis in mice.

RATIONALE AND OBJECTIVES: There is a trend toward the use of higher magnetic field strengths in magnetic resonance imaging procedures. Considering this trend and the lack of consensus on the biologic effects of static magnetic fields, it is of considerable interest to examine the biologic effects of a 1.5-tesla (T) static magnetic field on spermatogenesis and embryogenesis in mice. METHODS: Male and pregnant female Swiss Webster mice were exposed to a 1.5-T static magnetic field for 30 minutes. Effects on spermatogenesis in male mice were investigated by counting testicular spermheads and epididymal spermhead shape-abnormalities as a function of time after exposure. Pregnant female mice were exposed to the field at the two-cell embryo stage, sacrificed immediately, and the ability of these preimplantation embryos to mature into blastocysts was examined in vitro. RESULTS: Exposure to the static 1.5-T magnetic field caused a statistically significant reduction (15%) in testicular sperm on the 16th and 29th days after exposure. However, the increase in spermhead shape abnormalities above normal control values was minimal. A substantial effect was noted on the development of preimplantation embryos with a survival fraction of 0.56 compared with controls. CONCLUSIONS: A 30-minute exposure to a 1.5-T static magnetic field appears to cause some deleterious effects on spermatogenesis and embryogenesis in mice.

Animals↗

PubMed1996

Radioprotection by DMSO against the biological effects of incorporated radionuclides in vivo--Comparison with other radioprotectors and evidence for indirect action of Auger electrons.

Dimethyl sulfoxide (DMSO) was studied for its capacity to protect against the biological effects of chronic irradiation by incorporated radionuclides. Spermatogenesis in mice was used as experimental model and spermatogonial cell survival was the biological endpoint. DMSO was injected intratesticularly 4 h prior to a similar injection of the radiochemical and the spermhead survival determined. Iodine-125 was localized in either the cytoplasm (H125IPDM) or in the DNA (125IUdR) of the testicular cells. Protection was observed against the high-LET type effects of DNA-bound 125I as well as the low-LET effects of cytoplasmically localized 125I with dose modification factors (DMF) of 3.1+/-1.0 and 4.4+/-1.0 respectively. No protection (DMF = 1.1+/-0.1) was observed against the effects of high-LET 5.3 MeV alpha particles of 210Po. The present findings provide supporting evidence that the mechanism responsible for the extreme biological damage caused by DNA-bound Auger emitters is largely radical mediated and therefore indirect in nature.

Animals↗

PubMed1995

Radioprotection against biological effects of internal radionuclides in vivo by S-(2-aminoethyl)isothiouronium bromide hydrobromide (AET).

UNLABELLED: Radionuclides employed in diagnostic and therapeutic nuclear medicine impart radiation energy to tissue over an extended period of time, which depends on the physical half-life and the biological properties of the radiochemical employed. It is therefore important to examine the capacity of chemical radioprotectors to mitigate damage caused by chronic irradiation by incorporated radionuclides. METHODS: Spermatogenesis in mouse testis is used as the experimental model, and spermatogonial cell survival as measured by testicular spermhead count is the biological end point. The capacity of S-(2-aminoethyl)isothiouronium bromide hydrobromide (AET) to mitigate radiation damage caused by chronic irradiation by the radiochemicals 125IUdR, H125IPDM and 210Po-citrate, is investigated. RESULTS: The radioprotection provided by AET is substantial and similar for both of the radioiodinated compounds with dose modification factors (DMF) of 4.0 +/- 1.2 for 125IUdR and 3.4 +/- 0.4 for H125IPDM. In contrast, the damage caused by 210Po alpha particles is protected against to a lesser degree (DMF = 2.4 +/- 0.5). CONCLUSION: The present radioprotection data for AET, in conjunction with our earlier findings for the chemical protectors cysteamine and vitamin C in the same experimental model, suggest that such compounds may be clinically useful as mitigating agents against biological damage caused by incorporated radionuclides. The observed DMFs for AET also support our earlier premise that the mechanism by which DNA-incorporated Auger emitters impart biological damage is primarily radical mediated, and hence indirect in nature.

Animals↗

PubMed1994

Relative biological effectiveness of 99mTc radiopharmaceuticals.

The radiotoxicity of three 99mTc-labeled compounds is investigated using spermatogenesis in mouse testis as the experimental model, and spermatogonial cell survival as the biological end point. The radiopharmaceuticals studied are pertechnetate (99mTcO4-), pyrophosphate (99mTc-PYP), and hydroxyethylene diphosphate (99mTc-HDP). The mean lethal doses at 37% survival (D37) are 0.70 +/- 0.06, 0.84 +/- 0.13, and 0.59 +/- 0.08 Gy for 99mTcO4-, 99mTc-PYP, and 99mTc-HDP, respectively. When these results are compared with the D37 value obtained with external x rays or internal gamma rays, the relative biological effectiveness (RBE) of these compounds are 0.94 +/- 0.09, 0.79 +/- 0.13, and 1.1 +/- 0.16, respectively. These results show that the radiotoxicity of 99mTc in mouse testis is essentially similar to that of low-LET radiations (i.e., RBE approximately 1). To understand these results, the distribution of these radiocompounds in the testis is determined and correlated with the observed RBE values. The expected range of RBE values for 99mTc radiopharmaceuticals in organs is 0.95 to 1.5, depending on the fraction of organ activity that is bound to DNA. This suggests that the Auger electrons emitted in the decay of 99mTc are not capable of causing extreme toxicity in vivo. These results provide further support for 99mTc as the radionuclide of choice for imaging in nuclear medicine.

Animals↗

PubMed1994

Vitamins as radioprotectors in vivo. II. Protection by vitamin A and soybean oil against radiation damage caused by internal radionuclides.

Tissue-incorporated radionuclides impart radiation energy over extended periods of time depending on their effective half-lives. The capacity of vitamin A dissolved in soybean oil to protect against the biological effects caused by internal radionuclides is investigated. The radiochemicals examined are DNA-binding 125IdU, cytoplasmically localized H125IPDM and the alpha-particle emitter 210Po citrate. As in our previous studies, spermatogenesis in mice is used as the experimental model and spermatogonial cell survival is the biological end point. Surprisingly, soybean oil itself provides substantial and equal protection against the Auger effect of 125IdU, which is comparable to a high-LET radiation effect, as well as the low-LET effects of H125IPDM, the dose modification factors (DMFs) being 3.6 +/- 0.9 (SEM) and 3.4 +/- 0.9, respectively. The protection afforded by the oil against the effects of 5.3 MeV alpha particles emitted by 210Po is also significant (DMF = 2.2 +/- 0.4). The presence of vitamin A in the oil further enhanced the radioprotection against the effect of 125IdU (DMF = 4.8 +/- 1.3) and H125IPDM (DMF = 5.1 +/- 0.6); however, no enhancement is provided against the effects of alpha particles. These interesting results with soybean oil and vitamin A, together with data on the subcellular distribution of the protectors, provide clues regarding the mechanistic aspects of the protection. In addition, the data for vitamin A reaffirm our earlier conclusion that the mechanism by which DNA-bound Auger emitters impart biological damage is primarily indirect in nature.

Animals↗

PubMed1994

Relative biological effectiveness of alpha-particle emitters in vivo at low doses.

The therapeutic potential of radionuclides that emit alpha particles, as well as their associated health hazards, have attracted considerable attention. The 224Ra daughters 212Pb and 212Bi, by virtue of their radiation properties which involve emission of alpha and beta particles in their decay to stable 208Pb, have been proposed as candidates for radioimmunotherapy. Using mouse testes as the experimental model and testicular spermhead survival as the biological end point, the present work examines the radiotoxicity of 212Pb and its daughters. When 212Pb, in equilibrium with its daughters 212Bi, 212Po and 208Tl, was administered directly into the testis, the dose required to achieve 37% survival (D37) was 0.143 +/- 0.014 Gy and the corresponding RBE of the mixed radiation field was 4.7 when compared to the D37 for acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210Po, was used to obtain an RBE-LET relationship for alpha particles emitted by tissue-incorporated radionuclides: RBE alpha = 4.8 - 6.1 x 10(-2) LET + 1.0 x 10(-3) LET2. Similarly, the dependence of RBE on alpha-particle energy E alpha was given by RBE alpha = 22 E(-0.73) alpha. These relationships, based on in vivo experimental data, may be valuable in predicting biological effects of alpha-particle emitters.

Alpha Particles↗

PubMed1994

Vitamins as radioprotectors in vivo. I. Protection by vitamin C against internal radionuclides in mouse testes: implications to the mechanism of damage caused by the Auger effect.

The potential of vitamin C, an antioxidant, to protect the radiosensitive spermatogonial cells in mouse testes against the effects of chronic irradiation by radionuclides incorporated into tissue was investigated. Interestingly, when injected intratesticularly, a small and nontoxic amount of vitamin C (1.5 microgram in 3 microliters saline) protected the spermatogonia against the damage associated with high-LET radiation caused by Auger electrons from similarly administered 5-(125I)-iodo-2'-deoxyuridine (125IdU). A dose modification factor (DMF) of 2.3 was obtained. In contrast, no protection was observed when 210Po, an alpha-particle emitter, was administered similarly. These findings suggest that the mechanism of action of the Auger effect is of an indirect nature, which is in contrast to the direct action generally believed to be responsible for biological damage caused by high-LET radiations.

Alpha Particles↗

PubMed1993

[35S]cysteamine: facile synthesis, in vivo biokinetics, and subcellular distribution.

Whereas chemical radioprotection against external beams of ionizing radiation is well studied in radiobiology, the aspects relating to tissue incorporated radionuclides have received little attention. The increased use of radionuclides in diagnostic and therapeutic nuclear medicine, as well as the presence of both manmade and natural radioactivity in the environment, indeed call for such investigations. Our ongoing work on a variety of radioprotectors has revealed that cysteamine (MEA), S-2-aminoethylisothio uroniumbromide hydrobromide (AET), and others (e.g. ascorbic acid), protect spermatogonial cells in mouse testis from the effects of chronic irradiation with intratesticularly localized radionuclides. In these experiments, dose modification factors ranging from 2 to 4 and 10 to 14 were obtained using spermhead survival and induction of spermhead abnormalities, respectively, as the biological end points. Similar experiments were carried out by changing the mode of administration of cysteamine to oral intubation. In these studies a dose modification factor of approximately 3 was observed in the spermhead survival assay. In an effort to understand the protection offered by MEA, the present work describes a one-pot synthesis of high specific activity [35S]cysteamine from elemental [35S]sulphur and its use in determining the biokinetics and biodistribution of MEA following intratesticular (i.t.) or oral administration in mice.

Administration, Oral↗

PubMed1993

Vitamin C as a radioprotector against iodine-131 in vivo.

The capacity of vitamin C (ascorbic acid) to mitigate radiation damage resulting from the tissue-incorporated radionuclide 131I is examined. Spermatogenesis in mice is the experimental model and spermhead survival is the biological endpoint. When a small nontoxic amount of vitamin C was injected, followed by a similar injection of 131I, the 37% spermhead survival dose (D37) increased by a factor of 2.2 compared with the D37 in animals receiving only the radionuclide. Similar radioprotection was also observed when the animals were maintained on a diet enriched with 1% vitamin C (by weight). These results suggest that vitamin C may play an important role as a radioprotector against accidental or medical radiation exposures, especially when radionuclides are incorporated in the body and deliver the dose in a chronic fashion.

Animals↗

PubMed1993

On the equivalent dose for Auger electron emitters.

Radionuclides that emit Auger electrons are widely used in nuclear medicine (e.g., 99mTc, 123I, 201Tl) and biomedical research (e.g., 51Cr, 125I), and they are present in the environment (e.g., 40K, 55Fe). Depending on the subcellular distribution of the radionuclide, the biological effects caused by tissue-incorporated Auger emitters can be as severe as those from high-LET alpha particles. However, the recently adopted recommendations of the International Commission on Radiological Protection (ICRP) provide no guidance with regard to calculating the equivalent dose for these radionuclides. The present work, using spermatogenesis in mouse testis as the experimental model, shows that the lethality of the prolific Auger emitter 125I is linearly dependent on the fraction of the radioactivity in the organ that is bound to DNA. This suggests that the equivalent dose for Auger emitters may have a similar linear dependence. Accordingly, a formalism for calculating the equivalent dose for Auger emitters is advanced within the ICRP framework.

Animals↗

PubMed1992

Radiotoxicity of some iodine-123, iodine-125 and iodine-131-labeled compounds in mouse testes: implications for radiopharmaceutical design.

In this work, spermhead survival in mouse testis was used to investigate the radiotoxicity of several intratesticularly localized radioiodinated pharmaceuticals. Radioiodines that decay by electron capture and/or internal conversion (123I, 125I) as well as by beta- decay (131I) were coupled to pharmaceuticals that selectively localize in different cell compartments. Dose response curves yield D37 values of 62 cGy, 75 cGy, 61 cGy and 7.7 cGy for 123IMP (N-isopropyl-p-iodoamphetamine), 131IdU (iododeoxyuridine), H131IPDM (N,N,N'-trimethyl-N'-(2-hydroxyl-3-methyl-5-iodobenzyl)-1,3-propanediami ne) and 125IdC (iododeoxycytidine), respectively. At 37% survival, the relative biological effectiveness (RBE) of these radiochemicals, when compared to the pure gamma-emitting radiochemical 7Be-chloride (D37 = 65 cGy), are 1.0, 0.89, 1.1 and 8.4, respectively. Intratesticular 7Be, with an effective half-life of 430 hr in the organ, was used as the source of reference radiation to determine the RBE values because it solely emits 477 keV gamma rays, and the dose to the testis is delivered chronically, as in the case of the other radiocompounds. Subcellular distribution studies show that all of the cellular activity is localized in the cytoplasm in the cases of 123IMP and H131IPDM, while virtually all of 131IdU and 125IdC were bound to DNA in the cell nucleus. In agreement with our earlier in vivo studies, these data show that subcellular distribution plays a key role in the radiotoxicity of Auger electron emitters such as 123I and 125I, and has no role for beta emitters such as 131I. These findings may have implications in the design of radiopharmaceuticals for both diagnosis (localize Auger emitter in cytoplasm of cell) and therapy (localize Auger emitter in cell nucleus).

Amphetamines↗

PubMed1992

Absorbed dose calculations for rapidly growing tumors.

One of the most promising areas for cancer therapy with administered radiopharmaceuticals is the treatment of very small tumors and micrometastases. Small tumors and micrometastases, however, may be rapidly growing at the time of treatment, resulting in a substantial change in mass during the period of irradiation. In this work, the formalism required to calculate the average absorbed dose to rapidly growing tumors is developed and applied to an in vitro tumor model. Further application to in vivo human myeloma tumors reveals that tumor growth may have a significant effect on the average dose delivered to the tumor from incorporated radionuclides. These considerations may assist in establishing dose-response relationships necessary for radiopharmaceutical cancer therapy.

Cell Division↗

PubMed1991

Radiotoxicity of 125I-iododeoxyuridine in pre-implantation mouse embryos.

The radiotoxicity of DNA incorporated 125I in cultured pre-implantation two-cell mouse embryos was investigated and compared with external gamma-irradiation. The uptake of 125IdU in the two-cell stage embryos was determined as a function of incubation time and concentration of radioactivity (MBq/ml) in the medium. The absorbed dose to the embryos was calculated using conventional procedures. The embryo survival curves show that the dose at 37% survival is only about 15 cGy for 125IdU, whereas for 137Cs-photons it is 175 cGy. The extreme toxicity observed is thought to be due to the localized energy deposition of the numerous low energy Auger electrons emitted in the decay of 125I. These results are consistent with earlier observations in mouse testis and cultured cells and point to the need for assessing the radiation risk from incorporated Auger electron emitting radionuclides based on their subcellular distribution.

Animals↗

PubMed1991

The question of relative biological effectiveness and quality factor for auger emitters incorporated into proliferating mammalian cells.

The problem of determining RBE values for Auger emitters incorporated into proliferating mammalian cells is examined. In general, the reference radiation plays a key role in obtaining experimental RBE values. Using survival of cultured Chinese hamster V79 cells as the experimental model, new data are provided regarding selection of a reference radiation for internal Auger emitters. These data show that gamma rays delivered acutely (137Cs) are more than twice as lethal as gamma rays delivered chronically with an exponentially decreasing dose rate (99mTc). The results confirm that the reference radiation should be delivered chronically in a manner consistent with the extended exposure received by the cells in the case of incorporated radionuclides. Through a direct comparison of the radiotoxicity of Auger emitters and alpha emitters, the high RBE values reported for DNA-bound Auger emitters are confirmed. These studies reveal that the DNA binding compound [125I]iododeoxyuridine (125IdU) is about 1.6 times more effective in killing V79 cells than 5.3 MeV alpha particles from intracellularly localized 210Po-citrate. In addition, toxicity studies with the radiochemicals 125IdU and [125]-iododeoxycytidine (125IdC) establish the equivalence of the radiosensitivity of thymine and cytosine base sites in the DNA. In view of these results, and information already available, the question of establishing quality factors for Auger emitters is considered. Finally, a method for calculation of the dose equivalent for internal Auger emitters is advanced.

Animals↗

PubMed1991

Induction of sperm head abnormalities by incorporated radionuclides: dependence on subcellular distribution, type of radiation, dose rate, and presence of radioprotectors.

In contrast to the biological effects caused by exposure to external beams of radiation, the effects of tissue-incorporated radionuclides are highly dependent on the type of radiation emitted and on their distribution at the macroscopic, microscopic, and subcellular levels, which are in turn determined by the chemical nature of the radionuclides administered. Induction of abnormalities of sperm heads in mice is investigated in this work after the injection of a variety of radiochemicals including alpha emitters. When the initial slopes of the dose-response curves are used to compare the relative biological effectiveness (RBE) of different radiocompounds, the alpha particles emitted in the decay of 210Po are more effective than Auger electrons emitted by 125I incorporated in the DNA of the spermatogonial cells, and both emissions are more effective than X rays. It is also shown that the Auger emitters (125I, 111In) distributed in the cell nucleus are more efficient in producing abnormalities than the same radionuclides localized in the cytoplasm. These findings are consistent with our earlier observations, where spermatogonial cell survival is assayed as a function of the testicular absorbed dose. Further, chronic irradiation of testis with gamma rays from intratesticularly administered 7Be is about three times more effective in causing abnormalities than a single acute exposure to 120-kVp X rays. The resulting RBE values correlate well with our data on sperm head survival with the same radiocompounds. Finally, the radioprotector cysteamine, when administered in small, nontoxic amounts, significantly reduces the incidence of sperm abnormalities from alpha-particle radiation as well as emissions from 125I incorporated into DNA, the dose reduction factors being 10 and 14, respectively.

Alpha Particles↗

PubMed1990

Biological consequence of nuclear versus cytoplasmic decays of 125I: cysteamine as a radioprotector against Auger cascades in vivo.

When the radionuclide 125I is localized in mouse testis as 125I-iododeoxyuridine (an analogue of thymidine) and incorporated into the DNA of spermatogonial cells, the cytocidal effects are as severe as those due to densely ionizing alpha particles. In contrast, 125I confined to the cytoplasm of these cells is much less radiotoxic, the efficacy being the same as for selective irradiation of the testis with sparsely ionizing external X rays. The biological effects, in both cases, are strongly mitigated upon pretreatment of the testes with very small amounts (0.75 microgram) of cysteamine, a radioprotector. These findings suggest an important role for such chemical agents in radiation protection and in understanding the mechanisms of radiation damage involving radionuclides incorporated in tissue.

Animals↗