Rôle of the Blood and the Bone Marrow in Certain Forms of Gas Poisoning

Krumbhaar, E. B.

doi:10.1001/jama.1919.26110010018009f

Cited by 50 publications

(21 citation statements)

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“…Krumbhaar observed that among the first changes in the circulating blood of patients exposed to SM was an exhaustion of leukocyte forming centers [15,16]. Leukocytosis is common within the first few days after exposure.…”

Section: Discussionmentioning

confidence: 99%

Long-term hematological and immunological complications of sulfur mustard poisoning in Iranian veterans

Mahmoudi

Hefazi

Rastin

et al. 2005

International Immunopharmacology

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Section: Discussionmentioning

confidence: 99%

Long-term hematological and immunological complications of sulfur mustard poisoning in Iranian veterans

Mahmoudi

Hefazi

Rastin

et al. 2005

International Immunopharmacology

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“…Exposure to mustard gas induces severe injuries to the eyes, skin, and respiratory tract. In 1917, Krumbhaar, a Captain in the U.S. Medical Corps, noted the development of profound leukopenia in individuals who survived a gas attack for several days (Krumbhaar 1919;Krumbhaar and Krumbhaar 1919). Following up on this observation, a group from the U.S. Office of Scientific Research and Development (OSRD) at Yale Medical School secretly studied the effects of nitrogen mustard on lymphomata.…”

Section: Nitrogen Mustardsmentioning

confidence: 99%

DNA Damaging Drugs

Weber

2015

Molecular Therapies of Cancer

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The classical anti-cancer agents comprise cytotoxic compounds. Mostly, these drugs act by exerting DNA damage. In essence, there are two major response phenotypes available to a cell upon DNA damage, such as a chemotherapeutic drug action, -to arrest the cell cycle and repair the damage, -to initiate a pathway to apoptosis (programmed cell death).In either scenario, the uncontrolled growth of the tumor cells is curtailed. The major limitation of the cytotoxic anti-cancer drugs is the tumor non-specific action, and the suppression of all rapidly dividing cells 1 . Alkylating AgentsAlkylating agents 2 are electrophilic and bind covalently to electron-rich functional groups of various target molecules via first-order or second-order nucleophilic substitutions (nucleophiles are electron-rich molecules or ions, such as OH − , H 2 O, halogenides, alcohols, thiols and amines). The first order reactants include aromatic and aliphatic nitrogen and sulfur mustards. Second order reactants include ethylene 1 Because the desired drug actions (damage to rapidly proliferating cancer cells) and the adverse effects (damage to rapidly proliferating healthy cells) are identical in targets and mechanisms, they are not separable. 2 Alkyl designates a functional group (a "side chain") that consists solely of single-bonded carbon and hydrogen atoms. Alkylating anticancer agents attach alkyl groups to biomolecules. imines and epoxides, alkylmethane sulfonates of the busulfan (Myleran) type, and α-halogenated acids, ketones, and their derivatives.-For first-order reactions, the rate limiting step is the ionization of the alkylating agent to form a positively charged carbonium ion, which then rapidly reacts with water, or a negative center, or a nucleophilic center. Within DNA and RNA, the most reactive site is the N 7 position of guanine ( Fig. 2.1). In DNA, this is followed by N 3 of adenine, N 1 of adenine, N 1 of cytosine, and N 7 of adenine (Table 2.1). The rate limiting step of the reaction is the formation of positively charged cyclic immonium ions, whereas the rate of the reaction is essentially independent of the nature and concentration of the nucleophilic target being attacked. -For second order nucleophilic substitutions, both reactants interact to form a transition complex. No carbonium ion is formed. The rate of the reaction depends on both concentrations, with bond strengths, electron affinity, and accessibility of both reagents being important (Knock 1967).Alkylating agents exert cytotoxic effects by transferring alkyl groups to DNA, thereby damaging the DNA and interfering with DNA transcription and cell division. This class of drugs mainly works by three distinct mechanisms:-The attachment of alkyl groups to DNA bases prevents DNA synthesis and RNA transcription, and it results in the DNA being fragmented by repair enzymes in a process to replace the altered bases. -The two arms of mustard drugs can cross-link DNA strands. In this process, two bases are linked together. Bridges can be formed within a single molecule of...

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“…The poisoned soldiers demonstrated leukopenia, bone marrow aplasia, dissolution of lymphoid tissue and ulceration of the gastro-intestinal tract. Bronchopneumonia in these subjects was characterized by the absence of leucocyte response [1]. Subsequent studies revealed that the susceptible tissues were those with rapid regenerative capacity, such as bone marrow, lymphoid tissue and the epithelium of the gastro-intestinal tract.…”

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confidence: 99%

Stimulatory and Protective Effects of Alkylating Agents Applied in Ultra-Low Concentrations

Pukhalsky

Shmarina

2001

Pharmacology

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Alkylating drugs belonging to the nitrogen mustard family are known as cytostatic and immunosuppressive agents. Ultra-low doses of these drugs may demonstrate pharmacological effects unlike this category of drugs. In the case of a gradual dose decrease, the number of targets for alkylation is also reduced and the drug switches from cytostatic to cell growth modifier. We postulate that application of ultra-low doses of alkylating drugs may result in a beneficial effect in the therapy of diseases associated with chronic inflammation of the mucosa, especially with the signs of epithelial atrophy.

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Rôle of the Blood and the Bone Marrow in Certain Forms of Gas Poisoning

Cited by 50 publications

References 0 publications

Long-term hematological and immunological complications of sulfur mustard poisoning in Iranian veterans

Long-term hematological and immunological complications of sulfur mustard poisoning in Iranian veterans

DNA Damaging Drugs

Stimulatory and Protective Effects of Alkylating Agents Applied in Ultra-Low Concentrations

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