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This article co-authored by a number of scientists, ASAM physicians, clinicians, treatment center owners, geneticists, neurobiologists, psychologists, social workers, criminologists, nurses, nutritionist, and students, is dedicated to all the people who have lost loved ones in substance-abuse and "reward deficiency syndrome" related tragedies. Why are we failing at reducing the incidence of 'Bad Behaviors'? Are we aiming at the wrong treatment targets for behavioral disorders? We are proposing a paradigm shift and calling it "Reward Deficiency Solution System" providing evidence for its adoption.

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OBJECTIVES: Our purpose was to determine the effects of 17 alpha-dihydroequilenin on plasma lipid and lipoprotein, glucose, and insulin concentrations; coronary artery vasomotor function; and reproductive organ and mammary gland proliferation in atherosclerotic male and female rhesus macaques. STUDY DESIGN: Fifty adult female and 33 adult male rhesus macaques were randomized to treatment by lifetime dietary cholesterol exposure and ratio of total plasma cholesterol to high-density lipoprotein cholesterol. The female treatment groups were intact female controls (n = 9), ovariectomized controls (n = 16), ovariectomized plus 0.3 mg/kg/day 17 alpha-dihydroequilenin (n = 17) and ovariectomized plus subcutaneous estradiol (n = 7). The male treatment groups were control (n = 16) and 1.25 mg/kg/day 17 alpha-dihydroequilenin (n = 17). Treatment lasted 5 weeks. Longitudinal assessments of plasma lipid and lipoprotein and glucose and insulin concentrations were performed. Coronary artery vasomotor function was assessed by quantitative coronary angiography 1 week after initiation of treatment. Morphologic and immunohistochemical assessments of proliferation index values of reproductive organs and mammary glands were done at necropsy. RESULTS: 17 alpha-Dihydroequilenin prevented endothelium-dependent vasoconstriction in males (p < 0.05) and ovariectomized females (p < 0.08). 17 alpha-Dihydroequilenin treatment increased plasma apolipoprotein A-1 concentrations (p < 0.05) and lowered fasting insulin concentrations (p < 0.05) without changing fasting plasma glucose concentrations in males. 17 alpha-Dihydroequilenin had no other effects on plasma lipid and lipoprotein concentrations in either males or females. It had no trophic effects on uterus, endometrium, or breast. There was no effect on either prostatic or testicular weight. CONCLUSION: 17 alpha-Dihydroequilenin may represent a single-agent hormone therapy for reduction of ischemic hear disease risk for both menopausal women and men. It has no apparent trophic effects on reproductive organs or mammary glands of female and male rhesus macaques.

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A method for inducing sweating in the rat via heat stress and without the use of general anesthetics is presented. Five commonly used H1-blocking antihistamines were evaluated in this model for their antiperspirant efficacy. The antihistamines evaluated and their ED50 values (micrograms base/pad) were as follows: phenindamine, 3.02; diphenhydramine, 3.25; chlorpheniramine, 3.12; tripelennamine, 4.91; and pyrilamine, 13.03. Atropine sulfate, injected into the foot pads, was also found to inhibit the sweat response. The response to atropine varied directly with dose. The ED50 was estimated to be 0.4 ng base/foot pad. No systemic effects or contralateral involvement were seen. The rat foot pad contains eccrine sweat glands that are innervated by sympathetic cholinergic fibers. This relationship is analogous to that in the eccrine sweat glands of man. The rat data suggest that antihistamines, possibly via an anticholinergic effect, may be useful as potential antiperspirants in man.

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The medical services provided at the South African Railways and Harbour Ambulance Room in Table Bay Harbour are described. The excellent human relations that have developed in this service are stressed, and the use of selective employment to minimize loss of manpower and wages through sickness and accidents is also emphasized.

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Fv fragments prepared from the BALB/c anti-dinitrophenyl (DNP) myeloma proteins, produced by plasmacytoma MOPC 315 and XRPC 25, were used to raise anti-idiotypic antibodies in rabbits. Anti-idiotypes to these proteins were also prepared in the syngeneic BALB/c mice by injecting the intact proteins, whereas Fv fragment failed to induce antibodies in these mice. Rabbit anti-Fv of late bleedings did not show the presence of antibodies to "framework determinants" (determinants common to all V regions of mouse immunoglobulins), and they contained precipitating anti-idiotypes whereas mouse antisera contained non-precipitating anti-idiotypes. No cross-reaction was observed between anti-idiotypes to these myeloma proteins and induced anti-DNP antibodies from BALB/c mice, when either rabbit or mouse antisera were analyzed. The anti-sera were fractionated into anti-binding site and anti-non-binding site by adsorption onto the immunogen-Sepharose column and elution by DNP lysine, followed by elution with acetic acid. Only the anti-binding sites were inhibited by hapten in their interaction with the homologous myeloma protein. The rabbit anti-Fv antibodies were predominantly (over 90%) anti-non-binding site whereas the mouse anti-idiotypes were predominantly (60 to 70%) anti-binding site.

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Antibodies to nitrotyrosine were prepared in goats or rabbits by injecting a nitrotyrosine-protein conjugate. The antibodies were purified by using a protein that had been nitrated with tetranitromethane. These antibodies were used to isolate nitrotyrosine-containing peptides from nitrated lysozyme. The nitrotyrosine-containing peptides were thus purified (55% yield) in one step and the positions of nitration in lysozyme were found to be at tyrosine-20 and tyrosine-23. This method is of general applicability for the determination of the position of nitrotyrosine in proteins.

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