Effects on blood cells

Hydroxyurea, a chemotherapeutic agent, has many effects on blood cells, including the stimulation of HbF production. It is indicated for patients with frequent painful episodes, severe symptomatic anemia, acute chest syndrome, or other severe vasoocclusive complications. The dosage should be individualized based on response and toxicity (Fig. 34-1). 

Chlorpromazine is a tranquilizing and antiemetic agent that may cause a number of side effects in the circulatory and nervous system and adverse effects on blood cells, skin, and the eye. Recent studies suggest a possible genotoxic activity for chlorpromazine, whereas it has been established that certain reactive metabolic intermediates are capable of binding with macromolecules including DNA. 

Isopropanol has sensitizing properties but is not a dermal irritant. Volunteers inhaling this compound for several minutes developed irritation to the eyes and rhinopharynx. Oral intake of low doses (2.6-6 4 mg/kg bw) had no effect on blood cells, serum or urine and produced no symptoms (lARC, 1977). 

Immunosorbents, like other sorbents described above, also have problems when they contact blood directly. These problems inclnde embolisms of particnlates and adverse effects on blood cells. The same ultrathin coating nsed in sorbents has been applied to immnnosorbents to prevent these problems. This has been tested clinically in patients. ... 

Prus and Fibach (2012) demonstrated that fermented papaya preparation (FPP) exhibits reactive oxygen species (ROS) scavenging effect on blood cells in both an in vitro and in vivo model (in thalassemic patients and experimental animals). Fermented papaya effectively reduces ROS and it was suggested that its antioxidant mechanism is related, at least in part, to iron chelation. 

Nitrogen dioxide (NO2) at levels found in healthy subjects indoors caused mild airway inflammation, effects on blood cells, and increased susceptibility of airway epithelial cells to injury from respiratory viruses (Frampton et al. 2002). 

Lead biokinetics can potentially be affected by erythrocyte instability in ways such as increased erythrocyte fragility and brittleness due to lead s inhibitory effects on blood cell membrane stability, ionic pump activity, and ionic flux homeostasis. These abnormalities occur at chronic Pb exposures producing PbB of 50—60 pg/dl or higher, where numerous toxic endpoints have been triggered. 

Lead is toxic to the kidney, cardiovascular system, developiag red blood cells, and the nervous system. The toxicity of lead to the kidney is manifested by chronic nephropathy and appears to result from long-term, relatively high dose exposure to lead. It appears that the toxicity of lead to the kidney results from effects on the cells lining the proximal tubules. Lead inhibits the metaboHc activation of vitamin D in these cells, and induces the formation of dense lead—protein complexes, causing a progressive destmction of the proximal tubules (13). Lead has been impHcated in causing hypertension as a result of a direct action on vascular smooth muscle as well as the toxic effects on the kidneys (12,13). 

Hematology. The functional status of blood and of the blood-forming tissues can be assessed by tests which include red and white blood cell counts, platelet counts, clotting time, coagulation tests, and examination of bone marrow. Such tests, in addition to detecting abnormahties, may also allow differentiation between primary and secondary effects on blood and blood-forming tissues (75). 

Modern representations of the virtual heart, therefore, describe structural aspects like fibre orientation in cardiac muscle, together with the distribution of various cell types, active and passive electrical and mechanical properties, as well as the coupling between cells. This then allows accurate reproduction of the spread of the electrical wave, subsequent contraction of the heart, and effects on blood pressure, coronary perfusion, etc. It is important to point out, here, that all these parameters are closely interrelated, and changes in any one of them influence the behaviour of all others. This makes for an exceedingly complex system. 

Cyclosporine reduces production of cytokines involved in T-cell activation and has direct effects on B cells, macrophages, bone, and cartilage cells. Its onset appears to be 1 to 3 months. Important toxicities at doses of 1 to 10 mg/kg/day include hypertension, hyperglycemia, nephrotoxicity, tremor, GI intolerance, hirsutism, and gingival hyperplasia. Cyclosporine should be reserved for patients refractory to or intolerant of other DMARDs. It should be avoided in patients with current or past malignancy, uncontrolled hypertension, renal dysfunction, immunodeficiency, low white blood cell or platelet counts, or elevated Ever function tests. 

Follow-on studies are also recommended as needed. These include determination of potential test article effects on blood or tissue immunophenotypes (by flow cytometry or immunohistochemistry), natural killer cell, macrophage, or neutrophil function, host resistance to infection or tumors, and cell-mediated immunity. The important issue in all of these guidelines is this do not ignore signs of immunotoxicity, and assess these findings when observed. 

Atropine generally increases heart rate, but it may briefly and mildly decrease it initially, due to Ml receptors on postganglionic parasympathetic neurons. Larger doses of atropine produce greater tachycardia, due to M2 receptors on the sinoatrial node pacemaker cells. There are no changes in blood pressure, but arrhythmias may occur. Scopolamine produces more bradycardia and decreases arterial pressure, whereas atropine has little effect on blood pressure (Vesalainen et al. 1997 Brown and Taylor 1996). 

To characterize IRIV-elicited immune responses in vitro, we addressed cell proliferation and cytokine expression in peripheral blood mononuclear cell (PBMC) cultures, as well as IRIV effects on dendritic cells (DC). In all experiments, PBMC were obtained from healthy donors and, if needed, further separated into different cell subsets. Finally, cells were cultured in the presence or absence of IRIV as indicated. 

When Robert Noble carried out his studies on the periwinkle leaves, he found that they had no effect on blood sugar levels. However, they did appear to signihcantly reduce a subject s white blood cell count. Perhaps, Dr. Noble reasoned, the product could be used to treat diseases characterized by abnormally high white blood cell counts, such as leukemia. He was successful in isolating two chemicals from the periwinkle leaves, which he named vinblastine and vincristine, that markedly decreased white blood cell counts in patients with certain forms of cancer. The two chemicals were the first anticancer agents derived from natural sources to be approved for use with human patients. 

A. Atropine has little effect on blood pressure in the absence of a circulating muscarinic agonist because the muscarinic receptors on endothelial cells do not receive synaptic input. Therefore, the blood pressure of a healthy patient will not change with treatment with atropine. In contrast, patients being treated with an AQiE inhibitor may have slightly elevated plasma ACh levels, and patients being treated with bethanechol may be hypotensive because of its direct actions on the muscarinic receptors on endothelial cells. 

The antithrombotic effects of NO are also mediated by NO-dependent inhibition of platelet aggregation. Both endothelial cells and platelets contain eNOS, which acts to regulate thrombus formation. Thus, endothelial dysfunction and the associated decrease in NO generation may result in abnormal platelet function. As in vascular smooth muscle, cGMP mediates the effect of NO in platelets. NO may have an additional inhibitory effect on blood coagulation by enhancing fibrinolysis via an effect on plasminogen. 

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