Cisplatin excretion in human milk.
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Adult↗
Biomedical subjects
R Gorodetsky
Publications and source records attributed to R Gorodetsky.
A long-term follow-up of metallic intraocular foreign bodies, employing diagnostic x-ray spectrometry.
We describe 10 eyes harboring metallic intraocular foreign bodies (IOFBs) for 9 to 46 years that had undergone diagnostic x-ray spectrometry to measure metal dissolution 9 years before this study. Findings from the present clinical and laboratory examinations, including perimetry, electroretinography, electrooculography, and diagnostic x-ray spectrometry examinations are reported. Deterioration in visual acuity consequent to metal dissolution of the IOFB was found in only one eye. Visual fields and electrophysiologic performances deteriorated in two other eyes for reasons that were probably unrelated to IOFB dissolution. Visual functions remained stable during the follow-up period in seven eyes, although excess copper levels were demonstrated in one of them. Eight of 10 eyes retained visual acuity of 6/24 or better. Diagnostic x-ray spectrometry confirmed siderosis in one patient and ruled out metallosis in the two patients with deteriorated vision for reasons that were unrelated to metallosis. The favorable outcome of this series of patients may influence one to consider a more conservative approach in the decision to remove IOFBs. A careful, life-long follow-up might be considered with periodic electroretinographic and diagnostic x-ray spectrometry examinations; the IOFB should be promptly removed if and when metallosis with damage to visual functions is demonstrated.
Adult↗
Model for the regulation of platelet volume and responsiveness by the trans-membrane Na+/K(+)-pump.
The correspondence between K+ uptake in platelets to their responsiveness was studied using 86Rb+ as an analogue of K+. An average 86Rb+ uptake rate of 0.73 (+/- 0.140) x 10(-15) mole Rb+/min-plt (n = 20) was observed. By the use of K(+)-influx inhibitors, we were able to distinguish three distinct 86Rb+ uptake pathways: an ouabain-sensitive (61% +/- 2% inhibitable) pump and two equivalent channels, only one of which is sensitive to furosemide. Other platelet parameters were also examined in conjunction with K(+)-uptake. Platelets incubated with ouabain exhibited an overall rise in their cell volume (MPV) with incubation time (delta MPV = 7.4 x 10(-17) L/min-1 plt-1). Concomitantly, over 24 hours, a steady decrease in platelet number was recorded by blood cell coulter, which correlated inversely with the counts of particles, which by their size resemble white blood cells (r = 0.89). On a cellular level, incubation with ouabain induced greater expression of surface fibrinogen-receptor (GPIIb), increased binding of FITC-labelled fibrinogen, and increased responsiveness to ADP. Our observations suggest the following sequence of events: Ouabain turns off the Na+/K(+)-ATPase pump, which leads to water accumulation in platelets and concomitant increased MPV. Greater expression of fibrinogen receptors on the distended platelet surface corresponds to spontaneous microaggregate formation as well as greater responsiveness to agonists. Our model links volume regulation, the expression of fibrinogen receptors, and the sensitivity of platelets to agonists to the activity of the Na+/K(+)-ATPase pump.
Blood Platelets↗
Effect of ionizing radiation on neuromuscular junctions in mouse tongues.
Radiation damage to the neuromuscular junctions (NMJs) in mouse tongues was studied using local x-irradiation of the tongues with the rest of the body shielded. Transmission electron microscopy (TEM) revealed no significant morphological changes in the fine structures and organelles of the NMJs given 4 Gy. A dose of 8 Gy produced degenevative morphological changes associated with oxon terminal sprouting as early as 2 and 7 days following irradiation. Subsequently, 1-11 weeks later, severe degenerative changes were observed. The number of mitochondria was significantly decreased with increased occurrence of degenerative membranal features. The number of synaptic footplates without terminals or with multiple small terminals within one groove increased gradually with time. Most of these pathological changes persisted for at least 3 months after irradiation. However, the myofibres, blood vessels and interstitial cells appeared to be unaffected throughout the period of follow-up. The present study substantiates our previous reports of ageing-like changes in the tongues' NMJs induced by their excessive exposure to free radicals.
Animals↗
The biological reductive capacity of tissues is decreased following exposure to oxidative stress: a cyclic voltammetry study of irradiated rats.
The reductive capacity of rat tissue homogenates and body fluids was determined by cyclic voltammetric measurements. The reductive capacity of rat lung, liver and kidney homogenates was significantly reduced four days after total body gamma-ray irradiation with 5.5 Gy as compared to controls. In parallel, reduced ability of the irradiated organ homogenates to scavenge hydroxyl radicals and to destroy hydrogen peroxide was recorded. However, no difference in their superoxide dismutase activity was found. The possible use of cyclic voltammetry as a method for qualitative evaluation of the ability of biological tissues to cope with oxidative stress is discussed.
Animals↗
Reduced ouabain-sensitive potassium entry as a possible mechanism of multidrug-resistance in P388 cells.
Multidrug-resistant P388 cells were found to be resistant also to a variety of ammonium, phosphonium and arsonium compounds. As previously shown for anthracyclines and vinca alkaloids, the resistance to the permanently charged lipophilic cationic compounds could be circumvented by verapamil. Relative to drug-sensitive cells, K+ uptake and plasma membrane Mg-ATPase activity in multidrug-resistant cells are ouabain resistant. The intracellular K+ concentration in drug-resistant cells is maintained at a normal level by increased activity of the furosemide sensitive transport system. It is suggested that the reduced activity of the electrogenic Na(+)-K+ pump in multidrug-resistant, cells could result in a lower transmembrane potential and therefore reduced accumulation of cationic lipophilic compounds.
Animals↗
Reducing white cells in platelet units.
White cells (WBCs) constitute a significant contaminant of platelet concentrates (PCs). Various technologies, including apheresis and filtration, are currently being developed to minimize the carryover of WBCs into platelets. The aim is to reduce contamination of less than 10(8) WBCs per platelet unit. As part of quality control monitoring of the blood bank operations, the centrifugation protocols employed in the preparation of platelet-rich plasma (PRP) have been evaluated for their impact on the WBC content of the PCs. The WBC content, which is expressed throughout the PRP volume as well as in the PC, reflects the degree of braking. For example, after centrifugation (2500 rpm, 4 min) of whole blood into packed red cells (RBCs) and PRP, braking-induced mixing increases the WBC content of the expressed PRP. Variations in the braking rates of the centrifuges used also correlate with the WBC carryover into packed platelets. An alternative centrifugation protocol to minimize WBC carryover is suggested. Whole blood is centrifuged at 2500 rpm for 1.5 minutes (rather than 4 min) and allowed to stop with no braking. This procedure adds some 3 minutes to the total centrifugation time, but the relative integral of this centrifugation program is approximately 50 percent smaller than that of the normally employed centrifugation protocol (with braking). It was observed that the WBC content throughout the expressed PRP, or in the entire PC, is reduced by about 75 percent. These results show that an effective method of significantly decreasing the WBC content of platelet units is simply to prepare PRP with reduced centrifugation time and with the braking programs disengaged.
Blood Platelets↗
Effect of fibroblast implants on wound healing of irradiated skin: assay of wound strength and quantitative immunohistology of collagen.
The role of dermal fibroblasts in the expression of radiation-induced damage to the skin was studied. Fibroblasts from neonatal mice were cultured, harvested, and injected into full-depth surgical incisions in the dorsal area of mouse skin, which had been previously locally irradiated by 18 Gy X rays. As a control, cells irradiated with a dose of 20 Gy were also injected. The effect of radiation and fibroblast implants on the gain of skin wound strength was assayed. In an additional experiment freshly isolated cells were implanted. Two weeks following wounding the irradiated skin had reached only about a third of the strength of unirradiated skin. A significant increase of wound strength in irradiated skin was observed when 1.5-2 x 10(6) cultured fibroblasts or freshly isolated fibroblasts were injected into the 20-mm-long wound bed. Irradiated cells had significantly less effect. This suggests that implanting isolated syngeneic cells may "rescue" wounds from the effect of prior irradiation. Semiquantitative immunohistology of types I and III collagen was performed in parallel using a video image digitizing system. Levels of both types I and III collagen were altered in the dermis and the wound tissues in irradiated skin, but the implant of cultured fibroblasts did not affect notably the total levels and the disposition of the two collagen isotypes.
Animals↗
Radiation effect in mouse skin: dose fractionation and wound healing.
Radiation induced dermal injury was measured by the gain in the physical strength of healing wounds in mouse skin. A sigmoid dose response for the inhibition of wound healing 14 days after surgery was found for single doses of X rays. The sparing of dermal damage from fractionation of the X-ray dose was quantified in terms of the alpha/beta ratio in the linear-quadratic (LQ) model, at a wide range of doses per fraction reaching as low as about 1 Gy. The fit and the appropriateness of the LQ model for the skin wound healing assay was examined with the use of the Fe-plot in which inverse total dose is plotted versus dose per fraction for wound strength isoeffects. The alpha/beta ratio of the skin was about 2.5 Gy (95% confidence of less than +/- 1 Gy) and was appropriate over a dose range of 1 Gy to about 8 Gy. The low alpha/beta value is typical for a late responding tissue. This assay, therefore, has the advantage of measuring and forecasting late radiation responses of the dermis within a short time after irradiation.
Animals↗
Skin zinc concentrations in patients with varicose ulcers.
The concentration of zinc in the skin has been determined noninvasively in patients with varicose vein ulcers. The examinations were performed with the use of diagnostic x-ray spectrometry, a method based on x-ray fluorescence for in vivo noninvasive evaluation of trace elements. Four skin foci were examined: at the periphery of the ulcer and control areas in a nonulcerated area in the diseased leg, in the noninvolved leg, and in the proximal inner surface of the arm. Zinc levels around the ulcer (mean +/- SD, 9.8 +/- 4.0 micrograms of zinc in 1 g of wet tissue) were higher than those in the nonulcerated skin in the diseased leg (6.9 +/- 3.0 micrograms/g, p greater than 0.05) and those in the noninvolved leg (5.4 +/- 2.0 micrograms/g, p less than 0.01). The concentration of zinc in the inner proximal surface of the arm (9.8 +/- 2.8 micrograms/g) was significantly higher than those of a control group (5.3 +/- 1.9 micrograms/g, p less than 0.01). These results suggest a defect of zinc distribution in patients with varicose vein ulcers.
Adult↗
Assay of radiation effects in mouse skin as expressed in wound healing.
The effect of 150 kVp X irradiation on the healing of full depth surgical wounds in the lower dorsal skin of the mouse was assayed by measuring the wound strength of seven 2-mm-wide segments along each wound. The strength of unirradiated wounds increased with time in two phases: during the first 2 weeks it reached nearly half of the values recorded from unwounded skin, after which the rate of increase slowed for at least 2 weeks before beginning a second increase. By 150 days, the breaking strength of the wound was about 80% of that of unwounded skin. A single dose of 18 Gy prior to wounding reduced the strength of the wounds to about one-third to one-half that of an unirradiated wounds within the 3 months of follow-up. The effect of irradiation on wound strength did not change as the interval between exposure and wounding was increased to 2 months but decreased slightly when this interval was extended to 3 months. When the healing wound was irradiated within 5 days of surgery, the effect on healing was about the same as with preirradiation; if irradiation was delayed for 12 days after wounding the second phase of healing was only postponed and the wound strength ultimately approached the values recorded from unirradiated wounds. The wound strength of skin preirradiated by X rays and assayed 14 days after wounding showed a clear sigmoid dose response with a threshold between 8 and 10 Gy and a plateau at the maximum effect above 20 Gy. The persistence for at least 3 months of the effect of radiation on wound healing suggests that the tissues involved in the healing process are normally proliferating slowly. The accelerated expression of radiation injury through surgical wounding permits the early quantification of the radiation response of tissues that would normally be delayed in their expression of radiation damage.
Animals↗
Elevated concentrations of elements and abnormalities of neuromuscular junctions in tongue muscles of Down's syndrome.
X-ray spectrometry was used to measure the concentrations of calcium, iron, copper and zinc in tongue muscles from patients with Down's syndrome (DS) undergoing partial glossectomy. Similar measurements on samples from autopsies served as controls. Electron microscopy was used to examine neuromuscular junctions. The calcium and copper were significantly elevated and correlated in DS while the iron and zinc showed little change. The copper increase is probably connected with the known high level of Zn-Cu superoxide dismutase (SOD), coded for by chromosome 21. (In DS there is a trisomy 21). The excess of SOD may interfere with free radicals needed for excitation-contraction coupling and may be instrumental in damaging junctional membranes. The high calcium may result from such membrane damage. It is suggested that neuromuscular junction pathology, either genetic or free radical induced, may cause the tongue weakness in DS.
Adolescent↗
The status of zinc in malaria (Plasmodium falciparum) infected human red blood cells: stage dependent accumulation, compartmentation and effect of dipicolinate.
The inhibitory effect of metal chelators on intraerythrocytic malarial parasites imply that trace metal have a vital role in the biology of these organisms. In the present work X-ray fluorometry was used to study the status of zinc and iron in human red blood cells infected with Plasmodium falciparum in culture conditions. It was found that while the iron level remains constant throughout the parasite cell cycle, that of zinc increases in parallel with parasite maturation to reach a 2.3-fold higher level than that of uninfected red blood cells. Compartment analysis of infected red blood cells indicated that most of this gain was associated with the parasite and some with the host-cell membrane. Analysis of the malarial pigment showed that the zinc/iron ratio was similar to that of red blood cells, implying the this compound, which results from the digestion of host-cell cytosol, sequesters the zinc of host metalloenzymes. Dipicolinic acid (DPA), like other chelators, was found to inhibit the intracellular development of the parasite with an ED50 of 1 mM. DPA does not penetrate into normal red blood cells but readily permeates into infected cells, although it does not leach out their zinc. It is uncertain whether the inhibitory effect of DPA is exerted through alterations of host cell metabolism or by directly affecting that of the parasite. The putative receptors of zinc in the infected red blood cell are discussed.
Animals↗
Effects of red blood cell potassium and hypertonicity on the growth of Plasmodium falciparum in culture.
Malarial parasites reproduce asexually inside the erythrocytes of their vertebrate host. Relatively little is known about the interaction between host cell and parasite metabolism. In the present study the effect of host cell cation composition and osmotic shrinkage on in vitro growth and propagation of Plasmodium falciparum in human erythrocytes was investigated. It is shown that throughout the parasite cell cycle, infected cells lose potassium and gain sodium. Compartment analysis of infected cells revealed that host cell cytosol is poor in potassium and rich in sodium while in the parasite this relationship is reversed, indicating that the parasite is able to regulate its ionic composition independently. Parasites proceeded normally through their cell cycle in the presence of the sodium-pump inhibitor ouabain, although host cells lost up to 75-80% of their normal potassium content. Potassium-depleted erythrocytes harboring trophozoites and schizonts also display normal rates of protein synthesis as measured by isoleucine incorporation. Parasite growth was inhibited when infected cells were osmotically shrunken in hypertonic media, but this was not due to parasite dehydration. It is suggested that increased viscosity of host cell cytosol and/or hemoglobin gelation, are responsible for the effect, probably through interference with parasite feeding. The relevance of these results to understanding of the cellular mechanism involved in the inhibiton of parasite growth in deoxygenated sickle-trait erythrocytes is discussed.
Erythrocytes↗
Elevation of erythrocyte zinc- and free protoporphyrins with metastatic spread in cancer patients.
A sensitive fluorometric method for the evaluation of erythrocyte levels of zinc-protoporphyrin (ZPP) and free-protoporphyrin (FPP) in diluted whole blood was used to survey patients with carcinomas in different stages o metastatic dissemination. ZPP levels in patients with primary tumor or with no evidence of metastatic disease were not different from those of normal donors. However, significantly higher ZPP levels were found in patients with carcinomas in correlation with evidence of metastatic disease, irrespective of the histological origin of the tumor. FPP levels were elevated in all stages of malignancy but were found 4 times higher than the normal levels in patients with metastatic malignancies. Similar increases in ZPP and FPP were detected in patients with inflammatory processes, suggesting a common effector of erythropoiesis in these pathological conditions and in metastatic diseases. Simultaneous detection of higher than normal ZPP and FPP levels in the blood of cancer patients may serve as an additional marker of metastatic dissemination in patients without clinical evidence of infectious or autoimmune diseases.
Adult↗
Iron, copper, and zinc concentrations in normal skin and in various nonmalignant and malignant lesions.
The concentrations of zinc (Zn), copper (Cu), and iron (Fe) in the skin have been noninvasively determined in vivo by diagnostic x-ray spectrometry. The skin of healthy controls was divided into two major groups based upon the distribution of the concentrations of these elements. In the face and upper neck, the following wet weight concentrations were recorded: Fe, 14.2 +/- 3.3 ppm; Cu, 1.3 +/- 0.3 ppm; and Zn, 6.7 +/- 1.1 ppm. In the chest, abdomen, arm, axilla, and lower neck, the concentrations of these elements were as follows: Fe, 10.2 +/- 2.5 ppm; Cu, 0.8 +/- 0.3 ppm; and Zn, 4.5 +/- 1.7 ppm. In most lesions of solar dermatitis, solar keratosis, basal and squamous cell carcinomas, variable elevations of Zn and Fe (up to significant levels) were recorded in most of the contralateral, apparently uninvolved skin. In the majority of pigmented nevi and malignant melanomas, the levels of Fe and Zn were elevated. In some of these, the Cu concentration also was increased.
Carcinoma, Squamous Cell↗
Skin discoloration in chronic idiopathic thrombocytopenic purpura: detection of local iron deposition by X-ray spectrometry.
A forty-six-year-old woman with a 32 years' history of idiopathic thrombocytopenic purpura presented with black-brown discoloration of her lower limbs. Noninvasive diagnostic X-ray spectrometry (DXS) for determination of trace elements in external tissues revealed striking local iron deposition confined to the skin area with the pigmentary changes. Iron deposition in the skin was probably due to recurrent local purpura caused by longstanding bleeding disorder. Hence DXS proved useful in the detection of local iron load and eliminated the need for skin biopsy in this patient with bleeding tendency.
Female↗
Correlation of erythrocyte and plasma levels of zinc, copper, and iron with evidence of metastatic spread in cancer patients.
The level of plasma copper (Cu-Pl) and zinc (Zn-Pl) and the level of erythrocyte iron (Fe-RBC), copper (Cu-RBC), and zinc (Zn-RBC) were determined in the blood of 70 normal donors and 138 patients with various solid tumors by diagnostic x-ray spectrometry (DXS), a technique based on x-ray fluorescence spectrometry analysis. There were no significant changes in the mean values of Zn-Pl, Fe-RBC, and Cu-RBC in the patients when compared with those of normal donors. The mean level of Cu-Pl in the normal donors was 1.34 +/- 0.37 micrograms/ml; it was significantly increased in the patients, ranging between 1.47 +/- 0.34 micrograms/ml for patients without evidence of active cancer (NED) and 1.91 +/- 0.76 micrograms/ml for patients with hepatic metastases. The most significant change observed was an increase in the Zn-RBC found in the patients with clinical evidence of metastatic spread. Whereas the Zn-RBC level in the normal donors was 9.85 +/- 1.47 micrograms/g wet weight, and not significantly elevated in the NED patients, it was elevated to values of 11.37 +/- 1.55 micrograms/g (P less than 0.004) for patients with soft tissue and hepatic metastases and was 12.34 +/- 1.65 micrograms/g (P less than 0.001) for patients with bone metastases. The data suggest a clear correlation between Zn-RBC and metastatic spread in nonlymphomatous human cancer.
Bone Neoplasms↗